FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Hsu, CS Chen, HC Jeng, J Kao, JH Chen, DS AF Hsu, Ching-Sheng Chen, Hung-Chia Jeng, Jenher Kao, Jia-Horng Chen, Ding-Shinn TI Reply to Guedj et al.: Early transient increase of hepatitis C virus viral load in genotype 1 and 2 infections, and the use of mathematical modeling SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Letter ID THERAPY C1 [Hsu, Ching-Sheng; Kao, Jia-Horng; Chen, Ding-Shinn] Natl Taiwan Univ, Coll Med, Grad Inst Clin Med, Taipei 10002, Taiwan. [Hsu, Ching-Sheng] Buddhist Tzu Chi Gen Hosp, Dept Internal Med, Div Gastroenterol, Taipei 23142, Taiwan. [Hsu, Ching-Sheng] Tzu Chi Univ, Sch Med, Hualien 97004, Taiwan. [Kao, Jia-Horng; Chen, Ding-Shinn] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei 10002, Taiwan. [Kao, Jia-Horng] Natl Taiwan Univ, Coll Med, Dept Med Res, Taipei 10002, Taiwan. [Kao, Jia-Horng] Natl Taiwan Univ, Coll Med, Hepatitis Res Ctr, Taipei 10002, Taiwan. Natl Taiwan Univ Hosp, Taipei 10002, Taiwan. [Chen, Hung-Chia] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Jeng, Jenher] Natl Chiao Tung Univ, Ctr Math Modeling & Sci Comp, Hsinchu 30010, Taiwan. RP Chen, DS (reprint author), Natl Taiwan Univ, Coll Med, Grad Inst Clin Med, Taipei 10002, Taiwan. EM chends@ntu.edu.tw OI CHEN, DING-SHINN/0000-0001-7791-6154; KAO, JIA-HORNG/0000-0002-2442-7952 NR 4 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 19 PY 2011 VL 108 IS 29 BP E303 EP E303 DI 10.1073/pnas.1106498108 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 794DY UT WOS:000292876900006 ER PT J AU Xiao, S Kumar, M Yang, XL Akkoyunlu, M Collins, PL Samal, SK Pal, U AF Xiao, Sa Kumar, Manish Yang, Xiuli Akkoyunlu, Mustafa Collins, Peter L. Samal, Siba K. Pal, Utpal TI A host-restricted viral vector for antigen-specific immunization against Lyme disease pathogen SO VACCINE LA English DT Article DE Borrelia burgdorferi; Newcastle disease virus; Lyme disease; Immunization; Vaccine ID OUTER-SURFACE PROTEIN; AVIAN INFLUENZA-VIRUS; NEWCASTLE-DISEASE; BORRELIA-BURGDORFERI; VACCINE VECTOR; ACTIVE IMMUNIZATION; RESPIRATORY-TRACT; FOREIGN GENE; OSPC; MICE AB Newcastle disease virus (NDV) is an avian virus that is attenuated in primates and is a potential vaccine vector for human use. We evaluated NDV as a vector for expressing selected antigens of the Lyme disease pathogen Borrelia burgdorferi. A series of recombinant NDVs were generated that expressed intracellular or extracellular forms of two B. burgdorferi antigens: namely, the basic membrane protein A (BmpA) and the outer surface protein C (OspC). Expression of the intracellular and extracellular forms of these antigens was confirmed in cultured chicken cells. C3H or Balb/C mice that were immunized intranasally with the NDV vectors mounted vigorous serum antibody responses against the NDV vector, but failed to mount a robust response against either the intracellular or extracellular forms of BmpA or OspC. By contrast, a single immunization of hamsters with the NDV vectors via the intranasal, intramuscular, or intraperitoneal route resulted in rapid and rigorous antibody responses against the intracellular or extracellular forms of BmpA and OspC. When groups of hamsters were separately inoculated with various NDV vectors and challenged with B. burgdorferi (10(8) cells/animal), immunization with vector expressing either intracellular or extracellular BmpA was associated with a significant reduction of the pathogen load in the joints. Taken together, our studies highlighted the importance of NDV as vaccine vector that can be used for simple yet effective immunization of hosts against bacterial infections including Lyme disease. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Xiao, Sa; Kumar, Manish; Yang, Xiuli; Samal, Siba K.; Pal, Utpal] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA. [Akkoyunlu, Mustafa] US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Collins, Peter L.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Samal, SK (reprint author), Univ Maryland, Dept Vet Med, Bldg 795,Room 1341, College Pk, MD 20742 USA. EM ssamal@umd.edu; upal@umd.edu RI Akkoyunlu, Mustafa/I-5712-2012; Pal, Utpal/I-5265-2015 FU NIH/NIAID [AI080615, AR055323, N01A060009]; NIH FX This research was supported in part by NIH/NIAID Awards (AI080615 and AR055323), NIH/NIAID Contract N01A060009 and NIH Intramural Research Program. We sincerely thank Alexis Smith for her excellent assistance with this study. NR 65 TC 7 Z9 8 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUL 18 PY 2011 VL 29 IS 32 BP 5294 EP 5303 DI 10.1016/j.vaccine.2011.05.010 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 808OB UT WOS:000293987200028 PM 21600949 ER PT J AU Chandwani, S Beeler, J Li, H Audet, S Smith, B Moye, J Nalin, D Krasinski, K AF Chandwani, Sulachni Beeler, Judy Li, Hong Audet, Susette Smith, Betsy Moye, John Nalin, David Krasinski, Keith CA PACTG 225 Study Team TI Safety and Immunogenicity of Early Measles Vaccination in Children Born to HIV-Infected Mothers in the United States: Results of Pediatric AIDS Clinical Trials Group (PACTG) Protocol 225 SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Global Technical Consultation to Assess the Feasibility of Measles Eradication CY JUL 28-30, 2010 CL Washington, DC ID HUMAN-IMMUNODEFICIENCY-VIRUS; ACTIVE ANTIRETROVIRAL THERAPY; MATERNAL ANTIBODY; IMMUNE-RESPONSES; IMMUNIZATION; INFANTS; VACCINES; CELL; REVACCINATION; TITERS AB Background. PACTG (Pediatric AIDS Clinical Trials Group) 225, a multicenter, randomized, open-label trial in the United States evaluated reactogenicity and immunogenicity of 2 vaccination regimens: monovalent measles vaccine (Attenuvax) at 6 months of age and measles, mumps, and rubella, live attenuated (MMRII) vaccine at 12 months of age (2D), or only MMRII at 12 months of age (1D) in human immunodeficiency virus infected (HIV-infected) (POS) and uninfected (NEC) children in the pre-highly active antiretroviral therapy (pre-HAART) period. Methods. Plaque-reduction neutralization (PRN) of measles-neutralizing antibody titers were evaluated at study weeks 0, 6, 26, 32, 52, and 130 (similar to 3 years of age). Results. The 110 subjects included: 65 2DNEG; 30 1DNEG; 7 2DPOS and 8 1DPOS. Vaccinations (n = 175) were associated with no adverse experiences >Grade 2 except for Grade 3 fever (n = 2, 1 1DPOS and 1 1DNEG). Six weeks after Attenuvax, all 2DPOS subjects (7/7) seroresponded (PRN titers >= 120 mlU/mL) with median titers significantly exceeding 2DNEG titers (2115 vs 628 mlU/mL, respectively; P = .023). At similar to 3 years of age, 67% 1DPOS (4/6) and 83% 2DPOS (4/5) subjects maintained titers >= 120 mlU/mL. Prevaccination titers >= 25 mlU/mL among 2DNEG subjects correlated inversely with the likelihood of achieving titers >= 120 mlU/mL (56% vs 90%; P = .004). Conclusions. Among HIV-infected children pre-HAART, Attenuvax at 6 months was well tolerated and immunogenic. These data support the current World Health Organization (WHO) recommendation to administer a first dose of measles vaccine at 6 months of age to HIV-infected children. C1 [Chandwani, Sulachni; Krasinski, Keith] NYU, Dept Pediat, Sch Med, New York, NY 10016 USA. [Li, Hong] Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. [Beeler, Judy; Audet, Susette] US FDA, Bethesda, MD 20014 USA. [Smith, Betsy] NIAID, Bethesda, MD 20892 USA. [Moye, John] NICHHD, Bethesda, MD 20892 USA. [Nalin, David] Merck Vaccine Div, West Point, PA USA. RP Chandwani, S (reprint author), NYU, Dept Pediat, Sch Med, 550 1st Ave,8W46 NB Bldg, New York, NY 10016 USA. EM sulachni.chandwani@nyumc.org OI moye, john/0000-0001-9976-8586 FU NIAID [U01 AI068632]; Division of Microbiology and Infectious Diseases (DMID); Centers for Disease Control and Prevention; Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases [5 U01 AI41110]; PACTG; International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group [1 U01 AI068616]; National Institutes of Health (NIH); NICHD; Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD); National Institute of Mental Health (NIMH) [AI068632]; NICHD [N01-DK-9-001/HHSN267200800001C] FX J. B. is employed by CBER and FDA and receives financial support from NIAID and Division of Microbiology and Infectious Diseases (DMID) for other activities outside of this study. D. N. is a retired director of Vaccine Scientific Affairs, Merck Vaccine Division, and holds stocks and stock options in Merck Pharmaceuticals.; This article is part of a supplement entitled "Global Progress Toward Measles Eradication and Prevention of Rubella and Congenital Rubella Syndrome," which was sponsored by the Centers for Disease Control and Prevention.; This work was supported by the Statistical and Data Analysis Center at Harvard School of Public Health, under the National Institute of Allergy and Infectious Diseases cooperative agreement #5 U01 AI41110 with the PACTG, and #1 U01 AI068616 with the International Maternal Pediatric Adolescent AIDS Clinical Trials (IMPAACT) Group, and was also supported in part by a grant from National Institutes of Health (NIH) and NICHD (K. K.). Overall support for the International Maternal Pediatric Adolescent AIDS Clinical Trials Group (IMPAACT) was provided by the National Institute of Allergy and Infectious Diseases (NIAID) (U01 AI068632), the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD), and the National Institute of Mental Health (NIMH) (AI068632). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH. Support of the sites was provided by the NIAID and NICHD International and Domestic Pediatric and Maternal HIV Clinical Trials Network funded by NICHD (contract number N01-DK-9-001/HHSN267200800001C). Merck Vaccine Division supplied the Attenuvax and MMRII vaccines. NR 40 TC 7 Z9 7 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2011 VL 204 SU 1 BP S179 EP S189 DI 10.1093/infdis/jir089 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 802YT UT WOS:000293547600023 PM 21666159 ER PT J AU Fowlkes, A Witte, D Beeler, J Audet, S Garcia, P Curns, A Yang, CF Fudzulani, R Broadhead, R Bellini, WJ Cutts, F Helfand, RF AF Fowlkes, Ashley Witte, Desiree Beeler, Judy Audet, Susette Garcia, Philip Curns, Aaron Yang, Chunfu Fudzulani, Richard Broadhead, Robin Bellini, William J. Cutts, Felicity Helfand, Rita F. TI Persistence of Vaccine-Induced Measles Antibody Beyond Age 12 Months: A Comparison of Response to One and Two Doses of Edmonston-Zagreb Measles Vaccine Among HIV-Infected and Uninfected Children in Malawi SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Global Technical Consultation to Assess the Feasibility of Measles Eradication CY JUL 28-30, 2010 CL Washington, DC ID ZAMBIAN CHILDREN; 6-MONTH-OLD INFANTS; NEUTRALIZATION TEST; PLACENTAL-TRANSFER; IMMUNOGENICITY; IMMUNIZATION; IMMUNITY; MOTHERS; STRAIN; TITERS AB Background. Previously, we demonstrated that measles antibody prevalence was lower at age 12 months among children infected with human immunodeficiency virus (HIV) than uninfected children following measles vaccination (MV) at ages 6 and 9 months. Among HIV-uninfected children, measles antibody prevalence was lower among 1- than 2-dose MV recipients. Here, we report results through age 24 months. Methods. Children born to HIV-infected mothers received MV at 6 and 9 months, and children of HIV-uninfected mothers were randomized to MV at 6 and 9 months or MV at 9 months. We followed children through age 24 months. The child's HIV status was determined and measles immunoglobulin G (IgG) level was measured by enzyme immunoassay (PIA) and by plaque reduction neutralization (PRN) on a subset. Results. Among HIV-uninfected children, the difference in measles antibody prevalence at age 12 months between one- and two-dose recipients reported previously by EIA was shown to be smaller by PRN. By age 24 months, 84% and 87% of HIV-uninfected children receiving 1 or 2 doses, respectively, were seroprotected. Only 41% of 22 HIV-infected children were measles seroprotected at age 20 months. Discussion. Measles seroprotection persisted through age 24 months among HIV-uninfected children who received 1 or 2 doses of MV. HIV-infected children demonstrated seroprotection through age 12 months, but this was not sustained. C1 [Fowlkes, Ashley; Garcia, Philip; Curns, Aaron; Yang, Chunfu; Bellini, William J.; Helfand, Rita F.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Witte, Desiree; Fudzulani, Richard; Broadhead, Robin] Univ Malawi, Coll Med, Blantyre, Malawi. [Beeler, Judy; Audet, Susette] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Cutts, Felicity] London Sch Hyg & Trop Med, London, England. RP Fowlkes, A (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,MS A34, Atlanta, GA 30333 USA. EM afowlkes@cdc.gov RI Yang, Chunfu/G-6890-2013 FU Centers for Disease Control and Prevention; World Health Organization; CDC; Measles Steering Committee of the World Health Organization FX This article is part of a supplement entitled "Global Progress Toward Measles Eradication and Prevention of Rubella and Congenital Rubella Syndrome," which was sponsored by the Centers for Disease Control and Prevention.; This study was funded by the World Health Organization and CDC.; We would like to thank Drs Peter Strebel, Laura Walls, Sun Bae, and the Ndirande Health Centre staff for their many contributions to the research presented. We would also like to thank the following people and organizations for their technical guidance and support: Drs Robin Biellik, Pegi Henderson, Samuel Katz, Renu Lal, and Cathy Wilfert; the Measles Steering Committee of the World Health Organization; the members of the Data Safety Monitoring Board, and the Malawi Ministry of Health and Expanded Programme of Immunization. We would also like to acknowledge Carl Campbell for his logistic support. NR 31 TC 10 Z9 10 U1 1 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 EI 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD JUL 15 PY 2011 VL 204 SU 1 BP S149 EP S157 DI 10.1093/infdis/jir135 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 802YT UT WOS:000293547600020 PM 21666156 ER PT J AU Haughey, SA Campbell, K Yakes, BJ Prezioso, SM DeGrasse, SL Kawatsu, K Elliott, CT AF Haughey, Simon A. Campbell, Katrina Yakes, Betsy J. Prezioso, Samantha M. DeGrasse, Stacey L. Kawatsu, Kentaro Elliott, Christopher T. TI Comparison of biosensor platforms for surface plasmon resonance based detection of paralytic shellfish toxins SO TALANTA LA English DT Article DE Surface plasmon resonance; Biosensor; Paralytic shellfish poisoning; Saxitoxin ID SINGLE-LABORATORY VALIDATION; POISONING TOXINS; PRECHROMATOGRAPHIC OXIDATION; QUANTITATIVE-DETERMINATION; FLUORESCENCE DETECTION; LIQUID-CHROMATOGRAPHY; IMMUNOASSAY; MUSSELS; FOODS AB Paralytic shellfish poisoning (PSP) toxins are produced by certain marine dinoflagellates and may accumulate in bivalve molluscs through filter feeding. The Mouse Bioassay (MBA) is the internationally recognised reference method of analysis, but it is prone to technical difficulties and regarded with increasing disapproval due to ethical reasons. As such, alternative methods are required. A rapid surface plasmon resonance (SPR) biosensor inhibition assay was developed to detect PSP toxins in shellfish by employing a saxitoxin polyclonal antibody (R895). Using an assay developed for and validated on the Biacore Q biosensor system, this project focused on transferring the assay to a high-throughput, Biacore T100 biosensor in another laboratory. This was achieved using a prototype PSP toxin kit and recommended assay parameters based on the Biacore Q method. A monoclonal antibody (GT13A) was also assessed. Even though these two instruments are based on SPR principles, they vary widely in their mode of operation including differences in the integrated mu-fluidic cartridges, autosampler system, and sensor chip compatibilities. Shellfish samples (n = 60), extracted using a simple, rapid procedure, were analysed using each platform, and results were compared to AOAC high performance liquid chromatography (HPLC) and MBA methods. The overall agreement, based on statistical 2 x 2 comparison tables, between each method ranged from 85% to 94.4% using R895 and 77.8% to 100% using GT13A. The results demonstrated that the antibody based assays with high sensitivity and broad specificity to PSP toxins can be applied to different biosensor platforms. (C) 2011 Elsevier B.V. All rights reserved. C1 [Haughey, Simon A.; Campbell, Katrina; Elliott, Christopher T.] Queens Univ Belfast, Inst Agri Food & Land Use IA FLU, Belfast BT9 5AG, Antrim, North Ireland. [Yakes, Betsy J.; DeGrasse, Stacey L.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Prezioso, Samantha M.] Univ Maryland, Joint Inst Food Safety & Appl Nutr JIFSAN, College Pk, MD 20742 USA. [Kawatsu, Kentaro] Osaka Prefectural Inst Publ Hlth, Higashinari Ku, Osaka 5370025, Japan. RP Haughey, SA (reprint author), Queens Univ Belfast, Inst Agri Food & Land Use IA FLU, David Keir Bldg,Stranmillis Rd, Belfast BT9 5AG, Antrim, North Ireland. EM s.a.haughey@qub.ac.uk RI Yakes, Betsy/K-2646-2012; OI DeGrasse, Stacey/0000-0001-7808-4193 FU BIOCOP [IP FOOD-CT-2004-06988] FX This work was part-funded with Grant Number IP FOOD-CT-2004-06988 (BIOCOP). The authors would like to thank Cowan Higgins at Agri-Food and Biosciences Institute in Northern Ireland and the staff at the Fisheries Research Services in Scotland, and the Autonomous Government Laboratory for monitoring shellfish in Andalucia for providing shellfish tissue and their contribution in this study. NR 26 TC 18 Z9 19 U1 1 U2 38 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 J9 TALANTA JI Talanta PD JUL 15 PY 2011 VL 85 IS 1 BP 519 EP 526 DI 10.1016/j.talanta.2011.04.033 PG 8 WC Chemistry, Analytical SC Chemistry GA 793UH UT WOS:000292848900073 PM 21645735 ER PT J AU Doerge, DR AF Doerge, Daniel R. TI Bioavailability of soy isoflavones through placental/lactational transfer and soy food SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Genistein; Soy infant formula; Bioavailability; Perinatal ID SPRAGUE-DAWLEY RATS; GENISTEIN; DIETARY; BLOOD AB Isoflavones are non-nutritive components of soy responsible for estrogenic responses observed in vitro and in experimental animals. Possible beneficial effects (e.g., reduction of serum lipids, increased bone mineral density, relief of hot flashes and other menopausal symptoms, mammary and prostate cancer chemoprevention) in humans have been attributed to consumption of isoflavones but evidence for potential adverse effects (e.g., stimulation of estrogen-dependent mammary tumors and aberrant perinatal development) has also been reported in experimental animal models. Bioavailability from appropriate food matrices and exposure during different life stages are both critical determinants of isoflavone effects. For these reasons, it is important to compare isoflavone bioavailability in adults to that in fetal and neonatal animals for a more complete understanding of potential susceptibility issues. Studies of the major soy isoflavone genistein were conducted in pregnant and lactating Sprague-Dawley rats to quantify placental and lactational transfer to plasma and brain to understand better biological effects observed in multigenerational studies. In addition, studies were conducted with genistein in adult Balb/c mice to define absolute bioavailability from both gavage and soy protein isolate (SPI)-containing food. The information derived from these studies makes it possible to predict internal exposures of children to genistein from soy infant formula, which is manufactured using SPI. Published by Elsevier Inc. C1 US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov FU National Center for Toxicological Research/U.S. Food and Drug Administration [224-07-007]; National Institute for Environmental Health Sciences; National Institute on Aging FX This research was supported in part by Interagency Agreement 224-07-007 between the National Center for Toxicological Research/U.S. Food and Drug Administration and the National Institute for Environmental Health Sciences/National Toxicology Program and by the National Institute on Aging with additional support from National Institute for Complementary and Alternative Medicine, Office of Dietary Supplements, and Women's Health Initiative (P01 AG024387). The views presented do not necessarily reflect those of the U.S. Food and Drug Administration. NR 13 TC 3 Z9 3 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL 15 PY 2011 VL 254 IS 2 SI SI BP 145 EP 147 DI 10.1016/j.taap.2010.10.018 PG 3 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 793HJ UT WOS:000292810700009 PM 21034763 ER PT J AU Roach, JAG DiBussolo, JM Krynitsky, A Noonan, GO AF Roach, John A. G. DiBussolo, Joe M. Krynitsky, Alex Noonan, Gregory O. TI Evaluation and single laboratory validation of an on-line turbulent flow extraction tandem mass spectrometry method for melamine in infant formula SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Melamine; On-line turbulent flow extraction; Mass spectrometry ID SIMULTANEOUS QUANTIFICATION; MONOLITHIC COLUMN; CHROMATOGRAPHY; PESTICIDES; WATER; MILK AB This report presents the single-laboratory validation of a method for the determination of melamine in dairy-based products using on-line turbulent flow extraction-tandem mass spectrometry. Liquid or powder test portions were dissolved in water, enriched with (13)C(3)(15)N(3)-Melamine internal standard, followed by protein precipitation and withdrawal of an aliquot for analysis. The turbulent flow method was validated by analyses of liquid and powdered proficiency test portions containing up to 10 mg/kg melamine. Accuracy of results ranged from 96 to 106% of the assigned values for the 6 proficiency test portions tested with relative standard deviations of 4-8%. Apparent recoveries based on addition of amino-(15)N(3)-Melamine to prepared test portions were between 98 and 114%. Based on the repeat analysis of a known blank sample the limit of detection and limit of quantification were determined to be 27 and 87 mu g/kg, respectively. Additionally, this report demonstrates that turbulent flow chromatography is significantly faster than traditional LC-MS, with sample analysis times of less than 2 min. Published by Elsevier B.V. C1 [Roach, John A. G.; Krynitsky, Alex; Noonan, Gregory O.] USA Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [DiBussolo, Joe M.] Thermo Fisher Sci, Franklin, MA 02038 USA. RP Roach, JAG (reprint author), USA Food & Drug Adm, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM John.Roach@fda.hhs.gov FU FDA Center for National Toxicological Research, Jefferson, Arkansas FX The authors thank John Callahan for his useful reviews and comments. The authors appreciate the generous donation of 15N3-Melamine synthesized by Goncalo Gamboa, FDA Center for National Toxicological Research, Jefferson, Arkansas. NR 22 TC 12 Z9 17 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD JUL 15 PY 2011 VL 1218 IS 28 BP 4284 EP 4290 DI 10.1016/j.chroma.2011.05.025 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 792CT UT WOS:000292718800003 PM 21641603 ER PT J AU Soboleski, MR Gabbard, JD Price, GE Misplon, JA Lo, CY Perez, DR Ye, JQ Tompkins, SM Epstein, SL AF Soboleski, Mark R. Gabbard, Jon D. Price, Graeme E. Misplon, Julia A. Lo, Chia-Yun Perez, Daniel R. Ye, Jianqiang Tompkins, S. Mark Epstein, Suzanne L. TI Cold-Adapted Influenza and Recombinant Adenovirus Vaccines Induce Cross-Protective Immunity against pH1N1 Challenge in Mice SO PLOS ONE LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; A VIRUS; HETEROSUBTYPIC IMMUNITY; EXTRACELLULAR DOMAIN; MATRIX PROTEIN-2; M2 PROTEIN; CELL; NUCLEOPROTEIN; VACCINATION; RESPONSES AB Background: The rapid spread of the 2009 H1N1 pandemic influenza virus (pH1N1) highlighted problems associated with relying on strain-matched vaccines. A lengthy process of strain identification, manufacture, and testing is required for current strain-matched vaccines and delays vaccine availability. Vaccines inducing immunity to conserved viral proteins could be manufactured and tested in advance and provide cross-protection against novel influenza viruses until strain-matched vaccines became available. Here we test two prototype vaccines for cross-protection against the recent pandemic virus. Methodology/Principal Findings: BALB/c and C57BL/6 mice were intranasally immunized with a single dose of cold-adapted (ca) influenza viruses from 1977 or recombinant adenoviruses (rAd) expressing 1934 nucleoprotein (NP) and consensus matrix 2 (M2) (NP+M2-rAd). Antibodies against the M2 ectodomain (M2e) were seen in NP+M2-rAd immunized BALB/c but not C57BL/6 mice, and cross-reacted with pH1N1 M2e. The ca-immunized mice did not develop antibodies against M2e. Despite sequence differences between vaccine and challenge virus NP and M2e epitopes, extensive cross-reactivity of lung T cells with pH1N1 peptides was detected following immunization. Both ca and NP+M2-rAd immunization protected BALB/c and C57BL/6 mice against challenge with a mouse-adapted pH1N1 virus. Conclusion/Significance: Cross-protective vaccines such as NP+M2-rAd and ca virus are effective against pH1N1 challenge within 3 weeks of immunization. Protection was not dependent on recognition of the highly variable external viral proteins and could be achieved with a single vaccine dose. The rAd vaccine was superior to the ca vaccine by certain measures, justifying continued investigation of this experimental vaccine even though ca vaccine is already available. This study highlights the potential for cross-protective vaccines as a public health option early in an influenza pandemic. C1 [Soboleski, Mark R.; Price, Graeme E.; Misplon, Julia A.; Lo, Chia-Yun; Epstein, Suzanne L.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Gabbard, Jon D.; Tompkins, S. Mark] Univ Georgia, Dept Infect Dis, Athens, GA 30602 USA. [Perez, Daniel R.; Ye, Jianqiang] Univ Maryland, Dept Vet Med, College Pk, MD 20742 USA. RP Soboleski, MR (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM suzanne.epstein@fda.hhs.gov RI Tompkins, Stephen/A-3317-2008; OI Tompkins, Stephen/0000-0002-1523-5588; Perez, Daniel/0000-0002-6569-5689 FU National Institute of Allergy and Infectious Diseases Trans-National Institutes of Health/Food and Drug Administration (FDA); FDA's Center for Biologics Evaluation and Research pandemic influenza initiative FX This work was supported by grants from the National Institute of Allergy and Infectious Diseases Trans-National Institutes of Health/Food and Drug Administration (FDA) Intramural Biodefense Program and the FDA's Center for Biologics Evaluation and Research pandemic influenza initiative. The funding agencies had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 28 Z9 28 U1 1 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 15 PY 2011 VL 6 IS 7 AR e21937 DI 10.1371/journal.pone.0021937 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 793HT UT WOS:000292811700011 PM 21789196 ER PT J AU Ha, LA Ponnamperuma, RM Jay, S Ricci, MS Weinberg, WC AF Ha, Linan Ponnamperuma, Roshini M. Jay, Steven Ricci, M. Stacey Weinberg, Wendy C. TI Dysregulated Delta Np63 alpha Inhibits Expression of Ink4a/arf, Blocks Senescence, and Promotes Malignant Conversion of Keratinocytes SO PLOS ONE LA English DT Article ID SQUAMOUS-CELL CARCINOMA; P63 ISOFORMS; TUMOR-SUPPRESSOR; P53 HOMOLOG; EPIDERMAL DEVELOPMENT; DIFFERENTIATION; APOPTOSIS; ARREST; CANCER; MICE AB p63 is critical for squamous epithelial development, and elevated levels of the Delta Np63 alpha isoform are seen in squamous cell cancers of various organ sites. However, significant controversy exists regarding the role of p63 isoforms as oncoproteins or tumor suppressors. Here, lentiviruses were developed to drive long-term overexpression of Delta Np63 alpha in primary keratinocytes. Elevated levels of Delta Np63 alpha in vitro promote long-term survival and block both replicative and oncogene-induced senescence in primary keratinocytes, as evidenced by the expression of SA-beta-gal and the presence of nuclear foci of heterochromatin protein 1 gamma. The contribution of Delta Np63 alpha to cancer development was assessed using an in vivo grafting model of experimental skin tumorigenesis that allows distinction between benign and malignant tumors. Grafted lenti-Delta Np63 alpha keratinocytes do not form tumors, whereas lenti-GFP/v-ras(Ha) keratinocytes develop well-differentiated papillomas. Lenti-Delta Np63 alpha/v-ras(Ha) keratinocytes form undifferentiated carcinomas. The average volume of lenti-Delta Np63 alpha/v-ras(Ha) tumors was significantly higher than those in the lenti-GFP/v-ras(Ha) group, consistent with increased BrdU incorporation detected by immunohistochemistry. The block in oncogene-induced senescence corresponds to sustained levels of E2F1 and phosphorylated AKT, and is associated with loss of induction of p16(ink4a)/p19(arf). The relevance of p16(ink4a)/p19(arf) loss was demonstrated in grafting studies of p19(arf)-null keratinocytes, which develop malignant carcinomas in the presence of v-ras(Ha) similar to those arising in wildtype keratinocytes that express lenti-Delta Np63 alpha and v-ras(Ha). Our findings establish that Delta Np63 alpha has oncogenic activity and its overexpression in human squamous cell carcinomas contributes to the malignant phenotype, and implicate its ability to regulate p16(ink4a)/p19(arf) in the process. C1 [Ha, Linan; Ponnamperuma, Roshini M.; Ricci, M. Stacey; Weinberg, Wendy C.] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Jay, Steven] SAIC Frederick Inc, Frederick, MD USA. RP Ha, LA (reprint author), US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. EM wendy.weinberg@fda.hhs.gov FU Interagency Oncology Task Force Fellowship Program FX Supported by intramural funding to the Food and Drug Administration (FDA) and the National Cancer Institute (NCI). LH and MSR were fellows of the Interagency Oncology Task Force Fellowship Program. These funding providers had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Steven Jay is an employee of SAIC-Frederick Inc. and helped perform the experiments. NR 50 TC 12 Z9 12 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUL 15 PY 2011 VL 6 IS 7 AR e21877 DI 10.1371/journal.pone.0021877 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 793HT UT WOS:000292811700007 PM 21789189 ER PT J AU Gupta, S Devanarayan, V Finco, D Gunn, GR Kirshner, S Richards, S Rup, B Song, A Subramanyam, M AF Gupta, Shalini Devanarayan, Viswanath Finco, Deborah Gunn, George R., III Kirshner, Susan Richards, Susan Rup, Bonita Song, An Subramanyam, Meena TI Recommendations for the validation of cell-based assays used for the detection of neutralizing antibody immune responses elicited against biological therapeutics SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Review DE Neutralizing antibody bioassay; Cell-based assay; Serum-based bioassay; lmmunogenicity assay; NAb assay; NAb assay validation ID BIOTECHNOLOGY PRODUCTS; HOST ANTIBODIES; OPTIMIZATION; DESIGN AB The administration of biological therapeutics may result in the development of anti-drug antibodies (ADAs) in treated subjects. In some cases. ADA responses may result in the loss of therapeutic efficacy due to the formation of neutralizing ADAs (NAbs). An important characteristic of anti-drug NAbs is their direct inhibitory effect on the pharmacological activity of the therapeutic. Neutralizing antibody responses are of particular concern for biologic products with an endogenous homolog whose activity can be potentially dampened or completely inhibited by the NAbs leading to an autoimmune-type deficiency syndrome. Therefore, it is important that ADAs are detected and characterized appropriately using sensitive and reliable methods. The design, development and optimization of cell-based assays used for detection of NAbs have been published previously by Gupta et al. 2007 (1). This paper provides recommendations on best practices for the validation of cell-based NAb assay and suggested validation parameters based on the experience of the authors. (C) 2011 Elsevier B.V. All rights reserved. C1 [Gupta, Shalini] Amgen Inc, Clin Immunol, Thousand Oaks, CA 91320 USA. [Devanarayan, Viswanath] Abbott Labs, Parsippany, NJ 07054 USA. [Finco, Deborah] Pfizer, Drug Safety Res & Dev, Groton, CT 06340 USA. [Kirshner, Susan] US FDA, Off Biotechnol Prod, CDER, Bethesda, MD 20892 USA. [Richards, Susan] Genzyme Corp, Biol R&D, Clin Sci Lab, Framingham, MA 01701 USA. [Rup, Bonita] Pfizer, Pharmacokinet Dynam & Metab, Andover, MA 01810 USA. [Song, An] Genentech Inc, BioAnalyt Sci, San Francisco, CA USA. [Subramanyam, Meena] Biogen Idec Inc, Clin Sci & Technol, Cambridge, MA 02412 USA. RP Gupta, S (reprint author), Amgen Inc, Clin Immunol, Thousand Oaks, CA 91320 USA. EM shalinig@amgen.com FU Ligand Binding Assay Bioanalytical Focus Group (LBABFG) of the American Association of Pharmaceutical Scientists (AAPS) FX This work was sponsored by the Ligand Binding Assay Bioanalytical Focus Group (LBABFG) of the American Association of Pharmaceutical Scientists (AAPS). The authors would like to thank several individuals that have contributed to this manuscript and effort, namely, members of Pfizer's Drug Safety Research and Development group for contributing data, Dr. Matthew Szapacs (Glaxo) for assistance in manuscript preparation and Dr. Gopi Shankar (Centocor) for reviewing the manuscript and providing critical input. NR 19 TC 44 Z9 46 U1 0 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD JUL 15 PY 2011 VL 55 IS 5 BP 878 EP 888 DI 10.1016/j.jpba.2011.03.038 PG 11 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 771AN UT WOS:000291129700003 PM 21531522 ER PT J AU Kimoto, T Suzuki, K Kobayashi, XM Dobrovolsky, VN Heflich, RH Miura, D Kasahara, Y AF Kimoto, Takafumi Suzuki, Kumiko Kobayashi, Xiao Mei Dobrovolsky, Vasily N. Heflich, Robert H. Miura, Daishiro Kasahara, Yoshinori TI Manifestation of Pig-a mutant bone marrow erythroids and peripheral blood erythrocytes in mice treated with N-ethyl-N-nitrosourea: Direct sequencing of Pig-a cDNA from bone marrow cells negative for GPI-anchored protein expression SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Gene mutation; Phosphatidylinositol glycan complementation class A gene; Glycosylphosphatidyl inositol; CD24; Flow cytometry; Sorting ID GENE MUTATION ASSAY; FLOW-CYTOMETRIC DETECTION; SPLEEN T-CELLS; RAT; LYMPHOCYTES; HPRT; SPECTRUM; LOCUS; MOUSE AB Our previous rat studies indicate that the endogenous Pig-a gene is a promising reporter of in vivo mutation and potentially useful as the basis for an in vivo genotoxicity assay. The function of the Pig-a protein in the synthesis of glycosylphosphatidyl inositol (GPI) anchors is conserved in variety of eukaryotic cells, including human and rodent cells, which implies that Pig-a mutants can be measured in a similar manner in different mammalian species. In the present study, we developed a flow cytometric Pig-a assay for rapidly measuring gene mutation in the mouse. An antibody to TER-119, a specific cell-surface marker of murine erythroid lineage, was used to identify erythrocytes in peripheral blood (PB) and erythroids in bone marrow (BM). An antibody to CD24, a GPI-anchored protein, was used to identify Pig-a mutants as CD24-negative cells. CD-1 mice were administered a single dose of 100 mg/kg N-ethyl-N-nitrosourea (ENU), and PB and BM were collected at 1, 2, and 4 weeks after dosing. While the Pig-a mutant frequency (MF) in PB was increased moderately at 2 and 4 weeks after ENU dosing, the Pig-a MF in BM was strongly increased starting at 1 week after the dosing, with the elevated MF persisting for at least 4 weeks after the dosing. We also used flow cytometric sorting to isolate CD24-negative erythroids from the BM of ENU-treated mice. cDNA sequencing indicated that these cells have mutations in the Pig-a gene, with base-pair substitutions typical of ENU-induced mutation spectra. The results indicate that the Pig-a mutation assay can be adapted for measuring mutation in BM erythroids and PB of mice. Taken together, the data suggest that Pig-a mutants are fixed in the BM, where they further proliferate and differentiate; erythrocytes derived from these BM Pig-a mutants transit from the BM and accumulate in PB. (C) 2011 Elsevier B.V. All rights reserved. C1 [Kimoto, Takafumi; Suzuki, Kumiko; Kobayashi, Xiao Mei; Miura, Daishiro; Kasahara, Yoshinori] TEIJIN Pharma Ltd, Tokyo 1918512, Japan. [Dobrovolsky, Vasily N.; Heflich, Robert H.] US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. RP Kimoto, T (reprint author), TEIJIN Pharma Ltd, 4-3-2 Asahigaoka, Tokyo 1918512, Japan. EM t.kimoto@teijin.co.jp NR 19 TC 28 Z9 29 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 EI 1879-3592 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUL 14 PY 2011 VL 723 IS 1 BP 36 EP 42 DI 10.1016/j.mrgentox.2011.03.016 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 791NU UT WOS:000292672700005 PM 21549855 ER PT J AU Ali, R Mittelstaedt, RA Shaddock, JG Ding, W Bhalli, JA Khan, QM Heflich, RH AF Ali, Rahat Mittelstaedt, Roberta A. Shaddock, Joseph G. Ding, Wei Bhalli, Javed A. Khan, Qaiser M. Heflich, Robert H. TI Comparative analysis of micronuclei and DNA damage induced by Ochratoxin A in two mammalian cell lines SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Flow cytometry; Micronuclei; Oxidative DNA damage; Ochratoxin A; Mammalian cells ID IN-VITRO; COMET ASSAY; ABERRATION ASSAY; INDIVIDUAL CELLS; FLOW-CYTOMETRY; KIDNEY-CELLS; RAT-KIDNEY; INDUCTION; GENOTOXICITY; CYTOTOXICITY AB The fungal toxin, Ochratoxin A (OTA), is a common contaminant in human food and animal feed. The present study evaluated micronucleus (MN) induction by OTA in comparison with its ability to induce cytotoxicity and DNA damage in two mammalian cell lines, CHO-K1-BH(4) Chinese hamster ovary cells and TK6 human lymphoblastoid cells. Micronuclei were evaluated by flow cytometry, cytotoxicity was estimated by relative population doubling (RPD), while direct DNA damage and oxidative DNA damage were measured with the Comet assay, performed without and with digestion by formamidopyrimidine-DNA glycosylase (fpg). For the MN and cytotoxicity measurements, the cell lines were treated for 24h (CHO cells) or 27 h (TK6 cells) with 5-25 mu M OTA in the absence of exogenous metabolic activation. The OTA treatments resulted in concentration-responsive increases in cytotoxicity, with higher concentrations of the agent being more cytotoxic in CHO cells than TK6 cells. 15 mu M OTA produced positive responses for MN induction and hypodiploid events (a measure of aneugenicity) in both cell lines: this concentration of OTA also produced cytotoxicity near to the recommended limit for the assay (45 +/- 5% RPD). A time course assay with TK6 cells indicated that at least 4 h of OTA treatment were required to produce a positive MN response. For the Comet assay DNA damage assessments, the cell lines were treated with 5-50 mu M OTA for 4h. Direct DNA damage was detected in TK6 cells, but not CHO cells, while concentration-related increases in fpg-sensitive sites were detected for both cell lines. The consistent association of oxidative DNA damage with OTA exposure suggests its involvement in producing OTA-induced clastogenicity and aneugenicity; however, based on its detection in TK6 cells direct DNA damage could be involved in any human risk posed by OTA exposure. Published by Elsevier B.V. C1 [Heflich, Robert H.] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Ali, Rahat; Khan, Qaiser M.] NIBGE, Faisalabad, Pakistan. RP Heflich, RH (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR USA. EM Robert.Heflich@fda.hhs.gov RI Ding, Wei/L-1503-2014; Khan, Qaiser Mahmood/I-6401-2015 FU Higher Education Commission (HEC), Pakistan FX The authors are thankful to the Higher Education Commission (HEC), Pakistan, for providing financial support under the International Research Support Initiative Program (IRSIP) and to the Oak Ridge Institute for Scientific Education (ORISE) for hosting the scientific interaction that resulted in this study. The authors also wish to thank members of the Division of Genetic and Molecular Toxicology, National Center for Toxicological Research/U.S. Food and Drug Administration, including Martha M. Moore, Anane Aidoo, and Vasily N. Dobrovolsky, for their support and thoughtful discussions. The technical assistance of Mason G. Pearce is gratefully acknowledged. The views expressed in this report do not necessarily reflect those of the U.S. Food and Drug Administration. NR 54 TC 22 Z9 25 U1 1 U2 8 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 JUL 14 PY 2011 VL 723 IS 1 BP 58 EP 64 DI 10.1016/j.mrgentox.2011.04.002 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 791NU UT WOS:000292672700008 PM 21554981 ER PT J AU Theoret, MR Ning, YM Zhang, JJ Justice, R Keegan, P Pazdur, R AF Theoret, Marc R. Ning, Yang-Min Zhang, Jenny J. Justice, Robert Keegan, Patricia Pazdur, Richard TI The Risks and Benefits of 5 alpha-Reductase Inhibitors for Prostate-Cancer Prevention SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID CHEMOPREVENTION C1 [Theoret, Marc R.; Ning, Yang-Min; Justice, Robert; Keegan, Patricia; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Zhang, Jenny J.] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Theoret, MR (reprint author), US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 5 TC 80 Z9 82 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 14 PY 2011 VL 365 IS 2 BP 97 EP 99 DI 10.1056/NEJMp1106783 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 791SP UT WOS:000292685500001 PM 21675880 ER PT J AU Gray, RA Wikswo, JP AF Gray, Richard A. Wikswo, John P. TI CARDIOVASCULAR DISEASE Several small shocks beat one big one SO NATURE LA English DT Editorial Material ID ATRIAL-FIBRILLATION; FIELD STIMULATION; VIRTUAL ELECTRODES; CARDIAC TISSUE; DEFIBRILLATION; MECHANISM; FEEDBACK; HEART; TIME C1 [Gray, Richard A.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Wikswo, John P.] Vanderbilt Univ, Dept Biomed Engn, Nashville, TN 37235 USA. [Wikswo, John P.] Vanderbilt Univ, Dept Mol Physiol & Biophys, Nashville, TN 37235 USA. [Wikswo, John P.] Vanderbilt Univ, Dept Phys & Astron, Nashville, TN 37235 USA. RP Gray, RA (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM richard.gray@fda.hhs.gov; john.wikswo@vanderbilt.edu RI Gray, Richard/F-3916-2015 OI Gray, Richard/0000-0003-2798-6378 NR 18 TC 11 Z9 11 U1 0 U2 14 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 EI 1476-4687 J9 NATURE JI Nature PD JUL 14 PY 2011 VL 475 IS 7355 BP 181 EP 182 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 791UA UT WOS:000292690500039 PM 21753846 ER PT J AU Noonan, GO Ackerman, LK Begley, TH AF Noonan, Gregory O. Ackerman, Luke K. Begley, Timothy H. TI Concentration of Bisphenol A in Highly Consumed Canned Foods on the U.S. Market SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE bisphenol A; canned foods; LC-MS/MS ID DIGLYCIDYL ETHER BADGE; LIQUID-CHROMATOGRAPHY; JAPANESE MARKETS; CANADIAN MARKETS; COATINGS; MIGRATION; BPA; IDENTIFICATION; EPOXY; PRODUCTS AB Metal food and drink cans are commonly coated with epoxy films made from phenolic polymers produced from bisphenol A (BPA). It is well established that residual BPA monomer migrates into can contents during processing and storage. While a number of studies have reported BPA concentrations in foods from foreign markets and specialty foods on the U.S. market, very few peer-reviewed data for the BPA concentrations in canned food from the U.S. market were available. This study quantified BPA concentrations in 78 canned and two frozen food products from the U.S. market using an adaptation of a previously reported liquid chromatography-tandem mass spectrometry method. The tested products represented 16 different food types that are from the can food classifications that constitute approximately 65% of U.S. canned food sales and canned food consumption. BPA was detected in 71 of the 78 canned food samples but was not detected in either of the two frozen food samples. Detectable BPA concentrations across all foods ranged from 2.6 to 730 ng/g. Large variations in BPA concentrations were found between different products of the same food type and between different lots of the same product. Given the large concentration ranges, the only distinguishable trend was that fruits and tuna showed the lowest BPA concentrations. Experiments with fortified frozen vegetables and brine solutions, as well as higher BPA concentrations in canned food solids over liquid portions, clearly indicated that BPA partitions into the solid portion of foods. C1 [Noonan, Gregory O.; Ackerman, Luke K.; Begley, Timothy H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Noonan, GO (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. RI Ackerman, Luke/E-4597-2011 OI Ackerman, Luke/0000-0001-6626-3039 NR 32 TC 61 Z9 64 U1 2 U2 44 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 JUL 13 PY 2011 VL 59 IS 13 BP 7178 EP 7185 DI 10.1021/jf201076f PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 788AL UT WOS:000292417700048 PM 21598963 ER PT J AU Johmura, Y Soung, NK Park, JE Yu, LR Zhou, M Bang, JK Kim, BY Veenstra, TD Erikson, RL Lee, KS AF Johmura, Yoshikazu Soung, Nak-Kyun Park, Jung-Eun Yu, Li-Rong Zhou, Ming Bang, Jeong K. Kim, Bo-Yeon Veenstra, Timothy D. Erikson, Raymond L. Lee, Kyung S. TI Regulation of microtubule-based microtubule nucleation by mammalian polo-like kinase 1 SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE mitosis; spindle assembly; polo-box domain; distributive phosphorylation; Ser/Thr protein kinase ID MITOTIC SPINDLE; GAMMA-TUBULIN; BOX DOMAIN; HUMAN-CELLS; COMPLEX; PLK1; CENTROSOME; CYTOKINESIS; RECRUITMENT; AUGMIN AB Bipolar spindle formation is pivotal for accurate segregation of mitotic chromosomes during cell division. A growing body of evidence suggests that, in addition to centrosome-and chromatin-based microtubule (MT) nucleation, MT-based MT nucleation plays an important role for proper bipolar spindle formation in various eukaryotic organisms. Although a recently discovered Augmin complex appears to play a central role in this event, how Augmin is regulated remains unknown. Here we provide evidence that a mammalian polo-like kinase 1 (Plk1) localizes to mitotic spindles and promotes MT-based MT nucleation by directly regulating Augmin. Mechanistically, we demonstrated that Cdc2-dependent phosphorylation on a gamma-tubulin ring complex (gamma-TuRC) recruitment protein, Nedd1/GCP-WD, at the previously uncharacterized S460 residue induces the Nedd1-Plk1 interaction. This step appeared to be critical to allow Plk1 to phosphorylate the Hice1 subunit of the Augmin complex to promote the Augmin-MT interaction and MT-based MT nucleation from within the spindle. Loss of either the Nedd1 S460 function or the Plk1-dependent Hice1 phosphorylation impaired both the Augmin-MT interaction and gamma-tubulin recruitment to the spindles, thus resulting in improper bipolar spindle formation that ultimately leads to mitotic arrest and apoptotic cell death. Thus, via the formation of the Nedd1-Plk1 complex and subsequent Augmin phosphorylation, Plk1 regulates spindle MT-based MT nucleation to accomplish normal bipolar spindle formation and mitotic progression. C1 [Erikson, Raymond L.] Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. [Johmura, Yoshikazu; Soung, Nak-Kyun; Park, Jung-Eun; Lee, Kyung S.] NCI, Lab Metab, Ctr Canc Res, Bethesda, MD 20892 USA. [Soung, Nak-Kyun; Kim, Bo-Yeon] Korea Res Inst Biosci & Biotechnol, Chem Biol Res Ctr, Ochang 363883, Chung Buk, South Korea. [Yu, Li-Rong] US FDA, Natl Ctr Toxicol Res, Div Syst Biol, Ctr Prote, Jefferson, AR 72079 USA. [Zhou, Ming; Veenstra, Timothy D.] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21702 USA. [Bang, Jeong K.] Korean Basic Sci Inst, Div Magnet Resonance, Ochang 363883, Chung Bak, South Korea. RP Erikson, RL (reprint author), Harvard Univ, Dept Mol & Cellular Biol, Cambridge, MA 02138 USA. EM erikson@mcb.harvard.edu; kyunglee@mail.nih.gov FU National Cancer Institute; Food and Drug Administration (FDA); Korea Basic Science Institute [T3022B]; Ministry of Education, Science and Technology of Korea FX We are grateful to Mary Dasso, Dan L. Sackett, and Yasuhiko Terada for critical reading of the manuscript; Gohta Goshima, Jens Luders, Andreas Merdes, Dan L. Sackett, Tim Stearns, Ryota Uehara, and Michael B. Yaffe for reagents and technical assistance; and Susan Garfield, Valarie Barr, Brian Svedberg, and Elise Shumsky for their assistance in confocal and time-lapse microscopies. This work was supported in part by National Cancer Institute intramural grants (to K. S. L. and T. D. V.), a Food and Drug Administration (FDA) grant (to L.-R.Y.), Korea Basic Science Institute's high field NMR research program Grant T3022B (To J.K.B.), and the World Class Institute research program of the National Research Foundation of Korea, funded by the Ministry of Education, Science and Technology of Korea (B.Y.K.). NR 27 TC 35 Z9 36 U1 0 U2 4 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JUL 12 PY 2011 VL 108 IS 28 BP 11446 EP 11451 DI 10.1073/pnas.1106223108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 791BO UT WOS:000292635200035 PM 21690413 ER PT J AU Ghosh, P Nathoo, F Gonen, M Tiwari, RC AF Ghosh, Pulak Nathoo, Farouk Goenen, Mithat Tiwari, Ram C. TI Assessing noninferiority in a three-arm trial using the Bayesian approach SO STATISTICS IN MEDICINE LA English DT Article DE Bayesian methods; gold standard design; Markov chain Monte Carlo; noninferiority; home-based blood pressure interventions ID ASSESSING NON-INFERIORITY; FINITE NORMAL MIXTURES; THERAPEUTIC EQUIVALENCE; ISSUES; MODELS; PLACEBO; PRIORS AB Non-inferiority trials, which aim to demonstrate that a test product is not worse than a competitor by more than a pre-specified small amount, are of great importance to the pharmaceutical community. As a result, methodology for designing and analyzing such trials is required, and developing new methods for such analysis is an important area of statistical research. The three-arm trial consists of a placebo, a reference and an experimental treatment, and simultaneously tests the superiority of the reference over the placebo along with comparing this reference to an experimental treatment. In this paper, we consider the analysis of noninferiority trials using Bayesian methods which incorporate both parametric as well as semi-parametric models. The resulting testing approach is both flexible and robust. The benefit of the proposed Bayesian methods is assessed via simulation, based on a study examining home-based blood pressure interventions. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Ghosh, Pulak] Indian Inst Management, Dept Quantitat Methods & Informat Sci, Bangalore, Karnataka, India. [Nathoo, Farouk] Univ Victoria, Dept Math & Stat, Victoria, BC V8W 2Y2, Canada. [Goenen, Mithat] Mem Sloan Kettering Canc Ctr, New York, NY USA. [Tiwari, Ram C.] US FDA, Off Biostat, CDER, Rockville, MD 20857 USA. RP Ghosh, P (reprint author), Indian Inst Management, Dept Quantitat Methods & Informat Sci, Bangalore, Karnataka, India. EM satkahan@gmail.com RI Gonen, Mithat/E-4826-2012 NR 26 TC 6 Z9 7 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUL 10 PY 2011 VL 30 IS 15 BP 1795 EP 1808 DI 10.1002/sim.4244 PG 14 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 777EM UT WOS:000291598600002 PM 21520456 ER PT J AU Sherman, RB Woodcock, J Norden, J Grandinetti, C Temple, RJ AF Sherman, Rachel Behrman Woodcock, Janet Norden, Janet Grandinetti, Cheryl Temple, Robert J. TI New FDA Regulation to Improve Safety Reporting in Clinical Trials SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Sherman, Rachel Behrman; Norden, Janet; Grandinetti, Cheryl] US FDA, Ctr Drug Evaluat & Res, Off Med Policy, Silver Spring, MD USA. RP Sherman, RB (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Med Policy, Silver Spring, MD USA. NR 4 TC 18 Z9 18 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 JUL 7 PY 2011 VL 365 IS 1 BP 3 EP 5 DI 10.1056/NEJMp1103464 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 788QL UT WOS:000292459400002 PM 21651388 ER PT J AU Jackson, SA Patel, IR Barnaba, T LeClerc, JE Cebula, TA AF Jackson, Scott A. Patel, Isha R. Barnaba, Tammy LeClerc, Joseph E. Cebula, Thomas A. TI Investigating the global genomic diversity of Escherichia coli using a multi-genome DNA microarray platform with novel gene prediction strategies SO BMC GENOMICS LA English DT Article DE genome; diversity; microarray; Escherichia coli; Shigella; O157:H7; gene content; pathogenic determinants ID HEMORRHAGIC COLITIS; O157-H7; SEQUENCE; PERSPECTIVE; INFECTION; COMMENSAL; VIRULENCE; OUTBREAK; STRAINS; O157H7 AB Background: The gene content of a diverse group of 183 unique Escherichia coli and Shigella isolates was determined using the Affymetrix GeneChip (R) E. coli Genome 2.0 Array, originally designed for transcriptome analysis, as a genotyping tool. The probe set design utilized by this array provided the opportunity to determine the gene content of each strain very accurately and reliably. This array constitutes 10,112 independent genes representing four individual E. coli genomes, therefore providing the ability to survey genes of several different pathogen types. The entire ECOR collection, 80 EHEC-like isolates, and a diverse set of isolates from our FDA strain repository were included in our analysis. Results: From this study we were able to define sets of genes that correspond to, and therefore define, the EHEC pathogen type. Furthermore, our sampling of 63 unique strains of O157:H7 showed the ability of this array to discriminate between closely related strains. We found that individual strains of O157:H7 differed, on average, by 197 probe sets. Finally, we describe an analysis method that utilizes the power of the probe sets to determine accurately the presence/absence of each gene represented on this array. Conclusions: These elements provide insights into understanding the microbial diversity that exists within extant E. coli populations. Moreover, these data demonstrate that this novel microarray-based analysis is a powerful tool in the field of molecular epidemiology and the newly emerging field of microbial forensics. C1 [Jackson, Scott A.; Patel, Isha R.; Barnaba, Tammy; LeClerc, Joseph E.] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Cebula, Thomas A.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Jackson, SA (reprint author), US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM scott.jackson@fda.hhs.gov FU National Bioforensics Analysis Center (NBFAC) of the Department of Homeland Security FX We acknowledge Christopher A. Elkins and Mark K. Mammel for their helpful discussions and critical editing of the manuscript. We acknowledge David W. Lacher for sharing his stx confirmatory PCR results. We acknowledge Ravi Jain and Kumar Hari for their contributions towards the integration of our microarray data into The Microbial Rosetta Stone http://www.mrscentral.com. We acknowledge the National Bioforensics Analysis Center (NBFAC) of the Department of Homeland Security for supporting work on DNA microarray analyses of E. coli O157:H7 and Shigella strains. NR 35 TC 20 Z9 20 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2164 J9 BMC GENOMICS JI BMC Genomics PD JUL 6 PY 2011 VL 12 AR 349 DI 10.1186/1471-2164-12-349 PG 17 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 799IR UT WOS:000293280900001 PM 21733163 ER PT J AU Chen, D Li, ZG Chen, T AF Chen, David Li, Zhiguang Chen, Tao TI Increased expression of miR-34a in mouse spleen one day after exposure to N-ethyl-N-nitrosourea SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE miR-34a; p53; mutagen; N-ethyl-N-nitrosourea; Real-time PCR ID CELL-CYCLE CONTROL; GENOTOXIC STRESS; TUMOR-SUPPRESSOR; GENE-EXPRESSION; DOWN-REGULATION; MICRORNA; CANCER; P53; CARCINOGENESIS; APOPTOSIS AB MicroRNAs (miRNAs) are a class of single-stranded small RNA molecules (similar to 22 nucleotides) that are not translated into proteins and function as regulators of gene expression. Many miRNAs are involved in carcinogenesis. One of them, miR-34a, is associated with various p53-initiated biological processes and may act as a tumor suppressor miRNA. Its expression is generally down-regulated in tumor tissues and up-regulated in tissues exposed to carcinogens chronically or subchronically. However, the response of this miRNA to acute exposure of a genotoxic carcinogen is little known. In this study, miR-34a expression was evaluated in spleen tissues of mice treated with a dose of 120 mg kg(-1) body weight N-ethyl-N-nitrosourea (ENU), a potent mutagenic carcinogen. Real-time PCR analysis showed that the ENU exposure resulted in a 5.5-fold increase of miR-34a expression over the control one day after the treatment. The result suggests that miR-34a expression responds sensitively to genotoxic insults within a short period after exposure of the mutagen, and therefore, this gene has the potential to be used as an indicator for genotoxin exposure. Copyright (c) 2011 John Wiley & Sons, Ltd. C1 [Li, Zhiguang; Chen, Tao] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chen, David] Little Rock Cent High Sch, Little Rock, AR 72206 USA. RP Li, ZG (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM zhiguang.li@fda.hhs.gov NR 29 TC 8 Z9 10 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD JUL PY 2011 VL 31 IS 5 BP 496 EP 498 DI 10.1002/jat.1640 PG 3 WC Toxicology SC Toxicology GA 803NF UT WOS:000293587300013 PM 22297810 ER PT J AU Read, EK Park, JT Brorson, KA AF Read, Erik K. Park, Jun T. Brorson, Kurt A. TI Industry and regulatory experience of the glycosylation of monoclonal antibodies SO BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY LA English DT Review DE glycosylation; monoclonal antibodies ID EFFECTOR FUNCTIONS; THERAPEUTICS AB We surveyed 23 antibody-related marketing applications for glycoform analytical and functional information. Our database analysis shows a clear trend of increasing sophistication of analytical methods used to identify and quantify glycans. These have revealed a high degree of complexity and heterogeneity of glycans attached to antibody products. The nature of the complexity is influenced by product type and expression system, and may be associated with functional consequences in some but not all cases. C1 [Read, Erik K.; Park, Jun T.; Brorson, Kurt A.] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Brorson, KA (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. EM kurt.brorson@fda.hhs.gov FU Center for Drug Evaluation and Research Critical Path Initiative [1500] FX This project was funded by Center for Drug Evaluation and Research Critical Path Initiative, project number 1500. We thank Patrick Swann, Emily Shacter, and Pauline Rudd for their critical comments on this manuscript. Views in this article are presented by the authors for consideration. They do not necessarily reflect current or future FDA policy or official views of the US Government. NR 13 TC 21 Z9 23 U1 1 U2 20 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-4513 J9 BIOTECHNOL APPL BIOC JI Biotechnol. Appl. Biochem. PD JUL-AUG PY 2011 VL 58 IS 4 BP 213 EP 219 DI 10.1002/bab.35 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 816FI UT WOS:000294583700001 PM 21838794 ER PT J AU Jimenez-Alberto, A Parreiras, P Castelan-Vega, J Sirota, L Arciniega, J AF Jimenez-Alberto, Alicia Parreiras, Patricia Castelan-Vega, Juan Sirota, Lev Arciniega, Juan TI Feasibility of the use of ELISA in an immunogenicity-based potency test of anthrax vaccines SO BIOLOGICALS LA English DT Article DE Anthrax; AVA; rPA; Anti-PA ELISA; Potency test ID LETHAL TOXIN NEUTRALIZATION; RECOMBINANT PROTECTIVE ANTIGEN; BACILLUS-ANTHRACIS; ASSAY; MICE; IMMUNITY; MODEL; INACTIVATION; IMMUNIZATION; FORMALDEHYDE AB Complexities of lethal challenge animal models have prompted the investigation of immunogenicity assays as potency tests of anthrax vaccines. An ELISA was used to measure the antibody response to protective antigen (PA) in mice immunized once with a commercially available (AVA) or a recombinant PA vaccine (rPAV) formulated in-house with aluminum hydroxide. Results from the anti-PA ELISA were used to select a single dose appropriate for the development of a potency test. Immunization with 0.2 mL of AVA induced a measurable response in the majority of animals. This dose was located in the linear range of the vaccine dose-antibody response curve. In the case of rPAV, practical limitations prevented the finding of the best single dose for the potency testing of purified vaccines. In additional immunogenicity experiments neither the magnitude of the response to a single dose of vaccine, nor the estimation of the dose necessary to induce a measurable response were able to consistently detect brief exposure of vaccines to potentially damaging temperatures. However, differences detected for rPAV in the proportion of mice responding to the same dose of treated and untreated vaccine suggested that further assay development to increase the sensitivity of the latter design may be warranted. Published by Elsevier Ltd on behalf of The International Alliance for Biologicals. C1 [Jimenez-Alberto, Alicia; Parreiras, Patricia; Castelan-Vega, Juan; Sirota, Lev; Arciniega, Juan] Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Arciniega, J (reprint author), Ctr Biol Evaluat & Res, 1401 Rockville Pike,Mail Code HFM-443, Rockville, MD 20852 USA. EM juan.arciniega@fda.hhs.gov FU Biomedical Advanced Research and Development Authority; Center for Biologics Evaluation and Research; Instituto Politecnico Nacional (Mexico); COTEPABE; CBER FX This project was supported by the Biomedical Advanced Research and Development Authority and by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. AJ-A is grateful for the support from the Instituto Politecnico Nacional (Mexico). JC-V is grateful for the support from COTEPABE and the Instituto Politecnico Nacional (Mexico). LS was supported in part by a CBER director's Critical Path grant. NR 39 TC 2 Z9 2 U1 0 U2 3 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JUL PY 2011 VL 39 IS 4 BP 236 EP 241 DI 10.1016/j.biologicals.2011.05.001 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 815NG UT WOS:000294531700007 PM 21664832 ER PT J AU Gruber, MF AF Gruber, Marion F. TI US FDA review and regulation of preventive vaccines for infectious disease indications: impact of the FDA Amendments Act 2007 SO EXPERT REVIEW OF VACCINES LA English DT Review DE enhanced authorities; FDAAA 2007; Federal Food, Drug & Cosmetic Act; infectious disease; managed review process; Pediatric Research Equity Act; postmarketing drug safety; US FDA; vaccine; vaccine approval process AB Vaccines for prevention or treatment of infectious diseases are biological products that are regulated by the Office of Vaccines Research and Review in the Center for Biologics Evaluation and Research of the US FDA. The legal framework for the regulation of vaccines derives primarily from Section 351 of the Public Health Service Act and from certain sections of the Federal Food, Drug and Cosmetic Act (FFD & C Act). The FDA Amendments Act of 2007 (FDAAA 2007) includes extensive modifications to the FFD & C Act. This article provides an overview of the review process for preventive vaccines and highlights applicable statutory provisions. In addition, this article will discuss changes in the pre-and post-licensure evaluation process for preventive and therapeutic infectious disease vaccines since implementation of the FDAAA 2007. C1 US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, DHHS, Rockville, MD 20852 USA. RP Gruber, MF (reprint author), US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, DHHS, 1451 Rockville Pike,WOCII Room 3312, Rockville, MD 20852 USA. EM marion.gruber@fda.hhs.gov NR 3 TC 1 Z9 1 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD JUL PY 2011 VL 10 IS 7 BP 1011 EP 1019 DI 10.1586/ERV.11.52 PG 9 WC Immunology SC Immunology GA 813UD UT WOS:000294394800013 PM 21806396 ER PT J AU Chang, CW Beland, FA Hines, WM Fuscoe, JC Han, T Chen, JJ AF Chang, Ching-Wei Beland, Frederick A. Hines, Wade M. Fuscoe, James C. Han, Tao Chen, James J. TI Identification and Categorization of Liver Toxicity Markers Induced by a Related Pair of Drugs SO INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES LA English DT Article DE liver toxicity; biomarker; genomic; personalized medicine; population heterogeneity; entacapone; tolcapone ID GENE-EXPRESSION; INJURY; HEPATOTOXICITY; TOLCAPONE; PROTEIN; SAFETY; RAT; ENTACAPONE; BIOMARKER; ACID AB Drug-induced liver injury (DILI) is the primary adverse event that results in the withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in the pre-clinical or clinical phases of drug development. This paper presents an approach for identifying potential liver toxicity genomic biomarkers from a liver toxicity biomarker study involving the paired compounds entacapone ("non-liver toxic drug") and tolcapone ("hepatotoxic drug"). Molecular analysis of the rat liver and plasma samples, combined with statistical analysis, revealed many similarities and differences between the in vivo biochemical effects of the two drugs. Six hundred and ninety-five genes and 61 pathways were selected based on the classification scheme. Of the 61 pathways, 5 were specific to treatment with tolcapone. Two of the 12 animals in the tolcapone group were found to have high ALT, AST, or TBIL levels. The gene Vars2 (valyl-tRNA synthetase 2) was identified in both animals and the pathway to which it belongs, the aminoacyl-tRNA biosynthesis pathway, was one of the three most significant tolcapone-specific pathways identified. C1 [Chang, Ching-Wei; Chen, James J.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Beland, Frederick A.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Hines, Wade M.] BG Med Inc, Waltham, MA 02451 USA. [Fuscoe, James C.; Han, Tao] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, JJ (reprint author), US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM ching-wei.chang@fda.hhs.gov; FrederickBeland@fda.hhs.gov; wade.hines@gmail.com; James.Fuscoe@fda.hhs.gov; Tao.Han@fda.hhs.gov; jamesj.chen@fda.hhs.gov NR 35 TC 6 Z9 6 U1 0 U2 4 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 1422-0067 J9 INT J MOL SCI JI Int. J. Mol. Sci. PD JUL PY 2011 VL 12 IS 7 BP 4609 EP 4624 DI 10.3390/ijms12074609 PG 16 WC Biochemistry & Molecular Biology; Chemistry, Multidisciplinary SC Biochemistry & Molecular Biology; Chemistry GA 796SG UT WOS:000293071700029 PM 21845099 ER PT J AU Shestopal, SA Makover, DJ Lee, TK Sarafanov, AG AF Shestopal, S. A. Makover, D. J. Lee, T. K. Sarafanov, A. G. TI Suitability of insect cells for the expression of human coagulation factor VIII SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Shestopal, S. A.; Makover, D. J.; Lee, T. K.; Sarafanov, A. G.] US FDA, CBER, OBRR, DH,LH, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI BP 102 EP 102 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 800DU UT WOS:000293340800314 ER PT J AU Ferguson, S Law, C Abshire, J AF Ferguson, Sherry Law, Charles Abshire, Jordan TI Developmental Bisphenol A (BPA) or Ethinyl Estradiol Treatment at Relatively Low Doses Has No Effects on Early Preweaning Behaviors SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Neurobehavioral-Teratology-Society/51st Annual Meeting of the Teratology-Society/24th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 25-29, 2011 CL Coronado, CA SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Ferguson, Sherry; Law, Charles; Abshire, Jordan] Natl Ctr Toxicol Res FDA, Div Neurotoxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2011 VL 33 IS 4 BP 496 EP 497 DI 10.1016/j.ntt.2011.05.021 PG 2 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 815LU UT WOS:000294527900018 ER PT J AU Elayan, I AF Elayan, Ikram TI Nonclinical Testing for Pediatric Neuropharmaceuticals: a CDER Perspective SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Neurobehavioral-Teratology-Society/51st Annual Meeting of the Teratology-Society/24th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 25-29, 2011 CL Coronado, CA SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Elayan, Ikram] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2011 VL 33 IS 4 BP 506 EP 506 DI 10.1016/j.ntt.2011.05.053 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 815LU UT WOS:000294527900050 ER PT J AU Paule, M AF Paule, Merle TI Preclinical Neurotoxicity Assessments of Pediatric Anesthetics: Translational Approaches Using a Nonhuman Primate Model SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Neurobehavioral-Teratology-Society/51st Annual Meeting of the Teratology-Society/24th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 25-29, 2011 CL Coronado, CA SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Paule, Merle] FDAs Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2011 VL 33 IS 4 BP 506 EP 507 DI 10.1016/j.ntt.2011.05.054 PG 2 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 815LU UT WOS:000294527900051 ER PT J AU Chelonis, J Kubacak, B Osborn, S Edwards, M Baldwin, R Paule, M AF Chelonis, John Kubacak, Brian Osborn, Seth Edwards, Mark Baldwin, Ronald Paule, Merle TI The Effects of Stimulant Medication on Performance of an Incremental Repeated Acquisition Task in Children with ADHD SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 35th Annual Meeting of the Neurobehavioral-Teratology-Society/51st Annual Meeting of the Teratology-Society/24th Annual Meeting of the Organization-of-Teratology-Information-Specialists CY JUN 25-29, 2011 CL Coronado, CA SP Neurobehav Teratol Soc, Teratol Soc, Org Teratol Informat Specialists C1 [Chelonis, John; Paule, Merle] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chelonis, John; Kubacak, Brian; Osborn, Seth; Edwards, Mark; Baldwin, Ronald; Paule, Merle] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2011 VL 33 IS 4 BP 507 EP 507 DI 10.1016/j.ntt.2011.05.055 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 815LU UT WOS:000294527900052 ER PT J AU Zhou, YP Jia, YP Buehler, PW Chen, G Cabrales, P Palmer, AF AF Zhou, Yipin Jia, Yiping Buehler, Paul W. Chen, Guo Cabrales, Pedro Palmer, Andre F. TI Synthesis, Biophysical Properties, and Oxygenation Potential of Variable Molecular Weight Glutaraldehyde-Polymerized Bovine Hemoglobins with Low and High Oxygen Affinity SO BIOTECHNOLOGY PROGRESS LA English DT Article DE polymerized bovine hemoglobin; oxygen affinity; oxygen transport; oxygen carrier; tissue engineering; transfusion medicine ID TANGENTIAL FLOW FILTRATION; NITRIC-OXIDE CONCENTRATION; HEMORRHAGIC-SHOCK; IN-VITRO; TRANSFUSION TRIGGER; ENDOTHELIAL-CELLS; BLOOD SUBSTITUTES; PLASMA EXPANDERS; SHEAR-STRESS; VISCOSITY AB In a recent study, ultrahigh molecular weight (Mw) glutaraldehyde-polymerized bovine hemoglobins (PolybHbs) were synthesized with low O(2) affinity and exhibited no vasoactivity and a slight degree of hypertension in a 10% top-load model. 1 In this work, we systematically investigated the effect of varying the glutaraldehyde to hemoglobin (G: Hb) molar ratio on the biophysical properties of PolybHb polymerized in either the low or high O(2) affinity state. Our results showed that the Mw of the resulting PolybHbs increased with increasing G: Hb molar ratio. For low O(2) affinity PolybHbs, increasing the G: Hb molar ratio reduced the O(2) affinity and CO association rate constants in comparison to bovine hemoglobin (bHb). In contrast for high O(2) affinity PolybHbs, increasing the G: Hb molar ratio led to increased O(2) affinity and significantly increased the CO association rate constants compared to unmodified bHb and low O(2) affinity PolybHbs. The methemoglobin level and NO dioxygenation rate constants were insensitive to the G: Hb molar ratio. However, all PolybHbs displayed higher viscosities compared to unmodified bHb and whole blood, which also increased with increasing G: Hb molar ratio. In contrast, the colloid osmotic pressure of PolybHbs decreased with increasing G: Hb molar ratio. To preliminarily evaluate the ability of low and high O(2) affinity PolybHbs to potentially oxygenate tissues in vivo, an O(2) transport model was used to simulate O(2) transport in a hepatic hollow fiber (HF) bioreactor. It was observed that low O(2) affinity PolybHbs oxygenated the bioreactor better than high O(2) affinity PolybHbs. This result points to the suitability of low O(2) affinity PolybHbs for use in tissue engineering and transfusion medicine. Taken together, our results show the quantitative effect of varying the oxygen saturation of bHb and G: Hb molar ratio on the biophysical properties of PolybHbs and their ability to oxygenate a hepatic HF bioreactor. We suggest that the information gained from this study can be used to guide the design of the next generation of hemoglobin-based oxygen carriers (HBOCs) for use in tissue engineering and transfusion medicine applications. (C) 2011 American Institute of Chemical Engineers Biotechnol. Prog., 27: 1172-1184, 2011 C1 [Zhou, Yipin; Chen, Guo; Palmer, Andre F.] Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA. [Jia, Yiping; Buehler, Paul W.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, CBER, Bethesda, MD 20892 USA. [Cabrales, Pedro] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. RP Palmer, AF (reprint author), Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA. EM palmer.351@osu.edu RI Cabrales, Pedro/A-1930-2014 OI Cabrales, Pedro/0000-0002-8794-2839 FU National Institutes of Health [R01HL078840, R01DK070862] FX This work was supported by National Institutes of Health grants R01HL078840 and R01DK070862 to AFP. The authors would like to thank David R. Harris for purifying the bHb used for these studies. NR 74 TC 5 Z9 5 U1 0 U2 14 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JUL-AUG PY 2011 VL 27 IS 4 BP 1172 EP 1184 DI 10.1002/btpr.624 PG 13 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 810EG UT WOS:000294107600029 PM 21584950 ER PT J AU Kuselman, I Goldshlag, P Pennecchi, F Burns, C AF Kuselman, Ilya Goldshlag, Paulina Pennecchi, Francesca Burns, Cathy TI Multi-component out-of-specification test results: a case study of concentration of pesticide residues in tomatoes SO ACCREDITATION AND QUALITY ASSURANCE LA English DT Article; Proceedings Paper CT Conference on Isranalytica CY FEB, 2011 CL Tel Aviv, ISRAEL DE Pesticide residues; Tomatoes; Out-of-specification test results; Measurement uncertainty; Producer's and consumer's risks; Acceptance limits ID UNCERTAINTY AB A metrological approach is used for investigating multi-component out-of-specification (OOS) test results of pesticide residues concentration in tomatoes. As a case study, 169 test results were obtained in Israel in 2009. Five of the test results were OOS test results exceeding the national legal maximum residue limits (MRL). Only one of them was classified definitely (with more than 0.99 confidence) as caused by a farmer's/producer's problem. The other four OOS test results were probably metrologically related, i.e., compatible with MRL when considering the measurement uncertainty associated with the test results. A new parameter-the ratio of a test result to MRL-was proposed for analysis of tomatoes monitoring multi-residue data as a common statistical sample from the same population for different pesticide residues. Weibull distribution was found adequate for modeling the empirical distribution of the parameter values. Probability of future OOS test results was estimated, and global risks of farmer/producer and consumer/buyer were evaluated. Acceptance limits for the test results, such as warning and action lines" in quality control charts, were calculated by taking into account the measurement uncertainties. C1 [Kuselman, Ilya] Natl Phys Lab Israel INPL, IL-91904 Jerusalem, Israel. [Goldshlag, Paulina] Plant Protect & Inspect Serv PPIS, Lab Pesticide Residue Anal, IL-50250 Bet Dagan, Israel. [Pennecchi, Francesca] Ist Nazl Ric Metrol INRIM, I-10135 Turin, Italy. [Burns, Cathy] US FDA, Denver, CO 80225 USA. RP Kuselman, I (reprint author), Natl Phys Lab Israel INPL, IL-91904 Jerusalem, Israel. EM ilya.kuselman@moital.gov.il RI Pennecchi, Francesca/G-9812-2015 OI Pennecchi, Francesca/0000-0003-1328-3858 NR 27 TC 5 Z9 5 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0949-1775 J9 ACCREDIT QUAL ASSUR JI Accredit. Qual. Assur. PD JUL PY 2011 VL 16 IS 7 BP 361 EP 367 DI 10.1007/s00769-011-0780-3 PG 7 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA 799LG UT WOS:000293287600003 ER PT J AU Smith, J Ruha, AM Curry, SC Biswas, K Nasr, S Ye, W Caldwell, K LoVecchio, F Burkhart, K Westenberger, B AF Smith, Jennifer Ruha, Anne-Michelle Curry, Steven C. Biswas, Kallol Nasr, Samia Ye, Wei Caldwell, Kathleen LoVecchio, Frank Burkhart, Keith Westenberger, Benjamin TI DETERMINATION OF PLASMA DMPS CONCENTRATION AND URINE MERCURY EXCRETION AFTER DERMAL APPLICATION OF "TD-DMPS" SO CLINICAL TOXICOLOGY LA English DT Meeting Abstract C1 [Smith, Jennifer; Ruha, Anne-Michelle; Curry, Steven C.] Banner Good Samaritan Med Ctr, Phoenix, AZ USA. [Biswas, Kallol; Nasr, Samia; Ye, Wei; Burkhart, Keith; Westenberger, Benjamin] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Caldwell, Kathleen] CDC, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. [LoVecchio, Frank] Maricopa Cty Gen Hosp, Phoenix, AZ USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1556-3650 J9 CLIN TOXICOL JI Clin. Toxicol. PD JUL PY 2011 VL 49 IS 6 MA 72 BP 543 EP 543 PG 1 WC Toxicology SC Toxicology GA 804YS UT WOS:000293692600101 ER PT J AU Yasinskaya, Y Sacks, L AF Yasinskaya, Yuliya Sacks, Leonard TI Models and approaches for anti-TB drug testing SO EXPERT REVIEW OF ANTI-INFECTIVE THERAPY LA English DT Review DE biomarker(s); early bactericidal activity; EBA; end point(s); model(s); TB; tuberculosis ID EARLY BACTERICIDAL ACTIVITY; MULTIDRUG-RESISTANT TUBERCULOSIS; PULMONARY TUBERCULOSIS; MYCOBACTERIUM-TUBERCULOSIS; STERILIZING ACTIVITY; DIARYLQUINOLINE TMC207; TUBERCLE-BACILLI; ANIMAL-MODELS; GUINEA-PIG; RIFAMPIN AB Unique challenges remain in the development of new drugs for the treatment of TB. While existing multidrug treatment regimens are prolonged and difficult for patients to adhere to, they are highly efficacious, setting a high bar for the performance of new agents. Complicating matters more, regulatory standards have changed since the first drugs for TB were introduced, with a rigorous characterization of the effect of a new drug within a combination regimen expected. If these demands are to be satisfied, innovative models will be needed to demonstrate drug efficacy. In the past, mycobacterial cultures performed on solid media at the end of treatment have been used as critical biomarkers of drug efficacy, but their inability to predict long-term outcomes with precision has limited their utility. This article reviews a range of nonclinical and clinical models to characterize the bactericidal and/or sterilizing activity of new compounds. Novel approaches, using in vitro and animal models, sensitive biomarkers, as well as creative new clinical trial designs, are discussed. These promise a timely expansion of our TB treatment armamentarium to include potent new drugs and shorter, simpler treatment regimens. C1 [Yasinskaya, Yuliya; Sacks, Leonard] US FDA, Off Crit Path Programs, Off Chief Scientist, Silver Spring, MD 20993 USA. RP Yasinskaya, Y (reprint author), US FDA, Off Crit Path Programs, Off Chief Scientist, 10903 New Hampshire Ave,Bldg 32, Silver Spring, MD 20993 USA. EM yuliya.yasinskaya@fda.hhs.gov NR 72 TC 2 Z9 2 U1 0 U2 2 PU EXPERT REVIEWS PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-7210 J9 EXPERT REV ANTI-INFE JI Expert Rev. Anti-Infect. Ther. PD JUL PY 2011 VL 9 IS 7 BP 823 EP 831 DI 10.1586/ERI.11.64 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 806IE UT WOS:000293798800013 PM 21810054 ER PT J AU Lawrence, J AF Lawrence, John TI Testing non-inferiority and superiority for two endpoints for several treatments with a control SO PHARMACEUTICAL STATISTICS LA English DT Article DE multiple comparisons with a control; Dunnett's test; Gatekeeping tests AB Some multiple comparison procedures are described for multiple armed studies. The procedures are appropriate for testing all hypotheses for comparing two endpoints and multiple test arms to a single control group, for example three different fixed doses compared to a placebo. The procedure assumes that among the two endpoints, one is designated as a primary endpoint such that for a given treatment arm, no hypothesis for the secondary endpoint can be rejected unless the hypothesis for the primary endpoint was rejected. The procedures described control the family-wise error rate in the strong sense at a specified level alpha. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 US FDA, Silver Spring, MD 20993 USA. RP Lawrence, J (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM John.Lawrence@fda.hhs.gov NR 5 TC 4 Z9 4 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD JUL-AUG PY 2011 VL 10 IS 4 BP 318 EP 324 DI 10.1002/pst.468 PG 7 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 805QG UT WOS:000293743500005 PM 20949636 ER PT J AU King, RL Liu, YB Maruvada, S Herman, BA Wear, KA Harris, GR AF King, Randy L. Liu, Yunbo Maruvada, Subha Herman, Bruce A. Wear, Keith A. Harris, Gerald R. TI Development and Characterization of a Tissue-Mimicking Material for High-Intensity Focused Ultrasound SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID SOFT-TISSUES; ATTENUATION; BACKSCATTER; DEPENDENCE; SPEED; NONLINEARITY; TEMPERATURE; PROPAGATION; MHZ; GEL AB A tissue-mimicking material (TMM) for the acoustic and thermal characterization of high-intensity focused ultrasound (HIFU) devices has been developed. The material is a high-temperature hydrogel matrix (gellan gum) combined with different sizes of aluminum oxide particles and other chemicals. The ultrasonic properties (attenuation coefficient, speed of sound, acoustical impedance, and the thermal conductivity and diffusivity) were characterized as a function of temperature from 20 to 70 degrees C. The backscatter coefficient and nonlinearity parameter B/A were measured at room temperature. Importantly, the attenuation coefficient has essentially linear frequency dependence, as is the case for most mammalian tissues at 37 degrees C. The mean value is 0.64f (0.95) dB.cm(-1) at 20 degrees C, based on measurements from 2 to 8 MHz. Most of the other relevant physical parameters are also close to the reported values, although backscatter signals are low compared with typical human soft tissues. Repeatable and consistent temperature elevations of 40 degrees C were produced under 20-s HIFU exposures in the TMM. This TMM is appropriate for developing standardized dosimetry techniques, validating numerical models, and determining the safety and efficacy of HIFU devices. C1 [King, Randy L.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. [Liu, Yunbo; Maruvada, Subha; Herman, Bruce A.; Wear, Keith A.; Harris, Gerald R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Maruvada, Subha] Harvard Univ, Sch Med, Boston, MA USA. [Maruvada, Subha] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wear, Keith A.] Washington Univ, Dept Phys, St Louis, MO 63130 USA. [Wear, Keith A.] Georgetown Univ, Washington, DC 20057 USA. [Wear, Keith A.] IEEE Int Ultrason Symposium, Beijing, Peoples R China. RP King, RL (reprint author), Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. EM yunbo.liu@fda.hhs.gov FU Defense Advanced Research Projects Agency (DARPA) [224-05-6016] FX This research was supported by Defense Advanced Research Projects Agency (DARPA) through IAG # 224-05-6016. The views, opinions, and/or findings contained in this article/presentation are those of the author/presenter and should not be interpreted as representing the official views or policies, either expressed or implied, of the Defense Advanced Research Projects Agency or the Department of Defense. NR 34 TC 20 Z9 21 U1 1 U2 16 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JUL PY 2011 VL 58 IS 7 BP 1397 EP 1405 DI 10.1109/TUFFC.2011.1959 PG 9 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 804XP UT WOS:000293688700011 PM 21768024 ER PT J AU Hartzema, AG Racoosin, JA MaCurdy, TE Gibbs, JM Kelman, JA AF Hartzema, Abraham G. Racoosin, Judith A. MaCurdy, Thomas E. Gibbs, Jonathan M. Kelman, Jeffrey A. TI Utilizing Medicare claims data for real-time drug safety evaluations: is it feasible? SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE Medicare; active drug safety surveillance; real-time safety evaluation; claims adjudication; administrative claims data AB Purpose The Centers for Medicare & Medicaid Services claims comprise an administrative database of beneficiary-specific clinical information. This study evaluates the impacts of (i) claim information updates (claims adjudication) and (ii) delay in claim processing (claims delay) on real-time evaluation of health service and drug safety signals using the Medicare database. Methods Using Medicare claims data accumulated through May 2009 on health services rendered in 2006 and drugs dispensed in 2007, this study measures the frequency with which clinical information changes in the database as a result of (i) claims adjudication and (ii) claims delay. Results Over 85% of health services claims were processed within 8 weeks after the date of service, and 72% of drug claims were processed within 3 months after the dispense date. Clinical information changed for no more than 3% of unique claim groups in inpatient hospital, outpatient institutional, physician's office, and prescription drug Medicare claim settings. Conclusions Claims delay is consistent across time and is minimal. Claims adjudication does not substantially impact the content of clinical information in the Medicare claims database. Therefore, the Medicare claims database provides consistent information regarding health services and prescription drugs in a manner that is prompt enough to facilitate medical product safety evaluations in real time. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Hartzema, Abraham G.] Univ Florida, Coll Pharm, HPNP, Dept Pharmaceut Outcomes & Policy, Gainesville, FL 32610 USA. [Racoosin, Judith A.] US FDA, Silver Spring, MD USA. [MaCurdy, Thomas E.] Stanford Univ, Stanford, CA 94305 USA. [MaCurdy, Thomas E.; Gibbs, Jonathan M.] Acumen LLC, Burlingame, CA USA. [Kelman, Jeffrey A.] Ctr Medicare & Medicaid Serv, Off Administrator, Ctr Beneficiary Choices, Washington, DC USA. RP Hartzema, AG (reprint author), Univ Florida, Coll Pharm, HPNP, Dept Pharmaceut Outcomes & Policy, Rm 3339,101 S Newell Dr,POB 100496, Gainesville, FL 32610 USA. EM Hartzema@ufl.edu FU HHS Office of the Assistant Secretary for Planning and Evaluation; Centers for Medicare & Medicaid Services (CMS); US Food and Drug Administration (FDA); Office of the Assistant Secretary for Planning and Evaluation (ASPE) FX We thank the HHS Office of the Assistant Secretary for Planning and Evaluation for their analytic and financial support of this project. With respect to financial support, the SafeRx Project is a joint initiative of the Centers for Medicare & Medicaid Services (CMS), US Food and Drug Administration (FDA), and the Office of the Assistant Secretary for Planning and Evaluation (ASPE). Acumen LLC is a contractor to CMS. NR 4 TC 12 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JUL PY 2011 VL 20 IS 7 BP 684 EP 688 DI 10.1002/pds.2143 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 800PE UT WOS:000293374600002 PM 21847800 ER PT J AU Sheth, CM Enerson, BE Peters, D Lawton, MP Weaver, JL AF Sheth, Christopher M. Enerson, Bradley E. Peters, David Lawton, Michael P. Weaver, James L. TI Effects of Modulating In Vivo Nitric Oxide Production on the Incidence and Severity of PDE4 Inhibitor-Induced Vascular Injury in Sprague-Dawley Rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE drug-induced vascular injury; mesenteric artery; PDE4 inhibitor; nitric oxide; serum nitrite; nitrotyrosine ID PHOSPHODIESTERASE-IV; SCH 351591; TOXICITY; NO; PEROXYNITRITE; BIOMARKERS; BLOOD; ENOS; ACTIVATION; MECHANISMS AB Drug-induced vascular injury (DIVI) is observed in rat mesenteric arterioles in response to treatment with phosphodiesterase-4 inhibitors (PDE4i). However, the mechanisms responsible for causing the characteristic vascular lesions are unclear. Nitrotyrosine (NT) adducts, markers of local nitric oxide (NO) production, have been observed in close proximity to the arterial lesions and in the inflammatory cells associated with DIVI. To determine if NO has a direct role in DIVI, rats were treated with the PDE4i CI-1044 at 10, 20, or 40 mg/kg alone or in combination with the nitric oxide synthase inhibitor L-NAME (60 mg/kg) or the nitric oxide donor SIN-1 (30 mg/kg). Mesenteries were collected and processed for microscopic evaluation. NT formation was evaluated in situ via immunohistochemical staining. Serum nitrite (SN), a marker of in vivo NO production, was measured. Compared with vehicle controls, treatment with CI-1044 alone resulted in dose-related increases in the frequency and severity of vascular injury, SN levels, and NT residues. SIN-1 coadministration caused vascular injury to occur at lower doses of CI-1044, compared with CI-1044 alone, with the overall incidence and severity of injury being greater across all CI-1044-dose groups. Following administration of 20 or 40 mg/kg CI-1044, there were also increases in NT immunoreactivity when SIN-1 was coadministered and significant increases in SN. Conversely, coadministration of L-NAME resulted in marked reduction of injury, NT, and SN when compared with CI-1044 alone. The present study suggests that NO production is closely linked to PDE4i-induced vascular injury. C1 [Sheth, Christopher M.; Peters, David; Weaver, James L.] US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Enerson, Bradley E.; Lawton, Michael P.] Pfizer Worldwide Res & Dev, Groton, CT 06340 USA. RP Weaver, JL (reprint author), US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Life Sci Bldg 64,HFD-90,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM james.weaver@fda.hhs.gov FU Pfizer [124-07]; United States Food and Drug Administration [124-07] FX This work was supported by Cooperative Research and Development Agreement (124-07) between Pfizer and the United States Food and Drug Administration. Administrative support has been generously provided by the Oak Ridge Institute for Science and Education. NR 41 TC 8 Z9 8 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2011 VL 122 IS 1 BP 7 EP 15 DI 10.1093/toxsci/kfr082 PG 9 WC Toxicology SC Toxicology GA 800CT UT WOS:000293337500002 PM 21498876 ER PT J AU Jennings, TL Becker-Catania, SG Triulzi, RC Tao, GL Scott, B Sapsford, KE Spindel, S Oh, E Jain, V Delehanty, JB Prasuhn, DE Boeneman, K Algar, WR Medintz, IL AF Jennings, Travis L. Becker-Catania, Sara G. Triulzi, Robert C. Tao, Guoliang Scott, Bradley Sapsford, Kim E. Spindel, Samantha Oh, Eunkeu Jain, Vaibhav Delehanty, James. B. Prasuhn, Duane E. Boeneman, Kelly Algar, W. Russ Medintz, Igor L. TI Reactive Semiconductor Nanocrystals for Chemoselective Biolabeling and Multiplexed Analysis SO ACS NANO LA English DT Article DE nanocrystal; semiconductor; quantum dot; bioconjugation; chemoselective; probe; cellular imaging; multiplexing ID QUANTUM DOTS; BIOORTHOGONAL CHEMISTRY; DELIVERY; NANOPARTICLES; NANOTECHNOLOGY; BIOMOLECULES; STRATEGIES; LIGATION; PROTEINS; SURFACES AB Effective biological application of nanocrystalline semiconductor quantum dots continues to be hampered by the lack of easily implemented and widely applicable labeling chemistries. Here, we introduce two new orthogonal nanocrystal bioconjugation chemistries that overcome many of the labeling issues associated with currently utilized approaches. These chemistries specifically target either (1) the ubiquitous amines found on proteins or (2) thiols present In either antibody hinge regions or recombinantly introduced into other proteins to facilitate site-specific labeling. The amine chemistry incorporates aniline-catalyzed hydrazone bond formation, while the sulfhydryl chemistry utilizes nanouystals displaying surface activated maleimide groups. Both reactive chemistries are rapidly implemented, yielding purified nanocrystal protein bioconjugates in as little as 3 h. Following initial characterization of the nanocrystal materials, the wide applicability and strong multiplexing potential of these chemistries are demonstrated in an array of applications including immunoassays, immunolabeling in both cellular and tissue samples, in vivo cellular uptake, and flow cytometry. Side-by-side comparison of the immunolabeled cells suggested a functional equivalence between results generated with the amine and thiol-labeled antibody nanocrystal bioconjugates In that format. Three-color labeling was achieved in the cellular uptake format, with no significant toxicity observed while simultaneous five-color labeling of different epitopes was demonstrated for the immunolabeled tissue sample. Novel labeling applications are also facilitated by these chemistries, as highlighted by the ability to directly label cellular membranes in adherent cell cultures with the thiol-reactive chemistry. C1 [Jennings, Travis L.; Becker-Catania, Sara G.; Triulzi, Robert C.; Tao, Guoliang; Scott, Bradley] EBioscience Inc, San Diego, CA 92121 USA. [Sapsford, Kim E.; Spindel, Samantha] US FDA, Div Biol, Sci & Engn Labs, Silver Spring, MD 20993 USA. [Delehanty, James. B.; Prasuhn, Duane E.; Boeneman, Kelly; Algar, W. Russ; Medintz, Igor L.] USN, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC 20375 USA. [Oh, Eunkeu; Jain, Vaibhav] USN, Res Lab, Div Opt Sci, Washington, DC 20375 USA. [Algar, W. Russ] George Mason Univ, Coll Sci, Fairfax, VA 22030 USA. RP Jennings, TL (reprint author), EBioscience Inc, 10255 Sci Ctr Dr, San Diego, CA 92121 USA. EM travis.jennings@ebioscience.com; igor.medintz@nrl.navy.mil RI Gemmill, Kelly/G-2167-2012 FU CB Directorate/Physical S&T Division (DTRA), DARPA, ONR, NRL; NRL-NSI; Critical Path Initiative FDA; Natural Sciences and Engineering Research Council of Canada (NSERC) FX The authors acknowledge the CB Directorate/Physical S&T Division (DTRA), DARPA, ONR, NRL, and the NRL-NSI for financial support. K.B. and D.P. acknowledge ASEE fellowships through NRL. KS. and S.S. acknowledge the Critical Path Initiative FDA for financial support. T.L.J. is grateful to Drs. M. Fung and C. Funatake for helpful discussions and interpretations in flow cytometry. W.R.A. is grateful to the Natural Sciences and Engineering Research Council of Canada (NSERC) for support through a postdoctoral fellowship. NR 54 TC 47 Z9 47 U1 4 U2 51 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD JUL PY 2011 VL 5 IS 7 BP 5579 EP 5593 DI 10.1021/nn201050g PG 15 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 796ES UT WOS:000293035200036 PM 21692444 ER PT J AU Lacerda, SHD Semberova, J Holada, K Simakova, O Hudson, SD Simak, J AF Lacerda, Silvia H. De Paoli Semberova, Jana Holada, Karel Simakova, Olga Hudson, Steven D. Simak, Jan TI Carbon Nanotubes Activate Store-Operated Calcium Entry in Human Blood Platelets SO ACS NANO LA English DT Article DE platelet activation; intracellular calcium; carbon nanotubes; fullerene; nanotoxicity; thrombosis ID MEMBRANES; AGGREGATION; CHOLESTEROL; SIMULATION; THROMBOSIS; BILAYER; SURFACE; LENGTH AB Carbon nanotubes (CNTs) are known to potentiate arterial thrombosis in animal models, which raises serious safety Issues concerning environmental or occupational exposure to CNTs and their use in various biomedical applications. We have shown previously that different CNTs, but not fullerene (nC60), induce the aggregation of human blood platelets. To date, however, a mechanism of potentially thrombogenic CNT-induced platelet activation has not been elucidated. Here we show that pristine multiwalled CNTs (MWCNTs) penetrate platelet plasma membrane without any discernible damage but interact with the dense tubular system (DTS) causing depletion of platelet intracellular Ca(2+) stores. This process is accompanied by the clustering of stromal interaction molecule 1 (STIM1) colocalized with Orai1, indicating the activation of store-operated Ca(2+) entry (SOCE). Our findings reveal the molecular mechanism of CNT-induced platelet activation which is critical in the evaluation of the biocompatibility of carbon nanomaterials with blood. C1 [Lacerda, Silvia H. De Paoli; Semberova, Jana; Simak, Jan] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Holada, Karel] Charles Univ Prague, Fac Med 1, Prague, Czech Republic. [Semberova, Jana] Charles Univ Prague, Fac Med 3, Prague, Czech Republic. [Simakova, Olga] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Hudson, Steven D.] NIST, Gaithersburg, MD 20899 USA. RP Simak, J (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM jan.simak@fda.hhs.gov FU Ministry of Education, Youth and Sport of the Czech Republic [MSM 0021620806] FX We thank G. Sando, Malvern Instruments, Columbia, MD, for the flow particle image analysis of nanomaterial suspensions, M. Krumwiede, University of Minnesota, Minneapolis, MN, for the valuable consultations on the DAB-osmium labeling, and L. Diduch, National Institute of Standards and Technology, Gaithersburg, MD, for image processing. K. Holada was supported by Grant MSM 0021620806 of the Ministry of Education, Youth and Sport of the Czech Republic. NR 32 TC 25 Z9 26 U1 0 U2 23 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD JUL PY 2011 VL 5 IS 7 BP 5808 EP 5813 DI 10.1021/nn2015369 PG 6 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 796ES UT WOS:000293035200059 PM 21639133 ER PT J AU Xu, K Cote, TR AF Xu, Kui Cote, Timothy R. TI Database identifies FDA-approved drugs with potential to be repurposed for treatment of orphan diseases SO BRIEFINGS IN BIOINFORMATICS LA English DT Article DE orphan drug; rare disease; repurposing; Orphan Drug Act; efficacy; safety AB Facing substantial obstacles to developing new therapies for rare diseases, some sponsors are looking to 'repurpose' drugs already approved for other conditions and use those therapies to treat rare diseases. In an effort to facilitate such repurposing and speed the delivery of new therapies to people who need them, we have established a new resource, the Rare Disease Repurposing Database (RDRD). The advantages of repurposed compounds include their demonstrated efficacy (in some clinical contexts), their observed toxicity profiles and their clearly described manufacturing controls. To create the RDRD, we matched the US Food and Drug Administration (FDA) orphan designation database to FDA drug and biological product approval lists. The RDRD lists 236 products that have received orphan status designation that is, were found to be 'promising' for the treatment of a rare disease and though not yet approved for marketing for that rare disease, they are already approved for marketing to treat some other disease or condition. The RDRD contains three tables: Orphan-designated products with at least one marketing approval for a common disease indication (N = 109); orphan-designated products with at least one marketing approval for a rare disease indication (N = 76); and orphan-designated products with marketing approvals for both common and rare disease indications (N = 51). While the data included in the database is a re-configuration/cross-indexing of information already released by the FDA, it offers sponsors a new tool for finding special opportunities to develop niche therapies for rare disease patients. C1 [Cote, Timothy R.] US FDA, Off Orphan Prod Dev, Off Commissioner, Silver Spring, MD 20993 USA. RP Cote, TR (reprint author), US FDA, Off Orphan Prod Dev, Off Commissioner, 10903 New Hampshire Ave,WO32-5271, Silver Spring, MD 20993 USA. EM timothy.cote@fda.hhs.gov NR 3 TC 24 Z9 25 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1467-5463 EI 1477-4054 J9 BRIEF BIOINFORM JI Brief. Bioinform. PD JUL PY 2011 VL 12 IS 4 SI SI BP 341 EP 345 DI 10.1093/bib/bbr006 PG 5 WC Biochemical Research Methods; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Mathematical & Computational Biology GA 796UJ UT WOS:000293078100006 PM 21357612 ER PT J AU Li, ZG Fuscoe, JC Chen, T AF Li, Zhiguang Fuscoe, James C. Chen, Tao TI MicroRNAs and Their Predicted Target Messenger RNAs are Deregulated by Exposure to a Carcinogenic Dose of Comfrey in Rat Liver SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE microRNA; microRNA regulation; predicted mRNA; gene expression; genotoxic carcinogen ID ROOT EXTRACT OINTMENT; PYRROLIZIDINE ALKALOIDS; GENE-EXPRESSION; TUMOR-SUPPRESSOR; DOUBLE-BLIND; SYMPHYTUM-OFFICINALE; P53 TARGET; APOPTOSIS; CANCER; EFFICACY AB MicroRNAs (MiRNAs) are small noncoding RNAs that function as regulators of gene expression to control cell growth and differentiation. In this study, we analyzed miRNA and mRNA expression in the livers of rats treated with a carcinogenic dose of comfrey (Symphytum officinale) for 12 weeks. Groups of six rats were fed a normal diet or a diet containing 8% comfrey root. The animals were sacrificed 1 day after the last treatment and the livers were isolated for miRNA expression analysis using LC Sciences miRNA microarrays and for mRNA expression analysis using Affymetrix rat genome microarrays. MiRNA expression levels were significantly changed by comfrey treatment. The treated samples were separated clearly from the control samples in both principal component analysis (PCA) and hierarchical clustering analysis (HCA). Quantitative measurements of seven miRNAs using Taq-Man real-time PCR were consistent with the microarray results in terms of fold-change and the direction of the change in expression. Forty-five miRNAs (P < 0.01) and 1,921 mRNAs (q = 0) were significantly changed by comfrey treatment. Using a target prediction algorithm, 434 differentially expressed genes (DEGs) were predicted to be targeted by the differentially expressed miRNAs (DEMs). The DEM-targeted DEGs were more likely to be involved in carcinogenesis than the DEGs that were not targeted by the DEMs. The nontargeted DEGs were enriched in noncancer-related biological processes. Our data suggest that comfrey may exert its carcinogenic effects by disturbing miRNA expression resulting in altered mRNA levels of the DEM-targeted genes that are functionally associated with carcinogenesis. Environ. Mol. Mutagen. 52:469-478, 2011. (C) Published 2011 Wiley-Liss, Inc.(dagger) C1 [Li, Zhiguang; Chen, Tao] FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Fuscoe, James C.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Chen, T (reprint author), NCTR FDA, 3900 NCTR Rd,HFT 130, Jefferson, AR 72079 USA. EM tao.chen@fda.hhs.gov NR 73 TC 7 Z9 7 U1 0 U2 12 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUL PY 2011 VL 52 IS 6 BP 469 EP 478 DI 10.1002/em.20645 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 798ZI UT WOS:000293250700005 PM 21370286 ER PT J AU Au, S Yu, CW Booth, B AF Au, Stanley Yu, Chongwoo Booth, Brian TI Utilization of electronic resources in the NDA/BLA regulatory review of bioanalytical data: perspectives from US FDA reviewers SO BIOANALYSIS LA English DT Review AB The electronic common technical document (eCTD) format is frequently used in submitting bioanalytical information as part of a new drug application (NDA) or biologics license application (BLA). While the use of the eCTD format has many advantages, the potential for further improvement exists. This review highlights issues that are commonly encountered in reviewing bioanalytical information during the review process. In addition, the authors suggest potential strategies that illustrate how the ability to locate bioanalytical data or information can be enhanced and the summary information can be more consistently organized for a NDA or a BLA that is submitted in an eCTD format. C1 [Au, Stanley; Yu, Chongwoo; Booth, Brian] US FDA, Off Clin Pharmacol, Silver Spring, MD 20993 USA. RP Yu, CW (reprint author), US FDA, Off Clin Pharmacol, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM chongwoo.yu@fda.hhs.gov NR 3 TC 2 Z9 2 U1 0 U2 1 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD JUL PY 2011 VL 3 IS 13 BP 1441 EP 1445 DI 10.4155/BIO.11.150 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 795FS UT WOS:000292959700012 PM 21728769 ER PT J AU Booth, B Hill, H AF Booth, Brian Hill, Howard TI The best of Bioanalysis 2010 SO BIOANALYSIS LA English DT Editorial Material DE advisory panel; bioanalysis; editorial; journal ID LC-MS/MS; MASS-SPECTROMETRY; DRUG; QUANTIFICATION; ASSAY; CHROMATOGRAPHY; EXTRACTION; CHALLENGES; DISCOVERY; SAMPLES C1 [Booth, Brian] US FDA, Div Clin Pharmacol 5, Off Clin Pharmacol, Ctr Drug Res & Evaluat Res, Silver Spring, MD 20993 USA. [Hill, Howard] Huntingdon Life Sci, Pharmaceut Analyt Serv, Huntingdon PE16 5HS, Cambs, England. RP Booth, B (reprint author), US FDA, Div Clin Pharmacol 5, Off Clin Pharmacol, Ctr Drug Res & Evaluat Res, Silver Spring, MD 20993 USA. EM brian.booth@fda.hhs.gov; hillh@ukorg.huntingdon.com NR 43 TC 1 Z9 1 U1 0 U2 3 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD JUL PY 2011 VL 3 IS 14 BP 1533 EP 1540 DI 10.4155/BIO.11.145 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 795FW UT WOS:000292960300001 ER PT J AU Malik, SM Collins, B Pishvaian, M Ramzi, P Marshall, J Hwang, J AF Malik, Shakun M. Collins, Brian Pishvaian, Michael Ramzi, Pari Marshall, John Hwang, Jimmy TI A Phase I Trial of Bexarotene in Combination With Docetaxel in Patients With Advanced Solid Tumors SO CLINICAL LUNG CANCER LA English DT Article DE Apoptosis; Hypertriglyceridemia; Non-small cell lung cancer; Radiation recall; Retinoids ID RETINOID-X-RECEPTOR; CELL LUNG-CANCER; CHEMOTHERAPY-NAIVE PATIENTS; SELECTIVE LIGAND LGD1069; MAMMARY-CARCINOMA; ORAL BEXAROTENE; CLINICAL-TRIAL; APOPTOSIS; ACID; TARGRETIN AB Background: The purpose of this study was to identify dose-limiting toxicity (DLT) and maximum tolerated dose (MTD) of docetaxel with a fixed-dose of bexarotene. Patients and Methods: This was a phase I, single-center and open-label trial of dose-escalating docetaxel with a fixed-dose oral bexarotene. Successive cohorts of 3 patients (pts), with confirmed solid tumors refractory to standard therapy or for whom no standard therapy existed, received fixed-dose oral bexarotene (400 mg/m(2) daily) with escalating doses of docetaxel weekly (25, 30, or 35 mg/m(2)) for 3 weeks on a 4-week cycle. Cohorts were expanded to 6 pts if a DLT was noted. The MTD was determined based on the occurrence of DLT in at least 2 of 6 pts during the first cycle. Results: Nineteen pts were enrolled. Seven pts were treated at 25 mg/m(2), 6 at 30 mg/m(2), and 6 at 35 mg/m(2) of docetaxel. The MTD for docetaxel was 30 mg/m(2) with 400 mg/m2 of daily bexarotene. Hypothyroidism, hypertriglyceridemia, and fatigue were common toxicitiies. Three pts developed pulmonary toxicity (possible radiation recall pneumonitis [n = 2] and pulmonary hypertension because of tumor emboli [n = 1]). Two pts withdrew consent because of Grade 3 fatigue. Ten of 19 pts were noted to have stable disease and received more than 2 cycles of therapy. Of the 10 pts with stable disease, 5 had non-small-cell lung cancer (NSCLC), and of those 5 pts, 1 had a partial response that persisted for eight cycles. Conclusion: The MTD of docetaxel was 30mg/m(2) in combination with daily bexarotene at 400mg/m(2). Careful monitoring may be indicated in pts with previously irradiated lung tumors. C1 [Malik, Shakun M.] US FDA, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. [Collins, Brian; Pishvaian, Michael; Ramzi, Pari; Marshall, John; Hwang, Jimmy] Georgetown Univ Hosp, Lombardi Canc Ctr, Washington, DC 20007 USA. RP Malik, SM (reprint author), US FDA, Off Oncol Drug Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM smunshimalik@aol.com NR 39 TC 6 Z9 6 U1 0 U2 2 PU CIG MEDIA GROUP, LP PI DALLAS PA 3500 MAPLE AVENUE, STE 750, DALLAS, TX 75219-3931 USA SN 1525-7304 J9 CLIN LUNG CANCER JI Clin. Lung Cancer PD JUL PY 2011 VL 12 IS 4 BP 231 EP 236 DI 10.1016/j.cllc.2011.03.024 PG 6 WC Oncology SC Oncology GA 795PJ UT WOS:000292985800005 PM 21726822 ER PT J AU Morley, JE Abbatecola, AM Argiles, JM Baracos, V Bauer, J Bhasin, S Cederholm, T Coats, AJS Cummings, SR Evans, WJ Fearon, K Ferrucci, L Fielding, RA Guralnik, JM Harris, TB Inui, A Kalantar-Zadeh, K Kirwan, BA Mantovani, G Muscaritoli, M Newman, AB Rossi-Fanelli, F Rosano, GMC Roubenoff, R Schambelan, M Sokol, GH Storer, TW Vellas, B von Haehling, S Yeh, SS Anker, SD AF Morley, John E. Abbatecola, Angela Marie Argiles, Josep M. Baracos, Vickie Bauer, Juergen Bhasin, Shalender Cederholm, Tommy Coats, Andrew J. Stewart Cummings, Steven R. Evans, William J. Fearon, Kenneth Ferrucci, Luigi Fielding, Roger A. Guralnik, Jack M. Harris, Tamara B. Inui, Akio Kalantar-Zadeh, Kamyar Kirwan, Bridget-Anne Mantovani, Giovanni Muscaritoli, Maurizio Newman, Anne B. Rossi-Fanelli, Filippo Rosano, Giuseppe M. C. Roubenoff, Ronenn Schambelan, Morris Sokol, Gerald H. Storer, Thomas W. Vellas, Bruno von Haehling, Stephan Yeh, Shing-Shing Anker, Stefan D. CA Soc Sarcopenia Cachexia Wasting TI Sarcopenia With Limited Mobility: An International Consensus SO JOURNAL OF THE AMERICAN MEDICAL DIRECTORS ASSOCIATION LA English DT Article ID 6-MINUTE WALK DISTANCE; SKELETAL-MUSCLE STRENGTH; CROSS-SECTIONAL AREA; IANA TASK-FORCE; OLDER-ADULTS; BODY-COMPOSITION; PHYSICAL FUNCTION; GAIT SPEED; NEUROMUSCULAR ACTIVATION; PULMONARY-HYPERTENSION AB A consensus conference convened by the Society of Sarcopenia, Cachexia and Wasting Disorders has concluded that "Sarcopenia, le, reduced muscle mass, with limited mobility" should be considered an important clinical entity and that most older persons should be screened for this condition. "Sarcopenia with limited mobility" is defined as a person with muscle loss whose walking speed is equal to or less than 1 m/s or who walks less than 400 m during a 6-minute walk, and who has a lean appendicular mass corrected for height squared of 2 standard deviations or more below the mean of healthy persons between 20 and 30 years of age of the same ethnic group. The limitation in mobility should not clearly be a result of otherwise defined specific diseases of muscle, peripheral vascular disease with intermittent claudication, central and peripheral nervous system disorders, or cachexia. Clinically significant interventions are defined as an increase in the 6-minute walk of at least 50 meters or an increase of walking speed of at least 0.1 m/s. (J Am Med Dir Assoc 2011; 12: 403-409) C1 [Morley, John E.] St Louis Univ, Sch Med, Div Geriatr Med, St Louis, MO 63104 USA. [Morley, John E.] VA Med Ctr, GRECC, St Louis, MO USA. [Abbatecola, Angela Marie] INRCA, Sci Direct, Ancona, Italy. [Argiles, Josep M.] Univ Barcelona, Dept Biochem, Barcelona, Spain. [Baracos, Vickie] Univ Alberta, Dept Oncol, Edmonton, AB T6G 2M7, Canada. [Bauer, Juergen] Geriatr Ctr Oldenberg, Oldenburg, Germany. [Bauer, Juergen] Univ Erlangen Nurnberg, Dept Geriatr Med, Nurnberg, Germany. [Bhasin, Shalender; Storer, Thomas W.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Cederholm, Tommy] Univ Uppsala Hosp, Uppsala, Sweden. [Coats, Andrew J. Stewart] Univ E Anglia, Norwich NR4 7TJ, Norfolk, England. [Cummings, Steven R.] Univ Calif San Francisco, San Francisco Coordinating Ctr, San Francisco, CA 94143 USA. [Cummings, Steven R.; Schambelan, Morris] Univ Calif San Francisco, Dept Med, San Francisco, CA USA. [Cummings, Steven R.] Univ Calif San Francisco, Dept Epidemiol, San Francisco, CA 94143 USA. [Evans, William J.] GlaxoSmithKline Inc, Muscle Metab Discovery Performance Unit, Durham, NC USA. [Evans, William J.] Duke Univ, Dept Med, Durham, NC USA. [Evans, William J.] Duke Univ, Dept Geriatr, Durham, NC USA. [Fearon, Kenneth] Univ Edinburgh, Edinburgh, Midlothian, Scotland. [Fearon, Kenneth] Western Gen Hosp, Edinburgh EH4 2XU, Midlothian, Scotland. [Ferrucci, Luigi; Guralnik, Jack M.; Harris, Tamara B.] NIA, NIH, Bethesda, MD 20892 USA. [Fielding, Roger A.] Tufts Univ, Sch Med, Jean Mayer USDA Human Nutr Res Ctr Aging, Nutr Exercise Physiol & Sarcopenia Lab, Boston, MA 02111 USA. [Inui, Akio] Kagoshima Univ, Grad Sch Med & Dent Sci, Dept Psychosomat Internal Med, Kagoshima 890, Japan. [Kalantar-Zadeh, Kamyar] David Geffen UCLA Sch Med, Harold Simmons Ctr, Div Nephrol, Torrance, CA USA. [Kalantar-Zadeh, Kamyar] David Geffen UCLA Sch Med, Harold Simmons Ctr, Div Nephrol, Los Angeles, CA USA. [Kalantar-Zadeh, Kamyar] Harbor UCLA Med Ctr, Torrance, CA 90509 USA. [Kalantar-Zadeh, Kamyar] Harbor UCLA Med Ctr, Los Angeles, CA USA. [Kirwan, Bridget-Anne] SOCAR Res, Nyon, Switzerland. [Mantovani, Giovanni] Univ Cagliari, Sch Med, Dept Med Oncol, Cagliari, Italy. [Muscaritoli, Maurizio] Univ Roma La Sapienza, Internal Med & Clin Nutr Management Unit, Rome, Italy. [Newman, Anne B.] Univ Pittsburgh, Grad Sch Publ Hlth, Ctr Aging & Populat Hlth, Pittsburgh, PA USA. [Rossi-Fanelli, Filippo] Univ Rome, Rome, Italy. [Rosano, Giuseppe M. C.] IRCCS, Med Sci Ctr Clin & Expt Med, San Raffael, Italy. [Roubenoff, Ronenn] Novartis Inst Biomed Res, Boston, MA USA. [Roubenoff, Ronenn] Tufts Med Ctr, Dept Med, Boston, MA USA. [Schambelan, Morris] Univ Calif San Francisco, Div Endocrinol, San Francisco, CA 94143 USA. [Sokol, Gerald H.] Tampa Gen Hosp, Moffitt Canc Ctr, Tampa, FL 33606 USA. [Sokol, Gerald H.] US FDA, Tampa, FL USA. [Vellas, Bruno] Toulouse Univ Hosp, Toulouse, France. [von Haehling, Stephan] Charite, Dept Cardiol, Berlin, Germany. [Yeh, Shing-Shing] Stony Brook Univ Hosp, Northport VAMC & Med, Stony Brook, NY USA. [Anker, Stefan D.] Charite Campus Virchow Klinikum, Dept Cardiol, Berlin, Germany. RP Morley, JE (reprint author), St Louis Univ, Sch Med, Div Geriatr Med, 1402 S Grand Blvd,M238, St Louis, MO 63104 USA. EM morley@slu.edu RI morley, john/F-9177-2011; Newman, Anne/C-6408-2013; Rossi Fanelli, Filippo/E-9587-2011; OI morley, john/0000-0001-6444-2965; Newman, Anne/0000-0002-0106-1150; Rossi Fanelli, Filippo/0000-0002-8674-1672; Kirwan, Bridget-Anne/0000-0002-3814-3598; Baracos, Vickie/0000-0002-9609-1001; Kalantar-Zadeh, Kamyar/0000-0002-8666-0725 FU Intramural NIH HHS [Z01 AG000015-49] NR 93 TC 263 Z9 266 U1 14 U2 47 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1525-8610 J9 J AM MED DIR ASSOC JI J. Am. Med. Dir. Assoc. PD JUL PY 2011 VL 12 IS 6 BP 403 EP 409 DI 10.1016/j.jamda.2011.04.014 PG 7 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 795SS UT WOS:000292996700005 PM 21640657 ER PT J AU Newby, LK Rodriguez, I Finkle, J Becker, RC Hicks, KA Hausner, E Chesler, R Harper, C Targum, S Berridge, BR Lewis, E Walker, DB Dollery, C Turner, JR Krucoff, MW AF Newby, L. Kristin Rodriguez, Ignacio Finkle, John Becker, Richard C. Hicks, Karen A. Hausner, Elizabeth Chesler, Ruth Harper, Courtney Targum, Shari Berridge, Brian R. Lewis, Eric Walker, Dana B. Dollery, Colin Turner, J. Rick Krucoff, Mitchell W. TI Troponin measurements during drug development-considerations for monitoring and management of potential cardiotoxicity: An educational collaboration among the Cardiac Safety Research Consortium, the Duke Clinical Research Institute, and the US Food and Drug Administration SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE CORONARY SYNDROMES; MYOCARDIAL-INFARCTION; PROGNOSTIC VALUE; UNSTABLE ANGINA; HEART-FAILURE; I LEVELS; INJURY; ELEVATION; BIOMARKERS; MORTALITY AB Drug-induced cardiac toxicity is a recognized challenge in development and implementation of pharmacotherapy. Appropriate biomarkers are needed to detect these abnormalities early in development and to manage the risk of potentially cardiotoxic drugs or biologic agents. Circulating cardiac troponin (cTn) is the most widely used biomarker for detection of myocardial injury. Although most commonly used to detect myonecrosis in the setting of ischemia, cTns are also elevated with other acute and chronic disease processes, including heart failure, renal failure, sepsis, pulmonary embolic disease, and many others. High-sensitivity assays for both cTnI and cTnT are now available that achieve acceptable imprecision (coefficient of variation <10%) at the 99th percentile of a normal reference population. Even more sensitive assays are being developed that detect cTn in ranges that are near the level of normal cellular turnover (apoptosis). These properties of cTn and the continuing evolution of highly sensitive assays position cTn as a potentially uniquely informative marker for early detection of cardiac toxicity. This article summarizes collaborative discussions among key stakeholders in the Cardiac Safety Research Consortium about the use of cTn monitoring in drug development. (Am Heart J 2011;162:64-73.) C1 [Newby, L. Kristin; Becker, Richard C.; Krucoff, Mitchell W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27715 USA. [Rodriguez, Ignacio] F Hoffmann La Roche, Nutley, NJ USA. [Finkle, John] GlaxoSmithKline Inc, Upper Providence, PA USA. [Hicks, Karen A.; Hausner, Elizabeth; Chesler, Ruth; Harper, Courtney; Targum, Shari] US FDA, Silver Spring, MD USA. [Berridge, Brian R.; Lewis, Eric] GlaxoSmithKline Inc, Durham, NC USA. [Walker, Dana B.] Bristol Myers Squibb Co, Wallingford, CT 06492 USA. [Dollery, Colin] GlaxoSmithKline Inc, London, England. [Turner, J. Rick] Quintiles, Durham, NC USA. RP Newby, LK (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, POB 17969, Durham, NC 27715 USA. EM kristin.newby@duke.edu NR 39 TC 17 Z9 20 U1 1 U2 5 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUL PY 2011 VL 162 IS 1 BP 64 EP 73 DI 10.1016/j.ahj.2011.04.005 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 789UR UT WOS:000292542400019 PM 21742091 ER PT J AU Ahn, DG Lee, W Choi, JK Kim, SJ Plant, EP Almazan, F Taylor, DR Enjuanes, L Oh, JW AF Ahn, Dae-Gyun Lee, Wooseong Choi, Jin-Kyu Kim, Seong-Jun Plant, Ewan P. Almazan, Fernando Taylor, Deborah R. Enjuanes, Luis Oh, Jong-Won TI Interference of ribosomal frameshifting by antisense peptide nucleic acids suppresses SARS coronavirus replication SO ANTIVIRAL RESEARCH LA English DT Article DE SARS-CoV; Frameshifting; Peptide nucleic acids; RNA replication ID ACUTE RESPIRATORY SYNDROME; C VIRUS-RNA; ANTIVIRAL RESPONSES; GENE-EXPRESSION; VIRAL-RNA; PSEUDOKNOT; RECOGNITION; INHIBITION; SEQUENCE; GENOME AB The programmed -1 ribosomal frameshifting (-1 PRF) utilized by eukaryotic RNA viruses plays a crucial role for the controlled, limited synthesis of viral RNA replicase polyproteins required for genome replication. The viral RNA replicase polyproteins of severe acute respiratory syndrome coronavirus (SARS-CoV) are encoded by the two overlapping open reading frames 1a and 1b, which are connected by a -1 PRF signal. We evaluated the antiviral effects of antisense peptide nucleic acids (PNAs) targeting a highly conserved RNA sequence on the - PRF signal. The ribosomal frameshifting was inhibited by the PNA, which bound sequence-specifically a pseudoknot structure in the -1 PRF signal, in cell lines as assessed using a dual luciferase-based reporter plasmid containing the -1 PRF signal. Treatment of cells, which were transfected with a SARS-CoV-replicon expressing firefly luciferase, with the PNA fused to a cell-penetrating peptide (CPP) resulted in suppression of the replication of the SARS-CoV replicon, with a 50% inhibitory concentration of 4.4 mu M. There was no induction of type I interferon responses by PNA treatment, suggesting that the effect of PNA is not due to innate immune responses. Our results demonstrate that -1 PRF critical for SARS-CoV viral replication, can be inhibited by CPP-PNA, providing an effective antisense strategy for blocking -1 PRF signals. (C) 2011 Elsevier B.V. All rights reserved. C1 [Ahn, Dae-Gyun; Lee, Wooseong; Choi, Jin-Kyu; Kim, Seong-Jun; Oh, Jong-Won] Yonsei Univ, Dept Biotechnol & Translat Res, Ctr Prot Funct Control, Seoul 120749, South Korea. [Plant, Ewan P.; Taylor, Deborah R.] US FDA, Lab Hepatitis & Related Emerging Agents, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Almazan, Fernando; Enjuanes, Luis] CSIC, Dept Cell & Mol Biol, Ctr Nacl Biotecnol, E-28049 Madrid, Spain. RP Oh, JW (reprint author), Yonsei Univ, Dept Biotechnol & Translat Res, Ctr Prot Funct Control, Seoul 120749, South Korea. EM jwoh@yonsei.ac.kr RI Almazan, Fernando/K-8781-2015; OI Almazan, Fernando/0000-0002-5752-8469; Plant, Ewan/0000-0003-0166-5939; Enjuanes, Luis/0000-0002-0854-0226 FU Seoul RBD Program [10580]; National Research Foundation of Korea [NRF-2009-0092959]; Korean Ministry of Education, Science. and Technology FX We thank Dr. John Hiscott (McGill University, Montreal, Quebec, Canada) for providing the IFN beta-pGL3 luciferase reporter and a vector expressing an active form of IRF, and Dr. Naoya Sakamoto (Tokyo Medical and Dental University, Tokyo, Japan) for providing the pRep-Feo plasmid. This work was supported by a grant from the Seoul R&BD Program (Grant 10580) and a grant from Translation Research Center for Protein Function Control funded by the National Research Foundation of Korea (NRF-2009-0092959). D.G.A.. W.L. and J.K.C. were supported in part by the BK21 program of the Korean Ministry of Education, Science. and Technology. NR 56 TC 22 Z9 22 U1 2 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-3542 J9 ANTIVIR RES JI Antiviral Res. PD JUL PY 2011 VL 91 IS 1 BP 1 EP 10 DI 10.1016/j.antiviral.2011.04.009 PG 10 WC Pharmacology & Pharmacy; Virology SC Pharmacology & Pharmacy; Virology GA 791MS UT WOS:000292669900001 PM 21549154 ER PT J AU Rump, LV Fischer, M Gonzalez-Escalona, N AF Rump, Lydia V. Fischer, Markus Gonzalez-Escalona, Narjol TI Different IS629 Transposition Frequencies Exhibited by Escherichia coli O157:H7 Strains in the Stepwise Evolutionary Model SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID LINEAGES; O157-H7 AB The insertion sequence IS629, which is highly prevalent in Escherichia coli O157:H7 genomes, was found to be absent in O157:H- strains, which are on a divergent pathway in the emergence of O157:H7. Although O157:H- is deficient in IS629, it permits IS629 transposition, with an excision frequency higher than that of ancestral O55:H7 strains but significantly lower than that of pathogenic O157:H7 strains. C1 [Rump, Lydia V.; Gonzalez-Escalona, Narjol] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Fischer, Markus] Univ Hamburg, Inst Food Chem, Hamburg, Germany. RP Gonzalez-Escalona, N (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,21HFS-712, College Pk, MD 20740 USA. EM narjol.gonzalez-escalona@fda.hhs.gov RI Fischer, Markus/G-9477-2012; OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU FDA FX This project was supported by an appointment to L. V. R. through the Research Fellowship Program for the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Associated Universities through a contract with the FDA. NR 15 TC 5 Z9 5 U1 0 U2 3 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 JUL PY 2011 VL 77 IS 14 BP 5030 EP 5033 DI 10.1128/AEM.00249-11 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 789IZ UT WOS:000292510400039 PM 21622790 ER PT J AU Verghese, B Lok, M Wen, J Alessandria, V Chen, Y Kathariou, S Knabel, S AF Verghese, Bindhu Lok, Mei Wen, Jia Alessandria, Valentina Chen, Yi Kathariou, Sophia Knabel, Stephen TI comK Prophage Junction Fragments as Markers for Listeria monocytogenes Genotypes Unique to Individual Meat and Poultry Processing Plants and a Model for Rapid Niche-Specific Adaptation, Biofilm Formation, and Persistence (vol 77, pg 3279, 2011) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Correction C1 [Verghese, Bindhu] Penn State Univ, Dept Food Sci, University Pk, PA 16802 USA. Univ Turin, Dept Exploitat & Protect Agr & Forest Resources, Agr Microbiol & Food Technol Sector, Fac Agr, Turin, Italy. US FDA, Microbial Methods Dev Branch, Div Microbiol, Off Regulatory Sci,Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. RP Verghese, B (reprint author), Penn State Univ, Dept Food Sci, University Pk, PA 16802 USA. NR 1 TC 0 Z9 0 U1 1 U2 10 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2011 VL 77 IS 14 BP 5064 EP 5064 DI 10.1128/AEM.05513-11 PG 1 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 789IZ UT WOS:000292510400047 ER PT J AU Liu, ZC Kelly, R Fang, H Ding, D Tong, WD AF Liu, Zhichao Kelly, Reagan Fang, Hong Ding, Don Tong, Weida TI Comparative Analysis of Predictive Models for Nongenotoxic Hepatocarcinogenicity Using Both Toxicogenomics and Quantitative Structure-Activity Relationships SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID NATIONAL-TOXICOLOGY-PROGRAM; ESTROGEN-RECEPTOR BINDING; GENE-EXPRESSION PROFILES; LARGE DIVERSE SET; RODENT CARCINOGENICITY; IN-VIVO; CHEMICALS; GENOTOXICITY; CANCER; TECHNOLOGIES AB The primary testing strategy to identify nongenotoxic carcinogens largely relies on the 2-year rodent bioassay, which is time-consuming and labor-intensive. There is an increasing effort to develop alternative approaches to prioritize the chemicals for, supplement, or even replace the cancer bioassay. In silica approaches based on quantitative structure-activity relationships (QSAR) are rapid and inexpensive and thus have been investigated for such purposes. A slightly more expensive approach based on short-term animal studies with toxicogenomics (TGx) represents another attractive option for this application. Thus, the primary questions are how much better predictive performance using short-term TGx models can be achieved compared to that of QSAR models, and what length of exposure is sufficient for high quality prediction based on TGx. In this study, we developed predictive models for rodent liver carcinogenicity using gene expression data generated from short-term animal models at different time points and QSAR The study was focused on the prediction of nongenotoxic carcinogenicity since the genotoxic chemicals can be inexpensively removed from further development using various in vitro assays individually or in combination. We identified 62 chemicals whose hepatocarcinogenic potential was available from the National Center for Toxicological Research liver cancer database (NCTRlcdb). The gene expression profiles of liver tissue obtained from rats treated with these chemicals at different time points (1 day, 3 days, and 5 days) are available from the Gene Expression Omnibus (GEO) database. Both TGx and QSAR models were developed on the basis of the same set of chemicals using the same modeling approach, a nearest-centroid method with a minimum redundancy and maximum relevancy-based feature selection with performance assessed using compound-based 5-fold cross-validation. We found that the TGx models outperformed QSAR in every aspect of modeling. For example, the TGx models' predictive accuracy (0.77, 0.77, and 0.82 for the 1-day, 3-day, and 5-day models, respectively) was much higher for an independent validation set than that of a QSAR model (0.55). Permutation tests confirmed the statistical significance of the model's prediction performance. The study concluded that a short-term 5-day TGx animal model holds the potential to predict nongenotoxic hepatocarcinogenicity. C1 [Liu, Zhichao; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Ctr Excellence Bioinformat, Jefferson, AR 72079 USA. [Kelly, Reagan; Fang, Hong; Ding, Don] Z Tech, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, Ctr Excellence Bioinformat, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov RI Liu, Zhichao/C-4035-2011 FU National Center for Toxicological Research (NCTR) of U.S. Food and Drug Administration (FDA) through the Oak Ridge Institute for Science and Education (ORISE) FX Z.L. is grateful to the National Center for Toxicological Research (NCTR) of U.S. Food and Drug Administration (FDA) for postdoctoral support through the Oak Ridge Institute for Science and Education (ORISE). NR 43 TC 15 Z9 15 U1 0 U2 10 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL PY 2011 VL 24 IS 7 BP 1062 EP 1070 DI 10.1021/tx2000637 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 793TZ UT WOS:000292848100008 PM 21627106 ER PT J AU Felter, SP Conolly, RB Bercu, JP Bolger, PM Boobis, AR Bos, PMJ Carthew, P Doerrer, NG Goodman, JI Harrouk, WA Kirkland, DJ Lau, SS Llewellyn, GC Preston, RJ Schoeny, R Schnatter, AR Tritscher, A van Velsen, F Williams, GM AF Felter, Susan P. Conolly, Rory B. Bercu, Joel P. Bolger, P. Michael Boobis, Alan R. Bos, Peter M. J. Carthew, Philip Doerrer, Nancy G. Goodman, Jay I. Harrouk, Wafa A. Kirkland, David J. Lau, Serrine S. Llewellyn, G. Craig Preston, R. Julian Schoeny, Rita Schnatter, A. Robert Tritscher, Angelika van Velsen, Frans Williams, Gary M. TI A proposed framework for assessing risk from less-than-lifetime exposures to carcinogens SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Review DE Cancer risk assessment; dose-rate correction factors (DRCFs); Haber's Rule; intermittent exposure; less-than-lifetime exposure (LTL); short-term exposure; threshold of toxicological concern (TTC) ID NATIONAL-TOXICOLOGY-PROGRAM; SOLID CANCER INCIDENCE; ATOMIC-BOMB SURVIVORS; POTENCY-DATABASE CPDB; LUNG-CANCER; GENERAL LITERATURE; ANIMAL BIOASSAYS; DOSE-RATE; GENOTOXIC CARCINOGENS; METHYLENE-CHLORIDE AB Quantitative methods for estimation of cancer risk have been developed for daily, lifetime human exposures. There are a variety of studies or methodologies available to address less-than-lifetime exposures. However, a common framework for evaluating risk from less-than-lifetime exposures (including short-term and/or intermittent exposures) does not exist, which could result in inconsistencies in risk assessment practice. To address this risk assessment need, a committee of the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute conducted a multisector workshop in late 2009 to discuss available literature, different methodologies, and a proposed framework. The proposed framework provides a decision tree and guidance for cancer risk assessments for less-than-lifetime exposures based on current knowledge of mode of action and dose-response. Available data from rodent studies and epidemiological studies involving less-than-lifetime exposures are considered, in addition to statistical approaches described in the literature for evaluating the impact of changing the dose rate and exposure duration for exposure to carcinogens. The decision tree also provides for scenarios in which an assumption of potential carcinogenicity is appropriate (e.g., based on structural alerts or genotoxicity data), but bioassay or other data are lacking from which a chemical-specific cancer potency can be determined. This paper presents an overview of the rationale for the workshop, reviews historical background, describes the proposed framework for assessing less-than-lifetime exposures to potential human carcinogens, and suggests next steps. C1 [Doerrer, Nancy G.] ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. [Felter, Susan P.] Procter & Gamble Co, Cincinnati, OH USA. [Conolly, Rory B.; Preston, R. Julian] US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [Bercu, Joel P.] Eli Lilly & Co, Greenfield, IN USA. [Bolger, P. Michael] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Boobis, Alan R.] Univ London Imperial Coll Sci Technol & Med, London, England. [Bos, Peter M. J.] Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. [Carthew, Philip] Unilever, Bedford, England. [Goodman, Jay I.] Michigan State Univ, E Lansing, MI 48824 USA. [Harrouk, Wafa A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Lau, Serrine S.] Univ Arizona, Tucson, AZ USA. [Llewellyn, G. Craig] Kraft Gen Foods Inc, Glenview, IL 60025 USA. [Schoeny, Rita] US EPA, Off Water, Washington, DC 20460 USA. [Schnatter, A. Robert] ExxonMobil Biomed Sci Inc, Annandale, NJ USA. [Tritscher, Angelika] WHO, CH-1211 Geneva, Switzerland. [van Velsen, Frans] Johnson & Johnson Pharmaceut, Mechelen, Belgium. [Williams, Gary M.] New York Med Coll, Dept Pathol, Valhalla, NY 10595 USA. RP Doerrer, NG (reprint author), ILSI Hlth & Environm Sci Inst, 1156 15th St NW,Suite 200, Washington, DC 20005 USA. EM ndoerrer@hesiglobal.org OI Boobis, Alan/0000-0003-3371-386X NR 197 TC 16 Z9 18 U1 2 U2 12 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1040-8444 EI 1547-6898 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PD JUL PY 2011 VL 41 IS 6 BP 507 EP 544 DI 10.3109/10408444.2010.552063 PG 38 WC Toxicology SC Toxicology GA 791KA UT WOS:000292662900002 PM 21591905 ER PT J AU Albillos, SM Reddy, R Salter, R AF Albillos, S. M. Reddy, R. Salter, R. TI Evaluation of Alkaline Phosphatase Detection in Dairy Products Using a Modified Rapid Chemiluminescent Method and Official Methods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MILK; SHEEPS; GOATS; COWS AB Alkaline phosphatase is a ubiquitous milk enzyme that historically has been used to verify adequate pasteurization of milk for public health purposes. Current approved methods for detection of alkaline phosphatase in milk include the use of enzyme photoactivated substrates to give readings in milliunits per liter. The U.S. and European public health limit for alkaline phosphatase in pasteurized drinks is 350 mU/liter. A modified chemiluminescent method, fast alkaline phosphatase, was compared with the approved fluorometric and chemiluminescent alkaline phosphatase methods to determine whether the modified method was equivalent to the approved methods and suitable for detecting alkaline phosphatase in milk. Alkaline phosphatase concentrations in cow's, goat's, and sheep's milk and in flavored drinks and cream were determined by three methods. Evaluations in each matrix were conducted with pasteurized samples spiked with raw milk to produce alkaline phosphatase concentrations of 2 to 5,000 mU/liter. The tests were performed by the method developer and then reproduced at a laboratory at the National Center for Food Safety and Technology following the criteria for a single laboratory validation. The results indicated that the fast alkaline phosphatase method was not significantly different from the approved chemiluminescent method, with a limit of detection of 20 to 50 mU/liter in all the studied matrices. This modified chemiluminescent method detects alkaline phosphatase in the 350 mU/liter range with absolute differences from triplicate data that are lower and within the range of the allowed intralaboratory repeatability values published for the approved chemiluminescent method. C1 [Albillos, S. M.] Natl Ctr Food Safety & Technol, Summit Argo, IL 60455 USA. [Reddy, R.] US FDA, Summit Argo, IL 60455 USA. [Salter, R.] Charm Sci Inc, Lawrence, MA 01843 USA. RP Albillos, SM (reprint author), INBIOTEC, Av Real 1, Leon 24006, Spain. EM smalbg@unileon.es RI Albillos, Silvia/D-1276-2016 OI Albillos, Silvia/0000-0002-3273-0126 NR 24 TC 8 Z9 8 U1 2 U2 22 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 JUL PY 2011 VL 74 IS 7 BP 1144 EP 1154 DI 10.4315/0362-028X.JFP-10-422 PG 11 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 790GZ UT WOS:000292577800013 PM 21740717 ER PT J AU Bidzhieva, B Laassri, M Chumakov, K AF Bidzhieva, Bella Laassri, Majid Chumakov, Konstantin TI MAPREC assay for quantitation of mutants in a recombinant flavivirus vaccine strain using near-infrared fluorescent dyes SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE West Nile/Dengue 4 chimera; Oral polio vaccine; Non-radioactive; Quantitative method; Vaccine safety; Genetic stability ID ORAL POLIOVIRUS VACCINE; RNA VIRUSES; ENZYME CLEAVAGE; NEUROVIRULENCE; TYPE-3; HYBRIDIZATION; MUTATIONS; EVOLUTION; REVERSION; PCR AB Mutant analysis by PCR and restriction enzyme cleavage (MAPREC) is a quantitative assay of revertants in batches of live viral vaccines. The assay is highly sensitive and reliable but requires radioactive isotopes, which complicates its use in quality control laboratories. To quantify mutants in the cDNA of the West Nile (WN)/Dengue 4 chimera that was proposed as a new candidate of live vaccine against West Nile disease, alternative MAPREC protocols using non-radioactive dyes were explored. To compare the utility of different fluorescent dyes for MAPREC, the G(2337) -> C mutation that was revealed by microarray hybridization in WN/Dengue 4 chimera virus was used as a model. DNA fragments produced by restriction endonuclease digestion were visualized in polyacrylamide gels by visible-range fluorescent dyes including ethidium bromide (EtBr) and SYBR Green I as well as by near-infrared (NIR) dye SYTO 60 and NIR dyes 700 and 800. The MAPREC assay performed with SYTO 60 and SYBR Green I was more sensitive than with EtBr but less sensitive than with NIR dyes 700 or 800. The NIR dyes 700 and 800 exhibited a wide linear range that may enable the detection of 0.05% of mutants in viral stocks. The NIR-based MAPREC assay was validated by using World Health Organization (WHO) international references for poliovirus type 3 with known contents of mutants. Values of mutant content produced by the non-radioactive assay were similar to the values determined in a previous WHO international collaborative study. The modified MAPREC assay could be used as an alternative to the radioisotope-based standard protocol for quality control of live viral vaccines. Published by Elsevier B.V. C1 [Bidzhieva, Bella; Laassri, Majid; Chumakov, Konstantin] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA. EM konstantin.chumakov@fda.hhs.gov FU FDA FX We thank Dr. Glynis Dunn (NIBSC, UK) for the suggestion to use NIR dyes. This study was supported by the FDA intramural research funds. NR 29 TC 3 Z9 3 U1 1 U2 5 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 JUL PY 2011 VL 175 IS 1 BP 14 EP 19 DI 10.1016/j.jviromet.2011.04.008 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 791LG UT WOS:000292666100003 PM 21514323 ER PT J AU Liu, JM Kabadi, S Van Uitert, R Petrick, N Deriche, R Summers, RM AF Liu, Jiamin Kabadi, Suraj Van Uitert, Robert Petrick, Nicholas Deriche, Rachid Summers, Ronald M. TI Improved computer-aided detection of small polyps in CT colonography using interpolation for curvature estimation SO MEDICAL PHYSICS LA English DT Article DE curvature estimation; polyp detection; interpolation; Deriche filter ID COLONIC POLYPS; FALSE POSITIVES; OBSERVER; CAD; POPULATION; REDUCTION; IMAGES; PERFORMANCE; EVOLUTION; DIAGNOSIS AB Purpose: Surface curvatures are important geometric features for the computer-aided analysis and detection of polyps in CT colonography (CTC). However, the general kernel approach for curvature computation can yield erroneous results for small polyps and for polyps that lie on haustral folds. Those erroneous curvatures will reduce the performance of polyp detection. This paper presents an analysis of interpolation's effect on curvature estimation for thin structures and its application on computer-aided detection of small polyps in CTC. Methods: The authors demonstrated that a simple technique, image interpolation, can improve the accuracy of curvature estimation for thin structures and thus significantly improve the sensitivity of small polyp detection in CTC. Results: Our experiments showed that the merits of interpolating included more accurate curvature values for simulated data, and isolation of polyps near folds for clinical data. After testing on a large clinical data set, it was observed that sensitivities with linear, quadratic B-spline and cubic B-spline interpolations significantly improved the sensitivity for small polyp detection. Conclusions: The image interpolation can improve the accuracy of curvature estimation for thin structures and thus improve the computer-aided detection of small polyps in CTC. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3596529] C1 [Liu, Jiamin; Kabadi, Suraj; Van Uitert, Robert; Summers, Ronald M.] NIH, Imaging Biomarkers & Computer Aided Diag Lab, Ctr Clin, Bethesda, MD 20892 USA. [Petrick, Nicholas] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Deriche, Rachid] French Natl Inst Res Comp Sci & Control, Sophia Antipolis, France. RP Summers, RM (reprint author), NIH, Imaging Biomarkers & Computer Aided Diag Lab, Ctr Clin, Bldg 10, Bethesda, MD 20892 USA. EM rms@nih.gov FU NIH Clinical Center FX This research was supported by the Intramural Research Program of the NIH Clinical Center. We thank Dr. Perry Pickhardt, Dr. J. Richard Choi, and Dr. William Schindler for providing CT colonography data. NR 44 TC 5 Z9 5 U1 0 U2 5 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 JUL PY 2011 VL 38 IS 7 BP 4276 EP 4284 DI 10.1118/1.3596529 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 789NB UT WOS:000292521100044 PM 21859029 ER PT J AU Ryan, P Atreya, C AF Ryan, Patricia Atreya, Chintamani TI Blood Cell MicroRNAs: What Are They and What Future Do They Hold? SO TRANSFUSION MEDICINE REVIEWS LA English DT Review ID HUMAN PLATELETS; MICROPROCESSOR COMPLEX; PROTEIN-SYNTHESIS; EXPRESSION; STORAGE; ERYTHROCYTES; BIOGENESIS; BIOMARKERS; PATHWAYS; GENOMICS AB The advent of blood component storage revolutionized health care by allowing for a managed supply of transfusion quality blood products. During storage, blood components undergo a series of physiological changes that affect the product quality, which ultimately can interfere with the safety and efficacy of such products after transfusion. Despite continuous improvements in blood component quality and safety, it is still desirable to have in vitro standard markers of measurable characteristics that predict blood component safety and efficacy in vivo following their transfusion. Over the last decade, research on the feasibility of using microRNAs as biomarkers for various clinical manifestations and cellular pathologies has exploded. Here, we review the literature on blood cell microRNAs and discuss the potential of these molecules to act as measurable characteristics (product biomarkers) for stored blood component quality and safety. Published by Elsevier Inc. C1 [Ryan, Patricia; Atreya, Chintamani] US FDA, Sect Cell Biol, Lab Cellular Hematol, Div Hematol,Off Blood Res & Review,Ctr Biol Evalu, Rockville, MD 20857 USA. RP Atreya, C (reprint author), Bldg 29A,Room 2C-11,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. EM Chintamani.Atreya@fda.hhs.gov FU Center for Biologics Evaluation and Research FX PR is a recipient of-a postdoctoral fellowship at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an intra-agency agreement between the US Department of Energy and the US Food and Drug Administration. The authors thank Drs Ketha and Rao. Center for Biologics Evaluation and Research, Food and Drug Administration, for their review of this manuscript. NR 40 TC 3 Z9 3 U1 0 U2 2 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0887-7963 J9 TRANSFUS MED REV JI Transf. Med. Rev. PD JUL PY 2011 VL 25 IS 3 BP 247 EP 251 DI 10.1016/j.tmrv.2011.01.005 PG 5 WC Hematology SC Hematology GA 789AH UT WOS:000292485200007 PM 21419598 ER PT J AU Thelwell, C Marszal, E Rigsby, P Longstaff, C AF Thelwell, C. Marszal, E. Rigsby, P. Longstaff, C. TI An international collaborative study to establish the WHO 1st international standard for alpha-1-antitrypsin SO VOX SANGUINIS LA English DT Article DE alpha-1-proteinase inhibitor; alpha-1-antitrypsin; standardization ID ALPHA(1)-ANTITRYPSIN DEFICIENCY; BIOLOGICAL STANDARDS; TESTS AB Background and Objectives The aim was to establish the 1st International Standard (IS) for alpha-1-antitrypsin (AAT) to standardise potency assignment of therapeutic products, calibrated in moles and mg active AAT in line with product labelling practice. Assigning total protein and antigen values to the IS was also investigated. Materials and Methods The active concentration of four candidate AAT preparations was determined in an international collaborative study by inhibition of trypsin (calibrated by active-site titration). Total protein and antigen content were determined for each candidate using local methods and in-house standards, and a common AAT preparation. The total protein content of the IS was also determined by amino acid analysis. Potency determination of recombinant and transgenic materials against the IS was investigated in a follow-up study. Results Data analysis for potency determination indicated no statistical difference between any of the candidates, or between the results for recombinant and plasma-derived products. Total protein content of the IS determined by amino acid analysis was consistent with the potency value. The variability in the total protein and antigen results for the other candidates was reduced when the data were recalculated relative to the IS. Conclusions Candidate C (05/162) was established by the WHO Expert Committee on Biological Standardization (ECBS) in 2006 as the WHO 1st IS for AAT with a potency of 243 nmoles (12.4 mg) active inhibitor per ampoule. In 2008, ECBS approved the IS for potency determination of recombinant material and assigned a total protein and antigen value of 12.4 mg. C1 [Thelwell, C.; Longstaff, C.] Natl Inst Biol Stand & Controls, Haemostasis Sect, Biotherapeut Grp, S Mimms, Herts, England. [Marszal, E.] FDA CBER, Div Hematol, Bethesda, MD USA. [Rigsby, P.] Natl Inst Biol Stand & Controls, Biostat Grp, S Mimms, Herts, England. RP Thelwell, C (reprint author), Natl Inst Biol Stand & Controls, Biotherapeut Grp, Haemostasis Sect, Potters Bar EN6 3QG, Herts, England. EM craig.thelwell@nibsc.hpa.org.uk RI Longstaff, Colin/D-2413-2013; Thelwell, Craig/E-2572-2013 OI Longstaff, Colin/0000-0001-7608-208X; Thelwell, Craig/0000-0003-4802-2332 FU Alpha-1 Foundation FX We thank the Alpha-1 Foundation for sponsoring the Alpha-1 Foundation Workshop 2005 (Cincinnati, USA) and the attendees of the standardisation session for helpful discussions; the manufacturers that kindly donated candidate materials; the collaborative study participants listed in Appendix 1; and colleagues from the CBRM (NIBSC) for dispatch of collaborative study materials. NR 14 TC 4 Z9 4 U1 1 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0042-9007 EI 1423-0410 J9 VOX SANG JI Vox Sang. PD JUL PY 2011 VL 101 IS 1 BP 83 EP 89 DI 10.1111/j.1423-0410.2010.01459.x PG 7 WC Hematology SC Hematology GA 789VM UT WOS:000292545500012 PM 21668863 ER PT J AU Yetley, EA Pfeiffer, CM Phinney, KW Fazili, Z Lacher, DA Bailey, RL Blackmore, S Bock, JL Brody, LC Carmel, R Curtin, LR Durazo-Arvizu, RA Eckfeldt, JH Green, R Gregory, JF Hoofnagle, AN Jacobsen, DW Jacques, PF Molloy, AM Massaro, J Mills, JL Nexo, E Rader, JI Selhub, J Sempos, C Shane, B Stabler, S Stover, P Tamura, T Tedstone, A Thorpe, SJ Coates, PM Johnson, CL Picciano, MF AF Yetley, Elizabeth A. Pfeiffer, Christine M. Phinney, Karen W. Fazili, Zia Lacher, David A. Bailey, Regan L. Blackmore, Sheena Bock, Jay L. Brody, Lawrence C. Carmel, Ralph Curtin, L. Randy Durazo-Arvizu, Ramon A. Eckfeldt, John H. Green, Ralph Gregory, Jesse F., III Hoofnagle, Andrew N. Jacobsen, Donald W. Jacques, Paul F. Molloy, Anne M. Massaro, Joseph Mills, James L. Nexo, Ebba Rader, Jeanne I. Selhub, Jacob Sempos, Christopher Shane, Barry Stabler, Sally Stover, Patrick Tamura, Tsunenobu Tedstone, Alison Thorpe, Susan J. Coates, Paul M. Johnson, Clifford L. Picciano, Mary Frances TI Biomarkers of folate status in NHANES: a roundtable summary SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID TANDEM MASS-SPECTROMETRY; FOLIC-ACID FORTIFICATION; WHOLE-BLOOD FOLATE; BIO-RAD RADIOASSAY; B-VITAMIN STATUS; HUMAN SERUM; MICROBIOLOGIC ASSAY; INTERNATIONAL STANDARD; UNITED-STATES; HUMAN PLASMA AB A roundtable to discuss the measurement of folate status biomarkers in NHANES took place in July 2010. NHANES has measured serum folate since 1974 and red blood cell (RBC) folate since 1978 with the use of several different measurement procedures. Data on serum 5-methyltetrahydrofolate (5MTHF) and folic acid (FA) concentrations in persons aged >= 60 y are available in NHANES 1999-2002. The roundtable reviewed data that showed that folate concentrations from the Bio-Rad Quantaphase II procedure (Bio-Rad Laboratories, Hercules, CA; used in NHANES 1991-1994 and NHANES 1999-2006) were, on average, 29% lower for serum and 45% lower for RBC than were those from the microbiological assay (MA), which was used in NHANES 2007-2010. Round-table experts agreed that these differences required a data adjustment for time-trend analyses. The roundtable reviewed the possible use of an isotope-dilution liquid chromatography-tandem mass spectrometry (LC-MS/MS) measurement procedure for future NHANES and agreed that the close agreement between the MA and LC-MS/MS results for serum folate supported conversion to the LC-MS/MS procedure. However, for RBC folate, the MA gave 25% higher concentrations than did the LC-MS/MS procedure. The roundtable agreed that the use of the LC-MS/MS procedure to measure RBC folate is premature at this time. The roundtable reviewed the reference materials available or under development at the National Institute of Standards and Technology and recognized the challenges related to, and the scientific need for, these materials. They noted the need for a commutability study for the available reference materials for serum 5MTHF and FA. Am J Clin Nutr 2011;94(suppl):303S-12S. C1 [Yetley, Elizabeth A.; Bailey, Regan L.; Sempos, Christopher; Coates, Paul M.; Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Pfeiffer, Christine M.; Fazili, Zia] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Phinney, Karen W.] NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA. [Lacher, David A.; Curtin, L. Randy; Johnson, Clifford L.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Blackmore, Sheena] United Kingdom Natl External Qual Assessment Serv, Dept Haematol, Sutton, Coldfield, England. [Bock, Jay L.] SUNY Stony Brook, Dept Pathol, Med Ctr, Stony Brook, NY 11794 USA. [Carmel, Ralph] New York Methodist Hosp, Dept Med, Brooklyn, NY USA. [Carmel, Ralph] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Durazo-Arvizu, Ramon A.] Loyola Univ Chicago, Stritch Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL USA. [Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Green, Ralph] Univ Calif Davis, Dept Med Pathol & Lab Med & Med, Sacramento, CA 95817 USA. [Gregory, Jesse F., III] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Hoofnagle, Andrew N.] Univ Washington, Dept Med, Seattle, WA USA. [Jacobsen, Donald W.] Case Western Reserve Univ, Lerner Coll Med, Dept Mol Med, Cleveland Clin, Cleveland, OH 44106 USA. [Jacobsen, Donald W.] Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44106 USA. [Jacques, Paul F.; Selhub, Jacob] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Molloy, Anne M.] Trinity Coll Dublin, Sch Med, Dept Clin Med, Dublin, Ireland. [Massaro, Joseph] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Nexo, Ebba] Aarhus Univ Hosp, Dept Clin Biochem, DK-8000 Aarhus, Denmark. [Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Shane, Barry] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. [Stabler, Sally] Univ Colorado, Hlth Sci Ctr, Div Hematol, Dept Med, Aurora, CO USA. [Stover, Patrick] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Tamura, Tsunenobu] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Tedstone, Alison] Dept Hlth, London SE1 6TE, England. RP Coates, PM (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA. EM beth@yetley.com; coatesp@od.nih.gov RI Thorpe, Susan/E-1808-2013; OI Molloy, Anne/0000-0002-1688-9049 FU National Center for Health Statistics, Centers for Disease Control and Prevention; Office of Dietary Supplements, NIH FX Supported by the National Center for Health Statistics, Centers for Disease Control and Prevention, and the Office of Dietary Supplements, NIH. NR 52 TC 39 Z9 40 U1 0 U2 11 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2011 VL 94 IS 1 BP 303S EP 312S DI 10.3945/ajcn.111.013011 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 779QK UT WOS:000291794800045 PM 21593502 ER PT J AU Yetley, EA Pfeiffer, CM Phinney, KW Bailey, RL Blackmore, S Bock, JL Brody, LC Carmel, R Curtin, LR Durazo-Arvizu, R Eckfeldt, JH Green, R Gregory, JF Hoofnagle, AN Jacobsen, DW Jacques, PF Lacher, DA Molloy, AM Massaro, J Mills, JL Nexo, E Rader, JI Selhub, J Sempos, C Shane, B Stabler, S Stover, P Tamura, T Tedstone, A Thorpe, SJ Coates, PM Johnson, CL Picciano, MF AF Yetley, Elizabeth A. Pfeiffer, Christine M. Phinney, Karen W. Bailey, Regan L. Blackmore, Sheena Bock, Jay L. Brody, Lawrence C. Carmel, Ralph Curtin, L. Randy Durazo-Arvizu, Ramon Eckfeldt, John H. Green, Ralph Gregory, Jesse F., III Hoofnagle, Andrew N. Jacobsen, Donald W. Jacques, Paul F. Lacher, David A. Molloy, Anne M. Massaro, Joseph Mills, James L. Nexo, Ebba Rader, Jeanne I. Selhub, Jacob Sempos, Christopher Shane, Barry Stabler, Sally Stover, Patrick Tamura, Tsunenobu Tedstone, Alison Thorpe, Susan J. Coates, Paul M. Johnson, Clifford L. Picciano, Mary Frances TI Biomarkers of vitamin B-12 status in NHANES: a roundtable summary SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article ID PLASMA METHYLMALONIC ACID; TANDEM MASS-SPECTROMETRY; 3RD NATIONAL-HEALTH; TOTAL HOMOCYSTEINE; LIQUID-CHROMATOGRAPHY; COGNITIVE IMPAIRMENT; BIOCHEMICAL INDICATORS; SRM-1955 HOMOCYSTEINE; AUTOMATED-ASSAY; OLDER-ADULTS AB A roundtable to discuss the measurement of vitamin B-12 (cobalamin) status biomarkers in NHANES took place in July 2010. NHANES stopped measuring vitamin B-12-related biomarkers after 2006. The roundtable reviewed 3 biomarkers of vitamin B-12 status used in past NHANES-serum vitamin B-12, methylmalonic acid (MMA), and total homocysteine (tHcy)-and discussed the potential utility of measuring holotranscobalamin (holoTC) for future NHANES. The roundtable focused on public health considerations and the quality of the measurement procedures and reference methods and materials that past NHANES used or that are available for future NHANES. Roundtable members supported reinstating vitamin B-12 status measures in NHANES. They noted evolving concerns and uncertainties regarding whether subclinical (mild, asymptomatic) vitamin B-12 deficiency is a public health concern. They identified the need for evidence from clinical trials to address causal relations between subclinical vitamin B-12 deficiency and adverse health outcomes as well as appropriate cutoffs for interpreting vitamin B-12-related biomarkers. They agreed that problems with sensitivity and specificity of individual biomarkers underscore the need for including at least one biomarker of circulating vitamin B-12 (serum vitamin B-12 or holoTC) and one functional biomarker (MMA or tHcy) in NHANES. The inclusion of both serum vitamin B-12 and plasma MMA, which have been associated with cognitive dysfunction and anemia in NHANES and in other population-based studies, was preferable to provide continuity with past NHANES. Reliable measurement procedures are available, and National Institute of Standards and Technology reference materials are available or in development for serum vitamin B-12 and MMA. Am J Clin Nutr 2011;94(suppl):313S-21S. C1 [Yetley, Elizabeth A.; Bailey, Regan L.; Sempos, Christopher; Coates, Paul M.; Picciano, Mary Frances] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Pfeiffer, Christine M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. [Phinney, Karen W.] NIST, Div Analyt Chem, Gaithersburg, MD 20899 USA. [Blackmore, Sheena] United Kingdom Natl External Qual Assessment Serv, Dept Haematol, Sutton, Coldfield, England. [Bock, Jay L.] SUNY Stony Brook, Dept Pathol, Med Ctr, Stony Brook, NY 11794 USA. [Brody, Lawrence C.] NHGRI, Genome Technol Branch, NIH, Bethesda, MD 20892 USA. [Carmel, Ralph] New York Methodist Hosp, Dept Med, Brooklyn, NY USA. [Carmel, Ralph] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Curtin, L. Randy; Lacher, David A.; Johnson, Clifford L.] Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. [Durazo-Arvizu, Ramon] Loyola Univ Chicago, Stritch Sch Med, Dept Epidemiol & Prevent Med, Maywood, IL USA. [Eckfeldt, John H.] Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. [Green, Ralph] Univ Calif Davis, Dept Med Pathol & Lab Med & Med, Sacramento, CA 95817 USA. [Gregory, Jesse F., III] Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Jacobsen, Donald W.] Case Western Reserve Univ, Lerner Coll Med, Cleveland Clin, Dept Mol Med, Cleveland, OH 44106 USA. [Jacobsen, Donald W.] Cleveland Clin, Lerner Res Inst, Dept Cell Biol, Cleveland, OH 44106 USA. [Jacques, Paul F.; Selhub, Jacob] Tufts Univ, Jean Mayer US Dept Agr, Human Nutr Res Ctr Aging, Boston, MA 02111 USA. [Molloy, Anne M.] Trinity Coll Dublin, Dept Clin Med, Sch Med, Dublin, Ireland. [Massaro, Joseph] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA. [Mills, James L.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. [Nexo, Ebba] Aarhus Univ Hosp, Dept Clin Biochem, DK-8000 Aarhus, Denmark. [Rader, Jeanne I.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Shane, Barry] Univ Calif Berkeley, Dept Nutr Sci & Toxicol, Berkeley, CA 94720 USA. [Stabler, Sally] Univ Colorado, Hlth Sci Ctr, Div Hematol, Dept Med, Aurora, CO USA. [Stover, Patrick] Cornell Univ, Div Nutr Sci, Ithaca, NY 14853 USA. [Tamura, Tsunenobu] Univ Alabama, Dept Nutr Sci, Birmingham, AL 35294 USA. [Tedstone, Alison] Dept Hlth, London SE1 6TE, England. [Thorpe, Susan J.] Natl Inst Biol Stand & Controls, Potters Bar, Herts, England. RP Coates, PM (reprint author), NIH, Off Dietary Supplements, 6100 Execut Blvd,Room 3B01,MSC 7517, Bethesda, MD 20892 USA. EM beth@yetley.com; coatesp@od.nih.gov RI Thorpe, Susan/E-1808-2013; OI Molloy, Anne/0000-0002-1688-9049; Gregory, Jesse/0000-0002-9976-2085 FU National Center for Health Statistics, Centers for Disease Control and Prevention; Office of Dietary Supplements, National Institutes of Health; Axis Shield Diagnostics FX Supported by the National Center for Health Statistics, Centers for Disease Control and Prevention, and MFP, CLJ, EAY, and PMC: conceived and sponsored the roundtable project; MFP, CLJ, EAY, PMC, RLB, DAL, AMM, JLM, CMP, KWP, CS, BS, and TT: served on the planning committee; EAY, CLJ, JHE, JM, RAD- A, CS, BS, CMP, KWP, JS, RC, EN, RLB, and DAL: presented data and backgroundinformation; EAY: drafted the manuscript with considerable input from CMP and KWP; EAY, CLJ, and PMC: had primary responsibility for the final manuscript content; and all authors: fully participated in the roundtable discussions and read and approved the final manuscript. RG and DWJ serve on the Scientific Advisory Boards of Emisphere Technologies Inc of Cedar Knolls, NJ, and PARPharmaceuticals of Woodcliff Lake, NJ. DWJ also serves on the Scientific Advisory Board of Diazyme-GA, La Jolla, CA. For the past 3 y, AMM carried out a research project that was funded by Axis Shield Diagnostics and also carried a consulting agreement with this firm. RC's hospital filed a patent application for his work on the genetics of transcobalamin I deficiency. None of the other authors had any personal or financial conflicts of interest.Office of Dietary Supplements, National Institutes of Health. NR 58 TC 60 Z9 60 U1 0 U2 14 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD JUL PY 2011 VL 94 IS 1 BP 313S EP 321S DI 10.3945/ajcn.111.013243 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 779QK UT WOS:000291794800046 PM 21593512 ER PT J AU Li, JB Volpe, DA Wang, Y Zhang, W Bode, C Owen, A Hidalgo, IJ AF Li, Jibin Volpe, Donna A. Wang, Ying Zhang, Wei Bode, Chris Owen, Albert Hidalgo, Ismael J. TI Use of Transporter Knockdown Caco-2 Cells to Investigate the In Vitro Efflux of Statin Drugs SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID CANCER RESISTANCE PROTEIN; P-GLYCOPROTEIN; LACTONE FORMS; ATORVASTATIN; PHARMACOKINETICS; ROSUVASTATIN; ACID; FLUVASTATIN; EXPRESSION; INHIBITORS AB The objective of the present study was to determine the efflux transporters responsible for acid and lactone statin drug efflux using transporter knockdown Caco-2 cells. The bidirectional transport was determined in Caco-2 cell monolayers in which the expression of P-glycoprotein (P-gp), breast cancer resistance protein (BCRP), or multidrug resistance associated protein 2 (MRP2) was knocked down by transduction with lentivirus containing human transporter-targeted small hairpin RNAs (shRNAs). Cells transduced with lentivirus containing nontargeted shRNA served as the vector control. Atorvastatin, lovastatin, and rosuvastatin displayed extremely low apical-to-basolateral (A-to-B) transport, which made the P(app,A-B) values too unreliable to calculate the efflux ratio. Thus, transport comparisons were performed using the B-to-A permeability (P(app,B-A)) values. Presented in the order of vector control, P-gp, BCRP, and MRP2 knockdown Caco-2 cells, the P(app,B-A) values (x10(-6), cm/s) were 28.1 +/- 1.3, 8.6 +/- 2.9, 20.3 +/- 1.8, and 21.5 +/- 1.6 for atorvastatin; 96.1 +/- 7.1, 25.3 +/- 3.5, 57.3 +/- 9.8, and 48.2 +/- 2.3 for fluvastatin; and 14.1 +/- 1.9, 4.6 +/- 1.7, 5.8 +/- 0.7, and 6.6 +/- 1.8 for rosuvastatin, respectively. Lovastatin and simvastatin showed no efflux in the vector control or knockdown cell monolayers in either lactone or acid forms. Results indicate that atorvastatin, fluvastatin, and rosuvastatin were transported by P-gp, BCRP, and MRP2. On the other hand, neither the lactone nor the resulting acid of lovastatin and simvastatin was transported by P-gp, BCRP, or MRP2. The current study demonstrated that the transporter knockdown Caco-2 cells are useful tools for studying drug-transporter interactions and should help eliminate some of the ambiguity associated with the identification of drug-transporter interactions based on chemical inhibitors alone. C1 [Li, Jibin; Wang, Ying; Zhang, Wei; Bode, Chris; Owen, Albert; Hidalgo, Ismael J.] Absorpt Syst LP, Exton, PA 19341 USA. [Volpe, Donna A.] US FDA, Div Drug Safety Res, Silver Spring, MD USA. RP Hidalgo, IJ (reprint author), Absorpt Syst LP, 436 Creamery Way,Suite 600, Exton, PA 19341 USA. EM ihidalgo@absorption.com FU Food and Drug Administration [1R43FD003482-01] FX This work was supported in part by a research grant from the Food and Drug Administration [Grant 1R43FD003482-01]. NR 33 TC 42 Z9 50 U1 0 U2 9 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JUL PY 2011 VL 39 IS 7 BP 1196 EP 1202 DI 10.1124/dmd.111.038075 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 778PZ UT WOS:000291718000012 PM 21447733 ER PT J AU Bones, J Mittermayr, S McLoughlin, N Hilliard, M Wynne, K Johnson, GR Grubb, JH Sly, WS Rudd, PM AF Bones, Jonathan Mittermayr, Stefan McLoughlin, Niaobh Hilliard, Mark Wynne, Kieran Johnson, Gibbes R. Grubb, Jeffrey H. Sly, William S. Rudd, Pauline M. TI Identification of N-Glycans Displaying Mannose-6-Phosphate and their Site of Attachment on Therapeutic Enzymes for Lysosomal Storage Disorder Treatment SO ANALYTICAL CHEMISTRY LA English DT Article ID MANNOSE 6-PHOSPHATE RECEPTOR; HUMAN BETA-GLUCURONIDASE; ACID ALPHA-GLUCOSIDASE; REPLACEMENT THERAPY; MASS-SPECTROMETRY; POMPE MICE; PROTEINS; OLIGOSACCHARIDES; PHOSPHORYLATION; ELECTROPHORESIS AB Characterization of mono- and bis-mannose-6-phosphate (M6P) bearing oligosaccharides present on acid hydrolase enzymes poses a considerable analytical challenge. In the current paper, we investigated the use of UPLC profiling on a 1.7 mu m HILIC phase and capillary electrophoresis with laser induced fluorescence detection (CE-LIF) combined with exoglycosidase digestion and weak anion exchange fractionation for the characterization of M6P bearing glycans on recombinant beta-glucuronidase expressed in Chinese Hamster Ovary (CHO) cells. Using this multidimensional approach a number of peaks were observed to resist digestion, suggesting the presence and blocking activity of the M6P tag. To investigate further, mixed oxide affinity purification on a combined TiO2/ZrO2 resin facilitated the selective enrichment of oligosaccharides bearing mono- or diphospho-esters that corresponded to those peaks previously identified to resist exoglycosidase digestion. Alkaline phosphatase digestion identified Man(6)GlcNAc(2) and Man(7)GlcNAc(2) glycans as the primary carriers of the M6P tag. Site-specific glycoproteomic analysis revealed that Man(7)GlcNAc(2)-M6P oligosaccharides were present at asparagine 272 and 420, while asparagine 631 displayed Man(6)GlcNAc(2)-M6P. The analytical strategy applied herein represents a novel yet simple approach for the qualitative and semiquantitative structural characterization of M6P containing oligosaccharides on therapeutic enzymes. C1 [Bones, Jonathan; Mittermayr, Stefan; McLoughlin, Niaobh; Hilliard, Mark; Rudd, Pauline M.] Univ Coll Dublin, UCD Conway Inst Biomol & Biomed Res, NIBRT Natl Inst Bioproc Res & Training, NIBRT Dublin Oxford Glycobiol Lab, Dublin 4, Ireland. [Wynne, Kieran] Univ Coll Dublin, UCD Conway Inst Biomol & Biomed Res, Conway Inst Proteome Res Ctr, Dublin 4, Ireland. [Johnson, Gibbes R.] US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Grubb, Jeffrey H.; Sly, William S.] St Louis Univ, Sch Med, Edward A Doisy Dept Biochem & Mol Biol, St Louis, MO 63104 USA. RP Rudd, PM (reprint author), Univ Coll Dublin, UCD Conway Inst Biomol & Biomed Res, NIBRT Natl Inst Bioproc Res & Training, NIBRT Dublin Oxford Glycobiol Lab, Dublin 4, Ireland. EM pauline.rudd@nibrt.ie RI Mittermayr, Stefan/B-3722-2017 OI Mittermayr, Stefan/0000-0001-8950-0156 FU U.S. Food and Drug Administration [1499] FX This research was supported by a Critical Path grant from the U.S. Food and Drug Administration (Proposal #1499) to GRJ. Waters Corporation is kindly acknowledged for the donation of the Acquit), UPLC instrument. NR 41 TC 15 Z9 15 U1 1 U2 24 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUL 1 PY 2011 VL 83 IS 13 BP 5344 EP 5352 DI 10.1021/ac2007784 PG 9 WC Chemistry, Analytical SC Chemistry GA 786CN UT WOS:000292280900046 PM 21599028 ER PT J AU Foley, SL Nayak, R Hanning, IB Johnson, TJ Han, J Ricke, SC AF Foley, Steven L. Nayak, Rajesh Hanning, Irene B. Johnson, Timothy J. Han, Jing Ricke, Steven C. TI Population Dynamics of Salmonella enterica Serotypes in Commercial Egg and Poultry Production SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Review ID ANTIMICROBIAL RESISTANCE GENES; COLONIZE REPRODUCTIVE-ORGANS; ESCHERICHIA-COLI STRAINS; PATHOGENICITY ISLAND 2; III SECRETION SYSTEM; UNITED-STATES; COMPETITIVE-EXCLUSION; SEROVAR HEIDELBERG; BROILER-CHICKENS; ENTERITIDIS INFECTIONS AB Fresh and processed poultry have been frequently implicated in cases of human salmonellosis. Furthermore, increased consumption of meat and poultry has increased the potential for exposure to Salmonella enterica. While advances have been made in reducing the prevalence and frequency of Salmonella contamination in processed poultry, there is mounting pressure on commercial growers to prevent and/or eliminate these human pathogens in preharvest production facilities. Several factors contribute to Salmonella colonization in commercial poultry, including the serovar and the infectious dose. In the early 1900s, Salmonella enterica serovars Pullorum and Gallinarum caused widespread diseases in poultry, but vaccination and other voluntary programs helped eradicate pullorum disease and fowl typhoid from commercial flocks. However, the niche created by the eradication of these serovars was likely filled by S. Enteritidis, which proliferated in the bird populations. While this pathogen remains a significant problem in commercial egg and poultry production, its prevalence among poultry has been declining since the 1990s. Coinciding with the decrease of S. Enteritidis, S. Heidelberg and S. Kentucky have emerged as the predominant serovars in commercial broilers. In this review, we have highlighted bacterial genetic and host-related factors that may contribute to such shifts in Salmonella populations in commercial poultry and intervention strategies that could limit their colonization. C1 [Foley, Steven L.; Nayak, Rajesh; Han, Jing] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ricke, Steven C.] Univ Arkansas, Ctr Food Safety, Fayetteville, AR 72704 USA. [Hanning, Irene B.] Univ Tennessee, Dept Food Sci & Technol, Knoxville, TN 37996 USA. [Johnson, Timothy J.] Univ Minnesota, Dept Vet & Biomed Sci, St Paul, MN 55108 USA. RP Foley, SL (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM steven.foley@fda.hhsgov FU Oak Ridge Institute for Science and Education FX Jing Han is supported through the Oak Ridge Institute for Science and Education fellowship program. NR 126 TC 86 Z9 90 U1 4 U2 45 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 JUL PY 2011 VL 77 IS 13 BP 4273 EP 4279 DI 10.1128/AEM.00598-11 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 782CR UT WOS:000291985700001 PM 21571882 ER PT J AU Clement, T Inselman, A Willis, W Goulding, E Eddy, M AF Clement, Tracy Inselman, Amy Willis, William Goulding, Eugenia Eddy, Mitch TI Male Meiotic Progression Is Arrested at Diplotene Leading to Male Infertility in Cyclin Dependant Kinase 1 (Cdk1) Mutant Mice SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 44th Annual Meeting of the Society-for-the-Study-of-Reproduction (SSR) CY 2011 CL Portland, OR SP Soc Study Reproduct C1 NIEHS, NIH, Res Triangle Pk, NC 27709 USA. US FDA, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1691 MONROE ST,SUITE # 3, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PD JUL PY 2011 VL 85 SI SI MA 139 PG 2 WC Reproductive Biology SC Reproductive Biology GA 032VC UT WOS:000310746200515 ER PT J AU Jain, R Chung, SM Jain, L Khurana, M Lau, SWJ Lee, JE Vaidyanathan, J Zadezensky, I Choe, S Sahajwalla, CG AF Jain, R. Chung, S. M. Jain, L. Khurana, M. Lau, S. W. J. Lee, J. E. Vaidyanathan, J. Zadezensky, I. Choe, S. Sahajwalla, C. G. TI Implications of Obesity for Drug Therapy: Limitations and Challenges SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Review ID ORAL-CONTRACEPTIVE USE; LEAN BODY-WEIGHT; PHARMACOKINETIC CONSIDERATIONS; CLINICAL PHARMACOKINETICS; VENOUS THROMBOSIS; CYP2E1 ACTIVITY; DISPOSITION; HUMANS; WOMEN; CLEARANCE AB Obesity has become a worldwide challenge with significant health and socioeconomic implications. One of the major implications is its impact on drug therapy. In order to gain a better understanding of this impact, we surveyed the regulatory guidances, the newly approved molecular entity drug products, and drug product labels in the Physician's Desk Reference. This review summarizes the findings of the survey along with the existing knowledge on pharmacokinetic and pharmacodynamic changes associated with obesity. C1 [Jain, R.; Chung, S. M.; Jain, L.; Khurana, M.; Lau, S. W. J.; Lee, J. E.; Vaidyanathan, J.; Zadezensky, I.; Choe, S.; Sahajwalla, C. G.] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. [Jain, R.; Chung, S. M.; Jain, L.; Khurana, M.; Lau, S. W. J.; Lee, J. E.; Vaidyanathan, J.; Zadezensky, I.; Choe, S.; Sahajwalla, C. G.] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Silver Spring, MD USA. RP Sahajwalla, CG (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. EM Chandrahas.Sahajwalla@fda.hhs.gov NR 84 TC 51 Z9 56 U1 0 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 2011 VL 90 IS 1 BP 77 EP 89 DI 10.1038/clpt.2011.104 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 780KD UT WOS:000291853800017 PM 21633345 ER PT J AU Chen, YF Yang, Y Hung, HMJ Wang, SJ AF Chen, Yeh-Fong Yang, Yang Hung, H. M. James Wang, Sue-Jane TI Evaluation of performance of some enrichment designs dealing with high placebo response in psychiatric clinical trials SO CONTEMPORARY CLINICAL TRIALS LA English DT Article DE Placebo response; Placebo lead-in; Sequential parallel design; Missing data ID EFFICACY AB Dealing with high placebo response remains a big challenge to conventional clinical trials for psychiatric disorders. A widely-used design strategy is to implement a placebo lead-in phase prior to randomization. The sequentially parallel design (SPD) proposed by Fava et al., which contains two consecutive double-blind treatment stages, has recently been promoted to reduce both the high placebo response and the required sample size in clinical trials for psychiatric disorders. Our work aims to study these two design strategies and evaluate the relevant statistical approaches for continuous measures under SPD in the presence of missing data. Based on the FDA archived database, we found that a longer placebo lead-in period seemed to help in identifying more placebo responders and thus increase the chance to detect a drug-placebo difference on continuous efficacy endpoint. Using a simple weighted ordinary least square test statistic Z(OLS), we analytically showed that, under the SPD with re-randomization of placebo non-responders at the second stage (SPD-ReR), Z(OLS) can be used as a viable alternative to the weighted test statistic based on seemingly unrelated regression estimate Z(SUR) proposed by Tamura and Huang to assess treatment efficacy. Results from simulation study comparing three imputation methods (last-observation-carried-forward approach, multiple imputation, and mixed-effects model for repeated measures (MMRM)) demonstrate that, when data are missing-at-random under SPD-ReR and the dropout rate is moderate, the weighted test statistic based on MMRM estimates appears to be the most robust test statistic for SPD-ReR in terms of type I error control, power performance, and estimation accuracy. Published by Elsevier Inc. C1 [Chen, Yeh-Fong; Yang, Yang; Hung, H. M. James] US FDA, Div Biometr 1, Off Biostat, Off Translat Sci,CDER, Silver Spring, MD 20993 USA. RP Chen, YF (reprint author), US FDA, Div Biometr 1, Off Biostat, Off Translat Sci,CDER, HFD-710,10903 New Hampshire Ave,Bldg 21,Room 4610, Silver Spring, MD 20993 USA. EM yehfong.chen@fda.hhs.gov NR 10 TC 23 Z9 23 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1551-7144 J9 CONTEMP CLIN TRIALS JI Contemp. Clin. Trials PD JUL PY 2011 VL 32 IS 4 BP 592 EP 604 DI 10.1016/j.cct.2011.04.006 PG 13 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 785JY UT WOS:000292226500020 PM 21540126 ER PT J AU Zhang, J AF Zhang, Joanne TI Optimal Sample Size Allocation in a Thorough QTc Study SO DRUG INFORMATION JOURNAL LA English DT Article DE TQT study; Sample size allocation; Equal sample size allocation; Parallel design ID CLINICAL-TRIALS; QT/QTC; DESIGN; ISSUES; POWER AB It is important to calculate the proper sample size for a thorough QTc study to ensure adequate study power without enrolling unnecessary subjects. In current practice, at least two tasks need to be performed to rule out clinically relevant QT liability of the study drug: (a) demonstrate that the largest 90% two-sided upper confidence bound for the baseline-adjusted mean differences between the study drug and the placebo is less than 10 ms; and (b) establish assay sensitivity of the study. Traditionally, the sample size is determined by the primary task (a), and then subjects are equally assigned into each treatment arm. This practice might not be the most appropriate method. In this article, an optimal sample size allocation scheme is introduced and discussed. C1 US FDA, Ctr Drug Evaluat & Res, Div Biometr 6, Off Biostat,Off Translat Sci, Silver Spring, MD USA. RP Zhang, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Biometr 6, Off Biostat,Off Translat Sci, Silver Spring, MD USA. EM Joanne.Zhang@fda.hhs.gov NR 12 TC 2 Z9 2 U1 0 U2 2 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JUL PY 2011 VL 45 IS 4 BP 455 EP 468 PG 14 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 785OD UT WOS:000292237400007 ER PT J AU Zhen, B Ng, TH Hsu, H AF Zhen, Boguang Ng, Tie-Hua Hsu, Henry TI Multiple-stage Sampling Procedure for Lot Release With Consideration of Both Manufacturer's and Consumer's Risks SO DRUG INFORMATION JOURNAL LA English DT Article DE Multiple-stage sampling; Lot release; Manufacturer's risk; Consumer's risk ID SWITCHING RULES; MIL-STD-105D; PERFORMANCE AB Sampling inspection is implemented to ensure the quality of a biological product before its release to the market. However, the existing procedures in sampling inspection for lot release focus on the manufacturer's risk. If both risks are accounted for, a much larger sample size would be required under certain circumstances. Sometimes the sample size might be too large to be implemented in practice. This article first illustrates the sampling process using the American National Standard, and then proposes a multiple-stage sampling procedure for lot release with control of both manufacturer's and consumer's risks at prespecified levels. Examples are presented to illustrate the use of the proposed procedure. Issues for lot release and the use of different sampling procedures are discussed. C1 [Zhen, Boguang; Ng, Tie-Hua; Hsu, Henry] OBE CBER FDA, Div Biostat, Rockville, MD 20852 USA. RP Zhen, B (reprint author), OBE CBER FDA, Div Biostat, 1401 Rockville Pike,Rm 415S, Rockville, MD 20852 USA. EM boguang.zhen@fda.hhs.gov NR 9 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 JUL PY 2011 VL 45 IS 4 BP 469 EP 480 PG 12 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 785OD UT WOS:000292237400008 ER PT J AU Genualdi, SA Hageman, KJ Ackerman, LK Usenko, S Simonich, SLM AF Genualdi, Susan A. Hageman, Kimberly J. Ackerman, Luke K. Usenko, Sascha Simonich, Staci L. Massey TI SOURCES AND FATE OF CHIRAL ORGANOCHLORINE PESTICIDES IN WESTERN US NATIONAL PARK ECOSYSTEMS SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE Chiral; Organochlorine pesticides; Enantiomer fraction; Chlordane; Hexachlorocyclohexane ID ENANTIOMER FRACTIONS; ORGANIC-CHEMICALS; RAINBOW-TROUT; TRANS-PACIFIC; SNOW PACK; CONTAMINANTS; DEPOSITION; CHLORDANE; BIOACCUMULATION; SIGNATURES AB The enantiomer fractions (EFs) of alpha-hexachlorocyclohexane (alpha-HCH), cis-, trans-, and oxychlordane, and heptachlor epoxide were measured in 73 snow, fish, and sediment samples collected from remote lake catchments, over a wide range of latitudes, in seven western U.S. National Parks/Preserves to investigate their sources, fate, accumulation and biotransformation in these ecosystems. The present study is novel because these lakes had no inflow or outflow, and the measurement of chiral organochlorine pesticides (OCPs) EFs in snowpack from these lake catchments provided a better understanding of the OCP sources in the western United States, whereas their measurement in fish and sediment provided a better understanding of their biotic transformations within the lake catchments. Nonracemic alpha-HCH was measured in seasonal snowpack collected from continental U.S. National Parks, and racemic alpha-HCH was measured in seasonal snowpack collected from the Alaskan parks, suggesting the influence of regional sources to the continental U.S. parks and long-range sources to the Alaskan parks. The alpha-HCH EFs measured in trout collected from the lake catchments were similar to the alpha-HCH EFs measured in seasonal snowpack collected from the same lake catchments, suggesting that these fish did not biotransform alpha-HCH enantioselectively. Racemic cis-chlordane was measured in seasonal snowpack and sediment collected from Sequoia, indicating that it had not undergone significant enantioselective biotransformation in urban soils since its use as a termiticide in the surrounding urban areas. However, nonracemic cis-chlordane was measured in seasonal snowpack and sediments from the Rocky Mountains, suggesting that cis-chlordane does undergo enantioselective biotransformation in agricultural soils. The trout from these lakes showed preferential biotransformation of the (+)-enantiomer of cis-chlordane and the (-)-enantiomer of trans-chlordane. Environ. Toxicol. Chem. 2011;30:1533-1538. (C) 2011 SETAC C1 [Genualdi, Susan A.; Simonich, Staci L. Massey] Oregon State Univ, Dept Chem, Corvallis, OR 97331 USA. [Hageman, Kimberly J.] Univ Otago, Dept Chem, Dunedin, New Zealand. [Ackerman, Luke K.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Usenko, Sascha] Baylor Univ, Dept Environm Sci, Waco, TX 76798 USA. [Simonich, Staci L. Massey] Oregon State Univ, Dept Environm & Mol Toxicol, Corvallis, OR 97331 USA. RP Simonich, SLM (reprint author), Oregon State Univ, Dept Chem, Gilbert Hall 153, Corvallis, OR 97331 USA. EM staci.simonich@orst.edu RI Ackerman, Luke/E-4597-2011; Guenat, Heather/H-6528-2014; Usenko, Sascha/N-8730-2015; OI Ackerman, Luke/0000-0001-6626-3039; Hageman, Kimberly/0000-0001-9187-5256; Usenko, Sascha/0000-0003-3303-2909 FU United States National Institute of Environmental Health Sciences (NIEHS), National Institute of Health (NIH) [P30ES00210]; U.S. Environmental Protection Agency; Department of the Interior FX This work is part of the Western Airborne Contaminants Assessment Project. This publication was made possible in part by grant P30ES00210 from the United States National Institute of Environmental Health Sciences (NIEHS), part of the National Institute of Health (NIH). Its contents are solely the responsibility of the authors and do not necessarily represent the official view of the NIH, NIEHS. This work was partially funded by the U.S. Environmental Protection Agency and the Department of the Interior. It has been subjected to review by these government entities and approved for publication. Approval does not signify that the contents reflect the views of the U.S. government, nor does mention of trade names or commercial products constitute endorsement or recommendation. NR 38 TC 5 Z9 5 U1 2 U2 38 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD JUL PY 2011 VL 30 IS 7 BP 1533 EP 1538 DI 10.1002/etc.538 PG 6 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 782JL UT WOS:000292004400005 PM 21462235 ER PT J AU Bachtel, AD Gray, RA Stohlman, JM Bourgeois, EB Pollard, AE Rogers, JM AF Bachtel, Andrew D. Gray, Richard A. Stohlman, Jayna M. Bourgeois, Elliot B. Pollard, Andrew E. Rogers, Jack M. TI A Novel Approach to Dual Excitation Ratiometric Optical Mapping of Cardiac Action Potentials With Di-4-ANEPPS Using Pulsed LED Excitation SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE Light emitting diode; membrane potential; motion artifact; ratiometry ID FLUORESCENT DYE EMISSION; VOLTAGE-SENSITIVE DYES; LIGHT-EMITTING-DIODES; HIGH-SPEED; MEMBRANE; HEARTS; CALCIUM; SPECTRA; PROBES; CELLS AB We developed a new method for ratiometric optical mapping of transmembrane potential (V(m)) in cardiac preparations stainedwith di-4-ANEPPS. V(m)-dependent shifts of excitation and emission spectra establish two excitation bands (<481 and >481 nm) that produce fluorescence changes of opposite polarity within a single emission band (575-620 nm). The ratio of these positive and negative fluorescence signals (excitation ratiometry) increases V(m) sensitivity and removes artifacts common to both signals. We pulsed blue (450 +/- 10 nm) and cyan (505 +/- 15 nm) light emitting diodes (LEDs) at 375 Hz in alternating phase synchronized to a camera (750 frames-per-second). Fluorescence was bandpass filtered (585 +/- 20 nm). This produced signals with upright (blue) and inverted (cyan) action potentials (APs) interleaved in sequential frames. In four whole swine hearts with motion chemically arrested, fractional fluorescence for blue, cyan, and ratio signals was 1.2 +/- 0.3%, 1.2 +/- 0.3%, and 2.4 +/- 0.6%, respectively. Signal-to-noise ratios were 4.3 +/- 1.4, 4.0 +/- 1.2, and 5.8 +/- 1.9, respectively. After washing out the electromechanical uncoupling agent, we characterized motion artifact by cross-correlating blue, cyan, and ratio signals with a signal with normal AP morphology. Ratiometry improved cross-correlation coefficients from 0.50 +/- 0.48 to 0.81 +/- 0.25, but did not cancel all motion artifacts. These findings demonstrate the feasibility of pulsed LED excitation ratiometry in myocardium. C1 [Pollard, Andrew E.; Rogers, Jack M.] Univ Alabama, Birmingham, AL 35294 USA. [Bachtel, Andrew D.] Covidien, Boulder, CO 80301 USA. [Bourgeois, Elliot B.] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. [Gray, Richard A.; Stohlman, Jayna M.] US FDA, Silver Spring, MD 20993 USA. RP Rogers, JM (reprint author), Univ Alabama, Birmingham, AL 35294 USA. EM andrew.bachtel@covidien.com; richard.gray@fda.hhs.gov; jayna.stohlman@fda.hhs.gov; apollard@uab.edu; jrogers@uab.edu RI Gray, Richard/F-3916-2015; OI Gray, Richard/0000-0003-2798-6378; Rogers, Jack/0000-0002-3236-4154 FU NSF [CBET0756117]; NIH [HL64184] FX This work was supported in part by NSF grant CBET0756117 and NIH grant HL64184. NR 26 TC 17 Z9 17 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD JUL PY 2011 VL 58 IS 7 BP 2120 EP 2126 DI 10.1109/TBME.2011.2148719 PG 7 WC Engineering, Biomedical SC Engineering GA 780WL UT WOS:000291890000027 PM 21536528 ER PT J AU Yasinskaya, Y Plikaytis, B Sizemore, C Sacks, L AF Yasinskaya, Y. Plikaytis, B. Sizemore, C. Sacks, L. TI Advancing the development of diagnostic tests and biomarkers for tuberculosis SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE TB; tuberculosis; biomarkers AB High costs and limited returns on investment have hampered progress in developing new diagnostic tests and treatments for tuberculosis (TB). We need new biomarkers to develop assays that can rapidly, efficiently and reliably detect Mycobacterium tuberculosis infection and disease, identify drug resistance and expedite drug and vaccine development. This can only be accomplished through cross-disciplinary collaborations to facilitate access to human specimens. The Food and Drug Administration, Centers for Disease Control and Prevention, National Institutes of Health, the industry and academia experts came together in a June 2010 workshop to examine the field of TB diagnostic test development and biomarker discovery, identify areas of most urgent need and formulate strategies to address those needs. C1 [Yasinskaya, Y.; Sacks, L.] US FDA, Off Crit Path Programs, Silver Spring, MD 20903 USA. [Plikaytis, B.] Ctr Dis Control & Prevent, Mycobacteriol Lab Branch, Atlanta, GA USA. [Sizemore, C.] NIAID, TB & Other Mycobacterial Dis Sect, NIH, Bethesda, MD 20892 USA. RP Yasinskaya, Y (reprint author), US FDA, Off Crit Path Programs, Rm 4110,Bldg 32,10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM Yuliya.Yasinskaya@fda.hhs.gov NR 4 TC 5 Z9 5 U1 0 U2 1 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD JUL PY 2011 VL 15 IS 7 BP 985 EP 987 DI 10.5588/ijtld.10.0712 PG 3 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 785MV UT WOS:000292234000023 PM 21682977 ER PT J AU Fricke, WF Mammel, MK McDermott, PF Tartera, C White, DG LeClerc, JE Ravel, J Cebula, TA AF Fricke, W. Florian Mammel, Mark K. McDermott, Patrick F. Tartera, Carmen White, David G. LeClerc, J. Eugene Ravel, Jacques Cebula, Thomas A. TI Comparative Genomics of 28 Salmonella enterica Isolates: Evidence for CRISPR-Mediated Adaptive Sublineage Evolution SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI; UNITED-STATES; ANTIMICROBIAL RESISTANCE; SEROTYPE CHOLERAESUIS; HYDROGEN-SULFIDE; FLUOROQUINOLONE RESISTANCE; VIRULENCE PLASMIDS; HOST ADAPTATION; PARATYPHI-C; TYPHIMURIUM AB Despite extensive surveillance, food-borne Salmonella enterica infections continue to be a significant burden on public health systems worldwide. As the S. enterica species comprises sublineages that differ greatly in antigenic representation, virulence, and antimicrobial resistance phenotypes, a better understanding of the species' evolution is critical for the prediction and prevention of future outbreaks. The roles that virulence and resistance phenotype acquisition, exchange, and loss play in the evolution of S. enterica sublineages, which to a certain extent are represented by serotypes, remains mostly uncharacterized. Here, we compare 17 newly sequenced and phenotypically characterized nontyphoidal S. enterica strains to 11 previously sequenced S. enterica genomes to carry out the most comprehensive comparative analysis of this species so far. These phenotypic and genotypic data comparisons in the phylogenetic species context suggest that the evolution of known S. enterica sublineages is mediated mostly by two mechanisms, (i) the loss of coding sequences with known metabolic functions, which leads to functional reduction, and (ii) the acquisition of horizontally transferred phage and plasmid DNA, which provides virulence and resistance functions and leads to increasing specialization. Matches between S. enterica clustered regularly interspaced short palindromic repeats (CRISPR), part of a defense mechanism against invading plasmid and phage DNA, and plasmid and prophage regions suggest that CRISPR-mediated immunity could control short-term phenotype changes and mediate long-term sublineage evolution. CRISPR analysis could therefore be critical in assessing the evolutionary potential of S. enterica sublineages and aid in the prediction and prevention of future S. enterica outbreaks. C1 [Fricke, W. Florian; Ravel, Jacques] Univ Maryland, Sch Med, IGS, Baltimore, MD 21201 USA. [Mammel, Mark K.; Tartera, Carmen; LeClerc, J. Eugene] US FDA, CFSAN, Laurel, MD USA. [McDermott, Patrick F.; White, David G.] US FDA, CVM, Laurel, MD USA. [Cebula, Thomas A.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Fricke, WF (reprint author), Univ Maryland, Sch Med, IGS, 801 W Baltimore St, Baltimore, MD 21201 USA. EM wffricke@som.umaryland.edu OI Ravel, Jacques/0000-0002-0851-2233 FU National Institute of Allergy and Infectious Diseases (NIAID), National Institutes of Health, Department of Health and Human Services [N01-AI-30071] FX Sequencing of the 17 S. enterica genomes 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 81 TC 63 Z9 3585 U1 22 U2 114 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2011 VL 193 IS 14 BP 3556 EP 3568 DI 10.1128/JB.00297-11 PG 13 WC Microbiology SC Microbiology GA 784DQ UT WOS:000292134900015 PM 21602358 ER PT J AU Huang, Y Lei, YF Zhang, H Zhang, MJ Dayton, A AF Huang, Yong Lei, YingFeng Zhang, Hai Zhang, Mingjie Dayton, Andrew TI Interleukin-12 treatment down-regulates STAT4 and induces apoptosis with increasing ROS production in human natural killer cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE negative-feedback mechanism; transcription factors ID RECOMBINANT HUMAN INTERLEUKIN-12; CYTOKINE-INDUCED APOPTOSIS; NK-CELLS; IFN-GAMMA; T-CELLS; SIGNALING MOLECULES; NEGATIVE REGULATOR; IN-VITRO; PHASE-I; PROTEIN AB NK cells are prominent mediators of the immunomodulating and antiangiogenic activity of IL-12. However, the effect of prolonged IL-12 treatment on NK cells is unclear. In this study, we observed that IL-12 initially activates NK cells, but prolonged IL-12 treatment specifically down-regulates IL-12 signaling and induces NK cell apoptosis associated with a significant reduction in cytolytic activity and IFN-gamma production in response to further IL-12 stimulation. Further results demonstrate that prolonged IL-12 stimulation of NK cells specifically decreases the level of activated STAT4 protein, a critical IL-12 signaling component, through decreasing STAT4 mRNA and protein levels rather than inducing STAT4 protein degradation. IL-12 treatment induces NK cell activation as well as levels of ROS, but prolonged IL-12 treatment causes ROS accumulation, which in turn, results in the loss of Delta psi(m), the release of cytochrome c, and the activation of caspase-3, resulting in NK cell apoptosis. These findings provide new insights into IL-12 regulation in human NK cells, where IL-12 initially promotes NK cell activation but subsequently limits this response through a negative-feedback mechanism. J. Leukoc. Biol. 90: 87-97; 2011. C1 [Huang, Yong; Lei, YingFeng; Zhang, Hai; Zhang, Mingjie; Dayton, Andrew] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20892 USA. [Zhang, Mingjie; Dayton, Andrew] NW Polytech Univ, Dept Life Sci, Xian, Shaanxi, Peoples R China. RP Dayton, A (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20892 USA. EM ming.zhang@fda.hhs.gov; andrew.dayton@fda.hhs.gov RI Huang, Yong/G-9365-2011 NR 43 TC 16 Z9 17 U1 0 U2 2 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 JUL PY 2011 VL 90 IS 1 BP 87 EP 97 DI 10.1189/jlb.1210674 PG 11 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 785QQ UT WOS:000292244200011 PM 21543583 ER PT J AU Ji, K Wang, B Shao, YT Zhang, L Liu, YN Shao, C Li, XJ Li, X Hu, JD Zhao, XJ Xu, DQ Li, Y Cai, L AF Ji, Kun Wang, Bo Shao, Yue-ting Zhang, Ling Liu, Ya-nan Shao, Chen Li, Xiao-jie Li, Xin Hu, Jia-di Zhao, Xue-jian Xu, De-qi Li, Yang Cai, Lu TI Synergistic Suppression of Prostatic Cancer Cells by Coexpression of Both Murine Double Minute 2 Small Interfering RNA and Wild-Type p53 Gene In Vitro and In Vivo SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID ANDROGEN DEPRIVATION; SALMONELLA-TYPHIMURIUM; TUMOR SUPPRESSION; RETINOBLASTOMA PROTEIN; P53-MDM2 INTERACTION; GASTRIC-CANCER; MDM2; THERAPY; GROWTH; ONCOPROTEIN AB Our objective was to evaluate cell growth and death effects by inhibiting Murine Double Minute 2 (MDM2) expression in human prostate cancer cells overexpressing the wild-type (WT) p53 gene. Prostate PC-3 tumor cells were transfected with a plasmid containing either mdm2 small interfering (Si-mdm2) or the WT p53 gene (Pp53) alone, or both (Pmp53), using Lipofectamine in vitro and attenuated Salmonella enterica serovar Typhi vaccine strain Ty21a (Salmonella Typhi Ty21a) in vivo. Cell growth, apoptosis, and the expression of related genes and proteins were examined in vitro and in vivo by flow cytometry and Western blot assays. We demonstrated that human prostate tumors had increased expression of MDM2 and mutant p53 proteins. Transfection of the PC-3 cells with the Pmp53 plasmid in vitro offered significant inhibition of cell growth and an increase in apoptotic cell death compared with that of the Si-mdm2 or Pp53 group. These effects were associated with up-regulation of p21 and down-regulation of hypoxia-inducible factor 1 alpha expression in Pmp53-transfected cells. To validate the in vitro findings, the nude mice implanted with PC-3 cells were treated with attenuated Salmonella Typhi Ty21a carrying the plasmids, which showed that the Pmp53 plasmid significantly inhibited the tumor growth rate in vivo compared with that of the Si-mdm2 or Pp53 plasmid alone. Tumor tissues from mice treated with the Pmp53 plasmid showed increased expression of p21 and decreased expression of hypoxia-inducible factor 1 alpha proteins, with an increased apoptotic effect. These results suggest that knockdown of mdm2 expression by its specific small interfering RNA with overexpression of the WT p53 gene offers synergistic inhibition of prostate cancer cell growth in vitro and in vivo. C1 [Ji, Kun; Wang, Bo; Shao, Yue-ting; Zhang, Ling; Liu, Ya-nan; Shao, Chen; Li, Xiao-jie; Li, Xin; Zhao, Xue-jian; Li, Yang] Jilin Univ, Norman Bethune Coll Med, Prostate Dis Prevent Treatment Res Ctr, Dept Pathophysiol, Changchun 130021, Peoples R China. [Ji, Kun] Shenyang Med Coll, Dept Pathophysiol, Shenyang, Peoples R China. [Wang, Bo] Inner Mongolia Forestry Gen Hosp, Dept Pathol, Yakeshi, Inner Mongolia, Peoples R China. [Wang, Bo; Cai, Lu] Univ Louisville, Dept Pediat & Radiat Oncol, Louisville, KY 40292 USA. [Hu, Jia-di] Univ Maryland, Sch Dent, Dept Oncol & Diagnost Sci, Baltimore, MD 21201 USA. [Xu, De-qi] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Li, Y (reprint author), Jilin Univ, Norman Bethune Coll Med, Prostate Dis Prevent Treatment Res Ctr, Dept Pathophysiol, Changchun 130021, Peoples R China. EM lyang@jlu.edu.cn FU Research Fund for the Doctoral Program of Higher Education of China [20070183012]; Scientific and Technological Development Plan Project in Jilin Province [200705360] FX This work was supported by the Research Fund for the Doctoral Program of Higher Education of China [Grant 20070183012]; and the Scientific and Technological Development Plan Project in Jilin Province [Grant 200705360]. NR 40 TC 10 Z9 10 U1 1 U2 4 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD JUL PY 2011 VL 338 IS 1 BP 173 EP 183 DI 10.1124/jpet.111.180364 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 781IW UT WOS:000291925300019 PM 21444629 ER PT J AU Ovanesov, MV Shibeko, AM Woodle, SA Anderson, CM Hogwood, J Barson, H Gray, E Scott, D AF Ovanesov, M., V Shibeko, A. M. Woodle, S. A. Anderson, C. M. Hogwood, J. Barson, H. Gray, E. Scott, D. TI Association of factor XIa with intravenous immune globulin products implicated in thrombotic adverse events: biochemical root cause investigation SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Ovanesov, M., V] US FDA, CBER OBRR DH, Rockville, MD 20857 USA. [Shibeko, A. M.; Woodle, S. A.; Anderson, C. M.; Scott, D.] US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20857 USA. [Hogwood, J.; Barson, H.; Gray, E.] Natl Inst Biol Stand & Controls, London, England. NR 0 TC 5 Z9 5 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA O-TU-039 BP 272 EP 272 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992800071 ER PT J AU Dashkevich, NM Ovanesov, MV Panteleev, MA Ataullakhanov, FI AF Dashkevich, N. M. Ovanesov, M., V Panteleev, M. A. Ataullakhanov, F., I TI Measuring thrombin generation in a heterogeneous system as a function of space and time: a novel approach for basic and applied coagulation research SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Dashkevich, N. M.; Panteleev, M. A.] Russian Acad Sci, Ctr Theoret Problems Physicochem Pharmacol, Moscow 117901, Russia. [Ovanesov, M., V] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Ataullakhanov, F., I] Natl Res Ctr Hematol, Moscow, Russia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA O-TU-061 BP 279 EP 279 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992800092 ER PT J AU Shibeko, AM Woodle, SA Lee, TK Ovanesov, MV AF Shibeko, A. M. Woodle, S. A. Lee, T. K. Ovanesov, M., V TI Balance between factor VII competition for tissue factor and factor VII activation determines initiation and propagation of blood coagulation SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Shibeko, A. M.; Woodle, S. A.; Lee, T. K.; Ovanesov, M., V] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA P-WE-119 BP 556 EP 557 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992802029 ER PT J AU Ovanesov, MV William, LW Ataullakhanov, FI Gailani, D Shibeko, AM AF Ovanesov, M., V William, L. W. Ataullakhanov, F., I Gailani, D. Shibeko, A. M. TI Regulation of clot growth by factor XI through the generation of thrombin inside the clot SO JOURNAL OF THROMBOSIS AND HAEMOSTASIS LA English DT Meeting Abstract C1 [Ovanesov, M., V] US FDA, CBER, OBRR, DH, Rockville, MD 20857 USA. [William, L. W.; Shibeko, A. M.] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Ataullakhanov, F., I] Ctr Theoret Problems Physicochem Pharmacol, Moscow, Russia. [Ataullakhanov, F., I] Natl Res Ctr Hematol, Moscow, Russia. [Gailani, D.] Vanderbilt Univ, Div Hematol Oncol, Nashville, TN 37235 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1538-7933 EI 1538-7836 J9 J THROMB HAEMOST JI J. Thromb. Haemost. PD JUL PY 2011 VL 9 SU 2 SI SI MA O-TH-108 BP 757 EP 757 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA V33AX UT WOS:000208992803140 ER PT J AU Kanungo, J Paule, MG AF Kanungo, Jyotshnabala Paule, Merle G. TI Disruption of blastomeric F-actin: a potential early biomarker of developmental toxicity in zebrafish SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE Zebrafish; Biomarker; F-actin; Toxicity; Gastrulation ID MOUSE 8-CELL BLASTOMERES; VERTEBRATE GASTRULATION; EMBRYONIC-DEVELOPMENT; ENVELOPING LAYER; CELL MOVEMENTS; CYTOSKELETON; 2,3,7,8-TETRACHLORODIBENZO-P-DIOXIN; CANCER; GELSOLIN; CADMIUM AB The expression of at least some biomarkers of toxicity is generally thought to precede the appearance of frank pathology. In the context of developmental toxicity, certain early indicators may be predictive of later drastic outcome. The search for predictive biomarkers of toxicity in the cells (blastomeres) of an early embryo can benefit from the fact that for normal development to proceed, the maintenance of blastomere cellular integrity during the process of transition from an embryo to a fully functional organism is paramount. Actin microfilaments are integral parts of blastomeres in the developing zebrafish embryo and contribute toward the proper progression of early development (cleavage and epiboly). In early embryos, the filamentous actin (F-actin) is present and helps to define the boundary of each blastomere as they remain adhered to each other. In our studies, we observed that when blastomeric F-actin is depolymerized by agents like gelsolin, the blastomeres lose cellular integrity, which results in abnormal larvae later in development. There are a variety of toxicants that depolymerize F-actin in early mammalian embryos, the later consequences of which are, at present, not known. We propose that very early zebrafish embryos (similar to 5-h old) exposed to such toxicants will also respond in a like manner. In this review, we discuss the potential use of F-actin disruption as a predictive biomarker of developmental toxicity in zebrafish. C1 [Kanungo, Jyotshnabala; Paule, Merle G.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kanungo, J (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jyotshnabala.kanungo@fda.hhs.gov NR 73 TC 3 Z9 3 U1 0 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 JUL PY 2011 VL 353 IS 1-2 BP 283 EP 290 DI 10.1007/s11010-011-0797-2 PG 8 WC Cell Biology SC Cell Biology GA 785GJ UT WOS:000292215100029 PM 21461911 ER PT J AU Luo, H Chen, J Shi, LM Mikailov, M Zhu, H Wang, KJ He, L Yang, L AF Luo, Heng Chen, Jian Shi, Leming Mikailov, Mike Zhu, Huang Wang, Kejian He, Lin Yang, Lun TI DRAR-CPI: a server for identifying drug repositioning potential and adverse drug reactions via the chemical-protein interactome SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION; BREAST-CANCER; DISEASE; MINOCYCLINE; ROSIGLITAZONE; PREDICTION; SIGNATURES; DISCOVERY; PROFILES; THERAPY AB Identifying new indications for existing drugs (drug repositioning) is an efficient way of maximizing their potential. Adverse drug reaction (ADR) is one of the leading causes of death among hospitalized patients. As both new indications and ADRs are caused by unexpected chemical-protein interactions on off-targets, it is reasonable to predict these interactions by mining the chemical-protein interactome (CPI). Making such predictions has recently been facilitated by a web server named DRAR-CPI. This server has a representative collection of drug molecules and targetable human proteins built up from our work in drug repositioning and ADR. When a user submits a molecule, the server will give the positive or negative association scores between the user's molecule and our library drugs based on their interaction profiles towards the targets. Users can thus predict the indications or ADRs of their molecule based on the association scores towards our library drugs. We have matched our predictions of drug-drug associations with those predicted via gene-expression profiles, achieving a matching rate as high as 74%. We have also successfully predicted the connections between anti-psychotics and anti-infectives, indicating the underlying relevance of anti-psychotics in the potential treatment of infections, vice versa. This server is freely available at http://cpi.bio-x.cn/drar/. C1 [Luo, Heng; Chen, Jian; Zhu, Huang; Wang, Kejian; He, Lin; Yang, Lun] Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai 200030, Peoples R China. [Shi, Leming; Yang, Lun] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mikailov, Mike] US FDA, Ctr Devices & Radiol Hlth, Jefferson, AR 72079 USA. [He, Lin; Yang, Lun] Fudan Univ, Inst Biomed Sci, Shanghai 200433, Peoples R China. [He, Lin] Chinese Acad Sci, Inst Nutr Sci, Shanghai Inst Biol Sci, Shanghai, Peoples R China. RP He, L (reprint author), Shanghai Jiao Tong Univ, Bio X Inst, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai 200030, Peoples R China. EM helinhelin3@gmail.com; lun.yang@gmail.com RI Yang, Lun/B-4859-2012; Luo, Heng/D-3616-2016 OI Luo, Heng/0000-0001-5192-8878 FU National Natural Science Foundation of China [30900841]; 973 Program [2010CB529600] FX Funding for open access charge: The National Natural Science Foundation of China (30900841) and the 973 Program (2010CB529600). NR 51 TC 68 Z9 74 U1 2 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD JUL PY 2011 VL 39 SU 2 BP W492 EP W498 DI 10.1093/nar/gkr299 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 786RJ UT WOS:000292325300080 PM 21558322 ER PT J AU Gonzalez-Escalona, N Strain, EA De Jesus, AJ Jones, JL DePaola, A AF Gonzalez-Escalona, N. Strain, E. A. De Jesus, A. J. Jones, J. L. DePaola, A. TI Genome Sequence of the Clinical O4:K12 Serotype Vibrio parahaemolyticus Strain 10329 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID UNITED-STATES; O3-K6; EMERGENCE; DIARRHEA; SPREAD AB Vibrio parahaemolyticus is the leading cause of food-borne illnesses worldwide. Here, we report a draft genome of V. parahaemolyticus strain 10329 of the O4:K12 serotype. It belongs to the main U.S. West Coast clonal complex of V. parahaemolyticus (sequence type 36 [ST36]) causing oyster-associated human illness. It contains the virulence determinants tdh and trh but appears to infect at much lower doses than V. parahaemolyticus strains with these same determinants from other areas, such as the U.S. Gulf and Atlantic coasts. C1 [Gonzalez-Escalona, N.; De Jesus, A. J.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Strain, E. A.] US FDA, Div Math, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Jones, J. L.; DePaola, A.] US FDA, Gulf Coast Seafood Lab, Div Seafood Sci & Technol, Dauphin Isl, AL USA. RP Gonzalez-Escalona, N (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 712, College Pk, MD 20740 USA. EM narjol.gonzalez-escalona@fda.hhs.gov OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU FDA FX This work was supported by FDA Foods Program Intramural Funds. NR 12 TC 13 Z9 15 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2011 VL 193 IS 13 BP 3405 EP 3406 DI 10.1128/JB.05044-11 PG 2 WC Microbiology SC Microbiology GA 777CS UT WOS:000291592600036 PM 21551294 ER PT J AU Chen, Y Strain, EA Allard, M Brown, EW AF Chen, Y. Strain, E. A. Allard, M. Brown, E. W. TI Genome Sequences of Listeria monocytogenes Strains J1816 and J1-220, Associated with Human Outbreaks SO JOURNAL OF BACTERIOLOGY LA English DT Article ID EPIDEMIC CLONES; UNITED-STATES; VIRULENCE AB Listeria monocytogenes has caused numerous human outbreaks. Here we report draft genomes of L. monocytogenes J1816 and J1-220, which belong to epidemic clones II and IV, respectively. Whole-genome sequence analysis of these strains provides a tool for studying the short-term evolution of these epidemic clones. C1 [Chen, Y.; Allard, M.; Brown, E. W.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Strain, E. A.] US FDA, Div Math, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Chen, Y (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 712, College Pk, MD 20740 USA. EM yi.chen@fda.hhs.gov RI Zhou, Tian/J-7175-2012 NR 9 TC 11 Z9 11 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUL PY 2011 VL 193 IS 13 BP 3424 EP 3425 DI 10.1128/JB.05048-11 PG 2 WC Microbiology SC Microbiology GA 777CS UT WOS:000291592600046 PM 21551300 ER PT J AU Tornoe, CW Garnett, CE Wang, YN Florian, J Li, M Gobburu, JV AF Tornoe, Christoffer W. Garnett, Christine E. Wang, Yaning Florian, Jeffry Li, Michael Gobburu, Jogarao V. TI Creation of a Knowledge Management System for QT Analyses SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE QT/QTc; knowledge management; automated analysis; QT correction; central tendency analysis; concentration-QTc analysis; pharmacometrics ID DECISIONS; IMPACT AB An increasing number of thorough QT (TQT) reports are being submitted to the US Food and Drug Administration's interdisciplinary review team for QT (IRT-QT), requiring time-intensive quantitative analyses by a multidisciplinary review team within 45 days. This calls for systematic learning to guide future trials and policies by standardizing and automating the QT analyses to improve review efficiency, provide consistent advice, and enable pooled data analyses to answer key regulatory questions. The QT interval represents the time from initiation of ventricular depolarization to completion of ventricular repolarization recorded by electrocardiograph (ECG) and is used in the proarrhythmic risk assessment. The developed QT knowledge management system is implemented in the R package "QT." Data from 11 crossover TQT studies including time-matched ECGs and pharmacokinetic measurements following single doses of 400 to 1200 mg moxifloxacin were used for the QT analysis example. The automated workflow was divided into 3 components (data management, analysis, and archival). The generated data sets, scripts, tables, and graphs are automatically stored in a queryable repository and summarized in an analysis report. More than 100 TQT studies have been analyzed using the system since 2007. This has dramatically reduced the time needed to review TQT studies and has made the IRT-QT reviews consistent across reviewers. Furthermore, the system enables leveraging prior knowledge through pooled data analyses to answer policy-related questions and to understand the various effects that influence study results. C1 [Tornoe, Christoffer W.; Garnett, Christine E.; Wang, Yaning; Florian, Jeffry; Gobburu, Jogarao V.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Li, Michael] US FDA, Div Cardiovasc & Renal Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Garnett, CE (reprint author), 10903 New Hampshire Ave,Bldg 51,Room 1260, Silver Spring, MD 20993 USA. EM christine.garnett@fda.hhs.gov NR 7 TC 33 Z9 33 U1 0 U2 7 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 JUL PY 2011 VL 51 IS 7 BP 1035 EP 1042 DI 10.1177/0091270010378408 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 775NC UT WOS:000291465300008 PM 20978278 ER PT J AU Duan, JZ Jackson, AJ Zhao, P AF Duan, John Z. Jackson, Andre J. Zhao, Ping TI Bioavailability Considerations in Evaluating Drug-Drug Interactions Using the Population Pharmacokinetic Approach SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE drug interaction; NONMEM; SimCyp; bioavailability ID IN-VIVO; KETOCONAZOLE; MIDAZOLAM; INHIBITION; PREDICTION; METABOLISM; SIMULATION AB Applying a comedication (COMD) covariate to apparent clearance (CL(app) = CL/F) is a common practice when using population pharmacokinetics (PopPK) to study metabolism-based drug-drug interactions (DDI). This study evaluates the importance of independently applying COMD to F and CL to account for DDI at the level of first-pass metabolism. A known DDI between single oral doses of the CYP3A substrate midazolam (5 mg) and the inhibitor ketoconazole (400 mg) was simulated using a physiologically based pharmacokinetic simulator SimCyp in virtual subjects. The simulated midazolam data were analyzed by PopPK method under the following scenarios by applying COMD effect to (1) CL(app) only, (2) CL and F, and (3) CL(app) and apparent volume of distribution (V(app) = V/F), assuming V is unchanged. The mean simulated degree of interaction, measured by midazolam AUC ratio with and without ketoconazole (AUCR), was 10.28. Scenario 1 underestimated AUCR. When COMD was independently applied to F and Vapp in scenarios 2 and 3, lower objective function values of the PopPK analysis and more accurate AUCR estimates were achieved. AUCR estimates were also dependent on sampling. The authors conclude that when significant inhibition of the first-pass metabolism of the substrate is anticipated, COMD effects should be applied to both CL and F in PopPK analysis. C1 [Duan, John Z.] US FDA, CDER, OPS, ONDQA, Silver Spring, MD 20993 USA. [Jackson, Andre J.; Zhao, Ping] US FDA, CDER, OTS, OCP, Silver Spring, MD 20993 USA. RP Duan, JZ (reprint author), US FDA, CDER, OPS, ONDQA, WO Bldg 21,Room 1616,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM john.duan@fda.hhs.gov NR 23 TC 6 Z9 6 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUL PY 2011 VL 51 IS 7 BP 1087 EP 1100 DI 10.1177/0091270010377200 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 775NC UT WOS:000291465300014 PM 20864622 ER PT J AU Ma, HL Ma, YK Ma, WB Williams, DK Galvin, TA Khan, AS AF Ma, Hailun Ma, Yunkun Ma, Wenbin Williams, Dhanya K. Galvin, Teresa A. Khan, Arifa S. TI Chemical Induction of Endogenous Retrovirus Particles from the Vero Cell Line of African Green Monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; C VIRUS; NUCLEOTIDE-SEQUENCE; REVERSE-TRANSCRIPTASE; UNIQUE RETROVIRUS; VIRAL PARTICLES; BABOON PLACENTA; CULTURED-CELLS; RHESUS-MONKEYS; MASON-PFIZER AB Endogenous retroviral sequences are present in high copy numbers in the genomes of all species and may be expressed as RNAs; however, the majority are defective for virus production. Although virus has been isolated from various Old World monkey and New World monkey species, there has been no report of endogenous retroviruses produced from African green monkey (AGM) tissues or cell lines. We have recently developed a stepwise approach for evaluating the presence of latent viruses by chemical induction (Khan et al., Biologicals 37: 196-201, 2009). Based upon this strategy, optimum conditions were determined for investigating the presence of inducible, endogenous retroviruses in the AGM-derived Vero cell line. Low-level reverse transcriptase activity was produced with 5-azacytidine (AzaC) and with 5'-iodo-2'-deoxyuridine (IUdR); none was detected with sodium butyrate. Nucleotide sequence analysis of PCR-amplified fragments from the gag, pol, and env regions of RNAs, prepared from ultracentrifuged pellets of filtered supernatants, indicated that endogenous retrovirus particles related to simian endogenous type D betaretrovirus (SERV) sequences and baboon endogenous virus type C gammaretrovirus (BaEV) sequences were induced by AzaC, whereas SERV sequences were also induced by IUdR. Additionally, sequence heterogeneity was seen in the RNAs of SERV- and BaEV-related particles. Infectivity analysis of drug-treated AGM Vero cells showed no virus replication in cell lines known to be susceptible to type D simian retroviruses (SRVs) and to BaEV. The results indicated that multiple, inducible endogenous retrovirus loci are present in the AGM genome that can encode noninfectious, viruslike particles. C1 [Ma, Hailun; Ma, Yunkun; Ma, Wenbin; Williams, Dhanya K.; Galvin, Teresa A.; Khan, Arifa S.] US FDA, Ctr Biol Evaluat & Res, Retrovirus Lab, Div Viral Prod, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), US FDA, Ctr Biol Evaluat & Res, Retrovirus Lab, Div Viral Prod, 8800 Rockville Pike,HFM-454,Bldg 29B,Room 4NN10, Bethesda, MD 20892 USA. EM arifa.khan@fda.hhs.gov FU DMID/NIAID/NIH [Y1-A1-4893-02] FX The work was funded by DMID/NIAID/NIH Interagency Agreement no. Y1-A1-4893-02. NR 85 TC 10 Z9 11 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2011 VL 85 IS 13 BP 6579 EP 6588 DI 10.1128/JVI.00147-11 PG 10 WC Virology SC Virology GA 775CG UT WOS:000291434300045 PM 21543506 ER PT J AU Modric, T Modric, S Murphy, MJ Bright, SJ Shults, S AF Modric, Tomislav Modric, Sanja Murphy, Michael J. Bright, Susan J. Shults, Stacey TI Safety of Antibiotic Drugs in Food Animals: Comparison of Findings from Preapproval Studies and Postapproval Experience in the United States with Safety Information in Published Literature SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article DE Antibiotic drugs; Safety; Adverse events; Toxic; Food animals ID OPERATIONAL ASSESSMENT; IN-VITRO; TILMICOSIN; TIAMULIN; PHARMACOKINETICS; FLORFENICOL; ALGORITHM; TOXICITY; MICOTIL; CATTLE AB Antibiotics are among the most widely prescribed drugs and are generally considered safe for the target species. However, their use has been associated with various adverse toxic effects in target animals, such as allergic reactions, gastrointestinal signs, cardiovascular effects, hypoglycemia, hepatic/renal toxicity, thrombocytopenia, and anaphylaxis. This article provides a qualitative summary of the adverse events observed in target animals during the evaluation of antibiotics by the Food and Drug Administration during both preapproval and postapproval periods. As there is a marked scarcity of published data on safety of antibiotics in food animals, more research is needed in this area. C1 [Modric, Tomislav; Murphy, Michael J.; Bright, Susan J.; Shults, Stacey] US FDA, Off Surveillance & Compliance, CVM, Rockville, MD 20855 USA. [Modric, Sanja] US FDA, Off New Anim Drug Evaluat, CVM, Rockville, MD 20855 USA. RP Modric, T (reprint author), US FDA, Off Surveillance & Compliance, CVM, 7519 Standish Pl, Rockville, MD 20855 USA. EM tomislav.modric@fda.hhs.gov NR 29 TC 0 Z9 0 U1 3 U2 13 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD JUL PY 2011 VL 27 IS 2 BP 389 EP + DI 10.1016/j.cvfa.2011.02.005 PG 18 WC Veterinary Sciences SC Veterinary Sciences GA 776VE UT WOS:000291565900010 PM 21575776 ER PT J AU Bright, SJ Murphy, MJ Steinschneider, JC Lovell, RA Post, LO AF Bright, Susan J. Murphy, Michael J. Steinschneider, Janice C. Lovell, Randall A. Post, Lynn O. TI Treatment of Animal Toxicoses: A Regulatory Perspective SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article DE Toxicoses; Antidotes; Regulatory ID POISON-CONTROL-CENTERS AB This article focuses on the regulatory issues to consider when veterinarians are called upon to treat animal toxicoses, in particular those involving food-producing animals. The lack of Food and Drug Administration approved drugs to treat animal toxicoses has been a long-standing problem. This article reviews extralabel drug use regulations, and the responsibilities of the treating veterinarian. It discusses the legal implications of compounding and the use of unapproved drugs to treat animal toxicoses. Efforts should be made to increase the availability of life-saving antidotal therapies. C1 [Bright, Susan J.] US FDA, Div Vet Prod Safety, Off Surveillance & Compliance, Ctr Vet Med, Rockville, MD 20855 USA. [Murphy, Michael J.] US FDA, Div Surveillance, Off Surveillance & Compliance, Ctr Vet Med, Rockville, MD 20855 USA. [Lovell, Randall A.; Post, Lynn O.] US FDA, Div Anim Feeds, Off Surveillance & Compliance, Ctr Vet Med, Rockville, MD 20855 USA. RP Bright, SJ (reprint author), US FDA, Div Vet Prod Safety, Off Surveillance & Compliance, Ctr Vet Med, 7519 Standish Pl, Rockville, MD 20855 USA. EM susan.bright@fda.hhs.gov FU NRSP-7 FX The NRSP-7 is a program that provides funds for research to generate data in support of drug approvals for minor uses. NRSP-7 submits data from research projects to the FDA-CVM for inclusion in a public master file. Once accepted, the data are available for sponsors to refer to, in support of an NADA for minor use. Further information is available at http://www.nrsp-7.org. NR 28 TC 0 Z9 0 U1 1 U2 1 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD JUL PY 2011 VL 27 IS 2 BP 481 EP + DI 10.1016/j.cvfa.2011.02.002 PG 33 WC Veterinary Sciences SC Veterinary Sciences GA 776VE UT WOS:000291565900016 PM 21575782 ER PT J AU Woodburn, KW Schatz, PJ Wilson, S Fong, KL Wagner, VO Gudi, R Krsmanovic, L Paranjpe, M Shah, SA AF Woodburn, Kathryn W. Schatz, Peter J. Wilson, Susan Fong, Kei-Lai Wagner, Valentine O. Gudi, Ramadevi Krsmanovic, Ljubica Paranjpe, Madhav Shah, Sudhir A. TI Genotoxic assessment and toxicity evaluation of peginesatide in CByB6F1 hybrid mice SO DRUG AND CHEMICAL TOXICOLOGY LA English DT Article DE Erythropoiesis-stimulating agents; genotoxicity; toxicology; pharmacokinetics; safety ID ERYTHROPOIESIS-STIMULATING AGENT; SAFETY EVALUATION; TRANSGENIC MOUSE; ANEMIA; HEMATIDE(TM); IDENTIFICATION AB Peginesatide is a PEGylated, investigational, peptide-based erythropoiesis-stimulating agent (ESA) that was designed and engineered to stimulate specifically the erythropoietin receptor dimer that governs erythropoiesis. Clinical use of peginesatide is anticipated to result in chronic dosing in chronic kidney disease (CKD) patients, and the nonclinical data to support development should include an evaluation of carcinogenic potential evaluation. Peginesatide was not mutagenic or clastogenic in a standard genotoxicity battery of tests. Doses for a rasH2 transgenic mouse carcinogenicity assay were defined in a 28-day study in the wild-type littermates of the rasH2 transgenic mouse strain, using intravenous doses of 1-25 mg/kg on days 1 and 22. The findings were consistent with exaggerated pharmacology, including polycythemia, with associated increases in hemoglobin level and extramedullary hematopoiesis and bone marrow hypercellularity. C1 [Woodburn, Kathryn W.; Schatz, Peter J.] Affymax Inc, Palo Alto, CA 94304 USA. [Wilson, Susan] Aclairo Pharmaceut Dev Grp Inc, Vienna, VA USA. [Fong, Kei-Lai] Aptuit Consulting Inc, Berkeley, CA USA. [Wagner, Valentine O.; Krsmanovic, Ljubica; Paranjpe, Madhav; Shah, Sudhir A.] BioReliance, Rockville, MD USA. [Gudi, Ramadevi] Food & Drug Adm, College Pk, MD USA. RP Woodburn, KW (reprint author), Affymax Inc, 4001 Miranda Ave, Palo Alto, CA 94304 USA. EM Kathryn_woodburn@affymax.com NR 28 TC 3 Z9 3 U1 0 U2 2 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 0148-0545 J9 DRUG CHEM TOXICOL JI Drug Chem. Toxicol. PD JUL PY 2011 VL 34 IS 3 BP 240 EP 249 DI 10.3109/01480545.2010.510140 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy; Toxicology SC Chemistry; Pharmacology & Pharmacy; Toxicology GA 774AQ UT WOS:000291354100003 PM 21649477 ER PT J AU Balkam, JAJ Cadwell, K Fein, SB AF Balkam, Jane A. Johnston Cadwell, Karin Fein, Sara B. TI Effect of Components of a Workplace Lactation Program on Breastfeeding Duration Among Employees of a Public-Sector Employer SO MATERNAL AND CHILD HEALTH JOURNAL LA English DT Article DE Breastfeeding; Breastfeeding duration; Workplace lactation program; Public-sector employer ID MATERNAL EMPLOYMENT; UNITED-STATES; LOW-INCOME; WOMEN; SUPPORT; INITIATION; CHILDREN; MILK AB The purpose of this study was to evaluate the impact of the individual services offered via a workplace lactation program of one large public-sector employer on the duration of any breastfeeding and exclusive breastfeeding. Exclusive breastfeeding was defined as exclusive feeding of human milk for the milk feeding. A cross-sectional mailed survey approach was used. The sample (n = 128) consisted of women who had used at least one component of the lactation program in the past 3 years and who were still employed at the same organization when data were collected. Descriptive statistics included frequency distributions and contingency table analysis. Chi-square analysis was used for comparison of groups, and both analysis of variance (ANOVA) and univariate analysis of variance from a general linear model were used for comparison of means. The survey respondents were primarily older, white, married, well-educated, high-income women. More of the women who received each lactation program service were exclusively breastfeeding at 6 months of infant age in all categories of services, with significant differences in the categories of telephone support and return to work consultation. After adjusting for race and work status, logistic regression analysis showed the number of services received was positively related to exclusive breastfeeding at 6 months and participation in a return to work consultation was positively related to any breastfeeding at 6 months. The study demonstrated that the workplace lactation program had a positive impact on duration of breastfeeding for the women who participated. Participation in the telephone support and return to work consultation services, and the total number of services used were related to longer duration of exclusive and/or any breastfeeding. C1 [Balkam, Jane A. Johnston] Coll Notre Dame Maryland, Baltimore, MD 21210 USA. [Cadwell, Karin] Healthy Children Project, E Sandwich, MA USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Balkam, JAJ (reprint author), Coll Notre Dame Maryland, Baltimore, MD 21210 USA. EM jbalkam@ndm.edu NR 39 TC 11 Z9 11 U1 0 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1092-7875 J9 MATERN CHILD HLTH J JI Matern. Child Health J. PD JUL PY 2011 VL 15 IS 5 BP 677 EP 683 DI 10.1007/s10995-010-0620-9 PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 771NW UT WOS:000291168000016 PM 20552261 ER PT J AU Raw, AS Lionberger, R Yu, LX AF Raw, Andre Sirota Lionberger, Robert Yu, Lawrence X. TI Pharmaceutical Equivalence by Design for Generic Drugs: Modified-Release Products SO PHARMACEUTICAL RESEARCH LA English DT Article DE generic drugs; modified release; pharmaceutical equivalence; quality by design (QbD); quality target product profile (QTPP); therapeutic equivalence ID ENTERIC-COATED FORMULATIONS; OMEPRAZOLE; BIOEQUIVALENCE; BIOAVAILABILITY; QUALITY AB The Office of Generic Drugs has ensured the high quality of generic products based upon two requirements: pharmaceutical equivalence and bioequivalence to the reference listed drug (RLD). This paradigm has been used with success toward ensuring quality generic drug products that provide the same therapeutic benefit as the RLD. Drug products have increased in design complexity; as a result, approaches to ensure therapeutic equivalence must evolve to provide assurance of quality generic drug products. The Food and Drug Administration quality by design initiative (QbD) provides an enhanced evaluation approach by introducing the concept of a quality target product profile (QTPP). The QTPP introduces, within the context of the current regulatory framework, the quality concept of "pharmaceutical equivalence by design." This article illustrates through several examples how this QbD element in the evaluation of modified-release drug products enhances the current framework to ensure generic drug product equivalence. It achieves this by complementing the traditional paradigm, "equivalence by testing," where product equivalence is based upon inferences from a limited bioequivalence study, to one that also considers whether the drug product was developed to be an equivalent to the RLD, using appropriate quality surrogates that target "pharmaceutical equivalence by design.". C1 [Raw, Andre Sirota; Lionberger, Robert; Yu, Lawrence X.] US FDA, Off Gener Drugs, Rockville, MD 20855 USA. RP Raw, AS (reprint author), US FDA, Off Gener Drugs, 7519 Standish Pl, Rockville, MD 20855 USA. EM andre.raw@fda.hhs.gov NR 22 TC 11 Z9 11 U1 5 U2 29 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD JUL PY 2011 VL 28 IS 7 BP 1445 EP 1453 DI 10.1007/s11095-011-0397-6 PG 9 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 774CA UT WOS:000291357700001 PM 21387150 ER PT J AU Chen, ML Amidon, GL Benet, LZ Lennernas, H Yu, LX AF Chen, Mei-Ling Amidon, Gordon L. Benet, Leslie Z. Lennernas, Hans Yu, Lawrence X. TI The BCS, BDDCS, and Regulatory Guidances SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material DE BCS; BDDCS; biopharmaceutics classification system; biopharmaceutics drug disposition classification system; drug metabolism; drug permeability ID BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; DRUG DISPOSITION CLASSIFICATION; INTESTINAL PERMEABILITY; CHEMICAL BIOLOGY; ABSORPTION; MODELS C1 [Chen, Mei-Ling] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Amidon, Gordon L.] Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. [Benet, Leslie Z.] Univ Calif San Francisco, Sch Pharm & Med, Dept Bioengn & Therapeut Sci, San Francisco, CA 94143 USA. [Lennernas, Hans] Uppsala Univ, Dept Pharm, Uppsala, Sweden. [Yu, Lawrence X.] US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Chen, ML (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 51,Rm 4108, Silver Spring, MD 20993 USA. EM meiling.chen@fda.hhs.gov RI Benet, Leslie/K-8286-2016 NR 19 TC 40 Z9 41 U1 0 U2 19 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD JUL PY 2011 VL 28 IS 7 BP 1774 EP 1778 DI 10.1007/s11095-011-0438-1 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 774CA UT WOS:000291357700028 PM 21491148 ER PT J AU Yakes, BJ DeGrasse, SL Poli, M Deeds, JR AF Yakes, Betsy Jean DeGrasse, Stacey L. Poli, Mark Deeds, Jonathan R. TI Antibody characterization and immunoassays for palytoxin using an SPR biosensor SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE Palytoxin; Surface plasmon resonance; Biosensor; Antibody characterization; Immunoassay ID NEUTRALIZATION AB Palytoxin (PLTX), a polyether marine toxin originally isolated from the zoanthid Palythoa toxica, is one of the most toxic non-protein substances known. Fatal poisonings have been linked to ingestion of PLTX-contaminated seafood, and effects in humans have been associated with dermal and inhalational exposure to PLTX containing organisms and waters. Additionally, PLTX co-occurrence with other well-characterized seafood toxins (e.g., ciguatoxins, saxitoxins, tetrodotoxin) has hindered direct associations of PLTX to seafood-borne illnesses. There are currently no validated methods for the quantitative detection of PLTX(s). As such, a well-characterized, robust, specific analytical technique is needed for the detection of PLTX(s) in source organisms, surrounding waters, and clinical samples. Surface plasmon resonance (SPR) biosensors are ideally suited for antibody characterization and quantitative immunoassay detection. Herein, we describe a newly developed SPR assay for PLTX. An anti-mouse substrate was used to characterize the kinetic values for a previously developed monoclonal anti-PLTX. The characterized antibody was then incorporated into a sensitive, rapid, and selective PLTX assay. Buffer type, flow rate, analyte-binding time, and regeneration conditions were optimized for the antibody-PLTX system. Cross-reactivity to potentially co-occurring seafood toxins was also evaluated. We show that this optimized assay is capable of measuring low- to sub-ng/mL PLTX levels in buffer and two seafood matrices (grouper and clam). Preliminary results indicate that this SPR biosensor assay allows for (1) rapid characterization of antibodies and (2) rapid, sensitive PLTX concentration determination in seafood matrices. Method development information contained herein may be broadly applied to future PLTX detection and/or antibody characterization efforts. C1 [Yakes, Betsy Jean; DeGrasse, Stacey L.; Deeds, Jonathan R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Poli, Mark] USA, Integrated Toxicol Div, Med Res Inst Infect Dis, Frederick, MD 21702 USA. RP Yakes, BJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM betsy.yakes@fda.hhs.gov RI Yakes, Betsy/K-2646-2012; OI DeGrasse, Stacey/0000-0001-7808-4193 NR 17 TC 15 Z9 15 U1 2 U2 27 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 JUL PY 2011 VL 400 IS 9 BP 2865 EP 2869 DI 10.1007/s00216-011-5019-y PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 769SE UT WOS:000291037800019 PM 21523328 ER PT J AU Chowdhury, BA Seymour, SM Levenson, MS AF Chowdhury, Badrul A. Seymour, Sally M. Levenson, Mark S. TI Assessing the Safety of Adding LABAs to Inhaled Corticosteroids for Treating Asthma SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ACTING BETA-AGONISTS C1 [Chowdhury, Badrul A.; Seymour, Sally M.] US FDA, Ctr Drug Evaluat & Res, Div Pulm Allergy & Rheumatol Prod, Off New Drugs, Silver Spring, MD USA. [Levenson, Mark S.] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD USA. RP Chowdhury, BA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pulm Allergy & Rheumatol Prod, Off New Drugs, Silver Spring, MD USA. NR 5 TC 68 Z9 69 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 30 PY 2011 VL 364 IS 26 BP 2473 EP 2475 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 785AM UT WOS:000292199800001 PM 21714647 ER PT J AU Williams, RL AF Williams, Roger L. TI MEDICINE QUALITY FACES CHALLENGES SO CHEMICAL & ENGINEERING NEWS LA English DT Editorial Material C1 [Williams, Roger L.] USA, Washington, DC USA. [Williams, Roger L.] Walter Reed Army Inst Res, Silver Spring, MD USA. [Williams, Roger L.] US FDA, Rockville, MD 20857 USA. 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 0009-2347 J9 CHEM ENG NEWS JI Chem. Eng. News PD JUN 27 PY 2011 VL 89 IS 26 BP 58 EP 59 PG 2 WC Chemistry, Multidisciplinary; Engineering, Chemical SC Chemistry; Engineering GA 787BU UT WOS:000292352400051 ER PT J AU Girnita, DM Ohmann, EL Brooks, MM Webber, SA Burckart, GJ Ferrell, RE Ranganathan, S Chinnock, R Canter, C Addonizio, L Bernstein, D Kirklin, JK Naftel, DC Zeevi, A AF Girnita, Diana M. Ohmann, Erin L. Brooks, Maria M. Webber, Steven A. Burckart, Gilbert J. Ferrell, Robert E. Ranganathan, Sarangarajan Chinnock, Richard Canter, Charles Addonizio, Linda Bernstein, Daniel Kirklin, James K. Naftel, David C. Zeevi, Adriana TI Gene Polymorphisms Impact the Risk of Rejection With Hemodynamic Compromise: A Multicenter Study SO TRANSPLANTATION LA English DT Article DE Genetic polymorphism; Pediatric heart transplant; Rejection; Hemodynamic compromise; Clinical outcome ID PEDIATRIC HEART-TRANSPLANTATION; CARDIAC TRANSPLANTATION; INTERLEUKIN-10 GENE; PROMOTER; EXPRESSION; RECIPIENTS; DEATH; FAS; GENOTYPE; SURVIVAL AB Background. Rejection with hemodynamic compromise (RHC) is associated with high mortality in heart recipients. This study investigates the association between genetic polymorphisms and RHC in pediatric heart recipients. Methods. Data from 532 pediatric heart recipients from six centers in the Pediatric Heart Transplant Study were analyzed for time to RHC by recipient race, age at transplantation, and genotype at 13 genetic polymorphisms (TNF-alpha A-308G, IL-6 G-174C, INF-gamma T+874A, IL-10 G-1082A, C-819T, and C-592A; FAS A-670G, FASL C-843T, and ACE I/D; and VEGF A-2578C, C-1451T, C+405G, and -2549 I/D). Results. RHC occurred in 126 (23.7%) patients during the study period. Adjusting for age and race, IL-10 G-1082A, FAS A-670G, and ACE I/D genotypes were associated with RHC. IL-10 G-1082A GG genotype was associated with decreased risk of RHC with an adjusted hazard ratio (HR) of 0.49 (95% confidence interval [CI], 0.27-0.90; P=0.020). FAS A-670G AA genotype was associated with increased risk of RHC with an adjusted HR of 1.84 (95% CI, 1.25-2.69; P=0.002). ACE II genotype was associated with decreased risk of RHC with an adjusted HR of 0.58 (95% CI, 0.36-0.95; P=0.031). Conclusions. Recipients with a high anti-inflammatory and immune-regulatory genetic profile (high interleukin-10) were protected from RHC. Conversely, recipients with a pro-apoptotic genetic profile (high Fas) or high angiotensin-1-converting enzyme producing genotype were at increased risk of RHC. This represents progress toward understanding the genetic risk factors of posttransplantation outcomes in pediatric heart recipients. C1 [Zeevi, Adriana] Univ Pittsburgh, Dept Pathol, Div Transplant Pathol, Thomas E Starzl Transplant Inst, Pittsburgh, PA 15261 USA. [Ohmann, Erin L.; Webber, Steven A.] Univ Pittsburgh, Dept Pediat, Div Cardiol, Pittsburgh, PA 15261 USA. [Brooks, Maria M.] Univ Pittsburgh, Dept Epidemiol, Pittsburgh, PA 15261 USA. [Burckart, Gilbert J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD USA. [Ferrell, Robert E.] Univ Pittsburgh, Dept Human Genet, Pittsburgh, PA 15261 USA. [Ranganathan, Sarangarajan] Univ Pittsburgh, Childrens Hosp Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA. [Chinnock, Richard] Loma Linda Univ, Dept Pediat, Loma Linda, CA 92350 USA. [Canter, Charles] Washington Univ, St Louis Childrens Hosp, Sch Med, Dept Pediat Cardiol, St Louis, MO 63110 USA. [Addonizio, Linda] Columbia Univ, New York Presbyterian Hosp, Dept Pediat, Div Cardiol, New York, NY 10027 USA. [Bernstein, Daniel] Stanford Univ, Lucile Packard Childrens Hosp, Div Pediat Cardiol, Palo Alto, CA 94304 USA. [Kirklin, James K.; Naftel, David C.] Univ Alabama, Dept Surg, Birmingham, AL 35294 USA. RP Zeevi, A (reprint author), Univ Pittsburgh, Dept Pathol, Div Transplant Pathol, Thomas E Starzl Transplant Inst, W1551 Biomed Sci Tower, Pittsburgh, PA 15261 USA. EM zeevi@pitt.edu OI Brooks, Maria/0000-0002-2030-7873; Chinnock, Richard/0000-0002-9814-1762 NR 30 TC 8 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JUN 27 PY 2011 VL 91 IS 12 BP 1326 EP 1332 DI 10.1097/TP.0b013e31821c1e10 PG 7 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA 775BE UT WOS:000291430500007 PM 21659963 ER PT J AU McClenahan, SD Krause, PR Uhlenhaut, C AF McClenahan, Shasta D. Krause, Philip R. Uhlenhaut, Christine TI Molecular and infectivity studies of porcine circovirus in vaccines SO VACCINE LA English DT Article DE Adventitious agents; Porcine circovirus; Safety; Vaccine characterization; Rotavirus ID MULTISYSTEMIC WASTING SYNDROME; ROTAVIRUS-VACCINATION; CELL-LINES; DISEASE; TYPE-2; SV40; PIGS; GASTROENTERITIS; EXPOSURE; CHILDREN AB This report describes FDA's laboratory response to the 2010 reports that porcine circovirus type 1 (PCV-1) DNA was present in U.S.-licensed rotavirus vaccines and in cells used to produce inactivated poliovirus vaccines. In the present study, Rotarix (R) (GlaxoSmithKline, Rixenxart, Belgium) was found to contain full-length PCV-1 genomes that are particle-associated, and cell culture assays in swine testis (ST) and PCV-free porcine kidney (PK-15) cells confirmed that PCV-1 sequences in this vaccine represent infectious virus. RotaTeq (R) (Merck and Co., West Point, PA, USA) contained small PCV-1 and PCV-2 genome fragments, but did not contain detectable larger portions of (or full-length) PCV genomes, and cell culture assays did not amplify PCV from this vaccine. Inactivated poliovirus vaccine bulks (GlaxoSmithKline) were also negative for the presence of PCV by cell culture infectivity assay. In these vaccines, molecular characterization of PCV nucleic acids was useful for predicting the results of cell culture assays. Published by Elsevier Ltd. C1 [McClenahan, Shasta D.; Krause, Philip R.; Uhlenhaut, Christine] FDA CBER, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), Bldg 29A,Rm 1C16,HFM-457,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Philip.Krause@fda.hhs.gov OI Krause, Philip/0000-0002-1045-7536 FU Food and Drug Administration FX This work was supported by the Food and Drug Administration. We acknowledge GSK and Merck and Co. for providing vaccine samples. Merck and Co. for providing PCV-2 stock, Dr. Andrew Cheung (USDA) for providing PCV-free PK-15 cells and a plasmid containing the PCV-2 genome, Drs. Gordon Allan (Queens University, Belfast, United Kingdom) and Steve Krakowka (Ohio State University, Columbus, OH) for providing expert advice on PCV, Dr. Nga Nguyen of the FDA/CBER core facility for providing rapid and excellent support and Drs. Robin Levis, Arifa Khan, Haru Murata, Erik Henchal, Andrew Lewis, Keith Peden, and Jerry Weir (FDA) for providing helpful comments. We also thank Peyton I. McClenahan for her strong support. NR 40 TC 31 Z9 33 U1 1 U2 9 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 24 PY 2011 VL 29 IS 29-30 BP 4745 EP 4753 DI 10.1016/j.vaccine.2011.04.087 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 788VG UT WOS:000292471900015 PM 21569811 ER PT J AU Manzano, M Reichert, ED Polo, S Falgout, B Kasprzak, W Shapiro, BA Padmanabhan, R AF Manzano, Mark Reichert, Erin D. Polo, Stephanie Falgout, Barry Kasprzak, Wojciech Shapiro, Bruce A. Padmanabhan, Radhakrishnan TI Identification of Cis-Acting Elements in the 3 '-Untranslated Region of the Dengue Virus Type 2 RNA That Modulate Translation and Replication SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID WEST-NILE-VIRUS; PARALLEL GENETIC ALGORITHM; SECONDARY STRUCTURE-ANALYSIS; CAP-DEPENDENT TRANSLATION; 3 UNTRANSLATED REGION; STEM-LOOP STRUCTURE; DE-NOVO SYNTHESIS; CYCLIZATION SEQUENCES; VIRAL REPLICATION; FLAVIVIRUS RNA AB Using the massively parallel genetic algorithm for RNA folding, we show that the core region of the 3'-untranslated region of the dengue virus (DENV) RNA can form two dumbbell structures (5' - and 3' -DBs) of unequal frequencies of occurrence. These structures have the propensity to form two potential pseudoknots between identical five-nucleotide terminal loops 1 and 2 (TL1 and TL2) and their complementary pseudoknot motifs, PK2 and PK1. Mutagenesis using a DENV2 replicon RNA encoding the Renilla luciferase reporter indicated that all four motifs and the conserved sequence 2 (CS2) element within the 3' -DB are important for replication. However, for translation, mutation of TL1 alone does not have any effect; TL2 mutation has only a modest effect in translation, but translation is reduced by similar to 60% in the TL1/TL2 double mutant, indicating that TL1 exhibits a cooperative synergy with TL2 in translation. Despite the variable contributions of individual TL and PK motifs in translation, WT levels are achieved when the complementarity between TL1/PK2 and TL2/PK1 is maintained even under conditions of inhibition of the translation initiation factor 4E function mediated by LY294002 via a noncanonical pathway. Taken together, our results indicate that the cis-acting RNA elements in the core region of DENV2 RNA that include two DB structures are required not only for RNA replication but also for optimal translation. C1 [Shapiro, Bruce A.] NCI, Ctr Canc Res Nanobiol Program, NIH, Ft Detrick, MD 21702 USA. [Manzano, Mark; Reichert, Erin D.; Padmanabhan, Radhakrishnan] Georgetown Univ Sch Med, Dept Microbiol & Immunol, Washington, DC 20057 USA. [Polo, Stephanie; Falgout, Barry] US FDA, Ctr Biol Evaluat & Review, Bethesda, MD 20892 USA. [Kasprzak, Wojciech] SAIC Frederick Inc, Basic Sci Program, Frederick, MD USA. RP Shapiro, BA (reprint author), NCI, Ctr Canc Res Nanobiol Program, NIH, Ft Detrick, MD 21702 USA. EM shapirbr@mail.nih.gov; rp55@georgetown.edu FU National Institutes of Health (NIH) [AI 57705, AI 70791]; NCI, NIH [NO1-CO-12400, HHSN261200800001E]; NCI, NIH, Center for Cancer Research FX This work was supported, in whole or in part, by National Institutes of Health (NIH) Grants AI 57705 and AI 70791 (to R. P.); by NCI, NIH, Contracts NO1-CO-12400 and HHSN261200800001E (to W. K.); and by the Intramural Research Program of the NCI, NIH, Center for Cancer Research. This work constitutes a partial fulfillment of the requirements for the degree of Doctor of Philosophy at Georgetown University School of Medicine for E. R. and M. M. NR 88 TC 34 Z9 35 U1 0 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 24 PY 2011 VL 286 IS 25 BP 22521 EP 22534 DI 10.1074/jbc.M111.234302 PG 14 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 778QP UT WOS:000291719900060 PM 21515677 ER PT J AU Decker, KB Chen, Q Hsieh, ML Boucher, P Stibitz, S Hinton, DM AF Decker, Kimberly B. Chen, Qing Hsieh, Meng-Lun Boucher, Philip Stibitz, Scott Hinton, Deborah M. TI Different Requirements for sigma Region 4 in BvgA Activation of the Bordetella pertussis Promoters P-fim3 and P-fhaB SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE BvgA; fim; sigma; polymerase; promoter ID COLI RNA-POLYMERASE; BACTERIAL TRANSCRIPTION INITIATION; AMP RECEPTOR PROTEIN; AMINO-ACID CONTACTS; C-TERMINAL DOMAIN; ESCHERICHIA-COLI; DNA-BINDING; CRYSTAL-STRUCTURE; ALPHA-SUBUNITS; ABORTIVE INITIATION AB Bordetella pertussis BvgA is a global response regulator that activates virulence genes, including adhesin-encoding fim3 and fhaB. At the fhaB promoter, P-fhaB, a BvgA binding site lies immediately upstream of the -35 promoter element recognized by Region 4 of the sigma subunit of RNA polymerase (RNAP). We demonstrate that sigma Region 4 is required for BvgA activation of P-fhaB, a hallmark of Class II activation. In contrast, the promoter-proximal BvgA binding site at P-fim3 includes the -35 region, which is composed of a tract of cytosines that lacks specific sequence information. We demonstrate that sigma Region 4 is not required for BvgA activation at P-fim3. Nonetheless, Region 4 mutations that impair its typical interactions with core and with the -35 DNA affect P-fim3 transcription. Hydroxyl radical cleavage using RNAP with sigma D581C-FeBABE positions Region 4 near the -35 region of P-fim3; cleavage using RNAP with alpha 276C-FeBABE or alpha 302C-FeBABE also positions an alpha subunit C-terminal domain within the -35 region, on a different helical face from the promoter-proximal BvgA similar to P dimer. Our results suggest that the -35 region of P-fim3 accommodates a BvgA similar to P dimer, an alpha subunit C-terminal domain, and sigma Region 4. Molecular modeling suggests how BvgA, sigma Region 4, and alpha might coexist within this DNA in a conformation that suggests a novel mechanism of activation. Published by Elsevier Ltd. C1 [Decker, Kimberly B.; Hsieh, Meng-Lun; Hinton, Deborah M.] NIDDK, Gene Express & Regulat Sect, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. [Chen, Qing; Boucher, Philip; Stibitz, Scott] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Hinton, DM (reprint author), NIDDK, Gene Express & Regulat Sect, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. EM dhinton@helix.nih.gov FU National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases FX We are grateful to C. Meares for the Cys(-)rpoD plasmid, to D. Lewis and S. Adhya for pDL934, to S. Dove and A. Hochschild for pBR alpha - sigmaHYb4, to T. James for the molecular modeling, and to L. Knipling for the construction of pET sigmaflCF and pET sigmaHyb4 and purification of sigmaHYb4. We also thank R. Bonocora, L. Knipling, T. James, A. Boulanger-Castaing, S. Jha, and C. Jones for helpful discussions. K. Decker is a graduate student in the Graduate Partnership Program, Johns Hopkins University-National Institutes of Health. This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. NR 97 TC 10 Z9 10 U1 2 U2 2 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD JUN 24 PY 2011 VL 409 IS 5 BP 692 EP 709 DI 10.1016/j.jmb.2011.04.017 PG 18 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 781EL UT WOS:000291913300002 PM 21536048 ER PT J AU Ali, MM Amialchuk, A Heiland, FW AF Ali, Mir M. Amialchuk, Aliaksandr Heiland, Frank W. TI Weight-Related Behavior among Adolescents: The Role of Peer Effects SO PLOS ONE LA English DT Article ID NUTRITION EXAMINATION SURVEY; PHYSICAL-ACTIVITY; SOCIAL NETWORK; US CHILDREN; NATIONAL-HEALTH; BODY-WEIGHT; OBESITY; GAIN; PREVALENCE; OVERWEIGHT AB Purpose: To investigate whether social interactions in friendship networks influence the following weight-related behaviors of adolescents: exercising regularly, playing an active sport, hours of TV/Video viewing, sleeping six or fewer hours, eating breakfast on weekdays, frequency of eating at fast food restaurants, eating five servings of fruits/vegetables daily, and consuming calorie-dense snacks. Method: Data from a nationally representative sample of adolescents are used to examine the association between peer and individual weight-related behaviors. Evidence from multivariate regression analysis controlling for an extensive list of individual-and family-level factors as well as school-level unobserved heterogeneity is obtained. Results: We find a significant positive association between individuals' and friends' behaviors in terms of sports, exercise and fast food consumption. The estimated associations are robust to controls for individual-and family-level factors, unobserved heterogeneity at the school level and our attempts to account for non-random peer selection. Conclusions: The social transmission of weight-related behaviors is a viable explanation for the spread of obesity in friendship networks documented in recent research. Traditional weight reduction interventions may be fruitfully complemented with strategies that focus on harnessing peer support to modify behaviors. C1 [Ali, Mir M.; Amialchuk, Aliaksandr] Univ Toledo, Dept Econ, Toledo, OH 43606 USA. [Ali, Mir M.] US FDA, Off Regulat Policy & Social Sci, College Pk, MD USA. [Heiland, Frank W.] CUNY, Baruch Coll, Grad Ctr Econ, Inst Demog Res,Sch Publ Affairs, New York, NY 10021 USA. RP Ali, MM (reprint author), Univ Toledo, Dept Econ, 2801 W Bancroft St, Toledo, OH 43606 USA. EM mir.ali@fda.hhs.gov FU National Institute of Child Health and Human Development [P01-HD31921] FX The views expressed in this study are those of the authors and do not necessarily reflect the views of the Food and Drug Administration. The authors would like to thank Andrew Stivers (FDA-ORPSS) and Chung-Tung Jordan Lin (FDA-OPRSS) for helpful comments and suggestions. This research uses data from Add Health, a program project designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris, and funded by grant P01-HD31921 from the National Institute of Child Health and Human Development, with cooperative funding from 17 other agencies. Special acknowledgment is due to Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Persons interested in obtaining data files from Add Health should contact Add Health, Carolina Population Center, 123 W. Franklin Street, Chapel Hill, NC 27516-2524 (addhealth@unc.edu). NR 38 TC 44 Z9 44 U1 1 U2 36 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 23 PY 2011 VL 6 IS 6 AR e21179 DI 10.1371/journal.pone.0021179 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 782TT UT WOS:000292035400011 PM 21731665 ER PT J AU Kisby, GE Fry, RC Lasarev, MR Bammler, TK Beyer, RP Churchwell, M Doerge, DR Meira, LB Palmer, VS Ramos-Crawford, AL Ren, XF Sullivan, RC Kavanagh, TJ Samson, LD Zarbl, H Spencer, PS AF Kisby, Glen E. Fry, Rebecca C. Lasarev, Michael R. Bammler, Theodor K. Beyer, Richard P. Churchwell, Mona Doerge, Daniel R. Meira, Lisiane B. Palmer, Valerie S. Ramos-Crawford, Ana-Luiza Ren, Xuefeng Sullivan, Robert C. Kavanagh, Terrance J. Samson, Leona D. Zarbl, Helmut Spencer, Peter S. TI The Cycad Genotoxin MAM Modulates Brain Cellular Pathways Involved in Neurodegenerative Disease and Cancer in a DNA Damage-Linked Manner SO PLOS ONE LA English DT Article ID AMYOTROPHIC-LATERAL-SCLEROSIS; SPORADIC ALZHEIMERS-DISEASE; PARKINSONISM-DEMENTIA COMPLEX; PROBE LEVEL DATA; TRANSCRIPTION FACTORS; GENE-EXPRESSION; INDUCED COLON; P38 MAPK; O-6-METHYLGUANINE-DNA METHYLTRANSFERASE; 2 SIDES AB Methylazoxymethanol (MAM), the genotoxic metabolite of the cycad azoxyglucoside cycasin, induces genetic alterations in bacteria, yeast, plants, insects and mammalian cells, but adult nerve cells are thought to be unaffected. We show that the brains of adult C57BL6 wild-type mice treated with a single systemic dose of MAM acetate display DNA damage (O(6)-methyldeoxyguanosine lesions, O(6)-mG) that remains constant up to 7 days post-treatment. By contrast, MAM-treated mice lacking a functional gene encoding the DNA repair enzyme O(6)-mG DNA methyltransferase (MGMT) showed elevated O(6)-mG DNA damage starting at 48 hours post-treatment. The DNA damage was linked to changes in the expression of genes in cell-signaling pathways associated with cancer, human neurodegenerative disease, and neurodevelopmental disorders. These data are consistent with the established developmental neurotoxic and carcinogenic properties of MAM in rodents. They also support the hypothesis that early-life exposure to MAM-glucoside (cycasin) has an etiological association with a declining, prototypical neurodegenerative disease seen in Guam, Japan, and New Guinea populations that formerly used the neurotoxic cycad plant for food or medicine, or both. These findings suggest environmental genotoxins, specifically MAM, target common pathways involved in neurodegeneration and cancer, the outcome depending on whether the cell can divide (cancer) or not (neurodegeneration). Exposure to MAM-related environmental genotoxins may have relevance to the etiology of related tauopathies, notably, Alzheimer's disease. C1 [Kisby, Glen E.; Lasarev, Michael R.; Palmer, Valerie S.; Ramos-Crawford, Ana-Luiza; Spencer, Peter S.] Oregon Hlth & Sci Univ, Ctr Res Occupat & Environm Toxicol, Portland, OR 97201 USA. [Fry, Rebecca C.; Meira, Lisiane B.; Samson, Leona D.] MIT, Ctr Environm Hlth Sci, Cambridge, MA 02139 USA. [Fry, Rebecca C.; Meira, Lisiane B.; Samson, Leona D.] MIT, Biol Engn Div, Cambridge, MA 02139 USA. [Bammler, Theodor K.; Beyer, Richard P.] Univ Washington, Dept Environm & Occupat Hlth Sci, Ctr Ecogenet & Environm Hlth, Seattle, WA 98195 USA. [Churchwell, Mona; Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Palmer, Valerie S.; Spencer, Peter S.] Oregon Hlth & Sci Univ, Global Hlth Ctr, Portland, OR 97201 USA. [Sullivan, Robert C.; Zarbl, Helmut] Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Kisby, GE (reprint author), Western Univ Hlth Sci, Coll Osteopath Med Pacific NW, Lebanon, OR USA. EM gkisby@westernu.edu; spencer@ohsu.edu OI Meira, Lisiane/0000-0003-4289-2986; Lasarev, Michael R/0000-0002-1896-2705 FU National Institutes of Environmental Health Sciences [ES11384 (OHSU), ES11399 (MIT), ES011387 (FHCRC/UW), ES07033 (UW)] FX This work was funded by the National Institutes of Environmental Health Sciences: ES11384 (OHSU), ES11399 (MIT), ES011387 (FHCRC/UW) and ES07033 (UW) (http://www.niehs.nih.gov/research/supported/centers/trc/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 86 TC 10 Z9 11 U1 0 U2 11 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD JUN 23 PY 2011 VL 6 IS 6 AR e20911 DI 10.1371/journal.pone.0020911 PG 13 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 782TT UT WOS:000292035400006 PM 21731631 ER PT J AU Sack, C Smoker, M Chamkasem, N Thompson, R Satterfield, G Masse, C Mercer, G Neuhaus, B Cassias, I Chang, E Lin, Y MacMahon, S Wong, J Zhang, K Smith, RE AF Sack, Chris Smoker, Michael Chamkasem, Narong Thompson, Richard Satterfield, Greg Masse, Claude Mercer, Greg Neuhaus, Barbara Cassias, Irene Chang, Eugene Lin, Yi MacMahon, Shaun Wong, Jon Zhang, Kai Smith, Robert E. TI Collaborative Validation of the QuEChERS Procedure for the Determination of Pesticides in Food by LC-MS/MS SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE pesticides; QuEChERS; HPLC; LC-MS/MS ID CHROMATOGRAPHY-MASS-SPECTROMETRY; SOLID-PHASE EXTRACTION; EASY MULTIRESIDUE METHOD; RESIDUE ANALYSIS; VEGETABLES; FRUITS; PRODUCE AB Seven FDA pesticide laboratories collaborated to develop and validate an LC-MS/MS method to determine 173 pesticides in <20 mm. The average determination coefficient (r(2)) was >0.99 for all but two compounds tested. The limits of detection were <20 ng/mL for all compounds and <10 ng/mL for 363 of the 368 transitions reported. The method was used to determine pesticides in two AOAC sponsored proficiency samples. The LC-MS/MS determination was used for the analysis of oranges, carrots and spinach using the QuEChERS (Quick, Easy, Cheap, Effective, Rugged, Safe) method. Each matrix was fortified at 20, 100, 400, and 1000 ng/g. No false positive responses were detected in controls of the three matrices. 165 pesticides had recoveries between 70 and 130%, and 161 had minimum detection levels less than 10 ng/g. Recoveries of 169 compounds for the 1000 ng/g spikes were within 50-150%. A matrix effect study indicated all three matrices caused a small net suppressing effect, the most pronounced attributable to the citrus matrix. The procedure proved to be accurate, precise, linear, sensitive and rugged, and adds 100 pesticides to the scope of the FDA pesticide program. C1 [Sack, Chris; Smoker, Michael; Smith, Robert E.] US FDA, Total Diet & Pesticide Res Ctr, Kansas Dist Lab, KAN, Lenexa, KS 66214 USA. [Chamkasem, Narong] US FDA, SE Reg Lab, Atlanta, GA 30309 USA. [Thompson, Richard; Satterfield, Greg] US FDA, Arkansas Reg Lab, Jefferson, AR 72079 USA. [Masse, Claude] US FDA, NE Reg Lab, Jamaica, NY 11433 USA. [Mercer, Greg; Neuhaus, Barbara] US FDA, Pacific Reg Lab NW, Bothell, WA USA. [Cassias, Irene; Chang, Eugene; Lin, Yi] US FDA, Pacific Reg Lab SW, Irvine, CA 90015 USA. [MacMahon, Shaun; Wong, Jon; Zhang, Kai] US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. RP Smith, RE (reprint author), US FDA, Total Diet & Pesticide Res Ctr, Kansas Dist Lab, KAN, 11510 W 80th St, Lenexa, KS 66214 USA. EM robert.smith@fda.hhs.gov NR 23 TC 23 Z9 30 U1 2 U2 27 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 22 PY 2011 VL 59 IS 12 BP 6383 EP 6411 DI 10.1021/jf201618q PG 29 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 776WA UT WOS:000291568300007 PM 21520933 ER PT J AU Freed, M Badal, A Jennings, RJ de las Heras, H Myers, KJ Badano, A AF Freed, Melanie Badal, Andreu Jennings, Robert J. de las Heras, Hugo Myers, Kyle J. Badano, Aldo TI X-ray properties of an anthropomorphic breast phantom for MRI and x-ray imaging SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID INITIAL CLINICAL-EXPERIENCE; CONTRAST-ENHANCED MRI; DIGITAL MAMMOGRAPHY; DIGITIZED MAMMOGRAMS; 3D SIMULATION; GENETIC RISK; CANCER; TISSUES; TOMOSYNTHESIS; ATTENUATION AB The purpose of this study is to characterize the x-ray properties of a dual-modality, anthropomorphic breast phantom whose MRI properties have been previously evaluated. The goal of this phantom is to provide a platform for optimization and standardization of two-and three-dimensional x-ray and MRI breast imaging modalities for the purpose of lesion detection and discrimination. The phantom is constructed using a mixture of lard and egg whites, resulting in a variable, tissue-mimicking structure with separate adipose-and glandular-mimicking components. The phantom can be produced with either a compressed or uncompressed shape. Mass attenuation coefficients of the phantom materials were estimated using elemental compositions from the USDA National Nutrient Database for Standard Reference and the atomic interaction models from the Monte Carlo code PENELOPE and compared with human values from the literature. The image structure was examined quantitatively by calculating and comparing spatial covariance matrices of the phantom and patient mammography images. Finally, a computerized version of the phantom was created by segmenting a computed tomography scan and used to simulate x-ray scatter of the phantom in a mammography geometry. Mass attenuation coefficients of the phantom materials were within 20% and 15% of the values for adipose and glandular tissues, respectively, which is within the estimation error of these values. Matching was improved at higher energies (>20 keV). Tissue structures in the phantom have a size similar to those in the patient data, but are slightly larger on average. Correlations in the patient data appear to be longer than those in the phantom data in the anterior-posterior direction; however, they are within the error bars of the measurement. C1 [Freed, Melanie; Badal, Andreu; Jennings, Robert J.; Myers, Kyle J.; Badano, Aldo] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Freed, Melanie] Univ Maryland, College Pk, MD 20742 USA. [de las Heras, Hugo] US FDA, Div Radiol Devices, Off Vitro Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Freed, M (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM melanie.freed@fda.hhs.gov OI de las Heras, Hugo/0000-0003-3227-0032; badano, aldo/0000-0003-3712-6670 FU FDA's Office of Women Health; Center for Devices and Radiological Health FX The authors wish to thank Jennifer T Loud and Mark H Greene (NIH/NCI) for providing the coded, archived patient mammograms, B Lazzari and co-authors, especially G Belli, for providing the data for the clinical detector from their 2007 paper, Marios Gavrielides for acquiring the phantom CT data and FDA/Center for Veterinary Medicine for access to their CT scanner, Eugene O'Bryan for triggering of the x-ray generator in the laboratory system, and Randy Bidinger and Bruce Fleharty for machining the phantom jar lids and a variety of experimental components. The authors also acknowledge funding from the 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 US Department of Energy and the US Food and Drug Administration. NR 49 TC 9 Z9 9 U1 0 U2 8 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 JUN 21 PY 2011 VL 56 IS 12 BP 3513 EP 3533 DI 10.1088/0031-9155/56/12/005 PG 21 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 770OC UT WOS:000291095700006 PM 21606556 ER PT J AU Dodoo, D Hollingdale, MR Anum, D Koram, KA Gyan, B Akanmori, BD Ocran, J Adu-Amankwah, S Geneshan, H Abot, E Legano, J Banania, G Sayo, R Brambilla, D Kumar, S Doolan, DL Rogers, WO Epstein, J Richie, TL Sedegah, M AF Dodoo, Daniel Hollingdale, Michael R. Anum, Dorothy Koram, Kwadwo A. Gyan, Ben Akanmori, Bartholomew D. Ocran, Josephine Adu-Amankwah, Susan Geneshan, Harini Abot, Esteban Legano, Jennylyn Banania, Glenna Sayo, Renato Brambilla, Donald Kumar, Sanjai Doolan, Denise L. Rogers, William O. Epstein, Judith Richie, Thomas L. Sedegah, Martha TI Measuring naturally acquired immune responses to candidate malaria vaccine antigens in Ghanaian adults SO MALARIA JOURNAL LA English DT Article ID MEROZOITE SURFACE PROTEIN-1; T-CELL EPITOPES; FALCIPARUM CIRCUMSPOROZOITE PROTEIN; HEPATOCYTE ERYTHROCYTE PROTEIN; BLOOD-STAGE ANTIGEN; PLASMODIUM-FALCIPARUM; CLINICAL MALARIA; ANTIBODY-RESPONSES; ADHESIVE PROTEIN; INTERFERON-GAMMA AB Background: To prepare field sites for malaria vaccine trials, it is important to determine baseline antibody and T cell responses to candidate malaria vaccine antigens. Assessing T cell responses is especially challenging, given genetic restriction, low responses observed in endemic areas, their variability over time, potential suppression by parasitaemia and the intrinsic variability of the assays. Methods: In Part A of this study, antibody titres were measured in adults from urban and rural communities in Ghana to recombinant Plasmodium falciparum CSP, SSP2/TRAP, LSA1, EXP1, MSP1, MSP3 and EBA175 by ELISA, and to sporozoites and infected erythrocytes by IFA. Positive ELISA responses were determined using two methods. T cell responses to defined CD8 or CD4 T cell epitopes from CSP, SSP2/TRAP, LSA1 and EXP1 were measured by ex vivo IFN-g ELISpot assays using HLA-matched Class I-and DR-restricted synthetic peptides. In Part B, the reproducibility of the ELISpot assay to CSP and AMA1 was measured by repeating assays of individual samples using peptide pools and low, medium or high stringency criteria for defining positive responses, and by comparing samples collected two weeks apart. Results: In Part A, positive antibody responses varied widely from 17%-100%, according to the antigen and statistical method, with blood stage antigens showing more frequent and higher magnitude responses. ELISA titres were higher in rural subjects, while IFA titres and the frequencies and magnitudes of ex vivo ELISpot activities were similar in both communities. DR-restricted peptides showed stronger responses than Class I-restricted peptides. In Part B, the most stringent statistical criteria gave the fewest, and the least stringent the most positive responses, with reproducibility slightly higher using the least stringent method when assays were repeated. Results varied significantly between the two-week time-points for many participants. Conclusions: All participants were positive for at least one malaria protein by ELISA, with results dependent on the criteria for positivity. Likewise, ELISpot responses varied among participants, but were relatively reproducible by the three methods tested, especially the least stringent, when assays were repeated. However, results often differed between samples taken two weeks apart, indicating significant biological variability over short intervals. C1 [Hollingdale, Michael R.; Geneshan, Harini; Abot, Esteban; Legano, Jennylyn; Banania, Glenna; Sayo, Renato; Epstein, Judith; Richie, Thomas L.; Sedegah, Martha] USN, US Mil Malaria Vaccine Program, Med Res Ctr, Silver Spring, MD 20910 USA. [Dodoo, Daniel; Anum, Dorothy; Koram, Kwadwo A.; Gyan, Ben; Akanmori, Bartholomew D.; Ocran, Josephine; Adu-Amankwah, Susan; Rogers, William O.] Univ Ghana, Noguchi Mem Inst Med Res, Legon, Ghana. [Akanmori, Bartholomew D.] WHO Reg Off Africa, Brazzaville, Congo. [Brambilla, Donald] RTI Rockville, Rockville, MD 20852 USA. [Kumar, Sanjai] US FDA, Ctr Biol Review & Res, Rockville, MD 20892 USA. [Rogers, William O.] Naval Med Res Unit 3, Cairo, Egypt. [Doolan, Denise L.] Queensland Inst Med Res, Brisbane, Qld 4006, Australia. RP Sedegah, M (reprint author), USN, US Mil Malaria Vaccine Program, Med Res Ctr, Silver Spring, MD 20910 USA. EM martha.sedegah@med.navy.mil RI Doolan, Denise/F-1969-2015; OI Richie, Thomas/0000-0002-2946-5456 FU U.S. Naval Medical Research Center [6000.RAD1.F.A0309]; National Institutes of Allergy and Infectious Diseases, National Institutes of Health [NO1 AI95363] FX The studies were supported by U.S. Naval Medical Research Center work unit number 6000.RAD1.F.A0309 and National Institutes of Allergy and Infectious Diseases, National Institutes of Health contract NO1 AI95363. We thank David Lanar and David Narum for the gift of recombinant P. falciparum proteins and John Arko-Mensah and Eric Kyei-Baafour for technical assistance. The study was approved by the Institutional Review Boards of the Noguchi Memorial Institute for Medical Research and the U.S. Naval Medical Research Center and conducted in accordance with the International Conference on Harmonisation (ICH), current Good Clinical Practices (cGCP), and U.S. Navy regulations (SECNAVINST 3900.39B) governing the use of human subjects in medical research. The views expressed herein are the personal ones of the authors and do not purport to reflect the views of the U.S. Navy, the Department of Defense, or the Food and Drug Administration. NR 66 TC 21 Z9 21 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1475-2875 J9 MALARIA J JI Malar. J. PD JUN 20 PY 2011 VL 10 AR 168 DI 10.1186/1475-2875-10-168 PG 18 WC Infectious Diseases; Parasitology; Tropical Medicine SC Infectious Diseases; Parasitology; Tropical Medicine GA 789LQ UT WOS:000292517400001 PM 21689436 ER PT J AU Coleman, CN Simon, SL Noska, MA Telfer, JL Bowman, T AF Coleman, C. Norman Simon, Steven L. Noska, Michael A. Telfer, Jana L. Bowman, Thomas TI Disaster Preparation: Lessons from Japan SO SCIENCE LA English DT Letter C1 [Coleman, C. Norman] NCI, Washington, DC 20201 USA. [Coleman, C. Norman] US Dept HHS, Off Preparedness & Emergency Operat, Washington, DC 20201 USA. [Simon, Steven L.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [Noska, Michael A.] US PHS, US FDA, Silver Spring, MD 20993 USA. [Telfer, Jana L.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Agcy Tox Subst & Dis Registry, Atlanta, GA 30341 USA. [Bowman, Thomas] Ctr Dis Control & Prevent, US Publ Hlth Serv, Div Strateg Natl Stockpile, Off Publ Hlth Preparedness & Response, Atlanta, GA 30329 USA. RP Coleman, CN (reprint author), NCI, 200 Independence Ave SW, Washington, DC 20201 USA. EM ccoleman@mail.nih.gov NR 0 TC 5 Z9 6 U1 0 U2 14 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 17 PY 2011 VL 332 IS 6036 BP 1379 EP 1379 PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 778FT UT WOS:000291689000018 PM 21680826 ER PT J AU Koturbash, I Zemp, FJ Pogribny, I Kovalchuk, O AF Koturbash, Igor Zemp, Franz J. Pogribny, Igor Kovalchuk, Olga TI Small molecules with big effects: The role of the microRNAome in cancer and carcinogenesis SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE MicroRNA; Cancer; Carcinogenesis; Genome instability ID CHRONIC LYMPHOCYTIC-LEUKEMIA; ACUTE MYELOID-LEUKEMIA; PAPILLARY THYROID-CARCINOMA; EMBRYONIC STEM-CELLS; HUMAN BREAST-CANCER; CONTROLS MELANOMA PROGRESSION; EPITHELIAL OVARIAN-CANCER; TARGET MESSENGER-RNAS; REAL-TIME PCR; PROSTATE-CANCER AB Small non-coding RNAs-microRNAs, are potent negative regulators of gene expression. MicroRNAs are involved in multiple biological processes, metabolic regulation, including cell proliferation, differentiation, and programmed cell death. Since the dysregulation of these processes is a hallmark of cancer, microRNAs can be viewed as major contributors to the pathogenesis of cancer, including initiation and progression of cancer. This review focuses on microRNA biogenesis and function, and their role in cancer, metastasis, drug resistance, and tumorigenesis. (C) 2010 Elsevier B.V. All rights reserved. C1 [Koturbash, Igor; Zemp, Franz J.; Kovalchuk, Olga] Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. [Pogribny, Igor] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca FU Alberta Cancer Research Institute; Canadian Institutes for Health Research; Canadian Breast Cancer Research Foundation-Prairies/NWT Chapter; NSERC; USA Department of Energy FX We are grateful to Valentina Titova and Diane Harms for proofreading this manuscript. Research in Olga Kovalchuk's laboratory was supported by the Alberta Cancer Research Institute, Canadian Institutes for Health Research, Canadian Breast Cancer Research Foundation-Prairies/NWT Chapter, NSERC and the USA Department of Energy Operating Grants. Olga Kovalchuk is a CIHR Chair in Gender and Health. NR 190 TC 58 Z9 62 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUN 17 PY 2011 VL 722 IS 2 SI SI BP 94 EP 105 DI 10.1016/j.mrgentox.2010.05.006 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 787DH UT WOS:000292356300002 PM 20472093 ER PT J AU Pogribny, IP Muskhelishvili, L Tryndyak, VP Beland, FA AF Pogribny, Igor P. Muskhelishvili, Levan Tryndyak, Volodymyr P. Beland, Frederick A. TI The role of epigenetic events in genotoxic hepatocarcinogenesis induced by 2-acetylaminofluorene SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Rat; Liver carcinogenesis; 2-Acetylaminofluorene; Epigenetics; microRNA ID TERM TAMOXIFEN EXPOSURE; TRANSFERASE P-FORM; HEPATOCELLULAR-CARCINOMA; DNA METHYLATION; TUMOR-SUPPRESSOR; RAT-LIVER; CHEMICAL HEPATOCARCINOGENESIS; HEPATIC PRENEOPLASIA; HUMAN-DISEASE; HUMAN CANCER AB It is well established that genotoxic reactivity of chemical carcinogens or their metabolites is a critical event in the initiation of tumorigenesis. However, the underlying mechanisms of events following initiation are less well understood, and with respect to genotoxic liver carcinogenesis, it is largely unknown how the initiated cells progress to form preneoplastic hepatic foci. In the present study, we investigated the underlying events associated with tumor-promoting activity of 2-acetylaminofluorene (2-AAF), a powerful complete genotoxic rat liver carcinogen. Male Sprague-Dawley rats were fed NIH-31 diet containing 0.02% of 2-AAF for 24 weeks, and the status of cytosine DNA methylation, histone methylation, and microRNA expression was determined in the livers of control and 2-AAF-fed rats. The results demonstrate that stages of multistage carcinogenesis following the initiation are driven primarily by carcinogen-induced epigenetic alterations. This was evidenced by altered global histone lysine methylation patterns, increased histone H3 lysine 9 and histone H3 lysine 27 trimethylation in the promoter regions of Rassf1a, p16(INK4a), Socs1, Cdh1, and Cx26 tumor suppressor genes, early Rassf1a and p16(INK4a) promoter CpG island hypermethylation, and altered microRNA expression in preneoplastic livers of rats exposed to 2-AAF. These changes were accompanied by dysregulation of the balance between cell proliferation and apoptosis, a fundamental pro-tumorigenic event in hepatocarcinogenesis. These results signify the fundamental role of epigenetic alterations in genotoxic liver carcinogenesis. Published by Elsevier B.V. C1 [Pogribny, Igor P.; Tryndyak, Volodymyr P.; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 57 TC 14 Z9 15 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUN 17 PY 2011 VL 722 IS 2 SI SI BP 106 EP 113 DI 10.1016/j.mrgentox.2010.02.011 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 787DH UT WOS:000292356300003 PM 20188851 ER PT J AU Sapsford, KE Tyner, KM Dair, BJ Deschamps, JR Medintz, IL AF Sapsford, Kim E. Tyner, Katherine M. Dair, Benita J. Deschamps, Jeffrey R. Medintz, Igor L. TI Analyzing Nanomaterial Bioconjugates: A Review of Current and Emerging Purification and Characterization Techniques SO ANALYTICAL CHEMISTRY LA English DT Review ID FIELD-FLOW FRACTIONATION; DYNAMIC LIGHT-SCATTERING; RESONANCE ENERGY-TRANSFER; FLUORESCENCE CORRELATION SPECTROSCOPY; ATOMIC-FORCE MICROSCOPY; SOLID LIPID NANOPARTICLES; WALLED CARBON NANOTUBES; X-RAY-SCATTERING; QUANTUM DOTS; GOLD NANOPARTICLES C1 [Sapsford, Kim E.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Tyner, Katherine M.] US FDA, Div Drug Safety Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Dair, Benita J.] US FDA, Div Chem & Mat Sci, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Deschamps, Jeffrey R.; Medintz, Igor L.] USN, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC 20375 USA. RP Sapsford, KE (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Kim.Sapsford@fda.hhs.gov; Igor.Medintz@nrl.navy.mil OI Deschamps, Jeffrey/0000-0001-5845-0010 FU NRL-NSI; ONR; DTRA; DARPA FX I.L.M. and K.E.S thank F. Ligler at NRL for initial encouragement. I.L.M. acknowledges the NRL-NSI, ONR, DTRA, and DARPA for financial support. K.E.S would like to thank Dr. T. Umbreit and Dr. B. Casey (FDA) for their helpful comments during the preparation of this manuscript. This paper reflects the current thinking and experience of the authors. No official support or endorsement by the U.S. Food and Drug Administration is intended or should be inferred. NR 261 TC 138 Z9 138 U1 7 U2 166 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 EI 1520-6882 J9 ANAL CHEM JI Anal. Chem. PD JUN 15 PY 2011 VL 83 IS 12 BP 4453 EP 4488 DI 10.1021/ac200853a PG 36 WC Chemistry, Analytical SC Chemistry GA 775YP UT WOS:000291499800008 PM 21545140 ER PT J AU Wen, K Li, GH Zhang, W Azevedo, MSP Saif, LJ Liu, FN Bui, T Yousef, A Yuan, LJ AF Wen, Ke Li, Guohua Zhang, Wei Azevedo, Marli S. P. Saif, Linda J. Liu, Fangning Bui, Tammy Yousef, Ahmed Yuan, Lijuan TI Development of gamma delta T cell subset responses in gnotobiotic pigs infected with human rotaviruses and colonized with probiotic lactobacilli SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE Gamma delta (gamma delta) T cells; Rotaviruses; Lactobacilli; Gnotobiotic pigs ID LACTIC-ACID BACTERIA; LYMPHOCYTE SUBPOPULATIONS; PERIPHERAL-BLOOD; DENDRITIC CELLS; VIRUS-INFECTION; IMMUNITY; DIARRHEA; TISSUES; VACCINE; GASTROENTERITIS AB gamma delta T cell responses are induced by various viral and bacterial infections. Different gamma delta T cells contribute to activation and regulation of the inflammatory response and to epithelial repair. How gamma delta T cells respond to rotavirus infection and how the colonization of probiotics influences the gamma delta T cell response were unknown. In this study, we evaluated by multicolor flow cytometry the frequencies and distribution of total gamma delta T cells and three major subsets (CD2-CD8-, CD2+CD8- and CD2+CD8+) in ileum, spleen and blood of gnotobiotic (Gn) pigs at early (3-5 days) and late phases (28 days) after rotavirus infection. The Gn pigs were inoculated with the virulent human rotavirus Wa strain and colonized with a mixture of two strains of probiotics Lactobacillus acidophilus and Lactobacillus reuteri. In naive pigs, the highest frequency of total gamma delta T cells was found in blood, followed by spleen and ileum at the early age (8-10 days old) whereas in older pigs (32 days of age) the highest frequency of total gamma delta T cells was found in ileum and spleen followed by blood. Rotavirus infection significantly increased frequencies of intestinal total gamma delta T cells and the putatively regulatory CD2+CD8+ gamma delta T cell subset and decreased frequencies of the putatively proinflammatory CD8- subsets in ileum, spleen and blood at post-infection days (PID) 3 or 5. The three gamma delta T cell subsets distributed and responded differently after rotavirus infection and/or lacto-bacilli colonization. The CD2+CD8+ subset contributed the most to the expansion of total gamma delta T cells after rotavirus infection in ileum because more than 77% of the total gamma delta T cells there were CD2+CD8+ cells. There was an additive effect between lactobacilli and rotavirus in inducing total gamma delta T cell expansion in ileum at PID 5. The overall effect of lactobacilli colonization versus rotavirus infection on frequencies of the CD2+CD8+ gamma delta T cell subset in ileum was similar; however, rotavirus-infected pigs maintained significantly higher frequencies of CD8- subsets in ileum than lactobacilli-colonized pigs. The dynamic gamma delta T cell responses suggest that gamma delta T cell subsets may play important roles in different stages of immune responses after rotavirus infection and probiotic colonization. The knowledge on the kinetics and distribution patterns of gamma delta T cell subsets in naive pigs and after rotavirus infection or lactobacilli colonization provides the foundation for further mechanistic studies of their functions. (C) 2011 Elsevier B.V. All rights reserved. C1 [Wen, Ke; Li, Guohua; Liu, Fangning; Bui, Tammy; Yuan, Lijuan] Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Blacksburg, VA 24061 USA. [Zhang, Wei; Saif, Linda J.] Ohio State Univ, Food Anim Hlth Res Program, Ohio Agr Res & Dev Ctr, Wooster, OH 44691 USA. [Azevedo, Marli S. P.] US FDA, Natl Ctr Toxicol Res, Div Microbiol HFT 250, Jefferson, AR 72079 USA. [Yousef, Ahmed] Ohio State Univ, Dept Food Sci & Technol, Coll Food Agr & Environm Sci, Columbus, OH 43210 USA. RP Yuan, LJ (reprint author), Virginia Polytech Inst & State Univ, Virginia Maryland Reg Coll Vet Med, Dept Biomed Sci & Pathobiol, Integrated Life Sci Bldg 0913,1981 Kraft Dr, Blacksburg, VA 24061 USA. EM lyuan@vt.edu RI Yuan, Lijuan/A-2468-2008; Yousef, Ahmed/E-4358-2011; Wen, Ke /K-7101-2013 OI Yuan, Lijuan/0000-0003-0709-5228; FU National Institutes of Health [R21AT002524, R01AT004789, R01AI033561]; Ohio Agricultural Research and Development Center, The Ohio State University [OHOA1208]; Virginia Tech FX We thank Dr. Juliette Hanson and Rich McCormick from The Ohio State University and Dr. Marlice Vonck, Dr. Kevin Pelzer, Pete Jobst, and Andrea Aman from TRACSS, Virginia Tech for animal care. We thank Ana Gonzalez and Melissa Makris for technical advice and assistance in flow cytometry and Dr. Inyoung Kim for assistance in statistic analysis. This work was supported in part by grants from the National Institutes of Health (R21AT002524 and R01AT004789 to LY and R01AI033561 to US), an internal grant from Ohio Agricultural Research and Development Center, The Ohio State University (OHOA1208) to LY, and the start-up fund from Virginia Tech to LY. NR 45 TC 10 Z9 10 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD JUN 15 PY 2011 VL 141 IS 3-4 BP 267 EP 275 DI 10.1016/j.vetimm.2011.03.016 PG 9 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 771EE UT WOS:000291139200011 PM 21489639 ER PT J AU Wang, PG Krynitsky, AJ AF Wang, Perry G. Krynitsky, Alexander J. TI Rapid determination of para-phenylenediamine by gas chromatography-mass spectrometry with selected ion monitoring in henna-containing cosmetic products SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Para-phenylenediamine; Henna tattoo products; GC/MS-SIM; 1,4-Phenylenediamine-2,3,5,6-d(4) ID P-PHENYLENEDIAMINE; DYE AB A rapid method for the determination of para-phenylenediamine (PPD) in cosmetic products, such as henna tattoos has been developed and evaluated. This analytical procedure involved extracting a 10 mg test portion of cosmetic product in 10 mL of ethyl acetate, followed by determination by gas chromatography-mass spectrometry in the selected ion monitoring mode (GC/MS-SIM). 1,4-Phenylenediamine-2,3,5,6-d(4) was selected as an internal standard that was added at the beginning of the extraction procedure and used to correct for recovery and matrix effects. The linearity ranged from 1.0 to 1275 mu g/mL with a coefficient of determination (r(2)) greater than 0.999. LOQ and LOD were 1.0 and 0.10 mu g/mL, respectively. The recovery in a tattoo product containing PPD was 94% and that for a tattoo product containing no PPD reached 105%. Extraction efficiency of 98% was obtained. This method has been successfully applied to henna temporary tattoo and other henna-related cosmetic products for the determination and quantitation of PPD. Published by Elsevier B.V. C1 [Wang, Perry G.; Krynitsky, Alexander J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Wang, PG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-717, College Pk, MD 20740 USA. EM Perry.Wang@fda.hhs.gov NR 9 TC 12 Z9 14 U1 0 U2 14 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 JUN 15 PY 2011 VL 879 IS 20 BP 1795 EP 1801 DI 10.1016/j.jchromb.2011.04.030 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 784RY UT WOS:000292177100011 PM 21606006 ER PT J AU Hung, HMJ Wang, SJ O'Neill, R AF Hung, H. M. James Wang, Sue-Jane O'Neill, Robert TI Flexible design clinical trial methodology in regulatory applications SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT 6th International Meeting on Statistical Methods in Biopharmacy CY SEP, 2009 CL Biopharm & Hlth Grp French Soc Stat, Paris, FRANCE HO Biopharm & Hlth Grp French Soc Stat DE adaptive patient selection; sample size planning; sample size reassessment; statistical bias ID SAMPLE-SIZE; VIEW AB Adaptive designs or flexible designs in a broader sense have increasingly been considered in planning pivotal registration clinical trials. Sample size reassessment design and adaptive selection design are two of such designs that appear in regulatory applications. At the design stage, consideration of sample size reassessment at an interim time of the trial should lead to extensive discussion about how to appropriately size the trial. Additionally, careful attention needs to be paid to the issue of how the size of the trial is impacted by the requirement that the final p-value of the trial meets the specific threshold of a clinically meaningful effect. These issues are not straightforward and will be discussed in this work. In a trial design that allows selection between a pre-specified patient subgroup and the initially planned overall patient population based on the accumulating data, there is an issue of what the 'overall' population means. In addition, it is critically important to know how such selection influences the validity of statistical inferences on the potentially modified overall population. This work presents the biases that may incur under adaptive patient selection designs. Copyright (C) 2011 John Wiley & Sons, Ltd. C1 [Hung, H. M. James] US FDA, Div Biometr 1, OB OTS, CDER, Silver Spring, MD 20994 USA. RP Hung, HMJ (reprint author), US FDA, Div Biometr 1, OB OTS, CDER, 10903 New Hampshire Ave,WO21,Room 4616, Silver Spring, MD 20994 USA. EM hsienming.hung@fda.hhs.gov NR 20 TC 11 Z9 11 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 15 PY 2011 VL 30 IS 13 SI SI BP 1519 EP 1527 DI 10.1002/sim.4021 PG 9 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 766UC UT WOS:000290811000005 PM 21344470 ER PT J AU Rump, LV Fischer, M Gonzalez-Escalona, N AF Rump, Lydia V. Fischer, Markus Gonzalez-Escalona, Narjol TI Prevalence, distribution and evolutionary significance of the IS629 insertion element in the stepwise emergence of Escherichia coli O157:H7 SO BMC MICROBIOLOGY LA English DT Article ID HEMORRHAGIC COLITIS; COMPLETE SEQUENCE; MULTIPLEX PCR; O157-H7; STRAINS; IDENTIFICATION; ANTIGEN AB Background: Insertion elements (IS) are known to play an important role in the evolution and genomic diversification of Escherichia coli O157:H7 lineages. In particular, IS629 has been found in multiple copies in the E. coli O157:H7 genome and is one of the most prevalent IS in this serotype. It was recently shown that the lack of O157 antigen expression in two O rough E. coli O157:H7 strains was due to IS629 insertions at 2 different locations in the gne gene that is essential for the O antigen biosynthesis. Results: The comparison of 4 E. coli O157:H7 genome and plasmid sequences showed numerous IS629 insertion sites, although not uniformly distributed among strains. Comparison of IS629s found in O157:H7 and O55:H7 showed the presence of at least three different IS629 sub-types. O157:H7 strains carry IS629 elements sub-type I and III whereby the ancestral O55:H7 carries sub-type II. Analysis of strains selected from various clonal groups defined on the E. coli O157:H7 stepwise evolution model showed that IS629 was not observed in sorbitol fermenting O157 (SFO157) clones that are on a divergent pathway in the emergence of O157:H7. This suggests that the absence of IS629 in SFO157 strains probably occurred during the divergence of this lineage, albeit it remains uncertain if it contributed, in part, to their divergence from other closely related strains. Conclusions: The highly variable genomic locations of IS629 in O157:H7 strains of the A6 clonal complex indicates that this insertion element probably played an important role in genome plasticity and in the divergence of O157:H7 lineages. C1 [Rump, Lydia V.; Gonzalez-Escalona, Narjol] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Rump, Lydia V.; Fischer, Markus] Univ Hamburg, Inst Food Chem, Hamburg, Germany. RP Rump, LV (reprint author), US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Lydiarump@gmail.com RI Fischer, Markus/G-9477-2012; OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU Oak Ridge Associated Universities; FDA FX The authors thank Eric W. Brown for his helpful comments. This project was supported by an appointment to LVR through the Research Fellowship Program for the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Associated Universities through a contract with the FDA. NR 33 TC 7 Z9 7 U1 0 U2 7 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 JUN 14 PY 2011 VL 11 AR 133 DI 10.1186/1471-2180-11-133 PG 13 WC Microbiology SC Microbiology GA 795XL UT WOS:000293012200001 PM 21672218 ER PT J AU Hicks, KA Stockbridge, NL Targum, SL Temple, RJ AF Hicks, Karen A. Stockbridge, Norman L. Targum, Shari L. Temple, Robert J. TI Bleeding Academic Research Consortium Consensus Report The Food and Drug Administration Perspective SO CIRCULATION LA English DT Editorial Material DE Editorials; hemorrhage C1 [Hicks, Karen A.] US FDA, Div Cardiovasc & Renal Prod, Off Drug Evaluat 1, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Hicks, KA (reprint author), US FDA, Div Cardiovasc & Renal Prod, Off Drug Evaluat 1, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 4182, Silver Spring, MD 20993 USA. EM karen.hicks@fda.hhs.gov NR 1 TC 13 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 14 PY 2011 VL 123 IS 23 BP 2664 EP 2665 DI 10.1161/CIRCULATIONAHA.111.032433 PG 2 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 776PZ UT WOS:000291550600008 PM 21670240 ER PT J AU Sharma, D Fang, Y Zafar, F Karim, KS Badano, A AF Sharma, Diksha Fang, Yuan Zafar, Fahad Karim, Karim S. Badano, Aldo TI Recombination models for spatio-temporal Monte Carlo transport of interacting carriers in semiconductors SO APPLIED PHYSICS LETTERS LA English DT Article ID AMORPHOUS SELENIUM; PHOTOGENERATION; DETECTORS AB When the secondary electron generated from an x-ray interaction within a photoconductor deposits energy, clouds of charge carriers (electron-hole pairs) with random spatial and energy distributions are created. Even under high electric field bias, a fraction of the carriers recombine affecting the detection statistics. We propose and compare modeling approaches for recombination including a nearest-neighbor model (NN) and a first-hit model (FH) that recombines the first pair from the vector of candidate carriers. We find that the mean of the NN model correlates with the mean of the FH model but differs for individual clouds. (C) 2011 American Institute of Physics. [doi:10.1063/1.3599602] C1 [Sharma, Diksha; Fang, Yuan; Zafar, Fahad; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Fang, Yuan; Karim, Karim S.] Univ Waterloo, Dept Elect & Comp Engn, Waterloo, ON N2L 3G1, Canada. [Zafar, Fahad] Univ Maryland Baltimore Cty, Dept Comp Sci, Baltimore, MD 21228 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU Research Participation Program; Carl A. Pollock postgraduate fellowship award FX The authors are thankful to Andreu Badal and Christian Graff (CDRH/FDA) for their comments and suggestions. Y. Fang and F. Zafar were funded by the Research Participation Program administered by ORISE through an interagency agreement between DOE and FDA. This work was also supported in part (Y.F.) by the Carl A. Pollock postgraduate fellowship award. The mention of commercial products herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 15 TC 5 Z9 5 U1 0 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 0003-6951 J9 APPL PHYS LETT JI Appl. Phys. Lett. PD JUN 13 PY 2011 VL 98 IS 24 AR 242111 DI 10.1063/1.3599602 PG 3 WC Physics, Applied SC Physics GA 779SZ UT WOS:000291803600045 ER PT J AU Buehler, PW Butt, OI D'Agnillo, F AF Buehler, Paul W. Butt, Omer I. D'Agnillo, Felice TI Sodium nitrite induces acute central nervous system toxicity in guinea pigs exposed to systemic cell-free hemoglobin SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Hemolysis; Hemoglobin; Nitric oxide; Neurotoxicity; Oxidative stress; Blood-brain barrier ID OXIDATIVE STRESS; NEURONAL MARKER; BRAIN; DISEASE; RAT; DYSFUNCTION; EXCHANGE; THERAPY; KINASE; FLOW AB Systemic cell-free hemoglobin (Hb) released via hemolysis disrupts vascular homeostasis, in part, through the scavenging of nitric oxide (NO). Sodium nitrite (NaNO(2)) therapy can attenuate the hypertensive effects of Hb. However, the chemical reactivity of NaNO(2) with Hb may enhance heme- or iron-mediated toxicities. Here, we investigate the effect of NaNO(2) on the central nervous system (CNS) in guinea pigs exposed to systemic cell-free Hb. Intravascular infusion of NaNO(2), at doses sufficient to alleviate Hb-mediated blood pressure changes, reduced the expression of occludin, but not zona occludens-1 (ZO-1) or claudin-5, in cerebral tight junctions 4 h after Hb infusion. This was accompanied by increased perivascular heme oxygenase-1 expression, neuronal iron deposition, increased astrocyte and microglial activation, and reduced expression of neuron-specific nuclear protein (NeuN). These CNS changes were not observed in animals treated with Hb or NaNO(2) alone. Taken together, these findings suggest that the use of nitrite salts to treat systemic Hb exposure may promote acute CNS toxicity. Published by Elsevier Inc. C1 [Buehler, Paul W.; Butt, Omer I.; D'Agnillo, Felice] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP D'Agnillo, F (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, 29 Lincoln Dr,Bldg 29,Rm 129, Bethesda, MD 20892 USA. EM felice.dagnillo@fda.hhs.gov FU CBER/FDA FX This work was supported by a Critical Path Initiative award from CBER/FDA (F.D. and P.W.B.). NR 30 TC 4 Z9 4 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 10 PY 2011 VL 409 IS 3 BP 412 EP 417 DI 10.1016/j.bbrc.2011.05.009 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 783CQ UT WOS:000292059500010 PM 21575599 ER PT J AU Pantchenko, OS Seidman, SJ Guag, JW Witters, DM Sponberg, CL AF Pantchenko, Oxana S. Seidman, Seth J. Guag, Joshua W. Witters, Donald M., Jr. Sponberg, Curt L. TI Electromagnetic compatibility of implantable neurostimulators to RFID emitters SO BIOMEDICAL ENGINEERING ONLINE LA English DT Article AB Background: The objective of this study is to investigate electromagnetic compatibility (EMC) of implantable neurostimulators with the emissions from radio frequency identification (RFID) emitters. Methods: Six active implantable neurostimulators with lead systems were tested for susceptibility to electromagnetic fields generated by 22 RFID emitters. These medical devices have been approved for marketing in the U. S. for a number of intended uses that include: epilepsy, depression, incontinence, Parkinsonian tremor and pain relief. Each RFID emitter had one of the following carrier frequencies: 125 kHz, 134 kHz, 13.56 MHz, 433 MHz, 915 MHz and 2.45 GHz Results: The test results showed the output of one of the implantable neurostimulators was inhibited by 134 kHz RFID emitter at separation distances of 10 cm or less. The output of the same implantable neurostimulator was also inhibited by another 134 kHz RFID emitter at separation distances of 10 cm or less and also showed inconsistent pulsing rate at a separation distance of 15 cm. Both effects occurred during and lasted through out the duration of the exposure. Conclusions: The clinical significance of the effects was assessed by a clinician at the U. S. Food and Drug Administration. The effects were determined to be clinically significant only if they occurred for extended period of time. There were no observed effects from the other 5 implantable neurostimulators or during exposures from other RFID emitters. C1 [Pantchenko, Oxana S.; Seidman, Seth J.; Guag, Joshua W.; Witters, Donald M., Jr.] US FDA, Silver Spring, MD 20993 USA. [Pantchenko, Oxana S.] Univ Calif Santa Cruz, Baskin Sch Engn, Santa Cruz, CA 95064 USA. [Sponberg, Curt L.] Medtron Neuromodulat, Minneapolis, MN 55432 USA. RP Pantchenko, OS (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Oxana.S.Pantchenko@gmail.com NR 12 TC 10 Z9 10 U1 1 U2 6 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 JUN 9 PY 2011 VL 10 AR 50 DI 10.1186/1475-925X-10-50 PG 10 WC Engineering, Biomedical SC Engineering GA 792GW UT WOS:000292730600001 PM 21658266 ER PT J AU Self, RL Wu, WH Marks, HS AF Self, Randy L. Wu, Wen-Hsin Marks, Heidi S. TI Simultaneous Quantification of Eight Biogenic Amine Compounds in Tuna by Matrix Solid-Phase Dispersion followed by HPLC-Orbitrap Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE biogenic amine; matrix solid-phase dispersion; LC-MS; orbitrap; tuna ID LIQUID-CHROMATOGRAPHIC DETERMINATION; PRECOLUMN DERIVATIZATION; HISTAMINE; FRESH; EXTRACTION; STORAGE; CHEESE; BEER; MS AB A method for the extraction of agmatine, cadaverine, histamine, phenyethylamine, putrescine, tryptamine, tyramine, and urocanic acid from canned tuna and frozen tuna loin matrices by matrix solid-phase dispersion, followed by separation and quantification of these compounds by ultrahigh-performance hydrophilic interaction chromatography (UHPLC-HILIC) with orbitrap mass spectrometric detection, is described. Tuna samples are dispersed in a CN-silica sorbent and eluted with a mixture of aqueous ammonium formate buffer and acetonitrile. Separation and detection are carried out on an Agilent 1200 high-performance liquid chromatograph coupled to a Thermo Exactive orbitrap mass spectrometer, and metformin is used as the internal standard. Spike recoveries are determined across a range of 20-100 ppm for each compound, and the method is validated with respect to linearity, reproducibility, accuracy, and limits of quantitation and detection. The method is demonstrated to be suitable for use in quantifying these target compounds in the studied matrices. C1 [Self, Randy L.; Wu, Wen-Hsin; Marks, Heidi S.] US FDA, Appl Technol Ctr, Pacific Reg Lab NW, Off Regulatory Affairs, Bothell, WA 98021 USA. RP Wu, WH (reprint author), US FDA, Appl Technol Ctr, Pacific Reg Lab NW, Off Regulatory Affairs, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM cindy.wu@fda.hhs.gov NR 34 TC 24 Z9 26 U1 5 U2 49 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD JUN 8 PY 2011 VL 59 IS 11 BP 5906 EP 5913 DI 10.1021/jf200455r PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 770GJ UT WOS:000291074700016 PM 21534596 ER PT J AU Ren, DB Yu, SQ Gao, S Peng, DX Petralia, RS Muszynski, A Carlson, RW Robbins, JB Tsai, CM Lim, DJ Gu, XX AF Ren, Dabin Yu, Shengqing Gao, Song Peng, Daxin Petralia, Ronald S. Muszynski, Artur Carlson, Russell W. Robbins, John B. Tsai, Chao-Ming Lim, David J. Gu, Xin-Xing TI Mutant lipooligosaccharide-based conjugate vaccine demonstrates a broad-spectrum effectiveness against Moraxella catarrhalis SO VACCINE LA English DT Article DE Moraxella catarrhalis; Lipooligosaccharide mutant; Conjugate vaccine; Cross-reactivity; Conserved antigen ID OUTER-MEMBRANE PROTEIN; BRANHAMELLA-CATARRHALIS; PULMONARY CLEARANCE; SEROTYPE-A; DETOXIFIED LIPOOLIGOSACCHARIDE; LIPOPOLYSACCHARIDE ANTIGENS; IMMUNOLOGICAL-PROPERTIES; MUCOSAL PATHOGENS; MOLECULAR MIMICRY; OTITIS-MEDIA AB There is no licensed vaccine available against Moraxella catarrhalis, an exclusive human pathogen responsible for otitis media in children and respiratory infections in adults. We previously developed conjugate vaccine candidates based on lipooligosaccharides (LOSs) of M. catarrhalis serotypes A, B, and C, each of which was shown to cover a portion of the clinical strains. To generate conserved LOS antigens and eliminate a potential autoimmune response to a similar epitope between M. catarrhalis LOS moiety Gal alpha 1-4Gal beta 1-4Glc and human P(k) antigen, two LOS mutants from strain O35E were constructed. Mutant O35Elgt5 or O35EgalE revealed a deletion of one or two terminal galactose residues of wild type O35E LOS. Each LOS molecule was purified, characterized, detoxified, and coupled to tetanus toxoid (IT) to form conjugates, namely dLOS-TT. Three subcutaneous immunizations using dLOS-TT from O35Elgt5 or O35EgalE elicited significant increases (a 729- or 1263-fold above the preimmune serum levels) of serum immunoglobulin (Ig)G against O35E LOS in rabbits with an adjuvant or without an adjuvant (an 140- or 140-fold above the preimmune serum levels). Rabbit antisera demonstrated elevated complement-mediated bactericidal activities against the wild type strain O35E. The rabbit sera elicited by O35Elgt5 dLOS-TT were further examined and showed cross bactericidal activity against all additional 19 M. catarrhalis strains and clinical isolates studied. Moreover, the rabbit sera displayed cross-reactivity not only among three serotype strains but also clinical isolates in a whole-cell enzyme-linked immunosorbent assay (ELISA), which was further confirmed under transmission electron microscopy. In conclusion, O35Elgt5 dLOs-TT may act as a vaccine against most M. catarrhalis strains and therefore can be used for further in vivo efficacy studies. Published by Elsevier Ltd. C1 [Ren, Dabin; Yu, Shengqing; Gao, Song; Peng, Daxin; Gu, Xin-Xing] Natl Inst Deafness & Other Commun Disorders NIDCD, Vaccine Res Sect, NIH, Rockville, MD 20850 USA. [Petralia, Ronald S.] NIDCD, Sect Neurotransmitter Receptor Biol, NIH, Bethesda, MD 20892 USA. [Muszynski, Artur; Carlson, Russell W.] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. [Robbins, John B.] NICHHD, NIH, Bethesda, MD 20892 USA. [Tsai, Chao-Ming] US FDA, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. [Lim, David J.] House Ear Res Inst, Sect Pathogenesis Ear Dis, Los Angeles, CA 90057 USA. RP Gu, XX (reprint author), NIH, 6610 Rockledge Dr,Room 3200, Bethesda, MD 20817 USA. EM guxx@mail.nih.gov RI Ren, Dabin/H-6263-2013; OI Muszynski, Artur/0000-0003-3497-9977 FU National Institute on Deafness and Other Communication Disorders (NIDCD), NIH FX We are grateful to Eric J. Hansen at University of Texas, Dallas, TX and Goro Mogi (deceased) at Oita Medical University, Oita, Japan for providing strains. We thank Anup Datta at Glycobiology Research and Training Center, University of California, San Diego, La Jolla, California for the composition and structure analyses of LOSs. We thank the NIH Fellows Editorial Board for carefully reviewing and providing critical comments during the preparation of the manuscript. This research was supported by the Intramural Research Program of the National Institute on Deafness and Other Communication Disorders (NIDCD), NIH. NR 44 TC 10 Z9 10 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JUN 6 PY 2011 VL 29 IS 25 BP 4210 EP 4217 DI 10.1016/j.vaccine.2011.03.102 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 779KY UT WOS:000291777700008 PM 21501641 ER PT J AU Goncalves, R Zhang, X Cohen, H Debrabant, A Mosser, DM AF Goncalves, Ricardo Zhang, Xia Cohen, Heather Debrabant, Alain Mosser, David M. TI Platelet activation attracts a subpopulation of effector monocytes to sites of Leishmania major infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID CHEMOATTRACTANT PROTEIN-1 MCP-1; HUMAN PERIPHERAL-BLOOD; INFLAMMATORY MONOCYTES; DENDRITIC CELLS; ENDOTHELIAL-CELLS; HUMAN-FIBROBLASTS; GENE-EXPRESSION; SAND FLIES; RECRUITMENT; SECRETION AB Leishmania species trigger a brisk inflammatory response and efficiently induce cell-mediated immunity. We examined the mechanisms whereby leukocytes were recruited into lesions after Leishmania major infection of mice. We found that a subpopulation of effector monocytes expressing the granulocyte marker GR1 (Ly6C) is rapidly recruited into lesions, and these monocytes efficiently kill L. major parasites. The recruitment of this subpopulation of monocytes depends on the chemokine receptor CCR2 and the activation of platelets. Activated platelets secrete platelet-derived growth factor, which induces the rapid release of CCL2 from leukocytes and mesenchymal cells. This work points to a new role for platelets in host defense involving the selective recruitment of a subpopulation of effector monocytes from the blood to efficiently kill this intracellular parasite. C1 [Goncalves, Ricardo; Zhang, Xia; Cohen, Heather; Mosser, David M.] Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20782 USA. [Goncalves, Ricardo; Zhang, Xia; Cohen, Heather; Mosser, David M.] Univ Maryland, Maryland Pathogen Res Inst, College Pk, MD 20782 USA. [Debrabant, Alain] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Mosser, DM (reprint author), Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20782 USA. EM dmosser@umd.edu RI Zhang, Xia/B-8152-2008; Mosser, David/I-6697-2016 OI Zhang, Xia/0000-0002-9040-1486; Mosser, David/0000-0002-9503-4187 FU National Institutes of Health [AI49383] FX This work was supported in part by National Institutes of Health grant AI49383. NR 57 TC 41 Z9 41 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 6 PY 2011 VL 208 IS 6 BP 1253 EP 1265 DI 10.1084/jem.20101751 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 774ZB UT WOS:000291424200012 PM 21606505 ER PT J AU Silva, R Moir, S Kardava, L Debell, K Simhadri, VR Ferrando-Martinez, S Leal, M Pena, J Coligan, JE Borrego, F AF Silva, Rodolfo Moir, Susan Kardava, Lela Debell, Karen Simhadri, Venkateswara R. Ferrando-Martinez, Sara Leal, Manuel Pena, Jose Coligan, John E. Borrego, Francisco TI CD300a is expressed on human B cells, modulates BCR-mediated signaling, and its expression is down-regulated in HIV infection SO BLOOD LA English DT Article ID RECEPTOR IRP60 CD300A; INHIBITORY RECEPTOR; PERIPHERAL-BLOOD; NK CELLS; INDIVIDUALS; DISEASE; NEF; SUPERFAMILY; ACTIVATION; DYSREGULATION AB The immunomodulatory receptor CD300a is expressed on human B cells. Naive B cells express very low levels of this receptor, whereas memory B cells and plasmablasts/cells express variable levels of CD300a. Germinal center B cells are negative for CD300a expression. Stimulation of naive B cells via B-cell receptor (BCR) and Toll-like receptor 9, along with T-cell help, failed to up-regulate CD300a cell surface expression despite the increased expression of the memory marker CD27 and the down-regulation of CD305. However, Toll-like receptor 9 stimulation alone significantly increased CD300a expression on memory B cells, whereas interleukin-4 and transforming growth factor-beta 1 act as negative regulators of CD300a expression on memory B cells. Coligation of BCR and CD300a inhibits Ca(2+) mobilization and nuclear factor of activated T cell transcriptional activity evoked by BCR ligation alone. Suppression of CD300a expression in primary B cells with siRNA resulted in increased BCR-mediated proliferation, thereby con-firming the inhibitory capacity of CD300a. Finally, we show that CD300a expression levels are significantly down-regulated in the circulating B cells of HIV-infected patients. Altogether, these data demonstrate a novel mechanism for suppressing the activity of B cells and suggest a potential role for CD300a in the B-cell dysfunction observed in HIV-induced immunodeficiency. (Blood. 2011; 117(22): 5870-5880) C1 [Debell, Karen; Simhadri, Venkateswara R.; Borrego, Francisco] US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, OBP,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Silva, Rodolfo; Coligan, John E.] NIAID, Receptor Cell Biol Sect, Immunogenet Lab, NIH, Rockville, MD USA. [Moir, Susan; Kardava, Lela] NIAID, Immunopathogenesis Sect, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. [Ferrando-Martinez, Sara; Leal, Manuel] Virgen Rocio Univ Hosp, Infect Dis Serv, Lab Immunovirol, Biomed Inst Seville, Seville, Spain. [Pena, Jose] Hosp Reina Sofia, Serv Immunol, Cordoba, Spain. RP Borrego, F (reprint author), US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, OBP,Ctr Drug Evaluat & Res, Bldg 29B,Rm 3NN18,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Francisco.Borrego@fda.hhs.gov RI Leal, Manuel/C-8458-2015; IBIS, INMUNOVIROLOGI/O-9246-2015 FU Food and Drug Administration; National Institute of Allergy and Infectious Diseases; Redes Tematicas de Investigacion en SIDA, Spain [ISCIII RETIC RD06/0006/0021]; Fondo de Investigaciones Sanitarias, Spain [PS09/00424] FX This work was supported by the Food and Drug Administration (intramural program), the National Institute of Allergy and Infectious Diseases (intramural program), the Redes Tematicas de Investigacion en SIDA (grant ISCIII RETIC RD06/0006/0021), Spain, and Fondo de Investigaciones Sanitarias (PS09/00424), Spain. NR 51 TC 22 Z9 23 U1 0 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 2 PY 2011 VL 117 IS 22 BP 5870 EP 5880 DI 10.1182/blood-2010-09-310318 PG 11 WC Hematology SC Hematology GA 772BA UT WOS:000291203200015 PM 21482706 ER PT J AU Omeir, RL Teferedegne, B Foseh, GS Beren, JJ Snoy, PJ Brinster, LR Cook, JL Peden, K Lewis, AM AF Omeir, Romelda L. Teferedegne, Belete Foseh, Gideon S. Beren, Joel J. Snoy, Philip J. Brinster, Lauren R. Cook, James L. Peden, Keith Lewis, Andrew M., Jr. TI Heterogeneity of the Tumorigenic Phenotype Expressed by Madin-Darby Canine Kidney Cells SO COMPARATIVE MEDICINE LA English DT Article ID EPITHELIAL-MESENCHYMAL TRANSITIONS; MDCK CELLS; MODEL SYSTEM; TUMOR-CELLS; LINE MDCK; IN-VITRO; TRANSFORMATION; GROWTH; NUDE; TISSUE AB The mechanisms by which cells spontaneously immortalized in tissue culture develop the capacity to form tumors in vivo likely embody fundamental processes in neoplastic development. The evolution of Madin-Darby canine kidney (MDCK) cells from presumptively normal kidney cells to immortalized cells that become tumorigenic represents an example of neoplastic development in vitro. Studies of the mechanisms by which spontaneously immortalized cells develop the capacity to form tumors would benefit from quantitative in vivo assays. Most mechanistic correlations are evaluated by using single-dose tumor-induction experiments, which indicate only whether cells are or are not tumorigenic. Here we used quantitative tumorigenicity assays to measure dose- and time-dependent tumor development in nude mice of 3 lots of unmodified MDCK cells. The results revealed lot-to-lot variations in the tumorigenicity of MDCK cells, which were reflected by their tumor-inducing efficiency (threshold cell dose represented by mean tumor-producing dose; log(10) 50% endpoints of 5.2 for vial 1 and 4.4 for vial 2, and a tumor-producing dose of 5.8 for vial 3) and mean tumor latency (vial 1, 6.6 wk; vial 2, 2.9 wk; and vial 3, 3.8 wk). These studies provide a reference for further characterization of the MDCK cell neoplastic phenotype and may be useful in delineating aspects of neoplastic development in vitro that determine tumor-forming capacity. Such data also are useful when considering MDCK cells as a reagent for vaccine manufacture. C1 [Omeir, Romelda L.; Teferedegne, Belete; Foseh, Gideon S.; Peden, Keith; Lewis, Andrew M., Jr.] US FDA, Div Viral Prod, Off Vaccines Res & Review, Bethesda, MD 20014 USA. [Beren, Joel J.; Snoy, Philip J.] US FDA, Div Vet Serv, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Brinster, Lauren R.] NIH, Div Vet Resources, Bethesda, MD 20892 USA. [Cook, James L.] Univ Illinois, Dept Med, Sect Infect Dis Immunol & Int Med, Chicago, IL USA. RP Lewis, AM (reprint author), US FDA, Div Viral Prod, Off Vaccines Res & Review, Bethesda, MD 20014 USA. EM andrew.lewis@fda.hhs.gov FU Division of Microbiology and Infectious Diseases of the National Institute of Allergy and Infectious Diseases; University of Illinois at Chicago FX This research was supported in part 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 and by the support of the James A and Marion C Grant Fund at the University of Illinois at Chicago. NR 40 TC 13 Z9 13 U1 0 U2 3 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 1532-0820 J9 COMPARATIVE MED JI Comparative Med. PD JUN PY 2011 VL 61 IS 3 BP 243 EP 250 PG 8 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 915QQ UT WOS:000302042900008 PM 21819694 ER PT J AU Boyd, SD AF Boyd, Sarita D. TI Management of HIV infection in treatment-naive patients: A review of the most current recommendations SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Review DE Antiretroviral agents; Atazanavir; Combined therapy; Darunavir; Department of Health and Human Services; Dosage; Efavirenz; Emtricitabine; HIV infections; Mechanism of action; Protocols; Quality of life; Raltegravir; Ritonavir; Tenofovir; Toxicity ID ACTIVE ANTIRETROVIRAL THERAPY; REVERSE-TRANSCRIPTASE INHIBITORS; ONCE-DAILY DARUNAVIR/RITONAVIR; HIV-1-INFECTED PATIENTS; COLLABORATIVE ANALYSIS; MYOCARDIAL-INFARCTION; COMBINATION THERAPY; HETEROSEXUAL TRANSMISSION; RESISTANCE MUTATIONS; PROTEASE INHIBITORS AB Purpose. The most current guidelines issued by the Department of Health and Human Services (DHHS) on the management of human immunodeficiency virus (HIV) infection in treatment-naive patients are reviewed. Summary. Treatment guidelines are updated frequently because of the emergence of data demonstrating the risks and benefits of antiretroviral therapy. The DHHS guidelines strongly recommend initiating therapy in patients with certain conditions regardless of CD4 cell count and in patients with CD4 cell counts of <350 cells/mm(3). Although supporting data are less definitive, treatment is also recommended for patients with CD4 cell counts of 350-500 cells/mm(3). Treatment for patients with CD4 cell counts of >500 cells/mm3 is controversial. Although cumulative observational data and biological evidence support treatment it higher CD4 cell counts, randomized controlled trial data to support this are not available, and the risk of antiretroviral toxicities, resistance, non-adherence, and cost should be considered in individual patients. The preferred regimens have been consolidated to four options, including a dual-nucleoside reverse transcriptase inhibitor backbone (tenofovir plus emtricitabine) with a nonnucleoside reverse transcriptase inhibitor (efavirenz), a ritonavir-boosted protease inhibitor (atazanavir plus ritonavir or darunavir plus ritonavir), or an integrase strand-transfer inhibitor (raltegravir). Regimens are classified as alternative or acceptable when they have potential safety or efficacy concerns, have higher pill burdens, or require more-frequent administration compared with preferred regimens. Conclusion. The DHHS 2011 guidelines advocate earlier antiretroviral therapy initiation than recommended in recent years, and preferred regimens have been refined to maximize efficacy, safety, and quality of life for treatment-naive HIV-infected patients. C1 [Boyd, Sarita D.] US FDA, Off Safety & Epidemiol, Silver Spring, MD 20993 USA. [Boyd, Sarita D.] NIAID, SAIC Frederick, Div Clin Res, NIH, Frederick, MD USA. RP Boyd, SD (reprint author), US FDA, Off Safety & Epidemiol, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sarita.boyd@fda.hhs.gov FU National Cancer Institute, National Institutes of Health [HHSN261200800001E] FX Funded in whole or in part with federal funds from the National Cancer Institute, National Institutes of Health, under contract no. HHSN261200800001E. NR 76 TC 11 Z9 13 U1 0 U2 4 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 JUN 1 PY 2011 VL 68 IS 11 BP 991 EP 1001 DI 10.2146/ajhp100156 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 858CK UT WOS:000297773300008 PM 21593227 ER PT J AU Hoffman, MT Duan, Y Zhou, L Stocks, I Hall, D AF Hoffman, M. T. Duan, Y. Zhou, L. Stocks, I. Hall, D. TI Is the striped mealybug, Ferrisia virgata, a vector of huanglongbing bacterium Candidatus Liberibacter asiaticus? SO PHYTOPATHOLOGY LA English DT Meeting Abstract C1 [Hoffman, M. T.; Duan, Y.; Hall, D.] ARS, USDA, USHRL, Ft Pierce, FL USA. [Zhou, L.] Univ Florida, IFAS IRREC, Ft Pierce, FL USA. [Stocks, I.] FDACS DPI, Gainesville, FL USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD JUN PY 2011 VL 101 IS 6 SU S BP S73 EP S73 PG 1 WC Plant Sciences SC Plant Sciences GA 822KR UT WOS:000295045400427 ER PT J AU Kong, H Roberts, D Patterson, C Kuehn, S Heeb, S Lakshman, D Lydon, J AF Kong, H. Roberts, D. Patterson, C. Kuehn, S. Heeb, S. Lakshman, D. Lydon, J. TI Role of rsmA in virulence of phytotoxin-producing pathovars of Pseudomonas syringae SO PHYTOPATHOLOGY LA English DT Meeting Abstract C1 [Kong, H.] US FDA, Rockville, MD 20857 USA. [Roberts, D.; Patterson, C.; Lakshman, D.] USDA Sustainable Agr Syst Lab, Beltsville, MD USA. [Kuehn, S.; Heeb, S.] Univ Nottingham, Sch Mol Med Sci, Nottingham NG7 2RD, England. [Lydon, J.] USDA Natl Program Staff, Beltsville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 4 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD JUN PY 2011 VL 101 IS 6 SU S BP S93 EP S93 PG 1 WC Plant Sciences SC Plant Sciences GA 822KR UT WOS:000295045400545 ER PT J AU Furusawa, J Zhang, HH Vural, E Stone, A Fukuda, S Oridate, N Fang, H Ye, YB Suen, JY Fan, CY AF Furusawa, Jun Zhang, Haihong Vural, Emre Stone, Annjanette Fukuda, Satoshi Oridate, Nobuhiko Fang, Hong Ye, Yanbin Suen, James Y. Fan, Chun-Yang TI Distinct Epigenetic Profiling in Head and Neck Squamous Cell Carcinoma Stem Cells SO OTOLARYNGOLOGY-HEAD AND NECK SURGERY LA English DT Article DE DNA methylation; carcinoma stem cells; head and neck squamous cell carcinoma ID EXPRESSION AB Objective. To identify unique epigenetic signature in cancer stem cells (CSCs) in head and neck squamous cell carcinoma (HNSCC). Study Design. Molecular and microarray studies. Setting. Tertiary referral center. Subjects and Methods. Head and neck CSCs were isolated in HNSCC cells by CD44 staining and flow cytometry sorting. CSCs with highest CD44 expression (CD44(hi)) and non-stem cells (non-SCs) with lowest CD44 expression (CD44(low)) were then characterized for stemness gene expression and their responses to chemotherapeutic agents, followed by high-throughput epigenetic profiling using the Illumina Bead-Chip Array, targeting 28,544 CpG sites covering more than 14,956 genes. Results. CD44(hi) CSCs expressed higher levels of stem cell markers and were more resistant to chemotherapeutic agents as compared to CD44(low) non-SCs. By DNA methylation microarray analysis, 17 hypomethylated and 9 hypermethylated genes were identified in CD44(hi) CSCs as compared to non-SCs in most HNSCC cell lines. Cluster analysis using these 26 genes showed that CD44(hi) CSCs were epigenetically distinct from the CD44(low) non-SCs in all 5 HNSCC cell lines. Conclusion. A unique epigenetic profile consisting of 17 hypomethylated and 9 hypermethylated genes was seen in HNSCC CSCs. These genes may be critically required in maintaining the stemness or pluripotency of CSCs and may represent novel molecular targets for anticancer therapies aimed at eradicating CSCs in HNSCC. C1 [Zhang, Haihong; Fan, Chun-Yang] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. [Furusawa, Jun; Fukuda, Satoshi; Oridate, Nobuhiko] Hokkaido Univ, Dept Otolaryngol Head & Neck Surg, Grad Sch Med, Sapporo, Hokkaido, Japan. [Vural, Emre; Suen, James Y.] Univ Arkansas Med Sci, Dept Otolaryngol Head & Neck Surg, Little Rock, AR 72205 USA. [Fan, Chun-Yang] Cent Arkansas Vet Healthcare Syst, Dept Pathol, Little Rock, AR 72205 USA. [Fang, Hong; Ye, Yanbin] US FDA, Z Tech Corp, Natl Ctr Toxicol Res NCTR, Jefferson, AR USA. RP Fan, CY (reprint author), Univ Arkansas Med Sci, Dept Pathol, 4300 W 7th St,113-LR, Little Rock, AR 72205 USA. EM fanchunyang@uams.edu RI Fukuda, Satoshi/A-8433-2012; Oridate, Nobuhiko/G-5365-2012 FU Department of Veterans Affairs FX Merit award (CYF) from the Department of Veterans Affairs. NR 11 TC 6 Z9 6 U1 0 U2 1 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0194-5998 J9 OTOLARYNG HEAD NECK JI Otolaryngol. Head Neck Surg. PD JUN PY 2011 VL 144 IS 6 BP 900 EP 909 DI 10.1177/0194599811398786 PG 10 WC Otorhinolaryngology; Surgery SC Otorhinolaryngology; Surgery GA 808SN UT WOS:000293998800015 PM 21493336 ER PT J AU Herman, E Knapton, A Rosen, E Zhang, J Estis, J Agee, SJ Lu, QA Todd, JA Lipshultz, SE AF Herman, Eugene Knapton, Alan Rosen, Elliot Zhang, Jun Estis, Joel Agee, Sara J. Quynh-Anh Lu Todd, John A. Lipshultz, Steven E. TI Baseline Serum Cardiac Troponin I Concentrations in Sprague-Dawley, Spontaneous Hypertensive, Wistar, Wistar-Kyoto, and Fisher Rats as Determined with an Ultrasensitive Immunoassay SO TOXICOLOGIC PATHOLOGY LA English DT Article DE rat; cardiac troponin; myocardial injury; cardiotoxicity; immunoassay; single-molecule counting ID ACUTE MYOCARDIAL-INFARCTION; HIGH-SENSITIVITY ASSAY; DIFFERENTIAL REACTIVITY; BIOCHEMICAL MARKERS; GENDER DIFFERENCES; SKELETAL-MUSCLE; T IMMUNOASSAYS; HUMAN HEART; INJURY; ADRIAMYCIN AB Cardiac troponins have proved to be reliable blood biomarkers for identifying a variety of myocardial alterations in humans and animals. Recently, an ultrasensitive cTnI assay (Erenna IA) has been used to demonstrate increases in baseline cTnI resulting from drug-induced myocardial injury in rats, dogs, and monkeys, as well as to document baseline cTnI ranges in Sprague-Dawley (SD) rats. The present study was initiated to use the Erenna cTnI assay to further document baseline cTnI concentrations in normal control animals from multiple strains, including SD, Spontaneous Hypertensive (SHR), Wistar, Wistar-Kyoto (WKY), and Fisher strains. Baseline cTnI concentrations were quantified in all rats tested, and males had higher mean cTnI concentrations than females of the same strain. SHR males had the highest mean cTnI concentrations and the largest cTnI variability. Interestingly, cTnI concentrations increased in castrated SHR compared with unaltered male SHR, whereas cTnI concentrations decreased in ovariectomized SHR compared with unaltered female SHR. These results show significant differences in cTnI concentrations between strains, sexes, and noncardiac surgical alterations in control animals, and identify these as potential contributing factors to cTnI baseline variability that should be taken into account when using ultrasensitive cTnI as a biomarker to assess preclinical cardiotoxicity. C1 [Herman, Eugene; Knapton, Alan; Rosen, Elliot; Zhang, Jun] US FDA, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. [Estis, Joel; Agee, Sara J.; Quynh-Anh Lu; Todd, John A.] Singulex Inc, Alameda, CA USA. [Lipshultz, Steven E.] Univ Miami, Miami, FL USA. RP Herman, E (reprint author), US FDA, Div Appl Pharmacol Res, White Oak Life Sci Bldg 64,Room 2028,10903 New Ha, Silver Spring, MD 20993 USA. EM Eugene.Herman@fda.hhs.gov NR 44 TC 7 Z9 7 U1 0 U2 4 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 JUN PY 2011 VL 39 IS 4 BP 653 EP 663 DI 10.1177/0192623311406931 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 800RC UT WOS:000293381100008 PM 21558468 ER PT J AU Rahman, Z Agarabi, C Zidan, AS Khan, SR Khan, MA AF Rahman, Ziyaur Agarabi, Cyrus Zidan, Ahmed S. Khan, Saeed R. Khan, Mansoor A. TI Physico-mechanical and Stability Evaluation of Carbamazepine Cocrystal with Nicotinamide SO AAPS PHARMSCITECH LA English DT Article DE carbamazepine; cocrystal; mechanical property; nicotinamide; stability ID NONDESTRUCTIVE METHODS; SOLID DISPERSIONS; TENSILE-STRENGTH; DRUGS; DISSOLUTION; POLYMORPHS; DIHYDRATE; CRYSTALLIZATION; ENHANCEMENT; FORMULATION AB The focus of this investigation was to prepare the cocrystal of carbamazepine (CBZ) using nicotinamide as a coformer and to compare its preformulation properties and stability profile with CBZ. The cocrystal was prepared by solution cooling crystallization, solvent evaporation, and melting and cryomilling methods. They were characterized for solubility, intrinsic dissolution rate, chemical identification by Fourier transform infrared spectroscopy, crystallinity by differential scanning calorimetry, powder X-ray diffraction, and morphology by scanning electron microscopy. Additionally, mechanical properties were evaluated by tensile strength and Heckel analysis of compacts. The cocrystal and CBZ were stored at 40A degrees C/94% RH, 40A degrees C/75% RH, 25A degrees C/60% RH, and 60A degrees C to determine their stability behavior. The cocrystals were fluffy, with a needle-shaped crystal, and were less dense than CBZ. The solubility profiles of the cocrystals were similar to CBZ, but its intrinsic dissolution rate was lower due to the high tensile strength of its compacts. Unlike CBZ, the cocrystals were resistant to hydrate transformation, as revealed by the stability studies. Plastic deformation started at a higher compression pressure in the cocrystals than CBZ, as indicated by the high yield pressure. In conclusion, the preformulation profile of the cocrystals was similar to CBZ, except that it had an advantageous resistance to hydrate transformation. C1 [Rahman, Ziyaur; Agarabi, Cyrus; Zidan, Ahmed S.; Khan, Saeed R.; Khan, Mansoor A.] US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Zidan, Ahmed S.] Zagazig Univ, Fac Pharm, Zagazig, Egypt. RP Khan, MA (reprint author), US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, LS Bldg 64,Room 1070,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Mansoor.Khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012; OI Rahman, Ziyaur/0000-0002-0402-825X FU Oak Ridge Institute for Science and Education (ORISE) FX The authors would like to thank the Oak Ridge Institute for Science and Education (ORISE) for supporting the post doctoral research program. The authors also thank Mr. Alan Carlin for helping with the FTIR spectrum. NR 39 TC 24 Z9 25 U1 3 U2 28 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD JUN PY 2011 VL 12 IS 2 BP 693 EP 704 DI 10.1208/s12249-011-9603-4 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 791TN UT WOS:000292688700029 PM 21598082 ER PT J AU Brown, CK Friedel, HD Barker, AR Buhse, LF Keitel, S Cecil, TL Kraemer, J Morris, JM Reppas, C Stickelmeyer, MP Yomota, C Shah, VP AF Brown, Cynthia K. Friedel, Horst Dieter Barker, Amy R. Buhse, Lucinda F. Keitel, Susanne Cecil, Todd L. Kraemer, Johannes Morris, J. Michael Reppas, Christos Stickelmeyer, Mary P. Yomota, Chikako Shah, Vinod P. TI FIP/AAPS Joint Workshop Report: Dissolution/In Vitro Release Testing of Novel/Special Dosage Forms SO AAPS PHARMSCITECH LA English DT Article DE In vitro release testing; dissolution; novel dosage forms; special dosage forms ID IN-VITRO; DISINTEGRATION TIME; INHALER PRODUCTS; TEXTURE ANALYZER; DRUG-RELEASE; TABLETS; SUPPOSITORIES; SUSPENSIONS; SYSTEMS; PROFILE AB In 2003, the FIP Dissolution Working group published a position paper on dissolution/drug release testing for special/novel dosage forms that represented the scientific opinions of many experts in the field at that time (1). The position paper has supported activities, programs, and decisions in the scientific, technical, and regulatory community. Due to the rapid evolution of new practices and techniques for in vitro testing, the FIP Special Interest Group (SIG) on Dissolution/Drug Release decided to revise the previous paper and added proposals for further harmonization of in vitro release testing practices for different pharmaceutical dosage forms. This article represents the current updates to the previously published paper. This revision has been aligned to coincide with the USP taxonomy including route of administration, intended site of drug release, and dosage form. The revised paper includes information from current literature, expert discussions, and presentations from recent workshops (2,3). The authors acknowledge and expect further updates to be made as additional progress is made in the relevant areas. Thus, comments and additional contributions are welcome and may be considered for the next revision of the position paper. C1 [Brown, Cynthia K.; Barker, Amy R.; Stickelmeyer, Mary P.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Friedel, Horst Dieter] Bayer HealthCare, Berlin, Germany. [Buhse, Lucinda F.] US FDA, CDER, OPS, St Louis, MO USA. [Keitel, Susanne] Council Europe, EDQM, Strasbourg, France. [Cecil, Todd L.] US Pharmacopeia, Rockville, MD USA. [Kraemer, Johannes] PHAST, Homburg, Germany. [Morris, J. Michael] Irish Med Board, Dublin, Ireland. [Reppas, Christos] Univ Athens, Panepistimiopolis, Greece. [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 FU International Federation of Pharmaceutical Sciences (FIP); Royal Pharmaceutical Society of Great Britain (RPSGB); American Association of Pharmaceutical Sciences (AAPS); US Food and Drug Administration (FDA) FX This revision of this publication represents the scientific opinion of many experts and in particular, is derived from two key workshops (London, 2008 and Los Angeles, 2009) held under the auspices of the International Federation of Pharmaceutical Sciences (FIP) with cosponsorship from the Royal Pharmaceutical Society of Great Britain (RPSGB), American Association of Pharmaceutical Sciences (AAPS), and the US Food and Drug Administration (FDA). The authors would like to acknowledge the following workshop presenters for their technical contributions to the workshops which were fundamental to the revision of this publication. NR 61 TC 26 Z9 28 U1 0 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD JUN PY 2011 VL 12 IS 2 BP 782 EP 794 DI 10.1208/s12249-011-9634-x PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 791TN UT WOS:000292688700039 PM 21688063 ER PT J AU Samuelson, FW AF Samuelson, Frank W. TI Two-sample models with monotonic likelihood ratios for ordinal regression SO JOURNAL OF MATHEMATICAL PSYCHOLOGY LA English DT Article DE Likelihood ratio; ROC; Models; Regression ID OPERATING CHARACTERISTIC CURVE; ROC CURVES; PARAMETERS AB Signal detection experiments with human observers frequently generate ordinal data which are evaluated using receiver operating characteristic (ROC) methods. These methods may include regressing a continuous two-distribution model to the data set. Because we assume that human observers will not systematically select observations absent the signal, this model should have a monotonic likelihood ratio between the distributions. This paper gives a general method for constructing pairs of distributions that have monotonic likelihood ratios and a possibly large number flexible parameters. It suggests two specific simple parametric forms of monotonic likelihood ratios, constructs new distributions with those likelihood ratios using other standard distributions, and performs ordinal regression with those new distributions to model some example data from the literature. Published by Elsevier Inc. C1 US FDA, Silver Spring, MD 20993 USA. RP Samuelson, FW (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 62, Silver Spring, MD 20993 USA. EM frank.samuelson@fda.hhs.gov NR 20 TC 2 Z9 2 U1 1 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0022-2496 J9 J MATH PSYCHOL JI J. Math. Psychol. PD JUN PY 2011 VL 55 IS 3 BP 223 EP 228 DI 10.1016/j.jmp.2011.01.001 PG 6 WC Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods; Psychology, Mathematical SC Mathematics; Mathematical Methods In Social Sciences; Psychology GA 793DJ UT WOS:000292800300002 ER PT J AU Khurana, S Verma, N Yewdell, JW Hilbert, AK Castellino, F Lattanzi, M Del Giudice, G Rappuoli, R Golding, H AF Khurana, Surender Verma, Nitin Yewdell, Jonathan W. Hilbert, Anne Katrin Castellino, Flora Lattanzi, Maria Del Giudice, Giuseppe Rappuoli, Rino Golding, Hana TI MF59 Adjuvant Enhances Diversity and Affinity of Antibody-Mediated Immune Response to Pandemic Influenza Vaccines SO SCIENCE TRANSLATIONAL MEDICINE LA English DT Article ID SYNCYTIAL VIRUS-DISEASE; A H1N1 VACCINE; H5N1 VACCINE; MF59-ADJUVANTED VACCINE; CELL RESPONSE; OFF-RATE; IMMUNOGENICITY; MATURATION; SAFETY; NEUTRALIZATION AB Oil-in-water adjuvants have been shown to improve immune responses against pandemic influenza vaccines as well as reduce the effective vaccine dose, increasing the number of doses available to meet global vaccine demand. Here, we use genome fragment phage display libraries and surface plasmon resonance to elucidate the effects of MF59 on the quantity, diversity, specificity, and affinity maturation of human antibody responses to the swine-origin H1N1 vaccine in different age groups. In adults and children, MF59 selectively enhanced antibody responses to the hemagglutinin 1 (HA1) globular head relative to the more conserved HA2 domain in terms of increased antibody titers as well as a more diverse antibody epitope repertoire. Antibody affinity, as inferred by greatly diminished (>= 10-fold) off-rate constants, was significantly increased in toddlers and children who received the MF59-adjuvanted vaccine. Moreover, MF59 also improved antibody affinity maturation after each sequential vaccination against avian H5N1 in adults. For both pandemic influenza vaccines, there was a close correlation between serum antibody affinity and virus-neutralizing capacity. Thus, MF59 quantitatively and qualitatively enhances functional antibody responses to HA-based vaccines by improving both epitope breadth and binding affinity, demonstrating the added value of such adjuvants for influenza vaccines. C1 [Khurana, Surender; Verma, Nitin; Golding, Hana] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Yewdell, Jonathan W.] NIAID, Viral Dis Lab, NIH, Bethesda, MD 20892 USA. [Hilbert, Anne Katrin] Novartis Vaccines & Diagnost GmbH, D-35041 Marburg, Germany. [Castellino, Flora; Lattanzi, Maria; Del Giudice, Giuseppe; Rappuoli, Rino] Novartis Vaccines & Diagnost Res Ctr, I-53100 Siena, Italy. RP Golding, H (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM hana.golding@fda.hhs.gov RI yewdell, jyewdell@nih.gov/A-1702-2012 FU Division of Microbiology and Infectious Diseases, NIH [IAA 224-10-1006] FX This study was partly supported by IAA 224-10-1006 from the Division of Microbiology and Infectious Diseases, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 47 TC 80 Z9 85 U1 1 U2 11 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 1946-6234 J9 SCI TRANSL MED JI Sci. Transl. Med. PD JUN 1 PY 2011 VL 3 IS 85 AR 85ra48 DI 10.1126/scitranslmed.3002336 PG 9 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 795NE UT WOS:000292980100004 PM 21632986 ER PT J AU Chang, HC Doerge, DR Hsieh, CH Lin, YJ Tsai, FJ AF Chang, Hebron C. Doerge, Daniel R. Hsieh, ChengHong Lin YingJu Tsai, FuuJen TI The Covalent Binding of Genistein to the Non-prosthetic-heme-moiety of Bovine Lactoperoxidase Leads to Enzymatic Inactivation SO BIOMEDICAL AND ENVIRONMENTAL SCIENCES LA English DT Article DE Lactoperoxidase; Genistein; Modification of heme; Covalent binding; Peptide fragments ID SOY ISOFLAVONES; SALICYLHYDROXAMIC-ACID; HORSERADISH-PEROXIDASE; MAMMALIAN PEROXIDASES; THYROID PEROXIDASE; CRYSTAL-STRUCTURE; IN-VITRO; MYELOPEROXIDASE; RESOLUTION; BONDS AB Objective Genistein, a major soy isoflavone metabolite (SIF), inactivates oxidation activity of bovine lactoperoxidase (LPO). Modification of the heme moiety of LPO by nitrogen-containing compounds has been shown to inactivate LPO. In contrast, SIF mediated inactivation of LPO does not involve a heme modification and the mechanism of SIF inhibition is poorly understood. Methods After inactivation of LPO by genistein in the presence of H(2)O(2), trypsin-digested LPO peptide fragments were collected and analyzed by mALDI-TOF-MS to characterize the chemical binding of genistein(s) to LPO. Results The heme moiety of LPO was not modified by genistein. A covalent binding study showed that (3)H-genistein bound to LPO with a ratio of (similar to)12 to 1. After HPLC analysis and peak collection, trypsin-digested peptide fragments were analyzed by MALDI-TOF-MS. The 3H-genistein co-eluted peptide fragments (RT=24 min) were putatively identified as 199IVGYLDEEGVLDQNR214 with two bound genistein molecules or a genistein dimer (2 259 Da), 486TPDNIDIWIGGNAEPMVER504 with two bound genistein molecules or a genistein dinner (2 663 Da), and 161ARWLPAEYEDGLALPFGWTQR182 with three bound genistein molecules or a genistein trimer (3 060 Da). The fragment with a mass of 1 792 Da (RT=36 min) was identified as 132CDENSPYR139 with three genistein molecules or a genistein trimer. Conclusions The results suggest that LPO was inactivated by irreversible covalent binding of genistein or genistein polymers to particular peptide fragments constituting regions of the outward domain. No genistein interaction with the prosthetic heme moiety of LPO was observed. C1 [Doerge, Daniel R.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Hsieh, ChengHong] Asia Univ, Dept Hlth & Nutr Biotechnol, Taichung 41354, Taiwan. [Lin YingJu; Tsai, FuuJen] China Med Univ, Genet Ctr, Taichung 40402, Taiwan. [Chang, Hebron C.] Asia Univ, Dept Biotechnol, Taichung 41354, Taiwan. RP Chang, HC (reprint author), Asia Univ, Dept Biotechnol, Taichung 41354, Taiwan. EM hebronchang@asia.edu.tw RI Lin, Ying-Ju/F-4852-2010 OI Lin, Ying-Ju/0000-0003-4684-0585 FU National Science Council, Taiwan [NSC 95-2320-B-408001]; Interagency Agreement between NCTR/FDA; National Institute for Environmental Health Sciences/National Toxicology Program, USA FX This research was supported by the National Science Council, Taiwan #NSC 95-2320-B-408001 and in part by the Interagency Agreement between NCTR/FDA and the National Institute for Environmental Health Sciences/National Toxicology Program, USA. NR 19 TC 3 Z9 3 U1 0 U2 2 PU CHINESE CENTER DISEASE CONTROL & PREVENTION PI BEIJING PA 155 CHANGBAI RD, CHANGPING DISTRICT, BEIJING, 102206, PEOPLES R CHINA SN 0895-3988 J9 BIOMED ENVIRON SCI JI Biomed. Environ. Sci. PD JUN PY 2011 VL 24 IS 3 BP 284 EP 290 DI 10.3967/0895-3988.2011.03.012 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 788ZW UT WOS:000292484100012 PM 21784315 ER PT J AU Tsiatis, AA Davidian, M Cao, WH AF Tsiatis, Anastasios A. Davidian, Marie Cao, Weihua TI Improved Doubly Robust Estimation When Data Are Monotonely Coarsened, with Application to Longitudinal Studies with Dropout SO BIOMETRICS LA English DT Article DE Coarsening at random; Discrete hazard; Dropout; Longitudinal data; Missing at random ID SEMIPARAMETRIC REGRESSION; REPEATED OUTCOMES; PATTERN-MIXTURE; MISSING DATA; MODELS; NONRESPONSE; SELECTION AB A routine challenge is that of making inference on parameters in a statistical model of interest from longitudinal data subject to dropout, which are a special case of the more general setting of monotonely coarsened data. Considerable recent attention has focused on doubly robust (DR) estimators, which in this context involve positing models for both the missingness (more generally, coarsening) mechanism and aspects of the distribution of the full data, that have the appealing property of yielding consistent inferences if only one of these models is correctly specified. DR estimators have been criticized for potentially disastrous performance when both of these models are even only mildly misspecified. We propose a DR estimator applicable in general monotone coarsening problems that achieves comparable or improved performance relative to existing DR methods, which we demonstrate via simulation studies and by application to data from an AIDS clinical trial. C1 [Tsiatis, Anastasios A.; Davidian, Marie] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Cao, Weihua] US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Tsiatis, AA (reprint author), N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. EM davidian@ncsu.edu RI Cao, Weihua/A-1222-2012 FU NIH [R37 AI031789, R01 CA051962, R01 CA085848, P01 CA142538] FX This work is supported by NIH grants R37 AI031789, R01 CA051962, R01 CA085848, and P01 CA142538. NR 24 TC 17 Z9 17 U1 1 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2011 VL 67 IS 2 BP 536 EP 545 DI 10.1111/j.1541-0420.2010.01476.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 789GS UT WOS:000292504000021 PM 20731640 ER PT J AU McCabe, J Burton, E Morgan, A Budinich, C Woodard, G Liu, YB Myers, M Moratz, C AF McCabe, Joseph Burton, Ellen Morgan, Amy Budinich, Craig Woodard, Geoffrey Liu, Yunbo Myers, Matthew Moratz, Chantal TI MOUSE BLOOD-BRAIN BARRIER INTEGRITY AND NEURO-IMMUNE SEQUELAE FROM NON-IMPACT PRESSURE ALTERATIONS BY HIGH-INTENSITY FOCUSED ULTRASOUND SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 29th Annual National Neurotrauma Symposium CY JUL 10-13, 2011 CL Hollywood Beach, FL C1 [McCabe, Joseph; Budinich, Craig; Woodard, Geoffrey; Moratz, Chantal] Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. [Burton, Ellen; Morgan, Amy] Ctr Neurosci & Regenerat Med, Bethesda, MD USA. [Liu, Yunbo; Myers, Matthew] US FDA, White Oak, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN PY 2011 VL 28 IS 6 BP A76 EP A76 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 788PT UT WOS:000292457600243 ER PT J AU Moratz, C Burton, E Morgan, A Schrot, J McCarron, R Liu, YB Myers, M McCabe, J AF Moratz, Chantal Burton, Ellen Morgan, Amy Schrot, John McCarron, Richard Liu, Yunbo Myers, Matthew McCabe, Joseph TI RAT BLOOD-BRAIN BARRIER DISRUPTION AND NEUROIMMUNE ALTERATIONS FROM NON-IMPACT PRESSURE ALTERATIONS BY HIGH-INTENSITY FOCUSED ULTRASOUND AND BLAST OVERPRESSURE SHOCK TUBE EXPOSURE SO JOURNAL OF NEUROTRAUMA LA English DT Meeting Abstract CT 29th Annual National Neurotrauma Symposium CY JUL 10-13, 2011 CL Hollywood Beach, FL C1 [Moratz, Chantal] Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. [Burton, Ellen; Morgan, Amy] USUHS, Ctr Neurosci & Regenerat Med, Bethesda, MD USA. [Schrot, John; McCarron, Richard] USN, Med Res Ctr, Silver Spring, MD USA. [Liu, Yunbo; Myers, Matthew] US FDA, Ctr Devices & Radiol Hlth, White Oak, MD USA. [McCabe, Joseph] USUHS, Dept Anat Physiol & Genet, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0897-7151 J9 J NEUROTRAUM JI J. Neurotrauma PD JUN PY 2011 VL 28 IS 6 BP A76 EP A76 PG 1 WC Critical Care Medicine; Clinical Neurology; Neurosciences SC General & Internal Medicine; Neurosciences & Neurology GA 788PT UT WOS:000292457600241 ER PT J AU Chantry, CJ Wiedeman, J Buehring, G Peerson, JM Hayfron, K K'Aluoch, O Lonnerdal, B Israel-Ballard, K Coutsoudis, A Abrams, B AF Chantry, Caroline J. Wiedeman, Jean Buehring, Gertrude Peerson, Janet M. Hayfron, Kweku K'Aluoch, Okumu Lonnerdal, Bo Israel-Ballard, Kiersten Coutsoudis, Anna Abrams, Barbara TI Effect of Flash-Heat Treatment on Antimicrobial Activity of Breastmilk SO BREASTFEEDING MEDICINE LA English DT Article ID RECOMBINANT HUMAN LACTOFERRIN; HIV-INFECTED MOTHERS; COTE-DIVOIRE; CHILDREN; STORAGE; TEMPERATURE; MORTALITY; RICE; PASTEURIZATION; TRANSMISSION AB Background and Objectives: The World Health Organization recommends human immunodeficiency virus (HIV)-positive mothers in resource-poor regions heat-treat expressed breastmilk during periods of increased maternal-to-child transmission risk. Flash-heat, a "low tech" pasteurization method, inactivates HIV, but effects on milk protein bioactivity are unknown. The objectives were to measure flash-heat's effect on antimicrobial properties of lactoferrin, lysozyme, and whole milk and on the digestive resistance of lactoferrin and lysozyme. Methods: Flash-heated and unheated breastmilk aliquots from HIV-positive mothers in South Africa were "spiked" with Staphylococcus aureus and Escherichia coli and then cultured for 0, 3, and 6 hours. Lysozyme and lactoferrin activities were determined by lysis of Micrococcus luteus cells and inhibition of enteropathogenic E. coli, respectively, measured spectrophotometrically. Percentages of proteins surviving in vitro digestion, lactoferrin and lysozyme activity, and bacteriostatic activity of whole milk in heated versus unheated samples were compared. Results: There was no difference in rate of growth of E. coli or S. aureus in flash-heated versus unheated whole milk (p = 0.61 and p = 0.96, respectively). Mean (95% confidence interval) antibacterial activity of lactoferrin was diminished 11.1% (7.8%, 14.3%) and that of lysozyme by up to 56.6% (47.1%, 64.5%) by flash-heat. Digestion of lysozyme was unaffected (p = 0.12), but 25.4% less lactoferrin survived digestion (p < 0.0001). Conclusions: In summary, flash-heat resulted in minimally decreased lactoferrin and moderately decreased lysozyme bioactivity, but bacteriostatic activity of whole milk against representative bacteria was unaffected. This suggests flash-heated breastmilk likely has a similar profile of resistance to bacterial contamination as that of unheated milk. Clinical significance of the decreased bioactivity should be tested in clinical trials. C1 [Chantry, Caroline J.; Wiedeman, Jean] Univ Calif Davis, Med Ctr, Dept Pediat, Sacramento, CA 95817 USA. [Chantry, Caroline J.; Peerson, Janet M.; Lonnerdal, Bo] Univ Calif Davis, Dept Nutr, Program Int & Community Nutr, Davis, CA 95616 USA. [Buehring, Gertrude] Univ Calif Berkeley, Sch Publ Hlth, Div Infect Dis & Vaccinol, Berkeley, CA 94720 USA. [Hayfron, Kweku] Univ Arkansas Med Sci, Little Rock, AR 72205 USA. [K'Aluoch, Okumu] Food & Drug Adm San Francisco Dist Off, Alameda, CA USA. [Israel-Ballard, Kiersten] PATH, Seattle, WA USA. [Coutsoudis, Anna] Univ Kwazulu Natal, Nelson R Mandela Sch Med, Dept Paediat & Child Hlth, Durban, South Africa. [Abrams, Barbara] Univ Calif Berkeley, Sch Publ Hlth, Div Epidemiol, Berkeley, CA 94720 USA. RP Chantry, CJ (reprint author), Univ Calif Davis, Med Ctr, Dept Pediat, 2516 Stockton Blvd, Sacramento, CA 95817 USA. EM caroline.chantry@ucdmc.ucdavis.edu FU National Institute of Child Health and Human Development [HD051473-01]; University of California; Davis Children's Miracle Network; Thrasher Research Fund; James B. Pendleton Charitable Trust FX The authors would like to acknowledge the mothers who participated in this study and the Cato Manor Clinic staff for their time and dedication. We thank Lindiwe Sibeko for assistance with subject recruitment, Derek Lee for technical assistance with whole milk bacteriostatic experiments, and Andrew Hall for technical assistance with in vitro digestion and western blot assays. Funding for this project was provided by the National Institute of Child Health and Human Development (grant HD051473-01), the University of California, Davis Children's Miracle Network, the Thrasher Research Fund, and the James B. Pendleton Charitable Trust. NR 32 TC 16 Z9 16 U1 1 U2 7 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1556-8253 J9 BREASTFEED MED JI Breastfeed. Med. PD JUN PY 2011 VL 6 IS 3 BP 111 EP 116 DI 10.1089/bfm.2010.0078 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA 772AI UT WOS:000291201400002 PM 21091243 ER PT J AU Pouillot, R Lubran, MB AF Pouillot, Regis Lubran, Meryl B. TI Predictive microbiology models vs. modeling microbial growth within Listeria monocytogenes risk assessment: What parameters matter and why SO FOOD MICROBIOLOGY LA English DT Article; Proceedings Paper CT 6th International Conference of Predictive Modeling in Foods (6ICPMF) CY SEP 08-12, 2009 CL Washington, DC DE Quantitative risk assessment; Listeria monocytogenes; Predictive microbiology ID COLD-SMOKED SALMON; LAG TIME DISTRIBUTIONS; EXPOSURE ASSESSMENT; FOOD MICROBIOLOGY; BACTERIAL-GROWTH; TEMPERATURE; PRODUCTS; ENOUGH; PHASE; MEAT AB Predictive microbiology models are essential tools to model bacterial growth in quantitative microbial risk assessments. Various predictive microbiology models and sets of parameters are available: it is of interest to understand the consequences of the choice of the growth model on the risk assessment outputs. Thus, an exercise was conducted to explore the impact of the use of several published models to predict Listeria monocytogenes growth during food storage in a product that permits growth. Results underline a gap between the most studied factors in predictive microbiology modeling (lag, growth rate) and the most influential parameters on the estimated risk of listeriosis in this scenario (maximum population density, bacterial competition). The mathematical properties of an exponential dose response model for Listeria accounts for the fact that the mean number of bacteria per serving and, as a consequence, the highest achievable concentrations in the product under study, has a strong influence on the estimated expected number of listeriosis cases in this context. Published by Elsevier Ltd. C1 [Pouillot, Regis] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Lubran, Meryl B.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Pouillot, R (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Regis.Pouillot@fda.hhs.gov RI Pouillot, Regis/E-8103-2010 OI Pouillot, Regis/0000-0002-6107-5212 NR 32 TC 19 Z9 21 U1 5 U2 28 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD JUN PY 2011 VL 28 IS 4 SI SI BP 720 EP 726 DI 10.1016/j.fm.2010.06.002 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 768HI UT WOS:000290924300012 PM 21511132 ER PT J AU Myers, MR Giridhar, D AF Myers, Matthew R. Giridhar, Dushyanth TI Theoretical framework for quantitatively estimating ultrasound beam intensities using infrared thermography SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID FOCUSED ULTRASOUND AB In the characterization of high-intensity focused ultrasound (HIFU) systems, it is desirable to know the intensity field within a tissue phantom. Infrared (IR) thermography is a potentially useful method for inferring this intensity field from the heating pattern within the phantom. However, IR measurements require an air layer between the phantom and the camera, making inferences about the thermal field in the absence of the air complicated. For example, convection currents can arise in the air layer and distort the measurements relative to the phantom-only situation. Quantitative predictions of intensity fields based upon IR temperature data are also complicated by axial and radial diffusion of heat. In this paper, mathematical expressions are derived for use with IR temperature data acquired at times long enough that noise is a relatively small fraction of the temperature trace, but small enough that convection currents have not yet developed. The relations were applied to simulated IR data sets derived from computed pressure and temperature fields. The simulation was performed in a finite-element geometry involving a HIFU transducer sonicating upward in a phantom toward an air interface, with an IR camera mounted atop an air layer, looking down at the heated interface. It was found that, when compared to the intensity field determined directly from acoustic propagation simulations, intensity profiles could be obtained from the simulated IR temperature data with an accuracy of better than 10%, at pre-focal, focal, and post-focal locations. [DOI: 10.1121/1.3575600] C1 [Myers, Matthew R.; Giridhar, Dushyanth] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10993 New Hampshire Ave, Silver Spring, MD 20993 USA. EM matthew.myers@fda.hhs.gov NR 12 TC 7 Z9 7 U1 0 U2 0 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 JUN PY 2011 VL 129 IS 6 BP 4073 EP 4083 DI 10.1121/1.3575600 PG 11 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 778SW UT WOS:000291727000074 PM 21682428 ER PT J AU Mahadevan, B Snyder, RD Waters, MD Benz, RD Kemper, RA Tice, RR Richard, AM AF Mahadevan, Brinda Snyder, Ronald D. Waters, Michael D. Benz, R. Daniel Kemper, Raymond A. Tice, Raymond R. Richard, Ann M. TI Genetic Toxicology in the 21st Century: Reflections and Future Directions SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE genotoxicity; mutagenicity; toxicogenomics; high throughput screening ID DISCRIMINATE RODENT CARCINOGENS; VITRO GENOTOXICITY TESTS; SALMONELLA-MICROSOME TEST; DNA INTERCALATING AGENTS; E-STATE INDEXES; MDL-QSAR; NONGENOTOXIC CARCINOGENS; ENVIRONMENTAL CHEMICALS; DEVELOPMENTAL TOXICITY; RELATIVE PREDICTIVITY AB A symposium at the 40th anniversary of the Environmental Mutagen Society, held from October 24-28, 2009 in St. Louis, MO, surveyed the current status and future directions of genetic toxicology. This article summarizes the presentations and provides a perspective on the future. An abbreviated history is presented, highlighting the current standard battery of genotoxicity assays and persistent challenges. Application of computational toxicology to safety testing within a regulatory setting is discussed as a means for reducing the need for animal testing and human clinical trials, and current approaches and applications of in silico genotoxicity screening approaches across the pharmaceutical industry were surveyed and are reported here. The expanded use of toxicogenomics to illuminate mechanisms and bridge genotoxicity and carcinogenicity, and new public efforts to use high-throughput screening technologies to address lack of toxicity evaluation for the backlog of thousands of industrial chemicals in the environment are detailed. The Tox21 project involves coordinated efforts of four U. S. Government regulatory/research entities to use new and innovative assays to characterize key steps in toxicity pathways, including genotoxic and nongenotoxic mechanisms for carcinogenesis. Progress to date, highlighting preliminary test results from the National Toxicology Program is summarized. Finally, an overview is presented of ToxCast (TM), a related research program of the U. S. Environmental Protection Agency, using a broad array of high throughput and high content technologies for toxicity profiling of environmental chemicals, and computational toxicology modeling. Progress and challenges, including the pressing need to incorporate metabolic activation capability, are summarized. Environ. Mol. Mutagen. 52: 339-354, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Mahadevan, Brinda; Snyder, Ronald D.] Merck Res Labs, Genet Toxicol, Mech & Predict Toxicol, Summit, NJ USA. [Waters, Michael D.] Integrated Lab Syst Inc, Res Triangle Pk, NC USA. [Benz, R. Daniel] US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Appl Pharmacol Res, Silver Spring, MD USA. [Kemper, Raymond A.] Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT USA. [Tice, Raymond R.] Natl Inst Environm Hlth Sci, Natl Toxicol Program, Res Triangle Pk, NC USA. [Richard, Ann M.] US EPA, Natl Ctr Computat Toxicol, Off Res & Dev, Res Triangle Pk, NC 27711 USA. RP Mahadevan, B (reprint author), Abbott Labs Inc, Global Occupat Toxicol, Abbott Qual & Regulatory Dept, 03QW Bldg,AP6B-2,100 Abbott Pk Rd, Abbott Pk, IL 60064 USA. EM brinda.mahadevan@abbott.com FU Intramural NIH HHS [Z99 ES999999] NR 81 TC 39 Z9 41 U1 8 U2 36 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUN PY 2011 VL 52 IS 5 BP 339 EP 354 DI 10.1002/em.20653 PG 16 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 776SR UT WOS:000291558700001 PM 21538556 ER PT J AU McKinzie, PB Parsons, BL AF McKinzie, Page B. Parsons, Barbara L. TI Accumulation of K-Ras Codon 12 Mutations in the F344 Rat Distal Colon Following Azoxymethane Exposure SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE carcinogenesis; mode of action; spontaneous mutation; mutation detection method ID ABERRANT CRYPT FOCI; COMPETITIVE BLOCKER PCR; COLORECTAL-CANCER; CHEMOPREVENTIVE AGENTS; TUMOR DEVELOPMENT; ESCHERICHIA-COLI; GENE-MUTATIONS; GROWTH-FACTOR; MOUSE SKIN; CARCINOGENESIS AB Azoxymethane (AOM) administration to F344 male rats is a widely used model of human colon carcinogenesis. The current study investigates quantitatively the accumulation of K-Ras codon 12 mutations following AOM exposure. Male, 6-week-old F344 rats were treated subcutaneously with 30 mg/kg body weight of AOM, and colon tissue was collected at 1, 8, 24, and 32 weeks after treatment. The K-Ras codon 12 GGT to GAT and GGT to GTT mutant fractions (MFs) were measured using allele-specific competitive blocker polymerase chain reaction (ACB-PCR). Between 1 and 32 weeks after AOM treatment, the K-Ras codon 12 GGT to GAT geometric mean MF in the rat colon increased significantly from 12.9 x 10(-5) to 145 x 10(-5), and the GGT to GTT geometric mean MF increased significantly from 5.26 x 10(-5) to 180 x 10(-5). K-Ras codon 12 GGT to GAT MF also increased significantly in AOM-treated rat colon tissue at 1 week compared to controls (4.44 x 10(-5)). The accumulation of the GGT to GAT MF long after the DNA adduct repair phase suggests that a portion of cells containing this mutation have a proliferative advantage, allowing them to accumulate as nascent tumors progress. Also, the GGT to GAT background MF increased in untreated rats, indicating that there is accumulation with age. The ACB-PCR assay generates quantitative data of cancer-related mutations and thus provides insight into pathological processes following carcinogen exposure. Environ. Mol. Mutagen. 52: 409-418, 2011. (C) Published 2011 Wiley-Liss, Inc.(dagger) C1 [McKinzie, Page B.; Parsons, Barbara L.] Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. RP McKinzie, PB (reprint author), HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM page.mckinzie@fda.hhs.gov NR 45 TC 7 Z9 7 U1 1 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUN PY 2011 VL 52 IS 5 BP 409 EP 418 DI 10.1002/em.20644 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 776SR UT WOS:000291558700007 PM 21370285 ER PT J AU Miura, D Shaddock, JG Mittelstaedt, RA Dobrovolsky, VN Kimoto, T Kasahara, Y Heflich, RH AF Miura, Daishiro Shaddock, Joseph G. Mittelstaedt, Roberta A. Dobrovolsky, Vasily N. Kimoto, Takafumi Kasahara, Yoshinori Heflich, Robert H. TI Analysis of Mutations in the Pig-a Gene of Spleen T-cells from N-Ethyl-N-nitrosourea-Treated Fisher 344 Rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE phosphatidylinosital glycan; class A gene; N-ethyl-N-nitrosourea; mutation spectrum; proaerolysin; in vivo gene mutation assay ID ETHYLNITROSOUREA-INDUCED MUTATION; RED-BLOOD-CELLS; MOLECULAR ANALYSIS; TRANSGENIC MICE; LYMPHOCYTES; ASSAY; HPRT; DNA; REPLICATION; MUTAGENESIS AB A rapid in vivo somatic cell gene mutation assay is being developed that measures mutation in the endogenous X-linked phosphatidylinositol glycan, class A gene (Pig-a). The assay detects Pig-a mutants by flow cytometric identification of cells deficient in glycosylphosphatidyl inositol (GPI) anchor synthesis. GPI-deficient, presumed Pig-a mutant cells also can be detected in a cloning assay that uses proaerolysin (ProAER) selection. Previously, we demonstrated that ProAER-resistant (ProAER(r)) rat spleen T-cells have mutations in the Pig-a gene. In the present study, we report on a more complete analysis of ProAER(r) rat spleen T-cell mutants and describe a mutation spectrum for mutants isolated from rats 4 weeks after treatment with three consecutive doses of 35.6 mg/kg N-ethyl-N-nitrosourea (ENU). We identified a total of 55 independent mutations, with the largest percentage (69%) involving basepair substitution at A: T. The overall spectrum of Pig-a gene mutations was consistent with the types of DNA adducts formed by ENU and was very similar to what has been described for in vivo ENU-induced mutation spectra in other rodent reporter genes (e. g., in the endogenous Hprt gene and transgenic shuttle vectors). These data are consistent with the rat Pig-a assay detecting test-agent-induced mutational responses. Environ. Mol. Mutagen. 52: 419-423, 2011. Published 2011 Wiley-Liss, Inc.(dagger) C1 [Heflich, Robert H.] US FDA, NCTR, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. [Miura, Daishiro; Kimoto, Takafumi; Kasahara, Yoshinori] Teijin Pharma Ltd, Tokyo, Japan. RP Heflich, RH (reprint author), US FDA, NCTR, Div Genet & Mol Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM robert.heflich@fda.hhs.gov FU Teijin Pharma, Ltd.; U.S. FDA FX Grant sponsor: Cooperative Research and Development Agreement between Teijin Pharma, Ltd., and the U.S. FDA. NR 19 TC 12 Z9 13 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUN PY 2011 VL 52 IS 5 BP 419 EP 423 DI 10.1002/em.20654 PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 776SR UT WOS:000291558700008 PM 21542029 ER PT J AU Eydelman, MB Chen, EA AF Eydelman, Malvina B. Chen, Eric A. TI The FDA's Humanitarian Device Exemption Program SO HEALTH AFFAIRS LA English DT Letter C1 [Eydelman, Malvina B.] US FDA, Div Ophthalm Neurol & Ear Nose & Throat Devices, Washington, DC 20204 USA. [Chen, Eric A.] US FDA, Humanitarian Use Device Program, Washington, DC 20204 USA. RP Eydelman, MB (reprint author), US FDA, Div Ophthalm Neurol & Ear Nose & Throat Devices, Washington, DC 20204 USA. NR 0 TC 5 Z9 5 U1 0 U2 0 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD JUN PY 2011 VL 30 IS 6 BP 1210 EP U265 DI 10.1377/hlthaff.2011.0550 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 775CT UT WOS:000291436100028 PM 21653975 ER PT J AU Peters, SM Deaver, CM Jones, YL Yancy, HF Kenyon, E Esparza, J Chiesa, OA Stubs, JT Lancaster, VA Myers, MJ AF Peters, S. M. Deaver, C. M. Jones, Y. L. Yancy, H. F. Kenyon, E. Esparza, J. Chiesa, O. A. Stubs, J. T., III Lancaster, V. A. Myers, M. J. TI VALIDATION OF A SWINE SYSTEMIC MODEL OF INFLAMMATION AND THE IMPACT OF A NON-STEROIDAL ANTI-INFLAMMATORY DRUG ON THE EXPRESSION OF MRNA BIOMARKERS SO INFLAMMATION RESEARCH LA English DT Meeting Abstract CT 10th World Congress on Inflammation CY JUN 25-29, 2011 CL Paris, FRANCE SP Int Assoc Inflammation Soc, Grp Res & Study Mediators Inflammat C1 [Peters, S. M.; Deaver, C. M.; Jones, Y. L.; Yancy, H. F.; Kenyon, E.; Chiesa, O. A.; Myers, M. J.] US FDA, Div Appl Vet Res, Laurel, MD USA. [Peters, S. M.; Stubs, J. T., III] Howard Univ, Washington, DC 20059 USA. [Lancaster, V. A.] US FDA, Div Sci Support, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIRKHAUSER VERLAG AG PI BASEL PA VIADUKSTRASSE 40-44, PO BOX 133, CH-4010 BASEL, SWITZERLAND SN 1023-3830 J9 INFLAMM RES JI Inflamm. Res. PD JUN PY 2011 VL 60 SU 1 BP 278 EP 278 PG 1 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 774CM UT WOS:000291358900767 ER PT J AU Chen, Y Kumar, N Siddique, N AF Chen, Yi Kumar, Nishant Siddique, Nusrat TI Incorporation of an Internal Control into the PCR Assay Published in "Development of an Improved Protocol for the Isolation and Detection of Enterobacter sakazakii (Cronobacter) from Powdered Infant Formula," J. Food Prot. 73(6):1016-1022 (2010) SO JOURNAL OF FOOD PROTECTION LA English DT Letter ID REAL-TIME PCR C1 [Chen, Yi; Kumar, Nishant; Siddique, Nusrat] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Chen, Y (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. RI Zhou, Tian/J-7175-2012 NR 4 TC 2 Z9 3 U1 0 U2 3 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2011 VL 74 IS 6 BP 872 EP 873 DI 10.4315/0362-028X.74.6.872 PG 2 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 776HG UT WOS:000291524500001 PM 21669061 ER PT J AU Ou, W Delisle, J Konduru, K Bradfute, S Radoshitzky, SR Retterer, C Kota, K Bavari, S Kuhn, JH Jahrling, PB Kaplan, G Wilson, CA AF Ou, Wu Delisle, Josie Konduru, Krishnamurthy Bradfute, Steven Radoshitzky, Sheli R. Retterer, Cary Kota, Krishna Bavari, Sina Kuhn, Jens H. Jahrling, Peter B. Kaplan, Gerardo Wilson, Carolyn A. TI Development and characterization of rabbit and mouse antibodies against ebolavirus envelope glycoproteins SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Ebola; Ebolavirus; Envelope glycoprotein; Filovirus; sGP ID VIRUS INFECTION; MONOCLONAL-ANTIBODIES; PASSIVE TRANSFER; EPITOPES; ELISA; CELL; GP AB Ebolaviruses are the etiologic agents of severe viral hemorrhagic fevers in primates, including humans, and could be misused for the development of biological weapons. The ability to rapidly detect and differentiate these viruses is therefore crucial. Antibodies that can detect reliably the ebolavinis surface envelope glycoprotein GP(1,2) or a truncated variant that is secreted from infected cells (sGP) are required for advanced development of diagnostic assays such as sandwich ELISAs or Western blots (WB). We used a GP(1,2) peptide conserved among Bundibugyo, Ebola, Reston, Sudan, and Tai Forest viruses and a mucin-like domain-deleted Sudan virus GP(1,2) (SudanGP Delta Muc) to immunize mice or rabbits, and developed a panel of antibodies that either cross-react or are virus-specific. These antibodies detected full-length GP(1,2) and sGP in different assays such as ELISA, FACS, or WB. In addition, some of the antibodies were shown to have potential clinical relevance, as they detected ebolavirus-infected cells by immunofluorescence assay and gave a specific increase in signal by sandwich ELISA against sera from mouse-adapted Ebola virus-infected mice over uninfected mouse sera. Rabbit anti-SudanGP Delta Muc polyclonal antibody neutralized gammaretroviral particles pseudotyped with Sudan virus GP(1,2), but not particles pseudotyped with other ebolavirus GP(1,2). Together, our results suggest that this panel of antibodies may prove useful for both in vitro analyses of ebolavirus GP(1,2), as well as analysis of clinically relevant samples. Published by Elsevier B.V. C1 [Ou, Wu; Delisle, Josie; Wilson, Carolyn A.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Konduru, Krishnamurthy; Kaplan, Gerardo] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Bradfute, Steven; Radoshitzky, Sheli R.; Retterer, Cary; Kota, Krishna; Bavari, Sina] USA, Med Res Inst Infect Dis, Div Toxicol, Frederick, MD USA. [Kuhn, Jens H.; Jahrling, Peter B.] NIH NIAID Integrated Res Facil Ft Detrick, Frederick, MD USA. RP Wilson, CA (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bldg 29B,Room 5NN22,8800 Rockville Pike, Bethesda, MD 20892 USA. EM carolyn.wilson@fda.hhs.gov RI Kuhn, Jens H./B-7615-2011 OI Kuhn, Jens H./0000-0002-7800-6045 FU CBER/NIAID Interagency Agreement (IAG); Biomedical Advanced Research and Development Authority (BARDA); Joint Science and Technology Office Transformational Medical Technologies [TMT10048_09_RD_T]; Defense Threat Reduction Agency [4.10022_08_RD_B]; NIAID [HHSN2722002000161] FX We are grateful to Seton Pariser, Bertram W. Maidment III, and Evan Ewers for their technical assistance. This research was partially supported by CBER/NIAID Interagency Agreement (IAG) and the Biomedical Advanced Research and Development Authority (BARDA). This research was partially supported by the Joint Science and Technology Office Transformational Medical Technologies (proposal # TMT10048_09_RD_T) and Defense Threat Reduction Agency (proposal #4.10022_08_RD_B) to SB. JHK performed this work as an employee of Tunnel(Consulting, Inc., a subcontractor to Battelle Memorial Institute under its prime contract with NIAID, under Contract No. HHSN2722002000161. Opinions, interpretations, conclusions, and recommendations are those of the authors and are not necessarily endorsed by the US Army, the US Department of Health and Human Services or of the institutions and companies affiliated with the authors. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 25 TC 5 Z9 7 U1 4 U2 8 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 JUN PY 2011 VL 174 IS 1-2 BP 99 EP 109 DI 10.1016/j.jviromet.2011.04.003 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 776FX UT WOS:000291521000016 PM 21513741 ER PT J AU Dokmanovic, M Shen, Y Bonacci, TM Hirsch, DS Wu, WJ AF Dokmanovic, Milos Shen, Yi Bonacci, Tabetha M. Hirsch, Dianne S. Wu, Wen Jin TI Trastuzumab Regulates IGFBP-2 and IGFBP-3 to Mediate Growth Inhibition: Implications for the Development of Predictive Biomarkers for Trastuzumab Resistance SO MOLECULAR CANCER THERAPEUTICS LA English DT Article ID BREAST-CANCER CELLS; FACTOR-BINDING PROTEIN-2; FACTOR-I RECEPTOR; THERAPEUTIC TARGET; EPITHELIAL-CELLS; HERCEPTIN; DEGRADATION; APOPTOSIS; MARKER; CDC42 AB Activation of insulin-like growth factor-I receptor (IGF-IR) signaling is an important mechanism for trastuzumab resistance. IGF-binding proteins (IGFBP) modulate IGF-IR signaling and play important roles in the control of breast cancer progression. In this article, we report that trastuzumab treatment enhances the expression and secretion of IGFBP-3 in SKBR3 cells, a trastuzumab-sensitive breast cancer cell line, and that this upregulation of IGFBP-3 induced by trastuzumab correlates with trastuzumab-mediated growth inhibition. We describe a new role for IGFBP-3 in the regulation of IGF-I-mediated cross-talk between IGF-IR and ErbB2 signaling pathways. In particular, treatment of SKBR3 cells with recombinant IGFBP-3 blocks IGF-I-induced activation of IGF-IR and ErbB2, and stable expression of IGFBP-3 inhibits SKBR3 cell growth. We find an inverse relationship in the levels of secreted IGFBP-3 such that high levels of IGFBP-3 are associated with trastuzumab-sensitive breast cancer cells (SKBR3 and BT-474), whereas low levels of IGFBP-3 are found in trastuzumab-resistant cells (clone 3 and JIMT-1). In contrast to IGFBP-3, the secretion and expression of IGFBP-2 are upregulated in trastuzumab-resistant SKBR3 cells. Furthermore, we show that IGFBP-2 stimulates activation of ErbB2 and that trastuzumab reduces IGFBP-2-stimulated ErbB2 activation. Based on our data, we propose a novel mechanism of action whereby trastuzumab enhances the expression and secretion of IGFBP-3, which interferes with IGF-I-mediated mitogenic signaling via autocrine and paracrine mechanisms and reduces IGFBP-2-induced ErbB2 activation to mediate growth inhibition. Changes in secretion profiles of IGFBP-2 and IGFBP-3 in trastuzumab-sensitive and trastuzumab-resistant cells may promote the development of IGFBP-2 and IGFBP-3 as predictive biomarkers for trastuzumab resistance. Mol Cancer Ther; 10(6); 917-28. (C)2011 AACR. C1 [Dokmanovic, Milos; Shen, Yi; Bonacci, Tabetha M.; Hirsch, Dianne S.; Wu, Wen Jin] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Wu, WJ (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, HFD 123,29 Lincoln Dr,NIH Bldg 29B,Room 3 NN-15, Bethesda, MD 20892 USA. EM wen.wu@fda.hhs.gov FU U.S. Food and Drug Administration; National Cancer Institute (NIH) FX This study was supported by the U.S. Food and Drug Administration Critical Path Funding for FY2009 and FY2010 and the Interagency Oncology Task Force (IOTF) Joint Fellowship Program sponsored by the U.S. Food and Drug Administration and National Cancer Institute (NIH). T. M. Bonacci is an IOTF fellow. NR 43 TC 13 Z9 13 U1 1 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1535-7163 J9 MOL CANCER THER JI Mol. Cancer Ther. PD JUN PY 2011 VL 10 IS 6 BP 917 EP 928 DI 10.1158/1535-7163.MCT-10-0980 PG 12 WC Oncology SC Oncology GA 775AI UT WOS:000291428000001 PM 21487052 ER PT J AU Ivanciuc, O Gendel, SM Power, TD Schein, CH Braun, W AF Ivanciuc, Ovidiu Gendel, Steven M. Power, Trevor D. Schein, Catherine H. Braun, Werner TI AllerML: Markup language for allergens SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Allergen database; Allergen markup language; Risk assessment; Bioinformatics guidelines ID IGE BINDING EPITOPES; PEANUT ALLERGEN; FOOD ALLERGY; MOUSE MODEL; PROTEIN ALLERGENICITY; STRUCTURAL-ANALYSIS; SAFETY ASSESSMENT; SEQUENCE MOTIFS; ORAL TOLERANCE; CEDAR POLLEN AB Many concerns have been raised about the potential allergenicity of novel, recombinant proteins into food crops. Guidelines, proposed by WHO/FAO and EFSA, include the use of bioinformatics screening to assess the risk of potential allergenicity or cross-reactivities of all proteins introduced, for example, to improve nutritional value or promote crop resistance. However, there are no universally accepted standards that can be used to encode data on the biology of allergens to facilitate using data from multiple databases in this screening. Therefore, we developed AllerML a markup language for allergens to assist in the automated exchange of information between databases and in the integration of the bioinformatics tools that are used to investigate allergenicity and cross-reactivity. As proof of concept, AllerML was implemented using the Structural Database of Allergenic Proteins (SDAP; http://fermi.utmb.edu/SDAP/) database. General implementation of AllerML will promote automatic flow of validated data that will aid in allergy research and regulatory analysis. (C) 2011 Elsevier Inc. All rights reserved. C1 [Ivanciuc, Ovidiu; Power, Trevor D.; Schein, Catherine H.; Braun, Werner] Univ Texas Med Branch, Sealy Ctr Struct Biol & Mol Biophys, Dept Biochem & Mol Biol, Galveston, TX 77555 USA. [Gendel, Steven M.] US FDA, College Pk, MD 20740 USA. [Schein, Catherine H.] Univ Texas Med Branch, Dept Microbiol & Immunol, Galveston, TX 77555 USA. RP Braun, W (reprint author), Univ Texas Med Branch, Sealy Ctr Struct Biol & Mol Biophys, Dept Biochem & Mol Biol, 301 Univ Blvd, Galveston, TX 77555 USA. EM webraun@utmb.edu RI Schein, Catherine/A-1426-2012; Braun, Werner/A-6642-2012; OI Schein, Catherine/0000-0002-8290-2109 FU National Institute of Health [R01 AI 064913]; US Environmental Protection Agency [RD 83482301]; NIH/EPA [RE-83406601-0]; US Food and Drug Administration [HHSF223200111] FX This work was supported by Grants from the National Institute of Health (R01 AI 064913; W.B. and C.H.S.), the US Environmental Protection Agency STAR Research Assistance Agreement (No. RD 83482301 to W.B.), an NIH/EPA STAR joint program award (RE-83406601-0 to CHS), and a contract from the US Food and Drug Administration (HHSF223200111). The article has not been formally reviewed by the EPA, and the views expressed in this document are solely those of the authors. NR 68 TC 1 Z9 1 U1 0 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUN PY 2011 VL 60 IS 1 BP 151 EP 160 DI 10.1016/j.yrtph.2011.03.006 PG 10 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 774HQ UT WOS:000291376700015 PM 21420460 ER PT J AU Deng, KP Wang, SY Rui, XQ Zhang, W Tortorello, ML AF Deng, Kaiping Wang, Siyun Rui, Xiaoqian Zhang, Wei Tortorello, Mary Lou TI Functional Analysis of ycfR and ycfQ in Escherichia coli O157:H7 Linked to Outbreaks of Illness Associated with Fresh Produce SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID OXIDATIVE STRESS; GENE-EXPRESSION; GENOME SEQUENCE; O157-H7; K-12; O157H7; SPINACH; LIPOPOLYSACCHARIDE; HYDROPHOBICITY; HETEROGENEITY AB Fresh produce has been associated with multiple outbreaks of illness caused by Escherichia coli O157:H7. The mechanism of E. coli O157: H7 survival through postharvest processing of fresh produce needs to be understood to help develop more effective interventions. In our recent transcriptomic study of strain Sakai, an isolate from the 1996 sprout outbreak in Japan, and strain TW14359, an isolate from the 2006 spinach outbreak in the United States, we showed that ycfR was the most significantly upregulated gene in response to chlorine-based oxidative stress. YcfR is known to be a multiple stress resistance protein and a biofilm regulator in E. coli K-12 strains; however, its role in the pathogenic E. coli O157: H7 has not been clearly defined. In this study, ycfR was replaced with a chloramphenicol resistance cassette oriented in two different directions to construct polar and nonpolar ycfR::cat mutants of Sakai and TW14359. Chlorine resistance and survival on spinach leaf surfaces were assessed in the wild-type strains and the ycfR mutants. Both polar and nonpolar ycfR mutants of Sakai showed significantly less chlorine resistance than their parent strain. In contrast, deletion of ycfR in TW14359 did not change chlorine resistance, indicating that ycfR in these two outbreak-related E. coli O157: H7 strains may function differently. In addition, after a 24-h incubation on spinach leaves in a sublethal concentration of chlorine, the Sakai nonpolar ycfR mutant exhibited lower survival compared to the wild type. The results suggest a role for ycfR in survival of Sakai during chlorine exposure. We also found that the upstream ycfQ, which is annotated as a DNA-binding regulator, acted as a repressor of ycfR. These findings suggest that gene regulation may be a mechanism by which E. coli O157: H7 strain Sakai could survive in the postharvest processing environment. C1 [Deng, Kaiping; Tortorello, Mary Lou] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Wang, Siyun; Rui, Xiaoqian; Zhang, Wei] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Tortorello, ML (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM mary.tortorello@fda.hhs.gov FU U.S. Food and Drug Administration; Oak Ridge Institute for Science and Education Research in CFSAN/FDA FX This study was supported by a U.S. Food and Drug Administration cooperative agreement grant to the National Center for Food Safety and Technology of the Illinois Institute of Technology. Kaiping Deng is sponsored by the Oak Ridge Institute for Science and Education Research Participation Program in CFSAN/FDA. NR 36 TC 13 Z9 14 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUN PY 2011 VL 77 IS 12 BP 3952 EP 3959 DI 10.1128/AEM.02420-10 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 773WI UT WOS:000291341800006 PM 21498759 ER PT J AU Jarvis, KG Grim, CJ Franco, AA Gopinath, G Sathyamoorthy, V Hu, L Sadowski, JA Lee, CS Tall, BD AF Jarvis, K. G. Grim, C. J. Franco, A. A. Gopinath, G. Sathyamoorthy, V. Hu, L. Sadowski, J. A. Lee, C. S. Tall, B. D. TI Molecular Characterization of Cronobacter Lipopolysaccharide O-Antigen Gene Clusters and Development of Serotype-Specific PCR Assays SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID NEIGHBOR-JOINING METHOD; ENTEROBACTER-SAKAZAKII; ESCHERICHIA-COLI; SALMONELLA-ENTERICA; POLYSACCHARIDE; FOOD; IDENTIFICATION; BIOSYNTHESIS; SEQUENCE; TOPOLOGY AB Cronobacter (formerly Enterobacter sakazakii) is a recently defined genus consisting of six species, C. sakazakii, C. malonaticus, C. dublinensis, C. muytjensii, C. turicensis, and Cronobacter genomospecies 1. In this study, MboII restriction fragment length polymorphism (RFLP) patterns of O-antigen gene clusters, located between galF and gnd, were used to identify serotypes in Cronobacter spp. Seven O-antigen RFLP clusters were generated, including three C. sakazakii clusters, previously identified as serotypes O1, O2, and O3. The O-antigen regions of six strains with unique RFLP patterns, including two C. sakazakii strains, two C. malonaticus strains, one C. turicensis strain, and one C. muytjensii strain, revealed three O-antigen gene clusters shared among Cronobacter species. PCR assays were developed, targeting the wzx O-antigen polymerase gene, and used to screen 231 Cronobacter strains to determine the frequency of these newly identified serotypes. C1 [Jarvis, K. G.] US FDA, Lab 3412, MOD Facil 1,OARSA,Ctr Food Safety & Appl Nutr, Virulence Mech Branch HFS 025,Div Virulence Asses, Laurel, MD 20708 USA. [Jarvis, K. G.; Grim, C. J.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. RP Jarvis, KG (reprint author), US FDA, Lab 3412, MOD Facil 1,OARSA,Ctr Food Safety & Appl Nutr, Virulence Mech Branch HFS 025,Div Virulence Asses, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM karen.jarvis@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629 FU Department of Energy FX K. G. Jarvis, L. Hu, and C. J. Grim are Oak Ridge Institute for Science and Education fellows, and we thank the Department of Energy for their support. NR 49 TC 43 Z9 44 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUN PY 2011 VL 77 IS 12 BP 4017 EP 4026 DI 10.1128/AEM.00162-11 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 773WI UT WOS:000291341800014 PM 21531829 ER PT J AU Hampp, C Kauf, TL Saidi, AS Winterstein, AG AF Hampp, Christian Kauf, Teresa L. Saidi, Arwa S. Winterstein, Almut G. TI Cost-effectiveness of Respiratory Syncytial Virus Prophylaxis in Various Indications SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID HIGH-RISK INFANTS; PRETERM INFANTS; PALIVIZUMAB PROPHYLAXIS; YOUNG-CHILDREN; US CHILDREN; INFECTION; HOSPITALIZATION; ASSOCIATION; PREVENTION; REGISTRY AB Objectives: To evaluate the cost-effectiveness of immunoprophylaxis against respiratory syncytial virus (RSV) infections with palivizumab based on actual cost and observed incidence rates in various pediatric risk groups. Design: Decision tree analysis comparing children with various combinations of the following indications: chronic lung disease, congenital heart disease, or prematurity (<= 32 weeks gestation), and children with none of these indications. One-way sensitivity analyses and Monte Carlo simulations were used to quantify parameter uncertainty. Setting: Florida during the 2004-2005 RSV season. Participants: A total of 159 790 Medicaid-eligible children aged 0 to 2 years. Intervention: Palivizumab prophylaxis compared with no prophylaxis. Outcomes Measure: Incremental cost (2010 US dollars) per hospitalization for RSV infection avoided. Results: The mean cost of palivizumab per dose ranged from $1661 for infants younger than 6 months of age to $2584 for children in their second year of life. Among pre-term infants younger than 6 months of age without other indications, immunoprophylaxis with palivizumab cost $302 103 (95% confidence interval, $141 850-$914 798) to prevent 1 RSV-related hospitalization. Given a mean cost of $8910 for 1 RSV-related hospitalization in this subgroup, palivizumab would be cost-neutral at a per-dose cost of $47. Incremental cost-effectiveness ratios for the other subgroups ranged from $361 727 to more than $1.3 million per RSV-related hospitalization avoided in children up to 2 years of age with chronic lung disease and no additional risk factors. Younger age and multiple indications were associated with improvements in the incremental cost-effectiveness ratio. Conclusions: The cost of immunoprophylaxis with palivizumab far exceeded the economic benefit of preventing hospitalizations, even in infants at highest risk for RSV infection. C1 [Hampp, Christian] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Epidemiol, Silver Spring, MD 20993 USA. [Kauf, Teresa L.; Winterstein, Almut G.] Univ Florida, Coll Pharm, Dept Pharmaceut Outcomes & Policy, Gainesville, FL USA. [Saidi, Arwa S.] Univ Florida, Coll Med, Dept Pediat, Gainesville, FL USA. [Winterstein, Almut G.] Univ Florida, Coll Publ Hlth & Hlth Profess, Dept Epidemiol & Biostat, Gainesville, FL USA. RP Hampp, C (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Div Epidemiol, 10903 New Hampshire Ave,White Oak Bldg 22,Rm 2441, Silver Spring, MD 20993 USA. EM christian.hampp@fda.hhs.gov RI winterstein, Almut/A-3017-2014; OI winterstein, Almut/0000-0002-6518-5961; Hampp, Christian/0000-0002-1094-6364 FU Florida Agency for Healthcare Administration FX The study received funding from the Florida Agency for Healthcare Administration and was conducted in collaboration with the University of Florida Center for Medicaid and the Uninsured. NR 29 TC 36 Z9 39 U1 2 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUN PY 2011 VL 165 IS 6 BP 498 EP 505 DI 10.1001/archpediatrics.2010.298 PG 8 WC Pediatrics SC Pediatrics GA 773QC UT WOS:000291321000004 PM 21300647 ER PT J AU Yamamoto, M Sato, T Beren, J Verthelyi, D Klinman, DM AF Yamamoto, Masaki Sato, Takashi Beren, Joel Verthelyi, Daniela Klinman, Dennis M. TI The acceleration of wound healing in primates by the local administration of immunostimulatory CpG oligonucleotides SO BIOMATERIALS LA English DT Article DE CpG oligonucleotide; Primate; TLR9; Wound healing ID PLASMACYTOID DENDRITIC CELLS; BACTERIAL-DNA; GROWTH-FACTOR; ACTIVATION; SKIN; MOTIFS; REPAIR; ALPHA; OLIGODEOXYNUCLEOTIDES; IDENTIFICATION AB The process of wound healing involves complex interactions between circulating immune cells and local epithelial and endothelial cells. Studies in murine models indicate that cells of the innate immune system activated via their Toll-like receptors (TLR) can accelerate wound healing. This work examines whether immunostimulatory CpG oligodeoxynucleotides (ODN) designed to trigger human immune cells via TLR9 can promote the healing of excisional skin biopsies in rhesus macaques. Results indicate that 'K' type CpG ODN significantly accelerate wound closure in non-human primates (p < 0.05). Contributing to this outcome was a CpG-dependent increase in both the production of basic fibroblast growth factor and in keratinocyte migration. Of interest, IL-1 alpha and TGF alpha normally present at sites of skin injury facilitated these effects. Current findings support the conclusion that the local administration of CpG ODN may provide an effective strategy for accelerating wound healing in humans. Published by Elsevier Ltd. C1 [Yamamoto, Masaki; Sato, Takashi; Klinman, Dennis M.] NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. [Beren, Joel] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20894 USA. [Verthelyi, Daniela] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20894 USA. RP Klinman, DM (reprint author), NCI, Canc & Inflammat Program, Frederick, MD 21702 USA. EM klinmand@mail.nih.gov FU National Cancer Institute of the National Institutes of Health FX This research was supported by the Intramural Research Program of the National Cancer Institute of the National Institutes of Health. NR 44 TC 10 Z9 11 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD JUN PY 2011 VL 32 IS 18 BP 4238 EP 4242 DI 10.1016/j.biomaterials.2011.02.043 PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 771OW UT WOS:000291171600008 PM 21421264 ER PT J AU Potnis, PA Tesfamariam, B Wood, SC AF Potnis, Pushya A. Tesfamariam, Belay Wood, Steven C. TI Induction of Nicotinamide-Adenine Dinucleotide Phosphate Oxidase and Apoptosis by Biodegradable Polymers in Macrophages: Implications for Stents SO JOURNAL OF CARDIOVASCULAR PHARMACOLOGY LA English DT Article DE drug-eluting stents; biodegradable polymers; biocompatibility; NADPH oxidases; oxidative stress; apoptosis; monocyte adhesion ID NADPH OXIDASE; ENDOTHELIAL-CELLS; OXIDATIVE STRESS; IN-VITRO; EXPRESSION; IMPLANTATION; BIOMATERIAL; SUPEROXIDE; ACTIVATION; MECHANISMS AB The drug-eluting stent platform has a limited surface area, and a polymer carrier matrix is coated to enable sufficient loading of drugs. The development of a suitable polymer has been challenging because it must exhibit biocompatibility with the intravascular milieu. The use of biodegradable polymers seems to be attractive because it enables drug release as it degrades and is eventually eliminated from the body leaving the permanent metallic stent polymer-free. The aim of this study was to investigate the biocompatibility of biodegradable polymers using the human monocyte cell line. Cultured monocytes differentiated into functional macrophages (THP-1) were incubated with various polymers including poly-L-lactide (PLA), polycaprolactone (PCL), or poly-D, L-lactide-co-glycolide (PLGA) for up to 5 days. Exposure of cells to the polymers resulted in macrophage-polymer adhesion and induced marked pro-oxidant species as measured by calcein AM uptake assay and flow cytometric analysis of 2', 7'-dichlorofluorescin fluorescence, respectively. Real-time reverse-transcription polymerase chain reaction and Western blot analysis of expression of nicotinamide-adenine dinucleotide phosphate (NADPH) oxidases revealed enhanced expression of NADPH oxidase subunits in response to PLA and PLGA compared with that of PCL. Flow cytometric analysis of fluorescein isothiocyanate-Annexin V and propium iodide-stained PLA and PGLA polymer-exposed THP-1 cells showed early and late apoptotic changes. Similarly, exposure to the PLA and PGLA polymers, but not to the PCL polymer, resulted in enhanced staining for cleaved poly(ADPribose) polymerase-1, a protein fragment produced by caspase cleavage. These results indicate that biodegradable polymers are associated with cell adhesion, NADPH oxidase-induced generation of reactive oxygen species and excess apoptosis. C1 [Potnis, Pushya A.; Wood, Steven C.] US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Tesfamariam, Belay] US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Potnis, PA (reprint author), US FDA, Off Engn & Sci Lab, CDRH, Bldg 64,Rm 3022,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM pushya.potnis@fda.hhs.gov FU Office of Science and Engineering Laboratories; Food and Drug Administration FX Supported by funds provided by the Office of Science and Engineering Laboratories and the Food and Drug Administration. NR 39 TC 9 Z9 9 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0160-2446 J9 J CARDIOVASC PHARM JI J. Cardiovasc. Pharmacol. PD JUN PY 2011 VL 57 IS 6 BP 712 EP 720 DI 10.1097/FJC.0b013e31821a4f1e PG 9 WC Cardiac & Cardiovascular Systems; Pharmacology & Pharmacy SC Cardiovascular System & Cardiology; Pharmacology & Pharmacy GA 772AL UT WOS:000291201700013 PM 21436724 ER PT J AU Kolibab, K Derrick, SC Morris, SL AF Kolibab, Kristopher Derrick, Steven C. Morris, Sheldon L. TI Sensitivity to Isoniazid of Mycobacterium bovis BCG Strains and BCG Disseminated Disease Isolates SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Letter ID DRUG-RESISTANT TUBERCULOSIS; THERAPY C1 [Kolibab, Kristopher; Derrick, Steven C.; Morris, Sheldon L.] FDA CBER, Lab Mycobacterial Dis & Cellular Immunol, Beltsville, MD 20705 USA. RP Morris, SL (reprint author), FDA CBER, Lab Mycobacterial Dis & Cellular Immunol, Beltsville, MD 20705 USA. EM sheldon.morris@fda.hhs.gov NR 8 TC 6 Z9 9 U1 0 U2 0 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 JUN PY 2011 VL 49 IS 6 BP 2380 EP 2381 DI 10.1128/JCM.00648-11 PG 2 WC Microbiology SC Microbiology GA 769NZ UT WOS:000291024500064 PM 21508153 ER PT J AU Platisa, L Goossens, B Vansteenkiste, E Park, S Gallas, BD Badano, A Philips, W AF Platisa, Ljiljana Goossens, Bart Vansteenkiste, Ewout Park, Subok Gallas, Brandon D. Badano, Aldo Philips, Wilfried TI Channelized Hotelling observers for the assessment of volumetric imaging data sets SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID DISTRIBUTED LUMPY BACKGROUNDS; MODEL OBSERVERS; OBJECTIVE ASSESSMENT; TEXTURE SYNTHESIS; TASK-PERFORMANCE; LESION-DETECTION; GAUSSIAN SIGNAL; QUALITY; NOISE; MULTISLICE AB Current clinical practice is rapidly moving in the direction of volumetric imaging. For two-dimensional (2D) images, task-based medical image quality is often assessed using numerical model observers. For three-dimensional (3D) images, however, these models have been little explored so far. In this work, first, two novel designs of a multislice channelized Hotelling observer (CHO) are proposed for the task of detecting 3D signals in 3D images. The novel designs are then compared and evaluated in a simulation study with five different CHO designs: a single-slice model, three multislice models, and a volumetric model. Four different random background statistics are considered, both Gaussian (noncorrelated and correlated Gaussian noise) and non-Gaussian (lumpy and clustered lumpy backgrounds). Overall, the results show that the volumetric model outperforms the others, while the disparity between the models decreases for greater complexity of the detection task. Among the multislice models, the second proposed CHO could most closely approach the volumetric model, whereas the first new CHO seems to be least affected by the number of training samples. (C) 2011 Optical Society of America C1 [Platisa, Ljiljana; Goossens, Bart; Vansteenkiste, Ewout; Philips, Wilfried] Univ Ghent, TELIN IPI IBBT, B-9000 Ghent, Belgium. [Park, Subok; Gallas, Brandon D.; Badano, Aldo] US FDA, CDRH, Silver Spring, MD 20993 USA. RP Platisa, L (reprint author), Univ Ghent, TELIN IPI IBBT, St Pietersnieuwstr 41, B-9000 Ghent, Belgium. EM Ljiljana.Platisa@Telin.UGent.be OI badano, aldo/0000-0003-3712-6670 FU Interdisciplinary Institute for BroadBand Technology (IBBT) FX This work is financially supported by the Interdisciplinary Institute for BroadBand Technology (IBBT) in the context of the MEdical Virtual Imaging Chain (MEVIC) project. MEVIC is an IBBT project in cooperation with Barco, Hologic, and Philips. IBBT is an independent multidisciplinary research institute founded by the Flemish government to stimulate information and communication technologies innovation. NR 49 TC 45 Z9 46 U1 0 U2 11 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 JUN PY 2011 VL 28 IS 6 BP 1145 EP 1163 PG 19 WC Optics SC Optics GA 773JS UT WOS:000291303700023 PM 21643400 ER PT J AU Zhang, YT Fein, EB Fein, SB AF Zhang, Yuanting Fein, Elizabeth B. Fein, Sara B. TI Feeding of Dietary Botanical Supplements and Teas to Infants in the United States SO PEDIATRICS LA English DT Article DE infant; dietary supplements; pediatric herbs; herbal teas ID FOLK REMEDIES; HERB USE; CHILDREN; POPULATION; MILK; LEAD AB OBJECTIVES: To describe the use of dietary botanical supplements and teas among infants, the characteristics of mothers who give them the specific botanical supplements and teas used, reasons for use, and sources of information. METHODS: We used data from the Infant Feeding Practices Study II, a longitudinal survey of women studied from late pregnancy through their infant's first year of life conducted by the US Food and Drug Administration and the Centers for Disease Control and Prevention between 2005 and 2007. The sample was drawn from a nationally distributed consumer opinion panel and was limited to healthy mothers with healthy term or near-term singleton infants. The final analytical sample included 2653 mothers. Statistical techniques include frequencies, chi(2) tests, and ordered logit models. RESULTS: Nine percent of infants were given dietary botanical supplements or teas in their first year of life, including infants as young as 1 month. Maternal herbal use (P < .0001), longer breastfeeding (P < .0001), and being Hispanic (P < .016) were significantly associated with giving infants dietary botanical supplements or teas in the multivariate model. Many supplements and teas used were marketed and sold specifically for infants. Commonly mentioned information sources included friends or family, health professionals, and the media. CONCLUSIONS: A substantial proportion of infants in this sample was given a wide variety of supplements and teas. Because some supplements given to infants may pose health risks, health care providers need to recognize that infants under their care may be receiving supplements or teas. Pediatrics 2011; 127:1060-1066 C1 [Zhang, Yuanting; Fein, Sara B.] US FDA, Off Regulat Policy & Social Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Fein, Elizabeth B.] Univ Hosp Case Med Ctr, Dept Psychiat, Cleveland, OH USA. RP Zhang, YT (reprint author), US FDA, Off Regulat Policy & Social Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 002, College Pk, MD 20740 USA. EM Yuanting.zhang@fda.hhs.gov NR 22 TC 12 Z9 12 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 JUN PY 2011 VL 127 IS 6 BP 1060 EP 1066 DI 10.1542/peds.2010-2294 PG 7 WC Pediatrics SC Pediatrics GA 771GV UT WOS:000291146100046 PM 21536609 ER PT J AU Budnitz, DS Salis, S AF Budnitz, Daniel S. Salis, Spencer TI Preventing Medication Overdoses in Young Children: An Opportunity for Harm Elimination SO PEDIATRICS LA English DT Editorial Material C1 [Budnitz, Daniel S.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, Atlanta, GA 30333 USA. [Salis, Spencer] US FDA, Div New Drugs & Labeling Compliance, Off Compliance, Silver Spring, MD USA. RP Budnitz, DS (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Natl Ctr Emerging & Zoonot Infect Dis, 1600 Clifton Rd NE,Mail Stop A-24, Atlanta, GA 30333 USA. EM dbudnitz@cdc.gov NR 11 TC 16 Z9 16 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2011 VL 127 IS 6 BP E1597 EP E1599 DI 10.1542/peds.2011-0926 PG 3 WC Pediatrics SC Pediatrics GA 771GV UT WOS:000291146100031 PM 21555494 ER PT J AU Nambiar, S Rellosa, N Wassel, RT Borders-Hemphill, V Bradley, JS AF Nambiar, Sumathi Rellosa, Neil Wassel, Ronald T. Borders-Hemphill, Vicky Bradley, John S. TI Linezolid-Associated Peripheral and Optic Neuropathy in Children SO PEDIATRICS LA English DT Article DE linezolid; peripheral neuropathy; optic neuropathy; pediatrics ID PATIENT AB OBJECTIVE: Peripheral neuropathy (PN) and optic neuropathy (ON) associated with linezolid use are described in the adult literature; however limited information is available in pediatrics. The purpose of this communication is to summarize pediatric cases of linezolid-associated neuropathy and to increase awareness of these neurologic side effects so that clinicians can most appropriately balance the benefits and risks of linezolid in the pediatric population. METHODS: A search of the FDA Adverse Events Reporting System was performed for all pediatric cases of neuropathy from April 2000-2009. AERS includes both inpatient and outpatient data. Inpatient utilization patterns for linezolid were also assessed from January 2000 to December 2008. RESULTS: Eight pediatric cases of linezolid-associated neuropathy were identified. Treatment duration ranged from 4 weeks to 1 year. Five patients had PN alone, one had only ON and two had both. Symptoms of PN included pain, numbness, weakness, and paresthesias. Symptoms of ON included decreased visual acuity and color vision. Three children had other adverse events associated with linezolid including acidosis, anemia, and leukopenia. Outcomes were reported in 5 cases. Resolution of symptoms occurred between 2 weeks and 6 months after discontinuation of linezolid. Utilization data showed that during the study period, overall inpatient utilization of linezolid had increased. CONCLUSIONS: While linezolid may be used to treat serious infections often needing extended courses of therapy, potential safety concerns should be kept in mind. In the circumstance of prolonged use of linezolid in children, it is likely that more cases of neuropathy may occur. Pediatrics 2011;127:e1528-e1532 C1 [Nambiar, Sumathi; Rellosa, Neil] US FDA, Off New Drugs, Off Antimicrobial Prod, Silver Spring, MD 20993 USA. [Wassel, Ronald T.; Borders-Hemphill, Vicky] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Bradley, John S.] Univ Calif San Diego, San Diego, CA 92103 USA. [Bradley, John S.] Rady Childrens Hosp San Diego, San Diego, CA USA. RP Nambiar, S (reprint author), US FDA, Off New Drugs, Off Antimicrobial Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sumathi.nambiar@fda.hhs.gov NR 17 TC 19 Z9 19 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2011 VL 127 IS 6 BP E1528 EP E1532 DI 10.1542/peds.2010-2125 PG 5 WC Pediatrics SC Pediatrics GA 771GV UT WOS:000291146100021 PM 21555496 ER PT J AU Rodriguez, JD Westenberger, BJ Buhse, LF Kauffman, JF AF Rodriguez, Jason D. Westenberger, Benjamin J. Buhse, Lucinda F. Kauffman, John F. TI Quantitative Evaluation of the Sensitivity of Library-Based Raman Spectral Correlation Methods SO ANALYTICAL CHEMISTRY LA English DT Article ID SPECTROSCOPY; IDENTIFICATION; MIXTURES AB Library-based Raman spectral correlation methods are widely used in surveillance applications in multiple areas including the pharmaceutical industry, where Raman spectroscopy is commonly used in verification screening of incoming raw materials. While these spectral correlation methods are rapid and require little or no sample preparation, their sensitivity to the presence of contaminants has not been adequately evaluated. This is particularly important when dealing with pharmaceutical excipients, which are susceptible to economically motivated adulteration by substances having similar physical/chemical/spectroscopic properties. We report a novel approach to evaluating the sensitivity of library-based Raman spectral correlation methods to contaminants in binary systems using a hit-quality index model. We examine three excipient/contaminant systems, glycerin/diethylene glycol, propylene glycol/diethylene glycol, and lactose/melamine and find that the sensitivity to contaminant for each system is 18%, 32%, and 4%, respectively. These levels are well-correlated to the minimum contaminant composition that can be detected by both verification and identification methods. Our studies indicate that the most important factor that determines the sensitivity of a spectral correlation measurement to the presence of contaminant is the relative Raman scattering cross section of the contaminant. C1 [Rodriguez, Jason D.; Westenberger, Benjamin J.; Buhse, Lucinda F.; Kauffman, John F.] US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. RP Kauffman, JF (reprint author), US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM john.kauffman@fda.hhs.gov FU Research Participation Program FX The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. The authors would like to acknowledge Steven Wolfgang of the FDA for useful discussions concerning economically motivated adulteration. The authors would also like to thank Mr. Brendon M. Lyons for preparation of the lactose-melamine samples used in this study. This project was supported in part by an appointment (J.D.R) to the Research Participation Program at the Center for Drug Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 16 TC 16 Z9 16 U1 3 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JUN 1 PY 2011 VL 83 IS 11 BP 4061 EP 4067 DI 10.1021/ac200040b PG 7 WC Chemistry, Analytical SC Chemistry GA 768ZJ UT WOS:000290978500015 PM 21548558 ER PT J AU Chuk, MK Cole, DE McCully, C Loktionova, NA Pegg, AE Parker, RJ Pauly, G Widemann, BC Balis, FM Fox, E AF Chuk, Meredith K. Cole, Diane E. McCully, Cynthia Loktionova, Natalia A. Pegg, Anthony E. Parker, Robert J. Pauly, Gary Widemann, Brigitte C. Balis, Frank M. Fox, Elizabeth TI Plasma and CNS pharmacokinetics of O(4)-benzylfolic acid (O(4)BF) and metabolite in a non-human primate model SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE O(6)-alkylguanine-DNA alkyltransferase (AGT); O(4)-benzylfolic acid; Pharmacokinetics; CSF pharmacokinetics ID PROGRESSIVE MALIGNANT GLIOMA; PHASE-I TRIAL; O-6-ALKYLGUANINE-DNA ALKYLTRANSFERASE; PLUS O-6-BENZYLGUANINE; CEREBROSPINAL-FLUID; FOLATE RECEPTOR; CELL-LINES; CARMUSTINE; O(6)-BENZYLGUANINE; RECURRENT AB O(6)-alkylguanine-DNA alkyltransferase (AGT) repairs DNA damage from alkylating agents by transferring the alkyl adducts from the O(6)-position of guanine in DNA to AGT. The folate analog O(4)-benzylfolic acid (O(4)BF) is an inhibitor of AGT with reported selectivity of the alpha-folate receptor in tumors. We studied plasma and cerebrospinal fluid (CSF) pharmacokinetics and CSF penetration of O(4)BF in a non-human primate model. Rhesus monkeys (Macaca mulatta) received O(4)BF (10-50 mg/kg) intravenously, and serial blood and CSF samples were obtained. Analyte concentrations in plasma were measured by HPLC/photo diode array, and an HPLC/MS/MS assay was used for CSF samples. A putative metabolite of O(4)BF was detected in plasma and CSF. O(4)BF and the metabolite inactivated purified AGT with ED(50) of 0.04 mcM. The median clearance of O(4)BF was 8 ml/min/kg and half-life was 1.1 h. The metabolite had a substantially longer half-life (> 20 h) and greater AUC than O(4)BF. The AUC of the metabolite increased disproportionately to the dose of O(4)BF, suggesting saturable elimination. CSF penetration of O(4)BF and its metabolite was < 1%. At the 50 mg/kg dose level, the C(max) in CSF for O(4)BF was less than 0.09 mcM and for the metabolite the C(max) ranged from 0.02 to 0.04 mcM (O(4)BF equivalents). Concentrations of O(4)BF and the metabolite in CSF exceeded the ED(50) of AGT; however, recently reported lack of receptor specificity and pharmacokinetic data suggesting saturable elimination of both O(4)BF and its metabolite may limit dose-escalation and future clinical development of this agent. C1 [Chuk, Meredith K.; Cole, Diane E.; McCully, Cynthia; Widemann, Brigitte C.] NCI, Pediat Oncol Branch, Bethesda, MD 20892 USA. [Loktionova, Natalia A.; Pegg, Anthony E.] Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Dept Cellular & Mol Physiol, Hershey, PA 17033 USA. [Parker, Robert J.] US FDA, Lab Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Pauly, Gary] NCI, Biol Chem Lab, Frederick, MD 21702 USA. [Balis, Frank M.; Fox, Elizabeth] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. RP Chuk, MK (reprint author), NCI, Pediat Oncol Branch, 10 Ctr Dr,Bldg 10,Rm 1W-5750, Bethesda, MD 20892 USA. EM chukmk@gmail.com FU NIH [R01 CA-071976]; NIH, National Cancer Institute, Center for Cancer Research FX We would like to recognize Robert Moschel and John Strong for their contribution to this project and their enduring contributions to the advancement of pharmacology. This research was supported in part by the Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. The work of NAL and AEP was supported in part by NIH grant R01 CA-071976. NR 18 TC 0 Z9 0 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JUN PY 2011 VL 67 IS 6 BP 1291 EP 1297 DI 10.1007/s00280-010-1407-9 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 769RR UT WOS:000291036500009 PM 20725726 ER PT J AU Yang, MH Kwon, S Kostov, Y Rasooly, A Rao, G Ghosh, U AF Yang, Minghui Kwon, Seokjoon Kostov, Yordan Rasooly, Avraham Rao, Govind Ghosh, Upal TI Study of the biouptake of labeled single-walled carbon nanotubes using fluorescence-based method SO ENVIRONMENTAL CHEMISTRY LETTERS LA English DT Article DE Carbon nanotubes; Biouptake; Fluorescence ID PULMONARY TOXICITY; BIOACCUMULATION; VISUALIZATION; MICROSCOPY; CHEMISTRY; SEDIMENT; CELLS AB Single-wall carbon nanotubes (CNT) are one of the most attractive engineered nanomaterials due to their unique electrical, mechanical and thermal properties, and potential use in a variety of commercial products. Due to their small size, CNT could become easily airborne and reach the various environmental compartments and eventually the food chain and humans. However, the environmental fate processes and health impacts of CNT are not clear. This study investigated a method for the quantitative measurement of carbon nanotube (CNT) in natural media such soil and benthic organism tissues. Fluorescence dye Nile blue was used for noncovalent labeling of CNT to enable their fluorescence detection. Labeled nanotubes were successfully detected in soil samples as well as in worm tissue. We were also able to detect the presence of labeled carbon nanotubes in worms exposed for 1 week to CNT-laden soil, which indicates CNT may transfer through environmental food web. The method allows for laboratory measurements of CNT mass transfer and partitioning into various environmental systems. C1 [Yang, Minghui; Kostov, Yordan; Rao, Govind] Univ Maryland, Ctr Adv Sensor Technol, Baltimore, MD 21227 USA. [Yang, Minghui; Kostov, Yordan; Rao, Govind] Univ Maryland, Dept Chem & Biochem Engn, Baltimore, MD 21227 USA. [Kwon, Seokjoon; Ghosh, Upal] Univ Maryland, Dept Civil & Environm Engn, Baltimore, MD 21227 USA. [Rasooly, Avraham] FDA, Off Sci & Engn, Div Biol, Silver Spring, MD 20993 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. RP Kostov, Y (reprint author), Univ Maryland, Ctr Adv Sensor Technol, 5200 Westland Blvd, Baltimore, MD 21227 USA. EM kostov@umbc.edu FU Department of Health and Human Services [HHSF223200610765P] FX This work was partially supported by a subcontract to Dr Kostov from grant HHSF223200610765P, Department of Health and Human Services. NR 23 TC 7 Z9 7 U1 0 U2 17 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1610-3653 J9 ENVIRON CHEM LETT JI Environ. Chem. Lett. PD JUN PY 2011 VL 9 IS 2 BP 235 EP 241 DI 10.1007/s10311-009-0271-5 PG 7 WC Chemistry, Multidisciplinary; Engineering, Environmental; Environmental Sciences SC Chemistry; Engineering; Environmental Sciences & Ecology GA 769TJ UT WOS:000291040900013 ER PT J AU Kent, M Platt, SR Rech, RR Eagleson, JS Howerth, EW Shoff, M Fuerst, PA Booton, G Visvesvara, GS Schatzberg, SJ AF Kent, Marc Platt, Simon R. Rech, Raquel R. Eagleson, Joseph S. Howerth, Elizabeth W. Shoff, Megan Fuerst, Paul A. Booton, Greg Visvesvara, Govihda S. Schatzberg, Scott J. TI Multisystemic infection with an Acanthamoeba sp in a dog SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID RESPONSIVE MENINGITIS-ARTERITIS; REAL-TIME PCR; PRIMARY AMEBIC MENINGOENCEPHALITIS; URINARY-TRACT-INFECTION; FREE-LIVING AMEBAS; NAEGLERIA-FOWLERI; LONG-TERM; BALAMUTHIA-MANDRILLARIS; OPPORTUNISTIC AMEBAS; KERATITIS AB Case Description-A 10-month-old Boxer was evaluated for fever and signs of cervical pain. Clinical Findings-Physical examination revealed lethargy, fever, and mucopurulent ocular and preputial discharge. On neurologic examination, the gait was characterized by a short stride. The dog kept its head flexed and resisted movement of the neck, consistent with cervical pain. Clinicopathblogic findings included neutrophilic leukocytosis, a left shift, and monocytosis. Cervical radiographs were unremarkable. Cerebrospinal fluid analysis revealed neutrophilic pleocytosis and high total protein content. On the basis of signalment, history, and clinicopathologic data, a diagnosis of steroid-responsive meningitis-arteritis was made. Treatment and Outcome-The dog was treated with prednisone (3.2 mg/kg [1.45 mg/lb], PO, q 24 h), for 3 weeks with limited response. Consequently, azathioprine (2 mg/kg [0.9 mg/lb], PO, q 24 h) was administered. Three weeks later, the dog was evaluated for tachypnea and lethargy. Complete blood count revealed leukopenia, neutropenia, and a left shift. Thoracic radiography revealed a diffuse bronchointerstitial pattern. The dog subsequently went into respiratory arrest and died. On histologic evaluation, amoebic organisms were observed in the lungs, kidneys, and meninges of the brain and spinal cord. A unique Acanthamoeba sp was identified by use of PCR assay. Clinical Relevance-This dog developed systemic amoebic infection presumed to be secondary to immunosuppression. The development of secondary infection should be considered in animals undergoing immunosuppression for immune-mediated disease that develop clinical signs unrelated to the primary disease. Although uncommon, amoebic infection may develop in immunosuppressed animals. Use of a PCR assay for identification of Acanthamoeba spp may provide an antemortem diagnosis. (J Am Vet Med Assoc 2011;238:1476-1481) C1 [Kent, Marc; Platt, Simon R.; Eagleson, Joseph S.; Schatzberg, Scott J.] Univ Georgia, Coll Vet Med, Dept Small Anim Med & Surg, Athens, GA 30602 USA. [Rech, Raquel R.; Howerth, Elizabeth W.] Univ Georgia, Coll Vet Med, Dept Pathol, Athens, GA 30602 USA. [Shoff, Megan] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biol, Silver Spring, MD 20993 USA. [Fuerst, Paul A.] Ohio State Univ, Dept Evolut Ecol & Organismal Biol, Coll Biol Sci, Columbus, OH 43210 USA. [Booton, Greg] Ohio State Univ, Dept Mol Genet, Coll Biol Sci, Columbus, OH 43210 USA. [Visvesvara, Govihda S.] CDC, Div Parasit Dis, Natl Ctr Zoonot Vector Borne & Enter Dis, Atlanta, GA 30333 USA. RP Kent, M (reprint author), Univ Georgia, Coll Vet Med, Dept Small Anim Med & Surg, Athens, GA 30602 USA. EM Mkent1@uga.edu NR 41 TC 10 Z9 10 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD JUN 1 PY 2011 VL 238 IS 11 BP 1476 EP 1481 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 770GR UT WOS:000291075500019 PM 21627512 ER PT J AU Yu, BB Tiwari, RC Feuer, EJ AF Yu, Binbing Tiwari, Ram C. Feuer, Eric J. TI Estimating the personal cure rate of cancer patients using population-based grouped cancer survival data SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article ID PROPORTIONAL HAZARDS MODEL; INTERVAL-CENSORED DATA; REGRESSION-ANALYSIS; ALGORITHM; FAILURE; EM AB Cancer patients are subject to multiple competing risks of death and may die from causes other than the cancer diagnosed. The probability of not dying from the cancer diagnosed, which is one of the patients' main concerns, is sometimes called the 'personal cure' rate. Two approaches of modelling competing-risk survival data, namely the cause-specific hazards approach and the mixture model approach, have been used to model competing-risk survival data. In this article, we first show the connection and differences between crude cause-specific survival in the presence of other causes and net survival in the absence of other causes. The mixture survival model is extended to population-based grouped survival data to estimate the personal cure rate. Using the colorectal cancer survival data from the Surveillance, Epidemiology and End Results Programme, we estimate the probabilities of dying from colorectal cancer, heart disease, and other causes by age at diagnosis, race and American Joint Committee on Cancer stage. C1 [Yu, Binbing] NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. [Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Feuer, Eric J.] NCI, Stat Res & Applicat Branch, Bethesda, MD 20892 USA. RP Yu, BB (reprint author), NIA, Lab Epidemiol Demog & Biometry, Bethesda, MD 20892 USA. EM yubi@mail.nih.gov FU National Cancer Institute; National Institute on Aging FX The research of Dr Yu was carried out in part at the Information Management Services, Inc. and was supported in part by the contract with the National Cancer Institute and by the Intramural Research Programme of the National Institute on Aging. NR 17 TC 2 Z9 2 U1 1 U2 6 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 EI 1477-0334 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD JUN PY 2011 VL 20 IS 3 BP 261 EP 274 DI 10.1177/0962280209347046 PG 14 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 768TU UT WOS:000290962100006 ER PT J AU Boverhof, DR Chamberlain, MP Elcombe, CR Gonzalez, FJ Heflich, RH Hernandez, LG Jacobs, AC Jacobson-Kram, D Luijten, M Maggi, A Manjanatha, MG van Benthem, J Gollapudi, BB AF Boverhof, Darrell R. Chamberlain, Mark P. Elcombe, Clifford R. Gonzalez, Frank J. Heflich, Robert H. Hernandez, Lya G. Jacobs, Abigail C. Jacobson-Kram, David Luijten, Mirjam Maggi, Adriana Manjanatha, Mugimane G. van Benthem, Jan Gollapudi, B. Bhaskar TI Transgenic Animal Models in Toxicology: Historical Perspectives and Future Outlook SO TOXICOLOGICAL SCIENCES LA English DT Article DE transgenic models; knock-out models; humanized models; risk assessment ID PREGNANE-X-RECEPTOR; ARYL-HYDROCARBON RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; CYP1B1 DETERMINES SUSCEPTIBILITY; ZINC-FINGER NUCLEASES; EMBRYONIC STEM-CELLS; DNA-POLYMERASE ETA; IN-VIVO; DRUG-METABOLISM; TARGETED DISRUPTION AB Transgenic animal models are powerful tools for developing a more detailed understanding on the roles of specific genes in biological pathways and systems. Applications of these models have been made within the field of toxicology, most notably for the screening of mutagenic and carcinogenic potential and for the characterization of toxic mechanisms of action. It has long been a goal of research toxicologists to use the data from these models to refine hazard identification and characterization to better inform human health risk assessments. This review provides an overview on the applications of transgenic animal models in the assessment of mutagenicity and carcinogenicity, their use as reporter systems, and as tools for understanding the roles of xenobiotic-metabolizing enzymes and biological receptors in the etiology of chemical toxicity. Perspectives are also shared on the future outlook for these models in toxicology and risk assessment and how transgenic technologies are likely to be an integral tool for toxicity testing in the 21st century. C1 [Boverhof, Darrell R.; Gollapudi, B. Bhaskar] Dow Chem Co USA, Toxicol & Environm Res & Consulting, Midland, MI 48674 USA. [Chamberlain, Mark P.; Elcombe, Clifford R.] CXR Biosci Ltd, Dundee DD1 5JJ, Scotland. [Gonzalez, Frank J.] NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. [Heflich, Robert H.; Manjanatha, Mugimane G.] US FDA, Natl Ctr Toxicol Research, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. [Hernandez, Lya G.; Luijten, Mirjam; van Benthem, Jan] Natl Inst Publ Hlth & Environm RIVM, Lab Hlth Protect Res, NL-3720 BA Bilthoven, Netherlands. [Jacobs, Abigail C.; Jacobson-Kram, David; Maggi, Adriana] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20933 USA. [Maggi, Adriana] Univ Milan, Dept Pharmacol Sci 3, Milan, Italy. [Maggi, Adriana] Univ Milan, Ctr Excellence Neurodegenerat Dis, Milan, Italy. RP Boverhof, DR (reprint author), Dow Chem Co USA, Toxicol & Environm Res & Consulting, 1803 Bldg, Midland, MI 48674 USA. EM RBoverhof@dow.com NR 213 TC 31 Z9 35 U1 1 U2 15 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2011 VL 121 IS 2 BP 207 EP 233 DI 10.1093/toxsci/kfr075 PG 27 WC Toxicology SC Toxicology GA 768JS UT WOS:000290931000001 PM 21447610 ER PT J AU Murphy, AA Herrmann, E Osinusi, AO Wu, L Sachau, W Lempicki, RA Yang, J Chung, TL Wood, BJ Haagmans, BL Kottilil, S Polis, MA AF Murphy, Alison A. Herrmann, Eva Osinusi, Anu O. Wu, Lynn Sachau, William Lempicki, Richard A. Yang, Jun Chung, Tei L. Wood, Brad J. Haagmans, Bart L. Kottilil, Shyam Polis, Michael A. TI Twice-weekly pegylated interferon-alpha-2a and ribavirin results in superior viral kinetics in HIV/hepatitis C virus co-infected patients compared to standard therapy SO AIDS LA English DT Article DE hepatitis C virus; HIV; sustained virologic response; twice-weekly interferon; viral kinetics ID CHRONIC HEPATITIS-C; HUMAN-IMMUNODEFICIENCY-VIRUS; ALPHA-2A PLUS RIBAVIRIN; RANDOMIZED CONTROLLED-TRIAL; HIV-COINFECTED PERSONS; PEGINTERFERON ALPHA-2A; VIROLOGICAL RESPONSE; INDUCTION THERAPY; AFRICAN-AMERICAN; LIVER FIBROSIS AB Background: Hepatitis C virus (HCV)/HIV co-infected patients have more rapid progression of liver fibrosis and only modest cure rates (sustained virologic responses, SVRs) when compared to HCV monoinfected patients. Method: We compared the virologic responses of either twice-weekly peginterferon-alpha-2a 180 mu g/week (for 4 weeks, followed by weekly dosing) or weekly peginterferon-alpha-2a 180 mu g/week, and weight-based ribavirin (1-1.2 g/day), among HIV/HCV co-infected genotype-1 individuals. Results: Patients receiving the investigational dosing had lower levels of HCV RNA at all time points after initiation of therapy. More patients on this arm achieved clinically relevant early virological responses at weeks 1, 2, 4, 12, and 24. The enhanced early virologic response observed with the investigational arm was associated with a higher induction of interferon-stimulated genes. This early double dose regimen also resulted in a rapid normalization of liver enzymes. Twice-weekly peginterferon-a-2a was associated with more frequent early virological responses with similar safety profiles when compared with standard therapy. Conclusion: Our results, when confirmed in larger randomized clinical trials, may provide a novel therapeutic approach to improve SVR among HIV/HCV co-infected patients, especially African-American patients. (C) 2011 Wolters Kluwer Health | Lippincott Williams & Wilkins C1 [Polis, Michael A.] NIAID, Collaborat Clin Res Branch, LIR, NIH,DHHS, Bethesda, MD 20892 USA. [Herrmann, Eva; Chung, Tei L.] Goethe Univ Frankfurt, Dept Med, Inst Biostat & Math Modeling, Frankfurt, Germany. [Wu, Lynn] US FDA, Div Pulm Allergy & Rheumatol Prod, Silver Spring, MD USA. [Osinusi, Anu O.; Lempicki, Richard A.; Yang, Jun] NCI, SAIC Frederick Inc, Frederick, MD 21701 USA. [Wood, Brad J.] NIH, Div Radiol Radiol & Imaging Sci, Bethesda, MD 20892 USA. [Haagmans, Bart L.] Erasmus MC, Rotterdam, Netherlands. RP Polis, MA (reprint author), NIAID, Collaborat Clin Res Branch, LIR, NIH,DHHS, 6700B Rockledge Dr,1118, Bethesda, MD 20892 USA. EM mpolis@niaid.nih.gov RI Lempicki, Richard/E-1844-2012; OI Lempicki, Richard/0000-0002-7059-409X; Polis, Michael/0000-0002-9151-2268 FU NIH, (National Institute of Allergy and Infectious Diseases; National Cancer Institute, National Institutes of Health [HSN261200800001E]; German Research Foundation (DFG) FX The present research was supported in whole or in part by the Intramural Research Program of the NIH, (National Institute of Allergy and Infectious Diseases; National Cancer Institute, National Institutes of Health, under Contract No. HSN261200800001E). It was also supported in part by the German Research Foundation (DFG) as part of the clinical research unit KFO 129. NR 31 TC 13 Z9 14 U1 0 U2 4 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 1 PY 2011 VL 25 IS 9 BP 1179 EP 1187 DI 10.1097/QAD.0b013e3283471d53 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 766BN UT WOS:000290753700005 PM 21593619 ER PT J AU Althoff, KN Eichelberger, M Gange, SJ Sharp, GB Gao, J Glesby, MJ Young, M Greenblatt, RM French, AL Villacres, MC Minkoff, H AF Althoff, Keri N. Eichelberger, Maryna Gange, Stephen J. Sharp, Gerald B. Gao, Jin Glesby, Marshall J. Young, Mary Greenblatt, Ruth M. French, Audrey L. Villacres, Maria C. Minkoff, Howard TI Seroincidence of 2009 H1N1 infection in HIV-infected and HIV-uninfected women prior to vaccine availability SO AIDS LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFLUENZA-A; HIV-1-INFECTED PATIENTS; ANTIBODY-RESPONSES; INTERAGENCY HIV; MORTALITY; OUTBREAK; SEASON AB The 2009 H1N1 pandemic was a unique opportunity to investigate differences in influenza infection using serology by HIV status. Using serial serum specimens collected from 1 April to 30 September 2009 and the prior 2 years from Women's Interagency HIV study participants, there was no difference in serologic evidence of 2009 H1N1 infection among HIV-infected women with a CD4 cell count at least 350 cells/mu l compared with HIV-uninfected women. Owing to evidence showing a greater risk of influenza-related complications, HIV-infected individuals should continue to be a priority group for vaccination. C1 [Althoff, Keri N.; Gange, Stephen J.] Johns Hopkins Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Eichelberger, Maryna; Gao, Jin] US FDA, Bethesda, MD 20014 USA. [Sharp, Gerald B.] NIAID, NIH, Bethesda, MD 20892 USA. [Glesby, Marshall J.] Cornell Univ, Weill Med Coll, New York, NY 10021 USA. [Young, Mary] Georgetown Univ, Washington, DC USA. [Greenblatt, Ruth M.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [French, Audrey L.] Rush Univ, CORE Ctr Stroger Hosp, Chicago, IL 60612 USA. [Villacres, Maria C.] Univ Calif Los Angeles, Los Angeles, CA USA. [Minkoff, Howard] Maimonides Hosp, Brooklyn, NY 11219 USA. RP Althoff, KN (reprint author), 615 N Wolfe St,Rm E7137, Baltimore, MD 21231 USA. EM kalthoff@jhsph.edu OI Gange, Stephen/0000-0001-7842-512X FU NCRR NIH HHS [UL1 RR024131, UL1 RR024131-04S3]; NIAID NIH HHS [U01-AI-42590, U01-AI-34994, U01 AI035004, U01 AI034993-15, U01 AI034989, U01 AI031834-16, K24 AI078884, U01-AI-34989, U01 AI042590-15, U01 AI034989-15, U01 AI034994, U01 AI042590, U01-AI-31834, U01-AI-34993, K24 AI078884-03, U01 AI031834, U01 AI034993, U01 AI034994-15, U01 AI035004-13, U01-AI-35004]; NICHD NIH HHS [U01-HD-32632, U01 HD032632-16, U01 HD032632] NR 18 TC 3 Z9 3 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUN 1 PY 2011 VL 25 IS 9 BP 1229 EP 1232 DI 10.1097/QAD.0b013e3283471cf2 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 766BN UT WOS:000290753700012 PM 21505313 ER PT J AU Ali, AA Lewis, SM Badgley, HL Allaben, WT Leakey, JEA AF Ali, Akhtar A. Lewis, Sherry M. Badgley, Heidi L. Allaben, William T. Leakey, Julian E. A. TI Oral glucosamine increases expression of transforming growth factor beta 1 (TGF beta 1) and connective tissue growth factor (CTGF) mRNA in rat cartilage and kidney: Implications for human efficacy and toxicity SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE Glucosamine; TGF beta; CCN2/CTGF; Hexosamine; Osteoarthritis; Sclerosis ID HEXOSAMINE BIOSYNTHESIS PATHWAY; UDP-N-ACETYLGLUCOSAMINE; INSULIN-RESISTANCE; TGF-BETA; CHONDROITIN SULFATE; MESANGIAL CELLS; KNEE OSTEOARTHRITIS; ARTICULAR-CARTILAGE; GENE-EXPRESSION; DIABETIC-NEPHROPATHY AB Glucosamine is used for alleviating pain in osteoarthritis. Clinical trials have reported that glucosamine has equivocal efficacy. Glucosamine is also used in cell cultures to stimulate hexosamine flux and protein O-glycosylation, but at many-fold greater concentrations than those in human plasma following oral dosing. Lean Zucker rats were dosed orally for 6 weeks with glucosamine hydrochloride at doses (0-600 mg/ kg/day) that produced peak serum concentrations of <1-35 mu M, spanning the human exposure range. Relative expression of both TGF beta 1 and CTGF mRNA were significantly increased up to 2.3-fold in liver, kidney and articular cartilage when evaluated 4 h after final dose. Apparent threshold serum glucosamine (C) concentration required to increase TGF beta 1 expression in cartilage was 10-20 mu M. These increases were associated with significant increases in UDP-N-acetylglucosamine concentrations suggesting increased hexosamine flux. Both TGF beta 1 and CTGF are mediators of chondrocyte proliferation and cartilage repair. Study demonstrates that oral glucosamine doses that produce clinically relevant serum glucosamine concentrations can induce tissue TGF beta 1 and CTGF expression in vivo and provides a mechanistic rationale for reported beneficial effects of glucosamine therapy. Induction of renal TGF beta 1 and CTGF mRNA suggests that potential sclerotic side-effects may occur following consumption of potent glucosamine preparations. Published by Elsevier Inc. C1 [Ali, Akhtar A.; Lewis, Sherry M.; Badgley, Heidi L.; Allaben, William T.; Leakey, Julian E. A.] US FDA, Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. RP Leakey, JEA (reprint author), US FDA, Natl Ctr Toxicol Res, Off Sci Coordinat, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM julian.leakey@fda.hhs.gov FU NCTR/USFDA [IAG 224-07-007 NCTR/NTP]; National Toxicology Program [IAG 224-07-007 NCTR/NTP]; National Institute for Environmental Health Sciences, National Institutes of Health; Oak Ridge Institute of Science and Education FX This work was conducted at the NCTR and supported by an Interagency Agreement (IAG 224-07-007 NCTR/NTP) between the NCTR/USFDA and National Toxicology Program and the National Institute for Environmental Health Sciences, National Institutes of Health. The authors would like to thank Drs. P. Howard, V. Frankos, D. Levy and N. Walker for their critical review of the project; Ms. F. Lewis and Mr. C. Law and the staff of the Bionetics Corporation for animal husbandry support; Mr. A. Warbritton and Ms. A. Babb and the staff of Toxicologic Pathology Associates for assistance in preparation of cartilage and glucosamine analysis, Mr. P. Siitonen and Mr. R. Evans, Division of Biochemical Toxicology, NCTR for purity evaluation of glucosamine HCl. Dr. Ali was supported by funding administered by the Oak Ridge Institute of Science and Education. NR 86 TC 7 Z9 8 U1 1 U2 11 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 EI 1096-0384 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JUN 1 PY 2011 VL 510 IS 1 BP 11 EP 18 DI 10.1016/j.abb.2011.03.014 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 768JJ UT WOS:000290929900002 PM 21466783 ER PT J AU Abernethy, DR Woodcock, J Lesko, LJ AF Abernethy, D. R. Woodcock, J. Lesko, L. J. TI Pharmacological Mechanism-Based Drug Safety Assessment and Prediction SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID PHARMACOVIGILANCE; TOXICITY; BIOLOGY; SYSTEMS; EVENTS; CANCER; SIGNAL; DISCOVERY; MEDICINE AB Advances in cheminformatics, bioinformatics, and pharmacology in the context of biological systems are now at a point that these tools can be applied to mechanism-based drug safety assessment and prediction. The development of such predictive tools at the US Food and Drug Administration (FDA) will complement ongoing efforts in drug safety that are focused on spontaneous adverse event reporting and active surveillance to monitor drug safety. This effort will require the active collaboration of scientists in the pharmaceutical industry, academe, and the National Institutes of Health, as well as those at the FDA, to reach its full potential. Here, we describe the approaches and goals for the mechanism-based drug safety assessment and prediction program. C1 [Abernethy, D. R.; Woodcock, J.; Lesko, L. J.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Abernethy, D. R.; Woodcock, J.; Lesko, L. J.] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Abernethy, DR (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Darrell.abernethy@fda.hhs.gov; Lawrence.lesko@fda.hhs.gov NR 41 TC 28 Z9 28 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 2011 VL 89 IS 6 BP 793 EP 797 DI 10.1038/clpt.2011.55 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 766MG UT WOS:000290786000017 PM 21490594 ER PT J AU Aithal, GP Watkins, PB Andrade, RJ Larrey, D Molokhia, M Takikawa, H Hunt, CM Wilke, RA Avigan, M Kaplowitz, N Bjornsson, E Daly, AK AF Aithal, G. P. Watkins, P. B. Andrade, R. J. Larrey, D. Molokhia, M. Takikawa, H. Hunt, C. M. Wilke, R. A. Avigan, M. Kaplowitz, N. Bjornsson, E. Daly, A. K. TI Case Definition and Phenotype Standardization in Drug-Induced Liver Injury SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID E VIRUS-INFECTION; TERM-FOLLOW-UP; HEPATITIS-E; AUTOIMMUNE HEPATITIS; CAUSALITY ASSESSMENT; UNITED-STATES; NONALCOHOLIC STEATOHEPATITIS; INDUCED HEPATOTOXICITY; PSORIASIS PATIENTS; ADVERSE EVENTS AB Drug-induced liver injury (DILI) is the most frequent reason cited for the withdrawal of approved drugs from the market and accounts for up to 15% of the cases of acute liver failure. Investigators around the globe have begun to identify and study patients with DILI; several large registries and tissue banks are being established. In order to gain the maximum scientific benefit from these efforts, the definitions and terminology related to the clinical phenotypes of DILI must be harmonized. For this purpose, an international DILI Expert Working Group of clinicians and scientists reviewed current DILI terminology and diagnostic criteria so as to develop more uniform criteria that would define and characterize the spectrum of clinical syndromes that constitute DILI. Consensus was established with respect to the threshold criteria for definition of a case as being DILI, the pattern of liver injury, causality assessment, severity, and chronicity. Consensus was also reached on approaches to characterizing DILI in the setting of chronic liver diseases, including autoimmune hepatitis (AIH). C1 [Aithal, G. P.] Nottingham Univ Hosp Natl Hlth Serv Trust, Natl Inst Hlth Res Biomed Res Unit, Nottingham Digest Dis Ctr, Nottingham, England. [Watkins, P. B.] Univ N Carolina Hosp, Hamner Univ N Carolina Inst Drug Safety Sci, Res Triangle Pk, NC USA. [Andrade, R. J.] Hosp Univ Virgen de la Victoria, Hepatol Unit, Malaga, Spain. [Andrade, R. J.] CIBERehd, Barcelona, Spain. [Larrey, D.] Hop St Eloi, Serv Hepatogastroenterol & Transplantat, Montpellier, France. [Molokhia, M.] Kings Coll London, Div Hlth & Social Care Res, Dept Primary Care & Publ Hlth Sci, London WC2R 2LS, England. [Takikawa, H.] Teikyo Univ Sch Med, Dept Med, Tokyo, Japan. [Hunt, C. M.] GlaxoSmithKline Inc, Clin Safety Syst, Res Triangle Pk, NC USA. [Wilke, R. A.] Vanderbilt Univ, Dept Med, Div Clin Pharmacol, Nashville, TN USA. [Avigan, M.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kaplowitz, N.] Univ So Calif, Keck Sch Med, USC Res Ctr Liver Dis, Los Angeles, CA 90033 USA. [Bjornsson, E.] Landspitali Univ Hosp, Div Gastroenterol & Hepatol, Reykjavik, Iceland. [Daly, A. K.] Newcastle Univ Med Sch, Inst Cellular Med, Newcastle Upon Tyne, Tyne & Wear, England. RP Aithal, GP (reprint author), Nottingham Univ Hosp Natl Hlth Serv Trust, Natl Inst Hlth Res Biomed Res Unit, Nottingham Digest Dis Ctr, Nottingham, England. EM Guru.Aithal@nuh.nhs.uk RI Daly, Ann/H-3144-2011; OI Daly, Ann/0000-0002-7321-0629; Andrade Bellido, Raul Jesus/0000-0002-1565-0757 FU International Serious Adverse Event Consortium (iSAEC), US Food and Drug Administration (FDA); Wellcome Trust; SAEC; AstraZeneca; PfizerActelion; Alnara; BMS; Cempra; Esai; Furiex; Genzyme; GlaxoSmithKline; Gilead; Hoffmann-LaRoche; Idenix; Johnson Johnson, TEVA; Merck; Novartis; Nuon; Orixigen; Sanofi-Aventis; Takeda; Wyeth; Sepracor; Schering-Plough; Enanta FX This initiative was supported by the International Serious Adverse Event Consortium (iSAEC) in collaboration with the US Food and Drug Administration (FDA) and The Wellcome Trust. G.P.A., R.J.A., D. L., M. M., E. B., and A. D. are investigators in the International Drug-Induced Liver Injury Consortium (iDILIC), which is supported by the iSAEC. M. M. has received grants from the SAEC consortium and from AstraZeneca and Pfizer. P. B. W. has consulting contracts with Actelion, Alnara, BMS, Cempra, Esai, Furiex, Genzyme, GlaxoSmithKline, Gilead, Hoffmann-LaRoche, Idenix, Johnson & Johnson, TEVA, Merck, Novartis, Nuon, Orixigen, Pfizer, Sanofi-Aventis, Takeda, Wyeth, Sepracor, Schering-Plough, Genzyme, Elan, and Enanta but holds no stock in and has received no research support from these or other companies in the pharmaceutical industry. N.K. has consulting contracts with GlaxoSmithKline, Roche, TEVA, Merck, Novartis, BMS, Johnson & Johnson, Hepregen Biotech, Eisai, Karo-Bio, Wyeth, Dailchi Sankyo, Sanofi-Aventis, Pfizer, ISIS, Idenix, Sepracor, Schering-Plough, Genzyme, Elan, and Enanta but holds no stock in and has received no research support from these or other companies in the pharmaceutical industry. C. M. H. is a fulltime employee of GlaxoSmithKline. The other authors (R. A. W., H. T., and M. A.) declared no conflicts of interest. NR 76 TC 188 Z9 201 U1 4 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 2011 VL 89 IS 6 BP 806 EP 815 DI 10.1038/clpt.2011.58 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 766MG UT WOS:000290786000019 PM 21544079 ER PT J AU Pirmohamed, M Friedmann, PS Molokhia, M Loke, YK Smith, C Phillips, E La Grenade, L Carleton, B Papaluca-Amati, M Demoly, P Shear, NH AF Pirmohamed, M. Friedmann, P. S. Molokhia, M. Loke, Y. K. Smith, C. Phillips, E. La Grenade, L. Carleton, B. Papaluca-Amati, M. Demoly, P. Shear, N. H. TI Phenotype Standardization for Immune-Mediated Drug-Induced Skin Injury SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID STEVENS-JOHNSON-SYNDROME; GENERALIZED EXANTHEMATOUS PUSTULOSIS; TOXIC EPIDERMAL NECROLYSIS; HYPERSENSITIVITY-SYNDROME; HLA-B-ASTERISK-1502 ALLELE; SYSTEMIC SYMPTOMS; CARBAMAZEPINE; MARKER; HLA-A-ASTERISK-3101; EOSINOPHILIA AB Advances in genetic research and molecular biology techniques have made it possible to begin to characterize the underlying genetic factors that predispose patients to serious forms of drug-induced skin injury (DISI). To facilitate research in this area, we have set out standardized phenotypic definitions for (i) Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN), (ii) acute generalized exanthematous pustulosis (AGEP), and (iii) hypersensitivity syndrome (HSS; also known as drug reaction with eosinophilia and systemic symptoms (DRESS) and drug-induced hypersensitivity syndrome (DIHS)). A DISI Expert Working Group comprising participants with varied expertise reviewed and debated current terminology and diagnostic criteria for DISI and agreed on the minimum phenotypic criteria for selected forms of DISI (SJS/TEN, AGEP, and HSS). In addition, an algorithm has been developed to aid appropriate clinical categorization of patients with DISI. These standardized criteria will be important in facilitating adequate and accurate patient recruitment in order to advance research in pharmacogenomic, immunological, mechanistic, and epidemiological studies. C1 [Pirmohamed, M.] Univ Liverpool, Wolfson Ctr Personalised Med, Liverpool L69 3BX, Merseyside, England. [Friedmann, P. S.] Univ Southampton, Sch Med, Infect Inflammat & Immun Div, Southampton, Hants, England. [Molokhia, M.] London Sch Hyg & Trop Med, London WC1, England. [Loke, Y. K.] Univ E Anglia, Norwich, Norfolk, England. [Smith, C.] St Johns Inst Dermatol, Guys & St Thomas Fdn Trust, London, England. [Phillips, E.] Murdoch Univ, Perth, WA, Australia. [Phillips, E.] Univ Western Australia, Sir Charles Gairdner Hosp, Perth, WA 6009, Australia. [Phillips, E.] Royal Perth Hosp, Perth, WA, Australia. [La Grenade, L.] Food & Drug Adm, Silver Spring, MD USA. [Carleton, B.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Papaluca-Amati, M.] European Med Agcy, London, England. [Demoly, P.] Univ Hosp Montpellier, Hop Arnaud Villeneuve, INSERM U657, Dept Allergy, Montpellier, France. [Shear, N. H.] Univ Toronto, Toronto, ON, Canada. RP Pirmohamed, M (reprint author), Univ Liverpool, Wolfson Ctr Personalised Med, Liverpool L69 3BX, Merseyside, England. EM munirp@liv.ac.uk RI Pirmohamed, Munir/H-6004-2011; Smith, Catherine/G-5268-2012; OI Pirmohamed, Munir/0000-0002-7534-7266; Smith, Catherine/0000-0001-9918-1144; /0000-0002-4485-4054 FU International Serious Adverse Event Consortium in collaboration with the Food and Drug Administration; The Wellcome Trust; Abbott; Amgen; Astra-Zeneca; Daiichi Sankyo; GlaxoSmithKline; Merck; Novartis; Pfizer; Takeda; UK Department of Health (National Health Service Chair of Pharmacogenetics); Medical Research Council Centre for Drug Safety Science; EU; ALK; ALK, GlaxoSmithKline; MSD; Schering-Plough; Stallergenes; Therabel; BioXtract; Crucell; National Health and Medical Research Council of Australia; Wyeth; Serono; International Serious Adverse Events Consortium; AstraZeneca FX The authors gratefully acknowledge the following members of the DISI Expert Working Group for their contributions to this article: Andreas Bircher, Nick Craven, Michael Dunn, Jill Lindstrom, Efrosini Setakis, and Julie Papay. This initiative was supported by the International Serious Adverse Event Consortium in collaboration with the Food and Drug Administration and The Wellcome Trust. The iSAEC (http://www.saeconsortium.org) is dedicated to conducting research identifying and validating DNA variants useful in predicting the risk of drug-related serious adverse events. Its funding members include Abbott, Amgen, Astra-Zeneca, Daiichi Sankyo, GlaxoSmithKline, Merck, Novartis, Pfizer, Takeda, and The Wellcome Trust.; M.P. is a National Institute for Health Research senior investigator and has received funding from the UK Department of Health (National Health Service Chair of Pharmacogenetics), The Wellcome Trust, the Medical Research Council Centre for Drug Safety Science, and the EU Seventh Framework Programme. M. P. is also chair of the UK Pharmacovigilance Expert Advisory Group and a commissioner on Human Medicines; the views expressed in this article are his personal views and do not necessarily reflect the views of any of the organizations he represents. P. D. has received lecture fees from ALK, GlaxoSmithKline, MSD, Schering-Plough, Stallergenes, and Therabel and consultancy fees from ALK, BioXtract, Crucell, Schering-Plough, Stallergenes, and Therabel. E.P. has received honoraria from Merck, Viiv, GlaxoSmithKline, and Johnson & Johnson and has received grant funding from the National Health and Medical Research Council of Australia. C. S. has received research sponsorship from Schering-Plough, Wyeth, Abbott, Serono, and Pfizer. M. M. has received grants from the International Serious Adverse Events Consortium and from AstraZeneca and Pfizer. L. L. G. is employed full-time by the US Food and Drug Administration and has no financial interests to disclose; the views expressed are those of the author and are not necessarily those of the FDA. M.P.-A. is an employee of the European Medicines Agency; the views expressed in this article are the personal views of the author and may not be understood or quoted as being made on behalf of or reflecting the position of the European Medicines Agency or any of its committees or working parties. The other authors declared no conflict of interest. NR 30 TC 57 Z9 58 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 2011 VL 89 IS 6 BP 896 EP 901 DI 10.1038/clpt.2011.79 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 766MG UT WOS:000290786000030 PM 21562486 ER PT J AU Wang, W Kinkel, T Martens-Habbena, W Stahl, DA Fang, FC Hansen, EJ AF Wang, Wei Kinkel, Traci Martens-Habbena, Willm Stahl, David A. Fang, Ferric C. Hansen, Eric J. TI The Moraxella catarrhalis Nitric Oxide Reductase Is Essential for Nitric Oxide Detoxification SO JOURNAL OF BACTERIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; NONTYPABLE HAEMOPHILUS-INFLUENZAE; OBSTRUCTIVE PULMONARY-DISEASE; HUMAN EPITHELIAL-CELLS; IN-VITRO; NEISSERIA-MENINGITIDIS; BRANHAMELLA-CATARRHALIS; BIOFILM FORMATION; OTITIS-MEDIA; DENITRIFICATION GENES AB Moraxella catarrhalis is a Gram-negative obligate aerobe that is an important cause of human respiratory tract infections. The M. catarrhalis genome encodes a predicted truncated denitrification pathway that reduces nitrate to nitrous oxide. We have previously shown that expression of both the M. catarrhalis aniA (encoding a nitrite reductase) and norB (encoding a putative nitric oxide reductase) genes is repressed by the transcriptional regulator NsrR under aerobic conditions and that M. catarrhalis O35E nsrR mutants are unable to grow in the presence of low concentrations of nitrite (W. Wang, et al., J. Bacteriol. 190:7762-7772, 2008). In this study, we constructed an M. catarrhalis norB mutant and showed that planktonic growth of this mutant is inhibited by low levels of nitrite, whether or not an nsrR mutation is present. To determine the importance of NorB in this truncated denitrification pathway, we analyzed the metabolism of nitrogen oxides by norB, aniA norB, and nsrR norB mutants. We found that norB mutants are unable to reduce nitric oxide and produce little or no nitrous oxide from nitrite. Furthermore, nitric oxide produced from nitrite by the AniA protein is bactericidal for a Moraxella catarrhalis O35E norB mutant but not for wild-type O35E bacteria under aerobic growth conditions in vitro, suggesting that nitric oxide catabolism in M. catarrhalis is accomplished primarily by the norB gene product. Measurement of bacterial protein S-nitrosylation directly implicates nitrosative stress resulting from AniA-dependent nitric oxide formation as a cause of the growth inhibition of norB and nsrR mutants by nitrite. C1 [Wang, Wei] US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Bethesda, MD 20892 USA. [Wang, Wei; Hansen, Eric J.] Univ Texas SW Med Ctr Dallas, Dept Microbiol, Dallas, TX 75390 USA. [Kinkel, Traci; Fang, Ferric C.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Fang, Ferric C.] Univ Washington, Dept Microbiol, Seattle, WA 98195 USA. [Martens-Habbena, Willm; Stahl, David A.] Univ Washington, Dept Civil & Environm Engn, Seattle, WA 98195 USA. RP Wang, W (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM wei02.wang@fda.hhs.gov RI Martens-Habbena, Willm/I-7656-2013; OI Martens-Habbena, Willm/0000-0002-8495-9125; Fang, Ferric/0000-0002-3243-110X FU FDA; PHS [AI39557, AI036344] FX This study was supported by FDA operating funds to W. W., PHS grant AI39557 to F. C. F., and PHS grant AI036344 to E.J.H. NR 75 TC 15 Z9 15 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JUN PY 2011 VL 193 IS 11 BP 2804 EP 2813 DI 10.1128/JB.00139-11 PG 10 WC Microbiology SC Microbiology GA 763BL UT WOS:000290527900014 PM 21441505 ER PT J AU Malik, T Shegogue, CW Werner, K Ngo, L Sauder, C Zhang, C Duprex, WP Rubin, S AF Malik, Tahir Shegogue, Candie Wolbert Werner, Kellie Ngo, Laurie Sauder, Christian Zhang, Cheryl Duprex, William Paul Rubin, Steven TI Discrimination of Mumps Virus Small Hydrophobic Gene Deletion Effects from Gene Translation Effects on Virus Virulence SO JOURNAL OF VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; SH-PROTEIN; MEMBRANE-PROTEIN; IN-VITRO; PARAMYXOVIRUS; TRANSCRIPTION; INFECTION; SEQUENCES; CELLS; NS2 AB Deletion of the small hydrophobic (SH) protein of certain paramyxoviruses has been found to result in attenuation, suggesting that the SH protein is a virulence factor. To investigate the role of the mumps virus (MuV) SH protein in virulence, multiple stop codons were introduced into the open reading frame (ORF) of a MuV molecular clone (r88-1961(SHstop)), preserving genome structure but precluding production of the SH protein. No differences in neurovirulence were seen between the wild-type and the SH(stop) viruses. In contrast, upon deletion of the SH gene, significant neuroattenuation was observed. These data indicate that the MuV SH protein is not a neurovirulence factor and highlight the importance of distinguishing gene deletion effects from protein-specific effects. C1 [Malik, Tahir; Shegogue, Candie Wolbert; Werner, Kellie; Ngo, Laurie; Sauder, Christian; Zhang, Cheryl; Rubin, Steven] US FDA, DVP Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Duprex, William Paul] Boston Univ, Sch Med, Dept Microbiol, Boston, MA 02118 USA. RP Malik, T (reprint author), US FDA, DVP Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM tahir.malik@fda.hhs.gov OI Duprex, W Paul/0000-0003-1716-6376 FU Oak Ridge Institute for Science and Education; U.S. Department of Energy; U.S. Food and Drug Administration FX Salary support for C. Wolbert, K. Werner, L. Ngo, and C. Zhang was provided 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 26 TC 5 Z9 6 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 JUN PY 2011 VL 85 IS 12 BP 6082 EP 6085 DI 10.1128/JVI.02686-10 PG 4 WC Virology SC Virology GA 766CD UT WOS:000290756600038 PM 21471236 ER PT J AU Soltysik, DA Thomasson, D Rajan, S Gonzalez-Castillo, J DiCamillo, P Biassou, N AF Soltysik, David A. Thomasson, David Rajan, Sunder Gonzalez-Castillo, Javier DiCamillo, Paul Biassou, Nadia TI Head-repositioning does not reduce the reproducibility of fMRI activation in a block-design motor task SO NEUROIMAGE LA English DT Article DE fMRI; Reproducibility; Test-retest; Finger-tapping ID FUNCTIONAL MRI; REGISTRATION; VARIABILITY; RELIABILITY; RESOLUTION AB It is hypothesized that, based upon partial volume effects and spatial non-uniformities of the scanning environment, repositioning a subject's head inside the head coil between separate functional MRI scans will reduce the reproducibility of fMRI activation compared to a series of functional runs where the subject's head remains in the same position. Nine subjects underwent fMRI scanning where they performed a sequential, oppositional finger-tapping task. The first five runs were conducted with the subject's head remaining stable inside the head coil. Following this, four more runs were collected after the subject removed and replaced his/her head inside the head coil before each run. The coefficient of variation was calculated for four metrics: the distance from the anterior commisure to the center of mass of sensorimotor activation, maximum t-statistic, activation volume, and average percent signal change. These values were compared for five head-stabilization runs and five head-repositioning runs. Voxelwise intraclass correlation coefficients were also calculated to assess the spatial distribution of sources of variance. Interestingly, head repositioning was not seen to significantly affect the reproducibility of fMRI activation (p<0.05). In addition, the threshold level affected the reproducibility of activation volume and percent signal change. Published by Elsevier Inc. C1 [Soltysik, David A.; Rajan, Sunder] US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Thomasson, David; DiCamillo, Paul; Biassou, Nadia] NIH, Dept Radiol, Bethesda, MD 20892 USA. [Gonzalez-Castillo, Javier] NIMH, Sect Funct Imaging Methods, Lab Brain & Cognit, NIH, Bethesda, MD 20892 USA. RP Soltysik, DA (reprint author), US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM david.soltysik@fda.hhs.gov RI Gonzalez-Castillo, Javier/B-6903-2012; OI SOLTYSIK, DAVID/0000-0002-6597-5226; Gonzalez-Castillo, Javier/0000-0002-6520-5125 FU Radiology and Imaging Sciences Department of the Warren G. Magnuson Clinical Center at the National Institutes of Health FX This project is supported by the Radiology and Imaging Sciences Department of the Warren G. Magnuson Clinical Center at the National Institutes of Health. NR 33 TC 7 Z9 7 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 1053-8119 EI 1095-9572 J9 NEUROIMAGE JI Neuroimage PD JUN 1 PY 2011 VL 56 IS 3 BP 1329 EP 1337 DI 10.1016/j.neuroimage.2011.03.023 PG 9 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 764RF UT WOS:000290649300046 PM 21406235 ER PT J AU Reddy, UM Bettegowda, VR Dias, T Yamada-Kushnir, T Ko, CW Willinger, M AF Reddy, Uma M. Bettegowda, Vani R. Dias, Todd Yamada-Kushnir, Tomoko Ko, Chia-Wen Willinger, Marian TI Term Pregnancy A Period of Heterogeneous Risk for Infant Mortality SO OBSTETRICS AND GYNECOLOGY LA English DT Article ID BIRTH CERTIFICATES; GESTATIONAL-AGE AB OBJECTIVE: To estimate the trend of maternal racial and ethnic differences in mortality for early-term (37 0/7 to 38 6/7 weeks of gestation) compared with full-term births (39 0/7 to 41 6/7 weeks of gestation). METHODS: We analyzed 46,329,018 singleton live births using the National Center for Health Statistics U.S. period-linked birth and infant death data from 1995 to 2006. Infant mortality rates, neonatal mortality rates, and post-neonatal mortality rates were calculated according to gestational age, race and ethnicity, and cause of death. RESULTS: Overall, infant mortality rates have decreased for early-term and full-term births between 1995 and 2006. At 37 weeks of gestation, Hispanics had the greatest decline in infant mortality rates (35.4%; 4.8 per 1,000 to 3.1 per 1,000) followed by 22.4% for whites (4.9 per 1,000 to 3.8 per 1,000); blacks had the smallest decline (6.8%; 5.9 per 1,000 to 5.5 per 1,000) as a result of a stagnant neonatal mortality rate. At 37 weeks compared with 40 weeks of gestation, neonatal mortality rates increase. For Hispanics, the relative risk is 2.6 (95% confidence interval [CI] 2.0-3.3); for whites, the relative risk is 2.6 (95% CI 2.2-3.1); and for blacks, the relative risk is 2.9 (95% CI 2.2-3.8). Neonatal mortality rates are still increased at 38 weeks of gestation. At both early-and full-term gestations, neonatal mortality rates for blacks are 40% higher than for whites and post-neonatal mortality rates 80% higher, whereas Hispanics have a reduced post-neonatal mortality rate when compared with whites. CONCLUSION: Early-term births are associated with higher neonatal, postneonatal, and infant mortality rates compared with full-term births with concerning racial and ethnic disparity in rates and trends. (Obstet Gynecol 2011;117:1279-87) DOI: 10.1097/AOG.0b013e3182179e28 C1 Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD USA. US FDA, Silver Spring, MD USA. March Dimes, White Plains, NY USA. RP Reddy, UM (reprint author), 6100 Execut Blvd,Room 4B03F, Bethesda, MD 20892 USA. EM reddyu@mail.nih.gov NR 14 TC 81 Z9 82 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA TWO COMMERCE SQ, 2001 MARKET ST, PHILADELPHIA, PA 19103 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2011 VL 117 IS 6 BP 1279 EP 1287 DI 10.1097/AOG.0b013e3182179e28 PG 9 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 768AT UT WOS:000290904200006 PM 21606738 ER PT J AU Duggirala, HJ Herz, ND Canos, DA Sullivan, R Schaaf, R Pinnow, E Marinac-Dabic, D AF Duggirala, H. J. Herz, N. D. Canos, D. A. Sullivan, R. Schaaf, Richard Pinnow, E. Marinac-Dabic, D. TI DISPROPORTIONALITY ANALYSIS FOR PHARMACOVIGILANCE OF MEDICAL DEVICE RELATED ADVERSE EVENTS REPORTED TO THE FDA SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Duggirala, H. J.; Herz, N. D.; Canos, D. A.; Sullivan, R.; Schaaf, Richard; Pinnow, E.; Marinac-Dabic, D.] Ctr Devices & Radiol Hlth Food & Drug Adm, Silver Spring, MD 20993 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S131 EP S131 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600510 ER PT J AU Hu, L Grim, CJ Franco, AA Gopinath, G Jarvis, KG Kothary, MH McCardell, BA Tall, BD AF Hu, L. Grim, C. J. Franco, A. A. Gopinath, G. Jarvis, K. G. Kothary, M. H. McCardell, B. A. Tall, B. D. TI ANALYSIS OF THE ROLE OF CELLULOSE GENES BCSA, BCSB, AND BCSC IN BIOFILM FORMATION IN CRONOBACTER SPP. USING PCR ASSAY AND GENE MUTATION SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Hu, L.; Grim, C. J.; Franco, A. A.; Gopinath, G.; Jarvis, K. G.; Kothary, M. H.; McCardell, B. A.; Tall, B. D.] US FDA, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S181 EP S181 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114601002 ER PT J AU Krulewitch, CJ Ritchey, ME Cheng, H Marinac-Dabic, D Gross, T Gibbs, J AF Krulewitch, C. J. Ritchey, M. E. Cheng, H. Marinac-Dabic, D. Gross, T. Gibbs, J. TI A METHODOLOGY TO USE THE MEDICARE CLAIMS DATABASE TO EVALUATE MEDICAL DEVICE SAFETY: THE CASE OF UROGYNECOLOGIC SURGICAL MESH FOR REPAIR OF PELVIC ORGAN PROLAPSE. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Krulewitch, C. J.; Ritchey, M. E.; Cheng, H.; Marinac-Dabic, D.; Gross, T.; Gibbs, J.] US FDA, Ctr Devices & Radiol Hlth, Washington, DC 20204 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 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S159 EP S159 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114600621 ER PT J AU Marinac-Dabic, D Ritchey, ME Pinnow, E Wong, HL AF Marinac-Dabic, D. Ritchey, M. E. Pinnow, E. Wong, H. L. TI THE MEDICAL DEVICE EPIDEMIOLOGY NETWORK (MDEPINET)-IMPACTING THE FUTURE OF REGULATORY SCIENCE PRACTICE SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 3rd North American Congress of Epidemiology CY JUN 21-24, 2011 CL Montreal, CANADA C1 [Marinac-Dabic, D.; Ritchey, M. E.; Pinnow, E.; Wong, H. L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 EI 1476-6256 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2011 VL 173 SU 11 BP S286 EP S286 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 810GU UT WOS:000294114601404 ER PT J AU Porter, KL Olmstead, AW Kumsher, DM Dennis, WE Sprando, RL Holcombe, GW Korte, JJ Lindberg-Livingston, A Degitz, SJ AF Porter, Karen L. Olmstead, Allen W. Kumsher, David M. Dennis, William E. Sprando, Robert L. Holcombe, Gary W. Korte, Joseph J. Lindberg-Livingston, Annelie Degitz, Sigmund J. TI Effects of 4-tert-octylphenol on Xenopus tropicalis in a long term exposure SO AQUATIC TOXICOLOGY LA English DT Article DE Xenopus tropicalis; Octylphenol; Estrogenic; Vitellogenin; Oviducts ID CHROMATOGRAPHY-MASS SPECTROMETRY; MEDAKA ORYZIAS-LATIPES; FROG RANA-PIPIENS; ENDOCRINE DISRUPTION; BISPHENOL-A; IN-VITRO; ESTROGENIC ACTIVITY; REPRODUCTIVE TOXICITY; SEX-DIFFERENTIATION; POLYCHLORINATED-BIPHENYLS AB Endocrine disrupting chemicals that activate the estrogen receptor are routinely detected in the environment and are a concern for the health of both exposed humans and indigenous wildlife. We exposed the western clawed frog (Xenopus tropicalis) to the weak estrogen octylphenol from Nieuwkoop-Faber (NF) stage 46 tadpoles through adulthood in order to document the effects of a weak estrogen on the life history of an amphibian species. Frogs were exposed to 1, 3.3, 11 and 36 mu g/L octylphenol in a continuous flow-through water system. Just prior to completion of metamorphosis (NF 65), a random subsample of froglets was collected and assessed, while the remaining frogs received continued exposure through 31 weeks of exposure when the remaining animals were sampled. Significant induction of the female egg yolk protein precursor vitellogenin was observed in the high treatment at the larval subsampling for both males and females, but not at the final sampling for either sex. No significant deviation from the control sex ratio was observed for either sampling period, suggesting minimal to no effect of octylphenol exposure on gonad differentiation. No effects in the adult frogs were observed for mortality, body mass and size, liver somatic index, estradiol and testosterone serum levels, sperm counts, or oocyte counts. The development and growth of oviducts, a female-specific secondary sex characteristic, was observed in males exposed to octyl phenol. These results indicate that octylphenol exposure can induce vitellogenin in immature froglets and the development of oviducts in male adult frogs. The lack of effect observed on the developing gonads suggests that in amphibians, secondary sex characteristics are more susceptible to impact from estrogenic compounds than the developing gonads. Published by Elsevier B.V. C1 [Porter, Karen L.; Kumsher, David M.; Dennis, William E.] USA, Ctr Environm Hlth Res, Ft Detrick, MD 21702 USA. [Olmstead, Allen W.; Holcombe, Gary W.; Korte, Joseph J.; Lindberg-Livingston, Annelie; Degitz, Sigmund J.] US EPA, Natl Hlth & Environm Effects Res Lab, Midcontinent Ecol Div, Duluth, MN USA. [Sprando, Robert L.] US FDA, Ctr Food Safety & Appl Nutr, Div Toxicol, Laurel, MD USA. RP Porter, KL (reprint author), USA, Ctr Environm Hlth Res, 568 Doughten Dr, Ft Detrick, MD 21702 USA. EM karen.porter@amedd.army.mil NR 70 TC 12 Z9 13 U1 6 U2 23 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-445X J9 AQUAT TOXICOL JI Aquat. Toxicol. PD JUN PY 2011 VL 103 IS 3-4 BP 159 EP 169 DI 10.1016/j.aquatox.2011.02.019 PG 11 WC Marine & Freshwater Biology; Toxicology SC Marine & Freshwater Biology; Toxicology GA 781CL UT WOS:000291908100004 PM 21470552 ER PT J AU Chelonis, JJ Gravelin, CR Paule, MG AF Chelonis, John J. Gravelin, Claire R. Paule, Merle G. TI Assessing motivation in children using a progressive ratio task SO BEHAVIOURAL PROCESSES LA English DT Article DE Motivation; Progressive ratio; Age; Sex; Children ID BEHAVIORAL-TEST BATTERY; SCHEDULE REQUIREMENTS; DEVELOPMENTAL ASPECTS; REINFORCING EFFICACY; SEX-DIFFERENCES; FEMALE RATS; PERFORMANCE; PREFERENCE; MAGNITUDE AB The association of age and sex on the performance of a progressive ratio task was studied in 847 children, ages 4-14 years. Variations of this task have been used extensively with animals and to a lesser extent with humans to study factors that affect aspects of motivation. The participants in this study were required to press a response lever for nickel reinforcers during a 10 min period. One response was required to earn the first nickel and each subsequent nickel required an additional 10 more responses. Older children had a significantly higher breakpoint than younger children. This appeared to be mostly the result of older children having significantly shorter inter-response times than younger children. In addition, boys had significantly higher breakpoints than girls, especially at older ages. The results of this study illustrate that both age and sex influence the performance of this task and thus suggest that age and sex influence aspects of motivation in children. Further, characterization of performance of this task by humans facilitates comparisons with animal models and, thus, enhances its translational utility. Published by Elsevier B.V. C1 [Chelonis, John J.; Gravelin, Claire R.; Paule, Merle G.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Rockville, MD 20857 USA. [Chelonis, John J.; Paule, Merle G.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72205 USA. RP Chelonis, JJ (reprint author), Arkansas Childrens Hosp, Dept Pediat CARE, 1 Childrens Way,Slot 512-26, Little Rock, AR 72202 USA. EM john.chelonis@fda.hhs.gov FU National Center for Toxicological Research; U.S. Department of Energy; U.S. Food and Drug Administration FX This research was supported in part by an appointment (CRG) to the Summer Student Research Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. NR 29 TC 12 Z9 12 U1 3 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0376-6357 J9 BEHAV PROCESS JI Behav. Processes PD JUN PY 2011 VL 87 IS 2 BP 203 EP 209 DI 10.1016/j.beproc.2011.03.008 PG 7 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA 781AP UT WOS:000291903300007 PM 21507343 ER PT J AU Hansen, DK Juliar, BE White, GE Pellicore, LS AF Hansen, Deborah K. Juliar, Beth E. White, Gene E. Pellicore, Linda S. TI Developmental Toxicity of Citrus aurantium in Rats SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Article DE bitter orange; Citrus aurantium; synephrine; birth defects; rats; ephedra; dietary supplement ID PERFORMANCE LIQUID-CHROMATOGRAPHY; WEIGHT-LOSS SUPPLEMENTS; DIETARY-SUPPLEMENTS; CARDIOVASCULAR TERATOGENICITY; CHICK-EMBRYOS; UNITED-STATES; EPHEDRINE; CAFFEINE; ALKALOIDS; EFFICACY AB BACKGROUND: Ephedra was commonly used in herbal products marketed for weight loss until safety concerns forced its removal from products. Even before the ban, manufacturers had begun to replace ephedra with other compounds, including Citrus aurantium, or bitter orange. The major component in the bitter orange extract is synephrine which is chemically similar to ephedrine. The purpose of this study was to determine if relatively pure synephrine or synephrine present as a constituent of a bitter orange extract produced developmental toxicity in rats. METHOD: Sprague-Dawley rats were dosed daily by gavage with one of several different doses of synephrine from one of two different extracts. Caffeine was added to some doses. Animals were sacrificed on CD 21, and fetuses were examined for the presence of various developmental toxic endpoints. RESULTS AND CONCLUSION: At doses up to 100 mg synephrine/kg body weight, there were no adverse effects on embryolethality, fetal weight, or incidences of gross, visceral, or skeletal abnormalities. There was a decrease in maternal weight at 50 mg synephrine/kg body weight when given as the 6% synephrine extract with 25 mg caffeine/kg body weight; there was also a decrease in maternal weight in the caffeine only group. This decrease in body weight may have been due to decreased food consumption which was also observed in these two groups. Overall, doses of up to 100 mg synephrine/kg body weight did not produce developmental toxicity in Sprague-Dawley rats. Birth Defects Res (Part B) 92:216-223, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Hansen, Deborah K.; Juliar, Beth E.] US FDA, Div Personalized Nutr & Med, NCTR, Jefferson, AR 72079 USA. [White, Gene E.] Toxicol Pathol Associates, Jefferson, AR USA. [Pellicore, Linda S.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Hansen, DK (reprint author), US FDA, Div Personalized Nutr & Med, NCTR, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM deborah.hansen@fda.hhs.gov FU NIEHS/NTP; FDA/NCTR [NIH Y1ES1027, FDA, 224-07-0007] FX Grant sponsor: NIEHS/NTP and FDA/NCTR: Grant numbers NIH Y1ES1027; FDA, 224-07-0007. NR 33 TC 4 Z9 5 U1 0 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD JUN PY 2011 VL 92 IS 3 BP 216 EP 223 DI 10.1002/bdrb.20308 PG 8 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 787BB UT WOS:000292350500004 PM 21594979 ER PT J AU Davis-Bruno, K Tassinari, MS AF Davis-Bruno, Karen Tassinari, Melissa S. TI Essential Fatty Acid Supplementation of DHA and ARA and Effects on Neurodevelopment across Animal Species: A Review of the Literature SO BIRTH DEFECTS RESEARCH PART B-DEVELOPMENTAL AND REPRODUCTIVE TOXICOLOGY LA English DT Review DE embryo/fetal physiology; species extrapolation; safety assessment; risk assessment; regulatory; nutrition; modeling; maternal-fetal interactions ID DOCOSAHEXAENOIC ACID; RHESUS-MONKEYS; PHOSPHOLIPID SUPPLEMENTATION; RETINAL FUNCTION; FRONTAL-CORTEX; VISUAL-ACUITY; RAT-BRAIN; DEFICIENCY; BEHAVIOR; BIOCHEMISTRY AB Docosahexanoic acid (DHA) and arachidonic acid (ARA) are long chain essential fatty acids used as supplements in commercial infant formula. DHA/ARA deficient states are associated with adverse neurological outcomes in animals and humans. Preterm infants are at risk for DHA/ARA deficiency. A few clinical reports on the effects of fatty acid supplementation have shown benefit in preterm, low birth weight, and normal infants in the first year of life, whereas others did not. Studies in animals have reported shortened gestation, fetal growth retardation, reduced infant body mass, and increased fetal mortality with consumption of fatty acids during pregnancy. To understand the data that support fatty acid supplementation in infant formula, a review of the animal model literature was undertaken, to examine the effects of DHA/ARA on neurodevelopment, including the effects on visual acuity. Several points emerged from this review. (1) Animal studies indicate that requirements for DHA/ARA vary depending on developmental age. Alterations of the ratio of DHA/ARA can impact developmental outcome. (2) The available studies suggest that while supplementation of DHA/ARA in an appropriate ratio can increase tissue levels of these fatty acids in the brain and retina, tissues sensitive to depletion of fatty acids, the benefit of routine supplementation remains unclear. Few studies measure functional outcome relative to changes in physiologic pools of DHA/ARA after supplementation. (3) Animal literature does not support a clear long-term benefit of replenishing DHA/ARA tissue levels and administration of these fatty acids at concentrations above those in human milk suggests adverse effects on growth, survival, and neurodevelopment. Birth Defects Res (Part B) 92:240-250, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Davis-Bruno, Karen; Tassinari, Melissa S.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Davis-Bruno, K (reprint author), US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Karen.DavisBruno@fda.hhs.gov NR 45 TC 21 Z9 22 U1 3 U2 16 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-9733 J9 BIRTH DEFECTS RES B JI Birth Defects Res. Part B-Dev. Reprod. Toxicol. PD JUN PY 2011 VL 92 IS 3 BP 240 EP 250 DI 10.1002/bdrb.20311 PG 11 WC Oncology; Genetics & Heredity; Toxicology SC Oncology; Genetics & Heredity; Toxicology GA 787BB UT WOS:000292350500007 PM 21678548 ER PT J AU Morrison, BW Cochran, CJ White, JG Harley, J Kleppinger, CF Liu, A Mitchel, JT Nickerson, DF Zacharias, CR Kramer, JM Neaton, JD AF Morrison, Briggs W. Cochran, Chrissy J. White, Jennifer Giangrande Harley, Joan Kleppinger, Cynthia F. Liu, An Mitchel, Jules T. Nickerson, David F. Zacharias, Cynthia R. Kramer, Judith M. Neaton, James D. TI Monitoring the quality of conduct of clinical trials: a survey of current practices SO CLINICAL TRIALS LA English DT Article ID ASSURANCE; COSTS AB Background There is a little empirical evidence to determine which, if any, monitoring practices best achieve the goals of trial monitoring set forth in ICH E6 under the variable circumstances of different clinical trial settings. Purpose The purpose of this project was to describe current methods of monitoring clinical trials and to explore the rationale for the use of those methods. Methods An electronic survey of known monitoring practices was developed and sent to over 200 organizations involved in conducting clinical research. The survey collected information on institutional demographics, methods of overall study oversight, use of risk-based monitoring and factors that influence assessments of risk, and details on quality assurance and monitoring practices. Results Seventy-nine organizations completed the survey; our analysis included the 65 organizations that indicated they perform clinical trials. Data from the survey indicate that a wide variety of monitoring practices are currently being employed. Eighty-three percent of respondents use centrally available data to evaluate site performance, but only 12% of respondents always or frequently used centralized monitoring to replace on-site visits. Eighty-seven percent of respondents indicated that they always performed on-site visits. This varied by type of organization, with 31% of academic coordinating centers/cooperative groups/government organizations always performing on-site monitoring visits versus 84% of other organizations. The rationale for using a specific monitoring approach does not appear to be based on empirical evidence. Fifty-four percent of respondents stated that 'usual practice' determined the frequency with which they conducted on-site monitoring visits. Limitations The overall response rate to our survey was only 30%; thus, we may not have captured the full variance of current monitoring practices, and our responding sample may not be representative. Conclusion These findings underscore the necessity of research to provide an evidence base for monitoring practice. Clinical Trials 2011; 8: 342-349. http://ctj.sagepub.com C1 [Kramer, Judith M.] Duke Translat Med Inst, Durham, NC USA. [Morrison, Briggs W.; Nickerson, David F.] Pfizer Inc, New London, CT USA. [Cochran, Chrissy J.] US FDA, Div Biores Monitoring, Silver Spring, MD USA. [White, Jennifer Giangrande] Roche, Nutley, NJ USA. [Harley, Joan] Training Extens Pastor Consulting Inc, Wayne, PA USA. [Kleppinger, Cynthia F.] US FDA, Div Sci Invest, Silver Spring, MD USA. [Liu, An] Alquest LLC, Minneapolis, MN USA. [Mitchel, Jules T.] Target Hlth Inc, New York, NY USA. [Zacharias, Cynthia R.] Bristol Myers Squibb Co, Princeton, NJ USA. [Neaton, James D.] Univ Minnesota, Div Biostat, Minneapolis, MN USA. RP Kramer, JM (reprint author), Duke Translat Med Inst, Durham, NC USA. EM krame009@mc.duke.edu NR 8 TC 21 Z9 25 U1 1 U2 10 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 JUN PY 2011 VL 8 IS 3 BP 342 EP 349 DI 10.1177/1740774511402703 PG 8 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 787RN UT WOS:000292394500010 PM 21730082 ER PT J AU Haas, DM Gallauresi, B Shields, K Zeitlin, D Clark, SM Hebert, MF Ren, ZX Nallani, SC Meslin, EM Feibus, KB Koren, G Goebel, WS Easterling, T Denne, SC Flockhart, DA Renbarger, JL AF Haas, David M. Gallauresi, Beverly Shields, Kristine Zeitlin, Deborah Clark, Shannon M. Hebert, Mary F. Ren, Zhaoxia Nallani, Srikanth C. Meslin, Eric M. Feibus, Karen B. Koren, Gideon Goebel, W. Scott Easterling, Thomas Denne, Scott C. Flockhart, David A. Renbarger, Jamie L. TI Pharmacotherapy and Pregnancy: Highlights from the Third International Conference for Individualized Pharmacotherapy in Pregnancy SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Article ID PRESCRIPTION DRUG-USE; PRETERM LABOR; PHARMACOKINETICS; WOMEN; HYPERTENSION; ASSOCIATION; POSTPARTUM; MANAGEMENT; GLYBURIDE; METFORMIN AB To address provider struggles to provide evidence-based, rational drug therapy to pregnant women, this third Conference was convened to highlight the current progress and research in the field. Speakers from academic centers, industry, and governmental institutions spoke about: the Food and Drug Administration's role in pregnancy pharmacology and the new labeling initiative; drug registries in pregnancy; the pharmacist's role in medication use in pregnancy; therapeutic areas such as preterm labor, gestational diabetes, nausea and vomiting in pregnancy, and hypertension; breast-feeding and medications; ethical challenges for consent in pregnancy drug studies; the potential for cord blood banks; and concerns about the fetus when studying drugs in pregnancy. The Conference highlighted several areas of collaboration within the current Obstetrics Pharmacology Research Units Network and hoped to educate providers, researchers, and agencies with the common goal to improve the ability to safely and effectively use individualized pharmacotherapy in pregnancy. Clin Trans Sci 2011; Volume 4: 204-209 C1 [Haas, David M.; Meslin, Eric M.; Goebel, W. Scott; Denne, Scott C.; Flockhart, David A.; Renbarger, Jamie L.] Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. [Haas, David M.; Meslin, Eric M.; Denne, Scott C.; Flockhart, David A.; Renbarger, Jamie L.] Indiana Univ, Ctr Pharmacogenet & Therapeut Res Maternal & Chil, PREGMED, Indianapolis, IN 46204 USA. [Gallauresi, Beverly; Nallani, Srikanth C.; Feibus, Karen B.] US FDA, Silver Spring, MD USA. [Shields, Kristine] Merck & Co Inc, N Wales, PA USA. [Zeitlin, Deborah] Butler Univ, Indianapolis, IN 46208 USA. [Clark, Shannon M.] Univ Texas Med Branch, Galveston, TX USA. [Hebert, Mary F.; Easterling, Thomas] Univ Washington, Seattle, WA 98195 USA. [Ren, Zhaoxia] NIH, Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Bethesda, MD 20892 USA. [Meslin, Eric M.] Indiana Univ, Ctr Bioeth, Indianapolis, IN 46204 USA. [Koren, Gideon] Sick Kids Hosp, Motherisk Program, Toronto, ON, Canada. RP Haas, DM (reprint author), Indiana Univ, Sch Med, Indianapolis, IN 46204 USA. EM dahaas@iupui.edu FU Indiana University-Purdue University, Indianapolis Signature Center; Indiana University Center for Pharmacogenetics and Therapeutics Research in Maternal and Child Health; U.S. Food and Drug Administration, Office of Women's Health; National Institute for Child Health and Human Development, National Institutes of Health FX Funding for the conference was provided by an Indiana University-Purdue University, Indianapolis Signature Center Grant to PREGMED, the Indiana University Center for Pharmacogenetics and Therapeutics Research in Maternal and Child Health.; Speakers would like to acknowledge the U.S. Food and Drug Administration, Office of Women's Health and the National Institute for Child Health and Human Development, National Institutes of Health for providing travel funds for affiliated speakers. NR 31 TC 3 Z9 5 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD JUN PY 2011 VL 4 IS 3 BP 204 EP 209 DI 10.1111/j.1752-8062.2011.00280.x PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 783TR UT WOS:000292107400016 PM 21707952 ER PT J AU Flynn, TJ AF Flynn, Thomas J. TI Real Time Phenotypic Characterization of Cultured Cells SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Meeting Abstract C1 [Flynn, Thomas J.] US FDA, Div Toxicol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM thomas.flynn@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD JUN PY 2011 VL 47 SU 1 BP S9 EP S9 PG 1 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA 799IZ UT WOS:000293281700019 ER PT J AU Shuren, J AF Shuren, Jeffrey TI A better process for new medical devices SO ISSUES IN SCIENCE AND TECHNOLOGY LA English DT Letter C1 US FDA, Ctr Devices & Radiol Hlth, Washington, DC 20204 USA. RP Shuren, J (reprint author), US FDA, Ctr Devices & Radiol Hlth, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0748-5492 J9 ISSUES SCI TECHNOL JI Issues Sci. Technol. PD SUM PY 2011 VL 27 IS 4 BP 9 EP 10 PG 2 WC Engineering, Multidisciplinary; Engineering, Industrial; Multidisciplinary Sciences; Social Issues SC Engineering; Science & Technology - Other Topics; Social Issues GA 787AP UT WOS:000292349300003 ER PT J AU Le Nouen, C Hillyer, P Winter, CC McCarty, T Rabin, RL Collins, PL Buchholz, UJ AF Le Nouen, Cyril Hillyer, Philippa Winter, Christine C. McCarty, Thomas Rabin, Ronald L. Collins, Peter L. Buchholz, Ursula J. TI Low CCR7-Mediated Migration of Human Monocyte Derived Dendritic Cells in Response to Human Respiratory Syncytial Virus and Human Metapneumovirus SO PLOS PATHOGENS LA English DT Article ID CHEMOKINE-MEDIATED MIGRATION; UNITED-STATES; IN-VITRO; PARAINFLUENZA VIRUS; RECEPTOR SWITCH; GENE-EXPRESSION; INFLUENZA-VIRUS; CILIATED CELLS; MUCOSAL SITES; LYMPH-NODES AB Human respiratory syncytial virus ( HRSV) and, to a lesser extent, human metapneumovirus (HMPV) and human parainfluenza virus type 3 (HPIV3), can re-infect symptomatically throughout life without significant antigenic change, suggestive of incomplete or short-lived immunity. In contrast, re-infection by influenza A virus (IAV) largely depends on antigenic change, suggestive of more complete immunity. Antigen presentation by dendritic cells ( DC) is critical in initiating the adaptive immune response. Antigen uptake by DC induces maturational changes that include decreased expression of the chemokine receptors CCR1, CCR2, and CCR5 that maintain DC residence in peripheral tissues, and increased expression of CCR7 that mediates the migration of antigen-bearing DC to lymphatic tissue. We stimulated human monocyte-derived DC (MDDC) with virus and found that, in contrast to HPIV3 and IAV, HMPV and HRSV did not efficiently decrease CCR1, 2, and 5 expression, and did not efficiently increase CCR7 expression. Consistent with the differences in CCR7 mRNA and protein expression, MDDC stimulated with HRSV or HMPV migrated less efficiently to the CCR7 ligand CCL19 than did IAV-stimulated MDDC. Using GFP-expressing recombinant virus, we showed that the subpopulation of MDDC that was robustly infected with HRSV was particularly inefficient in chemokine receptor modulation. HMPV- or HRSV-stimulated MDDC responded to secondary stimulation with bacterial lipopolysaccharide or with a cocktail of proinflammatory cytokines by increasing CCR7 and decreasing CCR1, 2 and 5 expression, and by more efficient migration to CCL19, suggesting that HMPV and HRSV suboptimally stimulate rather than irreversibly inhibit MDDC migration. This also suggests that the low concentration of proinflammatory cytokines released from HRSV- and HMPV-stimulated MDDC is partly responsible for the low CCR7-mediated migration. We propose that inefficient migration of HRSV- and HMPV- stimulated DC to lymphatic tissue contributes to reduced adaptive responses to these viruses. C1 [Le Nouen, Cyril; Winter, Christine C.; McCarty, Thomas; Collins, Peter L.; Buchholz, Ursula J.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Hillyer, Philippa; Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Le Nouen, C (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM ubuchholz@niaid.nih.gov FU NIAID, NIH FX This research was supported by the Intramural Research Program of the NIAID, NIH. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 67 TC 16 Z9 16 U1 0 U2 1 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 JUN PY 2011 VL 7 IS 6 AR e1002105 DI 10.1371/journal.ppat.1002105 PG 13 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 787MC UT WOS:000292379600039 PM 21731495 ER PT J AU Wang, W Anderson, CM De Feo, CJ Zhuang, M Yang, H Vassell, R Xie, H Ye, ZP Scott, D Weiss, CD AF Wang, Wei Anderson, Christine M. De Feo, Christopher J. Zhuang, Min Yang, Hong Vassell, Russell Xie, Hang Ye, Zhiping Scott, Dorothy Weiss, Carol D. TI Cross-Neutralizing Antibodies to Pandemic 2009 H1N1 and Recent Seasonal H1N1 Influenza A Strains Influenced by a Mutation in Hemagglutinin Subunit 2 SO PLOS PATHOGENS LA English DT Article ID MEMBRANE-FUSION; VIRUS HEMAGGLUTININ; LENTIVIRAL VECTOR; RECEPTOR-BINDING; GENE DELIVERY; IN-VIVO; VACCINATION; PSEUDOTYPES; PROTECTION; RESPONSES AB Pandemic 2009 H1N1 influenza A virus (2009 H1N1) differs from H1N1 strains that circulated in the past 50 years, but resembles the A/New Jersey/1976 H1N1 strain used in the 1976 swine influenza vaccine. We investigated whether sera from persons immunized with the 1976 swine influenza or recent seasonal influenza vaccines, or both, neutralize 2009 H1N1. Using retroviral pseudovirions bearing hemagglutinins on their surface (HA-pseudotypes), we found that 77% of the sera collected in 1976 after immunization with the A/New Jersey/1976 H1N1 swine influenza vaccine neutralized 2009 H1N1. Forty five percent also neutralized A/New Caledonia/20/1999 H1N1, a strain used in seasonal influenza vaccines during the 2000/01-2006/07 seasons. Among adults aged 48-64 who received the swine influenza vaccine in 1976 and recent seasonal influenza vaccines during the 2004/05-2008/09 seasons, 83% had sera that neutralized 2009 H1N1. However, 68% of age-matched subjects who received the same seasonal influenza vaccines, but did not receive the 1976 swine influenza vaccine, also had sera that neutralized 2009 H1N1. Sera from both 1976 and contemporary cohorts frequently had cross-neutralizing antibodies to 2009 H1N1 and A/New Caledonia/20/1999 that mapped to hemagglutinin subunit 2 (HA2). A conservative mutation in HA2 corresponding to a residue in the A/Solomon Islands/3/2006 and A/Brisbane/59/2007 H1N1 strains that circulated in the 2006/07 and 2007/08 influenza seasons, respectively, abrogated this neutralization. These findings highlight a cross-neutralization determinant influenced by a point mutation in HA2 and suggest that HA2 may be evolving under direct or indirect immune pressure. C1 [Wang, Wei; De Feo, Christopher J.; Zhuang, Min; Vassell, Russell; Weiss, Carol D.] US FDA, Immunoregulat Lab, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Anderson, Christine M.; Scott, Dorothy] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Yang, Hong] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Xie, Hang; Ye, Zhiping] US FDA, Lab Pediat & Resp Dis, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Wang, W (reprint author), US FDA, Immunoregulat Lab, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM carol.weiss@fda.hhs.gov RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 FU FDA FX The studies were supported by institutional research funds from the FDA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 45 TC 20 Z9 21 U1 0 U2 2 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 JUN PY 2011 VL 7 IS 6 AR e1002081 DI 10.1371/journal.ppat.1002081 PG 12 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 787MC UT WOS:000292379600019 PM 21695241 ER PT J AU Kattke, MD Gao, EJ Sapsford, KE Stephenson, LD Kumar, A AF Kattke, Michele D. Gao, Elizabeth J. Sapsford, Kim E. Stephenson, Larry D. Kumar, Ashok TI FRET-Based Quantum Dot Immunoassay for Rapid and Sensitive Detection of Aspergillus amstelodami SO SENSORS LA English DT Article DE Fluorescence Resonance Energy Transfer (FRET); quantum dot (QD); displacement immunoassay; detection; biosensor; fluorescence; quenching; mold; fungi; spores ID RESONANCE ENERGY-TRANSFER; SEMICONDUCTOR NANOCRYSTALS; FUNGAL-INFECTIONS; FLUORESCENCE; AUTOFLUORESCENCE; DESIGN; SENSOR AB In this study, a fluorescence resonance energy transfer (FRET)-based quantum dot (QD) immunoassay for detection and identification of Aspergillus amstelodami was developed. Biosensors were formed by conjugating QDs to IgG antibodies and incubating with quencher-labeled analytes; QD energy was transferred to the quencher species through FRET, resulting in diminished fluorescence from the QD donor. During a detection event, quencher-labeled analytes are displaced by higher affinity target analytes, creating a detectable fluorescence signal increase from the QD donor. Conjugation and the resulting antibody: QD ratios were characterized with UV-Vis spectroscopy and QuantiT protein assay. The sensitivity of initial fluorescence experiments was compromised by inherent autofluorescence of mold spores, which produced low signal-to-noise and inconsistent readings. Therefore, excitation wavelength, QD, and quencher were adjusted to provide optimal signal-to-noise over spore background. Affinities of anti-Aspergillus antibody for different mold species were estimated with sandwich immunoassays, which identified A. fumigatus and A. amstelodami for use as quencher-labeled-and target-analytes, respectively. The optimized displacement immunoassay detected A. amstelodami concentrations as low as 10(3) spores/mL in five minutes or less. Additionally, baseline fluorescence was produced in the presence of 10(5) CFU/mL heat-killed E. coli O157:H7, demonstrating high specificity. This sensing modality may be useful for identification and detection of other biological threat agents, pending identification of suitable antibodies. Overall, these FRET-based QD-antibody biosensors represent a significant advancement in detection capabilities, offering sensitive and reliable detection of targets with applications in areas from biological terrorism defense to clinical analysis. C1 [Kattke, Michele D.; Gao, Elizabeth J.; Stephenson, Larry D.; Kumar, Ashok] Erdc, US Corps Engineers, CERL, Champaign, IL 61826 USA. [Sapsford, Kim E.] US FDA, CDRH OSEL DB, Silver Spring, MD 20993 USA. RP Kattke, MD (reprint author), Erdc, US Corps Engineers, CERL, 2902 Newmark Dr, Champaign, IL 61826 USA. EM Michele.D.Kattke@usace.army.mil; Elizabeth.J.Gao@usace.army.mil; kim.sapsford@fda.hhs.gov; Larry.D.Stephenson@usace.army.mil; Ashok.Kumar@usace.army.mil FU U.S. Army Engineer Research and Development Center-Construction Engineering Research Laboratory FX The authors sincerely thank Igor Medintz for his consultation and advice regarding the project. This research was supported in part by an appointment to the Postgraduate Research Participation Program at the U.S. Army Engineer Research and Development Center-Construction Engineering Research Laboratory administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and ERDC-CERL. NR 25 TC 23 Z9 23 U1 4 U2 60 PU MDPI AG PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1424-8220 J9 SENSORS-BASEL JI Sensors PD JUN PY 2011 VL 11 IS 6 BP 6396 EP 6410 DI 10.3390/s110606396 PG 15 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 782RB UT WOS:000292026400051 PM 22163961 ER PT J AU Xie, T Auth, RD Frucht, DM AF Xie, Tao Auth, Roger D. Frucht, David M. TI The Effects of Anthrax Lethal Toxin on Host Barrier Function SO TOXINS LA English DT Review DE anthrax lethal toxin; barrier function; bacteria; infection; intestine; endothelium; epithelium; blood-brain barrier ID T-LYMPHOCYTE ACTIVATION; BACILLUS-ANTHRACIS; INHALATION ANTHRAX; INTESTINAL BARRIER; BACTERIAL TRANSLOCATION; GASTROINTESTINAL-TRACT; NEUTROPHIL ELASTASE; SIGNALING PATHWAYS; VCAM-1 EXPRESSION; EPITHELIAL INJURY AB The pathological actions of anthrax toxin require the activities of its edema factor (EF) and lethal factor (LF) enzyme components, which gain intracellular access via its receptor-binding component, protective antigen (PA). LF is a metalloproteinase with specificity for selected mitogen-activated protein kinase kinases (MKKs), but its activity is not directly lethal to many types of primary and transformed cells in vitro. Nevertheless, in vivo treatment of several animal species with the combination of LF and PA (termed lethal toxin or LT) leads to morbidity and mortality, suggesting that LT-dependent toxicity is mediated by cellular interactions between host cells. Decades of research have revealed that a central hallmark of this toxicity is the disruption of key cellular barriers required to maintain homeostasis. This review will focus on the current understanding of the effects of LT on barrier function, highlighting recent progress in establishing the molecular mechanisms underlying these effects. C1 [Xie, Tao; Auth, Roger D.; Frucht, David M.] US FDA, Cell Biol Lab, Div Monoclonal Antibodies,Ctr Drug Evaluat & Res, Off Biotechnol Prod,Off Pharmaceut Sci, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), US FDA, Cell Biol Lab, Div Monoclonal Antibodies,Ctr Drug Evaluat & Res, Off Biotechnol Prod,Off Pharmaceut Sci, Bethesda, MD 20892 USA. EM tao.xie@fda.hhs.gov; roger.auth2@fda.hhs.gov; david.frucht@fda.hhs.gov NR 87 TC 11 Z9 11 U1 0 U2 2 PU MDPI AG PI BASEL PA POSTFACH, CH-4005 BASEL, SWITZERLAND SN 2072-6651 J9 TOXINS JI Toxins PD JUN PY 2011 VL 3 IS 6 BP 591 EP 607 DI 10.3390/toxins3060591 PG 17 WC Toxicology SC Toxicology GA 995AN UT WOS:000307978000006 PM 22069727 ER PT J AU Rouse, RL Zhang, J Stewart, SR Rosenzweig, BA Espandiari, P Sadrieh, NK AF Rouse, Rodney L. Zhang, Jun Stewart, Sharron R. Rosenzweig, Barry A. Espandiari, Parvaneh Sadrieh, Nakissa K. TI Comparative profile of commercially available urinary biomarkers in preclinical drug-induced kidney injury and recovery in rats SO KIDNEY INTERNATIONAL LA English DT Article DE gene expression; histopathology; proximal tubule; renal injury; urine proteomics ID GELATINASE-ASSOCIATED LIPOCALIN; IN-VITRO; NEPHROTOXICITY; GENTAMICIN; MOLECULE-1; OSTEOPONTIN; CLUSTERIN; EXPRESSION; DISEASE; ALBUMIN AB We designed a study to provide reversibility and comparative injury data for several candidate urinary biomarkers of kidney injury in the United States Food and Drug Administration biomarker qualification process. The nephrotoxin gentamicin was given to rats once on each of three days and the animals were killed during dosing or over the following 42 days. Between days one and three, all biomarkers except albumin were elevated, peaked at day 7, and returned to control levels by day 10 (mu- and alpha-glutathione S-transferases, and renal papillary antigen-1) or day 15 (kidney injury molecule-1, lipocalin-2, osteopontin, and clusterin). All biomarkers performed better during injury than during recovery except osteopontin, which performed equally well in both time periods. During the evolution of injury, kidney injury molecule-1, renal papillary antigen-1, and clusterin best mirrored the histopathologic lesions. During injury resolution, kidney injury molecule-1, osteopontin, and blood urea nitrogen best reflected recovery. Based on histopathology, necrosis, or apoptosis scoring, kidney injury molecule-1 was the best biomarker of overall renal injury. Evaluation by regeneration score showed that renal papillary antigen-1 best reflected tubular and/or collecting duct regeneration, especially during recovery. Thus, these biomarkers performed with different effectiveness when evaluated by individual pathological processes such as necrosis, apoptosis, and regeneration. Kidney International (2011) 79, 1186-1197; doi:10.1038/ki.2010.463; published online 8 December 2010 C1 [Rouse, Rodney L.; Zhang, Jun; Stewart, Sharron R.; Rosenzweig, Barry A.] US FDA, Div Appl Pharmacol Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evalut & Res, Silver Spring, MD 20993 USA. [Espandiari, Parvaneh] US FDA, Div Metab & Endocrinol Prod, Off Drug Evaluat 2, Off New Drugs,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Sadrieh, Nakissa K.] US FDA, Sci & Res Staff, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Rouse, RL (reprint author), US FDA, Div Appl Pharmacol Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evalut & Res, HFD 910,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Rodney.rouse@fda.hhs.gov FU Division of Applied Pharmacology Research, Office of Testing and Research, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, US Food and Drug Administration FX This work was supported by the Division of Applied Pharmacology Research (operating budget), Office of Testing and Research, Office of Pharmaceutical Science, Center for Drug Evaluation and Research, US Food and Drug Administration. We acknowledge the significant guidance and suggestions provided by Patricia Harlow and Li Zhang through insights gained as members of the FDA Biomarker Qualification Review Team for biomarkers of nephrotoxicity and Karol Thompson for her expert guidance in our gene expression studies and manuscript preparation. NR 35 TC 38 Z9 42 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 JUN PY 2011 VL 79 IS 11 BP 1186 EP 1197 DI 10.1038/ki.2010.463 PG 12 WC Urology & Nephrology SC Urology & Nephrology GA 763LW UT WOS:000290559400007 PM 21150870 ER PT J AU Ruzante, JM Majowicz, SE Fazil, A Davidson, VJ AF Ruzante, J. M. Majowicz, S. E. Fazil, A. Davidson, V. J. TI Hospitalization and deaths for select enteric illnesses and associated sequelae in Canada, 2001-2004 SO EPIDEMIOLOGY AND INFECTION LA English DT Article DE Epidemiology; foodborne infections; Guillain-Barre syndrome; surveillance ID ACUTE GASTROINTESTINAL ILLNESS; RISK-RANKING; BURDEN; FRAMEWORK; ONTARIO; DISEASE AB This paper describes morbidity and mortality parameters for Campylobacter spp., Salmonella spp., enterohaemorrhagic Escherichia coli, Listeria spp., norovirus infections and their primary associated sequelae [Guillain-Barre syndrome (GBS), haemolytic uraemic syndrome, reactive arthropathies and Reiter's syndrome]. Data from a period of 4 years were obtained from three national databases to estimate percentage of reported cases hospitalized, mean annual hospitalization incidence rate, frequency of hospitalization by age and sex, and number of deaths. The length of hospital stay, discharge disposition, hospitalization age, and number of diagnoses per case were also extracted and summarized. In addition, we estimated that each year in Canada, there are between 126 and 251 cases of Campylobacter-associated GBS. This study provides morbidity and mortality estimates for the top enteric pathogens in Canada, including their associated sequelae, which can contribute to the quantification of the burden of illness. C1 [Ruzante, J. M.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Majowicz, S. E.] Publ Hlth Agcy Canada, Off Publ Hlth Practice, Ottawa, ON, Canada. [Majowicz, S. E.] Univ Guelph, Dept Populat Med, Guelph, ON N1G 2W1, Canada. [Fazil, A.] Publ Hlth Agcy Canada, Lab Foodborne Zoonoses, Ottawa, ON, Canada. [Davidson, V. J.] Univ Guelph, Sch Engn, Guelph, ON N1G 2W1, Canada. RP Ruzante, JM (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, 2134 Patapsco Bldg, College Pk, MD 20742 USA. EM jruzante@umd.edu FU Natural Sciences and Engineering Research Council (Canada) FX This study used data and information provided by the Canadian Institute for Health Information. However, the analyses, conclusions, opinions and statements expressed herein are those of the authors, and not necessarily those of the Canadian Institute for Health Information. In addition, the study also used data provided to the Public Health Agency of Canada, from the Canadian Vital Statistics databases at Statistics Canada with the knowledge and consent of the provincial and territorial vital statistics registries which supply the data to Statistics Canada. Their cooperation is gratefully acknowledged. Financial support for this research from the Natural Sciences and Engineering Research Council (Canada) is gratefully acknowledged. The authors thank Merrilyn Allegakone from Health Canada for support with the databases. NR 23 TC 17 Z9 18 U1 0 U2 7 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0950-2688 EI 1469-4409 J9 EPIDEMIOL INFECT JI Epidemiol. Infect. PD JUN PY 2011 VL 139 IS 6 BP 937 EP 945 DI 10.1017/S0950268810001883 PG 9 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 757RT UT WOS:000290106100015 PM 20731884 ER PT J AU Tyner, KM Wokovich, AM Godar, DE Doub, WH Sadrieh, N AF Tyner, K. M. Wokovich, A. M. Godar, D. E. Doub, W. H. Sadrieh, N. TI The state of nano-sized titanium dioxide (TiO2) may affect sunscreen performance SO INTERNATIONAL JOURNAL OF COSMETIC SCIENCE LA English DT Article DE nanoparticle; permeability enhancer; sunscreen; titanium dioxide ID PARTICLE-SIZE; NANOPARTICLES; PENETRATION; MECHANISMS; RADIATION; SAFETY; FORMS; OXIDE AB Synopsis In the past several years, there has been a trend in the sunscreen/cosmetics industry to replace micron-sized titanium dioxide (TiO2) particles with nanoscale materials. The increased use of nanoscale TiO2 has resulted in questions about these and other nanoproducts. This study examines the effects of using nanoscale TiO2 on ultraviolet (UV) attenuation in simple to complex sunscreen formulations. UV light attenuation, product stability, and potential damage to the skin barrier were examined with both nanoscale and microscale TiO2 particles. Results indicate that none of the formulations decreased the barrier function of the skin and the best UV attenuation occurs when the TiO2 particles are stabilized with a coating and evenly distributed such as with non-agglomerated coated nanoscale materials. This indicates that nanoscale TiO2 may have better efficacy while lacking toxicity.Resume Au cours des dernieres annees, nous avons constate une tendance dans l'industrie solaire/cosmetique pour le remplacement des particules micron-taille de dioxyde de titane (TiO2) avec des materiaux de nano-echelle. L'utilisation accrue des particules de TiO2 l'echelle du nanometre a engendre des questions sur tous les produits contenant des materiaux nano-echelle. Cette etude examine les effets de l'utilisation de particule de TiO2 a l'echelle du nanometre sur l'attenuation des rayons UV dans les formulations de creme solaire simple et complexe. Nous avons etudie l'attenuation de la luminosite ultraviolet (UV), la stabilite du produit et les effets sur la fonction barriere de la peau, avec les particules de TiO2 nano-echelle et micro-echelle. Les resultats indiquent que les particules a l'echelle du nanometre, enduits et non-agglomere, fournissent une excellente attenuation UV, sans diminuer la fonction barriere de la peau. Ceci suggere que les particules de TiO2 a l'echelle du nanometre ont une meilleure efficacite, sans poser des inquietudes en ce qui concerne leur securite. C1 [Tyner, K. M.; Sadrieh, N.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Wokovich, A. M.; Doub, W. H.] US FDA, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. [Godar, D. E.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Sadrieh, N (reprint author), 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM nakissa.sadrieh@fda.hhs.gov OI GODAR, DIANNE/0000-0002-7690-5223 NR 27 TC 17 Z9 17 U1 1 U2 58 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0142-5463 J9 INT J COSMETIC SCI JI Int. J. Cosmetic Sci. PD JUN PY 2011 VL 33 IS 3 BP 234 EP 244 DI 10.1111/j.1468-2494.2010.00622.x PG 11 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA 760HL UT WOS:000290315300005 PM 21265867 ER PT J AU Sammour, OA Hammad, MA Zidan, AS Mowafy, AG AF Sammour, Omaima A. Hammad, Mohammed A. Zidan, Ahmed S. Mowafy, Ayman G. TI QbD approach of rapid disintegrating tablets incorporating indomethacin solid dispersion SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Article DE Indomethacin; polyvinyl pyrrolidone; solid dispersion; rapid disintegrating tablets; factorial design ID MOUTH DISSOLVE TABLETS; DISSOLUTION RATES; FORMULATION; DESIGN; POLYVINYLPYRROLIDONE; OPTIMIZATION; SOLUBILITY AB The development of rapid disintegrating tablets (RDT) requires the use of highly soluble components to support the intended use of these products. In an attempt to prepare RDT of indomethacin, its solid dispersion with polyvinyl pyrrolidone K25 (PVP) was incorporated in a fast disintegrating matrix. Drug polymer interactions were investigated using X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). Indomethacin 1: 1 solid dispersion with PVP was used to prepare its RDT. Two factors at 3 levels full factorial design were employed as a statistical approach to optimize the amount of superdisintegrant (Ac-di-sol) and hardness value regarding the desired disintegration and release characteristics. Drug to carrier ratio was the controlling factor for dissolution improvement. XRD and FTIR data revealed a remarkable interaction between the drug and the carrier that might be responsible for the dissolution enhancement. Multiple regression analysis revealed a significant effect of the polynomial terms for obtaining rapid disintegrating tablets. It was inferred that the hardness value is the most important factor controlling the disintegration time and the release characteristics. In conclusion, this study demonstrated that quality by design (QbD) is a potential paradigm for understanding the quality and optimizing the formulation of RDT containing indomethacin solid dispersion. C1 [Sammour, Omaima A.] Ain Shams Univ, Fac Pharm, Dept Drug Technol, Cairo, Egypt. [Hammad, Mohammed A.; Zidan, Ahmed S.] Zagazig Univ, Fac Pharm, Dept Pharmaceut, Zagazig, Egypt. [Zidan, Ahmed S.] US FDA, Div Product Qual & Res, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Mowafy, Ayman G.] Nile Co Pharmaceut & Chem Ind, Res & Dev Sector, Drug Design & Dev Dept, Cairo, Egypt. RP Zidan, AS (reprint author), 10903 New Hampshire Ave,Bldg 64,Room 1082, Silver Spring, MD 20993 USA. EM Ahmed.Zidan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012 NR 24 TC 6 Z9 6 U1 0 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1083-7450 EI 1097-9867 J9 PHARM DEV TECHNOL JI Pharm. Dev. Technol. PD JUN PY 2011 VL 16 IS 3 BP 219 EP 227 DI 10.3109/10837451003592209 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 758KT UT WOS:000290164300004 PM 20163325 ER PT J AU Zidan, AS Mokhtar, M AF Zidan, Ahmed S. Mokhtar, Mahmoud TI Multivariate Optimization of Formulation Variables Influencing Flurbiprofen Proniosomes Characteristics SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE membrane transport; factorial design; gels; percutaneous; surfactants ID DRUG-DELIVERY; IN-VITRO; CHOLESTEROL CONTENT; VESICLES NIOSOMES; PERMEATION; STABILITY; LIPOSOMES; ENCAPSULATION; PENETRATION; CARRIERS AB Flurbiprofen was formulated as a proniosomal transdermal gel with high drug loading (55.4%, w/w), using a series of nonionic surfactant and cholesterol. A two-factor, three-level randomized full factorial strategy was developed to optimize simultaneously the effect of surfactant fatty acid side chain length and the amount of cholesterol on the properties of the proniosomes, namely drug permeation characteristics such as steady-state transdermal flux (SSTF), permeability coefficient (PC), and drug entrapment efficiency. Graphical and mathematical analysis of the results allowed the identification and quantification of the formulation variables that showed significant effects on the selected responses. Polynomial equations fitted to the data were used to predict the responses in the optimal region. For maximizing the selected responses using a generalized desirability function, an optimum formulation was found to have a maximum side chain length and minimum cholesterol content. Optimized formulation showed highest entrapment of 39.45%, percentages drug permeated through cellulose ester membrane of 3.1 and 28.93 after 0.5 and 8 h, respectively, and SSTF and PC of 152 mu g/cm(2) h and 0.263 cm/h, respectively, through rabbit skin. These results demonstrated the efficacy of statistical experimental design to unveil the critical formulation interactions and variability affecting the performance of proniosomal formulations. (C) 2011 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:2212-2221, 2011 C1 [Zidan, Ahmed S.; Mokhtar, Mahmoud] Zagazig Univ, Dept Pharmaceut & Ind Pharm, Fac Pharm, Zagazig, Egypt. [Zidan, Ahmed S.] US FDA, Div Prod Qual & Res, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Zidan, AS (reprint author), Zagazig Univ, Dept Pharmaceut & Ind Pharm, Fac Pharm, Zagazig, Egypt. EM Azidoon@yahoo.com RI Zidan, Ahmed/I-1147-2012; OI Ibrahim, mahmoud/0000-0002-7925-4585 NR 29 TC 16 Z9 16 U1 0 U2 4 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUN PY 2011 VL 100 IS 6 BP 2212 EP 2221 DI 10.1002/jps.22453 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 749DL UT WOS:000289442200018 PM 21259237 ER PT J AU Modric, S Martinez, M AF Modric, S. Martinez, M. TI Patient variation in veterinary medicine - Part II - Influence of physiological variables SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Review ID AGE-RELATED-CHANGES; GENDER-BASED DIFFERENCES; BODY-SURFACE AREA; ADULT BEAGLE DOGS; P-GLYCOPROTEIN EXPRESSION; MIXED-BREED DOGS; DRUG-THERAPY; YOUNG-PIGS; COMPARATIVE PHARMACOKINETICS; DISPOSITION KINETICS AB In veterinary medicine, the characterization of a drug's pharmacokinetic properties is generally based upon data that are derived from studies that employ small groups of young healthy animals, often of a single breed. In Part I of the series, we focused on the potential influence of disease processes, stress, pregnancy and lactation on drug pharmacokinetics. In this Part II of the series, we consider other covariates, such as gender, heritable traits, age, body composition, and circadian rhythms. The impact of these factors with respect to predicting the relationship between dose and drug exposure characteristics within an animal population is illustrated through the use of Monte Carlo simulations. Ultimately, an appreciation of these potential influences will improve the prediction of situations when dose adjustments may be appropriate. C1 [Modric, S.; Martinez, M.] US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. RP Martinez, M (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, 7500 Standish Pl,HFV 130, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov NR 207 TC 6 Z9 6 U1 1 U2 6 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD JUN PY 2011 VL 34 IS 3 BP 209 EP 223 DI 10.1111/j.1365-2885.2010.01249.x PG 15 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 751OM UT WOS:000289627400001 PM 21083665 ER PT J AU Lim, H Dave, VS Kidder, L Lewis, EN Fahmy, R Hoag, SW AF Lim, Hanpin Dave, Vivek S. Kidder, Linda Lewis, E. Neil Fahmy, Raafat Hoag, Stephen W. TI Assessment of the critical factors affecting the porosity of roller compacted ribbons and the feasibility of using NIR chemical imaging to evaluate the porosity distribution SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Roller compaction; NIR chemical imaging; Porosity; Density; Roller compacted ribbon; Feed screw speed, Roller pressure, Roller speed, Quality by design, NIR-CI ID NEAR-INFRARED SPECTROSCOPY; TENSILE-STRENGTH; CONTENT UNIFORMITY; AMBIENT MOISTURE; POWDER; OPTIMIZATION; GRANULES; FRACTION; BEHAVIOR; DENSITY AB The purpose of this study was to assess the porosity variation of roller compacted ribbons made using different process parameters; in addition, the feasibility of using near-infrared chemical imaging (NIR-CI) to evaluate porosity variations was examined. Ribbons of neat microcrystalline cellulose were compacted using a range of roll pressures (RP), roll speeds (RS) and feed screw speeds (FSS). The ribbon porosity decreased as RP increased with the exception of ribbons produced by the combination of high RS and low FSS where increasing RP increases the porosity of the ribbons. Lower RS was found to produce ribbons with lower porosity and the porosity increases as the RS increased. Increased FSS will decrease ribbon porosity at higher RS while it slightly increase the ribbon porosity at lower RS. A simple linear regression model showed NIR-CI was able to predict the ribbon porosity with a correlation of 0.9258. NIR-CI is able to characterize differences in porosity as a function of position on the ribbon where regions with lower porosity show higher absorbance. Nevertheless. NIR-CI is able to show sinusoidal variation in intensities along the roller compacted ribbon among all settings studied. (C) 2011 Elsevier B.V. All rights reserved. C1 [Lim, Hanpin; Hoag, Stephen W.] Univ Maryland Baltimore, Sch Pharm, Baltimore, MD 21201 USA. [Dave, Vivek S.] Lubrizol Adv Mat, Brecksville, OH 44141 USA. [Kidder, Linda; Lewis, E. Neil] US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20855 USA. [Fahmy, Raafat] Malvern Instruments Inc, Columbia, MD 21046 USA. RP Hoag, SW (reprint author), Univ Maryland Baltimore, Sch Pharm, 20N Pine St, Baltimore, MD 21201 USA. EM shoag@rx.umaryland.edu FU Malvern Instrument, Inc.; FDA FX The authors gratefully acknowledge Nick Hayes of Volkmann, Inc. and Malvern Instrument, Inc., and the FDA for their support and advice. NR 24 TC 23 Z9 24 U1 1 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARMACEUT JI Int. J. Pharm. PD MAY 30 PY 2011 VL 410 IS 1-2 BP 1 EP 8 DI 10.1016/j.ijpharm.2011.02.028 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 771DV UT WOS:000291138300001 PM 21371542 ER PT J AU Lu, WY Callahan, JH Fry, FS Andrzejewski, D Musser, SM Harrington, PD AF Lu, Weiying Callahan, John H. Fry, Frederick S. Andrzejewski, Denis Musser, Steven M. Harrington, Peter de B. TI A discriminant based charge deconvolution analysis pipeline for protein profiling of whole cell extracts using liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry SO TALANTA LA English DT Article DE Liquid chromatography-electrospray ionization mass spectrometry; Fuzzy rule-building expert system; Molecular weight determination charge state deconvolution; Discriminant based charge deconvolution; Salmonella enterica serovar typhimurium ID BUILDING EXPERT-SYSTEMS; GAS-CHROMATOGRAPHY; INTACT PROTEINS; SPECTRA; CLASSIFICATION; VALIDATION; BACTERIA; PROGRAM AB A discriminant based charge deconvolution analysis pipeline is proposed. The molecular weight determination (MoWeD) charge deconvolution method was applied directly to the discrimination rules obtained by the fuzzy rule-building expert system (FuRES) pattern classifier. This approach was demonstrated with synthetic electrospray ionization-mass spectra. Identification of the tentative protein biomarkers by bacterial cell extracts of Salmonella enterica serovar typhimurium strains A1 and A19 by liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was also demonstrated. The data analysis time was reduced by applying this approach. In addition, this method was less affected by noise and baseline drift. (C) 2011 Elsevier B.V. All rights reserved. C1 [Lu, Weiying; Harrington, Peter de B.] Ohio Univ, Dept Chem & Biochem, Clippinger Labs, Ctr Intelligent Chem Instrumentat, Athens, OH 45701 USA. [Callahan, John H.; Fry, Frederick S.; Andrzejewski, Denis; Musser, Steven M.] US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Harrington, PD (reprint author), Ohio Univ, Dept Chem & Biochem, Clippinger Labs, Ctr Intelligent Chem Instrumentat, Athens, OH 45701 USA. EM Peter.Harrington@OHIO.edu OI Harrington, Peter/0000-0003-0268-8630 NR 31 TC 2 Z9 2 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 J9 TALANTA JI Talanta PD MAY 30 PY 2011 VL 84 IS 4 BP 1180 EP 1187 DI 10.1016/j.talanta.2011.03.024 PG 8 WC Chemistry, Analytical SC Chemistry GA 770HR UT WOS:000291078100025 PM 21530796 ER PT J AU Arasappan, D Tong, WD Mummaneni, P Fang, H Amur, S AF Arasappan, Dhivya Tong, Weida Mummaneni, Padmaja Fang, Hong Amur, Shashi TI Meta-analysis of microarray data using a pathway-based approach identifies a 37-gene expression signature for systemic lupus erythematosus in human peripheral blood mononuclear cells SO BMC MEDICINE LA English DT Article ID INDUCIBLE GENE-EXPRESSION; INTERFERON-ALPHA; DISEASE-ACTIVITY; RHEUMATOID-ARTHRITIS; CANCER; NEPHRITIS; ASSOCIATION; TARGETS; MICE AB Background: A number of publications have reported the use of microarray technology to identify gene expression signatures to infer mechanisms and pathways associated with systemic lupus erythematosus (SLE) in human peripheral blood mononuclear cells. However, meta-analysis approaches with microarray data have not been well-explored in SLE. Methods: In this study, a pathway-based meta-analysis was applied to four independent gene expression oligonucleotide microarray data sets to identify gene expression signatures for SLE, and these data sets were confirmed by a fifth independent data set. Results: Differentially expressed genes (DEGs) were identified in each data set by comparing expression microarray data from control samples and SLE samples. Using Ingenuity Pathway Analysis software, pathways associated with the DEGs were identified in each of the four data sets. Using the leave one data set out pathway-based meta-analysis approach, a 37-gene metasignature was identified. This SLE metasignature clearly distinguished SLE patients from controls as observed by unsupervised learning methods. The final confirmation of the metasignature was achieved by applying the metasignature to a fifth independent data set. Conclusions: The novel pathway-based meta-analysis approach proved to be a useful technique for grouping disparate microarray data sets. This technique allowed for validated conclusions to be drawn across four different data sets and confirmed by an independent fifth data set. The metasignature and pathways identified by using this approach may serve as a source for identifying therapeutic targets for SLE and may possibly be used for diagnostic and monitoring purposes. Moreover, the meta-analysis approach provides a simple, intuitive solution for combining disparate microarray data sets to identify a strong metasignature. Please see Research Highlight: http://genomemedicine.com/content/3/5/30 C1 [Arasappan, Dhivya; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mummaneni, Padmaja; Amur, Shashi] US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Fang, Hong] Z Tech Corp, Jefferson, AR 72079 USA. [Arasappan, Dhivya] Univ Texas Austin, Inst Drug & Diagnost Dev, Austin, TX 78712 USA. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM weida.tong@fda.hhs.gov; shashi.amur@fda.hhs.gov FU Office of Women's Health, US Food and Drug Administration (OWH) [07-09-0001-SA] FX The authors thank The Office of Women's Health, US Food and Drug Administration, for funding the research project (OWH study 07-09-0001-SA). The authors also thank all the prominent research groups in the SLE field who contributed data for the meta-analysis: Dr Thomas Aune, Dr Emily Baechler Gillespie, Dr Mary Crow, Dr Bernard Lauwerys, GeneLogic, Dr Dafna Gladman, Dr Virginia Pascual, and Dr Violeta Rus. Of all data sets, only data generated with oligonucleotide microarrays were selected for the meta-analysis described in this article. The views presented in this article do not necessarily reflect those of the US Food and Drug Administration. NR 34 TC 37 Z9 37 U1 2 U2 12 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1741-7015 J9 BMC MED JI BMC Med. PD MAY 30 PY 2011 VL 9 AR 65 DI 10.1186/1741-7015-9-65 PG 10 WC Medicine, General & Internal SC General & Internal Medicine GA 785VE UT WOS:000292258800001 PM 21624134 ER PT J AU Kirs, M DePaola, A Fyfe, R Jones, JL Krantz, J Van Laanen, A Cotton, D Castle, M AF Kirs, M. DePaola, A. Fyfe, R. Jones, J. L. Krantz, J. Van Laanen, A. Cotton, D. Castle, M. TI A survey of oysters (Crassostrea gigas) in New Zealand for Vibrio parahaemolyticus and Vibrio vulnificus SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Vibrio parahaemolyticus; Vibrio vulnificus; Pacific oysters; New Zealand ID THERMOSTABLE DIRECT HEMOLYSIN; TIME PCR ASSAY; UNITED-STATES; NORTHERN GULF; RAW OYSTERS; WATER; SEQUENCE; GENES AB A microbiological survey was conducted to determine the levels of total and pathogenic Vibrio parahaemolyticus (Vp) and Vibrio vulnificus (Vv) in Pacific oysters (Crassostrea gigas) collected from commercial growing areas in the North Island, New Zealand. The survey was intended to be geographically representative of commercial growing areas of Pacific oysters in New Zealand, while selecting the time frame most likely to coincide with the increased abundance of pathogenic vibrio species. Vp was detected in 94.8% of oyster samples examined (n = 58) with a geometric mean concentration of 99.3 MPN/g, while Vv was detected in 17.2% of oyster samples examined with a geometric mean concentration of 7.4 MPN/g. The frequency of Vp positive samples was 1.7 fold greater than reported in a study conducted three decades ago in New Zealand. Potentially virulent (tdh positive) Vp was detected in two samples (3.4%, n = 58) while no trh (another virulence marker) positive samples were detected. 16S rRNA genotype could be assigned only to 58.8% of Vv isolates (8:1:1 A: B:AB ratio, n = 10). There was a good agreement [98.2% of Vp (n=280) and 94.4% of Vv (n = 18) isolates] between molecular tests and cultivation based techniques used to identify Vibrio isolates and there was a significant (R(2) = 0.95. P < 0.001, n = 18) linear relationship between the MPN estimates by real-time PCR and cultivation. There was no significant correlation between any of the environmental parameters tested and Vp or Vv concentrations. (C) 2011 Elsevier B.V. All rights reserved. C1 [Kirs, M.; Fyfe, R.; Van Laanen, A.; Cotton, D.] Cawthron Inst, Nelson 7042, New Zealand. [DePaola, A.; Jones, J. L.; Krantz, J.] US FDA, Div Seafood Sci & Technol, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Castle, M.] New Zealand Food Safety Author, Wellington 6021, New Zealand. RP Kirs, M (reprint author), Cawthron Inst, 98 Halifax St E,Private Bag 2, Nelson 7042, New Zealand. EM marek.kirs@cawthron.org.nz FU New Zealand Food Safety Authority (NZFSA) [11133] FX We are very grateful to Dorothy-Jean McCoubrey for her work with the oyster industry to approach the growing sites to participate and to assist with the co-ordination of sampling. Also we acknowledge Elizabeth Watts (Northland Health Board) and Cameron Ormsby (Auckland Regional Public Health Service) for providing precipitation data. The authors thank Phil Busby (NZFSA) and Chris Cornelisen (Cawthron Institute) for valuable comments and discussions and to Ms A. Hadfield (Cawthron Institute) for technical assistance. We are very grateful to the anonymous oyster farms for providing the samples and environmental data. This research was designed and funded by the New Zealand Food Safety Authority (NZFSA Agreement 11133). NR 36 TC 25 Z9 25 U1 3 U2 19 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 MAY 27 PY 2011 VL 147 IS 2 BP 149 EP 153 DI 10.1016/j.ijfoodmicro.2011.03.012 PG 5 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 771BX UT WOS:000291133300009 PM 21501884 ER PT J AU Cho, S Lau, SWJ Tandon, V Kumi, K Pfuma, E Abernethy, DR AF Cho, Seongeun Lau, S. W. Johnny Tandon, Veneeta Kumi, Kofi Pfuma, Elimika Abernethy, Darrell R. TI Geriatric Drug Evaluation Where Are We Now and Where Should We Be in the Future? SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID CLINICAL-TRIALS; ATRIAL-FIBRILLATION; OLDER-ADULTS; AGE; PHARMACOLOGY; THERAPY; INDEX; RISK AB The older population is currently the fastest growing age group in the United States, and this trend is expected to continue for several decades. Older individuals, in general, have a higher disease burden compared with younger adults and are the major users of medications, yet premarketing drug clinical trials have often excluded them even for the drugs that have high utility in this age group. Extrapolation of clinical results from younger to older individuals does not provide adequate benefit-risk estimation, and the frequent need for dose adjustment in older patients from initially approved doses exemplifies the current lack of adequate clinical data in the elderly. Herein, we discuss the information gap for older individuals and the need for a better understanding of the effect of aging on drug responses. We also present cases for future directions, urging the implementation of improved clinical trial designs using new and emerging pharmacokinetic and pharmacodynamic methods to allow the provision of evidence-based individualized treatment to this high drug use group. Arch Intern Med. 2011;171(10):937-940 C1 [Cho, Seongeun; Lau, S. W. Johnny; Tandon, Veneeta; Kumi, Kofi; Pfuma, Elimika; Abernethy, Darrell R.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Cho, S (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM seongeun.cho@fda.hhs.gov NR 27 TC 20 Z9 24 U1 0 U2 3 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 23 PY 2011 VL 171 IS 10 BP 937 EP 940 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 767RT UT WOS:000290874400014 PM 21606098 ER PT J AU Harris, K Ream, R Gao, J Eichelberger, MC AF Harris, Katie Ream, Rebecca Gao, Jin Eichelberger, Maryna C. TI Intramuscular immunization of mice with live influenza virus is more immunogenic and offers greater protection than immunization with inactivated virus SO VIROLOGY JOURNAL LA English DT Article ID YOUNG-CHILDREN; RESPIRATORY-TRACT; T-CELLS; B-CELLS; ANTIBODY-RESPONSES; IMMUNE-RESPONSES; INNATE IMMUNITY; INFECTION; INTERFERON; VACCINE AB Background: Influenza virus continues to cause significant hospitalization rates in infants and young children. A 2-dose regime of trivalent inactivated vaccine is required to generate protective levels of hemagglutination inhibiting (HAI) antibodies. A vaccine preparation with enhanced immunogenicity is therefore desirable. Methods: Mice were inoculated intramuscularly (IM) with live and inactivated preparations of A/Wisconsin/67/2005 (H3N2). Serum cytokine levels, hemagglutinin (HA)-specific antibody responses and nucleoprotein (NP)-specific CD8+ T cell responses were compared between vaccinated groups, as well as to responses measured after intranasal infection. The protective efficacy of each vaccine type was compared by measuring virus titers in the lungs and weight loss of mice challenged intranasally with a heterosubtypic virus, A/PR/8/34 (H1N1). Results: Intramuscular administration of live virus resulted in greater amounts of IFN-alpha, IL-12 and IFN-gamma, HA-specific antibodies, and virus-specific CD8+ T cells, than IM immunization with inactivated virus. These increases corresponded with the live virus vaccinated group having significantly less weight loss and less virus in the lungs on day 7 following challenge with a sublethal dose of a heterosubtypic virus. Conclusions: Inflammatory cytokines, antibody titers to HA and CD8+ T cell responses were greater to live than inactivated virus delivered IM. These increased responses correlated with greater protection against heterosubtypic virus challenge, suggesting that intramuscular immunization with live influenza virus may be a practical means to increase vaccine immunogenicity and to broaden protection in pediatric populations. C1 [Harris, Katie; Ream, Rebecca; Gao, Jin; Eichelberger, Maryna C.] US FDA, Div Viral Prod, Off Vaccine Review & Res, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Eichelberger, MC (reprint author), US FDA, Div Viral Prod, Off Vaccine Review & Res, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. EM Maryna.Eichelberger@fda.hhs.gov FU CBER, FDA FX We thank the CBER animal resource team for excellent care of animals, Arash Hassantoufighi for technical support and Drs Graeme Price and Hang Xie for helpful comments in preparation of this manuscript. This project was funded by pandemic influenza funds provided by CBER, FDA. NR 29 TC 13 Z9 14 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD MAY 21 PY 2011 VL 8 AR 251 DI 10.1186/1743-422X-8-251 PG 11 WC Virology SC Virology GA 785GK UT WOS:000292215200002 PM 21600020 ER PT J AU Blumenthal, GM Orbach, RC Zineh, I Cortazar, P Justice, RL Pazdur, R AF Blumenthal, G. M. Orbach, R. Charlab Zineh, I. Cortazar, P. Justice, R. L. Pazdur, R. TI Early targeted drug development: Pilot FDA review of PI3K inhibitor phase I studies using a knowledge management database. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Blumenthal, G. M.; Orbach, R. Charlab; Zineh, I.; Cortazar, P.; Justice, R. L.; Pazdur, R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3060 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301489 PM 28022560 ER PT J AU Chang, J Rand, M Blumenthal, GM Cortazar, P Kulick, C Hausman, E Chang, S Pratt, R Habtemarium, B Chen, Y Bullock, J Orbach, RC Zineh, I Justice, RL Pazdur, R AF Chang, J. Rand, M. Blumenthal, G. M. Cortazar, P. Kulick, C. Hausman, E. Chang, S. Pratt, R. Habtemarium, B. Chen, Y. Bullock, J. Orbach, R. Charlab Zineh, I. Justice, R. L. Pazdur, R. TI FDA evaluation of hepatotoxicity related to tyrosine kinase inhibitors. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Chang, J.; Rand, M.; Blumenthal, G. M.; Cortazar, P.; Kulick, C.; Hausman, E.; Chang, S.; Pratt, R.; Habtemarium, B.; Chen, Y.; Bullock, J.; Orbach, R. Charlab; Zineh, I.; Justice, R. L.; Pazdur, R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 3106 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301535 ER PT J AU Cortazar, P Zhang, JJ Sridhara, R Justice, RL Pazdur, R AF Cortazar, P. Zhang, J. J. Sridhara, R. Justice, R. L. Pazdur, R. TI Relationship between OS and PFS in metastatic breast cancer (MBC): Review of FDA submission data SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Cortazar, P.; Zhang, J. J.; Sridhara, R.; Justice, R. L.; Pazdur, R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 1035 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300174 PM 28020713 ER PT J AU Huang, X Ning, YM Mulquin, M Madan, RA Gulley, JL Kluetz, PG Adelberg, D Arlen, PM Parnes, HL Adesunloye, B Steinberg, SM Wright, JJ Trepel, JB Chen, C Bassim, C Apolo, AB Figg, WD Dahut, WL AF Huang, X. Ning, Y. M. Mulquin, M. Madan, R. A. Gulley, J. L. Kluetz, P. G. Adelberg, D. Arlen, P. M. Parnes, H. L. Adesunloye, B. Steinberg, S. M. Wright, J. J. Trepel, J. B. Chen, C. Bassim, C. Apolo, A. B. Figg, W. D. Dahut, W. L. TI Phase II trial of bevacizumab (A), lenalidomide (R), docetaxel (D), and prednisone (P) in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 NCI, Med Oncol Branch, Bethesda, MD 20892 USA. NCI, US FDA, Silver Spring, MD USA. Neogenix Oncol Inc, Rockville, MD USA. NCI, Canc Prevent Div, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, NIH, Bethesda, MD 20892 USA. NCI, Rockville, MD USA. NIH, Dept Nucl Med, Ctr Clin, Bethesda, MD USA. Natl Inst Dent & Craniolfacial Res, NIH, Bethesda, MD USA. NCI, Mol Pharmacol Sect, Bethesda, MD 20892 USA. RI Gulley, James/K-4139-2016; Figg Sr, William/M-2411-2016 OI Gulley, James/0000-0002-6569-2912; NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 4574 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300615 PM 28023318 ER PT J AU Malik, SM Farrell, AT Xu, Q Sridhara, R Pazdur, R AF Malik, S. M. Farrell, A. T. Xu, Q. Sridhara, R. Pazdur, R. TI Gender, age, and ethnic representation in non-small cell lung cancer (NSCLC) US registration trials: FDA review SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Malik, S. M.; Farrell, A. T.; Xu, Q.; Sridhara, R.; Pazdur, R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 1530 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301145 PM 28024058 ER PT J AU Mehrotra, N Pfuma, E Garnett, C Liu, Q Booth, B Rahman, NA Shahlaee, AH Liu, K AF Mehrotra, N. Pfuma, E. Garnett, C. Liu, Q. Booth, B. Rahman, N. A. Shahlaee, A. H. Liu, K. TI Exposure-response analysis as evidence for anti-tumor activity of everolimus in the treatment of patients with subependymal giant-cell astrocytoma (SEGA) associated with tuberous sclerosis (TS). SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Mehrotra, N.; Pfuma, E.; Garnett, C.; Liu, Q.; Booth, B.; Rahman, N. A.; Shahlaee, A. H.; Liu, K.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 9550 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880302572 PM 28019761 ER PT J AU Orbach, RC Blumenthal, GM Cortazar, P Filipski, KK Grimstein, C Zhang, L Mummaneni, P Booth, B Zineh, I AF Orbach, R. Charlab Blumenthal, G. M. Cortazar, P. Filipski, K. K. Grimstein, C. Zhang, L. Mummaneni, P. Booth, B. Zineh, I. TI Key drug development features in the design of early-phase oncology trials: An FDA perspective. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Orbach, R. Charlab; Blumenthal, G. M.; Cortazar, P.; Filipski, K. K.; Grimstein, C.; Zhang, L.; Mummaneni, P.; Booth, B.; Zineh, I.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 2597 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880301412 ER PT J AU Yang, J Wang, Y Zhao, H Garnett, C Gobburu, J Pierce, W Schechter, G Summers, J Keegan, P Booth, B Rahman, NA AF Yang, J. Wang, Y. Zhao, H. Garnett, C. Gobburu, J. Pierce, W. Schechter, G. Summers, J. Keegan, P. Booth, B. Rahman, N. A. TI Combination of exposure-response and case-control analyses in regulatory decision making. SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Meeting Abstract C1 [Yang, J.; Wang, Y.; Zhao, H.; Garnett, C.; Gobburu, J.; Pierce, W.; Schechter, G.; Summers, J.; Keegan, P.; Booth, B.; Rahman, N. A.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 2318 MILL ROAD, STE 800, ALEXANDRIA, VA 22314 USA SN 0732-183X EI 1527-7755 J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY 20 PY 2011 VL 29 IS 15 SU S MA 4087 PG 1 WC Oncology SC Oncology GA V31JQ UT WOS:000208880300497 PM 28020462 ER PT J AU Gunther, VJ Putnak, R Eckels, KH Mammen, MP Scherer, JM Lyons, A Sztein, MB Sun, W AF Gunther, V. J. Putnak, R. Eckels, K. H. Mammen, M. P. Scherer, J. M. Lyons, A. Sztein, M. B. Sun, W. TI A human challenge model for dengue infection reveals a possible protective role for sustained interferon gamma levels during the acute phase of illness SO VACCINE LA English DT Article DE Dengue; Human challenge; Immune response ID CLINICAL LABORATORY RESPONSES; YELLOW FEVER VIRUSES; T-CELL CLONES; ATTENUATED DENGUE; CYTOKINE PRODUCTION; HEMORRHAGIC-FEVER; DISEASE SEVERITY; RHESUS-MONKEYS; MICE; PATHOGENESIS AB Dengue has recently been defined by the World Health Organization as a major international public health concern. Although several vaccine candidates are in various stages of development, there is no licensed vaccine available to assist in controlling the further spread of this mosquito borne disease. The need for a reliable animal model for dengue disease increases the risk to vaccine developers as they move their vaccine candidates into large-scale phase III testing. In this paper we describe the cellular immune responses observed in a human challenge model for dengue infection; a model that has the potential to provide efficacy data for potential vaccine candidates in a controlled setting. Serum levels of sIL-2R alpha and sTNF-RII were increased in volunteers who developed illness. Supernatants from in vitro stimulated PBMC were tested for cytokines associated with a T(H)1 or T(H)2 T-cell response (IL-2, TNF-alpha, IFN-gamma, IL-4, IL-10, IL-5) and only IFN-gamma was associated with protection against fever and/or viremia. Interestingly, IFN-gamma levels drop to 0 pg/mL for volunteers who develop illness after challenge suggesting that some mechanism of immunosuppression may play a role in dengue illness. The human challenge model provides an opportunity to test potential vaccine candidates for efficacy prior to large-scale phase III testing, and hints at a possible mechanism for immune suppression by dengue. (C) 2011 Published by Elsevier Ltd. C1 [Gunther, V. J.; Putnak, R.; Lyons, A.] Walter Reed Army Inst Res, Div Viral Dis, Silver Spring, MD 20910 USA. [Eckels, K. H.] Walter Reed Army Inst Res, Div Regulated Act, Pilot Bioprod Facil, Silver Spring, MD 20910 USA. [Mammen, M. P.] Natl Ctr Med Intelligence, Ft Detrick, MD 21702 USA. [Scherer, J. M.] MEDCOM Surety, Ft Detrick, MD 21702 USA. [Sztein, M. B.] Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. [Sztein, M. B.] Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. [Sztein, M. B.] Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. [Sun, W.] CBER, Off Vaccine Res & Review, Div Vaccines & Related Prod Applicat, Rockville, MD 20852 USA. RP Gunther, VJ (reprint author), Walter Reed Army Inst Res, Div Viral Dis, Silver Spring, MD 20910 USA. EM v_gunther@yahoo.com RI Lyons, Arthur/B-8923-2011 NR 58 TC 54 Z9 54 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 17 PY 2011 VL 29 IS 22 BP 3895 EP 3904 DI 10.1016/j.vaccine.2011.03.038 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 774FP UT WOS:000291370900015 PM 21443963 ER PT J AU Martin, OA Redon, CE Nakamura, AJ Dickey, JS Georgakilas, AG Bonner, WM AF Martin, Olga A. Redon, Christophe E. Nakamura, Asako J. Dickey, Jennifer S. Georgakilas, Alexandros G. Bonner, William M. TI Systemic DNA Damage Related to Cancer SO CANCER RESEARCH LA English DT Review ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; IN-VIVO; MCP-1; CCL2; INFLAMMATION; INDUCTION; DISEASE; GROWTH; CELLS; LEADS AB The importance of bystander effects is becoming more appreciated, as studies show they may affect the course of cancer and other chronic diseases. The term "bystander effects" refers to changes in naive cells sharing the same milieu with cells that have been damaged. Bystander cells may be in contact with, or distant from, damaged cells. In addition, it has been shown in culture that not only physically damaged cells, but also cells that have become abnormal (i.e., cancerous or senescent) may induce bystander effects. Recently, we have shown a similar effect in animals. Mice harboring subcutaneous tumors exhibited elevated levels of DNA damage in distant organs. In contrast to cell culture, immune cells seemed to be involved in tumor-induced bystander effects in animals because CCL2-null tumor-bearing mice did not exhibit increased distant DNA damage. Here, we discuss some of the implications of these observations. Cancer Res; 71(10); 3437-41. (C) 2011 AACR. C1 [Martin, Olga A.; Redon, Christophe E.; Nakamura, Asako J.; Dickey, Jennifer S.; Bonner, William M.] NCI, Mol Pharmacol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. [Dickey, Jennifer S.] US FDA, Biochem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Georgakilas, Alexandros G.] E Carolina Univ, Dept Biol, Greenville, NC USA. RP Martin, OA (reprint author), NCI, Mol Pharmacol Lab, Ctr Canc Res, Bldg 37,Room 5050,9000 Rockville Pike, Bethesda, MD 20892 USA. EM sedelnio@mail.nih.gov FU National Cancer Institute (NCI) Center for Cancer Research, NIH; NCI; Biology Department of East Carolina University FX This work was funded by the Intramural Research Program of the National Cancer Institute (NCI) Center for Cancer Research, NIH, by an NCI Career Development Award (to C.E. Redon and O.A. Martin), and a Research/Creative Activity grant and a College Research award from the Biology Department of East Carolina University (to A.G. Georgakilas). NR 30 TC 24 Z9 25 U1 1 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 MAY 15 PY 2011 VL 71 IS 10 BP 3437 EP 3441 DI 10.1158/0008-5472.CAN-10-4579 PG 5 WC Oncology SC Oncology GA 764EH UT WOS:000290610900001 PM 21558390 ER PT J AU Kang, ZG Chen, JJ Yu, YK Li, B Sun, SY Zhang, BL Cao, L AF Kang, Zhigang Chen, Jun-Jie Yu, Yunkai Li, Bo Sun, Shi-Yong Zhang, Baolin Cao, Liang TI Drozitumab, a Human Antibody to Death Receptor 5, Has Potent Antitumor Activity against Rhabdomyosarcoma with the Expression of Caspase-8 Predictive of Response SO CLINICAL CANCER RESEARCH LA English DT Article ID CELL-LINES; CANCER-CELLS; TUMOR-CELL; APOPTOSIS; GROWTH; APO2L/TRAIL; RECRUITMENT; RESISTANT; SURVIVAL; AGONISTS AB Purpose: Rhabdomyosarcoma (RMS) is a common pediatric soft-tissue tumor. In this study, we evaluated the efficacy and selectivity of drozitumab, a death receptor DR5-targeted therapeutic antibody, in RMS preclinical models. Experimental Design: A panel of 11 RMS cell lines was used for in vitro studies. The molecular marker predictive of response to drozitumab was interrogated. Selected RMS cell lines were injected into the gastrocnemius muscle of mice for in vivo assessment of the potency and selectivity of drozitumab. Results: We report that DR5, but not DR4, persisted at high levels and on the surface of all RMS cell lines. DR5 antibody drozitumab was effective in vitro against the majority of RMS cell lines. There was a strong correlation between caspase-8 expression and the sensitivity to drozitumab, which induced the rapid assembly of the death-induced signaling complex and the cleavage of caspase-8 only in sensitive cells. More importantly, caspase-8 catalytic activity was both necessary and sufficient for mediating the sensitivity to drozitumab. Furthermore, drozitumab had potent antitumor activity against established RMS xenografts with a specificity predicted from the in vitro analysis and with tumor-free status in half of the treated mice. Conclusion: Our study provides the first preclinical evaluation of the potency and selectivity of a death receptor antibody in RMS. Drozitumab is effective, in vitro, against the majority of RMS cell lines that express caspase-8 and, in vivo, may provide long-term control of RMS. Clin Cancer Res; 17(10); 3181-92. (C) 2011 AACR. C1 [Kang, Zhigang; Yu, Yunkai; Cao, Liang] NCI, Genet Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Chen, Jun-Jie; Zhang, Baolin] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. [Kang, Zhigang; Yu, Yunkai] NCI, Lab Prote & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. [Li, Bo; Sun, Shi-Yong] Emory Univ, Sch Med, Dept Hematol & Med Oncol, Atlanta, GA USA. [Li, Bo; Sun, Shi-Yong] Winship Canc Inst, Atlanta, GA USA. RP Cao, L (reprint author), NCI, Genet Branch, Ctr Canc Res, 37 Convent Dr,MSC 4265,Bldg 37,Rm 6134, Bethesda, MD 20892 USA. EM caoli@mail.nih.gov RI Chen, Jun-Jie/E-1894-2012 FU U.S. National Cancer Institute (NCI); NCI, NIH [N01-CO-12400] FX This research was supported by the Intramural Research Program of the U.S. National Cancer Institute (NCI). This project was also funded in part with federal funds from the NCI, NIH, under contract N01-CO-12400. NR 31 TC 18 Z9 19 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY 15 PY 2011 VL 17 IS 10 BP 3181 EP 3192 DI 10.1158/1078-0432.CCR-10-2874 PG 12 WC Oncology SC Oncology GA 764EA UT WOS:000290610000013 PM 21385927 ER PT J AU Marik, R Allu, M Anchoori, R Stearns, V Umbricht, CB Khan, S AF Marik, Radharani Allu, Madhan Anchoori, Ravi Stearns, Vered Umbricht, Christopher B. Khan, Saeed TI Potent genistein derivatives as inhibitors of estrogen receptor alpha-positive breast cancer SO CANCER BIOLOGY & THERAPY LA English DT Article DE structurally modified genistein; estrogen receptors; estrogen receptor alpha related breast cancer chemoprevention ID CELL-LINES; MESSENGER-RNA; BETA ISOFORMS; IN-VITRO; ER-ALPHA; EXPRESSION; CARCINOMA; GROWTH; PROLIFERATION; APOPTOSIS AB The estrogen receptor (ER) is a major target for the treatment of breast cancer cells. Genistein, a soy isoflavone, possesses a structure similar to estrogen and can both mimic and antagonize estrogen effects although at high concentrations it inhibits breast cancer cell proliferation. Hence, to enhance the anticancer activity of genistein at lower concentrations, we have synthesized seven structurally modified derivatives of genistein (MA-6, MA-8, MA-11, MA-19, MA-20, MA-21 and MA-22) based on the structural requirements for an optimal anticancer effect. Among those seven, three derivatives (MA-6, MA-8 and MA-19) showed high antiproliferative activity with IC(50) levels in the range of 1-2.5 mu M, i.e., at much lower concentrations range than genistein itself, in three ER-positive breast cancer cell lines (MCF-7, 21PT and T47D) studied. In our analysis, we noticed that at IC(50) concentrations, the MA-6, MA-8 and MA-19 genistein derivatives induced apoptosis, inhibited ER alpha messenger RNA expression and increased the ratio of ER beta to ER alpha levels in a manner comparable to the parent compound genistein. Of note, these three modified genistein derivatives exerted their effects at concentrations 10-15 times lower than the parent compound, decreasing the likelihood of significant ER alpha pathway activation, which has been a concern for genistein. Hence, these compounds might play a useful role in breast cancer chemoprevention. C1 [Marik, Radharani; Umbricht, Christopher B.] Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. [Khan, Saeed] FDA CDER OPS OTR DPQR, Silver Spring, MD USA. RP Umbricht, CB (reprint author), Johns Hopkins Univ, Sch Med, Dept Surg, Baltimore, MD 21205 USA. EM cumbrich@jhmi.edu; khansa@jhmi.edu FU Susan G. Komen Foundation; NCI [P50 CA088843-06A1]; Breast Cancer Research Foundation; FAMRI FX Financial Support: Susan G. Komen Foundation (C. B. U.), NCI P50 CA088843-06A1 (C. B. U., V. S.), Breast Cancer Research Foundation (V. S., C. B. U.), FAMRI (S.K.). NR 33 TC 10 Z9 13 U1 0 U2 4 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4047 J9 CANCER BIOL THER JI Cancer Biol. Ther. PD MAY 15 PY 2011 VL 11 IS 10 BP 883 EP 892 DI 10.4161/cbt.11.10.15184 PG 10 WC Oncology SC Oncology GA 764EX UT WOS:000290612900004 PM 21389782 ER PT J AU Ackerman, LK Noonan, GO Begley, TH Mazzola, EP AF Ackerman, Luke K. Noonan, Gregory O. Begley, Timothy H. Mazzola, Eugene P. TI Accurate mass and nuclear magnetic resonance identification of bisphenolic can coating migrants and their interference with liquid chromatography/tandem mass spectrometric analysis of bisphenol A SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID DIGLYCIDYL-ETHER BADGE; CANNED FOODS; EXPOSURE ASSESSMENT; POTENTIAL MIGRANTS; JAPANESE MARKETS; EPOXY-RESINS; DERIVATIVES; PRODUCTS; QUANTIFICATION; OIL AB Two unknown compounds were previously determined to be potential interferences in liquid chromatography/tandem mass spectrometry (LC/MS/MS) analysis of bisphenol A (BPA) in canned infant formula. Both yielded two identical MS/MS transitions to BPA. The identities of the unknowns were investigated using accurate mass LC/MS, LC/MS/MS, and elemental formula and structures proposed. Exact identities were confirmed through purification or synthesis followed by (1)H and (13)C nuclear magnetic resonance (NMR) experiments, as well as comparisons of one unknown with commercial standards. Comparisons of negative ion electrospray ionization (ESI) MS/MS and accurate mass spectra suggested both unknowns to be structurally identical (to BPA and each other). Positive ion ESI spectra confirmed both were larger molecules, suggesting that in the negative mode they likely fragmented to the BPA molecular ion in the source. Elemental composition of positive ion accurate mass spectra and NMR analysis concluded the unknowns were oxidized forms of the known epoxy can coating monomer, bisphenol A diglycidyl ether (BADGE). One of the unknowns, 2,2-[bis-4-(2,3-dihydroxypropoxy)phenyl]propane, commonly known as BADGE*2H(2)O, is widely reported as an epoxy-phenolic can coating migrant, but has not been suggested to interfere with the MS/MS analysis of BPA. The other unknown, 2-[4-(2,3-dihydroxypropoxy)phenyl]-2-[4'-hydroxyphenyl] propane, or the oxidized form of bisphenol A monoglycidyl ether (BAMGE*H(2)O), has not been previously reported in food or packaging. Published in 2011 by John Wiley & Sons, Ltd. C1 [Ackerman, Luke K.; Noonan, Gregory O.; Begley, Timothy H.; Mazzola, Eugene P.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Ackerman, LK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Luke.Ackerman@fda.hhs.gov RI Ackerman, Luke/E-4597-2011 OI Ackerman, Luke/0000-0001-6626-3039 NR 36 TC 5 Z9 5 U1 2 U2 18 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PD MAY 15 PY 2011 VL 25 IS 9 BP 1336 EP 1342 DI 10.1002/rcm.4997 PG 7 WC Biochemical Research Methods; Chemistry, Analytical; Spectroscopy SC Biochemistry & Molecular Biology; Chemistry; Spectroscopy GA 762DN UT WOS:000290452600026 PM 21488128 ER PT J AU Yang, X Salminen, WF AF Yang, Xi Salminen, William F. TI Kava extract, an herbal alternative for anxiety relief, potentiates acetaminophen-induced cytotoxicity in rat hepatic cells SO PHYTOMEDICINE LA English DT Article DE Acetaminophen; Kava extract; Hepatocytes; Hepatotoxicity; Mitochondrial toxicity; Oxidative stress ID MITOCHONDRIAL PERMEABILITY TRANSITION; INDUCED LIVER-INJURY; INDUCED HEPATOTOXICITY; PIPER-METHYSTICUM; OXIDATIVE STRESS; F344 RATS; IN-VITRO; COVALENT BINDING; ORAL TREATMENT; UNITED-STATES AB The widely used over-the-counter analgesic acetaminophen (APAP) is the leading cause of acute liver failure in the United States and due to this high incidence, a recent FDA Advisory Board recommended lowering the maximum dose of APAP. Kava herbal dietary supplements have been implicated in several human liver failure cases leading to the ban of kava-containing products in several Western countries. In the US, the FDA has issued warnings about the potential adverse effects of kava, but kava dietary supplements are still available to consumers. In this study, we tested the potential of kava extract to potentiate APAP-induced hepatocyte cytotoxicity. In rat primary hepatocytes, co-treatment with kava and APAP caused 100% loss of cell viability, while the treatment of kava or APAP alone caused similar to 50% and similar to 30% loss of cell viability, respectively. APAP-induced glutathione (GSH) depletion was also potentiated by kava. Co-exposure to kava decreased cellular ATP concentrations, increased the formation of reactive oxygen species, and caused mitochondrial damage as indicated by a decrease in mitochondrial membrane potential. In addition, similar findings were obtained from a cultured rat liver cell line, clone-9. These observations indicate that kava potentiates APAP-induced cytotoxicity by increasing the magnitude of GSH depletion, resulting in oxidative stress and mitochondrial dysfunction, ultimately leading to cell death. These results highlight the potential for drug-dietary supplement interactions even with widely used over-the-counter drugs. Published by Elsevier GmbH. C1 [Yang, Xi; Salminen, William F.] US FDA, Div Syst Biol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Salminen, WF (reprint author), US FDA, Div Syst Biol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM William.Salminen@fda.hhs.gov FU National Center for Toxicological Research through US Department of Energy and the US Food and Drug Administration FX Dr. Xi Yang is supported by the Research Participation Program at the National Center for Toxicological Research administrated by the Oak Ridge Institute for Science and Education through an inter-agency agreement between the US Department of Energy and the US Food and Drug Administration. NR 42 TC 8 Z9 8 U1 2 U2 16 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0944-7113 J9 PHYTOMEDICINE JI Phytomedicine PD MAY 15 PY 2011 VL 18 IS 7 BP 592 EP 600 DI 10.1016/j.phymed.2011.02.006 PG 9 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 780YZ UT WOS:000291899100010 PM 21397479 ER PT J AU Poole, SK Poole, CF AF Poole, Salwa K. Poole, Colin F. TI High performance stationary phases for planar chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Review DE Thin-layer chromatography; Stationary phases; Plate height measurements; Theory; Capillary flow; Forced flow; Planar electrochromatography; Ultra thin-layer chromatography; Particle membranes ID THIN-LAYER-CHROMATOGRAPHY; TLC PLATES; PHOTOACOUSTIC-SPECTROSCOPY; LIQUID-CHROMATOGRAPHY; QUANTITATIVE TLC; OPLC; HEIGHT; COLUMN; HPTLC AB The kinetic performance of stabilized particle layers, particle membranes, and thin films for thin-layer chromatography is reviewed with a focus on how layer characteristics and experimental conditions affect the observed plate height. Forced flow and pressurized planar electrochromatography are identified as the best candidates to overcome the limited performance achieved by capillary flow for stabilized particle layers. For conventional and high performance plates band broadening is dominated by molecular diffusion at low mobile phase velocities typical of capillary flow systems and by mass transfer with a significant contribution from flow anisotropy at higher flow rates typical of forced flow systems. There are few possible changes to the structure of stabilized particle layers that would significantly improve their performance for capillary flow systems while for forced flow a number of avenues for further study are identified. New media for ultra thin-layer chromatography shows encouraging possibilities for miniaturized high performance systems but the realization of their true performance requires improvements in instrumentation for sample application and detection. (C) 2010 Elsevier B.V. All rights reserved. C1 [Poole, Colin F.] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA. [Poole, Salwa K.] US FDA, Detroit Dist Lab, Detroit, MI 48207 USA. RP Poole, CF (reprint author), Wayne State Univ, Dept Chem, 5101 Cass Ave, Detroit, MI 48202 USA. EM cfp@chem.wayne.edu NR 91 TC 23 Z9 23 U1 3 U2 21 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAY 13 PY 2011 VL 1218 IS 19 SI SI BP 2648 EP 2660 DI 10.1016/j.chroma.2010.10.072 PG 13 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 762SB UT WOS:000290500300003 PM 21056422 ER PT J AU Beasley, BN Unger, EF Temple, R AF Beasley, B. Nhi Unger, Ellis F. Temple, Robert TI Anticoagulant Options - Why the FDA Approved a Higher but Not a Lower Dose of Dabigatran SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID ATRIAL-FIBRILLATION; WARFARIN C1 [Beasley, B. Nhi] US FDA, Div Cardiovasc & Renal Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Unger, Ellis F.; Temple, Robert] US FDA, Off Drug Evaluat 1, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Beasley, BN (reprint author), US FDA, Div Cardiovasc & Renal Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 6 TC 125 Z9 132 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 12 PY 2011 VL 364 IS 19 BP 1788 EP 1790 DI 10.1056/NEJMp1103050 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 762MM UT WOS:000290483000003 PM 21488759 ER PT J AU Song, FH AF Song, Fenhong TI "Cross-Talk" in Scheduled Multiple Reaction Monitoring Caused by In-Source Fragmentation in Herbicide Screening with Liquid Chromatography Electrospray Tandem Mass Spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE liquid chromatography mass spectrometry; herbicides; cross talk ID PESTICIDES AB Interferences, or "cross-talk", have been found for the liquid chromatorgraphy mass spectrometry (LC-MS) determination of chlorophenoxy acid (CPA) herbicides. The time-scheduled multiple reaction monitoring (MRM) of m/z 161.0 -> 125.0 and 163.0 -> 127.0 transitions were produced by 2,4-dichlorophenol and 2,4-dichlorophenoxyacetic acid. Although MRM reduces the possibility of false positives when two transitions for LC/MS-MS are used for quantification and qualitative confirmation, in the case of the structurally related CPAs here, false positives still occurred when using a mixture of standards to identify the residues. It was necessary to analyze pure individual standards to compare with the extracted retention times of the candidate CPAs in food samples. C1 [Song, Fenhong] US FDA, Total Diet & Pesticide Res Ctr, Lenexa, KS 66214 USA. RP Song, FH (reprint author), US FDA, Total Diet & Pesticide Res Ctr, 11510 W 80th St, Lenexa, KS 66214 USA. EM Fenhong.Song@fda.hhs.gov NR 6 TC 5 Z9 5 U1 0 U2 13 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 11 PY 2011 VL 59 IS 9 BP 4361 EP 4364 DI 10.1021/jf200592n PG 4 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 757WX UT WOS:000290120400004 PM 21417433 ER PT J AU Ohnuma, S Chufan, E Nandigama, K Jenkins, LMM Durell, SR Appella, E Sauna, ZE Ambudkar, SV AF Ohnuma, Shinobu Chufan, Eduardo Nandigama, Krishnamachary Jenkins, Lisa M. Miller Durell, Stewart R. Appella, Ettore Sauna, Zuben E. Ambudkar, Suresh V. TI Inhibition of Multidrug Resistance-Linked P-Glycoprotein (ABCB1) Function by 5 '-Fluorosulfonylbenzoyl 5 '-Adenosine: Evidence for an ATP Analogue That Interacts with Both Drug-Substrate-and Nucleotide-Binding Sites SO BIOCHEMISTRY LA English DT Article ID CATALYTIC CYCLE; CASSETTE TRANSPORTERS; INVARIANT LYSINE; TRANSITION-STATE; PROTEIN-KINASE; A-LOOP; HYDROLYSIS; AFFINITY; DOMAIN; IDENTIFICATION AB 5'-Fluorosulfonylbenzonyl 5'-adenosine (FSBA) is an ATP analogue that covalently modifies several residues in the nudeotide-binding domains (NBDs) of several ATPases, kinases, and other proteins. P-glycoprotein (P-gp, ABCB1) is a member of the ATP-binding cassette (ABC) transporter superfamily that anticancer agents from cancer cells. We investigated the interactions of FSBA with P-gp to study the catalytic cycle of ATP hydrolysis. Incubation of P-gp with FSBA inhibited ATP hydrolysis (IC(50) = 0.21 mM) and the binding of 8-azido[alpha-(32)P]ATP (IC(50) = 0.68 mM). In addition, (14)C-FSBA cross-links to P-gp, suggesting that FSBA-mediated inhibition of ATP hydrolysis is irreversible due to covalent modification of P-gp. However, when the NBDs were occupied with a saturating concentration of ATP prior to treatment, FSBA stimulated ATP hydrolysis by P-gp. Furthermore, FSBA inhibited the photo-cross-linking of P-gp with [(125)I]iodoarylazidoprazosin (IAAP; IC(50) = 0.17 mM). As IAAP is a transport substrate for P-gp, this suggests that FSBA affects not only the NBDs but also the transport-substrate site in the transmembrane domains. Consistent with these results, FSBA blocked efflux of rhodamine 123 from P-gp-expressing cells. Additionally, mass spectrometric analysis identified FSBA cross-links to residues within or nearby the NBDs but not in the transmembrane domains, and docking of FSBA in a homology model of human P-gp NBDs supports the biochemical studies. Thus, FSBA is an ATP analogue that interacts with both the drug-binding and ATP-binding sites of P-gp, but fluorosulfonyl-mediated cross-linking is observed only at the NBDs. C1 [Ohnuma, Shinobu; Chufan, Eduardo; Nandigama, Krishnamachary; Jenkins, Lisa M. Miller; Durell, Stewart R.; Appella, Ettore; Ambudkar, Suresh V.] NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Sauna, Zuben E.] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Ambudkar, SV (reprint author), NCI, Cell Biol Lab, Ctr Canc Res, NIH, Bldg 37, Bethesda, MD 20892 USA. EM ambudkar@helix.nih.gov FU National Institutes of Health, National Cancer Institute, Center for Cancer Research FX This research was supported by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, Center for Cancer Research. NR 52 TC 9 Z9 9 U1 0 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 10 PY 2011 VL 50 IS 18 BP 3724 EP 3735 DI 10.1021/bi200073f PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 757AK UT WOS:000290056000015 PM 21452853 ER PT J AU Gnjidic, D Le Couteur, DG Abernethy, DR Hilmer, SN AF Gnjidic, Danijela Le Couteur, David G. Abernethy, Darrell R. Hilmer, Sarah N. TI Reducing Drugs in Older Adults Is More SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter ID BURDEN INDEX; MEDICATIONS; PEOPLE C1 [Gnjidic, Danijela] Royal N Shore Hosp, Clin Pharmacol Dept, St Leonards, NSW 2065, Australia. [Le Couteur, David G.; Hilmer, Sarah N.] Univ Sydney, Sydney Medi cal Sch, Sydney, NSW, Australia. [Le Couteur, David G.] Concord Hosp, Ctr Educ & Res Ageing, Sydney, NSW, Australia. [Abernethy, Darrell R.] US FDA, Maryville, MO USA. RP Gnjidic, D (reprint author), Royal N Shore Hosp, Clin Pharmacol Dept, 11C Main Bldg,Sydney, St Leonards, NSW 2065, Australia. EM danijela.gnjidic@sydney.edu.au OI Hilmer, Sarah/0000-0002-5970-1501 NR 5 TC 1 Z9 1 U1 0 U2 2 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD MAY 9 PY 2011 VL 171 IS 9 BP 868 EP 869 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 761QS UT WOS:000290413400023 PM 21555673 ER PT J AU Kim, HY Tsai, S Lo, SC Wear, DJ Izadjoo, MJ AF Kim, Hyung-Yong Tsai, Shien Lo, Shyh-Ching Wear, Douglas J. Izadjoo, Mina J. TI Production and Characterization of Chimeric Monoclonal Antibodies against Burkholderia pseudomallei and B. mallei Using the DHFR Expression System SO PLOS ONE LA English DT Article ID IMMUNOGLOBULIN VARIABLE DOMAINS; CAPSULAR POLYSACCHARIDE; CHO-CELLS; MELIOIDOSIS; PROTEIN; LIPOPOLYSACCHARIDE; PATHOGENICITY; LIPOPROTEIN; VACCINES; VECTORS AB Burkholderia pseudomallei (BP) and B. mallei (BM) are closely related gram-negative, facultative anaerobic bacteria which cause life-threatening melioidosis in human and glanders in horse, respectively. Our laboratory has previously generated and characterized more than 100 mouse monoclonal antibodies (MAbs) against BP and BM, according to in vitro and in vivo assay. In this study, 3 MAbs (BP7 10B11, BP7 2C6, and BP1 7F7) were selected to develop into chimeric mouse-human monoclonal antibodies (cMAbs) against BP and/or BM. For the stable production of cMAbs, we constructed 4 major different vector systems with a dihydrofolate reductase (DHFR) amplification marker, and optimized transfection/selection conditions in mammalian host cells with the single-gene and/or double-gene expression system. These 3 cMAbs were stably produced by the DHFR double mutant Chinese hamster ovarian (CHO)-DG44 cells. By ELISA and Western blot analysis using whole bacterial antigens treated by heat (65 degrees C/90 min), sodium periodate, and proteinase K, the cMAb BP7 10B11 (cMAb CK1) reacted with glycoproteins (34, 38, 48 kDa in BP; 28, 38, 48 kDa in BM). The cMAb BP7 2C6 (cMAb CK2) recognized surface-capsule antigens with molecular sizes of 38 to 52 kDa, and 200 kDa in BM. The cMAb CK2 was weakly reactive to 14 similar to 28, 200 kDa antigens in BP. The cMAb BP1 7F7 (cMAb CK3) reacted with lipopolysaccharides (38 similar to 52 kDa in BP; 38 similar to 60 kDa in B. thailandensis). Western blot results with the outer surface antigens of the 3 Burkholderia species were consistent with results with the whole Burkholderia cell antigens, suggesting that these immunodominant antigens reacting with the 3 cMAbs were primarily present on the outer surface of the Burkholderia species. These 3 cMAbs would be useful for analyzing the role of the major outer surface antigens in Burkholderia infection. C1 [Kim, Hyung-Yong; Tsai, Shien; Wear, Douglas J.; Izadjoo, Mina J.] Armed Forces Inst Pathol, Dept Environm & Infect Dis Sci, Washington, DC 20306 USA. [Kim, Hyung-Yong; Tsai, Shien; Wear, Douglas J.; Izadjoo, Mina J.] Amer Registry Pathol, Washington, DC USA. [Lo, Shyh-Ching] US Food & Drug Adm FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Lo, Shyh-Ching] US Food & Drug Adm FDA, Div Human Tissues, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Kim, HY (reprint author), Armed Forces Inst Pathol, Dept Environm & Infect Dis Sci, Washington, DC 20306 USA. EM izadjoo@afip.osd.mil FU Defense Threat Reduction Agency-Joint Science and Technology Office [2.1_05_AF_B, 2.1_07_AF_B] FX This research was supported by grants 2.1_05_AF_B & 2.1_07_AF_B from the Defense Threat Reduction Agency-Joint Science and Technology Office. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 44 TC 0 Z9 1 U1 0 U2 8 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAY 9 PY 2011 VL 6 IS 5 AR e19867 DI 10.1371/journal.pone.0019867 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 761GX UT WOS:000290386800039 PM 21573027 ER PT J AU Watts, M Tabak, J Zimliki, C Sherman, A Bertram, R AF Watts, Margaret Tabak, Joel Zimliki, Charles Sherman, Arthur Bertram, Richard TI Slow variable dominance and phase resetting in phantom bursting SO JOURNAL OF THEORETICAL BIOLOGY LA English DT Article DE Bursting; Multi-scale; Islet; Oscillations ID PANCREATIC BETA-CELLS; MODEL; OSCILLATIONS; DEPENDENCE; NOISE AB Bursting oscillations are common in neurons and endocrine cells. One type of bursting model with two slow variables has been called 'phantom bursting' since the burst period is a blend of the time constants of the slow variables. A phantom bursting model can produce bursting with a wide range of periods: fast (short period), medium, and slow (long period). We describe a measure, which we call the 'dominance factor', of the relative contributions of the two slow variables to the bursting produced by a simple phantom bursting model. Using this tool, we demonstrate how the control of different phases of the burst can be shifted from one slow variable to another by changing a model parameter. We then show that the dominance curves obtained as a parameter is varied can be useful in making predictions about the resetting properties of the model cells. Finally, we demonstrate two mechanisms by which phase-independent resetting of a burst can be achieved, as has been shown to occur in the electrical activity of pancreatic islets. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Watts, Margaret; Bertram, Richard] Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. [Bertram, Richard] Florida State Univ, Program Neurosci, Tallahassee, FL 32306 USA. [Bertram, Richard] Florida State Univ, Program Mol Biophys, Tallahassee, FL 32306 USA. [Sherman, Arthur] NIDDK, Lab Biol Modeling, NIH, Bethesda, MD USA. [Zimliki, Charles] US FDA, Artificial Pancreas Working Grp, Gen Hosp Devices Branch, Silver Spring, MD USA. [Tabak, Joel] Florida State Univ, Dept Biol Sci, Tallahassee, FL 32306 USA. RP Bertram, R (reprint author), Florida State Univ, Dept Math, Tallahassee, FL 32306 USA. EM bertram@math.fsu.edu OI Tabak, Joel/0000-0002-0588-957X FU NSF [DMS0917664]; NIH [DA19356]; NIH (NIDDK) FX This work was partially supported by NSF Grant DMS0917664 and NIH Grant DA19356 to Richard Bertram. Arthur Sherman is supported by the Intramural Research Program of the NIH (NIDDK). NR 15 TC 10 Z9 10 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-5193 J9 J THEOR BIOL JI J. Theor. Biol. PD MAY 7 PY 2011 VL 276 IS 1 BP 218 EP 228 DI 10.1016/j.jtbi.2011.01.042 PG 11 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 750JW UT WOS:000289543400025 PM 21315733 ER PT J AU Liu, JY Zhang, DY Luo, WJ Yu, YH Yu, JX Li, JX Zhang, XH Zhang, BL Chen, JY Wu, XR Rosas-Acosta, G Huang, CS AF Liu, Jinyi Zhang, Dongyun Luo, Wenjing Yu, Yonghui Yu, Jianxiu Li, Jingxia Zhang, Xinhai Zhang, Baolin Chen, Jingyuan Wu, Xue-Ru Rosas-Acosta, German Huang, Chuanshu TI X-linked Inhibitor of Apoptosis Protein (XIAP) Mediates Cancer Cell Motility via Rho GDP Dissociation Inhibitor (RhoGDI)-dependent Regulation of the Cytoskeleton SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNOHISTOCHEMICAL DETECTION; ACTIN POLYMERIZATION; EXPRESSION; CARCINOMA; METASTASIS; DEGRADATION; IAPS; MESOTHELIOMA; RECURRENCE; MIGRATION AB X-linked inhibitor of apoptosis protein (XIAP) overexpression has been found to be associated with malignant cancer progression and aggression in individuals with many types of cancers. However, the molecular basis of XIAP in the regulation of cancer cell biological behavior remains largely unknown. In this study, we found that a deficiency of XIAP expression in human cancer cells by either knock-out or knockdown leads to a marked reduction in beta-actin polymerization and cytoskeleton formation. Consistently, cell migration and invasion were also decreased in XIAP-deficient cells compared with parental wildtype cells. Subsequent studies demonstrated that the regulation of cell motility by XIAP depends on its interaction with the Rho GDP dissociation inhibitor (RhoGDI) via the XIAP RING domain. Furthermore, XIAP was found to negatively regulate RhoGDI SUMOylation, which might affect its activity in controlling cell motility. Collectively, our studies provide novel insights into the molecular mechanisms by which XIAP regulates cancer invasion and offer a further theoretical basis for setting XIAP as a potential prognostic marker and specific target for treatment of cancers with metastatic properties. C1 [Liu, Jinyi; Zhang, Dongyun; Yu, Yonghui; Yu, Jianxiu; Li, Jingxia; Zhang, Xinhai; Huang, Chuanshu] NYU, Sch Med, Nelson Inst Environm Med, Tuxedo Pk, NY 10987 USA. [Liu, Jinyi] Third Mil Med Univ, Prevent Med Coll, Dept Hyg Toxicol, Chongqing 400038, Peoples R China. [Luo, Wenjing; Chen, Jingyuan] Fourth Mil Med Univ, Dept Occupat & Environm Hlth Sci, Xian 710032, Shanxi, Peoples R China. [Zhang, Baolin] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Wu, Xue-Ru] NYU, Sch Med, Dept Urol, New York, NY 10016 USA. [Wu, Xue-Ru] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. [Rosas-Acosta, German] Univ Texas El Paso, Dept Biol Sci, El Paso, TX 79968 USA. [Liu, Jinyi] Third Mil Med Univ, Prevent Med Coll, Toxicogenom Lab, Chongqing 400038, Peoples R China. RP Huang, CS (reprint author), NYU, Sch Med, Nelson Inst Environm Med, 57 Old Forge Rd, Tuxedo Pk, NY 10987 USA. EM chuanshu.huang@nyumc.org RI Yu, Jianxiu/A-7214-2012 FU National Institutes of Health, NCI [CA112557]; NIEHS [ES000260]; New York University Urology Center of Excellence; [ES012451]; [ES010344] FX This work was supported, in whole or in part, by National Institutes of Health Grant CA112557 from NCI and Grants ES012451, ES010344, and ES000260 from NIEHS. This work was also supported by the New York University Urology Center of Excellence. NR 51 TC 33 Z9 33 U1 1 U2 6 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 6 PY 2011 VL 286 IS 18 DI 10.1074/jbc.M110.176982 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 756ON UT WOS:000290022800003 PM 21402697 ER PT J AU Ball, R Horne, D Izurieta, H Sutherland, A Walderhaug, M Hsu, H AF Ball, Robert Horne, Dale Izurieta, Hector Sutherland, Andrea Walderhaug, Mark Hsu, Henry TI Statistical, Epidemiological, and Risk-Assessment Approaches to Evaluating Safety of Vaccines Throughout the Life Cycle at the Food and Drug Administration SO PEDIATRICS LA English DT Article DE vaccine; immunization; safety; statistics; epidemiology; risk assessment ID EVENT-REPORTING-SYSTEM; ADVERSE EVENTS; VACCINATION; TRIALS; INFORMATION; DISEASE AB The public health community faces increasing demands for improving vaccine safety while simultaneously increasing the number of vaccines available to prevent infectious diseases. The passage of the US Food and Drug Administration (FDA) Amendment Act of 2007 formalized the concept of life-cycle management of the risks and benefits of vaccines, from early clinical development through many years of use in large numbers of people. Harnessing scientific and technologic advances is necessary to improve vaccine-safety evaluation. The Office of Biostatistics and Epidemiology in the Center for Biologics Evaluation and Research is working to improve the FDA's ability to monitor vaccine safety by improving statistical, epidemiologic, and risk-assessment methods, gaining access to new sources of data, and exploring the use of genomics data. In this article we describe the current approaches, new resources, and future directions that the FDA is taking to improve the evaluation of vaccine safety. Pediatrics 2011;127:S31-S38 C1 [Ball, Robert; Horne, Dale; Izurieta, Hector; Sutherland, Andrea; Walderhaug, Mark; Hsu, Henry] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Ball, R (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, HFM 210,1401 Rockville Pike, Rockville, MD 20852 USA. EM robert.ball@fda.hhs.gov FU FDA FX Financial support of this work was provided by the FDA. NR 31 TC 7 Z9 7 U1 4 U2 6 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2011 VL 127 SU 1 BP S31 EP S38 DI 10.1542/peds.2010-1722F PG 8 WC Pediatrics SC Pediatrics GA 846QK UT WOS:000296918100006 PM 21502249 ER PT J AU Marshall, V Baylor, NW AF Marshall, Valerie Baylor, Norman W. TI Food and Drug Administration Regulation and Evaluation of Vaccines SO PEDIATRICS LA English DT Article DE vaccine; regulation; biologics licensing AB The vaccine-approval process in the United States is regulated by the Center for Biologics Evaluation and Research of the US Food and Drug Administration. Throughout the life cycle of development, from preclinical studies to after licensure, vaccines are subject to rigorous testing and oversight. Manufacturers must adhere to good manufacturing practices and control procedures to ensure the quality of vaccines. As mandated by Title 21 of the Code of Regulations, licensed vaccines must meet stringent criteria for safety, efficacy, and potency. Pediatrics 2011;127:S23-S30 C1 [Marshall, Valerie; Baylor, Norman W.] US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20850 USA. RP Baylor, NW (reprint author), US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 405, Rockville, MD 20850 USA. EM Norman.Baylor@fda.hhs.gov NR 17 TC 15 Z9 15 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2011 VL 127 SU 1 BP S23 EP S30 DI 10.1542/peds.2010-1722E PG 8 WC Pediatrics SC Pediatrics GA 846QK UT WOS:000296918100005 PM 21502242 ER PT J AU Salmon, DA Akhtar, A Mergler, MJ Vannice, KS Izurieta, H Ball, R Lee, GM Vellozzi, C Garman, P Cunningham, F Gellin, B Koh, H Lurie, N AF Salmon, Daniel A. Akhtar, Aysha Mergler, Michelle J. Vannice, Kirsten S. Izurieta, Hector Ball, Robert Lee, Grace M. Vellozzi, Claudia Garman, Patrick Cunningham, Francesca Gellin, Bruce Koh, Howard Lurie, Nicole CA H1N1 Working Grp Fed Immunization TI Immunization-Safety Monitoring Systems for the 2009 H1N1 Monovalent Influenza Vaccination Program SO PEDIATRICS LA English DT Article DE vaccine safety; H1N1 influenza ID DEFENSE MEDICAL SURVEILLANCE; EVENT REPORTING SYSTEM; VACCINES; DISEASE; COMPLICATIONS; EXPERIENCE AB The effort to vaccinate the US population against the 2009 H1N1 influenza virus hinged, in part, on public confidence in vaccine safety. Early in the vaccine program, >20% of parents reported that they would not vaccinate their children. Concerns about the safety of the vaccines were reported by many parents as a factor that contributed to their intention to forgo vaccination (see www.hsph.harvard.edu/news/press-releases/2009-releases/survey-40-adults-absolutely-certain-h1n1vaccine.html and www.med.umich.edu/mott/npch/reports/h1n1.htm). The safety profiles of 2009 H1N1 monovalent influenza vaccines were anticipated to be (and have been) similar to those of seasonal influenza vaccines, for which an excellent safety profile has been demonstrated. Here we describe steps taken by the US government to (1) assess the key federal systems in place before 2009 for monitoring the safety of vaccines and (2) integrate and upgrade those systems for optimal vaccine-safety monitoring during the 2009 H1N1 monovalent influenza vaccination program. These efforts improved monitoring of 2009 H1N1 vaccine safety, hold promise for enhancing future national monitoring of vaccine safety, and may ultimately help improve public confidence in vaccines. Pediatrics 2011;127:S78-S86 C1 [Salmon, Daniel A.] US Dept HHS, Natl Vaccine Program Off, Off Publ Hlth & Sci, Off Secretary, Washington, DC 20201 USA. [Izurieta, Hector] US FDA, Analyt Epidemiol Branch, Div Epidemiol, Rockville, MD 20857 USA. [Akhtar, Aysha; Ball, Robert] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Lee, Grace M.] Harvard Univ, Sch Med, Dept Populat Med, Harvard Pilgrim Hlth Care Inst, Boston, MA USA. [Lee, Grace M.] Childrens Hosp, Div Infect Dis, Boston, MA 02115 USA. [Lee, Grace M.] Dept Lab Med, Boston, MA USA. [Vellozzi, Claudia] Ctr Dis Control & Prevent, Immunizat Safety Off, Div Healthcare Qual Promot, Atlanta, GA USA. [Garman, Patrick] USA, Mil Vaccine Agcy, Falls Church, VA USA. [Cunningham, Francesca] Pharm Benefits Management Serv, Natl Ctr Patient Safety, Dept Vet Affairs, Washington, DC USA. RP Salmon, DA (reprint author), US Dept HHS, Natl Vaccine Program Off, Off Publ Hlth & Sci, Off Secretary, 200 Independence Ave,SW Room 715H, Washington, DC 20201 USA. EM daniel.salmon@hhs.gov OI Krause, Philip/0000-0002-1045-7536; Hughes, Michelle/0000-0002-4436-2236 NR 27 TC 29 Z9 30 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2011 VL 127 SU 1 BP S78 EP S86 DI 10.1542/peds.2010-1722L PG 9 WC Pediatrics SC Pediatrics GA 846QK UT WOS:000296918100012 PM 21502251 ER PT J AU Wang, SJ Hung, HMJ O'Neill, RT AF Wang, Sue-Jane Hung, H. M. James O'Neill, Robert T. TI Genomic Classifier for Patient Enrichment: Misclassification and Type I Error Issues in Pharmacogenomics Noninferiority Trial SO STATISTICS IN BIOPHARMACEUTICAL RESEARCH LA English DT Article DE Biomarker qualification; Disease prevalence; False positive classification; Nondifferential misclassification; Noninferiority; Positive predictive value; Type I error probability ID METASTATIC COLORECTAL-CANCER; CLINICAL-TRIALS; DESIGNS; EFFICIENCY; BIOMARKER AB Unlike the phenotypic characteristics, a genomic diagnostic assay is needed to assess whether a patient truly has the genomic characteristics of interest for therapeutic investigation. However, in reality, the diagnostic assay is not perfect without misclassification error. We consider a targeted or enrichment pharmacogenomics clinical trial with a noninferiority objective. We assume the probability of response of the misclassified subjects is identical in the treated and control groups because the blinding should yield no preferential misclassification. We show that the maximum Type I error rate associated with falsely concluding noninferiority can be substantially liberal if the accuracy of the diagnostic assay is much less than perfect. When the diagnostic assay has moderate to high sensitivity and specificity, a reasonable range of false nondisease prediction rate among test positives can be identified where the maximum Type I error rate inflation is much less. To achieve a prescribed level of positive predictive value, the feasibility of a genomic biomarker for enrichment in a noninferiority study is a function of disease prevalence. Given the evidential standard of much less inflation of Type I error rate can be shown, a genomic biomarker, if qualified, may be useful as an adjunct tool for patient selection. C1 [Wang, Sue-Jane] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Hung, H. M. James] US FDA, Div Biometr 1, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, HFD-700,WO 21,MailStop Room 3562,10903 New Hampsh, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov FU Center for Drug Evaluation and Research, U.S. Food and Drug Administration [08-48] FX The authors wish to thank UNC Gillings School of Global Public Health Department of Biostatistics for inviting this article to a special issue in celebration of their 60th Anniversary and a Festschrift in honor of Professor Gary Koch. This research work was supported by the RSR funds #08-48 awarded by the Center for Drug Evaluation and Research, U.S. Food and Drug Administration. NR 15 TC 8 Z9 9 U1 0 U2 2 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 732 N WASHINGTON ST, ALEXANDRIA, VA 22314-1943 USA SN 1946-6315 J9 STAT BIOPHARM RES JI Stat. Biopharm. Res. PD MAY PY 2011 VL 3 IS 2 BP 310 EP 319 DI 10.1198/sbr.2010.10012 PG 10 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 791QX UT WOS:000292680800017 ER PT J AU Lo, SC Tsai, SE AF Lo, Shyh-Ching Tsai, Shien TI Mycoplasmas and Human prostate cancer: An exciting but cautionary note SO ONCOTARGET LA English DT Editorial Material ID LEUKAEMIC BONE-MARROW; MALIGNANT-TRANSFORMATION; INFECTION; CELLS; ONCOGENESIS; LEUKEMIA; AGENTS C1 [Lo, Shyh-Ching; Tsai, Shien] US FDA, Ctr Biol Evaluat & Res, Tissue Microbiol Lab, Div Cellular & Gene Therapies,Off Cellular Tissue, Bethesda, MD 20892 USA. RP Lo, SC (reprint author), US FDA, Ctr Biol Evaluat & Res, Tissue Microbiol Lab, Div Cellular & Gene Therapies,Off Cellular Tissue, Bethesda, MD 20892 USA. EM shyhching.lo@fda.hhs.gov NR 23 TC 2 Z9 2 U1 1 U2 2 PU IMPACT JOURNALS LLC PI ALBANY PA 6211 TIPTON HOUSE, STE 6, ALBANY, NY 12203 USA SN 1949-2553 J9 ONCOTARGET JI Oncotarget PD MAY PY 2011 VL 2 IS 5 BP 352 EP 355 PG 4 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 802KN UT WOS:000293509800001 PM 21789784 ER PT J AU Sarazan, RD Mittelstadt, S Guth, B Koerner, J Zhang, J Pettit, S AF Sarazan, R. Dustan Mittelstadt, Scott Guth, Brian Koerner, John Zhang, Joanne Pettit, Syril TI Cardiovascular Function in Nonclinical Drug Safety Assessment: Current Issues and Opportunities SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE cardiovascular; hemodynamics; safety assessment ID BLOOD-PRESSURE; CARDIAC-FUNCTION; QT INTERVAL; RISK; DOGS; PHARMACOLOGY; METAANALYSIS; TOXICOLOGY; ANIMALS AB There are several recent examples where clinically significant, safety-related, drug effects on hemodynamics or cardiac function were not apparent until large clinical trials were completed or the drugs entered the consumer market. Such late-stage safety issues can have significant impact on patient health and consumer confidence, as well as ramifications for the regulatory, pharmaceutical, and financial communities. This manuscript provides recommendations that evolved from a 2009 HESI workshop on the need for improved translation of nonclinical cardiovascular effects to the clinical arena. The authors conclude that expanded and improved efforts to perform sensitive yet specific evaluations of functional cardiovascular parameters in nonclinical studies will allow pharmaceutical companies to identify suspect drugs early in the discovery and development process while allowing promising drugs to proceed into clinical development. C1 [Sarazan, R. Dustan] Data Sci Int, St Paul, MN USA. [Mittelstadt, Scott] Abbott Labs, Abbott Pk, IL 60064 USA. [Guth, Brian] Boehringer Ingelheim GmbH & Co KG, Ingelheim, Germany. [Koerner, John; Zhang, Joanne] US FDA, Silver Spring, MD USA. [Pettit, Syril] HESI, Washington, DC USA. RP Pettit, S (reprint author), 1156 15th St NW,2nd Floor, Washington, DC 20005 USA. EM spettit@ilsi.org NR 45 TC 29 Z9 29 U1 1 U2 3 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY PY 2011 VL 30 IS 3 BP 272 EP 286 DI 10.1177/1091581811398963 PG 15 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 795OB UT WOS:000292982400002 PM 21527643 ER PT J AU Booth, B AF Booth, Brian TI Incurred sample reanalysis FOREWORD SO BIOANALYSIS LA English DT Editorial Material C1 US FDA, Silver Spring, MD 20993 USA. RP Booth, B (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 51,Room 2186, Silver Spring, MD 20993 USA. EM brian.booth@fda.hhs.gov NR 4 TC 3 Z9 3 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 MAY PY 2011 VL 3 IS 9 SI SI BP 927 EP 928 DI 10.4155/BIO.11.69 PG 2 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 775FB UT WOS:000291443000001 PM 21545337 ER PT J AU Vallejos, JR Brorson, KA Moreira, AR Rao, G AF Vallejos, Jose R. Brorson, Kurt A. Moreira, Antonio R. Rao, Govind TI Integrating a 250 mL-Spinner Flask with Other Stirred Bench-Scale Cell Culture Devices: A Mass Transfer Perspective SO BIOTECHNOLOGY PROGRESS LA English DT Article DE bioprocess development; mass transfer; minibioreactors; scale-up; spinner flasks ID OXYGEN-TRANSFER; MINIATURE BIOREACTOR; SULFITE OXIDATION; MICROTITER PLATES; SHAKE FLASKS; VESSELS; GROWTH; POWER; FUTURE; SENSOR AB The bioprocess development cycle is a complex task that requires a complete understanding of the engineering of the process (e. g., mass transfer, mixing, CO(2) removal, process monitoring, and control) and its affect on cell biology and product quality. Despite their widespread use in bioprocess development, spinner flasks generally lack engineering characterization of critical physical parameters such as k(L)a, P/V, or mixing time. In this study, mass transfer characterization of a 250-mL spinner flask using optical patch-based sensors is presented. The results quantitatively show the effect of the impeller type, liquid filling volume, and agitation speed on the volumetric mass transfer coefficient (k(L)a) in a 250-mL spinner flask, and how they can be manipulated to match mass transfer capability at large culture devices. Thus, process understanding in spinner flasks can be improved, and these devices can be seamlessly integrated in a rational scale-up strategy from cell thawing to bench-scale bioreactors (and beyond) in biomanufacturing. (C) 2011 American Institute of Chemical Engineers Biotechnol. Prog., 27: 803-810, 2011 C1 [Vallejos, Jose R.; Moreira, Antonio R.; Rao, Govind] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. [Brorson, Kurt A.] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Rao, G (reprint author), Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. EM grao@umbc.edu FU Sartorius-Stedim Biotech FX Funding from Sartorius-Stedim Biotech is gratefully acknowledged. G. Rao has an equity position in Flurometrix. Views expressed in this article are those of the authors and not necessarily of the US FDA or the US government. Discussion of the individual cell culture devices does not constitute endorsement by the US FDA or the US government. NR 36 TC 5 Z9 5 U1 1 U2 10 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD MAY-JUN PY 2011 VL 27 IS 3 BP 803 EP 810 DI 10.1002/btpr.578 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 776NZ UT WOS:000291544000024 PM 21523928 ER PT J AU Antonovic, L Martinez, M AF Antonovic, Leposava Martinez, Marilyn TI Role of the cytochrome P450 enzyme system in veterinary pharmacokinetics: where are we now? Where are we going? SO FUTURE MEDICINAL CHEMISTRY LA English DT Article ID DRUG-METABOLIZING-ENZYMES; PHASE-I; SUBSTRATE-SPECIFICITY; SPECIES-DIFFERENCES; PATIENT VARIATION; LIVER-MICROSOMES; AFLATOXIN B-1; EXPRESSION; CYP1A2; DOGS AB Drug metabolism is a core determinant of the dose-effectiveness-toxicity relationship of many compounds. It is also critical to the human food safety assessment of drug residues in the edible tissues of food-producing animals. This article describes the current state of knowledge regarding the role of the cytochrome P450 superfamily of enzymes in determining the metabolic profile of compounds administered to companion animals (e.g., dog and cat) and to food-producing animal species (e.g., cattle, swine, chickens). In turn, this knowledge reflects the collection of insights derived from the recognized population variability observed in human drug metabolism, our general understanding of the kinetics of various drug-metabolism pathways, emerging tools that enable the role of pharmacogenetics to be studied and the characterization of drug metabolism in individual veterinary species. Ultimately, by increasing our insights with regard to factors that can influence drug metabolism, our knowledge of metabolic pathways, sources of within-and between-species variability in pharmacokinetics and the development of in silico models that can be used to predict pharmacokinetic profiles from these diverse sources of information. We will improve our ability to generate the population inferences needed to insure the target animal safety, product effectiveness and the human food safety of veterinary pharmaceuticals. C1 [Antonovic, Leposava; Martinez, Marilyn] US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Silver Spring, MD 20855 USA. RP Martinez, M (reprint author), US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, 7500 Standish Pl,MPN2,HFV-130, Silver Spring, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov NR 97 TC 15 Z9 15 U1 1 U2 22 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 EI 1756-8927 J9 FUTURE MED CHEM JI Future Med. Chem. PD MAY PY 2011 VL 3 IS 7 BP 855 EP 879 DI 10.4155/FMC.11.37 PG 25 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 775EQ UT WOS:000291441800018 PM 21644832 ER PT J AU Lee, SH Lillehoj, HS Park, MS Baldwin, C Tompkins, D Wagner, B Del Cacho, E Babu, U Min, W AF Lee, Sung Hyen Lillehoj, Hyun S. Park, Myeong Seon Baldwin, Cynthia Tompkins, Dannielle Wagner, Bettina Del Cacho, Emilio Babu, Uma Min, Wongi TI Development and characterization of mouse monoclonal antibodies reactive with chicken CD80 SO COMPARATIVE IMMUNOLOGY MICROBIOLOGY AND INFECTIOUS DISEASES LA English DT Article DE Chicken; CD80; Monoclonal antibody; Hybridoma; Biological function ID ACERVULINA-INDUCED CHANGES; T-CELL PROLIFERATION; MHC CLASS-II; DENDRITIC CELLS; B-CELLS; MOLECULE CD80; EXPRESSION; CTLA-4; INTERLEUKIN-2; ACTIVATION AB This study was carried out to develop and characterize mouse monoclonal antibodies (mAbs) against chicken CD80 (chCD80). A recombinant plasmid containing a chCD80/horse IgG4 fusion gene was constructed and expressed in CHO cells to produce recombinant cliCD80/IgG4 protein. Chicken CD80 was purified from the chCD80/IgG4 fusion protein following enterokinase digestion, and used to immunize BALB/c mice, resulting in 158 hybridomas that produced mAbs against chCD80. Three mAbs with high binding specificity for recombinant chCD80/IgG4-transfected CHO cells were identified by flow cytometry, and one of these (#112) was selected for further characterization. Immunoprecipitation of CD80/IgG4-CI-10 cell extract, or lipopolysaccharide (LPS)-treated monocytes identified 35.0 kDa proteins. Immunohistochemical analysis revealed chCD80-expressing cells exclusively in the bursal follicles at the outer portion of the cortex, and throughout the red pulp and the outer boundary of the white pulp in the spleen. By immunofluorescence microscopy, chCD80 was observed on intestinal dendritic cells. LPS treatment of bursa or spleen monocytes for 24 or 48 h increased chCD80 expression. Finally, addition of chCD80 mAb to Con A-stimulated spleen cells inhibited the expression of major histocompatibility complex class II antigens and IL-2-driven proliferation of lymphoblast cells. In summary, these chCD80 mAbs will serve as valuable immunological reagents for basic and applied poultry immunology research. Published by Elsevier Ltd. C1 [Lillehoj, Hyun S.] USDA ARS, Anim Parasit Dis Lab, Anim & Nat Resources Inst, BARC E, Beltsville, MD 20705 USA. [Baldwin, Cynthia; Tompkins, Dannielle] Univ Massachusetts, Dept Vet & Anim Sci, Amherst, MA 01003 USA. [Wagner, Bettina] Cornell Univ, Coll Vet Med, Dept Populat Med & Diagnost Sci, Ithaca, NY 14853 USA. [Del Cacho, Emilio] Univ Zaragoza, Dept Anim Pathol, Fac Vet Sci, Zaragoza 500015, Spain. [Babu, Uma] US FDA, Immunobiol Branch, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Min, Wongi] Gyeongsang Natl Univ, Coll Vet Med, Jinju 660701, Gyeongsangnamdo, South Korea. [Min, Wongi] Gyeongsang Natl Univ, Life Sci Res Inst, Jinju 660701, Gyeongsangnamdo, South Korea. RP Lillehoj, HS (reprint author), USDA ARS, Anim Parasit Dis Lab, Anim & Nat Resources Inst, BARC E, Bldg 1043, Beltsville, MD 20705 USA. EM Hyun.Lillehoj@ars.usda.gov OI Min, Wongi/0000-0003-2437-7366 FU USDA [2005-01812]; U.S. Veterinary Immune Reagent Network; Ministry of Education, Science and Technology [R33-10013] FX This project is funded by USDA-CSREES proposal 2005-01812, the U.S. Veterinary Immune Reagent Network (http://www.umass.edu/vetimm), and partially by the WCU Program through the National Research Foundation of Korea funded by the Ministry of Education, Science and Technology (R33-10013). The authors thank Dr. Erik P. Lillehoj for editorial assistance and Dr. Seung I. Jang, Dr. Duk Kyung Kim, Dr. Kyung Woo Lee, Ms. Marjorie Nichols, Ms. Stacy Torreyson, and Ms. Caroline Chen for their contributions to this research. NR 39 TC 10 Z9 10 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0147-9571 J9 COMP IMMUNOL MICROB JI Comp. Immunol. Microbiol. Infect. Dis. PD MAY PY 2011 VL 34 IS 3 BP 273 EP 279 DI 10.1016/j.cimid.2011.01.003 PG 7 WC Immunology; Microbiology; Veterinary Sciences SC Immunology; Microbiology; Veterinary Sciences GA 771VD UT WOS:000291187900009 PM 21334748 ER PT J AU Weng, ZQ Suda, M Ohtani, K Mei, N Kawamoto, T Nakajima, T Wang, RS AF Weng, Zuquan Suda, Megumi Ohtani, Katsumi Mei, Nan Kawamoto, Toshihiro Nakajima, Tamie Wang, Rui-Sheng TI Aldh2 Knockout Mice Were More Sensitive to DNA Damage in Leukocytes due to Ethyl Tertiary Butyl Ether Exposure SO INDUSTRIAL HEALTH LA English DT Article DE Ethyl tertiary butyl ether; Genotoxicity; Aldh2 knockout mice; Comet assay; Leukocyte; Aldehyde dehydrogenase; Acetaldehyde ID GENE TARGETING MOUSE; ALDEHYDE DEHYDROGENASE; HUMAN-LYMPHOCYTES; ALCOHOL-DRINKING; IN-VITRO; ACETALDEHYDE; RATS; POLYMORPHISMS; LIVER; CARCINOGENICITY AB To clarify the genotoxicity of ethyl tertiary butyl ether (ETBE), a gasoline additive, male and female C57BL/6 mice of Aldh2+/+ and Aldh2-/- genotypes, aged 8 wk, were exposed to 0, 500, 1,750, or 5,000 ppm ETBE for 6 h/day, 5 d per week for 13 wk. DNA damage in leukocytes was measured by the alkaline comet assay and expressed quantitatively as Tail Intensity (TI). For male mice, TI was significantly higher in all three groups exposed to ETBE than in those without exposure within Aldh2-/- mice, whereas within Aldh2+/+ mice, TI increased only in those exposed to 5,000 ppm of ETBE as compared with mice without exposure. For female mice, a significant increase in TI values was observed in the group exposed to 5,000 ppm of ETBE as compared with those without exposure within Aldh2-/- mice; TI in Aldh2-/- mice exposed to 1,750 and 5,000 ppm was significantly higher than in Aldh2+/+ mice without exposure. TI did not significantly increase in any of the groups exposed to ETBE within female Aldh2+/+ mice. Based on the results we suggest that Aldh2-/- mice are more sensitive to DNA damage caused by ETBE than Aldh2+/+ mice and that males seem more susceptible to this effect than females. C1 [Weng, Zuquan; Suda, Megumi; Ohtani, Katsumi; Wang, Rui-Sheng] NIOSH, Kawasaki, Kanagawa 2148585, Japan. [Mei, Nan] Natl Ctr Toxicol Res, Dept Genet & Mol Toxicol, Jefferson, AR 72079 USA. [Kawamoto, Toshihiro] Univ Occupat & Environm Hlth, Dept Environm Hlth, Kitakyushu, Fukuoka 807, Japan. [Nakajima, Tamie] Nagoya Univ, Dept Occupat & Environm Hlth, Nagoya, Aichi 4648601, Japan. RP Wang, RS (reprint author), NIOSH, 6-21-1 Nagao, Kawasaki, Kanagawa 2148585, Japan. EM wang@h.jniosh.go.jp RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 FU National Institute of Occupational Safety and Health, Japan [P21-03] FX We are grateful to Ms. S. Watanabe for her assistance in the manipulation of the animals. The present study was supported by grant-in-aid for project research from the National Institute of Occupational Safety and Health, Japan (P21-03). The views presented in this paper do not necessarily reflect those of the U.S. Food and Drug Administration. NR 22 TC 5 Z9 5 U1 0 U2 3 PU NATL INST OCCUPATIONAL SAFETY & HEALTH, JAPAN PI KAWASAKI KANAGAWA PA 21-1 NAGAO 6-CHOME TAMA-KU, KAWASAKI KANAGAWA, 214, JAPAN SN 0019-8366 J9 IND HEALTH JI Ind. Health PD MAY PY 2011 VL 49 IS 3 SI SI BP 396 EP 399 DI 10.2486/indhealth.MS1188 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 771VU UT WOS:000291189600017 PM 21372431 ER PT J AU Bigelow, TA Church, CC Sandstrom, K Abbott, JG Ziskin, MC Edmonds, PD Herman, B Thomenius, KE Teo, TJ AF Bigelow, Timothy A. Church, Charles C. Sandstrom, Kurt Abbott, John G. Ziskin, Marvin C. Edmonds, Peter D. Herman, Bruce Thomenius, Kai E. Teo, Tat Jin TI The Thermal Index Its Strengths, Weaknesses, and Proposed Improvements SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE thermal index; thermal index strengths; thermal index weaknesses ID DIAGNOSTIC ULTRASOUND; SOFT-TISSUE; TEMPERATURE RISE; SAFETY PARAMETER; RADIATION; PROPAGATION; MODELS; HEAT; TIME AB The thermal index (TI) has been used as a relative indicator of thermal risk during diagnostic ultrasound examinations for many years. It is useful in providing feedback to the clinician or sonographer, allowing assessment of relative, potential risks to the patient of an adverse effect due to a thermal mechanism. Recently, several shortcomings of the TI formulations in quantifying the risk to the patient have been identified by members of the basic scientific community, and possible improvements to address these shortcomings have been proposed. For this reason, the Output Standards Subcommittee of the American Institute of Ultrasound in Medicine convened a subcommittee to review the strengths of the TI formulations as well as their weaknesses and proposed improvements. This article summarizes the findings of this subcommittee. After a careful review of the literature and an assessment of the cost of updating the TI formulations while maximizing the quality of patient care, the Output Standards Subcommittee makes the following recommendations: (1) some inconsistencies in the current TI formulations should be resolved, and the break point distance should be redefined to take focusing into consideration; (2) an entirely new indicator of thermal risk that incorporates the time dependence not be implemented at this time but be included in continuing efforts toward standards or consensus documents; (3) the exponential dependence of risk on temperature not be incorporated into a new definition of the TI formulations at this time but be included in continuing efforts toward standards or consensus documents; (4) the TI formulations not be altered to include nonlinear propagation at this time but be included in continuing efforts toward standards or consensus documents; and (5) a new indicator for risk from thermal mechanisms should be developed, distinct from the traditional TI formulations, for new imaging modalities such as acoustic radiation force impulse imaging, which have more complicated pulsing sequences than traditional imaging. C1 [Bigelow, Timothy A.] Iowa State Univ, Dept Elect & Comp Engn, Ames, IA 50011 USA. [Bigelow, Timothy A.] Iowa State Univ, Dept Mech Engn, Ames, IA 50011 USA. [Church, Charles C.] Univ Mississippi, Natl Ctr Phys Acoust, University, MS 38677 USA. [Sandstrom, Kurt] Medison Co Ltd, Seoul, South Korea. [Abbott, John G.] Philips Healthcare, Dept Stand & Regulat, Bothell, WA USA. [Ziskin, Marvin C.] Temple Univ, Ctr Biomed Phys, Sch Med, Philadelphia, PA 19122 USA. [Edmonds, Peter D.] SRI Int, Menlo Pk, CA 94025 USA. [Herman, Bruce] US FDA, Div Solid & Fluid Mech, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Thomenius, Kai E.] GE Global Res, Niskayuna, NY USA. [Teo, Tat Jin] Boston Sci, Imaging, Fremont, CA USA. RP Bigelow, TA (reprint author), Iowa State Univ, Dept Elect & Comp Engn, 2215 Coover Hall, Ames, IA 50011 USA. EM bigelow@iastate.edu NR 40 TC 7 Z9 7 U1 0 U2 3 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAY PY 2011 VL 30 IS 5 BP 714 EP 734 PG 21 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 770ZL UT WOS:000291126900019 PM 21527623 ER PT J AU Dang, Y Moore, J Huang, G Lipp, M Jones, B Griffiths, JC AF Dang, Yi Moore, Jeffrey Huang, Gloria Lipp, Markus Jones, Barbara Griffiths, James C. TI Establishing USP Rebaudioside A and Stevioside Reference Standards for the Food Chemicals Codex SO LC GC NORTH AMERICA LA English DT Article AB The United States Pharmacopeial Convention (USP) publishes the Food Chemicals Codex (FCC), which is a compendium of food ingredient documentary standards (monographs) that provide tests, procedures, and acceptance criteria to indicate the safety and quality of a food ingredient. Physical reference standards can be associated with the procedures of an FCC monograph and the reference standards are needed for conducting the procedures. This article describes characterization and collaborative testing of new USP rebaudioside A and stevioside reference standards and their suitability for intended uses in the FCC rebaudioside A monograph. C1 [Dang, Yi; Moore, Jeffrey; Lipp, Markus; Jones, Barbara; Griffiths, James C.] US Pharmacopeial Convent Inc, Rockville, MD USA. [Huang, Gloria] US FDA, Rockville, MD 20857 USA. RP Dang, Y (reprint author), US Pharmacopeial Convent Inc, Rockville, MD USA. EM yd@usp.org; jm@usp.org RI Markus, Lipp/A-1404-2011 NR 2 TC 0 Z9 0 U1 0 U2 3 PU ADVANSTAR COMMUNICATIONS INC PI WOODLAND HILLS PA 6200 CANOGA AVE, 2ND FLR, WOODLAND HILLS, CA 91367 USA SN 1527-5949 J9 LC GC N AM JI LC GC N. AM. PD MAY PY 2011 VL 29 IS 5 BP 430 EP + PG 6 WC Chemistry, Analytical SC Chemistry GA 773AF UT WOS:000291278700005 ER PT J AU Krucoff, MW Mehran, R van Es, GA Boam, AB Cutlip, DE AF Krucoff, Mitchell W. Mehran, Roxana van Es, Gerrit-Anne Boam, Ashley B. Cutlip, Donald E. TI The Academic Research Consortium Governance Charter SO JACC-CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material C1 [Krucoff, Mitchell W.] Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. [Mehran, Roxana] Cardiovasc Res Fdn, New York, NY USA. [Mehran, Roxana] Mt Sinai Med Ctr, New York, NY 10029 USA. [van Es, Gerrit-Anne] Cardialysis, Rotterdam, Netherlands. [Boam, Ashley B.] US FDA, Silver Spring, MD USA. [Cutlip, Donald E.] Harvard Clin Res Inst, Boston, MA USA. RP Krucoff, MW (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, 508 Fulton St,Room A3006 Cardiol, Durham, NC 27705 USA. EM kruco001@mc.duke.edu NR 0 TC 11 Z9 11 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1936-8798 J9 JACC-CARDIOVASC INTE JI JACC-Cardiovasc. Interv. PD MAY PY 2011 VL 4 IS 5 BP 595 EP 596 DI 10.1016/j.jcin.2011.03.008 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 769KR UT WOS:000291012500024 PM 21596341 ER PT J AU Pontone, GM Williams, JR Anderson, KE Chase, G Goldstein, SR Grill, S Hirsch, ES Lehmann, S Little, JT Margolis, RL Rabins, PV Weiss, HD Marsh, L AF Pontone, Gregory M. Williams, James R. Anderson, Karen E. Chase, Gary Goldstein, Susanne R. Grill, Stephen Hirsch, Elaina S. Lehmann, Susan Little, John T. Margolis, Russell L. Rabins, Peter V. Weiss, Howard D. Marsh, Laura TI Anxiety and self-perceived health status in Parkinson's disease SO PARKINSONISM & RELATED DISORDERS LA English DT Article DE Parkinson's disease; Non-motor symptoms; Anxiety; Psychiatric disorders; Quality of life; Fluctuations ID QUALITY-OF-LIFE; NONMOTOR FLUCTUATIONS; COMORBIDITY; DEPRESSION; SYMPTOMS; DEMENTIA; MOOD; QUESTIONNAIRE; POPULATION; PREVALENCE AB Both anxiety and depression are associated with lower self-perceived health status (HS) in persons with Parkinson's disease (PD). Given the high co-morbidity with depression and other non-motor symptoms, it is unclear whether anxiety disorders, in general, versus specific anxiety subtypes have an independent effect on HS in PD. To examine this question, comprehensive assessments of motor and non-motor symptoms from 249 subjects with idiopathic PD followed in three community-based movement disorders neurology practices were analyzed. HS was measured using the 8-item PD Questionnaire (PDQ-8). Psychiatric diagnoses were established by consensus using a panel of six psychiatrists with expertise in geriatric psychiatry and movement disorders. Stepwise multiple regression analyses were used, with the PDQ-8 score as the dependent variable, to identify independent predictors of HS among motor, psychiatric, and other non-motor variables. Among the anxiety disorders, only anxiety associated with motor fluctuations was an independent predictor of HS after accounting for co-morbid depression and other clinical features. In addition, depressive disorders were also an independent predictor of lower HS. Prevention or treatment of state-dependent anxiety may improve HS in persons with PD. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Pontone, Gregory M.; Hirsch, Elaina S.; Lehmann, Susan; Little, John T.; Margolis, Russell L.; Rabins, Peter V.; Marsh, Laura] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21287 USA. [Williams, James R.] Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mental Hlth, Baltimore, MD 21287 USA. [Williams, James R.] Food & Drug Adm, Silver Spring, MD USA. [Anderson, Karen E.] Univ Maryland, Med Ctr, Dept Psychiat, Baltimore, MD 21201 USA. [Anderson, Karen E.] Univ Maryland, Med Ctr, Dept Neurol, Baltimore, MD 21201 USA. [Chase, Gary] Penn State Univ, Dept Hlth Evaluat Sci, Hershey, PA USA. [Goldstein, Susanne R.; Grill, Stephen] Parkinsons & Movement Disorders Ctr Maryland, Elkridge, MD USA. [Goldstein, Susanne R.; Grill, Stephen; Weiss, Howard D.; Marsh, Laura] Johns Hopkins Univ, Sch Med, Dept Neurol & Neurol Sci, Baltimore, MD 21287 USA. [Little, John T.] Georgetown Univ, Sch Med, Dept Psychiat, Washington, DC USA. [Little, John T.] Georgetown Univ, Sch Med, Dept Neurol, Washington, DC USA. [Weiss, Howard D.] Sinai Hosp, Dept Neurol, Baltimore, MD 21215 USA. [Marsh, Laura] Baylor Coll Med, Dept Psychiat, Houston, TX 77030 USA. [Marsh, Laura] Baylor Coll Med, Dept Neurol, Houston, TX 77030 USA. RP Pontone, GM (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 600 N Wolfe St,Phipps 300, Baltimore, MD 21287 USA. EM gponton1@jhmi.edu FU NIH, Morris K. Udall Parkinson's Disease Research Center of Excellence at Johns Hopkins [R01-MH069666, IH-P50-NS-08377, NIH-5T32-AG-027668-02]; Parkinson's Disease Foundation/Parkinson Study Group; Donna Jeanne Gault Baumann Fund; National Institutes of Health, Forest Research Institute, Parkinson's Disease Foundation/Parkinson Study Group; Maryland VA; National Institutes of Health; Neuro Hi-Tech FX Supported by: NIH grants [R01-MH069666, the Morris K. Udall Parkinson's Disease Research Center of Excellence at Johns Hopkins (NIH-P50-NS-08377) and the Age-Related Cognitive Disorders Training Grant (NIH-5T32-AG-027668-02) to J.R. Williams], the Parkinson's Disease Foundation/Parkinson Study Group Mentored Clinical Research Award (Gregory M. Pontone, MD), and the Donna Jeanne Gault Baumann Fund. The views expressed in this manuscript do not necessarily represent the views of the Food and Drug Administration or the United States.; Stock Ownership in medically-related fields: none; Consultancies: none; Advisory Boards: none; Partnerships: none; Honoraria (for lectures only): none; Grants: National Institutes of Health, Forest Research Institute, Parkinson's Disease Foundation/Parkinson Study Group; Intellectual Property Rights: none; Expert Testimony: none; Employment: Johns Hopkins University; Contracts (research): none; Royalties: none; Other: none.; Stock Ownership in medically-related fields: none; Consultancies: CHDI Foundation (Cure Huntington's Disease Initiative), Lundbeck Pharmaceuticals, Boehringer Ingelheim; Advisory Boards: none; Partnerships: none; Honoraria (for lectures only): none; Grants: Maryland VA (clinical time and funded Merit Proposal); Intellectual Property Rights: none; Expert Testimony: none; Employment: University of Maryland; Contracts (research): none; Royalties: none; Other: none.; Stock Ownership in medically-related fields: none; Consultancies: none; Advisory Boards: none; Partnerships: none; Honoraria (for lectures only): none; Grants: National Institutes of Health; Intellectual Property Rights: none; Expert Testimony: none; Employment: Johns Hopkins University; Contracts (research): none; Royalties: none; Other: none.; Stock Ownership in medically-related fields: none; Consultancies: none; Advisory Boards: none; Partnerships: none; Honoraria (for lectures only): none; Grants: Neuro Hi-Tech; Intellectual Property Rights: none; Expert Testimony: none; Employment: Georgetown University Hospital; Contracts (research): none; Royalties: none; Other: none. NR 32 TC 23 Z9 24 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1353-8020 J9 PARKINSONISM RELAT D JI Parkinsonism Relat. Disord. PD MAY PY 2011 VL 17 IS 4 BP 249 EP 254 DI 10.1016/j.parkreldis.2011.01.005 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 770FV UT WOS:000291073300006 PM 21292531 ER PT J AU Wei, SK Loyo-Berrios, NI Haigney, MCP Cheng, H Pinnow, EE Mitchell, KR Beachy, JH Woodward, AM Wang, YF Curtis, JP Marinac-Dabic, D AF Wei, Shaokui Loyo-Berrios, Nilsa I. Haigney, Mark C. P. Cheng, Hong Pinnow, Ellen E. Mitchell, Kristi R. Beachy, James H. Woodward, Albert M. Wang, Yongfei Curtis, Jeptha P. Marinac-Dabic, Danica TI Elevated B-Type Natriuretic Peptide Is Associated With Increased In-Hospital Mortality or Cardiac Arrest in Patients Undergoing Implantable Cardioverter-Defibrillator Implantation SO CIRCULATION-CARDIOVASCULAR QUALITY AND OUTCOMES LA English DT Article DE heart failure; implantable cardioverter-defibrillator; mortality; natriuretic peptides; registries ID CONGESTIVE-HEART-FAILURE; NATIONAL ICD REGISTRY; MYOCARDIAL-INFARCTION; INDEPENDENT PREDICTOR; THERAPY; FUTURE; COMPLICATIONS; GENDER; DEATH; TRIAL AB Background-The implantable cardioverter-defibrillator (ICD) is the most effective treatment for preventing arrhythmic deaths in patients with heart failure, but periprocedural complications, including in-hospital mortality or cardiac arrest, may occur, and little is known about risk factors. We asked whether elevated B-type natriuretic peptide (BNP) level is associated with increased risk of in-hospital mortality or cardiac arrest in patients undergoing ICD implantation. Methods and Results-From the National Cardiovascular Data Registry ICD Registry, we identified 53 198 patients who received ICD implants and underwent preoperative BNP measurement from 2006 to 2008. The patients were categorized into 4 groups by BNP levels (<100, 100 to <300, 300 to <1000, and >= 1000 pg/mL). Complication rates were compared among groups, and odds ratios for in-hospital mortality or cardiac arrest were estimated by multiple hierarchical logistic regressions. There were 2952 complications reported, including 510 in-hospital deaths and 365 cardiac arrests. The rate of in-hospital mortality or cardiac arrest significantly increased with elevated BNP level (P<0.001). The adjusted odds ratios of in-hospital mortality or cardiac arrest were statistically significant in all 3 higher BNP groups [odds ratio (95% CI), 1.99 (1.17 to 3.39), 2.49 (1.50 to 4.13), and 4.25 (2.57 to 7.06) in the second, third, and fourth groups using <100 as reference]. Among subgroups, the association was more significant in men, patients with renal dysfunction, and patients undergoing biventricular ICD implantation. Conclusions-Elevated BNP level was significantly associated with increased risk of in-hospital mortality or cardiac arrest in patients undergoing ICD implant. Strategies aimed at reducing preprocedural BNP or creating systems to manage procedural risk merit further investigation. (Circ Cardiovasc Qual Outcomes. 2011; 4: 346-354.) C1 [Wei, Shaokui; Loyo-Berrios, Nilsa I.; Cheng, Hong; Pinnow, Ellen E.; Marinac-Dabic, Danica] US FDA, Div Epidemiol, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Haigney, Mark C. P.] Uniformed Serv Univ Hlth Sci, Dept Med, Div Cardiol, Bethesda, MD 20814 USA. [Mitchell, Kristi R.; Beachy, James H.; Woodward, Albert M.] Amer Coll Cardiol, Washington, DC USA. [Wang, Yongfei; Curtis, Jeptha P.] Yale Univ, Sch Med, Dept Internal Med, Sect Cardiovasc Med, New Haven, CT 06510 USA. RP Wei, SK (reprint author), US FDA, Div Epidemiol, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM shaokui.wei@fda.hhs.gov FU Food and Drug Administration [HHSF223200610010I/TO4] FX This study was supported by Food and Drug Administration research grant HHSF223200610010I/TO4. NR 22 TC 2 Z9 2 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1941-7713 J9 CIRC-CARDIOVASC QUAL JI Circ.-Cardiovasc. Qual. Outcomes PD MAY PY 2011 VL 4 IS 3 BP 346 EP U157 DI 10.1161/CIRCOUTCOMES.110.943621 PG 12 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 765NX UT WOS:000290716100016 PM 21487093 ER PT J AU Contreras, CA Ochoa, TJ Ruiz, J Lacher, DW Rivera, FP Saenz, Y Chea-Woo, E Zavaleta, N Gil, AI Lanata, CF Huicho, L Maves, RC Torres, C DebRoy, C Cleary, TG AF Contreras, C. A. Ochoa, T. J. Ruiz, J. Lacher, D. W. Rivera, F. P. Saenz, Y. Chea-Woo, E. Zavaleta, N. Gil, A. I. Lanata, C. F. Huicho, L. Maves, R. C. Torres, C. DebRoy, C. Cleary, T. G. TI Phylogenetic relationships of Shiga toxin-producing Escherichia coli isolated from Peruvian children SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; MOLECULAR ANALYSIS; VIRULENCE FACTORS; STRAINS; OUTBREAK; SEROPATHOTYPES; EVOLUTIONARY; ASSOCIATION; INFECTIONS; SEQUENCES AB The aim of this study was to determine the prevalence, virulence factors (stx, eae, ehxA and astA) and phylogenetic relationships [PFGE and multilocus sequence typing (MLST)] of Shiga toxin-producing Escherichia coli (STEC) strains isolated from four previous cohort studies in 221 2 Peruvian children aged <36 months. STEC prevalence was 0.4% (14/3219) in diarrhoeal and 0.60/o (15/2695) in control samples. None of the infected children developed haemolytic uraemic syndrome (HUS) or other complications of STEC. stx1 was present in 83% of strains, stx2 in 17 %, eae in 72%, ehxA in 59% and astA in 14%. The most common serotype was 026 : H11 (14%) and the most common seropathotype was B (45%). The strains belonged mainly to phylogenetic group B1 (52%). The distinct combinations of alleles across the seven MLST loci were used to define 13 sequence types among 19 STEC strains. PFGE typing of 20 STEC strains resulted in 19 pulsed-field patterns. Comparison of the patterns revealed 11 clusters (I XI), each usually including strains belonging to different serotypes; one exception was cluster VI, which gathered exclusively seven strains of seropathotype B, clonal group enterohaemorrhagic E. coli (EHEC) 2 and phylogenetic group B1. In summary, STEC prevalence was low in Peruvian children with diarrhoea in the community setting. The strains were phylogenetically diverse and associated with mild infections. However, additional studies are needed in children with bloody diarrhoea and HUS. C1 [Contreras, C. A.; Ochoa, T. J.; Rivera, F. P.] 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. [Ruiz, J.] Hosp Clin Inst Invest Biomed August Pi & Sunyer, Ctr Recerca Salut Int Barcelona, Barcelona, Spain. [Ruiz, J.] CIBERESP, Barcelona, Spain. [Lacher, D. W.] US FDA, Laurel, MD USA. [Saenz, Y.; Torres, C.] Ctr Invest Biomed La Rioja, Area Microbiol Mol, Logrono, Spain. [Zavaleta, N.; Gil, A. I.; Lanata, C. F.] Inst Invest Nutr, Lima, Peru. [Lanata, C. F.] Univ Peruana Ciencias Aplicadas, Escuela Med, Lima, Peru. [Huicho, L.] Univ Nacl Mayor San Marcos, Lima 14, Peru. [Huicho, L.] Inst Nacl Salud Nino, Lima, Peru. [Maves, R. C.] US Naval Med Res Ctr Detachment, Dept Bacteriol, Lima, Peru. [DebRoy, C.] Penn State Univ, Ecoil Reference Ctr, Dept Vet & Biomed Sci, University Pk, PA 16802 USA. RP Ochoa, TJ (reprint author), Univ Peruana Cayetano Heredia, Inst Med Trop Alexander von Humboldt, Lima, Peru. EM Theresa.J.Ochoa@uth.tmc.edu RI Torres, Carmen/C-9027-2013; Valle, Ruben/A-7512-2013; Saenz, Yolanda/G-8847-2016; Ruiz, Joaquin/D-2704-2013 OI Torres, Carmen/0000-0003-3709-1690; Saenz, Yolanda/0000-0002-2457-4258; Ruiz, Joaquin/0000-0002-4431-2036 FU Agencia Espanola de Cooperacion Internacional (AECID), Spain; Programa de Cooperacion Interuniversitaria e Investigacion Cientifica con lberoamerica [D/019499/08, D/024648/09]; Universidad Peruana Cayetano Heredia, Peru; Instituto Nacional de Salud del Nino, Peru; Military Infectious Disease Research Program work unit [60000.000.0.B0017]; Instituto de Investigacion Nutricional, Peru; Programa Miguel Servet [CP05/00130]; National Institutes of Health, USA, Public Health Service [IK0ITW007405, R01-HD051716] FX The authors wish to thank Maruja Bernal, Rina Meza and David Cepeda for their help in laboratory analysis. This work was partially funded by: Agencia Espanola de Cooperacion Internacional (AECID), Spain, Programa de Cooperacion Interuniversitaria e Investigacion Cientifica con lberoamerica (D/019499/08 and D/024648/09); Institutional Research Funds from Universidad Peruana Cayetano Heredia, Peru (T.J.O.) and Instituto Nacional de Salud del Nino, Peru (L. H.); Military Infectious Disease Research Program work unit # 60000.000.0.B0017 (R. C. M.); Instituto de Investigacion Nutricional, Peru (N. Z. and C. F. L.); Programa Miguel Servet (CP05/00130) (J. R.); and the National Institutes of Health, USA, Public Health Service awards IK0ITW007405 (T. J. O.) and R01-HD051716 (T. G. C. and E.C.-W.). NR 29 TC 11 Z9 12 U1 0 U2 8 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 MAY PY 2011 VL 60 IS 5 BP 639 EP 646 DI 10.1099/jmm.0.026666-0 PG 8 WC Microbiology SC Microbiology GA 767DN UT WOS:000290835600011 PM 21292859 ER PT J AU Friedman, SD Cooper, EM Calci, KR Genthner, FJ AF Friedman, Stephanie D. Cooper, Emilie M. Calci, Kevin R. Genthner, Fred J. TI Design and assessment of a real time reverse transcription-PCR method to genotype single-stranded RNA male-specific coliphages (Family Leviviridae) SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Genotype; Male-specific RNA coliphage; FRNA; F plus coliphage; Real-time RT-PCR; Fecal source-tracking ID RIBONUCLEIC-ACID COLIPHAGES; MICROBIAL SOURCE TRACKING; LINE BLOT HYBRIDIZATION; F+-RNA; RT-PCR; FECAL POLLUTION; WASTE-WATER; OLIGONUCLEOTIDE PROBES; INDICATOR BACTERIA; ESCHERICHIA-COLI AB A real-time, reverse transcription-PCR (RT-qPCR) assay was developed to differentiate the four genogroups of male-specific ssRNA coliphages (FRNA) (family Leviviridae). As FRNA display a trend of source-specificity (human sewage or animal waste) at the genogroup level, this assay provides a tool to help identify the origin of fecal contamination. Primers and probes were designed using complete genomic sequences from 29 FRNA phages. The final selection of primer/probe sets were based on (i) ability to amplify a single, specific product, (ii) genogroup specificity, (iii) lack of cross-reactivity, and (iv) experimental reproducibility and sensitivity over a range of target concentrations. Assay time was reduced by using heat-released viral RNA rather than purified RNA. For quality assurance, a custom RNA molecule was employed as an internal, non-competitive control. The usefulness of this method to identify sources of fecal contamination was tested on a total of 49 FRNA phages isolated from various warm-blooded animals, sewage and combined sewage overflow. FRNA phages from animal wastes were genotyped as 86% I, 4% III Q-like and 9% IV. Two sewage isolates typed to genogroup I and combined sewage overflow isolates genotyped as 40% II and 52% III. Primer specificity designed from this comprehensive sequence database may better discriminate FRNA from different sources. Published by Elsevier B.V. C1 [Friedman, Stephanie D.; Genthner, Fred J.] US EPA, Gulf Ecol Div, Gulf Breeze, FL 32561 USA. [Cooper, Emilie M.] Ctr Dis Control & Prevent, Natl Calicivirus Lab, Gastroenteritis & Resp Viruses Lab Branch, Div Viral Dis, Atlanta, GA 30333 USA. [Calci, Kevin R.] US PHS, Food & Drug Adm, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Friedman, SD (reprint author), US EPA, Gulf Ecol Div, 1 Sabine Isl Dr, Gulf Breeze, FL 32561 USA. EM friedman.stephanie@epa.gov; irw2@cdc.gov; Kevin.Calci@fda.hhs.gov; genthner.fred@epa.gov FU US Environmental Protection Agency; EPA's New England Regional Applied Research Effort (RARE) FX The information in this document has been funded wholly (or in part) by the US Environmental Protection Agency. It has been subjected to review by the National Health and Environmental Effects Research Laboratory and approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. This is contribution number 1402 from the Gulf Ecology Division.; This research was funded, in part, through EPA's New England Regional Applied Research Effort (RARE). We gratefully acknowledge the assistance of Jack Paar, III, U.S. EPA New England Regional Laboratory, for initiating and sponsoring this program. NR 60 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD MAY PY 2011 VL 173 IS 2 BP 196 EP 202 DI 10.1016/j.jviromet.2011.02.005 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 767DV UT WOS:000290836400006 PM 21320531 ER PT J AU Panigaj, M Brouckova, A Glierova, H Dvorakova, E Simak, J Vostal, JG Holada, K AF Panigaj, Martin Brouckova, Adela Glierova, Hana Dvorakova, Eva Simak, Jan Vostal, Jaroslav G. Holada, Karel TI Underestimation of the expression of cellular prion protein on human red blood cells SO TRANSFUSION LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; PLATELETS; INFECTIVITY; PRPC; HAMSTER; MOUSE; CONFORMATION; TRANSFUSION; LYMPHOCYTES AB BACKGROUND: Recent transmissions of variant Creutzfeldt-Jakob disease by blood transfusion emphasize the need for the development of prion screening tests. The detection of prions in blood is complicated by the presence of poorly characterized cellular prion protein (PrP(C)) in both plasma and blood cells. According to published studies, most of PrP(C) in blood cells resides in platelets (PLTs) and white blood cells. STUDY DESIGN AND METHODS: To clarify conflicting reports about the quantity of PrP(C) associated with human red blood cells (RBCs), quantitative flow cytometry, Western blot (WB), and enzyme-linked immunosorbent assay (ELISA) were used to measure protein levels in healthy donors. RESULTS: RBCs expressed 290 +/- 140 molecules of PrP(C) per cell, assuming equimolar binding of monoclonal antibody (MoAb) 6H4 to PrP(C). Binding of alternate PrP(C) MoAbs, FH11 and 3F4, was substantially lower. WB estimated the level of PrP(C) per cell on RBCs to be just four times lower than in PLTs. A similar level of PrP(C) was detected using ELISA. The weak binding of commonly used MoAb 3F4 was not caused by PrP(C) conformation, truncation, or glycosylation, suggesting a covalent modification, likely glycation, of the 3F4 epitope. CONCLUSIONS: Taken together, human RBCs express low but significant amounts of PrP(C)/cell, which makes them, due to high RBC numbers, major contributors to the pool of cell-associated PrP(C) in blood. Previous reports utilizing MoAb 3F4 may have underestimated the amount of PrP(C) in RBCs. Likewise, screening tests for the presence of the abnormal prion protein in blood may be difficult if the abnormal protein is modified similar to RBC PrP(C). C1 [Holada, Karel] Charles Univ Prague, Inst Microbiol & Immunol, Fac Med 1, Prague 12820 2, Czech Republic. US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Holada, K (reprint author), Charles Univ Prague, Inst Microbiol & Immunol, Fac Med 1, Studnickova 7, Prague 12820 2, Czech Republic. EM karel.holada@lf1.cuni.cz RI Panigaj, Martin/G-6492-2013 FU [GACR 310/08/0878]; [GACR 203/07/1517]; [MSM0021620806,]; [SVV-2010-260506] FX This work was supported by Grants GACR 310/08/0878, GACR 203/07/1517, MSM0021620806, and SVV-2010-260506. NR 40 TC 10 Z9 10 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2011 VL 51 IS 5 BP 1012 EP 1021 DI 10.1111/j.1537-2995.2010.02924.x PG 10 WC Hematology SC Hematology GA 759SC UT WOS:000290267700018 PM 21058954 ER PT J AU Gelderman, MP Vostal, JG AF Gelderman, Monique P. Vostal, Jaroslav G. TI Rejuvenation improves roller pump-induced physical stress resistance of fresh and stored red blood cells SO TRANSFUSION LA English DT Article ID CARDIAC-SURGERY; CARDIOPULMONARY BYPASS; STORAGE; TRANSFUSION; REGENERATION; SURVIVAL; AGE; OXYGENATION; HEMOLYSIS; IMPACT AB BACKGROUND: Retrospective studies on transfusion recipients suggested that transfusion of older red blood cells (RBCs) was associated with higher morbidity. Similar studies were also done on cardiac surgery patients who were placed on cardiac bypass pumps. It is possible that stored RBCs are more fragile and could be more easily damaged by these pumps, thus leading to additional morbidity. STUDY DESIGN AND METHODS: Fresh and stored (42 days) RBCs, rejuvenated and nonrejuvenated, were compared in resistance to physical stress, induced by a roller pump, and osmotic fragility changes during physical stress to model RBCs going through cardiac bypass instruments. In addition, posttransfusion in vivo recovery was evaluated in an immunodeficient mouse model to minimize species differences between transfusion product and recipient. RESULTS: Fresh RBCs were more resistant to both osmotic and physical stress than stored cells. After 2 hours of physical stress, the osmotic stress resistance of fresh cells declined and was the same as for stored cells. Rejuvenated fresh cells did not demonstrate a decline in osmotic resistance during the stress test and both fresh and stored cells had the same improved resistance to osmotic stress before and after the physical stress. Rejuvenation slightly improved recovery of fresh RBCs but almost doubled the recovery of stored cells in the mouse model. CONCLUSIONS: Our studies suggest that rejuvenation improves roller pump-induced physical and osmotic stress resistance of stored RBCs. C1 [Gelderman, Monique P.] US FDA, Lab Cellular Hematol, Div Hematol, OBRR,CBER, Rockville, MD 20852 USA. RP Gelderman, MP (reprint author), US FDA, Lab Cellular Hematol, Div Hematol, OBRR,CBER, 1401 Rockville Pike,HFM-335, Rockville, MD 20852 USA. EM Monique.Gelderman-Fuhrmann@fda.hhs.gov NR 29 TC 5 Z9 5 U1 0 U2 3 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 EI 1537-2995 J9 TRANSFUSION JI Transfusion PD MAY PY 2011 VL 51 IS 5 BP 1096 EP 1104 DI 10.1111/j.1537-2995.2010.02972.x PG 9 WC Hematology SC Hematology GA 759SC UT WOS:000290267700027 PM 21133931 ER PT J AU Archdeacon, P Chan, M Neuland, C Velidedeoglu, E Meyer, J Tracy, L Cavaille-Coll, M Bala, S Hernandez, A Albrecht, R AF Archdeacon, P. Chan, M. Neuland, C. Velidedeoglu, E. Meyer, J. Tracy, L. Cavaille-Coll, M. Bala, S. Hernandez, A. Albrecht, R. TI Summary of FDA Antibody-Mediated Rejection Workshop SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Article DE Antibody-mediated rejection; clinical trials; evidence-based medicine; regulatory issues; surrogate endpoints; transplantation research ID ACUTE HUMORAL REJECTION; RENAL-ALLOGRAFT REJECTION; DONOR-SPECIFIC ANTIBODIES; HUMAN-LEUKOCYTE ANTIGEN; POSITIVE CROSS-MATCH; KIDNEY-TRANSPLANTATION; CLINICAL-RELEVANCE; THERAPY; PLASMAPHERESIS; RECIPIENTS AB The Food and Drug Administration (FDA) held an open public workshop in June 2010 to discuss the current state of science related to antibody-mediated rejection (AMR) in kidney transplantation. Desensitization, acute AMR and chronic AMR (CAMR) were considered in the context of clinical trial design. Participants discussed experiences with HLA antibody detection and quantitation and the utility of monitoring donor-specific antibodies (DSAs) to inform the management of patients with AMR. The role for animal models was discussed. Diagnostic and prognostic features of histology were presented, followed by discussion of sensitivity and specificity of various criteria. The published literature on treatment of acute AMR was summarized, which consisted of case series and limited data from controlled clinical trials. Considerations for future clinical trials were presented, including endpoints and statistical evaluations of outcome. Although many issues need further consideration, the meeting enabled an important exchange of ideas between experts in the field. C1 [Archdeacon, P.; Velidedeoglu, E.; Meyer, J.; Cavaille-Coll, M.; Bala, S.; Hernandez, A.; Albrecht, R.] US FDA, Div Special Pathogen & Transplant Prod, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Chan, M.] US FDA, Div Immunol & Hematol Devices, Off Vitro Diagnost Devices Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Neuland, C.] US FDA, Gastroenterol & Renal Devices Branch, Div Reprod Abdominal & Radiol Devices, Off Device Evaluat,Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Tracy, L.] US FDA, Div Biometr 7, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Albrecht, R (reprint author), US FDA, Div Special Pathogen & Transplant Prod, Off Antimicrobial Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM Renata.Albrecht@fda.hhs.gov NR 45 TC 85 Z9 89 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAY PY 2011 VL 11 IS 5 BP 896 EP 906 DI 10.1111/j.1600-6143.2011.03525.x PG 11 WC Surgery; Transplantation SC Surgery; Transplantation GA 754ZS UT WOS:000289897000010 PM 21521465 ER PT J AU Franco, AA Hu, L Grim, CJ Gopinath, G Sathyamoorthy, V Jarvis, KG Lee, C Sadowski, J Kim, J Kothary, MH McCardell, BA Tall, BD AF Franco, A. A. Hu, L. Grim, C. J. Gopinath, G. Sathyamoorthy, V. Jarvis, K. G. Lee, C. Sadowski, J. Kim, J. Kothary, M. H. McCardell, B. A. Tall, B. D. TI Characterization of Putative Virulence Genes on the Related RepFIB Plasmids Harbored by Cronobacter spp. SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID PATHOGENIC ESCHERICHIA-COLI; ENTEROBACTER-SAKAZAKII INFECTIONS; POWDERED INFANT FORMULA; GRAM-NEGATIVE BACTERIA; VI SECRETION SYSTEM; NEONATAL MENINGITIS; YERSINIA-PESTIS; VIBRIO-CHOLERAE; INTESTINAL INFLAMMATION; SALMONELLA-TYPHIMURIUM AB Cronobacter spp. are emerging neonatal pathogens that cause meningitis, sepsis, and necrotizing enterocolitis. The genus Chronobacter consists of six species: C. sakazakii, C. malonaticus, C. muytjensii, C. turicensis, C. dublinensis, and Cronobacter genomospecies group 1. Whole-genome sequencing of C. sakazakii BAA-894 and C. turicensis z3032 revealed that they harbor similarly sized plasmids identified as pESA3 (131 kb) and pCTU1 (138 kb), respectively. In silico analysis showed that both plasmids encode a single RepFIB-like origin of replication gene, repA, as well as two iron acquisition systems (eitCBAD and iucABCD/iutA). In a chrome azurol S agar diffusion assay, it was demonstrated that siderophore activity was associated with the presence of pESA3 or pCTU1. Additionally, pESA3 contains a cpa (Cronobacter plasminogen activator) gene and a 17-kb type 6 secretion system (T6SS) locus, while pCTU1 contains a 27-kb region encoding a filamentous hemagglutinin gene (fhaB), its specifc transporter gene (fhaC), and associated putative adhesins (FHA locus), suggesting that these are virulence plasmids. In a repA-targeted PCR assay, 97% of 229 Cronobacter species isolates were found to possess a homologous RepFIB plasmid. All repA PCR-positive strains were also positive for the eitCBAD and iucABCD/iutA iron acquisition systems. However, the presence of cpa, T6SS, and FHA loci depended on species, demonstrating a strong correlation with the presence of virulence traits, plasmid type, and species. These results support the hypothesis that these plasmids have evolved from a single archetypical plasmid backbone through the cointegration, or deletion, of specific virulence traits in each species. C1 [Tall, B. D.] US FDA, Ctr Food Safety & Appl Nutr, Virulence Mech Branch HFS 025, Div Virulence Assessment,MOD Facil 1,OARSA, Laurel, MD 20708 USA. [Grim, C. J.; Jarvis, K. G.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. [Kim, J.] Washington Internship Program, Washington, DC USA. RP Tall, BD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Virulence Mech Branch HFS 025, Div Virulence Assessment,MOD Facil 1,OARSA, 8301 MuirKirk Rd,Room 3607, Laurel, MD 20708 USA. EM ben.tall@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629 FU FDA's Office of the Commissioner; Department of Energy; Institute of Food Safety and Applied Nutrition; Washington Internship Programs FX When this study started, L. Hu was an FDA Commissioner's Fellow; she is now an Oak Ridge Institute for Science and Education (ORISE) fellow. K. G. Jarvis and C. J. Grim are also ORISE fellows, and we thank the FDA's Office of the Commissioner and the Department of Energy for their support. We also thank the Joint Institute of Food Safety and Applied Nutrition Internship and Washington Internship Programs for the support of undergraduate students J. Sadowski, C. Lee, and J. Kim, respectively. NR 68 TC 29 Z9 31 U1 3 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAY PY 2011 VL 77 IS 10 BP 3255 EP 3267 DI 10.1128/AEM.03023-10 PG 13 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 762JT UT WOS:000290473200012 PM 21421789 ER PT J AU Verghese, B Lok, M Wen, J Alessandria, V Chen, Y Kathariou, S Knabel, S AF Verghese, Bindhu Lok, Mei Wen, Jia Alessandria, Valentina Chen, Yi Kathariou, Sophia Knabel, Stephen TI comK Prophage Junction Fragments as Markers for Listeria monocytogenes Genotypes Unique to Individual Meat and Poultry Processing Plants and a Model for Rapid Niche-Specific Adaptation, Biofilm Formation, and Persistence SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; SINGLE-NUCLEOTIDE POLYMORPHISMS; MOLECULAR EPIDEMIOLOGIC SURVEY; HORIZONTAL GENE-TRANSFER; FOOD-BORNE PATHOGEN; GENOMIC ISLANDS; BACTERIOPHAGE GENOMICS; SEROTYPE 1/2A; STRAINS; BACTERIAL AB Different strains of Listeria monocytogenes are well known to persist in individual food processing plants and to contaminate foods for many years; however, the specific genotypic and phenotypic mechanisms responsible for persistence of these unique strains remain largely unknown. Based on sequences in comK prophage junction fragments, different strains of epidemic clones (ECs), which included ECII, ECIII, and ECV, were identified and shown to be specific to individual meat and poultry processing plants. The comK prophage-containing strains showed significantly higher cell densities after incubation at 30 degrees C for 48 h on meat and poultry food-conditioning films than did strains lacking the comK prophage (P < 0.05). Overall, the type of strain, the type of conditioning film, and the interaction between the two were all highly significant (P < 0.001). Recombination analysis indicated that the comK prophage junction fragments in these strains had evolved due to extensive recombination. Based on the results of the present study, we propose a novel model in which the concept of defective comK prophage was replaced with the rapid adaptation island (RAI). Genes within the RAI were recharacterized as "adaptons," as these genes may allow L. monocytogenes to rapidly adapt to different food processing facilities and foods. If confirmed, the model presented would help explain Listeria's rapid niche adaptation, biofilm formation, persistence, and subsequent transmission to foods. Also, comK prophage junction fragment sequences may permit accurate tracking of persistent strains back to and within individual food processing operations and thus allow the design of more effective intervention strategies to reduce contamination and enhance food safety. C1 [Verghese, Bindhu; Lok, Mei; Wen, Jia; Knabel, Stephen] Penn State Univ, Dept Food Sci, University Pk, PA 16802 USA. [Alessandria, Valentina] Univ Turin, Dept Exploitat & Protect Agr & Forest Resources, Agr Microbiol & Food Technol Sector, Fac Agr, Turin, Italy. [Chen, Yi] US FDA, Microbial Methods Dev Branch, Div Microbiol, Ctr Food Safety & Appl Nutr,Off Regulatory Sci, College Pk, MD 20740 USA. [Kathariou, Sophia] N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. RP Knabel, S (reprint author), Penn State Univ, Dept Food Sci, 437 Food Sci Bldg, University Pk, PA 16802 USA. EM sjk9@psu.edu FU United States Department of Agriculture; American Meat Institute Foundation FX S. Knabel was supported by a United States Department of Agriculture Special Grant on Milk Safety to the Pennsylvania State University, and S. Kathariou was supported by a grant from the American Meat Institute Foundation. NR 106 TC 50 Z9 50 U1 2 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 MAY PY 2011 VL 77 IS 10 BP 3279 EP 3292 DI 10.1128/AEM.00546-11 PG 14 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 762JT UT WOS:000290473200014 PM 21441318 ER PT J AU Schwartz, SB Rothrock, M Barron-Vaya, Y Bendell, C Kamat, A Midgett, M Abshire, J Biebighauser, K Staiano-Coico, LF Yurt, RW AF Schwartz, Suzanne B. Rothrock, Michelanne Barron-Vaya, Yolanda Bendell, Chelsea Kamat, Ameet Midgett, Marianne Abshire, Jill Biebighauser, Kitra Staiano-Coico, Lisa F. Yurt, Roger W. TI Impact of Diabetes on Burn Injury: Preliminary Results From Prospective Study SO JOURNAL OF BURN CARE & RESEARCH LA English DT Article ID HYPERGLYCEMIA; MELLITUS; TRAUMA AB Reducing diabetes mellitus complications has been a major focus for Healthy People 2010. A prior retrospective cohort of our burn center's admissions revealed worse outcomes among diabetic patients, that is, increased infection rates, grafting and graft complications, and increased length of hospital stay. Therefore, a prospective study has been designed to carefully assess wound repair and recovery of diabetic and nondiabetic burn patients. Our long-term aim is to determine the characteristics of the wound milieu along with global responses to injury that may predict poor outcome among diabetic patients. This is an initial phase of a larger observational study of in-hospital diabetic (types 1 and 2) and nondiabetic patients, prospectively matched for age (18-70 and > 70 years) and burn size (< 5, 5-15, and 16-25%). Time (days) to complete index wound closure, documented through serial photography, is the main outcome measure. Secondary measures compare delays in presentation, prevalence of infections, graft rates, wound and graft complications, adverse events, and length of hospital stay. Detailed history, physical, and baseline hemoglobin A1C are elicited from all subjects who are assessed daily over the initial 72 hours poststudy entry, then weekly until complete index wound closure, and finally monthly through 3 months. Forty subjects are presented herein, 24 diabetic and 16 nondiabetic patients. Time to index wound closure was significantly prolonged in diabetic patients, despite increased grafting. These findings suggest that excision and grafting in diabetic patients may not alone be sufficient to ensure rapid closure, as graft complications may contribute to protracted closure. Evaluating graft need may be more complex among diabetic patients, suggesting the need for alternative management strategies. The current prospective study confirms our previous retrospective analysis, notably manifested by significant delays in index wound closure. Our efforts continue in identifying the most important predictors of outcome, especially modifiable factors that would create a basis of intervention to improve care. (J Burn Care Res 2011;32:435-441) C1 [Schwartz, Suzanne B.; Rothrock, Michelanne; Bendell, Chelsea; Kamat, Ameet; Midgett, Marianne; Abshire, Jill; Biebighauser, Kitra; Yurt, Roger W.] Cornell Univ, Dept Surg, Ithaca, NY 14853 USA. [Barron-Vaya, Yolanda] Cornell Univ, Dept Publ Hlth, Joan & Sanford I Weill Med Coll, Ithaca, NY 14853 USA. [Staiano-Coico, Lisa F.] CUNY, City Coll, New York, NY 10021 USA. RP Schwartz, SB (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Suzanne.Schwartz@fda.hhs.gov FU NIH [K23 GM073728]; New York Firefighters Burn Center Foundation FX Supported, in part, by NIH grant K23 GM073728 and the New York Firefighters Burn Center Foundation. NR 24 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1559-047X J9 J BURN CARE RES JI J. Burn Care Res. PD MAY-JUN PY 2011 VL 32 IS 3 BP 435 EP 441 DI 10.1097/BCR.0b013e318217f954 PG 7 WC Emergency Medicine; Dermatology; Surgery SC Emergency Medicine; Dermatology; Surgery GA 760EZ UT WOS:000290308500028 PM 21436717 ER PT J AU Behringer, MG Thungrat, K Shaheen, BW Boothe, DM AF Behringer, Megan G. Thungrat, Kamoltip Shaheen, Bashar W. Boothe, Dawn M. TI ABILITY OF A FRET-PCR ASSAY TARGETING GYRA TO DETECT FLUOROQUINOLONE RESISTANCE IN VETERINARY CLINICAL URINE SAMPLES CONTAINING ESCHERICHIA COLI SO JOURNAL OF VETERINARY INTERNAL MEDICINE LA English DT Meeting Abstract C1 [Behringer, Megan G.; Thungrat, Kamoltip; Boothe, Dawn M.] Auburn Univ, Coll Vet Med, Dept Anat Physiol & Pharmacol, Auburn, AL 36849 USA. [Shaheen, Bashar W.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0891-6640 J9 J VET INTERN MED JI J. Vet. Intern. Med. PD MAY-JUN PY 2011 VL 25 IS 3 BP 711 EP 711 PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 758QE UT WOS:000290179100255 ER PT J AU Bhattacharyya, L AF Bhattacharyya, Lokesh TI Application of Ion Chromatography with Electrochemical Detection in Optimization and Control of Fermentation and Cell Culture SO BIOPHARM INTERNATIONAL LA English DT Article ID PULSED AMPEROMETRIC DETECTION; EXCHANGE LIQUID-CHROMATOGRAPHY; AMINO-ACIDS; MEDIA; BROTH C1 US FDA, Div Prod Qual, Off Compliance & Biol Qual, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Bhattacharyya, L (reprint author), US FDA, Div Prod Qual, Off Compliance & Biol Qual, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS INC PI WOODLAND HILLS PA 6200 CANOGA AVE, 2ND FLR, WOODLAND HILLS, CA 91367 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD MAY PY 2011 SU S BP S12 EP + PG 7 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 758UC UT WOS:000290191400002 ER PT J AU Zhang, SM Feng, SH Li, BJ Kim, HY Rodriguez, J Tsai, SE Lo, SC AF Zhang, Shimin Feng, Shaw-Huey Li, Bingjie Kim, Hyung-Yong Rodriguez, Joe Tsai, Shien Lo, Shyh-Ching TI In Vitro and In Vivo Studies of Monoclonal Antibodies with Prominent Bactericidal Activity against Burkholderia pseudomallei and Burkholderia mallei SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID HL-60 CELLS; MELIOIDOSIS; DIFFERENTIATION; DIMETHYLSULFOXIDE; POLYSACCHARIDE; PATHOGENICITY; PROTECTION; GROWTH; SERUM; MODEL AB Our laboratory has developed more than a hundred mouse monoclonal antibodies (MAbs) against Burkholderia pseudomallei and Burkholderia mallei. These antibodies have been categorized into different groups based on their specificities and the biochemical natures of their target antigens. The current study first examined the bactericidal activities of a number of these MAbs by an in vitro opsonic assay. Then, the in vivo protective efficacy of selected MAbs was evaluated using BALB/c mice challenged intranasally with a lethal dose of the bacteria. The opsonic assay using dimethyl sulfoxide-treated human HL-60 cells as phagocytes revealed that 19 out of 47 tested MAbs (40%) have prominent bactericidal activities against B. pseudomallei and/or B. mallei. Interestingly, all MAbs with strong opsonic activities are those with specificity against either the capsular polysaccharides (PS) or the lipopolysaccharides (LPS) of the bacteria. On the other hand, none of the MAbs reacting to bacterial proteins or glycoproteins showed prominent bactericidal activity. Further study revealed that the antigenic epitopes on either the capsular PS or LPS molecules were readily available for binding in intact bacteria, while the epitopes on proteins/glycoproteins were less accessible to the MAbs. Our in vivo study showed that four MAbs reactive to either the capsular PS or LPS were highly effective in protecting mice against lethal bacterial challenge. The result is compatible with that of our in vitro study. The MAbs with the highest protective efficacy are those reactive to either the capsular PS or LPS of the Burkholderia bacteria. C1 [Zhang, Shimin; Feng, Shaw-Huey; Li, Bingjie; Kim, Hyung-Yong; Rodriguez, Joe; Tsai, Shien; Lo, Shyh-Ching] Armed Forces Inst Pathol, Amer Registry Pathol, Dept Environm & Infect Dis Sci, Washington, DC 20306 USA. RP Lo, SC (reprint author), FDA, Tissue Safety Lab Program, Div Cellular & Gene Therapies, NIH Bldg 29B,Room 1NN06,29 Lincoln Dr,MSC4555, Bethesda, MD 20892 USA. EM shyhching.lo@fda.hhs.gov RI Rodriguez Herrera, Juan Jose/I-3210-2015 FU American Registry of Pathology and Defense Threat Reduction Agency-Joint Science and Technology Office, Medical S&T Division, U.S. Department of Defense [2.10014_05_AF_B] FX This research was supported by the American Registry of Pathology and Defense Threat Reduction Agency-Joint Science and Technology Office, Medical S&T Division (2.10014_05_AF_B) of the U.S. Department of Defense. NR 30 TC 26 Z9 28 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD MAY PY 2011 VL 18 IS 5 BP 825 EP 834 DI 10.1128/CVI.00533-10 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 758IB UT WOS:000290156600019 PM 21450976 ER PT J AU Smith, F Hammerstrom, T Soon, G Zhou, S Chen, BB Mai, YB Struble, K Huque, M AF Smith, Fraser Hammerstrom, Thomas Soon, Greg Zhou, Susan Chen, Baibai Mai, Yabing Struble, Kimberly Huque, Mohammad TI A Meta-analysis to Assess the FDA DAVP's TLOVR Algorithm in HIV Submissions SO DRUG INFORMATION JOURNAL LA English DT Article; Proceedings Paper CT 44th Annual Meeting of the Drug-Information-Association CY JUN, 2008 CL Boston, MA SP Drug Info Assoc DE TLOVR algorithm; Snapshot approach; HIV; Meta-analysis ID RNA; AIDS AB The first meta-analysis of pivotal HIV study results utilizing data from 1 8 clinical trials involving seven NDAs with 8,046 patients of multiple NDA submissions for the treatment of HIV infection was used to determine if we can use a simplified version of the TLOVR algorithm for accelerated approval at week 24 and possibly for traditional approval at week 48. Standardized data sets for HIV RNA viral load, demography, CD4 counts, and discontinuation were created. These raw data sets used CDISC study data tabulation model naming conventions for most of the variables. Results obtained using the TLOVR algorithm, which utilized data from every visit to consider the pattern of HIV responses, were compared to a less complicated snapshot approach that only utilized HIV RNA data at the visit of interest. Given the similarity in results between the TLOVR and snapshot approaches, it appears that correcting for intermittent spikes in HIV RNA levels with the TLOVR algorithm does not have much regulatory impact. C1 [Smith, Fraser; Hammerstrom, Thomas; Soon, Greg; Zhou, Susan; Chen, Baibai; Mai, Yabing; Huque, Mohammad] FDA CDER, Off Translat Sci, Off Biostat, Div Biometr 4, Silver Spring, MD 20993 USA. [Struble, Kimberly] FDA CDER, Off New Drugs, Off Antimicrobial Prod, Div Antiviral Prod, Silver Spring, MD 20993 USA. RP Smith, F (reprint author), FDA CDER, Off Translat Sci, Off Biostat, Div Biometr 4, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM fraser.smith@fda.hhs.gov NR 9 TC 23 Z9 23 U1 1 U2 6 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD MAY PY 2011 VL 45 IS 3 BP 291 EP 300 PG 10 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 759ZP UT WOS:000290290700009 ER PT J AU Yuan, JC Tong, TJ Ng, TH AF Yuan, Jiacheng Tong, Tiejun Ng, Tie-Hua TI Conditional Type I Error Rate for Superiority Test Conditioned on Establishment of Noninferiority in Clinical Trials SO DRUG INFORMATION JOURNAL LA English DT Article DE Clinical trial; Conditional test; Noninferiority; Superiority; Type I error rate AB In clinical trials, it is often desirable to test for superiority conditioned on establishment of noninferiority based on the same primary endpoint. According to a guidance document issued by the European regulatory agency Committee for Proprietary Medicinal Products in 2001, no type I error rate adjustment is necessary for switching between superiority and noninferiority because the family-wise type I error rate is controlled at the same nominal level. However, Ng raised the issues of switching between superiority and noninferiority even though there is no inflation of the family-wise type I error rate and showed that the false discovery rate could be increased. To alleviate these concerns, we propose to control the conditional type I error rate of the second-step superiority test at the nominal significance level, which leads to a lower (unconditional) significance level of the second-step superiority test. The suggested adjustment posts a more rigorous condition to claim superiority, which is an effort to decrease the number of erroneous claims of superiority. C1 [Yuan, Jiacheng] Astellas Pharma Global Dev Inc, Res Data Sci, Deerfield, IL USA. [Tong, Tiejun] Univ Colorado, Dept Appl Math, Boulder, CO 80309 USA. [Ng, Tie-Hua] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Yuan, JC (reprint author), Care of Yuan J, Astellas Pharma Global Dev Inc, Res Data Sci, 3 Pkwy N, Deerfield, IL 60015 USA. EM jason.yuan@us.astellas.com RI Tong, Tiejun/F-3880-2010; HKBU, Mathematics/B-5086-2009 NR 6 TC 1 Z9 1 U1 0 U2 6 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD MAY PY 2011 VL 45 IS 3 BP 331 EP 336 PG 6 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 759ZP UT WOS:000290290700012 ER PT J AU Koturbash, I Scherhag, A Sorrentino, J Sexton, K Bodnar, W Tryndyak, V Latendresse, JR Swenberg, JA Beland, FA Pogribny, IP Rusyn, I AF Koturbash, Igor Scherhag, Anne Sorrentino, Jessica Sexton, Kenneth Bodnar, Wanda Tryndyak, Volodymyr Latendresse, John R. Swenberg, James A. Beland, Frederick A. Pogribny, Igor P. Rusyn, Ivan TI Epigenetic Alterations in Liver of C57BL/6J Mice after Short-Term Inhalational Exposure to 1,3-Butadiene SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE 1,3-butadiene; DNA damage; epigenetics; liver; mouse ID GLOBAL DNA METHYLATION; MOLECULAR DOSIMETRY; HEME OXYGENASE-1; B6C3F1 MICE; RATS; METHYLTRANSFERASES; BUTADIENE; DNMT1; DAMAGE; SITES AB BACKGROUND: 1,3-Butadiene (BD) is a high-volume industrial chemical and a known human carcinogen. The main mode of BD carcinogenicity is thought to involve formation of genotoxic epoxides. OBJECTIVES: In this study we tested the hypothesis that BD may be epi-genotoxic (i.e., cause changes in DNA and histone methylation) and explored the possible molecular mechanisms for the epi-genetic changes. METHODS AND RESULTS: We administered BD (6.25 and 625 ppm) to C57BL/6J male mice by inhalation for 2 weeks (6 hr/day, 5 days a week) and then examined liver tissue from these mice for signs of toxicity using histopathology and gene expression analyses. We observed no changes in mice exposed to 6.25 ppm BD, but glycogen depletion and dysregulation of hepato-toxicity biomarker genes were observed in mice exposed to 625 ppm BD. We detected N-7-(2,3,4-trihydroxybut-1-yl) guanine (THB-Gua) adducts in liver DNA of exposed mice in a dose-responsive manner, and also observed extensive alterations in the cellular epigenome in the liver, including demethylation of global DNA and repetitive elements and a decrease in histone H3 and H4 lysine methylation. In addition, we observed down-regulation of DNA methyltransferase 1 (Dnmt1) and suppressor of variegation 3-9 homolog 1, a histone lysine methyltransferase (Suv39h1), and up-regulation of the histone demethylase Jumonji domain 2 (Jmjd2a), proteins responsible for the accurate maintenance of the epigenetic marks. Although the epigenetic effects were most pronounced in the 625-ppm exposure group, some effects were evident in mice exposed to 6.25 ppm BD. CONCLUSIONS: This study demonstrates that exposure to BD leads to epigenetic alterations in the liver, which may be important contributors to the mode of BD carcinogenicity. C1 [Sexton, Kenneth; Bodnar, Wanda; Swenberg, James A.; Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. [Koturbash, Igor; Scherhag, Anne; Tryndyak, Volodymyr; Beland, Frederick A.; Pogribny, Igor P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Scherhag, Anne] Tech Univ Kaiserslautern, Kaiserslautern, Rheinland Pfalz, Germany. [Sorrentino, Jessica; Swenberg, James A.; Rusyn, Ivan] Univ N Carolina, Curriculum Toxicol, Chapel Hill, NC 27599 USA. RP Rusyn, I (reprint author), Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. EM iir@unc.edu RI Rusyn, Ivan/S-2426-2016 FU National Institutes of Health [ES005948, ES012689, ES015241] FX This work was supported, in part, by National Institutes of Health grants ES005948, ES012689, and ES015241. NR 54 TC 16 Z9 16 U1 0 U2 8 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 MAY PY 2011 VL 119 IS 5 BP 635 EP 640 DI 10.1289/ehp.1002910 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 757MK UT WOS:000290089800027 PM 21147608 ER PT J AU Liu, F Zou, X Sadovova, N Zhang, X Shi, L Guo, L Qian, F Wen, Z Patterson, TA Hanig, JP Paule, MG Slikker, W Wang, C AF Liu, F. Zou, X. Sadovova, N. Zhang, X. Shi, L. Guo, L. Qian, F. Wen, Z. Patterson, T. A. Hanig, J. P. Paule, M. G. Slikker, W., Jr. Wang, C. TI Changes in gene expression after phencyclidine administration in developing rats: a potential animal model for schizophrenia SO INTERNATIONAL JOURNAL OF DEVELOPMENTAL NEUROSCIENCE LA English DT Article DE Apoptosis; Neuronal development; DNA microarray; Gene expression; Phencyclidine (PCP); Schizophrenia ID BDNF MESSENGER-RNA; METHYL-D-ASPARTATE; NEUROTROPHIC FACTOR; INDUCED APOPTOSIS; CELL-DEATH; KETAMINE; MICROARRAY; RECEPTOR; DEFICITS; NEURONS AB Repeated administration of phencyclidine (PCP), an N-methyl-n-aspartate (NMDA) receptor antagonist, during development, may result in neuronal damage that leads to behavioral deficits in adulthood. The present study examined the potential neurotoxic effects of PCP exposure (10 mg/kg) in rats on postnatal days (PNDs) 7, 9 and 11 and the possible underlying mechanism(s) for neurotoxicity. Brain tissue was harvested for RNA extraction and morphological assessments. RNA was collected from the frontal cortex for DNA microarray analysis and quantitative RT-PCR. Gene expression profiling was determined using Illumina Rat Ref-12 Expression BeadChips containing 22,226 probes. Based on criteria of a fold-change greater than 1.4 and a P-value less than 0.05, 19 genes including NMDAR1 (N-methyl-n-aspartate receptor) and four pro-apoptotic genes were up-regulated, and 25 genes including four anti-apoptotic genes were down-regulated, in the PCP-treated group. In addition, the schizophrenia-relevant genes, Bdnf (Brain-derived neurotrophic factor) and Bhlhb2 (basic helix-loop-helix domain containing, class B, 2), were significantly different between the PCP and the control groups. Quantitative RT-PCR confirmed the microarray results. Elevated neuronal cell death was further confirmed using Fluoro-Jade C staining. These findings support the hypothesis that neurodegeneration caused by PCP occurs, at least in part, through the up-regulation of NMDA receptors, which makes neurons possessing these receptors more vulnerable to endogenous glutamate. The changes in schizophrenia-relevant genes after repeated PCP exposure during development may provide important information concerning the validation of an animal model for this disorder. Published by Elsevier Ltd on behalf of ISDN C1 [Liu, F.; Zou, X.; Zhang, X.; Patterson, T. A.; Paule, M. G.; Slikker, W., Jr.; Wang, C.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Sadovova, N.] US FDA, Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Shi, L.; Wen, Z.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Guo, L.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Qian, F.] ICF Int Co NCTR, Z Tech, Jefferson, AR USA. [Hanig, J. P.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 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 RI Guo, Lei/E-9232-2011 NR 59 TC 13 Z9 14 U1 1 U2 5 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 MAY PY 2011 VL 29 IS 3 SI SI BP 351 EP 358 DI 10.1016/j.ijdevneu.2010.07.234 PG 8 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 758BQ UT WOS:000290135200017 PM 20691775 ER PT J AU Sommers, CD Mans, DJ Mecker, LC Keire, DA AF Sommers, Cynthia D. Mans, Daniel J. Mecker, Laura C. Keire, David A. TI Sensitive Detection of Oversulfated Chondroitin Sulfate in Heparin Sodium or Crude Heparin with a Colorimetric Microplate Based Assay SO ANALYTICAL CHEMISTRY LA English DT Article ID ADVERSE CLINICAL EVENTS; CAPILLARY-ELECTROPHORESIS; CONTAMINANTS; QUANTIFICATION; SPECTROSCOPY; IMPURITIES; SENSORS AB In this work we describe a 96-well microplate assay for oversulfated chondroitin sulfate A (OSCS) in heparin, based on a water-soluble cationic polythiophene polymer(3-(2-(N-(N'-methylimidazole))ethoxy)-4-methylthiophene (LPTP)) and heparinase digestion of heparin. The assay takes advantage of several unique properties of heparin, OSCS, and LPTP, including OSCS inhibition of heparinase I and II activity, the molecular weight dependence of heparin-LPTP spectral shifts, and the distinct association of heparin fragments and OSCS to LPTP. These factors combine to enable detection of the presence of 0.003% w/w spiked OSCS in 10 mu g of heparin sodium active pharmaceutical ingredient (API) using a plate reader and with visual detection to 0.1% levels. The same detection limit for OSCS was observed in the presence of 10% levels of dermatan sulfate (DS) or chondroitin sulfate A (CSA) impurities. In addition, we surveyed a selection of crude heparin samples received by the agency in 2008 and 2009 to determine average and extreme DS, CSA, and galactosamine weight percent levels. In the presence of these impurities and the variable heparin content in the crude heparin samples, spiked OSCS was reliably detected to the 0.1% w/w level using a plate reader. Finally, authentically OSCS contaminated heparin sodium API and crude samples were distinguished visually by color from control samples using the LPTP/heparinase test. C1 [Sommers, Cynthia D.; Mans, Daniel J.; Mecker, Laura C.; Keire, David A.] US FDA, CDER, DPA, St Louis, MO 63101 USA. RP Keire, DA (reprint author), US FDA, CDER, DPA, 1114 Market St, St Louis, MO 63101 USA. EM David.Keire@fda.hhs.gov NR 41 TC 22 Z9 22 U1 5 U2 32 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAY 1 PY 2011 VL 83 IS 9 BP 3422 EP 3430 DI 10.1021/ac200011s PG 9 WC Chemistry, Analytical SC Chemistry GA 755SN UT WOS:000289956800031 PM 21449571 ER PT J AU Mazzola, EP Parkinson, A Kennelly, EJ Coxon, B Einbond, LS Freedberg, DI AF Mazzola, Eugene P. Parkinson, Ainsley Kennelly, Edward J. Coxon, Bruce Einbond, Linda S. Freedberg, Daron I. TI Utility of coupled-HSQC experiments in the intact structural elucidation of three complex saponins from Blighia sapida SO CARBOHYDRATE RESEARCH LA English DT Article DE Ackee; Blighia sapida; Coupled-HSQC; Triterpene glycosides; Saponins ID MAGNETIC RESONANCE SPECTRA; NMR-SPECTROSCOPY; CANCER-CELLS; ACKEE; ASSIGNMENT; CONSTANTS; VACCINES; SEEDS; H-1 AB The structures of three complex saponins from the fruit pods of Blighia sapida have been elucidated and their (1)H and (13)C NMR spectra assigned employing a variety of one- and two-dimensional NMR techniques without degradative chemistry. The saponins have either four or six monosaccharide units linked to a triterpene aglycone. High-resolution, proton-coupled-HSQC spectra were important for determining both the identities of the intact monosaccharide units and coupling constants in strongly coupled proton spin systems. These NMR experiments will prove crucial as the complexity of saponin structures reaches the limit that can be determined solely by NMR. (C) 2011 Published by Elsevier Ltd. C1 [Mazzola, Eugene P.] Univ Maryland, FDA Joint Inst, College Pk, MD 20742 USA. [Parkinson, Ainsley; Kennelly, Edward J.] CUNY Herbert H Lehman Coll, Bronx, NY 10468 USA. [Coxon, Bruce] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, Bethesda, MD 20892 USA. [Einbond, Linda S.] Columbia Univ Coll Phys & Surg, Herbert Irving Comprehens Canc Ctr, New York, NY 10032 USA. [Freedberg, Daron I.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Mazzola, EP (reprint author), Univ Maryland, FDA Joint Inst, College Pk, MD 20742 USA. EM emazzola@umd.edu; ainsley.parkinson@lehman.cuny.edu; Edward.kennelly@lehman.cuny.edu; coxonb@mail.nih.gov; l.einbond@gmail.com; daron-freedberg@nih.gov FU Intramural NIH HHS [Z01 HD008849-01] NR 35 TC 8 Z9 8 U1 1 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD MAY 1 PY 2011 VL 346 IS 6 BP 759 EP 768 DI 10.1016/j.carres.2011.02.019 PG 10 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 754AB UT WOS:000289821900010 PM 21439554 ER PT J AU AlAama, J Smith, TD Lo, A Howard, H Kline, AA Lange, M Kaput, J Cotton, RGH AF AlAama, Jumana Smith, Timothy D. Lo, Alan Howard, Heather Kline, Alexandria A. Lange, Matthew Kaput, Jim Cotton, Richard G. H. TI Initiating a Human Variome Project Country Node SO HUMAN MUTATION LA English DT Article DE variation; standard; data collection; human variome project ID MUTATIONS AB Genetic diseases are a pressing global health problem that requires comprehensive access to basic clinical and genetic data to counter. The creation of regional and international databases that can be easily accessed by clinicians and diagnostic labs will greatly improve our ability to accurately diagnose and treat patients with genetic disorders. The Human Variome Project is currently working in conjunction with human genetics societies to achieve this by establishing systems to collect every mutation reported by a diagnostic laboratory, clinic, or research laboratory in a country and store these within a national repository, or HVP Country Node. Nodes have already been initiated in Australia, Belgium, China, Egypt, Malaysia, and Kuwait. Each is examining how to systematically collect and share genetic, clinical, and biochemical information in a country-specific manner that is sensitive to local ethical and cultural issues. This article gathers cases of genetic data collection within countries and takes recommendations from the global community to develop a procedure for countries wishing to establish their own collection system as part of the Human Variome Project. We hope this may lead to standard practices to facilitate global collection of data and allow efficient use in clinical practice, research and therapy. Hum Mutat 32:501-506, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Smith, Timothy D.] Univ Melbourne, Genom Disorders Res Ctr, Florey Neurosci Inst, Carlton, Vic 3053, Australia. [AlAama, Jumana] King Abdulaziz Univ, Fac Med, Dept Med Genet, Jeddah 21413, Saudi Arabia. [AlAama, Jumana] King Abdulaziz Univ, Princess Al Jawhara Ctr Excellence Res Hereditary, Jeddah 21413, Saudi Arabia. [Smith, Timothy D.; Cotton, Richard G. H.] Univ Melbourne, Dept Med St Vincents, Carlton, Vic 3053, Australia. [Smith, Timothy D.] Univ Melbourne, Dept Informat Syst, Carlton, Vic 3053, Australia. [Lo, Alan] Victorian Partnership Adv Comp, Carlton, Vic, Australia. [Lange, Matthew; Kaput, Jim] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Smith, TD (reprint author), Univ Melbourne, Genom Disorders Res Ctr, Florey Neurosci Inst, Level 2,161 Barry St, Carlton, Vic 3053, Australia. EM tim@variome.org OI Smith, Timothy/0000-0001-9068-4642 FU Australian National Data Service (ANDS) through the Education Investment Fund (EIF) Super Science Initiative; Australian Research Collaboration Service (ARCS) FX This work is part of a National eResearch Architecture Taskforce (NeAT) project, supported by the Australian National Data Service (ANDS) through the Education Investment Fund (EIF) Super Science Initiative, and the Australian Research Collaboration Service (ARCS) through the National Collaborative Research Infrastructure Strategy Program. Note: The views in this article do not necessarily represent those of the U.S. FDA. NR 5 TC 8 Z9 8 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1059-7794 J9 HUM MUTAT JI Hum. Mutat. PD MAY PY 2011 VL 32 IS 5 SI SI BP 501 EP 506 DI 10.1002/humu.21463 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 756AP UT WOS:000289984100002 PM 21305654 ER PT J AU Nolin, TD Arya, V Sitar, DS Pfister, M AF Nolin, Thomas D. Arya, Vikram Sitar, Daniel S. Pfister, Marc TI Optimizing Drug Development and Use in Patients With Kidney Disease SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Editorial Material ID CREATININE CLEARANCE; RENAL IMPAIRMENT; HEMODIALYSIS; PHARMACOKINETICS; EVENTS; TRIALS C1 [Nolin, Thomas D.] Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, Pittsburgh, PA 15261 USA. [Arya, Vikram] US FDA, Div Clin Pharmacol, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Sitar, Daniel S.] Univ Manitoba, Winnipeg, MB, Canada. [Pfister, Marc] Quantitat Solut Inc, Bridgewater, NJ USA. RP Nolin, TD (reprint author), Univ Pittsburgh, Sch Pharm, Dept Pharm & Therapeut, 808 Salk Hall,3501 Terrace St, Pittsburgh, PA 15261 USA. EM nolin@pitt.edu NR 24 TC 2 Z9 2 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 2011 VL 51 IS 5 BP 628 EP 630 DI 10.1177/0091270011402500 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 755OK UT WOS:000289942400001 PM 21525394 ER PT J AU Trumbo, PR Shimakawa, T AF Trumbo, Paula R. Shimakawa, Tomoko TI Tolerable upper intake levels for trans fat, saturated fat, and cholesterol SO NUTRITION REVIEWS LA English DT Review DE cholesterol; saturated fatty acid; tolerable upper intake levels; trans fatty acids ID CORONARY-HEART-DISEASE; LOW-DENSITY-LIPOPROTEIN; DIETARY-FAT; PLASMA-LIPIDS; HEALTHY-SUBJECTS; STEARIC-ACID; SERUM-LIPIDS; RISK; MEN; WOMEN AB Tolerable upper intake levels (ULs) set by the Institute of Medicine (IOM) are important, in part because they are used for estimating the percentage of the population at potential risk of adverse effects from excessive nutrient intake. The IOM did not set ULs for trans fat, saturated fat, and cholesterol because any intake level above 0% of energy increased LDL cholesterol concentration and these three food components are unavoidable in ordinary diets. The purpose of the analysis presented in this review was to evaluate clinical trial and prospective observational data that were not previously considered for setting a UL with the aim of determining whether the current UL model could be used for saturated fat, trans fat, and cholesterol. The results of this analysis confirm the limitations of the risk assessment model for setting ULs because of its inability to identify a UL for food components, such as cholesterol, that lack an intake threshold associated with increased chronic disease risk. C1 [Trumbo, Paula R.; Shimakawa, Tomoko] US FDA, Off Nutr Labeling & Dietary Supplements, 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 40 TC 11 Z9 15 U1 1 U2 8 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 2011 VL 69 IS 5 BP 270 EP 278 DI 10.1111/j.1753-4887.2011.00389.x PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 754XV UT WOS:000289892100003 PM 21521229 ER PT J AU Simon, K Kondratovich, MV Hojvat, S Gutierrez, A AF Simon, Kate Kondratovich, Marina V. Hojvat, Sally Gutierrez, Alberto TI Patient Safety and the Next Generation of HPV DNA Tests SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter C1 [Simon, Kate; Kondratovich, Marina V.; Hojvat, Sally; Gutierrez, Alberto] US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Dept Hlth & Human Serv, Silver Spring, MD 20993 USA. RP Simon, K (reprint author), US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Dept Hlth & Human Serv, Silver Spring, MD 20993 USA. NR 2 TC 1 Z9 2 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 2011 VL 135 IS 5 BP 798 EP 799 DI 10.1309/AJCPMF4DSDIW3ILO PG 2 WC Pathology SC Pathology GA 753CV UT WOS:000289743400020 PM 21502437 ER PT J AU Eppinger, M Mammel, MK LeClerc, JE Ravel, J Cebula, TA AF Eppinger, Mark Mammel, Mark K. LeClerc, Joseph E. Ravel, Jacques Cebula, Thomas A. TI Genome Signatures of Escherichia coli O157:H7 Isolates from the Bovine Host Reservoir SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SHIGA-LIKE-TOXIN; HEMOLYTIC-UREMIC SYNDROME; ENTEROCYTE EFFACEMENT; SALMONELLA-TYPHIMURIUM; O157-H7 STRAINS; ETHANOLAMINE UTILIZATION; GENETIC-CHARACTERIZATION; MICROARRAY ANALYSIS; DISEASE OUTBREAKS; VIRULENCE FACTORS AB Cattle comprise a main reservoir of Shiga toxin-producing Escherichia coli O157:H7 (STEC). The significant differences in host prevalence, transmissibility, and virulence phenotypes among strains from bovine and human sources are of major interest to the public health community and livestock industry. Genomic analysis revealed divergence into three lineages: lineage I and lineage I/II strains are commonly associated with human disease, while lineage II strains are overrepresented in the asymptomatic bovine host reservoir. Growing evidence suggests that genotypic differences between these lineages, such as polymorphisms in Shiga toxin subtypes and synergistically acting virulence factors, are correlated with phenotypic differences in virulence, host ecology, and epidemiology. To assess the genomic plasticity on a genome-wide scale, we have sequenced the whole genome of strain EC869, a bovine-associated E. coli O157:H7 isolate. Comparative phylogenomic analysis of this key isolate enabled us to place accurately bovine lineage II strains within the genetically homogenous E. coli O157:H7 clade. Identification of polymorphic loci that are anchored both in the chromosomal backbone and horizontally acquired regions allowed us to associate bovine genotypes with altered virulence phenotypes and host prevalence. This study catalogued numerous novel lineage II-specific genome signatures, some of which appear to be associated intimately with the altered pathogenic potential and niche adaptation within the bovine rumen. The presented extended list of polymorphic markers is valuable in the development of a robust typing system critical for forensic, diagnostic, and epidemiological studies of this emerging human pathogen. C1 [Eppinger, Mark; Ravel, Jacques] Univ Maryland, IGS, Sch Med, Baltimore, MD 21201 USA. [Mammel, Mark K.; LeClerc, Joseph E.] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Cebula, Thomas A.] Johns Hopkins Univ, Dept Biol, Baltimore, MD 21218 USA. RP Ravel, J (reprint author), Univ Maryland, IGS, Sch Med, Baltimore, MD 21201 USA. EM jravel@som.umaryland.edu; tcebula1@jhu.edu OI Ravel, Jacques/0000-0002-0851-2233 FU National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services [N01 AI-30071] FX This work was supported with federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under NIAID contract N01 AI-30071. NR 90 TC 14 Z9 17 U1 0 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAY PY 2011 VL 77 IS 9 BP 2916 EP 2925 DI 10.1128/AEM.02554-10 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 753KU UT WOS:000289773100013 PM 21421787 ER PT J AU Simon, K Kondratovich, MV Hojvat, S Gutierrez, A AF Simon, Kate Kondratovich, Marina V. Hojvat, Sally Gutierrez, Alberto TI Postscript SO AMERICAN JOURNAL OF CLINICAL PATHOLOGY LA English DT Letter C1 [Simon, Kate; Kondratovich, Marina V.; Hojvat, Sally; Gutierrez, Alberto] US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Dept Hlth & Human Serv, Silver Spring, MD 20993 USA. RP Simon, K (reprint author), US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Dept Hlth & Human Serv, Silver Spring, MD 20993 USA. NR 1 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC CLINICAL PATHOLOGY PI CHICAGO PA 2100 W HARRISON ST, CHICAGO, IL 60612 USA SN 0002-9173 J9 AM J CLIN PATHOL JI Am. J. Clin. Pathol. PD MAY PY 2011 VL 135 IS 5 BP 803 EP 803 PG 1 WC Pathology SC Pathology GA 753CV UT WOS:000289743400022 ER PT J AU Ma, WB Galvin, TA Ma, HL Ma, YK Muller, J Khan, AS AF Ma, Wenbin Galvin, Teresa A. Ma, Hailun Ma, Yunkun Muller, Jacqueline Khan, Arifa S. TI Optimization of chemical induction conditions for human herpesvirus 8 (HHV-8) reactivation with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) from latently-infected BC-3 cells SO BIOLOGICALS LA English DT Article DE HHV-8 reactivation; TPA; Latent virus; Chemical induction; BC-3 cells ID SARCOMA-ASSOCIATED HERPESVIRUS; EPSTEIN-BARR-VIRUS; PRIMARY EFFUSION LYMPHOMA; MULTICENTRIC CASTLEMANS-DISEASE; LYTIC GENE-EXPRESSION; KAPOSIS-SARCOMA; DNA-SEQUENCES; NUCLEAR ANTIGEN; ENDOTHELIAL-CELLS; REPLICATION AB Human herpesvirus 8 (HHV-8) persists as episomal DNA in latently-infected cells and can establish two alternative life cycles, latent or lytic. 12-O-tetradecanoyl-phorbol-13-acetate (TPA) is a known inducer of HHV-8 in several human primary effusion lymphoma cell lines and has been widely used for HHV-8 reactivation; however, induction conditions have differed, resulting in varying levels of virus expression. We have used HHV-8 latently-infected BC-3 cells as a model to determine critical parameters for optimizing virus reactivation by TPA. We found that cell growth properties and drug treatment conditions were important for maximum reactivation of HHV-8. Addition of TPA to cells in the early log phase of a sigmoidal growth curve, which was tightly associated with high percentage of the cells in early S phase and with lower histone deacetylase activity in the cells, provided the optimum cell conditions for latent virus to switch to lytic replication. Furthermore, increasing TPA concentration (up to 320 ng per ml) at 48 h exposure time resulted in increased virus production. The results demonstrate the use of a step-wise strategy with chemical induction that may facilitate broad detection of latent DNA viruses and novel virus discovery. Published by Elsevier Ltd on behalf of The International Alliance for Biologicals. C1 [Ma, Wenbin; Galvin, Teresa A.; Ma, Hailun; Ma, Yunkun; Khan, Arifa S.] US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Khan, AS (reprint author), US FDA, Lab Retroviruses, Div Viral Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM arifa.khan@fda.hhs.gov FU DMID/NIAID/NIH [Y1-A1-4893-02] FX We thank Dr. Alonzo Garcia for technical assistance in HDAC activity measurements, Mrs. Dhanya K. Williams for laboratory and technical support, Mrs. Marilyn Lundquist for technical assistance with TEM, and Dr. Keith Peden and Dr. Andrew Dayton for comments on the manuscript. The work was funded by DMID/NIAID/NIH Interagency Agreement no. Y1-A1-4893-02. NR 55 TC 1 Z9 1 U1 0 U2 4 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAY PY 2011 VL 39 IS 3 BP 158 EP 166 DI 10.1016/j.biologicals.2011.03.001 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 785IT UT WOS:000292223400005 PM 21470875 ER PT J AU Martinez, MN AF Martinez, Marilyn N. TI Welcome to the animal pharmaceuticals special focus SO FUTURE MEDICINAL CHEMISTRY LA English DT Editorial Material C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, 7519 Standish Pl,HFV-12, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov NR 10 TC 1 Z9 1 U1 1 U2 2 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1756-8919 J9 FUTURE MED CHEM JI Future Med. Chem. PD MAY PY 2011 VL 3 IS 7 BP 845 EP 846 DI 10.4155/FMC.11.56 PG 2 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 775EQ UT WOS:000291441800015 PM 21644829 ER PT J AU Choudhuri, S AF Choudhuri, Supratim TI Editorial: Special issue on epigenetics and toxicology SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Editorial Material C1 US FDA, Ctr Food Safety & Appl Nutr, OFAS DBGNR, College Pk, MD 20740 USA. RP Choudhuri, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, OFAS DBGNR, HFS 255,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Supratim.Choudhuri@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 3 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD MAY PY 2011 VL 21 IS 4 SI SI BP 251 EP 251 DI 10.3109/15376516.2011.559693 PG 1 WC Toxicology SC Toxicology GA 751PL UT WOS:000289629900001 PM 21495864 ER PT J AU Tournas, VH Kohn, JS Katsoudas, EJ AF Tournas, V. H. Kohn, J. S. Katsoudas, E. J. TI Interactions between various microbes and ginseng botanicals SO CRITICAL REVIEWS IN MICROBIOLOGY LA English DT Review DE Ginseng botanicals; bacterial/fungal spoilage; ginsenoside biotransformation; microbial inhibition ID HELICOBACTER-PYLORI INFECTION; HUMAN INTESTINAL BACTERIA; PANAX-GINSENG; ELEUTHEROCOCCUS-SENTICOSUS; ACIDIC POLYSACCHARIDE; ANTIADHESIVE ACTIVITY; AMERICAN GINSENG; RED GINSENG; RUSTED ROOT; METABOLISM AB Three kinds of interactions occur between ginseng botanicals and microorganisms: a) spoilage of the botanical by various fungi (e. g., Aspergillus, Penicillium, Alternaria, and Eurotium species) and bacteria; b) transformation of ginsenosides into more bioactive forms by bacteria such as Intrasporangium sp. GS603, Microbacterium sp. GS514, Caulobacter leidyia, Bifidobacterium sp. Int57, Bifidobacterium sp. SJ32, Fusobacterium sp. and Bacteroides sp., and moulds (e. g., Aspergillus niger, Fusarium sacchari, Paecilomyces bainier sp. 229, Rhizopus stolonifer, Myrothecium verrucaria and Acremonium strictum); and c) inhibition of certain bacteria (Propionibacterium acnes, Porphyromonas gingivalis, Staphylococcus aureus, Pseudomonas aeruginosa), fungi (Candida albicans, Aspergillus fumigatus, Fusarium oxysporum) and viruses by ginseng constituents C1 [Tournas, V. H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Kohn, J. S.; Katsoudas, E. J.] US FDA, NE Reg Lab, Jamaica, NY 11433 USA. RP Tournas, VH (reprint author), CFSAN Food & Drug Adm HFS 712, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM valerie.tournas@fda.hhs.gov NR 65 TC 3 Z9 3 U1 2 U2 22 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1040-841X EI 1549-7828 J9 CRIT REV MICROBIOL JI Crit. Rev. Microbiol. PD MAY PY 2011 VL 37 IS 2 BP 113 EP 120 DI 10.3109/1040841X.2010.520670 PG 8 WC Microbiology SC Microbiology GA 748AT UT WOS:000289363100002 PM 21254831 ER PT J AU Elespuru, RK AF Elespuru, Rosalie K. TI Assessment of Heritable Genetic Effects Using New Genetic Tools and Sentinels in an Era of Personalized Medicine SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material DE germ cell mutations; personalized medicine; heritable genetic disease; birth defects monitoring; sentinel mutations ID CYSTIC-FIBROSIS GENE; CHILDHOOD-CANCER; BIRTH-DEFECTS; CONGENITAL-MALFORMATIONS; PATERNAL SMOKING; PARENTAL SMOKING; POSTGENOME ERA; TOBACCO-SMOKE; FACTOR-IX; MUTATION AB The challenge of estimating human health effects from damage to the germ line may be met in the genomic era. Understanding the genetic, as opposed to postconception developmental basis of birth defects is critical to their use in monitoring heritable genetic damage. The causes of common birth defects are analyzed here: mendelian genetic, multigenic, developmental, inherited, or combinational. Only a small fraction of these (noninherited, mendelian genetic) are likely to be informative relative to germ cell mutagenesis, and these won't be discernible against the general background of birth defects. Targeted genetic testing as part of personalized medicine could be integrated into a strategy for assessing germ cell alterations in populations. Thus, "sentinel mutations,'' as originally proposed by Mulvihill and Ceizel, need not be restricted to X-linked or dominant mutations or conditions visible at birth. Several new sentinels related to personalized medicine are proposed, based on health impact (likelihood of monitoring), frequency, and genetic target suitability (responsiveness to diverse mutational mechanisms). Candidates could include CYP genes (related to metabolism of xenobiotics) important in optimizing drug doses and avoiding adverse reactions. High frequency LDLR mutations (related to familial high cholesterol) predict myocardial infarction in similar to 50% of individuals. The more common recessive genetic diseases (cystic fibrosis, phenylketonuria, and others) monitored in newborn screening programs could be informative given parental analysis. New opportunities for genetic analyses need to be coupled with epidemiological studies on environmental exposures. These could focus on adverse outcomes related to tobacco, the most ubiquitous and potent environmental mutagen. Environ. Mol. Mutagen. 52:253-263, 2011. Published 2011 Wiley-Liss, Inc.(dagger) C1 US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Elespuru, RK (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 64 Room 3020, Silver Spring, MD 20993 USA. EM rosalie.elespuru@fda.hhs.gov NR 80 TC 1 Z9 1 U1 0 U2 5 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0893-6692 EI 1098-2280 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD MAY PY 2011 VL 52 IS 4 BP 253 EP 263 DI 10.1002/em.20637 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 747XB UT WOS:000289353400001 PM 21472782 ER PT J AU Easterbrook, JD Kash, JC Sheng, ZM Qi, L Gao, J Kilbourne, ED Eichelberger, MC Taubenberger, JK AF Easterbrook, Judith D. Kash, John C. Sheng, Zong-Mei Qi, Li Gao, Jin Kilbourne, Edwin D. Eichelberger, Maryna C. Taubenberger, Jeffery K. TI Immunization with 1976 swine H1N1-or 2009 pandemic H1N1-inactivated vaccines protects mice from a lethal 1918 influenza infection SO INFLUENZA AND OTHER RESPIRATORY VIRUSES LA English DT Article DE 1918 influenza; 1976 influenza; 2009 pandemic H1N1; cross-protection; microneutralization ID NEURAMINIDASE ANTIBODY; VIRUS; ORIGIN; IMMUNITY; GENES; PATHOGENICITY; HEMAGGLUTININ; RECOMBINANT; PERSPECTIVE; VACCINATION AB Background Zoonotic infections with H1N1 influenza viruses that evolved initially from the 1918 virus (1918) and adapted to swine threatened a pandemic in 1976 (1976 swH1N1) and a novel reassortant H1N1 virus caused a pandemic in 2009-2010 (2009 pH1N1). Epidemiological and laboratory animal studies show that protection from severe 2009 pH1N1 infection is conferred by vaccination or prior infection with 1976 swH1N1 or 1918. Objectives Our aim was to demonstrate cross-protection by immunization with 2009 pH1N1 or 1976 swH1N1 vaccines following a lethal challenge with 1918. Further, the mechanisms of cross-protective antibody responses were evaluated. Methods Mice were immunized with 1976 swH1N1, 2009 pH1N1, 2009 seasonal trivalent, or 1918 vaccines and challenged with 1918. Cross-reactive antibody responses were assessed and protection monitored by survival, weight loss, and pathology in mice. Results and Conclusions Vaccination with the 1976 swH1N1 or 2009 pH1N1 vaccines protected mice from a lethal challenge with 1918, and these mice lost no weight and had significantly reduced viral load and pathology in the lungs. Protection was likely due to cross-reactive antibodies detected by microneutralization assay. Our data suggest that the general population may be protected from a future 1918-like pandemic because of prior infection or immunization with 1976 swH1N1 or 2009 pH1N1. Also, influenza protection studies generally focus on cross-reactive hemagglutination-inhibiting antibodies; while hemagglutinin is the primary surface antigen, this fails to account for other influenza viral antigens. Neutralizing antibody may be a better correlate of human protection against pathogenic influenza strains and should be considered for vaccine efficacy. C1 [Easterbrook, Judith D.; Kash, John C.; Sheng, Zong-Mei; Qi, Li; Taubenberger, Jeffery K.] NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Gao, Jin; Eichelberger, Maryna C.] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. [Kilbourne, Edwin D.] New York Med Coll, Valhalla, NY 10595 USA. RP Taubenberger, JK (reprint author), NIAID, Viral Pathogenesis & Evolut Sect, Infect Dis Lab, NIH, 33 North Dr,MSC 3203, Bethesda, MD 20892 USA. EM taubenbergerj@niaid.nih.gov FU NIH; NIAID FX We thank the Comparative Medicine Branch (NIH/NIAID) for their assistance with animal studies. This work was supported by the Intramural Research Program of the NIH and the NIAID. NR 40 TC 11 Z9 11 U1 0 U2 1 PU WILEY-BLACKWELL 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 MAY PY 2011 VL 5 IS 3 BP 198 EP 205 DI 10.1111/j.1750-2659.2010.00191.x PG 8 WC Infectious Diseases; Virology SC Infectious Diseases; Virology GA 747BT UT WOS:000289296000009 PM 21477139 ER PT J AU Zhang, WJ Wu, CM Wang, Y Shen, ZQ Dai, L Han, J Foley, SL Shen, JZ Zhang, QJ AF Zhang, Wan-Jiang Wu, Cong-Ming Wang, Yang Shen, Zhang-Qi Dai, Lei Han, Jing Foley, Steven L. Shen, Jian-Zhong Zhang, Qijing TI The new genetic environment of cfr on plasmid pBS-02 in a Bacillus strain SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Letter DE florfenicol resistance; IS256; restriction-modification system ID RESTRICTION-MODIFICATION SYSTEMS; RESISTANT STAPHYLOCOCCUS-AUREUS; INSERTION SEQUENCES; 1ST REPORT; IDENTIFICATION; BEHAVIOR; ELEMENTS; FEXA C1 [Zhang, Wan-Jiang; Wu, Cong-Ming; Wang, Yang; Dai, Lei; Shen, Jian-Zhong] China Agr Univ, Coll Vet Med, Key Lab Dev & Evaluat Chem & Herbal Drugs Anim Us, Beijing 100193, Peoples R China. [Shen, Zhang-Qi; Dai, Lei; Zhang, Qijing] Iowa State Univ, Coll Vet Med, Dept Vet Microbiol & Prevent Med, Ames, IA 50011 USA. [Han, Jing; Foley, Steven L.] FDA Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Shen, JZ (reprint author), China Agr Univ, Coll Vet Med, Key Lab Dev & Evaluat Chem & Herbal Drugs Anim Us, Beijing 100193, Peoples R China. EM sjz@cau.edu.cn RI Zhang, Qijing/B-7530-2012 NR 10 TC 24 Z9 26 U1 0 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-7453 J9 J ANTIMICROB CHEMOTH JI J. Antimicrob. Chemother. PD MAY PY 2011 VL 66 IS 5 BP 1174 EP 1175 DI 10.1093/jac/dkr037 PG 2 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 750YK UT WOS:000289584000033 PM 21393171 ER PT J AU Xia, X Meng, J McDermott, PF Zhao, S AF Xia, X. Meng, J. McDermott, P. F. Zhao, S. TI Escherichia coli from retail meats carry genes associated with uropathogenic Escherichia coli, but are weakly invasive in human bladder cell culture SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE adhesion; invasion; retail meats; uropathogenic Escherichia coli; virulence factor ID URINARY-TRACT-INFECTION; INNATE IMMUNE-RESPONSE; ANTIMICROBIAL-RESISTANT; EPITHELIAL-CELLS; IN-VIVO; MULTIDRUG-RESISTANT; UNITED-STATES; VIRULENCE; STRAINS; IDENTIFICATION AB Aims: The aim of this study was to determine the uropathogenic potential of Escherichia coli isolated from retail meats. Methods and Results: Two hundred E. coli isolates recovered from retail meats, which were previously identified molecularly as extraintestinal pathogenic E. coli, were investigated for the presence of 21 uropathogenic E. coli (UPEC) virulence-associated genes. Twenty-three E. coli isolates were selected based on their serogroups and the number of virulence genes they contained, and further characterized using multilocus sequence typing, and by tissue culture assays for adherence to and invasion of T-24 human bladder cells and for their induction of interleukin (IL)-6 secretion. All virulence genes tested, except afa/dra and hlyD, were detected among the E. coli isolates. Multilocus sequence typing analysis of 23 selected isolates revealed that 17 isolates belonged to STs associated with human UPEC. Nearly all 23 isolates exhibited lower level of adherence and invasion compared to a clinical strain, UPEC CFT073. Conclusions: These observations suggested that a small proportion of E. coli isolates from retail meats carry uropathogenic associated virulence genes and thus may serve as a reservoir of these genes to UPEC in the human intestine. Their virulence potential seemed limited as they were only weakly invasive in human bladder cell culture. Significance and Impact of the Study: These findings support the hypothesis that retail meat E. coli may play a role in relation to urinary tract infection (UTI) and may be considered in development of a UTI prevention strategy. C1 [Xia, X.; Meng, J.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Xia, X.; Meng, J.] NW A&F Univ, Coll Food Sci & Engn, Yangling, Shaanxi, Peoples R China. [Meng, J.] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. [McDermott, P. F.; Zhao, S.] US FDA, Ctr Vet Med, Laurel, MD USA. RP Meng, J (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM jmeng@umd.edu FU Joint Institute for Food Safety and Applied Nutrition of the University of Maryland; US Food and Drug Administration; Northwest AF University FX This study was supported in part by the Joint Institute for Food Safety and Applied Nutrition of the University of Maryland and the US Food and Drug Administration. This work was also partly supported by Special Funds for Talents from Northwest A&F University. We are indebted to Dr James R. Johnson of the University of Minnesota for providing clinical strains and sharing multiple PCR protocols. NR 42 TC 9 Z9 10 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1364-5072 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD MAY PY 2011 VL 110 IS 5 BP 1166 EP 1176 DI 10.1111/j.1365-2672.2011.04978.x PG 11 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 746RR UT WOS:000289265100005 PM 21332898 ER PT J AU Chen, ZC Chumakov, K Dragunsky, E Kouiavskaia, D Makiya, M Neverov, A Rezapkin, G Sebrell, A Purcell, R AF Chen, Zhaochun Chumakov, Konstantin Dragunsky, Eugenia Kouiavskaia, Diana Makiya, Michelle Neverov, Alexander Rezapkin, Gennady Sebrell, Andrew Purcell, Robert TI Chimpanzee-Human Monoclonal Antibodies for Treatment of Chronic Poliovirus Excretors and Emergency Postexposure Prophylaxis SO JOURNAL OF VIROLOGY LA English DT Article ID VACCINE-DERIVED POLIOVIRUS; POTENT NEUTRALIZATION; POLIOMYELITIS; IMMUNIZATION; ERADICATION; RECEPTOR; TYPE-1; VIRUS; ELISA; MUTANTS AB Six poliovirus-neutralizing Fabs were recovered from a combinatorial Fab phage display library constructed from bone marrow-derived lymphocytes of immunized chimpanzees. The chimeric chimpanzee-human full-length IgGs (hereinafter called monoclonal antibodies [MAbs]) were generated by combining a chimpanzee IgG light chain and a variable domain of heavy chain with a human constant Fc region. The six MAbs neutralized vaccine strains and virulent strains of poliovirus. Five MAbs were serotype specific, while one MAb cross-neutralized serotypes 1 and 2. Epitope mapping performed by selecting and sequencing antibody-resistant viral variants indicated that the cross-neutralizing MAb bound between antigenic sites 1 and 2, thereby covering the canyon region containing the receptor-binding site. Another serotype 1-specific MAb recognized a region located between antigenic sites 2 and 3 that included parts of capsid proteins VP1 and VP3. Both serotype 2-specific antibodies recognized antigenic site 1. No escape mutants to serotype 3-specific MAbs could be generated. The administration of a serotype 1-specific MAb to transgenic mice susceptible to poliovirus at a dose of 5 mu g/mouse completely protected them from paralysis after challenge with a lethal dose of wild-type poliovirus. Moreover, MAb injection 6 or 12 h after virus infection provided significant protection. The MAbs described here could be tested in clinical trials to determine whether they might be useful for treatment of immunocompromised chronic virus excretors and for emergency protection of contacts of a paralytic poliomyelitis case. C1 [Chumakov, Konstantin; Dragunsky, Eugenia; Kouiavskaia, Diana; Neverov, Alexander; Rezapkin, Gennady] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Chen, Zhaochun; Makiya, Michelle; Sebrell, Andrew; Purcell, Robert] NIAID, NIH, Bethesda, MD 20892 USA. RP Chumakov, K (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA. EM konstantin.chumakov@fda.hhs.gov FU NIAID/NIH; CBER/FDA FX The work was supported by intramural research funding from NIAID/NIH and CBER/FDA. NR 43 TC 18 Z9 18 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2011 VL 85 IS 9 BP 4354 EP 4362 DI 10.1128/JVI.02553-10 PG 9 WC Virology SC Virology GA 751LG UT WOS:000289618600027 PM 21345966 ER PT J AU Tang, S Bertke, AS Patel, A Margolis, TP Krause, PR AF Tang, Shuang Bertke, Andrea S. Patel, Amita Margolis, Todd P. Krause, Philip R. TI Herpes Simplex Virus 2 MicroRNA miR-H6 Is a Novel Latency-Associated Transcript-Associated MicroRNA, but Reduction of Its Expression Does Not Influence the Establishment of Viral Latency or the Recurrence Phenotype SO JOURNAL OF VIROLOGY LA English DT Article ID SPONTANEOUS REACTIVATION; INFECTION; LAT; NEURONS; REGION; HSV-1; MODEL AB The herpes simplex virus 2 (HSV-2) viral microRNA (miRNA) designated miR-H6 is located upstream of the latency-associated transcript (LAT) promoter region on the strand opposite the LAT. Deletion of the LAT promoter and part of LAT exon 1 abolished HSV-2 miR-H6 expression in acutely and latently infected guinea pig dorsal root ganglia (DRG), suggesting that this region is needed both for the expression of LAT-encoded miRNAs and for miR-H6 expression in vivo. Relative to cells infected with a viral rescuant, miR-H6 expression was significantly reduced in cells infected with a mutant HSV-2 virus, NotPolyA, with an insertion of a simian virus (SV40) polyadenylation signal sequence between the LAT promoter and miR-H6 sequences. In addition, expression of miR-H6, but not LAT or viral DNA, was significantly reduced in both mouse trigeminal ganglia (TG) and guinea pig DRG latently infected with the NotPolyA mutant. Guinea pigs infected with NotPolyA experienced reduced neurological complications of acute infection relative to those infected with the rescuant, but the recurrence phenotype of the NotPolyA mutant was similar to those of its rescuant and wild-type HSV-2, indicating that reduction of miR-H6 expression is not by itself able to alter the establishment of latency for the wild-type virus or the recurrence phenotype. Furthermore, the mutation in NotPolyA did not affect the propensity of wild-type HSV-2 to establish latency in neurons positive for subtype marker KH10. In contrast to published reports regarding its HSV-1 homolog, HSV-2 miR-H6 did not affect ICP4 expression in transfected or infected cells. We hypothesize that viral miRNAs associated with LAT expression are likely to work collectively, contributing to the phenotype attributed to the LAT. C1 [Tang, Shuang; Bertke, Andrea S.; Patel, Amita; Krause, Philip R.] US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Bertke, Andrea S.; Margolis, Todd P.] Univ Calif San Francisco, Francis I Proctor Fdn, San Francisco, CA 94143 USA. RP Krause, PR (reprint author), US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, HFM-457,29 Lincoln Dr, Bethesda, MD 20892 USA. EM philip.krause@fda.hhs.gov RI Tang, Shuang/F-9115-2014; OI Tang, Shuang/0000-0002-3084-0903; Krause, Philip/0000-0002-1045-7536 FU Center for Biologics Evaluation and Research; Littlefield Trust FX This study was supported by the intramural research program of the Center for Biologics Evaluation and Research and the Littlefield Trust. NR 27 TC 18 Z9 20 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2011 VL 85 IS 9 BP 4501 EP 4509 DI 10.1128/JVI.01997-10 PG 9 WC Virology SC Virology GA 751LG UT WOS:000289618600041 PM 21325410 ER PT J AU Goske, MJ Charkot, E Herrmann, T John, SD Mills, TT Morrison, G Smith, SN AF Goske, Marilyn J. Charkot, Ellen Herrmann, Tracy John, Susan D. Mills, Thalia T. Morrison, Gregory Smith, Susan N. TI Image Gently: Challenges for radiologic technologists when performing digital radiography in children SO PEDIATRIC RADIOLOGY LA English DT Article DE Digital radiography; Radiologic technologists; Pediatric; Education; Training ID EXPOSURE AB The development of digital radiography (DR) has provided numerous benefits for pediatric imaging, including the ability to post-process images and to make images immediately available for access by care providers. However, DR presents several significant challenges for the radiologic technologists who are responsible for operating the equipment and producing high-quality images in children. This paper discusses those challenges, including lack of standardization among vendors, particularly with regard to the exposure indicator; lack of pediatric-specific educational materials and pediatric techniques; the need for manual technique instead of the use of automatic exposure control in smaller children; and complications related to field size, collimation and shielding in small children. Specific actions and design modifications that might facilitate the effective management of these challenges will be also described. The implementation of measures to promote the production of optimal images while minimizing radiation exposure requires cooperation and communication among imaging professionals, manufacturers and regulatory agencies. C1 [Goske, Marilyn J.; Smith, Susan N.] Cincinnati Childrens Hosp Med Ctr, Dept Radiol, Cincinnati, OH 45229 USA. [Charkot, Ellen] Hosp Sick Children, Toronto, ON M5G 1X8, Canada. [Herrmann, Tracy] Univ Cincinnati Raymond Walters Coll, Radiol Technol Program Allied Hlth Dept, Blue Ash, OH USA. [John, Susan D.] Univ Texas Houston Med Sch, Houston, TX USA. [Mills, Thalia T.] FDA Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Morrison, Gregory] Amer Soc Radiol Technologists, Albuquerque, NM USA. RP Goske, MJ (reprint author), Cincinnati Childrens Hosp Med Ctr, Dept Radiol, 3333 Burnet Ave,Mailcode 5031, Cincinnati, OH 45229 USA. EM Marilyn.Goske@cchmc.org NR 11 TC 6 Z9 6 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0301-0449 EI 1432-1998 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD MAY PY 2011 VL 41 IS 5 BP 611 EP 619 DI 10.1007/s00247-010-1957-3 PG 9 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 750EN UT WOS:000289527900011 PM 21491201 ER PT J AU Duan, JZ Riviere, K Marroum, P AF Duan, John Z. Riviere, Kareen Marroum, Patrick TI In Vivo Bioequivalence and In Vitro Similarity Factor (f2) for Dissolution Profile Comparisons of Extended Release Formulations: How and When Do They Match? SO PHARMACEUTICAL RESEARCH LA English DT Article DE bioequivalence; dissolution; f2 similarity factor; IVIVC; modeling and simulation ID MICROSOFT EXCEL; DECONVOLUTION AB To investigate how likely two extended release formulations are to be bioequivalent when they demonstrate f2 similarity. Dissolution profiles were simulated using the Weibull model and varying model parameters around those of a reference profile. The f2 values were calculated for the comparisons of each simulation with the reference profile. The in vivo inputs obtained from an in vitro-in vivo correlation model were convolved with a unit impulse response function. The AUC, Cmax, and Tmax from each simulated in vivo concentration profile were compared to the reference profile. The AUCR (AUC ratio) and CmaxR (Cmax ratio) were determined. The consistency between f2 and bioequivalence was investigated. The relationships between AUCR, CmaxR, f2 and the Weibull model parameters demonstrate that the bioequivalence regions enclosed by the contour lines of 80% and 125% of AUCR and CmaxR were generally close to the regions enclosed by the f2 = 50 contour line, but did not exactly match, especially when Dmax and B deviated from the reference values. When f2 is used for in vitro dissolution profile comparison, the completeness of the dissolution profiles should not differ more than 10%, and the shapes of the dissolution profiles should not be significantly different. C1 [Duan, John Z.; Riviere, Kareen; Marroum, Patrick] US FDA, Off New Drug Qual Assessment, Silver Spring, MD 20993 USA. RP Duan, JZ (reprint author), US FDA, Off New Drug Qual Assessment, 10903 New Hampshire Ave,Bldg 21,Room 1620, Silver Spring, MD 20993 USA. EM John.Duan@fda.hhs.gov NR 20 TC 11 Z9 13 U1 0 U2 10 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 EI 1573-904X J9 PHARM RES-DORDR JI Pharm. Res. PD MAY PY 2011 VL 28 IS 5 BP 1144 EP 1156 DI 10.1007/s11095-011-0377-x PG 13 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 747EB UT WOS:000289302000019 PM 21287250 ER PT J AU Choudhuri, S AF Choudhuri, Supratim TI From Waddington's epigenetic landscape to small noncoding RNA: some important milestones in the history of epigenetics research SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Review DE Epigenetics; waddington; history; epigenetic landscape; canalization; DNA methylation; histone modification; noncoding RNA ID TRANSCRIPTIONALLY ACTIVE CHROMATIN; MURINE ERYTHROLEUKEMIA-CELLS; BINDING PROTEIN MECP2; EMBRYONIC STEM-CELLS; DOUBLE-STRANDED-RNA; MOUSE H19 GENE; DNA METHYLTRANSFERASE; CAENORHABDITIS-ELEGANS; DE-NOVO; CHROMOSOMAL PROTEIN AB The term epigenetics was coined in 1942 by C. H. Waddington in the context of studies on development. Since then, the meaning of epigenetics changed over time. In the beginning, epigenetics was viewed as a phenomenon above and beyond genetics. Epigenetic explanations were invoked when genetics could not explain a phenomenon. From the mid-seventies, the state of understanding started changing. Epigenetics has now morphed from a phenomenon to a branch of science whose molecular underpinnings are well understood. The current state of knowledge of epigenetics has evolved as our understanding of DNA methylation, chromatin modifications, and noncoding RNA, and their effects on gene expression increased. At this time in the annals of epigentics research, it is appropriate to revisit some of the important discoveries that have helped advance the field to its current state. This is a very brief review of some early discoveries, and by no means is a complete account of the history of epigenetics. In this review, the early history has also been emphasized in order to underscore the transformation of the science of epigenetics from a phenomenon to a modern field of intense research. C1 US FDA, Ctr Food Safety & Appl Nutr, OFAS, DBGNR, College Pk, MD 20740 USA. RP Choudhuri, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, OFAS, DBGNR, HFS 255,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Supratim.Choudhuri@fda.hhs.gov NR 183 TC 24 Z9 30 U1 3 U2 38 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD MAY PY 2011 VL 21 IS 4 SI SI BP 252 EP 274 DI 10.3109/15376516.2011.559695 PG 23 WC Toxicology SC Toxicology GA 751PL UT WOS:000289629900002 PM 21495865 ER PT J AU Koturbash, I Beland, FA Pogribny, IP AF Koturbash, Igor Beland, Frederick A. Pogribny, Igor P. TI Role of epigenetic events in chemical carcinogenesis-a justification for incorporating epigenetic evaluations in cancer risk assessment SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Review DE Epigenetics; DNA methylation; histone modifications; chemical carcinogenesis; tobacco smoke; benzene; 2-acetylaminofluorene; phenobarbital; metals ID DNA METHYLATION PATTERNS; LUNG-CANCER; GENE-EXPRESSION; MOUSE-LIVER; MUTATIONAL HOTSPOTS; BENZENE EXPOSURE; HISTONE H3; RAT-LIVER; PROMOTER HYPERMETHYLATION; MALIGNANT-TRANSFORMATION AB Recent advances in field of cancer research have established that all major human cancers, in addition to having a large number of genetic alterations, exhibit prominent epigenetic abnormalities that can be used as biomarkers for the molecular diagnosis of cancer. Currently, epigenetic markers have shown promise in establishing the diagnosis and prognosis of all major human cancers. Additionally, accumulating evidence suggests that epigenetic alterations may be early indicators of genotoxic and non-genotoxic carcinogenic exposure and may be used as biomarkers in the assessment of the carcinogenic potential of environmental chemical and physical agents. This review presents current evidence on the role of epigenetic alterations in chemical carcinogenesis and highlights a number of advantages of epigenetic biomarkers over traditionally used methods in cancer risk assessment. C1 [Koturbash, Igor; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 126 TC 33 Z9 34 U1 0 U2 12 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1537-6516 EI 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD MAY PY 2011 VL 21 IS 4 SI SI BP 289 EP 297 DI 10.3109/15376516.2011.557881 PG 9 WC Toxicology SC Toxicology GA 751PL UT WOS:000289629900004 PM 21495867 ER PT J AU Buehler, PW Karnaukhova, E Gelderman, MP Alayash, AI AF Buehler, Paul W. Karnaukhova, Elena Gelderman, Monique P. Alayash, Abdu I. TI Blood Aging, Safety, and Transfusion: Capturing the "Radical'' Menace SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID HUMAN-SERUM-ALBUMIN; HAPTOGLOBIN-HEMOGLOBIN COMPLEX; CELL-FREE HEMOGLOBIN; ALPHA-HEMOGLOBIN; NITRIC-OXIDE; HEME-DEGRADATION; LIPOCALIN ALPHA(1)-MICROGLOBULIN; LIPOPROTEIN OXIDATION; STABILIZING PROTEIN; SCAVENGER RECEPTOR AB Throughout their life span, circulating red blood cells (RBCs) transport oxygen (O-2) primarily from the lungs to tissues and return with carbon dioxide (CO2) from respiring tissues for final elimination by lungs. This simplistic view of RBCs as O-2 transporter has changed in recent years as other gases, for example, nitric oxide (NO), and small molecules, such as adenosine triphosphate (ATP), have been shown to either be produced and/or carried by RBCs to perform other signaling and O-2 sensing functions. In spite of the numerous biochemical and metabolic changes occurring within RBCs during storage, prior to, and after transfusion, perturbations of RBC membrane are likely to affect blood flow in the microcirculation. Subsequent hemolysis due to storage conditions and/or hemolytic disorders may have some pathophysiological consequences as a result of the release of Hb. In this review, we show that evolution has provided a multitude of protection and intervention strategies against free Hb from "cradle'' to "death''; from early biosynthesis to its final degradation and a lot more in between. Furthermore, some of the same naturally occurring protective mechanisms can potentially be employed to oxidatively inactivate this redox active protein and control its damaging side reactions when released outside of the RBC. Antioxid. Redox Signal. 14, 1713-1728. C1 [Buehler, Paul W.; Karnaukhova, Elena; Gelderman, Monique P.; Alayash, Abdu I.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, NIH Bldg 29,Rm 112 8800 Rockville Pike, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov NR 117 TC 18 Z9 19 U1 2 U2 10 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD MAY PY 2011 VL 14 IS 9 BP 1713 EP 1728 DI 10.1089/ars.2010.3447 PG 16 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 746WL UT WOS:000289278900012 PM 20954814 ER PT J AU Meier, KL Gitterman, S AF Meier, Kristen L. Gitterman, Steven TI Drug-Device Trials for Infectious Diseases: CDRH Perspective SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID DIAGNOSTIC-ACCURACY; CHALLENGES; VALIDATION; BIOMARKERS; DESIGNS; ISSUES AB Assessing the performance of new diagnostic tests for infectious diseases has traditionally focused on comparing the new assay against a reference standard such as culture. In this paper, we suggest that clinical trial designs with both a diagnostic and therapeutic component may be necessary to evaluate the safety and effectiveness of nonmicrobiologically based assays, with a specific emphasis on the test/marker-stratified design. General design challenges for trials of infectious diseases that simultaneously study both diagnostic and therapeutic components (eg, both devices and drugs) are also discussed. C1 [Meier, Kristen L.] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, CDRH OSB, Silver Spring, MD 20993 USA. [Gitterman, Steven] US FDA, Div Microbiol Devices, CDRH OIVD, Silver Spring, MD 20993 USA. RP Meier, KL (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, CDRH OSB, 10903 New Hampshire Ave,Bldg 66,Room 2212, Silver Spring, MD 20993 USA. EM kristen.meier@fda.hhs.gov FU Food and Drug Administration; Infectious Diseases Society of America; AstraZeneca Pharmaceuticals; Bio Merieux, Inc.; Cepheid; Gilead Sciences; Intelligent MDX, Inc.; Inverness Medical Innovations; Roche Molecular Systems FX This article was published as part of a supplement entitled "Workshop on Molecular Diagnostics for Respiratory Tract Infections.'' The Food and Drug Administration and the Infectious Diseases Society of America sponsored the workshop. AstraZeneca Pharmaceuticals, Bio Merieux, Inc., Cepheid, Gilead Sciences, Intelligent MDX, Inc., Inverness Medical Innovations, and Roche Molecular Systems provided financial support solely for the purpose of publishing the supplement. NR 28 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2011 VL 52 SU 4 BP S367 EP S372 DI 10.1093/cid/cir053 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 745KT UT WOS:000289165000014 PM 21460298 ER PT J AU Russek-Cohen, E Feldblyum, T Whitaker, KB Hojvat, S AF Russek-Cohen, Estelle Feldblyum, Tamara Whitaker, Kathleen B. Hojvat, Sally TI FDA Perspectives on Diagnostic Device Clinical Studies for Respiratory Infections SO CLINICAL INFECTIOUS DISEASES LA English DT Article AB Two pathways are described for submission to FDA for clearance of a diagnostic device: a Premarket Application (PMA), which can lead to approval of a diagnostic device, and a Premarket Notification, which can lead to clearance. The latter is often called a 510(k), named for the statute providing for this path. Recent FDA clearance of molecular-based multiplex panels represents the beginning of a new era for the diagnosis of respiratory infections. The ability to test for multiple pathogens simultaneously, accompanied by the increasing availability of molecular-based assays for newly recognized respiratory pathogens will likely have a major impact on patient care, drug development, and public health epidemiology. We provide a general overview of how FDA evaluates new diagnostics for respiratory tract infections and the agency's expectations for sponsors developing new tests in this area. C1 [Russek-Cohen, Estelle] Ctr Biol Evaluat & Res, Div Biostat, Off Biostat & Epidemiol, Rockville, MD 20852 USA. [Feldblyum, Tamara; Whitaker, Kathleen B.; Hojvat, Sally] US FDA, Div Microbiol Devices, Off Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Russek-Cohen, E (reprint author), Ctr Biol Evaluat & Res, Div Biostat, Off Biostat & Epidemiol, 1401 Rockville Pike HFM-215, Rockville, MD 20852 USA. EM estelle.russek-cohen@fda.hhs.gov FU Food and Drug Administration; Infectious Diseases Society of America; AstraZeneca Pharmaceuticals; Bio Merieux, Inc.; Cepheid; Gilead Sciences; Intelligent MDX, Inc.; Inverness Medical Innovations; Roche Molecular Systems FX This article was published as part of a supplement entitled "Workshop on Molecular Diagnostics for Respiratory Tract Infections.'' The Food and Drug Administration and the Infectious Diseases Society of America sponsored the workshop. AstraZeneca Pharmaceuticals, Bio Merieux, Inc., Cepheid, Gilead Sciences, Intelligent MDX, Inc., Inverness Medical Innovations, and Roche Molecular Systems provided financial support solely for the purpose of publishing the supplement. NR 6 TC 4 Z9 4 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2011 VL 52 SU 4 BP S305 EP S311 DI 10.1093/cid/cir056 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 745KT UT WOS:000289165000005 PM 21460289 ER PT J AU Bjornsdottir-Butler, K Jones, JL Benner, R Burkhardt, W AF Bjornsdottir-Butler, Kristin Jones, Jessica L. Benner, Ronald Burkhardt, William, III TI Development of a real-time PCR assay with an internal amplification control for detection of Gram-negative histamine-producing bacteria in fish SO FOOD MICROBIOLOGY LA English DT Article DE Histamine; Biogenic amines; Histidine decarboxylase; Real-time PCR; Bacteria; Fish ID LACTIC-ACID BACTERIA; HISTIDINE-DECARBOXYLASE; BIOGENIC-AMINES; QUANTITATIVE DETECTION; FORMING BACTERIA; SUBSP DAMSELAE; TUNA; IDENTIFICATION; PURIFICATION; OYSTERS AB Prompt detection of bacteria that contribute to scombrotoxin (histamine) fish poisoning can aid in the detection of potentially toxic fish products and prevent the occurrence of illness. We report development of the first real-time PCR method for rapid detection of Gram-negative histamine-producing bacteria (HPB) in fish. The real-time PCR assay was 100% inclusive for detecting high-histamine producing isolates and did not detect any of the low- or non-histamine producing isolates. The efficiency of the assay with/without internal amplification control ranged from 96-104% and in the presence of background flora and inhibitory matrices was 92/100% and 73-96%, respectively. This assay was used to detect HPB from naturally contaminated yellowfin tuna, bluefish, and false albacore samples. Photobacterium damselae (8), Plesiomonas shigelloides (2), Shewanella sp. (1), and Morganella morganii (1) were subsequently isolated from the real-time PCR positive fish samples. These results indicate that the real-time PCR assay developed in this study is a rapid and sensitive method for detecting high-HPB. The assay may be adapted for quantification of HPB, either directly or with an MPN-PCR method. (C) 2010 Published by Elsevier Ltd. C1 [Bjornsdottir-Butler, Kristin; Jones, Jessica L.; Benner, Ronald; Burkhardt, William, III] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Bjornsdottir-Butler, K (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM Kristin.Butler@fda.hha.gov NR 45 TC 14 Z9 18 U1 0 U2 15 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD MAY PY 2011 VL 28 IS 3 BP 356 EP 363 DI 10.1016/j.fm.2010.06.013 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 739PW UT WOS:000288731200003 PM 21356438 ER PT J AU Danyluk, MD Friedrich, LM Jouquand, C Goodrich-Schneider, R Parish, ME Rouseff, R AF Danyluk, Michelle D. Friedrich, Loretta M. Jouquand, Celine Goodrich-Schneider, Renee Parish, Mickey E. Rouseff, Russell TI Prevalence, concentration, spoilage, and mitigation of Alicyclobacillus spp. in tropical and subtropical fruit juice concentrates SO FOOD MICROBIOLOGY LA English DT Article DE Alicyclobacillus; Chlorine dioxide; Citrus; Pineapple; Mango ID THERMO-ACIDOPHILIC BACTERIA; ACIDOTERRESTRIS SPORES; ORANGE JUICE; APPLE JUICE; PROCESSING ENVIRONMENT; CHLORINE DIOXIDE; HEAT-RESISTANCE; IDENTIFICATION; ACIDOCALDARIUS; SURFACES AB The presence of Alicyclobacillus in fruit juices and concentrates poses a serious problem for the juice industry. This study was undertaken to determine the (i) prevalence, concentration, and species of Alicyclobacillus in tropical and subtropical concentrates; (ii) efficacy of aqueous chlorine dioxide in reducing Alicyclobacillus spp. spores on tropical and subtropical fruit surfaces; and (iii) fate of and off-flavor production by Alicyclobacillus acidoterrestris in mango and pineapple juices. One hundred and eighty tropical and subtropical juice concentrates were screened for the presence and concentration of Alicyclobacillus spp. If found, the species of Alicyclobacillus was determined by 16S rDNA sequencing and analysis with NCl BLAST. Of these samples, 6.1% were positive for Alicyclobacillus, and nine A. acidoterrestris strains and two Alicyclobacillus acidocaldarius strains were identified. A five-strain cocktail of Alicyclobacillus spp. was inoculated onto the surface of fruits (grapefruit, guava, limes, mangoes, oranges and pineapple), which were then washed with 0, 50, or 100 ppm aqueous chlorine dioxide. Significant reductions due to chlorine dioxide were only seen on citrus fruits. A five-strain cocktail of A. acidoterrestris was inoculated into mango and pineapple juices. Microbial populations were enumerated over a 16-day period. Aroma compounds in the juice were analyzed by GC-olfactometry (GC-O) and confirmed using GC-MS. GC-O of mango juice identified previously reported medicinal/antiseptic compounds. GC-O of pineapple juice revealed an unexpected "cheese" off-aroma associated with 2-methylbutyric acid and 3-methylbutyric acid. (C) 2010 Elsevier Ltd. All rights reserved. C1 [Danyluk, Michelle D.; Friedrich, Loretta M.; Jouquand, Celine; Rouseff, Russell] Univ Florida, Inst Food & Agr Sci, Ctr Citrus Res & Educ, Lake Alfred, FL 33850 USA. [Danyluk, Michelle D.; Goodrich-Schneider, Renee; Rouseff, Russell] Univ Florida, Inst Food & Agr Sci, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. [Parish, Mickey E.] FDA CFSAN Off Food Safety, College Pk, MD USA. RP Danyluk, MD (reprint author), Univ Florida, Inst Food & Agr Sci, Ctr Citrus Res & Educ, 700 Expt Stn Rd, Lake Alfred, FL 33850 USA. EM mddanyluk@ufl.edu FU United States Department of Agriculture, Cooperative State Research, Education and Extension Service, Tropical Sub-Tropical Agricultural Research (TSTAR) [2004-34135-14799] FX This study was supported by the United States Department of Agriculture, Cooperative State Research, Education and Extension Service, Tropical Sub-Tropical Agricultural Research (TSTAR) grant number 2004-34135-14799. The technical support of Gwen Lundy is greatly appreciated. NR 31 TC 16 Z9 17 U1 3 U2 30 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD MAY PY 2011 VL 28 IS 3 BP 472 EP 477 DI 10.1016/j.fm.2010.10.008 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 739PW UT WOS:000288731200018 PM 21356453 ER PT J AU Lin, A Sultan, O Lau, HK Wong, E Hartman, G Lauzon, CR AF Lin, Andrew Sultan, Omar Lau, Henry K. Wong, Evelyn Hartman, Gary Lauzon, Carol R. TI O serogroup specific real time PCR assays for the detection and identification of nine clinically relevant non-O157 STECs SO FOOD MICROBIOLOGY LA English DT Article DE Shiga toxin; Foodborne disease; Escherichia coli surveillance ID ENTEROHEMORRHAGIC ESCHERICHIA-COLI; ANTIGEN GENE-CLUSTER; HEMOLYTIC-UREMIC SYNDROME; SHIGA TOXIN; HEMORRHAGIC COLITIS; MINCED BEEF; INFECTIONS; O145; O111; FOOD AB TaqMan (TM) real time PCR assays were designed for each of the non-O157 STEC O serogroups most commonly associated with human illness: O26, O45, O91, O103, O111, O113, O121, O128, and O145. The nine RT-PCR assays can be run as single assays when a known pathogen is of concern, or multiplexed in three reactions, to quickly screen for the most clinically relevant O serogroups. All assays included an internal amplification control constructed from the green fluorescent protein gene as an indicator of PCR inhibition. Of 103 strains tested, the inclusive tests accurately identified the O serogroup for 101 strains. The exclusive tests for each assay yielded no false positives for over 120 Escherichia coli strains and 23 non-E. coli bacteria tested. Furthermore, the RT-PCR assays were tested by inoculating four food matrices, milk, apple juice, lettuce, and ground beef, at <= 30 CFU/25 g or mL Following a 24 h selective enrichment, the RT-PCR assays detected STECs in all foods except for one ground beef sample inoculated with O111, and all apple juice samples inoculated with O113. The assays could also detect each O serogroup in human stool specimens inoculated with STECs at 1000 CFU/0.5 g of stool following 24 h enrichment. Published by Elsevier Ltd. C1 [Lin, Andrew; Lau, Henry K.; Wong, Evelyn; Hartman, Gary] US FDA, San Francisco Dist Lab, Alameda, CA 94502 USA. [Sultan, Omar; Lauzon, Carol R.] Calif State Univ Hayward, Dept Biol Sci, Hayward, CA 94542 USA. RP Lin, A (reprint author), US FDA, San Francisco Dist Lab, 1431 Harbor Bay Pkwy, Alameda, CA 94502 USA. EM andrew.lin@fda.hhs.gov FU California State University FX The authors would like to thank the STEC Center at Michigan State University's National Food Safety and Toxicology Center, East Lansing, MI, Robert Mandrell, United States Department of Agriculture-Agricultural Research Services (USDA-ARS), Albany, CA, the Ohio Department of Agriculture, Reynoldsburg, OH, and Atin Datta, U.S. Food and Drug Administration (FDA), Center for Food Safety and Applied Nutrition, College Park, MD for generously sharing their bacterial cultures. We would also like to thank David K. Lau, Roderick V. Asmundson, and Thomas H. Sidebottom of the FDA, and Laurie Clotilde and Mark J. Carter of the USDA-ARS. This work was primarily supported by the California State University Program for Education and Research in Biotechnology. NR 32 TC 22 Z9 23 U1 1 U2 11 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 EI 1095-9998 J9 FOOD MICROBIOL JI Food Microbiol. PD MAY PY 2011 VL 28 IS 3 BP 478 EP 483 DI 10.1016/j.fm.2010.10.007 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 739PW UT WOS:000288731200019 PM 21356454 ER PT J AU Wu, HQ Khan, MA AF Wu, Huiquan Khan, Mansoor A. TI Quality-by-Design: An Integrated Process Analytical Technology Approach to Determine the Nucleation and Growth Mechanisms During a Dynamic Pharmaceutical Coprecipitation Process SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Quality-by-Design; process analytical technology; coprecipitation; homogeneous nucleation; heterogeneous nucleation; kinetics; thermodynamics; regulatory science; mathematical modeling; induction ID METASTABLE ZONE WIDTH; INDUCTION TIME; RELEASE TABLETS; PARTICLE-SIZE; PRECIPITATION; NAPROXEN; FBRM; MODEL; MICROSPHERES; VARIABLES AB The objective of this study was to demonstrate the feasibility of using an integrated process analytical technology (PAT) approach to determine nucleation and growth mechanisms of a dynamic naproxen (drug)-Eudragit L100 (polymer) coprecipitation process. The influence of several thermodynamically important formulation and process variables (drug/polymer ratio, alcohol, and water usages) on coprecipitation process characteristics was investigated via real-time in situ focused beam reflectance measurement (FBRM) monitoring and near real-time particle vision microscopy measurement. The final products were characterized by near-infrared (NIR) spectroscopy and NIR chemical imaging microscopy. The coprecipitation nucleation induction time (t(ind)) was measured by both FBRM trend statistics and process trajectory method, respectively. Furthermore, nucleation kinetics was evaluated based on t(ind) measurement and corresponding supersaturation ratio (S) estimated. It was found that plots of ln(t(ind)) versus (ln(2)S)(-1) consist of two linear segments and are consistent with classical primary nucleation mechanisms. Apparently, the coprecipitation process is governed by heterogeneous primary nucleation mechanism at low S (14 <= S <= 503) and by homogeneous primary nucleation mechanism at high S (1216 <= S <= 3649). Off-line characterizations collectively supported this statement. Therefore, it demonstrated that integration real-time PAT process monitoring with first-principles modeling and off-line product characterization could enhance understanding to coprecipitation process dynamics and nucleation/growth mechanisms, which is impossible via off-line techniques alone. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100: 1969-1986, 2011 C1 [Wu, Huiquan; Khan, Mansoor A.] US FDA, Div Prod Qual Res HFD 940, Off Testing & Res, Off Pharmaceut Sci,CDER, Silver Spring, MD 20993 USA. RP Wu, HQ (reprint author), US FDA, Div Prod Qual Res HFD 940, Off Testing & Res, Off Pharmaceut Sci,CDER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM huiquan.wu@fda.hhs.gov NR 47 TC 9 Z9 9 U1 1 U2 27 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD MAY PY 2011 VL 100 IS 5 BP 1969 EP 1986 DI 10.1002/jps.22430 PG 18 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 736TL UT WOS:000288516900034 PM 21374627 ER PT J AU Laassri, M Bidzhieva, B Speicher, J Pletnev, AG Chumakov, K AF Laassri, Majid Bidzhieva, Bella Speicher, James Pletnev, Alexander G. Chumakov, Konstantin TI Microarray Hybridization for Assessment of the Genetic Stability of Chimeric West Nile/Dengue 4 Virus SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE flavivirus vaccine; mutants screening; mutants quantitation; molecular consistency; quality control ID BORNE ENCEPHALITIS-VIRUS; YELLOW-FEVER VIRUS; DENGUE VIRUS; NILE-VIRUS; OLIGONUCLEOTIDE MICROARRAY; POLIOVIRUS VACCINE; ATTENUATED VACCINE; NONHUMAN-PRIMATES; RHESUS-MONKEYS; LIVE AB Genetic stability is an important characteristic of live viral vaccines because an accumulation of mutants can cause reversion to a virulent phenotype as well as a loss of immunogenic properties. This study was aimed at evaluating the genetic stability of a live attenuated West Nile (WN) virus vaccine candidate that was generated by replacing the pre-membrane and envelope protein genes of dengue 4 virus with those from WN. Chimeric virus was serially propagated in Vero, SH-SY5Y human neuroblastoma and HeLa cells and screened for point mutations using hybridization with microarrays of overlapping oligonucleotide probes covering the entire genome. The analysis revealed several spontaneous mutations that led to amino acid changes, most of which were located inthe envelope (E) and non-structural NS4A, NS4B, and NS5 proteins. Viruses passaged in Vero and SH-SY5Y cells shared two common mutations: G(2337)C (Met(457)Ile) in the E gene and A(6751)G (Lys(125)Arg) in the NS4A gene. Quantitative assessment of the contents of these mutants in viral stocks indicated that they accumulated independently with different kinetics during propagation in cell cultures. Mutant viruses grew better in Vero cells compared to the parental virus, suggesting that they have a higher fitness. When tested in newborn mice, the cell culture-passaged viruses did not exhibit increased neurovirulence. The approach described in this article could be useful for monitoring the molecular consistency and quality control of vaccine strains. J. Med. Virol. 83:910-920, 2011. (C) 2011 Wiley-Liss, Inc. C1 [Laassri, Majid; Bidzhieva, Bella; Chumakov, Konstantin] US FDA, Lab Method Dev, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Speicher, James; Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Chumakov, K (reprint author), US FDA, Lab Method Dev, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM-470, Rockville, MD 20852 USA. EM apletnev@niaid.nih.gov; konstantin.chumakov@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases [224-06-1322/Y1-AI-6153-01] FX Grant sponsor: National Institute of Allergy and Infectious Diseases, Division of Microbiology and Infectious Diseases; Grant number: Interagency agreement number between FDA and NIH, 224-06-1322/Y1-AI-6153-01. NR 32 TC 8 Z9 9 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD MAY PY 2011 VL 83 IS 5 BP 910 EP 920 DI 10.1002/jmv.22033 PG 11 WC Virology SC Virology GA 736BL UT WOS:000288464400025 PM 21360544 ER PT J AU Tournas, VH Calo, JR Memon, S AF Tournas, V. H. Calo, J. Rivera Memon, S. TI Comparison of the SimPlate yeast and mould color indicator to the BAM method for quantification of fungi in naturally-contaminated foods SO FOOD CONTROL LA English DT Article DE SimPlate YM-CI; BAM method; Yeast and mould quantification ID TOTAL PLATE-COUNT; ENUMERATION AB A total of 260 samples from six food groups (grains and grain products, tree nuts, dried fruits, fresh produce, fruit juice, and dairy products) were tested for levels of fungal contamination using the SimPlate Yeast and Mould Color Indicator (YM-CI) and the FDA official (BAM) method. Results showed that the SimPlate, in most cases, gave higher yeast and mould (YM) counts than the FDA (reference) method. Statistical analysis of the data (paired t-test) revealed that there were significant differences (alpha = 0.05) between the two methods for several foods tested. The SimPlate was easy to use, saved time during sample preparation and inoculation and gave results faster than the reference method. Some difficulties were encountered when spreading moulds were present. Published by Elsevier Ltd. C1 [Tournas, V. H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Calo, J. Rivera] Univ Puerto Rico, Mayaguez, PR USA. [Memon, S.] Univ Maryland, College Pk, MD 20742 USA. RP Tournas, VH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-712,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM valerie.tournas@fda.hhs.gov NR 9 TC 2 Z9 2 U1 3 U2 8 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD MAY PY 2011 VL 22 IS 5 BP 775 EP 777 DI 10.1016/j.foodcont.2010.11.013 PG 3 WC Food Science & Technology SC Food Science & Technology GA 715BU UT WOS:000286856200021 ER PT J AU Huang, PP Khan, I Suhail, MSA Malkmus, S Yaksh, TL AF Huang, Polly P. Khan, Imran Suhail, Mohammed S. A. Malkmus, Shelle Yaksh, Tony L. TI Spinal Botulinum Neurotoxin B: Effects on Afferent Transmitter Release and Nociceptive Processing SO PLOS ONE LA English DT Article ID SUBSTANCE-P RELEASE; LIGHT-CHAIN PROTEASE; INTRATHECAL MORPHINE; TACTILE ALLODYNIA; NEUROPATHIC PAIN; NERVE LIGATION; FORMALIN TEST; DORSAL-HORN; RAT; RECEPTOR AB Botulinum neurotoxin B (BoNT-B) mediates proteolytic cleavage of VAMP I/II (synaptobrevins I/II), which prevents vesicle-membrane fusion and blocks neurotransmitter release. In the present study, we investigated the effects of BoNT-B on neurotransmitter release in vivo from spinal primary afferent sensory fibers and the effects of this blockade on nociception. With intrathecally (IT) delivered BoNT-B in C57B/l6 mice, we characterized the effects of such block on the release of substance P (SP) from spinal afferent nociceptors (as measured by neurokinin-1 receptor, NK1-R, internalization), spinal neuronal activation (as indicated by spinal C-Fos expression) and nociceptive behavior after intraplantar (IPLT) formalin. In addition, we investigated the effect of IT BoNT-B on spinal nerve ligation-induced tactile allodynia. A single percutaneous IT injection of BoNT-B 0.5 U at 2 or 5 days prior to IPLT formalin reduced NK1-R internalization and C-Fos expression. These effects correlated with BoNT-B cleavage of VAMPI/II protein in tissue lysate. IT BoNT-B also produced a corresponding reduction in phase 2 of formalin-evoked flinching behavior for over 30 days after IT injection. In mice with spinal nerve ligation (SNL), tactile allodynia was observed, which was attenuated by IT BoNT-B 0.5 U over the next 15 days, as compared to vehicle animals. These effects were observed without effects upon motor function. The specificity of the IT BoNT-B effect is indicated by: i) IT co-injection of BoNT-B and anti-BoNTB antibody prevented effects on SP release, and ii) IT BoNT-B 50 U in the Sprague Dawley rats showed no effect on formalin-evoked flinching or SNL-induced tactile allodynia, which is consistent with rat resistance to BoNT-B. IT BoNT-B blocks transmitter release from spinal primary afferents, and attenuates inflammatory nociceptive response and spinal nerve injury-induced neuropathic pain, in the absence of motor impairment. These observations provide an initial assessment of the ability of IT BoNT-B to regulate spinal nociceptive processing. C1 [Huang, Polly P.] Univ Calif San Diego, Dept Biol Sci, La Jolla, CA 92093 USA. [Khan, Imran] US FDA, Dept Hlth & Human Serv, Bethesda, MD 20014 USA. [Suhail, Mohammed S. A.] Univ Calif San Diego, Sch Med, La Jolla, CA 92093 USA. [Malkmus, Shelle; Yaksh, Tony L.] Univ Calif San Diego, Dept Anesthesiol, La Jolla, CA 92093 USA. RP Huang, PP (reprint author), Univ Calif San Diego, Dept Biol Sci, La Jolla, CA 92093 USA. EM tyaksh@ucsd.edu FU National Institutes of Health, Bethesda, MD [NIH-DA02110]; Solstice Neurosciences; National Institutes of Health [DA02110] FX This research was supported by funding from the National Institutes of Health: NIH-DA02110, Bethesda, MD (TLY); Solstice Neurosciences, 701 Gateway Boulevard, Suite 250, South San Francisco, CA 94080. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.; A portion of the funds and drugs used in this work was supplied by Solstice Neuroscience and by the National Institutes of Health (DA02110). The support by Solstice did not involve any compensation for consulting nor any restriction on the publication of the results or on the contents of this manuscript. The authors have no patent position associated with this product or research. This does not alter the authors' adherence to all the PLoS ONE policies on sharing data and materials. NR 50 TC 22 Z9 22 U1 0 U2 0 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 29 PY 2011 VL 6 IS 4 AR e19126 DI 10.1371/journal.pone.0019126 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 756OZ UT WOS:000290024700070 PM 21559464 ER PT J AU Ryabinin, VA Kostina, EV Maksakova, GA Neverov, AA Chumakov, KM Sinyakov, AN AF Ryabinin, Vladimir A. Kostina, Elena V. Maksakova, Galiya A. Neverov, Alexander A. Chumakov, Konstantin M. Sinyakov, Alexander N. TI Universal Oligonucleotide Microarray for Sub-Typing of Influenza A Virus SO PLOS ONE LA English DT Article ID FLUCHIP DIAGNOSTIC MICROARRAY; DNA MICROARRAYS; SUBTYPE IDENTIFICATION; RT-PCR; HYBRIDIZATION; SURVEILLANCE; SELECTION; ASSAY; SET AB A universal microchip was developed for genotyping Influenza A viruses. It contains two sets of oligonucleotide probes allowing viruses to be classified by the subtypes of hemagglutinin (H1-H13, H15, H16) and neuraminidase (N1-N9). Additional sets of probes are used to detect H1N1 swine influenza viruses. Selection of probes was done in two steps. Initially, amino acid sequences specific to each subtype were identified, and then the most specific and representative oligonucleotide probes were selected. Overall, between 19 and 24 probes were used to identify each subtype of hemagglutinin (HA) and neuraminidase (NA). Genotyping included preparation of fluorescently labeled PCR amplicons of influenza virus cDNA and their hybridization to microarrays of specific oligonucleotide probes. Out of 40 samples tested, 36 unambiguously identified HA and NA subtypes of Influenza A virus. C1 [Ryabinin, Vladimir A.; Kostina, Elena V.; Maksakova, Galiya A.; Sinyakov, Alexander N.] Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Branch, Novosibirsk, Russia. [Neverov, Alexander A.; Chumakov, Konstantin M.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Ryabinin, VA (reprint author), Russian Acad Sci, Inst Chem Biol & Fundamental Med, Siberian Branch, Novosibirsk, Russia. EM konstantin.chumakov@fda.hhs.gov RI Sinyakov, Aleksandr /H-1129-2013; OI Tripp, Ralph/0000-0002-2924-9956 FU Department of Health and Human Services [140/3803]; International Science and Technology Center FX The work was supported by grant 140/3803 from the Department of Health and Human Services Biotechnology Engagement Program and the International Science and Technology Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 34 TC 12 Z9 12 U1 0 U2 4 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 29 PY 2011 VL 6 IS 4 AR e17529 DI 10.1371/journal.pone.0017529 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 756OZ UT WOS:000290024700005 PM 21559081 ER PT J AU Gilbert, ME McLanahan, ED Hedge, J Crofton, KM Fisher, JW Valentin-Blasini, L Blount, BC AF Gilbert, M. E. McLanahan, E. D. Hedge, J. Crofton, K. M. Fisher, J. W. Valentin-Blasini, L. Blount, B. C. TI Marginal iodide deficiency and thyroid function: Dose-response analysis for quantitative pharmacokinetic modeling SO TOXICOLOGY LA English DT Article DE Thyroid; Iodine; Hypothyroidism; Biologically based dose-response modeling; Hypothyroidism; Brain development ID MICROSOMAL-ENZYME INDUCERS; TANDEM MASS-SPECTROMETRY; ION CHROMATOGRAPHY; DIETARY IODIDE; UNITED-STATES; ADULT-RAT; PERCHLORATE; HORMONE; TISSUE; INHIBITION AB Severe iodine deficiency (ID) results in adverse health outcomes and remains a benchmark for understanding the effects of developmental hypothyroidism. The implications of marginal ID, however, remain less well known. The current study examined the relationship between graded levels of ID in rats and serum thyroid hormones, thyroid iodine content, and urinary iodide excretion. The goals of this study were to provide parametric and dose-response information for development of a quantitative model of the thyroid axis. Female Long Evans rats were fed casein-based diets containing varying iodine (I) concentrations for 8 weeks. Diets were created by adding 975, 200, 125, 25. or 0 mu g/kg I to the base diet (similar to 25 mu g I/kg chow) to produce 5 nominal I levels, ranging from excess (basal + added I, Treatment 1: 1000 mu g I/kg chow) to deficient (Treatment 5: 25 mu g I/kg chow). Food intake and body weight were monitored throughout and on 2 consecutive days each week over the 8-week exposure period, animals were placed in metabolism cages to capture urine. Food, water intake, and body weight gain did not differ among treatment groups. Serum T4 was dose-dependently reduced relative to Treatment 1 with significant declines (19 and 48%) at the two lowest I groups, and no significant changes in serum T3 or TSH were detected. Increases in thyroid weight and decreases in thyroidal and urinary iodide content were observed as a function of decreasing I in the diet. Data were compared with predictions from a recently published biologically based dose-response (BBDR) model for ID. Relative to model predictions, female Long Evans rats under the conditions of this study appeared more resilient to low I intake. These results challenge existing models and provide essential information for development of quantitative BBDR models for ID during pregnancy and lactation. Published by Elsevier Ireland Ltd. C1 [Gilbert, M. E.] US EPA, Tox Assessment Div MD B105 05, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. [McLanahan, E. D.] US EPA, Natl Ctr Environm Assessment, Res Triangle Pk, NC 27711 USA. [Hedge, J.; Crofton, K. M.] US EPA, Integrated Syst Biol Div, Res Triangle Pk, NC 27711 USA. [Fisher, J. W.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Valentin-Blasini, L.; Blount, B. C.] Ctr Dis Control & Prevent, Atlanta, GA USA. RP Gilbert, ME (reprint author), US EPA, Tox Assessment Div MD B105 05, Natl Hlth & Environm Effects Res Lab, 109 TW Alexander Dr, Res Triangle Pk, NC 27711 USA. EM gilbert.mary@epa.gov RI Crofton, Kevin/J-4798-2015 OI Crofton, Kevin/0000-0003-1749-9971 NR 40 TC 9 Z9 9 U1 3 U2 12 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD APR 28 PY 2011 VL 283 IS 1 BP 41 EP 48 DI 10.1016/j.tox.2011.02.001 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 756ZJ UT WOS:000290053000006 PM 21315791 ER PT J AU Moore, HM Kelly, AB Jewell, SD McShane, LM Clark, DP Greenspan, R Hayes, DF Hainaut, P Kim, P Mansfield, EA Potapova, O Riegman, P Rubinstein, Y Seijo, E Somiari, S Watson, P Weier, HU Zhu, C Vaught, J AF Moore, Helen M. Kelly, Andrea B. Jewell, Scott D. McShane, Lisa M. Clark, Douglas P. Greenspan, Renata Hayes, Daniel F. Hainaut, Pierre Kim, Paula Mansfield, Elizabeth A. Potapova, Olga Riegman, Peter Rubinstein, Yaffa Seijo, Edward Somiari, Stella Watson, Peter Weier, Heinz-Ulrich Zhu, Claire Vaught, Jim TI Biospecimen Reporting for Improved Study Quality (BRISQ) SO CANCER CYTOPATHOLOGY LA English DT Article DE BRISQ; best practices; biobank; biospecimen; human; quality; research; guidelines ID APPROACHING CLINICAL PROTEOMICS; FUTURE FIELDS; CURRENT STATE; CANCER; TISSUE AB Human biospecimens are subjected to collection, processing, and storage that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research that uses human tissues, it is crucial that information on the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality (BRISQ) recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The BRISQ guidelines are proposed as an important and timely resource tool to strengthen communication and publications on biospecimen-related research and to help reassure patient contributors and the advocacy community that their contributions are valued and respected. Cancer (Cancer Cytopathol) 2011;119:92-101. Published 2011 by the American Cancer Society.* C1 [Clark, Douglas P.] Johns Hopkins Univ Hosp, Dept Pathol, Baltimore, MD 21287 USA. [Moore, Helen M.; Vaught, Jim] Natl Canc Inst, Off Biorepositories & Biospecimen Res, Bethesda, MD USA. [Kelly, Andrea B.] Rose Li & Associates Inc, Bethesda, MD USA. [Jewell, Scott D.] Van Andel Res Inst, Program Biospecimen Sci, Grand Rapids, MI USA. [McShane, Lisa M.] NCI, Div Canc Treatment & Diag, Biometr Res Branch, Bethesda, MD 20892 USA. [Greenspan, Renata] Henry M Jackson Fdn Adv Mil Med, US Mil Canc Inst, Rockville, MD USA. [Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Ann Arbor, MI 48109 USA. [Hainaut, Pierre] World Hlth Org, IARC, Lyon, France. [Kim, Paula] Paula Kim Inc, TRAC, Solana Beach, CA USA. [Mansfield, Elizabeth A.] US Dept HHS, Ctr Devices & Radiol Hlth, US FDA, Silver Spring, MD USA. [Potapova, Olga] Cureline Inc, San Francisco, CA USA. [Riegman, Peter] Erasmus MC Tissue Bank, Dept Pathol, Rotterdam, Netherlands. [Rubinstein, Yaffa] NIH, Off Rare Dis Res, Bethesda, MD 20892 USA. [Seijo, Edward] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Somiari, Stella] Windber Res Inst, Windber, PA USA. [Watson, Peter] British Columbia Canc Agcy, Vancouver Isl Ctr, Victoria, BC, Canada. [Weier, Heinz-Ulrich] US DOE, Div Life Sci, Lawrence Berkeley Natl Lab, Berkeley, CA USA. [Zhu, Claire] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Clark, DP (reprint author), Johns Hopkins Univ Hosp, Dept Pathol, 600 N Wolfe St,PATH 406, Baltimore, MD 21287 USA. EM dclark@jhmi.edu RI Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 FU National Cancer Institute, National Institutes of Health [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 Contract No. HHSN261200800001E. NR 11 TC 62 Z9 62 U1 0 U2 7 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1934-662X EI 1934-6638 J9 CANCER CYTOPATHOL JI Cancer Cytopathol. PD APR 25 PY 2011 VL 119 IS 2 BP 92 EP 101 DI 10.1002/cncy.20147 PG 10 WC Oncology; Pathology SC Oncology; Pathology GA 751SB UT WOS:000289636800004 PM 21433001 ER PT J AU Ragupathy, V Zhao, JQ Wood, O Tang, SX Lee, S Nyambi, P Hewlett, I AF Ragupathy, Viswanath Zhao, Jiangqin Wood, Owen Tang, Shixing Lee, Sherwin Nyambi, Phillipe Hewlett, Indira TI Identification of new, emerging HIV-1 unique recombinant forms and drug resistant viruses circulating in Cameroon SO VIROLOGY JOURNAL LA English DT Article ID REVERSE-TRANSCRIPTASE; BLOOD-DONORS; SUBTYPE-A; INTERSUBTYPE RECOMBINANTS; GENETIC DIVERSITY; GENOME SEQUENCES; STRAINS; TYPE-1; TRANSMISSION; PROTEASE AB Background: The HIV epidemic in Cameroon is characterized by a high degree of viral genetic diversity with circulating recombinant forms (CRFs) being predominant. The goal of our study was to determine recent trends in virus evolution and emergence of drug resistance in blood donors and HIV positive patients. Methodology: Blood specimens of 73 individuals were collected from three cities and a few villages in Cameroon and viruses were isolated by co-cultivation with PBMCs. Nested PCR was performed for gag p17 (670 bp) pol (840 bp) and Env gp41 (461 bp) genes. Sequences were phylogenetically analyzed using a reference set of sequences from the Los Alamos database. Results: Phylogenetic analysis based on partial sequences revealed that 65% (n = 48) of strains were CRF02_AG, 4% (n = 3) subtype F2, 1% each belonged to CRF06 (n = 1), CRF11 (n = 1), subtype G (n = 1), subtype D (n = 1), CRF22_01A1 (n = 1), and 26% (n = 18) were Unique Recombinant Forms (URFs). Most URFs contained CRF02_AG in one or two HIV gene fragments analyzed. Furthermore, pol sequences of 61 viruses revealed drug resistance in 55.5% of patients on therapy and 44% of drug nave individuals in the RT and protease regions. Overall URFs that had a primary HIV subtype designation in the pol region showed higher HIV-1 p24 levels than other recombinant forms in cell culture based replication kinetics studies. Conclusions: Our results indicate that although CRF02_AG continues to be the predominant strain in Cameroon, phylogenetically the HIV epidemic is continuing to evolve as multiple recombinants of CRF02_AG and URFs were identified in the individuals studied. CRF02_AG recombinants that contained the pol region of a primary subtype showed higher replicative advantage than other variants. Identification of drug resistant strains in drug-nave patients suggests that these viruses are being transmitted in the population studied. Our findings support the need for continued molecular surveillance in this region of West Central Africa and investigating impact of variants on diagnostics, viral load and drug resistance assays on an ongoing basis. C1 [Ragupathy, Viswanath; Zhao, Jiangqin; Wood, Owen; Tang, Shixing; Lee, Sherwin; Hewlett, Indira] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Nyambi, Phillipe] NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. RP Hewlett, I (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Indira.Hewlett@fda.hhs.gov NR 46 TC 12 Z9 12 U1 0 U2 5 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 APR 23 PY 2011 VL 8 AR 185 DI 10.1186/1743-422X-8-185 PG 11 WC Virology SC Virology GA 780UB UT WOS:000291883700001 PM 21513545 ER PT J AU Telias, A White, JR Pahl, DM Ottesen, AR Walsh, CS AF Telias, Adriana White, James R. Pahl, Donna M. Ottesen, Andrea R. Walsh, Christopher S. TI Bacterial community diversity and variation in spray water sources and the tomato fruit surface SO BMC MICROBIOLOGY LA English DT Article ID AMPLICON PYROSEQUENCING BTEFAP; GRADIENT GEL-ELECTROPHORESIS; MICROBIAL DIVERSITY; PATHOGENIC BACTERIA; RARE BIOSPHERE; DEEP-SEA; PHYLLOSPHERE; ALIGNMENT; PLANTS; MANAGEMENT AB Background: Tomato (Solanum lycopersicum) consumption has been one of the most common causes of produce-associated salmonellosis in the United States. Contamination may originate from animal waste, insects, soil or water. Current guidelines for fresh tomato production recommend the use of potable water for applications coming in direct contact with the fruit, but due to high demand, water from other sources is frequently used. We sought to describe the overall bacterial diversity on the surface of tomato fruit and the effect of two different water sources (ground and surface water) when used for direct crop applications by generating a 454-pyrosequencing 16S rRNA dataset of these different environments. This study represents the first in depth characterization of bacterial communities in the tomato fruit surface and the water sources commonly used in commercial vegetable production. Results: The two water sources tested had a significantly different bacterial composition. Proteobacteria was predominant in groundwater samples, whereas in the significantly more diverse surface water, abundant phyla also included Firmicutes, Actinobacteria and Verrucomicrobia. The fruit surface bacterial communities on tomatoes sprayed with both water sources could not be differentiated using various statistical methods. Both fruit surface environments had a high representation of Gammaproteobacteria, and within this class the genera Pantoea and Enterobacter were the most abundant. Conclusions: Despite the major differences observed in the bacterial composition of ground and surface water, the season long use of these very different water sources did not have a significant impact on the bacterial composition of the tomato fruit surface. This study has provided the first next-generation sequencing database describing the bacterial communities living in the fruit surface of a tomato crop under two different spray water regimes, and therefore represents an important step forward towards the development of science-based metrics for Good Agricultural Practices. C1 [Telias, Adriana; Pahl, Donna M.; Walsh, Christopher S.] Univ Maryland, Plant Sci & Landscape Architecture Dept, Baltimore, MD 21201 USA. [White, James R.] Univ Maryland, Sch Med, Inst Genome Sci, Baltimore, MD 21201 USA. [Ottesen, Andrea R.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Telias, A (reprint author), Univ Maryland, Plant Sci & Landscape Architecture Dept, 2102 Plant Sci Bldg, Baltimore, MD 21201 USA. EM atelias@umd.edu FU JIFSAN (Joint Institute of Food Safety and Applied Nutrition) FX Authors are indebted to Michael Newell and the farm crew at Wye Research and Education Center for their assistance with the tomato field research plots. This work was supported by JIFSAN (Joint Institute of Food Safety and Applied Nutrition) through their competitive grant program. NR 48 TC 23 Z9 24 U1 3 U2 40 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 APR 21 PY 2011 VL 11 AR 81 DI 10.1186/1471-2180-11-81 PG 13 WC Microbiology SC Microbiology GA 774EB UT WOS:000291363000001 PM 21510867 ER PT J AU Volokhov, DV Norris, T Rios, C Davidson, MK Messick, JB Gulland, FM Chizhikov, VE AF Volokhov, Dmitriy V. Norris, Tenaya Rios, Carlos Davidson, Maureen K. Messick, Joanne B. Gulland, Frances M. Chizhikov, Vladimir E. TI Novel hemotrophic mycoplasma identified in naturally infected California sea lions (Zalophus californianus) SO VETERINARY MICROBIOLOGY LA English DT Article DE Hemoplasma; Blood; California sea lions ID ANAPLASMA-PHAGOCYTOPHILUM; UNITED-STATES; HEMOPLASMA; PREVALENCE; CANDIDATUS; CATS; EPERYTHROZOON; HAEMOLAMAE; HAEMOBARTONELLA; ERYTHROCYTES AB The hemoplasmas are the trivial name for a group of erythrocyte-parasitizing, non-cultivable in vitro bacteria of the genus Mycoplasma that have been described in several mammalian hosts worldwide. This study is the first report of hemoplasmas in marine mammals. EDTA anticoagulated whole blood samples from 137 California sea lions (Zalophus cahlornianus) and 20 northern elephant seals (Mirounga angustirostris) admitted to the Marine Mammal Center (Sausalito, CA: www.marinemammalcenter.org) or live captured in Oregon were collected during 2008. Hemoplasma-specific genomic DNA was detected in blood samples from 12.4% California sea lions tested using PCR. Hemoplasma PCR positive blood specimens also were tested in reverse transcription polymerase chain reaction (RT-PCR) using the hemoplasma-specific primers for the 16S and 23S rRNA genes. The RT-PCR showed the presence the hemoplasmal rRNA, strongly suggesting the presence of potentially viable hemoplasmas in the bloodstream of the animals. BLAST search and phylogenetic analysis of the 16S rRNA sequences of the hemoplasma from California sea lions revealed that the organism is a novel hemoplasma species with only 92.1% of its nucleotide similarity to the 16S rRNA gene of the previously described hemoplasma species of alpacas, Candidatus Mycoplasma haemolamae. Thus, due to low level of genetic similarity of the hemoplasma to other described hemoplasmas and the mammalian host in which the hemoplasma was detected we propose that this novel hemoplasma species has been given the provisional name Candidatus Mycoplasma haemozalophi sp. nov. Published by Elsevier B.V. C1 [Volokhov, Dmitriy V.] US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Lab Methods Dev, Rockville, MD 20852 USA. [Norris, Tenaya; Rios, Carlos; Gulland, Frances M.] Marine Mammal Ctr, Sausalito, CA 94965 USA. [Davidson, Maureen K.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Messick, Joanne B.] Purdue Univ, Sch Vet Med, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. RP Volokhov, DV (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Lab Methods Dev, HFM-470,1401 Rockville Pike, Rockville, MD 20852 USA. EM dmitriy.volokhov@fda.hhs.gov OI Norris, Tenaya/0000-0003-1682-7881 NR 30 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD APR 21 PY 2011 VL 149 IS 1-2 BP 262 EP 268 DI 10.1016/j.vetmic.2010.10.026 PG 7 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 743PS UT WOS:000289031600035 PM 21111543 ER PT J AU Lee, H Kashyap, VL van Dyk, DA Connors, A Drake, JJ Izem, R Meng, XL Min, SD Park, T Ratzlaff, P Siemiginowska, A Zezas, A AF Lee, Hyunsook Kashyap, Vinay L. van Dyk, David A. Connors, Alanna Drake, Jeremy J. Izem, Rima Meng, Xiao-Li Min, Shandong Park, Taeyoung Ratzlaff, Pete Siemiginowska, Aneta Zezas, Andreas TI ACCOUNTING FOR CALIBRATION UNCERTAINTIES IN X-RAY ANALYSIS: EFFECTIVE AREAS IN SPECTRAL FITTING SO ASTROPHYSICAL JOURNAL LA English DT Article DE methods: data analysis; methods: statistical; techniques: miscellaneous; X-rays: general ID MULTIPLE-IMPUTATION; SYSTEMATIC-ERRORS; SHERPA; VALUES AB While considerable advance has been made to account for statistical uncertainties in astronomical analyses, systematic instrumental uncertainties have been generally ignored. This can be crucial to a proper interpretation of analysis results because instrumental calibration uncertainty is a form of systematic uncertainty. Ignoring it can underestimate error bars and introduce bias into the fitted values of model parameters. Accounting for such uncertainties currently requires extensive case-specific simulations if using existing analysis packages. Here, we present general statistical methods that incorporate calibration uncertainties into spectral analysis of high-energy data. We first present a method based on multiple imputation that can be applied with any fitting method, but is necessarily approximate. We then describe a more exact Bayesian approach that works in conjunction with a Markov chain Monte Carlo based fitting. We explore methods for improving computational efficiency, and in particular detail a method of summarizing calibration uncertainties with a principal component analysis of samples of plausible calibration files. This method is implemented using recently codified Chandra effective area uncertainties for low-resolution spectral analysis and is verified using both simulated and actual Chandra data. Our procedure for incorporating effective area uncertainty is easily generalized to other types of calibration uncertainties. C1 [Lee, Hyunsook; Kashyap, Vinay L.; Drake, Jeremy J.; Ratzlaff, Pete; Siemiginowska, Aneta] Smithsonian Astrophys Observ, Cambridge, MA 02138 USA. [van Dyk, David A.; Min, Shandong] Univ Calif Irvine, Dept Stat, Irvine, CA 92697 USA. [Connors, Alanna] Eureka Sci, Oakland, CA 94602 USA. [Izem, Rima] US FDA, Ctr Drug Evaluat & Res, Div Biometr, Silver Spring, MD 20903 USA. [Meng, Xiao-Li] Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. [Park, Taeyoung] Yonsei Univ, Dept Appl Stat, Seoul 120749, South Korea. [Zezas, Andreas] IESL, Fdn Res & Technol, Iraklion 71110, Crete, Greece. [Zezas, Andreas] Univ Crete, Dept Phys, Iraklion 71003, Crete, Greece. RP Lee, H (reprint author), Smithsonian Astrophys Observ, 60 Garden St, Cambridge, MA 02138 USA. EM hlee@cfa.harvard.edu; vkashyap@cfa.harvard.edu; dvd@ics.uci.edu; aconnors@eurekabayes.com; jdrake@cfa.harvard.edu; rima.izem@fda.hhs.gov; meng@stat.harvard.edu; shandonm@uci.edu; taeyoung.t.park@gmail.com; rpete@head.cfa.harvard.edu; asiemiginowska@cfa.harvard.edu; azezas@physics.uoc.edu RI Zezas, Andreas/C-7543-2011; OI Zezas, Andreas/0000-0001-8952-676X; Van Dyk, David/0000-0002-0816-331X FU NASA AISRP [NNG06GF17G]; CXC NASA [NAS8-39073]; NSF [DMS 04-06085, DMS 09-07522, DMS-0405953, DMS-0907185] FX This work was supported by NASA AISRP grant NNG06GF17G (H.L., A.C., V.L.K.), and CXC NASA contract NAS8-39073 (V.L.K., A.S., J.J.D., P.R.), NSF grants DMS 04-06085 and DMS 09-07522 (D.v.D., A.C., S.M., T.P.), and NSF grants DMS-0405953 and DMS-0907185 (X.L.M.). We acknowledge useful discussions with Herman Marshall, Alex Blocker, Jonathan McDowell, and Arnold Rots. NR 52 TC 12 Z9 12 U1 0 U2 3 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0004-637X EI 1538-4357 J9 ASTROPHYS J JI Astrophys. J. PD APR 20 PY 2011 VL 731 IS 2 AR 126 DI 10.1088/0004-637X/731/2/126 PG 19 WC Astronomy & Astrophysics SC Astronomy & Astrophysics GA 753MM UT WOS:000289779600049 ER PT J AU Liu, SL Kielian, T AF Liu, Shuliang Kielian, Tammy TI MyD88 is pivotal for immune recognition of Citrobacter koseri and astrocyte activation during CNS infection SO JOURNAL OF NEUROINFLAMMATION LA English DT Article DE MyD88 Toll-like receptor 4 (TLR4); C. koseri; meningitis; brain abscess; astrocyte ID TOLL-LIKE RECEPTOR-4; TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; BRAIN-ABSCESS; INNATE IMMUNITY; STREPTOCOCCUS-PNEUMONIAE; INFLAMMATORY RESPONSES; STAPHYLOCOCCUS-AUREUS; NEONATAL MENINGITIS; MICE AB Citrobacter koseri (C. koseri) is a Gram-negative bacterium that can cause a highly aggressive form of neonatal meningitis, which often progresses to establish multi-focal brain abscesses. The roles of Toll-like receptor 4 (TLR4) and its signaling adaptor MyD88 during CNS C. koseri infection have not yet been examined, which is important since recent evidence indicates that innate immune responses are tailored towards specific pathogen classes. Here TLR4 WT (C3H/FeJ) and TLR4 mutant (C3H/HeJ) mice as well as MyD88 KO animals were infected intracerebrally with live C. koseri, resulting in meningitis and ventriculitis with accompanying brain abscess formation. MyD88 KO mice were exquisitely sensitive to C. koseri, demonstrating enhanced mortality rates and significantly elevated bacterial burdens compared to WT animals. Interestingly, although early proinflammatory mediator release (i.e. 12 h) was MyD88-dependent, a role for MyD88-independent signaling was evident at 24 h, revealing a compensatory response to CNS C. koseri infection. In contrast, TLR4 did not significantly impact bacterial burdens or proinflammatory mediator production in response to C. koseri. Similar findings were obtained with primary astrocytes, where MyD88-dependent pathways were essential for chemokine release in response to intact C. koseri, whereas TLR4 was dispensable; implicating the involvement of alternative TLRs since highly enriched astrocytes did not produce IL-1 upon bacterial exposure, which also signals via MyD88. Collectively, these findings demonstrate the importance of MyD88-dependent mechanisms in eliciting maximal proinflammatory responses, astrocyte activation, and bacterial containment during CNS C. koseri infection, as well as a late-phase MyD88-independent signaling pathway for cytokine/chemokine production. C1 [Kielian, Tammy] Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. [Liu, Shuliang] Univ Arkansas Med Sci, Dept Neurobiol & Dev Sci, Little Rock, AR 72205 USA. [Liu, Shuliang] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Kielian, T (reprint author), Univ Nebraska Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. EM tkielian@unmc.edu RI Liu, Shuliang/J-4696-2014 FU NIH National Institute of Neurological Disorders and Stroke (NINDS) [R01NS055385]; UAMS Graduate School FX The authors thank Dr. Charles Kuszynski, Megan Michalak, and Victoria Smith in the UNMC Cell Analysis Facility for assistance with FACS analysis, Teresa Fritz for performing immunostaining techniques, Amanda Angle for mouse colony maintenance, Debbie Vidlak for performing the Milliplex microbead arrays, and Ms. Kari Nelson for grammatical review of the manuscript. This work was supported by the NIH National Institute of Neurological Disorders and Stroke (NINDS) [R01NS055385] to T. K. Shuliang Liu was the recipient of a GSRF award from the UAMS Graduate School. NR 54 TC 10 Z9 12 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD APR 16 PY 2011 VL 8 AR 35 DI 10.1186/1742-2094-8-35 PG 14 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 768MA UT WOS:000290937600001 PM 21496301 ER PT J AU Ackerman, LK Noonan, GO AF Ackerman, Luke K. Noonan, Gregory O. TI Comment on "Bisphenol A (BPA) in U.S. Food" SO ENVIRONMENTAL SCIENCE & TECHNOLOGY LA English DT Letter ID CANADIAN MARKETS; PRODUCTS C1 [Ackerman, Luke K.; Noonan, Gregory O.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Ackerman, LK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RI Ackerman, Luke/E-4597-2011 OI Ackerman, Luke/0000-0001-6626-3039 NR 11 TC 0 Z9 0 U1 0 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0013-936X J9 ENVIRON SCI TECHNOL JI Environ. Sci. Technol. PD APR 15 PY 2011 VL 45 IS 8 BP 3812 EP 3813 DI 10.1021/es2002869 PG 2 WC Engineering, Environmental; Environmental Sciences SC Engineering; Environmental Sciences & Ecology GA 747SZ UT WOS:000289341300087 PM 21428397 ER PT J AU Cacciola, F Delmonte, P Jaworska, K Dugo, P Mondello, L Rader, JI AF Cacciola, Francesco Delmonte, Pierluigi Jaworska, Karolina Dugo, Paola Mondello, Luigi Rader, Jeanne I. TI Employing ultra high pressure liquid chromatography as the second dimension in a comprehensive two-dimensional system for analysis of Stevia rebaudiana extracts SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Stevia rebaudiana; Comprehensive LC; UHPLC column; Glycosides ID GRADIENT ELUTION; PEAK-CAPACITY; IN-VITRO; SEPARATION; PERFORMANCE; BERTONI; COLUMN; GLYCOSIDES; LEAVES; ANTIOXIDANTS AB Stevia rebaudiana extracts and plant materials are increasingly used as natural sweeteners. Polyphenolic and stevioside compounds contained in S. rebaudiana extracts were separated by comprehensive LC. A polyamine column operated in normal phase mode was used for the first dimension separation (D1), and a UHPLC C18 column operated in reversed phase mode was used for the second dimension separation (D2). The sub-2 mu m column (2.1 mm x 30 mm, maintained at 70 degrees C) and the UHPLC pump employed for D2 elution allowed a separation/cycle time of 20s, with a backpressure oscillating between 805 and 922 bar at 3.4 mL/min. The reduced D2 cycle time allowed 3-12 D2 samplings for each peak eluted by D1. Polyphenolic and stevioside compounds were identified by combining the information coming from the position of the compounds in the 2D plot and UV spectra with that of reference materials. (C) 2010 Elsevier B.V. All rights reserved. C1 [Cacciola, Francesco; Dugo, Paola; Mondello, Luigi] Univ Messina, Dipartimento Farmacochim, Fac Farm, I-98168 Messina, Italy. [Cacciola, Francesco; Delmonte, Pierluigi; Jaworska, Karolina; Rader, Jeanne I.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Cacciola, F (reprint author), Univ Messina, Dipartimento Farmacochim, Fac Farm, Viale Annunziata, I-98168 Messina, Italy. EM fcacciola@pharma.unime.it RI Mondello, Luigi/C-6891-2008; OI Mondello, Luigi/0000-0002-8890-675X; Dugo, Paola/0000-0002-9432-1782; Cacciola, Francesco/0000-0003-1296-7633 NR 43 TC 47 Z9 50 U1 4 U2 31 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 EI 1873-3778 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 15 PY 2011 VL 1218 IS 15 BP 2012 EP 2018 DI 10.1016/j.chroma.2010.08.081 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 747PF UT WOS:000289331200012 PM 20883998 ER PT J AU Degheidy, HA Venzon, D Farooqui, M Abbasi, F Arthur, D Wiestner, A Stetler-Stevenson, M Gerald, M AF Degheidy, Heba A. Venzon, David Farooqui, Mohammed Abbasi, Fatima Arthur, Diane Wiestner, Adrian Stetler-Stevenson, Maryalice Gerald, Marti TI Improved ZAP-70 assay using two clones: Multiple methods of analysis, and a scoring system SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Degheidy, Heba A.; Abbasi, Fatima; Gerald, Marti] US FDA, CBER, Bethesda, MD 20014 USA. [Venzon, David] NCI, Biostatistc & Data Management, Bethesda, MD 20892 USA. [Farooqui, Mohammed; Wiestner, Adrian] NHLBI, NIH, Bethesda, MD 20892 USA. [Arthur, Diane; Stetler-Stevenson, Maryalice] NCI, Pathol Lab, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA 5080 DI 10.1158/1538-7445.AM2011-5080 PG 1 WC Oncology SC Oncology GA V43SP UT WOS:000209701405060 ER PT J AU Joshi, BH Leland, P Puri, RK AF Joshi, Bharat H. Leland, Pamela Puri, Raj K. TI Identification of interleukin 4 receptor alpha (IL-4R alpha) as a biomarker of advanced stage human bladder carcinoma SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Joshi, Bharat H.; Leland, Pamela; Puri, Raj K.] US FDA, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA 1663 DI 10.1158/1538-7445.AM2011-1663 PG 1 WC Oncology SC Oncology GA V43SP UT WOS:000209701401077 ER PT J AU Kang, ZG Chen, JJ Yu, YK Zhang, BL Cao, L AF Kang, Zhigang Chen, Junjie Yu, Yunkai Zhang, Baolin Cao, Liang TI A human antibody to death receptor 5 has potent antitumor activity against rhabdomyosarcoma with the expression of caspase-8 predictive of response SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Kang, Zhigang; Yu, Yunkai; Cao, Liang] NCI, Bethesda, MD 20892 USA. [Chen, Junjie; Zhang, Baolin] US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA 4094 DI 10.1158/1538-7445.AM2011-4094 PG 1 WC Oncology SC Oncology GA V43SP UT WOS:000209701402066 ER PT J AU Lyn-Cook, B Mohammed, S Word, B Hammons, G AF Lyn-Cook, Beverly Mohammed, Sulma Word, Beverly Hammons, George TI Indole-3-carbinol (I3C) and gemcitabine as potential combinatorial therapy in pancreatic cancer SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Lyn-Cook, Beverly; Word, Beverly; Hammons, George] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Mohammed, Sulma] Purdue Univ, W Lafayette, IN 47907 USA. [Mohammed, Sulma] Purdue Univ, Canc Res Ctr, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA 2556 DI 10.1158/1538-7445.AM2011-2556 PG 1 WC Oncology SC Oncology GA V43SP UT WOS:000209701401236 ER PT J AU Muchmore, B Park, H Dickensheets, H O'Brien, T Rehermann, B Donnelly, R Prokunina-Olsson, L AF Muchmore, Brian Park, Heiyoung Dickensheets, Harold O'Brien, Thomas Rehermann, Barbara Donnelly, Raymond Prokunina-Olsson, Ludmila TI Expression analysis of the IL28A, IL28B, IL29 and IL28L genes in primary human peripheral blood mononuclear cells and hepatocytes: Effects of activation mode, time-course and genotypes SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Muchmore, Brian; Prokunina-Olsson, Ludmila] NCI, Lab Translat Genom, DCEG, NIH, Gaithersburg, MD USA. [Park, Heiyoung; Rehermann, Barbara] NIDDK, Immunol Sect, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Dickensheets, Harold; Donnelly, Raymond] US FDA, Div Therapeut Prot, CDER, Bethesda, MD 20014 USA. [O'Brien, Thomas] NCI, Infect & Immunoepidemiol Branch, DCEG, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA 3751 DI 10.1158/1538-7445.AM2011-3751 PG 2 WC Oncology SC Oncology GA V43SO UT WOS:000209701305068 ER PT J AU Nakashima, H Joshi, BH Husain, SR Puri, RK AF Nakashima, Hideyuki Joshi, Bharat H. Husain, Syed R. Puri, Raj K. TI A novel combination therapeutic approach for targeting murine cancers with IL-13 receptor alpha 2 DNA vaccine and an immunotoxin SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Nakashima, Hideyuki; Joshi, Bharat H.; Husain, Syed R.; Puri, Raj K.] US FDA, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA 1794 DI 10.1158/1538-7445.AM2011-1794 PG 2 WC Oncology SC Oncology GA V43SO UT WOS:000209701302170 ER PT J AU Shpyleva, SI Muskhelishvili, L Tryndyak, V Beland, FA Pogribny, I AF Shpyleva, Svitlana I. Muskhelishvili, Levan Tryndyak, Volodymyr Beland, Frederick A. Pogribny, Igor TI Role of the aberrant intracellular iron metabolism in rat liver carcinogenesis SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Shpyleva, Svitlana I.; Tryndyak, Volodymyr; Beland, Frederick A.; Pogribny, Igor] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Muskhelishvili, Levan] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA 5556 DI 10.1158/1538-7445.AM2011-5556 PG 2 WC Oncology SC Oncology GA V43SO UT WOS:000209701305313 ER PT J AU Simpson, NE Tryndyak, VP Beland, FA Pogribny, IP AF Simpson, Natalie E. Tryndyak, Volodymyr P. Beland, Frederick A. Pogribny, Igor P. TI An in vitro investigation of metabolically sensitive epigenetic biomarkers in breast cancer progression SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Simpson, Natalie E.; Tryndyak, Volodymyr P.; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA 3021 DI 10.1158/1538-7445.AM2011-3021 PG 1 WC Oncology SC Oncology GA V43SP UT WOS:000209701403086 ER PT J AU Tryndyak, VP Beland, FA Pogribny, IP AF Tryndyak, Volodymyr P. Beland, Frederick A. Pogribny, Igor P. TI Over-expression of microRNA-221 causes neoplastic cell transformation through induction of the epithelial-mesenchymal transition in non-tumorigenic liver cells SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Tryndyak, Volodymyr P.; Beland, Frederick A.; Pogribny, Igor P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA 120 DI 10.1158/1538-7445.AM2011-120 PG 1 WC Oncology SC Oncology GA V43SP UT WOS:000209701404043 ER PT J AU Wang, HG Word, B Lyn-Cook, B AF Wang, Honggang Word, Beverly Lyn-Cook, Berverly TI Upregulation of the human equilibrative nucleoside transporter 1 (hENT1) expression by indole-3-carbinol (I3C) in pancreatic cancer cell lines SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wang, Honggang; Word, Beverly; Lyn-Cook, Berverly] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA 704 DI 10.1158/1538-7445.AM2011-704 PG 1 WC Oncology SC Oncology GA V43SO UT WOS:000209701300332 ER PT J AU Wang, YY Myers, MB Meng, FX McKinzie, PB Mckim, KL Parsons, BL AF Wang, Yiying Myers, Meagan B. Meng, Fanxue McKinzie, Page B. McKim, Karen L. Parsons, Barbara L. TI ACB-PCR quantification of PIK3CA codon 1047 CAT to CGT mutant fraction in human tumor and non-tumor tissues SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Wang, Yiying; Myers, Meagan B.; Meng, Fanxue; McKinzie, Page B.; McKim, Karen L.; Parsons, Barbara L.] US FDA, NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA 3179 DI 10.1158/1538-7445.AM2011-3179 PG 1 WC Oncology SC Oncology GA V43SP UT WOS:000209701404403 ER PT J AU Yu, LR Li, ZG Gao, Y Chen, T AF Yu, Li-Rong Li, Zhiguang Gao, Yuan Chen, Tao TI Proteomic analysis of aristolochic acid-induced nephrotoxicity in rats SO CANCER RESEARCH LA English DT Meeting Abstract C1 [Yu, Li-Rong; Li, Zhiguang; Gao, Yuan; Chen, Tao] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 EI 1538-7445 J9 CANCER RES JI Cancer Res. PD APR 15 PY 2011 VL 71 SU 8 MA LB-438 DI 10.1158/1538-7445.AM2011-LB-438 PG 2 WC Oncology SC Oncology GA V43SO UT WOS:000209701305398 ER PT J AU Sakamoto, N Rosenberg, AS AF Sakamoto, Norihisa Rosenberg, Amy S. TI Apolipoprotein B Binding Domains: Evidence That They Are Cell-Penetrating Peptides That Efficiently Deliver Antigenic Peptide for Cross-Presentation of Cytotoxic T Cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; PROTEIN TRANSDUCTION DOMAINS; DENDRITIC CELLS; RECEPTOR-ACTIVITY; HEPARAN-SULFATE; TUMOR ESCAPE; IN-VIVO; B-100; SURFACE; PROTEOGLYCANS AB Low-density lipoproteins (LDLs) are a good source of cholesterol, which is important in cellular homeostasis and production of steroids. Apolipoprotein B-100 (ApoB-100), the sole protein component of LDL, is known to bind to cell surface LDL receptor (LDLR) or cell surface-bound proteoglycans and to be internalized into cells. We found that APCs, consisting of macrophages and dendritic cells, upregulate LDLR on culture in vitro without obvious stimulation. In contrast, T cell populations only upregulate LDLR on activation. Thus, we strategized that tagging immunogens to ApoB-100 might be a useful means to target Ag to APCs. We generated fusion proteins consisting of receptor binding sites in ApoB-100, coupled to OVA peptide (ApoB-OVA), as Ag delivery vehicles and demonstrated that this novel delivery method successfully cross-presented OVA peptides in eliciting CTL responses. Surprisingly, internalization of ApoB-OVA peptide occurred via cell surface proteoglycans rather than LDLRs, consistent with evidence that structural elements of ApoB-100 indicate it to have cell-penetrating peptide properties. Finally, we used this strategy to assess therapeutic vaccination in a tumor setting. OVA-expressing EL-4 tumors grew progressively in mice immunized with ApoB-100 alone but regressed in mice immunized with ApoB-OVA fusion protein, coinciding with development of OVA-specific CTLs. Thus, to our knowledge, this is the first article to describe the cell-penetrating properties of a conserved human origin cell penetrating peptide that may be harnessed as a novel vaccination strategy as well as a therapeutics delivery device. The Journal of Immunology, 2011, 186: 5004-5011. C1 [Sakamoto, Norihisa; Rosenberg, Amy S.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Sakamoto, N (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM norihisa.sakamoto@fda.hhs.gov NR 52 TC 2 Z9 2 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2011 VL 186 IS 8 BP 5004 EP 5011 DI 10.4049/jimmunol.1003557 PG 8 WC Immunology SC Immunology GA 744FY UT WOS:000289081500052 PM 21402897 ER PT J AU Rappaport, B Mellon, RD Simone, A Woodcock, J AF Rappaport, Bob Mellon, R. Daniel Simone, Arthur Woodcock, Janet TI Defining Safe Use of Anesthesia in Children SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID COHORT C1 [Rappaport, Bob; Mellon, R. Daniel; Simone, Arthur] US FDA, Off New Drugs, Div Anesthesia & Analgesia Prod, Silver Spring, MD 20993 USA. [Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Rappaport, B (reprint author), US FDA, Off New Drugs, Div Anesthesia & Analgesia Prod, Silver Spring, MD 20993 USA. NR 5 TC 85 Z9 88 U1 0 U2 2 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 14 PY 2011 VL 364 IS 15 BP 1387 EP 1390 DI 10.1056/NEJMp1102155 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 749LD UT WOS:000289467200002 PM 21388302 ER PT J AU Andersen, WC Turnipseed, SB Karbiwnyk, CM Evans, E Hasbrouck, N Mayer, TD Gieseker, CM Nochetto, C Stine, CB Reimschuessel, R AF Andersen, Wendy C. Turnipseed, Sherri B. Karbiwnyk, Christine M. Evans, Eric Hasbrouck, Nicholas Mayer, Tamara D. Gieseker, Charles M. Nochetto, Cristina Stine, Cynthia B. Reimschuessel, Renate TI Bioaccumulation of Melamine in Catfish Muscle Following Continuous, Low-Dose, Oral Administration SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE melamine; cyanuric acid; fish; dosing study ID CYANURIC ACID; RESIDUE DEPLETION; CONTAMINATED FEED; LAYING HENS; PET FOOD; TOXICITY; TISSUES; CATS; EGGS; NEPHROTOXICITY AB In this study, catfish muscle was analyzed for melamine (MEL) and cyanuric acid (CYA) residues following experimental feeding with low doses of MEL and MEL and CYA (MEL+CYA) and with the insoluble melamine cyanurate complex (MEL=CYA). Catfish were daily fed 0.1 mg/kg BW of MEL for 15, 28, or 42 days, 0.1 mg/kg BW of MEL+CYA for 28 days, 2.5 mg/kg BW of MEL+CYA for 14 days, or 400 mg/kg BW of MEL=CYA for 3 days. Residues in the tissue were determined by LC-MS/MS. MEL was extracted with acidic acetonitrile, followed by defatting with dichloromethane, and isolated with cation exchange solid phase extraction (SPE). For CYA analysis, fish were extracted with dilute acetic acid, defatted with hexane, and cleaned up with a graphitic carbon SPE. Catfish fed 0.1 mg/kg BW of MEL reached a maximum muscle residue concentration of 0.33 +/- 0.04 mg/kg (ppm) after 28 days of continuous feeding. The same concentration was found for MEL+CYA feeding at the 0.1 mg/kg BW level for 28 days. Feeding at 2.5 mg/kg BW of MEL+CYA yielded muscle concentrations above the 2.5 mg/kg level of concern for most of the study fish. Finally, catfish fed high levels of the MEL=CYA complex (400 mg/kg BW) accumulated relatively little MEL in the muscle (0.14 +/- 0.07 mg/kg) and, unlike treatment with MEL+CYA, did not form renal melamine-cyanurate crystals. Appreciable concentrations of CYA were not detected in any of the muscles tested. These studies provide data to model the bioaccumulation of triazine residues into edible fish tissue as a result of the continuous consumption of adulterated feed. C1 [Evans, Eric; Hasbrouck, Nicholas; Mayer, Tamara D.; Gieseker, Charles M.; Nochetto, Cristina; Stine, Cynthia B.; Reimschuessel, Renate] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Andersen, Wendy C.; Turnipseed, Sherri B.; Karbiwnyk, Christine M.] US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. RP Reimschuessel, R (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM renate.reimschuessel@fda.hhs.gov RI Stine, Cynthia/F-1040-2011 NR 49 TC 5 Z9 5 U1 0 U2 5 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 APR 13 PY 2011 VL 59 IS 7 SI SI BP 3111 EP 3117 DI 10.1021/jf104385d PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 743WQ UT WOS:000289050400049 PM 21341666 ER PT J AU Pine, PS Rosenzweig, BA Thompson, KL AF Pine, P. Scott Rosenzweig, Barry A. Thompson, Karol L. TI An adaptable method using human mixed tissue ratiometric controls for benchmarking performance on gene expression microarrays in clinical laboratories SO BMC BIOTECHNOLOGY LA English DT Article ID RNA REFERENCE SAMPLES; ART. NO. 3; QUALITY; REPRODUCIBILITY; AMPLIFICATION; VALIDATION; SIGNATURE; STANDARDS; ACCURACY; SYSTEMS AB Background: Molecular biomarkers that are based on mRNA transcripts are being developed for the diagnosis and treatment of a number of diseases. DNA microarrays are one of the primary technologies being used to develop classifiers from gene expression data for clinically relevant outcomes. Microarray assays are highly multiplexed measures of comparative gene expression but have a limited dynamic range of measurement and show compression in fold change detection. To increase the clinical utility of microarrays, assay controls are needed that benchmark performance using metrics that are relevant to the analysis of genomic data generated with biological samples. Results: Ratiometric controls were prepared from commercial sources of high quality RNA from human tissues with distinctly different expression profiles and mixed in defined ratios. The samples were processed using six different target labeling protocols and replicate datasets were generated on high density gene expression microarrays. The area under the curve from receiver operating characteristic plots was calculated to measure diagnostic performance. The reliable region of the dynamic range was derived from log(2) ratio deviation plots made for each dataset. Small but statistically significant differences in diagnostic performance were observed between standardized assays available from the array manufacturer and alternative methods for target generation. Assay performance using the reliable range of comparative measurement as a metric was improved by adjusting sample hybridization conditions for one commercial kit. Conclusions: Process improvement in microarray assay performance was demonstrated using samples prepared from commercially available materials and two metrics - diagnostic performance and the reliable range of measurement. These methods have advantages over approaches that use a limited set of external controls or correlations to reference sets, because they provide benchmark values that can be used by clinical laboratories to help optimize protocol conditions and laboratory proficiency with microarray assays. C1 [Pine, P. Scott; Rosenzweig, Barry A.; Thompson, Karol L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Pine, P. Scott] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. RP Thompson, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM karol.thompson@fda.hhs.gov RI Sanders, Susan/G-1957-2011 FU CDER FX This project was funded in part by the CDER Regulatory Science and Review Enhancement program. 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 26 TC 4 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PD APR 12 PY 2011 VL 11 AR 38 DI 10.1186/1472-6750-11-38 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 769NB UT WOS:000291020900001 PM 21486464 ER PT J AU Murata, H Macauley, J Lewis, AM Peden, K AF Murata, Haruhiko Macauley, Juliete Lewis, Andrew M., Jr. Peden, Keith TI Plaque purification as a method to mitigate the risk of adventitious-agent contamination in influenza vaccine virus seeds SO VACCINE LA English DT Article DE Influenza vaccine; Seed virus; Plaque purification; Adventitious agent ID EMBRYONATED CHICKEN EGGS; CANINE KIDNEY-CELLS; HYBRID VIRUSES; MDCK CELLS; A VIRUSES; HEMAGGLUTININ; VERO; SV40; GENERATION; VARIANTS AB At present, the seed viruses for the manufacture of licensed seasonal inactivated influenza vaccines in the United States are derived from primary egg isolates as a result of concerns associated with adventitious agents. According to the prevailing view, the passage of influenza viruses through eggs serves as a filtering step to remove potential contaminating viruses. We have investigated the feasibility of addressing adventitious-agent risk by subjecting influenza virus to a plaque-purification procedure using MDCK cells. SV40 and canine adenovirus-1 (representing viruses for which MOCK cells are non-permissive and permissive, respectively) were used as challenge viruses to model agents of concern that might be co-isolated along with the influenza virus. By mixing influenza virus strain A/PR/8/34 with varying amounts of each challenge virus and then performing a plaque assay for influenza virus using MDCK cells, we have attempted to determine the efficiency by which the challenge virus is removed. Our data suggest that substantial removal can be achieved even after a single round of plaque purification. If cell-derived isolates were deemed to be acceptable following a plaque-purification procedure, the manufacture of seasonal influenza vaccine would be facilitated by: (1) the expansion of the repertoire of viruses from which seed virus candidates could be generated for licensed egg-derived vaccines as well as for vaccines manufactured in mammalian cells; and (2) the mitigation of adventitious-agent risk associated with the seed virus, and hence the elimination of the need to passage seed viruses in eggs for vaccines manufactured in mammalian cells. Published by Elsevier Ltd. C1 [Murata, Haruhiko; Macauley, Juliete; Lewis, Andrew M., Jr.; Peden, Keith] US FDA, Lab DNA Viruses, Div Viral Prod, CBER, Bethesda, MD 20892 USA. RP Murata, H (reprint author), US FDA, Lab DNA Viruses, Div Viral Prod, CBER, Bldg 29A,Room 1A01,29 Lincoln Dr, Bethesda, MD 20892 USA. EM haruhiko.murata@fda.hhs.gov FU Division of Microbiology and Infectious Diseases, NIAID, NIH [YI-AI-4893-02NIAID] FX We thank Judy Beeler, Maryna Eichelberger, Hana Golding, and Jerry Weir for comments on the manuscript. We thank Zhiping Ye, Xing Li, and Jackeline Soto for sharing reagents and expertise. This study was funded in part by a contract from the Division of Microbiology and Infectious Diseases, NIAID, NIH (YI-AI-4893-02NIAID). NR 29 TC 3 Z9 3 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 12 PY 2011 VL 29 IS 17 BP 3155 EP 3161 DI 10.1016/j.vaccine.2011.02.041 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 764BJ UT WOS:000290603100012 PM 21354480 ER PT J AU Fujisawa, T Joshi, BH Puri, RK AF Fujisawa, Toshio Joshi, Bharat H. Puri, Raj K. TI Histone modification enhances the effectiveness of IL-13 receptor targeted immunotoxin in murine models of human pancreatic cancer SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID SUBEROYLANILIDE HYDROXAMIC ACID; CHIMERIC FUSION PROTEINS; INTERLEUKIN-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; DEACETYLASE INHIBITORS; ALPHA-2 CHAIN; ANTITUMOR-ACTIVITY; MALIGNANT GLIOMA; CARCINOMA-CELLS; IN-VIVO AB Background: Interleukin-13 Receptor alpha 2 (IL-13R alpha 2) is a tumor-associated antigen and target for cancer therapy. Since IL-13R alpha 2 is heterogeneously overexpressed in a variety of human cancers, it would be highly desirable to uniformly upregulate IL-13R alpha 2 expression in tumors for optimal targeting. Methods: We examined epigenetic regulation of IL-13R alpha 2 in a murine model of human pancreatic cancer by Bisulfite-PCR, sequencing for DNA methylation and chromatin immunoprecipitation for histone modification. Reverse transcription-PCR was performed for examining changes in IL-13R alpha 2 mRNA expression after treatment with histone deacetylase (HDAC) and c-jun inhibitors. In vitro cytotoxicity assays and in vivo testing in animal tumor models were performed to determine whether HDAC inhibitors could enhance anti-tumor effects of IL-13-PE in pancreatic cancer. Mice harboring subcutaneous tumors were treated with HDAC inhibitors systemically and IL-13-PE intratumorally. Results: We found that CpG sites in IL-13R alpha 2 promoter region were not methylated in all pancreatic cancer cell lines studied including IL-13R alpha 2-positive and IL-13R alpha 2-negative cell lines and normal cells. On the other hand, histones at IL-13R alpha 2 promoter region were highly-acetylated in IL-13R alpha 2-positive but much less in receptor-negative pancreatic cancer cell lines. When cells were treated with HDAC inhibitors, not only histone acetylation but also IL-13R alpha 2 expression was dramatically enhanced in receptor-negative pancreatic cancer cells. In contrast, HDAC inhibition did not increase IL-13R alpha 2 in normal cell lines. In addition, c-jun in IL-13R alpha 2-positive cells was expressed at higher level than in negative cells. Two types of c-jun inhibitors prevented increase of IL-13R alpha 2 by HDAC inhibitors. HDAC inhibitors dramatically sensitized cancer cells to immunotoxin in the cytotoxicity assay in vitro and increased IL-13R alpha 2 in the tumors subcutaneously implanted in the immunodeficient animals but not in normal mice tissues. Combination therapy with HDAC inhibitors and immunotoxin synergistically inhibited growth of not only IL-13R alpha 2-positive but also IL-13R alpha 2-negative tumors. Conclusions: We have identified a novel function of histone modification in the regulation of IL-13R alpha 2 in pancreatic cancer cell lines in vitro and in vivo. HDAC inhibition provides a novel opportunity in designing combinatorial therapeutic approaches not only in combination with IL-13-PE but with other immunotoxins for therapy of pancreatic cancer and other cancers. C1 [Fujisawa, Toshio; Joshi, Bharat H.; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM raj.puri@fda.hhs.gov NR 34 TC 14 Z9 15 U1 0 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD APR 8 PY 2011 VL 9 AR 37 DI 10.1186/1479-5876-9-37 PG 13 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 765LU UT WOS:000290708600001 PM 21477288 ER PT J AU Akkoyunlu, M AF Akkoyunlu, Mustafa TI Detection of naturally occurring antibodies against Protein D of Haemophilus influenzae SO VACCINE LA English DT Letter C1 US FDA, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20852 USA. RP Akkoyunlu, M (reprint author), US FDA, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20852 USA. EM mustafa.akkoyunlu@fda.hhs.gov RI Akkoyunlu, Mustafa/I-5712-2012 NR 4 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 5 PY 2011 VL 29 IS 16 BP 2834 EP 2834 DI 10.1016/j.vaccine.2011.01.073 PG 1 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 757CU UT WOS:000290062700002 PM 21292006 ER PT J AU Rubin, SA Afzal, MA AF Rubin, S. A. Afzal, M. A. TI Neurovirulence safety testing of mumps vaccines-Historical perspective and current status SO VACCINE LA English DT Review DE Mumps; Vaccine; Neurovirulence; Safety; Monkeys ID CENTRAL-NERVOUS-SYSTEM; ASEPTIC-MENINGITIS; RUBELLA VACCINE; VIRUS NEUROVIRULENCE; MASS VACCINATION; MOUSE-BRAIN; IN-VIVO; STRAINS; MEASLES; CHILDREN AB Many live, attenuated viral vaccines are derived from wild type viruses with known neurovirulent properties. To assure the absence of residual neurotoxicity, pre-clinical neurovirulence safety testing of candidate vaccines is performed. For mumps virus, a highly neurotropic virus, neurovirulence safety testing is performed in monkeys. However, laboratory studies suggest an inability of this test to correctly discern among virus strains of varying neurovirulence potential in man, and, further, some vaccines found to be neuroattenuated in monkeys were later found to be neurovirulent in humans when administered in large numbers. Over the past decade, concerted efforts have been made to replace monkey-based neurovirulence safety testing with more informative, alternative methods. This review summarizes the current status of mumps vaccine neurovirulence safety testing and insights into models currently approved and those under development. Published by Elsevier Ltd. C1 [Rubin, S. A.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Afzal, M. A.] Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. RP Rubin, SA (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM steven.rubin@fda.hhs.gov FU National Vaccine Program Office; Center for Biologics Evaluation and Research; U.S. Department of Energy; U.S. Food and Drug Administration FX This work was supported in part by a grant from the National Vaccine Program Office and in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 72 TC 5 Z9 6 U1 3 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 5 PY 2011 VL 29 IS 16 BP 2850 EP 2855 DI 10.1016/j.vaccine.2011.02.005 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 757CU UT WOS:000290062700007 PM 21334386 ER PT J AU Derrick, SC Yabe, IM Yang, A Morris, SL AF Derrick, Steven C. Yabe, Idalia M. Yang, Amy Morris, Sheldon L. TI Vaccine-induced anti-tuberculosis protective immunity in mice correlates with the magnitude and quality of multifunctional CD4 T cells SO VACCINE LA English DT Article DE Tuberculosis; Cytokines; BCG; Vaccine ID BACILLUS-CALMETTE-GUERIN; MYCOBACTERIUM-BOVIS BCG; TUBERCULOSIS VACCINE; CYTOKINE; MEMORY; INFECTION; PROTEIN; IMMUNOGENICITY; CHALLENGE; MVA85A AB The development of improved vaccines against Mycobacterium tuberculosis has been hindered by a limited understanding of the immune correlates of anti-tuberculosis protective immunity. In this study, we examined the relationship between long-term anti-tuberculosis protection and the mycobacterial-specific CD4 multifunctional T (MFT) cell responses induced by five different TB vaccines (live-attenuated, subunit, viral vectored, plasmid DNA, and combination vaccines) in a mouse model of pulmonary tuberculosis. In a 14-month experiment, we showed that TB vaccine-induced CD4 T cell responses were heterogenous. Antigen-specific monofunctional CD4 T cells expressing single cytokines and MFT CD4 T cells expressing multiple cytokines (IFN-gamma and TNF-alpha, IFN-gamma and IFN-gamma, TNF-alpha, and IL-2, and all three cytokines) were identified after the immunizations. Interestingly, compared to the monofunctional cells, significantly higher median fluorescent intensities (MFIs) for IFN-gamma and TNF-alpha were detected for triple-positive MFT CD4 T cells induced by the most protective vaccines while modest differences in relative MFI values were seen for the less protective preparations. Most importantly during the 14-month study, the levels of vaccine-induced pulmonary and splenic protective immunity correlated with the frequency and the integrated MFI (iMFI, frequency x MFI) values of triple-positive CD4 T cells that were induced by the same vaccines. These data support efforts to use MFT cell analyses as a measure of TB vaccine immunogenicity in human immunization studies. Published by Elsevier Ltd. C1 [Derrick, Steven C.; Yabe, Idalia M.; Yang, Amy; Morris, Sheldon L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Morris, SL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bldg 29,Room 502,CBER FDA,29 Lincoln Dr, Bethesda, MD 20892 USA. EM sheldon.morris@fda.hhs.gov RI Rivet, Catherine/M-7978-2014 NR 32 TC 59 Z9 61 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 APR 5 PY 2011 VL 29 IS 16 BP 2902 EP 2909 DI 10.1016/j.vaccine.2011.02.010 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 757CU UT WOS:000290062700014 PM 21338678 ER PT J AU Konduru, K Bradfute, SB Jacques, J Manangeeswaran, M Nakamura, S Morshed, S Wood, SC Bavari, S Kaplan, GG AF Konduru, Krishnamurthy Bradfute, Steven B. Jacques, Jerome Manangeeswaran, Mohanraj Nakamura, Siham Morshed, Sufi Wood, Steven C. Bavari, Sina Kaplan, Gerardo G. TI Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice SO VACCINE LA English DT Article DE Filoviridae; Glycoprotein; Fc fusion protein; Vaccine; Mouse model; Zaire Ebola virus; Neutralizing antibodies; T-cell immunity; Interferon-gamma ID ATTENUATED RECOMBINANT VACCINE; VESICULAR STOMATITIS VIRUSES; T-CELL RESPONSES; NONHUMAN-PRIMATES; MARBURG VIRUS; HEMORRHAGIC-FEVER; GUINEA-PIGS; POSTEXPOSURE PROTECTION; PARTICLES PROTECT; INFECTION AB Ebola virus is a Filoviridae that causes hemorrhagic fever in humans and induces high morbidity and mortality rates. Filoviruses are classified as "Category A bioterrorism agents", and currently there are no licensed therapeutics or vaccines to treat and prevent infection. The Filovirus glycoprotein (GP) is sufficient to protect individuals against infection, and several vaccines based on GP are under development including recombinant adenovirus, parainfluenza virus, Venezuelan equine encephalitis virus, vesicular stomatitis virus (VSV) and virus-like particles. Here we describe the development of a GP Fc fusion protein as a vaccine candidate. We expressed the extracellular domain of the Zaire Ebola virus (ZEBOV) GP fused to the Fc fragment of human IgG1 (ZEBOVGP-Fc) in mammalian cells and showed that GP undergoes the complex furin cleavage and processing observed in the native membrane-bound GP. Mice immunized with ZEBOVGP-Fc developed T-cell immunity against ZEBOV GP and neutralizing antibodies against replication-competent VSV-G deleted recombinant VSV containing ZEBOV GP. The ZEBOVGP-Fc vaccinated mice were protected against challenge with a lethal dose of ZEBOV. These results show that vaccination with the ZEBOVGP-Fc fusion protein alone without the need of a viral vector or assembly into virus-like particles is sufficient to induce protective immunity against ZEBOV in mice. Our data suggested that Filovirus GP Fc fusion proteins could be developed as a simple, safe, efficacious, and cost effective vaccine against Filovirus infection for human use. Published by Elsevier Ltd. C1 [Konduru, Krishnamurthy; Jacques, Jerome; Manangeeswaran, Mohanraj; Nakamura, Siham; Morshed, Sufi; Kaplan, Gerardo G.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Wood, Steven C.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Bradfute, Steven B.; Bavari, Sina] USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. RP Kaplan, GG (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM gk@helix.nih.gov FU CBER/FDA - NIAID/NIH [Y1-AI-6153-01, Y1-AI-0664-01]; Biomedical Advanced Research and Development Authority (BARDA); Food and Drug Administration; USAMRIID FX This work was supported by CBER/FDA - NIAID/NIH Interagency Agreements Y1-AI-6153-01 and Y1-AI-0664-01, grants from the Biomedical Advanced Research and Development Authority (BARDA) to GGK, intramural funding from the Food and Drug Administration to GGK, and USAMRIID to SB. This article reflects the views of the author and should not be construed to represent FDA's views or policies. NR 50 TC 24 Z9 28 U1 0 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD APR 5 PY 2011 VL 29 IS 16 BP 2968 EP 2977 DI 10.1016/j.vaccine.2011.01.113 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 757CU UT WOS:000290062700022 PM 21329775 ER PT J AU Li, XA Arzhantsev, S Kauffman, JF Spencer, JA AF Li, Xiang Arzhantsev, Sergey Kauffman, John F. Spencer, John A. TI Detection of diethylene glycol adulteration in propylene glycol-Method validation through a multi-instrument collaborative study SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Near infrared transmission; Propylene glycol; Diethylene glycol; Partial least squares; Hand-held instruments AB Four portable NIR instruments from the same manufacturer that were nominally identical were programmed with a PLS model for the detection of diethylene glycol (DEG) contamination in propylene glycol (PG)-water mixtures. The model was developed on one spectrometer and used on other units after a calibration transfer procedure that used piecewise direct standardization. Although quantitative results were produced, in practice the instrument interface was programmed to report in Pass/Fail mode. The Pass/Fail determinations were made within 10 s and were based on a threshold that passed a blank sample with 95% confidence. The detection limit was then established as the concentration at which a sample would fail with 95% confidence. For a 1% DEG threshold one false negative (Type II) and eight false positive (Type I) errors were found in over 500 samples measured. A representative test set produced standard errors of less than 2%. Since the range of diethylene glycol for economically motivated adulteration (EMA) is expected to be above 1%, the sensitivity of field calibrated portable NIR instruments is sufficient to rapidly screen out potentially problematic materials. Following method development, the instruments were shipped to different sites around the country for a collaborative study with a fixed protocol to be carried out by different analysts. NIR spectra of replicate sets of calibration transfer, system suitability and test samples were all processed with the same chemometric model on multiple instruments to determine the overall analytical precision of the method. The combined results collected for all participants were statistically analyzed to determine a limit of detection (2.0% DEG) and limit of quantitation (6.5%) that can be expected for a method distributed to multiple field laboratories. Published by Elsevier B.V. C1 [Li, Xiang; Arzhantsev, Sergey; Kauffman, John F.; Spencer, John A.] US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. [Li, Xiang] Penn State Univ, University Pk, PA 16802 USA. RP Spencer, JA (reprint author), US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM john.spencer@fda.hhs.gov NR 20 TC 5 Z9 6 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 5 PY 2011 VL 54 IS 5 BP 1001 EP 1006 DI 10.1016/j.jpba.2010.11.042 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 716EO UT WOS:000286952100012 PM 21177057 ER PT J AU Zang, QD Keire, DA Wood, RD Buhse, LF Moore, CMV Nasr, M Al-Hakim, A Trehy, ML Welsh, WJ AF Zang, Qingda Keire, David A. Wood, Richard D. Buhse, Lucinda F. Moore, Christine M. V. Nasr, Moheb Al-Hakim, Ali Trehy, Michael L. Welsh, William J. TI Combining H-1 NMR spectroscopy and chemometrics to identify heparin samples that may possess dermatan sulfate (DS) impurities or oversulfated chondroitin sulfate (OSCS) contaminants SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Heparin; Proton nuclear magnetic resonance spectroscopy; Pattern recognition; Principal components analysis; Linear discriminant analysis ID NUCLEAR-MAGNETIC-RESONANCE; MULTIVARIATE CALIBRATION METHODS; ARTIFICIAL NEURAL-NETWORKS; ADVERSE CLINICAL EVENTS AB Heparin is a naturally produced, heterogeneous compound consisting of variably sulfated and acetylated repeating disaccharide units. The structural complexity of heparin complicates efforts to assess the purity of the compound, especially when differentiating between similar glycosaminoglycans. Recently, heparin sodium contaminated with oversulfated chondroitin sulfate A (OSCS) has been associated with a rapid and acute onset of an anaphylactic reaction. In addition, naturally occurring dermatan sulfate (DS) was found to be present in these and other heparin samples as an impurity due to incomplete purification. The present study was undertaken to determine whether chemometric analysis of these NMR spectral data would be useful for discrimination between USP-grade samples of heparin sodium API and those deemed unacceptable based on their levels of DS, OSCS, or both. Several multivariate chemometric methods for clustering and classification were evaluated; specifically, principal components analysis (PCA), partial least squares discriminant analysis (PLS-DA), linear discriminant analysis (LDA), and the k-nearest-neighbor (kNN) method. Data dimension reduction and variable selection techniques, implemented to avoid over-fitting the training set data, markedly improved the performance of the classification models. Under optimal conditions, a perfect classification (100% success rate) was attained on external test sets for the Heparin vs OSCS model. The predictive rates for the Heparin vs DS, Heparin vs [DS + OSCS], and Heparin vs DS vs OSCS models were 89%, 93%, and 90%, respectively. In most cases, misclassifications can be ascribed to the similarity in NMR chemical shifts of heparin and DS. Among the chemometric methods evaluated in this study, we found that the LDA models were superior to the PLS-DA and kNN models for classification. Taken together, the present results demonstrate the utility of chemometric methods when applied in combination with H-1 NMR spectral analysis for evaluating the quality of heparin APIs. (C) 2010 Elsevier B.V. All rights reserved. C1 [Zang, Qingda; Welsh, William J.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, Piscataway, NJ 08854 USA. [Zang, Qingda; Wood, Richard D.] Snowdon Inc, Monmouth Jct, NJ 08852 USA. [Zang, Qingda] Univ Med & Dent New Jersey, Sch Hlth Related Profess, Dept Hlth Informat, Newark, NJ 07107 USA. [Keire, David A.; Buhse, Lucinda F.; Trehy, Michael L.] US FDA, CDER, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Moore, Christine M. V.; Nasr, Moheb; Al-Hakim, Ali] US FDA, CDER, Off New Drug Qual Assessment, Silver Spring, MD 20993 USA. RP Welsh, WJ (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pharmacol, 661 Hoes Lane W,Room SRB-125, Piscataway, NJ 08854 USA. EM welshwj@umdnj.edu NR 32 TC 12 Z9 12 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 5 PY 2011 VL 54 IS 5 BP 1020 EP 1029 DI 10.1016/j.jpba.2010.12.008 PG 10 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 716EO UT WOS:000286952100015 PM 21215547 ER PT J AU Deeds, JR Handy, SM White, KD Reimer, JD AF Deeds, Jonathan R. Handy, Sara M. White, Kevin D. Reimer, James D. TI Palytoxin Found in Palythoa sp Zoanthids (Anthozoa, Hexacorallia) Sold in the Home Aquarium Trade SO PLOS ONE LA English DT Article ID PUTATIVE PALYTOXIN; MOLECULAR EVIDENCE; MASS-SPECTROMETRY; OSTREOPSIS-OVATA; PHYLOGENIES; ZOANTHARIA; SEQUENCES; OUTBREAK; EXPOSURE; SKIN AB Zoanthids (Anthozoa, Hexacorallia) are colonial anemones that contain one of the deadliest toxins ever discovered, palytoxin (LD50 in mice 300 ng/kg), but it is generally believed that highly toxic species are not sold in the home aquarium trade. We previously showed that an unintentionally introduced zoanthid in a home aquarium contained high concentrations of palytoxin and was likely responsible for a severe respiratory reaction when an individual attempted to eliminate the contaminant colonies using boiling water. To assess the availability and potential exposure of palytoxin to marine aquarium hobbyists, we analyzed zoanthid samples collected from local aquarium stores for palytoxin using liquid chromatography and high resolution mass spectrometry and attempted to identify the specimens through genetic analysis of 16S and cytochrome c oxidase 1 (COI) markers. We found four specimens of the same apparent species of zoanthid, that we described previously to be responsible for a severe respiratory reaction in a home aquarium, to be available in three aquarium stores in the Washington D. C. area. We found all of these specimens (n = 4) to be highly toxic with palytoxin or palytoxin-like compounds (range 0.5-3.5 mg crude toxin/g zoanthid). One of the most potent non-protein compounds ever discovered is present in dangerous quantities in a select species of zoanthid commonly sold in the home aquarium trade. C1 [Deeds, Jonathan R.; Handy, Sara M.; White, Kevin D.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Reimer, James D.] Univ Ryukyus, Dept Chem Biol & Marine Sci, Okinawa, Japan. RP Deeds, JR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM jonathan.deeds@fda.hhs.gov RI Handy, Sara/C-6195-2008 FU United States Food and Drug Administration Center for Food Safety and Applied Nutrition FX This study was funded by the United States Food and Drug Administration Center for Food Safety and Applied Nutrition. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 39 TC 15 Z9 15 U1 1 U2 9 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 4 PY 2011 VL 6 IS 4 AR e18235 DI 10.1371/journal.pone.0018235 PG 9 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743ZC UT WOS:000289058700015 PM 21483745 ER PT J AU Ma, L Zhang, GD Doyle, MP AF Ma, Li Zhang, Guodong Doyle, Michael P. TI Green Fluorescent Protein Labeling of Listeria, Salmonella, and Escherichia coli O157:H7 for Safety-Related Studies SO PLOS ONE LA English DT Article ID SPECIES-SPECIFIC MARKER; GRAM-POSITIVE BACTERIA; ECOMETRIC TECHNIQUE; IN-VITRO; EXPRESSION; VECTORS; MONOCYTOGENES; GFP; PSEUDOMONAS; BIOFILMS AB Many food safety-related studies require tracking of introduced foodborne pathogens to monitor their fate in complex environments. The green fluorescent protein (GFP) gene (gfp) provides an easily detectable phenotype so has been used to label many microorganisms for ecological studies. The objectives of this study were to label major foodborne pathogens and related bacteria, including Listeria monocytogenes, Listeria innocua, Salmonella, and Escherichia coli O157:H7 strains, with GFP and characterize the labeled strains for stability of the GFP plasmid and the plasmid's effect on bacterial growth. GFP plasmids were introduced into these strains by a CaCl(2) procedure, conjugation or electroporation. Stability of the label was determined through sequential propagation of labeled strains in the absence of selective pressure, and rates of plasmid-loss were calculated. Stability of the GFP plasmid varied among the labeled species and strains, with the most stable GFP label observed in E. coli O157:H7. When grown in nonselective media for two consecutive subcultures (ca. 20 generations), the rates of plasmid loss among labeled E. coli O157:H7, Salmonella and Listeria strains ranged from 0%-30%, 15.8%-99.9% and 8.1%-93.4%, respectively. Complete loss (>99.99%) of the plasmid occurred in some labeled strains after five consecutive subcultures in the absence of selective pressure, whereas it remained stable in others. The GFP plasmid had an insignificant effect on growth of most labeled strains. E. coli O157:H7, Salmonella and Listeria strains can be effectively labeled with the GFP plasmid which can be stable in some isolates for many generations without adversely affecting growth rates. C1 [Ma, Li] Oklahoma State Univ, Dept Entomol & Plant Pathol, Natl Inst Microbial Forens & Food & Agr Biosecur, Stillwater, OK 74078 USA. [Zhang, Guodong] Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Doyle, Michael P.] Univ Georgia, Ctr Food Safety, Griffin, GA USA. RP Ma, L (reprint author), Oklahoma State Univ, Dept Entomol & Plant Pathol, Natl Inst Microbial Forens & Food & Agr Biosecur, Stillwater, OK 74078 USA. EM mdoyle@uga.edu FU University of Georgia Center for Food Safety FX The University of Georgia Center for Food Safety supported this research. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 26 TC 33 Z9 33 U1 3 U2 36 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD APR 4 PY 2011 VL 6 IS 4 AR e18083 DI 10.1371/journal.pone.0018083 PG 7 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743ZC UT WOS:000289058700008 PM 21483738 ER PT J AU Meng, FX Wang, YY Myers, MB Wong, BA Gross, EA Clewell, HJ Dodd, DE Parsons, BL AF Meng, Fanxue Wang, Yiying Myers, Meagan B. Wong, Brian A. Gross, Elizabeth A. Clewell, Harvey J., III Dodd, Darol E. Parsons, Barbara L. TI p53 codon 271 CGT to CAT mutant fraction does not increase in nasal respiratory and olfactory epithelia of rats exposed to inhaled naphthalene SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE p53 mutation; Naphthalene; Dose-response; Risk assessment; Mode of action; Cytotoxicity ID GLUTATHIONE DEPLETION; GENETIC TOXICITY; CANCER-RISK; MUTATIONS; LIVER; FORMALDEHYDE; CARCINOGENS; INHALATION; APOPTOSIS; VAPORS AB A 2-year rat tumor bioassay testing whole body exposure to naphthalene (NA) vapor found a significant increase in nasal respiratory epithelial adenomas in male rats and in olfactory epithelial neuroblastomas in female rats. To obtain mechanistic insight into NA-induced nasal carcinogenesis. NA dose-response was characterized in nasal epithelium using a tumor-relevant endpoint. Specifically, levels of p53 codon 271 CGT to CAT mutation were measured in nasal respiratory and olfactory epithelium of NA-exposed male and female rats by allele-specific competitive blocker-PCR (ACB-PCR). Male and female, 8-9 week-old F344 rats (5 rats/group) were exposed to 0, 0.1, 1.0, 10, and 30 ppm NA vapor for 13 weeks (6 h/day, 5 days/week). The geometric mean p53 mutant fraction (MF) levels in nasal epithelium of control treatment groups ranged between 2.05 x 10(-5) and 3.05 x 10(-5). No significant dose-related changes in p53 mutant fraction (MF) were observed in the olfactory or respiratory epithelia of female rats. However, statistically significant treatment-related differences were observed in male respiratory and olfactory epithelium, with the p53 MF in the respiratory epithelium of male rats exposed to 30 ppm NA significantly lower than that in controls. Further, a significant trend of decreasing p53 MF with increasing dose was observed in the male respiratory epithelium. Of the tissue types analyzed, respiratory epithelium is the most sensitive to the cytotoxic effects of NA, suggesting cytotoxicity may be responsible for the loss of p53 mutation. Because ACB-PCR has been used successfully to detect the effects of known mutagenic carcinogens, the absence of any significant increases in p53 MF associated with NA exposure adds to the weight of evidence that NA does not operate through a directly mutagenic mode of action. Published by Elsevier B.V. C1 [Meng, Fanxue; Wang, Yiying; Myers, Meagan B.; Parsons, Barbara L.] US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, Jefferson, AR 72079 USA. [Wong, Brian A.; Gross, Elizabeth A.; Dodd, Darol E.] Hamner Inst Hlth Sci, Div Toxicol & Preclin Studies, Res Triangle Pk, NC 27709 USA. [Clewell, Harvey J., III] Hamner Inst Hlth Sci, Ctr Human Hlth Assessment, Res Triangle Pk, NC 27709 USA. RP Parsons, BL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Mol Toxicol, HFT 120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM barbara.parsons@fda.hhs.gov FU Naphthalene Research Committee; NCTR/US FDA [E07269.01]; The Hammer Institutes for Health Sciences FX This study was conducted as part of a cooperative research and development agreement between the US Food and Drug Administration (FDA) and the Hamner Institutes for Health Sciences. The research was supported in part by the Naphthalene Research Committee. The contents of the manuscript do not necessarily reflect the views or policies of the U.S. FDA, nor does the mention of trade names or commercial products constitute endorsement or recommendation for use. This study was partially funded by NCTR/US FDA under Protocol E07269.01 evaluating the utility of ACB-PCR in dose-response assessment and MOA evaluation and, partially funded by The Hammer Institutes for Health Sciences, under a cooperative research and development agreement. The Hammer Institutes received funding to support this research from the Naphthalene Research Committee. NR 45 TC 10 Z9 10 U1 0 U2 3 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 APR 3 PY 2011 VL 721 IS 2 BP 199 EP 205 DI 10.1016/j.mrgentox.2011.02.004 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 756JX UT WOS:000290008600013 PM 21324376 ER PT J AU Zhang, HH Xie, CH Spencer, HJ Zuo, CL Higuchi, M Ranganathan, G Kern, PA Chou, MW Huang, Q Szczesny, B Mitra, S Watson, AJ Margison, GP Fan, CY AF Zhang, Haihong Xie, Chenghui Spencer, Horace J. Zuo, Chunlai Higuchi, Masahiro Ranganathan, Gouri Kern, Philip A. Chou, Ming W. Huang, Qin Szczesny, Bartosz Mitra, Sankar Watson, Amanda J. Margison, Geoffrey P. Fan, Chun-Yang TI Obesity and Hepatosteatosis in Mice with Enhanced Oxidative DNA Damage Processing in Mitochondria SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID BASE-EXCISION-REPAIR; ESCHERICHIA-COLI; ADIPOSE-TISSUE; MESSENGER-RNA; IN-VIVO; GLYCOSYLASE; 8-OXOGUANINE; CELLS; EXPRESSION; OGG1 AB Mitochondria play critical roles in oxidative phosphorylation and energy metabolism. Increasing evidence supports that mitochondrial DNA (mtDNA) damage and dysfunction play vital roles in the development of many mitochondria-related diseases, such as obesity, diabetes mellitus, infertility, neurodegenerative disorders, and malignant tumors in humans. Human 8-oxoguanine-DNA glycosylase 1 (hOGG1) transgenic (TG) mice were produced by nuclear microinjection. Transgene integration was analyzed by PCR. Transgene expression was measured by RT-PCR and Western blot analysis. Mitochondrial DNA damage was analyzed by mutational analyses and measurement of mtDNA copy number. Total fat content was measured by a whole-body scan using dual-energy X-ray absorptiometry. The hOGG1 overexpression in mitochondria increased the abundance of intracellular free radicals and major deletions in mtDNA. Obesity in hOGG1 TG mice resulted from increased fat content in tissues, produced by hyperphagia. The molecular mechanisms of obesity involved overexpression of genes in the central orexigenic (appetite-stimulating) pathway, peripheral lipogenesis, down-regulation of genes in the central anorexigenic (appetite-suppressing) pathway, peripheral adaptive thermogenesis, and fatty acid oxidation. Diffuse hepatosteatosis, female infertility, and increased frequency of malignant lymphoma were also seen in these hOGG1 TG mice. High levels of hOGG1 expression in mitochondria, resulting in enhanced oxidative DNA damage processing, may be an important factor in human metabolic syndrome, infertility, and malignancy. (Am J Pathol 2011, 178:1715-1727; DOI: 10.1016/j.ajpath.2010.12.038) C1 [Zhang, Haihong; Xie, Chenghui; Zuo, Chunlai; Fan, Chun-Yang] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. [Spencer, Horace J.] Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. [Higuchi, Masahiro] Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. [Ranganathan, Gouri] Univ Arkansas Med Sci, Dept Internal Med, Little Rock, AR 72205 USA. [Kern, Philip A.] Univ Kentucky, Div Endocrinol, Lexington, KY USA. [Chou, Ming W.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Huang, Qin] City Hope Natl Med Ctr, Dept Pathol, Duarte, CA 91010 USA. [Szczesny, Bartosz; Mitra, Sankar] Univ Texas Med Branch, Dept Biochem & Mol Biol, Galveston, TX USA. [Watson, Amanda J.; Margison, Geoffrey P.] Univ Manchester, Paterson Inst Canc Res, Canc Res UK Carcinogenesis Grp, Manchester, Lancs, England. [Fan, Chun-Yang] Cent Arkansas Vet Healthcare Systeur, Dept Pathol, Little Rock, AR 72205 USA. RP Fan, CY (reprint author), Univ Arkansas Med Sci, Dept Pathol LR 113, 4300 W 7th St, Little Rock, AR 72205 USA. EM fanchunyang@uams.edu RI Szczesny, Bartosz/D-1026-2012 FU South Central Veterans' Health Care Network [VISN16]; NIH [CA100846, DK39176, P01AG10514, CA53791]; Cancer Research-UK; Department of Veterans' Affairs FX Supported by a pilot grant from the South Central Veterans' Health Care Network (VISN16), NIH grants (CA100846 to M.H.; DK39176 to P.A.K.; P01AG10514 to B.S. and S.M.; CA53791 to S.M.), Cancer Research-UK (G.P.M.); and a merit review grant from the Department of Veterans' Affairs (C.-Y.F.). NR 55 TC 9 Z9 10 U1 0 U2 10 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD APR PY 2011 VL 178 IS 4 BP 1715 EP 1727 DI 10.1016/j.ajpath.2010.12.038 PG 13 WC Pathology SC Pathology GA 865JH UT WOS:000298306700029 PM 21435453 ER PT J AU Pincock, LL Montello, MJ Tarosky, MJ Pierce, WF Edwards, CW AF Pincock, Laura L. Montello, Michael J. Tarosky, Matthew J. Pierce, William F. Edwards, Calvin W. TI Pharmacist readiness roles for emergency preparedness SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Editorial Material ID HURRICANE-KATRINA C1 [Pierce, William F.] US FDA, Div Biol Oncol Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Pincock, Laura L.] US FDA, Off Commun, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Montello, Michael J.] NCI, Clin Invest Branch, Canc Therapy Evaluat Program, Div Canc Treatment & Diag, Rockville, MD USA. [Tarosky, Matthew J.] US FDA, Div Biores Monitoring, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Tarosky, Matthew J.] US FDA, PHS Rapid Deployment Force 1, CDER, Planning Sect, Silver Spring, MD 20993 USA. [Edwards, Calvin W.] US FDA, Off Regulatory Affairs, Silver Spring, MD 20993 USA. RP Pierce, WF (reprint author), US FDA, Div Biol Oncol Prod, Off New Drugs, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 5219, Silver Spring, MD 20993 USA. EM william.pierce@fda.hhs.gov NR 13 TC 3 Z9 3 U1 0 U2 5 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD APR 1 PY 2011 VL 68 IS 7 BP 620 EP 623 DI 10.2146/ajhp090659 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 858CF UT WOS:000297772800014 PM 21411804 ER PT J AU Kamp, DW Shacter, E Weitzman, SA AF Kamp, David W. Shacter, Emily Weitzman, Sigmund A. TI Chronic Inflammation and Cancer: The Role of the Mitochondria SO ONCOLOGY-NEW YORK LA English DT Review ID TUMOR-NECROSIS-FACTOR; NF-KAPPA-B; IDIOPATHIC PULMONARY-FIBROSIS; COLITIS-ASSOCIATED CANCER; DNA-STRAND BREAKS; LUNG-CANCER; ULCERATIVE-COLITIS; COLORECTAL-CANCER; EPITHELIAL-CELLS; FACTOR-ALPHA AB Accumulating evidence shows that chronic inflammation can promote all stages of tumorigenesis, including DNA damage, limitless replication, apoptosis evasion, sustained angiogenesis, self-sufficiency in growth signaling, insensitivity to anti-growth signaling, and tissue invasion/metastasis. Chronic inflammation is triggered by environmental (extrinsic) factors (eg, infection, tobacco, asbestos) and host mutations (intrinsic) factors (eg, Ras, Myc, p53). Extensive investigations over the past decade have uncovered many of the important mechanistic pathways underlying cancer-related inflammation. However, the precise molecular mechanisms involved and the interconnecting crosstalk between pathways remain incompletely understood. We review the evidence implicating a strong association between chronic inflammation and cancer, with an emphasis on colorectal and lung cancer. We summarize the current knowledge of the important molecular and cellular pathways linking chronic inflammation to tumorigenesis. Specifically, we focus on the role of the mitochondria in coordinating life-and death-signaling pathways crucial in cancer-related inflammation. Activation of Ras, Myc, and p53 cause mitochondrial dysfunction, resulting in mitochondrial reactive oxygen species (ROS) production and downstream signaling (eg, NF kappa B, STAT3, etc.) that promote inflammation-associated cancer. A recent murine transgenic study established that mitochondrial metabolism and ROS production are necessary for K-Ras-induced tumorigenicity. Collectively, inflammation-associated cancers resulting from signaling pathways coordinated at the mitochondrial level are being identified that may prove useful for developing innovative strategies for both cancer prevention and cancer treatment. C1 [Kamp, David W.] Jesse Brown VA Med Ctr, Chicago, IL USA. [Kamp, David W.; Weitzman, Sigmund A.] Northwestern Univ, Feinberg Sch Med, Chicago, IL 60611 USA. [Shacter, Emily] Ctr Drug Evaluat & Res, Food & Drug Adm, Bethesda, MD USA. RP Kamp, DW (reprint author), McGaw M-330,240 E Huron St, Chicago, IL 60611 USA. EM d-kamp@northwestern.edu FU Department of Veterans Affairs FX This work was supported by a Merit Review grant from the Department of Veterans Affairs (DWK). NR 117 TC 84 Z9 86 U1 2 U2 17 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 APR PY 2011 VL 25 IS 5 BP 400 EP 413 PG 12 WC Oncology SC Oncology GA 800EU UT WOS:000293343400006 PM 21710835 ER PT J AU Chen, JJ AF Chen, James J. TI Consistency of predictive signature genes and classifiers SO PHARMACOGENOMICS LA English DT News Item ID VALIDATION C1 US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, JJ (reprint author), US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov NR 5 TC 0 Z9 0 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 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD APR PY 2011 VL 12 IS 4 BP 461 EP 462 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 770YR UT WOS:000291124900009 PM 21521018 ER PT J AU Lin, WJ Chen, JJ AF Lin, Wei-Jiun Chen, James J. TI An approach to identifying preclinical biomarkers of susceptibility to drug-induced toxicity SO PHARMACOGENOMICS LA English DT Article DE biomarkers of exposure; biomarkers of susceptibility; drug-induced toxicity; preclinical studies; safety assessment ID SAMPLE-SIZE; HEPATOTOXICITY; MICROARRAY; PREDICTS; INJURY AB Aim: Drug-induced toxicity that leads to termination of candidate drugs or postmarketing removal of approved drugs can potentially be explained by the existence of susceptible subpopulations. If the susceptible subpopulations are identified in advance, the drug's benefits could be maximized by optimal treatment decisions. This article presents a statistical model and an approach for identifying pharmacogenomic biomarkers of susceptibility to drug-induced toxicity for detecting the susceptible subpopulations. Materials & methods: Biomarkers are categorized into three disjoint sets: biomarkers of both susceptibility and exposure (A); biomarkers of susceptibility only (B); and biomarkers of exposure only (C). Set B contains the most useful biomarkers to identify susceptible subpopulations prior to drug exposure; these markers demonstrate no change in response before and after drug exposure. We present a sample size analysis to illustrate the issues and challenges facing identifying biomarker set B. Results: The required sample size increases as the proportion of the susceptible subpopulation decreases. The examples demonstrated that at least 75 subjects per group are needed for a population with a 5% susceptible subpopulation and more than 1000 are often necessary. Conclusion: This study demonstrates that the biomarkers identified by common methods are a mixture of biomarkers of exposure and susceptibility (A and C), it further demonstrates that the proposed approach could be used to identify biomarkers of susceptibility (B), where a large sample size may be required for adequate power and low false-positive rate. C1 [Lin, Wei-Jiun; Chen, James J.] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chen, James J.] China Med Univ, Grad Inst Biostat, Taichung, Taiwan. [Chen, James J.] China Med Univ, Ctr Biostat, Taichung, Taiwan. RP Chen, JJ (reprint author), US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM jamesj.chen@fda.hhs.gov NR 23 TC 3 Z9 3 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 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD APR PY 2011 VL 12 IS 4 BP 493 EP 501 DI 10.2217/PGS.10.204 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 770YR UT WOS:000291124900015 PM 21521022 ER PT J AU Trickler, WJ Munt, DJ Jain, N Joshi, SS Dash, AK AF Trickler, William J. Munt, Daniel J. Jain, Neha Joshi, Shantaram S. Dash, Alekha K. TI Antitumor efficacy, tumor distribution and blood pharmacokinetics of chitosan/glyceryl-monooleate nanostructures containing paclitaxel SO NANOMEDICINE LA English DT Article DE blood pharmacokinetic parameters; chitosan/glyceryl-monooleate; nanostructures; hematological alterations; histopathological studies; paclitaxel; tumor distribution ID CHITOSAN-COATED LIPOSOMES; IN-VIVO EVALUATION; DRUG-DELIVERY; BREAST-CANCER; NANOPARTICLE FORMULATION; POLYMERIC MICELLES; CREMOPHOR-EL; VITRO; THERAPY; BIODISTRIBUTION AB Aims: This investigation compared the tumor distribution, efficacy, blood pharmacokinetic parameters and hematological alterations following treatment with chitosan/glyceryl-monooleate (GMO) nanostructures containing paclitaxel (PTX) to a conventional formulation of PTX (Taxol (R)) in BALB/c female mice. Materials & methods: The tumor and blood concentrations of PTX were evaluated by HPLC and the pharmacokinetic parameters were determined through noncompartmental methods. Tumor development was evaluated by histopathological methods and hematological composition was monitored through differential white blood cells counts. Results: Lower localized or intravenous doses of PTX-chitosan/GMO nanostructures significantly increased the antitumor activity of paclitaxel. The tumor distribution studies showed effective concentrations in the tumors with the chitosan/GMO formulation while systemic blood levels remained lower than after administration of the conventional formulation. Conclusion: Delivery systems consisting of chitosan/GMO and PTX are safe and effective administered locally (intratumorally) or intravenously. C1 [Trickler, William J.; Munt, Daniel J.; Jain, Neha; Dash, Alekha K.] Creighton Univ, Sch Pharm & Hlth Profess, Dept Pharm Sci, Omaha, NE 68178 USA. [Trickler, William J.] US FDA, Dept Neurochem, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Joshi, Shantaram S.] Univ Nebraska, Med Ctr, Dept Genet Cell Biol & Anat, Omaha, NE 68198 USA. RP Dash, AK (reprint author), Creighton Univ, Sch Pharm & Hlth Profess, Dept Pharm Sci, 2500 Calif Plaza, Omaha, NE 68178 USA. EM adash@creighton.edu FU Department of Defense [BC045664]; Health Future Foundation FX This work was partially supported by a Department of Defense Concept Award BC045664 and Health Future Foundation. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. NR 42 TC 6 Z9 6 U1 0 U2 16 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 EI 1748-6963 J9 NANOMEDICINE-UK JI Nanomedicine PD APR PY 2011 VL 6 IS 3 BP 437 EP 448 DI 10.2217/NNM.10.135 PG 12 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 764AW UT WOS:000290601800013 PM 21542683 ER PT J AU Volokhov, DV Graham, LJ Brorson, KA Chizhikov, VE AF Volokhov, Dmitriy V. Graham, Laurie J. Brorson, Kurt A. Chizhikov, Vladimir E. TI Mycoplasma testing of cell substrates and biologics: Review of alternative non-microbiological techniques SO MOLECULAR AND CELLULAR PROBES LA English DT Review DE Mycoplasma; Cell substrates; Biologics; Detection; NAT assays ID REVERSE TRANSCRIPTION-PCR; REAL-TIME PCR; SEQUENCE-BASED AMPLIFICATION; POLYMERASE-CHAIN-REACTION; MEDIATED AMPLIFICATION; RAPID DETECTION; QUALITY-CONTROL; TOUCHDOWN PCR; MOLLICUTES; CULTURES AB Mycoplasmas, particularly species of the genera Mycoplasma and Acholeplasma, are known to be occasional microbial contaminants of cell cultures that produce biologics. This presents a serious concern regarding the risk of mycoplasma contamination for research laboratories and commercial facilities developing and manufacturing cell-derived biological and biopharmaceutical products for therapeutic use. Potential undetected contamination of these products or process intermediates with mycoplasmas represents a potential safety risk for patients and a business risk for producers of biopharmaceuticals. To minimize these risks, monitoring for adventitious agents, such as viruses and mycoplasmas, is performed during the manufacture of biologics produced in cell culture substrates. The "gold standard" microbiological assay, currently recommended by the USP, EP, JP and the US FDA, for the mycoplasma testing of biologics, involves the culture of viable mycoplasmas in broth, agar plates and indicator cells. Although the procedure enables highly efficient mycoplasma detection in cell substrates and cell-derived products, the overall testing strategy is time consuming (a minimum of 28 days) and requires skilled interpretation of the results. The long time period required for these conventional assays does not permit their use for products with short shelf-lives or for timely 'go/no-go' decisions during routine in-process testing. PCR methodology has existed for decades, however PCR based and other alternative methods for mycoplasma detection have only recently been considered for application to biologics manufacture. The application of alternative nucleic acid-based, enzyme-based and/or recombinant cell-culture methods, particularly in combination with efficient sample preparation procedures, could provide advantages over conventional microbiological methods in terms of analytical throughput, simplicity, and turnaround time. However, a challenge to the application of alternative methods for detection of mycoplasmas remains whether these alternative methods can provide a limit of detection comparable or superior to those of the culture methods. An additional challenge is that nucleic acid amplification technique (NAT) methods do not allow for accurate discrimination between viable and non-viable mycoplasma contaminants, which might lead to false-positive results (e.g. from inactivated raw materials, etc.). Our review provides an overview of these alternative methods and discusses the pros and cons of their application for the testing of mycoplasmas in biologics and cell substrates. Published by Elsevier Ltd. C1 [Volokhov, Dmitriy V.; Chizhikov, Vladimir E.] US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Lab Methods Dev, Rockville, MD 20852 USA. [Graham, Laurie J.; Brorson, Kurt A.] Food & Drug Adm, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Volokhov, DV (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Lab Methods Dev, HEM 470,1401 Rockville Pike, Rockville, MD 20852 USA. EM dmitriy.volokhov@fda.hhs.gov NR 77 TC 19 Z9 21 U1 1 U2 24 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD APR-JUN PY 2011 VL 25 IS 2-3 BP 69 EP 77 DI 10.1016/j.mcp.2011.01.002 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 764DR UT WOS:000290609100001 PM 21232597 ER PT J AU Khan, SA Sung, K Nawaz, MS AF Khan, Saeed A. Sung, Kidon Nawaz, Mohamed S. TI Detection of aacA-aphD, qacE delta 1, marA, floR, and tetA genes from multidrug-resistant bacteria: Comparative analysis of real-time multiplex PCR assays using EvaGreen (R) and SYBR (R) Green I dyes SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE Antibiotic; Genes; Resistance; Real-time PCR; EvaGreen; SYBR Green ID ESCHERICHIA-COLI; STAPHYLOCOCCUS-AUREUS; ANTIBIOTIC-RESISTANCE; SALMONELLA-ENTERICA; RAPID DETECTION; EFFLUX PUMPS; IDENTIFICATION; TYPHIMURIUM; METHICILLIN; INTEGRONS AB We have developed multiplex real-time PCR assays that utilize DNA-intercalating dyes, SYBR Green I (SG) and EvaGreen (EG), with two primer sets (set 1 = qacE delta 1, tetA and aacA-aphD; set 2 = tetA, marA, and floR) to simultaneously amplify the qacE delta 1, tetA, aacA-aphD, marA, and floR genes. Validity of the multiplex PCR assays was confirmed by testing 83 bacterial isolates, including Staphylococcus aureus (28 isolates), Enterococcus spp. (17 isolates), Salmonella enterica serovar Typhimurium (8 isolates), Citrobacter spp. (9 isolates), Escherichia coli (14 isolates) and Aeromonas veronii (7 isolates), and performing sequence analysis of representative PCR products. Agarose gel analysis revealed the presence of correct size PCR products, and the differences in their thermal melting (T(m)) curves were used to distinguish various PCR products. Although T(m), peaks of different amplicons after EG-based singleplex and multiplex PCR assays were resolved nicely, only one or two peaks were seen for SG-bound amplicons. EG-based multiplex real-time PCR assays provided better peak resolution. There was a good correlation with a better linear relationship between the C(t) and log input DNA concentration for the set 1 and set 2 genes in EG-based assays (R(EG)(2) = 0.9813 and 0.9803) than in SG-based assays (R(SG)(2) = 0.5276 and 0.6255). The sensitivities of detection were 2.5-25 fg and 25-250 fg of template DNA in EG and SG-based singleplex and multiplex PCR assays, respectively. The assays, which could be completed in less than 45 min, offer sensitive and rapid detection of qacE delta 1, aacA-aphD, marA, floR, and tetA genes from a diverse group of multiple antibiotic-resistant bacterial strains. Published by Elsevier Ltd. C1 [Khan, Saeed A.; Sung, Kidon; Nawaz, Mohamed S.] Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Khan, SA (reprint author), Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM saeed.khan@fda.hhs.gov NR 32 TC 15 Z9 15 U1 4 U2 17 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD APR-JUN PY 2011 VL 25 IS 2-3 BP 78 EP 86 DI 10.1016/j.mcp.2011.01.004 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 764DR UT WOS:000290609100002 PM 21256956 ER PT J AU Calleo, J Bush, AL Williams, JR Hirsch, ER Anderson, K Goldstein, SR Grill, S Lehmann, S Little, JT Margolis, RL Palanci, J Pontone, G Weiss, H Rabins, P Marsh, L AF Calleo, J. Bush, A. L. Williams, J. R. Hirsch, E. R. Anderson, K. Goldstein, S. R. Grill, S. Lehmann, S. Little, J. T. Margolis, R. L. Palanci, J. Pontone, G. Weiss, H. Rabins, P. Marsh, L. TI Screening Accuracy of Comorbid Anxiety and Depression in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 25th Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinsons Disease and Other Movement Disorders CY MAY 13, 2011 CL Irving, TX C1 [Calleo, J.; Bush, A. L.; Marsh, L.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Calleo, J.; Bush, A. L.; Marsh, L.] Baylor Coll Med, Houston, TX 77030 USA. [Williams, J. R.] US FDA, Silver Spring, MD USA. [Hirsch, E. R.; Goldstein, S. R.; Grill, S.; Lehmann, S.; Little, J. T.; Margolis, R. L.; Palanci, J.; Pontone, G.; Weiss, H.; Rabins, P.] Johns Hopkins Univ, Sch Med, Baltimore, MD USA. [Anderson, K.; Goldstein, S. R.] Univ Maryland, Med Ctr, Baltimore, MD 21201 USA. [Goldstein, S. R.; Grill, S.] Parkinsons & Movement Disorder Ctr Maryland, Baltimore, MD USA. [Little, J. T.] Georgetown Univ, Med Ctr, Washington, DC 20007 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2011 VL 26 IS 5 BP VI EP VII PG 2 WC Clinical Neurology SC Neurosciences & Neurology GA 762AT UT WOS:000290445400018 ER PT J AU Bush, AL Williams, JR Calleo, J Marsh, L AF Bush, A. L. Williams, J. R. Calleo, J. Marsh, L. CA MOOD-PD Study Grp TI Identifying Persistent Depression in Parkinson's Disease SO MOVEMENT DISORDERS LA English DT Meeting Abstract CT 25th Annual Symposium on Etiology, Pathogenesis, and Treatment of Parkinsons Disease and Other Movement Disorders CY MAY 13, 2011 CL Irving, TX C1 [Bush, A. L.; Calleo, J.; Marsh, L.] Michael E DeBakey VA Med Ctr, Houston, TX USA. [Bush, A. L.; Calleo, J.; Marsh, L.] Baylor Coll Med, Houston, TX 77030 USA. [Williams, J. R.] Johns Hopkins Univ, Dept Mental Hlth, Bloomberg Sch Publ Hlth, Baltimore, MD USA. [Williams, J. R.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0885-3185 J9 MOVEMENT DISORD JI Mov. Disord. PD APR PY 2011 VL 26 IS 5 BP VII EP VII PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 762AT UT WOS:000290445400019 ER PT J AU Ahn, J Park, JW McConnell, JA Ahn, YB Haggblom, MM AF Ahn, Joanne Park, Joong-Wook McConnell, Jennifer A. Ahn, Young-Beom Haeggblom, Max M. TI Kangiella spongicola sp. nov., a halophilic marine bacterium isolated from the sponge Chondrilla nucula SO INTERNATIONAL JOURNAL OF SYSTEMATIC AND EVOLUTIONARY MICROBIOLOGY LA English DT Article ID SEA AB A novel halophilic bacterium of the genus Kangiella was isolated from a marine sponge collected from the Florida Keys, USA. Strain A79(T), an aerobic, Gram-negative, non-motile, rod-shaped bacterium, grew in 2-15% (w/v) NaCl, at a temperature of 10-49 degrees C and at pH 4.5-10. Phylogenetic analysis placed strain A79(T) in the family Alcanivoraceae in the class Gammaproteobacteria. Strain A79(T) showed 98.5% 16S rRNA gene sequence similarity to Kangiella japonica KMM 3899(T), 96.6% similarity to Kangiella koreensis DSM 16069(T) and 95.6% similarity to Kangiella aquimarina DSM 16071(T). The major cellular fatty acids were iso-C-11:0, iso-C-11:0 3-OH, iso-C-15:0, iso-C-17:0 and iso-C-17:1 omega 9c and the G+C content of the genomic DNA was 44.9 mol%. On the basis of physiological, chemotaxonomic and phylogenetic comparisons, strain A79(T) represents a novel species in the genus Kangiella, for which the name Kangiella spongicola sp. nov. is proposed. The type strain is A79(T) (=ATCC BAA-2076(T)=DSM 23219(T)). C1 [Ahn, Joanne; Park, Joong-Wook; McConnell, Jennifer A.; Haeggblom, Max M.] Rutgers State Univ, Dept Biochem & Microbiol, New Brunswick, NJ 08901 USA. [Ahn, Young-Beom] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Haggblom, MM (reprint author), Rutgers State Univ, Dept Biochem & Microbiol, New Brunswick, NJ 08901 USA. EM haggblom@aesop.rutgers.edu RI Haggblom, Max/E-7597-2010 OI Haggblom, Max/0000-0001-6307-7863 FU Aresty Research Center at Rutgers University; National Science Foundation [OCE-451708]; Department of Defense [ER-1492] FX J. A. was supported by the Aresty Research Center at Rutgers University. The study was supported in part by the National Science Foundation (OCE-451708) and the Department of Defense Strategic Environmental Research and Development Program (ER-1492). Special thanks to the members of the Haggblom Lab for their encouragement and assistance. NR 18 TC 9 Z9 9 U1 1 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1466-5026 J9 INT J SYST EVOL MICR JI Int. J. Syst. Evol. Microbiol. PD APR PY 2011 VL 61 BP 961 EP 964 DI 10.1099/ijs.0.021733-0 PN 4 PG 4 WC Microbiology SC Microbiology GA 758BP UT WOS:000290135000046 PM 20511465 ER PT J AU Khin, NA Chen, YF Yang, Y Yang, PL Laughren, TP AF Khin, Ni A. Chen, Yeh-Fong Yang, Yang Yang, Peiling Laughren, Thomas P. TI Exploratory Analyses of Efficacy Data From Major Depressive Disorder Trials Submitted to the US Food and Drug Administration in Support of New Drug Applications SO JOURNAL OF CLINICAL PSYCHIATRY LA English DT Article ID ANTIDEPRESSANT CLINICAL-TRIALS; PLACEBO RUN-IN; RATING-SCALE; PATIENT CHARACTERISTICS; HEART-FAILURE; DOUBLE-BLIND; SEVERITY; DESIGN; VARIABILITY; IMPACT AB Objective: There has been concern about a high rate of placebo response and a substantial failure rate in recent clinical trials in major depressive disorder (MDD). This report explores differences in efficacy data from placebo-controlled MDD trials submitted in support of new drug applications (NDAs) over a 25-year period. Method: We compiled efficacy data from 81 randomized, double-blind clinical trials, with 21,611 evaluable patients, that were submitted to the US Food and Drug Administration as part of NDAs for an antidepressant claim between 1983 and 2008. Trial data were limited to completed, randomized, multicenter, double-blind, placebo-controlled clinical trials in adult patients diagnosed with MDD according to DSM-III or DSM-IV criteria. The database was further limited to patients who were involved in clinical trials for drugs widely viewed as effective antidepressants and for doses of these drugs also viewed as effective doses. Trials were rated as successful if they showed statistical superiority vs placebo for the investigational drug on change in Hamilton Depression Rating Scale (HDRS) score (last-observation-carried-forward data). (Trials with multiple investigational drug groups were successful if there was superiority in at least 1 drug group after adjustment for multiplicity.) In particular, we explored differences in effect size and success rate of these trials, based on when the studies were conducted, geographic location of the study sites (US vs non-US), trial duration, dosing regimen, study size, and baseline disease characteristics. Results: Eighty-one percent of MDD patients were enrolled in US sites. Although the observed placebo and drug responses at non-US sites tended to be larger than at US sites, the treatment effect (drug-placebo difference) was similar (mean change from baseline of about -2.5 units in HDRS total score) in US and non-US trials. In both US and non-US trials, the placebo response showed a modest increase over the observation period (1983-2008). Treatment effect clearly diminished over this same period, at a similar rate for both US and non-US trials despite a marked increase in the sample size of the trials. Our analysis showed that 53% of all MDD trials in the last 25 years were successful. US trials had a higher success rate than non-US trials (58% vs 33%). Before 1995, the overall success rate was 55%, compared to 50% for trials in 1995 or later, and, in general, 6-week trials had a higher success rate than 8-week trials (55% vs 42%). It should be noted that the earlier trials were mostly 6 weeks, and the 6-week trials had higher mean baseline HDRS scores than the 8-week trials. Study size did not seem to influence trial success rates. Mean baseline HDRS total scores declined over the 25-year observation period for patients in both US and non-US trials, as did treatment effect in these trials, again, regardless of region. Fixed-dose trials had a numerically slightly greater success rate than flexible-dose trials (57% vs 51%), although on average treatment effect was numerically larger in the flexible-dose trials than in fixed-dose trials (mean of -2.9 vs -2.0 on HDRS units). Conclusions: Treatment effect has declined over time in MDD trials, and there has been a high failure rate for these trials during the entire period, but the reasons for these findings remain elusive. Baseline disease severity seems to be a more important factor in study outcome than study duration, dosing regimen, sample size, time when studies were conducted, and regions where data were generated. Close attention is needed to a variety of factors in the design and conduct of these studies, including patient population, diagnostic considerations, patient assessment, and clinical practice differences. These considerations become increasingly important as globalization of clinical trials continues to increase. J Clin Psychiatry 2011;72(4):464-472 (C) Copyright 2011 Physicians Postgraduate Press, Inc. C1 [Khin, Ni A.; Laughren, Thomas P.] US FDA, Div Psychiat Prod, Off Drug Evaluat 1, Off New Drugs,CDER, Silver Spring, MD 20993 USA. [Chen, Yeh-Fong; Yang, Yang; Yang, Peiling] US FDA, Div Biometr 1, Off Biostat, Off Translat Sci,CDER, Silver Spring, MD 20993 USA. RP Khin, NA (reprint author), US FDA, Div Psychiat Prod, Off Drug Evaluat 1, Off New Drugs,CDER, 10903 New Hampshire Ave,Bldg 22,Rm 4110,HFD-130, Silver Spring, MD 20993 USA. EM ni.khin@fda.hhs.gov NR 45 TC 85 Z9 89 U1 2 U2 7 PU PHYSICIANS POSTGRADUATE PRESS PI MEMPHIS PA P O BOX 240008, MEMPHIS, TN 38124 USA SN 0160-6689 J9 J CLIN PSYCHIAT JI J. Clin. Psychiatry PD APR PY 2011 VL 72 IS 4 BP 464 EP 472 DI 10.4088/JCP.10m06191 PG 9 WC Psychology, Clinical; Psychiatry SC Psychology; Psychiatry GA 756LK UT WOS:000290012500005 PM 21527123 ER PT J AU Munir, S Hillyer, P Le Nouen, C Buchholz, UJ Rabin, RL Collins, PL Bukreyev, A AF Munir, Shirin Hillyer, Philippa Le Nouen, Cyril Buchholz, Ursula J. Rabin, Ronald L. Collins, Peter L. Bukreyev, Alexander TI Respiratory Syncytial Virus Interferon Antagonist NS1 Protein Suppresses and Skews the Human T Lymphocyte Response SO PLOS PATHOGENS LA English DT Article ID NF-KAPPA-B; DENDRITIC CELLS; I INTERFERON; IFN-ALPHA; NONSTRUCTURAL PROTEINS; CLONAL EXPANSION; EPITHELIAL-CELLS; ALPHA(E)BETA(7) INTEGRIN; REGULATORY FACTOR-3; PRIMARY INFECTION AB We recently demonstrated that the respiratory syncytial virus (RSV) NS1 protein, an antagonist of host type I interferon (IFN-I) production and signaling, has a suppressive effect on the maturation of human dendritic cells (DC) that was only partly dependent on released IFN-I. Here we investigated whether NS1 affects the ability of DC to activate CD8+ and CD4+ T cells. Human DC were infected with RSV deletion mutants lacking the NS1 and/or NS2 genes and assayed for the ability to activate autologous T cells in vitro, which were analyzed by multi-color flow cytometry. Deletion of the NS1, but not NS2, protein resulted in three major effects: (i) an increased activation and proliferation of CD8+ T cells that express CD103, a tissue homing integrin that directs CD8+ T cells to mucosal epithelial cells of the respiratory tract and triggers cytolytic activity; (ii) an increased activation and proliferation of Th17 cells, which have recently been shown to have anti-viral effects and also indirectly attract neutrophils; and (iii) decreased activation of IL-4-producing CD4+ T cells - which are associated with enhanced RSV disease - and reduced proliferation of total CD4+ T cells. Except for total CD4+ T cell proliferation, none of the T cell effects appeared to be due to increased IFN-I signaling. In the infected DC, deletion of the NS1 and NS2 genes strongly up-regulated the expression of cytokines and other molecules involved in DC maturation. This was partly IFN-I-independent, and thus might account for the T cell effects. Taken together, these data demonstrate that the NS1 protein suppresses proliferation and activation of two of the protective cell populations (CD103+ CD8+ T cells and Th17 cells), and promotes proliferation and activation of Th2 cells that can enhance RSV disease. C1 [Munir, Shirin; Le Nouen, Cyril; Buchholz, Ursula J.; Collins, Peter L.; Bukreyev, Alexander] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. [Hillyer, Philippa; Rabin, Ronald L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Munir, S (reprint author), NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. EM alexander.bukreyev@utmb.edu FU NIAID, NIH FX This project was funded by the NIAID, NIH, Intramural Program. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 89 TC 44 Z9 44 U1 3 U2 5 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1553-7374 J9 PLOS PATHOG JI PLoS Pathog. PD APR PY 2011 VL 7 IS 4 AR e1001336 DI 10.1371/journal.ppat.1001336 PG 17 WC Microbiology; Parasitology; Virology SC Microbiology; Parasitology; Virology GA 755ZE UT WOS:000289979900008 PM 21533073 ER PT J AU Sapsford, KE Granek, J Deschamps, JR Boeneman, K Blanco-Canosa, JB Dawson, PE Susumu, K Stewart, MH Medintz, IL AF Sapsford, Kim E. Granek, Jessica Deschamps, Jeffrey R. Boeneman, Kelly Blanco-Canosa, Juan Bautista Dawson, Philip E. Susumu, Kimihiro Stewart, Michael H. Medintz, Igor L. TI Monitoring Botulinum Neurotoxin A Activity with Peptide-Functionalized Quantum Dot Resonance Energy Transfer Sensors SO ACS NANO LA English DT Article DE Forster resonance energy transfer; FRET; quantum dot; peptide; protease; metal affinity; botulinum neurotoxin A; biosensor; fluorescence; biothreat agent; nanocrystal; semiconductor ID SEROTYPE-A; PROTEIN; SEMICONDUCTOR; STABILITY; LIGANDS; NANOCRYSTALS; CDSE; DIAGNOSTICS; BIOSENSORS; CHEMISTRY AB Botulinum neurotoxins (BoNTs) are extremely potent bacterial toxins that contaminate food supplies along with having a high potential for exploitation as bioterrorism agents. There is a continuing need to rapidly and sensitively, detect exposure to these toxins and to verify their active state, as the latter directly affects diagnosis and helps provide effective treatments. We investigate the use of semiconductor quantum dot (QD)-peptide Forster resonance energy transfer (FRET) assemblies to monitor the activity of the BoNT serotype A light chain protease (La). A modular LcA peptide substrate was designed and optimized to contain a central LcA recognition/cleavage region, a unique residue to allow, labeling with a Cy3 acceptor dye, an extended linker-spacer sequence, and a terminal oligohistidine that allows for final ratiometric peptide-QD-self-assembly. A number of different QD materials displaying charged or PEGylated surface coatings were,. evaluated for their ability to self-assemble dye-labeled LA peptide substrates by monitoring FRET interactions. Proteolytic assays were performed utilizing either a direct peptide-on-QD format or alternatively an indirect pre-exposure of peptide to LcA prior to QD assembly. Variable activities were obtained depending on QD materials and formats used with the most sensitive pre-exposure assay result demonstrating a 350 pM LcA limit of detection. Modeling the various QD-peptide sensor constructs provided insight into how the resulting assembly architecture influenced LcA recognition interactions and subsequent activity. These results also highlight the unique roles that both peptide design and QD features, especially surface-capping agents, contribute to overall sensor activity. C1 [Sapsford, Kim E.; Granek, Jessica] US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Deschamps, Jeffrey R.; Boeneman, Kelly; Medintz, Igor L.] USN, Res Lab, Ctr Bio Mol Sci & Engn, Washington, DC 20375 USA. [Susumu, Kimihiro; Stewart, Michael H.] USN, Res Lab, Div Opt Sci, Washington, DC 20375 USA. [Blanco-Canosa, Juan Bautista; Dawson, Philip E.] Scripps Res Inst, Dept Cell Biol, La Jolla, CA 92037 USA. [Blanco-Canosa, Juan Bautista; Dawson, Philip E.] Scripps Res Inst, Dept Chem, La Jolla, CA 92037 USA. RP Sapsford, KE (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM Kim.Sapsford@fda.hhs.gov; Igor.Medintz@nrl.navy.mil RI Gemmill, Kelly/G-2167-2012; OI Deschamps, Jeffrey/0000-0001-5845-0010 FU NRL-NSI, ONR, DTRA; Office of Public Health Emergency Preparedness; FDA [HHSF223200610765P]; NIH [P41 RR-01081] FX The authors acknowledge the NRL-NSI, ONR, DTRA and the Office of Public Health Emergency Preparedness and FDA contract HHSF223200610765P for financial support. Molecular graphics images were produced using the UCSF Chimera package from the Resource for Biocomputing, Visualization, and Informatics at the University of California, San Francisco (supported by NIH P41 RR-01081). J.B.B.-C. acknowledges a Marie Curie IOF. NR 60 TC 70 Z9 72 U1 11 U2 104 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 EI 1936-086X J9 ACS NANO JI ACS Nano PD APR PY 2011 VL 5 IS 4 BP 2687 EP 2699 DI 10.1021/nn102997b PG 13 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 753CJ UT WOS:000289742100032 PM 21361387 ER PT J AU Forrey, C Yager, KG Broadaway, SP AF Forrey, Christopher Yager, Kevin G. Broadaway, Samuel P. TI Molecular Dynamics Study of the Role of the Free Surface on Block Copolymer Thin Film Morphology and Alignment SO ACS NANO LA English DT Article DE block copolymer; thin film morphology; lamellar alignment; molecular dynamics (MD); simulation ID SYMMETRIC DIBLOCK COPOLYMERS; MONTE-CARLO SIMULATIONS; DRUG-RELEASE; PHOTONIC GELS; ORIENTATION; COATINGS; TEMPERATURE; MEMBRANES; KINETICS AB Next-generation applications of block copolymer thin films will require a better understanding of the driving forces unique to thin film coatings, specifically time arising from the polymer-air Interface. Previous modeling studies of film morphology have treated rigidly confined films, neglecting free surface considerations altogether. We report in this article the first systematic molecular dynamics investigation of block copolymer thin film ordering for unconfined films. We investigate the molecular basis of the formation of a number of experimentally relevant coating features, including surface islands and vertical lamellae.. Surface islands are found to form in response to film incommensurability, whereas commensurability considerations are insufficient to explain vertical lamellar formation. Dynamics of lamellar formation presented herein demonstrate that vertical lamellar orientation Is' Initiated In the surface regions of the film, most strikingly at the free surface. We conclude that the free surface plays a pivotal role In the free energy balance determining overall film morphology, and that confinement models provide an incomplete explanation of the physical basis of morphology selection In block copolymer coatings. C1 [Forrey, Christopher] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Yager, Kevin G.] Brookhaven Natl Lab, Ctr Funct Nanomat, Upton, NY 11973 USA. [Broadaway, Samuel P.] Wesleyan Univ, Dept Math & Comp Sci, Middletown, CT 06459 USA. RP Forrey, C (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM christopher.forrey@fda.hhs.gov RI Yager, Kevin/F-9804-2011 OI Yager, Kevin/0000-0001-7745-2513 FU U.S. Department of Energy, Office of Basic Energy Sciences [DE-AC02-98CH10886] FX We thank the Division of Electrical and Software Engineering (FDA) for use of the high performance computing facilities and the Division of Imaging and Applied Mathematics (FDA) for computational time. We also thank A. Bosse (NIST) and D. Saylor (FDA) for providing insightful comments. Research carried out in part at the Center for Functional Nanomaterials, Brookhaven National Laboratory, which is supported by the U.S. Department of Energy, Office of Basic Energy Sciences, under Contract No. DE-AC02-98CH10886. NR 36 TC 16 Z9 16 U1 1 U2 34 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1936-0851 J9 ACS NANO JI ACS Nano PD APR PY 2011 VL 5 IS 4 BP 2895 EP 2907 DI 10.1021/nn103502a PG 13 WC Chemistry, Multidisciplinary; Chemistry, Physical; Nanoscience & Nanotechnology; Materials Science, Multidisciplinary SC Chemistry; Science & Technology - Other Topics; Materials Science GA 753CJ UT WOS:000289742100055 PM 21395316 ER PT J AU Strauss, DG Selvester, RH DiBernardo, LR AF Strauss, David G. Selvester, Ronald H. DiBernardo, Louis R. TI Myocardial Scar in Sarcoidosis by 12-lead ECG and Pathology SO ANNALS OF NONINVASIVE ELECTROCARDIOLOGY LA English DT Article DE noninvasive techniques - electrocardiography; clinical; implantable devices - biventricular pacing; defibrillation; Clinical; electrophysiology - ventricular tachycardia; clinical ID CARDIAC RESYNCHRONIZATION THERAPY; MAGNETIC-RESONANCE AB This case demonstrates the use of QRS scoring to quantify myocardial scar in a patient with cardiac sarcoidosis and left bundle branch block who progressively received an implantable defibrillator, cardiac resynchronization therapy (CRT), left ventricular assist device and cardiac transplantation. QRS scoring has been shown to correlate with magnetic resonance imaging measurements of scar, identify arrhythmogenic substrate and predict response to CRT, but had not previously been compared to pathology-documented scar in nonischemic cardiomyopathies. Further study is warranted to assess the ability of QRS scoring to guide therapy for individual patients. Ann Noninvasive Electrocardiol 2011;16(2):219-222. C1 [Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Strauss, David G.] Duke Univ, Sch Med, Durham, NC USA. [Selvester, Ronald H.] Mem Hosp Res Ctr, Long Beach, CA USA. [DiBernardo, Louis R.] Duke Univ, Dept Pathol, Durham, NC 27706 USA. RP Strauss, DG (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO66-1305, Silver Spring, MD 20993 USA. EM david.strauss@fda.hhs.gov RI Strauss, David/A-9211-2012 NR 4 TC 5 Z9 5 U1 2 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1082-720X J9 ANN NONINVAS ELECTRO JI Ann. Noninvasive Electrocardiol. PD APR PY 2011 VL 16 IS 2 BP 219 EP 222 DI 10.1111/j.1542-474X.2011.00425.x PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 751TM UT WOS:000289640500016 PM 21496175 ER PT J AU Wang, X Zhao, S Harbottle, H Tran, T Blickenstaff, K Abbott, J Meng, J AF Wang, X. Zhao, S. Harbottle, H. Tran, T. Blickenstaff, K. Abbott, J. Meng, J. TI Antimicrobial Resistance and Molecular Subtyping of Campylobacter jejuni and Campylobacter coil from Retail Meats SO JOURNAL OF FOOD PROTECTION LA English DT Article ID FIELD GEL-ELECTROPHORESIS; UNITED-STATES; SALMONELLA SEROVARS; COLI; SPP.; PREVALENCE; CHICKEN AB Campylobacter isolates (n = 297; 202 C. jejuni and 95 C. coli isolates) recovered from 2,513 retail meat samples (chicken breasts, ground turkey, ground beef, and pork chops) were examined for antimicrobial susceptibility. The isolates were further analyzed for genetic relatedness by pulsed-field gel electrophoresis (PFGE) using SmaI and KpnI restriction enzymes, and a subset of isolates (n = 174) were subtyped by multilocus sequence typing (MLST). The resistance most frequently observed was that to doxycycline (27.6%), followed by ciprofloxacin (13.8%) and erythromycin (6.4%). All isolates were susceptible to gentamicin and meropenem. C. coli showed higher resistance to doxycycline than did C. jejuni (42.1 versus 20.8%) and lower resistance to ciprofloxacin than did C. jejuni (10.5 versus 15.3%). Erythromycin resistance was only observed in C. coil. PFGE using SmaI plus KpnI digestion generated 168 clusters from 297 isolates: 115 from C. jejuni and 53 from C. coli. MLST revealed 44 sequence types (STs) under 10 clonal complexes from 120 C. jejuni and 27 STs under two clonal complexes from 54 C. coli. There was a positive association between PFGE and STs; however, PFGE showed greater discriminatory power than MLST. Subtyping data did not correlate with antimicrobial resistance phenotypes. C1 [Wang, X.; Meng, J.] NW A&F Univ, Coll Food Sci & Engn, Yanglin, Shaanxi, Peoples R China. [Zhao, S.; Harbottle, H.; Tran, T.; Blickenstaff, K.; Abbott, J.] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. [Meng, J.] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Meng, J.] Univ Maryland, JIFSAN, College Pk, MD 20742 USA. RP Meng, J (reprint author), NW A&F Univ, Coll Food Sci & Engn, Yanglin, Shaanxi, Peoples R China. EM jmeng@umd.edu FU Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland; U.S. Food and Drug Administration FX The authors thank Dr. Collette Fitzgerald of the U.S. Centers for Disease Control and Prevention for reviewing the manuscript. This study was supported in part by the Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland and the U.S. Food and Drug Administration. NR 16 TC 14 Z9 15 U1 3 U2 12 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 2011 VL 74 IS 4 BP 616 EP 621 DI 10.4315/0362-028X.JFP-10-432 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 752OC UT WOS:000289700800014 PM 21477476 ER PT J AU Darney, S Fowler, B Grandjean, P Heindel, J Mattison, D Slikker, W AF Darney, Sally Fowler, Bruce Grandjean, Philippe Heindel, Jerrold Mattison, Donald Slikker, William, Jr. TI Prenatal Programming and Toxicity II (PPTOX II): Role of environmental stressors in the developmental origins of disease SO REPRODUCTIVE TOXICOLOGY LA English DT Editorial Material C1 [Heindel, Jerrold] NIEHS, NIH, HHS, Res Triangle Pk, NC 27709 USA. [Darney, Sally] US EPA, Off Res & Dev, Washington, DC USA. [Fowler, Bruce] Ctr Dis Control, Div Toxicol & Environm Med, ATSDR, Atlanta, GA 30333 USA. [Grandjean, Philippe] Univ So Denmark, Odense, Denmark. [Mattison, Donald] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, NIH, HHS, Bethesda, MD USA. [Slikker, William, Jr.] US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. RP Heindel, J (reprint author), NIEHS, NIH, HHS, Res Triangle Pk, NC 27709 USA. EM heindelj@niehs.nih.gov RI Mattison, Donald/L-4661-2013; OI Mattison, Donald/0000-0001-5623-0874; Grandjean, Philippe/0000-0003-4046-9658 NR 0 TC 5 Z9 5 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD APR PY 2011 VL 31 IS 3 SI SI BP 271 EP 271 DI 10.1016/j.reprotox.2010.10.010 PG 1 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 753EQ UT WOS:000289749100001 PM 21035539 ER PT J AU Moore, HM Kelly, A Jewell, SD McShane, LM Clark, DP Greenspan, R Hainaut, P Hayes, DF Kim, P Mansfield, E Potapova, O Riegman, P Rubinstein, Y Seijo, E Somiari, S Watson, P Weier, HU Zhu, C Vaught, J AF Moore, Helen M. Kelly, Andrea Jewell, Scott D. McShane, Lisa M. Clark, Douglas P. Greenspan, Renata Hainaut, Pierre Hayes, Daniel F. Kim, Paula Mansfield, Elizabeth Potapova, Olga Riegman, Peter Rubinstein, Yaffa Seijo, Edward Somiari, Stella Watson, Peter Weier, Heinz-Ulrich Zhu, Claire Vaught, Jim TI Biospecimen Reporting for Improved Study Quality SO BIOPRESERVATION AND BIOBANKING LA English DT Article ID PARAFFIN-EMBEDDED TISSUES; FLIGHT-MASS-SPECTROMETRY; APPROACHING CLINICAL PROTEOMICS; GENE-EXPRESSION PROFILES; NEEDLE-ASPIRATION BIOPSY; HUMAN POSTMORTEM TISSUES; LONG-TERM STORAGE; MESSENGER-RNA; HUMAN BRAIN; MICROARRAY ANALYSIS AB Human biospecimens are subject to a number of different collection, processing, and storage factors that can significantly alter their molecular composition and consistency. These biospecimen preanalytical factors, in turn, influence experimental outcomes and the ability to reproduce scientific results. Currently, the extent and type of information specific to the biospecimen preanalytical conditions reported in scientific publications and regulatory submissions varies widely. To improve the quality of research utilizing human tissues, it is critical that information regarding the handling of biospecimens be reported in a thorough, accurate, and standardized manner. The Biospecimen Reporting for Improved Study Quality recommendations outlined herein are intended to apply to any study in which human biospecimens are used. The purpose of reporting these details is to supply others, from researchers to regulators, with more consistent and standardized information to better evaluate, interpret, compare, and reproduce the experimental results. The Biospecimen Reporting for Improved Study Quality guidelines are proposed as an important and timely resource tool to strengthen communication and publications around biospecimen-related research and help reassure patient contributors and the advocacy community that the contributions are valued and respected. C1 [Moore, Helen M.; Vaught, Jim] NCI, Off Biorepositories & Biospecimen Res, NIH, Dept Hlth & Human Serv, Rockville, MD 20852 USA. [Kelly, Andrea] Rose Li & Associates Inc, Brookeville, MD USA. [Jewell, Scott D.] Van Andel Res Inst, Program Biospecimen Sci, Grand Rapids, MI USA. [McShane, Lisa M.] NCI, Biometr Res Branch, Rockville, MD USA. [Clark, Douglas P.] Johns Hopkins Univ Hosp, Div Cytopathol, Baltimore, MD 21287 USA. [Greenspan, Renata] Walter Reed Army Med Ctr, USMCI, Washington, DC 20307 USA. [Hainaut, Pierre] WHO, Int Agcy Res Canc, Lyon, France. [Hayes, Daniel F.] Univ Michigan, Ctr Comprehens Canc, Breast Canc Res, Breast Oncol Program, Ann Arbor, MI 48109 USA. [Kim, Paula] TRAC Translating Res Communities, Green Cove Springs, FL USA. [Mansfield, Elizabeth] Ctr Devices & Radiol Hlth, CDRH Off Vitro Diagnost Device Evaluat & Safety, Silver Spring, MD USA. [Potapova, Olga] Cureline Inc, San Francisco, CA USA. [Riegman, Peter] Erasmus MC Tissue Bank, Rotterdam, Netherlands. [Rubinstein, Yaffa] NIH, Off Rare Dis Res, Rockville, MD USA. [Seijo, Edward] H Lee Moffitt Canc Ctr & Res Inst, Tampa, FL USA. [Somiari, Stella] Windber Res Inst, Windber, PA USA. [Watson, Peter] Univ British Columbia, Dept Pathol & Lab Med, Victoria, BC, Canada. [Weier, Heinz-Ulrich] Lawrence Berkeley Natl Lab, Berkeley, CA USA. [Zhu, Claire] NCI, Canc Prevent Div, Rockville, MD USA. RP Vaught, J (reprint author), NCI, Off Biorepositories & Biospecimen Res, NIH, Dept Hlth & Human Serv, 11400 Rockville Pike,Suite 700, Rockville, MD 20852 USA. EM vaughtj@mail.nih.gov RI Hainaut, Pierre /B-6018-2012 OI Hainaut, Pierre /0000-0002-1303-1610 FU NCI, National Institutes of Health [HHSN261200800001E]; NIH [CA136685]; Lawrence Berkeley National Laboratory [DE-AC002-05CH11231] FX This project has been funded in whole or in part with Federal Funds from the NCI, National Institutes of Health, under contract no. HHSN261200800001E and by NIH grant CA136685 (HUW) carried out at the Lawrence Berkeley National Laboratory under contract DE-AC002-05CH11231. The content of this publication does not necessarily reflect the views or policies of the Department of Health and Human Services, and mention of trade names, commercial products, or organizations does not imply endorsement by the U.S. Government. NR 81 TC 49 Z9 49 U1 2 U2 6 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1947-5535 J9 BIOPRESERV BIOBANK JI Biopreserv. Biobank. PD APR PY 2011 VL 9 IS 1 BP 57 EP 70 DI 10.1089/bio.2010.0036 PG 14 WC Cell Biology; Chemistry, Applied; Medical Laboratory Technology SC Cell Biology; Chemistry; Medical Laboratory Technology GA 751KS UT WOS:000289617000010 ER PT J AU Gerald, N Mahajan, B Kumar, S AF Gerald, Noel Mahajan, Babita Kumar, Sanjai TI Mitosis in the Human Malaria Parasite Plasmodium falciparum SO EUKARYOTIC CELL LA English DT Review ID ASEXUAL BLOOD STAGES; CELL-CYCLE; SEXUAL DEVELOPMENT; DNA-SYNTHESIS; ERYTHROCYTIC SCHIZOGONY; PROTEIN-KINASE; SPINDLE POLES; LIFE-CYCLE; S-PHASE; DIVISION AB Malaria is caused by intraerythrocytic protozoan parasites belonging to Plasmodium spp. (phylum Apicomplexa) that produce significant morbidity and mortality, mostly in developing countries. Plasmodium parasites have a complex life cycle that includes multiple stages in anopheline mosquito vectors and vertebrate hosts. During the life cycle, the parasites undergo several cycles of extreme population growth within a brief span, and this is critical for their continued transmission and a contributing factor for their pathogenesis in the host. As with other eukaryotes, successful mitosis is an essential requirement for Plasmodium reproduction; however, some aspects of Plasmodium mitosis are quite distinct and not fully understood. In this review, we will discuss the current understanding of the architecture and key events of mitosis in Plasmodium falciparum and related parasites and compare them with the traditional mitotic events described for other eukaryotes. C1 [Kumar, Sanjai] US FDA, DETTD, OBRR, CBER, Rockville, MD 20852 USA. RP Kumar, S (reprint author), US FDA, DETTD, OBRR, CBER, 1401 Rockville Pike HFM 313, Rockville, MD 20852 USA. EM sanjai.kumar@fda.hhs.gov FU Food and Drug Administration FX This work was supported by intramural funding from the Food and Drug Administration. NR 83 TC 35 Z9 35 U1 2 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1535-9778 J9 EUKARYOT CELL JI Eukaryot. Cell PD APR PY 2011 VL 10 IS 4 BP 474 EP 482 DI 10.1128/EC.00314-10 PG 9 WC Microbiology; Mycology SC Microbiology; Mycology GA 748RP UT WOS:000289408900002 PM 21317311 ER PT J AU Chelonis, JJ Johnson, TA Ferguson, SA Berry, KJ Kubacak, B Edwards, MC Paule, MG AF Chelonis, John J. Johnson, Teresa A. Ferguson, Sherry A. Berry, Kimberly J. Kubacak, Brian Edwards, Mark C. Paule, Merle G. TI Effect of Methylphenidate on Motivation in Children With Attention-Deficit/Hyperactivity Disorder SO EXPERIMENTAL AND CLINICAL PSYCHOPHARMACOLOGY LA English DT Article DE motivation; progressive ratio; methylphenidate; Attention Deficit Hyperactivity Disorder; children ID DEFICIT-HYPERACTIVITY DISORDER; PROGRESSIVE-RATIO PERFORMANCE; ACCUMBENS DOPAMINE DEPLETIONS; STIMULANT MEDICATION; EXECUTIVE FUNCTIONS; NUCLEUS-ACCUMBENS; DELAY AVERSION; BEHAVIORAL-INHIBITION; RESPONSE-INHIBITION; TIME REPRODUCTION AB The effects of methylphenidate (MPH) on motivation were examined using a progressive ratio (PR) task in children who were prescribed MPH for the treatment of ADHD. Twenty-one children, 7 to 12 years of age, completed two test sessions, one under the effects of medication and one not. During each session, children pressed a lever to earn nickel reinforcers, where the first press resulted in a reinforcer and 10 additional presses were required for each subsequent reinforcer. Children on MPH had a significantly higher breakpoint than when off medication. This MPH-associated increase in the breakpoint manifested as a significant decrease in the interresponse times (IRT). Further, MPH administration resulted in a significant decrease in IRT variability. In contrast, MPH administration had no significant effects on the means and variability of postreinforcement pause duration. These results suggest that MPH increased motivation in children being treated for ADHD. Further, the inability of MPH to significantly reduce postreinforcement pause duration while simultaneously decreasing IRTs suggests that while MPH may increase motivation to perform an ongoing task, it may have little effect on the initiation of that task. C1 [Chelonis, John J.; Ferguson, Sherry A.; Berry, Kimberly J.; Paule, Merle G.] Univ Arkansas Med Sci, Div Neurotoxicol, Natl Ctr Toxicol Res, Arkansas Childrens Hosp, Little Rock, AR 72205 USA. [Chelonis, John J.; Johnson, Teresa A.; Ferguson, Sherry A.; Berry, Kimberly J.; Kubacak, Brian; Edwards, Mark C.; Paule, Merle G.] Univ Arkansas Med Sci, Arkansas Childrens Hosp, Dept Pediat, Little Rock, AR 72205 USA. RP Chelonis, JJ (reprint author), AR Childrens Hosp, Dept Pediat CARE, 1 Childrens Way,Slot 512-26, Little Rock, AR 72202 USA. EM john.chelonis@fda.hhs.gov NR 66 TC 9 Z9 9 U1 2 U2 13 PU AMER PSYCHOLOGICAL ASSOC PI WASHINGTON PA 750 FIRST ST NE, WASHINGTON, DC 20002-4242 USA SN 1064-1297 J9 EXP CLIN PSYCHOPHARM JI Exp. Clin. Psychopharmacol. PD APR PY 2011 VL 19 IS 2 BP 145 EP 153 DI 10.1037/a0022794 PG 9 WC Psychology, Biological; Psychology, Clinical; Pharmacology & Pharmacy; Psychiatry SC Psychology; Pharmacology & Pharmacy; Psychiatry GA 744WX UT WOS:000289127000008 PM 21463072 ER PT J AU Su, ZQ Ning, BT Fang, H Hong, HX Perkins, R Tong, WD Shi, LM AF Su, Zhenqiang Ning, Baitang Fang, Hong Hong, Huixiao Perkins, Roger Tong, Weida Shi, Leming TI Next-generation sequencing and its applications in molecular diagnostics SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE ChIP-Seq; massively parallel sequencing; molecular diagnostics; next-generation sequencing; RNA-Seq; single-nucleotide variant; transcriptome ID CHIP-SEQ EXPERIMENTS; RNA-SEQ; CANCER GENOME; PERSONALIZED MEDICINE; QUALITY ASSESSMENT; FETAL ANEUPLOIDY; DNA; REVEALS; TOOL; ALIGNMENT AB DNA sequencing is a powerful approach for decoding a number of human diseases, including cancers. The advent of next-generation sequencing (NGS) technologies has reduced sequencing cost by orders of magnitude and significantly increased the throughput, making whole-genome sequencing a possible way for obtaining global genomic information about patients on whom clinical actions may be taken. However, the benefits offered by NGS technologies come with a number of challenges that must be adequately addressed before they can be transformed from research tools to routine clinical practices. This article provides an overview of four commonly used NGS technologies from Roche Applied Science//454 Life Sciences, Illumina, Life Technologies and Helicos Biosciences. The challenges in the analysis of NGS data and their potential applications in clinical diagnosis are also discussed. C1 [Su, Zhenqiang; Fang, Hong; Shi, Leming] US FDA, Natl Ctr Toxicol Res, Z Tech, Jefferson, AR 72079 USA. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, Z Tech, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM leming.shi@gmail.com RI Su, Zhenqiang/H-3914-2012 NR 76 TC 75 Z9 83 U1 6 U2 69 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 1473-7159 EI 1744-8352 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD APR PY 2011 VL 11 IS 3 BP 333 EP 343 DI 10.1586/ERM.11.3 PG 11 WC Pathology SC Pathology GA 750JY UT WOS:000289543600009 PM 21463242 ER PT J AU Rump, LV Strain, EA Cao, G Allard, MW Fischer, M Brown, EW Gonzalez-Escalona, N AF Rump, L. V. Strain, E. A. Cao, G. Allard, M. W. Fischer, M. Brown, E. W. Gonzalez-Escalona, N. TI Draft Genome Sequences of Six Escherichia coli Isolates from the Stepwise Model of Emergence of Escherichia coli O157:H7 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID O157-H7 AB Enterohemorrhagic Escherichia coli (EHEC) of serotype O157:H7 has been implicated in food-borne illnesses worldwide. An evolutionary model was proposed in which the highly pathogenic EHEC O157:H7 serotype arose from its ancestor, enteropathogenic E. coli (EPEC) O55:H7 (sorbitol fermenting [SOR+] and beta-glucuronidase positive [GUD(+)]), through sequential gain of virulence, phenotypic traits, and serotype change. Here we report six draft genomes of strains belonging to this evolutionary model:two EPEC O55:H7 (SOR+ GUD(+)) strains, two nonmotile EHEC O157:H- strains (SOR+ GUD(+)) containing plasmid pSFO157, one EHEC O157:H7(SOR- GUD(+)) strain, and one O157:H7 strain containing plasmid pSFO157 (SOR+ GUD(+)). C1 [Rump, L. V.; Allard, M. W.; Brown, E. W.; Gonzalez-Escalona, N.] US FDA, Div Microbiol, CFSAN, College Pk, MD 20740 USA. [Strain, E. A.] US FDA, CFSAN, Biostat Branch, College Pk, MD 20740 USA. [Cao, G.] Univ Maryland, JIFSAN, College Pk, MD 20742 USA. [Rump, L. V.; Fischer, M.] Univ Hamburg, Inst Food Chem, Hamburg, Germany. RP Gonzalez-Escalona, N (reprint author), US FDA, Div Microbiol, CFSAN, 5100 Paint Branch Pkwy,HFS-712, College Pk, MD 20740 USA. EM narjol.gonzalez-escalona@fda.hhs.gov RI Fischer, Markus/G-9477-2012; OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU Research Fellowship Program for the Center for Food Safety and Applied Nutrition FX This project was supported by an appointment to the Research Fellowship Program for the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Associated Universities through a contract with the FDA. NR 11 TC 10 Z9 10 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2011 VL 193 IS 8 BP 2058 EP 2059 DI 10.1128/JB.00118-11 PG 2 WC Microbiology SC Microbiology GA 746GA UT WOS:000289229900029 PM 21317333 ER PT J AU Lei, YF Huang, Y Zhang, H Yu, L Zhang, MJ Dayton, A AF Lei, Yingfeng Huang, Yong Zhang, Hai Yu, Li Zhang, Mingjie Dayton, Andrew TI Functional interaction between cellular p100 and the dengue virus 3 ' UTR SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID TRACT-BINDING-PROTEIN; WEST-NILE VIRUS; 3'-UNTRANSLATED REGION; UNTRANSLATED REGION; RNA REPLICATION; CYCLIZATION SEQUENCES; VIRAL REPLICATION; HOST FACTORS; STRAND RNA; TRANSLATION AB Host factors interacting with the dengue virus (DENV) 3' UTR are involved in virus replication, but their roles remain poorly understood. We used RNA affinity capture and mass spectrometry to identify p100 as a host cellular protein associated with the DENV 3' UTR. By using RNA immunoprecipitation and confocal immunofluorescence analysis we demonstrated an interaction between p100 and the 3' UTR in DEN V-infected cells. We identified the A4 region (the extensive stem loop structure at the 3' end) as the binding site of p100 by studying deletion mutants. p100 knockdown specifically reduced the levels of viral RNA and viral protein in DENV-infected cells. Furthermore, downregulation of p100 reduced the expression of a heterologously expressed luciferase-3' UTR(DENV) mRNA in an A4-dependent manner, confirming the binding data and the effects of p100 knockdown on viral replication. These results provide evidence that p100 interacts with the 3' UTR of DENV and is required for normal DENV replication. C1 [Lei, Yingfeng; Huang, Yong; Zhang, Hai; Yu, Li; Zhang, Mingjie; Dayton, Andrew] US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Lei, Yingfeng] Fourth Mil Med Univ, Dept Microbiol, Xian 710032, Shaanxi, Peoples R China. [Huang, Yong; Zhang, Mingjie; Dayton, Andrew] NW Polytech Univ, Dept Life Sci, Xian 710072, Shaanxi, Peoples R China. [Zhang, Hai] Fourth Mil Med Univ, Ctr Anim Facil, Xian 710032, Shaanxi, Peoples R China. [Yu, Li] US FDA, Ctr Biol Evaluat & Res, Lab Vector Borne Dis, Rockville, MD 20852 USA. RP Dayton, A (reprint author), US FDA, Mol Virol Lab, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM ming.zhang@fda.hhs.gov; andrew.dayton@fda.hhs.gov RI Huang, Yong/G-9365-2011 NR 45 TC 27 Z9 28 U1 0 U2 2 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 APR PY 2011 VL 92 BP 796 EP 806 DI 10.1099/vir.0.028597-0 PN 4 PG 11 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 748KP UT WOS:000289389800008 PM 21148275 ER PT J AU Modi, B Lewis, J Filler, R Fu, P Cai, L Hayday, A Girardi, M AF Modi, B. Lewis, J. Filler, R. Fu, P. Cai, L. Hayday, A. Girardi, M. TI Initiation with DMBA metabolite bypasses requirement for Langerhans cell in two-stage chemical carcinogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Modi, B.; Lewis, J.; Filler, R.; Girardi, M.] Yale Univ, New Haven, CT USA. [Fu, P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Cai, L.] Biotranex, Monmouth Jct, NJ USA. [Hayday, A.] GKT, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 097 BP S17 EP S17 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600097 ER PT J AU Poole, CF Poole, SK AF Poole, Colin F. Poole, Salwa K. TI Ionic liquid stationary phases for gas chromatography SO JOURNAL OF SEPARATION SCIENCE LA English DT Review DE Gas chromatography; Ionic liquids; Solvation parameter model; Stationary phases ID OPEN-TUBULAR COLUMNS; SOLUTE-SOLVENT INTERACTIONS; MICELLAR ELECTROKINETIC CHROMATOGRAPHY; QUATERNARY PHOSPHONIUM COMPOUNDS; SOLVATION ENERGY RELATIONSHIP; N-BUTYLAMMONIUM SALTS; ORGANIC SALTS; PHYSICOCHEMICAL PROPERTIES; PARTITION CHROMATOGRAPHY; AMMONIUM-SALTS AB This article provides a summary of the development of ionic liquids as stationary phases for gas chromatography beginning with early work on packed columns that established details of the retention mechanism and established working methods to characterize selectivity differences compared with molecular stationary phases through the modern development of multi-centered cation and cross-linked ionic liquids for high-temperature applications in capillary gas chromatography. Since there are many reviews on ionic liquids dealing with all aspects of their chemical and physical properties, the emphasis in this article is placed on the role of gas chromatography played in the design of ionic liquids of low melting point, high thermal stability, high viscosity, and variable selectivity for separations. Ionic liquids provide unprecedented opportunities for extending the selectivity range and temperature-operating range of columns for gas chromatography, an area of separation science that has otherwise been almost stagnant for over a decade. C1 [Poole, Colin F.] Wayne State Univ, Dept Chem, Detroit, MI 48202 USA. [Poole, Salwa K.] US FDA, Detroit Dist Lab, Detroit, MI USA. RP Poole, CF (reprint author), Wayne State Univ, Dept Chem, Rm 183,5101 Cass Ave, Detroit, MI 48202 USA. EM cfp@chem.wayne.edu NR 106 TC 101 Z9 103 U1 9 U2 76 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1615-9306 J9 J SEP SCI JI J. Sep. Sci. PD APR PY 2011 VL 34 IS 8 BP 888 EP 900 DI 10.1002/jssc.201000724 PG 13 WC Chemistry, Analytical SC Chemistry GA 749PO UT WOS:000289481000004 PM 21290604 ER PT J AU Duncan, JR Balter, S Becker, GJ Brady, J Brink, JA Bulas, D Chatfield, MB Choi, S Connolly, BL Dixon, RG Gray, JE Kee, ST Miller, DL Robinson, DW Sands, MJ Schauer, DA Steele, JR Street, M Thornton, RH Wise, RA AF Duncan, James R. Balter, Stephen Becker, Gary J. Brady, Jeffrey Brink, James A. Bulas, Dorothy Chatfield, Mythreyi B. Choi, Simon Connolly, Bairbre L. Dixon, Robert G. Gray, Joel E. Kee, Stephen T. Miller, Donald L. Robinson, Donald W. Sands, Mark J. Schauer, David A. Steele, Joseph R. Street, Mandie Thornton, Raymond H. Wise, Robert A. TI Optimizing Radiation Use during Fluoroscopic Procedures: Proceedings from a Multidisciplinary Consensus Panel SO JOURNAL OF VASCULAR AND INTERVENTIONAL RADIOLOGY LA English DT Article ID INTERVENTIONAL RADIOLOGY PROCEDURES; BOARD-OF-RADIOLOGY; COMPUTED-TOMOGRAPHY; IONIZING-RADIATION; PEDIATRIC CT; CANCER-RISKS; RAD-IR; DIAGNOSTIC-RADIOLOGY; QUALITY IMPROVEMENT; DOSE AWARENESS C1 [Duncan, James R.; Street, Mandie] Washington Univ, Mallinckrodt Inst Radiol, Sch Med, St Louis, MO 63110 USA. [Balter, Stephen] Columbia Univ, Dept Med, Med Ctr, New York, NY 10027 USA. [Thornton, Raymond H.] Mem Sloan Kettering Canc Ctr, Dept Med Phys, New York, NY 10021 USA. [Becker, Gary J.] Amer Board Radiol, Tucson, AZ USA. [Brady, Jeffrey] Agcy Healthcare Res & Qual, Rockville, MD USA. [Choi, Simon] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Miller, Donald L.] Natl Naval Med Ctr, Dept Radiol, Bethesda, MD USA. [Miller, Donald L.] Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, F Edward Hebert Sch Med, Bethesda, MD USA. [Schauer, David A.] Natl Council Radiat Protect & Measurements, Bethesda, MD USA. [Brink, James A.] Yale Univ, Dept Diagnost Radiol, New Haven, CT 06510 USA. [Bulas, Dorothy] Childrens Natl Med Ctr, Div Diagnost Imaging, Washington, DC USA. [Robinson, Donald W.] US Dept Def, Patient Safety Program, Washington, DC 20305 USA. [Chatfield, Mythreyi B.] Amer Coll Radiol, Reston, VA USA. [Connolly, Bairbre L.] Hosp Sick Children, Dept Diagnost Imaging, Toronto, ON M5G 1X8, Canada. [Dixon, Robert G.] Univ N Carolina, Dept Vasc & Intervent Radiol, Chapel Hill, NC USA. [Gray, Joel E.] Mayo Clin, Coll Med, Rochester, MN USA. [Kee, Stephen T.] Ronald Regan Univ Calif Los Angeles, Dept Radiol, Med Ctr, Los Angeles, CA USA. [Sands, Mark J.] Cleveland Clin, Sect Intervent Radiol, Imaging Inst, Cleveland, OH 44106 USA. [Steele, Joseph R.] Univ Texas MD Anderson Canc Ctr, Dept Intervent Radiol, Houston, TX 77030 USA. [Wise, Robert A.] Joint Commiss, Div Stand & Survey Methods, Oak Brook Terrace, IL USA. RP Duncan, JR (reprint author), Washington Univ, Mallinckrodt Inst Radiol, Sch Med, 510 S Kingshighway Blvd, St Louis, MO 63110 USA. EM duncanj@mir.wustl.edu OI Duncan, James/0000-0002-0337-8805 NR 52 TC 7 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1051-0443 EI 1535-7732 J9 J VASC INTERV RADIOL JI J. Vasc. Interv. Radiol. PD APR PY 2011 VL 22 IS 4 BP 425 EP 429 DI 10.1016/j.jvir.2010.12.008 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging; Peripheral Vascular Disease SC Radiology, Nuclear Medicine & Medical Imaging; Cardiovascular System & Cardiology GA 747SQ UT WOS:000289340100001 PM 21463753 ER PT J AU Rosman, NP Tarquinio, DC Datseris, M Hou, W Mannheim, GB Emigh, CE Rivkin, MJ AF Rosman, N. Paul Tarquinio, Daniel C. Datseris, Marianna Hou, Wei Mannheim, Glenn B. Emigh, Christie E. Rivkin, Michael J. TI Postnatal-Onset Microcephaly: Pathogenesis, Patterns of Growth, and Prediction of Outcome SO PEDIATRICS LA English DT Article DE microcephaly; growth; anthropometry; intelligence; prognosis factors ID RETT-SYNDROME; HEAD CIRCUMFERENCE; WEIGHT-GAIN; LMS METHOD; RESTRICTION; IQ; INFANTS; BRAIN; TERM; AGE AB OBJECTIVE: Although children with postnatal-onset microcephaly (POM) generally have poor development, we speculated that better somatic growth would predict better development in these children. PATIENTS AND METHODS: We followed 57 children with POM for an average of 4.2 years (13 encephaloclastic, 14 dysgenetic, 6 with Rett syndrome, 24 idiopathic) and calculated the developmental quotient (DQ) at each visit (DQ > 0.70 was considered normal). SD scores (SDS) for measurements were analyzed using a repeated measures mixed-effects model to assess effect of weight, height, head circumference (HC), and age on DQ. Pearson's correlation was used to examine the independent influence of each variable on final DQ. RESULTS: Forty-four children (77%) had a low DQ (mean: 0.33), but 13 (23%) had a normal DQ (mean: 0.93), including 10 idiopathic and 3 encephaloclastic. Mean HC fell below -2 SDS in all before 1 year (destructive at 3.3 months, idiopathic low-DQ at 7.5 months, dysgenetic at 8.5 months, Rett syndrome at 11 months, and idiopathic normal-DQ at 11.5 months). Mean weights and heights both fell below -2 SDS for all low-DQ groups but remained normal in both normal-DQ groups. Weight, height, and HC were independent predictors of DQ (P < .0001). Final DQ correlated with weight (r = 0.27), height (r = 0.41), and HC (r = 0.13). CONCLUSIONS: Most children with POM have poor later development. Whatever the cause of POM, persons in whom postnatal body growth (weight, height, HC) is better sustained have more favorable development, and in one-quarter of such persons (mostly idiopathic POM), final DQ is normal. Pediatrics 2011; 127:665-671 C1 [Rosman, N. Paul; Tarquinio, Daniel C.] Boston Univ, Sch Med, Boston Med Ctr, Div Pediat Neurol,Dept Pediat, Boston, MA 02118 USA. [Rosman, N. Paul; Tarquinio, Daniel C.] Boston Univ, Sch Med, Boston Med Ctr, Div Pediat Neurol,Dept Neurol, Boston, MA 02118 USA. [Datseris, Marianna] Long Isl Jewish Med Ctr, Albert Einstein Coll Med, Dept Child & Adolescent Psychiat, Glen Oaks, NY USA. [Hou, Wei] Univ Florida, Dept Epidemiol & Hlth Policy Res, Gainesville, FL USA. [Mannheim, Glenn B.] US FDA, Div Psychiat Prod, Silver Spring, MD USA. [Emigh, Christie E.] Dorothea Dix Psychiat Ctr, Bangor, ME USA. [Rivkin, Michael J.] Harvard Univ, Sch Med, Dept Neurol, Childrens Hosp Boston, Boston, MA 02115 USA. RP Rosman, NP (reprint author), Boston Univ, Sch Med, Boston Med Ctr, Div Pediat Neurol,Dept Pediat, 1 Boston Med Ctr Pl,Dowling 3 S, Boston, MA 02118 USA. EM npaul.rosman@bmc.org OI Tarquinio, Daniel/0000-0002-3392-0327 NR 26 TC 8 Z9 8 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD APR PY 2011 VL 127 IS 4 BP 665 EP 671 DI 10.1542/peds.2010-1576 PG 7 WC Pediatrics SC Pediatrics GA 744DQ UT WOS:000289074800047 PM 21422087 ER PT J AU Volpe, DA Tobin, GAM Mellon, RD Katki, AG Parker, RJ Colatslcy, T Kropp, TJ Verbois, SL AF Volpe, Donna A. Tobin, Grainne A. McMahon Mellon, R. Daniel Katki, Aspandiar G. Parker, Robert J. Colatslcy, Thomas Kropp, Timothy J. Verbois, S. Leigh TI Uniform assessment and ranking of opioid Mu receptor binding constants for selected opioid drugs SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE Opioids; Receptor; Mu; Binding; K(i) ID RAT-BRAIN; SPECIES-DIFFERENCES; ACTIVE METABOLITES; OPIATE RECEPTORS; MORPHINE; AFFINITY; OXYCODONE; AGONIST; TRAMADOL; FENTANYL AB The safe disposal of unused opioid drugs is an area of regulatory concern. While toilet flushing is recommended for some drugs to prevent accidental exposure, there is a need for data that can support a more consistent disposal policy based on an assessment of relative risk. For drugs acting at the Mu-opioid receptor (MOR), published measurements of binding affinity (K(i)) are incomplete and inconsistent due to differences in methodology and assay system, leading to a wide range of values for the same drug thus precluding a simple and meaningful relative ranking of drug potency. Experiments were conducted to obtain K(i)'s for 19 approved opioid drugs using a single binding assay in a cell membrane preparation expressing recombinant human MOR. The K(i) values obtained ranged from 0.1380 (sufentanil) to 12.486 mu M (tramadol). The drugs were separated into three categories based upon their K(i) values: K(i) > 100 nM (tramadol, codeine, meperidine, propoxyphene and pentazocine), K(i) =1-100 nM (hydrocodone, oxycodone, diphenoxylate, alfentanil, methadone, nalbuphine, fentanyl and morphine) and K(i) < 1 nM (butorphanol, levorphanol, oxymorphone, hydromorphone, buprenorphine and sufentanil). These data add to the understanding of the pharmacology of opioid drugs and support the development of a more consistent labeling policies regarding safe disposal. Published by Elsevier Inc. C1 [Volpe, Donna A.; Tobin, Grainne A. McMahon; Katki, Aspandiar G.; Parker, Robert J.; Colatslcy, Thomas] US FDA, Lab Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Mellon, R. Daniel] US FDA, Div Anesthesia & Analgesia Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Kropp, Timothy J.; Verbois, S. Leigh] US FDA, Div Drug Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Volpe, DA (reprint author), US FDA, Lab Clin Pharmacol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM donna.volpe@fda.hhs.gov NR 51 TC 51 Z9 53 U1 6 U2 28 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 2011 VL 59 IS 3 BP 385 EP 390 DI 10.1016/j.yrtph.2010.12.007 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 742YO UT WOS:000288981500004 PM 21215785 ER PT J AU Kaman, WE Hulst, AG van Alphen, PTW Roffel, S van der Schans, MJ Merkel, T van Belkum, A Bikker, FJ AF Kaman, Wendy E. Hulst, Albert G. van Alphen, Pleunie T. W. Roffel, Sanne van der Schans, Marcel J. Merkel, Tod van Belkum, Alex Bikker, Floris J. TI Peptide-Based Fluorescence Resonance Energy Transfer Protease Substrates for the Detection and Diagnosis of Bacillus Species SO ANALYTICAL CHEMISTRY LA English DT Article ID ANTHRAX LETHAL FACTOR; RAPID-DETECTION; PLASMID; ASSAY; INFECTION; ANTIGEN; TOXIN; SERUM AB We describe the development of a highly specific enzyme-based fluorescence resonance energy transfer (FRET) assay for easy and rapid detection both in vitro and in vivo of Bacillus spp., among which are the members of the B. cereus group. Synthetic substrates for B. anthracis proteases were designed and exposed to secreted enzymes of a broad spectrum of bacterial species. The rational design of the substrates was based on the fact that the presence of D-amino acids in the target is highly specific for bacterial proteases. The designed D-amino acids containing substrates appeared to be specific for B. anthracis but also for several other Bacillus spp. and for both vegetative cells and spores. With the use of mass spectrometry (MS), cleavage products of the substrates could be detected in sera of B. anthracis infected mice but not in healthy mice. Due to the presence of mirrored amino acids present in the substrate, the substrates showed high species specificity, and enzyme isolation and purification was redundant. The substrate wherein the D-amino acid was replaced by its L-isomer showed a loss of specificity. In conclusion, with the use of these substrates a rapid tool for detection of B. anthracis spores and diagnosis of anthrax infection is at hand. We are the first who present fluorogenic substrates for detection of bacterial proteolytic enzymes that can be directly applied in situ by the use of D-oriented amino acids. C1 [Kaman, Wendy E.; van Belkum, Alex] Erasmus MC, Dept Med Microbiol & Infect Dis, NL-3015 CE Rotterdam, Netherlands. [Kaman, Wendy E.; Hulst, Albert G.; van Alphen, Pleunie T. W.; Roffel, Sanne; van der Schans, Marcel J.; Bikker, Floris J.] TNO Def Secur & Safety, NL-2288 GJ Rijswijk, Netherlands. [Kaman, Wendy E.; Roffel, Sanne; Bikker, Floris J.] Univ Amsterdam, Dept Oral Biochem, Acad Ctr Dent Amsterdam, NL-1081 LA Amsterdam, Netherlands. [Kaman, Wendy E.; Roffel, Sanne; Bikker, Floris J.] Vrije Univ Amsterdam, NL-1081 LA Amsterdam, Netherlands. [Merkel, Tod] US FDA, CBER Lab, Bethesda, MD 20892 USA. [van Belkum, Alex] BioMerieux, F-38390 La Balme Les Grottes, France. RP Kaman, WE (reprint author), Erasmus MC, Dept Med Microbiol & Infect Dis, S Gravendijkwal 230, NL-3015 CE Rotterdam, Netherlands. EM w.kaman@erasmusmc.nl RI Bikker, Floris/B-1187-2012; Kaman, Wendy/B-2976-2012 FU Dutch Ministry of Defence [V502] FX This work was financially supported by the V502 program of the Dutch Ministry of Defence. We thank Ingrid Visser-Voskamp for her help on the preparation of the B. anthracis and B. subtilis spores. NR 32 TC 22 Z9 23 U1 0 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD APR 1 PY 2011 VL 83 IS 7 BP 2511 EP 2517 DI 10.1021/ac102764v PG 7 WC Chemistry, Analytical SC Chemistry GA 741TM UT WOS:000288887700017 PM 21370823 ER PT J AU Boja, ES Jortani, SA Ritchie, J Hoofnagle, AN Tezak, Z Mansfield, E Keller, P Rivers, RC Rahbar, A Anderson, NL Srinivas, P Rodriguez, H AF Boja, Emily S. Jortani, Saeed A. Ritchie, James Hoofnagle, Andrew N. Tezak, Zivana Mansfield, Elizabeth Keller, Penny Rivers, Robert C. Rahbar, Amir Anderson, N. Leigh Srinivas, Pothur Rodriguez, Henry TI The Journey to Regulation of Protein-Based Multiplex Quantitative Assays SO CLINICAL CHEMISTRY LA English DT Article ID BIOMARKER DISCOVERY; MASS-SPECTROMETRY; VALIDATION; QUANTIFICATION; ACTIVATION; ENRICHMENT; MODELS; PLASMA; SERUM AB BACKGROUND: Clinical proteomics presents great promise in biology and medicine because of its potential for improving our understanding of diseases at the molecular level and for detecting disease-related biomarkers for diagnosis, prognosis, and prediction of therapeutic responses. To realize its full potential to improve clinical outcome for patients, proteomic studies have to be well designed, from biosample cohorts to data and statistical analyses. One key component in the biomarker development pipeline is the understanding of the regulatory science that evaluates diagnostic assay performance through rigorous analytical and clinical review criteria. CONTENT: The National Cancer Institute's Clinical Proteomic Technologies for Cancer (CPTC) initiative has proposed an intermediate preclinical "verification" step to close the gap between protein-based biomarker discovery and clinical qualification. In collaboration with the US Food and Drug Administration (FDA), the CPTC network investigators recently published 2 mock submission review documents, first-of-their-kind educational materials that may help the scientific community interested in developing products for the clinic in understanding the likely analytical evaluation requirements for multiplex protein technology-based diagnostic tests. CONCLUSIONS: Building on this momentum, the CPTC continues with this report its collaboration with the FDA, as well as its interactions with the AACC and the Centers for Medicare and Medicaid Services, to further the understanding of regulatory requirements for approving multiplex proteomic platform-based tests and analytically validating multiple analytes.(C) 2011 American Association for Clinical Chemistry C1 [Boja, Emily S.; Rivers, Robert C.; Rahbar, Amir; Rodriguez, Henry] NCI, Off Canc Clin Prote Res, NIH, Bethesda, MD 20892 USA. [Jortani, Saeed A.] Univ Louisville, Dept Pathol & Lab Med, Louisville, KY 40292 USA. [Ritchie, James] Emory Univ, Sch Med, Atlanta, GA USA. [Hoofnagle, Andrew N.] Univ Washington, Dept Lab Med, Seattle, WA 98195 USA. [Tezak, Zivana; Mansfield, Elizabeth] US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Keller, Penny] Ctr Medicare & Medicaid Serv, Baltimore, MD USA. [Anderson, N. Leigh] Plasma Proteome Inst, Washington, DC USA. [Srinivas, Pothur] NHLBI, NIH, Bethesda, MD 20892 USA. RP Boja, ES (reprint author), NCI, Off Canc Clin Prote Res, NIH, Bethesda, MD 20892 USA. EM bojae@mail.nih.gov FU Waters FX A.N. Hoofnagle, Waters. NR 21 TC 25 Z9 26 U1 0 U2 10 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 EI 1530-8561 J9 CLIN CHEM JI Clin. Chem. PD APR PY 2011 VL 57 IS 4 BP 560 EP 567 DI 10.1373/clinchem.2010.156034 PG 8 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 741HE UT WOS:000288854000008 PM 21300740 ER PT J AU Zhang, L Huang, SM Lesko, LJ AF Zhang, L. Huang, S-M Lesko, L. J. TI Transporter-Mediated Drug-Drug Interactions SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB Transporters are membrane-bound proteins that control the access of endogenous and xenobiotics (drugs) to various sites in the human body. They influence drug pharmacokinetics and pharmacodynamics (both benefit and risk) by affecting a drug's absorption, distribution, metabolism (via control of access to metabolizing enzymes), and excretion (ADME) and by controlling drug concentrations at the site of action. Like metabolizing enzymes, transporters have binding sites that are saturable and can be inhibited or induced. C1 [Zhang, L.; Huang, S-M; Lesko, L. J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Zhang, L (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM leik.zhang@fda.hhs.gov NR 5 TC 29 Z9 30 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 2011 VL 89 IS 4 BP 481 EP 484 DI 10.1038/clpt.2010.359 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 738OK UT WOS:000288649600008 PM 21423238 ER PT J AU Molzon, JA Giaquinto, A Lindstrom, L Tominaga, T Ward, M Doerr, P Hunt, L Rago, L AF Molzon, J. A. Giaquinto, A. Lindstrom, L. Tominaga, T. Ward, M. Doerr, P. Hunt, L. Rago, L. TI The Value and Benefits of the International Conference on Harmonisation to Drug Regulatory Authorities: Advancing Harmonization for Better Public Health SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID COMMON TECHNICAL DOCUMENT AB The International Conference on Harmonisation (ICH) is an unparalleled undertaking, which has brought together drug regulatory authorities and pharmaceutical trade associations from Europe, Japan, and the United States, to discuss the scientific and technical aspects of medical product registration. Launched in 1990, the value and benefits of ICH to regulators are being realized. ICH has harmonized submission requirements and created a harmonized submission format that is relieving both companies and regulatory authorities of the burdens of assembling and reviewing separate submissions for each region. As more countries embrace ICH guidelines, we anticipate additional benefits, including the promotion of good review practices and, ultimately, a common regulatory language that will facilitate further interactions among global drug regulatory authorities. C1 [Molzon, J. A.] US FDA, Silver Spring, MD USA. [Lindstrom, L.] Commiss European Communities, B-1049 Brussels, Belgium. [Tominaga, T.] Pharmaceut & Med Devices Agcy, Tokyo, Japan. [Ward, M.] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Doerr, P.] Swiss Agcy Therapeut Prod, Bern, Switzerland. [Hunt, L.] Australian Therapeut Goods Adm, Woden, ACT, Australia. [Rago, L.] WHO, CH-1211 Geneva, Switzerland. RP Molzon, JA (reprint author), US FDA, Silver Spring, MD USA. EM justina.molzon@fda.hhs.gov RI Hunt, Liam/C-7344-2017 NR 7 TC 11 Z9 11 U1 2 U2 13 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 2011 VL 89 IS 4 BP 503 EP 512 DI 10.1038/clpt.2011.10 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 738OK UT WOS:000288649600017 PM 21326288 ER PT J AU Lando, AM Zhang, YT AF Lando, Amy M. Zhang, Yuanting TI Awareness and knowledge of methylmercury in fish in the United States SO ENVIRONMENTAL RESEARCH LA English DT Article DE Methylmercury; National survey; Fish consumption; Women of childbearing age ID MERCURY LEVELS; CONSUMPTION ADVISORIES; RISK COMMUNICATION; CHILDBEARING AGE; SPORT-FISH; WOMEN; POPULATION; CONSUMERS; CHILDREN AB In the 1970s several states in the Great Lakes region became concerned about mercury contamination in lakes and rivers and were the first to issue local fish consumption advisories. In 2001, the Food and Drug Administration (FDA) advised pregnant women, nursing mothers, young children, and women who may become pregnant not to consume shark, swordfish, king mackerel, and tilefish and recommended that these women not exceed 12 ounces of other fish per week. In 2004, FDA reissued this advice jointly with the U.S. Environmental Protection Agency (EPA) and modified it slightly to provide information about consumption of canned tuna and more details about consumption of recreationally caught fish. Though several studies have examined consumers' awareness of the joint FDA and EPA advisory as well as different state advisories, few used representative data. We examined the changes in awareness and knowledge of mercury as a problem in fish using the pooled nationally representative 2001 and 2006 Food Safety Surveys (FSS) with sample sizes of 4482 in 2001 and 2275 in 2006. Our results indicated an increase in consumers' awareness of mercury as a problem in fish (69% in 2001 to 80% in 2006, p < .001). In our regression models, we found that in both years, parents having children less than 5 years of age were more aware of mercury in fish and knowledgeable about the information contained in the national advisories about mercury in fish (p < .01) than other adults. In both 2001 and 2006, women of childbearing age (aged 18-45) were less aware and knowledgeable about this information than other women. However, women of all age groups had larger gains in awareness and knowledge than their male counterparts during this time. Participants' race, education, income, region, fish preparation experiences, having a foodborne illness in the past year, and risk perceptions about the safety of food were significant predictors of their awareness and knowledge. Published by Elsevier Inc. C1 [Lando, Amy M.; Zhang, Yuanting] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Lando, AM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM amy.lando@fda.hhs.gov FU United States Food and Drug Administration; United States Environmental Protection Agency; United Stated Department of Agriculture, Food Safety Inspection Service FX United States Food and Drug Administration: United States Environmental Protection Agency: United Stated Department of Agriculture, Food Safety Inspection Service. The FDA's Research Involving Human Subjects Protection committee exempted this study from full Institutional Review Board review. NR 36 TC 15 Z9 15 U1 1 U2 18 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD APR PY 2011 VL 111 IS 3 BP 442 EP 450 DI 10.1016/j.envres.2011.01.004 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 743OC UT WOS:000289026700017 PM 21257163 ER PT J AU Abel, D Morales, JP AF Abel, Dorothy Morales, Jose Pablo TI Food and Drug Administration commentary on the SVS masterfile for acute complicated type B aortic dissections and transections SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ENDOVASCULAR STENT-GRAFTS; PLACEMENT; REPAIR C1 [Abel, Dorothy; Morales, Jose Pablo] US FDA, Div Cardiovasc Devices, Silver Spring, MD USA. RP Abel, D (reprint author), US FDA, Div Cardiovasc Devices, Silver Spring, MD USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD APR PY 2011 VL 53 IS 4 BP 1079 EP 1081 DI 10.1016/j.jvs.2010.11.125 PG 3 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 743IS UT WOS:000289012600027 PM 21439458 ER PT J AU Cho, HC Hadjiiski, L Sahiner, B Chan, HP Helvie, M Paramagul, C Nees, AV AF Cho, Hyun-chong Hadjiiski, Lubomir Sahiner, Berkman Chan, Heang-Ping Helvie, Mark Paramagul, Chintana Nees, Alexis V. TI Similarity evaluation in a content-based image retrieval (CBIR) CADx system for characterization of breast masses on ultrasound images SO MEDICAL PHYSICS LA English DT Article DE computer-aided diagnosis; ultrasonography; breast mass characterization; content-based image retrieval ID COMPUTER-AIDED DIAGNOSIS; HIGH FAMILIAL RISK; NEURAL-NETWORKS; RADIOLOGISTS CHARACTERIZATION; SONOGRAPHIC FEATURES; MAMMOGRAPHIC MASSES; SERIAL MAMMOGRAMS; BI-RADS; CANCER; LESIONS AB Purpose: The authors are developing a content-based image retrieval (CBIR) CADx system to assist radiologists in characterization of breast masses on ultrasound images. In this study, the authors compared seven similarity measures to be considered for the CBIR system. The similarity between the query and the retrieved masses was evaluated based on radiologists' visual similarity assessments. Methods: The CADx system retrieves masses that are similar to a query mass from a reference library based on computer-extracted features using a k-nearest neighbor (k-NN) approach. Among seven similarity measures evaluated for the CBIR system, four similarity measures including linear discriminant analysis (LDA), Bayesian neural network (BNN), cosine similarity measure (Cos), and Euclidean distance (ED) similarity measure were compared by radiologists' visual assessment. For LDA and BNN, the features of a query mass were combined first into a malignancy score and then masses with similar scores were retrieved. For Cos and ED, similar masses were retrieved based on the normalized dot product and the Euclidean distance, respectively, between two feature vectors. For the observer study, three most similar masses were retrieved for a given query mass with each method. All query-retrieved mass pairs were mixed and presented to the radiologists in random order. Three Mammography Quality Standards Act (MQSA) radiologists rated the similarity between each pair using a nine-point similarity scale (1=very dissimilar, 9=very similar). The accuracy of the CBIR CADx system using the different similarity measures to characterize malignant and benign masses was evaluated by ROC analysis. Results: The BNN measure used with the k-NN classifier provided slightly higher performance for classification of malignant and benign masses (A(z) values of 0.87) than those with the LDA, Cos, and ED measures (A(z) of 0.86, 0.84, and 0.81, respectively). The average similarity ratings of all radiologists for LDA, BNN, Cos, and ED were 4.71, 4.95, 5.18, and 5.32, respectively. The k-NN with the ED measures retrieved masses of significantly higher similarity (p < 0.008) than LDA and BNN. Conclusions: Similarity measures using the resemblance of individual features in the multidimensional feature space can retrieve visually more similar masses than similarity measures using the resemblance of the classifier scores. A CBIR system that can most effectively retrieve similar masses to the query may not have the best A(z). (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3560877] C1 [Cho, Hyun-chong; Hadjiiski, Lubomir; Sahiner, Berkman; Chan, Heang-Ping; Helvie, Mark; Paramagul, Chintana; Nees, Alexis V.] Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. [Sahiner, Berkman] US FDA, Silver Spring, MD 20993 USA. RP Cho, HC (reprint author), Univ Michigan, Dept Radiol, Ann Arbor, MI 48109 USA. EM hyunchon@umich.edu FU USPHS [CA 118305] FX This work was supported by USPHS under Grant No. CA 118305. The authors are grateful to Charles E. Metz, Ph.D., for the LABROC program. NR 47 TC 14 Z9 15 U1 3 U2 10 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 APR PY 2011 VL 38 IS 4 BP 1820 EP 1831 DI 10.1118/1.3560877 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 745GI UT WOS:000289153500010 PM 21626916 ER PT J AU Badano, A Freed, M Fang, YA AF Badano, Aldo Freed, Melanie Fang, Yuan TI Oblique incidence effects in direct x-ray detectors: A first-order approximation using a physics-based analytical model SO MEDICAL PHYSICS LA English DT Article DE direct detectors; indirect detector oblique incidence; detector response ID ANISOTROPIC IMAGING PERFORMANCE; BREAST TOMOSYNTHESIS; RESOLUTION; SYSTEMS; MANTIS AB Purpose: The authors describe the modifications to a previously developed analytical model of indirect CsI:Tl-based detector response required for studying oblique x-ray incidence effects in direct semiconductor-based detectors. This first-order approximation analysis allows the authors to describe the associated degradation in resolution in direct detectors and compare the predictions to the published data for indirect detectors. Methods: The proposed model is based on a physics-based analytical description developed by Freed et al. ["A fast, angle-dependent, analytical model of CsI detector response for optimization of 3D x-ray breast imaging systems," Med. Phys. 37(6), 2593-2605 (2010)] that describes detector response functions for indirect detectors and oblique incident x rays. The model, modified in this work to address direct detector response, describes the dependence of the response with x-ray energy, thickness of the transducer layer, and the depth-dependent blur and collection efficiency. Results: The authors report the detector response functions for indirect and direct detector models for typical thicknesses utilized in clinical systems for full-field digital mammography (150) m for indirect CsI: Tl and 200 mu m for a-Se direct detectors). The results suggest that the oblique incidence effect in a semiconductor detector differs from that in indirect detectors in two ways: The direct detector model produces a sharper overall PRF compared to the response corresponding to the indirect detector model for normal x-ray incidence and a larger relative increase in blur along the x-ray incidence direction compared to that found in indirect detectors with respect to the response at normal incidence angles. Conclusions: Compared to the effect seen in indirect detectors, the direct detector model exhibits a sharper response at normal x-ray incidence and a larger relative increase in blur along the x-ray incidence direction with respect to the blur in the orthogonal direction. The results suggest that the oblique incidence effect in direct detectors can be considered to be caused mostly by the geometry of the path where the x-ray beam and its secondary particles deposit energy in the semiconductor layer. [DOI: 10.1118/1.3567497] C1 [Badano, Aldo; Freed, Melanie; Fang, Yuan] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Freed, Melanie] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. [Fang, Yuan] Univ Waterloo, Dept Elect & Comp Engn, Waterloo, ON N2L 3G1, Canada. RP Badano, A (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 FU FDA's Office of Women's Health; Center for Devices and Radiological Health; U.S. Department of Energy; U.S. Food and Drug Administration; Carl A. Pollock postgraduate fellowship FX The authors thank the support of K. Karim (University of Waterloo) and acknowledge funding from the FDA's Office of Women's Health. The authors also acknowledge funding by appointments 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. This work was also supported, in part, by the Carl A. Pollock postgraduate fellowship award (Y.F.). NR 11 TC 15 Z9 15 U1 0 U2 9 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 APR PY 2011 VL 38 IS 4 BP 2095 EP 2098 DI 10.1118/1.3567497 PG 4 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 745GI UT WOS:000289153500036 PM 21626942 ER PT J AU Freed, M Park, S Badano, A AF Freed, M. Park, S. Badano, A. TI A fast, angle-dependent, analytical model of CsI detector response for optimization of 3D x-ray breast imaging systems (vol 37, pg 2593, 2010) SO MEDICAL PHYSICS LA English DT Correction C1 [Freed, M.; Park, S.; Badano, A.] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Freed, M.] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. RP Freed, M (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM melanie.freed@fda.hhs.gov NR 1 TC 4 Z9 4 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 APR PY 2011 VL 38 IS 4 BP 2307 EP 2307 DI 10.1118/1.3566011 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 745GI UT WOS:000289153500060 ER PT J AU Aydanian, A Tang, L Morris, JG Johnson, JA Stine, OC AF Aydanian, Antonina Tang, Li Morris, J. Glenn Johnson, Judith A. Stine, O. Colin TI Genetic Diversity of O-Antigen Biosynthesis Regions in Vibrio cholerae SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYSACCHARIDE PORTION; SUGAR COMPOSITION; O139; SEQUENCE; LIPOPOLYSACCHARIDES; NON-O1; O22; BACTERIOPHAGE; CONVERSION; EVOLUTION AB O-antigen biosynthetic (wbf) regions for Vibrio cholerae serogroups O5, O8, and O108 were isolated and sequenced. Sequences were compared to those of other published V. cholerae O-antigen regions. These wbf regions showed a high degree of heterogeneity both in gene content and in gene order. Genes identified frequently showed greater similarities to polysaccharide biosynthesis genes from species other than V. cholerae. Our results demonstrate the plasticity of O-antigen genes in V. cholerae, the diversity of the genetic pool from which they are drawn, and the likelihood that new pandemic serogroups will emerge. C1 [Aydanian, Antonina; Tang, Li; Stine, O. Colin] Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. [Aydanian, Antonina] US FDA, Bethesda, MD 20014 USA. [Morris, J. Glenn; Johnson, Judith A.] Univ Florida, Coll Med, Emerging Pathogens Inst, Gainesville, FL USA. [Johnson, Judith A.] Univ Florida, Coll Med, Dept Pathol, Gainesville, FL USA. RP Stine, OC (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 596 Howard Hall,660 W Redwood St, Baltimore, MD 21201 USA. EM ostin001@umaryland.edu FU NIH [RO1 GM060791]; National Institute of Allergy and Infectious Diseases, National Institutes of Health [N01-AI-40014] FX This research was supported in part by an NIH grant (RO1 GM060791) to J.G. Morris and the University of Maryland Clinical Research Unit of the Food and Waterborne Diseases Integrated Research Network, which is funded by the National Institute of Allergy and Infectious Diseases, National Institutes of Health, under contract number N01-AI-40014. NR 46 TC 6 Z9 7 U1 0 U2 2 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 APR PY 2011 VL 77 IS 7 BP 2247 EP 2253 DI 10.1128/AEM.01663-10 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 741HT UT WOS:000288855500007 PM 21317260 ER PT J AU Van Stelten, A Simpson, JM Chen, Y Scott, VN Whiting, RC Ross, WH Nightingale, KK AF Van Stelten, A. Simpson, J. M. Chen, Y. Scott, V. N. Whiting, R. C. Ross, W. H. Nightingale, K. K. TI Significant Shift in Median Guinea Pig Infectious Dose Shown by an Outbreak-Associated Listeria monocytogenes Epidemic Clone Strain and a Strain Carrying a Premature Stop Codon Mutation in inlA SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID TO-EAT FOODS; VIRULENCE GENE-CLUSTER; POSITIVE SELECTION; REDUCED INVASION; POLYMORPHISM; INTERNALIN; DISTINCT; EVOLUTION; EXPOSURE; MODEL AB Listeria monocytogenes contains (i) epidemic clone (EC) strains, which have been linked to the majority of listeriosis outbreaks worldwide and are overrepresented among sporadic cases in the United States, and (ii) strains commonly isolated from ready-to-eat foods that carry a mutation leading to a premature stop codon (PMSC) in inlA, which encodes the key virulence factor internalin A (InlA). Internalin A binds certain isoforms of the cellular receptor E-cadherin to facilitate crossing the intestinal barrier during the initial stages of an L. monocytogenes infection. Juvenile guinea pigs, which express the human isoform of E-cadherin that binds InlA, were intragastrically challenged with a range of doses of (i) an EC strain associated with a listeriosis outbreak or (ii) a strain carrying a PMSC mutation in inlA. Recovery of L. monocytogenes from tissues (i. e., liver, spleen, mesenteric lymph nodes, and ileum) was used to develop strain-specific dose-response curves on the basis of individual and combined organ data. Modeling of individual and combined organ data revealed an approximate 1.2 to 1.3 log10 increase in the median infectious dose for the strain carrying a PMSC in inlA relative to that for the EC strain. Inclusion of the strain parameter significantly improved the goodness of fit for individual and combined organ models, indicating a significant shift in median infectious dose for guinea pigs challenged with an inlA PMSC strain compared to that for guinea pigs challenged with an EC strain. Results from this work provide evidence that the L. monocytogenes dose-response relationship is strain specific and will provide critical data for enhancement of current risk assessments and development of future risk assessments. C1 [Van Stelten, A.; Simpson, J. M.; Nightingale, K. K.] Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. [Chen, Y.; Scott, V. N.] Grocery Mfg Assoc, Washington, DC 20005 USA. [Chen, Y.; Scott, V. N.] US FDA, College Pk, MD 20740 USA. [Whiting, R. C.] Exponent, Bowie, MD 20715 USA. [Ross, W. H.] Hlth Canada, Ottawa, ON K1A OJ0, Canada. RP Nightingale, KK (reprint author), Colorado State Univ, Dept Anim Sci, 108B Anim Sci Bldg, Ft Collins, CO 80523 USA. EM kendra.nightingale@colostate.edu FU National Research Initiative of the USDA-Cooperative State Research, Education; Extension Service-National Research Initiative [2005-35201-16266]; USDA-Cooperative State Research, Education; Extension Service Special Research Grant [2008-56341-8789] FX The project was supported by the National Research Initiative of the USDA-Cooperative State Research, Education, and Extension Service-National Research Initiative grant number 2005-35201-16266 and USDA-Cooperative State Research, Education, and Extension Service Special Research Grant 2008-56341-8789. NR 51 TC 15 Z9 15 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 APR PY 2011 VL 77 IS 7 BP 2479 EP 2487 DI 10.1128/AEM.02626-10 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 741HT UT WOS:000288855500034 PM 21296943 ER PT J AU Hariharan, P Giarra, M Reddy, V Day, SW Manning, KB Deutsch, S Stewart, SFC Myers, MR Berman, MR Burgreen, GW Paterson, EG Malinauskas, RA AF Hariharan, Prasanna Giarra, Matthew Reddy, Varun Day, Steven W. Manning, Keefe B. Deutsch, Steven Stewart, Sandy F. C. Myers, Matthew R. Berman, Michael R. Burgreen, Greg W. Paterson, Eric G. Malinauskas, Richard A. TI Multilaboratory Particle Image Velocimetry Analysis of the FDA Benchmark Nozzle Model to Support Validation of Computational Fluid Dynamics Simulations SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article DE particle image velocimetry; computational fluid dynamics; FDA critical path initiative; sudden expansion; shear stress; transitional flow; turbulent flow measurement ID VENTRICULAR ASSIST DEVICE; MECHANICAL HEART-VALVES; CENTRIFUGAL BLOOD PUMP; WALL SHEAR-STRESS; PIV MEASUREMENTS; PULSATILE FLOW; STEADY FLOW; IN-VITRO; HEMOLYSIS; DAMAGE AB This study is part of a FDA-sponsored project to evaluate the use and limitations of computational fluid dynamics (CFD) in assessing blood flow parameters related to medical device safety. In an interlaboratory study, fluid velocities and pressures were measured in a nozzle model to provide experimental validation for a companion round-robin CFD study. The simple benchmark nozzle model, which mimicked the flow fields in several medical devices, consisted of a gradual flow constriction, a narrow throat region, and a sudden expansion region where a fluid jet exited the center of the nozzle with recirculation zones near the model walls. Measurements of mean velocity and turbulent flow quantities were made in the benchmark device at three independent laboratories using particle image velocimetry (PIV). Flow measurements were performed over a range of nozzle throat Reynolds numbers (Re(throat)) from 500 to 6500, covering the laminar, transitional, and turbulent flow regimes. A standard operating procedure was developed for performing experiments under controlled temperature and flow conditions and for minimizing systematic errors during PIV image acquisition and processing. For laminar (Re(throat) = 500) and turbulent flow conditions (Re(throat) >= 3500), the velocities measured by the three laboratories were similar with an interlaboratory uncertainty of similar to 10% at most of the locations. However, for the transitional flow case (Re(throat) = 2000), the uncertainty in the size and the velocity of the jet at the nozzle exit increased to similar to 60% and was very sensitive to the flow conditions. An error analysis showed that by minimizing the variability in the experimental parameters such as flow rate and fluid viscosity to less than 5% and by matching the inlet turbulence level between the laboratories, the uncertainties in the velocities of the transitional flow case could be reduced to similar to 15%. The experimental procedure and flow results from this interlaboratory study (available at http://fdacfd.nci.nih.gov) will be useful in validating CFD simulations of the benchmark nozzle model and in performing PIV studies on other medical device models. [DOI: 10.1115/1.4003440] C1 [Hariharan, Prasanna; Stewart, Sandy F. C.; Myers, Matthew R.; Berman, Michael R.; Malinauskas, Richard A.] US FDA, Silver Spring, MD 20993 USA. [Giarra, Matthew; Day, Steven W.] Rochester Inst Technol, Rochester, NY 14623 USA. [Reddy, Varun; Manning, Keefe B.; Deutsch, Steven; Paterson, Eric G.] Penn State Univ, University Pk, PA 16802 USA. [Burgreen, Greg W.] Mississippi State Univ, Mississippi State, MS 39762 USA. RP Hariharan, P (reprint author), US FDA, Silver Spring, MD 20993 USA. EM prasanna.hariharan@fda.hhs.gov NR 64 TC 21 Z9 21 U1 3 U2 19 PU ASME-AMER SOC MECHANICAL ENG PI NEW YORK PA THREE PARK AVE, NEW YORK, NY 10016-5990 USA SN 0148-0731 J9 J BIOMECH ENG-T ASME JI J. Biomech. Eng.-Trans. ASME PD APR PY 2011 VL 133 IS 4 AR 041002 DI 10.1115/1.4003440 PG 14 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 739HU UT WOS:000288706600003 PM 21428676 ER PT J AU Qian, L Wu, HM Chen, SH Zhang, D Ali, SF Peterson, L Wilson, B Lu, RB Hong, JS Flood, PM AF Qian, Li Wu, Hung-ming Chen, Shih-Heng Zhang, Dan Ali, Syed F. Peterson, Lynda Wilson, Belinda Lu, Ru-Band Hong, Jau-Shyong Flood, Patrick M. TI beta 2-Adrenergic Receptor Activation Prevents Rodent Dopaminergic Neurotoxicity by Inhibiting Microglia via a Novel Signaling Pathway SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LIPOPOLYSACCHARIDE-INDUCED NEUROTOXICITY; BETA-ADRENERGIC AGONISTS; TUMOR-NECROSIS-FACTOR; REGULATORY T-CELLS; PARKINSONS-DISEASE; NADPH OXIDASE; MEDIATED NEUROTOXICITY; REACTIVE MICROGLIOSIS; SELECTIVE-INHIBITION; CYTOKINE PRODUCTION AB The role of the beta 2 adrenergic receptor (beta 2AR) in the regulation of chronic neurodegenerative inflammation within the CNS is poorly understood. The purpose of this study was to determine neuroprotective effects of long-acting beta 2AR agonists such as salmeterol in rodent models of Parkinson's disease. Results showed salmeterol exerted potent neuroprotection against both LPS and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine/1-methyl-4-phenylpyridinium-induced dopaminergic neurotoxicity both in primary neuron-glia cultures (at subnanomolar concentrations) and in mice (1-10 mu g/kg/day doses). Further studies demonstrated that salmeterol-mediated neuroprotection is not a direct effect on neurons; instead, it is mediated through the inhibition of LPS-induced microglial activation. Salmeterol significantly inhibited LPS-induced production of microglial proinflammatory neurotoxic mediators, such as TNF-alpha, superoxide, and NO, as well as the inhibition of TAK1-mediated phosphorylation of MAPK and p65 NF-kappa B. The anti-inflammatory effects of salmeterol required beta 2AR expression in microglia but were not mediated through the conventional G protein-coupled receptor/cAMP pathway. Rather, salmeterol failed to induce microglial cAMP production, could not be reversed by either protein kinase A inhibitors or an exchange protein directly activated by cAMP agonist, and was dependent on beta-arrestin2 expression. Taken together, our results demonstrate that administration of extremely low doses of salmeterol exhibit potent neuroprotective effects by inhibiting microglial cell activation through a beta 2AR/beta-arrestin2-dependent but cAMP/protein kinase A-independent pathway. The Journal of Immunology, 2011, 186: 4443-4454. C1 [Qian, Li; Peterson, Lynda; Flood, Patrick M.] Univ N Carolina, N Carolina Oral Hlth Inst, Chapel Hill, NC 27599 USA. [Qian, Li; Wu, Hung-ming; Chen, Shih-Heng; Zhang, Dan; Wilson, Belinda; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Toxicol & Pharmacol, NIH, Res Triangle Pk, NC 27709 USA. [Ali, Syed F.] US FDA, Neurochem Lab, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lu, Ru-Band] Natl Cheng Kung Univ, Dept Psychiat, Coll Med & Hosp, Tainan 70428, Taiwan. RP Flood, PM (reprint author), Univ N Carolina, N Carolina Oral Hlth Inst, CB 7454, Chapel Hill, NC 27599 USA. EM pat_flood@dentistry.unc.edu FU National Institutes of Health, National Institute for Dental and Craniofacial Research [DE-13079]; Michael J. Fox Foundation; National Institutes of Health/National Institute on Environmental Health Sciences FX This work was supported by National Institutes of Health Grant DE-13079 from the National Institute for Dental and Craniofacial Research and a grant from the Michael J. Fox Foundation. This work was also supported in part by the Intramural Research Program of the National Institutes of Health/National Institute on Environmental Health Sciences. NR 56 TC 26 Z9 27 U1 2 U2 11 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2011 VL 186 IS 7 BP 4443 EP 4454 DI 10.4049/jimmunol.1002449 PG 12 WC Immunology SC Immunology GA 739WH UT WOS:000288751200072 PM 21335487 ER PT J AU Martinez, M Hunter, RP Baynes, R Bermingham, E Claxton, R Cole, C del Castillo, J Gehring, R Harshman, K Lainesse, C Lucas, A Modric, S Robinson, J AF Martinez, M. Hunter, R. P. Baynes, R. Bermingham, E. Claxton, R. Cole, C. del Castillo, J. Gehring, R. Harshman, K. Lainesse, C. Lucas, A. Modric, S. Robinson, J. TI The 2010 AAVPT/EAVPT/ECVPT bioequivalence workshop SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Editorial Material C1 [Martinez, M.; Hunter, R. P.; Baynes, R.; Bermingham, E.; Claxton, R.; Cole, C.; del Castillo, J.; Gehring, R.; Harshman, K.; Lainesse, C.; Lucas, A.; Modric, S.; Robinson, J.] FDA CVM, Rockville, MD 20855 USA. RP Martinez, M (reprint author), FDA CVM, HFV 130,7500 Standish Pl, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov RI del Castillo, Jerome/J-6976-2013; OI del Castillo, Jerome/0000-0001-5046-7926; Hunter, Robert/0000-0003-1224-2376 NR 1 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD APR PY 2011 VL 34 IS 2 BP 105 EP 107 DI 10.1111/j.1365-2885.2011.01281.x PG 3 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 734XR UT WOS:000288376500001 PM 21395599 ER PT J AU Harris, GR Herman, BA Myers, MR AF Harris, Gerald R. Herman, Bruce A. Myers, Matthew R. TI A COMPARISON OF THE THERMAL-DOSE EQUATION AND THE INTENSITY-TIME PRODUCT, It(m), FOR PREDICTING TISSUE DAMAGE THRESHOLDS SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE HIFU; Thermal dose; Thermal damage threshold ID FOCUSED ULTRASOUND; SURGERY; DOSAGES AB Thermal dose is the most generally accepted concept for estimating temperature-related tissue damage thresholds in high-intensity focused ultrasound (HIFU) procedures. However, another approach based on the intensity-time product I t(m) = D has been used, where D is a tissue-dependent damage threshold, I is the spatial-peak, temporal-average intensity and t is time. In this study, these two approaches were compared analytically by substituting a well-known soft-tissue solution for temperature vs. time into the thermal dose equation. From power law fits of I vs. t, m was found to fall between about 0.3 and 0.8. In terms of the intensity required for cell death for a given exposure time, the standard deviation of the error between the full thermal-dose formulation and the I t(m) = D prediction based upon the power-law fit was less than 5% for focal beam diameters up to 3 mm. Thus, for the practical range of HIFU parameters examined, the intensity-time product relationship is equivalent to the thermal dose formulation. (E-mail: gerald.harris@fda.hhs.gov) Published by Elsevier Inc. on behalf of World Federation for Ultrasound in Medicine & Biology. C1 [Harris, Gerald R.; Herman, Bruce A.; Myers, Matthew R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Harris, GR (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Room WO62-2104, Silver Spring, MD 20993 USA. EM gerald.harris@fda.hhs.gov NR 16 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD APR PY 2011 VL 37 IS 4 BP 580 EP 586 DI 10.1016/j.ultrasmedbio.2011.01.005 PG 7 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 738NL UT WOS:000288646400008 PM 21376450 ER PT J AU Baek, JH Reiter, CEN Manalo, DJ Buehler, PW Hider, RC Alayash, AI AF Baek, Jin Hyen Reiter, Chad E. N. Manalo, Dominador J. Buehler, Paul W. Hider, Robert C. Alayash, Abdu I. TI Induction of hypoxia inducible factor (HIF-1 alpha) in rat kidneys by iron chelation with the hydroxypyridinone, CP94 SO BIOCHIMICA ET BIOPHYSICA ACTA-GENE REGULATORY MECHANISMS LA English DT Article DE Iron chelator; Hypoxia inducible factor; Erythropoietin ID PROLYL HYDROXYLATION; THALASSEMIA MAJOR; FACTOR 1-ALPHA; O-2 TENSION; HIF; INHIBITION; VHL; THERAPEUTICS; ANGIOGENESIS; PURIFICATION AB Hypoxia inducible factor (HIF-1 alpha) is a master regulator of tissue adaptive responses to hypoxia whose stability is controlled by an iron containing prolyl hydroxylase domain (PHD) protein. A catalytic redox cycle in the PHD's iron center that results in the formation of a ferryl (Fe+4) intermediate has been reported to be responsible for the hydroxylation and subsequent degradation of HIF-1 alpha under normoxia. We show that induction of HIF-1 alpha in rat kidneys can be achieved by iron reduction by the hydroxypyridin-4 one (CP94), an iron chelator administered intraperitoneally in rats. The extent of HIP protein stabilization as well as the expression of HIF target genes, including erythropoietin (EPO), in kidney tissues was comparable to those induced by known inhibitors of the PHD enzyme, such as desferrioxamine (DFO) and cobalt chloride (CoCl2). In human kidney cells and in vitro PHD activity assay, we were able to show that the HIF-1 alpha protein can be stabilized by addition of CP94. This appears to inactivate PHD; and thus prevents the hydroxylation of HIF-1 alpha. In conclusion, we have identified the inhibition of iron-binding pocket of PHD as an underlying mechanism of HIF induction in vivo and in vitro by a bidentate hydroxypyridinone. Published by Elsevier B.V. C1 [Baek, Jin Hyen; Reiter, Chad E. N.; Manalo, Dominador J.; Buehler, Paul W.; Alayash, Abdu I.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Hider, Robert C.] Coll London, Div Pharmaceut Sci, London SE1 9NH, England. RP Alayash, AI (reprint author), US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, NIH Bldg 29,Rm 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov FU Defense Advanced Research Projects Agency (DARPA); CBER FX This work was supported in part by the Defense Advanced Research Projects Agency (DARPA) and CBER Critical Path Research Program. NR 43 TC 9 Z9 10 U1 0 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1874-9399 J9 BBA-GENE REGUL MECH JI Biochim. Biophys. Acta-Gene Regul. Mech. PD APR-JUN PY 2011 VL 1809 IS 4-6 BP 262 EP 268 DI 10.1016/j.bbagrm.2011.04.010 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 780ZK UT WOS:000291900200006 PM 21558026 ER PT J AU Lesko, LJ Huang, SM AF Lesko, L. J. Huang, S-M TI Response to "Prevalence and Clinical Utility" SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Letter C1 [Lesko, L. J.; Huang, S-M] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM lawrence.lesko@fda.hhs.gov; shiewmei.huang@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 2011 VL 89 IS 4 BP 489 EP 490 DI 10.1038/clpt.2011.5 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 738OK UT WOS:000288649600015 ER PT J AU Pariser, AR Xu, K Milto, J Cote, TR AF Pariser, Anne R. Xu, Kui Milto, John Cote, Timothy R. TI Regulatory Considerations for Developing Drugs for Rare Diseases: Orphan Designations and Early Phase Clinical Trials SO DISCOVERY MEDICINE LA English DT Article AB The development of drug and biological products intended to treat rare diseases (Orphan diseases) is one of the fastest growing areas of clinical research, and also one of the most challenging. This article provides an introduction to two important regulatory considerations for Orphan drugs: Orphan status designations and general considerations for the administration of investigational agents in early phase clinical trials. Incentives available to orphan drug developers under the Orphan Drug Act (ODA) and requirements for obtaining an orphan status designation are discussed. An introductory overview of ethical and statutory considerations for investigational drugs, requirements for initiating investigational new drug applications (INDs), and sources of information and advice from the US Food and Drug Administration (FDA) are also described. [Discovery Medicine 11(59):367-375, April 2011] C1 [Pariser, Anne R.] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Xu, Kui; Milto, John; Cote, Timothy R.] US FDA, Off Orphan Prod Dev, Off Commissioner, Silver Spring, MD 20993 USA. RP Xu, K (reprint author), US FDA, Off Orphan Prod Dev, Off Commissioner, Silver Spring, MD 20993 USA. EM kui.xu@fda.hhs.gov NR 15 TC 6 Z9 6 U1 2 U2 2 PU DISCOVERY MEDICINE PI TIMONIUM PA 10 GERARD AVE, STE 201, TIMONIUM, MD 21093 USA SN 1539-6509 EI 1944-7930 J9 DISCOV MED JI Discov. Med. PD APR PY 2011 VL 11 IS 59 BP 367 EP 375 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA V27UZ UT WOS:000208639400010 PM 21524390 ER PT J AU An, YM Cipollo, J AF An, Yanming Cipollo, John TI A general approach for glycoprotein analysis: glycopeptide analysis by LC/MS with HILIC enrichment and glycan permethylation profiling SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [An, Yanming; Cipollo, John] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 8 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404598 ER PT J AU Babu, US Garthoff, LH Balan, KV AF Babu, Uma S. Garthoff, Larry H. Balan, Kannan V. TI Vitamin D2 enriched mushrooms significantly reduced inflammatory cytokine and chemokine expression in the spleens of LPS challenged rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Babu, Uma S.; Garthoff, Larry H.; Balan, Kannan V.] US FDA, OARSA, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708406683 ER PT J AU Banerjee, S Latendresse, JR Mehendale, HM AF Banerjee, Sudip Latendresse, John R. Mehendale, Harihara M. TI Therapeutic rescue of mice treated with a lethal dose of acetaminophen SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Banerjee, Sudip; Mehendale, Harihara M.] NE Louisiana Univ, Monroe, LA 71209 USA. [Latendresse, John R.] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400194 ER PT J AU Chang, CWJ Edirisinghe, I Jablonski, JE Tadapaneni, RK Tulio, AZ Burton-Freeman, B Jackson, LS AF Chang, Claire Wei-Ju Edirisinghe, Indika Jablonski, Joseph E. Tadapaneni, Ravi K. Tulio, Artemio Z. Burton-Freeman, Britt Jackson, Lauren S. TI Polyphenol-rich fruit modulate endothelial cell function via PI3 Kinase/Akt Pathway in Vitro in Human Umbilical Vein Endothelial Cell (HUVEC) SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Chang, Claire Wei-Ju; Jablonski, Joseph E.; Tulio, Artemio Z.; Jackson, Lauren S.] US FDA, Ctr Food Safety & Appl Nutr, Summit Argo, IL USA. [Edirisinghe, Indika; Tadapaneni, Ravi K.; Burton-Freeman, Britt] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708404981 ER PT J AU Chung, CS Juan, WY Yamini, S Trumbo, P AF Chung, Carolyn Sue Juan, WenYen Yamini, Sedigheh Trumbo, Paula TI Prevalence of nutrient adequacy for US infants and toddlers, NHANES 2003-2006 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Chung, Carolyn Sue; Juan, WenYen; Yamini, Sedigheh; Trumbo, Paula] US FDA, Ctr Food Safety & Nutr, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403309 ER PT J AU Herman, E Knapton, A Rosen, E Lu, QA Estis, J Agee, S Todd, J Lipshultz, S Zhang, J AF Herman, Eugene Knapton, Alan Rosen, Elliot Lu, Quynh-Ahn Estis, Joel Agee, Sara Todd, John Lipshultz, Steven Zhang, Jun TI Baseline serum cardiac troponin I concentrations in various strains of rats as determined with an ultrasensitive immunoassay SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Herman, Eugene; Knapton, Alan; Rosen, Elliot; Zhang, Jun] US FDA, Silver Spring, MD USA. [Lu, Quynh-Ahn; Estis, Joel; Agee, Sara; Todd, John] Singulex Inc, Alameda, CA USA. [Lipshultz, Steven] Univ Miami, Sch Med, Miami, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708401146 ER PT J AU Juan, WY Trumbo, P Rasnake, C Boyer, M Yamini, S AF Juan, WenYen Trumbo, Paula Rasnake, Crystal Boyer, Marc Yamini, Sedigheh TI Prevalence of nutrient adequacy and sodium intake in the US, 2003-2008 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Juan, WenYen; Trumbo, Paula; Rasnake, Crystal; Yamini, Sedigheh] US FDA, Off Nutr Labeling & Dietary Supplements, College Pk, MD USA. [Boyer, Marc] US FDA, Off Food Def Commun & Emergency Response, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402182 ER PT J AU Knapton, A Peters, D Rosen, E Lu, QA Estis, J Agee, S Todd, J Herman, E AF Knapton, Alan Peters, David Rosen, Elliot Lu, Quynh-Ahn Estis, John Agee, Sara Todd, John Herman, Eugene TI Skeletal muscle troponin I as a biomarker of skeletal muscle injury SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Knapton, Alan; Peters, David; Rosen, Elliot; Herman, Eugene] US FDA, DAPR, Silver Spring, MD USA. [Lu, Quynh-Ahn; Estis, John] Singulex Inc, Alameda, CA USA. [Agee, Sara; Todd, John] Singulex, Alameda, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708400199 ER PT J AU Kranz, S Juan, WY Zuercher, J Wall-Bassett, E Buhman, KK AF Kranz, Sibylle Juan, Wen Yen Zuercher, Jennifer Wall-Bassett, Elizabeth Buhman, Kimberly K. TI Added sugar intake and chronic disease risk in plausible diet reporters in the US adult population, 2003-2006 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kranz, Sibylle; Zuercher, Jennifer; Buhman, Kimberly K.] Purdue Univ, W Lafayette, IN 47907 USA. [Juan, Wen Yen] US FDA, College Pk, MD USA. [Wall-Bassett, Elizabeth] E Carolina Unviers, Dept Nutr Sci, Greenville, NC USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708405196 ER PT J AU Kranz, S Juan, WY Zuercher, J Wall-Bassett, E Buhman, KK AF Kranz, Sibylle Juan, Wen Yen Zuercher, Jennifer Wall-Bassett, Elizabeth Buhman, Kimberly K. TI Added sugar intake and health risk factors of plausible diet intake reporters ages 2-18 years old, 2003-2006 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Kranz, Sibylle; Zuercher, Jennifer; Buhman, Kimberly K.] Purdue Univ, W Lafayette, IN 47907 USA. [Juan, Wen Yen] US FDA, College Pk, MD USA. [Wall-Bassett, Elizabeth] E Carolina Univ, Dept Nutr Sci, Greenville, NC USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402124 ER PT J AU McCarthy, P Saksena, R Peterson, DC Vionnet, J Vann, WF AF McCarthy, Pumtiwitt Saksena, Rina Peterson, Dwight C. Vionnet, Justine Vann, Willie F. TI Preparation of a meningococcal group C polysialic acid-tetanus Hc fragment glycoconjugate vaccine candidate by chemoenzymatic synthesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [McCarthy, Pumtiwitt; Saksena, Rina; Peterson, Dwight C.; Vionnet, Justine; Vann, Willie F.] CBER FDA, Lab Bacterial Polysaccharides, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402844 ER PT J AU Rahman, M Jankowska, E Hodgkin, J O'Rourke, D Stroud, D AF Rahman, Miznaur Jankowska, Ewa Hodgkin, Jonathan O'Rourke, Delia Stroud, David TI The Core-1 O-glycans of Microbacterium nematophilum Resistant Caenorhabditis elegans bus-4 mutants are altered SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Rahman, Miznaur; Jankowska, Ewa] US FDA, CBER, Bethesda, MD 20014 USA. [Hodgkin, Jonathan; O'Rourke, Delia; Stroud, David] Univ Oxford, Dept Biochem, Oxford OX1 3QU, England. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708402846 ER PT J AU Weigand, AJ Gaines, DW Babu, US Garthoff, LH Calvo, MS AF Weigand, AuBrei J. Gaines, Dennis W. Babu, Uma S. Garthoff, Larry H. Calvo, Mona S. TI Plasma lipid response to LPS challenge in rats fed vitamin D2 enriched white button mushrooms SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology Meeting 2011 CY APR 09-13, 2011 CL Washington, DC SP Amer Assoc Anatomists (AAA), Amer Physiolog Soc (APS), Amer Soc Biochem & Mol Biol (ASBMB), Amer Soc Investigat Pathol (ASIP), Amer Soc Nutrit (ASN), Amer Soc Pharmacol & Expt Therapeut (ASPET) C1 [Weigand, AuBrei J.; Gaines, Dennis W.; Babu, Uma S.; Garthoff, Larry H.; Calvo, Mona S.] US FDA, OARSA, Laurel, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2011 VL 25 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 032IE UT WOS:000310708403020 ER PT J AU Franco, AA Kothary, MH Gopinath, G Jarvis, KG Grim, CJ Hu, L Datta, AR McCardell, BA Tall, BD AF Franco, A. A. Kothary, M. H. Gopinath, G. Jarvis, K. G. Grim, C. J. Hu, L. Datta, A. R. McCardell, B. A. Tall, B. D. TI Cpa, the Outer Membrane Protease of Cronobacter sakazakii, Activates Plasminogen and Mediates Resistance to Serum Bactericidal Activity SO INFECTION AND IMMUNITY LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; POWDERED INFANT FORMULA; ENTEROBACTER-SAKAZAKII; YERSINIA-PESTIS; ESCHERICHIA-COLI; SALMONELLA-ENTERICA; SURFACE PROTEASE; O-ANTIGEN; ENDOTHELIAL-CELLS; COMPLEMENT AB Cronobacter spp. are emerging neonatal pathogens in humans, associated with outbreaks of meningitis and sepsis. To cause disease, they must survive in blood and invade the central nervous system by penetrating the blood-brain barrier. C. sakazakii BAA-894 possesses an similar to 131-kb plasmid (pESA3) that encodes an outer membrane protease (Cpa) that has significant identity to proteins that belong to the Pla subfamily of omptins. Members of this subfamily of proteins degrade a number of serum proteins, including circulating complement, providing protection from the complement-dependent serum killing. Moreover, proteins of the Pla subfamily can cause uncontrolled plasmin activity by converting plasminogen to plasmin and inactivating the plasmin inhibitor alpha 2-antiplasmin (alpha 2-AP). These reactions enhance the spread and invasion of bacteria in the host. In this study, we found that an isogenic cpa mutant showed reduced resistance to serum in comparison to its parent C. sakazakii BAA-894 strain. Overexpression of Cpa in C. sakazakii or Escherichia coli DH5 alpha showed that Cpa proteolytically cleaved complement components C3, C3a, and C4b. Furthermore, a strain of C. sakazakii overexpressing Cpa caused a rapid activation of plasminogen and inactivation of alpha 2-AP. These results strongly suggest that Cpa may be an important virulence factor involved in serum resistance, as well as in the spread and invasion of C. sakazakii. C1 [Franco, A. A.] US FDA, MOD Facil 1, Virulence Mech Branch HFS 025, Div Virulence Assessment,OARSA,Ctr Food Safety &, Laurel, MD 20708 USA. [Jarvis, K. G.; Grim, C. J.] Oak Ridge Inst Sci & Educ, Oak Ridge, TN USA. RP Franco, AA (reprint author), US FDA, MOD Facil 1, Virulence Mech Branch HFS 025, Div Virulence Assessment,OARSA,Ctr Food Safety &, 8301 MuirKirk Rd, Laurel, MD 20708 USA. EM augusto.franco-mora@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629 FU Department of Energy FX L.H. is an FDA Commissioner's Fellow. K.G.J. and C.J.G. are Oak Ridge Institute for Science and Education fellows, and we thank the Department of Energy for their support. NR 63 TC 24 Z9 26 U1 1 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2011 VL 79 IS 4 BP 1578 EP 1587 DI 10.1128/IAI.01165-10 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 736YX UT WOS:000288532300019 PM 21245266 ER PT J AU Peterson, DC Arakere, G Vionnet, J McCarthy, PC Vann, WF AF Peterson, Dwight C. Arakere, Gayathri Vionnet, Justine McCarthy, Pumtiwitt C. Vann, Willie F. TI Characterization and Acceptor Preference of a Soluble Meningococcal Group C Polysialyltransferase SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI K1; B NEISSERIA-MENINGITIDIS; POLYSIALIC ACID CAPSULES; K92 POLYSIALYLTRANSFERASE; SEROGROUP-B; SIALIC-ACID; EXPRESSION; BIOSYNTHESIS; ELONGATION; BACTERIA AB Vaccines against Neisseria meningitidis group C are based on its alpha-2,9-linked polysialic acid capsular polysaccharide. This polysialic acid expressed on the surface of N. meningitidis and in the absence of specific antibody serves to evade host defense mechanisms. The polysialyltransferase (PST) that forms the group C polysialic acid (NmC PST) is located in the cytoplasmic membrane. Until recently, detailed characterization of bacterial polysialyltransferases has been hampered by a lack of availability of soluble enzyme preparations. We have constructed chimeras of the group C polysialyltransferase that catalyzes the formation alpha-2,9-polysialic acid as a soluble enzyme. We used site-directed mutagenesis to determine the region of the enzyme necessary for synthesis of the alpha-2,9 linkage. A chimera of NmB and NmC PSTs containing only amino acids 1 to 107 of the NmB polysialyltransferase catalyzed the synthesis of alpha-2,8-polysialic acid. The NmC polysialyltransferase requires an exogenous acceptor for catalytic activity. While it requires a minimum of a disialylated oligosaccharide to catalyze transfer, it can form high-molecular-weight alpha-2,9-polysialic acid in a nonprocessive fashion when initiated with an alpha-2,8-polysialic acid acceptor. De novo synthesis in vivo requires an endogenous acceptor. We attempted to reconstitute de novo activity of the soluble group C polysialyltransferase with membrane components. We found that an acapsular mutant with a defect in the polysialyltransferase produces outer membrane vesicles containing an acceptor for the alpha-2,9-polysialyltransferase. This acceptor is an amphipathic molecule and can be elongated to produce polysialic acid that is reactive with group C-specific antibody. C1 [Peterson, Dwight C.; Vionnet, Justine; McCarthy, Pumtiwitt C.; Vann, Willie F.] US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA. [Arakere, Gayathri] Indian Inst Sci, Sir Dorabji Tata Ctr Res Trop Dis, Bangalore 560012, Karnataka, India. RP Vann, WF (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Bldg 29,Room 103,8800 Rockville Pike, Bethesda, MD 20892 USA. EM wvann@helix.nih.gov NR 34 TC 14 Z9 14 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 2011 VL 193 IS 7 BP 1576 EP 1582 DI 10.1128/JB.00924-10 PG 7 WC Microbiology SC Microbiology GA 734DW UT WOS:000288314400009 PM 21278299 ER PT J AU Alam, M Gaines, D Kuo, J Pereira, M Bigley, E Ernst, P Williams, K AF Alam, Mohammad Gaines, Dennis Kuo, Jennifer Pereira, Marion Bigley, Elmer Ernst, Peter Williams, Kristina TI Adenosine synthesized by CD73 and CD39 regulates inflammation during murine Salmonella infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Alam, Mohammad; Gaines, Dennis; Kuo, Jennifer; Pereira, Marion; Bigley, Elmer; Williams, Kristina] US FDA, Immunobiol DVA, Ctr Food Safety & Nutr, Laurel, MD USA. [Ernst, Peter] Univ Virginia, Dept Med, Charlottesville, VA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR PY 2011 VL 186 SU 1 MA 162.10 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751707116 ER PT J AU Dhawan, S AF Dhawan, Subhash TI Heme oxygenase-1 induction stimulates host defense mechanism against infections SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Dhawan, Subhash] US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR PY 2011 VL 186 SU 1 MA 110.3 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751704143 ER PT J AU Manirarora, J Wei, CH AF Manirarora, Jean Wei, Cheng-Hong TI Characterization of antigen-specific CD4+CD25+regulatory T-cells expanded with IL-2/IL-2mAb complexes in NOD mice SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Manirarora, Jean; Wei, Cheng-Hong] US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR PY 2011 VL 186 SU 1 MA 115.9 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751705062 ER PT J AU Nazarov, C LoSurdo, J Bauer, S Wei, CH AF Nazarov, Cristina LoSurdo, Jessica Bauer, Steven Wei, Cheng-Hong TI Human multipotent stromal cells inhibit the activation of antigen specific murine CD4+and CD8+T cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Nazarov, Cristina; LoSurdo, Jessica; Bauer, Steven; Wei, Cheng-Hong] US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR PY 2011 VL 186 SU 1 MA 147.7 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751705165 ER PT J AU Prabhakara, R Mocca, C Brady, R Plaut, R Burns, D Stibitz, S Merkel, T AF Prabhakara, Ranjani Mocca, Christopher Brady, Rebecca Plaut, Roger Burns, Drusilla Stibitz, Scott Merkel, Tod TI Development of three murine models of Staphylococcus aureus infection to aid in the characterization of a broadly protective vaccine and elucidation of immune responses to different routes of infection SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Prabhakara, Ranjani; Mocca, Christopher; Brady, Rebecca; Burns, Drusilla; Merkel, Tod] US FDA, CBER, OVRR, DBPAP,Lab Resp & Special Pathogens, Bethesda, MD 20014 USA. [Plaut, Roger; Stibitz, Scott] US FDA, CBER, OVRR, DBPAP,Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR PY 2011 VL 186 SU 1 MA 155.29 PG 2 WC Immunology SC Immunology GA V44LY UT WOS:000209751706181 ER PT J AU Tolnay, M Dement-Brown, J Newton, C Ise, T Nagata, S AF Tolnay, Mate Dement-Brown, Jessica Newton, Christopher Ise, Tomoko Nagata, Satoshi TI Human Fc receptor-like 5 promotes B cell proliferation and the development of cells displaying surface IgG and IgA SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Tolnay, Mate; Dement-Brown, Jessica; Newton, Christopher] FDA, Div Monoclonal Antibodies, Silver Spring, MD USA. [Ise, Tomoko; Nagata, Satoshi] Sanford Res USD, Sioux Falls, SD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR PY 2011 VL 186 SU 1 MA 45.10 PG 1 WC Immunology SC Immunology GA V44LY UT WOS:000209751700049 ER PT J AU Ha, L King, KE Ponnamperuma, RM Jay, S Ricci, S Weinberg, WC AF Ha, L. King, K. E. Ponnamperuma, R. M. Jay, S. Ricci, S. Weinberg, W. C. TI Oncogenic activity of dysregulated Delta Np63 alpha in squamous carcinogenesis SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2011 CL Phoenix, AZ SP Soc Investigat Dermatol C1 [Ha, L.; King, K. E.; Ponnamperuma, R. M.; Ricci, S.; Weinberg, W. C.] US FDA, CDER, Bethesda, MD 20014 USA. [Jay, S.] SAIC Frederick Inc, Frederick, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2011 VL 131 SU 1 MA 154 BP S26 EP S26 PG 1 WC Dermatology SC Dermatology GA 743RE UT WOS:000289035600155 ER PT J AU Tan, ZW Li, JB Pang, RF He, SS He, MZ Tang, SX Hewlett, I Yang, M AF Tan, Zhiwu Li, Jiebo Pang, Ruifang He, Shanshan He, Meizi Tang, Shixing Hewlett, Indira Yang, Ming TI Screening and evaluation of thiourea derivatives for their HIV capsid and human cyclophilin A inhibitory activity SO MEDICINAL CHEMISTRY RESEARCH LA English DT Article DE HIV-1; Capsid; Cyclophilin A; Thiourea derivatives; Inhibitory activity evaluation ID HUMAN-IMMUNODEFICIENCY-VIRUS; ESCHERICHIA-COLI; CYCLOSPORINE-A; PROTEIN; TYPE-1; INFECTIVITY; STABILITY; THERAPY; VIRIONS; HIV-1CA AB New anti-HIV-1 drugs that target different viral proteins or genes at various steps in the viral life cycle are highly expected. HIV-1 assembly and disassembly (uncoating) processes are critical for the HIV-1 replication. HIV-1 capsid (CA) and human cyclophilin A (CypA) play essential roles in these processes. Using an in vitro screening system, we evaluated 52 thiourea derivatives for their potential CA and CypA-inhibiting activities. The antiviral activity of these compounds is correlated with their CA assembly inhibitory ability and with their anti-PPIase activity, suggesting that these compounds could block HIV-1 replication by disrupting CA assembly and inhibiting the PPIase activity of CypA to interfere with capsid disassembly. Among them, three compounds D4, D5, and D6 displayed the most promising potency with CA-assembly rate 15.78, 18.42, and 7.97(x10(-5)) OD/s, and their IC(50) for inhibition of PPIase activity 0.45, 0.65, and 0.33 mu M, respectively. The potent protein inhibitory activity resulted in their very low EC(50) values (a parts per thousand currency sign1.00 mu M). They can be used for rational design of novel anti-HIV-1 drugs. C1 [Tan, Zhiwu; Li, Jiebo; Pang, Ruifang; He, Shanshan; He, Meizi; Yang, Ming] Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China. [Tang, Shixing; Hewlett, Indira] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Yang, M (reprint author), Peking Univ, Hlth Sci Ctr, State Key Lab Nat & Biomimet Drugs, Beijing 100871, Peoples R China. EM yangm@bjmu.edu.cn RI Li, Jiebo/D-1516-2015 OI Li, Jiebo/0000-0001-8124-8769 NR 35 TC 5 Z9 5 U1 1 U2 8 PU BIRKHAUSER BOSTON INC PI CAMBRIDGE PA 675 MASSACHUSETTS AVE, CAMBRIDGE, MA 02139 USA SN 1054-2523 J9 MED CHEM RES JI Med. Chem. Res. PD APR PY 2011 VL 20 IS 3 BP 314 EP 320 DI 10.1007/s00044-010-9315-4 PG 7 WC Chemistry, Medicinal SC Pharmacology & Pharmacy GA 735FN UT WOS:000288398900008 ER PT J AU Kurillova, L Bacik, I Cervenak, J Patel, D McMahon, D Pomeroy, K Cervenakova, L Piccardo, P Gregori, L Asher, DM AF Kurillova, Lubica Bacik, I. Cervenak, J. Patel, D. McMahon, D. Pomeroy, K. Cervenakova, L. Piccardo, P. Gregori, L. Asher, D. M. TI Validation of Protocol Assessing Infection of Cell Lines with TSE Agents SO PRION LA English DT Meeting Abstract C1 [Kurillova, Lubica; Bacik, I.; Cervenak, J.; Patel, D.; McMahon, D.; Pomeroy, K.; Piccardo, P.; Gregori, L.; Asher, D. M.] US FDA, Kensington, MD USA. [Cervenakova, L.] Amer Red Cross, Washington, DC 20006 USA. EM Lubica.kurillova@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Bio.089 BP 58 EP 59 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300131 ER PT J AU King, DJ Barron, RM Agarwal, S Gill, A Piccardo, P AF King, Declan J. Barron, Rona M. Agarwal, Sonya Gill, Andrew Piccardo, Pedro TI Seeding PrP Amyloid Formation in the Absence of TSE Disease SO PRION LA English DT Meeting Abstract C1 [King, Declan J.; Barron, Rona M.; Agarwal, Sonya; Gill, Andrew; Piccardo, Pedro] Univ Edinburgh, Roslin Inst, Roslin Bioctr, Edinburgh, Midlothian, Scotland. [King, Declan J.; Barron, Rona M.; Agarwal, Sonya; Gill, Andrew; Piccardo, Pedro] Univ Edinburgh, Royal Dick Sch Vet Studies, Roslin Bioctr, Edinburgh EH9 1QH, Midlothian, Scotland. [Piccardo, Pedro] US FDA, Ctr Biol Evaluat, Rockville, MD 20857 USA. EM declan.king@roslin.ed.ac.uk NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA PPPM.14 BP 118 EP 118 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300268 ER PT J AU Abrams, J Schonberger, LB Belay, ED Maddox, RA Leschek, EW Mills, JL Wysowski, DK Fradkin, JE AF Abrams, Joseph Schonberger, Lawrence B. Belay, Ermias D. Maddox, Ryan A. Leschek, Ellen W. Mills, James L. Wysowski, Diane K. Fradkin, Judith E. TI Lower Risk of Creutzfeldt-Jakob Disease in Pituitary Growth Hormone Recipients Initiating Treatment After 1977 SO PRION LA English DT Meeting Abstract C1 [Abrams, Joseph; Schonberger, Lawrence B.; Belay, Ermias D.; Maddox, Ryan A.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Leschek, Ellen W.; Mills, James L.; Fradkin, Judith E.] NIH, Bethesda, MD 20892 USA. [Wysowski, Diane K.] US FDA, Rockville, MD 20857 USA. EM hus4@cdc.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Risk.01 BP 123 EP 123 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300279 ER PT J AU McDowell, K Pomeroy, K Nemecek, J Piccardo, P Gregori, DMAL AF McDowell, Kristy Pomeroy, Kitty Nemecek, Julie Piccardo, Pedro Gregori, David M. Asher Luisa TI Update on Macaque-Adapted vCJD Blood Panels SO PRION LA English DT Meeting Abstract C1 [McDowell, Kristy; Pomeroy, Kitty; Nemecek, Julie; Piccardo, Pedro; Gregori, David M. Asher Luisa] US FDA, CBER, OBRR, Rockville, MD 20857 USA. EM luisa.gregori@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1933-6896 EI 1933-690X J9 PRION JI Prion PD APR-JUN PY 2011 VL 5 SU S MA Risk.18 BP 129 EP 129 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V34DE UT WOS:000209066300293 ER PT J AU Zhang, N Jia, Y Chen, G Cabrales, P Palmer, AF AF Zhang, Ning Jia, Yiping Chen, Guo Cabrales, Pedro Palmer, Andre F. TI Biophysical Properties and Oxygenation Potential of High-Molecular-Weight Glutaraldehyde-Polymerized Human Hemoglobins Maintained in the Tense and Relaxed Quaternary States SO TISSUE ENGINEERING PART A LA English DT Article ID TANGENTIAL FLOW FILTRATION; BOVINE HEMOGLOBIN; NITRIC-OXIDE; EXCHANGE-TRANSFUSION; HEMORRHAGIC-SHOCK; BLOOD SUBSTITUTE; RANDOMIZED-TRIAL; CARDIAC-SURGERY; CROSS-LINKING; ACUTE TRAUMA AB Recent clinical evaluation of commercial glutaraldehyde-polymerized hemoglobins (PolyHbs) as transfusion solutions has demonstrated several adverse side effects. Chief among these is the hypertensive effect. Fortunately, previous studies have shown that the hypertensive effect can be attenuated by removing free hemoglobin (Hb) and low-molecular-weight (low-MW) PolyHbs from the PolyHb mixture. In this work, polymerized human Hb (PolyhHb) solutions were synthesized in two distinct quaternary states with high MW and subjected to extensive diafiltration to remove free Hb and low-MW PolyhHb components (<500 kDa). The resultant PolyhHb solutions possessed high MW, distinct quaternary state, distinct reactivities with O-2 and CO, similar NO deoxygenating rate constants, distinct autoxidation rate constants, high viscosity, and low colloid osmotic pressure. To preliminarily assess the ability of PolyhHb solutions to oxygenate surrounding tissues fed by a blood vessel, we evaluated the ability of PolyhHbs to transport O-2 to cultured hepatocytes in a mathematical model of a hollow fiber bioreactor. The structure of individual hollow fibers in the bioreactor is similar to that of a blood vessel and provides an easy way to assess the oxygenation potential of PolyhHbs without the need for expensive and time-consuming animal studies. It was observed that PolyhHbs with low O-2 affinities were more effective in oxygenating cultured hepatocytes inside the bioreactor than high O-2 affinity PolyhHbs. Taken together, our results show that it is possible to synthesize high-MW PolyhHbs with no free Hb and low-MW PolyhHb components that are capable of transporting O-2 to cultured cells/tissues. C1 [Zhang, Ning; Chen, Guo; Palmer, Andre F.] Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA. [Jia, Yiping] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. [Cabrales, Pedro] Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA. RP Palmer, AF (reprint author), Ohio State Univ, William G Lowrie Dept Chem & Biomol Engn, Columbus, OH 43210 USA. EM palmer.351@osu.edu RI Cabrales, Pedro/A-1930-2014; Zhang, Ning/E-8643-2014 OI Cabrales, Pedro/0000-0002-8794-2839; Zhang, Ning/0000-0002-5219-7285 FU National Institutes of Health [R01HL078840, R01DK070862] FX This work was supported by National Institutes of Health Grants R01HL078840 and R01DK070862 to A.F.P. The authors would like to thank David R. Harris for purifying the hHb for these studies. NR 35 TC 1 Z9 1 U1 0 U2 9 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1937-3341 J9 TISSUE ENG PT A JI Tissue Eng. Part A PD APR PY 2011 VL 17 IS 7-8 BP 927 EP 940 DI 10.1089/ten.tea.2010.0353 PG 14 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology SC Cell Biology; Biotechnology & Applied Microbiology GA 741GX UT WOS:000288853300006 PM 20979534 ER PT J AU Dearfield, KL Thybaud, V Cimino, MC Custer, L Czich, A Harvey, JS Hester, S Kim, JH Kirkland, D Levy, DD Lorge, E Moore, MM Ouedraogo-Arras, G Schuler, M Suter, W Sweder, K Tarlo, K van Benthem, J van Goethem, F Witt, KL AF Dearfield, Kerry L. Thybaud, Veronique Cimino, Michael C. Custer, Laura Czich, Andreas Harvey, James S. Hester, Susan Kim, James H. Kirkland, David Levy, Dan D. Lorge, Elisabeth Moore, Martha M. Ouedraogo-Arras, Gladys Schuler, Maik Suter, Willi Sweder, Kevin Tarlo, Kirk van Benthem, Jan van Goethem, Freddy Witt, Kristine L. TI Follow-Up Actions from Positive Results of In Vitro Genetic Toxicity Testing SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE genotoxicity assays; in vitro positives; strategy; follow-up; ILSI HESI ID ERYTHROCYTE MICRONUCLEUS ASSAY; GENOTOXICITY TEST PROCEDURES; TANDEM REPEAT INSTABILITY; BACTERIAL MUTATION ASSAYS; THYMIDINE KINASE LOCUS; TERM TEST INFORMATION; MOUSE LYMPHOMA-CELLS; IWGT WORKING GROUP; VIVO COMET ASSAY; TOX PROGRAM AB Appropriate follow-up actions and decisions are needed when evaluating and interpreting clear positive results obtained in the in vitro assays used in the initial genotoxicity screening battery (i.e., the battery of tests generally required by regulatory authorities) to assist in overall risk-based decision making concerning the potential effects of human exposure to the agent under test. Over the past few years, the International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing developed a decision process flow chart to be applied in case of clear positive results in vitro. It provides for a variety of different possibilities and allows flexibility in choosing follow-up action(s), depending on the results obtained in the initial battery of assays and available in-formation. The intent of the Review Subgroup was not to provide a prescriptive testing strategy, but rather to reinforce the concept of weighing the totality of the evidence. The Review Subgroup of the IVGT committee highlighted the importance of properly analyzing the existing data, and considering potential confounding factors (e. g., possible interactions with the test systems, presence of impurities, irrelevant metabolism), and chemical modes of action when analyzing and interpreting positive results in the in vitro genotoxicity assays and determining appropriate follow-up testing. The Review Subgroup also examined the characteristics, strengths, and limitations of each of the existing in vitro and in vivo genotoxicity assays to determine their usefulness in any follow-up testing. Environ. Mol. Mutagen. 52: 177-204, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Dearfield, Kerry L.] USDA, Food Safety & Inspect Serv, Washington, DC 20250 USA. [Thybaud, Veronique] Vitry Alfortville Res Ctr, Vitry Sur Seine, France. [Cimino, Michael C.] US EPA, Off Pollut Prevent & Tox, Washington, DC 20460 USA. [Custer, Laura; Sweder, Kevin] Bristol Myers Squibb Co, Res & Dev, Dept Genet Toxicol, E Syracuse, NY USA. [Czich, Andreas] Deutschland GmbH, R&D Drug Safety Evaluat FFM, Sanofi Aventis, Hattersheim, Germany. [Hester, Susan] US EPA, Res Unit Cores IO, Res Triangle Pk, NC 27711 USA. [Kim, James H.] ILSI HESI, Washington, DC USA. [Kirkland, David] Covance Labs Ltd, Harrogate, England. [Levy, Dan D.] US FDA, Off Nutr Labeling & Dietary Supplements, College Pk, MD USA. [Lorge, Elisabeth] Servier Grp, Biol Servier, France. [Moore, Martha M.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ouedraogo-Arras, Gladys] LOreal, Int Safety Res Dept, Aulnay Sous Bois, France. [Schuler, Maik] Pfizer Global Res & Dev, Drug Safety Res & Dev, Groton, CT USA. [Suter, Willi] Novartis Pharma AG, Preclin Safety GeneSafe, Basel, Switzerland. [Tarlo, Kirk] Amgen Inc, Thousand Oaks, CA 91320 USA. [van Benthem, Jan] Natl Inst Publ Hlth & Environm RIVM, Lab Hlth Protect Res, Bilthoven, Netherlands. [van Goethem, Freddy] Johnson & Johnson Pharmaceut R&D, Genet & Exploratory Toxicol, Beerse, Belgium. [Witt, Kristine L.] NIEHS, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Kim, JH (reprint author), 1156 15th St NW,2nd Floor, Washington, DC 20005 USA. EM jkim@hesiglobal.org NR 138 TC 22 Z9 24 U1 7 U2 17 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR PY 2011 VL 52 IS 3 DI 10.1002/em.20617 PG 28 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 731GZ UT WOS:000288095600003 PM 20963811 ER PT J AU Lynch, AM Sasaki, JC Elespuru, R Jacobson-Kram, D Thybaud, V De Boeck, M Aardema, MJ Aubrecht, J Benz, RD Dertinger, SD Douglas, GR White, PA Escobar, PA Fornace, A Honma, M Naven, RT Rusling, JF Schiestl, RH Walmsley, RM Yamamura, E van Benthem, J Kim, JH AF Lynch, Anthony M. Sasaki, Jennifer C. Elespuru, Rosalie Jacobson-Kram, David Thybaud, Veronique De Boeck, Marlies Aardema, Marilyn J. Aubrecht, Jiri Benz, R. Daniel Dertinger, Stephen D. Douglas, George R. White, Paul A. Escobar, Patricia A. Fornace, Albert, Jr. Honma, Masamitsu Naven, Russell T. Rusling, James F. Schiestl, Robert H. Walmsley, Richard M. Yamamura, Eiji van Benthem, Jan Kim, James H. TI New and Emerging Technologies for Genetic Toxicity Testing SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Review DE new technologies; genetic toxicity; testing; alternatives; ILSI HESI ID FLOW-CYTOMETRIC ANALYSIS; PERIPHERAL-BLOOD RETICULOCYTES; VITRO MICRONUCLEUS ASSAY; LUNG EPITHELIAL-CELLS; GADD45-ALPHA-GFP INDICATOR ASSAY; DISCRIMINATE RODENT CARCINOGENS; MONITORING CHROMOSOMAL DAMAGE; EXPRESSION PROFILE ANALYSIS; VIVO COMET ASSAY; HUMAN SKIN MODEL AB The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) Project Committee on the Relevance and Follow-up of Positive Results in In Vitro Genetic Toxicity (IVGT) Testing established an Emerging Technologies and New Strategies Workgroup to review the current State of the Art in genetic toxicology testing. The aim of the workgroup was to identify promising technologies that will improve genotoxicity testing and assessment of in vivo hazard and risk, and that have the potential to help meet the objectives of the IVGT. As part of this initiative, HESI convened a workshop in Washington, DC in May 2008 to discuss mature, maturing, and emerging technologies in genetic toxicology. This article collates the abstracts of the New and Emerging Technologies Workshop together with some additional technologies subsequently considered by the workgroup. Each abstract (available in the online version of the article) includes a section addressed specifically to the strengths, weaknesses, opportunities, and threats associated with the respective technology. Importantly, an overview of the technologies and an indication of how their use might be aligned with the objectives of IVGT are presented. In particular, consideration was given with regard to follow-up testing of positive results in the standard IVGT tests (i.e., Salmonella Ames test, chromosome aberration assay, and mouse lymphoma assay) to add weight of evidence and/or provide mechanism of action for improved genetic toxicity risk assessments in humans. Environ. Mol. Mutagen. 52: 205-223, 2011. (C) 2010 Wiley-Liss, Inc. C1 [Kim, James H.] ILSI Hlth & Environm Sci Inst, Washington, DC USA. [Lynch, Anthony M.] GlaxoSmithKline R&D, Ware, Herts, England. [Sasaki, Jennifer C.] Johnson & Johnson Pharmaceut Res & Dev, Raritan, NJ USA. [Elespuru, Rosalie] US FDA, Genom & Genet Lab, FDA CDRH OSEL, Div Biol, Silver Spring, MD USA. [Jacobson-Kram, David] US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Thybaud, Veronique] Vitry Alfortville Res Ctr, F-94400 Vitry Sur Seine, France. [De Boeck, Marlies] Johnson & Johnson Pharmaceut Res & Dev, Div Janssen Pharmaceut NV, Genet & Exploratory Toxicol, Beerse, Belgium. [Aardema, Marilyn J.] Procter & Gamble Co, Cincinnati, OH USA. [Aubrecht, Jiri] Pfizer Inc, Groton, CT 06340 USA. [Benz, R. Daniel] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Sci & Res Staff,Informat & Computat Safety Anal S, Silver Spring, MD USA. [Dertinger, Stephen D.] Litron Labs, Rochester, NY USA. [Douglas, George R.] Hlth Canada, Ctr Environm Hlth, Ottawa, ON K1A 0K9, Canada. [White, Paul A.] Hlth Canada, Mechanist Studies Div, Environm Hlth Sci & Res Div, Ottawa, ON K1A 0K9, Canada. [Escobar, Patricia A.] Boehringer Ingelheim Pharmaceut Inc, Toxicol & Safety Assessment, Ridgefield, CT 06877 USA. [Fornace, Albert, Jr.] Georgetown Univ, Lombardi Comprehens Canc Ctr, Washington, DC USA. [Honma, Masamitsu] Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo, Japan. [Naven, Russell T.] Pfizer Global Res & Dev, Drug Safety R&D, Sandwich, Kent, England. [Rusling, James F.] Univ Connecticut, Dept Chem, Storrs, CT USA. [Schiestl, Robert H.] Univ Calif Los Angeles, Sch Med, Los Angeles, CA USA. [Schiestl, Robert H.] Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. [Walmsley, Richard M.] Univ Manchester, Fac Life Sci, Manchester M13 9NT, Lancs, England. [Walmsley, Richard M.] Gentronix Ltd, Manchester, Lancs, England. [Yamamura, Eiji] Mitsubishi Tanabe Pharma Corp, Tokyo, Japan. [van Benthem, Jan] Natl Inst Publ Hlth & Environm RIVM, Lab Hlth Protect Res, Bilthoven, Netherlands. RP Kim, JH (reprint author), ILSI Hlth & Environm Sci Inst, Washington, DC USA. EM jkim@hesiglobal.org RI Fornace, Albert/A-7407-2008; OI Fornace, Albert/0000-0001-9695-085X; white, paul/0000-0001-5853-4759 FU National Centre for the Replacement, Refinement and Reduction of Animals in Research [G0600339/1] NR 123 TC 41 Z9 44 U1 4 U2 45 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR PY 2011 VL 52 IS 3 DI 10.1002/em.20614 PG 19 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 731GZ UT WOS:000288095600004 PM 20740635 ER PT J AU Landry, RJ Bostrom, RG Miller, SA Shi, DX Sliney, DH AF Landry, Robert J. Bostrom, Robert G. Miller, Sharon A. Shi, Dexiu Sliney, David H. TI RETINAL PHOTOTOXICITY: A REVIEW OF STANDARD METHODOLOGY FOR EVALUATING RETINAL OPTICAL RADIATION HAZARDS SO HEALTH PHYSICS LA English DT Review DE optics; photons; radiation damage; safety standards AB Optical radiation (light) safety standards can be difficult to use for the evaluation of light hazards to the retina, even for persons experienced in radiometry and photometry. This paper reviews terminology and methodology for evaluating optical radiation hazards to the retina in accordance with international standard ISO 15004-2 Ophthalmic instruments-Fundamental requirements and test methods, Part 2: Light hazard protection (2007). All optical radiation safety standards use similar methods. Specifically, this paper illustrates how to evaluate the retinal hazards from various ophthalmic instruments including the following: diffuse illumination of the cornea; incident light diverging at the cornea (direct ophthalmoscope, operation microscope, fixation lamp); and incident light converging at the cornea (indirect ophthalmoscope, fundus camera, slit lamp biomicroscope). A brief review of radiometry and the use of certified optical components by manufacturers as specified by the ISO standard is also provided. Finally, the authors provide examples of the use of photometric measurements in hazard evaluation. Health Phys. 100(4): 417-434; 2011 C1 [Landry, Robert J.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Landry, RJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 61, Silver Spring, MD 20993 USA. EM sharona.miller@fda.hhs.gov NR 7 TC 2 Z9 2 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD APR PY 2011 VL 100 IS 4 BP 417 EP 434 DI 10.1097/HP.0b013e3181f4993d PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 726QO UT WOS:000287741400004 PM 21350347 ER PT J AU Yang, MH Sun, S Kostov, Y Rasooly, A AF Yang, Minghui Sun, Steven Kostov, Yordan Rasooly, Avraham TI A simple 96-well microfluidic chip combined with visual and densitometry detection for resource-poor point of care testing SO SENSORS AND ACTUATORS B-CHEMICAL LA English DT Article DE Lab-on-a-chip; Staphylococcal enterotoxins; Resource-poor; Silver enhancement; Carbon nanotubes; Food safety ID STAPHYLOCOCCAL-ENTEROTOXIN-B; CARBON NANOTUBES; FILM DOSIMETRY; IMMUNOASSAY; LABEL; SCANNERS; IMAGE; ASSAY; FOOD AB There is a well-recognized need for low cost biodetection technologies for resource-poor settings with minimal medical infrastructure. Lab-on-a-chip (LOC) technology has the ability to perform biological assays in such settings. The aim of this work is to develop a low cost, high-throughput detection system for the analysis of 96 samples simultaneously outside the laboratory setting. To achieve this aim, several biosensing elements were combined: a syringe operated ELISA lab-on-a-chip (ELISA-LOC) which integrates fluid delivery system into a miniature 96-well plate: a simplified non-enzymatic reporter and detection approach using a gold nanoparticle-antibody conjugate as a secondary antibody and silver enhancement of the visual signal; and carbon nanotubes (CNT) to increase primary antibody immobilization and improve assay sensitivity. Combined, these elements obviate the need for an ELISA washer, electrical power for operation and a sophisticated detector. We demonstrate the use of the device for detection of Staphylococcal enterotoxin B, a major foodborne toxin using three modes of detection, visual detection, CCD camera and document scanner. With visual detection or using a document scanner to measure the signal, the limit of detection (LOD) was 0.5 ng/ml. In addition to visual detection, for precise quantitation of signal using densitometry and a CCD camera, the LOD was 0.1 ng/ml for the CCD analysis and 0.5 ng/ml for the document scanner. The observed sensitivity is in the same range as laboratory-based ELISA testing. The point of care device can analyze 96 samples simultaneously, permitting high throughput diagnostics in the field and in resource poor areas without ready access to laboratory facilities or electricity. Published by Elsevier B.V. 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. [Yang, Minghui] Univ Jinan, Sch Chem & Chem Engn, Jinan 250022, Peoples R China. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. RP Rasooly, A (reprint author), US FDA, Div Biol, Off Sci & Engn, 6130 Execut, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 23 TC 13 Z9 13 U1 3 U2 20 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 0925-4005 J9 SENSOR ACTUAT B-CHEM JI Sens. Actuator B-Chem. PD MAR 31 PY 2011 VL 153 IS 1 BP 176 EP 181 DI 10.1016/j.snb.2010.10.027 PG 6 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 743LH UT WOS:000289019300026 PM 21503269 ER PT J AU Zhang, JI Talaty, N Costa, AB Xia, Y Tao, WA Bell, R Callahan, JH Cooks, RG AF Zhang, J. Isabella Talaty, Nari Costa, Anthony B. Xia, Yu Tao, W. Andy Bell, Rebecca Callahan, John H. Cooks, R. Graham TI Rapid direct lipid profiling of bacteria using desorption electrospray ionization mass spectrometry SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY LA English DT Article DE DESI-MS; Bacteria; Lipid ID FAST-ATOM-BOMBARDMENT; LINKED-IMMUNOSORBENT-ASSAY; PROBE SAMPLE PRETREATMENT; GRAM-TYPE DIFFERENTIATION; PATHOGENIC BACTERIA; BACILLUS-SUBTILIS; WHOLE CELLS; IDENTIFICATION; SALMONELLA; INTACT AB Desorption electrospray ionization (DESI) was employed to measure lipids directly from sixteen bacterial samples without extraction or other sample preparation. Differentiation of different bacterial species and some sub-species was achieved using either the positive or the negative ion mode DESI mass spectra covering the mass/charge range up to m/z 1000. The data were confirmed by electrospray mass spectrometry (ESI-MS) of lipid extracts from the same bacterial samples. Although the signals were lower, the quality of the direct ionization DESI spectra compared favorably with that of the ESI spectra extracts prepared using chloroform/methanol. The use of unit mass resolution in these experiments allows for overlaps of nominally isobaric and isomeric lipids at particular m/z values. Tandem mass spectrometry was performed to validate the presence of particular lipids falling into several classes of phospholipids, including phosphatidylethanolamines (PE), phosphatidylglycerols (PG) and lysophospholipids. In addition. lysyl-phosphatidylglycerol (LPG) and lipopeptides were observed in the cases of gram-positive bacteria. DESI-MS lipid profiling was applied to the characterization of four different bacterial species including thirteen Salmonella strains. Two bacterial samples Escherichia coli K-12 and Salmonella typhimurium INSP24 were also grown in three different media. Data were compared using principal component analysis (PCA), which indicated that the different species are readily distinguished and that different growth media do not prevent bacterial species differentiation in the cases examined. Several different Salmonella strains are also distinguishable from each other based on the PCA results. (C) 2010 Published by Elsevier B.V. C1 [Zhang, J. Isabella; Talaty, Nari; Costa, Anthony B.; Xia, Yu; Tao, W. Andy; Cooks, R. Graham] Purdue Univ, Dept Chem, W Lafayette, IN 47907 USA. [Tao, W. Andy] Purdue Univ, Dept Biochem, W Lafayette, IN 47907 USA. [Bell, Rebecca; Callahan, John H.] US FDA, Off Regulatory Sci, CFSAN, College Pk, MD 20740 USA. RP Cooks, RG (reprint author), Purdue Univ, Dept Chem, 560 Oval Dr, W Lafayette, IN 47907 USA. EM cooks@purdue.edu RI Costa, Anthony/C-5471-2009; Cooks, R/G-1051-2015 OI Costa, Anthony/0000-0002-2202-6450; Cooks, R/0000-0002-9581-9603 FU Office of Naval Research [N00014-05-1-0454]; US National Science Foundation NSF [CHE-0848650] FX This work is supported by the Office of Naval Research (grant number N00014-05-1-0454) and US National Science Foundation NSF (grant number CHE-0848650). NR 52 TC 45 Z9 46 U1 5 U2 70 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-3806 EI 1873-2798 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. PD MAR 30 PY 2011 VL 301 IS 1-3 SI SI BP 37 EP 44 DI 10.1016/j.ijms.2010.06.014 PG 8 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 758TQ UT WOS:000290190000006 ER PT J AU Wen, ZN Wang, ZJ Wang, S Ravula, R Yang, L Xu, J Wang, C Zuo, Z Chow, MSS Shi, LM Huang, Y AF Wen, Zhining Wang, Zhijun Wang, Steven Ravula, Ranadheer Yang, Lun Xu, Jun Wang, Charles Zuo, Zhong Chow, Moses S. S. Shi, Leming Huang, Ying TI Discovery of Molecular Mechanisms of Traditional Chinese Medicinal Formula Si-Wu-Tang Using Gene Expression Microarray and Connectivity Map SO PLOS ONE LA English DT Article ID ANTIOXIDANT RESPONSE; HEME OXYGENASE-1; UP-REGULATION; CELLS; CONSTITUENTS; NRF2; DETOXIFICATION; CONSISTENCY; PROFILES; THERAPY AB To pursue a systematic approach to discovery of mechanisms of action of traditional Chinese medicine (TCM), we used microarrays, bioinformatics and the "Connectivity Map" (CMAP) to examine TCM-induced changes in gene expression. We demonstrated that this approach can be used to elucidate new molecular targets using a model TCM herbal formula Si-Wu-Tang (SWT) which is widely used for women's health. The human breast cancer MCF-7 cells treated with 0.1 mu M estradiol or 2.56 mg/ml of SWT showed dramatic gene expression changes, while no significant change was detected for ferulic acid, a known bioactive compound of SWT. Pathway analysis using differentially expressed genes related to the treatment effect identified that expression of genes in the nuclear factor erythroid 2-related factor 2 (Nrf2) cytoprotective pathway was most significantly affected by SWT, but not by estradiol or ferulic acid. The Nrf2-regulated genes HMOX1, GCLC, GCLM, SLC7A11 and NQO1 were upreguated by SWT in a dose-dependent manner, which was validated by real-time RT-PCR. Consistently, treatment with SWT and its four herbal ingredients resulted in an increased antioxidant response element (ARE)-luciferase reporter activity in MCF-7 and HEK293 cells. Furthermore, the gene expression profile of differentially expressed genes related to SWT treatment was used to compare with those of 1,309 compounds in the CMAP database. The CMAP profiles of estradiol-treated MCF-7 cells showed an excellent match with SWT treatment, consistent with SWT's widely claimed use for women's diseases and indicating a phytoestrogenic effect. The CMAP profiles of chemopreventive agents withaferin A and resveratrol also showed high similarity to the profiles of SWT. This study identified SWT as an Nrf2 activator and phytoestrogen, suggesting its use as a nontoxic chemopreventive agent, and demonstrated the feasibility of combining microarray gene expression profiling with CMAP mining to discover mechanisms of actions and to identify new health benefits of TCMs. C1 [Wen, Zhining; Yang, Lun; Shi, Leming] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Wen, Zhining] Sichuan Univ, Coll Chem, Chengdu 610064, Sichuan, Peoples R China. [Wang, Zhijun; Wang, Steven; Ravula, Ranadheer; Chow, Moses S. S.; Huang, Ying] Western Univ Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Pomona, CA USA. [Wang, Zhijun; Wang, Steven; Ravula, Ranadheer; Chow, Moses S. S.; Huang, Ying] Western Univ Hlth Sci, Coll Pharm, Ctr Adv Drug Res & Evaluat, Pomona, CA USA. [Yang, Lun; Shi, Leming] Fudan Univ, Sch Pharm, Dept Clin Pharm, Shanghai 200433, Peoples R China. [Yang, Lun; Shi, Leming] Fudan Univ, Sch Pharm, Ctr Pharmacogenom, Shanghai 200433, Peoples R China. [Xu, Jun] Univ Calif Los Angeles, Cedars Sinai Med Ctr, Inst Med Genet, David Geffen Sch Med, Los Angeles, CA 90048 USA. [Wang, Charles] City Hope Comprehens Canc Ctr, Beckman Res Inst, Duarte, CA USA. [Zuo, Zhong] Chinese Univ Hong Kong, Fac Med, Sch Pharm, Hong Kong, Hong Kong, Peoples R China. RP Wen, ZN (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM leming.shi@gmail.com; yhuang@westernu.edu RI Yang, Lun/B-4859-2012; Zuo, Zhong/B-6884-2008; Wang, zhijun/G-8543-2015 OI Wang, zhijun/0000-0001-8783-8946 FU U.S. Food and Drug Administration; Innovation and Technology Commission of the Hong Kong Special Administrative Region of the People's Republic of China [ITS/112/07, ITS/446/09] FX This work was supported by the U.S. Food and Drug Administration. The preparation of Si-Wu-Tang product was supported by the Innovation and Technology Fund (ITS/112/07) from the Innovation and Technology Commission of the Hong Kong Special Administrative Region of the People's Republic of China. This study was partially supported by the Innovation and Technology Grant (ITS/446/09) from the Innovation and Technology Commission of the Hong Kong Special Administrative Region of the People's Republic of China. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The views presented in this article do not necessarily reflect those of the U.S. Food and Drug Administration. NR 56 TC 67 Z9 73 U1 3 U2 46 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 1160 BATTERY STREET, STE 100, SAN FRANCISCO, CA 94111 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 28 PY 2011 VL 6 IS 3 AR e18278 DI 10.1371/journal.pone.0018278 PG 14 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 743XV UT WOS:000289053800036 PM 21464939 ER PT J AU Barchi, JJ Adams, KM Mallajosyula, S Mackerel, AD Freedberg, DI AF Barchi, Joseph J., Jr. Adams, Kristie M. Mallajosyula, Sairam Mackerel, Alexander D., Jr. Freedberg, Daron I. TI Structural studies of antiproliferative factor glycopeptide analogs: Conformational effects of both the sugar on the peptide and the peptide on the sugar SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 NCI, Frederick, MD 21701 USA. Univ Maryland, Baltimore, MD 21201 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. 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 MAR 27 PY 2011 VL 241 MA 49-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982802361 ER PT J AU Barnette, D Hart, M AF Barnette, Dustyn Hart, Mark TI Effect of SigB transcriptional regulators in hyaluronidase regulation in Staphylococcus aureus SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 Ouachita Baptist Univ, Dept Chem, Arkadelphia, AR USA. Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. 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 MAR 27 PY 2011 VL 241 MA 442-CHED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982800463 ER PT J AU Brorson, K Read, E Park, J AF Brorson, Kurt Read, Erik Park, Jun TI PAT in bioprocessing- current status & future directions SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 [Brorson, Kurt; Read, Erik; Park, Jun] CDER FDA, Div Monoclonal Antibodies, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 2 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 MAR 27 PY 2011 VL 241 MA 54-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982801838 ER PT J AU Harp, BP Baron, CI Miranda-Bermudez, E Richard, GI AF Harp, Bhakti Petigara Baron, Carolina I. Miranda-Bermudez, Enio Richard, Gerald I. TI Screening method for the separation and identification of permitted and non-permitted color additives in foods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 US FDA, Off Cosmet & Colors, College Pk, MD USA. US FDA, NE Reg Lab, Jamaica, NY USA. NR 0 TC 0 Z9 0 U1 2 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 223-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982801290 ER PT J AU Jackson, LS Banaszewski, K Chang, C Tolleson, W AF Jackson, Lauren S. Banaszewski, Katarzyna Chang, Claire Tolleson, William TI Effect of sanitizer solutions on the stability of ricin dried on a stainless steel surface in the absence and presence of food matrices SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 US FDA, NCFST, ORISE, Summit Argo, IL USA. US FDA, NCTR, Jefferson, AR USA. IIT, NCFST, Summit Argo, IL USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 106-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982800111 ER PT J AU Kondragunta, B Joshi, BH Brorson, KA Puri, RK Moreira, AR Rao, G AF Kondragunta, Bhargavi Joshi, Bharat H. Brorson, Kurt A. Puri, Raj K. Moreira, Antonio R. Rao, Govind TI Evaluation of scale-down to novel stirred high-throughput mini-bioreactors using genomic profiling of a hybridoma cell-line SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol Chem & Biochem Engn, Baltimore, MD 21228 USA. US FDA, Div Cellular & Gene Therapies, CBER, Bethesda, MD 20014 USA. US FDA, Div Monoclonal Antibodies, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 467-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982802245 ER PT J AU Lute, S Miesegaes, G Kaushal, S Strauss, D Chen, DY Shamlou, P Brorson, K AF Lute, Scott Miesegaes, George Kaushal, Simran Strauss, Daniel Chen, Dayue Shamlou, Parviz Brorson, Kurt TI Evaluation of cation exchange chromatography as a capture step for monoclonal antibody purification SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 US FDA, Div Monoclonal Antibodies, CDER, Silver Spring, MD USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. 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 MAR 27 PY 2011 VL 241 MA 398-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982802190 ER PT J AU Miesegaes, G AF Miesegaes, George TI Characterization of virus spike preparations used in viral clearance studies SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 [Miesegaes, George] US FDA, CDER, DMA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 125-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982801853 ER PT J AU Read, EK Brorson, KA AF Read, Erik K. Brorson, Kurt A. TI Challenges in developing process analytical technologies for a cell culture unit operation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 [Read, Erik K.; Brorson, Kurt A.] US FDA, Off Biotechnol Prod, CDER FDA, Silver Spring, MD USA. 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 MAR 27 PY 2011 VL 241 MA 79-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982801971 ER PT J AU Uplekar, SD Brorson, KA LaCourse, WR Moreira, AR Rao, G AF Uplekar, Shaunak D. Brorson, Kurt A. LaCourse, William R. Moreira, Antonio R. Rao, Govind TI Effect of culture conditions on N-glycan profiles of a monoclonal antibody produced by mammalian cell culture SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21228 USA. US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Silver Spring, MD USA. Univ Maryland Baltimore Cty, Dept Chem & Biochem, Baltimore, MD 21228 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 279-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982802156 ER PT J AU Vallejos, JR Brorson, KA Moreira, AR Rao, G AF Vallejos, Jose R. Brorson, Kurt A. Moreira, Antonio R. Rao, Govind TI Enabling process scouting devices (PSDs) with low cost dissolved oxygen and pH sensors for bioprocess development SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21228 USA. US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 291-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982802166 ER PT J AU Yu, BW Van Ingen, H Vivekanandan, S Norris, SE Rademacher, C Freedberg, DI AF Yu, Bingwu Van Ingen, Hugo Vivekanandan, Subramanian Norris, Scott E. Rademacher, Christoph Freedberg, Daron I. TI Accurate J coupling measurements for reliable carbohydrate structures SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 US FDA, DBPAP, OVRR, CBER, Bethesda, MD 20014 USA. Univ Toronto, Dept Biochem, Toronto, ON, Canada. Univ LAbeck, Inst Chem, Labeck, Germany. RI S, Vivekanandan/E-5197-2011; Subramanian, Vivekanandan/F-5865-2012; Rademacher, Christoph/H-3101-2012; van Ingen, Hugo/Q-2883-2016 OI Rademacher, Christoph/0000-0001-7082-7239; van Ingen, Hugo/0000-0002-0808-3811 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 27 PY 2011 VL 241 MA 66-CARB PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982802370 ER PT J AU Zhao, YW Xia, QS Yin, JJ Lin, G Fu, PP AF Zhao, Yuewei Xia, Qingsu Yin, Jun Jie Lin, Ge Fu, Peter P. TI Photoirradiation of dehydropyrrolizidine alkaloids: Formation of reactive oxygen species and induction of lipid peroxidation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 241st National Meeting and Exposition of the American-Chemical-Society (ACS) CY MAR 27-31, 2011 CL Anaheim, CA SP Amer Chem Soc C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Chinese Univ Hong Kong, Sch Biomed Sci, Hong Kong, Hong Kong, Peoples R China. RI Yin, Jun Jie /E-5619-2014 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 MAR 27 PY 2011 VL 241 MA 191-ENVR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 782BO UT WOS:000291982804470 ER PT J AU Ohtake, S Martin, R Saxena, A Pham, B Chiueh, G Osorio, M Kopecko, D Xu, DQ Lechuga-Ballesteros, D Truong-Le, V AF Ohtake, Satoshi Martin, Russell Saxena, Atul Binh Pham Chiueh, Gary Osorio, Manuel Kopecko, Dennis Xu, DeQi Lechuga-Ballesteros, David Truong-Le, Vu TI Room temperature stabilization of oral, live attenuated Salmonella enterica serovar Typhi-vectored vaccines SO VACCINE LA English DT Article DE Salmonella; Foam drying; Freeze drying; Oral vaccine; Live bacterial vaccine; Temperature-stability ID DRYING-INDUCED VARIATIONS; CONTROLLED FIELD TRIAL; BINARY LIPID MIXTURE; LOW WATER ACTIVITIES; PHYSICOCHEMICAL PROPERTIES; AMORPHOUS PHARMACEUTICALS; MONOCLONAL-ANTIBODY; BACTERIAL VACCINES; PHASE-TRANSITIONS; BIVALENT VACCINE AB Foam drying, a modified freeze drying process, was utilized to produce a heat-stable, live attenuated Salmonella Typhi 'Ty21a' bacterial vaccine. Ty21a vaccine was formulated with pharmaceutically approved stabilizers, including sugars, plasticizers, amino acids, and proteins. Growth media and harvesting conditions of the bacteria were also studied to enhance resistance to desiccation stress encountered during processing as well as subsequent storage at elevated temperatures. The optimized Ty21a vaccine, formulated with trehalose, methionine, and gelatin, demonstrated stability for approximately 12 weeks at 37 degrees C (i.e., time required for the vaccine to decrease in potency by 1 logo CFU) and no loss in titer at 4 and 25 degrees C following storage for the same duration. Furthermore, the foam dried Ty21a elicited a similar immunogenic response in mice as well as protection in challenge studies compared to Vivotif (TM), the commercial Ty21a vaccine. The enhanced heat stability of the Ty21a oral vaccine, or Ty21a derivatives expressing foreign antigens (e.g. anthrax), could mitigate risks of vaccine potency loss during long-term storage, shipping, delivery to geographical areas with warmer climates or during emergency distribution following a bioterrorist attack. Because the foam drying process is conducted using conventional freeze dryers and can be readily implemented at any freeze drying manufacturing facility, this technology appears ready and appropriate for large scale processing of foam dried vaccines. (C) 2011 Elsevier Ltd. All rights reserved. C1 [Ohtake, Satoshi; Martin, Russell; Saxena, Atul; Binh Pham; Chiueh, Gary; Lechuga-Ballesteros, David; Truong-Le, Vu] Aridis Pharmaceut, San Jose, CA 95138 USA. [Osorio, Manuel; Kopecko, Dennis; Xu, DeQi] FDA CBER, Lab Enter & Sexually Transmitted Dis, Bethesda, MD 20892 USA. RP Truong-Le, V (reprint author), Aridis Pharmaceut, 5941 Opt Court, San Jose, CA 95138 USA. EM truongv@aridispharma.com FU NIAID NIH HHS [R43 AI063829-02, R43 AI063829-01A1] NR 78 TC 17 Z9 19 U1 0 U2 16 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD MAR 24 PY 2011 VL 29 IS 15 BP 2761 EP 2771 DI 10.1016/j.vaccine.2011.01.093 PG 11 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 745CE UT WOS:000289140700017 PM 21300096 ER PT J AU Choi, CH Schoenfeld, BP Bell, AJ Hinchey, P Kollaros, M Gertner, MJ Woo, NH Tranfaglia, MR Bear, MF Zukin, RS McDonald, TV Jongens, TA McBride, SMJ AF Choi, Catherine H. Schoenfeld, Brian P. Bell, Aaron J. Hinchey, Paul Kollaros, Maria Gertner, Michael J. Woo, Newton H. Tranfaglia, Michael R. Bear, Mark F. Zukin, R. Suzanne McDonald, Thomas V. Jongens, Thomas A. McBride, Sean M. J. TI Pharmacological reversal of synaptic plasticity deficits in the mouse model of Fragile X syndrome by group II mGluR antagonist or lithium treatment SO BRAIN RESEARCH LA English DT Article DE Fragile X syndrome; Long-term depression; Lithium; Metabotropic glutamate receptor; LY341495 ID METABOTROPIC GLUTAMATE RECEPTORS; LONG-TERM DEPRESSION; MENTAL-RETARDATION PROTEIN; FREELY MOVING RATS; HIPPOCAMPAL CA1 REGION; IN-VIVO; DENTATE GYRUS; COGNITIVE IMPAIRMENT; SELECTIVE ANTAGONIST; SPATIAL MEMORY AB Fragile X syndrome is the leading single gene cause of intellectual disabilities. Treatment of a Drosophila model of Fragile X syndrome with metabotropic glutamate receptor (mGluR) antagonism or lithium rescues social and cognitive impairments. A hallmark feature of the Fragile X mouse model is enhanced mGluR-dependent long-term depression (LTD) at Schaffer collateral to CA1 pyramidal synapses of the hippocampus. Here we examine the effects of chronic treatment of Fragile X mice in vivo with lithium or a group II mGluR antagonist on mGluR-LTD at CA1 synapses. We find that long-term lithium treatment initiated during development (5-6 weeks of age) and continued throughout the lifetime of the Fragile X mice until 9-11 months of age restores normal mGluR-LTD. Additionally, chronic short-term treatment beginning in adult Fragile X mice (8 weeks of age) with either lithium or an mGluR antagonist is also able to restore normal mGluR-LTD. Translating the findings of successful pharmacologic intervention from the Drosophila model into the mouse model of Fragile X syndrome is an important advance, in that this identifies and validates these targets as potential therapeutic interventions for the treatment of individuals afflicted with Fragile X syndrome. (C) 2010 Elsevier B.V. All rights reserved. C1 [Choi, Catherine H.; Schoenfeld, Brian P.; Bell, Aaron J.; Hinchey, Paul; Kollaros, Maria; McDonald, Thomas V.; McBride, Sean M. J.] Albert Einstein Coll Med, Sect Mol Cardiol, Dept Med, Bronx, NY 10461 USA. [Choi, Catherine H.; Schoenfeld, Brian P.; Bell, Aaron J.; Hinchey, Paul; Kollaros, Maria; McDonald, Thomas V.; McBride, Sean M. J.] Albert Einstein Coll Med, Sect Mol Cardiol, Dept Mol Pharmacol, Bronx, NY 10461 USA. [Choi, Catherine H.] Lehigh Valley Hosp, Lehigh Valley Hlth Syst, Dept Med, Allentown, PA 18103 USA. [Choi, Catherine H.] Drexel Univ, Coll Med, Dept Dermatol, Philadelphia, PA 19102 USA. [Gertner, Michael J.; Zukin, R. Suzanne] Albert Einstein Coll Med, Dominick P Purpura Dept Neurosci, Bronx, NY 10461 USA. [Woo, Newton H.] OND CDER FDA, Div Anesthesia & Analgesia Prod, Off Drug Evaluat 2, Silver Spring, MD 20993 USA. [Tranfaglia, Michael R.] FRAXA Res Fdn, Newburyport, MA USA. [Bear, Mark F.] MIT, Howard Hughes Med Inst, Picower Inst Learning & Memory, Cambridge, MA 02139 USA. [Bear, Mark F.] MIT, Dept Brain & Cognit Sci, Cambridge, MA 02139 USA. [Jongens, Thomas A.] Univ Penn, Sch Med, Dept Genet, Philadelphia, PA 19104 USA. [McBride, Sean M. J.] Univ Penn, Sch Med, Dept Psychiat, Philadelphia, PA 19104 USA. RP McBride, SMJ (reprint author), Albert Einstein Coll Med, Sect Mol Cardiol, Dept Med, Forcheimer G236,1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jongens@mail.med.upenn.edu; smcbride@aecom.yu.edu FU FRAXA Research Foundation; National Fragile X Foundation; Autism Speaks; Albert Einstein College of Medicine; NIH-NINDS; NIGMS FX We would like to thank Myles Akabas, Allison Terlizzi, Neal Ferrick, Thomas Dockendorff, Pablo Castillo, Graham Ellis-Davies, Eric Koenigsberg, Alex Harris, Boris Heifets, Kanji Takahashi, Diana Petit, Randi Hagerman, David Nelson, Peter Davies, Peter Klein, Peter Vanderklish, Eric Klann, and Sumantra Chattarji for critical comments during this project. We would like to thank Melanie Talent for the use of space and equipment. We would like to thank the Animal Care Facility at Drexel College of Medicine and Albert Einstein College of Medicine; specifically, we would like to thank Janet Schulenberg, Andy Nelson, Charlene Glenn, and Carlton Reed for assistance with animal care. We would like to acknowledge funding from the FRAXA Research Foundation to S.M.J.M., C.H. C., and T.A.J. We thank the National Fragile X Foundation for a summer fellowship award to Eric Koenigsberg. We would like to acknowledge funding from Autism Speaks to T.V.M and S. M.J.M. We would like to thank the Albert Einstein College of Medicine MSTP grant for funding S.M.J.M and NIH-NINDS and NIGMS funding to T.A.J. The views expressed in the article do not necessarily represent the views of the agency or the United States. NR 81 TC 46 Z9 46 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 22 PY 2011 VL 1380 SI SI BP 106 EP 119 DI 10.1016/j.brainres.2010.11.032 PG 14 WC Neurosciences SC Neurosciences & Neurology GA 745AH UT WOS:000289135800010 PM 21078304 ER PT J AU Macadangdang, B Zhang, N Lund, PE Marple, AH Okabe, M Gottesman, MM Appella, DH Kimchi-Sarfaty, C AF Macadangdang, Benjamin Zhang, Ning Lund, Paul E. Marple, Andrew H. Okabe, Mitsunori Gottesman, Michael M. Appella, Daniel H. Kimchi-Sarfaty, Chava TI Inhibition of Multidrug Resistance by SV40 Pseudovirion Delivery of an Antigene Peptide Nucleic Acid (PNA) in Cultured Cells SO PLOS ONE LA English DT Article ID P-GLYCOPROTEIN; GENE-EXPRESSION; IN-VITRO; SV40-DERIVED VECTORS; LOCALIZATION SIGNAL; CELLULAR DELIVERY; ANTICANCER DRUGS; CHROMOSOMAL DNA; CANCER-CELLS; SEQUENCE AB Peptide nucleic acid (PNA) is known to bind with extraordinarily high affinity and sequence-specificity to complementary nucleic acid sequences and can be used to suppress gene expression. However, effective delivery into cells is a major obstacle to the development of PNA for gene therapy applications. Here, we present a novel method for the in vitro delivery of antigene PNA to cells. By using a nucleocapsid protein derived from Simian virus 40, we have been able to package PNA into pseudovirions, facilitating the delivery of the packaged PNA into cells. We demonstrate that this system can be used effectively to suppress gene expression associated with multidrug resistance in cancer cells, as shown by RT-PCR, flow cytometry, Western blotting, and cell viability under chemotherapy. The combination of PNA with the SV40-based delivery system is a method for suppressing a gene of interest that could be broadly applied to numerous targets. C1 [Macadangdang, Benjamin; Lund, Paul E.; Marple, Andrew H.; Okabe, Mitsunori; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Zhang, Ning; Appella, Daniel H.] NIDDK, Bioorgan Chem Lab, NIH, US Dept HHS, Bethesda, MD 20892 USA. [Kimchi-Sarfaty, Chava] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Macadangdang, B (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37, Bethesda, MD 20892 USA. EM appellad@niddk.nih.gov; chava.kimchi-sarfaty@fda.hhs.gov FU National Institutes of Health; National Cancer InstituteNational Institute of Diabetes and Digestive and Kidney Diseases; Food and Drug Administration FX This work was supported in part by the Intramural Research Program of the National Institutes of Health, National Cancer Institute, and the National Institute of Diabetes and Digestive and Kidney Diseases, and the Food and Drug Administration. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent an Agency determination or policy. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 48 TC 4 Z9 4 U1 1 U2 13 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD MAR 22 PY 2011 VL 6 IS 3 AR e17981 DI 10.1371/journal.pone.0017981 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 740QI UT WOS:000288809100021 PM 21445346 ER PT J AU Sultana, I Gao, J Markoff, L Eichelberger, MC AF Sultana, Ishrat Gao, Jin Markoff, Lewis Eichelberger, Maryna C. TI Influenza neuraminidase-inhibiting antibodies are induced in the presence of zanamivir SO VACCINE LA English DT Article DE Influenza; Neuraminidase; Potency test; Immunogenicity ID HONG-KONG INFLUENZA; VIRUS NEURAMINIDASE; A VIRUS; 3-DIMENSIONAL STRUCTURE; VIRAL NEURAMINIDASE; N2 NEURAMINIDASE; VACCINE; RECOMBINANT; PROTECTION; RESISTANCE AB Seasonal influenza epidemics cause illness and death each year, and the emergence of antigenically novel influenza A viruses are a continual pandemic threat. Disease and death can be averted by vaccination. The potency of killed virus vaccines is based on hemagglutinin (HA) content. However, antibodies that inhibit enzyme activity of the neuraminidase (NA) also reduce virus replication and protect against disease. Monoclonal NA-inhibiting (NI) antibodies recognize conformational epitopes, and it is anticipated that native tertiary structure is required for their induction. NA assembles as a tetramer and only this form has enzyme activity. Since small inhibitors of NA do not significantly alter conformation, we sought to determine whether neuraminidase-inhibiting (NI) antibodies would be induced by inhibitor-inactivated NA. We therefore evaluated responses of mice immunized with purified NA that was either inactivated by addition of zanamivir or denatured by heat treatment. NI antibodies were induced following immunization with NA from A/Wisconsin/67/2005 (H3N2) in which enzyme activity was inhibited by the former method but not the latter. Protection of mice against challenge with virus containing an antigenically matched NA correlated with the detection of NI antibodies in serum. Similar results were obtained when mice were immunized with whole H1N1 virus in which NA activity had been inhibited by the same two modalities. This demonstrates that native conformation of NA is necessary for induction of NI antibodies; enzyme activity provides a useful marker of intact structure, but absence of activity in NA that is correctly folded does not result in loss of immunogenicity. Thus any assay to assess potency of influenza vaccines with respect to NA content should consider the proportion of NA that is in a structurally native state. Published by Elsevier Ltd. C1 [Sultana, Ishrat; Gao, Jin; Markoff, Lewis; Eichelberger, Maryna C.] US FDA, Div Viral Prod, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Eichelberger, MC (reprint author), US FDA, Div Viral Prod, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Maryna.Eichelberger@fda.hhs.gov FU CBER, FDA FX We thank Arash Hassantoufighi, Laura Nerret, Kevin Yang and Katie Harris for technical assistance, and Drs. Bert Johansson and Vladimir Lugovtsev for helpful suggestions in preparation of the manuscript. We are also indebted to Matt Sandbulte for construction of the H6 reassortant viruses used in challenge studies and NI assays. This project was funded by pandemic influenza funds from CBER, FDA. NR 36 TC 11 Z9 11 U1 3 U2 10 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 21 PY 2011 VL 29 IS 14 BP 2601 EP 2606 DI 10.1016/j.vaccine.2011.01.047 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 745CD UT WOS:000289140600014 PM 21288802 ER PT J AU Alayash, AI AF Alayash, Abdu I. TI Haptoglobin: Old protein with new functions SO CLINICA CHIMICA ACTA LA English DT Review DE Hemoglobin; Haptoglobin; Redox reactions ID RED-BLOOD-CELLS; HUMAN-HEMOGLOBIN; NITRIC-OXIDE; SCAVENGER RECEPTOR; NITROGEN-OXIDES; OXIDATION; PATHWAY; BINDING; THERAPEUTICS; LOCALIZATION AB When released from red blood cells (RBCs), hemoglobin (Hb) is extremely toxic due in large part to the redox activity of its heme center. Mature however, has provided a multitude of protective mechanisms that can detoxify free Hb effectively under physiological conditions. Chief amongst them is haptoglobin (Hp) which chaperones Hb subunits to the macrophages for safe degradation. Recent research on the interactions between Hb and Hp under oxidative conditions revealed that Hp specifically shields key amino acids on the Hb molecule, allowing the heme to consume oxidants and short-circuits the emerging and damaging radicals. Moreover, animal studies showed that the infusion of Hb complexed with Hp prevents Hb-induced systemic hypertension and tissue injury. It may prove necessary to explore these protective clearing mechanisms to counter the toxicity associated with free Hb when used as oxygen therapeutics in hemolytic anemias and in RBC storage lesions. Published by Elsevier B.V. C1 [Alayash, Abdu I.] US Food & Drug Adm FDA, Lab Biochem & Vasc Biol, Div Hematol, CBER, Bethesda, MD USA. RP Alayash, AI (reprint author), FDA, CBER, NIH Bldg 29,Rm 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov NR 42 TC 35 Z9 38 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0009-8981 J9 CLIN CHIM ACTA JI Clin. Chim. Acta PD MAR 18 PY 2011 VL 412 IS 7-8 BP 493 EP 498 DI 10.1016/j.cca.2010.12.011 PG 6 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 727YZ UT WOS:000287840600002 PM 21159311 ER PT J AU Woodcock, J Griffin, JP Behrman, RE AF Woodcock, Janet Griffin, Joseph P. Behrman, Rachel E. TI Development of Novel Combination Therapies SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 [Woodcock, Janet] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Griffin, Joseph P.; Behrman, Rachel E.] US FDA, Off Med Policy, 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 100 Z9 101 U1 3 U2 20 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 17 PY 2011 VL 364 IS 11 BP 985 EP 987 DI 10.1056/NEJMp1101548 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 735SX UT WOS:000288439000001 PM 21323535 ER PT J AU Reimschuessel, R Gieseker, C Poynton, S AF Reimschuessel, Renate Gieseker, Charles Poynton, Sarah TI In vitro effect of seven antiparasitics on Acolpenteron ureteroecetes (Dactylogyridae) from largemouth bass Micropterus salmoides (Centrarchidae) SO DISEASES OF AQUATIC ORGANISMS LA English DT Article DE Parasite; Largemouth bass; In vitro; Antiparasitic; Bioassay ID TROUT ONCORHYNCHUS-MYKISS; MICROCOTYLE-SEBASTIS MONOGENEA; LICE LEPEOPHTHEIRUS-SALMONIS; ORAL PHARMACOLOGICAL-TREATMENTS; NEMATODE HAEMONCHUS-CONTORTUS; HEARTWORM DIROFILARIA-IMMITIS; PRAZIQUANTEL BATH TREATMENTS; LARVAL DEVELOPMENT TEST; GATED CHLORIDE CHANNEL; EEL ANGUILLA-ANGUILLA AB Few drugs are approved by the United States Food and Drug Administration for treating parasite infections in minor species such as fish, due in part to the high cost of developing such drugs and to a relatively small market share for drug sponsors. Because in vivo effectiveness trials for antiparasitic drugs are costly, time consuming, and use many animals, a systematic in vitro screening approach to describe parasite motility could help find promising drug candidates. We evaluated the effects of 7 antiparasitics on the activity and survival of the endoparasitic monogenean Acolpenteron ureteroecetes (Dactylogyridae) collected from the posterior kidneys of juvenile largemouth bass Micropterus salmoides (Lacepede, 1802) (Centrarchidae) held in the laboratory. Tests were conducted in 12 well tissue culture plates; each well had 3 parasites, and we tested 3 concentrations and 1 control for each of the 7 antiparasitics. The parasites were observed immediately after adding the drug, at 1 to 3 h, and 17 to 26 h, and video recordings were made. Drug effects were recorded by documenting morbidity (reduced movement, tremors, contracted body, abnormal morphology) and mortality. A. ureteroecetes was strongly affected by the quinoline praziquantel, the imidazothiazide levamisole, and the organophosphates dichlorvos and trichlorfon. The parasites were moderately affected by the macrocyclic lactones ivermectin and emamectin, and generally unaffected by the benzimidazole mebendazole. Our study demonstrates the utility of characterizing in vitro responses with video microscopy to document responses of fish parasites for initial screens of drug effects on a fish monogenean. C1 [Reimschuessel, Renate; Gieseker, Charles] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. [Poynton, Sarah] Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA. RP Gieseker, C (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM charles.gieseker@fda.hhs.gov NR 127 TC 4 Z9 4 U1 1 U2 14 PU INTER-RESEARCH PI OLDENDORF LUHE PA NORDBUNTE 23, D-21385 OLDENDORF LUHE, GERMANY SN 0177-5103 EI 1616-1580 J9 DIS AQUAT ORGAN JI Dis. Aquat. Org. PD MAR 16 PY 2011 VL 94 IS 1 BP 59 EP 72 DI 10.3354/dao02303 PG 14 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 738AW UT WOS:000288612700006 PM 21553568 ER PT J AU Strauss, DG Selvester, RH Wagner, GS AF Strauss, David G. Selvester, Ronald H. Wagner, Galen S. TI Defining Left Bundle Branch Block in the Era of Cardiac Resynchronization Therapy SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Review ID LEFT-VENTRICULAR ACTIVATION; HEART-FAILURE; CONDUCTION DISTURBANCES; ENDOCARDIAL ACTIVATION; MYOCARDIAL SCAR; ELECTROCARDIOGRAPHY AB Cardiac resynchronization therapy (CRT) has emerged as an attractive intervention to improve left ventricular mechanical function by changing the sequence of electrical activation. Unfortunately, many patients receiving CRT do not benefit but are subjected to device complications and costs. Thus, there is a need for better selection criteria. Current criteria for CRT eligibility include a QRS duration >= 120 ms. However, QRS morphology is not considered, although it can indicate the cause of delayed conduction. Recent studies have suggested that only patients with left bundle branch block (LBBB) benefit from CRT, and not patients with right bundle branch block or nonspecific intraventricular conduction delay. The authors review the pathophysiologic and clinical evidence supporting why only patients with complete LBBB benefit from CRT. Furthermore, they review how the threshold of 120 ms to define LBBB was derived subjectively at a time when criteria for LBBB and right bundle branch block were mistakenly reversed. Three key studies over the past 65 years have suggested that 1/3 of patients diagnosed with LBBB by conventional electrocardiographic criteria may not have true complete LBBB, but likely have a combination of left ventricular hypertrophy and left anterior fascicular block. On the basis of additional insights from computer simulations, the investigators propose stricter criteria for complete LBBB that include a QRS duration >= 140 ms for men and >= 130 ms for women, along with mid-QRS notching or slurring in >= 2 contiguous leads. Further studies are needed to reinvestigate the electrocardiographic criteria for complete LBBB and the implications of these criteria for selecting patients for CRT. Published by Elsevier Inc. (Am J Cardiol 2011;107:927-934) C1 [Strauss, David G.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Selvester, Ronald H.] Mem Hosp Res Ctr, Long Beach, CA USA. [Wagner, Galen S.] Duke Clin Res Inst, Durham, NC USA. RP Strauss, DG (reprint author), Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. EM david.strauss@fda.hhs.gov RI Strauss, David/A-9211-2012 NR 28 TC 135 Z9 139 U1 0 U2 6 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 15 PY 2011 VL 107 IS 6 BP 927 EP 934 DI 10.1016/j.amjcard.2010.11.010 PG 8 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 740WO UT WOS:000288825300021 PM 21376930 ER PT J AU Jacob, CC da Costa, GG AF Jacob, Cristina C. da Costa, Goncalo Gamboa TI Low-level quantification of melamine and cyanuric acid in limited samples of rat serum by UPLC-electrospray tandem mass spectrometry SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Melamine; Cyanuric acid; Rat serum; UPLC-ESI-MS/MS ID SPRAGUE-DAWLEY RATS; CHROMATOGRAPHY; TOXICITY; CATS AB This paper reports the development and validation of a methodology for the low-level quantification of melamine and cyanuric acid in limited samples of rat serum. The methodology, based upon ion-exchange solid phase extraction (SPE) and ultra-performance liquid chromatography (UPLC) coupled with electrospray tandem mass spectrometry (MS/MS) in multiple reaction monitoring (MRM) mode, relies on the use of stable isotope-labeled internal standards and requires only 15 mu L samples of serum. The method provides a recovery of 80-110% of melamine with a signal suppression of ca. 55%, and a recovery of 50-90% of cyanuric acid with a signal suppression ca. 40-60%, affording lower limits of quantification (LLOQ) for melamine or cyanuric acid of, respectively, 5 ppb (mean accuracy 109%; CV = 4.9%) and 10 ppb (mean accuracy 96%; CV = 8.6%). The small sample requirements, excellent sensitivity, accuracy and precision, and high-throughput (5 min of instrument run time) make this methodology optimal for toxicokinetic or exposure assessments studies. Published by Elsevier B.V. C1 [Jacob, Cristina C.; da Costa, Goncalo Gamboa] US FDA Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP da Costa, GG (reprint author), US FDA Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-233,3900 NCTR Rd, Jefferson, AR 72079 USA. EM goncalo.gamboa@fda.hhs.gov RI Jacob, Cristina/A-3885-2015 OI Jacob, Cristina/0000-0003-2652-3865 FU FDA [FDA IAG:224-07-0007, NIH Y1ES1027]; NIEHS [FDA IAG:224-07-0007, NIH Y1ES1027] FX This study was supported through an interagency agreement between the FDA and the National Toxicology Program at NIEHS (FDA IAG:224-07-0007; NIH Y1ES1027). NR 14 TC 6 Z9 6 U1 1 U2 6 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 MAR 15 PY 2011 VL 879 IS 9-10 BP 652 EP 656 DI 10.1016/j.jchromb.2011.01.035 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 739NA UT WOS:000288723500015 PM 21345750 ER PT J AU DeGrasse, SL van de Riet, J Hatfield, R Turner, A AF DeGrasse, Stacey L. van de Riet, Jeffrey Hatfield, Robert Turner, Andrew TI Pre- versus post-column oxidation liquid chromatography fluorescence detection of paralytic shellfish toxins SO TOXICON LA English DT Article DE LC; Oxidation; Paralytic shellfish toxins; Saxitoxin; Validation ID SINGLE-LABORATORY VALIDATION; POISONING TOXINS; PRECHROMATOGRAPHIC OXIDATION; QUANTITATIVE-DETERMINATION; MASS-SPECTROMETRY; ALEXANDRIUM; GULF; OYSTERS; MUSSELS; MAINE AB Both pre- and post-column oxidation liquid chromatography methods with fluorescence detection are available for detecting paralytic shellfish toxins. Each method has been evaluated in multiple laboratories and validated as a potential alternative to the mouse bioassay. This communication compares the advantages and limitations of both methods. For a given laboratory, the selection of either method may be based primarily on practicality and less on any deficiencies in scientific merit. Published by Elsevier Ltd. C1 [DeGrasse, Stacey L.] US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Analyt Chem,Spect & Mass Spectrometry Branch, College Pk, MD 20740 USA. [van de Riet, Jeffrey] Canadian Food Inspect Agcy, Dartmouth Lab, Dartmouth, NS B3B 1Y9, Canada. [Hatfield, Robert; Turner, Andrew] Ctr Environm Fisheries & Aquaculture Sci, Weymouth DT4 8UB, Dorset, England. RP DeGrasse, SL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Analyt Chem,Spect & Mass Spectrometry Branch, 5100 Paint Branch Pkwy,HFS 707, College Pk, MD 20740 USA. EM Stacey.Etheridge@fda.hhs.gov RI Toxinas, Inct/I-1933-2013; Turner, Andrew/J-5658-2015; OI Turner, Andrew/0000-0003-1390-0924; DeGrasse, Stacey/0000-0001-7808-4193 NR 29 TC 17 Z9 17 U1 1 U2 12 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 MAR 15 PY 2011 VL 57 IS 4 BP 619 EP 624 DI 10.1016/j.toxicon.2010.12.017 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 742HN UT WOS:000288932300013 PM 21194540 ER PT J AU Miller, HI AF Miller, Henry I. TI NIH Pharma Co. Is a Bad Idea SO GENETIC ENGINEERING & BIOTECHNOLOGY NEWS LA English DT Editorial Material C1 [Miller, Henry I.] Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. [Miller, Henry I.] US FDA, Off Biotechnol, Rockville, MD 20857 USA. RP Miller, HI (reprint author), Stanford Univ, Hoover Inst, Stanford, CA 94305 USA. EM henry.miller@stanford.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1935-472X J9 GENET ENG BIOTECHN N JI Genet. Eng. Biotechnol. News PD MAR 15 PY 2011 VL 31 IS 6 BP 6 EP 7 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 740TE UT WOS:000288816500003 ER PT J AU Bhave, VS Donthamsetty, S Latendresse, JR Cunningham, ML Mehendale, HM AF Bhave, Vishakha S. Donthamsetty, Shashikiran Latendresse, John R. Cunningham, Michael L. Mehendale, Harihara M. TI Secretory phospholipase A(2)-mediated progression of hepatotoxicity initiated by acetaminophen is exacerbated in the absence of hepatic COX-2 SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Acetaminophen; Cycloxygenase-2; Hepatotoxicity; Prostaglandin E-2; Secretory Phospholipase A(2); TNF-alpha ID ACUTE LIVER-INJURY; NECROSIS-FACTOR-ALPHA; HEPATOCELLULAR REGENERATION; MODEL HEPATOTOXICANTS; MEDIATES PROGRESSION; ACUTE-INFLAMMATION; RECEPTOR-ALPHA; NITRIC-OXIDE; RAT-LIVER; CYCLOOXYGENASE-2 AB We have previously reported that among the other death proteins, hepatic secretory phospholipase A(2) (sPLA(2)) is a leading mediator of progression of liver injury initiated by CCI4 in rats. The aim of our present study was to test the hypothesis that increased hepatic sPLA(2) released after acetaminophen (APAP) challenge mediates progression of liver injury in wild type (WT) and COX-2 knockout (KO) mice. COX-2 WT and KO mice were administered a normally non lethal dose (400 mg/kg) of acetaminophen. The COX-2 1(0 mice suffered 60% mortality compared to 100% survival of the WT mice, suggesting higher susceptibility of COX-2 KO mice to sPLA(2)-mediated progression of acetaminophen hepatotoxicity. Liver injury was significantly higher at later time points in the KO mice compared to the WT mice indicating that the abatement of progression of injury requires the presence of COX-2. This difference in hepatotoxicity was not due to increased bioactivation of acetaminophen as indicated by unchanged cyp2E1 protein and covalently bound C-14-APAP in the livers of KO mice. Hepatic sPLA(2) activity and plasma TNF-alpha were significantly higher after APAP administration in the KO mice. This was accompanied by a corresponding fall in hepatic PGE(2) and lower compensatory liver regeneration and repair (H-3-thymidine incorporation) in the KO mice. These results suggest that hindered compensatory tissue repair and poor resolution of inflammation for want of beneficial prostaglandins render the liver very vulnerable to sPLA(2)-mediated progression of liver injury. These findings are consistent with the destructive role of sPLA(2) in the progression and expansion of tissue injury as a result of continued hydrolytic breakdown of plasma membrane phospholipids of perinecrotic hepatocytes unless mitigated by sufficient co-induction of COX-2. (C) 2011 Published by Elsevier Inc. C1 [Bhave, Vishakha S.; Donthamsetty, Shashikiran; Mehendale, Harihara M.] Univ Louisiana Monroe, Dept Toxicol, Coll Pharm, Monroe, LA 71209 USA. [Latendresse, John R.] Toxicol Pathol Associates, Natl Ctr Toxicol Res, Jefferson, AR USA. [Cunningham, Michael L.] NIEHS, Res Triangle Pk, NC 27709 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Dept Toxicol, Coll Pharm, 700 Univ Ave,Bienville 259, Monroe, LA 71209 USA. EM mehendale@ulm.edu OI Bhave, Vishakha/0000-0003-0149-579X FU Louisiana Board of Regents; DeGree Endowed Chair in Toxicology Fund; NIH, National Institute of Environmental Health Sciences (NIEHS) FX This work was supported in part by the Louisiana Board of Regents Support Funds, DeGree Endowed Chair in Toxicology, and by the Intramural Research Program of the NIH, National Institute of Environmental Health Sciences (NIEHS). NR 43 TC 8 Z9 8 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 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 15 PY 2011 VL 251 IS 3 BP 173 EP 180 DI 10.1016/j.taap.2011.01.013 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 735NC UT WOS:000288421000001 PM 21277885 ER PT J AU Tsai, DH DelRio, FW Keene, AM Tyner, KM MacCuspie, RI Cho, TJ Zachariah, MR Hackley, VA AF Tsai, De-Hao DelRio, Frank W. Keene, Athena M. Tyner, Katherine M. MacCuspie, Robert I. Cho, Tae Joon Zachariah, Michael R. Hackley, Vincent A. TI Adsorption and Conformation of Serum Albumin Protein on Gold Nanoparticles Investigated Using Dimensional Measurements and in Situ Spectroscopic Methods SO LANGMUIR LA English DT Article ID DIFFERENTIAL MOBILITY ANALYSIS; DIRECTED DRUG-DELIVERY; COLLOIDAL GOLD; ENHANCED FLUORESCENCE; GAMMA-GLOBULIN; X-RAY; SURFACE; ACID; BINDING; SCATTERING AB The adsorption and conformation of bovine serum albumin (BSA) on gold nanoparticles (AuNPs) were interrogated both qualitatively and quantitatively via complementary physicochemical characterization methods. Dynamic light scattering (DLS), asymmetric-flow field flow fractionation (AFFF), fluorescence spectrometry, and attenuated total reflectance Fourier transform infrared (ATR-FTIR) spectroscopy were combined to characterize BSA-AuNP conjugates under fluid conditions, while conjugates in the aerosol state were characterized by electrospray-differential mobility analysis (ES-DMA). The presence of unbound BSA molecules interferes with DLS analysis of the conjugates, particularly as the AuNP size decreases (i.e., below 30 nm in diameter). Under conditions where the gamma value is high, where gamma is defined as the ratio of scattering intensity by AuNPs to the scattering intensity by unbound BSA, DLS size results are consistent with results obtained after fractionation by AFFF. Additionally, the AuNP hydrodynamic size exhibits a greater proportional increase due to BSA conjugation at pH values below 2.5 compared with less acidic pH values (3.4-7.3), corresponding with the reversibly denatured (E or F form) conformation of BSA below pH 2.5. Over the pH range from 3.4 to 7.3, the hydrodynamic size of the conjugate is nearly constant, suggesting conformational stability over this range. Because of the difference in the measurement environment, a larger increase of AuNP size is observed following BSA conjugation when measured in the wet state (i.e., by DLS and AFFF) compared to the dry state (by ES-DMA). Molecular surface density for BSA is estimated based on ES-DMA and fluorescence measurements. Results from the two techniques are consistent and similar, but slightly higher for ES-DMA, with an average adsorbate density of 0.015 nm(-2). Moreover, from the change of particle size, we determine the extent of adsorption for BSA on AuNPs using DLS and ES-DMA at 21 degrees C, which show that increasing the concentration of BSA increases the measured change in AuNP size. Using ES-DMA, we observe that the BSA surface density reaches 90% of saturation at a solution phase concentration between 10 and 30 mu mol/L, which is roughly consistent with fluorescence and AM-FTIR results. The equilibrium binding constant for BSA on AuNPs is calculated by applying the Langmuir equation, with resulting values ranging from 0.51 x 10(6) to 1.65 x 10(6) L/mol, suggesting a strong affinity due to bonding between the single free exterior thiol on N-form BSA (associated with a cysteine residue) and the AuNP surface. Moreover, the adsorption interaction induces a conformational change in BSA secondary structure, resulting in less a-helix content and more open structures (beta-sheet, random, or expanded). C1 [Tsai, De-Hao; DelRio, Frank W.; MacCuspie, Robert I.; Cho, Tae Joon; Zachariah, Michael R.; Hackley, Vincent A.] Natl Inst Stand & Technol, Mat Measurement Lab, Gaithersburg, MD 20899 USA. [Keene, Athena M.; Tyner, Katherine M.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Zachariah, Michael R.] Univ Maryland, Dept Mech Engn, College Pk, MD 20740 USA. [Zachariah, Michael R.] Univ Maryland, Dept Chem, College Pk, MD 20740 USA. RP Hackley, VA (reprint author), Natl Inst Stand & Technol, Mat Measurement Lab, Gaithersburg, MD 20899 USA. EM vince.hackley@nist.gov RI Sanders, Susan/G-1957-2011; Tsai, De-Hao/K-6702-2012; OI Tsai, De-Hao/0000-0002-2669-3007; MacCuspie, Robert/0000-0002-6618-6499; Hackley, Vincent/0000-0003-4166-2724 NR 79 TC 158 Z9 162 U1 22 U2 173 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD MAR 15 PY 2011 VL 27 IS 6 BP 2464 EP 2477 DI 10.1021/la104124d PG 14 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 730NE UT WOS:000288039500057 PM 21341776 ER PT J AU Zhang, K Hu, XN Liu, JB Yin, JJ Hou, SA Wen, T He, WW Ji, YL Guo, YT Wang, Q Wu, XC AF Zhang, Ke Hu, Xiaona Liu, Jianbo Yin, Jun-Jie Hou, Shuai Wen, Tao He, Weiwei Ji, Yinglu Guo, Yuting Wang, Qi Wu, Xiaochun TI Formation of PdPt Alloy Nanodots on Gold Nanorods: Tuning Oxidase-like Activities via Composition SO LANGMUIR LA English DT Article ID SHAPE-CONTROLLED SYNTHESIS; OXYGEN REDUCTION; CATALYTIC-ACTIVITY; GLUCOSE DETECTION; AU NANORODS; PLATINUM NANOPARTICLE; BIMETALLIC NANORODS; OPTICAL-PROPERTIES; SUPEROXIDE ANION; SEEDED GROWTH AB The island growth mode of Pt was employed to guide the forma-tion of PdPt alloy nanodots on gold nanorods (Au@PdPt NRs). Well-defined alloy. nanodots, with tunable Pd/Pt ratios from 0.2 to 5, distribute homogeneously on the surface of the Au NR Formation of nanodots shell leads to the red shift and broadening of the longitudinal surface plasmon resonance (LSPR) band of the Au NRs. The Au@PdPt alloy NRs exhibit catalytic activity toward oxidation,: of often used chromogenic substrates by dissolved oxygen under mild conditions, suggesting a new type of oxidase mimics Composition dependence catalytic activity is observed for the oxidation of ascorbic acid (AA) and 3,3',5,5'-tetramethylbenzidine (TMB) and for the reduction of p-nitrophenol. For AA and TMB, catalytic activity enhances quickly at lower Pd/Pt ratios and tends to saturate at higher Pd/Pt ratios. For p-nitrophenol reduction, catalytic activity shows a nice linear relationship with Pd/Pt ratio owing to much higher catalytic activity of Pd. In Conclusion, proper alloying of Pd and Pt presents' an effective route to tailor the catalytic activity. Interesting, alloy nanodots can also catalyze the oxidation of Fe (H) to Fe (III) by dissolved oxygen. Thus, based on the competitive oxidation of TMB and Fe (II), selective detection of the latter can be achieved. C1 [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Zhang, Ke; Hu, Xiaona; Liu, Jianbo; Hou, Shuai; Wen, Tao] Chinese Acad Sci, Grad Sch, Beijing 100190, Peoples R China. [Zhang, Ke; Hu, Xiaona; Liu, Jianbo; Hou, Shuai; Wen, Tao; He, Weiwei; Ji, Yinglu; Guo, Yuting; Wang, Qi; Wu, Xiaochun] Natl Ctr Nanosci & Technol, CAS Key Lab Standardizat & Measurement Nanotechno, Beijing 100190, Peoples R China. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM JunJie.Yin@fda.hhs.gov; wuxc@nanoctr.cn RI Yin, Jun Jie /E-5619-2014 FU National Natural Science Foundation of China [20773032, 0874015]; State Key Basic Research Program of China [2011CB932802] FX The work was supported by National Natural Science Foundation of China (Grant No. 20773032 and 0874015) and State Key Basic Research Program of China (2011CB932802). Herman Lutterodt, from the Department of Food Science & Nutrition, University of Maryland, is thanked for running the ESR measurements. This article reflects the views of the author and should not be construed to represent FDA's views or policies. NR 55 TC 63 Z9 64 U1 11 U2 105 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0743-7463 J9 LANGMUIR JI Langmuir PD MAR 15 PY 2011 VL 27 IS 6 BP 2796 EP 2803 DI 10.1021/la104566e PG 8 WC Chemistry, Multidisciplinary; Chemistry, Physical; Materials Science, Multidisciplinary SC Chemistry; Materials Science GA 730NE UT WOS:000288039500096 PM 21332216 ER PT J AU Iverson, AR Boyd, KL McAuley, JL Plano, LR Hart, ME McCullers, JA AF Iverson, Amy R. Boyd, Kelli L. McAuley, Julie L. Plano, Lisa R. Hart, Mark E. McCullers, Jonathan A. TI Influenza Virus Primes Mice for Pneumonia From Staphylococcus aureus SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID SECONDARY BACTERIAL PNEUMONIA; COMMUNITY-ACQUIRED PNEUMONIA; PANTON-VALENTINE LEUKOCIDIN; ACTIVATING-FACTOR RECEPTOR; A VIRUS; STREPTOCOCCUS-PNEUMONIAE; INCREASED SUSCEPTIBILITY; PNEUMOCOCCAL PNEUMONIA; PANDEMIC INFLUENZA; LETHAL SYNERGISM AB Superinfections from Staphylococcus aureus following influenza are an increasing concern. We assessed several laboratory and clinical strains in a mouse coinfection model with influenza virus. A methicillin-resistant USA300 clone and several recent clinical strains from patients with necrotizing pneumonia caused high mortality following influenza virus infection in mice. Both viral and bacterial lung titers were enhanced during coinfections compared with single infections. However, differences in titers did not correspond with differences in disease outcomes in a comparison of superinfections from a highly pathogenic strain with those from a poorly pathogenic strain. These strains did differ, however, in expression of Panton-Valentine leukocidin and in the degree of inflammatory lung damage each engendered. The viral cytotoxin PB1-F2 contributed to the negative outcomes. These data suggest that additional study of specific bacterial virulence factors involved in the pathogenesis of inflammation and lung damage during coinfections is needed. C1 [Iverson, Amy R.; McAuley, Julie L.; McCullers, Jonathan A.] St Jude Childrens Hosp, Dept Infect Dis, Memphis, TN 38105 USA. [Boyd, Kelli L.] Vanderbilt Univ, Dept Pathol, Div Comparat Med, Nashville, TN USA. [Plano, Lisa R.] Univ Miami, Dept Pediat, Miami, FL 33152 USA. [Plano, Lisa R.] Univ Miami, Dept Microbiol & Immunol, Miami, FL 33152 USA. [Hart, Mark E.] Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP McCullers, JA (reprint author), St Jude Childrens Hosp, Dept Infect Dis, 262 Danny Thomas Pl, Memphis, TN 38105 USA. EM jon.mccul-lers@stjude.org RI Hart, Mark/B-8976-2013; OI McAuley, Julie/0000-0003-2493-3465 FU Public Health Service [AI-66349]; ALSAC FX This work was supported by the Public Health Service (AI-66349 to J.A.M.) and by ALSAC. NR 50 TC 70 Z9 73 U1 0 U2 7 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR 15 PY 2011 VL 203 IS 6 BP 880 EP 888 DI 10.1093/infdis/jiq113 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 726RB UT WOS:000287742700019 PM 21278211 ER PT J AU Ghosh, P Ghosh, K Tiwari, RC AF Ghosh, Pulak Ghosh, Kaushik Tiwari, Ram C. TI Joint modeling of longitudinal data and informative dropout time in the presence of multiple changepoints SO STATISTICS IN MEDICINE LA English DT Article DE longitudinal data; dropout; joint model; multiple changepoint; Dirichlet process prior; clustering ID SURVIVAL-DATA; FAILURE; MIXTURES; PROGRESSION; PROFILES AB In longitudinal studies of patients with the human immunodeficiency virus (HIV), objectives of interest often include modeling of individual-level trajectories of HIV ribonucleic acid (RNA) as a function of time. Such models can be used to predict the effects of different treatment regimens or to classify subjects into subgroups with similar trajectories. Empirical evidence, however, suggests that individual trajectories often possess multiple points of rapid change, which may vary from subject to subject. Additionally, some individuals may end up dropping out of the study and the tendency to drop out may be related to the level of the biomarker. Modeling of individual viral RNA profiles is challenging in the presence of these changes, and currently available methods do not address all the issues such as multiple changes, informative dropout, clustering, etc. in a single model. In this article, we propose a new joint model, where a multiple-changepoint model is proposed for the longitudinal viral RNA response and a proportional hazards model for the time of dropout process. Dirichlet process (DP) priors are used to model the distribution of the individual random effects and error distribution. In addition to robustifying the model against possible misspecifications, the DP leads to a natural clustering of subjects with similar trajectories which can be of importance in itself. Sharing of information among subjects with similar trajectories also results in improved parameter estimation. A fully Bayesian approach for model fitting and prediction is implemented using MCMC procedures on the ACTG 398 clinical trial data. The proposed model is seen to give rise to improved estimates of individual trajectories when compared with a parametric approach. Copyright (C) 2010 John Wiley & Sons, Ltd. C1 [Ghosh, Kaushik] Univ Nevada, Dept Math Sci, Las Vegas, NV 89154 USA. [Ghosh, Pulak] Indian Inst Management, Dept Quantitat Methods & Informat Syst, Bangalore 560076, Karnataka, India. [Tiwari, Ram C.] US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD 20993 USA. [Tiwari, Ram C.] NCI, Bethesda, MD 20892 USA. RP Ghosh, K (reprint author), Univ Nevada, Dept Math Sci, 4505 Maryland Pkwy,Box 454020, Las Vegas, NV 89154 USA. EM kaushik.ghosh@unlv.edu NR 29 TC 1 Z9 1 U1 1 U2 11 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD MAR 15 PY 2011 VL 30 IS 6 BP 611 EP 626 DI 10.1002/sim.4119 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 724YJ UT WOS:000287612100002 PM 21337357 ER PT J AU Lienau, EK Strain, E Wang, C Zheng, J Ottesen, AR Keys, CE Hammack, TS Musser, SM Brown, EW Allard, MW Cao, GJ Meng, JH Stones, R AF Lienau, E. Kurt Strain, Errol Wang, Charles Zheng, Jie Ottesen, Andrea R. Keys, Christine E. Hammack, Thomas S. Musser, Steven M. Brown, Eric W. Allard, Marc W. Cao, Guojie Meng, Jianghong Stones, Robert TI Identification of a Salmonellosis Outbreak by Means of Molecular Sequencing SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Lienau, E. Kurt; Strain, Errol; Wang, Charles; Zheng, Jie; Ottesen, Andrea R.; Keys, Christine E.; Hammack, Thomas S.; Musser, Steven M.; Brown, Eric W.; Allard, Marc W.] Food & Drug Adm, College Pk, MD USA. [Cao, Guojie; Meng, Jianghong] Univ Maryland, College Pk, MD 20742 USA. [Stones, Robert] Food & Environm Res Agcy, York, N Yorkshire, England. RP Lienau, EK (reprint author), Food & Drug Adm, College Pk, MD USA. EM marc.allard@fda.hhs.gov NR 5 TC 72 Z9 72 U1 2 U2 23 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 10 PY 2011 VL 364 IS 10 BP 981 EP 982 DI 10.1056/NEJMc1100443 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 732FL UT WOS:000288170300033 PM 21345093 ER PT J AU McCrane, MP Weinert, EE Lin, Y Mazzola, EP Lam, YF Scholl, PF Rokita, SE AF McCrane, Michael P. Weinert, Emily E. Lin, Ying Mazzola, Eugene P. Lam, Yiu-Fai Scholl, Peter F. Rokita, Steven E. TI Trapping a Labile Adduct Formed between an ortho-Quinone Methide and 2 '-Deoxycytidine SO ORGANIC LETTERS LA English DT Article ID HYPERVALENT IODINE OXIDATION; OXIDE-DONATING ASPIRIN; SINGLET OXYGEN; DNA ALKYLATION; CROSS-LINKING; PRODUCT; PHENOL; INSIGHTS; SYSTEMS AB Selective oxidation by bis[(trifluoroacetoxy)iodo]benzene (BTI) provides an effective trap for quenching adducts formed reversibly between dC and an ortho-quinone methide (QM) under physiological conditions. A model adduct generated by 4-methyl-o-QM and 2'-deoxycytidine is rapidly converted by intramolecular cyclization and loss of aromaticity to a characteristic product for quantifying QM alkylation. However, BTI induces a surprising rearrangement driven by overoxidation of a derivative lacking an alkyl substituent at the 4-position of the QM. C1 [McCrane, Michael P.; Weinert, Emily E.; Lin, Ying; Lam, Yiu-Fai; Rokita, Steven E.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Mazzola, Eugene P.] Univ Maryland, Joint Inst Food Safety & Appl Nutr JIFSAN, College Pk, MD 20742 USA. [Scholl, Peter F.] Ctr Food Safety & Nutr, Food & Drug Adm, Spect & Mass Spect Branch, Div Analyt Chem, College Pk, MD 20740 USA. RP Rokita, SE (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM Rokita@umd.edu RI Rokita, Steven/C-4793-2009; OI Weinert, Emily/0000-0002-4986-8682; Scholl, Peter/0000-0002-8870-3266 FU NSF [CHE-0517498] FX We thank Michael Novak (Miami University) for suggesting use of the methyl-substituted quinone methide and the NSF (CHE-0517498) for financial support. NR 35 TC 10 Z9 10 U1 2 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 EI 1523-7052 J9 ORG LETT JI Org. Lett. PD MAR 4 PY 2011 VL 13 IS 5 BP 1186 EP 1189 DI 10.1021/ol200071p PG 4 WC Chemistry, Organic SC Chemistry GA 725LI UT WOS:000287645800094 PM 21306149 ER PT J AU Liu, JH Chung, HJ Vogt, M Jin, YT Malide, D He, LS Dundr, M Levens, D AF Liu, Juhong Chung, Hye-Jung Vogt, Matthew Jin, Yetao Malide, Daniela He, Liusheng Dundr, Miroslav Levens, David TI JTV1 co-activates FBP to induce USP29 transcription and stabilize p53 in response to oxidative stress SO EMBO JOURNAL LA English DT Article DE apoptosis; FBP; JTV1; p53; USP29 ID TRANSFER-RNA SYNTHETASE; ELEMENT-BINDING PROTEIN-1; LEUKEMIA NUCLEAR-BODIES; DEUBIQUITINATING ENZYMES; PARKINSONS-DISEASE; MYC EXPRESSION; UBIQUITINATION; DYNAMICS; PATHWAY; COMPLEX AB c-myc and p53 networks control proliferation, differentiation, and apoptosis and are responsive to, and cross-regulate a variety of stresses and metabolic and biosynthetic processes. At c-myc, the far upstream element binding protein (FBP) and FBP-interacting repressor (FIR) program transcription by looping to RNA polymerase II complexes engaged at the promoter. Another FBP partner, JTV1/AIMP2, a structural subunit of a multi-aminoacyl-tRNA synthetase (ARS) complex, has also been reported to stabilize p53 via an apparently independent mechanism. Here, we show that in response to oxidative stress, JTV1 dissociates from the ARS complex, translocates to the nucleus, associates with FBP and co-activates the transcription of a new FBP target, ubiquitin-specific peptidase 29 (USP29). A previously uncharacterized deubiquitinating enzyme, USP29 binds to, cleaves poly-ubiquitin chains from, and stabilizes p53. The accumulated p53 quickly induces apoptosis. Thus, FBP and JTV1 help to coordinate the molecular and cellular response to oxidative stress. The EMBO Journal (2011) 30, 846-858. doi: 10.1038/emboj.2011.11; Published online 1 February 2011 C1 [Liu, Juhong; Jin, Yetao] US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Liu, Juhong; Chung, Hye-Jung; Vogt, Matthew; He, Liusheng; Levens, David] NCI, Gene Regulat Sect, Pathol Lab, Bethesda, MD 20892 USA. [Malide, Daniela] NHLBI, Light Microscopy Core Facil, Cell Biol & Physiol Ctr, Bethesda, MD 20892 USA. [He, Liusheng] St Jude Childrens Hosp, Dept Tumor Cell Biol, Flow Cytometry Shared Facil, Memphis, TN 38105 USA. [Dundr, Miroslav] Rosalind Franklin Univ Med & Sci, Dept Cell Biol & Anat, N Chicago, IL USA. RP Liu, JH (reprint author), US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bldg 29A,Room 1C11, Bethesda, MD 20892 USA. EM juhong.liu@fda.hhs.gov; levens@helix.nih.gov RI Levens, David/C-9216-2009 OI Levens, David/0000-0002-7616-922X FU NCI; NIH, NCI, CCR FX We thank Dr Barbara Taylor of NCI Flow Core Facility for cell sorting. We thank Dr Xin W Wang for providing p53 and Hdm2 expression vectors. We thank Dr Lixin Zhang for help with FACS analysis. We thank Dr Ashutosh Rao of the Food and Drug Administration for help with confocal microscopy. HCT-116 p53+/+ and p53-/- cells were kind gifts from Dr Bert Vogelstein. We thank Drs Mark Cookson, John Brady and Dinah Singer for their helpful suggestions for the experiments and comments on this manuscript. We thank one of the reviewers for suggesting that the JTV1-mediated p53 stabilization may be oxidative stress specific. This work was supported in part by 2006 NCI Director's Intramural Innovation Award to Juhong Liu. This work was supported by Research Program of the NIH, NCI, CCR. NR 43 TC 48 Z9 49 U1 0 U2 4 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 MAR 2 PY 2011 VL 30 IS 5 BP 846 EP 858 DI 10.1038/emboj.2011.11 PG 13 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 746IP UT WOS:000289239000006 PM 21285945 ER PT J AU Laughren, T AF Laughren, Thomas TI FDA Perspective on the DSM-5 Approach to Classification of "Cognitive" Disorders SO JOURNAL OF NEUROPSYCHIATRY AND CLINICAL NEUROSCIENCES LA English DT Article ID SCHIZOPHRENIA; DEMENTIA; SYMPTOMS AB Primary "cognitive" disorders (e.g., Alzheimer's disease) often have behavioral features, just as primary behavioral disorders (e.g., schizophrenia) often have cognitive features. Drug research in recent years has expanded into targeting the full range of symptoms of both types of disorders. DSM-5 should include these associated features of each type of disorder, because acknowledging the full range of symptoms for each type of disorder has important research and treatment implications. (The Journal of Neuropsychiatry and Clinical Neurosciences 2011; 23: 126-131) C1 US FDA, Silver Spring, MD 20993 USA. RP Laughren, T (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Thomas.Laughren@fda.hhs.gov NR 8 TC 2 Z9 2 U1 1 U2 2 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 0895-0172 J9 J NEUROPSYCH CLIN N JI J. Neuropsychiatr. Clin. Neurosci. PD SPR PY 2011 VL 23 IS 2 BP 126 EP 131 PG 6 WC Clinical Neurology; Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 777VF UT WOS:000291652500126 PM 21677238 ER PT J AU Guerraty, MA Grant, GR Karanian, JW Chiesa, OA Pritchard, WF Davies, PF AF Guerraty, Marie A. Grant, Gregory R. Karanian, John W. Chiesa, Oscar A. Pritchard, William F. Davies, Peter F. TI Side-Specific Expression of Activated Leukocyte Adhesion Molecule (ALCAM; CD166) in Pathosusceptible Regions of Swine Aortic Valve Endothelium SO JOURNAL OF HEART VALVE DISEASE LA English DT Article AB Aortic valve sclerosis (AVS), an early form of aortic valve disease, develops preferentially on the aortic side of valve leaflets, a predilection that is reflected in an heterogeneous side-specific gene expression profile. It has been ascertained that hypercholesterolemia is sufficient to initiate the endothelial expression of activated leukocyte adhesion molecule (ALCAM; CD166), restricted to the aortic side of the leaflet. Intercellular adhesion molecule-1 (ICAM-1) or vascular cell adhesion molecule-1 (VCAM-1) both of which are more typically associated with early arterial inflammation - are not differentially expressed. ALCAM up-regulation by hypercholesterolemia suggests a side-specific spatial role in the recruitment of leukocytes to AVS sites. C1 [Davies, Peter F.] Univ Penn, Inst Med & Engn, Vagelos Labs 1010, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Guerraty, Marie A.; Davies, Peter F.] US FDA, Inst Med & Engn, Laurel, MD USA. [Grant, Gregory R.] US FDA, Ctr Bioinformat, Laurel, MD USA. [Karanian, John W.; Chiesa, Oscar A.; Pritchard, William F.] US FDA, Lab Cardiovasc & Intervent Therapeut, Laurel, MD USA. RP Davies, PF (reprint author), Univ Penn, Inst Med & Engn, Vagelos Labs 1010, Dept Pathol & Lab Med, 3340 Smith Walk, Philadelphia, PA 19104 USA. EM pfd@pobox.upenn.edu OI Davies, Peter/0000-0003-4842-6417 FU NIH [F31 HL079877, P01 HL62250] FX These studies were supported by NIH Fellowship F31 HL079877 (to M.A.G.) and NIH grant P01 HL62250 (to P.F.D.). NR 5 TC 2 Z9 2 U1 0 U2 1 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD MAR PY 2011 VL 20 IS 2 BP 165 EP 167 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 768YK UT WOS:000290975600008 PM 21560815 ER PT J AU Lee, SL Yu, LX Cai, B Johnsons, GR Rosenberg, AS Cherney, BW Guo, W Raw, AS AF Lee, Sau L. Yu, Lawrence X. Cai, Bing Johnsons, Gibbes R. Rosenberg, Amy S. Cherney, Barry W. Guo, Wei Raw, Andre S. TI Scientific Considerations for Generic Synthetic Salmon Calcitonin Nasal Spray Products SO AAPS JOURNAL LA English DT Article DE bioequivalence; generic; immunogenicity; nasal spray; pharmaceutical equivalence; salmon calcitonin ID MONOCLONAL-ANTIBODY; SECONDARY STRUCTURE; AGGREGATION; PROTEIN; IMMUNOGENICITY; INTERFERON-ALPHA-2A; CONFORMATION; BENZALKONIUM; DEAMIDATION; PEPTIDES AB Under the Abbreviated New Drug Application pathway, a proposed generic salmon calcitonin nasal spray is required to demonstrate pharmaceutical equivalence and bioequivalence to the brand-name counterpart or the reference listed drug. This review discusses two important aspects of pharmaceutical equivalence for this synthetic peptide nasal spray product. The first aspect is drug substance sameness, in which a proposed generic salmon calcitonin product is required to demonstrate that it contains the same active ingredient as that in the brand-name counterpart. The second aspect is comparability in product- and process-related factors that may influence immunogenicity (i.e., peptide-related impurities, aggregates, formulation, and leachates from the container/closure system). The comparability of these factors helps to ensure the product safety, particularly with respect to immunogenicity. This review also highlights the key features of in vitro and/or in vivo studies for establishing bioequivalence for a solution nasal spray containing a systemically acting salmon calcitonin. C1 [Lee, Sau L.; Yu, Lawrence X.; Cai, Bing; Raw, Andre S.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. [Johnsons, Gibbes R.; Rosenberg, Amy S.; Cherney, Barry W.; Guo, Wei] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Yu, LX (reprint author), US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, 7519 Standish Pl, Rockville, MD 20855 USA. EM lawrence.yu@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 55 TC 7 Z9 7 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD MAR PY 2011 VL 13 IS 1 BP 14 EP 19 DI 10.1208/s12248-010-9242-9 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 758YP UT WOS:000290204800002 PM 21052882 ER PT J AU Zhang, XY Lionberger, RA Davit, BM Yu, LX AF Zhang, Xinyuan Lionberger, Robert A. Davit, Barbara M. Yu, Lawrence X. TI Utility of Physiologically Based Absorption Modeling in Implementing Quality by Design in Drug Development SO AAPS JOURNAL LA English DT Article DE advanced compartmental absorption and transit (ACAT) model; gastroplus (TM); modified release (MR); quality by design (QbD) ID IN-VITRO DATA; PHARMACOKINETIC SIMULATION; INTESTINAL PERMEABILITY; BIOWAIVER EXTENSION; SOLUBLE DRUG; DOSAGE FORMS; CARBAMAZEPINE; PREDICTION; DISSOLUTION; BIOAVAILABILITY AB To implement Quality by Design (QbD) in drug development, scientists need tools that link drug products properties to in vivo performance. Physiologically based absorption models are potentially useful tools; yet, their utility of QbD implementation has not been discussed or explored much in the literature. We simulated pharmacokinetics (PK) of carbamazepine (CBZ) after administration of four oral formulations, immediate-release (IR) suspension, IR tablet, extended-release (XR) tablet and capsule, under fasted and fed conditions and presented a general diagram of a modeling and simulation strategy integrated with pharmaceutical development. We obtained PK parameters and absorption scale factors (ASFs) by deconvolution of the PK data for IR suspension under fasted condition. The model was validated for other PK profiles of IR formulations and used to predict PK for XR formulations. We explored three key areas where a modeling and simulation approach impacts QbD. First, the model was used to help identify optimal in vitro dissolution conditions for XR formulations. Second, identification of critical formulations variables was illustrated by a parameter sensitivity analysis of mean particle radius for the IR tablet that showed a PK shift with decreased particle radius, C-max was increased and T-max was decreased. Finally, virtual trial simulations allowed incorporation of inter-subject variability in the model. Virtual bioequivalence studies performed for two test formulations suggested that an in vitro dissolution test may be a more sensitive discriminative method than in vivo PK studies. In summary, a well-validated predictive model is a potentially useful tool for QbD implementation in drug development. C1 [Zhang, Xinyuan; Lionberger, Robert A.; Davit, Barbara M.; Yu, Lawrence X.] US FDA, OGD, Rockville, MD 20857 USA. RP Lionberger, RA (reprint author), US FDA, OGD, Rockville, MD 20857 USA. EM Robert.Lionberger@fda.hhs.gov NR 52 TC 51 Z9 53 U1 3 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD MAR PY 2011 VL 13 IS 1 BP 59 EP 71 DI 10.1208/s12248-010-9250-9 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 758YP UT WOS:000290204800007 PM 21207216 ER PT J AU Lee, SL Adams, WP Li, BV Conner, DP Chowdhury, BA Yu, LX AF Lee, S. L. Adams, W. P. Li, B. V. Conner, D. P. Chowdhury, B. A. Yu, L. X. TI In Vitro Considerations to Support Bioequivalence of Locally Acting Drugs in Dry Powder Inhalers for Lung Diseases (vol 11, pg 414, 2009) SO AAPS JOURNAL LA English DT Correction C1 [Lee, S. L.; Adams, W. P.; Li, B. V.; Conner, D. P.; Chowdhury, B. A.; Yu, L. X.] US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. RP Lee, SL (reprint author), US FDA, Off Gener Drugs, Ctr Drug Evaluat & Res, Rockville, MD 20855 USA. EM sau.lee@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 3 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J JI AAPS J. PD MAR PY 2011 VL 13 IS 1 BP 141 EP 141 DI 10.1208/s12248-010-9243-8 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 758YP UT WOS:000290204800015 ER PT J AU Burkhart, K Pitts, M Marchick, J Kashoki, M Szarfman, A AF Burkhart, K. Pitts, M. Marchick, J. Kashoki, M. Szarfman, A. TI The P-glycoprotein Activity of Drugs Highly Associated with Torsade de Pointes SO CLINICAL TOXICOLOGY LA English DT Meeting Abstract C1 [Burkhart, K.; Pitts, M.; Marchick, J.; Kashoki, M.; Szarfman, A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1556-3650 J9 CLIN TOXICOL JI Clin. Toxicol. PD MAR PY 2011 VL 49 IS 3 MA 230 BP 252 EP 252 PG 1 WC Toxicology SC Toxicology GA 751OY UT WOS:000289628600235 ER PT J AU Shaikh, B AF Shaikh, Badar TI Analytical Methods for the Determination of Veterinary Drug Residues in Food Products of Animal Origin SO JOURNAL OF AOAC INTERNATIONAL LA English DT Editorial Material C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. EM badaruddin.shaikh@fda.hhs.gov NR 0 TC 0 Z9 0 U1 1 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 MAR-APR PY 2011 VL 94 IS 2 BP 359 EP 359 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 750KH UT WOS:000289544500001 PM 21563668 ER PT J AU Clark, SB Storey, JM Turnipseed, SB AF Clark, Susan B. Storey, Joseph M. Turnipseed, Sherri B. TI Optimization and Validation of a Multiclass Screening and Confirmation Method for Drug Residues in Milk Using High-Performance Liquid Chromatography/Tandem Mass Spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID VETERINARY DRUGS; ANTIBIOTICS; STRATEGIES; ANIMALS AB The further optimization and validation of a multiresidue veterinary drug screening method for milk is described. The drug residues of regulatory interest in milk include beta-lactams, sulfonamides, tetracyclines, fluoroquinolones, and macrolides. A previously published procedure has been modified to incorporate new compounds and to collect both screening and confirmatory ion transitions in one acquisition method. Milk samples were extracted with an equal volume of acetonitrile. The samples were then subjected to cleanup with a bonded SPE cartridge and a MW cutoff filter. The SPE protocol was modified to effectively recover a metabolite of flunixin. Established tolerance levels are set for most of these drugs in milk; thus, the screening procedure was semi:quantitative, using positive controls for comparison. The positive controls, consisting of extracts from milk fortified with the drugs at their tolerance or safe level, were used to set statistically valid minimum response criteria for unknown samples. This updated method was validated with fortified milk, as well as with milk samples from animals administered veterinary drugs. C1 [Turnipseed, Sherri B.] US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. [Clark, Susan B.; Storey, Joseph M.] US FDA, Denver Sci Branch, Denver, CO 80225 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, POB 25087, Denver, CO 80225 USA. EM sherri.turnipseed@fda.hhs.gov NR 20 TC 11 Z9 11 U1 2 U2 12 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2011 VL 94 IS 2 BP 383 EP 393 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 750KH UT WOS:000289544500004 PM 21563671 ER PT J AU Li, H Kijak, PJ AF Li, Hui Kijak, Philip J. TI Development of a Quantitative Multiclass/Multiresidue Method for 21 Veterinary Drugs in Shrimp SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; ELECTROSPRAY-IONIZATION; FLUORESCENCE DETECTION; RESIDUE CONFIRMATION; SAMPLE PREPARATION; MALACHITE GREEN; PRODUCTS; SUPPRESSION; ENVIRONMENT AB A multiclass/multiresidue method has been developed and validated for the determination of 21 veterinary drug residues in shrimp, including sulfonamides (sulfadiazine, sulfamerazine, sulfamethazine, sulfachloropyridazine, sulfadimethoxine, and sulfaquinoxaline); tetracyclines (oxytetracycline, tetracycline, and chlortetracycline); (fluoro)quinolones (norfloxacin, ciprofloxacin, enrofloxacin, sarafloxacin, difloxacin, flumequine, oxolinic acid, and nalidixic acid); and cationic dyes (malachite green, gentian violet, leucomalachite green, and leucogentian violet), using HPLC/MS/MS. All drugs were quantifiable over a no less than 10-fold range with matrix-matched standards for linear external calibration, except for oxytetracycline, tetracycline, norfloxacin, and ciprofloxacin, for which norfloxacin-d(5) was used as an internal standard. Two grams of preground shrimp sample was extracted twice with extractant at two different pH values. The combined supernatant was further diluted with an aqueous internal standard solution, and 50 mu L extract was injected into the HPLC instrument. An online SPE system was set up for automated sample cleanup. A triple quadrupole mass spectrometer equipped with an electrospray ionization source was operated in the multiple-reaction-monitoring mode to acquire data. The method has been validated at three levels within the designated linear ranges for each drug, with accuracies between 77 and 115%, and most CV values below 15%. C1 [Li, Hui; Kijak, Philip J.] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Li, H (reprint author), US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. EM hui.li@fda.hhs.gov RI 志琴, 江/I-6431-2012 NR 23 TC 9 Z9 9 U1 2 U2 13 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2011 VL 94 IS 2 BP 394 EP 406 PG 13 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 750KH UT WOS:000289544500005 PM 21563672 ER PT J AU Yu, DL Rummel, N Shaikh, B AF Yu, Donglei Rummel, Nathan Shaikh, Badar TI Development of a Method to Determine Albendazole and Its Metabolites in the Muscle Tissue of Yellow Perch Using High-Performance Liquid Chromatography with Fluorescence Detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ATLANTIC SALMON; RAINBOW-TROUT; DEPLETION; TILAPIA; PLASMA AB An HPLC method was developed for the determination of albendazole (ABZ) and its metabolites, a sulfoxide (ABZSO), a sulfone (ABZSO(2)), and albendazole-2-aminosulfone (ABZ-2-NH2SO2), from yellow perch muscle tissue with adhering skin. The muscle tissue samples were made alkaline with potassium carbonate and extracted with ethyl acetate, followed by a series of liquid liquid extraction steps. After solvent evaporation, the residue was reconstituted in the initial mobile phase combination of the gradient. The mobile phase consisted of a buffer, 50 mM ammonium acetate (pH = 4.0) in 10% methanol water, and 100% acetonitrile. The gradient was from 20% acetonitrile to 85% acetonitrile. The analytes were chromatographed on an RP Luna C18(2) column and detected by fluorescence with excitation and emission wavelengths of 290 and 330 nm, respectively. The average recoveries from fortified muscle tissue for ABZ (20-100 ppb), ABZ-SO (20-200 ppb), ABZSO(2) (8-100 ppb), and ABZ-2-NH2SO2 (20-100 ppb) were 85, 95, 101, and 86%, respectively, with corresponding CV values of 9, 3, 6, and 4%, respectively. Their LOQ values were 10, 10, 1, and 10 ppb, respectively. The procedure was applied to determine ABZ and its major metabolites in the incurred muscle tissue of yellow perch obtained after orally dosing the fish with ABZ. C1 [Yu, Donglei; Rummel, Nathan; Shaikh, Badar] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Yu, DL (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM donglei.yu@fda.hhs.gov NR 7 TC 4 Z9 4 U1 1 U2 5 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2011 VL 94 IS 2 BP 446 EP 452 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 750KH UT WOS:000289544500010 PM 21563677 ER PT J AU Liao, BS Sram, J Cain, TT Halcrow, KR AF Liao, Benjamin S. Sram, Jackie Cain, Teresa T. Halcrow, Kenneth R. TI Aqueous Sulfuric Acid as the Mobile Phase in Cation Ion Chromatography for Determination of Histamine, Putrescine, and Cadaverine in Fish Samples SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID AMINES AB Aqueous sulfuric acid can be used as the mobile phase in cation ion chromatography to separate the three biogenic amines, putrescine, cadaverine, and histamine, from fish. Various concentrations of aqueous sulfuric acid were investigated to optimize the separation of these three biogenic amines. Aqueous sulfuric acid (5.0 mM) was found to be optimum for the separation and was used to determine the three biogenic amines in fish. The LOQ, defined as the lowest level of the standard calibration curve, was 0.055 ppm (equivalent to 0.55 mu g/g sample) for putrescine, 0.05 ppm (equivalent to 0.5 mu g/g sample) for cadaverine, and 1.0 ppm (equivalent to 10 mu g/g sample) for histamine. From statistical analysis of the LOQ, the method detection limit was 0.003 ppm for putrescine, 0.009 ppm for cadaverine, and 0.16 ppm for histamine. For sample preparation, the fish was composited, homogenized in methanol water (75 + 25, v/v), incubated for 15 min at 60 degrees C, and centrifuged. The sample solution was micron-filtered before injection. The mobile phase flow rate was 0.8 mL/min under isocratic conditions at room temperature (15-25 degrees C). The three biogenic amines were separated in the order of increasing retention time, i.e., putrescine, cadaverine, and histamine, within 30 min. The chromatograms showed complete peak separation of the three amines regardless of the difference in fish matrixes. C1 [Liao, Benjamin S.; Sram, Jackie; Cain, Teresa T.; Halcrow, Kenneth R.] US FDA, Pacific Reg Lab SW, Irvine, CA 92612 USA. RP Liao, BS (reprint author), US FDA, Pacific Reg Lab SW, Irvine, CA 92612 USA. EM benjamin.liao@fda.hhs.gov NR 18 TC 1 Z9 1 U1 1 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 MAR-APR PY 2011 VL 94 IS 2 BP 565 EP 571 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 750KH UT WOS:000289544500025 PM 21563692 ER PT J AU Vaisocherova, H Taylor, AD Jiang, SY Hegnerova, K Vala, M Homola, J Yakes, BJ Deeds, J DeGrasse, S AF Vaisocherova, Hana Taylor, Allen D. Jiang, Shaoyi Hegnerova, Katerina Vala, Milan Homola, Jiri Yakes, Betsy Jean Deeds, Jonathan DeGrasse, Stacey TI Surface Plasmon Resonance Biosensor for Determination of Tetrodotoxin: Prevalidation Study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MOUSE BIOASSAY; SHELLFISH; TOXINS; ASSAY; ACID; IMMUNOASSAY; ANTIBODY; ANALOGS; FOOD; TTX AB A label-free surface plasmon resonance biosensor method was applied to determine tetrodotoxin (TTX) in pufferfish matrixes using an antibody inhibition assay format. A prevalidation study was conducted to demonstrate the assay performance characteristics, such as selectivity, LOD, LOQ, repeatability, reproducibility, and accuracy. Three participating laboratories reported standard curves in buffer and pufferfish matrix. A set of blind samples with TTX spiked into buffer as well as in 10% pufferfish extract were analyzed. Additionally, three blind naturally contaminated samples were analyzed, and the results were compared to those obtained using a reference method (HPLC/electrospray ionization-selected reaction monitoring-MS). The developed method was demonstrated to be capable of detecting TTX in pufferfish matrix standard samples in a broad concentration range (2-9000 ng/mL) with an LOD of 1.5 ng/mL. Between-laboratory recovery values were in the range of 51-190% with a mean of 107%, and 64-180% with a mean of 103% for TTX-spiked samples in buffer and pufferfish matrix, respectively. Between-laboratory recoveries were in the satisfactory range of 101-119% for naturally contaminated samples. This robust, rapid, and noninvasive method may serve as an attractive alternative to established methods for detection of TTX in pufferfish extracts. C1 [Yakes, Betsy Jean; Deeds, Jonathan; DeGrasse, Stacey] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Vaisocherova, Hana; Taylor, Allen D.; Jiang, Shaoyi] Univ Washington, Dept Chem Engn, Seattle, WA 98195 USA. [Vaisocherova, Hana; Hegnerova, Katerina; Vala, Milan; Homola, Jiri] Acad Sci Czech Republic, Inst Photon & Elect, CR-18251 Prague, Czech Republic. RP DeGrasse, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM stacey.etheridge@fda.hhs.gov RI Yakes, Betsy/K-2646-2012; Vala, Milan/D-4748-2009; Lisalova, Hana/H-4706-2014; Homola, Jiri/F-3683-2014; OI Lisalova, Hana/0000-0002-8755-2398; Homola, Jiri/0000-0001-6258-015X; DeGrasse, Stacey/0000-0001-7808-4193 FU FDA [HHSF223200610012I/0002]; Grant Agency of the Czech Republic [KAN200670701]; U.S. Department of Energy FX We would like to thank Nhu-Chi Thuc Ha (University of Washington, Seattle, WA) for her help with the SPR experiments, and Kevin White (FDA Center for Food Safety and Applied Nutrition) for HPLC/ESI-SRM-MS analysis of TTX. This project was supported by the FDA (Contract HHSF223200610012I/0002) and the Grant Agency of the Czech Republic (Contract KAN200670701).; Betsy Jean Yakes was supported during the initial part of this project by an appointment with the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the FDA. NR 31 TC 6 Z9 7 U1 0 U2 15 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2011 VL 94 IS 2 BP 596 EP 604 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 750KH UT WOS:000289544500028 PM 21563695 ER PT J AU Sutherland, JB Heinze, TM Schnackenberg, LK Freeman, JP Williams, AJ AF Sutherland, John B. Heinze, Thomas M. Schnackenberg, Laura K. Freeman, James P. Williams, Anna J. TI Biotransformation of quinazoline and phthalazine by Aspergillus niger SO JOURNAL OF BIOSCIENCE AND BIOENGINEERING LA English DT Article DE Aspergillus niger; Azaarene; Benzodiazine; Biotransformation; Phthalazine; Quinazoline ID MOLYBDENUM-CONTAINING HYDROXYLASE; CUNNINGHAMELLA-ELEGANS; HETEROCYCLIC-COMPOUNDS; PSEUDOMONAS-PUTIDA; ALDEHYDE OXIDASE; OXIDATION; AZAARENES; ISOQUINOLINE; QUINOXALINE; METABOLISM AB Cultures of Aspergillus niger NRRL-599 in fluid Sabouraud medium were grown with quinazoline and phthalazine for 7 days. Metabolites were purified by high-performance liquid chromatography and identified by mass spectrometry and proton nuclear magnetic resonance spectroscopy. Quinazoline was oxidized to 4-quinazolinone and 2,4-quinazolinedione, and phthalazine was oxidized to 1-phthalazinone. @ 2010, The Society for Biotechnology, Japan. All rights reserved. C1 [Sutherland, John B.; Heinze, Thomas M.; Schnackenberg, Laura K.; Freeman, James P.; Williams, Anna J.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov NR 20 TC 3 Z9 5 U1 1 U2 13 PU SOC BIOSCIENCE BIOENGINEERING JAPAN PI OSAKA PA OSAKA UNIV, FACULTY ENGINEERING, 2-1 YAMADAOKA, SUITA, OSAKA, 565-0871, JAPAN SN 1389-1723 J9 J BIOSCI BIOENG JI J. Biosci. Bioeng. PD MAR PY 2011 VL 111 IS 3 BP 333 EP 335 DI 10.1016/j.jbiosc.2010.11.017 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 747NL UT WOS:000289326600015 PM 21169055 ER PT J AU Sanetti, LMH Gritter, KL Dobey, LM AF Sanetti, Lisa M. Hagermoser Gritter, Katie L. Dobey, Lisa M. TI Treatment Integrity of Interventions With Children in the School Psychology Literature from 1995 to 2008 SO SCHOOL PSYCHOLOGY REVIEW LA English DT Article ID APPLIED-BEHAVIOR-ANALYSIS; IMPLEMENTATION; PREVENTION; PROGRAM; DIMENSIONS; VARIABLES; FIDELITY AB Increased accountability in education has resulted in a focus on implementing interventions with strong empirical support. Both student outcome and treatment integrity data are needed to. draw valid conclusions about intervention effectiveness. Reviews of the literature in other fields (e.g., applied behavior analysis, prevention science) suggest that most researchers fail to report treatment integrity data. The purpose of this study was to review the treatment integrity data reported in all experimental intervention studies published in four school psychology journals between 1995 and 2008. Results indicate that a majority of published studies do not include a definition of the independent variable and half do not include quantitative treatment integrity data. C1 [Sanetti, Lisa M. Hagermoser] Univ Connecticut, Dept Educ Psychol, Neag Sch Educ, Storrs, CT 06269 USA. [Sanetti, Lisa M. Hagermoser] Univ Connecticut, CBER, Storrs, CT 06269 USA. [Gritter, Katie L.; Dobey, Lisa M.] Univ Connecticut, Sch Psychol Program, Storrs, CT 06269 USA. RP Sanetti, LMH (reprint author), Univ Connecticut, Dept Educ Psychol, Neag Sch Educ, U-2064, Storrs, CT 06269 USA. EM isa.sanetti@uconn.edu NR 34 TC 20 Z9 20 U1 3 U2 6 PU NATL ASSOC SCHOOL PSYCHOLOGISTS PI BETHESDA PA 4340 EAST WEST HWY, STE 402, BETHESDA, MD 20814 USA SN 0279-6015 J9 SCHOOL PSYCHOL REV JI Sch. Psychol. Rev. PD MAR PY 2011 VL 40 IS 1 BP 72 EP 84 PG 13 WC Psychology, Educational SC Psychology GA 743IO UT WOS:000289012200005 ER PT J AU Ali, SF Onaivi, E Kim, HC Kuhar, MJ Koob, G AF Ali, Syed F. Onaivi, Emmanuel Kim, Hyoung-Chun Kuhar, Michael J. Koob, George TI New Research Frontiers and Advances in Drug Addiction PREFACE SO CURRENT NEUROPHARMACOLOGY LA English DT Editorial Material C1 [Ali, Syed F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Onaivi, Emmanuel] NIDA, Mol Neurobiol Branch, Baltimore, MD USA. [Onaivi, Emmanuel] William Paterson Univ, Wayne, NJ USA. [Kim, Hyoung-Chun] Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea. [Koob, George] Scripps Res Inst, La Jolla, CA 92037 USA. [Kuhar, Michael J.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. RP Ali, SF (reprint author), US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM syed.ali@fda.hhs.gov; Onaivie@wpunj.edu; kimhc@kangwon.ac.kr; mkuhar@emory.edu; gkoob@scripps.edu RI koob, george/P-8791-2016 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD MAR PY 2011 VL 9 IS 1 BP 1 EP 1 PG 1 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400001 ER PT J AU Ali, SF Onaivi, ES Dodd, PR Cadet, JL Schenk, S Kuhar, MJ Koob, GF AF Ali, S. F. Onaivi, E. S. Dodd, P. R. Cadet, J. L. Schenk, S. Kuhar, M. J. Koob, G. F. TI Understanding the Global Problem of Drug Addiction is a Challenge for IDARS Scientists SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE International Drug Abuse Research Society; IDARS; addiction; alcohol; marijuana; psychostimulants ID D2 RECEPTOR GENE; POSTTRAUMATIC-STRESS-DISORDER; CHRONIC PARANOID PSYCHOSIS; CORTICAL NMDA RECEPTOR; ALCOHOL-DEPENDENCE; HUMAN BRAIN; MOLECULAR-GENETICS; SUBUNIT EXPRESSION; IONOPHORE COMPLEX; CEREBRAL-CORTEX AB IDARS is an acronym for the International Drug Abuse Research Society. Apart from our scientific and educational purposes, we communicate information to the general and scientific community about substance abuse and addiction science and treatment potential. Members of IDARS are research scientists and clinicians from around the world, with scheduled meetings across the globe. IDARS is developing a vibrant and exciting international mechanism not only for scientific interactions in the domain of addiction between countries but also ultimately as a resource for informing public policy across nations. Nonetheless, a lot more research needs to be done to better understand the neurobiological basis of drug addiction - A challenge for IDARS scientists. C1 [Ali, S. F.] US FDA, Neurochem Lab, NCTR, Jefferson, AR 72079 USA. [Onaivi, E. S.] William Paterson Univ, Wayne, NJ USA. [Onaivi, E. S.] NIDA, Mol Neurobiol Branch, NIH, Baltimore, MD USA. [Dodd, P. R.] Univ Queensland, Brisbane, Qld, Australia. [Cadet, J. L.] NIDA, Mol Neuropsychiat Branch, NIH, US Dept HHS, Baltimore, MD USA. [Schenk, S.] Victoria Univ Wellington, Wellington, New Zealand. [Kuhar, M. J.] Emory Univ, Yerkes Natl Primate Res Ctr, Atlanta, GA 30322 USA. [Koob, G. F.] Scripps Res Inst, La Jolla, CA 92037 USA. RP Ali, SF (reprint author), US FDA, Neurochem Lab, NCTR, Jefferson, AR 72079 USA. EM Syed.Ali@fda.hhs.gov RI Dodd, Peter/A-4865-2010; koob, george/P-8791-2016 OI Dodd, Peter/0000-0001-5970-0181; FU William Paterson University center for research; National Health and Medical Research Council (NHMRC) [401551]; University of Sydney; Schizophrenia Research Institute; National Institutes of Alcoholism and Alcohol Abuse USA (NIAAA); NSW Department of Health; NIAAA under NIH [AA12404]; DHHS/NIH/NIDA; Neurological Foundation of New Zealand; Royal Society of New Zealand; Pearson Center for Alcoholism and Addiction Research; National Institutes of Health from the National Institute on Alcohol Abuse and Alcoholism [AA013517, AA006420, DA010072, DA004398, DA023597]; National Institute on Drug Abuse FX Dr. Onaivi acknowledges financial support from William Paterson University center for research, the Dean, Dr. Sandra DeYoung for continued student worker support and the Provost office for release time. Dr. Dodd's group in Australia are grateful to Neuropathologists from the Queensland Brain Bank, SCMB, University of Queensland, and from the NSW Tissue Resource Centre, for providing tissue samples; and to the next of kin, for informed written consent for the studies. The tissue banks are part of Australian Brain Bank Network supported by the National Health and Medical Research Council (NHMRC). The NSW Centre and Australian Brain Donor Program are supported by The University of Sydney, NHMRC, Schizophrenia Research Institute, National Institutes of Alcoholism and Alcohol Abuse USA (NIAAA), and NSW Department of Health. Financial support was provided by the NIAAA under grant NIH AA12404 and the NHMRC under grant #401551. Work in Dr. Cadet's laboratory is supported by the DHHS/NIH/NIDA Intramural Research Program. Dr. Schenk's studies on the behavioral and neurochemical consequences of MDMA self-administration are supported by the Neurological Foundation of New Zealand and the Royal Society of New Zealand Marsden Fund. Dr. Koob was supported by the Pearson Center for Alcoholism and Addiction Research and National Institutes of Health grants AA013517 and AA006420 from the National Institute on Alcohol Abuse and Alcoholism and DA010072, DA004398, and DA023597 from the National Institute on Drug Abuse. NR 96 TC 2 Z9 2 U1 3 U2 4 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD MAR PY 2011 VL 9 IS 1 BP 2 EP 7 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400002 PM 21886551 ER PT J AU Shin, EJ Bach, JH Nguyen, TTL Jung, BD Oh, KW Kim, MJ Jang, CG Ali, SF Ko, SK Yang, CH Kim, HC AF Shin, E. -J. Bach, J. -H. Nguyen, T. -T. L. Jung, B. -D. Oh, K. -W. Kim, M. J. Jang, C. G. Ali, S. F. Ko, S. K. Yang, C. H. Kim, H. -C. TI Gastrodia Elata Bl Attenuates Cocaine-Induced Conditioned Place Preference and Convulsion, but not Behavioral Sensitization in Mice: Importance of GABA(A) Receptors SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Gastrodia elata Bl; cocaine; seizure; conditioned place preference; GABA(A) receptors ID PREFRONTAL CORTEX; INDUCED SEIZURES; MIMETIC DRUGS; RATS; HIPPOCAMPUS; MODULATION AB It has been suggested that GABAergic neurotransmission can modulate cocaine dependence and seizure activity. Since Gastrodia elata Bl (GE), an oriental herb agent, has been shown to enhance GABAergic transmission, we examined whether GE affects cocaine-induced seizures, conditioned place preference (CPP), and behavioral sensitization in mice. Treatment with GE (500 or 1000 mg/kg, p.o.) significantly delayed seizure onset time and significantly shortened seizure duration induced by cocaine (90 mg/kg, i.p.). In addition, cocaine (15 mg/kg, i.p.)-induced CPP was significantly attenuated by GE in a dose-dependent manner. However, GE did not significantly alter behavioral sensitization induced by cocaine (15 mg/kg, i.p.). In order to understand whether GABAergic receptors are implicated in GE-mediated pharmacological action in response to cocaine, GABA(A) receptor antagonist bicuculline and GABA B receptor antagonist SCH 50911 were employed in the present study. GE-mediated attenuations on the cocaine-induced seizures and CPP were significantly reversed by bicuculline (0.25 or 0.5 mg/kg, i.p.), but not by SCH 50911 (1.5 or 3.0 mg/kg, i.p.). Therefore, our results suggest that GE attenuates cocaine-induced seizures and CPP via, at least in part, GABA(A) receptor activation. C1 [Shin, E. -J.; Bach, J. -H.; Nguyen, T. -T. L.; Kim, H. -C.] Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea. [Jung, B. -D.] Kangwon Natl Univ, Sch Vet Med, Chunchon 200701, South Korea. [Oh, K. -W.] Chungbuk Natl Univ, Core Res Inst, Coll Pharm, Cheongju 361763, South Korea. [Kim, M. J.] Kangwon Natl Univ, Div Bioresources Technol, Chunchon 200701, South Korea. [Jang, C. G.] Sungkyunkwan Univ, Coll Pharm, Dept Pharmacol, Suwon 440746, South Korea. [Ali, S. F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ko, S. K.] Semyung Univ, Dept Oriental Med Food & Nutr, Jecheon 390711, South Korea. [Yang, C. H.] Daegu Haany Univ, Coll Oriental Med, Dept Physiol, Taegu 706828, South Korea. RP Kim, HC (reprint author), Kangwon Natl Univ, Coll Pharm, Neuropsychopharmacol & Toxicol Program, Chunchon 200701, South Korea. EM kimhc@kangwon.ac.kr FU Ministry of Science and Technology, Republic of Korea [2010K000812]; BK 21 program FX This study was supported by a grant (#2010K000812) from the Brain Research Center from 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea. Thuy-Ty Lan Nguyen and Jae-Hyung Bach were supported by BK 21 program. Equipment at the Institute of Pharmaceutical Science (Kangwon National University) was used for this study. NR 25 TC 8 Z9 8 U1 1 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD MAR PY 2011 VL 9 IS 1 BP 26 EP 29 PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400007 PM 21886556 ER PT J AU Kanthasamy, K Gordon, R Jin, HJ Anantharam, V Ali, S Kanthasamy, AG Kanthasamy, A AF Kanthasamy, Kavin Gordon, Richard Jin, Huajun Anantharam, Vellareddy Ali, Syed Kanthasamy, Anumantha G. Kanthasamy, Arthi TI Neuroprotective Effect of Resveratrol Against Methamphetamine-Induced Dopaminergic Apoptotic Cell Death in a Cell Culture Model of Neurotoxicity SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Resveratrol; drug abuse; neuroprotection; neurotoxicity; oxidative stress; apoptosis ID OXIDATIVE STRESS; EXTRACELLULAR DOPAMINE; PROTEOLYTIC ACTIVATION; ANTIOXIDANT ENZYMES; PARKINSONS-DISEASE; STRIATAL DOPAMINE; QUINONE FORMATION; ANIMAL-MODELS; PC12 CELLS; PROTECTS AB A growing body of evidence suggests that oxidative stress-mediated cell death signaling mechanisms may exert neurotoxic effects of methamphetamine (MA)-induced dopaminergic neuronal loss. However, the means by which oxidative stress induced by MA causes neurodegeneration remains unclear. In recent years, resveratrol has garnered considerable attention owing to its antioxidant, anti-inflammatory, anti-aging, and neuroprotective properties. In the present study, we sought to investigate the neuroprotective effects of resveratrol against apoptotic cell death in a mesencephalic dopaminergic neuronal cell culture model of MA neurotoxicity. MA treatment in the N27 dopaminergic neuronal cell model produced a time-dependent activation of the apoptotic cascade involving caspase-3 and DNA fragmentation. We found that the caspase-3 activation preceded DNA fragmentation. Notably, treatment with resveratrol almost completely attenuated MA-induced caspase-3 activity, but only partially reduced apoptotic cell death. We conclude that the neuroprotective effect of resveratrol is at least in part mediated by suppression of caspase-3 dependent cell death pathways. Collectively, our results demonstrate that resveratrol can attenuate MA-induced apoptotic cell death and suggest that resveratrol or its analogs may have therapeutic benefits in mitigating MA-induced dopaminergic neurodegeneration. C1 [Kanthasamy, Arthi] Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicol, Parkinsons Disorder Res Lab, Ames, IA 50011 USA. [Ali, Syed] US FDA, Neurochem Lab, Div Neurotox, NCTR, Jefferson, AR USA. RP Kanthasamy, A (reprint author), Iowa State Univ, Dept Biomed Sci, Iowa Ctr Adv Neurotoxicol, Parkinsons Disorder Res Lab, 2062 Vet Med Bldg, Ames, IA 50011 USA. EM arthik@iastate.edu FU National Institute of Health (NIH) [NS38644, ES10586, NS065167] FX This study was supported by National Institute of Health (NIH) grants NS38644, ES10586, and NS065167. The W. Eugene and Linda Lloyd Endowed Chair to AGK is also acknowledged. NR 50 TC 12 Z9 14 U1 1 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD MAR PY 2011 VL 9 IS 1 BP 49 EP 53 PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400012 PM 21886561 ER PT J AU Shin, EJ Bach, JH Nguyen, TTL Nguyen, XKT Jung, BD Oh, KW Kim, MJ Ko, SK Jang, CG Ali, SF Kim, HC AF Shin, E. -J. Bach, J. -H. Nguyen, T. -T. L. Nguyen, X. -K. T. Jung, B. -D. Oh, K. -W. Kim, M. J. Ko, S. K. Jang, C. G. Ali, S. F. Kim, H. -C. TI Gastrodia Elata Bl Attenuates Methamphetamine-Induced Dopaminergic Toxicity Via Inhibiting Oxidative Burdens SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Gastrodia elata Bl; methamphetamine; dopamine; oxidative stress ID RADICAL SCAVENGING ACTIVITIES; BRAIN; SELENIUM; NEUROTOXICITY; ANTIOXIDANT; MODEL AB It has been recognized that Gastrodia elata Bl (GE), an oriental herb medicine, ameliorates various neurological disorders, that GE modulates the monoaminergic and GABAergic systems, and that GE possess antioxidant activities. We examined whether GE affects methamphetamine (MA)-induced striatal dopaminergic toxicity in mice. Treatment with MA (7.5 mg/kg, i.p. x 4) resulted in significant decreases in behavioural activity (as shown by locomotor activity and rota rod performance), dopamine level, tyrosine hydroxylase (TH) activity, and TH protein expression (as evaluated by immunocytochemistry and western blot analysis). In addition, MA treatment showed significant increases in lipid peroxidation [as evaluated by 4-hydroxy-2-nonenal (4-HNE) expression and malondialdehyde formation], protein oxidation (as shown by protein carbonyl expression and its formation), and reactive oxygen species (ROS) formation. Treatment with GE significantly attenuates MA-induced behavioural and dopaminergic impairments, and oxidative stresses in a dose-dependent manner. Our results suggest that GE treatment shows anti-dopaminergic effects in response to MA insult via, at least in part, inhibiting oxidative stresses in the striatum of the mice. C1 [Shin, E. -J.; Bach, J. -H.; Nguyen, T. -T. L.; Nguyen, X. -K. T.; Kim, H. -C.] Kangwon Natl Univ, Neuropsychopharmacol & Toxicol Program, Coll Pharm, Chunchon 200701, South Korea. [Jung, B. -D.] Kangwon Natl Univ, Sch Vet Med, Chunchon 200701, South Korea. [Oh, K. -W.] Chungbuk Natl Univ, Core Res Inst, Coll Pharm, Cheongju 361763, South Korea. [Kim, M. J.] Kangwon Natl Univ, Div Bioresources Technol, Chunchon 200701, South Korea. [Ko, S. K.] Semyung Univ, Dept Oriental Med Food & Nutr, Jecheon 390711, South Korea. [Jang, C. G.] Sungkyunkwan Univ, Dept Pharmacol, Coll Pharm, Suwon 440746, South Korea. [Ali, S. F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kim, HC (reprint author), Kangwon Natl Univ, Neuropsychopharmacol & Toxicol Program, Coll Pharm, Chunchon 200701, South Korea. EM kimhc@kangwon.ac.kr FU Ministry of Science and Technology, Republic of Korea [2010K000812]; BK 21 program FX This study was supported by a grant (#2010K000812) from the Brain Research Center from 21st Century Frontier Research Program funded by the Ministry of Science and Technology, Republic of Korea. Thuy-Ty Lan Nguyen, Xuan-Khanh Thi and Jae-Hyung Bach were supported by BK 21 program. Equipment at the Institute of Pharmaceutical Science (Kangwon National University) was used for this study. NR 20 TC 13 Z9 14 U1 1 U2 6 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD MAR PY 2011 VL 9 IS 1 BP 118 EP 121 PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400026 PM 21886575 ER PT J AU Virmani, A Koverech, A Ali, SF Binienda, ZK AF Virmani, A. Koverech, A. Ali, S. F. Binienda, Z. K. TI Acetyl-L-Carnitine Modulates TP53 and IL10 Gene Expression Induced by 3-NPA Evoked Toxicity in PC12 Cells SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE 3-Nitropropionic acid; Acetyl-L-carnitine; Neuroprotection; Gene expression; TP53; Il10 ID TOXIN 3-NITROPROPIONIC ACID; SUCCINATE-DEHYDROGENASE; INDUCED NEUROTOXICITY; RAT-BRAIN; METHAMPHETAMINE; VULNERABILITY; DYSFUNCTION; PROTECTION; INHIBITORS; DOPAMINE AB The neurotoxicity induced by the mitochondrial inhibitor 3-nitropropionic acid (3-NPA) is associated with a decrease of ATP synthesis and an increase of free radical production which can lead to apoptosis or necrosis. We have used the PC12, neuron-like rat pheochromocytoma cell line, to study further the mechanism of 3-NPA-evoked neurotoxicity and the effects of acetyl-L-carnitine (ALC) which has neuroprotective actions against various types of mitochondrial inhibitors. Cultured PC 12 cells were exposed to a low dose of 3-NPA 50 (microM) in the presence or absence of 5 mM ALC. The dose of 3-NPA was sub toxic and no changes in pro-apoptotic Bax or anti-apoptotic Bcl-2 gene expression were observed. We followed specific genetic markers to look for changes evoked by 3-NPA toxicity and also changes associated with neuroprotection exerted by the ALC treatment, using RT-PCR arrays (delta-delta method). 3-NPA exposure evoked a decrease in expression of the Tp53 gene. This down regulation was prevented by pretreatment of the cells with ALC. The Tp53 gene responds to cellular stresses and the effects seen here are possibly associated with the 3-NPA evoked changes in mitochondrial metabolism. Other genes associated with stress and apoptosis, Parp-1, Bcl-2, and Bax were not affected by 3-NPA or ALC. The decrease of inflammatory response Il-10 gene expression due to 3-NPA was further lowered by presence of ALC. Other inflammation related genes, Il1rn, Nr3c1 and Cxcr4 were not affected. Interestingly, the glutamate transporter slc17a7, carnitine-acylcarnitine translocase Slc25a20 and heat shock proteins genes, Hsp27, Hmox1 (Hsp32, HO1) as well as Hspa 1a (Hsp 70) increased only when both ALC and small dose of 3-NPA were present. The alterations in gene expression detected in this study suggest role of several intracellular pathways in the neurotoxicity of 3-NPA and the neuroprotection against 3-NPA-induced neurotoxicity by ALC. C1 [Virmani, A.; Koverech, A.] Sigma Tau Pharmaceut Co, Sci & Med Affairs, I-00040 Rome, Italy. [Ali, S. F.] US FDA, Neurochem Lab, Div Neurotoxicol, NCTR, Jefferson, AR USA. [Binienda, Z. K.] US FDA, Neurophysiol Lab, Div Neurotoxicol, NCTR, Jefferson, AR USA. RP Virmani, A (reprint author), Innovat & Dev Dept, Via Pontina,Km 30-400, I-00040 Rome, Italy. EM ashraf.virmani@sigma-tau.it NR 17 TC 3 Z9 3 U1 0 U2 1 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD MAR PY 2011 VL 9 IS 1 BP 195 EP 199 PG 5 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400040 PM 21886589 ER PT J AU Onaivi, ES Benno, R Halpern, T Mehanovic, M Schanz, N Sanders, C Yan, X Ishiguro, H Liu, QR Berzal, AL Viveros, MP Ali, SF AF Onaivi, E. S. Benno, R. Halpern, T. Mehanovic, M. Schanz, N. Sanders, C. Yan, X. Ishiguro, H. Liu, Q-R Berzal, A. L. Viveros, M. P. Ali, S. F. TI Consequences of Cannabinoid and Monoaminergic System Disruption in a Mouse Model of Autism Spectrum Disorders SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Cannabinoid; Monoamines; Delta(9)-THC; Psychostimulants; MPTP; Behavior; Autism; BTBR T plus tf/J mice ID METHYLATION; BEHAVIOR; GENES AB Autism spectrum disorders (ASDs) are heterogenous neurodevelopmental disorders characterized by impairment in social, communication skills and stereotype behaviors. While autism may be uniquely human, there are behavioral characteristics in ASDs that can be mimicked using animal models. We used the BTBR T+tf/J mice that have been shown to exhibit autism-like behavioral phenotypes to 1). Evaluate cannabinoid-induced behavioral changes using forced swim test (FST) and spontaneous wheel running (SWR) activity and 2). Determine the behavioral and neurochemical changes after the administration of MDMA (20 mg/kg), methamphetamine (10 mg/kg) or MPTP (20 mg/kg). We found that the BTBR mice exhibited an enhanced basal spontaneous locomotor behavior in the SWR test and a reduced depressogenic profile. These responses appeared to be enhanced by the prototypic cannabinoid, Delta(9)-THC. MDMA and MPTP at the doses used did not modify SWR behavior in the BTBR mice whereas MPTP reduced SWR activity in the control CB57BL/6J mice. In the hippocampus, striatum and frontal cortex, the levels of DA and 5-HT and their metabolites were differentially altered in the BTBR and C57BL/6J mice. Our data provides a basis for further studies in evaluating the role of the cannabinoid and monoaminergic systems in the etiology of ASDs. C1 [Onaivi, E. S.] William Paterson Univ, Dept Biol, Wayne, NJ 07470 USA. [Onaivi, E. S.; Ishiguro, H.] Natl Inst Drug Abuse, Mol Neurobiol Branch, NIH, Baltimore, MD USA. [Ishiguro, H.] Ikeda Hosp, Happoukai Med Corp, Ryugasaki, Japan. [Liu, Q-R] Natl Inst Drug Abuse, Behav Neurobiol Branch, NIH, Baltimore, MD USA. [Berzal, A. L.; Viveros, M. P.] Univ Complutense, Dept Fisiol Fisiol Anim 2, Fac Biol, E-28040 Madrid, Spain. [Ali, S. F.] US FDA, Neurochem Lab, NCTR, Jefferson, AR USA. RP Onaivi, ES (reprint author), William Paterson Univ, Dept Biol, Wayne, NJ 07470 USA. EM Onaivie@wpunj.edu RI Liu, Qing-Rong/A-3059-2012; Viveros, Maria-Paz/S-6855-2016 OI Liu, Qing-Rong/0000-0001-8477-6452; FU William Paterson University center; NIDA-NIH; Red de Trastornos adictivos [RD06/0001/1013]; GRUPOS UCM-BSCH [951579]; Plan Nacional sobre Drogas; Ministerio de Sanidad y Politica Social [PR10/09-16583] FX ESO acknowledges financial support from William Paterson University center for research, the Dean, Dr. Sandra DeYoung for continued student worker support and the Provost office for release time. ESO acknowledges Guest Scientist support at NIDA-NIH. QRL is supported by NIDA-NIH. ALB and MPV acknowledges support from Red de Trastornos adictivos RD06/0001/1013; GRUPOS UCM-BSCH: 951579; Plan Nacional sobre Drogas, Ministerio de Sanidad y Politica Social 2010-2012. Ref.: PR10/09-16583 NR 17 TC 10 Z9 10 U1 0 U2 5 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD MAR PY 2011 VL 9 IS 1 BP 209 EP 214 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400043 PM 21886592 ER PT J AU Sharma, HS Ali, SF Patnaik, R Zimmermann-Meinzingen, S Sharma, A Muresanu, DF AF Sharma, Hari S. Ali, Syed F. Patnaik, Ranjana Zimmermann-Meinzingen, Sibilla Sharma, Aruna Muresanu, Dafin F. TI Cerebrolysin Attenuates Heat Shock Protein (HSP 72 KD) Expression in the Rat Spinal Cord Following Morphine Dependence and Withdrawal: Possible New Therapy for Pain Management SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Morphine; heat shock proteins (HSP 72 kD); morphine tolerance; withdrawal symptoms; stress reaction; cerebrolysin; growth factors; pain perception; analgesia ID BLOOD-BRAIN-BARRIER; VENTRAL TEGMENTAL AREA; ACUTE METHAMPHETAMINE INTOXICATION; ANTIOXIDANT COMPOUND H-290/51; NORMOTENSIVE YOUNG-RATS; WHOLE-BODY HYPERTHERMIA; CENTRAL-NERVOUS-SYSTEM; UP-REGULATION; CONSTITUTIVE ISOFORM; NEUROTROPHIC FACTORS AB The possibility that pain perception and processing in the CNS results in cellular stress and may influence heat shock protein (HSP) expression was examined in a rat model of morphine dependence and withdrawal. Since activation of pain pathways result in exhaustion of growth factors, we examined the influence of cerebrolysin, a mixture of potent growth factors (BDNF, GDNF, NGF, CNTF etc,) on morphine induced HSP expression. Rats were administered morphine (10 mg/kg, s.c. /day) for 12 days and the spontaneous withdrawal symptoms were developed by cessation of the drug administration on day 13(th) that were prominent on day 14(th) and continued up to day 15(th) (24 to 72 h periods). In a separate group of rats, cerebrolysin was infused intravenously (5 ml/kg) once daily from day one until day 15(th). In these animals, morphine dependence and withdrawal along with HSP immunoreactivity was examined using standard protocol. In untreated group mild HSP immunoreaction was observed during morphine tolerance, whereas massive upregulation of HSP was seen in CNS during withdrawal phase that correlated well with the withdrawal symptoms and neuronal damage. Pretreatment with cerebrolysin did not affect morphine tolerance but reduced the HSP expression during this phase. Furthermore, cerebrolysin reduced the withdrawal symptoms on day 14(th) to 15(th). Taken together these observations suggest that cellular stress plays an important role in morphine induced pain pathology and exogenous supplement of growth factors, i.e. cerebrolysin attenuates HSP expression in the CNS and induce neuroprotection. This indicates a new therapeutic role of cerebrolysin in the pathophysiology of drugs of abuse, not reported earlier. C1 [Sharma, Hari S.; Sharma, Aruna] Uppsala Univ, Lab Cerebrovasc Res, Dept Surg Sci Anesthesiol & Intens Care Med, Univ Hosp, SE-75185 Uppsala, Sweden. [Ali, Syed F.] US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Patnaik, Ranjana] Banaras Hindu Univ, Inst Technol, Dept Biomat, Sch Biomed Engn, Varanasi 221005, Uttar Pradesh, India. [Zimmermann-Meinzingen, Sibilla] Ever NeuroPharma, Unterach, Austria. [Muresanu, Dafin F.] Univ Med & Pharm, Dept Neurol, Cluj Napoca, Romania. RP Sharma, HS (reprint author), Frodingsgatan 12 28, SE-75421 Uppsala, Sweden. EM Sharma@surgsci.uu.se RI Muresanu, Dafin Fior/C-4092-2011; Sharma, Aruna/D-4430-2011; Sharma, Hari/G-4508-2016; OI Patnaik, Ranjana/0000-0002-8131-177X FU Swedish Medical Research Council [2710]; Goran Gustafsson Foundation, Stockholm, Sweden; Alexander von Humboldt Foundation, Bonn, Germany; University Grants Commission, New Delhi, India; Indian Council of Medical Research, New Delhi, India; US FDA, Jefferson, AR, USA; Society for Study on Neuroprotection and Neuroplasticity (SSNN), Romania; Ever NeuroPharma, Unterach, Austria; Acure Pharma, Uppsala, Sweden; AstraZeneca Molndal. Sweden FX This research is partially supported by Grants from Swedish Medical Research Council (no 2710, HSS), Goran Gustafsson Foundation, Stockholm, Sweden; Alexander von Humboldt Foundation, Bonn, Germany; The University Grants Commission, New Delhi, India; Indian Council of Medical Research, New Delhi, India; US FDA, Jefferson, AR, USA; and Society for Study on Neuroprotection and Neuroplasticity (SSNN), Romania; Ever NeuroPharma, Unterach, Austria; Acure Pharma, Uppsala, Sweden; AstraZeneca Molndal. Sweden. Technical assistance of Karstin Flink, Kerstin Rystedt, Ingmarie Olsson, Mari-Anne Carlsson, Uppsala, Sweden; Franziska Drum, Berlin, Germany; Shiv Mandir Singh, Aftab Ahmed, Varanasi, India; Bonnie Robinson, Becky Divine, US FDA, Jefferson, USA are highly appreciated. NR 65 TC 12 Z9 12 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD MAR PY 2011 VL 9 IS 1 BP 223 EP 235 PG 13 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400046 PM 21886595 ER PT J AU Binienda, ZK Beaudoin, MA Thorn, BT Ali, SF AF Binienda, Z. K. Beaudoin, M. A. Thorn, B. T. Ali, S. F. TI Analysis of Electrical Brain Waves in Neurotoxicology: Gamma-Hydroxybutyrate SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE Domoic acid; ibogaine; cocaine; gamma hydroxybutyrate; cerebral cortex; electrocorticogram; power spectra ID RAT; ACID; EEG; RECEPTOR; SLEEP; GABA AB Advances in computer technology have allowed quantification of the electroencephalogram (EEG) and expansion of quantitative EEG (qEEG) analysis in neurophysiology, as well as clinical neurology, with great success. Among the variety of techniques in this field, frequency (spectral) analysis using Fast Fourier Transforms (FFT) provides a sensitive tool for time-course studies of different compounds acting on particular neurotransmitter systems. Studies presented here include Electrocorticogram (ECoG) analysis following exposure to a glutamic acid analogue-domoic acid (DOM), psychoactive indole alkaloid-ibogaine, as well as cocaine and gamma-hydroxybutyrate (GHB). The ECoG was recorded in conscious rats via a tether and swivel system. The EEG signal frequency analysis revealed an association between slow-wave EEG activity delta and theta and the type of behavioral seizures following DOM administration. Analyses of power spectra obtained in rats exposed to cocaine alone or after pretreatment with ibogaine indicated the contribution of the serotonergic system in ibogaine mediated response to cocaine (increased power in alpha 1 band). Ibogaine also lowered the threshold for cocaine-induced electrographic seizures (increased power in the low-frequency bands, delta and theta). Daily intraperitoneal administration of cocaine for two weeks was associated with a reduction in slow-wave ECoG activity 24 hrs following the last injection when compared with controls. Similar decreased cortical activity in low-frequency bands observed in chronic cocaine users has been associated with reduced metabolic activity in the frontal cortex. The FFT analyses of power spectra relative to baseline indicated a significant energy increase over all except beta 2 frequency bands following exposure to 400 and 800 mg/kg GHB. The EEG alterations detected in rats following exposure to GHB resemble absence seizures observed in human petit mal epilepsy. Spectral analysis of the EEG signals combined with behavioral observations may prove to be a useful approach in studying chronic exposure to drugs of abuse and treatment of drug dependence. C1 [Binienda, Z. K.] US FDA, Neurophysiol Lab, Div Neurotoxicol, NCTR, Jefferson, AR 72079 USA. [Beaudoin, M. A.] US FDA, Z Tech Co, NCTR, Jefferson, AR 72079 USA. [Thorn, B. T.] US FDA, Div Personalized Nutr & Med, NCTR, Jefferson, AR 72079 USA. RP Binienda, ZK (reprint author), US FDA, Neurophysiol Lab, Div Neurotoxicol, NCTR, HFT-132, Jefferson, AR 72079 USA. EM zbigniew.binienda@fda.hhs.gov NR 21 TC 1 Z9 2 U1 1 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD MAR PY 2011 VL 9 IS 1 BP 236 EP 239 PG 4 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400047 PM 21886596 ER PT J AU Liu, F Paule, MG Ali, S Wang, C AF Liu, Fang Paule, Merle G. Ali, Syed Wang, Cheng TI Ketamine-Induced Neurotoxicity and Changes in Gene Expression in the Developing Rat Brain SO CURRENT NEUROPHARMACOLOGY LA English DT Article DE N-methyl-D-aspartate (NMDA) receptor; ketamine; apoptosis; in situ hybridization; microarray analysis ID D-ASPARTATE RECEPTORS; INDUCED APOPTOSIS; NMDA RECEPTORS; NEURONS; BLOCKADE; GLUTAMATE; NECROSIS; CULTURE; MONKEY; DEATH AB Ketamine, an N-methyl-D-aspartate (NMDA) receptor antagonist, is widely used for analgesia and anesthesia in obstetric and pediatric practice. Recent reports indicate that ketamine causes neuronal cell death in developing rodents and nonhuman primates. The present study assessed the potential dose-and time-dependent neurotoxic effects and associated changes in gene expression after ketamine administration to postnatal day 7 (PND-7) rat pups. Pups were exposed to ketamine subcutaneously at doses of 5, 10, or 20 mg/kg, in one, three or six injections respectively. Control animals received the same volume of saline at the same time points. The animals were sacrificed 6 h after the last ketamine or saline administration and brain tissues were collected for RNA isolation and histochemical examination. Six injections of 20 mg/kg ketamine significantly increased neuronal cell death in frontal cortex, while lower doses and fewer injections did not show significant effects. The ketamine induced cell death seemed to be apoptotic in nature. In situ hybridization demonstrated that NMDA receptor NR1 subunit expression was dramatically increased in the frontal cortex of ketamine treated rats. Microarray analysis revealed altered expression of apoptotic relevant genes and increased NMDA receptor gene expression in brains from ketamine treated animals. Quantitative RT-PCR confirmed the microarray results. These data suggest that repeated exposures to high doses of ketamine can cause compensatory up-regulation of NMDA receptors and subsequently trigger apoptosis in developing neurons. C1 [Liu, Fang; Paule, Merle G.; Ali, Syed; Wang, Cheng] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 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 NCTR/FDA [IAG 224-07-007]; National Institute for Environmental Health Sciences (NIEHS)/National Toxicology Program (NTP); Center for Drug Evaluation and Research (CDER)/FDA; National Institute of Child Health and Human Development (NICHD) FX This work was supported in part by an Interagency Agreement (IAG 224-07-007) between NCTR/FDA and the National Institute for Environmental Health Sciences (NIEHS)/National Toxicology Program (NTP), the Center for Drug Evaluation and Research (CDER)/FDA, and the National Institute of Child Health and Human Development (NICHD). NR 21 TC 6 Z9 6 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1570-159X J9 CURR NEUROPHARMACOL JI Curr. Neuropharmacol. PD MAR PY 2011 VL 9 IS 1 BP 260 EP 265 PG 6 WC Neurosciences; Pharmacology & Pharmacy SC Neurosciences & Neurology; Pharmacology & Pharmacy GA 743DB UT WOS:000288996400053 ER PT J AU DiCarlo, AL Maher, C Hick, JL Hanfling, D Dainiak, N Chao, N Bader, JL Coleman, CN Weinstock, DM AF DiCarlo, Andrea L. Maher, Carmen Hick, John L. Hanfling, Dan Dainiak, Nicholas Chao, Nelson Bader, Judith L. Coleman, C. Norman Weinstock, David M. TI Radiation Injury After a Nuclear Detonation: Medical Consequences and the Need for Scarce Resources Allocation SO DISASTER MEDICINE AND PUBLIC HEALTH PREPAREDNESS LA English DT Review DE nuclear detonation; radiation injury; acute radiation syndrome ID COLONY-STIMULATING FACTOR; BONE-MARROW TRANSPLANTATION; WHOLE-BODY IRRADIATION; IONIZING-RADIATION; RHESUS-MONKEYS; SUPPORTIVE CARE; GAMMA-RADIATION; X-IRRADIATION; G-CSF; EXPOSURE AB A 10- kiloton (kT) nuclear detonation within a US city could expose hundreds of thousands of people to radiation. The Scarce Resources for a Nuclear Detonation Project was undertaken to guide community planning and response in the aftermath of a nuclear detonation, when demand will greatly exceed available resources. This article reviews the pertinent literature on radiation injuries from human exposures and animal models to provide a foundation for the triage and management approaches outlined in this special issue. Whole-body doses >2 Gy can produce clinically significant acute radiation syndrome (ARS), which classically involves the hematologic, gastrointestinal, cutaneous, and cardiovascular/central nervous systems. The severity and presentation of ARS are affected by several factors, including radiation dose and dose rate, interindividual variability in radiation response, type of radiation (eg, gamma alone, gamma plus neutrons), partial-body shielding, and possibly age, sex, and certain preexisting medical conditions. The combination of radiation with trauma, burns, or both (ie, combined injury) confers a worse prognosis than the same dose of radiation alone. Supportive care measures, including fluid support, antibiotics, and possibly myeloid cytokines (eg, granulocyte colony-stimulating factor), can improve the prognosis for some irradiated casualties. Finally, expert guidance and surge capacity for casualties with ARS are available from the Radiation Emergency Medical Management Web site and the Radiation Injury Treatment Network. (Disaster Med Public Health Preparedness. 2011;5:S32-S44) C1 [DiCarlo, Andrea L.] NIAID, Radiat Nucl Countermeasures Program, NIH, Bethesda, MD 20892 USA. [Maher, Carmen] US FDA, Off Counterterrorism & Emerging Threats, Rockville, MD 20857 USA. [Hick, John L.] Univ Minnesota, Hennepin Cty Med Ctr, Minneapolis, MN 55455 USA. [Hanfling, Dan] George Washington Univ, Dept Emergency Med, Washington, DC 20052 USA. [Dainiak, Nicholas] Yale Univ, Sch Med, Bridgeport Hosp, New Haven, CT 06520 USA. [Chao, Nelson] Duke Univ, Bone Marrow & Stem Cell Transplant Program, Durham, NC 27706 USA. [Bader, Judith L.; Coleman, C. Norman] US Dept HHS, Off Assistant Secretary Preparedness & Response, Washington, DC USA. [Weinstock, David M.] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. RP Weinstock, DM (reprint author), Harvard Univ, Sch Med, Dana Farber Canc Inst, 45 Brookline Ave,D510B, Boston, MA 02115 USA. EM DavidM_Weinstock@dfci.harvard.edu FU Genzyme; Novartis FX Dr Weinstock is a paid consultant by Genzyme and Novartis. NR 90 TC 68 Z9 69 U1 1 U2 21 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60654-0946 USA SN 1935-7893 J9 DISASTER MED PUBLIC JI Dis. Med. Public Health Prep. PD MAR PY 2011 VL 5 SU 1 BP S32 EP S44 PG 13 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 739VM UT WOS:000288748000005 PM 21402810 ER PT J AU Ali, MM Dwyer, DS Rizzo, JA AF Ali, Mir M. Dwyer, Debra S. Rizzo, John A. TI The Social Contagion Effect of Suicidal Behavior in Adolescents: Does it Really Exist? SO JOURNAL OF MENTAL HEALTH POLICY AND ECONOMICS LA English DT Article ID RISK BEHAVIOR; NETWORK; EXPOSURE; SMOKING; FRIENDS; HEALTH AB Background: Suicide is the third leading cause of death among adolescents and a non-trivial percentage of adolescents report knowing someone who has attempted suicide. In light of this, a growing body of literature has explored whether suicidal behavior in one person may be imitated by others in their social networks. Aim: We seek to determine the extent to which suicidal behavior in individuals is influenced by suicidal behaviors of their peer and family members. Methodology: Using a nationally-representative sample of adolescents, we employ multivariate regression analysis with controls for known factors associated with suicidal behaviors to help isolate the effects of peer and family members on suicidal behaviors. Our methodology allows us to account for environmental confounders, simultaneity and to a limited extent, non-random peer selection. Our peer measures are drawn from the nomination of close friends by the individuals and suicidal behaviors among the peer group were constructed using the peers' own responses. Results and Discussion: We find that a 10% increase in suicide attempts by family members were associated with a 2.13% and 1.23% increase in adolescent suicidal ideation and attempts, respectively. Our results also show that a 10% increase in peer suicidal ideation and attempts lead to a 0.7% and 0.3% increase in such behavior by the individuals. However, these positive associations between peer and individual suicide behavior become smaller and insignificant after adjustments were made for environmental confounders and peer selection. Limitations: Although we are able to establish the overall importance of environmental confounding factors, we are unable to identify the specific components or characteristics of the surroundings that can explain suicidality. The complex relationships between peer selection and suicidality also limit the determination of causality. Conclusions and Implications: An increase in suicidal behavior by family members is positively associated with suicidal behavior among adolescents and effective policies aimed at reducing suicidal rates should consider these impacts. However, attributing correlations in suicidal behaviors among peers to social network effects should be undertaken with caution, especially when environmental confounders are not adequately controlled for in the analysis. Future Research: Recent studies have found evidence that family connectedness and parent-child relationships have a significant impact in deterring risky behaviors among adolescents. This motivates future work aimed at designing policies that would utilize these findings in order to effectively reduce suicidal behavior among adolescents. C1 [Dwyer, Debra S.; Rizzo, John A.] SUNY Stony Brook, Dept Econ, Stony Brook, NY 11794 USA. [Rizzo, John A.] SUNY Stony Brook, Dept Prevent Med, Stony Brook, NY 11794 USA. [Dwyer, Debra S.] SUNY Stony Brook, Sch Hlth Technol & Management, Stony Brook, NY 11794 USA. [Ali, Mir M.] US FDA, Off Regulat Policy & Social Sci, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Ali, Mir M.] Univ Toledo, Dept Econ, Toledo, OH 43606 USA. RP Rizzo, JA (reprint author), SUNY Stony Brook, Dept Econ, Stony Brook, NY 11794 USA. EM john.rizzo@stonybrook.edu FU NICHD NIH HHS [P01-HD31921] NR 27 TC 12 Z9 12 U1 2 U2 4 PU INT CTR MENTAL HEALTH POLICY & ECONOMICS-ICMPE PI MILANO PA VIA DANIELE CRESPI 7, MILANO, 20123, ITALY SN 1091-4358 J9 J MENT HEALTH POLICY JI J. Ment. Health Policy Econ. PD MAR PY 2011 VL 14 IS 1 BP 3 EP 12 PG 10 WC Health Policy & Services; Psychiatry SC Health Care Sciences & Services; Psychiatry GA 740ZB UT WOS:000288831800002 PM 21642746 ER PT J AU Riley, BS Li, XH AF Riley, Bryan S. Li, Xuhong TI Quality by Design and Process Analytical Technology for Sterile Products-Where Are We Now? SO AAPS PHARMSCITECH LA English DT Review DE process analytical technology (PAT); quality by design (QbD); sterile product AB Quality by design (QbD) and process analytical technology (PAT) have become priorities for the Center for Drug Evaluation and Research (CDER) at the Food and Drug Administration (FDA). Numerous recent initiatives within CDER and FDA have had the objective of encouraging the pharmaceutical industry to utilize QbD and PAT in their product development and manufacturing processes. Although sterile products may be a minority compared to non-sterile dosage forms (e.g., solid orals), their absolute requirement for sterility make design and control of the manufacturing processes extremely critical. This emphasis on the manufacturing process makes the sterile drug product an obvious target for QbD and PAT. Although the FDA encourages QbD submissions, the utilization of QbD and PAT for sterile products so far is still limited. This paper will examine the present state of QbD and PAT for sterile products and review some examples currently in use. Additional potential applications of QbD and PAT for sterile product development and manufacturing will also be discussed. C1 [Riley, Bryan S.; Li, Xuhong] FDA, CDER, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. RP Riley, BS (reprint author), FDA, CDER, Off Pharmaceut Sci, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM xuhong.li@fda.hhs.gov NR 25 TC 11 Z9 12 U1 4 U2 16 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD MAR PY 2011 VL 12 IS 1 BP 114 EP 118 DI 10.1208/s12249-010-9566-x PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742ON UT WOS:000288954100013 PM 21181513 ER PT J AU Cantor, SL Hoag, SW Ellison, CD Khan, MA Lyon, RC AF Cantor, Stuart L. Hoag, Stephen W. Ellison, Christopher D. Khan, Mansoor A. Lyon, Robbe C. TI NIR Spectroscopy Applications in the Development of a Compacted Multiparticulate System for Modified Release SO AAPS PHARMSCITECH LA English DT Article DE chemical imaging; controlled release beads; partial least squares (PLS); principal component analysis (PCA); segregation ID NEAR-INFRARED SPECTROSCOPY; TABLET HARDNESS; CONTENT UNIFORMITY; INTACT TABLETS; REFLECTANCE SPECTROSCOPY; PARTICLE-SIZE; MOISTURE-CONTENT; BED GRANULATION; DRUG CONTENT; PREDICTION AB The purpose of this study was to utilize near-infrared spectroscopy and chemical imaging to characterize extrusion-spheronized drug beads, lipid-based placebo beads, and modified release tablets prepared from blends of these beads. The tablet drug load (10.5-19.5 mg) of theophylline (2.25 mg increments) and cimetidine (3 mg increments) could easily be differentiated using univariate analyses. To evaluate other tablet attributes (i.e., compression force, crushing force, content uniformity), multivariate analyses were used. Partial least squares (PLS) models were used for prediction and principal component analysis (PCA) was used for classification. The PLS prediction models (R (2) > 0.98) for content uniformity of uncoated compacted theophylline and cimetidine beads produced the most robust models. Content uniformity data for tablets with drug content ranging between 10.5 and 19.5 mg showed standard error of calibration (SEC), standard error of cross-validation, and standard error of prediction (SEP) values as 0.31, 0.43, and 0.37 mg, and 0.47, 0.59, and 0.49 mg, for theophylline and cimetidine, respectively, with SEP/SEC ratios less than 1.3. PCA could detect blend segregation during tableting for preparations using different ratios of uncoated cimetidine beads to placebo beads (20:80, 50:50, and 80:20). Using NIR chemical imaging, the 80:20 formulations showed the most pronounced blend segregation during the tableting process. Furthermore, imaging was capable of quantitating the cimetidine bead content among the different blend ratios. Segregation testing (ASTM D6940-04 method) indicated that blends of coated cimetidine beads and placebo beads (50:50 ratio) also tended to segregate. C1 [Cantor, Stuart L.; Hoag, Stephen W.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Ellison, Christopher D.; Khan, Mansoor A.; Lyon, Robbe C.] US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Hoag, SW (reprint author), Univ Maryland, Sch Pharm, 20 N Pine St, Baltimore, MD 21201 USA. EM shoag@rx.umaryland.edu OI cantor, stuart/0000-0001-6506-1419 FU Parenteral Drug Association (PDA); Maryland Consortium for Industrial Pharmaceutics and Training (CIPET) FX The opinions expressed in this article are those of the authors and do not necessarily reflect the views and policies of the US Food and Drug Administration. The authors gratefully acknowledge research funding from the Parenteral Drug Association (PDA) Fellowship and the Maryland Consortium for Industrial Pharmaceutics and Training (CIPET) as well as the generous donation of ethylcellulose from Dow Chemical Co. and Eudragit (R) samples from Evonik Rohm Degussa GmbH. NR 54 TC 9 Z9 9 U1 1 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD MAR PY 2011 VL 12 IS 1 BP 262 EP 278 DI 10.1208/s12249-010-9580-z PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742ON UT WOS:000288954100029 PM 21240575 ER PT J AU Mockus, L LeBlond, D Basu, PK Shah, RB Khan, MA AF Mockus, Linas LeBlond, David Basu, Prabir K. Shah, Rakhi B. Khan, Mansoor A. TI A QbD Case Study: Bayesian Prediction of Lyophilization Cycle Parameters SO AAPS PHARMSCITECH LA English DT Article DE Bayesian; lyophilization; quality by design ID FROZEN AB As stipulated by ICH Q8 R2 (1), prediction of critical process parameters based on process modeling is a part of enhanced, quality by design approach to product development. In this work, we discuss a Bayesian model for the prediction of primary drying phase duration. The model is based on the premise that resistance to dry layer mass transfer is product specific, and is a function of nucleation temperature. The predicted duration of primary drying was experimentally verified on the lab scale lyophilizer. It is suggested that the model be used during scale-up activities in order to minimize trial and error and reduce costs associated with expensive large scale experiments. The proposed approach extends the work of Searles et al. (2) by adding a Bayesian treatment to primary drying modeling. C1 [Mockus, Linas] Purdue Univ, W Lafayette, IN 47907 USA. [LeBlond, David] Abbott Labs, Abbott Pk, IL 60064 USA. [Basu, Prabir K.] NIPTE Inc, Rosemont, IL 60018 USA. [Shah, Rakhi B.; Khan, Mansoor A.] FDA CDER OPS OTR, Silver Spring, MD USA. RP Mockus, L (reprint author), Purdue Univ, Discovery Pk, W Lafayette, IN 47907 USA. EM lmockus@purdue.edu FU FDA [HHSF223200811270P] FX The project was partially supported by FDA grant #HHSF223200811270P, "Study on the development of Quality by Design (QbD) and how this can be applied to the most common parenteral process". NR 12 TC 4 Z9 4 U1 0 U2 6 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PD MAR PY 2011 VL 12 IS 1 BP 442 EP 448 DI 10.1208/s12249-011-9598-x PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 742ON UT WOS:000288954100048 PM 21373766 ER PT J AU Swann, PG Shapiro, MA AF Swann, Patrick G. Shapiro, Marjorie A. TI Regulatory considerations for development of bioanalytical assays for biotechnology products SO BIOANALYSIS LA English DT Article ID LIGAND-BINDING ASSAYS; THERAPEUTIC MONOCLONAL-ANTIBODIES; HUMAN SERUM; IMMUNO-PCR; RECOMMENDATIONS; IMMUNOGENICITY; QUANTIFICATION; VALIDATION; PHARMACOKINETICS; TRASTUZUMAB AB Ligand-binding assays are the predominant method used for determination of concentrations of biotechnology products in serum or other matrices, as well as for the determination of antidrug antibodies in nonclinical and clinical studies. The challenges regarding the design and validation of these assays are well understood. The US FDA published a Guidance for Industry on Bioanalytical Method Validation and a Draft Guidance for Industry on Assay Development for Immunogenicity Testing of Therapeutic Proteins. The purpose of this article is to highlight specific elements in these guidance documents that should also apply to new methods, discuss the application of new generation ligand-binding methods and LC-MS for these purposes and provide a scientific and regulatory perspective on the specific challenges assessing the pharmacokinetics and immunogenicity of monoclonal antibodies. C1 [Swann, Patrick G.; Shapiro, Marjorie A.] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Ctr Drugs Evaluat & Res, Rockville, MD 20857 USA. RP Shapiro, MA (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Ctr Drugs Evaluat & Res, Rockville, MD 20857 USA. EM marjorie.shapiro@fda.hhs.gov NR 43 TC 12 Z9 12 U1 0 U2 4 PU FUTURE SCI LTD PI LONDON PA UNITED HOUSE, 2 ALBERT PL, LONDON, N3 1QB, ENGLAND SN 1757-6180 J9 BIOANALYSIS JI Bioanalysis PD MAR PY 2011 VL 3 IS 6 SI SI BP 597 EP 603 DI 10.4155/BIO.11.27 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 743LW UT WOS:000289020800011 PM 21417729 ER PT J AU Copeland, V Yu, M Fadiran, E Parekh, A AF Copeland, Vanessa Yu, Monica Fadiran, Emmanuel Parekh, Ameeta TI Review of HIV Funded Studies by the FDA Office of Women's Health (OWH) SO JOURNAL OF WOMENS HEALTH LA English DT Meeting Abstract C1 [Copeland, Vanessa] FDA OC, Mexico City, DF, Mexico. [Yu, Monica; Fadiran, Emmanuel; Parekh, Ameeta] FDA OWH, Salt Lake City, UT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAR PY 2011 VL 20 IS 3 MA P84 BP 485 EP 485 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 735RS UT WOS:000288435400104 ER PT J AU Chattopadhyay, R Majam, VF Kumar, S AF Chattopadhyay, Rana Majam, Victoria F. Kumar, Sanjai TI Survival of Plasmodium falciparum in human blood during refrigeration SO TRANSFUSION LA English DT Article ID UNITED-STATES; MALARIA; TRANSFUSION AB BACKGROUND: Transfusion-transmitted malaria remains a serious concern for blood safety. Viable Plasmodium parasites must be present in human blood to transmit malaria, but their survival in blood over time stored under refrigeration has never been carefully investigated. STUDY DESIGN AND METHODS: We spiked leukoreduced normal human blood with Plasmodium falciparum (3D7 strain) asexual ring-stage parasites and stored it at 4 degrees C for 28 days, taking samples at different days intervals. We evaluated the samples for parasitemia by blood film microscopy and by culturing red blood cells (RBCs) to allow further development of parasites. RESULTS: We observed a significant reduction in parasitemia (0.5% vs. 0.12%) after only 1 day in storage at 4 degrees C. Thereafter, reduction in parasitemia was relatively gradual. Microscopically detectable parasites were present even after 28 days of storage. However, after storing for more than 14 days at 4 degrees C, parasites no longer replicated when cultured in vitro. CONCLUSION: Although the storage of asexual blood-stage P. falciparum parasites at 4 degrees C is detrimental to their survival (a 7.1-fold reduction in parasitemia after 14 days in storage), parasites remained microscopically detectable for 28 days, the end time point of our study. Further in vitro and in vivo studies will be needed to confirm loss of viability of P. falciparum after 14 days in storage, but our initial efforts repeatedly failed to show maturation and development of the parasites in cultured RBCs after that time. C1 [Chattopadhyay, Rana; Majam, Victoria F.; Kumar, Sanjai] US FDA, DETTD, OBRR, CBER, Rockville, MD 20852 USA. RP Kumar, S (reprint author), US FDA, DETTD, OBRR, CBER, 1401 Rockville Pike, Rockville, MD 20852 USA. EM Sanjai.kumar@fda.hhs.gov NR 16 TC 9 Z9 9 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 2011 VL 51 IS 3 BP 630 EP 635 DI 10.1111/j.1537-2995.2010.02872.x PG 6 WC Hematology SC Hematology GA 732DZ UT WOS:000288166200026 PM 20849405 ER PT J AU Strauss, DG AF Strauss, David G. TI Understanding ventricular activation SO JOURNAL OF ELECTROCARDIOLOGY LA English DT Editorial Material ID CARDIAC-RESYNCHRONIZATION THERAPY; BUNDLE-BRANCH BLOCK; MAGNETIC-RESONANCE; MYOCARDIAL SCAR; HEART-FAILURE; DYSSYNCHRONY; IMPROVEMENT; CONDUCTION C1 [Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Strauss, DG (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM david.strauss@fda.hhs.gov RI Strauss, David/A-9211-2012 NR 21 TC 2 Z9 2 U1 0 U2 0 PU CHURCHILL LIVINGSTONE INC MEDICAL PUBLISHERS PI PHILADELPHIA PA CURTIS CENTER, INDEPENDENCE SQUARE WEST, PHILADELPHIA, PA 19106-3399 USA SN 0022-0736 J9 J ELECTROCARDIOL JI J. Electrocardiol. PD MAR-APR PY 2011 VL 44 IS 2 BP 282 EP 284 DI 10.1016/j.jelectrocard.2010.12.165 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 733SK UT WOS:000288282900035 PM 21353069 ER PT J AU Tracy, LA Furuno, JP Harris, AD Singer, M Langenberg, P Roghmann, MC AF Tracy, LaRee A. Furuno, Jon P. Harris, Anthony D. Singer, Mary Langenberg, Patricia Roghmann, Mary-Claire TI Staphylococcus aureus Infections in US Veterans, Maryland, USA, 1999-2008 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID BLOOD-STREAM INFECTIONS; SOFT-TISSUE INFECTIONS; INTENSIVE-CARE UNITS; METHICILLIN-RESISTANT; RISK-FACTORS; EPIDEMIOLOGY; STATES; SKIN; HOSPITALIZATIONS; HOSPITALS AB Trends in Staphylococcus aureus infections are not well described. To calculate incidence in overall S. aureus infection and invasive and noninvasive infections according to methicillin susceptibility and location, we conducted a 10-year population-based retrospective cohort study (1999-2008) using patient-level data in the Veterans Affairs Maryland Health Care System. We found 3,674 S. aureus infections: 2,816 (77%) were noninvasive; 2,256 (61%) were methicillin-resistant S. aureus (MRSA); 2,517 (69%) were community onset, and 1,157 (31%) were hospital onset. Sixty-one percent of noninvasive infections were skin and soft tissue infections; 1,112 (65%) of these were MRSA. Ten-year averaged incidence per 100,000 veterans was 749 (+/- 132 SD, range 549-954) overall, 178 (+/- 41 SD, range 114-259) invasive, and 571 (+/- 152 SD, range 364-801) noninvasive S. aureus infections. Incidence of all S. aureus infections significantly increased (p < 0.001), driven by noninvasive, MRSA, and community-onset infections (p < 0.001); incidence of invasive S. aureus infection significantly decreased (p < 0.001). C1 [Tracy, LaRee A.] Univ Maryland, Dept Epidemiol & Publ Hlth, Baltimore, MD 21201 USA. [Roghmann, Mary-Claire] Vet Adm Maryland Hlth Care Syst, Baltimore, MD USA. [Singer, Mary] US FDA, Silver Spring, MD USA. RP Tracy, LA (reprint author), Univ Maryland, Dept Epidemiol & Publ Hlth, 685 W Baltimore St,MSTF 336, Baltimore, MD 21201 USA. EM laree.tracy@fda.hhs.gov FU VA Clinical Science Research and Development; National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) [5K01AI071015-02, 1K24AI079040-01A1] FX This work was supported by a VA Clinical Science Research and Development Merit Award awarded to M.R. J.P.F. was supported by National Institutes of Health (NIH) National Institute of Allergy and Infectious Diseases (NIAID) K01 award (5K01AI071015-02) and A.D.H. by an NIH NIAID K24 award (1K24AI079040-01A1) while this work was performed. NR 24 TC 22 Z9 23 U1 0 U2 3 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 MAR PY 2011 VL 17 IS 3 BP 441 EP 448 DI 10.3201/eid1703.100502 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 731YP UT WOS:000288147000015 PM 21392435 ER PT J AU Tadesse, DA Bahnson, PB Funk, JA Thakur, S Morrow, WEM Wittum, T DeGraves, F Rajala-Schultz, P Gebreyes, WA AF Tadesse, Daniel A. Bahnson, Peter B. Funk, Julie A. Thakur, Siddhartha Morrow, William E. Morgan Wittum, Thomas DeGraves, Fred Rajala-Schultz, Paivi Gebreyes, Wondwossen A. TI Prevalence and Antimicrobial Resistance Profile of Campylobacter Spp. Isolated from Conventional and Antimicrobial-Free Swine Production Systems from Different U.S. Regions SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID FOOD-PRODUCING ANIMALS; ANTIBIOTIC-RESISTANCE; UNITED-STATES; EFFLUX PUMP; COLI; JEJUNI; PIGS; BACTERIA; FARMS; TRANSMISSION AB We conducted a study to compare the prevalence and antimicrobial resistance profile of Campylobacter isolated from 34 farm-slaughter pair cohorts of pigs raised in conventional and antimicrobial-free (ABF) production systems. Isolates originated from four different states of two geographic regions (region 1-Ohio and Michigan; region 2-Wisconsin and Iowa). A total of 838 fecal and 1173 carcass samples were examined. Campylobacter isolates were speciated using multiplex polymerase chain reaction targeting ceuE and hipO genes. The minimum inhibitory concentration was determined using agar dilution to a panel of six antimicrobials: chloramphenicol, erythromycin, gentamicin, ciprofloxacin, nalidixic acid, and tetracycline. Campylobacter spp. was isolated from 472 of 838 pigs (56.3%). Campylobacter prevalence did not vary significantly based on production system (conventional [58.9%] and ABF [53.7%], odds ratio [OR] 1.4, 95% confidence interval [CI] 0.8-2.6, p = 0.24) or geographic region (region 1 [54.1%] and region 2 [58.2%], OR 1.02, 95% CI 0.6-1.9, p = 0.92). At slaughter plant, Campylobacter prevalence varied based on processing stages (19.4% at pre-evisceration, 25.3% at postevisceration, and 3.2% at postchill). Resistance was common to tetracycline (64.5%), erythromycin (47.9%), and nalidixic acid (23.5%). Campylobacter isolates from conventional production systems were more likely to be erythromycin resistant than from ABF (OR 3.2, 95% CI 1.4-7.2, p = 0.01). The proportion of ciprofloxacin-resistant Campylobacter coli isolates were 3.7% and 1.2% from ABF and conventional production systems, respectively. Thirty-seven out of 1257 C. coli (2.9%) were resistant to both erythromycin and ciprofloxacin, drugs of choice for treatment of invasive human campylobacteriosis. The finding of ciprofloxacin resistance, particularly from ABF herds, has significant implications on the potential role of risk factors other than mere antimicrobial use for production purposes. C1 [Wittum, Thomas; DeGraves, Fred; Rajala-Schultz, Paivi; Gebreyes, Wondwossen A.] Ohio State Univ, Dept Vet Prevent Med, Columbus, OH 43210 USA. [Tadesse, Daniel A.] Res Off, Food & Drug Adm, Ctr Vet Med, Laurel, MD USA. [Bahnson, Peter B.] Univ Wisconsin, Madison, WI USA. [Funk, Julie A.] Michigan State Univ, Coll Vet Med, E Lansing, MI 48824 USA. [Thakur, Siddhartha; Morrow, William E. Morgan] N Carolina State Univ, Coll Agr & Life Sci, Raleigh, NC 27695 USA. RP Gebreyes, WA (reprint author), Ohio State Univ, Dept Vet Prevent Med, 1920 Coffey Rd, Columbus, OH 43210 USA. EM gebreyes@cvm.osu.edu FU National Integrated Food Safety Initiative [2002-51110-5118]; U.S. Department of Agriculture FX This study was funded by National Integrated Food Safety Initiative (2002-51110-5118), U.S. Department of Agriculture. We sincerely thank the pig producers and abattoir personnel who participated in this project. We gratefully acknowledge the technical support of Heather Lowman, Pamela Fry, and Narry Tiao. NR 49 TC 11 Z9 12 U1 1 U2 10 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD MAR PY 2011 VL 8 IS 3 BP 367 EP 374 DI 10.1089/fpd.2010.0665 PG 8 WC Food Science & Technology SC Food Science & Technology GA 731OP UT WOS:000288119300003 PM 21133777 ER PT J AU Tran, QT Nawaz, MS Deck, J Foley, S Kiet, N Cerniglia, CE AF Tran, Quynh T. Nawaz, Mohamed S. Deck, Joanna Foley, Steven Kiet Nguyen Cerniglia, Carl E. TI Detection of Type III Secretion System Virulence and Mutations in gyrA and parC Genes Among Quinolone-Resistant Strains of Pseudomonas aeruginosa Isolated from Imported Shrimp SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID TOPOISOMERASE MUTATIONS; BACTERIA AB Twenty Pseudomonas aeruginosa isolates were recovered from imported frozen raw shrimp sold in the United States. Isolates were tested for antimicrobial susceptibility to quinolones and analyzed for mutations in quinolone resistance-determining regions, presence of type III secretion system genes, and genetic relatedness using pulsed-field gel electrophoresis. All isolates were resistant to nalidixic acid. Polymerase chain reaction assays detected exoS, exoT, exoU, and exoY among isolates. Eight unique pulsed-field gel electrophoresis clusters were generated. Mutations were found in gyrA at codon 83 (Ile to Thr) and in parC at codon 87 (Leu to Ser). Together, these findings reveal that imported shrimp may harbor virulent and quinolone-resistant strains of P. aeruginosa. C1 [Tran, Quynh T.; Nawaz, Mohamed S.; Deck, Joanna; Foley, Steven; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Kiet Nguyen] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Tran, QT (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM qttran@mdanderson.org FU National Center for Toxicological Research; U.S. Food and Drug Administration; FDA Commissioner FX We thank Steve Yan and John B. Sutherland for critical review of the manuscript. This work was supported by the National Center for Toxicological Research, U.S. Food and Drug Administration. Q. T. T. and K.T.N. were supported by the FDA Commissioner's Fellowship Program. Views presented here do not necessarily reflect those of the FDA. NR 12 TC 5 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD MAR PY 2011 VL 8 IS 3 BP 451 EP 453 DI 10.1089/fpd.2010.0687 PG 3 WC Food Science & Technology SC Food Science & Technology GA 731OP UT WOS:000288119300015 PM 21117986 ER PT J AU Han, J David, DE Deck, J Lynne, AM Kaldhone, P Nayak, R Stefanova, R Foley, SL AF Han, Jing David, Donna E. Deck, Joanna Lynne, Aaron M. Kaldhone, Pravin Nayak, Rajesh Stefanova, Rossina Foley, Steven L. TI Comparison of Salmonella enterica Serovar Heidelberg Isolates from Human Patients with Those from Animal and Food Sources SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID ANTIMICROBIAL RESISTANCE; UNITED-STATES; RETAIL MEATS; INFECTIONS; POULTRY AB Seventy-eight Salmonella enterica serovar Heidelberg isolates from humans were tested for antimicrobial susceptibility, resistance genes, and plasmids and genotyped by pulsed-field gel electrophoresis (PFGE). Most (88%) contained plasmids, and 47% were resistant to antimicrobials. The overall results were compared to those of previous S. Heidelberg studies of food-and animal-related sources, and multiple similarities were observed. C1 [Han, Jing; Deck, Joanna; Nayak, Rajesh; Foley, Steven L.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [David, Donna E.; Kaldhone, Pravin] Marshfield Clin Res Fdn, Marshfield, WI 54449 USA. [Lynne, Aaron M.] Sam Houston State Univ, Dept Biol Sci, Huntsville, TX 77341 USA. [Stefanova, Rossina] Arkansas Dept Hlth, Arkansas Publ Hlth Labs, Little Rock, AR 72205 USA. RP Foley, SL (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM steven.foley@fda.hhs.gov FU Marshfield Clinic Research Foundation; U.S. Food and Drug Administration; Oak Ridge Institute for Science and Education FX We thank the Marshfield Clinic Research Foundation and the U.S. Food and Drug Administration for financial support of the research. Jing Han is supported through the Oak Ridge Institute for Science and Education. NR 24 TC 10 Z9 10 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 MAR PY 2011 VL 49 IS 3 BP 1130 EP 1133 DI 10.1128/JCM.01931-10 PG 4 WC Microbiology SC Microbiology GA 729RA UT WOS:000287967100060 PM 21177888 ER PT J AU Clotilde, LM Bernard, C Hartman, GL Lau, DK Carter, JM AF Clotilde, Laurie M. Bernard, Clay Hartman, Gary L. Lau, David K. Carter, J. Mark TI Microbead-Based Immunoassay for Simultaneous Detection of Shiga Toxins and Isolation of Escherichia coli O157 in Foods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID SUSPENSION ARRAY TECHNOLOGY; BIOLOGICAL WARFARE AGENTS; HEMOLYTIC-UREMIC SYNDROME; BIOSENSOR; INFECTION; IDENTIFICATION; PURIFICATION; ASSOCIATION; NOVOBIOCIN; PROTEINS AB Shiga toxin-producing Escherichia coli (STEC) is a significant foodborne pathogen with great economic consequences. There has been an increased food safety concern with this organism since outbreaks of human illnesses caused by this pathogen were first reported in 1982. Therefore, developing a reliable, sensitive, and rapid assay capable of detecting E. call O157 and the main toxins produced by STEC (i.e., Shiga toxins 1 [Stx(1)] and 2 [Stx(2)]) will directly benefit regulatory agencies by minimizing analysis time. Here, we use Luminex technology to detect multiple analytes in a single 50-ml sample. Using commercially available monoclonal antibodies coupled to carboxylated magnetic microbeads, we developed an immunoassay capable of simultaneously serotyping E. coli O157 and detecting Stx(1) and/or Stx(2). The specificity and sensitivity of this immunoassay was tested against a collection of 34 E. call isolates belonging to various O serogroups phenotypically different for Stx. The results were compared with microplate sandwich enzyme-linked immunosorbent assay (ELISA), and no cross-reactivity was observed for any of the monoclonal antibodies used. An increased sensitivity up to 1,000 times was observed in the microbead-based immunoassay when compared with the microplate sandwich ELISA. The results indicate that Luminex technology has the potential to simultaneously detect multiple targets without loss of specificity and/or sensitivity. A blind experiment was conducted with 48 samples of ground beef, lettuce, and milk spiked with <= 2 CFU/g E. coli. All the samples were correctly identified, with no false positives or false negatives. This microbead-based immunoassay could be extended to simultaneously detect additional foodborne pathogens and their toxic markers. C1 [Clotilde, Laurie M.; Bernard, Clay; Carter, J. Mark] Agr Res Serv, Western Reg Res Ctr, USDA, Albany, CA 94710 USA. [Hartman, Gary L.; Lau, David K.] US FDA, Alameda, CA 94502 USA. RP Carter, JM (reprint author), Agr Res Serv, Western Reg Res Ctr, USDA, Albany, CA 94710 USA. EM j.mark.carter@ars.usda.gov RI Carter, John Mark/K-2485-2015 OI Carter, John Mark/0000-0001-8251-4168 FU U.S. Department of Agriculture, Agricultural Research Service (USDA-ARS) [108, 5325-42000-043-00] FX The work presented in this article was supported by the U.S. Department of Agriculture, Agricultural Research Service (USDA-ARS), National Program 108, under Current Research Information System 5325-42000-043-00. We thank Drs. Robert Mandrell and Beatriz Quinones (USDA-ARS, Produce Safety Microbiology Research Unit, Albany, CA) for providing STEC strains. We thank Drs. Larry Stanker, David Brandon. and Robert Hnasko (USDA-ARS, Foodborne Contaminants Research Unit, Albany CA) for technical advice. We thank Henry Lau, Lillian Hsu, Myriam Lonhienne, Robert Gee, and You Jin Lee for technical assistance. We thank the Bio-Rad BioPlex team for repairing our Luminex instrument. NR 55 TC 13 Z9 15 U1 2 U2 58 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 2011 VL 74 IS 3 BP 373 EP 379 DI 10.4315/0362-028X.JFP-10-344 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 734DK UT WOS:000288313200004 PM 21375872 ER PT J AU Tryndyak, VP Han, T Muskhelishvili, L Fuscoe, JC Ross, SA Beland, FA Pogribny, IP AF Tryndyak, Volodymyr P. Han, Tao Muskhelishvili, Levan Fuscoe, James C. Ross, Sharon A. Beland, Frederick A. Pogribny, Igor P. TI Coupling global methylation and gene expression profiles reveal key pathophysiological events in liver injury induced by a methyl-deficient diet SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Article DE Gene expression; Gene methylation; Liver injury; Methyl-deficient diet; Mice ID DNA METHYLATION; S-ADENOSYLHOMOCYSTEINE; CHOLINE DEFICIENCY; HUMAN-DISEASE; GC-RICH; HYPOMETHYLATION; CARCINOGENESIS; HOMOCYSTEINE; MICE; ADENOSYLMETHIONINE AB Scope: A methyl-deficient diet induces liver injury similar to human nonalcoholic steatohepatitis, one of the main risk factors for the development of hepatocellular carcinoma. Previous studies have demonstrated that this diet perturbs DNA methylation by causing a profound loss of global cytosine methylation, predominantly at heavily methylated repetitive sequences. However, whether methyl deficiency affects the methylation status of gene promoters has not been explored. Methods and results: Mouse gene expression and CpG island microarrays were used to characterize the gene expression and CpG island methylation profiles in the livers of C57BL/6J mice fed a methyl-deficient diet. We detected 164 genes that were differentially expressed and exhibited an inverse relationship between the gene expression and the extent of CpG island methylation. Furthermore, these genes were associated with altered lipid and glucose metabolism, DNA damage and repair, apoptosis, the development of fibrosis, and liver tissue remodeling. Although there were both increased and decreased levels of CpG island methylation, the number of hypomethylated genes was substantially greater than the number of hypermethylated genes. Conclusion: The results this study demonstrate that pairing methylation profiles with gene expression profiles is a powerful approach to identify dysregulated high-priority fundamental pathophysiological pathways associated with disease development. C1 [Tryndyak, Volodymyr P.; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Han, Tao; Fuscoe, James C.] Natl Ctr Toxicol Res, Div Syst Biol, Jefferson, AR 72079 USA. [Muskhelishvili, Levan] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov NR 43 TC 25 Z9 25 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD MAR PY 2011 VL 55 IS 3 BP 411 EP 418 DI 10.1002/mnfr.201000300 PG 8 WC Food Science & Technology SC Food Science & Technology GA 732IE UT WOS:000288177400007 PM 20938992 ER PT J AU Pease, LF Tsai, DH Brorson, KA Guha, S Zachariah, MR Tarlov, MJ AF Pease, Leonard F., III Tsai, De-Hao Brorson, Kurt A. Guha, Suvajyoti Zachariah, Michael R. Tarlov, Michael J. TI Physical Characterization of Icosahedral Virus Ultra Structure, Stability, and Integrity Using Electrospray Differential Mobility Analysis SO ANALYTICAL CHEMISTRY LA English DT Article ID MASS-SPECTROMETRY; PROTEIN COMPLEXES; ION MOBILITY; IONIZATION; APPROXIMATION; PARTICLES; GEMMA AB We present a rapid and quantitative method to physically characterize the structure and stability of viruses. Electrospray differential mobility analysis (ES-DMA) is used to determine the size of capsomers (i.e., hexons) and complete capsids. We demonstrate how to convert the measured mobility size into the icosahedral dimensions of a virus, which for PR772 become 68.4 nm for vertex-to-vertex, 54.4 nm for facet-to-facet, and 58.2 nm for edge-to-edge lengths, in reasonable agreement with dimensions from transmission electron microscopy for other members of the family Tectiviridae (e.g., PRD1). These results indicate ES-DMA's mobility diameter most closely approximates the edge-to-edge length. Using PR772's edge length (36.0 nm) and the size of the major capsid hexon (approximate to 8.4 nm) from ES-DMA with icosahedral geometry, PR772's T = 25 symmetry is confirmed and the number of proteins in the capsid shell is determined. We also demonstrate the use of ES-DMA to monitor the temporal disintegration of PR772, the thermal degradation of PP7, and the appearance of degradation products, essential to viral stability assays. These results lay groundwork essential for the use of ES-DMA for a variety of applications including monitoring of vaccine and gene therapy vector products, confirmation of viral inactivation, and theoretical studies of self-assembling macromolecular structures. C1 [Pease, Leonard F., III] Univ Utah, Dept Chem Engn, Salt Lake City, UT 84112 USA. [Pease, Leonard F., III] Univ Utah, Dept Pharmaceut & Pharmaceut Chem, Salt Lake City, UT 84112 USA. [Pease, Leonard F., III] Univ Utah, Dept Internal Med, Salt Lake City, UT 84112 USA. [Pease, Leonard F., III; Tsai, De-Hao; Guha, Suvajyoti; Zachariah, Michael R.; Tarlov, Michael J.] NIST, Gaithersburg, MD 20899 USA. [Tsai, De-Hao; Guha, Suvajyoti; Zachariah, Michael R.] Univ Maryland, Dept Chem, College Pk, MD 20742 USA. [Tsai, De-Hao; Guha, Suvajyoti; Zachariah, Michael R.] Univ Maryland, Dept Mech Engn, College Pk, MD 20742 USA. [Brorson, Kurt A.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. RP Pease, LF (reprint author), Univ Utah, Dept Chem Engn, Cent Campus Dr,3290 MEB, Salt Lake City, UT 84112 USA. EM pease@eng.utah.edu; michael.tarlov@nist.gov RI Tsai, De-Hao/K-6702-2012; OI Tsai, De-Hao/0000-0002-2669-3007; Guha, Suvajyoti/0000-0002-7622-2721 FU National Research Council FX L.F.P. would like to acknowledge support of a postdoctoral fellowship through the National Research Council. We ex-press appreciation for helpful suggestions and conversations with Anton P. J. Middelberg John T. Elliott, and Kenneth D. Cole and Scott Lute (CDER/FDA) for providing the virus preps. Views expressed are not necessarily those of the FDA or the US government. NR 38 TC 17 Z9 17 U1 3 U2 18 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD MAR 1 PY 2011 VL 83 IS 5 BP 1753 EP 1759 DI 10.1021/ac1030094 PG 7 WC Chemistry, Analytical SC Chemistry GA 725ZQ UT WOS:000287685800038 PM 21302934 ER PT J AU Tran, QT Nawaz, MS Deck, J Nguyen, KT Cerniglia, CE AF Tran, Quynh T. Nawaz, Mohamed S. Deck, Joanna Nguyen, Kiet T. Cerniglia, Carl E. TI Plasmid-Mediated Quinolone Resistance in Pseudomonas putida Isolates from Imported Shrimp SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FLUOROQUINOLONE RESISTANCE; ESCHERICHIA-COLI; KLEBSIELLA-PNEUMONIAE; ANTIMICROBIAL RESISTANCE; TRANSFERABLE PLASMID; GYRA MUTATIONS; QNR; ENTEROBACTERIACEAE; PREVALENCE; ENVIRONMENTS AB Fourteen quinolone-resistant Pseudomonas putida isolates were recovered from imported frozen shrimp sold in the United States. Two isolates harbored plasmids with qnrA and qnrB genes. PCR and DNA sequencing of quinolone resistance-determining regions identified novel substitutions in GyrA (His1393 -> Glu and Thr128 -> Ala) and GyrB (Thr442 -> Asn, Gly470 -> Ala, and Ile487 -> Pro) and previously reported substitutions in GyrB (Asp489 -> Glu) and ParC (Thr105 -> Pro). C1 [Tran, Quynh T.; Nawaz, Mohamed S.; Deck, Joanna; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Nguyen, Kiet T.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Tran, QT (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM quynhtien.n.tran@gmail.com FU National Center for Toxicological Research, U.S. Food and Drug Administration (FDA) FX This work was supported by the National Center for Toxicological Research, U.S. Food and Drug Administration (FDA). Q.T.T. and K.T.N. were supported by the FDA Commissioner's Fellowship Program. NR 31 TC 4 Z9 4 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAR PY 2011 VL 77 IS 5 BP 1885 EP 1887 DI 10.1128/AEM.01176-10 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 726DX UT WOS:000287700100044 PM 21193671 ER PT J AU Temple, R AF Temple, Robert TI Cancer Chemoprevention-the Cardiovascular Model SO CANCER PREVENTION RESEARCH LA English DT Editorial Material ID CORONARY-HEART-DISEASE; ESTROGEN PLUS PROGESTIN; CHRONIC KIDNEY-DISEASE; GLYCOPROTEIN IIB/IIIA; POSTMENOPAUSAL WOMEN; BLOOD-PRESSURE; BREAST-CANCER; TRIAL; RISK; MORTALITY C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Temple, R (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Robert.Temple@fda.hhs.gov NR 32 TC 5 Z9 5 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1940-6207 J9 CANCER PREV RES JI Cancer Prev. Res. PD MAR PY 2011 VL 4 IS 3 BP 307 EP 310 DI 10.1158/1940-6207.CAPR-11-0049 PG 4 WC Oncology SC Oncology GA 729PV UT WOS:000287963800007 PM 21372030 ER PT J AU Jasper, GA Arun, I Venzon, D Kreitman, RJ Wayne, AS Yuan, CM Marti, GE Stetler-Stevenson, M AF Jasper, Gregory A. Arun, Indu Venzon, David Kreitman, Robert J. Wayne, Alan S. Yuan, Constance M. Marti, Gerald E. Stetler-Stevenson, Maryalice TI Variables Affecting the Quantitation of CD22 in Neoplastic B Cells SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE CD22; quantitative flow cytometry; QuantiBRITE; ABC ID IMMUNOTOXIN RFB4(DSFV)-PE38 BL22; CHRONIC LYMPHOPROLIFERATIVE DISORDERS; CHRONIC LYMPHOCYTIC-LEUKEMIA; FLOW-CYTOMETRY; T-CELLS; EXPRESSION; MALIGNANCIES; TRIAL; STANDARDIZATION; PERFORMANCE AB Background: Quantitative flow cytometry (QFCM) is being applied in the clinical flow cytometry laboratory for diagnosis, prognosis, and assessment of patients receiving antibody-based therapy. ABC values and the, effect of technical variables on CD22 quantitation in acute lymphoblastic leukemia (ALL), chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), follicular lymphoma (FCL), hairy cell leukemia (HCL) and normal B cells were studied. Methods: The QuantiBrite System (R) was used to determine the level of CD22 expression (mean antibody bound per cell, ABC) by malignant and normal B cells. The intra-assay variability, number of cells required for precision, effect of delayed processing as well as shipment of peripheral blood specimens (delayed processing and exposure to noncontrolled environments), and the effect of paraformaldehyde fixation on assay results were studied. Results: The QuantiBRITE method of measuring CD22 ABC is precise (median CV 1.6%, 95% confidence interval, 1.2-2.3%) but a threshold of 250 malignant cells is required for reliable CD22 ABC values. Delayed processing and overnight shipment of specimens resulted in significantly different ABC values whereas fixation for up to 12 h had no significant effect. ABC measurements determined that CD22 expression is lower than normal in ALL, CLL, FCL, and MCL but higher than normal in HCL. Conclusions: CD22 expression was atypical in the hematolymphoid malignancies studied and may have diagnostic utility. Technical variables such as cell number analyzed and delayed processing or overnight shipment of specimens impact significantly on the measurement of antigen expression by QFCM in the clinical laboratory. Published 2010 Wiley-Liss, Inc. C1 [Jasper, Gregory A.; Arun, Indu; Yuan, Constance M.; Stetler-Stevenson, Maryalice] NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Venzon, David] NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. [Kreitman, Robert J.] NCI, Clin Immunotherapy Sect, Mol Biol Lab, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Wayne, Alan S.] NCI, Pediat Oncol Branch, Hematol Dis Sect, Ctr Canc Res,NIH, Bethesda, MD 20892 USA. [Marti, Gerald E.] CBER FDA, Flow & Image Cytometry Sect, Cellular & Tissue Therapy Branch, Div Cell & Gene Therapies,Off Cellular Tissues &, Bethesda, MD USA. RP Stetler-Stevenson, M (reprint author), NCI, Flow Cytometry Unit, Pathol Lab, Ctr Canc Res,NIH, Bldg 10,Room 2A-33,Mail Stop 1500, Bethesda, MD 20892 USA. EM stetler@mail.nih.gov FU NIH, National Cancer Institute, Center for Cancer Research FX Grant sponsor: Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research. NR 25 TC 29 Z9 29 U1 1 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD MAR PY 2011 VL 80B IS 2 BP 83 EP 90 DI 10.1002/cyto.b.20567 PG 8 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 728RC UT WOS:000287891200003 PM 20872890 ER PT J AU Chu, HT Nie, L Cole, SR AF Chu, Haitao Nie, Lei Cole, Stephen R. TI Estimating the Relative Excess Risk Due to Interaction A Bayesian Approach SO EPIDEMIOLOGY LA English DT Article ID CONFIDENCE-INTERVALS; INEQUALITY CONSTRAINTS; EPIDEMIOLOGIC RESEARCH; REGRESSION-ANALYSIS; MODEL; IDENTIFICATION; PERSPECTIVES; METAANALYSIS; PERFORMANCE; ANTAGONISM AB The relative excess odds or risk due to interaction (ie, RERI(OR) and RERI) play an important role in epidemiologic data analysis and interpretation. Previous authors have advocated frequentist approaches based on nonparametric bootstrap, the method of variance estimates recovery, and profile likelihood for estimating confidence intervals. As an alternative, we propose a Bayesian approach that accounts for parameter constraints and estimates the RERI OR in a case-control study from a linear additive odds-ratio model, or the RERI in a cohort study from a linear additive risk-ratio model. We show that Bayesian credible intervals can often be obtained more easily than frequentist confidence intervals. Furthermore, the Bayesian approach can be easily extended to adjust for confounders. Because posterior computation with inequality constraints can be accomplished easily using free software, the proposed Bayesian approaches may be useful in practice. C1 [Chu, Haitao] Univ Minnesota, Sch Publ Hlth, Div Biostat, Minneapolis, MN 55455 USA. [Nie, Lei] Off Biometr CDER OTS FDA, Div Biometr 4, Spring, MD USA. [Cole, Stephen R.] Univ N Carolina, Dept Epidemiol, Chapel Hill, NC USA. RP Chu, HT (reprint author), Univ Minnesota, Sch Publ Hlth, Div Biostat, A460 Mayo Bldg,MMC 303, Minneapolis, MN 55455 USA. EM chux0051@umn.edu RI Chu, Haitao /J-7576-2012; OI Chu, Haitao/0000-0003-0932-598X NR 45 TC 10 Z9 11 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAR PY 2011 VL 22 IS 2 BP 242 EP 248 DI 10.1097/EDE.0b013e318208750e PG 7 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 716LR UT WOS:000286970700016 PM 21228700 ER PT J AU Gao, ZM Ahadi, S Moore, TW Doub, WH Westenberger, BJ Buhse, LF AF Gao, Zongming Ahadi, Shafiq Moore, Terry W. Doub, William H. Westenberger, B. J. Buhse, Lucinda F. TI Effects of Vessel Geometric Irregularity on Dissolution Test Results SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE dissolution; analysis; physical characterization; solid dosage form; apparatus 2; in vitro method; geometric irregularity; VMM ID VARIABILITY; APPARATUS-2 AB Dissolution testing of pharmaceutical products is an important technique used extensively for both product development and quality control, but there are many variables that can affect dissolution results. In this study, the effect of the inner shape of standard 1-L dissolution vessels on drug dissolution results was investigated. The geometric dimensions and irregularities of commercially available vessels (obtained from four different manufacturers) were examined using a three-dimensional video-based measuring machine (VMM). The same analyst, dissolution test assembly, and experimental conditions were used for dissolution testing involving 10 mg of prednisone tablets (NCDA #2) with dissolution apparatus 2 (paddle). Mechanical calibration of the dissolution apparatus was performed prior to dissolution testing with each set of vessels. Geometric characteristics varied within and among the sets of vessels, but the overall averages and standard deviations of dissolution results (six vessels) showed no statistical significant differences among the vessel sets. However, some dissolution differences were noted when comparing individual vessels. With these types of comparisons, the vessel concentricity, sphericity, and radius of sphere were found to possibly influence the amount of prednisone dissolved, but flatness of vessel flange, cylindricity, and circularity showed no effect on dissolution results. The study shows that VMM is a technique that could be used to qualify dissolution vessels. (C) 2010 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:1093-1101, 2011 C1 [Gao, Zongming; Ahadi, Shafiq; Moore, Terry W.; Doub, William H.; Westenberger, B. J.; Buhse, Lucinda F.] US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. RP Gao, ZM (reprint author), US FDA, Div Pharmaceut Anal, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. EM zongming.gao@fda.hhs.gov NR 19 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD MAR PY 2011 VL 100 IS 3 BP 1093 EP 1101 DI 10.1002/jps.22319 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 729JZ UT WOS:000287947100029 PM 20803604 ER PT J AU Payne, JB Li, X Santos, FBO Williams, M Sheldon, BW AF Payne, J. B. Li, X. Santos, F. B. O. Williams, M. Sheldon, B. W. TI Survey of Salmonella populations from swine waste-treatment technologies SO JOURNAL OF SWINE HEALTH AND PRODUCTION LA English DT Article DE swine; Salmonella; waste management; manure ID CAROLINA TURKEY FARMS; TYPHIMURIUM; PATHOGEN; MANURE; SYSTEMS AB Salmonella presence, populations, sero-types, and antibiotic susceptibilities in untreated and treated swine manure were determined for farms implementing environmentally superior waste-treatment technologies. The waste-treatment systems surveyed showed potential in reducing Salmonella populations. C1 [Payne, J. B.] Oklahoma State Univ, Dept Biosyst & Agr Engn, Stillwater, OK 74078 USA. [Li, X.] FDA Ctr Vet Med, Div Anim Feeds, Rockville, MD USA. [Santos, F. B. O.] EMBRAPA Swine & Poultry, Natl Ctr Swine & Poultry Res, Concordia, SC, Brazil. [Williams, M.; Sheldon, B. W.] N Carolina State Univ, Dept Poultry Sci, Raleigh, NC 27695 USA. RP Payne, JB (reprint author), Oklahoma State Univ, Dept Biosyst & Agr Engn, 111 Agr Hall, Stillwater, OK 74078 USA. EM joshua.payne@okstate.edu NR 16 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC SWINE VETERINARIANS PI PERRY PA 902 1ST AVE, PERRY, IA 50220-1703 USA SN 1537-209X J9 J SWINE HEALTH PROD JI J. Swine. Health Prod. PD MAR-APR PY 2011 VL 19 IS 2 BP 100 EP 106 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 727GE UT WOS:000287785200008 ER PT J AU Larkin, C AF Larkin, Catherine TI Is the Battle Over Bevacizumab Coverage Looming? SO JOURNAL OF THE NATIONAL COMPREHENSIVE CANCER NETWORK LA English DT Editorial Material C1 [Larkin, Catherine] Bloomberg News, Washington, DC USA. [Larkin, Catherine] US FDA, Rockville, MD 20857 USA. RP Larkin, C (reprint author), Bloomberg News, Washington, DC USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU HARBORSIDE PRESS PI COLD SPRING HARBOR PA 37 MAIN ST, COLD SPRING HARBOR, NY 11724 USA SN 1540-1405 J9 J NATL COMPR CANC NE JI J. Natl. Compr. Cancer Netw. PD MAR PY 2011 VL 9 IS 3 BP 261 EP 263 PG 3 WC Oncology SC Oncology GA 729YS UT WOS:000287991200002 PM 21393437 ER PT J AU Wasserberg, G Poche, R Miller, D Chenault, M Zollner, G Rowton, ED AF Wasserberg, Gideon Poche, Richard Miller, David Chenault, Michelle Zollner, Gabriela Rowton, Edgar D. TI Imidacloprid as a potential agent for the systemic control of sand flies SO JOURNAL OF VECTOR ECOLOGY LA English DT Article DE Systemic control; sand fly larva control; imidacloprid; sand rat; feed-through ID CALIFORNIA GROUND-SQUIRRELS; FEED-THROUGH INSECTICIDE; IMPREGNATED DOG COLLARS; CUTANEOUS LEISHMANIASIS; PHLEBOTOMINE SANDFLIES; LABORATORY EVALUATION; CANINE LEISHMANIASIS; PSYCHODIDAE; DIPTERA; CERATOPHYLLIDAE AB Our goal was to study the effectiveness of the insecticide imidacloprid as a systemic control agent. First, to evaluate the blood-feeding effect, we fed adult female Phlebotomus papatasi with imidacloprid-treated rabbit blood and monitored blood-feeding success and survival. Second, to evaluate the feed-through effectiveness of this insecticide, we fed laboratory rats and sand rats with insecticide-treated food and evaluated the survival of sand fly larvae feeding on rodents' feces. In the blood-feeding experiment, 89.8% mortality was observed with the higher dose (5 mg/ml) and 81.3% with the lower dose (1 mg/ml). In the larvicide experiments, both sand fly species demonstrated a typical dose-response curve with the strongest lethal effect for the 250 ppm samples. Lutzomyia longipalpis larvae, however, were less sensitive. In all experiments, 1st instar larvae were more sensitive than the older stages. First instar P. papatasi larvae feeding on sand rat feces passed the larvicidal threshold of 90% mortality at doses higher than 50 ppm. In comparison, in older stages 90% mortality was obtained with a dose of only 250 ppm. Overall, results support the feasibility of imidacloprid as a systemic control agent that takes advantage of the tight ecological association between the reservoir host and the sand fly vector. C1 [Wasserberg, Gideon; Zollner, Gabriela; Rowton, Edgar D.] Walter Reed Army Inst Res, Div Entomol, Silver Spring, MD 20910 USA. [Poche, Richard; Miller, David] Genesis Labs, Wellington, CO 80549 USA. [Chenault, Michelle] US FDA, Silver Spring, MD 20993 USA. RP Wasserberg, G (reprint author), Univ N Carolina, Dept Biol, Greensboro, NC 27402 USA. RI Rowton, Edgar/A-1975-2011 OI Rowton, Edgar/0000-0002-1979-1485 FU U.S. Department of Defense through Armed Forces Pest Management Board FX This research was funded by a grant from the U.S. Department of Defense, Deployed War Fighter Protection Program, through the Armed Forces Pest Management Board. Studies were conducted while G. Wasserberg held a National Research Council (NRC) Research Associateship at the Walter Reed Army Institute of Research. The opinions or assertions contained herein are the private views of the author, and are not to be construed as official, or as reflecting true views of the Department of the Army or the Department of Defense. Research was conducted in compliance with the Animal Welfare Act and other federal statutes and regulations relating to animals and experiments involving animals and adheres to principles stated in the Guide for the Care and Use of Laboratory Animals, MRC Publication, 1996 edition. NR 37 TC 5 Z9 5 U1 0 U2 7 PU SOC VECTOR ECOLOGY PI CORONA PA 1966 COMPTON AVE, CORONA, CA 92881 USA SN 1081-1710 J9 J VECTOR ECOL JI J. Vector Ecol. PD MAR PY 2011 VL 36 SU 1 SI SI BP S148 EP S156 DI 10.1111/j.1948-7134.2011.00125.x PG 9 WC Entomology SC Entomology GA 729CZ UT WOS:000287927300020 PM 21366768 ER PT J AU Berkower, I Spadaccini, A Chen, H Al-Awadi, D Muller, J Gao, Y Feigelstock, D Virnik, K Ni, Y AF Berkower, Ira Spadaccini, Angelo Chen, Hong Al-Awadi, Danah Muller, Jacqueline Gao, Yamei Feigelstock, Dino Virnik, Konstantin Ni, Yisheng TI Hepatitis B Virus Surface Antigen Assembly Function Persists when Entire Transmembrane Domains 1 and 3 Are Replaced by a Heterologous Transmembrane Sequence SO JOURNAL OF VIROLOGY LA English DT Article ID PROXIMAL EXTERNAL REGION; HUMAN MONOCLONAL-ANTIBODY; NEUTRALIZING ANTIBODY; ENVELOPE GLYCOPROTEINS; GP41 EPITOPE; TYPE-1; MEMBRANE; PARTICLES; VACCINE; HIV-1 AB Native hepatitis B surface antigen (HBsAg) spontaneously assembles into 22-nm subviral particles. The particles are lipoprotein micelles, in which HBsAg is believed to span the lipid layer four times. The first two transmembrane domains, TM1 and TM2, are required for particle assembly. We have probed the requirements for particle assembly by replacing the entire first or third TM domain of HBsAg with the transmembrane domain of HIV gp41. We found that either TM domain of HBsAg could be replaced, resulting in HBsAg-gp41 chimeras that formed particles efficiently. HBsAg formed particles even when both TM1 and TM3 were replaced with the gp41 domain. The results indicate remarkable flexibility in HBsAg particle formation and provide a novel way to express heterologous membrane proteins that are anchored to a lipid surface by their own membrane-spanning domain. The membrane-proximal exposed region (MPER) of gp41 is an important target of broadly reactive neutralizing antibodies against HIV-1, and HBsAg-MPER particles may provide a good platform for future vaccine development. C1 [Berkower, Ira; Spadaccini, Angelo; Chen, Hong; Al-Awadi, Danah; Muller, Jacqueline; Gao, Yamei; Feigelstock, Dino; Virnik, Konstantin; Ni, Yisheng] US FDA, Ctr Biol, Bethesda, MD 20892 USA. RP Berkower, I (reprint author), US FDA, Ctr Biol, Bldg 29,Rm 523,NIH Campus, Bethesda, MD 20892 USA. EM ira.berkower@fda.hhs.gov FU NIH FX This research was supported in part by the NIH Intramural AIDS Targeted Research Program. NR 50 TC 7 Z9 8 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2011 VL 85 IS 5 BP 2439 EP 2448 DI 10.1128/JVI.02061-10 PG 10 WC Virology SC Virology GA 716MT UT WOS:000286974900048 PM 21177825 ER PT J AU Balter, S Rosenstein, M Miller, DL Schueler, B Spelic, D AF Balter, Stephen Rosenstein, Marvin Miller, Donald L. Schueler, Beth Spelic, David TI Patient radiation dose audits for fluoroscopically guided interventional procedures SO MEDICAL PHYSICS LA English DT Article DE interventional procedure; skin injury; dose audit; diagnostic reference levels; quality improvement ID DIAGNOSTIC REFERENCE LEVELS; RADIOLOGY PROCEDURES; RAD-IR; EXPOSURE; GUIDELINES; MANAGEMENT; COMPLEXITY; SKIN AB Purpose: Quality management for any use of medical x-ray imaging should include monitoring of radiation dose. Fluoroscopically guided interventional (FGI) procedures are inherently clinically variable and have the potential for inducing deterministic injuries in patients. The use of a conventional diagnostic reference level is not appropriate for FGI procedures. A similar but more detailed quality process for management of radiation dose in FGI procedures is described. Methods: A method that takes into account both the inherent variability of FGI procedures and the risk of deterministic injuries from these procedures is suggested. The substantial radiation dose level (SRDL) is an absolute action level (with regard to patient follow-up) below which skin injury is highly unlikely and above which skin injury is possible. The quality process for FGI procedures collects data from all instances of a given procedure from a number of facilities into an advisory data set (ADS). An individual facility collects a facility data set (FDS) comprised of all instances of the same procedure at that facility. The individual FDS is then compared to the multifacility ADS with regard to the overall shape of the dose distributions and the percent of instances in both the ADS and the FDS that exceed the SRDL. Results: Samples of an ADS and FDS for percutaneous coronary intervention, using the dose metric of reference air kerma (K(a,r)) (i.e., the cumulative air kerma at the reference point), are used to illustrate the proposed quality process for FGI procedures. Investigation is warranted whenever the FDS is noticeably different from the ADS for the specific FGI procedure and particularly in two circumstances: (1) When the facility's local median K(a,r) exceeds the 75th percentile of the ADS and (2) when the percent of instances where K(a,r) exceeds the facility-selected SRDL is greater for the FDS than for the ADS. Conclusions: Analysis of the two data sets (ADS and FDS) and of the percent of instances that exceed the SRDL provides a means for the facility to better manage radiation dose (and therefore both deterministic and stochastic radiation risk) to the patient during FGI procedures. (C) 2011 American Association of Physicists in Medicine. [DOI: 10.1118/1.3557868] C1 [Balter, Stephen] Columbia Univ, Dept Radiol, New York, NY 10032 USA. [Balter, Stephen] Columbia Univ, Dept Med, New York, NY 10032 USA. [Miller, Donald L.] Uniformed Serv Univ Hlth Sci, F Edward Hebert Sch Med, Dept Radiol, Bethesda, MD 20814 USA. [Schueler, Beth] Mayo Clin & Mayo Fdn, Dept Radiol, Rochester, MN 55905 USA. [Spelic, David] US FDA, Div Mammog Qual & Radiat Programs, Silver Spring, MD 20903 USA. RP Balter, S (reprint author), Columbia Univ, Dept Radiol, New York, NY 10032 USA. EM sb2455@columbia.edu; smrmr@msn.com; donald.miller@med.navy.mil; schueler.beth@mayo.edu; david.spelic@fda.hhs.gov FU NCI [5R 24 CA 074296] FX This article was developed as part of the work of National Council on Radiation Protection and Measurements Scientific Committee 2-3 and expands the materials presented in Report 168. The work of SC 2-3 was funded by NCI under Grant No. 5R 24 CA 074296. NR 40 TC 7 Z9 7 U1 3 U2 4 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAR PY 2011 VL 38 IS 3 BP 1611 EP 1618 DI 10.1118/1.3557868 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 728MY UT WOS:000287879400050 ER PT J AU Hsu, CS Hsu, SJ Chen, HC Tseng, TC Liu, CH Niu, WF Jeng, JH Liu, CJ Lai, MY Chen, PJ Kao, JH Chen, DS AF Hsu, Ching-Sheng Hsu, Shih-Jer Chen, Hung-Chia Tseng, Tai-Chung Liu, Chen-Hua Niu, Wei-Fang Jeng, Jenher Liu, Chun-Jen Lai, Ming-Yang Chen, Pei-Jer Kao, Jia-Horng Chen, Ding-Shinn TI Association of IL28B gene variations with mathematical modeling of viral kinetics in chronic hepatitis C patients with IFN plus ribavirin therapy SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID PEGYLATED INTERFERON-ALPHA; VIRUS-INFECTION; IMPORTANT PREDICTOR; ANTIVIRAL THERAPY; CLEARANCE; GENOTYPE; MANAGEMENT; DYNAMICS; DECLINE; LAMBDA AB Asian patients with chronic hepatitis C (CHC) are known to have better virological responses to pegylated (Peg) IFN-based therapy than Western patients. Although IL28B gene polymorphisms may contribute to this difference, whether favorable hepatitis C virus (HCV) kinetics during treatment plays a role remains unclear. We enrolled 145 consecutive Taiwanese patients with CHC receiving Peg-IFN alpha-2a plus ribavirin for the study. Blood samples were taken more frequently at defined intervals in the first 3 d. Peg-IFN was administered at week 1. It was then administered weekly in combination with daily ribavirin for 24 or 48 wk. A mathematical model fitted to the observed HCV kinetics was constructed, which could interpret the transient HCV titer elevation after Peg-IFN treatment. The results demonstrated a comparable viral clearance rate (c = 3.45 +/- 3.73) (day(-1), mean +/- SD) but lower daily viral production rate (P = 10(6)-10(12)) in our patients than those reported previously in Western patients. Of 110 patients with a sustained virological response (SVR), 47 (43%) had a transient elevation of viral titer within 12 h (proportion of 12 h/3 d: 44% in non-SVR vs. 70% in SVR; P = 0.029). Among 91 patients with available rs8099917 data, patients with the TT genotype had an early surge of viral titer after therapy and a higher SVR and viral clearance rate than those with the GT genotype. In conclusion, Taiwanese patients with CHC receiving Peg-IFN plus ribavirin therapy have a lower daily viral production rate than Western patients, and the rs8099917 TT genotype may contribute to the increased viral clearance rate and better virological responses in these patients. C1 [Hsu, Ching-Sheng; Hsu, Shih-Jer; Tseng, Tai-Chung; Liu, Chen-Hua; Liu, Chun-Jen; Lai, Ming-Yang; Chen, Pei-Jer; Kao, Jia-Horng; Chen, Ding-Shinn] Natl Taiwan Univ, Coll Med, Grad Inst Clin Med, Taipei 10002, Taiwan. [Liu, Chen-Hua; Liu, Chun-Jen; Lai, Ming-Yang; Chen, Pei-Jer; Kao, Jia-Horng; Chen, Ding-Shinn] Natl Taiwan Univ, Coll Med, Dept Internal Med, Taipei 10002, Taiwan. [Lai, Ming-Yang; Kao, Jia-Horng] Natl Taiwan Univ, Coll Med, Dept Med Res, Taipei 10002, Taiwan. [Chen, Pei-Jer; Kao, Jia-Horng] Natl Taiwan Univ, Coll Med, Hepatitis Res Ctr, Taipei 10002, Taiwan. [Chen, Pei-Jer; Kao, Jia-Horng] Natl Taiwan Univ Hosp, Taipei 10002, Taiwan. [Hsu, Ching-Sheng; Tseng, Tai-Chung] Buddhist Tzu Chi Gen Hosp, Dept Internal Med, Div Gastroenterol, Taipei 23142, Taiwan. [Hsu, Ching-Sheng] Tzu Chi Univ, Sch Med, Hualien 97002, Taiwan. [Hsu, Shih-Jer] Natl Taiwan Univ Hosp, Yun Lin Branch, Dept Internal Med, Yun Lin Cty 64041, Taiwan. [Chen, Hung-Chia] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Niu, Wei-Fang; Jeng, Jenher] Natl Chiao Tung Univ, Ctr Math Modeling & Sci Comp, Hsinchu 30010, Taiwan. RP Kao, JH (reprint author), Natl Taiwan Univ, Coll Med, Grad Inst Clin Med, Taipei 10002, Taiwan. EM kaojh@ntu.edu.tw; chends@ntu.edu.tw OI LIU, CHUN-JEN/0000-0002-6202-0993; Liu, Chen-Hua/0000-0003-3622-9707; CHEN, DING-SHINN/0000-0001-7791-6154; KAO, JIA-HORNG/0000-0002-2442-7952; Chen, Pei-Jer/0000-0001-8316-3785 FU National Taiwan University Hospital; Department of Health; National Science Council, Executive Yuan, Taiwan FX We thank our colleagues at the National Taiwan University Hospital and its Yun-Lin Branch who helped to enroll and follow the patients, and the research assistants who assisted in laboratory analyses and collected clinical information. This work was supported by grants from the National Taiwan University Hospital; the Department of Health; and the National Science Council, Executive Yuan, Taiwan. NR 46 TC 46 Z9 47 U1 0 U2 2 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAR 1 PY 2011 VL 108 IS 9 BP 3719 EP 3724 DI 10.1073/pnas.1100349108 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 728AD UT WOS:000287844400053 PM 21321200 ER PT J AU Wu, QE Beland, FA Chang, CW Fang, JL AF Wu, Qiangen Beland, Frederick A. Chang, Ching-Wei Fang, Jia-Long TI XPC is essential for nucleotide excision repair of zidovudine-induced DNA damage in human hepatoma cells SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE DNA repair; Nucleotide excision repair; XPC; Zidovudine ID HPRT LYMPHOCYTE MUTANTS; BONE-MARROW MICRONUCLEI; C PROTEIN COMPLEX; CYCLE PROGRESSION; IN-VITRO; 3'-AZIDO-3'-DEOXYTHYMIDINE AZT; TELOMERASE ACTIVITY; TERM EXPOSURE; MICE; FREQUENCY AB Zidovudine (3'-azido-3'-dexoythymidine, AZT), a nucleoside reverse transcriptase inhibitor, can be incorporated into DNA and cause DNA damage. The mechanisms underlying the repair of AZT-induced DNA damage are unknown. To investigate the pathways involved in the recognition and repair of AZT-induced DNA damage, human hepatoma HepG2 cells were incubated with AZT for 2 weeks and the expression of DNA damage signaling pathways was determined using a pathway-based real-time PCR array. Compared to control cultures, damaged DNA binding and nucleotide excision repair (NER) pathways showed significantly increased gene expression. Further analysis indicated that AZT treatment increased the expression of genes associated with NER, including XPC, XPA, RPA1, GTF2H1, and ERCC1. Western blot analysis demonstrated that the protein levels of XPC and GTF2H1 were also significantly up-regulated. To explore further the function of XPC in the repair of AZT-induced DNA damage, XPC expression was stably knocked down by 71% using short hairpin RNA interference. In the XPC knocked-down cells, 100 mu M AZT treatment significantly increased [(3)H] AZT incorporation into DNA, decreased the total number of viable cells, increased the release of lactate dehydrogenase, induced apoptosis, and caused a more extensive G2/M cell cycle arrest when compared to non-transfected HepG2 cells or HepG2 cells transfected with a scrambled short hairpin RNA sequence. Overall, these data indicate that XPC plays an essential role in the NER repair of AZT-induced DNA damage. Published by Elsevier Inc. C1 [Wu, Qiangen; Beland, Frederick A.; Fang, Jia-Long] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Chang, Ching-Wei] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. RP Fang, JL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM jia-long.fang@fda.hhs.gov RI Wu, Qiangen/F-7581-2014 OI Wu, Qiangen/0000-0002-7595-2837 FU Division of Biochemical Toxicology at the National Center for Toxicological Research; National Center for Toxicological Research/U.S. Food and Drug Administration [224-07-0007]; National Institute for Environmental Health Sciences FX QW was supported by an appointment to the Postgraduate Research Program in the Division of Biochemical Toxicology at the National Center for Toxicological Research administered by Oak Ridge Institute for Science Education through an interagency agreement between the U. S. Department of Energy and the FDA.; This research was supported by 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 53 TC 12 Z9 12 U1 0 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAR 1 PY 2011 VL 251 IS 2 BP 155 EP 162 DI 10.1016/j.taap.2010.12.009 PG 8 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 730TI UT WOS:000288056900008 PM 21192964 ER PT J AU Mettler, FA Brenner, D Coleman, CN Kaminski, JM Kennedy, AR Wagner, LK AF Mettler, Fred A., Jr. Brenner, David Coleman, C. Norman Kaminski, Joseph M. Kennedy, Ann R. Wagner, Louis K. TI Can Radiation Risks to Patients Be Reduced Without Reducing Radiation Exposure? The Status of Chemical Radioprotectants SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE chemical radioprotectants; radiation risk ID VITAMIN-E SUPPLEMENTATION; CANCER-RISKS; CT; AGENTS AB OBJECTIVE. Medical radiation exposure has increased sixfold since 1980 and is the largest controllable source of exposure. Many efforts have been devoted to reducing dose or eliminating unnecessary examinations but with limited success. The concern regarding nuclear terrorism has focused a large amount of attention on radioprotective drugs. The purpose of this article is twofold: to review the current concepts, potential, and limitations of chemical radioprotectants in reducing stochastic and deterministic effects and to assess the potential application to diagnostic and interventional medical radiation procedures. CONCLUSION. There are a wide variety of chemical compounds that have been studied for radioprotective effects. Although there is promising research, chemical radioprotectants have not been shown to be very effective and, with one limited exception, are not the standard of care in medicine. C1 [Mettler, Fred A., Jr.] New Mexico VA Hlth Care Serv, Dept Radiol, Albuquerque, NM 87108 USA. [Mettler, Fred A., Jr.] New Mexico VA Hlth Care Serv, Nucl Med Serv, Albuquerque, NM 87108 USA. [Brenner, David] Columbia Univ, Dept Radiol, New York, NY USA. [Coleman, C. Norman] NCI, Dept Radiol, NIH, Rockville, MD USA. [Kaminski, Joseph M.] US FDA, Div Med Imaging Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Kennedy, Ann R.] Univ Penn, Sch Med, Dept Radiat Oncol, Philadelphia, PA 19104 USA. [Wagner, Louis K.] Univ Texas Houston, Sch Med, Dept Radiol, Houston, TX 77030 USA. RP Mettler, FA (reprint author), New Mexico VA Hlth Care Serv, Dept Radiol, 1501 San Pedro Blvd SE, Albuquerque, NM 87108 USA. EM fmettler@salud.unm.edu NR 20 TC 13 Z9 13 U1 0 U2 6 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD MAR PY 2011 VL 196 IS 3 BP 616 EP 618 DI 10.2214/AJR.10.4959 PG 3 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 724OC UT WOS:000287585100038 PM 21343505 ER PT J AU Tian, BH He, MZ Tan, ZW Tang, SX Hewlett, I Chen, SG Jin, YX Yang, M AF Tian, Baohe He, Meizi Tan, Zhiwu Tang, Shixing Hewlett, Indira Chen, Shuguang Jin, Yinxue Yang, Ming TI Synthesis and Antiviral Evaluation of New N-acylhydrazones Containing Glycine Residue SO CHEMICAL BIOLOGY & DRUG DESIGN LA English DT Article DE antiviral activity; HIV-1 capsid assembly; N-acylhydrazone derivatives; synthesis ID HIV-1 CAPSID PROTEIN; HUMAN-IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; IN-VITRO; DERIVATIVES; HYDRAZONE; CYCLOPHILIN; INHIBITION; CHEMISTRY; DISCOVERY AB N-acylhydrazones containing glycine residue 3a-j and 8a-h were synthesized as HIV-1 capsid protein assembly inhibitors. The structures of the novel N-acylhydrazone derivatives were characterized using different spectroscopic methods. Antiviral activity demonstrated that compound 8c bearing 4-methylphenyl moiety was the most active with low cytotoxicity. C1 [Tian, Baohe; He, Meizi; Tan, Zhiwu; Chen, Shuguang; Jin, Yinxue; Yang, Ming] Peking Univ, State Key Lab Nat & Biomimet Drugs, Hlth Sci Ctr, Beijing 100191, Peoples R China. [Tang, Shixing; Hewlett, Indira] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Yang, M (reprint author), Peking Univ, State Key Lab Nat & Biomimet Drugs, Hlth Sci Ctr, POB 261, Beijing 100191, Peoples R China. EM mingy@bjmu.edu.cn FU National Natural Science Foundation of China [30670415] FX This project was supported by the National Natural Science Foundation of China (No. 30670415). NR 33 TC 12 Z9 13 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1747-0277 J9 CHEM BIOL DRUG DES JI Chem. Biol. Drug Des. PD MAR PY 2011 VL 77 IS 3 BP 189 EP 198 DI 10.1111/j.1747-0285.2010.01050.x PG 10 WC Biochemistry & Molecular Biology; Chemistry, Medicinal SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA 718SJ UT WOS:000287146200005 PM 21306567 ER PT J AU Puschner, B Reimschuessel, R AF Puschner, Birgit Reimschuessel, Renate TI Toxicosis Caused by Melamine and Cyanuric Acid in Dogs and Cats: Uncovering the Mystery and Subsequent Global Implications SO CLINICS IN LABORATORY MEDICINE LA English DT Article DE Melamine; Cyanuric acid; Acute renal failure; Crystals; Food adulteration; Toxicosis ID CHROMATOGRAPHY/TANDEM MASS-SPECTROMETRY; TUMOR LYSIS SYNDROME; RENAL-FAILURE; PET FOOD; URINARY-BLADDER; KIDNEY TISSUE; TOXICITY; NEPHROTOXICOSIS; NEPHROLITHIASIS; RATS AB Several major pet-food and human-food safety incidents occurred worldwide between 2003 and 2008, causing illnesses and deaths in children, cats, dogs, and pigs. During the 2007 outbreak of renal failure in dogs and cats in the United States, veterinary diagnostic laboratories helped identify melamine and melamine analogues as contaminants in implicated food. In 2008, thousands of infants developed renal failure from exposure to melamine alone. Management of these outbreaks depends on the collaboration of veterinary and human laboratories and clinics, government agencies, academic institutions, and food industries, along with prompt communication and sharing of data. C1 [Puschner, Birgit] Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, Davis, CA 95616 USA. [Reimschuessel, Renate] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Puschner, B (reprint author), Univ Calif Davis, Sch Vet Med, Dept Mol Biosci, 1120 Haring Hall, Davis, CA 95616 USA. EM bpuschner@ucdavis.edu OI Puschner, Birgit/0000-0001-6765-5085 NR 84 TC 29 Z9 32 U1 2 U2 18 PU W B SAUNDERS CO-ELSEVIER INC PI PHILADELPHIA PA 1600 JOHN F KENNEDY BOULEVARD, STE 1800, PHILADELPHIA, PA 19103-2899 USA SN 0272-2712 J9 CLIN LAB MED JI Clin. Lab. Med. PD MAR PY 2011 VL 31 IS 1 BP 181 EP + DI 10.1016/j.cll.2010.10.003 PG 20 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 727TW UT WOS:000287826400013 PM 21295730 ER PT J AU Oakley, MS Anantharaman, V Venancio, TM Zheng, H Mahajan, B Majam, V McCutchan, TF Myers, TG Aravind, L Kumar, S AF Oakley, Miranda S. Anantharaman, Vivek Venancio, Thiago M. Zheng, Hong Mahajan, Babita Majam, Victoria McCutchan, Thomas F. Myers, Timothy G. Aravind, L. Kumar, Sanjai TI Molecular Correlates of Experimental Cerebral Malaria Detectable in Whole Blood SO INFECTION AND IMMUNITY LA English DT Article ID EXPRESSION; CELLS; ERYTHROPOIETIN; ANGIOPOIETIN-1; SEQUESTRATION; ERYTHROCYTES; PATHOGENESIS; PATHWAYS; CHILDREN; IMMUNE AB Cerebral malaria (CM) is a primary cause of deaths caused by Plasmodium falciparum in young children in sub-Saharan Africa. Laboratory tests based on early detection of host biomarkers in patient blood would help in the prognosis and differential diagnosis of CM. Using the Plasmodium berghei ANKA murine model of experimental cerebral malaria (ECM), we have identified over 300 putative diagnostic biomarkers of ECM in the circulation by comparing the whole-blood transcriptional profiles of resistant mice (BALB/c) to those of two susceptible strains (C57BL/6 and CBA/CaJ). Our results suggest that the transcriptional profile of whole blood captures the molecular and immunological events associated with the pathogenesis of disease. We find that during ECM, erythropoiesis is dysfunctional, thrombocytopenia is evident, and glycosylation of cell surface components may be modified. Furthermore, analysis of immunity-related genes suggests that slightly distinct mechanisms of immunopathogenesis may operate in susceptible C57BL/6 and CBA/CaJ mice. Furthermore, our data set has allowed us to create a molecular signature of ECM composed of a subset of circulatory markers. Complement component C1q, beta-chain, nonspecific cytotoxic cell receptor protein 1, prostate stem cell antigen, DnaJC, member 15, glutathione S-transferase omega-1, and thymidine kinase 1 were overexpressed in blood during the symptomatic phase of ECM, as measured by quantitative real-time PCR analysis. These studies provide the first host transcriptome database that is uniquely altered during the pathogenesis of ECM in blood. A subset of these mediators of ECM warrant validation in P. falciparum-infected young African children as diagnostic markers of CM. C1 [Kumar, Sanjai] FDA, Malaria Res Program, Lab Emerging Pathogens, DETTD,CBER, Rockville, MD 20852 USA. [Oakley, Miranda S.] US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Anantharaman, Vivek; Venancio, Thiago M.; Aravind, L.] NIH, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD 20892 USA. [McCutchan, Thomas F.] NIH, Lab Malaria & Vector Res, Bethesda, MD 20892 USA. [Myers, Timothy G.] NIH, Microarray Res Facil, Res & Technol Branch, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), FDA, Malaria Res Program, Lab Emerging Pathogens, DETTD,CBER, Rockville, MD 20852 USA. EM sanjai.kumar@fda.hhs.gov RI Venancio, Thiago/B-5003-2011; Entomologiamolecular, Inct/J-8214-2013; OI Anantharaman, Vivek/0000-0001-8395-0009 NR 45 TC 8 Z9 10 U1 1 U2 3 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 MAR PY 2011 VL 79 IS 3 BP 1244 EP 1253 DI 10.1128/IAI.00964-10 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 726DY UT WOS:000287700200027 PM 21149594 ER PT J AU Fujisawa, T Nakashima, H Nakajima, A Joshi, BH Puri, RK AF Fujisawa, Toshio Nakashima, Hideyuki Nakajima, Atsushi Joshi, Bharat H. Puri, Raj K. TI Targeting IL-13R alpha 2 in human pancreatic ductal adenocarcinoma with combination therapy of IL-13-PE and gemcitabine SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE interleukin-13 cytotoxin; pancreatic ductal adenocarcinoma; IL-13R alpha 2; gemcitabine; orthotopic mice model ID INTERLEUKIN-13 RECEPTOR ALPHA-2; PHASE-III TRIAL; SQUAMOUS-CELL CARCINOMA; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; ANTITUMOR-ACTIVITY; CANCER-THERAPY; NECK-CANCER; MOUSE MODEL; HUMAN HEAD AB Pancreatic: cancer is an aggressive disease with only limited therapeutic options available. We have identified that 71% pancreatic ductal adenocarcinoma (PDA) express high levels of IL-13R alpha 2, a high-affinity receptor for IL-13. To target IL-13R alpha 2, we have developed a recombinant immunotoxin, which is a fusion of IL-13 and Pseudomonas exotoxin (IL-13-PE). Since IL-13-PE and a commonly used cytotoxic drug gemcitabine act by a different mechanism, we hypothesized that they synergize in mediating antitumor response. Both IL-13-PE and gemcitabine-mediated cytotoxicity to two pancreatic cancer cell lines and when combined synergistic cytotoxicity was observed. This synergism was also demonstrated in vivo in an orthotopic mouse model of human PDA. IL-13-PE and gemcitabine showed complete eradiation of tumors as assessed by whole body imaging of GFP-transfected tumors in 57% of mice in an early cancer model resulting into prolongation of survival. In contrast, monotherapy with either agent did not produce complete eradiation, but tumor volumes were significantly decreased. In advanced PDA model, combination therapy also produced dramatic reduction in tumor growth and enhanced survival compared to animals treated with either agent alone. When IL-13R alpha 2 was knocked-down by RNAi prior to tumor implantation, IL-13-PE and gemcitabine did not synergize indicating that IL-13R alpha 2 is essential. Mechanistically, gemcitabine increased IL-13R alpha 2 expression in vitro and in vivo, which resulted in a synergism of combination therapy. Interestingly, PDA cancer stem cells were resistant to gemcitabine, but not to IL-13-PE. These results suggest that combination therapy with IL-13-PE and gemcitabine may be a useful strategy for PDA therapy. C1 [Fujisawa, Toshio; Nakashima, Hideyuki; Joshi, Bharat H.; 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, Grad 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 38 TC 12 Z9 15 U1 0 U2 2 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 1 PY 2011 VL 128 IS 5 BP 1221 EP 1231 DI 10.1002/ijc.25437 PG 11 WC Oncology SC Oncology GA 716HS UT WOS:000286960300022 PM 20473925 ER PT J AU Guo, XQ Verkler, TL Chen, Y Richter, PA Polzin, GM Moore, MM Mei, N AF Guo, Xiaoqing Verkler, Tracie L. Chen, Ying Richter, Patricia A. Polzin, Gregory M. Moore, Martha M. Mei, Nan TI Mutagenicity of 11 cigarette smoke condensates in two versions of the mouse lymphoma assay SO MUTAGENESIS LA English DT Article ID GENE MUTATION ASSAY; THYMIDINE KINASE LOCUS; GENOTOXICITY TEST PROCEDURES; INTERNATIONAL WORKSHOP; MAINSTREAM SMOKE; TOBACCO-SMOKE; IN-VITRO; REPRESENTATIVE SAMPLE; WORKGROUP REPORT; CELLS AB Cigarette smoke condensate (CSC) is genotoxic in nearly all assays in which it has been tested. In this study, we investigated the mutagenicity of 11 CSCs using the microwell and soft-agar versions of the mouse lymphoma assay (MLA). These CSCs were prepared from commercial or experimental cigarettes, 10 of them were produced using International Organisation for Standardisation (ISO) conditions and one CSC was generated using intense Massachusetts Department of Public Health (MDPH) conditions. In the presence of rat liver S9, the L5178Y/Tk(+/-) mouse lymphoma cells were treated with 11 CSCs at different concentrations (25-200 mu g/ml) for 4 h. All CSCs resulted in dose-dependent increases of both cytotoxicity and mutagenicity in both versions of the MLA. The mutagenic potencies of the CSCs were calculated as mutant frequency per microgram CSC from the slope of the linear regression of the dose-response curves and showed no correlations with the tar yield of the cigarette or nicotine concentrations of the CSCs. Comparing two CSCs produced from the same commercial cigarettes using two different smoking conditions, the one generated under ISO conditions was more mutagenic than the other generated under intense conditions on a per microgram CSC basis. We also examined the loss of heterozygosity (LOH) at four microsatellite loci spanning the entire chromosome 11 for the mutants induced by 11 CSCs. The most common type of mutation observed was LOH with chromosome damage spanning less than similar to 34 Mbp. These results indicate that the MLA identifies different genotoxic potencies among a variety of CSCs and that the results from both versions of the assay are comparable. C1 [Guo, Xiaoqing; Verkler, Tracie L.; Chen, Ying; Moore, Martha M.; Mei, Nan] US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Richter, Patricia A.] Natl Ctr Chron Dis Prevent & Hlth Promot, Off Smoking & Hlth, Atlanta, GA 30341 USA. [Polzin, Gregory M.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA. RP Mei, N (reprint author), US FDA, Div Genet & Mol Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM nan.mei@fda.hhs.gov RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 FU US CDC through the CDC and the U S Food and Drug Administration (FDA)/National Center for Toxicological Research (NCTR); NCTR FX This work was supported by internal funds of the US CDC through an interagency agreement between the CDC and the U S Food and Drug Administration (FDA)/National Center for Toxicological Research (NCTR) and also partly supported by an appointment (X.G.) to the Postgraduate Research Program at the NCTR administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the FDA. NR 47 TC 19 Z9 21 U1 0 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD MAR PY 2011 VL 26 IS 2 BP 273 EP 281 DI 10.1093/mutage/geq083 PG 9 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 726SF UT WOS:000287745700004 PM 20980367 ER PT J AU Xia, Y Bernert, JT Jain, RB Ashley, DL Pirkle, JL AF Xia, Yang Bernert, John T. Jain, Ram B. Ashley, David L. Pirkle, James L. TI Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL) in smokers in the united states: NHANES 2007-2008 SO BIOMARKERS LA English DT Article DE NNAL; NNK; 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone; TSNA; NHANES; smoking; tobacco ID LUNG CARCINOGEN 4-(METHYLNITROSAMINO)-1-(3-PYRIDYL)-1-BUTANONE; NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; CIGARETTE SMOKERS; LIGHT CIGARETTES; WHITE SMOKERS; US POPULATION; HUMAN URINE; EXPOSURE; METABOLITES AB The tobacco-specific carcinogen 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), a metabolite of the tobacco-specific nitrosamine (TSNA) 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), has been measured in urine samples from all participants aged 6 years and older from the National Health and Nutrition Examination Survey 2007--2008. Participants with a serum cotinine concentration of >= a parts per thousand yen10 ng/mL were identified as tobacco users, primarily cigarette smokers. Regression models were developed to calculate geometric mean NNAL concentrations adjusted for serum cotinine, urinary creatinine, cigarettes per day, and Federal Trade Commission tar values of the cigarettes smoked. Significant differences were found by gender (p == 0.003) and race/ethnicity (p == 0.022 for non-Hispanic white versus non-Hispanic black smokers), but not by menthol type of the cigarettes. Females and non-Hispanic white smokers had the highest adjusted means for urinary NNAL (353 and 336 pg/mL, respectively). The results from this study demonstrated significant relationships between NNAL concentrations and serum cotinine (p < 0.001) and urine creatinine (p < 0.001). The joint effect of linear and quadratic terms for number of cigarettes smoked per day was also statistically significant (p == 0.001). In addition to addressing current NNK exposure levels, these results will form a baseline for future estimates of tobacco users'' exposure to this carcinogen.= 2 points had particularly good sensitivity and specificity (95% and 83%, respectively) for prediction of large CMR-LGE, and a QRS score >= 7 points had particularly high specificity (92% and 89%, respectively) for predicting significant left ventricular dysfunction and history of VT. Conclusions The wide availability of 12-lead ECG makes it an attractive screening tool and may enhance clinical risk stratification of patients at risk for more severe, symptomatic Chagas' heart disease. C1 [Strauss, David G.; Lima, Joao A. C.; Wu, Katherine C.] Johns Hopkins Med Inst, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Strauss, David G.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Cardoso, Savio; Rochitte, Carlos E.] Univ Sao Paulo, Sch Med, Heart Inst InCor, Sao Paulo, Brazil. RP Wu, KC (reprint author), Johns Hopkins Univ Hosp, Div Cardiol, 600 N Wolfe St,Carnegie 568, Baltimore, MD 21287 USA. EM kwu@jhmi.edu RI Strauss, David/A-9211-2012 FU Sarnoff Cardiovascular Research Foundation (Great Falls, Virginia, USA); FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brazil) [01/04358-0]; Donald W. Reynolds Cardiovascular Research Center at Johns Hopkins University (Baltimore, Maryland, USA); Zerbini Foundation FX DGS was supported by the Sarnoff Cardiovascular Research Foundation (Great Falls, Virginia, USA), and has subsequently moved to the US Food and Drug Administration. CER was supported by FAPESP (Fundacao de Amparo a Pesquisa do Estado de Sao Paulo, Brazil) grant 01/04358-0 and the Zerbini Foundation. KCW was supported by the Donald W. Reynolds Cardiovascular Research Center at Johns Hopkins University (Baltimore, Maryland, USA). NR 30 TC 23 Z9 23 U1 0 U2 3 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 1355-6037 J9 HEART JI Heart PD MAR PY 2011 VL 97 IS 5 BP 357 EP 361 DI 10.1136/hrt.2010.210047 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 716KX UT WOS:000286968600004 PM 21245474 ER PT J AU Yang, L Wang, KJ Wang, LS Jegga, AG Qin, SY He, G Chen, J Xiao, Y He, L AF Yang, Lun Wang, Ke-Jian Wang, Li-Shan Jegga, Anil G. Qin, Sheng-Ying He, Guang Chen, Jian Xiao, Yue He, Lin TI Chemical-protein Interactome and Its Application in Off-target Identification SO INTERDISCIPLINARY SCIENCES-COMPUTATIONAL LIFE SCIENCES LA English DT Article DE drug repositioning; adverse drug reaction; chemical-protein interactome; off-target; off-system AB Drugs exert their therapeutic and adverse effects by interacting with molecular targets. Although designed to interact with specific targets in a desirable manner, drug molecules often bind to unexpected proteins (off-targets). By activating or inhibiting off-targets and the associated biological processes and pathways, the resulting chemical-protein interactions can influence drug reaction directly or indirectly. Exploring the relationship between drug and off-targets and the downstream drug reaction can help understand the polypharmacology of the drug, hence significantly advance the drug repositioning pipeline and the application of personalized medicine in understanding and preventing adverse drug reaction. This review summarizes works on predicting off-targets via chemical-protein interactome (CPI), an interaction strength matrix of drugs across multiple human proteins aiming at exploring the unexpected drug-protein interactions, with a variety of computational strategies, including docking, chemical structure comparison and text-mining etc. Effective recall on previous knowledge, de novo prediction and subsequent experimental validation conferred us strong confidence in these methods. Such studies present prospect of large scale in silico methodologies for off-target discovery with low cost and high efficiency. C1 [Yang, Lun; Wang, Ke-Jian; Wang, Li-Shan; Qin, Sheng-Ying; He, Guang; Chen, Jian; Xiao, Yue; He, Lin] Shanghai Jiao Tong Univ, Bio X Ctr, Key Lab Genet Dev & Neuropsychiat Disorders, Minist Educ, Shanghai 200030, Peoples R China. [Yang, Lun; He, Lin] Fudan Univ, Inst Biomed Sci, Shanghai 200032, Peoples R China. [Jegga, Anil G.] Cincinnati Childrens Hosp Med Ctr, Div Biomed Informat, Cincinnati, OH 45229 USA. [Jegga, Anil G.] Univ Cincinnati, Dept Pediat, Cincinnati, OH 45221 USA. [Jegga, Anil G.] Univ Cincinnati, Dept Comp Sci, Cincinnati, OH 45221 USA. [He, Lin] Chinese Acad Sci, Shanghai Inst Biol Sci, Inst Nutr Sci, Shanghai 200031, Peoples R China. RP Yang, L (reprint author), US FDA, Ctr Bioinformat, Div Syst Biol, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. EM lun.yang@gmail.com; helinhelin3@gmail.com RI Jegga, Anil/H-6140-2011 OI Jegga, Anil/0000-0002-4881-7752 FU National Natural Science foundation of China [30900841, 30900799] FX We thank National Natural Science foundation of China (No. 30900841 and No. 30900799) for the financial support of this work. We acknowledge the help of Ron Bryson, Technical Writer, Division of Biomedical Informatics, CCHMC, OH, USA, in language editing this article. NR 59 TC 17 Z9 19 U1 1 U2 12 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1913-2751 J9 INTERDISCIP SCI JI Interdiscip. Sci. PD MAR PY 2011 VL 3 IS 1 BP 22 EP 30 DI 10.1007/s12539-011-0051-8 PG 9 WC Mathematical & Computational Biology SC Mathematical & Computational Biology GA V28VX UT WOS:000208709400003 PM 21369884 ER EF