FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Cederroth, CR Vinciguerra, M Kuhne, F Madani, R Doerge, DR Visser, TJ Foti, M Rohner-Jeanrenaud, F Vassalli, JD Nef, S AF Cederroth, Christopher R. Vinciguerra, Manlio Kuehne, Francoise Madani, Rime Doerge, Daniel R. Visser, Theo J. Foti, Michelangelo Rohner-Jeanrenaud, Francoise Vassalli, Jean-Dominique Nef, Serge TI A phytoestrogen-rich diet increases energy expenditure and decreases adiposity in mice SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE AgRP; endocrine disruptors; isoflavones; lipid oxidation; obesity; phytoestrogens ID AGOUTI-RELATED PROTEIN; ESTROGEN-RECEPTOR-ALPHA; POSTMENOPAUSAL WOMEN; SOY ISOFLAVONES; NEUROPEPTIDE-Y; BODY-WEIGHT; TISSUE; BETA; GENISTEIN; OBESITY AB BACKGROUND: Obesity is an increasingly prevalent health problem, and natural effective therapeutic approaches are required to prevent its occurrence. Phytoestrogens are plant-derived compounds with estrogenic activities; they can bind to both estrogen receptors alpha and beta and mimic the action of estrogens on target organs. OBJECTIVES: The purpose of this study was to examine the influence of soy-derived phytoestrogens on energy balance and metabolism. METHODS: Male outbred mice (CD-1) were allowed ad libitum access to either a high soy-containing diet or a soy-free diet from conception to adulthood. We measured circulating serum isoflavone levels using reverse-phase solid-phase extraction for subsequent liquid chromatography electrospray tandem mass spectrometry analysis. Adult animals were analyzed for body composition by dual-energy X-ray absorptiometry, locomotor activity by running-wheel experiments, respiratory exchange rate by indirect calorimetry, and food intake using metabolic cages. Quantitative reverse transcriptase-polymerase chain reaction was performed to determine the expression of hypothalamic neuropeptide genes. RESULTS: We found that adult mice fed a soy-rich diet had reduced body weight, adiposity, and resistance to cold. This lean phenotype was associated with an increase in lipid oxidation due to a preferential use of lipids as fuel source and an increase in locomotor activity. The modulation of energy balance was associated with a central effect of phytoestrogens on the expression of hypothalamic neuropeptides, including agouti-related protein. CONCLUSION: The data suggest that dietary soy could have beneficial effects on obesity, but they also emphasize the importance of monitoring the phytoestrogen content of diets as a parameter of variability in animal experiments. C1 Univ Geneva, Dept Genet Med & Dev, Geneva, Switzerland. Univ Geneva, Natl Ctr Competence Res Frontiers Genet, Geneva, Switzerland. Univ Geneva, Fac Med, Dept Cellular Physiol & Metab, Geneva, Switzerland. Natl Ctr Toxicol Res, Jefferson, AR USA. Dept Internal Med, Erasmus Med Ctr, Rotterdam, Netherlands. Univ Geneva, Dept Internal Med, CH-1211 Geneva 4, Switzerland. RP Nef, S (reprint author), Univ Geneva, Fac Med, Dept Genet Med & Dev, Rue Michel Servet 1, CH-1211 Geneva, Switzerland. EM Serge.Nef@medecine.unige.ch RI Cederroth, Christopher/B-9539-2008; Cederroth, Christopher/B-9932-2011; OI Cederroth, Christopher/0000-0001-7267-5136 NR 35 TC 64 Z9 66 U1 0 U2 7 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 OCT PY 2007 VL 115 IS 10 BP 1467 EP 1473 DI 10.1289/ehp.10413 PG 7 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 216UQ UT WOS:000249904900039 PM 17938737 ER PT J AU Stafstrom, CE Rho, JM Patel, MN Bough, KJ Roopra, A AF Stafstrom, Carl E. Rho, Jong M. Patel, Manisha N. Bough, Kristopher J. Roopra, Avtar TI Metabolic control of epilepsy SO EPILEPSIA LA English DT Meeting Abstract CT 61st Annual Meeting of the American-Epilepsy-Society CY NOV 13-DEC 04, 2007 CL Philadelphia, PA SP Amer Epilepsy Soc C1 [Stafstrom, Carl E.; Roopra, Avtar] Univ Wisconsin, Dept Neurol, Madison, WI USA. [Rho, Jong M.] Barrow Neurol Inst, Phoenix, AZ 85013 USA. [Patel, Manisha N.] Univ Colorado, Dept Med, Denver, CO 80202 USA. [Bough, Kristopher J.] US FDA, Ctr Drug Evaluat & Res, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0013-9580 J9 EPILEPSIA JI Epilepsia PD OCT PY 2007 VL 48 SU 6 BP 407 EP 407 PG 1 WC Clinical Neurology SC Neurosciences & Neurology GA 259CY UT WOS:000252917901092 ER PT J AU Lee, N Gannavaram, S Selvapandiyan, A Debrabant, A AF Lee, Nancy Gannavaram, Sreenivas Selvapandiyan, Angamuthu Debrabant, Alain TI Characterization of metacaspases with trypsin-like activity and their putative role in programmed cell death in the protozoan parasite Leishmania SO EUKARYOTIC CELL LA English DT Article ID VACUOLAR H+-PYROPHOSPHATASE; CASPASE-LIKE ACTIVITY; TRYPANOSOMA-CRUZI; APOPTOSIS; DONOVANI; YEAST; ACIDOCALCISOMES; DOMAINS; IDENTIFICATION; PROMASTIGOTES AB In this report, we have characterized two metacaspases of Leishmania donovani, L. donovani metacaspase-1 (LdMC1) and LdMC2. These two proteins show 98% homology with each other, and both contain a characteristic C-terminal proline-rich domain. Both genes are transcribed in promastigotes and axenic amastigotes of L. donovani; however, LdMC1 shows increased mRNA levels in axenic amastigotes. An anti-LdMC antibody was obtained and showed reactivity with a single similar to 42-kDa protein band in both promastigote and axenic amastigote parasite whole-cell lysates by Western blotting. Pulse-chase experiments suggest that LdMCs are not synthesized as proenzymes, and immunofluorescence studies show that LdMCs are associated with the acidocalcisome compartments of L. donovani. Enzymatic assays of immunoprecipitated LdMCs show that native LdMCs efficiently cleave trypsin substrates and are unable to cleave caspase-specific substrates. Consistently, LdMC activity is insensitive to caspase inhibitors and is efficiently inhibited by trypsin inhibitors, such as leupeptin, antipain, and N-alpha-tosyl-L-lysine-chloromethyl ketone (TLCK). In addition, our results show that LdMC activity was induced in parasites treated with hydrogen peroxide, a known trigger of programmed cell death (PCD) in Leishmania and that parasites overexpressing metacaspases are more sensitive to hydrogen peroxide-induced PCD. These findings suggest that Leishmania metacaspases are not responsible for the caspase-like activities reported in this organism and suggest a possible role for LdMCs as effector molecules in Leishmania PCD. C1 Ctr Biol Evaluat & Res, US FDA, Lab Bacter Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. RP Debrabant, A (reprint author), CBER, FDA, 29 Lincoln Dr, Bldg 29 Rm 425,HFM-310, Bethesda, MD 20892 USA. EM alain.debrabant@fda.hhs.gov NR 43 TC 85 Z9 86 U1 1 U2 6 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 OCT PY 2007 VL 6 IS 10 BP 1745 EP 1757 DI 10.1128/EC.00123-07 PG 13 WC Microbiology; Mycology SC Microbiology; Mycology GA 220XO UT WOS:000250190800005 PM 17715367 ER PT J AU Gilbert, JM White, DG McDermott, PF AF Gilbert, Jeffrey M. White, David G. McDermott, Patrick F. TI The US national antimicrobial resistance monitoring system SO FUTURE MICROBIOLOGY LA English DT Article DE antimicrobial resistance; foodborne pathogens; risk assessment ID CAMPYLOBACTER-JEJUNI; UNITED-STATES; ESCHERICHIA-COLI; FOOD ANIMALS; CIPROFLOXACIN RESISTANCE; SUSCEPTIBILITY PATTERNS; SALMONELLA-TYPHIMURIUM; ENTEROCOCCUS-FAECIUM; GENETIC RELATEDNESS; DNA MICROARRAY AB The use of antimicrobial agents in food animals can select for resistant bacterial pathogens that may be transmitted to humans via the commercial meat supply. In the USA, the FDA's Center for Veterinary Medicine regulatory duties require a determination that antimicrobial drugs are safe and effective for use in food animals. In addition, a qualitative assessment of risks to human health from antimicrobial resistance requires development. This risk assessment process is supported by data generated by the FDA's National Antimicrobial Resistance Monitoring System (NARMS) for enteric bacteria. NARMS data on antimicrobial susceptibility among Salmonella, Campylobacter, Escherichia coli and Enterococcus is collected. Research activities defining the genetic bases of resistance helps to understand the potential public health risks posed by the spread of antimicrobial resistance from food animal antimicrobial use. These activities help insure that antimicrobials are used judiciously to promote human and animal health. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. RP McDermott, PF (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM patrick.mcdermort@fda.bhs.gov NR 39 TC 20 Z9 20 U1 2 U2 5 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1746-0913 J9 FUTURE MICROBIOL JI Future Microbiol. PD OCT PY 2007 VL 2 IS 5 BP 493 EP 500 DI 10.2217/17460913.2.5.493 PG 8 WC Microbiology SC Microbiology GA 224UD UT WOS:000250471100012 PM 17927472 ER PT J AU Oki, M Ma, L Wang, Y Hatanaka, A Miyazato, C Tatebayashib, K Nishitani, H Uchida, H Nishirnoto, T AF Oki, Masaya Ma, Li Wang, Yoriggang Hatanaka, Akira Miyazato, Chic Tatebayashib, Kazuo Nishitani, Hideo Uchida, Hiroyuki Nishirnoto, Takeharu TI Identification of novel suppressors for Mog1 implies its involvement in RNA metabolism, lipid metabolism and signal transduction SO GENE LA English DT Article DE Cid13; Crp79; Ntf2p/Nxt2; Ran; Ssp1 ID RAN-BINDING-PROTEIN; SACCHAROMYCES-CEREVISIAE; SCHIZOSACCHAROMYCES-POMBE; CRYSTAL-STRUCTURE; MESSENGER-RNA; FISSION YEAST; NUCLEAR IMPORT; NTF2; HOMOLOG; GENE AB Mog1 is conserved from yeast to mammal, but its function is obscure. We isolated yeast genes that rescued a temperature-sensitive death of S. cerevisiae Scmog1 Delta, and of S. pombe Spmog1(ts). Scmog1 Delta was rescued by Opi3p, a phospholipid N-methyltransferase, in addition to S. cerevisiae Ran-homologue Gsp1p, and a RanGDP binding protein Ntf2p. On the other hand, Spmog1(ts) was rescued by Cid13 that is a poly (A) polymerase specific for suc22(+) mRNA encoding a subunit of ribonucleotide reductase, SspI that is a protein kinase involved in stress response pathway, and Crp79 that is required for mRNA export, in addition to Spi1, S. pombe Ran-homologue, and Nxt2, S. pombe homologue of Ntf2p. Consistent with the identification of those suppressors, lack of ScMog1p dislocates Opi3p from the nuclear membrane and all of Spmog1(ts) showed the nuclear accumulation of mRNA. Furthermore, SpMog1 was co-precipitated with Nxt2 and Cid13. (c) 2007 Elsevier B.V. All rights reserved. C1 Kyushu Univ, Grad Sch Med Sci, Dept Mol Biol, Fukuoka 812, Japan. Univ Tokyo, Inst Med Sci, Div Mol Cell Signaling, Tokyo 108, Japan. Univ Fukui, Fac Engn, Dept Appl Chem & Biotechnol, Fukui 910, Japan. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NIH, NICHD, Lab Gene Regulat & Dev, Bethesda, MD 20892 USA. Univ Hyogo, Grad Sch Life Sci, Lab Biol Signaling, Hyogo 678, Japan. RP Nishirnoto, T (reprint author), Kyushu Univ, Grad Sch Med Sci, Dept Mol Biol, Fukuoka 812, Japan. EM tnishi@molbiol.med.kyushu-u.ac.jp NR 36 TC 3 Z9 3 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD OCT 1 PY 2007 VL 400 IS 1-2 BP 114 EP 121 DI 10.1016/j.gene.2007.06.012 PG 8 WC Genetics & Heredity SC Genetics & Heredity GA 211QY UT WOS:000249539600014 PM 17651922 ER PT J AU Lu, H Choudhuri, S Ogura, K Csanaky, I Song, PZ Lei, XH Chen, C Cheng, XG Klaassen, C AF Lu, Hong Choudhuri, Supratim Ogura, Kenichiro Csanaky, Ivan Song, Pei-zhen Lei, Xioohong Chen, Chuan Cheng, Xingguo Klaassen, Curtis TI Characterization of mice null for liver-specific uptake transporter organic anion transporting polypeptide 1b2 (Oatp1b2) SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 Univ Kansas, Med Ctr, Kansas City, KS 66103 USA. Food & Drug Adm, College Pk, MD USA. RI Csanaky, Ivan/N-5312-2015 OI Csanaky, Ivan/0000-0001-7870-4129 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 174 BP 314A EP 314A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400180 ER PT J AU Witanabe, H Wells, F Zhang, P Major, ME AF Witanabe, Hisayoshi Wells, Frances Zhang, Pei Major, Marian E. TI Neutralizing antibody induction in monotypic hepatitis C virus infections in chimpanzees does not correlate with outcome SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 US FDA, CBER, Lab Hepatitis Viruses, Div Viral Prod, Bethesda, MD 20014 USA. US FDA, CBER, Div Hematol, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 446 BP 437A EP 437A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910400452 ER PT J AU Brown, CA Smith, F Laessig, KA AF Brown, Charlene A. Smith, Fraser Laessig, Katherine A. TI Creatine kinase (CK) elevations and muscle toxicities associated with chronic telbivudine (LDT) use in prospective clinical trials SO HEPATOLOGY LA English DT Meeting Abstract CT 58th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY NOV 02-06, 2007 CL Boston, MA SP Amer Assoc Study Liver Dis C1 US FDA, Ctr Drug Evaluat & Res, Off Antimicrobial Prod, Div Antiviral Prod, Silver Spring, MD USA. US FDA, Ctr Drug Evaluat & Res, Off Biostat, Div Biometr 4, Silver Spring, MD USA. US FDA, Ctr Drug Evaluat & Res, Off Antimicrobial Prod, Div Antiinfect & Ophthalmol Prod, Silver Spring, MD USA. NR 0 TC 3 Z9 4 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD OCT PY 2007 VL 46 IS 4 SU S MA 940 BP 655A EP 655A PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 216WT UT WOS:000249910401203 ER PT J AU Tornoe, CW Tworzyanski, JJ Imoisili, MA Alexander, JJ Korth-Bradley, JM Gobburu, JVS AF Tornoe, Christoffer W. Tworzyanski, Jeffrey J. Imoisili, Menfo A. Alexander, John J. Korth-Bradley, Joan M. Gobburu, Jogarao V. S. TI Optimising piperacillin/tazobactam dosing in paediatrics SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE paediatric dosing; anti-infectives; pharmacometric analysis ID PHARMACOKINETICS; CHILDREN; INFANTS AB Piperacillin/tazobactam, an intravenous antibacterial combination product, has recently been approved for paediatric (age 2 months to 17 years) use in the USA. The purpose of this analysis is to describe the basis for the dosing recommendations in this age group. Pharmacokinetic (PK) parameters and demographic covariates from 53 children enrolled in two paediatric studies were used in the analysis. Individual drug clearance (CL) values calculated by non-compartmental methods were available. The influence of demographic covariates on CL was investigated by non-linear regression. The analysis identified CL to be dependent on body weight. CL was also found to be influenced by age in paediatric patients <= 2 years, which is consistent with the expectation based on maturation of renal function. The population PK analysis and simulations, milising comparable adult exposures as a basis to explore optimal dosing, resulted in the following dosing recommendations: for paediatric patients >= 9 months, a dose of 100/12.5 mg/kg every 8h showed exposures similar to adults; for paediatric patients aged 2-9 months, the dose of 100/12.5 ma/kg should be reduced by a factor of 0.8 (i.e. 80/10mg/kg), likely due to immature renal function. Based upon this analysis, dosing recommendations for paediatric patients down to 2 months of age were incorporated in the labelling. No data were available to allow additional recommendations for paediatric patients <2 months of age to be made. (C) 2007 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD USA. Wyeth Ayerst Res, Early Dev & Clin Pharmacol, Collegeville, PA 19426 USA. RP Tornoe, CW (reprint author), US FDA, Off Clin Pharmacol, 10903 New Hampshire Ave,Bldg 21,Rm 3665, Silver Spring, MD 20993 USA. EM christoffer.tornoe@fda.hhs.gov NR 8 TC 16 Z9 16 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0924-8579 J9 INT J ANTIMICROB AG JI Int. J. Antimicrob. Agents PD OCT PY 2007 VL 30 IS 4 BP 320 EP 324 DI 10.1016/j.ijantimicag.2007.05.014 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 220LM UT WOS:000250158200005 PM 17631983 ER PT J AU Wu, H Heilweil, EJ Hussain, AS Khan, MA AF Wu, Huiquan Heilweil, Edwin J. Hussain, Ajaz S. Khan, Mansoor A. TI Process analytical technology (PAT): Effects of instrumental and compositional variables on terahertz spectral data quality to characterize pharmaceutical materials and tablets SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE process analytical technology (PAT); terahertz spectroscopy; measurement process; crystalline materials; amorphous state; characterization; masstransfer analysis ID NEAR-INFRARED SPECTROSCOPY; LIQUID WATER; CRYSTALLIZATION PROCESSES; PULSED SPECTROSCOPY; DYNAMICS; DESIGN; CRYSTALLINITY; POLYMORPHISM; PERSPECTIVE; UNIFORMITY AB The aim of this study was to use terahertz spectroscopy to characterize pharmaceutical materials and tablets, and to understand the effects of measuring conditions and compositional variability on the data quality. Tests were performed on five formulation components (theophylline, lactose, starch, Avicel, magnesium stearate) and a series of tablets composed of various concentrations of theophylline and excipients. Transmission spectra of polyethylene (PE) disks derived from each of the samples were analyzed. Three factors (component loading, component chemistry, and disk drying time) were screened as critical factors associated with the magnitude and location of THz absorbance peaks. Applying the standard sample spectra divided by PE reference spectra ratio method revealed that, to a large extent, PE was responsible for the disk drying time dependence. Direct spectral feature analysis along with mass-transfer analysis of the disk drying process revealed THz absorption peak maxima of lactose (255 cm(-1)) and water (54 and 210 cm(-1)) which is also supported by literature values for the peak maxima assignment for water. Particle scattering due to specimen and PE was found to be also partially responsible for the observed spectral intensities. The importance of THz spectroscopy was demonstrated for characterization of pharmaceutical materials and tablet. Published by Elsevier B.V. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Prod Qual Res,HFD 940,Off Testing & Res, Silver Spring, MD 20993 USA. Natl Inst Stand & Technol, Phys Lab, Opt Technol Div, Gaithersburg, MD 20899 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Wu, H (reprint author), US FDA, CDER, OPS, OTR,DPQR,HFD 940,Div Prod Qual Res, Life Sci Bldg 64,Room 1080,FDA White Oak Campus, Silver Spring, MD 20993 USA. EM huiquan.wu@fda.hhs.gov FU PHS HHS [CDER RSR-04-16] NR 37 TC 45 Z9 46 U1 0 U2 28 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD OCT 1 PY 2007 VL 343 IS 1-2 BP 148 EP 158 DI 10.1016/j.ijpharm.2007.05.014 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 219BV UT WOS:000250060600018 PM 17590292 ER PT J AU Tang, SX Zhao, JQ Storhoff, JJ Norris, PJ Little, RF Yarchoan, R Stramer, SL Patno, T Domanus, M Dhar, A Mirkin, CA Hewlett, IK AF Tang, Shixing Zhao, Jiangqin Storhoff, James J. Norris, Philip J. Little, Richard F. Yarchoan, Robert Stramer, Susan L. Patno, Tim Domanus, Marc Dhar, Arindam Mirkin, Chad A. Hewlett, Indira K. TI Nanoparticle-based biobarcode amplification assay (BCA) for sensitive and early detection of human immunodeficiency type 1 capsid (p24) antigen SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE HIV-1; p24 antigen; nanoparticle; biobarcode; detection ID HEAT-DENATURED PLASMA; VIRUS TYPE-1; HIV-1 P24; ANTIRETROVIRAL THERAPY; SIGNAL AMPLIFICATION; DNA DETECTION; VIRAL-RNA; PROBES; PROTEINS; ANTIBODY AB Nanotechnology-based techniques are being widely evaluated in medical testing and could provide a new generation of diagnostic assays due to their high degrees of sensitivity, high specificity, multiplexing capabilities, and ability to operate without enzymes. In this article, we have modified a nanoparticle-based biobarcode amplification (BCA) assay for early and sensitive detection of HIV-1 capsid (p24) antigen by using antip24 antibody-coated microplates to capture viral antigen (p24) and streptavidin-coated nanoparticle-based biobarcode DNAs for signal amplification, followed by detection using a chip-based scanometric method. The modified BCA assay exhibited a linear dose-dependent pattern within the detection range of 0.1 to 500 pg/ml and was approximately 150-fold more sensitive than conventional enzyme-linked immunosorbent assay (ELISA). No false positive results were observed in 30 HIV-1-negative samples, while all 45 HIV-1 RNA positive samples were found HIV-1 p24 antigen positive by the BCA assay. In addition, the BCA assay detected HIV-1 infection 3 days earlier than ELISA in seroconversion samples. Preliminary evaluation based on testing a small number of samples indicates that the HIV-1 p24 antigen BCA may provide a new tool for sensitive and early detection of HIV 1 p24 antigen in settings where HIV-1 RNA testing is currently not routinely performed. C1 US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bethesda, MD 20892 USA. Nanosphere, N Brook, IL USA. Univ Calif San Francisco, Blood Syst Res Inst, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA. Univ Calif San Francisco, Dept Med, San Francisco, CA USA. NCI, Natl Inst Hlth, HIV & AIDS Malilgnancy Branch, Bethesda, MD 20892 USA. Amer Red Cross, Biomed Serv Sci Support Off, Gaithersburg, MD USA. US FDA, NCI, Interagcy Oncol Task Force, Bethesda, MD 20014 USA. Northwestern Univ, Dept Chem, Evanston, IL USA. Northwestern Univ, Int Inst Nanotechnol, Evanston, IL USA. RP Tang, SX (reprint author), US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Bldg 29B,Rm 4NN16,8800 Rcokville Pike, Bethesda, MD 20892 USA. EM shixing.tang@fda.hhs.gov; indira.hewlett@fda.hhs.gov RI Mirkin, Chad/E-3911-2010 NR 39 TC 49 Z9 54 U1 5 U2 28 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD OCT 1 PY 2007 VL 46 IS 2 BP 231 EP 237 DI 10.1097/QAI.0b013e31814a554b PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 215LO UT WOS:000249810100015 PM 17693896 ER PT J AU Brzezinski, JL Craft, DL AF Brzezinski, Jennifer L. Craft, David L. TI Evaluation of an in vitro bioassay for the detection of purified ricin and castor bean in beverages and liquid food matrices SO JOURNAL OF FOOD PROTECTION LA English DT Article ID RIBOSOME-INACTIVATING PROTEINS; LEUKEMIC T-CELLS; NORMAL LYMPHOCYTES; ENZYMATIC-ACTIVITY; T-2 TOXIN; ASSAY; AGENTS; QUANTITATION; BIOWARFARE; TOXICITY AB The potential use of ricin as a biological weapon in food highlights the necessity for the development of food-specific detection methods. Current methods for the detection of ricin consist of various immunoassays, which detect only one subunit of the ricin toxin and therefore may not be indicative of a biologically active molecule. An in vivo assay, such as a mouse bioassay, can indicate the biological activity of the toxin; however, this method is not feasible for laboratories that do not have animal testing facilities. The purpose of this study was to develop an in vitro assay for the detection of biologically active ricin in beverages and liquid foods. Acidic and high-protein beverages were spiked with either purified ricin or ground castor beans and added to cultured human Jurkat cells. After an overnight incubation, the supernatant was tested for lactate dehydrogenase (LDH) activity with a colorimetric assay. LDH was released from the cytosol upon cell damage and was positively correlated with cell death. Ricin was detectable in all the matrices tested, with a sensitivity of 10 to 100 pg/ml. Biologically active ricin was detectable in all the matrices incubated with ground castor bean material. This method provides a confirmatory way to detect biologically active ricin that can be utilized by laboratories lacking animal facilities. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Brzezinski, JL (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM jennifer.brzezinski@fda.hhs.gov NR 38 TC 15 Z9 15 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 OCT PY 2007 VL 70 IS 10 BP 2377 EP 2382 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 219WN UT WOS:000250119000021 PM 17969621 ER PT J AU Juang, YT Sumibcay, L Tolnay, M Wang, Y Kyttaris, VC Tsokos, GC AF Juang, Yuang-Taung Sumibcay, Laarni Tolnay, Mate Wang, Ying Kyttaris, Vasileios C. Tsokos, George C. TI Elf-1 binds to GGAA elements on the FcR gamma promoter and represses its expression SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR ZETA-CHAIN; T-CELL-RECEPTOR; SYSTEMIC-LUPUS-ERYTHEMATOSUS; AFFINITY IGE RECEPTOR; GENE; TRANSCRIPTION; ETS; SYK; STIMULATION; SUBUNIT AB The Fe receptor (FcR) gamma-chain has been shown to be up-regulated in T cells when the TCR zeta-chain is decreased. We demonstrate that Elf-1, but not other Ets family transcription factors, bind to a cluster of GGAA sites located within the 200 bp upstream from the transcription initiation site of the FcR gamma promoter. Forced expression of Elf-1 results in the suppression of FcR gamma expression, whereas silencing its expression with small interfering RNA Elf-1 results in increased FcR gamma expression. Elf-1 represents the first transcription factor identified to be involved in the transcriptional regulation of FcR gamma, and cells that fail to express Elf-1, as is the case with human systemic lupus erythematosus T cells, will express FcR gamma-chain. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02115 USA. Walter Reed Army Inst Res, Dept Cellular Injury, Silver Spring, MD 20910 USA. Beth Israel Deaconess Med Ctr, Div Rheumatol, Boston, MA 02115 USA. Ctr Drug Evaluat & Res, Food & Drug Adm, Div Monoclonal Antibodies, Rockville, MD 20857 USA. RP Tsokos, GC (reprint author), Beth Israel Deaconess Med Ctr, 4 Blackfan Circle,HIM-244, Boston, MA 02115 USA. EM gtsokos@bidmc.harvard.edu FU NIAID NIH HHS [R01 AI42269, R01 AI49954] NR 19 TC 9 Z9 12 U1 2 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD OCT 1 PY 2007 VL 179 IS 7 BP 4884 EP 4889 PG 6 WC Immunology SC Immunology GA 214QB UT WOS:000249752100067 PM 17878388 ER PT J AU He, Y Manischewitz, J Meseda, CA Merchlinsky, M Vassell, RA Sirota, L Berkower, I Golding, H Weiss, CD AF He, Yong Manischewitz, Jody Meseda, Clement A. Merchlinsky, Michael Vassell, Russell A. Sirota, Lev Berkower, Ira Golding, Hana Weiss, Carol D. TI Antibodies to the A27 protein of vaccinia virus neutralize and protect against infection but represent a minor component of Dryvax vaccine-induced immunity SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Meeting on Antibodies for Poxviral Infections CY JAN 30, 2006 CL Bethesda, MD ID 14-KILODALTON ENVELOPE PROTEIN; INTRANASAL POXVIRUS CHALLENGE; MONOCLONAL-ANTIBODIES; SMALLPOX VACCINE; ESCHERICHIA-COLI; ORTHOPOX VIRUSES; MEMBRANE-PROTEIN; FUSION PROTEIN; MICE; IDENTIFICATION AB The smallpox vaccine Dryvax, which consists of replication-competent vaccinia virus, elicits antibodies that play a major role in protection. Several vaccinia proteins generate neutralizing antibodies, but their importance for protection is unknown. We investigated the potency of antibodies to the A27 protein of the mature virion in neutralization and protection experiments and the contributions of A27 antibodies to Dryvax-induced immunity. Using a recombinant A27 protein (rA27), we confirmed that A27 contains neutralizing determinants and that vaccinia immune globulin (VIG) derived from Dryvax recipients contains reactivity to A27. However, VIG neutralization was not significantly reduced when A27 antibodies were removed, and antibodies elicited by an rA27 enhanced the protection conferred by VIG in passive transfer experiments. These findings demonstrate that A27 antibodies do not represent the major fraction of neutralizing activity in VIG and suggest that immunity may be augmented by vaccines and immune globulins that include strong antibody responses to A27. C1 US FDA, CBER, Rockville, MD 20852 USA. RP Weiss, CD (reprint author), US FDA, CBER, 1401 Rockville PIke, Rockville, MD 20852 USA. EM carol.weiss@fda.hhs.go RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 39 TC 22 Z9 23 U1 1 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD OCT 1 PY 2007 VL 196 IS 7 BP 1026 EP 1032 DI 10.1086/520936 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 212CZ UT WOS:000249572500014 PM 17763325 ER PT J AU Wang, YN AF Wang, Yaning TI Derivation of various NONMEM estimation methods SO JOURNAL OF PHARMACOKINETICS AND PHARMACODYNAMICS LA English DT Article DE nonlinear mixed-effects; likelihood approximation; Laplacian; first-order conditional method (FOCE); first-order method (FO) AB Various estimation methods and the lack of a systematic derivation of the core objective function implemented in NONMEM for nonlinear mixed effect modeling has caused consistent confusion and inquiry among scientists who routinely use NONMEM for data analysis. This paper provides a detailed derivation of the objective functions for the most commonly used estimation methods in NONMEM, such as the Laplacian method, the first-order conditional estimation method (FOCE) with or without interaction, and the first-order method (FO). In addition, models with homogenous or heterogeneous residual error were used to demonstrate the relationship between the objective functions derived from two different types of approximation, namely Laplacian approximation of log-likelihood and linearized model approximation. The relationship between these estimation methods and those implemented in SAS and Splus is discussed. C1 US FDA, Off Clin Pharmacol, CDER, Silver Spring, MD 20993 USA. RP Wang, YN (reprint author), US FDA, Off Clin Pharmacol, CDER, WO21 RM3662 HFD-880,1093 New Hampshire Ave, Silver Spring, MD 20993 USA. EM yaning.wang@fda.hhs.gov NR 8 TC 36 Z9 37 U1 0 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1567-567X J9 J PHARMACOKINET PHAR JI J. Pharmacokinet. Pharmacodyn. PD OCT PY 2007 VL 34 IS 5 BP 575 EP 593 DI 10.1007/s10928-007-9060-6 PG 19 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 213KH UT WOS:000249665200001 PM 17620001 ER PT J AU Buehler, PW D'Agnillo, F Hoffman, V Alayash, AI AF Buehler, Paul W. D'Agnillo, Felice Hoffman, Victoria Alayash, Abdu I. TI Effects of endogenous ascorbate on oxidation, oxygenation, and toxicokinetics of cell-free modified hemoglobin after exchange transfusion in rat and guinea pig SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CROSS-LINKED HEMOGLOBIN; BOVINE HEMOGLOBIN; BLOOD-VOLUME; URIC-ACID; IN-VITRO; PHASE-I; CARRIERS; METHEMOGLOBIN; BIOSYNTHESIS; SUBSTITUTES AB Chemically modified hemoglobin (Hb) solutions are promising oxygen therapeutics; however, these agents are prone to intravascular oxidation. Using a 50% exchange transfusion ( ET) model with bovine polymerized hemoglobin (PolyHbBv), we examined heme oxidation, oxygenation markers, and toxicokinetics in rats, an ascorbic acid (AA)- producing species, and in guinea pigs, a non-AA-producing species. Plasma AA decreased by 50% in guinea pigs after ET, but it was unchanged in rats for the first 20 h post-ET. Both species cleared PolyHbBv from the circulation at similar rates. However, exposure to ferric PolyHbBv over time was 5-fold greater in the guinea pig. Mass spectrometry analysis of plasma revealed oxidative modifications within the tetrameric fraction of PolyHbBv in guinea pig. Oxygen equilibrium curves of PolyHbBv measured in plasma after ET were more left-shifted in guinea pigs compared with rats, consistent with increased ferric PolyHbBv formation. Renal hypoxia-inducible factor (HIF)-1 alpha, whose activity strictly depends on the partial pressure of oxygen increased over time, and it correlated inversely with circulating ferrous PolyHbBv in both species. Interestingly, HIF-1 alpha activity was greater in guinea pigs compared with rats at 72 h post-ET. Mean arterial pressure increases were also greater in guinea pigs; however, minimal differences in cardiac and renal pathology were observed in either species. The present findings suggest the importance of plasma AA in maintaining the stability of acellular Hb susceptible to oxidation, and they may be relevant to humans, which display a similar plasma/tissue antioxidant status to guinea pig. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. NIH, Div Vet Sci, Off Ctr Director, Bethesda, MD 20892 USA. RP Buehler, PW (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, 8800 Rockville Pike,Bldg 29,Rm 129, Bethesda, MD 20892 USA. EM paul.buehler@fda.hhs.gov NR 34 TC 44 Z9 44 U1 0 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 OCT PY 2007 VL 323 IS 1 BP 49 EP 60 DI 10.1124/jpet.107.126409 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 212IF UT WOS:000249588900006 PM 17622572 ER PT J AU Costello, CE Contado-Miller, JM Cipollo, JF AF Costello, Catherine E. Contado-Miller, Joy May Cipollo, John F. TI A glycomics platform for the analysis of permethylated oligosaccharide alditols SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID TANDEM MASS-SPECTROMETRY; N-LINKED GLYCANS; CAENORHABDITIS-ELEGANS; LIQUID-CHROMATOGRAPHY; STRUCTURAL-CHARACTERIZATION; PROTEIN GLYCOSYLATION; FRAGMENTATION CHARACTERISTICS; CONGRUENT STRATEGIES; CONGENITAL DISORDERS; SOURCE DECAY AB This communication reports the development of an LC/MS platform for the analysis of permethylated oligosaccharicle alditols that, for the first time, demonstrates routine online oligosaccharide isomer separation of these compounds before introduction into the mass spectrometer. The method leverages a high-resolution liquid chromatography system with the superior fragmentation pattern characteristics of permethylated oligosaccharide alditols that are dissociated under low-energy collision conditions using quadrupole orthogonal time-of-flight (QoTOF) instrumentation and up to pseudo MS' mass spectrometry. Glycoforms, including isomers, are readily identified and their structures assigned. The isomer-specific spectra include highly informative cross-ring and elimination fragments, branch position specific signatures, and glycosidic bond fragments, thus facilitating linkage, branch, and sequence assignment. The method is sensitive and can be applied using as little as 40 fmol of derivatized oligosaccharide. Because permethylation renders oligosaccharides nearly chemically equivalent in the mass spectrometer, the method is semiquantitative and, in this regard, is comparable to methods reported using high field NMR and capillary electrophoresis. In this postgenomic age, the importance of glycosylation in biological processes has become clear. The nature of many of the important questions in glycomics is such that sample material is often extremely limited, thus necessitating the development of highly sensitive methods for rigorous structural assignment of the oligosaccharides in complex mixtures. The glycomics platform presented here fulfills these criteria and should lead to more facile glycomics analyses. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. Boston Univ, Sch Med, Dept Biochem, Mass Spectrometry Resource, Boston, MA 02215 USA. RP Cipollo, JF (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, 8800 Rockville Pike,Bldg 29A, Bethesda, MD 20892 USA. EM John.cipollo@fda.hhs.gov OI Costello, Catherine/0000-0003-1594-5122 FU NCRR NIH HHS [S10 RR015942, P41 RR010888, P41 RR10888]; NIGMS NIH HHS [P41 GM104603] NR 53 TC 88 Z9 88 U1 1 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD OCT PY 2007 VL 18 IS 10 BP 1799 EP 1812 DI 10.1016/j.jasms.2007.07.016 PG 14 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 219PW UT WOS:000250098100008 PM 17719235 ER PT J AU Markovitz, NS AF Markovitz, Nancy S. TI The herpes simplex virus type 1 UL3 transcript starts within the UL3 open reading frame and encodes a 224-amino-acid protein SO JOURNAL OF VIROLOGY LA English DT Article ID URACIL-DNA GLYCOSYLASE; VIRAL REPLICATION; BREAST-CANCER; GENE; CELLS; BRAIN; SEQUENCE; KINASE; SITE; PHOSPHOPROTEIN AB Several different herpes simplex viruses (HSVs) and vectors are being explored as therapeutic products for use in the treatment of cancer and neurological disorders. The viral strain and the combination of mutant viral genes that ultimately may serve as a safe and optimal backbone for such products are still being explored. The large genome size and complexity of the viral life cycle make such determinations difficult, because the significance of differences between proposed products is difficult to evaluate. For example, we previously reported that two lineages of gamma 34.5-deleted HSVs used in clinical studies differ from each other in the size of the UL3 protein expressed (M. J. Dambach et al., Mol. Ther. 13:891-898, 2006). Because the function of UL3 is not known and UL3 gene expression is poorly understood, the significance of such a difference cannot be predicted. Here, I begin to address the function of UL3 by investigating UL3 gene expression. I report that the transcript start site of UL3 mRNA isolated from HSV type 1 (HSV-1) -infected cells maps to a position downstream of the predicted translation start site. By constructing and characterizing the recombinant virus CB8116, which has a mutation in the first in-frame start codon of this UL3 transcript, I demonstrated that UL3 protein translation initiates at the second in-frame start codon of the UL3 open reading frame. This information adds to the body of basic knowledge of HSV-1 biology that forms the foundation for our current understanding of HSV-based products. Future research on HSV-1 biology will facilitate the rational design and evaluation of future generations of therapeutic viruses. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Markovitz, NS (reprint author), US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, HFM-725,1401 Rockville Pike, Rockville, MD 20852 USA. EM nancy.markovitz@fda.hhs.gov FU Intramural NIH HHS NR 39 TC 2 Z9 5 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 OCT PY 2007 VL 81 IS 19 BP 10524 EP 10531 DI 10.1128/JVI.00123-07 PG 8 WC Virology SC Virology GA 212SP UT WOS:000249617400031 PM 17626086 ER PT J AU Klinman, DM Currie, D Lee, G Grippe, V Merkel, T AF Klinman, Dennis M. Currie, Debra Lee, Gloria Grippe, Vanessa Merkel, Tod TI Systemic but not mucosal immunity induced by AVA prevents inhalational anthrax SO MICROBES AND INFECTION LA English DT Article DE anthrax; vaccine; protection ID BACILLUS-ANTHRACIS; CPG MOTIFS; PROTECTIVE ANTIGEN; RHESUS MACAQUES; VACCINE; INFECTION; MICE; OLIGODEOXYNUCLEOTIDES; IMMUNOGENICITY; IMMUNIZATION AB Improved vaccines and adjuvants are being developed to reduce the threat posed by a terrorist attack involving aerosolized anthrax spores. Nevertheless, uncertainty persists concerning the relative benefits of inducing mucosal vs systemic immunity to host survival following inhalational exposure to anthrax spores. This work examines the effect of delivering the licensed human vaccine (anthrax vaccine adsorbed, AVA) combined with a CpG oligodeoxynucleotide (ODN) adjuvant intraperitoneally or intranasally to A/J mice. Results indicate that protection from inhalational anthrax correlates with the induction of a strong systemic rather than mucosal immune response, and demonstrate that protection is significantly improved and accelerated by the addition of CpG ODN. (c) 2007 Elsevier Masson SAS. All rights reserved. C1 Natl Canc Inst, Expt Immunol Lab, Ft Detrick, MD 21702 USA. Ctr Biol Evaluat & Res, Food & Drug Adm, Lab Respirat & Special Pathogens, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), Natl Canc Inst, Expt Immunol Lab, Ft Detrick, MD 21702 USA. EM klinmand@niail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 28 TC 19 Z9 19 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD OCT PY 2007 VL 9 IS 12-13 BP 1478 EP 1483 DI 10.1016/j.micinf.2007.08.002 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 238WU UT WOS:000251479900012 PM 17913545 ER PT J AU Srividya, G Duncan, R Sharma, P Raju, BVS Nakhasi, HL Salotra, P AF Srividya, G. Duncan, R. Sharma, P. Raju, B. V. S. Nakhasi, H. L. Salotra, P. TI Transcriptome analysis during the process of in vitro differentiation of Leishmania donovani using genomic microarrays SO PARASITOLOGY LA English DT Article DE Leishinania donovani; kala-azar; genomic microarray; differentially expressed genes. ID AZAR DERMAL LEISHMANIASIS; NITRIC-OXIDE SYNTHASE; GENE-EXPRESSION; AXENIC AMASTIGOTES; FLAGELLAR-LENGTH; SURFACE-PROTEINS; DNA MICROARRAYS; REGULATED GENES; KALA-AZAR; IDENTIFICATION AB Leishmania donovani causes visceral disease (kala-azar), a major health problem throughout the tropics with 500000 new cases every year. Leishmania differentiates from the promastigote to the amastigote form to establish infection in a mammalian host. To understand the process of differentiation, we assessed the global variation in gene expression in promastigotes, an intermediate stage of differentiation (PA24) and axenic amastigotes in culture using an L. donovani genomic microarray with 4224 clones printed in triplicate. During an intermediate stage of differentiation 24 h after shifting the promastigotes into amastigotes (PA24), there were 41 (similar to 1 %) clones with expression >= 2-0-fold higher than promastigotes, whereas in terminally differentiated amastigotes there were 130 (similar to 3%) such clones. Of particular interest were certain genes that exhibited a transient increase or decrease in expression at the PA24 stage. Kinases showed a transient increase, and surface molecules, PSA and amino acid permease, were prominent clones among those showing a brief decrease at the PA24 stage. The microarray results have been validated using Northern blots or RT-PCR. In summary, our results provide important clues about the genes involved in the differentiation process of L. donovani that may contribute to virulence. C1 Indian Council Med Res, Inst Pathol, New Delhi 110029, India. US FDA, CBER, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20014 USA. RP Salotra, P (reprint author), Indian Council Med Res, Inst Pathol, Safdarjung Hosp Campus, New Delhi 110029, India. EM salotra@vsnl.com RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 42 TC 19 Z9 19 U1 1 U2 4 PU CAMBRIDGE UNIV PRESS PI NEW YORK PA 32 AVENUE OF THE AMERICAS, NEW YORK, NY 10013-2473 USA SN 0031-1820 J9 PARASITOLOGY JI Parasitology PD OCT PY 2007 VL 134 BP 1527 EP 1539 DI 10.1017/S003118200700296X PN 11 PG 13 WC Parasitology SC Parasitology GA 216MI UT WOS:000249881700002 PM 17553180 ER PT J AU Drever, Z Dinndorf, P Sather, H Steuber, C Carroll, W Hilden, J Camitta, B AF Drever, ZoAnn Dinndorf, P. Sather, H. Steuber, C. Carroll, W. Hilden, J. Camitta, B. TI Shortened, intensified therapy in infant ALL: A pediatric oncology group study SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA. US FDA, Silver Spring, MD USA. Stat Off, COG, Arcadia, CA USA. NY Med Ctr, New York, NY USA. Cleveland Clin, Cleveland, OH 44106 USA. Midwest Canc Ctr, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD OCT 1 PY 2007 VL 49 IS 4 BP 399 EP 399 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 205LU UT WOS:000249116100003 ER PT J AU Viswanathan, CT Bansal, S Booth, B DeStefano, AJ Rose, MJ Sailstad, J Shah, VP Skelly, JP Swann, PG Weiner, R AF Viswanathan, C. T. Bansal, Surendra Booth, Brian DeStefano, Anthony J. Rose, Mark J. Sailstad, Jeffrey Shah, Vinod P. Skelly, Jerome P. Swann, Patrick G. Weiner, Russell TI Quantitative bioanalytical methods validation and implementation: Best practices for chromatographic and ligand binding assays SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material DE bioanalytical; bioequivalence; LC-MS; MS; ligand binding; validation AB The Third AAPS/FDA Bioanalytical Workshop, entitled "Quantitative Bioanalytical Methods Validation and Implementation: Best Practices for Chromatographic and Ligand Binding Assays" was held on May 1-3, 2006 in Arlington, VA. The format of this workshop consisted of presentations on bioanalytical topics, followed by discussion sessions where these topics could be debated, with the goal of reaching consensus, or identifying subjects where addition input or clarification was required. The discussion also addressed bioanalytical validation requirements of regulatory agencies, with the purpose of clarifying expectations for regulatory submissions. The proceedings from each day were reviewed and summarized in the evening sessions among the speakers and moderators of the day. The consensus summary was presented back to the workshop on the last day and was further debated. This communication represents the distillate of the workshop proceedings and provides the summary of consensus reached and also contains the validation topics where no consensus was reached. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Procter & Gamble Pharmaceuts, Mason, OH 45040 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Sailstad & Associates, Durham, NC 27707 USA. US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. Bristol Myers Squibb Inc, Pennsauken, NJ 08534 USA. RP Rose, MJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM marose@amgen.com NR 5 TC 424 Z9 441 U1 6 U2 36 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD OCT PY 2007 VL 24 IS 10 BP 1962 EP 1973 DI 10.1007/s11095-007-9291-7 PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 209SI UT WOS:000249407900019 PM 17458684 ER PT J AU Wang, SJ AF Wang, Sue-Jane TI Biomarker as a classifier in pharmacogenomics clinical trials: a tribute to 30th anniversary of PSI SO PHARMACEUTICAL STATISTICS LA English DT Article DE adaptive vs guided design; companion diagnostic; prognostic-predictive; prospective/retrospective; clinical utility ID SURROGATE END-POINTS; BREAST-CANCER; VALIDATION; DESIGNS; CHALLENGES; STRATEGIES; EFFICIENCY; SIGNATURE; WORKSHOP; DISEASES AB Pharmacogenetics is one of many evolving sciences that have come to the fore since the formation of the Statisticians in the Pharmaceutical Industry (PSI) 30 years ago. Following the completion of the human genome project and the HapMap in the early 21st century, pharmacogenetics has gradually focused on studies of whole-genome single-nucleotide-polymorphisms screening associating disease pathophysiology with potential therapeutic interventions. Around this time, transcription profiling aiming at similar objectives has also been actively pursued, known as pharmacogenomics. It has become increasingly apparent that treatment effects between different genomic patient subsets can be dissimilar and the value and need for genomic biomarkers to help predict effects, particularly in cancer clinical studies, have become issues of paramount importance. Pharmacogenomics/pharmaogenetics has thus become intensely focused on the search for genomic biomarkers for use as classifiers to select patients in randomized-controlled trials. We highlight that the predictive utility of a genomic classifier has tremendous clinical appeal and that there will be growing examples in which use of a companion diagnostic will need to he considered and may become an integral part in the utilization of drugs in medical practice. The credible mechanism to test the clinical utility of a genomic classifier is to employ the study results from a prospective trial that recruits all patients. Such investigations, if well designed, will allow analysis of all relevant performance factors in the drug and diagnostic combination including the sensitivity, specificity, positive and negative predictive values of the diagnostic test and the efficacy of the drug. Published in 2007 by John Wiley & Sons, Ltd. C1 [Wang, Sue-Jane] US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov FU PHS HHS [05-14, 05-02, 04-06, 02-06] NR 40 TC 28 Z9 28 U1 0 U2 2 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 OCT-DEC PY 2007 VL 6 IS 4 BP 283 EP 296 DI 10.1002/pst.316 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 243HX UT WOS:000251788500003 PM 17957727 ER PT J AU Miller, HI Henderson, DR AF Miller, Henry I. Henderson, David R. TI The FDA's risky risk-aversion SO POLICY REVIEW LA English DT Article C1 NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Naval Postgrad Sch, Monterey, CA USA. RP Miller, HI (reprint author), NIH, Bethesda, MD 20892 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU HOOVER INST PI STANFORD PA STANFORD UNIV, STANFORD, CA 94305-601 USA SN 0146-5945 J9 POLICY REV JI Policy Rev. PD OCT-NOV PY 2007 IS 145 BP 3 EP 27 PG 25 WC Political Science SC Government & Law GA 222JQ UT WOS:000250292800001 ER PT J AU Huber, AM Dugan, EM Lachenbruch, PA Feldman, BM Perez, MD Zemel, LS Lindsley, CB Rennebohm, RM Wallace, CA Passo, MH Reed, AM Bowyer, SL Ballinger, SH Miller, FW Rider, LG AF Huber, A. M. Dugan, E. M. Lachenbruch, P. A. Feldman, B. M. Perez, M. D. Zemel, L. S. Lindsley, C. B. Rennebohm, R. M. Wallace, C. A. Passo, M. H. Reed, A. M. Bowyer, S. L. Ballinger, S. H. Miller, F. W. Rider, L. G. CA Juvenile Dermatomyositis Dis Activ TI The Cutaneous Assessment Tool: development and reliability in juvenile idiopathic inflammatory myopathy SO RHEUMATOLOGY LA English DT Article DE juvenile idiopathic inflammatory myopathy; juvenile dermatomyositis; skin disease; Cutaneous Assessment Tool; assessment ID DISEASE-ACTIVITY; SKIN INVOLVEMENT; DERMATOMYOSITIS; VALIDATION; PSORIASIS; CHILDREN AB Objectives. Clinical care and therapeutic trials in idiopathic inflammatory myopathies (IIM) require accurate and consistent assessment of cutaneous involvement. The Cutaneous Assessment Tool (CAT) was designed to measure skin activity and damage in IIM. We describe the development and inter-rater reliability of the CAT, and the frequency of lesions endorsed in a large population of juvenile IN patients. Methods. The CAT includes 10 activity, 4 damage and 7 combined lesions. Thirty-two photographic slides depicting IN skin lesions were assessed by 11 raters. One hundred and twenty-three children were assessed by 11 paediatric rheumatologists; at 10 centres. Inter-rater reliability was assessed using simple agreements and intra-class correlation coefficients (ICC). Results. Simple agreements in recognizing lesions as present or absent were generally high (0.5-1.0). ICCs for CAT lesions were moderate (0.4-0.75) in both slides and real patients. ICCs for the CAT activity and damage scores were 0.71 and 0.81, respectively. CAT activity scores ranged from 0 to 44 (median 7, potential range 0-96) and CAT damage scores ranged from 0 to 13 (median 1, potential range 0-22). The most common cutaneous lesions endorsed were periungual capillary loop changes (63%), Gottron's papules/sign (53%), heliotrope rash (49%) and malar/facial erythema (49%). Conclusions. Total CAT activity and damage scores have moderate to good reliability. Assessors generally agree on the presence of a variety of cutaneous lesions. The CAT is a promising, semi-quantitative tool to comprehensively assess skin disease activity and damage in IIM. C1 IWK Hlth Ctr, Div Pediat Rheumatol, Halifax, NS B3K 6R8, Canada. Dalhousie Univ, Halifax, NS, Canada. Washington Hosp Ctr, Washington, DC 20010 USA. DHHS, Ctr Biol Evaluat & Res, US FDA, Rockville, MD USA. Univ Toronto, Toronto, ON, Canada. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Texas Childrens Hosp, Houston, TX 77030 USA. Baylor Coll Med, Houston, TX 77030 USA. Univ Connecticut, Hartford, CT 06112 USA. Connecticut Childrens Med Ctr, Hartford, CT USA. Univ Kansas, Kansas City, KS USA. Ohio State Univ, Columbus, OH 43210 USA. British Columbia Childrens Hosp, Columbus, OH USA. Univ Washington, Seattle, WA 98195 USA. Childrens Hosp, Seattle, WA USA. Univ Cincinnati, Cincinnati, OH USA. Childrens Hosp, Cincinnati, OH 45229 USA. Indiana Univ, Sch Med, Indianapolis, IN USA. James Whitcomb Riley Hosp Children, Indianapolis, IN 46202 USA. NIEHS, Environm Autoimmun Grp, Res Triangle Pk, NC 27709 USA. RP Huber, AM (reprint author), IWK Hlth Ctr, Div Pediat Rheumatol, 5850 Univ Ave, Halifax, NS B3K 6R8, Canada. EM adam.huber@iwk.nshealth.ca RI Feldman, Brian/A-8586-2011; OI Sundel, Robert/0000-0002-0083-5695; Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 FU Intramural NIH HHS [Z01 ES101081-06] NR 17 TC 19 Z9 24 U1 1 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1462-0324 EI 1462-0332 J9 RHEUMATOLOGY JI RHEUMATOLOGY PD OCT PY 2007 VL 46 IS 10 BP 1606 EP 1611 DI 10.1093/rheumatology/kem179 PG 6 WC Rheumatology SC Rheumatology GA 226XX UT WOS:000250622900020 PM 17890275 ER PT J AU Espandiari, P Zhang, J Rosenzweig, BA Vaidya, VS Sun, J Schnackenberg, L Herman, EH Knapton, A Bonventre, JV Beger, RD Thompson, KL Hanig, J AF Espandiari, Parvaneh Zhang, Jun Rosenzweig, Barry A. Vaidya, Vishal S. Sun, Jinchun Schnackenberg, Laura Herman, Eugene H. Knapton, Alan Bonventre, Joseph V. Beger, Richard D. Thompson, Karol L. Hanig, Joseph TI The utility of a rodent model in detecting pediatric drug-induced nephrotoxicity SO TOXICOLOGICAL SCIENCES LA English DT Article DE gentamicin; age-related nephrotoxicity; biomarkers; Kim-1 ID ACUTE-RENAL-FAILURE; GENTAMICIN-INDUCED NEPHROTOXICITY; KIDNEY INJURY; CHILDRENS SUSCEPTIBILITY; MELATONIN; H-1-NMR; RAT; IDENTIFICATION; METABOLITES; MOLECULE-1 AB A multi-age rat model was used to identify potential age-related differences in renal injury following exposure to gentamicin (GM). In this study, 10-, 25-, 40-, and 80-day-old Sprague-Dawley rats were dosed with GM at 0, 50, or 100 mg kg(-1) body weight per day (mkd) sc for 6 or 14 days. Urine samples were collected up to 72 h after initial dosing. The maximum tolerated dose was lower in 10-day-old rats than for other ages (none survived 11 days of treatment). Eighty-day-old rats given the highest dose showed a diminished rate of growth and an increase in serum creatinine, blood urea nitrogen (BUN), urinary kidney injury molecule-1 (Kim-1), and renal pathology. Ten-and 40-day-old rats given 100 mkd of GM for 6-or 14 days also had increased levels of serum BUN and Cr and renal pathology, whereas only mild renal alterations were found in 25-day-old rats. After 6 days of treatment with 100 mkd GM, significant increases in Havcr-1 (Kim-1) gene expression were detected only in 10- and 80-day-old rats. In urine samples, nuclear magnetic resonance and ultra performance liquid chromatography/mass spectrometry analysis detected changes related to GM efficacy (e. g., hippurate) and increases in metabolites related to antioxidant activity, which was greatest in the 80-day-old rats. The magnitude of the genomic, metabonomic, and serum chemistry changes appeared to correlate with the degree of nephropathy. These findings indicate that an experimental animal model that includes several developmental stages can detect age-related differences in drug-induced organ toxicities and may be a useful predictor of pediatric drug safety in preclinical studies. C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD 910, Silver Spring, MD 20993 USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Boston, MA 02115 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Espandiari, P (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD 910, Life Sci Lab Bldg 64,Room 2086,10903 New Hampshir, Silver Spring, MD 20993 USA. EM parvaneh.espandiari@fda.hhs.gov FU NIDDK NIH HHS [R21 DK074099, DK 074099, R33 DK074099]; NIEHS NIH HHS [R00 ES016723, R00 ES016723-02] NR 39 TC 27 Z9 28 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD OCT PY 2007 VL 99 IS 2 BP 637 EP 648 DI 10.1093/toxsci/kfm184 PG 12 WC Toxicology SC Toxicology GA 216NW UT WOS:000249885900025 PM 17636248 ER PT J AU Li, H Campbell, A Ali, SF Cong, P Bondy, SC AF Li, H. Campbell, A. Ali, S. F. Cong, P. Bondy, S. C. TI Chronic exposure to low levels of aluminum alters cerebral cell signaling in response to acute MPTP administration SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article DE aluminum; cell signaling; inflammation; MPTP ID PROTEIN-KINASE MAPK; DRINKING-WATER; PARKINSONS-DISEASE; MOLECULAR-MECHANISMS; ALZHEIMERS-DISEASE; IMMUNE-RESPONSE; RISK-FACTOR; KAPPA-B; JNK; BRAIN AB Two-month-old male B/6C3F1 mice were treated for 10 weeks with 100 mu M aluminum lactate (Al) in drinking water. This dose of Al did not alter body weight, and there was no evidence of systemic toxicity. The degree of phosphorylation of several kinases which lead to transcription factor activation (reflecting the extent of their activation) was studied. The proportion of extracellular signal-regulated kinase (ERK) that was activated was depressed in cortex but not in the hippocampus following treatment but c-Jun N-terminal kinase (JNK), p38, I kappa B phosphorylation was unaltered in either tissue. Treatment of mice with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) alone produced no significant changes in the degree of activation of any transcription factor studied. When MPTP dosing had been preceded by extended exposure to low levels of Al in drinking water, ERK activation was profoundly depressed in cortex and hippocampus, whereas JNK in hippocampus and I kappa B in cortex were greatly elevated. These changes consequent to exposure to both Al and MPTP were accompanied by an increase in NF-kappa B in both regions, whereas AP-1 was elevated in the hippocampus alone. Neither agent alone modulated AP-1 or NF-kappa B. Thus a synergistic interaction occurred between the toxicants. This interaction tended to promote the functioning of a kinase largely associated with inflammation and to depress that of ERK, which is associated with maintenance of cell survival. It is concluded that exposure to levels of Al with no evident toxicity can worsen the response to an acute challenge with MPTP. Al treatment alone was able to increase striatal 3,4-dihydroxyphenylacetic acid levels, suggesting an elevation of the rate of dopamine turnover in the striatum. However, no interaction in alteration of monoamine levels was found between Al and MPTP. C1 [Li, H.; Bondy, S. C.] Univ Calif Irvine, Dept Community & Environm Med, Ctr Occupat & Environm Hlth, Irvine, CA 92697 USA. [Campbell, A.] Western Univ Hlth Sci, Pomona, CA USA. [Ali, S. F.] Natl Ctr Toxicol Res Food & Drug Adm, Neurochem Lab, Div Neurotoxicol, Jefferson, AR USA. RP Bondy, SC (reprint author), Univ Calif Irvine, Dept Community & Environm Med, Ctr Occupat & Environm Hlth, Irvine, CA 92697 USA. EM scbondy@uci.edu FU NIA NIH HHS [AG 16794]; NIEHS NIH HHS [ES 7992] NR 33 TC 4 Z9 4 U1 1 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD OCT PY 2007 VL 23 IS 9 BP 515 EP 524 DI 10.1177/0748233708089027 PG 10 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 319OS UT WOS:000257174000002 PM 18681236 ER PT J AU Brayden, DJ Martinez, MN AF Brayden, David J. Martinez, Marilyn N. TI Prediction of therapeutic and drug delivery outcomes using animal models - Preface SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Editorial Material C1 Univ Coll Dublin, Sch Agr Food Sci & Vet Med, Dublin, Ireland. Ctr Vet Med, Food & Drug Adm, Rockville, MD 20855 USA. RP Brayden, DJ (reprint author), Univ Coll Dublin, Sch Agr Food Sci & Vet Med, Dublin, Ireland. EM david.braydcn@ucd.ie; MMartin1@cvm.fda.gov OI Brayden, David/0000-0002-8781-8344 NR 0 TC 0 Z9 0 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD SEP 30 PY 2007 VL 59 IS 11 BP 1071 EP 1072 DI 10.1016/j.addr.2007.08.010 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 237ED UT WOS:000251355400001 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Application of allometric principles for the prediction of pharmacokinetics in human and veterinary drug development SO ADVANCED DRUG DELIVERY REVIEWS LA English DT Review DE pharmacokinetic interspecies scaling; clearance; volume of distribution; elimination half-life; first-in-human dose; veterinary medicine; large animals ID IN-VITRO DATA; ANIMAL DATA; CLEARANCE; PARAMETERS; RAT; DISPOSITION; INTEGRATION; SELECTION; MAMMALS; MONKEY AB The concept of correlating pharmacokinetic parameters with body weight (termed as pharmacokinetic interspecies scaling) from different animal species has become a useful tool in drug development. Interspecies scaling is based on the power function, where the body weight of the species is plotted against the pharmacokinetic parameter of interest. Clearance, volume of distribution, and elimination half-life are the three most frequently extrapolated pharmacokinetic parameters. The predicted pharmacokinetic parameter clearance can be used for estimating a first-inhuman dose. Over the years, many approaches have been suggested to improve the prediction of aforementioned pharmacokinetic parameters in humans from animal data. A literature review indicates that there are different degrees of success with different methods for different drugs. Interspecies scaling is also a very useful tool in veterinary medicine. The knowledge of pharmacokinetics in veterinary medicine is important for dosage selection, particularly in the treatment of large animals such as horses, carrels, elephants, or other large zoo animals. Despite the potential for extrapolation error, the reality is that interspecies scaling is needed across many veterinary practice situations, and therefore will be used. For this reason, it is important to consider mechanisms for reducing the risk of extrapolation errors that can seriously affect animal safety and therapeutic response. Overall, although interspecies scaling requires continuous refinement and better understanding, the rationale approach of interspecies scaling has a lot of potential during the drug development process. Published by Elsevier B.V. C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Revie & Res, Rockville, MD 20857 USA. RP Mahmood, I (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Revie & Res, Rockville, MD 20857 USA. EM Iftekhar.mahmood@cfda.hhs.gov NR 47 TC 57 Z9 58 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0169-409X J9 ADV DRUG DELIVER REV JI Adv. Drug Deliv. Rev. PD SEP 30 PY 2007 VL 59 IS 11 BP 1177 EP 1192 DI 10.1016/j.addr.2007.05.015 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 237ED UT WOS:000251355400010 PM 17826864 ER PT J AU De Jesus-Bonilla, W Jia, YP Alayash, AI Lopez-Garriga, J AF De Jesus-Bonilla, Walleska Jia, Yiping Alayash, Abdu I. Lopez-Garriga, Juan TI The heme pocket geometry of Lucina pectinata hemoglobin II restricts nitric oxide and peroxide entry: Model of ligand control for the design of a stable oxygen carrier SO BIOCHEMISTRY LA English DT Article ID CROSS-LINKED HEMOGLOBIN; SPERM-WHALE MYOGLOBIN; BLOOD SUBSTITUTES; TYROSINE B10; INVERTEBRATE HEMOGLOBINS; BINDING PROPERTIES; REDOX PROPERTIES; NO; POLYMERIZATION; REACTIVITY AB Blood pressure elevation has been attributed in large part to the consumption of nitric oxide (NO) by extracellular hemoglobin (Hb) therapeutics following infusion in humans. We studied NO and hydrogen peroxide (H2O2) oxidative reaction kinetics of monomeric Hbs isolated from the clam Lucina pectinata to probe the effects of their distinctive heme pocket chemistries on ligand controls and heme oxidative stability. HbI (Phe43(CD1), Gln64(E7), Phe29(B10), and Phe68(E11)) reacted with high avidity with NO (k'(ox,NO) = 91 mu M-1 s(-1)), whereas HbII (Phe44(CD1), Gln65(E7), Tyr30(B10), and Phe69(El 1)) reacted at a much slower rate (ko'(ox,NO) = 2.8 mu M-1 s(-1)). However, replacing B10 (Phe) by Tyr in recombinant HbI (HbI PheB10Tyr) produced only a 2-fold reduction in the NO-induced oxidation rate (k'(ox,NO) = 49.9 mu M-1 s(-1)). Among the clam Hbs, HbII exhibited the fastest NO dissociation and the slowest NO association with ferrous iron. Autoxidation, H2O2-mediated ferryl iron (Fe-IV) formation, and the subsequent heme degradation kinetics were much slower in HbII and HbI PheB10Tyr when compared to those of HbI. The Tyr(B10) residue appears to afford a greater heme oxidative stability advantage toward H2O2, whereas the close proximity of this residue together with Gln(E7) to the heme iron contributes largely to the distal control of NO binding. Engineering of second-generation Hb-based oxygen therapeutics that are resistant to NO/H2O2-driven oxidation may ultimately require further optimization of the heme pocket architecture to limit heme exposure to solvent. C1 US FDA, CBER, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. Univ Puerto Rico, Dept Chem, Mayaguez, PR 00681 USA. RP Alayash, AI (reprint author), US FDA, CBER, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov FU NIGMS NIH HHS [S06GM08103-34] NR 45 TC 13 Z9 13 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD SEP 18 PY 2007 VL 46 IS 37 BP 10451 EP 10460 DI 10.1021/bi7003262 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 210CA UT WOS:000249433100006 PM 17718508 ER PT J AU Kane, RC Dagher, R Farrell, A Ko, CW Sridhara, R Justice, R Pazdur, R AF Kane, Robert C. Dagher, Ramzi Farrell, Ann Ko, Chia-Wen Sridhara, Rajeshwari Justice, Robert Pazdur, Richard TI Bortezomib for the treatment of mantle cell lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article ID PROTEASOME INHIBITOR BORTEZOMIB; NON-HODGKINS-LYMPHOMA; MULTIPLE-MYELOMA; PHASE-II AB Purpose: To describe the Food and Drug Administration review and marketing approval considerations for bortezomib (Velcade) for the treatment of patients with mantle cell lymphoma. Experimental Design: Food and Drug Administration reviewed a multicenter study of bortezomib in 155 patients with progressive mantle cell lymphoma after at least one prior therapy. Results: Seventy-seven percent were stage IV, and 75% had one or more extranodal sites of disease. Prior therapy included an anthracycline or mitoxantrone, cyclophosphamide, and rituximab. Median age was 65 years. All received bortezomib 1.3 mg/m(2) i.v. on days 1, 4, 8, and 11 of each 3-week cycle. The primary end point was response. Response and progression were determined by independent review of serial computed tomography scans using International Lymphoma Workshop Response Criteria. The overall response rate was 31 %, including complete response (CR) plus CR unconfirmed (CRu) plus partial response; median response duration was 9.3 months. The CR plus CRu response rate was 8% with a median duration of 15.4 months. Adverse events were similar to those observed previously for bortezomib. The most commonly reported treatment- emergent adverse events were asthenia (72%), peripheral neuropathies (55%), constipation (50%), diarrhea (47%), nausea (44%), and anorexia (39%). The most common adverse event leading to discontinuation was neuropathy. Conclusions: Bortezomib received regular approval for the treatment of patients with mantle cell lymphoma in relapse after prior therapy. C1 US FDA, Ctr Drug Evaluat & Res, Div Drug Oncol Prod, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. RP Kane, RC (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Drug Oncol Prod, Off Oncol Drug Prod, Room 2109,Bldg 22,10903 New Hamsphire Ave, Silver Spring, MD 20993 USA. EM robert.kane@fda.hhs.gov NR 8 TC 196 Z9 202 U1 0 U2 7 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 SEP 15 PY 2007 VL 13 IS 18 BP 5291 EP 5294 DI 10.1158/1078-0432.CCR-07-0871 PN 1 PG 4 WC Oncology SC Oncology GA 214JV UT WOS:000249734700012 PM 17875757 ER PT J AU Thompson, KL Pine, PS Rosenzweig, BA Turpaz, Y Retief, J AF Thompson, Karol L. Pine, P. Scott Rosenzweig, Barry A. Turpaz, Yaron Retief, Jacques TI Characterization of the effect of sample quality on high density oligonucleotide microarray data using progressively degraded rat liver RNA SO BMC BIOTECHNOLOGY LA English DT Article ID GENE-EXPRESSION PROFILES; MESSENGER-RNA; WARM ISCHEMIA; AMPLIFIED RNA; DEGRADATION; AMPLIFICATION; IMPACT; CELLS AB Background: The interpretability of microarray data can be affected by sample quality. To systematically explore how RNA quality affects microarray assay performance, a set of rat liver RNA samples with a progressive change in RNA integrity was generated by thawing frozen tissue or by ex vivo incubation of fresh tissue over a time course. Results: Incubation of tissue at 37 degrees C for several hours had little effect on RNA integrity, but did induce changes in the transcript levels of stress response genes and immune cell markers. In contrast, thawing of tissue led to a rapid loss of RNA integrity. Probe sets identified as most sensitive to RNA degradation tended to be located more than 1000 nucleotides upstream of their transcription termini, similar to the positioning of control probe sets used to assess sample quality on Affymetrix GeneChip (R) arrays. Samples with RNA integrity numbers less than or equal to 7 showed a significant increase in false positives relative to undegraded liver RNA and a reduction in the detection of true positives among probe sets most sensitive to sample integrity for in silico modeled changes of 1.5-, 2-, and 4-fold. Conclusion: Although moderate levels of RNA degradation are tolerated by microarrays with 3'-biased probe selection designs, in this study we identify a threshold beyond which decreased specificity and sensitivity can be observed that closely correlates with average target length. These results highlight the value of annotating microarray data with metrics that capture important aspects of sample quality. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. Affymetrix Inc, Santa Clara, CA USA. Illumina Inc, San Diego, CA USA. RP Thompson, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM thompson@fda.hhs.gov; p.scott.pine@fda.hhs.gov; barry.rosenzweig@fda.hhs.gov; Yaron_Turpaz@Affymetrix.com; jretief@illumina.com NR 22 TC 40 Z9 40 U1 0 U2 10 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 SEP 13 PY 2007 VL 7 AR 57 DI 10.1186/1472-6750-7-57 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 238CB UT WOS:000251423800001 PM 17854504 ER PT J AU Miller, NB Raychaudhuri, G Toerner, JG AF Miller, Nancy B. Raychaudhuri, Gopa Toerner, Joseph G. TI Human papillomavirus vaccine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID QUADRIVALENT VACCINE C1 US FDA, Rockville, MD 20850 USA. RP Miller, NB (reprint author), US FDA, Rockville, MD 20850 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 13 PY 2007 VL 357 IS 11 BP 1154 EP 1155 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 209KK UT WOS:000249387200017 PM 17855679 ER PT J AU Pfeiffer, CM Johnson, CL Jain, RB Yetley, EA Picciano, MF Rader, JI Fisher, KD Mulinare, J Osterloh, JD AF Pfeiffer, Christine M. Johnson, Clifford L. Jain, Ram B. Yetley, Elizabeth A. Picciano, Mary Frances Rader, Jeanne I. Fisher, Kenneth D. Mulinare, Joseph Osterloh, John D. TI Trends in blood folate and vitamin B-12 concentrations in the United States, 1988-2004 SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE nutrition survey; age; sex; race; ethnic groups; National Health and Nutrition Examination Survey; NHANES; fortification; neural tube defects ID FOLIC-ACID FORTIFICATION; TOTAL HOMOCYSTEINE CONCENTRATIONS; FOOD FORTIFICATION; NATIONAL-HEALTH; MYOCARDIAL-INFARCTION; COGNITIVE IMPAIRMENT; CONTROLLED-TRIAL; DIETARY-FOLATE; SERUM FOLATE; B-VITAMINS AB Background: Monitoring the folate status of US population groups over time has been a public health priority for the past 2 decades, and the focus has been enhanced since the implementation of a folic acid fortification program in the mid-1990s. Objective: We aimed to determine how population concentrations of serum and red blood cell (RBC) folate and serum vitamin B-12 have changed over the past 2 decades. Design: Measurement of blood indicators of folate and vitamin B-12 status was conducted in approximate to 23 000 participants in the prefortification third National Health and Nutrition Examination Survey (NHANES 111; 1988-1994) and in approximate to 8000 participants in 3 postfortification NHANES periods (together covering 1999-2004). Results: Serum and RBC folate concentrations increased substantially (by 119-161 % and 44-64%, respectively) in each age group in the first postfortification survey period and then declined slightly (by 5-13% and 6-9%, respectively) in most age groups between the first and third postfortification survey periods. Serum vitamin 13-12 concentrations did not change appreciably. Prevalence estimates of low serum and RBC folate concentrations declined in women of childbearing age from before to after fortification (from 21 % to < 1 % and from 38% to 5%, respectively) but remained unchanged thereafter. Prevalence estimates of high serum folate concentrations increased in children and older persons from before to after fortification (from 5% to 42% and from 7% to 38%, respectively) but decreased later after fortification. Conclusions: The decrease in folate concentrations observed longer after fortification is small compared with the increase soon after the introduction of fortification. The decrease is not at the low end of concentrations and therefore does not raise concerns about inadequate status. C1 Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Natl Ctr Birth Defects & Dev Disabilities, Atlanta, GA USA. US FDA, College Pk, MD USA. Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD USA. RP Pfeiffer, CM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, 4770 Buford Hwy,NE MS F55, Atlanta, GA 30341 USA. EM cpfeiffer@cdc.gov NR 47 TC 172 Z9 176 U1 3 U2 12 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 SEP PY 2007 VL 86 IS 3 BP 718 EP 727 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 210WC UT WOS:000249485300027 PM 17823438 ER PT J AU Karnaukhova, E AF Karnaukhova, E. TI Non-inhibitory properties of alpha 1-proteinase inhibitor: binding with lipophilic ligands SO AMINO ACIDS LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0939-4451 J9 AMINO ACIDS JI Amino Acids PD SEP PY 2007 VL 33 IS 3 BP XLVII EP XLVIII PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 206UH UT WOS:000249207900150 ER PT J AU Rader, JI Delmonte, P Trucksess, MW AF Rader, Jeanne I. Delmonte, Pierluigi Trucksess, Mary W. TI Recent studies on selected botanical dietary supplement ingredients SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE botanical ingredients; Ephedra; Hoodia; Teucrium; isoflavones; Mycotoxins ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TEUCRIUM-CHAMAEDRYS L; L. VAR. AMARA; CAPILLARY-ELECTROPHORESIS; RED-CLOVER; ADRENERGIC AMINES; MASS-SPECTROMETRY; NEOCLERODANE DITERPENOIDS; NUTRITIONAL SUPPLEMENTS; MEDICINAL-PLANTS AB The market for botanical dietary supplements in the US has grown rapidly during the last 15 years. Use of newly introduced botanical ingredients has often outpaced an adequate scientific understanding of the ingredients themselves. This may lead to problems, including misidentification, mislabeling, adulteration, and toxicity related to the intended ingredient or one substituted for it. This article reviews recent work with several botanical ingredients (Ephedra, Citrus species, Hoodia gordonii, Teucrium, isoflavones) that illustrates the complexity of the current situation and approaches that contribute to ensuring the quality of botanical ingredients. Recent work with contamination of botanical products by mycotoxins is also reviewed. The need for tools for botanical authentication and methods for reproducible extraction of bioactive constituents is critical. Such tools, and improved analytical techniques for identifying potentially bioactive constituents in fresh plant material and in concentrated extracts and for detection of hazardous contaminants, are expected to improve the overall quality and safety of botanical dietary supplement ingredients. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, College Pk, MD 20740 USA. RP Rader, JI (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Regulatory Sci, Div Bioanalyt Chem, 5100 Paint Branch Parkway, College Pk, MD 20740 USA. EM Jeanne.Rader@fda.hhs.gov NR 65 TC 24 Z9 29 U1 2 U2 21 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2007 VL 389 IS 1 BP 27 EP 35 DI 10.1007/s00216-007-1254-7 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 203KU UT WOS:000248974300006 PM 17390125 ER PT J AU Dwyer, JT Holden, J Andrews, K Roseland, J Zhao, C Schweitzer, A Perry, CR Harnly, J Wolf, WR Picciano, MF Fisher, KD Saldanha, LG Yetley, EA Betz, JM Coates, PM Milner, JA Whitted, J Burt, V Radimer, K Wilger, J Sharpless, KE Hardy, CJ AF Dwyer, Johanna T. Holden, Joanne Andrews, Karen Roseland, Janet Zhao, Cuiwei Schweitzer, Amy Perry, Charles R. Harnly, James Wolf, Wayne R. Picciano, Mary Frances Fisher, Kenneth D. Saldanha, Leila G. Yetley, Elizabeth A. Betz, Joseph M. Coates, Paul M. Milner, John A. Whitted, Jackie Burt, Vicki Radimer, Kathy Wilger, Jaime Sharpless, Katherine E. Hardy, Constance J. TI Measuring vitamins and minerals in dietary supplements for nutrition studies in the USA SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE dietary supplements; dietary supplement ingredient database; multivitamin mineral supplements; analytical values ID MULTIVITAMIN-MULTIMINERAL SUPPLEMENTS; ACCURACY; HEALTH AB This article illustrates the importance of having analytical data on the vitamin and mineral contents of dietary supplements in nutrition studies, and describes efforts to develop an analytically validated dietary supplement ingredient database (DSID) by a consortium of federal agencies in the USA. Preliminary studies of multivitamin mineral supplements marketed in the USA that were analyzed as candidates for the DSID are summarized. Challenges are summarized, possible future directions are outlined, and some related programs at the Office of Dietary Supplements, National Institutes of Health are described. The DSID should be helpful to researchers in assessing relationships between intakes of vitamins and minerals and health outcomes. C1 US Dept HHS, Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. US Dept HHS, Natl Canc Inst, Nutr Sci Res Grp, Bethesda, MD 20892 USA. US Dept HHS, Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Natl Hlth & Nutr Examinat Survey, Hyattsville, MD 20782 USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. USDA, Agr Res Serv, Beltsville Human Nutr Res Ctr, Nutr Data Lab, Beltsville, MD 20705 USA. USDA, Agr Res Serv, Beltsville Human Nutr Res Ctr, Food Composit Lab, Beltsville, MD 20705 USA. USDA, Natl Agr Stat Serv, Div Res & Dev, Fairfax, VA 22030 USA. US Dept HHS, US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20850 USA. RP Dwyer, JT (reprint author), US Dept HHS, Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. EM dwyerj1@od.nih.gov OI Sharpless, Katherine/0000-0001-6569-198X; Dwyer, Johanna/0000-0002-0783-1769 NR 29 TC 26 Z9 26 U1 3 U2 7 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2007 VL 389 IS 1 BP 37 EP 46 DI 10.1007/s00216-007-1456-z PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 203KU UT WOS:000248974300007 PM 17641882 ER PT J AU Delmonte, P Rader, JI AF Delmonte, Pierluigi Rader, Jeanne I. TI Evaluation of gas chromatographic methods for the determination of trans fat SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE trans fat; fatty acids; gas chromatography ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ACID METHYL-ESTERS; HYDROGENATED VEGETABLE-OILS; CONJUGATED LINOLEIC ACIDS; TANDEM MASS-SPECTROMETRY; CP-SIL 88; OCTADECENOIC ACIDS; RAPID ANALYSIS; ISOMERS; CIS AB Consumption of trans fat has been associated with increased risk of coronary heart disease. For nutrition labeling purposes, the US Food and Drug Administration (FDA) defines trans fat as the sum of all the fatty acids with at least one nonconjugated double bond in the trans configuration. The FDA regulation states that label declarations of trans fat are not required for products that contain less than 0.5 g of trans fat per serving if no claims are made about fat, fatty acids or cholesterol. While attenuated total reflection Fourier-transformed infrared spectroscopy (ATR-FT-IR) provides reproducible measurements for samples containing more than 5% trans fat, methods based on gas chromatography (GC) are needed to measure lower trans fat levels. Trans fat quantitation by GC has recently been updated by considering more fatty acids, focusing more attention on fatty acids present in low amounts, and by using 100-m high-polarity capillary columns for optimal separation. The consistently high interlaboratory relative standard deviations (RSD, e.g., 21% at 1% trans fatty acids (TFA), 60% at 0.17% TFA), and intralaboratory RSD values (e.g., 10% at 1% TFA, 16% at 0.17% TFA) for trans fat at 1% or less of total fat reported in the collaborative study data for American Oil Chemists Society Official Method Ce 1h-05 suggest the need to carefully define the parameters associated with GC analysis of fatty acids. C1 US FDA, College Pk, MD 20740 USA. RP Delmonte, P (reprint author), US FDA, HFS 717,Room 1E006,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM pierluigi.delmonte@fda.hhs.gov NR 40 TC 36 Z9 41 U1 0 U2 22 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2007 VL 389 IS 1 BP 77 EP 85 DI 10.1007/s00216-007-1392-y PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 203KU UT WOS:000248974300010 PM 17572885 ER PT J AU Mossoba, MM Milosevic, V Milosevic, M Kramer, JKG Azizian, H AF Mossoba, M. M. Milosevic, V. Milosevic, M. Kramer, J. K. G. Azizian, H. TI Determination of total trans fats and oils by infrared spectroscopy for regulatory compliance SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE fourier transform infrared; attenuated total reflection; trans fats; validated official methods ID RAPID-DETERMINATION; ACIDS AB The mandatory requirement in many countries to declare the amount of trans fat present in food products and dietary supplements has led to a need for sensitive and accurate methodologies for the rapid quantitation of total trans fats and oils. Capillary gas chromatography (GC) and infrared spectroscopy (IR) are the two methods most commonly used to identify and quantify trans fatty acids for food labeling purposes (see the article by Delmonte and Rader in this ABC issue for a detailed presentation of GC methodology). The present article provides a comprehensive review of the IR technique and the current attenuated total reflection (ATR) Fourier-transform (FT) IR methodologies for the rapid determination of total trans fats and oils. This review also addresses potential sources of interferences and inaccuracies in FTIR determinations, particularly those done at low trans levels. Recent observations have shown that the presence of saturated fats caused interferences in the FTIR spectra observed for trans triacylglycerols. The recognition and resolution of previously unresolved quantitative issues improved the accuracy and sensitivity of the FTIR methodology. Once validated, it is anticipated that the new negative second-derivative ATR-FTIR procedure will make IR spectroscopy more suitable than ever, and a rapid alternative and/or complementary method to GC, for the rapid determination of total trans fats for regulatory compliance. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. MeV Photon, Westport, CT 06880 USA. Agr & Agri Food Canada, Guelph, ON N16 5C9, Canada. NIR Technol, Oakville, ON L6M 2M2, Canada. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Mail Stop HFS 717,Room BE-012,5100 Paint Branch P, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov NR 20 TC 36 Z9 40 U1 3 U2 25 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2007 VL 389 IS 1 BP 87 EP 92 DI 10.1007/s00216-007-1262-7 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 203KU UT WOS:000248974300011 PM 17431592 ER PT J AU Capar, SG Mindak, WR Cheng, J AF Capar, Stephen G. Mindak, William R. Cheng, John TI Analysis of food for toxic elements SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Review DE review; food; analysis; toxic elements ID ATOMIC-ABSORPTION-SPECTROMETRY; PLASMA-MASS SPECTROMETRY; STANDARD REFERENCE MATERIALS; TOTAL ARSENIC DETERMINATION; HPLC-ICP-MS; MICROWAVE DIGESTION; BIOLOGICAL SAMPLES; TRACE-ELEMENTS; TOTAL MERCURY; MULTIELEMENTAL ANALYSIS AB The levels of the toxic elements Al, As, Cd, Hg, Pb and Sn are routinely monitored in food to protect the consumer. Increasingly, the chemical forms of As and Hg are also monitored. Analyses are performed to enforce regulatory standards and to accumulate background levels for assessing long-term exposure. The analytical procedures used for these activities evolve as requirements to determine lower levels arise and as both the types and sheer number of different foods that need to be analyzed increase. This review highlights recent work addressing improvements in the analysis of toxic elements in food. The topics covered include contamination control, analytical sample treatment and the common analytical techniques used for food analysis. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Capar, SG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Harvey W Wiley Fed Bldg,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM stephen.capar@fda.hhs.gov NR 137 TC 23 Z9 26 U1 1 U2 37 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2007 VL 389 IS 1 BP 159 EP 169 DI 10.1007/s00216-007-1433-6 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 203KU UT WOS:000248974300017 PM 17609933 ER PT J AU Rimmer, CA Howerton, SB Sharpless, KE Sander, LC Long, SE Murphy, KE Porter, BJ Putzbach, K Rearick, MS Wise, SA Wood, LJ Zeisler, R Hancock, DK Yen, JH Betz, JM NguyenPho, A Yang, L Scriver, C Willie, S Sturgeon, R Schaneberg, B Nelson, C Skamarack, J Pan, M Levanseler, K Gray, D Waysek, EH Blatter, A Reich, E AF Rimmer, Catherine A. Howerton, Samuel B. Sharpless, Katherine E. Sander, Lane C. Long, Stephen E. Murphy, Karen E. Porter, Barbara J. Putzbach, Karsten Rearick, Michael S. Wise, Stephen A. Wood, Laura J. Zeisler, Rolf Hancock, Diane K. Yen, James H. Betz, Joseph M. NguyenPho, Agnes Yang, Lu Scriver, Christine Willie, Scott Sturgeon, Ralph Schaneberg, Brian Nelson, Christina Skamarack, Jules Pan, Meide Levanseler, Kerri Gray, Dean Waysek, Edward H. Blatter, Anne Reich, Eike TI Characterization of a suite of ginkgo-containing standard reference materials SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE liquid chromatography; mass spectrometry; Ginkgo biloba; standard reference material; dietary supplements ID PERFORMANCE LIQUID-CHROMATOGRAPHY; EVAPORATIVE LIGHT-SCATTERING; PLASMA-MASS SPECTROMETRY; ID ICP-MS; BILOBA LEAVES; FLAVONOL AGLYCONES; EXTRACTS; CERTIFICATION; PHYTOPHARMACEUTICALS; TERPENELACTONES AB A suite of three ginkgo-containing dietary supplement Standard Reference Materials (SRMs) has been issued by the National Institute of Standards and Technology (NIST) with certified values for flavonoid aglycones, ginkgolides, bilobalide, and selected toxic trace elements. The materials represent a range of matrices (i.e., plant, extract, and finished product) that provide different analytical challenges. The constituents have been determined by at least two independent analytical methods with measurements performed by NIST and at least one collaborating laboratory. The methods utilized different extractions, chromatographic separations, modes of detection, and approaches to quantitation. The SRMs are primarily intended for method validation and for use as control materials to support the analysis of dietary supplements and related botanical materials. C1 NIST, Gaithersburg, MD 20899 USA. NIH, Off Dietary Supplement, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Natl Res Council Canada, Ottawa, ON K1A 0R9, Canada. ChromaDex Inc, Boulder, CO 80301 USA. Eurofins, Petaluma, CA 94952 USA. NSF Int, Ann Arbor, MI 48105 USA. Midwest Res Inst, Kansas City, MO 64110 USA. Caravan Prod, Totowa, NJ 07512 USA. CAMAG, Muttenz, Switzerland. RP Rimmer, CA (reprint author), NIST, Gaithersburg, MD 20899 USA. EM Catherine.Rimmer@nist.gov OI Yang, Lu/0000-0002-4351-2503; Sharpless, Katherine/0000-0001-6569-198X; Sturgeon, Ralph/0000-0001-7304-3034; Willie, Scott/0000-0002-3376-0722 NR 33 TC 17 Z9 17 U1 0 U2 6 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2007 VL 389 IS 1 BP 179 EP 196 DI 10.1007/s00216-007-1398-5 PG 18 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 203KU UT WOS:000248974300019 PM 17619180 ER PT J AU Andrews, KW Schweitzer, A Zhao, C Holden, JM Roseland, JM Brandt, M Dwyer, JT Picciano, MF Saldanha, LG Fisher, KD Yetley, E Betz, JM Douglass, L AF Andrews, Karen W. Schweitzer, Amy Zhao, Cuiwei Holden, Joanne M. Roseland, Janet M. Brandt, Mary Dwyer, Johanna T. Picciano, Mary Frances Saldanha, Leila G. Fisher, Kenneth D. Yetley, Elizabeth Betz, Joseph M. Douglass, Larry TI The caffeine contents of dietary supplements commonly purchased in the US: analysis of 53 products with caffeine-containing ingredients SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE caffeine; HPLC; UV; VIS; Dietary supplement; reference material ID CAMELLIA-SINENSIS; PURINE ALKALOIDS; HPLC; TEA; THEOBROMINE; CATECHINS; SAMPLES; COLUMN; SYSTEM AB As part of a study initiating the development of an analytically validated Dietary Supplement Ingredient Database (DSID) in the United States (US), a selection of dietary supplement products were analyzed for their caffeine content. Products sold as tablets, caplets, or capsules and listing at least one caffeine-containing ingredient (including botanicals such as guarana, yerba mate, kola nut, and green tea extract) on the label were selected for analysis based on market share information. Two or three lots of each product were purchased and analyzed using high-pressure liquid chromatography (HPLC). Each analytical run included one or two National Institute of Standards and Technology (NIST) Standard Reference Materials (SRMs) and two products in duplicate. Caffeine intake per serving and per day was calculated using the maximum recommendations on each product label. Laboratory analysis for 53 products showed product means ranging from 1 to 829 mg caffeine/day. For products with a label amount for comparison (n=28), 89% (n=25) of the products had analytically based caffeine levels/day of between -16% and +16% of the claimed levels. Lot-to-lot variability (n=2 or 3) for caffeine in most products (72%) was less than 10%. C1 USDA, Agr Res Serv, Beltsville Human Nutr Res Ctr, Nutrient Data Lab, Beltsville, MD 20705 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. US Dept HHS, Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD USA. Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. RP Andrews, KW (reprint author), USDA, Agr Res Serv, Beltsville Human Nutr Res Ctr, Nutrient Data Lab, Beltsville, MD 20705 USA. EM karen.andrews@ars.usda.gov OI Dwyer, Johanna/0000-0002-0783-1769 NR 19 TC 34 Z9 35 U1 0 U2 17 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD SEP PY 2007 VL 389 IS 1 BP 231 EP 239 DI 10.1007/s00216-007-1437-2 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 203KU UT WOS:000248974300023 PM 17676317 ER PT J AU Shafer, SL AF Shafer, Steven L. TI Neurotoxicity of anesthetic agents in children - Response SO ANESTHESIA AND ANALGESIA LA English DT Letter C1 Stanford Univ, FDA Anesthesia & Life Support Drugs, Stanford, CA 94305 USA. RP Shafer, SL (reprint author), Stanford Univ, FDA Anesthesia & Life Support Drugs, Stanford, CA 94305 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD SEP PY 2007 VL 105 IS 3 BP 882 EP 883 DI 10.1213/01.ane.0000269694.05481.68 PG 2 WC Anesthesiology SC Anesthesiology GA 202SS UT WOS:000248924400063 ER PT J AU Cohen, ALV Oliver, JD DePaola, A Feil, EJ Boyd, EF AF Cohen, Ana Luisa V. Oliver, James D. DePaola, Angelo Feil, Edward J. Boyd, E. Fidelma TI Emergence of a virulent clade of Vibrio vulnificus and correlation with the presence of a 33-kilobase genomic island SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FIELD GEL-ELECTROPHORESIS; POLYMORPHIC DNA PCR; FRAGMENT-LENGTH-POLYMORPHISM; NUCLEOTIDE SUBSTITUTIONS; ENVIRONMENTAL STRAINS; POPULATION-GENETICS; SEQUENCE ALIGNMENT; HUMAN PATHOGEN; UNITED-STATES; IN-VITRO AB Vibrio vulnificus is a ubiquitous inhabitant of the marine coastal environment, and an important pathogen of humans. We characterized a globally distributed sample of environmental isolates from a range of habitats and hosts and compared these with isolates recovered from cases of human infection. Multilocus sequence typing data using six housekeeping genes divided 63 of the 67 isolates into the two main lineages previously noted for this species, and this division was also confirmed using the 16S rRNA and open reading frame VV0401 markers. Lineage I was comprised exclusively of biotype I isolates, whereas lineage H contained biotype I and all biotype 2 isolates. Four isolates did not cluster within either lineage: two biotype 3 and two biotype I isolates. The proportion of isolates recovered from a clinical setting was noted to be higher in lineage I than in lineage H. Lineage I isolates were also associated with a 33-kb genomic island (region XII), one of three regions identified by genome comparisons as unique to the species. Region XII contained an arylsulfatase gene cluster, a sulfate reduction system, two chondroitinase genes, and an oligopeptide ABC transport system, all of which are absent from the majority of lineage 11 isolates. Arylsulfatases and the sulfate reduction system, along with performing a scavenging role, have been hypothesized to play a role in pathogenic processes in other bacteria. Our data suggest that lineage I may have a higher pathogenic potential and that region XII, along with other regions, may give isolates a selective advantage either in the human host or in the aquatic environment or both. C1 Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. Natl Univ Ireland, Dept Microbiol, Cork, Ireland. Univ N Carolina, Dept Biol, Charlotte, NC 28223 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Univ Bath, Dept Biol & Biochem, Bath BA2 7AY, Avon, England. RP Boyd, EF (reprint author), Univ Delaware, Dept Biol Sci, Newark, DE 19716 USA. EM fboyd@udel.edu NR 79 TC 59 Z9 59 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD SEP PY 2007 VL 73 IS 17 BP 5553 EP 5565 DI 10.1128/AEM.00635-07 PG 13 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 207JF UT WOS:000249246700021 PM 17616611 ER PT J AU Nordstrom, JL Vickery, MCL Blackstone, GM Murray, SL DePaola, A AF Nordstrom, Jessica L. Vickery, Michael C. L. Blackstone, George M. Murray, Shelley L. DePaola, Angelo TI Development of a multiplex real-time PCR assay with an internal amplification control for the detection of total and pathogenic Vibrio parahaemolyticus bacteria in oysters SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; THERMOLABILE HEMOLYSIN; NUCLEOTIDE-SEQUENCE; ALASKAN OYSTERS; UNITED-STATES; GENE TRH; TDH GENE; SHELLFISH; QUANTIFICATION; SEAFOOD AB Vibrio parahaemolyticus is an estuarine bacterium that is the leading cause of shellfish-associated cases of bacterial gastroenteritis in the United States. Our laboratory developed a real-time multiplex PCR assay for the simultaneous detection of the thermolabile hemolysin (tlh), thermostable direct hemolysin (tdh), and thermostable-related hemolysin (trh) genes of V. parahaemolyticus. The tlh gene is a speciesspecific marker, while the tdh and trh genes are pathogenicity markers. An internal amplification control (IAC) was incorporated to ensure PCR integrity and eliminate false-negative reporting. The assay was tested for specificity against > 150 strains representing eight bacterial species. Only V. parahaemolyticus strains possessing the appropriate target genes generated a fluorescent signal, except for a late tdh signal generated by three strains of V. hollisae. The multiplex assay detected < 10 CFU/reaction of pathogenic V. parahaemolyticus in the presence of > 10(4) CFU/reaction of total V. parahaemolyticus bacteria. The real-time PCR assay was utilized with a most-probable-number format, and its results were compared to standard V. parahaemolyticus isolation methodology during an environmental survey of Alaskan oysters. The IAC was occasionally inhibited by the oyster matrix, and this usually corresponded to negative results for V. parahaemolyticus targets. V. parahaemolyticus tlh, tdh, and trh were detected in 44, 44, and 52% of the oyster samples, respectively. V. parahaemolyticus was isolated from 33% of the samples, and tdh(+) and trh(+) strains were isolated from 19 and 26%, respectively. These results demonstrate the utility of the real-time PCR assay in environmental surveys and its possible application to outbreak investigations for the detection of total and pathogenic V. parahaemolyticus. C1 US FDA, Gulf Coast Seafood Lab, Div Seafood Sci & Technol, Dauphin Isl, AL 36528 USA. Alaska Dept Environm Conservat, Anchorage, AK 99501 USA. RP Nordstrom, JL (reprint author), US FDA, Gulf Coast Seafood Lab, Div Seafood Sci & Technol, POB 158, Dauphin Isl, AL 36528 USA. EM jessica.nordstrom@fda.hhs.gov NR 45 TC 170 Z9 189 U1 1 U2 17 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD SEP PY 2007 VL 73 IS 18 BP 5840 EP 5847 DI 10.1128/AEM.00460-07 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 211VC UT WOS:000249550400018 PM 17644647 ER PT J AU Zhukovsky, MA Markovic, I Bailey, AL AF Zhukovsky, Mikhail A. Markovic, Ingrid Bailey, Austin L. TI Influence of calcium on lipid mixing mediated by influenza hemagglutinin SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; VIRAL MEMBRANE-FUSION; CONFORMATIONAL CHANGE; CRYSTAL-STRUCTURE; CYTOPLASMIC TAIL; TEMPERATURE; EXOCYTOSIS; LIPOSOMES; MECHANISM; PROTEINS AB We studied the influence of calcium on lipid mixing mediated by influenza hemagglutinin (HA). Lipid mixing between HA-expressing cells and liposomes containing disialoganglioside, influenza virus receptor, was studied at 37 C and neutral pH after a low-pH pulse at 4 C. With DSPC/cholesterol liposomes, calcium present after raising the temperature significantly promoted lipid mixing only when it was triggered by a short low-pH application. In case of DOPC/cholesterol liposomes, calcium promotion was observed regardless of the duration of the low-pH pulse. Calcium present during a short, but not long, low-pH application to HA-expressing cells with bound DSPC/cholesterol liposomes at 4 C inhibited subsequent lipid mixing. We hypothesize that calcium influences lipid mixing because it binds to a vestigial esterase domain of hemagglutinin or causes expulsion of the fusion peptide from an electronegative cavity. We suggest that calcium promotes the transition from early and reversible conformation(s) of low pH-activated HA towards an irreversible conformation that underlies both HA-mediated lipid mixing and HA inactivation. (c) 2007 Elsevier Inc. All rights reserved. C1 Sci Commuicat Cephalon Inc, Hoboken, NJ 07030 USA. Max Planck Inst Biophys Chem, Abt Spektroskopie & Photochem Kinetik Struckturdy, D-37077 Gottingen, Germany. NICHHD, Natl Inst Hlth, Lab Cellular & Mol Biol, Sect Membrane Biol, Bethesda, MD 20892 USA. Harvard Univ, Sch Med, Dana Farber Canc Inst, Dept Canc Immunol & AIDS, Boston, MA 02115 USA. RP Zhukovsky, MA (reprint author), Ctr Drug Evaluat & Res, US FDA, Bethesda, MD 20892 USA. EM mzhukov@gwdg.de FU Intramural NIH HHS [Z01 HD001501-16] NR 58 TC 1 Z9 1 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD SEP 1 PY 2007 VL 465 IS 1 BP 101 EP 108 DI 10.1016/j.abb.2007.05.005 PG 8 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 206IF UT WOS:000249176400012 PM 17585869 ER PT J AU Abdo, AA Allen, BT Berley, D Blaufuss, E Casanova, S Dingus, BL Ellsworth, RW Gonzalez, MM Goodman, JA Hays, E Hoffman, CM Kolterman, BE Lansdell, CP Linnemann, JT McEnery, JE Mincer, AI Nemethy, P Noyes, D Ryan, JM Samuelson, FW Parkinson, PMS Shoup, A Sinnis, G Smith, AJ Sullivan, GW Vasileiou, V Walker, GP Williams, DA Xu, XW Yodh, GB AF Abdo, A. A. Allen, B. T. Berley, D. Blaufuss, E. Casanova, S. Dingus, B. L. Ellsworth, R. W. Gonzalez, M. M. Goodman, J. A. Hays, E. Hoffman, C. M. Kolterman, B. E. Lansdell, C. P. Linnemann, J. T. McEnery, J. E. Mincer, A. I. Nemethy, P. Noyes, D. Ryan, J. M. Samuelson, F. W. Parkinson, P. M. Saz Shoup, A. Sinnis, G. Smith, A. J. Sullivan, G. W. Vasileiou, V. Walker, G. P. Williams, D. A. Xu, X. W. Yodh, G. B. TI Milagro constraints on very high energy emission from short-duration gamma-ray bursts SO ASTROPHYSICAL JOURNAL LA English DT Article DE gamma rays : bursts; gamma rays : observations ID GRB 970417A; HOST GALAXY; TEV; AFTERGLOW; DISCOVERY; GRB-050709; TELESCOPE; SEARCH; FLARES; ARRAY AB Recent rapid localizations of short, hard gamma-ray bursts (GRBs) by the Swift and HETE satellites have led to the observation of the first afterglows and the measurement of the first redshifts from this type of burst ( Fox et al. 2005; Gehrels et al. 2005; Villasenor et al. 2005; Berger et al. 2005; Barthelmy et al. 2005). Detection of > 100 GeV counterparts would place powerful constraints on GRB mechanisms. Seventeen short-duration (< 5 s) GRBs detected by satellites occurred within the field of view of the Milagro gamma-ray observatory between 2000 January and 2006 December. We have searched the Milagro data for > 100 GeV counterparts to these GRBs and find no significant emission correlated with these bursts. Due to the absorption of high-energy gamma rays by the extragalactic background light (EBL), detections are only expected for redshifts less than similar to 0.5. While most long-duration GRBs occur at redshifts higher than 0.5, the opposite is thought to be true of short GRBs. Lack of a detected VHE signal thus allows setting meaningful fluence limits. One GRB in the sample (050509b) has a likely association with a galaxy at a redshift of 0.225, while another ( 051103) has been tentatively linked to the nearby galaxy M81. Fluence limits are corrected for EBL absorption, either using the known measured redshift, or computing the corresponding absorption for a redshift of 0.1 and 0.5, as well as for the case of z = 0. C1 Argonne Natl Lab, Div High Energy Phys, Argonne, IL 60439 USA. Univ Calif Irvine, Dept Phys & Astron, Irvine, CA 92697 USA. Univ Maryland, Dept Phys, College Pk, MD 20742 USA. Los Alamos Natl Lab, Dept Phys, Los Alamos, NM 87545 USA. George Mason Univ, Dept Phys, Fairfax, VA 22030 USA. Univ Nacl Autonoma Mexico, Inst Astron, Mexico City 04510, DF, Mexico. Argonne Natl Lab, Div High Energy Phys, Argonne, IL 60439 USA. NYU, Dept Phys, New York, NY 10003 USA. NASA, Goddard Space Flight Ctr, Greenbelt, MD 20771 USA. US FDA, Ctr Devices & Radiol Hlth, Office Sci & Engn Lab, Rockville, MD 20857 USA. Univ Calif Santa Cruz, Inst Particle Phys, Santa Cruz, CA 95064 USA. Ohio State Univ, Lima, OH 45804 USA. Michigan State Univ, Dept Phys & Astron, E Lansing, MI 48824 USA. RP Abdo, AA (reprint author), Argonne Natl Lab, Div High Energy Phys, 9700 S Cass Ave, Argonne, IL 60439 USA. RI McEnery, Julie/D-6612-2012; Hays, Elizabeth/D-3257-2012; Casanova, Sabrina/J-8935-2013; OI Casanova, Sabrina/0000-0002-6144-9122; Dingus, Brenda/0000-0001-8451-7450; Mincer, Allen/0000-0002-6307-1418 NR 51 TC 29 Z9 29 U1 0 U2 4 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0004-637X J9 ASTROPHYS J JI Astrophys. J. PD SEP 1 PY 2007 VL 666 IS 1 BP 361 EP 367 DI 10.1086/519763 PN 1 PG 7 WC Astronomy & Astrophysics SC Astronomy & Astrophysics GA 204QH UT WOS:000249058600034 ER PT J AU Breslow, RA Falk, DE Fein, SB Grummer-Strawn, LM AF Breslow, Rosalind A. Falk, Daniel E. Fein, Sara B. Grummer-Strawn, Laurence M. TI Alcohol Consumption Among Breastfeeding Women SO BREASTFEEDING MEDICINE LA English DT Article AB Purpose: To determine the prevalence of alcohol consumption among breastfeeding and non-breastfeeding women at 3 months postpartum. Methods: We analyzed the most recent data available, which were from the 1993-1994 Food and Drug Administration Infant Feeding Practices Study I, a longitudinal panel study of infant-mother pairs. Self-reported data on alcohol consumption were analyzed for 772 breastfeeding women and 776 non-breastfeeding women age >= 14 years. Results: At 3 months postpartum, 36% of breastfeeding women and 40% of non-breastfeeding women consumed alcohol (p = 0.09). In multinomial regression models adjusted for age, race, education, income, marital status, region, smoking, and alcohol consumption before and during pregnancy, breastfeeding women were significantly less likely than non-breastfeeding women to consume two drinks per week (p < 0.01), or equal to or more than three drinks per week (p < 0.01), but equally likely to consume one drink (p = 0.23). Conclusions: A substantial percentage of breastfeeding women consumed alcohol. Their infants may or may not have been exposed, as some women may have used alcohol avoidance strategies. Nationally representative data are needed on alcohol consumption and infant feeding practices among breastfeeding women. C1 [Breslow, Rosalind A.] NIAAA, Div Epidemiol & Prevent Res, NIH, Bethesda, MD 20892 USA. [Falk, Daniel E.] CSR Inc, Arlington, VA USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Grummer-Strawn, Laurence M.] Ctr Dis Control & Prevent, Div Nutr & Phys Act, Atlanta, GA USA. RP Breslow, RA (reprint author), NIAAA, Div Epidemiol & Prevent Res, NIH, 5635 Fishers Lane,Room 2860, Bethesda, MD 20892 USA. EM rbreslow@mail.nih.gov NR 12 TC 11 Z9 12 U1 1 U2 8 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 SEP PY 2007 VL 2 IS 3 BP 152 EP 157 DI 10.1089/bfm.2007.0012 PG 6 WC Obstetrics & Gynecology; Pediatrics SC Obstetrics & Gynecology; Pediatrics GA V11LU UT WOS:000207533900005 PM 17903101 ER PT J AU Deeb, KK Michalowska, AM Yoon, CY Krummey, SM Hoenerhoff, MJ Kavanaugh, C Li, MC Demayo, FJ Linnoila, I Deng, CX Lee, EYHP Medina, D Shih, JH Green, JE AF Deeb, Kristin K. Michalowska, Aleksandra M. Yoon, Cheol-yong Krummey, Scott M. Hoenerhoff, Mark J. Kavanaugh, Claudine Li, Ming-chung Demayo, Francesco J. Linnoila, Ilona Deng, Chu-xia Lee, Eva Y. -H. P. Medina, Daniel Shih, Joanna H. Green, Jeffrey E. TI Identification of an integrated SV40 T/t-antigen cancer signature in aggressive human breast, prostate, and lung carcinomas with poor prognosis SO CANCER RESEARCH LA English DT Article ID LARGE T-ANTIGEN; GENE-EXPRESSION PATTERNS; MAMMARY EPITHELIAL-CELLS; TRANSGENIC MICE; CELLULAR-TRANSFORMATION; MICROARRAY ANALYSIS; METASTATIC-DISEASE; FUSION GENE; TUMORS; MOUSE AB Understanding the genetic architecture of cancer pathways that distinguishes subsets of human cancer is critical to developing new therapies that better target tumors based on their molecular expression profiles. In this study, we identify an integrated gene signature from multiple transgenic models of epithelial cancers intrinsic to the functions of the Simian virus 40 T/t-antigens that is associated with the biological behavior and Prognosis for several human epithelial tumors. This genetic signature, composed primarily of genes regulating cell replication, proliferation, DNA repair, and apoptosis, is not a general cancer signature. Rather, it is uniquely activated primarily in tumors with aberrant p53, Rb, or BRCA1 expression but not in tumors initiated through the overexpression of myc, ras, her2/neu, or polyoma middle T oncogenes. Importantly, human breast, lung, and prostate tumors expressing this set of genes represent subsets of tumors with the most aggressive phenotype and with poor prognosis. The T/t-antigen signature is highly predictive of human breast cancer prognosis. Because this class of epithelial tumors is generally intractable to currentiv existing standard therapies, this genetic signature identifies potential targets for novel therapies directed against these lethal forms of cancer. Because these genetic targets have been discovered using mammary, prostate, and lung T/t-antigen mouse cancer models, these models are rationale candidates for use in preclinical testing of therapies focused on these biologically important targets. C1 Roswell Park Canc Inst, Buffalo, NY USA. SUNY Stony Brook, Dept Biol, Stony Brook, NY USA. US FDA, College Pk, MD USA. NIH, NIDDK, Lab Cell Regulation & Carcinogenes, Bethesda, MD USA. NIH, NIDDK, Cell & Canc Biol Branch, Bethesda, MD USA. NIH, NIDDK, Ctr Canc Res, Natl Canc Inst,Biometrics Res Branch, Bethesda, MD USA. NIH, NIDDK, Ctr Canc Res, Genet Dev & Dis Branch, Bethesda, MD USA. EMMES Corp, Rockville, MD USA. Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA. Baylor Univ, Ctr Canc, Houston, TX USA. Univ Calif Irvine, Irvine, CA USA. RP Green, JE (reprint author), NCI, Transgenic Oncogenes & Genomics Sect, Canc Biol Lab & Genet, Room 4054,Bldg 37,37 Convent Dr, Bethesda, MD 20892 USA. EM JEGreen@nih.gov RI deng, chuxia/N-6713-2016 FU Intramural NIH HHS NR 49 TC 74 Z9 75 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD SEP 1 PY 2007 VL 67 IS 17 BP 8065 EP 8080 DI 10.1158/0008-5472.CAN-07-1515 PG 16 WC Oncology SC Oncology GA 209RW UT WOS:000249406700022 PM 17804718 ER PT J AU Su, ZQ Hong, HX Tong, WD Perkins, R Shao, XG Cai, WS AF Su Zhen-Qiang Hong Hui-Xiao Tong Wei-Da Perkins Roger Shao Xue-Guang Cai Wen-Sheng TI Identification of differentially expressed genes using disjoint principal component analysis coupled with genetic algorithm SO CHEMICAL JOURNAL OF CHINESE UNIVERSITIES-CHINESE LA Chinese DT Article DE microarray; principal component analysis(PCA); genetic algorithm(GA); significance analysis of microarrays (SAM); chance correlation ID MODELS; NUMBER AB A new method for the feature selection using disjoint principal component analysis(PCA) coupled with genetic algorithm(CA) was proposed and was used to identify differentially expressed genes based on microarray gene expression profiles. The discriminatory power of combination of genes is assessed with using disjoint PCA, the combinatorial optimization problem of genes is solved by using GA, and the chance correlation of genes is assessed by a statistic method. Due to considering the cooperation between genes which is a way to approximate the synergistic regulation by genes during the biological processes, the genes identified by our method are capable of powerful ability to express the differences. This method has been applied to analyze the gene microarray data of hepatocellular caricinoma(HCC). It is found that the genes identified by the proposed method has more discriminatory power in distinguishing two-class samples than those identified by SAM (significance analysis of microarrays), which is very popular in the analysis of microarray data. C1 US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Jefferson, AR 72079 USA. Univ Sci & Technol China, Dept Chem, Hefei 230026, Peoples R China. Natl Ctr Toxicol Res, Z Tech FDA, Div Bioinformat, Jefferson, AR 72079 USA. Nankai Univ, Dept Chem, Tianjin 300071, Peoples R China. RP Tong, WD (reprint author), US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Jefferson, AR 72079 USA. EM tong@fda.hhs.gov; wscai@nankai.edu.cn RI Su, Zhenqiang/H-3914-2012 NR 9 TC 2 Z9 2 U1 0 U2 2 PU HIGHER EDUCATION PRESS PI BEIJING PA SHATANHOU ST 55, BEIJING 100009, PEOPLES R CHINA SN 0251-0790 J9 CHEM J CHINESE U JI Chem. J. Chin. Univ.-Chin. PD SEP PY 2007 VL 28 IS 9 BP 1640 EP 1644 PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 212XF UT WOS:000249629600009 ER PT J AU Sunenshine, RH Tan, ET Terashita, DM Jensen, BJ Kacica, MA Sickbert-Bennett, EE Noble-Wang, JA Palmieri, MJ Bopp, DJ Jernigan, DB Kazakova, S Bresnitz, EA Tan, CG McDonald, LC AF Sunenshine, Rebecca H. Tan, Esther T. Terashita, Dawn M. Jensen, Bette J. Kacica, Marilyn A. Sickbert-Bennett, Emily E. Noble-Wang, Judith A. Palmieri, Michael J. Bopp, Dianna J. Jernigan, Daniel B. Kazakova, Sophia Bresnitz, Eddy A. Tan, Christina G. McDonald, L. Clifford TI A multistate outbreak of Serratia marcescens bloodstream infection associated with contaminated intravenous magnesium sulfate from a compounding pharmacy SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the Infectious-Diseases-Society-of-America CY OCT 06-09, 2005 CL San Francisco, CA SP Infect Dis Soc Amer ID EPIDEMIC SEPTIC ARTHRITIS; FIELD GEL-ELECTROPHORESIS; BENZALKONIUM CHLORIDE AB Background. In contrast to pharmaceutical manufacturers, compounding pharmacies adhere to different quality-control standards, which may increase the likelihood of undetected outbreaks. In 2005, the Centers for Disease Control and Prevention received reports of cases of Serratia marcescens bloodstream infection occurring in patients who underwent cardiac surgical procedures in Los Angeles, California, and in New Jersey. An investigation was initiated to determine whether there was a common underlying cause. Methods. A matched case-control study was conducted in Los Angeles. Case record review and environmental testing were conducted in New Jersey. The Centers for Disease Control and Prevention performed a multistate case-finding investigation; isolates were compared using pulsed-field gel electrophoresis analysis. Results. Nationally distributed magnesium sulfate solution (MgSO4) from compounding pharmacy X was the only significant risk factor for S. marcescens bloodstream infection ( odds ratio, 6.4; 95% confidence interval, 1.1-38.3) among 6 Los Angeles case patients and 18 control subjects. Five New Jersey case patients received MgSO4 from a single lot produced by compounding pharmacy X; culture of samples from open and unopened 50-mL bags in this lot yielded S. marcescens. Seven additional case patients from 3 different states were identified. Isolates from all 18 case patients and from samples of MgSO4 demonstrated indistinguishable pulsed-field gel electrophoresis patterns. Compounding pharmacy X voluntarily recalled the product. Neither the pharmacy nor the US Food and Drug Administration could identify a source of contamination in their investigations of compounding pharmacy X. Conclusions. A multistate outbreak of S. marcescens bloodstream infection was linked to contaminated MgSO4 distributed nationally by a compounding pharmacy. Health care personnel should take into account the different quality standards and regulation of compounded parenteral medications distributed in large quantities during investigations of outbreaks of bloodstream infection. C1 Arizona Dept Hlth Serv, Ctr Dis Control & Prevent, Phoenix, AZ 85007 USA. New Jersey Dept Hlth & Senior Serv, Trenton, NJ USA. Los Angeles Cty Dept Hlth Serv, Los Angeles, CA USA. New York State Dept Hlth, Wadsworth Ctr Labs & Res, New York, NY USA. US FDA, NE Reg Lab, Jamaica, NY USA. Univ N Carolina, Chapel Hill, NC USA. RP Sunenshine, RH (reprint author), Arizona Dept Hlth Serv, Ctr Dis Control & Prevent, 150 N 18th Ave,Ste 150, Phoenix, AZ 85007 USA. EM Sunensr@azdhs.gov NR 22 TC 37 Z9 37 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD SEP 1 PY 2007 VL 45 IS 5 BP 527 EP 533 DI 10.1086/520664 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 197LM UT WOS:000248557000010 PM 17682984 ER PT J AU Shim, YK Vogt, RF Middleton, D Abbasi, F Slade, B Lee, KY Marti, GE AF Shim, Youn K. Vogt, Robert F. Middleton, Dan Abbasi, Fatima Slade, Barbara Lee, Kyung Y. Marti, Gerald E. TI Prevalence and natural history of monoclonal and polyclonal B-Cell lymphocytosis in a residential adult population SO CYTOMETRY PART B-CLINICAL CYTOMETRY LA English DT Article DE monoclonal B-cell lymphocytosis; MBL; chronic lymphocytic leukemia; B-cell lymphoproliferative disease; hazardous waste sites; follow-up study ID GENE MUTATION STATUS; IMMUNOPHENOTYPIC ANALYSIS; CD38 EXPRESSION; FLOW-CYTOMETRY; LEUKEMIA; DISEASE; BLOOD; LYMPHOMA; CLL; PROGRESSION AB Background: Monoclonal B-cells can be detected in the peripheral blood of some adults without B-cell malignancies, a condition recently termed monoclonal B-cell lymphocytosis (MBL). The risk of individuals with MBL progressing to a B-cell malignancy is unknown. Polyclonal B-cell lymphocytosis (PCBL) has not been systematically studied in the general population. Methods: We obtained lymphocyte subset counts on 1,926 residential adults aged 40-76 years in a series of environmental health studies between 1991 and 1994. We then conducted two follow-ups in 1997 and 2003 on consenting participants with B-cell lymphocytosis, which included nine participants with MBL. To ascertain the clinical implications of MBL, we reviewed medical records and death certificates. Results: The overall prevalence of MBL was 0.57% (11/1,926): nine cases at baseline and two additional cases identified at follow-up. Two (19%) MBL cases subsequently developed a B-cell malignancy; MBL persisted in the remaining nine cases (81%). All PCBL cases where no clone emerged regressed to normal B-cell counts over the follow-up period. MBL was significantly more frequent in residents near a hazardous waste site than in the control populations (age-adjusted OR 6.2; 95%CI 1.1-36.2). Conclusion: MBL confers an elevated risk for developing a B-cell malignancy, although it occurs only in a minority of cases. PCBL is most often a transient state, but a monoclonal population can emerge and persist. Prospective studies are needed to distinguish stable from progressive forms of B-cell lymphocytosis and to clarify the etiologic role of environmental exposures. Published 2007 Wiley-Liss, Inc. C1 Agcy Toxic Subst & Dis Registry, Div Hlth Studies, Atlanta, GA USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Environm Hlth Lab Sci, Toxicol Branch, Atlanta, GA 30341 USA. Ctr Biol Evaluat & Res, Off Cellular Tissue & Gene Therapeut, US FDA, Rockville, MD USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Div HIV AIDS, Atlanta, GA 30333 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmacoepidemiol & Stat Sci, Rockville, MD 20857 USA. RP Shim, YK (reprint author), ATSDR, Div Hlth Studies, 1600 Clifton Rd,NE, Atlanta, GA 30333 USA. EM yshim@cdc.gov NR 45 TC 46 Z9 47 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4949 J9 CYTOM PART B-CLIN CY JI Cytom. Part B-Clin. Cytom. PD SEP PY 2007 VL 72B IS 5 BP 344 EP 353 DI 10.1002/cyto.b.20174 PG 10 WC Medical Laboratory Technology; Pathology SC Medical Laboratory Technology; Pathology GA 205HJ UT WOS:000249104300006 PM 17266153 ER PT J AU Markovic, I AF Markovic, Ingrid TI Evaluation of safety and quality impact of extractable and leachable substances in therapeutic biologic protein products: a risk-based perspective SO EXPERT OPINION ON DRUG SAFETY LA English DT Editorial Material DE extractables; leachables; patient safety; product quality attributes; therapeutic biologics ID RED-CELL APLASIA; PHTHALATE AB Leachables are chemical entities that migrate spontaneously from the final container closure system, packaging components and/or processing equipment under recommended conditions of product use and storage. Unlike leachables, extractables are generated under exaggerated temperature and time conditions in the presence of an appropriate solvent. increasing evidence suggests that leachables may pose a safety risk by causing toxicity, carcinogenicity, immunogenicity and/or endocrine dysregulation. These substances may also alter product physico-chemical properties via interaction with the active pharmaceutical ingredient or the excipients in product vehicle, thereby adversely affecting the final product quality. The evaluation of leachable compounds begins with a thorough identification of extractable compounds released from the production and packaging components under exaggerated conditions. The set of observed extractables helps to identify possible targets to be monitored in a subsequent leachables study over extended time periods. Although extractables and leachables also present a challenge for the safe use of device components (e.g., metered dose inhalers, dry powder inhalers, nasal spray devices or various implants), this review focusses on a safety risk assessment for specified therapeutic biological protein products. Regulatory, safety and scientific considerations in evaluating extractables and leachables are discussed, along with strategies for the analytical identification, quantification and monitoring. C1 Ctr Drug Evaluat & Res, Div Therapeut Proteins, Off Biotechnol Prod,Off Pharmaceut Sci, Food & Grug Adm, Bethesda, MD 20892 USA. RP Markovic, I (reprint author), Ctr Drug Evaluat & Res, Div Therapeut Proteins, Off Biotechnol Prod,Off Pharmaceut Sci, Food & Grug Adm, Bethesda, MD 20892 USA. EM ingrid.markovic@fda.hhs.gov NR 13 TC 11 Z9 12 U1 2 U2 11 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD SEP PY 2007 VL 6 IS 5 BP 487 EP 491 DI 10.1517/14740338.6.5.487 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 216DF UT WOS:000249857600004 PM 17877437 ER PT J AU Chattopadhyay, R Mahajan, B Kumar, S AF Chattopadhyay, Rana Mahajan, Babita Kumar, Sanjai TI Assessment of safety of the major antimalarial drugs SO EXPERT OPINION ON DRUG SAFETY LA English DT Review DE adverse effects; antimalarial drug; Plasmodium; safety ID PLASMODIUM-FALCIPARUM MALARIA; PLUS SULFADOXINE-PYRIMETHAMINE; PLACEBO-CONTROLLED TRIAL; CONTROL AUDITORY EVALUATION; SUB-SAHARAN AFRICA; QUININE-DEPENDENT ANTIBODIES; RANDOMIZED CONTROLLED-TRIAL; TOXIC EPIDERMAL NECROLYSIS; STEVENS-JOHNSON SYNDROME; CONTROLLED FIELD TRIAL AB Antimalarial drugs remain the major intervention tool for the global malaria control efforts that save millions of lives. Nonetheless, emergence and spread of Plasmodium parasites resistant against chloroquine and other major antimalarial drugs has brought the urgency to develop a new generation of safe and effective drugs against malaria. In this article, the safety data for major antimalarial drugs is reviewed. Although an ample amount of clinical data regarding the safety and tolerability of several of these drugs in older children and adults is available, more critical safety and tolerability studies in pregnant women and young children is desirable. To offset the partial loss in efficacy due to drug resistance in malaria parasites acquired against specific drugs, treatment regimens often rely upon the combination of two or more drugs. However, combination therapy requires additional safety, toxicity and tolerability studies in all population groups where these drugs are administered. A uniform standard in assessing the safety and tolerability of antimalarial drugs will be useful in the formulation and implementation of malaria treatment policies that are based on the drug effectiveness, safety and tolerability. C1 Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmit Dis, US FDA, Rockville, MD 20895 USA. Sanaria Inc, Rockville, MD 20852 USA. RP Kumar, S (reprint author), Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmit Dis, US FDA, Rockville, MD 20895 USA. EM Sanjai.kumar@fda.hhs.gov NR 244 TC 8 Z9 8 U1 1 U2 5 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD SEP PY 2007 VL 6 IS 5 BP 505 EP 521 DI 10.1517/14740338.6.5.505 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 216DF UT WOS:000249857600006 PM 17877439 ER PT J AU Sprando, RL Collins, TFX Black, T Olejnlk, N Ramos-Valle, M Ruggles, D AF Sprando, R. L. Collins, T. F. X. Black, T. Olejnlk, N. Ramos-Valle, M. Ruggles, D. TI Acute toxicity of sodium arsenite in a complex food matrix SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE rat; sodium arsenite; fetus; male rat; non-pregnant female rat; pregnant female rat; complex food matrix ID PREGNANT MICE; SEX-RATIO; METABOLISM; HEMODIALYSIS; INTOXICATION; FAILURE; MOUSE AB Acute toxicity of a single oral dose of sodium arsenite (As), administered in half and half cream (HH), was assessed in male and nonpregnant female rats (0.41, 4.1, 41.0 and 410.0 mg/kg body weight) and pregnant rats (0.41, 4.1 and 41.0 mg/kg body weight). Control rats received deionized water alone, HH alone or 41.0 mg/kg As in deionized water (41 mg/kg As-water). Male and non-pregnant rats were monitored for 14 consecutive days post-dosing. Pregnant rats, dosed on gestation day 10 (GD-10), were monitored until fetuses were collected on GD 20. High mortality (100%) was observed in male and non-pregnant female rats exposed to 410.0 mg/kg As-HH. Low mortality (25%) was observed in non-pregnant female rats exposed to 41 mg/kg As-water. No mortality was observed in other control or treated groups. Reduced female fetal numbers were observed in the 41 mg/kg As-water group but not in the other control groups. Developmental effects were not observed in the controls or the As-HH treatment groups. In conclusion, As toxicity was not reduced when a high dose (410 mg/kg) was administered in HH however, at lower doses (41 mg/kg), HH reduced acute As oral toxicity in the female and developing fetus. Published by Elsevier Ltd. C1 Off Appl Res & Safety Assessment, Div Toxicol, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sprando, RL (reprint author), Off Appl Res & Safety Assessment, Div Toxicol, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM rsprando@cfsan.fda.gov NR 27 TC 4 Z9 5 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD SEP PY 2007 VL 45 IS 9 BP 1606 EP 1613 DI 10.1016/j.fct.2007.02.026 PG 8 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 204XT UT WOS:000249078000008 PM 17418926 ER PT J AU Foley, SL Zhao, SH Walker, RD AF Foley, Steven L. Zhao, Shaohua Walker, Robert D. TI Comparison of molecular typing methods for the differentiation of Salmonella foodborne pathogens SO FOODBORNE PATHOGENS AND DISEASE LA English DT Review ID FIELD GEL-ELECTROPHORESIS; FRAGMENT-LENGTH-POLYMORPHISM; ENTERICA SEROVAR TYPHIMURIUM; SINGLE NUCLEOTIDE POLYMORPHISMS; NUMBER TANDEM-REPEATS; ESCHERICHIA-COLI O157-H7; RESTRICTION-SITE PCR; SEQUENCE-BASED PCR; RESISTANT SALMONELLA; VARIABLE-NUMBER AB Bacteria belonging to the genus Salmonella are among the leading causes of foodborne disease of bacterial etiology. These bacteria are also widely disseminated throughout the animal kingdom. The ability to identify the food source from which a human pathogen originated would be of great value in reducing the incidence of foodborne disease and the extent of disease outbreaks due to Salmonella. To date, efforts to identify the origin of these pathogens have centered on phenotypic and genotypic characterization of Salmonella isolates. This review focuses molecular or genotypic techniques that are currently being used for typing, and examines their strengths and weaknesses for determining the source of Salmonella foodbome infections. C1 Marshfield Clin Res Fdn, Natl Farm Med Ctr, Marshfield, WI 54449 USA. US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD USA. RP Foley, SL (reprint author), Marshfield Clin Res Fdn, Natl Farm Med Ctr, 1000 N Oak Ave, Marshfield, WI 54449 USA. EM foley.steven@mcrf.mfldclin.edu NR 159 TC 39 Z9 41 U1 2 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 FAL PY 2007 VL 4 IS 3 BP 253 EP 276 DI 10.1089/fpd.2007.0085 PG 24 WC Food Science & Technology SC Food Science & Technology GA 212ZW UT WOS:000249636700002 PM 17883310 ER PT J AU Gonzalez-Escalona, N Jaykus, LA DePaola, A AF Gonzalez-Escalona, Narjol Jaykus, Lee-Ann DePaola, Angelo TI Typing of Vibrio vulnificus strains by variability in their 16S-23S rRNA Intergenic Spacer regions SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID PCR-AMPLIFICATION; ESCHERICHIA-COLI; IDENTIFICATION; PARAHAEMOLYTICUS; BACTERIA; SEQUENCE; OPERONS; GENES; POLYMORPHISM; PATHOGEN AB Amplification of the 16S-23S rDNA spacer region (ISR1) is a simple and rapid procedure for subtyping bacteria, especially those with several ribosomal operons including Vibrio vulnificus. V. vulnificus contains nine ribosomal operons with four or five ISR1 classes that differ in size and sequence. In the present study, 47 V. vulnificus strains of both shellfish and clinical origin were subtyped by their ISR1 patterns using,universal" primers, which target conserved sequences located in the 16S and the 23S rRNA genes. Sixteen different ISR1 patterns were observed that were grouped into two major clusters. Most (21/27, 77.8%) clinical isolates examined in this study grouped into a single cluster containing ISR1 patterns I, V, XI, and XII and these were highly similar (75%). This cluster was restricted to strains carrying the type B 16S rDNA (rrs) sequence which has been associated with human illness in previous studies. The remaining cluster consisted primarily of shellfish isolates. The highest variability in the ISR1 patterns was observed among shellfish isolates. Sequence analysis of the ISR1 region of selected strains demonstrated that all of them possess five ISR1 classes, with two "conserved sequence blocks" at the 5' and 3' end of the ISR1. All of these strains carried at least one tRNA gene and different classes differed in their tRNA gene composition. Some of the same ISR1 classes differed in size mainly due to an insertion of 35 bp in either of the conserved sequence blocks. These results demonstrate the feasibility of the ISR1 technique for V. vulnificus subtyping and suggest that ISR1 patterns appear to be linked to rrs sequence types and perhaps with virulence. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. N Carolina State Univ, Dept Food Sci, Raleigh, NC 27695 USA. RP Gonzalez-Escalona, N (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr, Dauphin Isl, AL 36528 USA. EM narjol@gmail.com RI Gonzalez-Escalona, Narjol/A-7598-2009; OI Gonzalez-Escalona, Narjol/0000-0003-4568-0022 NR 31 TC 9 Z9 9 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 FAL PY 2007 VL 4 IS 3 BP 327 EP 337 DI 10.1089/fpd.2007.0005 PG 11 WC Food Science & Technology SC Food Science & Technology GA 212ZW UT WOS:000249636700008 PM 17883316 ER PT J AU Buzduga, V Witters, DA Casamento, JP Kainz, W AF Buzduga, Valentin Witters, Donald A. Casamento, Jon P. Kainz, Wolfgang TI Testing the immunity of active implantable medical devices to CW magnetic fields up to 1 MHz by an immersion method SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE electromagnetic compatibility (EMC); electromagnetic interference (EMI); implantable biomedical devices; magnetic fields; pacemakers AB This paper presents a magnetic-field system and the method developed for testing the immunity of the active implantable medical devices to continuous-wave magnetic fields in the frequency range up to I MHz. The system is able to produce magnetic fields of 150 A/m for frequencies up to 100 kHz and strengths decreasing as 1/f between 100 kHz and 1 MHz, with uniformity of the field within +/- 2.5% in the volume for tests. To simulate human tissue, the medical device, together with its leads, is placed on a plastic grid in a saline tank that is introduced in the magnetic field of the induction coil. This paper offers an alternative for the injection voltage methods provided in the actual standards for assessing the protection of the implantable medical devices from the effects of the magnetic fields up to 1 MHz. This paper presents the equipment and signals used, the test procedure, and results from the preliminary tests performed at the Food and Drug Administration-Center for Devices and Radiological Health on implantable pacemakers and neurostimulators. The new system and test method are useful for the EMC research on the implantable medical devices. C1 Scantek Inc, Columbia, MD 21046 USA. Capitol Coll, Laurel, MD 20708 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Buzduga, V (reprint author), Scantek Inc, Columbia, MD 21046 USA. EM buzdugav@yahoo.com; donaid.witters@fda.hhs.gov; jon.casamento@fda.hhs.gov; wolfgang.kainz@fda.hhs.gov NR 8 TC 3 Z9 3 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD SEP PY 2007 VL 54 IS 9 BP 1679 EP 1686 DI 10.1109/TBME.2007.893502 PG 8 WC Engineering, Biomedical SC Engineering GA 204TW UT WOS:000249067900015 PM 17867360 ER PT J AU Pena, C Bowsher, K Costello, A De Luca, R Doll, S Li, K Schroeder, M Stevens, T AF Pena, Carlos Bowsher, Kristen Costello, Ann De Luca, Robert Doll, Sara Li, Khan Schroeder, Marie Stevens, Theodore TI An overview of FDA medical device regulation as it relates to deep brain stimulation devices SO IEEE TRANSACTIONS ON NEURAL SYSTEMS AND REHABILITATION ENGINEERING LA English DT Article DE deep brain stimulation (DBS); food and drug; administration (FDA); medical devices AB The United States Food and Drug Administration (FDA) is charged with assuring the safety and effectiveness of a variety of medical products and the FDA's Center for Devices and Radiological Health is responsible for premarket and postmarket regulation of medical devices. In this paper, we review-from device classification and clinical studies to the final marketing application-FDA's premarket requirements and postmarket requirements as they relate to deep brain stimulation devices. C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Johns Hopkins Univ, Baltimore, MD 21205 USA. RP Pena, C (reprint author), US FDA, Off Commissioner, Rockville, MD 20857 USA. EM carlos.pena@fda.hhs.gov; kristen.bowsher@fda.hhs.gov; ann.costello@fda.hhs.gov; robert.deluca@fda.hhs.gov; sara.doll@fda.hhs.gov; kli@jhmi.edu; marie.schroeder@fda.hhs.gov; ted.stevens@fda.hhs.gov NR 14 TC 12 Z9 13 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1534-4320 EI 1558-0210 J9 IEEE T NEUR SYS REH JI IEEE Trans. Neural Syst. Rehabil. Eng. PD SEP PY 2007 VL 15 IS 3 BP 421 EP 424 DI 10.1109/TNSRE.2007.903973 PG 4 WC Engineering, Biomedical; Rehabilitation SC Engineering; Rehabilitation GA 212JU UT WOS:000249593400011 PM 17894274 ER PT J AU Poly, F Read, T Tribble, DR Baqar, S Lorenzo, M Guerry, P AF Poly, Frederic Read, Timothy Tribble, David R. Baqar, Shahida Lorenzo, Maria Guerry, Patricia TI Genome sequence of a clinical isolate of Campylobacter jejuni from Thailand (vol 75, pg 3425, 2007) SO INFECTION AND IMMUNITY LA English DT Correction C1 Naval Med Res Ctr, Enter Dis & Biol Def Res Diectorates, Silver Spring, MD 20910 USA. US FDA, Beltsville, MD USA. RP Poly, F (reprint author), Naval Med Res Ctr, Enter Dis & Biol Def Res Diectorates, Silver Spring, MD 20910 USA. RI Read, Timothy/E-6240-2011 NR 1 TC 1 Z9 1 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 SEP PY 2007 VL 75 IS 9 BP 4671 EP 4671 DI 10.1128/IAI.00920-07 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 205RG UT WOS:000249131700057 ER PT J AU Savage, JH Limb, SL Brereton, NH Wood, RA AF Savage, Jessica H. Limb, Susan L. Brereton, Nga H. Wood, Robert A. TI The natural history of peanut allergy: Extending our knowledge beyond childhood SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter ID IGE; POLLEN C1 Johns Hopkins Univ, Sch Med, Div Allergy & Immunol, Dept Pediat, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Gen Clin Res Ctr, Baltimore, MD USA. US FDA, Ctr Drug Evaluat & Res, Div Pulmonary & Allergy Prod, Rockville, MD 20857 USA. RP Savage, JH (reprint author), Johns Hopkins Univ, Sch Med, Div Allergy & Immunol, Dept Pediat, Baltimore, MD 21218 USA. EM rwood@jhmi.edu FU NCRR NIH HHS [M01RR00052] NR 7 TC 33 Z9 35 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD SEP PY 2007 VL 120 IS 3 BP 717 EP 719 DI 10.1016/j.jaci.2007.07.027 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 211DV UT WOS:000249505400036 PM 17765758 ER PT J AU Fedio, W Blackstone, GM Kikuta-Oshima, L Wendakoon, C McGrath, TH DePaola, A AF Fedio, Willis Blackstone, George M. Kikuta-Oshima, Lynne Wendakoon, Chitra McGrath, Timothy H. DePaola, Angelo TI Rapid detection of the Vibrio cholerae ctx gene in food enrichments using real-time polymerase chain reaction SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TEMPERATURE; RECOVERY; OYSTERS AB A real-time polymerase chain reaction (qPCR) assay for the detection of the ctxA gene of toxigenic Vibrio cholerae (Vc) was validated against standard culture techniques. The first experimental phase determined optimal enrichment conditions for detection by culture and qPCR of Vc in shrimp, bottled water, milk, and potato salad. The conditions tested included temperature (35 and 42 degrees C), time (6 and 18 h), and effect of shaking (0 and 100 rpm). No definitive trends were found with enrichment temperature or shaking on Vc isolation frequency or detection by qPCR. Generally, Vc was detected by qPCR more frequently than Vc was isolated, but this difference was significant only in the 35 degrees C 6 h enrichment without shaking. In the second phase of experiments, shrimp, bottled water, milk, potato salad, and oysters were inoculated with each of 3 toxigenic Vc strains (Latin American O1 strain, an O139 strain, and an O1 strain from the U.S. Gulf Coast) and enriched under static conditions at 42 degrees C for 6 and 18 h. Overall, detection frequency of ctx by qPCR was 98% (88/90) and 100% (90/90) after 6 and 18 h enrichments, respectively, while Vc isolation frequency was 87% (78/90) and 83% (75/90) after 6 and 18 h, respectively. Toxigenic Vc can be detected by qPCR within an 8 h work day using the 6 h enrichment procedure, assuming an initial level of at least 1-2 colony-forming units/g; however, overnight enrichment may be necessary to detect lower levels. These data indicate that the qPCR assay for ctx is a more reliable, sensitive, and rapid alternative to standard Vc culture methods and is applicable to diverse food products. C1 New Mexico State Univ, Phys Sci Lab, Las Cruces, NM 88003 USA. US FDA, Gulf Coast Seafoo Lab, Dauphin Isl, AL 36528 USA. US FDA, Div Field Sci, Rockville, MD 20857 USA. RP Blackstone, GM (reprint author), New Mexico State Univ, Phys Sci Lab, Las Cruces, NM 88003 USA. EM george.blackstone@fda.hhs.gov NR 14 TC 10 Z9 11 U1 0 U2 1 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2007 VL 90 IS 5 BP 1278 EP 1283 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 214QI UT WOS:000249752800011 PM 17955973 ER PT J AU Petigara, BR Scher, AL AF Petigara, Bhakti R. Scher, Alan L. TI Direct method for determination of Sudan I in FD&C Yellow No. 6 and D&C Orange No. 4 by reversed-phase liquid chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TANDEM MASS-SPECTROMETRY; ARRAY DETECTION; PRODUCTS; DYES; CONFIRMATION; FOODSTUFF; WATER; HPLC AB A reversed-phase liquid chromatographic method was developed to determine parts-per-million and higher levels of Sudan I, 1-(phenylazo)-2-naphthalenol, in the disulfo monoazo color additive FD&C Yellow No. 6 and in a related monosulfo monoazo color additive, D&C Orange No. 4. Sudan I, the corresponding unsulfonated monoazo dye, is a known impurity in these color additives. The color additives are dissolved in water and methanol, and the filtered solutions are directly chromatographed, without extraction or concentration, by using gradient elution at 0.25 mL/min. Calibrations from peak areas at 485 nm were linear. At a 99% confidence level, the limits; of determination were 0.008 mu g Sudan l/mL (0.4 ppm) in FD&C Yellow No. 6 and 0.011 mu g Sudan l/mL (0.00011%) in D&C Orange No. 4. The confidence intervals were 0.202 +/- 0.002 mu g Sudan l/mL (10.1 +/- 0.1 ppm) near the specification level for Sudan I in FD&C Yellow No. 6 and 20.0 +/- 0.2 mu g Sudan l/mL (0.200 +/- 0.002%) near the highest concentration of Sudan I found in D&C Orange No. 4. A survey was conducted to determine Sudan I in 28 samples of FD&C Yellow No. 6 from 17 international manufacturers over 3 years, and in a pharmacology-tested sample. These samples were found to contain undetected levels (16 samples), 0.5-9.7 ppm Sudan 1 (0.01-.0.194 mu g Sudan l/mL in analyzed solutions; 11 samples including the pharmacology sample), and 10 ppm Sudan 1 (>= 0.2 mu g Sudan l/mL; 2 samples). Analyses of 21 samples of D&C Orange No. 4 from 8 international manufacturers over 4 years found Sudan I at undetected levels (8 samples), 0.0005 to <0.005% Sudan I (0.05 to <0.5 mu g Sudan l/mL in analyzed solutions; 3 samples, including a pharmacology batch), 0.005 to <0.05% Sudan I (0.5 to <5 mu g Sudan l/mL; 9 samples), and 0.18% Sudan I(18 mu g Sudan l/mL; 1 sample). C1 US FDA, Office Cosmet & Colors, College Pk, MD 20740 USA. RP Scher, AL (reprint author), US FDA, Office Cosmet & Colors, HFS-106,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM alan.scher@fda.hhs.gov NR 14 TC 8 Z9 8 U1 0 U2 4 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD SEP-OCT PY 2007 VL 90 IS 5 BP 1373 EP 1378 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 214QI UT WOS:000249752800019 PM 17955981 ER PT J AU Wiesenfeld, PL Garthoff, LH Sobotka, TJ Suagee, JK Barton, CN AF Wiesenfeld, Paddy L. Garthoff, Larry H. Sobotka, Thomas J. Suagee, Jessica K. Barton, Curtis N. TI Acute oral toxicity of colchicine in rats: effects of gender, vehicle matrix and pre-exposure to lipopolysaccharide SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE colchicine; lethality; lipopolysaccharide; Half and Half cream; rats; oral; toxicity ID PITUITARY-ADRENAL AXIS; NECROSIS-FACTOR-ALPHA; SEXUAL-DIMORPHISM; INNATE IMMUNITY; ENDOTOXIN; MECHANISMS; BACTERIAL; SYSTEM; MODEL; PHARMACOKINETICS AB The oral toxicity of a single administration by gavage (10, 20 or 30 mg kg(-1) body weight) of colchicine (COL) was determined in young, mature mate and female Sprague-Dawley rats. The effect of COL was evaluated in the presence or absence of additional treatment variables that included vehicle and lipopolysaccharide (LPS) pre-exposure. The vehicle for COL was either Half and Half cream (H & H) or saline, and each group included pretreatment with either saline or a low, minimally toxic dose (83 mu g kg(-1) body weight) of LPS. Colchicine toxicity in both male and female age-matched rats was characterized by progressively more severe dose-related clinical signs of toxicity. These included mortality, decreased body weight and feed intake during the first several days after dosing, with recovery thereafter in surviving animals. There were differences in the severity of the toxic response to COL between male and female rats. The most notable sex-related difference was in COL lethality. Female rats were two times more susceptible to the lethal effects of COL than male rats. Saline or H & H delivery vehicles did not result in any apparent qualitative or quantitative differences in COL toxicity. LPS pretreatment significantly potentiated COL lethality in both males and females, although the potentiation in males was greater than in females. LPS pretreatment modestly increased the COL induced anorexic effect in surviving males, but not in surviving female animals. LPS did not appear to modulate either the body weights or clinical signs of COL induced toxicity in surviving males or females. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol Neurotoxic & In Vitro Toxicol Branch, Laurel, MD USA. RP Wiesenfeld, PL (reprint author), 8301 Muirkirk Rd,Mod 1,HFS-025, Laurel, MD 20708 USA. EM paddy.wiesenfeld@fda.hhs.gov RI Suagee, Jessica/A-6407-2013 OI Suagee, Jessica/0000-0003-0829-7868 NR 61 TC 6 Z9 6 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD SEP-OCT PY 2007 VL 27 IS 5 BP 421 EP 433 DI 10.1002/jat.1198 PG 13 WC Toxicology SC Toxicology GA 201IP UT WOS:000248825000002 PM 17345587 ER PT J AU Gieseker, CM Serfling, SG Poynton, SL Reimschuessel, R AF Gieseker, Charles M. Serfling, Stanley G. Poynton, Sarah L. Reimschuessel, Renate TI Laboratory transmission of the monogenean Acolpenteron ureteroecetes infecting the posterior kidneys of largemouth bass: Time course and pathology SO JOURNAL OF AQUATIC ANIMAL HEALTH LA English DT Article ID GALAXIAS-MACULATUS OSMERIFORMES; URINARY-BLADDER; PHILURETER-TRIGONIOPSIS; PATAGONIA ARGENTINA; DACTYLOGYRIDAE; ANCYROCEPHALINAE; URETERS; PARASITE; DYNAMICS; BRAZIL AB Acolpenteron ureteroecetes infections in the kidneys of largemouth bass Micropterus salmoides have been reported, but the time course of infection and progression of pathology in experimentally infected fish remain unknown. We exposed 299 naive juvenile largemouth bass at 19.8 degrees C to A. ureteroecetes-infected largemouth bass via recirculating water without direct contact. For 7 months, prevalence and density were determined monthly in squashes of posterior kidney (20 exposed fish, 20 nonexposed fish), and histopathology was assessed in 5 fish from each group. Prevalence increased steadily from months 1 (5%) to 4 (85%), thereafter remaining relatively stable. Mean density of infection doubled monthly (month 1, 0.1 individuals/2 cm(2) squash; month 7, 15.1 individuals/2 cm(2) squash). Eggs were first observed at month 3, and mean density increased markedly from month 4 to month 5 (2.9-15.3 eggs/2 cm(2) squash). Histopathology showed damage in renal collecting ducts that got progressively worse between 5 and 7 months. The infected ducts were dilated, had a hyperplastic epithelium, and were surrounded by chronic inflammation, including eosinophilic granular cells and varying degrees of fibrosis. Eggs within granulomas were present in the interstitium; this response is newly reported. The infection system developed in this study provides a reproducible and consistent source of infected individuals that will facilitate further study of the parasite and potential treatments. C1 Ctr Vet Med, US FDA, Res Off, Laurel, MD 20708 USA. US FDA, Off Commissioner, Off Sci & Hlth Coordinat, Rockville, MD 20857 USA. Johns Hopkins Univ, Sch Med, Dept Mol & Comparat Pathobiol, Baltimore, MD 21205 USA. Leibniz Inst Gewasserokol & Binnenfischerei, D-12587 Berlin, Germany. RP Gieseker, CM (reprint author), Ctr Vet Med, US FDA, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM charles.gieseker@fda.hhs.gov NR 29 TC 1 Z9 1 U1 0 U2 5 PU AMER FISHERIES SOC PI BETHESDA PA 5410 GROSVENOR LANE SUITE 110, BETHESDA, MD 20814-2199 USA SN 0899-7659 J9 J AQUAT ANIM HEALTH JI J. Aquat. Anim. Health PD SEP PY 2007 VL 19 IS 3 BP 141 EP 150 DI 10.1577/1-106-049.1 PG 10 WC Fisheries; Veterinary Sciences SC Fisheries; Veterinary Sciences GA 233UI UT WOS:000251115400001 PM 18201055 ER PT J AU Wear, KA AF Wear, K. A. TI Improved standardization of calcaneal speed-of-sound measurements: Results in 73 women SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Wear, K. A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA T304 BP S306 EP S306 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101525 ER PT J AU Wear, KA AF Wear, K. A. TI Improved accuracy of broadband ultrasound attenuation measurement using phase insensitive detection: Results in 73 women SO JOURNAL OF BONE AND MINERAL RESEARCH LA English DT Meeting Abstract CT 29th Annual Meeting of the American-Society-for-Bone-and-Mineral-Research CY SEP 16-19, 2007 CL Honolulu, HI SP Amer Soc Bone & Mineral Res C1 [Wear, K. A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0884-0431 J9 J BONE MINER RES JI J. Bone Miner. Res. PD SEP PY 2007 VL 22 SU 1 MA T305 BP S306 EP S306 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 225IA UT WOS:000250509101526 ER PT J AU Knudsen, J Flowers, C Kortepeter, C Awaad, Y AF Knudsen, James Flowers, Charlene Kortepeter, Cindy Awaad, Yasser TI Angioneurotic edema associated with an antiepileptic drug; Reporting rates in the United States. SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Meeting Abstract CT 36th Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP 09-11, 2007 CL San Francisco, CA SP Amer Coll Clin Pharm C1 US FDA, Silver Spring, MD USA. Oakwood Healthcare Syst, Dearborn, MI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD SEP PY 2007 VL 47 IS 9 MA 22 BP 1187 EP 1187 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 205GC UT WOS:000249101000028 ER PT J AU Egan, SK Bolger, PM Carrington, CD AF Egan, Sara Kathleen Bolger, Philip Michael Carrington, Clark Dewitt TI Update of USFDA's Total Diet Study food list and diets SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE Total Diet Study (TDS); TDS food list; TDS diets; dietary exposure; monitoring. ID REVISION; HISTORY AB The US Food and Drug Administration's (FDA) Total Diet Study (TDS) has been conducted continuously since the early 1960s to measures levels of various pesticide residues, contaminants, and nutrients in foods and to estimate the dietary exposures to these compounds. Both the TDS food list and the consumption amounts used for estimating exposures are based on results of nationwide food consumption surveys, and they are updated periodically to reflect changes in food consumption patterns. The most recent update was completed in 2003 using the same methodology employed in the previous update ( 1990). The updated food list includes approximately the same number of foods ( 285) as the previous list ( 290). Although most (75%) foods are the same in both versions, the new list reflects trends in consumption of foods containing less fat. The updated diets reflect an increase in total food consumption, with most notable increases in consumption of grains and beverages. A case study comparing cadmium exposures calculated from both the 1990 and 2003 versions of the TDS demonstrated the potential impact of changes in both the food list and consumption amounts on TDS exposure estimates. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Egan, SK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Parkway, College Pk, MD 20740 USA. EM Katie.Egan@fda.hhs.gov NR 12 TC 53 Z9 55 U1 4 U2 15 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD SEP PY 2007 VL 17 IS 6 BP 573 EP 582 DI 10.1038/sj.jes.7500554 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 209PQ UT WOS:000249400900009 PM 17410117 ER PT J AU Halbert, MK Archer, JC AF Halbert, Mary Kim Archer, Jeffrey C. TI Dioxin and furan contamination of deodorizer distillates and natural vitamin E supplements SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article DE vitamin E; tocopherol; deodorizer distillate; bleaching clay; dioxin; furan; PCDD; PCDF ID DIBENZO-P-DIOXINS; SOYBEAN OIL; SUPERCRITICAL CO2; VEGETABLE-OIL; PCBS; TOCOPHEROLS; PESTICIDES; BIPHENYLS; PRODUCTS; PCDDS AB Thirty-five samples of vitamin E supplement softgels, obtained from store shelves, were analyzed for 17 dioxin and furan congeners. Of these samples, 14 were identified as natural vitamin E, containing D-alpha-tocopherol, as well as lesser amounts of beta-, alpha-, and delta-tocopherols, and the remaining 21 were labeled as synthetic vitamin E, containing a mixture of D- and L-alpha-tocopherol. The supplements were collected during the years of 2002 and 2004. The seven natural vitamin E supplements collected in 2002 were found to contain significant quantities of dioxins and furans, with an average total toxic equivalence (TEQ) of 0.79 pg/g, compared to 0.10 g/g for the 2004 natural vitamin E supplements. The 21 synthetic vitamin E supplements collected during the same time period showed little or no contamination, with an average TEQ of 0.057 pg/g. Eight samples of deodorizer distillate, from which natural vitamin E is derived, were also collected and analyzed. The distillates exhibit an overall congener pattern similar to that found in the natural vitamin E, but at a much higher average TEQ of 3.4 pg/g. This suggests the possibility of carryover of contamination to the vitamin E samples from the deodorizer distillate during the extraction process. The natural vitamin E supplements collected in 2004 have much lower levels of contamination, suggesting that improved extraction processes may be in use, effectively reducing contamination. (c) 2007 Elsevier Inc. All rights reserved. C1 Arkansas Reg Lab, Food & Drug Adm, Jefferson, AR 72079 USA. RP Halbert, MK (reprint author), Arkansas Reg Lab, Food & Drug Adm, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM mary.halbert@fda.hhs.gov NR 27 TC 1 Z9 1 U1 2 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD SEP PY 2007 VL 20 IS 6 BP 506 EP 514 DI 10.1016/j.jfca.2007.02.010 PG 9 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 186DI UT WOS:000247758900009 ER PT J AU Malik, T Wolbert, C Mauldin, J Sauder, C Carbone, KM Rubin, SA AF Malik, Tahir Wolbert, Candie Mauldin, Jeremy Sauder, Christian Carbone, Kathryn M. Rubin, Steven A. TI Functional consequences of attenuating mutations in the haemagglutinin-neuraminidase, fusion and polymerase proteins of a wild-type mumps virus strain SO JOURNAL OF GENERAL VIROLOGY LA English DT Article ID RESPIRATORY SYNCYTIAL VIRUS; ASEPTIC-MENINGITIS; RNA-POLYMERASE; N-GLYCANS; OLIGOSACCHARIDE CHAINS; MONOCLONAL-ANTIBODIES; AQUEDUCTAL STENOSIS; MOLECULAR-CLONING; SEQUENCE-ANALYSIS; MAMMALIAN-CELLS AB Wild-type mumps viruses (MuVs) are highly neurotropic and, prior to widespread vaccination programmes, were a major cause of viral meningitis and encephalitis in most developed countries. At present, there are no markers for virus attenuation, apart from the failure of a passaged isolate to produce clinical symptoms in vaccinees. Indeed, some MuV vaccines have retained residual neurovirulence properties and have caused aseptic meningitis in vaccinees. Three amino acid changes associated with the neuroattenuation of a wild-type MuV strain were identified previously. This study evaluated the impact of these changes on the function of the respective proteins. The data demonstrated that the Ser -> Asp amino acid substitution at position 466 in the haemagglutinin-neuraminidase protein resulted in decreased receptor binding and neuraminiclase activity, the Ala/Thr -> Thr selection in the fusion protein resulted in decreased fusion activity, and the Ile -> Val substitution in the polymerase resulted in increased replicative/transcriptional activity. These data suggest a polygenic component (i.e. specific and inter-related roles of these amino acid changes) to MuV neuroattenuation. C1 US FDA, Ctr Biol Evaluat & Res, DVP, Off Vaccines Res & Review, Bethesda, MD 20892 USA. Univ Virginia, Dept Pharmacol, Charlottesville, VA 22908 USA. RP Malik, T (reprint author), US FDA, Ctr Biol Evaluat & Res, DVP, Off Vaccines Res & Review, Bethesda, MD 20892 USA. EM tahir.malik@fda.hhs.gov NR 64 TC 13 Z9 13 U1 0 U2 1 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 SEP PY 2007 VL 88 BP 2533 EP 2541 DI 10.1099/vir.0.82935-0 PN 9 PG 9 WC Biotechnology & Applied Microbiology; Virology SC Biotechnology & Applied Microbiology; Virology GA 207BK UT WOS:000249226400020 PM 17698664 ER PT J AU Asturias, EJ Dueger, EL Omer, SB Melville, A Nates, SV Laassri, M Chumakov, K Halsey, NA AF Asturias, Edwin J. Dueger, Erica L. Omer, Saad B. Melville, Arturo Nates, Silvia V. Laassri, Majid Chumakov, Konstantin Halsey, Neal A. TI Randomized trial of inactivated and live polio vaccine schedules in Guatemalan infants SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID OPV CESSATION; POLIOMYELITIS; ERADICATION; IMMUNOGENICITY; EXCRETION; STRATEGY; STRAINS; WORLD AB Background. The immunogenicity of inactivated poliovirus vaccine (IPV) in developing countries is not well documented. This study compared the immune response to IPV with that to oral poliovirus vaccine (OPV) in Guatemalan infants. Methods. This was an open-label, randomized comparison of IPV only, OPV only, or IPV followed by OPV in Guatemalan public health clinics. Serum samples were tested for neutralizing antibodies, and stool samples were tested for Sabin strain polioviruses. Results. Seropositivity rates 2 months after 2 doses of IPV were 98%-100% for polio types 1, 2, and 3 and were 97.1%, 99.3%, and 92.1% for OPV-only recipients (P < .001 for the response to type 3). One month after the third dose, 100% of IPV-only recipients had protective antibodies against all 3 types, compared with 99%, 100%, and 97% against polio types 1, 2, and 3 respectively, among recipients of OPV only. Infants who received IPV only had higher geometric mean titers than infants who received OPV only. Maternal antibodies lowered the final antibody responses to IPV but did not prevent the development of protective levels of antibody. Of 191 stool samples from infants who received IPV only, 5 (2.6%) were positive for poliovirus vaccine strains. Conclusions. IPV alone and IPV followed by OPV are safe and effective for Guatemalan infants. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Univ Valle Guatemala, Ctr Hlth Studies, Guatemala City, Guatemala. Hosp Roosevelt Guatemala, Dept Pediat, Guatemala City, Guatemala. Univ Nacl Cordoba, Fac Ciencias Med, Inst Virol Dr JM Vanella, RA-5000 Cordoba, Argentina. RP Halsey, NA (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Int Hlth, 615 N Wolfe St,W5515, Baltimore, MD 21205 USA. EM nhalsey@jhsph.edu RI Omer, Saad/K-1182-2012 OI Omer, Saad/0000-0002-5383-3474 FU FIC NIH HHS [K01 TW006659] NR 22 TC 23 Z9 26 U1 1 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD SEP 1 PY 2007 VL 196 IS 5 BP 692 EP 698 DI 10.1086/520546 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 197LS UT WOS:000248557600007 PM 17674310 ER PT J AU Kainz, W AF Kainz, Wolfgang TI MR heating tests of MR critical implants SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, Silver Spring, MD USA. RP Kainz, W (reprint author), 10903 New Hamspshire Ave,Bldg 62,Room 1132, Silver Spring, MD 20993 USA. EM wolfgang.kainz@fda.hhs.gov NR 7 TC 20 Z9 20 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD SEP PY 2007 VL 26 IS 3 BP 450 EP 451 DI 10.1002/jmri.21020 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 207NH UT WOS:000249257300001 PM 17729357 ER PT J AU Marzella, L Gelperin, K AF Marzella, Louis Gelperin, Kate TI Safety risks with gadolinium-based contrast agents SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Letter ID MEDIA; ANGIOGRAPHY C1 US FDA, FDA Ctr Drug Evaluat & Res CDER, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. US FDA, FDA Ctr Drug Evaluat & Res CDER, Off Oncol Drug Prod, Div Med Imaging & Hematol Prod, Silver Spring, MD USA. RP Gelperin, K (reprint author), US FDA, FDA Ctr Drug Evaluat & Res CDER, Off Surveillance & Epidemiol, 10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM kate.gelperin@fda.hhs.gov NR 8 TC 4 Z9 4 U1 0 U2 1 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1053-1807 J9 J MAGN RESON IMAGING JI J. Magn. Reson. Imaging PD SEP PY 2007 VL 26 IS 3 BP 816 EP 816 DI 10.1002/jmri.21021 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 207NH UT WOS:000249257300046 PM 17685423 ER PT J AU Zidan, AS Sammour, OA Hammad, MA Megrab, NA Habib, MJ Khan, MA AF Zidan, Ahmed S. Sammour, Omaima A. Hammad, Muhammad A. Megrab, Nagia A. Habib, Mohamed J. Khan, Mansoor A. TI Quality by design: Understanding the product variability of a self-nanoemulsified drug delivery system of cyclosporine A SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE cyclosporine; self-nanoemulsification; variability; permeability and near; infrared ID FREQUENCY DIELECTRIC-SPECTROSCOPY; PH-SENSITIVE NANOPARTICLES; PARTICLE-SIZE ANALYSIS; TRANSDERMAL DELIVERY; EMULSIFYING SYSTEMS; ORAL DELIVERY; BIOAVAILABILITY; MICROEMULSIONS; FORMULATION; WATER AB The objective of this work was to understand the product variability due to size and other characteristics of the SNEDDS by utilizing near infrared (NIR) and chemometric analysis, as well as several other well-known procedures. Pseudo-ternary phase diagrams were constructed to identify the efficient self-emulsification region using CyA solutions in sweet orange oil (oily phase), Emulphor EL-620 (surfactant), and Capmul MCM-C8 (cosurfactant). The formulated SNEDDS were characterized by droplet size, turbidity, zeta potential, and Fourier transform infrared (FTIR) analysis. Drug release studies were performed by dissolution in conjunction with turbidimetry. Permeability studies were performed in a Franz diffusion cell assembly. The results indicated an optimum surfactant to cosurfactant ratio of 2:1. Above this ratio, the resultant nanoemulsions had a particle size of 10 nm and turbidity of 10 nephlometric units (NTU). All the prepared systems were positively charged. The FTIR spectra and the DSC thermograms obtained showed no incompatibility between the SNEDDS ingredients. Turbidity time profiles revealed three distinctive regions: lag phase, plateau, and pseudolinear phase. Emulsification rate was obtained from the corrected slope of the pseudolinear phase of the profile. Permeability data indicated that the product variability is more with smaller droplet size. The size of the droplets showed good correlation with NIR spectral data by partial least square (PLS) regression plots. In conclusion, this study demonstrated the ability to understand the impact of nanodroplets size on the SNEDDS variability by different product analyzing tools. (c) 2007 Wiley-Liss, Inc. C1 US FDA, Div Prod Qual Res, Silver Spring, MD USA. Zagazig Univ, Fac Pharm, Zagazig, Sharqiyyah Prov, Egypt. Howard Univ, Sch Pharm, Washington, DC 20059 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Silver Spring, MD USA. EM Mansoor.Khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012 NR 32 TC 21 Z9 21 U1 1 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD SEP PY 2007 VL 96 IS 9 BP 2409 EP 2423 DI 10.1002/jps.20824 PG 15 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 206LB UT WOS:000249183800019 PM 17628495 ER PT J AU Sumner, LW Amberg, A Barrett, D Beale, MH Beger, R Daykin, CA Fan, TWM Fiehn, O Goodacre, R Griffin, JL Hankemeier, T Hardy, N Harnly, J Higashi, R Kopka, J Lane, AN Lindon, JC Marriott, P Nicholls, AW Reily, MD Thaden, JJ Viant, MR AF Sumner, Lloyd W. Amberg, Alexander Barrett, Dave Beale, Michael H. Beger, Richard Daykin, Clare A. Fan, Teresa W. -M. Fiehn, Oliver Goodacre, Royston Griffin, Julian L. Hankemeier, Thomas Hardy, Nigel Harnly, James Higashi, Richard Kopka, Joachim Lane, Andrew N. Lindon, John C. Marriott, Philip Nicholls, Andrew W. Reily, Michael D. Thaden, John J. Viant, Mark R. TI Proposed minimum reporting standards for chemical analysis SO METABOLOMICS LA English DT Article DE metabolomics; metabolite profiling; metabolite identification; minimum reporting standards; chemical analysis; mass spectrometry; nuclear magnetic resonance; flux; isotopomer analysis; GC-MS; LC-MS; CE-MS; NMR; quality control; method validation ID PLANT METABOLOMICS AB There is a general consensus that supports the need for standardized reporting of metadata or information describing large-scale metabolomics and other functional genomics data sets. Reporting of standard metadata provides a biological and empirical context for the data, facilitates experimental replication, and enables the re-interrogation and comparison of data by others. Accordingly, the Metabolomics Standards Initiative is building a general consensus concerning the minimum reporting standards for metabolomics experiments of which the Chemical Analysis Working Group (CAWG) is a member of this community effort. This article proposes the minimum reporting standards related to the chemical analysis aspects of metabolomics experiments including: sample preparation, experimental analysis, quality control, metabolite identification, and data pre-processing. These minimum standards currently focus mostly upon mass spectrometry and nuclear magnetic resonance spectroscopy due to the popularity of these techniques in metabolomics. However, additional input concerning other techniques is welcomed and can be provided via the CAWG on-line discussion forum at http://msi-workgroups.sourceforge.net/ or http://Msi-workgroups-feedback@lists.sourceforge.net. Further, community input related to this document can also be provided via this electronic forum. C1 Samuel Roberts Noble Fdn Inc, Ardmore, OK USA. Sanofi Aventis Deutsch GmbH, Frankfurt, Germany. Univ Nottingham, Sch Pharm, Ctr Analyt Biosci, Nottingham NG7 2RD, England. Rothamsted Res, Natl Ctr Plant & Microbial Metab, Harpenden, Herts, England. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Nottingham, Sch Pharm, Div Mol & Cellular Sci, Nottingham NG7 2RD, England. Univ Louisville, Dept Chem, Louisville, KY 40292 USA. Univ Calif Davis, Genome Ctr, Davis, CA 95616 USA. Univ Manchester, Sch Chem, Manchester, Lancs, England. Univ Manchester, Manchester Interdisciplinary Bioctr, Manchester, Lancs, England. RP Sumner, LW (reprint author), Samuel Roberts Noble Fdn Inc, Ardmore, OK USA. EM lwsumner@noble.org; Alexander.Amberg@sanofi-aventis.com; David.Barrett@nottingham.ac.uk; mike.beale@bbsrc.ac.uk; richard.beger@fda.hhs.gov; Clare.Daykin@nottingham.ac.uk; teresa.fan@louisville.edu; ofiehn@ucdavis.edu; Roy.Goodacre@manchester.ac.uk; jlg40@mole.bio.cam.ac.uk; hankemeier@chem.leidenuniv.nl; nwh@aber.ac.uk; james.harnly@ars.usda.gov; rick.higashi@louisville.edu; Kopka@mpimp-golm.mpg.de; anlane01@gwise.louisville.edu; j.lindon@imperial.ac.uk; philip.marriott@rmit.edu.au; andrew.w.nicholls@gsk.com; Michael.Reily@pfizer.com; m.viant@bham.ac.uk RI Marriott, Philip/E-7462-2010; Viant, Mark/B-6339-2009; Goodacre, Roy/J-1600-2012; Sumner, Lloyd/A-3270-2013; Marriott, Philip/H-6426-2013; Barrett, David/C-9922-2011; OI Viant, Mark/0000-0001-5898-4119; Goodacre, Roy/0000-0003-2230-645X; Marriott, Philip/0000-0001-5180-1041; Barrett, David/0000-0001-6900-9474; Kopka, Joachim/0000-0001-9675-4883 FU Biotechnology and Biological Sciences Research Council [BB/C519038/1, BB/D525121/1, BBS/E/C/00004559, BB/D006422/1]; Medical Research Council [MC_QA137293]; NIH HHS [Y01 OD001298-01] NR 12 TC 605 Z9 611 U1 27 U2 235 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1573-3882 J9 METABOLOMICS JI Metabolomics PD SEP PY 2007 VL 3 IS 3 BP 211 EP 221 DI 10.1007/s11306-007-0082-2 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 217JZ UT WOS:000249945500006 PM 24039616 ER PT J AU Goodacre, R Broadhurst, D Smilde, AK Kristal, BS Baker, JD Beger, R Bessant, C Connor, S Calmani, G Craig, A Ebbels, T Kell, DB Manetti, C Newton, J Paternostro, G Somorjai, R Sjostrom, M Trygg, J Wulfert, F AF Goodacre, Royston Broadhurst, David Smilde, Age K. Kristal, Bruce S. Baker, J. David Beger, Richard Bessant, Conrad Connor, Susan Calmani, Giorgio Craig, Andrew Ebbels, Tim Kell, Douglas B. Manetti, Cesare Newton, Jack Paternostro, Giovanni Somorjai, Ray Sjostrom, Michael Trygg, Johan Wulfert, Florian TI Proposed minimum reporting standards for data analysis in metabolomics SO METABOLOMICS LA English DT Article DE chemometrics; multivariate; megavariate; unsupervised learning; supervised learning; informatics; bioinformatics; statistics; biostatistics; machine learning; statistical learning ID PATTERN-RECOGNITION; TIME-DOMAIN; DATA SETS; NMR; BIOMARKERS; SPECTROSCOPY; VALIDATION; REPRODUCIBILITY; IDENTIFICATION; DECONVOLUTION AB The goal of this group is to define the reporting requirements associated with the statistical analysis (including univariate, multivariate, informatics, machine learning etc.) of metabolite data with respect to other measured/collected experimental data (often called metadata). These definitions will embrace as many aspects of a complete metabolomics study as possible at this time. In chronological order this will include: Experimental Design, both in terms of sample collection/matching, and data acquisition scheduling of samples through whichever spectroscopic technology used; Deconvolution (if required); Pre-processing, for example, data cleaning, outlier detection, row/column scaling, or other transformations; Definition and parameterization of subsequent visualizations and Statistical/Machine learning Methods applied to the dataset; If required, a clear definition of the Model Validation Scheme used (including how data are split into training/validation/test sets); Formal indication on whether the data analysis has been Independently Tested (either by experimental reproduction, or blind hold out test set). Finally, data interpretation and the visual representations and hypotheses obtained from the data analyses. C1 Univ Manchester, Sch Chem, Manchester M1 7ND, Lancs, England. Univ Manchester, Manchester Interdisciplinary Bioctr, Manchester M1 7ND, Lancs, England. Univ Amsterdam, Swammerdam Inst Life Sci, NL-1018 WV Amsterdam, Netherlands. TNO Qual Life, NL-3700 AJ Zeist, Netherlands. Brigham & Womens Hosp, Dept Neurosurg, Boston, MA 02115 USA. Pfizer Inc, Ann Arbor, MI USA. Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. Cranfield Univ, Bedford MK45 4DT, England. GlaxoSmithKline Inc, Safety Assessment, Ware SG12 0DP, Herts, England. Univ Roma La Sapienza, Dipartimento Chim, I-00185 Rome, Italy. BlueGnome Ltd, Cambridge CB2 5LD, England. Univ London Imperial Coll Sci Technol & Med, Dept Biomol Med, London SW7 2AZ, England. Chenomx Inc, Edmonton, AB T5K 2J1, Canada. Burnham Inst Med Res, La Jolla, CA 92037 USA. Natl Res Council Canada, Inst Biodiagnost, Winnipeg, MB R3B 1Y6, Canada. Umea Univ, Dept Chem, Chemometr Res Grp, S-90187 Umea, Sweden. Univ Nottingham, Div Food Sci, Loughborough LE12 5RD, Leics, England. RP Broadhurst, D (reprint author), Univ Manchester, Sch Chem, 131 Princess St, Manchester M1 7ND, Lancs, England. EM david.broadhurst@manchester.ac.uk RI Bessant, Conrad/E-7620-2010; Kell, Douglas/E-8318-2011; Goodacre, Roy/J-1600-2012; Capuani, Giorgio/B-7738-2015 OI Kell, Douglas/0000-0001-5838-7963; Goodacre, Roy/0000-0003-2230-645X; Capuani, Giorgio/0000-0002-6992-2578 NR 68 TC 155 Z9 157 U1 6 U2 86 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1573-3882 J9 METABOLOMICS JI Metabolomics PD SEP PY 2007 VL 3 IS 3 BP 231 EP 241 DI 10.1007/s11306-007-0081-3 PG 11 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 217JZ UT WOS:000249945500008 ER PT J AU Rasooly, A Sergeev, N Herold, KE AF Rasooly, A. Sergeev, N. Herold, K. E. TI Biosensor technologies for microbial and environmental analysis SO MINERVA BIOTECNOLOGICA LA English DT Article DE biosensing techniques; surface plasmon resonance; resonant crystal ID SURFACE-PLASMON RESONANCE; STAPHYLOCOCCAL-ENTEROTOXIN-B; ESCHERICHIA-COLI O157-H7; PHAGE-DISPLAYED PEPTIDES; OPTIC-BASED BIOSENSOR; ARRAY BIOSENSOR; ELECTROCHEMICAL BIOSENSORS; REAL-TIME; SALMONELLA-TYPHIMURIUM; RAPID IDENTIFICATION AB Microbial and environmental analysis, including the identification and characterization of contaminants, microbial pathogens and their toxins, is critical in many environmental and health-related settings. Biosensors are currently being developed for a wide range of environmental and microbial diagnostic applications. The term "biosensor" is defined by the international Union of Pure and Applied Chemistry (IUFAC) as a "device that uses specific biochemical reactions mediated by isolated enzymes, immunosystems, tissues, organelles or whole cells to detect chemical compounds usually by electrical, thermal or optical signals". In general, biosensors consist of two main components: a biological recognition element and a signal conversion unit (transducer). Numerous types of biosensors have been developed and the design variations are growing, at a rapid rate. Biosensors enable fast detection, portability and versatility for both field and laboratory applications. Biosensors provide several advantages over standard methods of environmental and microbial diagnostics with the primary benefits being assay speed, miniaturization, sensitivity, and low sample volume needed for analysis. The paper describes various biosensors and biosensor applications for microbial and environmental analysis and the expected future trends in the technology. C1 [Rasooly, A.] NCI, Canc Diag Program, DCTD, NIH, Rockville, MD 20852 USA. [Rasooly, A.; Sergeev, N.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. [Herold, K. E.] Univ Maryland, Dept Bioengn, College Pk, MD 20742 USA. RP Rasooly, A (reprint author), NCI, Canc Diag Program, DCTD, NIH, EPN 6035A,6130 Execut Blvd, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 75 TC 0 Z9 0 U1 1 U2 1 PU EDIZIONI MINERVA MEDICA PI TURIN PA CORSO BRAMANTE 83-85 INT JOURNALS DEPT., 10126 TURIN, ITALY SN 1120-4826 J9 MINERVA BIOTECNOL JI Minerva Biotechnol. PD SEP PY 2007 VL 19 IS 3 BP 105 EP 116 PG 12 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 333JA UT WOS:000258147600004 ER PT J AU Desai, VG Lee, T Delongchamp, RR Moland, CL Branham, WS Fuscoe, JC Leakey, JEA AF Desai, Varsha G. Lee, Taewon Delongchamp, Robert R. Moland, Carrie L. Branham, William S. Fuscoe, James C. Leakey, Julian E. A. TI Development of mitochondria-specific mouse oligonucleotide microarray and validation of data by real-time PCR SO MITOCHONDRION LA English DT Article DE mitochondria; mouse MitoChip; microarray; Zidovudine (AZT); Lamivudine (3TC) ID GENE-EXPRESSION DATA; TOXICITY; MODEL; INHIBITION; COMPLEXES; INSIGHTS; DISEASES; DRUGS; RATS; DNA AB This study describes the development of a mitochondria-specific microarray, MitoChip, to measure transcripts of mitochondria-associated genes in various diseases and drug-induced toxicities in the mouse. The array consists of 542 oligonucleotides that represent genes from the mitochondrial and nuclear genomes associated with mitochondrial structure and functions. The expression of mitochondrial genes was measured in the liver of both p53 haplodeficient (+/-) and wild-type (+/+) C3B6F(1) female mice exposed to antiretroviral agents, Zidovudine (AZT) and Lamivudine (3TC). Among genes whose expression was significantly altered, a set was selected for real-time PCR analysis to verify their differential gene expression. The real-time PCR data confirmed the observations by microarray analysis suggesting that the MitoChip may be an important tool for examining mitochondrial involvement in diseases and drug-induced toxicities. (c) 2007 Elsevier B.V. and Mitochondria Research Society. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Ctr Funct Genom, Div Syst Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Off Sci Co ordinat, Jefferson, AR 72079 USA. RP Desai, VG (reprint author), US FDA, Natl Ctr Toxicol Res, Ctr Funct Genom, Div Syst Toxicol, Jefferson, AR 72079 USA. EM varsha.desai@fda.hhs.gov NR 26 TC 14 Z9 15 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1567-7249 J9 MITOCHONDRION JI Mitochondrion PD SEP PY 2007 VL 7 IS 5 BP 322 EP 329 DI 10.1016/j.mito.2007.02.004 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 217RG UT WOS:000249964400004 PM 17526437 ER PT J AU Selvapandiyan, A Kumar, P Morris, JC Salisbury, JL Wang, CC Nakhasi, HL AF Selvapandiyan, Angamuthu Kumar, Praveen Morris, James C. Salisbury, Jeffrey L. Wang, Ching C. Nakhasi, Hira L. TI Centrin1 is required for organelle segregation and cytokinesis in Trypanosoma brucei SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID BASAL-BODY DUPLICATION; SPINDLE POLE BODY; NUCLEOTIDE EXCISION-REPAIR; HUMAN BREAST-TUMORS; CELL-CYCLE; CHLAMYDOMONAS-REINHARDTII; SACCHAROMYCES-CEREVISIAE; FLAGELLUM ATTACHMENT; PARAFLAGELLAR ROD; GOLGI DUPLICATION AB Centrin is a calcium-binding centrosome/basal body-associated protein involved in duplication and segregation of these organelles in eukaryotes. We had shown that disruption of one of the centrin genes (centrin1) in Leishmania amastigotes resulted in failure of both basal body duplication and cytokinesis. Here, we undertook to define the role of centrin1 (TbCen1) in the duplication and segregation of basal body and its associated organelles kinetoplast and Golgi, as well as its role in cytokinesis of the procyclic form of Trypanosoma brucei by depleting its protein using RNA inhibition methodology. TbCen1-depleted cells showed significant reduction in growth compared with control cells. Morphological analysis of these cells showed they were large and pleomorphic with multiple detached flagella. Both immunofluorescence assays using organelle-specific antibodies and electron microscopic analysis showed that TbCen1-deficient cells contained multiple basal bodies, kinetoplasts, Golgi, and nuclei. These multiple organelles were, however, closely clustered together, indicating duplication without segregation in the absence of centrin. This failure in organelle segregation may be the likely cause of inhibition of cytokinesis, suggesting for the first time a new and unique role for centrin in the segregation of organelles without affecting their multiplication in the procyclic form of T. brucei. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. Clemson Univ, Dept Biochem & Genet, Clemson, SC 29634 USA. Mayo Clin, Coll Med, Tumor Biol Program, Rochester, MN 55905 USA. RP Selvapandiyan, A (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. EM angamuthu.selvapandiyan@fda.hhs.gov; hira.nakhasi@fda.hhs.gov NR 64 TC 48 Z9 49 U1 0 U2 1 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD SEP PY 2007 VL 18 IS 9 BP 3290 EP 3301 DI 10.1091/mbc.E07-01-0022 PG 12 WC Cell Biology SC Cell Biology GA 206CT UT WOS:000249162200006 PM 17567955 ER PT J AU Freiberger, F Claus, H Gunzel, A Oltmann-Norden, I Vionnet, J Muhlenhoff, M Vogel, U Vann, WF Gerardy-Schahn, R Stummeyer, K AF Freiberger, Friedrich Claus, Heike Gunzel, Almut Oltmann-Norden, Imke Vionnet, Justine Muhlenhoff, Martina Vogel, Ulrich Vann, Willie F. Gerardy-Schahn, Rita Stummeyer, Katharina TI Biochemical characterization of a Neisseria meningitidis polysialyltransferase reveals novel functional motifs in bacterial sialyltransferases SO MOLECULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI K1; POLYSIALIC ACID CAPSULES; SIALIC-ACID; SEROGROUP-B; K92 POLYSIALYLTRANSFERASE; SERUM RESISTANCE; PASTEURELLA-MULTOCIDA; COLOMINIC ACID; GROUP-C; LIPOOLIGOSACCHARIDE AB The extracellular polysaccharide capsule is an essential virulence factor of Neisseria meningitidis, a leading cause of severe bacterial meningitis and sepsis. Serogroup B strains, the primary disease causing isolates in Europe and America, are encapsulated in alpha-2,8 polysialic acid (polySia). The capsular polymer is synthesized from activated sialic acid by action of a membrane-associated polysialyltransferase (NmB-polyST). Here we present a comprehensive characterization of NmB-polyST. Different from earlier studies, we show that membrane association is not essential for enzyme functionality. Recombinant NmB-polyST was expressed, purified and shown to synthesize long polySia chains in a non-processive manner in vitro. Subsequent structure-function analyses of NmB-polyST based on refined sequence alignments allowed the identification of two functional motifs in bacterial sialyltransferases. Both (D/E-D/E-G and HP motif) are highly conserved among different sialyltransferase families with otherwise little or no sequence identity. Their functional importance for enzyme catalysis and CMP-Neu5Ac binding was demonstrated by mutational analysis of NmB-polyST and is emphasized by structural data available for the Pasteurella multocida sialyltransferase PmST1. Together our data are the first description of conserved functional elements in the highly diverse families of bacterial (poly)sialyltransferases and thus provide an advanced basis for understanding structure-function relations and for phylogenetic sorting of these important enzymes. C1 Hannover Med Sch, Abt Zellulare Chem, D-30625 Hannover, Germany. Univ Wurzburg, Inst Hyg & Microbiol, D-97080 Wurzburg, Germany. US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Toxins, Bethesda, MD 20892 USA. RP Stummeyer, K (reprint author), Hannover Med Sch, Abt Zellulare Chem, Carl Neuberg Str 1, D-30625 Hannover, Germany. EM stummeyer.katharina@mh-hannover.de NR 52 TC 51 Z9 51 U1 1 U2 9 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD SEP PY 2007 VL 65 IS 5 BP 1258 EP 1275 DI 10.1111/j.1365-2958.2007.05862.x PG 18 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 207HN UT WOS:000249242300009 PM 17662040 ER PT J AU Woodcock, J Witter, J Dionne, RA AF Woodcock, Janet Witter, James Dionne, Raymond A. TI Stimulating the development of mechanism-based, individualized pain therapies SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; SEROTONIN REUPTAKE INHIBITORS; IMMPACT RECOMMENDATIONS; CLINICAL-TRIALS; GASTROINTESTINAL TOXICITY; POSTOPERATIVE PAIN; NEUROPATHIC PAIN; OUTCOME MEASURES; REMISSION RATES; SEX-DIFFERENCES AB Biomedical science has greatly improved our understanding of pain in recent decades, but few novel molecular entities that address fundamentally new pain mechanisms have entered the clinic, despite dramatically increased pharmaceutical investment. Indeed, virtually all new analgesics approved over the past 25 years are derivatives or reformulations of opioids or aspirin- like drugs, existing drugs given for a new indication or older drugs given by a different route of administration. Here, we discuss factors contributing to this lack of innovation in therapies for pain and advocate public-private partnerships ( PPPs) to translate new knowledge into more efficacious and safer treatments. C1 NIH, Dept Hlth & Human Serv, Bethesda, MD 20892 USA. US FDA, Dept Hlth & Human Serv, Rockville, MD 20857 USA. RP Dionne, RA (reprint author), NIH, Dept Hlth & Human Serv, Bldg 10, Bethesda, MD 20892 USA. EM dionner@mail.nih.gov NR 43 TC 52 Z9 53 U1 1 U2 5 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD SEP PY 2007 VL 6 IS 9 BP 703 EP 710 DI 10.1038/nrd2335 PG 8 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 207FG UT WOS:000249236400015 PM 17762885 ER PT J AU Wang, HY Xu, ZJ Fang, H Duhart, HM Patterson, TA Ali, SF AF Wang, Hanyong Xu, Zengjun Fang, Hong Duhart, Helen M. Patterson, Tucker A. Ali, Syed F. TI Gene expression profiling of MPP+-treated MN9D cells: A mechanism of toxicity study SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR DE MPP+; MN9D cells; microarray; gene expression; neurotoxicity; Parkinson's disease ID NF-KAPPA-B; MESENCEPHALIC DOPAMINERGIC-NEURONS; ALPHA-KETOGLUTARATE DEHYDROGENASE; ENDOPLASMIC-RETICULUM STRESS; MITOCHONDRIAL COMPLEX-I; UP-REGULATED PROTEIN-1; PARKINSONS-DISEASE; OXIDATIVE STRESS; TRANSCRIPTION FACTORS; SUBSTANTIA-NIGRA AB Parkinson's disease (PD) is a common neurodegenerative disease characterized by progressive loss of midbrain dopaminergic neurons with unknown etiology. MPP+ (1-methyl-4-phenylpyridinium) is the active metabolite of the neurotoxin 1-methyl-4-phenyl- 1,2,3,6-tetrahydropytidine (MPTP), which induces Parkinson's-like syndromes in humans and animals. MPTP/MPP+ treatment produces selective dopaminergic neuronal degeneration, therefore, these agents are commonly used to study the pathogenesis of PD. However, the mechanisms of their toxicity have not been elucidated. In order to gain insights into MPP+-induced neurotoxicity, a gene expression microarray study was performed using a midbrain-derived dopaminergic neuronal cell line, MN9D. Utilizing a two-color reference design, Agilent mouse oligonucleotide microarrays were used to examine relative gene expression changes in MN9D cells treated with 40 mu M MPP+ compared with controls. Bioinformatics tools were used for data evaluation. Briefly, raw data were imported into the NCTR ArrayTrack database, normalized using a Lowess method and data quality was assessed. The Student's t-test was used to determine significant changes in gene expression (set as p < 0.05, fold change >1.5). Gene Ontology for Function Analysis (GOFFA) and Ingenuity Pathway Analysis were employed to analyze the functions and roles of significant genes in biological processes. Of the 51 significant genes identified, 44 were present in the GOFFA or Ingenuity database. These data indicate that multiple pathways are involved in the underlying mechanisms of MPP+-induced neurotoxicity, including apoptosis, oxidative stress, iron binding, cellular metabolism, and signal transduction. These data also indicate that MPP+-induced toxicity shares common molecular mechanisms with the pathogenesis of PD and further pathway analyses will be conducted to explore these mechanisms. (C) 2007 Elsevier Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, HFT 132, Div Neurotoxicol,Neurochem Lab, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Z Tech Corp, Div Bioinformat, Jefferson, AR 72079 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, HFT 132, Div Neurotoxicol,Neurochem Lab, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM syed.ali@fda.hhs.gov NR 101 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2007 VL 28 IS 5 BP 979 EP 987 DI 10.1016/j.neuro.2007.02.013 PG 9 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 230VU UT WOS:000250905100010 ER PT J AU Garey, J Paule, MG AF Garey, Joan Paule, Merle G. TI Effects of chronic low-dose acrylamide exposure on progressive ratio performance in adolescent rats SO NEUROTOXICOLOGY LA English DT Article; Proceedings Paper CT 23rd International Neurotoxicology Conference CY SEP 17-21, 2006 CL Little Rock, AR DE acrylamide; neurotoxicity; behavior; development; progressive ratio; motivation ID YOUNG-ADULT RATS; FOOD; MOTIVATION; DOPAMINE; METABOLISM; BEHAVIOR; REGIONS; HUMANS; BRAIN AB Acrylamide (ACR) is a neurotoxicant known to produce peripheral neuropathy in rats and humans, but little is known of its potential for. nu cognitive or motivational alterations. Chronic exposure to low doses of ACR as a food contaminant is known to occur widely in humans. product. This research evaluated the effects of daily ACR exposure on food-motivated behavior, with exposures beginning prenatally on gestation day 6 and continuing through approximately postnatal day (PND) 85. Plug-positive Fischer 344 dams (9-10 per dose) were gavaged daily with 0, 0.1, 0.3, 1.0 or 5.0 mg/kg/day ACR. On PNDs 1-22, pups were gavaged with the same dose their dam had received. On PND 22, pups were weaned and pair-housed with a same-sex littermate and ACR exposure continued at 0, 1, 3, 10 and 50 ppm via drinking water. One male and one female pup per litter were tested in an operant chamber under a progressive ratio (PR) schedule of food reinforcement from approximately 6 to 12 weeks of age. Results over 6 weeks of testing indicated a significant treatment effect of ACR on number of reinforcers earned, with Tukey HSD post hoc tests revealing significantly fewer reinforcers earned in the 5.0 mg/kg/day dose group than in controls. A significant effect of ACR on response rate was also observed, with the Tukey HSD post hoc tests revealing a significantly lower response rate in the 5.0 mg/kg/day group than in controls. No effects of ACR were observed on post-reinforcement pause. These data suggest that daily ACR exposure at 5.0 mg/kg/day can produce measurable decrements on aspects of food-motivated behavior. Published by Elsevier Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Garey, J (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, HFT-132, Jefferson, AR 72079 USA. EM joan.garey@fda.hhs.gov NR 27 TC 8 Z9 10 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD SEP PY 2007 VL 28 IS 5 BP 998 EP 1002 DI 10.1016/j.neuro.2007.07.004 PG 5 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 230VU UT WOS:000250905100012 PM 17720246 ER PT J AU Ferguson, SA Paule, MG Cada, A Fogle, CM Gray, EP Berry, KJ AF Ferguson, Sherry A. Paule, Merle G. Cada, Amy Fogle, C. Matthew Gray, Erika P. Berry, Kimberly J. TI Baseline behavior, but not sensitivity to stimulant drugs, differs among Spontaneously Hypertensive, Wistar-Kyoto, and Sprague-Dawley rat strains SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Spontaneously Hypertensive Rat; Wistar-Kyoto rat; time estimation; amphetamine; methylphenidate; progressive ratio ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT HYPERACTIVITY DISORDER; TEMPORAL RESPONSE DIFFERENTIATION; ANIMAL-MODEL; TIME PERCEPTION; ORAL METHYLPHENIDATE; RUNNING RESPONSE; SEX-DIFFERENCES; DELAY AVERSION; RHESUS-MONKEYS AB Deficits in temporal processing are implicated in Attention Deficit Hyperactivity Disorder (ADHD) for which the most common rodent model is the Spontaneously Hypertensive Rat (SHR). To assess strain differences in temporal processing, males and females of the SHR, Wistar-Kyoto (WKY), and Sprague-Dawley (SD) strains were compared on two timing tasks: one requiring maintenance of a lever press for 10-14 s (TRD, temporal response differentiation) and the other requiring withholding of a lever press for 10-14 s (DRL, differential reinforcement of low rates). Performance of the progressive ratio (PR) task more directly assessed food-motivated behavior. Strains did not differ in task acquisition; however, steady state TRD and DRL performance of the SHR and WKY strains was less accurate which was related to increased burst (non-timing related) responses in those strains relative to the SD. PR performance demonstrated that the SHR and WKY strains exhibited higher response rates and breakpoints than the SD. Subsequently, methylphenidate (1, 3.25, 4.50, 7.50, and 12.0 mg/kg) and D-amphetamine (0.1, 0.25, 0.65, 1.0, and 2.0 mg/kg) were administered intraperitoneally pre-testing. Both drugs disrupted TRD and DRL performances by increasing burst response frequency; however, the strains were not differentially sensitive to either drug. Strain differences were generally maintained throughout the drug and extinction portions of the study. These results indicate increased similarity between the SHR and WKY strains relative to the SD in performance of timing and motivation tasks. Further, the current results do not support continued use of the SHR as a model for ADHD. (c) 2007 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Bayer Cropsci LP, Stilwell, KS 66085 USA. Rosalind Franklin Univ Med & Sci, Dept Psychol, N Chicago, IL 60064 USA. RP Ferguson, SA (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov NR 86 TC 27 Z9 27 U1 0 U2 4 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 SEP-OCT PY 2007 VL 29 IS 5 BP 547 EP 561 DI 10.1016/j.ntt.2007.07.001 PG 15 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 237EM UT WOS:000251356600003 PM 17689921 ER PT J AU Freas, S Chelonis, J Forzano, L Paule, M AF Freas, S. L. Chelonis, J. J. Forzano, L. B. Paule, M. G. TI Effects of reinforcer type on performance of psychological tasks SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the Neurobehavioral-Teratology-Society/26th Annual Meeting of the Behavioral-Toxicology-Society held in Conjunction with the 47th Annual Meeting of the Teratology-Society/20th Organization-of-Teratology-Information-Specialists CY JUN 23-27, 2007 CL Pittsburgh, PA SP Neurobehav Teratol Soc, Behav Toxicol Soc, Teratol Soc, Org Teratol Informat Specialists C1 SUNY Coll Brockport, Brockport, NY USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD SEP-OCT PY 2007 VL 29 IS 5 BP 588 EP 589 DI 10.1016/j.ntt.2007.08.022 PG 2 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 237EM UT WOS:000251356600011 ER PT J AU Huang, Y Blower, PE Liu, RQ Dai, ZY Pham, AN Moon, H Fang, JL Sadee, W AF Huang, Ying Blower, Paul E. Liu, Ruqing Dai, Zunyan Pham, Anh-Nhan Moon, Hojin Fang, Jialong Sadee, Wolfgang TI Chemogenomic analysis identifies geldanamycins as substrates and inhibitors of ABCB1 SO PHARMACEUTICAL RESEARCH LA English DT Article DE ABCB1; chemogenomics; geldanamycin; membrane transporter and chemoresistance ID P-GLYCOPROTEIN; MEMBRANE TRANSPORTERS; CANCER CHEMOSENSITIVITY; MOLECULAR PHARMACOLOGY; MULTIDRUG-RESISTANCE; GENE-EXPRESSION; IN-VITRO; CHEMORESISTANCE; 17-ALLYLAMINO-17-DEMETHOXYGELDANAMYCIN; SENSITIVITY AB A prerequisite for geldanamycin (GA, NSC122750) to targeting heat shock protein 90 and inhibiting tumor growth is sufficient intracellular drug accumulation. We hypothesized that membrane transporters on tumor cells determine at least in part the response to GA analogues. To facilitate a systematic study of chemosensitivity across a group of GA analogues with similar chemical structures, we correlated mRNA expression profiles of most known transporters with growth inhibitory potencies of compounds in 60 tumor cell lines (NCI-60). We subsequently validated the gene-drug correlations using cytotoxicity and transport assays. Geldanamycin analogues displayed a range of negative correlations coefficients with ABCB1 (MDR1, or P-glycoprotein) expression. Suppressing ABCB1 in multidrug resistant cells (NCI/ADR-RES and K562/DOX) and ABCB1-transfected cells (BC19) increased sensitivity to GA analogues, as expected for substrates. Moreover, ABCB1-mediated efflux of daunorubicin in K562/DOX cells could be blocked markedly by GA analogues in a dose-dependent fashion. The IC50 values (half-maximum inhibition of daunorubicin efflux) were 5.5, 7.3 and 12 mu M for macbecin II (NSC330500), 17-AAG (NSC330507) and GA, respectively. These observations demonstrate that GA analogues are substrates as well as inhibitors of ABCB1, suggesting that drug interactions between GA analogues and other agents that are ABCB1 substrates may occur via ABCB1 in normal or tumor cells. C1 Western Univ Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Pomona, CA 91766 USA. Leadscope Inc, Columbus, OH 43212 USA. Ohio State Univ, Coll Med & Publ Hlth, Ctr Comprehens Canc, Dept Pharmacol, Columbus, OH 43210 USA. Ohio State Univ, Coll Med & Publ Hlth, Ctr Comprehens Canc, Program Pharmacogenom, Columbus, OH 43210 USA. Sun Yat Sen Univ, Sch Publ Hlth, Guangzhou, Peoples R China. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Huang, Y (reprint author), Western Univ Hlth Sci, Coll Pharm, Dept Pharmaceut Sci, Pomona, CA 91766 USA. EM yhuang@westernu.edu FU NIGMS NIH HHS [GM61390] NR 35 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD SEP PY 2007 VL 24 IS 9 BP 1702 EP 1712 DI 10.1007/s11095-007-9300-x PG 11 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 198HX UT WOS:000248618700011 PM 17457659 ER PT J AU Badal, A Kyprianou, I Badano, A Sempau, J AF Badal, A. Kyprianou, I. Badano, A. Sempau, J. TI Monte Carlo simulation with penelope and a realistic anthropomorphic phantom described by triangle meshes SO RADIOTHERAPY AND ONCOLOGY LA English DT Meeting Abstract CT 9th Biennial Meeting on Physics and Radiation Technology for Clinical Radiotherapy CY SEP 08-13, 2007 CL Barcelona, SPAIN SP European Soc Therapeut Radiol & Oncol C1 [Badal, A.; Sempau, J.] Univ Politecn Cataluna, Inst Tech Energet, Barcelona, Spain. [Kyprianou, I.; Badano, A.] US FDA, NIIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20857 USA. RI Sempau, Josep/J-7834-2013 OI Sempau, Josep/0000-0002-2754-7685 NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0167-8140 J9 RADIOTHER ONCOL JI Radiother. Oncol. PD SEP PY 2007 VL 84 SU 1 MA 99 BP S46 EP S46 PG 1 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 237SU UT WOS:000251397500093 ER PT J AU Ilev, I Waynant, R Gannot, I Gandjbakhche, A AF Ilev, Ilko Waynant, Ronald Gannot, Israel Gandjbakhche, Amir TI Simple fiber-optic confocal microscopy with nanoscale depth resolution beyond the diffraction barrier SO REVIEW OF SCIENTIFIC INSTRUMENTS LA English DT Article ID SCANNING OPTICAL MICROSCOPY AB A novel fiber-optic confocal approach for ultrahigh depth-resolution (<= 2 nm) microscopy beyond the diffraction barrier in the subwavelength nanometric range below 200 nm is presented. The key idea is based on a simple fiber-optic confocal microscope approach that is compatible with a differential confocal microscope technique. To improve the dynamic range of the resolving laser power and to achieve a high resolution in the nanometric range, we have designed a simple apertureless reflection confocal microscope with a highly sensitive single-mode-fiber confocal output. The fiber-optic design is an effective alternative to conventional pinhole-based confocal systems and offers a number of advantages in terms of spatial resolution, flexibility, miniaturization, and scanning potential. Furthermore, the design is compatible with the differential confocal pinhole microscope based on the use of the sharp diffraction-free slope of the axial confocal response curve rather than the area around the maximum of that curve. Combining the advantages of ultrahigh-resolution fiber-optic confocal microscopy, we can work beyond the diffraction barrier in the subwavelength (below 200 nm) nanometric range exploiting confocal nanobioimaging of single cell and intracellular analytes. (c) 2007 American Institute of Physics. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, Silver Spring, MD 20993 USA. George Washington Univ, Sch Engn & Appl Sci, Dept Elect & Comp Engn, Program Biomed Engn, Washington, DC 20052 USA. NICHHD, Lab Integrat & Med Biophys, NIH, Bethesda, MD 20892 USA. RP Ilev, I (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, 10903 New Hampshire Ave,Bldg 62, Silver Spring, MD 20993 USA. FU Intramural NIH HHS NR 15 TC 10 Z9 10 U1 1 U2 5 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0034-6748 J9 REV SCI INSTRUM JI Rev. Sci. Instrum. PD SEP PY 2007 VL 78 IS 9 AR 093703 DI 10.1063/1.2777173 PG 4 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 215DF UT WOS:000249787800012 PM 17902951 ER PT J AU Laughren, T AF Laughren, Thomas TI Wayne fenton: Impact on food and drug administration SO SCHIZOPHRENIA BULLETIN LA English DT Editorial Material C1 US FDA, Div Psychiat Prod, Rockville, MD 20857 USA. RP Laughren, T (reprint author), US FDA, Div Psychiat Prod, Rockville, MD 20857 USA. EM thomas.laughren@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD SEP PY 2007 VL 33 IS 5 BP 1153 EP 1153 DI 10.1093/schbul/sbm073 PG 1 WC Psychiatry SC Psychiatry GA 214HD UT WOS:000249726700016 PM 17578891 ER PT J AU Roberts, DP McKenna, LF Lakshman, DK Meyer, SLF Kong, H de Souza, JT Lydon, J Baker, CJ Buyer, JS Chung, S AF Roberts, D. P. McKenna, L. F. Lakshman, D. K. Meyer, S. L. F. Kong, H. de Souza, J. T. Lydon, J. Baker, C. J. Buyer, J. S. Chung, S. TI Suppression of damping-off of cucumber caused by Pythium ultimum with live cells and extracts of Serratia marcescens N4-5 SO SOIL BIOLOGY & BIOCHEMISTRY LA English DT Article DE biological control; cucumber; damping-off; Meloidogyne incognita; prodigiosin; Pythium ultimurn; seed treatments; Serratia marcescens ID PSEUDOMONAS-CEPACIA; BIOLOGICAL-CONTROL; ANTIBIOTIC SUSCEPTIBILITY; NONPATHOGENIC FUSARIUM; ENTEROBACTER-CLOACAE; ANTIFUNGAL ACTIVITY; BROAD-SPECTRUM; PRODIGIOSIN; BIOCONTROL; STRAIN AB Environmentally friendly control measures are needed for the soil-borne pathogen, Pythium ultimum. This pathogen can cause severe losses to field- and greenhouse-grown cucumber and other cucurbits. Live cells and ethanol extracts of cultures of the bacterium Serratia marcescens N4-5 provided significant suppression of damping-off of cucumber caused by P. ultimum when applied as a seed treatment. Live cells of this bacterium also suppressed damping-off caused by P. ultimum on cantaloupe, muskmelon, and pumpkin. Culture filtrates from strain N4-5 contained chitinase and protease activities while ethanol extracts contained the antibiotic prodigiosin, the surfactant serrawettin W1, and possibly other unidentified surfactants. Production of prodigiosin and serrawettin W1 was temperature-dependent, both compounds being detected in extracts from N4-5 grown at 28 degrees C but not in extracts from N4-5 grown at 37 degrees C. Ethanol extracts from strain N4-5 grown at 28 degrees C inhibited germination of sporangia and mycelial growth by P. ultimum in in vitro experiments. There was no in vitro inhibition of P. ultimum associated with ethanol extracts of strain N4-5 grown at 37 degrees C. Prodigiosin, purified from two consecutive thin-layer chromatography runs using different solvent systems, inhibited germination of sporangia and mycelial growth of P. ultimum. Another unidentified compound(s) also inhibited germination of sporangia but did not inhibit mycelial growth. There was no in vitro inhibition associated with serrawettin W1. These results demonstrate that live cells and cell-free extracts of S. marcescens N4-5 are effective for suppression of damping-off of cucumber caused by P. ultimum possibly due in part to the production of the antibiotic prodigiosin. (C) 2007 Elsevier Ltd. All rights reserved. C1 US FDA, CBER, Lab Methods Dev, Rockville, MD 20850 USA. Univ Fed Reconcavo Bahia, BR-44380000 Cruz das Almas, BA, Brazil. USDA ARS, Beltsville Agr Res Ctr, Sustainable Agr Syst Labs, Beltsville, MD 20705 USA. USDA ARS, Beltsville Agr Res Ctr, Floral & Nursery Plants Unit, Beltsville, MD 20705 USA. Univ Maryland, Wye Res & Educ Ctr, Queenstown, MD 21658 USA. USDA ARS, Beltsville Agr Res Ctr, Mol Plant Pathol Lab, Beltsville, MD 20705 USA. Yeungnam Univ, Dept Appl Microbiol, Gyeongbuk 712749, South Korea. RP Roberts, DP (reprint author), US FDA, CBER, Lab Methods Dev, Rockville, MD 20850 USA. EM dan.roberts@ars.usda.gov NR 73 TC 24 Z9 29 U1 0 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0038-0717 J9 SOIL BIOL BIOCHEM JI Soil Biol. Biochem. PD SEP PY 2007 VL 39 IS 9 BP 2275 EP 2288 DI 10.1016/j.soilbio.2007.03.029 PG 14 WC Soil Science SC Agriculture GA 191AP UT WOS:000248102500008 ER PT J AU Fostel, JM Burgoon, L Zwickl, C Lord, P Corton, JC Bushel, PR Cunningham, M Fan, LJ Edwards, SW Hester, S Stevens, J Tong, WD Waters, M Yang, CH Termant, R AF Fostel, Jennifer M. Burgoon, Lyle Zwickl, Craig Lord, Peter Corton, J. Christopher Bushel, Pierre R. Cunningham, Michael Fan, Liju Edwards, Stephen W. Hester, Susan Stevens, James Tong, Weida Waters, Michael Yang, ChiHae Termant, Raymond TI Toward a checklist for exchange and interpretation of data from a toxicology study SO TOXICOLOGICAL SCIENCES LA English DT Article DE toxicogenomics; MIAME; data integration; database ID MICROARRAY DATA; ACETAMINOPHEN TOXICITY; HEPATOTOXICITY; MIAME; MICE; METABOLISM; LIVER; RATS AB Data from toxicology and toxicogenomics studies are valuable, and can be combined for meta-analysis using public data repositories such as Chemical Effects in Biological Systems Knowledgebase, ArrayExpress, and Gene Expression Omnibus. In order to fully utilize the data for secondary analysis, it is necessary to have a description of the study and good annotation of the accompanying data. This study annotation permits sophisticated cross-study comparison and analysis, and allows data from comparable subjects to be identified and fully understood. The Minimal Information About a Microarray Experiment Standard was proposed to permit deposition and sharing of microarray data. We propose the first step toward an analogous standard for a toxicogenomics/toxicology study, by describing a checklist of information that best practices would suggest be included with the study data. When the information in this checklist is deposited together with the study data, the checklist information helps the public explore the study data in context of time, or identify data from similarly treated subjects, and also explore/identify potential sources of experimental variability. The proposed checklist summarizes useful information to include when sharing study data for publication, deposition into a database, or electronic exchange with collaborators. It is not a description of how to carry out an experiment, but a definition of how to describe an experiment. It is anticipated that once a toxicology checklist is accepted and put into use, then toxicology databases can be configured to require and output these fields, making it straightforward to annotate data for interpretation by others. C1 NIEHS, Res Triangle Pk, NC 27709 USA. NIEHS, LMIT ITSS Contract, Res Triangle Pk, NC 27709 USA. Michigan State Univ, Dept Biochem & Mol Biol, E Lansing, MI 48824 USA. Johnson & Johnson PRD, Raritan, NJ 08869 USA. US EPA, Res Triangle Pk, NC 27711 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Ontology Worshop LLC, Columbia, MD 21045 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Integrated Life Sci, Res Triangle Pk, NC 27709 USA. Leadscope, Columbus, OH 43212 USA. RP Fostel, JM (reprint author), NIEHS, POB 12233, 111 Alexander Drive, Res Triangle Pk, NC 27709 USA. EM fostel@niehs.nih.gov OI Burgoon, Lyle/0000-0003-4977-5352 FU Intramural NIH HHS NR 18 TC 12 Z9 13 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD SEP PY 2007 VL 99 IS 1 BP 26 EP 34 DI 10.1093/toxsci/kfm090 PG 9 WC Toxicology SC Toxicology GA 205XK UT WOS:000249148300004 PM 17442663 ER PT J AU Selvapandiyan, A Duncan, R Mendez, J Card, LJ Nakhasil, H AF Selvapandiyan, A. Duncan, R. Mendez, J. Card, L. J. Nakhasil, H. TI Evaluation of a sensitive PCIR assay for rapid identification of leishmania SP ecies from blood samples SO TRANSFUSION LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 20-23, 2007 CL Anaheim, CA SP Amer Assoc Blood Banks C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Walter Reed Army Inst Res, Silver Spring, MD USA. EM lisa.cardo@us.army.mil NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2007 VL 47 IS 3 SU S BP 8A EP 9A PG 2 WC Hematology SC Hematology GA 209OJ UT WOS:000249397600023 ER PT J AU Yu, MW Virata-Theimer, ML Geng, Y Schechtetly, CA Colvin, CA Alter, HJ Luban, NL AF Yu, M. W. Virata-Theimer, M. L. Geng, Y. Schechtetly, C. A. Colvin, C. A. Alter, H. J. Luban, N. L. TI Transmission of parvovirus b19 by blood transfusion confirmed by DNA sequencing SO TRANSFUSION LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 20-23, 2007 CL Anaheim, CA SP Amer Assoc Blood Banks C1 US FDA, Div Hematol, OBRR, CBER, Bethesda, MD 20014 USA. NIH, Dept Transfus Med, Bethesda, MD 20892 USA. CNMC, Div Lab Med, Washington, DC USA. NIH, Bethesda, MD 20892 USA. EM marialuisa.virata@fda.hhs.gov NR 0 TC 2 Z9 2 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2007 VL 47 IS 3 SU S BP 16A EP 16A PG 1 WC Hematology SC Hematology GA 209OJ UT WOS:000249397600044 ER PT J AU Grinev, A Daniel, S Stramer, SL Rios, M AF Grinev, A. Daniel, S. Stramer, S. L. Rios, M. TI Genetic study of WNV (WNV) human isolates from 2006 reveals a new isolate carrying a deletion at the 3' NCR SO TRANSFUSION LA English DT Meeting Abstract CT 60th Annual Meeting of the American-Association-of-Blood-Banks CY OCT 20-23, 2007 CL Anaheim, CA SP Amer Assoc Blood Banks C1 FDA, CBER, Bethesda, MD USA. Amer Red Cross, Gaithersburg, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD SEP PY 2007 VL 47 IS 3 SU S BP 24A EP 24A PG 1 WC Hematology SC Hematology GA 209OJ UT WOS:000249397600066 ER PT J AU Lugovtsev, VY Vodeiko, GM Strupczewski, CM Ye, ZP Levandowski, RA AF Lugovtsev, Vladimir Y. Vodeiko, Galina M. Strupczewski, Caryn M. Ye, Zhiping Levandowski, Roland A. TI Generation of the influenza B viruses with improved growth phenotype by substitution of specific amino acids of hemagglutinin SO VIROLOGY LA English DT Article DE influenza B virus; growth characteristics; antigenic properties; reverse genetics ID RECEPTOR-BINDING PROPERTIES; A VIRUS; EGG-ADAPTATION; GLYCOSYLATION SITE; CHICKEN EGGS; 8 PLASMIDS; VARIANTS; HOSPITALIZATIONS; REASSORTANTS; SELECTION AB Variability in growth characteristics of influenza B viruses remains a serious limitation in the manufacture of inactivated influenza vaccines. Currently, serial passage in eggs is the strategy used in most instances for selection of high growth virus variants. In previous studies we found that adaptation of the strain B/Victoria/504/2000 to high growth in eggs was associated with changes only in hemagglutinin (HA). The high growth phenotype was associated with acquisition of either two (R162M and D196Y) or three (G141E, R162M and D196Y) amino acid (AA) substitutions, predicted to be near the receptor-binding domain of HA. In the present study we analyzed, using reverse genetics, the contribution to virus growth of each of these AA substitutions and determined their effect on antigenic properties. We found that G 141 E and R162M were most favorable for virus growth; however, only R162M could improve virus growth without antigenic alteration. Substitution D196Y had least effect on virus growth but substantially altered antigenic properties. Additional virus variants with AA substitutions at positions 126, 129, 137 and 141 were generated and characterized. The AA changes advantageous for growth of B/Victoria/504/2000 were also tested in the context of the HA of the B/ Beijing/184/93, a virus with stable low-growth phenotype. All of the tested AA substitutions improved the replicative capabilities of the corresponding viruses, but only N126D and K129E had no effect on antigenicity. The results of our studies demonstrate that introduction of specific AA substitutions into viral HA can improve viral replicative efficiency while preserving the original antigenic properties. Published by Elsevier Inc. C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review,Div Viral Prod, Pediat Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review,Div Viral Prod, Resp Viral Dis, Bethesda, MD 20892 USA. RP Lugovtsev, VY (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review,Div Viral Prod, Pediat Lab, 8800 Rockville Pike,Bldg 29A,Room 1D22, Bethesda, MD 20892 USA. EM vladimir.lugovtsev@fda.hhs.gov NR 43 TC 18 Z9 19 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 0042-6822 J9 VIROLOGY JI Virology PD SEP 1 PY 2007 VL 365 IS 2 BP 315 EP 323 DI 10.1016/j.virol.2007.04.006 PG 9 WC Virology SC Virology GA 203OZ UT WOS:000248985200008 PM 17490701 ER PT J AU Elbaz, B Alperovitch, A Sarfaty, CK Gottesman, MM Rahamimoff, H AF Elbaz, Benayahu Alperovitch, Ariella Sarfaty, Chava Kimchi Gottesman, Michael M. Rahamimoff, Hannah TI The effect of Cyclosporin A (CsA) and FK506 on the expression of the Na+-Ca2+ exchangers NCX1, NCX2 and NCX3 SO XENOTRANSPLANTATION LA English DT Meeting Abstract CT Joint Meeting of the International-Xenotransplantation-Association/International-Pancrcas-and -Islet-Transplant-Association/Cell-Transplant-Society CY SEP 15-20, 2007 CL Minneapolis, MN SP Int Xenotransplantat Assoc, Int Pancreas & Islet Transplant Assoc, Cell Transplant Soc C1 Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Biochem, IL-91905 Jerusalem, Israel. Div Hematol, US FDA, Bethesda, MD USA. NCI, NIH, Cell Biol Lab, Bethesda, MD USA. EM Hannah.Rahamimoff@huji.ac.il NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD SEP PY 2007 VL 14 IS 5 BP 498 EP 498 PG 1 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 206RX UT WOS:000249201700385 ER PT J AU Unger, EF AF Unger, Ellis F. TI All is not well in the world of translational research SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Editorial Material AB It is not unusual for novel treatment strategies to fail in clinical trials, despite highly encouraging results in preclinical proof-of-concept studies. Typically, such "failures of translation" are blamed on the poor predictiveness of animal models. Often, however, the poor predictiveness of today's preclinical proof-of-concept studies is related not to limitations of the models but to investigator bias and a lack of scientific rigor. The resulting false-positive results only serve to mislead the field and impede medical progress. With the resurgence of translational research, it is useful to examine some of the problems that plague these studies and consider their solutions. With thoughtful planning, execution, and analysis, it is possible to generate reliable and predictive data from preclink cal proof-of-concept studies, results that should more rapidly advance medical progress. C1 US FDA, Ctr Cardiovasc Renal Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Unger, EF (reprint author), HFD 110,Bldg 22,10903 New Hamshire Ave, Silver Spring, MD USA. EM eflis.unger@fda.hhs.gov NR 0 TC 14 Z9 15 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD AUG 21 PY 2007 VL 50 IS 8 BP 738 EP 740 DI 10.1016/jjacc.2007.04.067 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 201DQ UT WOS:000248812100002 PM 17707177 ER PT J AU Chen, F Dong, WJ Cogbill, A Padilla, C Ali, S Tian, ZR AF Chen, Feng Dong, Wenjun Cogbill, Andrew Padilla, Carmen Ali, Syed Tian, Z. Ryan TI INOR 820-Ceramic nanowires for diagnostic, therapeutic, and regenerative nanomedicines SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Chen, Feng; Dong, Wenjun; Cogbill, Andrew; Tian, Z. Ryan] Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA. [Ali, Syed] US FDA, Natl Ctr Toxicol Res, Div Neurotox, Jefferson, AR 72079 USA. EM fchen@uark.edu; wdong@uark.edu; wdong@uark.edu; rtian@uark.edu RI Tian, Z. Ryan /R-6671-2016 OI Tian, Z. Ryan /0000-0002-5644-8483 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 820-INOR PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593909691 ER PT J AU Chen, F Dong, WJ Zhang, TR Ali, S Duhart, HM Tian, ZR AF Chen, Feng Dong, Wenjun Zhang, Tierui Ali, Syed Duhart, Helen M. Tian, Z. Ryan TI A smart bioscaffold of nanowires for monitoring proteins SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Chen, Feng; Dong, Wenjun; Zhang, Tierui; Tian, Z. Ryan] Univ Arkansas, Dept Chem & Biochem, Fayetteville, AR 72701 USA. [Ali, Syed] US FDA, Natl Ctr Toxicol Res, Div Neurotox, Jefferson, AR 72079 USA. [Duhart, Helen M.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM fchen@uark.edu; rtian@uark.edu; rtian@uark.edu RI Tian, Z. Ryan /R-6671-2016 OI Tian, Z. Ryan /0000-0002-5644-8483 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 47-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593901234 ER PT J AU Chu, PS Lopez, MI Abraham, A El Said, KR Plakas, SM AF Chu, Pak-Sin Lopez, Mayda I. Abraham, Ann El Said, Kathleen R. Plakas, Steven M. TI AGRO 13-Analysis of nitrofuran residues in shrimp, channel catfish, and milk using liquid chromatography-tandem mass spectrometry SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Chu, Pak-Sin; Lopez, Mayda I.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Abraham, Ann; El Said, Kathleen R.; Plakas, Steven M.] US FDA, Ctr Food Safety & Appl Nutr, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 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 AUG 19 PY 2007 VL 234 MA 13-AGRO PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593900411 ER PT J AU Dejager, L Perfetti, GA Diachenko, GW AF Dejager, Lowri Perfetti, Gracia A. Diachenko, Gregory W. TI ANYL 17-Evaluation of modern extraction methods for the analysis of tetramethylene disulfotetramine in foods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Dejager, Lowri; Perfetti, Gracia A.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 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 AUG 19 PY 2007 VL 234 MA 17-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593901412 ER PT J AU Doerge, DR AF Doerge, Danie R. TI AGFD 99-PBPK/PD modeling of acrylamide: Integration of kinetic and biomarker data for use in risk assessment SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Doerge, Danie R.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 99-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593900178 ER PT J AU Evans, RL Siitonen, PH AF Evans, Ronald L. Siitonen, Paul H. TI AGFD 128-Analysis of usnic acid from Usnea sp dispersed in rodent diet by HPLC SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Evans, Ronald L.; Siitonen, Paul H.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Food & Drug Adm, HFT 230, Jefferson, AR 72079 USA. EM ronald.evans@fda.hhs.gov; paul.siitonen@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 128-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593900226 ER PT J AU Hanson, MA Vallejos, J Ge, XD Brorson, K Moreira, AR Rao, G AF Hanson, Michael A. Vallejos, Jose Ge, Xudong Brorson, Kurt Moreira, Antonio R. Rao, Govind TI BIOT 203-Impact of scale and bioreactor type on cell growth, productivity, product quality, and global gene expression SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Hanson, Michael A.; Vallejos, Jose; Ge, Xudong; Moreira, Antonio R.; Rao, Govind] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Brorson, Kurt] US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Silver Spring, MD 20903 USA. EM m.hanson@umbc.edu; jose7@umbc.edu; xge1@umbc.edu; kurt.brorson@fda.hhs.gov; moreira@umbc.edu; grao@umbc.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 203-BIOT PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593903122 ER PT J AU Johnson, ML Casas, R Patwardhan, DV Pollack, SK Uhrich, KE AF Johnson, Michelle L. Casas, Rachel Patwardhan, Dinesh V. Pollack, Steven K. Uhrich, Kathryn E. TI POLY 583-Ampicillin-based poly(anhydride-amide) coatings for medical devices SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Johnson, Michelle L.; Uhrich, Kathryn E.] Rutgers State Univ, Dept Chem & Chem Biol, Piscataway, NJ 08854 USA. [Casas, Rachel; Patwardhan, Dinesh V.; Pollack, Steven K.] US FDA, Div Chem & Mat Sci, CDRH, OSEL, Silver Spring, MD 20993 USA. EM keuhrich@rutgers.edu RI Uhrich, Kathryn/I-2099-2013 OI Uhrich, Kathryn/0000-0001-7273-7528 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 583-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593908160 ER PT J AU Kaur, N Svoronos, P Devy, P Abbruscato, V AF Kaur, Navreet Svoronos, Paris Devy, Paula Abbruscato, Victor TI Mycotoxins: Identification procedures established by the Food and Drug Administration SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kaur, Navreet; Svoronos, Paris] CUNY Queensborough Community Coll, Dept Chem, Bayside, NY 11364 USA. [Devy, Paula; Abbruscato, Victor] Food & Drug Adm, Jamaica, NY USA. EM psvoronos@qcc.cuny.edu; psvoronos@qcc.cuny.edu; psvoronos@qcc.cuny.edu; psvoronos@qcc.cuny.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 187-CHED PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593904270 ER PT J AU Lee, FSC Wang, XR Chen, JH Fu, P AF Lee, Frank Sen Chun Wang, Xiaoru Chen, Junhui Fu, Peter TI ANYL 280-Chemical fingerprinting for the authentication and quality evaluation of Oriental medicinal herbs SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Lee, Frank Sen Chun; Wang, Xiaoru; Chen, Junhui] SOA, FIO, QingDao Key Lab Modern Analyt Technol & Standardi, Qingdao, Peoples R China. [Fu, Peter] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM fsclee@yahoo.com NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 280-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593901193 ER PT J AU Liu, YF Showalter, H Khachik, F AF Liu, Yufa Showalter, Holly Khachik, Frederick TI ORGN 685-Synthesis of beta-cryptoxanthin via unusual regioselective catalytic hydrogenation SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Liu, Yufa; Showalter, Holly] Kemin Hlth, R&D, Des Moines, IA 50317 USA. [Khachik, Frederick] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. EM Yufa.Liu@Kemin.com; Holly.Showalter@Kemin.com; khachik@umd.edu NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 685-ORGN PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593909814 ER PT J AU McDermott, MK Patwardhan, DV Casas, R Dair, BJ Kim, CS Pollack, SK Saylor, DM Soffer, JM Toy, J Wang, CX AF McDermott, Martin K. Patwardhan, Dinesh V. Casas, Rachel Dair, Benita J. Kim, Chang-Soo Pollack, Steven K. Saylor, Dave M. Soffer, Jeffrey M. Toy, Jeff Wang, Christine X. TI POLY 674-Microstructure characterization of drug-polymer composite coatings SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [McDermott, Martin K.; Patwardhan, Dinesh V.; Casas, Rachel; Dair, Benita J.; Kim, Chang-Soo; Pollack, Steven K.; Saylor, Dave M.] US FDA, Div Chem & Mat Sci, CDRH, OSEL, Silver Spring, MD 20993 USA. [Soffer, Jeffrey M.] George Washington Univ, Washington, DC 20052 USA. [Toy, Jeff] US FDA, Off Device Evaluat, Rockville, MD 20850 USA. [Wang, Christine X.] NYU, New York, NY 10003 USA. EM Martin.McDermott@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 674-POLY PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593908041 ER PT J AU Noonan, GO Begley, TH Diachenko, GW AF Noonan, Gregory O. Begley, Timothy H. Diachenko, Gregory W. TI ANYL 23-Characterization of perfluorochemicals in food packaging by direct analysis in real time-mass spectrometry (dart-MS) SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Noonan, Gregory O.; Begley, Timothy H.; Diachenko, Gregory W.] US FDA, Ctr Food Safety & Appl Nutr, HFS 706, College Pk, MD 20740 USA. NR 0 TC 0 Z9 0 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 23-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593901446 ER PT J AU Tareke, E Ali, S Lyn-Cook, B Duhart, HM AF Tareke, Eden Ali, Syed Lyn-Cook, Beverly Duhart, Helen M. TI Role of dietary components on acrylamide induced neurotransmitter turnover alterations in PC 12 cells SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Tareke, Eden] US FDA, Div Personalized Nutr & Med, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Ali, Syed] US FDA, Div Neurotox, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Lyn-Cook, Beverly] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Duhart, Helen M.] US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM etareke@nctr.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 127-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593905124 ER PT J AU Taylor, AD Ladd, J Etheridge, S Homola, J Jiang, SY AF Taylor, Allen D. Ladd, Jon Etheridge, Stacey Homola, Jiri Jiang, Shaoyi TI ANYL 20-Development of label-free arrayed SPR sensors for food safety monitoring SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Taylor, Allen D.; Ladd, Jon; Jiang, Shaoyi] Univ Washington, Dept Chem Engn, Seattle, WA 98195 USA. [Etheridge, Stacey] US Food & Drug, Food Safety & Appl Nutr 2Ctr, College Pk, MD 20740 USA. [Homola, Jiri] Acad Sci Czech Republic, Inst Radio Engn & Elect, CR-18251 Prague, Czech Republic. EM adtaylor@u.washington.edu; sjiang@u.washington.edu RI Homola, Jiri/F-3683-2014 OI Homola, Jiri/0000-0001-6258-015X NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 20-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593901385 ER PT J AU Wong, JW Krynitsky, AJ AF Wong, Jon W. Krynitsky, Alexander J. TI ANYL 38-Some applications of GC-MS/MS and LC-MS/MS to analyze pesticides and chemical contaminants in foods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Wong, Jon W.] US FDA, Off Regulatory Sci, College Pk, MD 20740 USA. [Krynitsky, Alexander J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM jon.wong@fda.hhs.gov; Alex.Krynitsky@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 38-ANYL PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593901436 ER PT J AU Xia, QS Yin, JJ Cherng, SH Freeman, JP Yu, HT Boudreau, MD Wamer, WG Fu, PP AF Xia, Qingsu Yin, Jun Jie Cherng, Shu-Hui Freeman, James P. Yu, Hongtao Boudreau, Mary D. Wamer, Wayne G. Fu, Peter P. TI Irradiation of retinol in ethanol with UVA light: Formation of photodecomposition products, reactive oxygen species, and lipid peroxides SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Xia, Qingsu; Cherng, Shu-Hui; Freeman, James P.; Boudreau, Mary D.; Fu, Peter P.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Yin, Jun Jie; Wamer, Wayne G.] US FDA, CFSAN, College Pk, MD 20740 USA. [Yu, Hongtao] Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. EM qingsu.xia@fda.hhs.gov; junjie.yin@fda.hhs.gov; jfreeman@nctr.fda.gov; mboudreau@fda.hhs.gov; wwamer@fda.hhs.gov; pfu@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 86-TOXI PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593905090 ER PT J AU Yu, LL Cheng, ZH Zhou, HP Yin, JJ AF Yu, Liangli Lucy Cheng, Zhihong Zhou, Huiping Yin, Jun-Jie TI AGFD 229-Effect of wheat antioxidants on oxygen diffusion-concentration products in liposomes and its cholesterol-lowering property SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Yu, Liangli Lucy] Univ Maryland, Dept Food Sci & Nutr, College Pk, MD 20742 USA. [Cheng, Zhihong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Zhou, Huiping] Virginia Commonwealth Univ, Dept Microbiol & Immunol, Sch Med, Richmond, VA 23298 USA. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM lyu5@umd.edu; zcheng@umd.edu; hzhou@vcu.edu; jyin@cfsan.fda.gov RI Yin, Jun Jie /E-5619-2014 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD AUG 19 PY 2007 VL 234 MA 229-AGFD PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V12IW UT WOS:000207593900274 ER PT J AU Shah, RB Zidan, AS Funck, T Tawakkul, MA Nguyenpho, A Khan, MA AF Shah, R. B. Zidan, A. S. Funck, T. Tawakkul, M. A. Nguyenpho, A. Khan, M. A. TI Quality by design: Characterization of self-nano-emulsified drug delivery systems (SNEDDs) using ultrasonic resonator technology SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE self-nano-emulsified drug delivery systems; ultrasonic absorption; ultrasonic velocity; characterization ID LIGHT-SCATTERING; MICROEMULSION SYSTEMS; DROPLET SIZE; EMULSIONS; SPECTROSCOPY; SUSPENSIONS AB In the present work, a novel application of ultrasonic measurements is detailed to characterize nano-emulsion formulations as a part of the overall Quality by Design (QbD) goal. Ultrasonic resonator technology (URT) was utilized to measure sound velocity and absorption of self-nanoemulsified drug delivery systems (SNEDDs) consisting of various ratios of oil:surfactant:co-surfactant. A QbD concept was used to create different SNEDDs formulations utilizing sweet orange oil (oil), Emulphor-620 (surfactant), and Capmul (co-surfactant) by dissolving Cyclosporine A in oil. The mixture was emulsified in water and ultrasonic measurements were carried out in an ultrasonic resonator system isothermally for a period of about 15-20 min. Compressibility of the individual Components in the droplets, hydration of the droplets and the influence of the composition on droplet stability were studied by systematic ultrasonic measurements at a single resonator frequency. The adiabetic compressibilities for the oil, aqueous and interfacial components were 68, 44.6, and 53 [10(-11) Pa-1], respectively as calculated using Urick's equation. Also the ultrasonic absorption correlated droplet size of nano-emulsions linearly with R-2 of 0.84 indicating this can be used as an additional technique to measure the droplet size of nano-emulsions. Correlation of ultrasonic data with formulation components indicated that the ultrasonic velocity correlated negatively with increasing oil amount in the formulation as well as surfactant-to-cosurfactant ratios where as droplet diameter correlated positively with these formulation factors. It can be envisioned from the results that the compressibility of the media increases with the addition of the oily component and thus reducing the sound velocity. Thus URT enabled direct and convenient analysis of the physical properties as well as influence of formulation factors of nano-emulsions which is an important indication of stability of these nano-emulsions. (c) 2007 Published by Elsevier B.V. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off Testing & Res,Div Prod Qual Res, Silver Spring, MD 20993 USA. TF Instruments Inc, Heidelberg, Germany. RP Khan, MA (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off Testing & Res,Div Prod Qual Res, 10903 New Hanshire ave,Life Sci Bldg 64, Silver Spring, MD 20993 USA. EM Mansoor.khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012 NR 20 TC 30 Z9 31 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD AUG 16 PY 2007 VL 341 IS 1-2 BP 189 EP 194 DI 10.1016/j.ijpharm.2007.04.009 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 205TU UT WOS:000249138300022 PM 17521836 ER PT J AU Chang, JT AF Chang, Jennie T. TI Yearly zoledronic acid in postmenopausal osteoporosis SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Silver Spring, MD 20993 USA. RP Chang, JT (reprint author), US FDA, Silver Spring, MD 20993 USA. EM jennie.chang@fda.hhs.gov NR 4 TC 0 Z9 0 U1 1 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 AUG 16 PY 2007 VL 357 IS 7 BP 713 EP 714 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 200EF UT WOS:000248746000019 PM 17703528 ER PT J AU Chen, JJ Lee, T Delongchamp, RR Chen, T Tsai, CA AF Chen, James J. Lee, Taewon Delongchamp, Robert R. Chen, Tao Tsai, Chen-An TI Significance analysis of groups of genes in expression profiling studies SO BIOINFORMATICS LA English DT Article ID MULTIPLE END-POINTS; CLINICAL-TRIALS; ONTOLOGY AB Motivation: Gene class testing (GCT) is a statistical approach to determine whether some functionally predefined classes of genes express differently under two experimental conditions. GCT computes the P-value of each gene class based on the null distribution and the gene classes are ranked for importance in accordance with their P-values. Currently, two null hypotheses have been considered: the Q1 hypothesis tests the relative strength of association with the phenotypes among the gene classes, and the Q2 hypothesis assesses the statistical significance. These two hypotheses are related but not equivalent. Method: We investigate three one-sided and two two-sided test statistics under Q1 and Q2. The null distributions of gene classes under Q1 are generated by permuting gene labels and the null distributions under Q2 are generated by permuting samples. Results: We applied the five statistics to a diabetes dataset with 143 gene classes and to a breast cancer dataset with 508 GO ( Gene Ontology) terms. In each statistic, the null distributions of the gene classes under Q1 are different from those under Q2 in both datasets, and their rankings can be different too. We clarify the one-sided and two-sided hypotheses, and discuss some issues regarding the Q1 and Q2 hypotheses for gene class ranking in the GCT. Because Q1 does not deal with correlations among genes, we prefer test based on Q2. Contact: jchen@nctr.fda.gov Supplementary information: Supplementary data are available at Bioinformatics online. C1 US FDA, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Acad Sinica, Inst Stat Sci, Taipei, Taiwan. China Med Univ, Ctr Biostat, Taichung, Taiwan. RP Chen, JJ (reprint author), US FDA, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov OI Tsai, Chen-An/0000-0002-7490-4331 NR 20 TC 16 Z9 16 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD AUG 15 PY 2007 VL 23 IS 16 BP 2104 EP 2112 DI 10.1093/bioinformatics/btm310 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Computer Science, Interdisciplinary Applications; Mathematical & Computational Biology; Statistics & Probability SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Computer Science; Mathematical & Computational Biology; Mathematics GA 215OG UT WOS:000249818300010 PM 17553853 ER PT J AU Kovalchuk, O Tryndyak, VP Montgomery, B Boyko, A Kutanzi, K Zemp, F Warbritton, AR Latendresse, JR Kovalchuk, I Beland, FA Pogribny, IP AF Kovalchuk, Olga Tryndyak, Volodymyr P. Montgomery, Beverly Boyko, Alex Kutanzi, Kristy Zemp, Franz Warbritton, Alan R. Latendresse, John R. Kovalchuk, Igor Beland, Frederick A. Pogribny, Igor P. TI Estrogen-induced rat breast carcinogenesis is characterized by alterations in DNA methylation, histone modifications and aberrant MicroRNA expression SO CELL CYCLE LA English DT Article DE (17)beta-estradiol; breast carcinogenesis; rat; DNA methylation; histone methylation; microRNA ID HUMAN CANCER-CELLS; GENE-EXPRESSION; GLOBAL DNA; AURORA-A; HYPOMETHYLATION; CHROMATIN; PATTERNS; EPIGENETICS; INSTABILITY; CARCINOMA AB Breast cancer is the most common malignancy in women continuing to rise worldwide. Breast cancer emerges through a multi-step process, encompassing progressive changes from a normal cell to hyperplasia (with and without atypia), carcinoma in situ, invasive carcinoma, and metastasis. In the current study, we analyzed the morphological changes and alterations of DNA methylation, histone methylation and microRNA expression during estradiol-17 beta (E-2)-induced mammary carcinogenesis in female August Copenhagen Irish (ACI) rats. E-2-induced breast carcinogenesis in ACI rats provides a physiologically relevant and genetically defined animal model for studying human sporadic breast cancer. The pattern of morphological changes in mammary glands during E-2-induced carcinogenesis was characterized by transition from normal appearing alveolar and ductular hyperplasia to focal hyperplastic areas of atypical glands and ducts accompanied by a rapid and sustained loss of global DNA methylation, LINE-1 hypomethylation, loss of histone H3 lysine 9 and histone H4 lysine 20 trimethylation, and altered microRNAs expression. More importantly, these alterations in the mammary tissue occurred after six weeks of E-2-treatment, whereas the atypical hyperplasia, which represents a putative precursor lesion to mammary carcinoma in this model, was detected only after twelve weeks of exposure, demonstrating clearly that these events are directly associated with the effects of E-2 and are not a consequence of the preexisting preneoplastic lesions. The results of this study show that deregulation of cellular epigenetic processes plays a crucial role in the mechanism of E-2-induced mammary carcinogenesis in ACI rats, especially in the tumor initiation process. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. RP Kovalchuk, O (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM olga.kovalchuk@uleth.ca; igor.pogribny@fda.hhs.gov RI Latendresse, John/A-9215-2009 NR 50 TC 68 Z9 75 U1 0 U2 7 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD AUG 15 PY 2007 VL 6 IS 16 BP 2010 EP 2018 PG 9 WC Cell Biology SC Cell Biology GA 208LL UT WOS:000249320700010 PM 17700064 ER PT J AU Ahn, H Moon, H Fazzari, MJ Lim, N Chen, JJ Kodell, RL AF Ahn, Hongshik Moon, Hojin Fazzari, Melissa J. Lim, Noha Chen, James J. Kodell, Ralph L. TI Classification by ensembles from random partitions of high-dimensional data SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE class prediction; classification tree; cross validation; logistic regression; majority voting; risk profiling ID GENE-EXPRESSION DATA; ESTROGEN-RECEPTOR; PREDICTION; SELECTION; CANCER; GENOME; TUMOR; MODEL AB A robust classification procedure is developed based on ensembles of classifiers, with each classifier constructed from a different set of predictors determined by a random partition of the entire set of predictors. The proposed methods combine the results of multiple classifiers to achieve a substantially improved prediction compared to the optimal single classifier. This approach is designed specifically for high-dimensional data sets for which a classifier is sought. By combining classifiers built from each subspace of the predictors, the proposed methods achieve a computational advantage in tackling the growing problem of dimensionality. For each subspace of the predictors, we build a classification tree or logistic regression tree. Our study shows, using four real data sets from different areas, that our methods perform consistently well compared to widely used classification methods. For unbalanced data, our approach maintains the balance between sensitivity and specificity more adequately than many other classification methods considered in this study. (C) 2007 Elsevier B.V. All rights reserved. C1 SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. RP Ahn, H (reprint author), SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. EM hahn@ams.sunysb.edu NR 43 TC 34 Z9 35 U1 2 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 EI 1872-7352 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD AUG 15 PY 2007 VL 51 IS 12 BP 6166 EP 6179 DI 10.1016/j.csda.2006.12.043 PG 14 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 208JQ UT WOS:000249316000056 ER PT J AU Tournas, VH Kohn, JS Katsoudas, EJ AF Tournas, V. H. Kohn, J. S. Katsoudas, E. J. TI The identification of antibacterial compounds for the development of enhanced media for the detection of foodborne fungi SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE chloramphenicol; chlortetracycline; gentamicin; bacterial and fungal resistance ID ANTIMICROBIAL SUSCEPTIBILITY AB In an effort to identify a more suitable antibiotic for utilization in mycological media, 12 food home fungal species from various genera including Alternaria alternata, Aspergillus flavus, A. niger, Eurotium chevalieri, Fusarium monoili forme, Penicillium sp., Rhizopus stolonifer, Saccharomyces, cerevisiae, Candida tropicalis, Geotrichum candidum, Rhodotorula glutinis and Kluyveromyces thermotolerans along with 21 chloramphenicol-resistant bacterial isolates from fresh produce and ATCC cultures of Pseudomonas aeruginosa, P fluorescens, E. coli, Pectobacterium carotovorum, Bacillus cereus and Stapkylococcus spp. were tested for their abilities to grow on dichloran rose bengal agar containing various levels of gentamicin, chlortetracycline or chloramphenicol. Results indicated that all fungal isolates except for Rh. glutinis and R. stolonifer grew well on all media tested. Rh. glutinis did not grow on media containing gentamicin whereas R. stolonifer produced very restricted or no growth on these media. All bacterial isolates from fresh produce, P. aeruginosa (ATCC 27853) and P. fluorescens (ATCC BAA-477) grew well at 100, 125 and 150 mg chloramphenicol/liter medium, but they did not grow on media containing chlortetracycline (100, 125, or 150 mg/L) or gentamicin (15, 25, or 35 mg/L). P. aeruginosa (ATCC 10145) grew well on media containing chloramphenicol or gentamicin, but not in the presence of chlortetracycline. P. carotovorum, E. coli, B. cereus and Staphylococcus spp. did not grow on any of the selective media tested. (c) 2007 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, NE Reg Lab, Jamaica, NY 11433 USA. RP Tournas, VH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM valerie.tournas@fda.hhs.gov NR 9 TC 3 Z9 3 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD AUG 15 PY 2007 VL 118 IS 1 BP 83 EP 86 DI 10.1016/j.ijfoodmicro.2007.04.013 PG 4 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 206DF UT WOS:000249163400011 PM 17574697 ER PT J AU Reepmeyer, JC Woodruff, JT AF Reepmeyer, John C. Woodruff, Jeffrey T. TI Use of liquid chromatography-mass spectrometry and a chemical cleavage reaction for the structure elucidation of a new sildenafil analogue detected as an adulterant in an herbal dietary supplement SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE sildenafil analogue; acetildenafil; nor-acetildenafil; erectile dysfunction; phosphodiesterase-5 inhibitor; dietary supplement; liquid chromatography-mass spectrometry (LC-MS) ID SYNTHETIC PHOSPHODIESTERASE-5 INHIBITORS; ERECTILE DYSFUNCTION; DESIGNER DRUG; IDENTIFICATION; VARDENAFIL; TADALAFIL; PRODUCTS; MATRICES; DRINKS AB An herbal dietary supplement, marketed as a natural product for the enhancement of sexual function, was analyzed by HPLC with photodiode array and mass spectral detection and found to contain a compound related to the synthetic phosphodiesterase-5 (PDE-5) inhibitors. Based on UV spectra, mass spectra and direct infusion MSn, the structure of the compound was tentatively identified as a sildenafil analogue in which the sulfonyl group had been replaced with an acetyl group. This new analogue is similar to acetildenafil, a previously reported sildenafil analogue, but differs in that it contains an N-methyl group where acetildenatil contains an N-ethyl group. The structure of the unknown was unequivocally established by chemical cleavage of the phenacylamine group of the molecule to generate N-methylpiperazine; other cleavage products matched those generated from acefildenafil. Since the new compound has one less CH2 group than acetildenafil, it was named nor-acetildenafil. (c) 2007 Elsevier B.V. All rights reserved. C1 US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Reepmeyer, JC (reprint author), US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM john.reepmeyer@fda.hhs.gov NR 16 TC 56 Z9 60 U1 1 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD AUG 15 PY 2007 VL 44 IS 4 BP 887 EP 893 DI 10.1016/j.jpba.2007.04.011 PG 7 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 206KK UT WOS:000249182100008 PM 17532168 ER PT J AU Graham, J Ahn, C Hai, N Buch, BD AF Graham, Jove Ahn, Chul Hai, Nabila Buch, Barbara D. TI Effect of bone density on vertebral strength and stiffness after percutaneous vertebroplasty SO SPINE LA English DT Article DE vertebroplasty; vertebral compression fractures; osteoporosis; bone density ID OSTEOPOROTIC COMPRESSION FRACTURES; VIVO BIOMECHANICAL EVALUATION; MECHANICAL-BEHAVIOR; CEMENT; POLYMETHYLMETHACRYLATE; KYPHOPLASTY; AUGMENTATION; MANAGEMENT; HEIGHT; PAIN AB Study Design. An ex vivo biomechanical study using cadaveric vertebral bodies. Objective. To determine how bone mineral density (BMD) affects mechanical strength and stiffness of the vertebral body after vertebroplasty, and to determine how the association between mechanical properties and BMD varies with amount of cement injected. Summary of Background Data. Adverse events associated with vertebroplasty include cement leakage and adjacent fractures. Understanding effects of bone density and cement volume on mechanical properties may be important clinically to identify the minimum cement volume that will benefit the patient while minimizing risks of adverse events. Methods. The bone mineral density of 13 vertebral columns from adult white female cadavers was measured with DEXA. Vertebral bodies (n = 126) were assigned to 5 groups based on cement treatment: intact, untreated, 4% fill, 12% fill, and 24% fill. Treated specimens were first loaded asymmetrically to simulate a wedge compression fracture before injection with polymethylmethacrylate cement. Strength and stiffness were measured in axial compression. Results. Only the highest cement dose used (24% fill, 7 mL on average) had an effect on mechanical stiffness or strength. Within this group, stiffness was improved relative to untreated fractures but not restored to prefracture levels, and strength was enhanced beyond intact values. These improvements in stiffness and strength depended significantly on bone density, with highly osteoporotic samples benefitting the least. Conclusion. Results suggest that highly osteoporotic patients may receive the least amount of improvement in mechanical properties after vertebroplasty. It is recommended, therefore, that cement volume be restricted to the amount needed for fracture reduction only because there may be a limit to the mechanical benefits that additional cement can offer, depending on patient bone density. Understanding these limitations can potentially minimize risks of adverse events. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Solid & Fluid Mech, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biostat, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Gen Neurol & Restorat Devices, Rockville, MD 20857 USA. George Washington Univ, Dept Biomed Engn, Washington, DC USA. RP Graham, J (reprint author), Geisinger Ctr Hlth Res, 100 N Acad Ave, Danville, PA 17822 USA. EM jhgraham1@geisinger.edu NR 39 TC 19 Z9 23 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0362-2436 J9 SPINE JI SPINE PD AUG 15 PY 2007 VL 32 IS 18 BP E505 EP E511 DI 10.1097/BRS.0b013e318133fc73 PG 7 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 201CT UT WOS:000248809800023 PM 17700430 ER PT J AU Xu, DQ Cisar, JO Osorio, M Wai, TT Kopecko, DJ AF Xu, De Qi Cisar, John O. Osorio, Manuel Wai, Tint T. Kopecko, Dennis J. TI Core-linked LPS expression of Shigella dysenteriae serotype 1 O-antigen in live Salmonella Typhi vaccine vector Ty21a: Preclinical evidence of immunogenicity and protection SO VACCINE LA English DT Article DE bifunctional vaccine; oral vaccine; Typhoid-Shigella vaccine; heterologous LPS expression; Shigella dysenteriae 1; Salmonella Typhi Ty21a; live bacterial vector ID FORM-I ANTIGEN; CHROMOSOMAL GENES; IMMUNE-RESPONSES; BIVALENT VACCINE; LIPOPOLYSACCHARIDE; PLASMID; SHIGELLA-DYSENTERIAE-1; STRAIN; CONSTRUCTION; CLONING AB Shigella dysenteriae serotype 1 (S. dysenteriae 1) causes severe shigellosis that is typically associated with high mortality. Antibodies against Shigella serotype-specific O-polysaccharide (O-Ps) have been shown to be host protective. In this study, the rfb locus and the rfp gene with their cognate promoter regions were PCR-amplified from S. dysenteriae 1, cloned, and sequenced. Deletion analysis showed that eight rfb ORFs plus rfp are necessary for biosynthesis of this O-Ps. A tandemly-linked rfb-rfp gene cassette was cloned into low copy plasmid pGB2 to create pSd1. Avirulent Salmonella enterica serovar Typhi (S. Typhi) Ty21a harboring pSd1 synthesized S. Typhi 9, 12 LPS as well as typical core-linked S. dysenteriae 1 LPS. Animal immunization studies showed that Ty21 a (pSd1) induces protective immunity against high stringency challenge with virulent S. dysentericte 1 strain 1617. These data further demonstrate the utility of S. Typhi Ty21 a as a live, bacterial vaccine delivery system for heterologous O-antigens, supporting the promise of a bifunctional oral vaccine for prevention of shigellosis and typhoid fever. (c) Published by Elsevier Ltd. C1 FDA CBER, Lab Enter & STDs, Bethesda, MD 20892 USA. Natl Inst Dental & Carniofac Res, NIH, Oral Infect & Immun Branch, Bethesda, MD 20892 USA. RP Kopecko, DJ (reprint author), FDA CBER, Lab Enter & STDs, Bldg 29,NIH Campus,HFM440 Rockville Pike, Bethesda, MD 20892 USA. EM dennis.kopecko@fda.hhs.gov FU Intramural NIH HHS NR 45 TC 11 Z9 11 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 14 PY 2007 VL 25 IS 33 BP 6167 EP 6175 DI 10.1016/j.vaccine.2007.06.003 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 202MN UT WOS:000248905900005 PM 17629369 ER PT J AU Wang, CY Wang, SY Yin, JJ Parry, J Yu, LL AF Wang, Chien Y. Wang, Shiow Y. Yin, Jun-Jie Parry, John Yu, Liangli Lucy TI Enhancing antioxidant, antiproliferation, and free radical scavenging activities in strawberries with essential oils SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE strawberries; eugenol; menthol; thymol; antioxidant; antiproliferation ID LUMINESCENCE ASSAY; VOLATILE COMPOUNDS; TABLE GRAPES; CELL-LINES; THYMOL; INHIBITION; EUGENOL; CARVACROL; CAPACITY; EXTRACTS AB Several natural antimicrobial compounds derived from essential oils of plants were investigated for their efficacies in inhibiting decay and extending the shelf life of strawberries (Fragaria x ananassas Duch.). The severity of decay in strawberries stored at 10 degrees C was significantly reduced by treatment with thymol. Treatments with menthol or eugenol also suppressed the fungal growth, but to a lesser extent. All of these three natural antimicrobial compounds extended shelf life of strawberries as compared to the control. Strawberries treated with thymol, menthol, or eugenol also maintained better fruit quality with higher levels of sugars, organic acids, phenolics, anthocyanins, flavonoids, and oxygen radical absorbance capacity than the untreated fruits. The free radical scavenging properties of strawberry fruit were evaluated against 2,2-diphenyl-1-picryhydrazyl (DPPH center dot), hydroxyl (HO center dot), and superoxide radicals (O-2(center dot-)) using electron spin resonance measurements. Higher radical scavenging capacities were found against DPPH center dot and HO center dot in all treated fruit, particularly in berries treated with thymol, compared to those in the control groups. In addition, strawberry extracts were evaluated for their antiproliferative activities using HT-29 colon cancer cells. Extracts from all treated fruit exhibited significantly stronger inhibition on HT-29 cell proliferation than those from the control fruit. These data provide evidence that, in addition to possessing antimicrobial activity, the essential oils also increase free radical scavenging capacity and antiproliferative activity in fruit and, in turn, enhance the resistance of fruit tissues to deterioration and spoilage. C1 US Dept Agr, Prod Qual & Safety Lab, Beltsville, MD 20705 USA. US Dept Agr, Fruit Lab, Beltsville, MD 20705 USA. Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Virginia Polytech Inst & State Univ, Agr Res Stn, Petersburg, VA 23806 USA. RP Wang, CY (reprint author), US Dept Agr, Prod Qual & Safety Lab, Beltsville, MD 20705 USA. EM ChienYi.Wang@ars.usda.gov RI Yin, Jun Jie /E-5619-2014 NR 40 TC 52 Z9 56 U1 0 U2 26 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 AUG 8 PY 2007 VL 55 IS 16 BP 6527 EP 6532 DI 10.1021/jf070429a PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 196JB UT WOS:000248476400018 PM 17636936 ER PT J AU Temple, R AF Temple, Robert TI BiDil for heart failure in black patients SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 US FDA, Silver Spring, MD 20993 USA. RP Temple, R (reprint author), US FDA, Silver Spring, MD 20993 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD AUG 7 PY 2007 VL 147 IS 3 BP 215 EP 216 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 196AV UT WOS:000248454700015 ER PT J AU Powell, RLR Zhao, JQ Konings, FAJ Tang, S Nanfack, A Burda, S Urbanski, MM Saa, DR Hewlett, I Nyambi, PN AF Powell, Rebecca L. R. Zhao, Jiangqin Konings, Frank A. J. Tang, Shixing Nanfack, Aubin Burda, Sherri Urbanski, Mateusz M. Saa, D. R. Hewlett, Indira Nyambi, Phillipe N. TI Identification of a novel circulating recombinant form (CRF) 36_cpx in Cameroon that combines two CRFs (01_AE and 02_AG) with ancestral lineages of subtypes A and G SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; EQUATORIAL RAIN-FORESTS; INJECTING DRUG-USERS; INTERSUBTYPE RECOMBINANT; SEQUENCE ALIGNMENT; GENOME SEQUENCES; RURAL VILLAGES; CENTRAL-AFRICA; HIV-1; CRF02-AG AB An array of CRFs have been identified in Cameroon, the most notable being CRF02_AG. HIV-1 in the East Province of Cameroon is particularly diverse: in a recent study, we found a high proportion of unique recombinant forms (URFs). Herein we describe the analysis of the full-length sequences of two of these URFs, which, after preliminary analysis of gag, pol, and env fragments, appeared to be a novel CRF. This novel strain, CRF36_cpx, contains fragments that can be assigned to the CRF01_AE, CRF02_AG, and subtype A and G radiations. Forty percent of the genome can be classified as CRF02_AG, including regions in gag, pol, env, and the accessory genes. Twenty-seven percent is CRF01_AE, comprising the majority of gag, the beginning of env, and the end of env into the 3' LTR. Twenty percent of the genome can be assigned to subtype A, with segments in pol and env. The remaining 13% of the sequence is classifiable as subtype G, in pol and vpu. The subtype A and G lineages formed by the CRF36_cpx sequences are unique and appear ancestral in nature. CRF36_cpx is both the first to combine more than one CRF and the first to include fragments of CRF02_AG. The ancestral sequences present in CRF36_cpx represent a link to extinct strains, and, potentially, insight into the evolution of HIV-1. C1 NYU, VA Med Ctr, Dept Pathol, Sch Med, New York, NY 10010 USA. NYU, Sch Med, Dept Microbiol, New York, NY 10010 USA. US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. Lab Sante Hyg Mobile, Yaounde, Cameroon. Minist Publ Hlth, Yaounde, Cameroon. Vet Affairs New York Harbor Healthcare Syst, New York, NY USA. RP Nyambi, PN (reprint author), NYU, VA Med Ctr, Dept Pathol, Sch Med, 423 E 23rd St,Room 18124N, New York, NY 10010 USA. EM phillipe.nyambi@med.nuy.edu FU FIC NIH HHS [TW01409, TW01254]; NHLBI NIH HHS [BY1-HB-5026-01]; NIAID NIH HHS [AI027742-17, AI47053] NR 39 TC 24 Z9 25 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD AUG PY 2007 VL 23 IS 8 BP 1008 EP 1019 DI 10.1089/aid.2006.0289 PG 12 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 205VR UT WOS:000249143200008 PM 17725418 ER PT J AU Howell, S Westergaard, G Hoos, B Chavanne, TJ Shoaf, SE Cleveland, A Snoy, PJ Suomi, SJ Higley, JD AF Howell, Sue Westergaard, Greg Hoos, Beth Chavanne, Tara J. Shoaf, Susan E. Cleveland, Allison Snoy, Philip J. Suomi, Stephen J. Higley, J. Dee TI Serotonergic influences on life-history outcomes in free-ranging male rhesus Macaques SO AMERICAN JOURNAL OF PRIMATOLOGY LA English DT Article ID 5-HYDROXYINDOLEACETIC ACID CONCENTRATIONS; CEREBROSPINAL-FLUID MONOAMINE; NONHUMAN PRIMATE MODEL; DIMINISHED SOCIAL COMPETENCE; AMINE METABOLITES; VIOLENT OFFENDERS; FIRE SETTERS; CSF 5-HIAA; INTERINDIVIDUAL DIFFERENCES; HEALTHY-VOLUNTEERS AB Several studies have demonstrated that nonhuman primate males with low cerebrospinal fluid (CSF) levels of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA) exhibit antisocial behavior patterns. Included in these deleterious patterns are impulse control deficits associated with violence and premature death. No studies to date have longitudinally studied the long-term outcome of young subjects with low CSF 5-HIAA concentrations as they mature into adults. In this study we examined longitudinal relations among serotonergic and dopaminergic functioning, as reflected in CSF metabolite concentrations, aggression, age at emigration, dominance rank, and mortality in free-ranging rhesus macaque (Macaca mulatta) males. Our results indicate long-term consistency of individual differences in levels of 5-HIAA in CSF in the subject population from the juvenile period of development through adulthood. We found a significant negative correlation between 5-HIAA concentrations measured in juveniles and rates of high-intensity aggression in the same animals as adults. Further, CSF 5-HIAA concentrations were lower in juveniles that died than in animals that survived. For the young animals that migrated there was a positive correlation between CSF 5-HIAA concentration and age at emigration, whereas for the animals that remained in their troop until later in sexual maturity there was a negative correlation between CSF 5-HIAA concentration and age of emigration. After animals emigrated to a new troop, social dominance rank in the new troop was positively correlated with early family social dominance rank, but inversely correlated with juvenile CSF 5-HIAA concentrations. Taken together, our findings suggest that males with low central serotonin levels early in life delay migration and show high levels of violence and premature death, but the males that survive achieve high rank. These findings indicate that longitudinal measures of serotonergic and dopaminergic functioning are predictive of major life-history outcomes in nonhuman primate males. Low concentrations of CSF 5-HIAA are associated with negative life-history patterns characterized by social instability and excessive aggression, and positive life-history patterns characterized by higher dominance rank. C1 Alpha Genesis Inc, Div Res & Dev, Yemassee, SC USA. NIAAA, Lab Clin & Translat Studies, Sect Study Primate Models Psychopathol, NIH, Poolesville, MD USA. US FDA, Div Vet Sci, Ctr Biol Evaluat & Res, Rockville, MD USA. NICHHD, Comparat Ethol Lab, NIH, Poolesville, MD USA. RP Howell, S (reprint author), Mannheimer Fdn Inc, POB 1235, Clewiston, FL 33440 USA. EM suehowell@bellsouth.net NR 53 TC 30 Z9 31 U1 0 U2 13 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0275-2565 J9 AM J PRIMATOL JI Am. J. Primatol. PD AUG PY 2007 VL 69 IS 8 BP 851 EP 865 DI 10.1002/ajp.20369 PG 15 WC Zoology SC Zoology GA 193LY UT WOS:000248276700002 PM 17330868 ER PT J AU Zhang, Y Xu, W Shen, K Xie, Z Sun, L Lu, Q Liu, C Liang, G Beeler, JA Anderson, LJ AF Zhang, Y. Xu, W. Shen, K. Xie, Z. Sun, L. Lu, Q. Liu, C. Liang, G. Beeler, J. A. Anderson, L. J. TI Genetic variability of group A and B human respiratory syncytial viruses isolated from 3 provinces in China SO ARCHIVES OF VIROLOGY LA English DT Article ID G-PROTEIN GENE; SUBGROUP-A; MOLECULAR EPIDEMIOLOGY; CIRCULATION PATTERNS; G-GLYCOPROTEIN; ATTACHMENT-G; 60 NUCLEOTIDES; DIVERSITY; EVOLUTION; IDENTIFICATION AB The genetic variability of HRSV in China was studied using nucleotide sequencing of the hypervariable C-terminal region of the G protein gene and phylogenetic analysis on 80 isolates obtained from three children's hospitals over a period of three epidemic seasons, 1990/1991, 2000/2001, and 2003/2004. The results showed that 76/80 of these isolates belonged to group A and 4/80 belonged to group B. Phylogenetic analysis revealed that most of the group A isolates were genotype GA2 (74/76 isolates), and the other two isolates were GA3 and GA5. All group B isolates clustered into genotype GB3. There was substantial variation among the GA2 isolates, with nucleotide sequence and amino acid homologies ranging from 88.1-100% and 78.4-100%, respectively, in the hypervariable C-terminal region of the G protein gene. One group B virus, HRSV/Beijing/B/04/11, contained a 60-nucleotide duplication in the C-terminal region of the G protein, which was similar to what has been reported previously for isolates in several countries. This is the first report on the genetic diversity of human respiratory syncytial virus isolated during epidemic periods from children in China. These data provided a preliminary evaluation of patterns of circulation and the genetic diversity of isolates associated with HRSV epidemics within China. C1 Natl Inst Viral Dis, China Ctr Dis Control & Prevent, Beijing, Peoples R China. Childrens Hosp, Beijing, Peoples R China. Childrens Hosp, Changchun, Peoples R China. Ctr Biol Evaluat & Res, FDA, Div Viral Prod, Off Vaccines Res & Review, Bethesda, MD USA. Ctr Dis Control & Prevent, Natl Ctr Immunizat & Resp Dis, Div Viral Dis, Atlanta, GA USA. RP Xu, W (reprint author), 509 Room,27 Nanwei Rd,Xuanwu Dist, Beijing 100050, Peoples R China. EM wenbo_xu1@yahoo.com.cn NR 35 TC 16 Z9 19 U1 0 U2 2 PU SPRINGER WIEN PI WIEN PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 WIEN, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PD AUG PY 2007 VL 152 IS 8 BP 1425 EP 1434 DI 10.1007/s00705-007-0984-3 PG 10 WC Virology SC Virology GA 194WN UT WOS:000248374600001 PM 17510775 ER PT J AU Lute, S Bailey, M Combs, J Sukumar, M Brorson, K AF Lute, Scott Bailey, Mark Combs, Jessica Sukumar, Muppalla Brorson, Kurt TI Phage passage after extended processing in small-virus-retentive filters SO BIOTECHNOLOGY AND APPLIED BIOCHEMISTRY LA English DT Article DE biopharmaceuticals; phage; process validation; viral safety; virus-retentive filters ID ANION-EXCHANGE CHROMATOGRAPHY; MEMBRANE-FILTER; CELL-CULTURE; INACTIVATION; FILTRATION; PLASMA; PHAGE-PHI-X174; CONTAMINATION; PERFORMANCE; CLEARANCE AB Retention of a two small phages (phi X- 174 and pp7) by direct-flow small-virus-retentive filters [Viresolve NFP (normal-flow parvovirus), Virosart CPV (canine parvovirus), Ultipor DV20 and Planova 20N] was studied using a commercial-process fluid. Phage passage occurred in each filter type, particularly when overloaded with phage. Clearances of pp7 and phi X-174 were similar for any given filter brand, arguing that the two phages are equivalent for testing small-virus-retentive filters. The patterns of flux under constant pressure and instantaneous LRV (log reduction value) in relationship to cumulative phage load differed between brands, consistent with the current industry understanding that each brand possesses specific performance attributes. Phages are a powerful and universal tool for evaluating filter performance. Validation of filter performance with phages such as pp7 or phi X- 174 as models for small mammalian viruses represents an attractive alternative to the current practice. C1 US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Div Monoclonal Antibodies, Silver Spring, MD 20993 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Lute, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Div Monoclonal Antibodies, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kurt.brorson@fda.hhs.gov NR 37 TC 37 Z9 37 U1 0 U2 5 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0885-4513 J9 BIOTECHNOL APPL BIOC JI Biotechnol. Appl. Biochem. PD AUG PY 2007 VL 47 BP 141 EP 151 DI 10.1042/BA20060254 PN 3-4 PG 11 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 201NP UT WOS:000248839300001 PM 17286554 ER PT J AU Koturbash, I Boyko, A Rodriguez-Juarez, R McDonald, RJ Tryndyak, VP Kovalchuk, I Pogribny, IP Kovalchuk, O AF Koturbash, Igor Boyko, Alex Rodriguez-Juarez, Rocio McDonald, Robert J. Tryndyak, Volodymyr P. Kovalchuk, Igor Pogribny, Igor P. Kovalchuk, Olga TI Role of epigenetic effectors in maintenance of the long-term persistent bystander effect in spleen in vivo SO CARCINOGENESIS LA English DT Article ID INDUCED GENOMIC INSTABILITY; NOVO DNA METHYLTRANSFERASES; IONIZING-RADIATION; GENE-EXPRESSION; LET RADIATION; METHYLATION; EXPOSURE; CANCER; IRRADIATION; MICRORNAS AB Radiation therapy is a primary treatment modality for brain tumors, yet it has been linked to the increased incidence of secondary, post-radiation therapy cancers. These cancers are thought to be linked to indirect radiation-induced bystander effect. Bystander effect occurs when irradiated cells communicate damage to nearby, non-irradiated 'bystander' cells, ultimately contributing to genome destabilization in the non-exposed cells. Recent evidence suggests that bystander effect may be epigenetic in nature; however, characterization of epigenetic mechanisms involved in bystander effect generation and its long-term persistence has yet to be defined. To investigate the possibility that localized X-ray irradiation induces persistent bystander effects in distant tissue, we monitored the induction of epigenetic changes (i.e. alterations in DNA methylation, histone methylation and microRNA (miRNA) expression) in the rat spleen tissue 24 h and 7 months after localized cranial exposure to 20 Gy of X-rays. We found that localized cranial radiation exposure led to the induction of bystander effect in lead-shielded, distant spleen tissue. Specifically, this exposure caused the profound epigenetic dysregulation in the bystander spleen tissue that manifested as a significant loss of global DNA methylation, alterations in methylation of long interspersed nucleotide element-1 (LINE-1) retrotransposable elements and down-regulation of DNA methyltransferases and methyl-binding protein methyl CpG binding protein 2 (MeCP2). Further, irradiation significantly altered expression of miR-194, a miRNA putatively targeting both DNA methyltransferase-3a and MeCP2. This study is the first to report conclusive evidence of the long-term persistence of bystander effects in radiation carcinogenesis target organ (spleen) upon localized distant exposure using the doses comparable with those used for clinical brain tumor treatments. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Univ Lethbridge, Dept Neurosci, Lethbridge, AB T1K 3M4, Canada. 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 NR 64 TC 100 Z9 109 U1 1 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD AUG PY 2007 VL 28 IS 8 BP 1831 EP 1838 DI 10.1093/carcin/bgm053 PG 8 WC Oncology SC Oncology GA 209DY UT WOS:000249370400032 PM 17347136 ER PT J AU Garcia, AD Meseda, CA Mayer, AE Kumar, A Merchlinsky, M Weir, JP AF Garcia, Alonzo D. Meseda, Clement A. Mayer, Anne E. Kumar, Arunima Merchlinsky, Michael Weir, Jerry P. TI Characterization and use of mammalian-expressed vaccinia virus extracellular membrane proteins for quantification of the humoral immune response to smallpox vaccines SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID 2 INFECTIOUS FORMS; TO-CELL SPREAD; ENVELOPED VIRUS; RESPIRATORY CHALLENGE; NONHUMAN-PRIMATES; LETHAL CHALLENGE; PROTECTS MICE; STRAIN MVA; A33R GENE; VACCINATION AB The licensed smallpox vaccine Dryvax is used as the standard in comparative immunogenicity and protection studies of new smallpox vaccine candidates. Although the correlates of protection against smallpox are unknown, recent studies have shown that a Immoral response against the intracellular mature virion and extracellular enveloped virion (EV) forms of vaccinia virus is crucial for protection. Using a recombinant Semliki Forest virus (rSFV) vector system, we expressed a set of full-length EV proteins for the development of EV antigen-specific enzyme-linked immunosorbent assays (ELISAs) and the production of monospecific antisera. The EV-specific ELISAs were used to evaluate the EV Immoral response elicited by Dryvax and the nonreplicating modified vaccinia virus Ankara (WA) in mouse vaccination experiments comparing doses and routes of vaccination. Quantitatively similar titers of antibodies against EV antigens A33R, A56R, and B5R were measured in mice vaccinated with Dryvax and WA when MVA was administered at a dose of 108 plaque-forming units. Further, a substantial increase in the EV-specific antibody response was induced in mice inoculated with WA by using a prime-boost schedule. Finally, we investigated the abilities of the EV-expressing rSFV vectors to elicit the production of polyclonal monospecific antisera against the corresponding EV proteins in mice. The monospecific serum antibody levels against A33R, A5611, and 13511 were measurably higher than the antibody levels induced by Dryvax. The resulting polyclonal antisera were used in Western blot analysis and immunofluorescence assays, indicating that rSFV particles are useful vectors for generating monospecific antisera. C1 US FDA, Ctr Biol & Evaluat & Res, Div Viral Prod, Rockville, MD 20892 USA. US FDA, Ctr Biol & Evaluat & Res, Div Viral Prod, Lab DNA Viruses, Bethesda, MD 20892 USA. RP Garcia, AD (reprint author), US FDA, Ctr Biol & Evaluat & Res, Div Viral Prod, 1401 Rockville Pike,HRM-457, Rockville, MD 20892 USA. EM alonzo.garcia@fda.hhs.gov NR 63 TC 3 Z9 3 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD AUG PY 2007 VL 14 IS 8 BP 1032 EP 1044 DI 10.1128/CVI.00050-07 PG 13 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 200XM UT WOS:000248796100014 PM 17596428 ER PT J AU Temple, R AF Temple, R. TI Quantitative decision analysis: A work in progress SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Temple, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM robert.temple@fda.hhs.gov NR 4 TC 11 Z9 11 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2007 VL 82 IS 2 BP 127 EP 130 DI 10.1038/sj.clpt.2007.6100239 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 191AJ UT WOS:000248101800004 PM 17632535 ER PT J AU Mathis, LL Iyasu, S AF Mathis, L. L. Iyasu, S. TI Safety monitoring of drugs granted exclusivity under the best pharmaceuticals for children act: What the FDA has learned SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material AB The Best Pharmaceuticals for Children Act (BPCA) was signed into law on 4 January 2002, shortly after the pediatric exclusivity provision of the Food and Drug Administration (FDA) Modernization Act expired on 1 January 2002. This Act provides six months of marketing exclusivity for a drug when a pharmaceutical company studies that drug for use in the pediatric population as requested by the FDA. Section 17 of the BPCA specifically requires that the FDA review all adverse events reported for drugs that receive pediatric exclusivity. In most of the cases, no unexpected adverse events were reported in the pediatric population; however, in some cases, this focused safety review provided information important to the safety of medication use in children. C1 US PHS, Pediat & Maternal Hlth Staff, Off New Drugs, Silver Spring, MD USA. US FDA, CDER, Div Surveillance Res & Commun Support, Off Surveillance & Epidemiol, Silver Spring, MD USA. RP Mathis, LL (reprint author), US PHS, Pediat & Maternal Hlth Staff, Off New Drugs, Silver Spring, MD USA. EM Lisa.Mathis@fda.hhs.gov NR 2 TC 8 Z9 8 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2007 VL 82 IS 2 BP 133 EP 134 DI 10.1038/sj.clpt.2007.6100285 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 191AJ UT WOS:000248101800006 PM 17632537 ER PT J AU Meyer, RJ AF Meyer, R. J. TI Regulatory considerations for determining postmarketing study commitments SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID TRIAL AB Postmarketing Study Commitments (PMCs) are, most commonly, agreements made by pharmaceutical companies at the time of an FDA approval to perform a study or studies to elucidate further characteristics of the drug under consideration. The role of PMCs in drug regulation has come under considerable scrutiny in recent years, particularly as discussions of drug safety have intensified. Although these agreed-upon PMCs are described in FDA regulations, 1 such PMCs are not sought by FDA with every approval, and completion of the agreed-upon studies is not a requirement for the drug's sponsor (there are required PMCs under certain regulatory provisions and these are discussed below). Requests by FDA at the time of regulatory approval for studies under PMCs have been a common practice for many years. When made, PMCs are described in the approval letters and are therefore publicly available. Concerns over whether PMCs were being duly performed, reported, and reviewed by FDA were addressed in the FDA Modernization Act of 1997, which required more detailed reporting by manufacturers on their progress in meeting the PMCs and required FDA to report certain information publicly. C1 US FDA, Off Drug Evaluat 2, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Meyer, RJ (reprint author), US FDA, Off Drug Evaluat 2, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM robert.meyer@fda.hhs.gov NR 2 TC 3 Z9 3 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD AUG PY 2007 VL 82 IS 2 BP 228 EP 230 DI 10.1038/sj.clpt.2007.6100238 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 191AJ UT WOS:000248101800020 PM 17538552 ER PT J AU Pogribny, IP AF Pogribny, I. P. TI Role of MicroRNAs alterations in genotoxic and non-genotoxic rodent hepatocarcinogenesis. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 FDA Natl Ctr Toxicol Res, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 526 EP 526 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500013 ER PT J AU Levy, DD AF Levy, D. D. TI Antimutagenesis data and dietary ingredients. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 528 EP 528 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500019 ER PT J AU Chen, T Mei, N Guo, L AF Chen, T. Mei, N. Guo, L. TI Determination of marker genes for the exposure of aristolochic acid in rat kidney by cross-platform comparison and biological function choice. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 544 EP 544 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500062 ER PT J AU Filkowski, JN Merservey, J Ilnytsky, Y Chekhun, VF Pogribny, IP Kovalchuk, O AF Filkowski, J. N. Merservey, J. Ilnytsky, Y. Chekhun, V. F. Pogribny, I. P. Kovalchuk, O. TI MicroRNAome de-regulation in breast cancer drug resistance. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Univ Lethbridge, Lethbridge, AB T1K 3M4, Canada. Inst Expt Pathol Oncol & Radiobiol, Kiev, Ukraine. NCTR, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 555 EP 555 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500085 ER PT J AU McKinzie, PB Delongchamp, RR Parsons, BL AF McKinzie, P. B. Delongchamp, R. R. Parsons, B. L. TI Accumulation of K-Ras mutation in rat colon after azoxymethane exposure. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Personalized & Nutr Med, Jefferson, AR 72079 USA. NR 0 TC 2 Z9 2 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 587 EP 587 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500153 ER PT J AU Myers, M Bishop, M Hotchkiss, C Lin, CJ Chen, J Mattison, D Morris, S AF Myers, M. Bishop, M. Hotchkiss, C. Lin, C-J Chen, J. Mattison, D. Morris, S. TI Frequency of micronucleated erythrocytes in the peripheral blood of juvenile male rhesus monkeys, Macaca mulatta, determined by flow cytometry. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Natl Ctr Toxicol Res, FDA HHS, Jefferson, AR 72079 USA. NICHD, NIH, HHS, Bethesda, MD USA. Bionetics Corp, Jefferson, AR USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 589 EP 589 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500158 ER PT J AU Mei, N Guo, L Fuscoe, JC Chen, T AF Mei, N. Guo, L. Fuscoe, J. C. Chen, T. TI Mutagenicity and gene expression changes induced by comfrey in rat liver. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 2 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 590 EP 590 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500160 ER PT J AU Meng, F Knapp, G Green, T Ross, J Parsons, B AF Meng, F. Knapp, G. Green, T. Ross, J. Parsons, B. TI ACB-PCR measurement of K-Ras codon 12 mutation in A/J mouse lung exposed to benzo[a]pyrene: A dose-response assessment. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US EPA, Res Triangle Pk, NC 27711 USA. RI Ross, Jeffrey/E-4782-2010 OI Ross, Jeffrey/0000-0002-7002-4548 NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 591 EP 591 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500162 ER PT J AU Miura, D Dobrovolsky, V Mei, N Kasahara, Y Katsuura, Y Heflick, R AF Miura, D. Dobrovolsky, V Mei, N. Kasahara, Y. Katsuura, Y. Heflick, R. TI Development of a method for measuring pig-A gene mutants in rat lymphocytes using selection with proaerolysin. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. TEIJIN Pharma Ltd, Tokyo, Japan. NR 0 TC 1 Z9 1 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 591 EP 591 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500161 ER PT J AU Karakas, B Elespuru, RK Weaver, J Diehl, F Park, BH AF Karakas, B. Elespuru, R. K. Weaver, J. Diehl, F. Park, B. H. TI Detection of mutant tumor cancer biomarkers by BEAMing SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. US FDA, Ctr Drugs, Silver Spring, MD USA. Johns Hopkins Univ, Sidney Kimmel Canc Ctr, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 594 EP 594 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500167 ER PT J AU Kunugita, N Mittelstaedt, RA Von, TLS Beland, FA Heflich, RH AF Kunugita, N. Mittelstaedt, R. A. Von, Tungeln L. S. Beland, F. A. Heflich, R. H. TI Mitochondrial DNA sequence variants in mice treated transplacentally with AZT. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Univ Occupat & Environm Hlth, Kitakyushu, Fukuoka 807, Japan. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 600 EP 600 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500180 ER PT J AU Valentine, CR Rainey, HF Farrell, JM Shaddock, JG Dobrovolsky, VN Delongchamp, RR AF Valentine, C. R. Rainey, H. F. Farrell, J. M. Shaddock, J. G. Dobrovolsky, V. N. Delongchamp, R. R. TI Spontaneous mutation frequencies in spleen in the lacl and Phi X174 transgenic mouse mutation assays. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc ID MICE; AGE C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 605 EP 605 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500192 ER PT J AU Torous, D Bishop, J Fiedler, R Heflich, R Krsmanovic, L MacGregor, J Recio, L Dertinger, S AF Torous, D. Bishop, J. Fiedler, R. Heflich, R. Krsmanovic, L. MacGregor, J. Recio, L. Dertinger, S. TI Recent advances using the CD71 based flow cytometric micronucleus analysis method. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Litron Labs, Rochester, NY USA. Integrated Syst Lab, Res Triangle Pk, NC USA. Toxicol Consulting Serv, Arnold, MD USA. NIEHS, Res Triangle Pk, NC 27709 USA. NCTR, Jefferson, AR USA. Pfizer, Groton, CT USA. BioReliance, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 614 EP 614 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500213 ER PT J AU Petibone, DM Morris, SM Hotchkiss, CE Mattison, DR Tucker, JD AF Petibone, D. M. Morris, S. M. Hotchkiss, C. E. Mattison, D. R. Tucker, J. D. TI Technique for culturing Macaca mulatta peripheral lymphocytes for FISH and classical cytogenetic analyses. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 Wayne State Univ, Detroit, MI 48202 USA. US FDA, Jefferson, AR USA. Bionet Corp, Jefferson, AR USA. US Dept HHS, NIH, Bethesda, MD USA. RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 620 EP 620 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500226 ER PT J AU Fuscoe, JC Han, T Melvin, CD Desai, VG Moland, CL Scully, AT AF Fuscoe, J. C. Han, T. Melvin, C. D. Desai, V. G. Moland, C. L. Scully, A. T. TI Environmental effects on the quality of microarray gene expression measurements. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 627 EP 627 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500242 ER PT J AU Whittaker, P Clarke, J Dunkel, V Jaeger, L Seifiried, H Betz, J San, R AF Whittaker, P. Clarke, J. Dunkel, V Jaeger, L. Seifiried, H. Betz, J. San, R. TI Evaluation of kava extracts and kavalactone standards for mutagenicity and toxicity. SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Meeting Abstract CT 38th Annual Meeting of the Environmental-Mutagen-Society CY OCT 20-24, 2007 CL Atlanta, GA SP Environm Mutagen Soc C1 BioReliance, Rockville, MD USA. US FDA, CFSAN, College Pk, MD USA. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD AUG PY 2007 VL 48 IS 7 BP 627 EP 627 PG 1 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 201XI UT WOS:000248865500243 ER PT J AU Gopee, NV Howard, PC AF Gopee, Neera V. Howard, Paul C. TI A time course study demonstrating RNA stability in postmortem skin SO EXPERIMENTAL AND MOLECULAR PATHOLOGY LA English DT Article DE skin; postmortem; RNA integrity; 28S/18S ribosomal RNA; qRT-PCR ID GENE-EXPRESSION; ROOM-TEMPERATURE; GROWTH-FACTOR; BRAIN-TISSUE; RT-PCR; DNA; DEGRADATION; QUANTITATION; EXTRACTION; STORAGE AB Knowledge of the factors regulating the rate of mRNA degradation, including postmortem delay, is important in determining the reliability of gene expression patterns in dermal tissue. Since RNA stability can be tissue dependent, this study evaluates the effect of postmortem interval on the integrity of total RNA or the levels of representative mRNA species in murine cutaneous tissue. Pieces of fresh skin tissue were excised for periods of 0-60 min from SKH-1 female hairless mice that were maintained at room temperature post-sacrifice. Total RNA was subsequently isolated and RNA integrity from each specimen was evaluated. Bioanalyzer profiles showed no apparent change in 28S/18S rRNA ratio or RNA integrity number at time points up to 60 min. Changes in mRNA expression levels of five selected genes were determined by real-time quantitative PCR. There were no statistical differences in the relative gene expressions of Ccnd1, Hif1 alpha, cMyc and Cyr61 as a function of postmortem interval. Our data suggest that the molecular quality of cutaneous tissue is well preserved for at least 60 min after death, which can be regarded as important information for consideration of the order for tissue procurement in in vivo studies and acute ex vivo dermal studies. (c) 2006 Published by Elsevier Inc. C1 US FDA, Dept Hlth & Human Serv, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Dept Hlth & Human Serv, Natl Toxicol Program, Ctr Phototoxicol,Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Howard, PC (reprint author), US FDA, Dept Hlth & Human Serv, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd,HFT-110, Jefferson, AR 72079 USA. EM Paul.Howard@fda.hhs.gov NR 38 TC 6 Z9 8 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 0014-4800 J9 EXP MOL PATHOL JI Exp. Mol. Pathol. PD AUG PY 2007 VL 83 IS 1 BP 4 EP 10 DI 10.1016/j.yexamp.2006.11.001 PG 7 WC Pathology SC Pathology GA 185ND UT WOS:000247716800002 PM 17174950 ER PT J AU Wolffe, M Landry, RJ Alpar, JJ AF Wolffe, M. Landry, R. J. Alpar, J. J. TI Identification of the source of permanent glare form a three-piece IOL SO EYE LA English DT Article DE haptic-glare; line glare image; diffuse glare image; three-piece intraocular lenses ID LENSES REQUIRING EXPLANTATION; INTRAOCULAR-LENS; SECONDARY INTERVENTION; DESIGN; COMPLICATIONS; DYSPHOTOPSIA; SHARP AB Objective To identify the source of unwanted glare images from a three-piece intraocular lens (IOL) implant following cataract surgery. Method The IOL and posterior capsule were examined under mydriatic and nonmydriatic conditions using direct focal illumination from a slit lamp biomicroscope. Direct focal illumination was undertaken with both a narrow beam (0.1 mm in width) and small spot (0.1 mm in diameter) to identify the points at which the glare images were stimulated. While observing the location of the beam with the slit lamp biomicroscope, the patient indicated when the glare images were stimulated. Results The nasal haptic insertion into the optic was identified as the source of temporal line images arising from lights such as headlamps from oncoming cars and street lamps. The adjacent edge of the IOL was also identified as the likely source of additional cob web-like light rays. Conclusions The haptic insertions in three-piece IOLs may, under certain conditions, interfere with light entering the pupil and produce extraneous images. Large mesopic pupils and decentred IOLs are conditions that increase the likelihood of unwanted glare images. C1 Ctr Devices & Radiol Hlth, FDA, Div Phys, HFZ 13, Rockville, MD 20850 USA. St Luke Eye Inst, Amarillo, TX USA. RP Landry, RJ (reprint author), Ctr Devices & Radiol Hlth, FDA, Div Phys, HFZ 13, 9200 Corp Blvd, Rockville, MD 20850 USA. EM robert.landry@fda.hhs.gov NR 17 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD AUG PY 2007 VL 21 IS 8 BP 1078 EP 1082 DI 10.1038/sj.eye.6702539 PG 5 WC Ophthalmology SC Ophthalmology GA 199DB UT WOS:000248675300011 PM 16936648 ER PT J AU Landry, RJ Ilev, IK Pfefer, TJ Wolffe, M Alpar, JJ AF Landry, R. J. Ilev, I. K. Pfefer, T. J. Wolffe, M. Alpar, J. J. TI Characterizing reflections from intraocular lens implants SO EYE LA English DT Article DE IOL glare test method; IOL haptic glare; IOL Line glare image; IOL diffuse glare image AB Objective To develop a test method for characterizing glare from intraocular lenses (IOLs) and to confirm a clinical finding that the haptic insertion in the optic of a three-piece IOL produces extraneous line images. Method The method consists of directing a collimated Gaussian laser beam to various parts of the IOL to be tested in a water-filled model eye. Reflected images produced in the retinal plane are photographed with a digital camera. Results A test method was developed to characterize the source of glare images from IOLs. The test method developed was used to confirm a clinical finding that the haptic insertion in the optic of a three-piece IOL produces extraneous line images. Conclusions The method developed can be used to characterize and pin point the source of extraneous glare images from intraocular lens implants. The haptic insertion in the optic of a three-piece IOL has been identified as a source of line images. C1 Ctr Devices & Radiol Hlth, FDA, Div Phys, HFZ 130, Rockville, MD 20850 USA. St Luke Eye Inst, Amarillo, TX USA. RP Landry, RJ (reprint author), Ctr Devices & Radiol Hlth, FDA, Div Phys, HFZ 130, 9200 Corp Blvd, Rockville, MD 20850 USA. EM robert.landry@fda.hhs.gov RI Pfefer, Josh/I-9055-2012 NR 5 TC 3 Z9 8 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD AUG PY 2007 VL 21 IS 8 BP 1083 EP 1086 DI 10.1038/sj.eye.6702540 PG 4 WC Ophthalmology SC Ophthalmology GA 199DB UT WOS:000248675300012 PM 16936647 ER PT J AU Khan, AA Melvin, CD Dagdag, EB AF Khan, Ashraf A. Melvin, Cathy D. Dagdag, Elsie B. TI Identification and molecular characterization of Salmonella spp. from unpasteurized orange juices and identification of new serotype Salmonella strain S-enterica serovar Tempe SO FOOD MICROBIOLOGY LA English DT Article DE Salmonella enterica serovar Muenchen; Salmonella enterica serovar Tempe; orange juice; pulsed-field gel electrophoresis; Polymerase Chain Reaction ID FIELD GEL-ELECTROPHORESIS; FRAGMENT LENGTH POLYMORPHISM; ESCHERICHIA-COLI O157-H7; TYPHIMURIUM DT104; OUTBREAK; PRODUCTS; POULTRY; DNA AB Several Salmonella enterica serotypes were isolated from unpasteurized orange juice samples analysed as a follow-up to an outbreak in 1999 of S. enterica serotype Muenchen in the Pacific Northwest regions of United States. Eleven S. enterica strains were serotyped and identified as S. enterica serotype Muenchen (2), S. enterica serotype Hidalgo (2), S. enterica serotype Alamo (1), S. enterica serotype Gaminera (2), S. enterica serotype Javiana (2) and a new serotyped strain S. enterica serotype Tempe (2). The identity of the new serotype S. enterica serovar Tempe serotype 30:b:1,7:z33 was confirmed by the National Salmonella Reference Laboratory at NCID/CDC, Atlanta. These strains were sensitive to ampicillin, chloramphenicol, kanamycin, tetracycline, streptomycin and sulfisoxazole antibiotics. Isolates were screened for invasion (invA) and virulence (spvC) genes using specific primers for these two genes by polymerase chain reaction. All strains were positive for invA gene giving 321-bp fragment, however negative to virulence spvC gene. For pulsed-field gel electrophoresis (PFGE) analysis, Salmonella strain plugs were made and digested with XbaI and subjected to 18-h electrophoresis. The PFGE patterns were different for each S. enterica serotypes suggesting the several origins of contamination in outbreak. S. enterica serotype. (C) 2006 Elsevier Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, ORA, Arkansas Reg Lab, Jefferson, AR 72079 USA. US FDA, Pacific Reg Lab SW, Los Angeles, CA USA. RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM Ashraf.khan@fda.hhs.gov NR 19 TC 16 Z9 24 U1 0 U2 4 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 AUG PY 2007 VL 24 IS 5 BP 539 EP 543 DI 10.1016/j.fm.2006.09.002 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 171TQ UT WOS:000246758700012 PM 17367687 ER PT J AU Singh, UP Singh, S Singh, R Karls, RK Quinn, FD Potter, ME Lillard, JW AF Singh, Udai P. Singh, Shailesh Singh, Rajesh Karls, Russell K. Quinn, Frederick D. Potter, Morris E. Lillard, James W., Jr. TI Influence of Mycobacterium avium subsp paratuberculosis on colitis development and specific immune responses during disease SO INFECTION AND IMMUNITY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INFLAMMATORY BOWEL-DISEASE; CROHNS-DISEASE; T-CELLS; CYTOKINE PRODUCTION; FACTOR-ALPHA; ANTIGEN; MICE; INTERLEUKIN-12; TUBERCULOSIS AB The granulomatous and intramural inflammation observed in cases of inflammatory bowel diseases (IBD) and veterinary Johne's disease suggests that Mycobacterium avium subsp. paratuberculosis is a causative agent. However, an incomplete understanding of the immunological steps responsible for the pathologies of IBD makes this conclusion uncertain. Sera from interleukin-10-deficient (IL-10(-/-)) mice with spontaneous colitis displayed significantly higherM. avium subsp.paratuberculosis-specific immunoglobulin G2a antibody responses than did sera from similar mice without disease. Pathogen-free IL-10(-/-) mice received control vehicle or the vehicle containing heat-killed or live M. avium subsp. paratuberculosis. Mucosal CD4(+) T cells from the mice that developed colitis proliferated and secreted higher levels of gamma interferon and tumor necrosis factor alpha after ex vivo stimulation with a V beta 11(+) T-cell receptor-restricted peptide from the MPT59 antigen (Ag85B) than those secreted from cells from mice before the onset of colitis. The data from this study provide important information regarding the mechanisms of colitis in IL-10(-/-) mice, which are driven in part by Ag85B-specific T cells. The data suggest a plausible mechanism of Ag-specific T-cell responses in colitis driven by potent Ags conserved in Mycobacterium species. C1 Univ Louisville, Brown Canc Ctr, Dept Microbiol & Immunol, Louisville, KY 40202 USA. Morehouse Sch Med, Dept Microbiol Biochem & Immunol, Atlanta, GA 30310 USA. Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA USA. US FDA, Ctr Food Safety & Appl Nutr, Atlanta, GA USA. RP Lillard, JW (reprint author), Univ Louisville, Brown Canc Ctr, Dept Microbiol & Immunol, 580 S Preston St,Baxter 2 Room 304 C, Louisville, KY 40202 USA. EM james.lillard@louisville.edu FU NCRR NIH HHS [G12 RR003034, RR 03034]; NIAID NIH HHS [AI 57808, R01 AI057808]; NIGMS NIH HHS [GM 08248, S06 GM008248]; NIMHD NIH HHS [P60 MD000525, MD 000525] NR 33 TC 14 Z9 16 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2007 VL 75 IS 8 BP 3722 EP 3728 DI 10.1128/W.01770-06 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 194PB UT WOS:000248355200006 PM 17502388 ER PT J AU Tait, AS Dalton, M Geny, B D'Agnillo, F Popoff, MR Sternberg, EM AF Tait, A. Sasha Dalton, Monique Geny, Blandine D'Agnillo, Felice Popoff, Michel R. Sternberg, Esther M. TI The large clostridial toxins from Clostridium sordellii and C-difficile repress glucocorticoid receptor activity SO INFECTION AND IMMUNITY LA English DT Article ID ACTIVATED PROTEIN-KINASE; PITUITARY-ADRENAL AXIS; ANTHRAX LETHAL FACTOR; DIPHTHERIA TOXIN; SHOCK-SYNDROME; P38 MAPK; CELLS; PHOSPHORYLATION; SUSCEPTIBILITY; BACTERIAL AB We have previously shown that Bacillus anthracis lethal toxin represses glucocorticoid receptor (GR) transactivation. We now report that repression of GR activity also occurs with the large clostridial toxins produced by Clostridium sordellii and C.difficile. This was demonstrated using a transient transfection assay system for GR transactivation. We also report that C sordellii lethal toxin inhibited GR function in an ex vivo assay, where toxin reduced the dexamethasone suppression of the proinflammatory cytokine tumor necrosis factor alpha (TNF-alpha). Furthermore, the glucocorticoid antagonist RU-486 in combination with C. sordellii lethal toxin additively prevented glucocorticoid suppression of TNF-alpha. These findings corroborate the fact that GR is a target for the toxin and suggest a physiological role for toxin-associated GR repression in inflammation. Finally, we show that this repression is associated with toxins that inactivate p38 mitogen-activated protein kinase (MAPK). C1 NIMH, Natl Inst Hlth, Sect Neuroendocrine Immunol & Behav, Rockville, MD 20852 USA. Inst Pasteur, Unite Bacteries Anaerobes & Toxines, Paris, France. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20892 USA. RP Sternberg, EM (reprint author), NIMH, Natl Inst Hlth, Sect Neuroendocrine Immunol & Behav, 5625 Fishers Lane MSC 9401, Rockville, MD 20852 USA. EM sternbee@mail.nih.gov FU Intramural NIH HHS NR 27 TC 8 Z9 8 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2007 VL 75 IS 8 BP 3935 EP 3940 DI 10.1128/IAI.00291-07 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 194PB UT WOS:000248355200028 PM 17517870 ER PT J AU Cole, LE Shirey, KA Barry, E Santiago, A Rallabhandi, P Elkins, KL Puche, AC Michalek, SM Vogel, SN AF Cole, Leah E. Shirey, Kari Ann Barry, Eileen Santiago, Araceli Rallabhandi, Prasad Elkins, Karen L. Puche, Adam C. Michalek, Suzanne M. Vogel, Stefanie N. TI Toll-like receptor 2-mediated signaling requirements for Francisella tularensis live vaccine strain infection of murine macrophages SO INFECTION AND IMMUNITY LA English DT Article ID INNATE IMMUNE-RESPONSE; KAPPA-B ACTIVATION; GENE-EXPRESSION; BACTERIAL LIPOPOLYSACCHARIDE; INTRACELLULAR BACTERIUM; CHLAMYDIA-TRACHOMATIS; PROTECTIVE IMMUNITY; CYTOKINE EXPRESSION; ENDOTHELIAL-CELLS; TULAREMIA VACCINE AB Francisella tularensis, an aerobic, non-spore-forming, gram-negative coccobacillus, is the causative agent of tularemia. We reported previously that F. tularensis live vaccine strain (LVS) elicited strong, dose-dependent NF-kappa B reporter activity in Toll-like receptor 2 (TLR2) -expressing HEK293T cells and proinflammatory gene expression in primary murine macrophages. Herein, we report that F. tularensis LVS-induced murine macrophage proinflammatory cytokine gene and protein expression are overwhelmingly TLR2 dependent, as evidenced by the abrogated responses of TLR2(-/-) macrophages. F. tularensis LVS infection also increased expression of TLR2 both in vitro, in mouse macrophages, and in vivo, in livers from F. tularensis LVS-infected mice. Colocalization of intracellular F. tularensis LVS, TLR2, and MyD88 was visualized by confocal microscopy. Signaling was abrogated if the F. tularensis LVS organisms were heat or formalin killed or treated with chloramphenicol, indicating that the TLR2 agonist activity is dependent on new bacterial protein synthesis. F. tularensis LVS replicates in macrophages; however, bacterial replication was not required for TLR2 signaling because LVS Delta guaA, an F. tularensis LVS guanine auxotroph that fails to replicate in the absence of exogenous guanine, activated NF-kappa B in TLR2-transfected HEK293T cells and induced cytokine expression in wild-type macrophages comparably to wild-type F. tularensis LVS. Collectively, these data indicate that the primary macrophage response to F. tularensis LVS is overwhelmingly TLR2 dependent, requires de novo bacterial protein synthesis, and is independent of intracellular F. tularensis replication. C1 Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. US FDA, CBER, Div Bacterial Allergen & Parasit Prod, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20852 USA. RP Vogel, SN (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, 660 W Redwood St,Room324, Baltimore, MD 21201 USA. EM svogel@som.umaryland.edu FU NIAID NIH HHS [AI 56460, U01 AI056460, U54 AI 057168, U54 AI057168]; NIDCD NIH HHS [DC 05739, R03 DC005739]; NIDCR NIH HHS [DE 09081, R01 DE009081] NR 61 TC 81 Z9 83 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD AUG PY 2007 VL 75 IS 8 BP 4127 EP 4137 DI 10.1128/IAI.01868-06 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 194PB UT WOS:000248355200049 PM 17517865 ER PT J AU Zaidi, MB Leon, V Canche, C Perez, C Zhao, S Hubert, SK Abbott, J Blickenstaff, K McDermott, PF AF Zaidi, Mussaret B. Leon, Veronica Canche, Claudia Perez, Carolina Zhao, Shaohua Hubert, Susannah K. Abbott, Jason Blickenstaff, Karen McDermott, Patrick F. TI Rapid and widespread dissemination of multidrug-resistant bla(CMY-2) Salmonella Typhimurium in Mexico SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article; Proceedings Paper CT 107th General Meeting of the American-Society-for-Microbiology CY 2007 CL Toronto, CANADA SP Amer Soc Microbiol DE swine; humans; PFGE; mortality; developing countries ID SPECTRUM CEPHALOSPORINS; NONTYPHOIDAL SALMONELLA; ESCHERICHIA-COLI; BETA-LACTAMASE; INFECTIONS; ANIMALS; CMY-2 AB Objectives: We describe the emergence and dissemination of multidrug-resistant (MDR) Salmonella Typhimurium in humans, retail meat and food animals from Yucatan, Mexico. Methods: Salmonella Typhimurium isolates were collected through an active surveillance system and tested for susceptibility to 12 antimicrobial agents. Isolates that were non-susceptible to ceftriaxone were tested with 10 additional antimicrobials and assayed by PCR for the presence of CMY, CTX-M, SHV, TEM and OXA beta-lactamase genes. Plasmid-borne phenotypes were identified by transfer to susceptible Escherichia coli. Isolates from humans, retail meat and food animals were compared by PFGE to determine genetic relatedness. Results: MDR Salmonella Typhimurium containing a plasmid-mediated bla(CMY-2) AmpC P-lactamase rose from 0% (0/27) during 2000 and 2001 to 75% (63/84) in 2004 and 2005 (P < 0.0001). MDR bla(CMY-2) Salmonella Typhimurium (n = 115) was most common in ill children (44.3%) and pork or swine intestine (36.5%). In several cities, MDR bla(CMY-2) Salmonella Typhimurium from retail meat or swine intestine exhibited PFGE patterns and antibiograms indistinguishable from those in strains recovered from hospitalized children. The CMY gene was transferred to E. coli by electroporation, along with resistance to three to six other antimicrobials. Children with MDR bla(CMY-2) Salmonella Typhimurium infection (n = 39) had a higher frequency of systemic infection (13% versus 0%), mortality (8% versus 0%) and hospital re-admission due to protracted diarrhoea (28% versus 17%) than children with non-MDR-Salmonella Typhimurium (n = 24), although the difference was not statistically significant. Conclusions: The rapid and widespread dissemination of MDR bla(CMY-2) Salmonella Typhimurium in Mexico calls for urgent interventions to contain this potentially fatal pathogen. C1 Hosp Gen Ohoran, Lab Invest, Dept Invest, Merida 97000, Yucatan, Mexico. Ctr Vet Med Food Drug Adm, Laurel, MD USA. RP Zaidi, MB (reprint author), Hosp Gen Ohoran, Lab Invest, Dept Invest, Av Itzaes x Jacinto Canek, Merida 97000, Yucatan, Mexico. EM mbzaidi@prodigy.net.mx FU FDA HHS [FD-U-001934] NR 10 TC 38 Z9 39 U1 2 U2 5 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 AUG PY 2007 VL 60 IS 2 BP 398 EP 401 DI 10.1093/jac/dkm168 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 203PM UT WOS:000248986500027 PM 17526503 ER PT J AU Hinchey, J Lee, S Jeon, BY Basaraba, RJ Venkataswamy, MM Chen, B Chan, J Braunstein, M Orme, IM Derrick, SC Morris, SL Jacobs, WR Porcelli, SA AF Hinchey, Joseph Lee, Sunhee Jeon, Bo Y. Basaraba, Randall J. Venkataswamy, Manjunatha M. Chen, Bing Chan, John Braunstein, Miriam Orme, Ian M. Derrick, Steven C. Morris, Sheldon L. Jacobs, William R., Jr. Porcelli, Steven A. TI Enhanced priming of adaptive immunity by a proapoptotic mutant of Mycobacterium tuberculosis SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID CD8 T-CELLS; BACILLUS-CALMETTE-GUERIN; SUPEROXIDE-DISMUTASE; PATHOGENIC MYCOBACTERIA; PANTOTHENATE AUXOTROPH; ANTIMICROBIAL ACTIVITY; MACROPHAGE APOPTOSIS; DNA VACCINE; INFECTION; EXPRESSION AB The inhibition of apoptosis of infected host cells is a well-known but poorly understood function of pathogenic mycobacteria. We show that inactivation of the secA2 gene in Mycobacterium tuberculosis, which encodes a component of a virulence-associated protein secretion system, enhanced the apoptosis of infected macrophages by diminishing secretion of mycobacterial superoxide dismutase. Deletion of secA2 markedly increased priming of antigen-specific CD8(+) T cells in vivo, and vaccination of mice and guinea pigs with a secA2 mutant significantly increased resistance to M. tuberculosis challenge compared with standard M. bovis bacille Calmette-Guerin vaccination. Our results define a mechanism for a key immune evasion strategy of M. tuberculosis and provide what we believe to be a novel approach for improving mycobacterial vaccines. C1 Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10461 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Colorado State Univ, Dept Microbiol Immunol & Pathol, Ft Collins, CO 80523 USA. Albert Einstein Coll Med, Dept Med, New York, NY USA. Univ N Carolina, Dept Microbiol, Chapel Hill, NC USA. RP Jacobs, WR (reprint author), Yeshiva Univ Albert Einstein Coll Med, Howard Hughes Med Inst, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jacobs@aecom.yu.edu; porcelli@aecom.yu.edu FU NCI NIH HHS [CA 13330, P30 CA013330]; NIAID NIH HHS [AI54540, AI 051519, AI054697, AI063537, HHSN266200400091C, P01 AI063537, P30 AI051519, R01 AI054540, R01 AI054697]; PHS HHS [HHSN266200400091C] NR 47 TC 184 Z9 192 U1 0 U2 5 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD AUG PY 2007 VL 117 IS 8 BP 2279 EP 2288 DI 10.1172/JCI31947 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 196JS UT WOS:000248478100036 PM 17671656 ER PT J AU Honma, S Chizhikov, V Santos, N Tatsumi, M Timenetsky, MDCST Linhares, AC Mascarenhas, JDP Ushijima, H Armah, GE Gentsch, JR Hoshino, Y AF Honma, Shinjiro Chizhikov, Vladimir Santos, Norma Tatsumi, Masatoshi Timenetsky, Maria do Carmo S. T. Linhares, Alexandre C. Mascarenhas, Joana D'Arc P. Ushijima, Hiroshi Armah, George E. Gentsch, Jon R. Hoshino, Yasutaka TI Development and validation of DNA microarray for genotyping group A rotavirus VP4 (P[4], P[6], P[8], P[9], and p[14]) and VP7 (G1 to G6, G8 to G10, and G12) genes SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; OLIGONUCLEOTIDE-MICROARRAY; MONOCLONAL-ANTIBODIES; VACCINE DEVELOPMENT; STRAINS BEARING; P-GENOTYPE; IDENTIFICATION; VIRUS; DIVERSITY; SEROTYPES AB Previously, we reported the development of a microarray-based method for the identification of five clinically relevant G genotypes (G1 to G4 and G9) (V. Chizhikov et al., J. Clin. Microbiol. 40:2398-2407, 2002). The expanded version of the rotavirus microarray assay presented herein is capable of identifying (I) five clinically relevant human rotavirus VP4 genotypes (P[4], P[61, P[8], P[9], and P[14]) and (ii) five additional human rotavirus VP7 genotypes (G5, G6, G8, G10, and G12) on one chip. Initially, a total of 80 cell culture-adapted human and animal reference rotavirus strains of known P (P[1] to P[12], P[14], P[16], and P[20]) and G (G1-6, G8 to G12, and G14) genotypes isolated in various parts of the world were employed to evaluate the new microarray assay. All rotavirus strains bearing P[4], P[6], P[8], P[9], or P[14] and/or G1 to G6, G8 to GIO, or G12 specificity were identified correctly. In addition, cross-reactivity to viruses of genotype G11, G13, or G14 or P[1] to P[3], P[5], P[7], P[10] to P[12], P[16], or P[20] was not observed. Next, we analyzed a total of 128 rotavirus-positive human stool samples collected in three countries (Brazil, Ghana, and the United States) by this assay and validated its usefulness. The results of this study showed that the assay was sensitive and specific and capable of unambiguously discriminating mixed rotavirus infections from nonspecific cross-reactivity; the inability to discriminate mixed infections from nonspecific cross-reactivity is one of the inherent shortcomings of traditional multiplex reverse transcription-PCR genotyping. Moreover, because the hybridization patterns exhibited by rotavirus strains of different genotypes can vary, this method may be ideal for analyzing the genetic polymorphisms of the VP7 or VP4 genes of rotaviruses. C1 NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Method Dev, Rockville, MD USA. Univ Fed Rio de Janeiro, Inst Microbiol, BR-21941 Rio De Janeiro, Brazil. Ins Adolf Lutz, Sao Paulo, Brazil. Secretaria Vigilancia Saude, Inst Evandro Chagas, Belem, Para, Brazil. Univ Tokyo, Tokyo, Japan. Univ Ghana, Legon, Ghana. Ctr Dis Control & Prevent, Gastroenteritis Resp Viruses Lab Branch, Atlanta, GA USA. RP Hoshino, Y (reprint author), NIAID, Epidemiol Sect, Infect Dis Lab, NIH, Bldg 50,Room 6308,50 S Dr,MSC 8026, Bethesda, MD 20892 USA. EM thoshino@niaid.nih.gov RI TIMENETSKY, MARIA/I-7593-2013; Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 FU Intramural NIH HHS NR 60 TC 20 Z9 24 U1 0 U2 2 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 AUG PY 2007 VL 45 IS 8 BP 2641 EP 2648 DI 10.1128/JCM.00736-07 PG 8 WC Microbiology SC Microbiology GA 200WK UT WOS:000248793300041 PM 17567783 ER PT J AU Fritsche, TR McDermott, PF Shryock, TR Walker, RD AF Fritsche, Thomas R. McDermott, Patrick F. Shryock, Thomas R. Walker, Robert D. TI Agar dilution and disk diffusion susceptibility testing of Campylobacter spp. SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Letter ID QUALITY-CONTROL RANGES C1 JMI Labs, Beaver Kreek Ctr 345, N Liberty, IA 52317 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Elanco Anim Hlth, Greenfield, IN 46140 USA. Mesa State Coll, Grand Junction, CO 81501 USA. RP Fritsche, TR (reprint author), JMI Labs, Beaver Kreek Ctr 345, Suite A, N Liberty, IA 52317 USA. NR 10 TC 31 Z9 32 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 AUG PY 2007 VL 45 IS 8 BP 2758 EP 2759 DI 10.1128/JCM.00569-07 PG 2 WC Microbiology SC Microbiology GA 200WK UT WOS:000248793300071 PM 17675457 ER PT J AU Mahabir, S Abnet, CC Qiao, YL Ratnasinghe, LD Dawsey, SM Dong, ZW Taylor, PR Mark, SD AF Mahabir, Somdat Abnet, Christian C. Qiao, You-Lin Ratnasinghe, Luke D. Dawsey, Sanford M. Dong, Zhi-Wei Taylor, Philip R. Mark, Steven D. TI A prospective study of polymorphisms of DNA repair genes XRCC1, XPD23 and APE/ref-1 and risk of stroke in Linxian, China SO JOURNAL OF EPIDEMIOLOGY AND COMMUNITY HEALTH LA English DT Article ID VITAMIN MINERAL SUPPLEMENTATION; NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; GASTRIC CARDIA CANCER; CEREBRAL-ISCHEMIA; ESOPHAGEAL CANCER; DYSPLASIA TRIAL; HOMOCYSTEINE; COHORT; DETERMINANTS AB Background: Stroke is the leading cause of death in Linxian, China. Although there is evidence of DNA damage in experimental stroke, no data exist on DNA repair and stroke in human populations. Aim: To assess the risk of stroke conferred by polymorphisms in the DNA repair genes, XRCC1, XPD23 and APE/ref-1 in a cohort of individuals originally assembled as subjects in two cancer prevention trials in Linxian, China. Methods: The subjects for this prospective study were sampled from a cohort of 4005 eligible subjects who were alive and cancer free in 1991 and had blood samples available for DNA extraction. Using real-time Taqman analyses, all incident cases of stroke (n = 118) that developed from May 1996, and an age-and a sex-stratified random sample (n = 454) drawn from all eligible subjects were genotyped. Cox proportional hazards models were used to estimate relative risks (RRs) and 95% CIs. Results: No association was observed between polymorphisms in APE/ref-1 codon 148 and XRCC1*6 codon 194, and stroke. Polymorphisms in XRCC1*10 codon 399 were associated with a significantly reduced risk of stroke (RR 0.59, 95% CI 0.36 to 0.96, p = 0.033), whereas XPD23 codon 312 was associated with a significantly increased risk of stroke (RR 2.18, 95% CI 1.14 to 4.17, p = 0.010). Conclusions: Polymorphisms in DNA repair genes may be important in the aetiology of stroke. These data should stimulate research on DNA damage and repair in stroke. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. Chinese Acad Med Sci, Dept Epidemiol, Inst Canc, Beijing 100037, Peoples R China. UAMS, NCTR, Ctr Struct Genom, Jefferson & Arkansas Canc Res Ctr, Little Rock, AR USA. NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Bethesda, MD 20892 USA. RP Mahabir, S (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, CPB4,3247,Unit 1340,1155 Pressler Blvd, Houston, TX 77030 USA. EM smahabir@mdanderson.org RI Mahabir, Somdat/A-9788-2008; Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 37 TC 9 Z9 10 U1 0 U2 2 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0143-005X J9 J EPIDEMIOL COMMUN H JI J. Epidemiol. Community Health PD AUG PY 2007 VL 61 IS 8 BP 737 EP 741 DI 10.1136/jech.2006.048934 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 190CT UT WOS:000248036300016 PM 17630376 ER PT J AU Moss, WJ Scott, S Mugala, N Ndhlovu, Z Beeler, JA Audet, SA Ngala, M Mwangala, S Nkonga-Mwangilwa, C Ryon, JJ Monze, M Kasolo, F Quinn, TC Cousens, S Griffin, DE Cutts, FT AF Moss, William J. Scott, Susana Mugala, Nanthalile Ndhlovu, Zaza Beeler, Judy A. Audet, Susette A. Ngala, Mirriam Mwangala, Sheila Nkonga-Mwangilwa, Chansa Ryon, Judith J. Monze, Mwaka Kasolo, Francis Quinn, Thomas C. Cousens, Simon Griffin, Diane E. Cutts, Felicity T. TI Immunogenicity of standard-titer measles vaccine in HIV-1-infected and uninfected Zambian children: An observational study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTED CHILDREN; ANTIBODY; IMMUNIZATION; ERADICATION AB Background. Achieving the level of population immunity required for measles elimination may be difficult in regions of high human immunodeficiency virus type 1 (HIV-1) prevalence, because HIV-1- infected children may be less likely to respond to or maintain protective antibody levels after vaccination. Methods. We conducted a prospective study of the immunogenicity of standard- titer measles vaccine administered at 9 months of age to HIV-1- infected and uninfected children in Lusaka, Zambia. Results. From May 2000 to November 2002, 696 children aged 2-8 months were enrolled. Within 6 months of vaccination, 88% of 50 HIV-1- infected children developed antibody levels of >= 120 mIU/ mL, compared with 94% of 98 HIV-seronegative children and 94% of 211 HIV- seropositive but uninfected children (P = .3). By 27 Pp. 3 months after vaccination, however, only half of the 18 HIV- 1 - infected children who survived and returned for follow- up maintained measles antibody levels >= 120 mIU/ mL, compared with 89% of 71 uninfected children (P =.001) and in contrast with 92% of 12 HIV-1- infected children revaccinated during a supplemental measles Pp. 001 immunization activity. Conclusions. Although HIV-1- infected children showed good primary antibody responses to measles vaccine, their rapid waning of antibody suggests that measles vaccination campaigns may need to be repeated more frequently in areas of high HIV-1 prevalence. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. Johns Hopkins Univ, W Harry Feinstone Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Div Infect Dis, Baltimore, MD 21205 USA. NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. London Sch Hyg & Trop Med, London WC1, England. Univ Teaching Hosp, Virol Lab, Lusaka, Zambia. RP Moss, WJ (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. EM wmoss@jhsph.edu FU NIAID NIH HHS [AI23047]; Wellcome Trust [gr059114ma] NR 21 TC 47 Z9 48 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD AUG 1 PY 2007 VL 196 IS 3 BP 347 EP 355 DI 10.1086/519169 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 186UH UT WOS:000247803300004 PM 17597448 ER PT J AU Donnelly, RP Sheikh, F Dickensheets, H Gao, B AF Donnelly, Raymond P. Sheikh, Faruk Dickensheets, Harold Gao, Bin TI Interferon-lambda (IFN-lambda) is a potent inducer of type IIFN-stimulated genes in primary hepatocytes SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 CDER, FDA, Div Therapeut Proteins, Bethesda, MD USA. NIH, NIAAA, Lab Physiol Studies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 702 EP 702 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500050 ER PT J AU Baron, S Poast, J Suzuki, F Kobayashi, M Clouse, K Bacot, S Tiffany, L Lankford, C Boekhoudt, G Morrow, A Nie, H Schmeisser, H Hernandez, J Bekisz, J Goldman, N Zoon, K AF Baron, S. Poast, J. Suzuki, F. Kobayashi, M. Clouse, K. Bacot, S. Tiffany, L. Lankford, C. Boekhoudt, G. Morrow, A. Nie, H. Schmeisser, H. Hernandez, J. Bekisz, J. Goldman, N. Zoon, K. TI Innate immunity: Preclinical study of conditions required for eradication of tumor cells by activated monocytes in vitro and in vivo SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 Univ Texas, Med Branch, Dept Microbiol & Immunol & Internal Med, Galveston, TX 77550 USA. US FDA, Bethesda, MD 20014 USA. NIAID, NIH, Bethesda, 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 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 709 EP 709 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500075 ER PT J AU Maheshwari, RK Sharma, A Bhattacharya, B Puri, RK AF Maheshwari, Radha K. Sharma, Anuj Bhattacharya, Bhaskar Puri, Raj K. TI Microarray analysis of gene expression in Venezuelan equine encephalitis virus infection SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. Birla Inst Technol & Sci, Pilani, Rajasthan, India. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 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 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 723 EP 723 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500126 ER PT J AU Pedras-Vasconcelos, JA Puig, M Sauder, C Verthelyi, D AF Pedras-Vasconcelos, Joao A. Puig, Montserrat Sauder, Christian Verthelyi, Daniela TI Virus-host interactions in the CNS [or the pros and cons of eliciting TNFA and IFNA in the brain] SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Meeting Abstract C1 US FDA, Lab Immunol, Div Therapeut Prot, CDER, Bethesda, MD 20014 USA. US FDA, Lab Methods Dev, CBER, Bethesda, MD 20014 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 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD AUG PY 2007 VL 27 IS 8 BP 736 EP 736 PG 1 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 206UN UT WOS:000249208500177 ER PT J AU Sahu, SC Gaines, DW Williams, KM Raybourne, RB AF Sahu, Saura C. Gaines, Dennis W. Williams, Kristina M. Raybourne, Richard B. TI A synthetic polypeptide based on human E-cadherin inhibits invasion of human intestinal and liver cell lines by Listeria monocytogenes SO JOURNAL OF MEDICAL MICROBIOLOGY LA English DT Article ID EPITHELIAL-CELLS; SURFACE PROTEIN; INTERNALIN; ENTRY; EXPRESSION; INLB; HEPATOCYTES; SPECIFICITY; RECEPTOR; MODEL AB Internalin A is a surface protein of the facultative intracellular pathogen Listeria monocytogenes that interacts with the human host cell protein E-cadherin to facilitate invasion of epithelial cells. A single amino acid substitution at position 16 in mouse E-cadherin prevents this interaction. Synthetic polypeptides of 30 aa encompassing position 16 of human and mouse E-cadherin were tested for their ability to inhibit in vitro invasion of Caco-2, HepG2 and TIB73 cell lines by L. monocytogenes. Only the human-derived peptide was capable of inhibiting invasion in the human-origin Caco-2 and HepG2 cell lines. These findings demonstrate that small polypeptides can inhibit invasion of biologically relevant cell types by L. monocytogenes in vitro and may be potentially useful as therapeutic agents in vivo. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Immunol Branch, Laurel, MD 20708 USA. RP Raybourne, RB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Immunol Branch, Laurel, MD 20708 USA. EM richard.raybourne@fda.hhs.gov NR 20 TC 7 Z9 8 U1 0 U2 0 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 AUG PY 2007 VL 56 IS 8 BP 1011 EP 1016 DI 10.1099/jmm.0.47194-0 PG 6 WC Microbiology SC Microbiology GA 201HE UT WOS:000248821300002 PM 17644706 ER PT J AU Galvin, T Khan, AS AF Galvin, Teresa Khan, Arifa S. TI Contribution of internal promoter to simian foamy virus fitness SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 US FDA, CBER, Lab Retrovirus Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 59 BP 309 EP 309 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700073 ER PT J AU Khan, AS Skinner-Harris, B Williams, DK AF Khan, Arifa S. Skinner-Harris, Brianna Williams, Dhanya K. TI Role of neutralizing antibodies in simian foamy virus infection SO JOURNAL OF MEDICAL PRIMATOLOGY LA English DT Meeting Abstract C1 US FDA, CBER, Lab Retrovirus Res, Bethesda, MD 20892 USA. US FDA, CBER, Div Vet Serv, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0047-2565 J9 J MED PRIMATOL JI J. Med. Primatol. PD AUG PY 2007 VL 36 IS 4-5 MA 92 BP 322 EP 322 PG 1 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 196LJ UT WOS:000248482700106 ER PT J AU Ali, S Li, H Campbell, A Bondy, S AF Ali, S. Li, H. Campbell, A. Bondy, S. TI Chronic exposure to low levels of aluminum alters the response of cerebral transcription factors to acute MPTP-treatment in mice SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract CT 21st Biennial Meeting of the International-Society-for-Neurochemistry/38th Annual Meeting of the American-Society-for-Neurochemistry CY AUG 19-24, 2007 CL Cancun, MEXICO SP Int Sco Neurochem, Amer Soc Neurochem C1 NCTR FDA, Neurochem Lab, Div Neurotoxicol, Jefferson, AR USA. Univ Calif Irvine, Dept Community & Environm Med, Irvine, CA 92717 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD AUG PY 2007 VL 102 SU 1 BP 136 EP 136 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 203RL UT WOS:000248991600328 ER PT J AU Rubin, SA Amexis, G Pletnikov, M Vanderzanden, J Mauldin, J Sauder, C Malik, T Chumakov, K Carbone, KM AF Rubin, Steven A. Amexis, Georgios Pletnikov, Mikhail Vanderzanden, Jacqueline Mauldin, Jeremy Sauder, Christian Malik, Tahir Chumakov, Konstantin Carbone, Kathryn M. TI Changes in mumps virus gene sequence associated with variability in neurovirulent phenotype (vol 77, pg 11616, 2003) SO JOURNAL OF VIROLOGY LA English DT Correction C1 Food & Drug Admn, Ctr biol & Evaluat & Res, Off Vaccines Res & Review, DVP, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Psychiat Med, Baltimore, MD 21205 USA. RP Rubin, SA (reprint author), Food & Drug Admn, Ctr biol & Evaluat & Res, Off Vaccines Res & Review, DVP, Bethesda, MD 20892 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD AUG PY 2007 VL 81 IS 16 BP 8849 EP 8849 DI 10.1128/JVI.01303-07 PG 1 WC Virology SC Virology GA 198SZ UT WOS:000248649100051 ER PT J AU Monday, SR Beisaw, A Feng, PCH AF Monday, S. R. Beisaw, A. Feng, P. C. H. TI Identification of Shiga toxigenic Escherichia coli seropathotypes A and B by multiplex PCR SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE multiplex PCR; enterohemorrhagic E. coli; seropathotypes ID HEMOLYTIC-UREMIC-SYNDROME; VIRULENCE FACTORS; ASSOCIATION; STRAINS; DISEASE; GENES AB A multiplex PCR assay was developed to identify the six clinically important enterohemorrhagic Escherichia coli (EHEC) serotypes classified in seropathotypes A and B and to differentiate these from Shiga toxigenic E coli. The assay simultaneously detects genes for Shiga toxin (stx) and intimin (eae), including allelic variants of both genes, 16S internal amplification control, as well as unique sequences in the wzx genes that are specific for serotypes O157, O26 O1 11, O103, O121 and O145. PCR analysis of 40 representative strains showed that the assay correctly identified the virulence genes, if present, and the respective O antigen type of all the strains, including some atypical EHEC, as well as enteropathogenic E coli and E coli strains examined. Published by Elsevier Ltd. C1 US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. RP Feng, PCH (reprint author), US FDA, Div Microbiol Studies, College Pk, MD 20740 USA. EM peter.feng@fda.hhs.gov NR 13 TC 38 Z9 40 U1 0 U2 3 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 AUG PY 2007 VL 21 IS 4 BP 308 EP 311 DI 10.1016/j.mcp.2007.02.002 PG 4 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 176QG UT WOS:000247099400009 PM 17383154 ER PT J AU King, KE Weinberg, WC AF King, Kathryn E. Weinberg, Wendy C. TI p63: Defining roles in morphogenesis, homeostasis, and neoplasia of the epidermis SO MOLECULAR CARCINOGENESIS LA English DT Article DE p63; epidermis; keratinocyte growth regulation; p53 homologues; squamous neoplasia ID SQUAMOUS-CELL CARCINOMA; BETA-CATENIN; P53 HOMOLOG; DNA-DAMAGE; P53-DEPENDENT APOPTOSIS; NUCLEAR ACCUMULATION; HUMAN KERATINOCYTES; DOWN-REGULATION; UP-REGULATION; HUMAN CANCER AB p63 is a member of a gene family also including the p53 tumor suppressor and p73. In contrast to p53, p63 is rarely mutated in human cancers. Rather, gene amplification and dysregulated expression of p63 protein have been observed, particularly in squamous cell carcinomas. p63 is essential for development of stratified squamous epithelium, including the epidermis. The p63 gene is expressed as multiple protein isoforms with different functional capacities, and the balance of these isoforms, along with the presence or absence of the other family members, p53 and p73, can impact biological outcome. Both gene silencing and overexpression approaches have been utilized to elucidate the contributions of specific p63 isoforms to normal epidermal morphogenesis and tissue maintenance. While numerous studies have established the essential nature of p63 in the epidermis, the basis of this requirement, and the unique, as well as, overlapping functions of the individual isoforms, remain controversial. In this review, we summarize the current understanding of roles played by specific p63 isoforms within the context of epidermal morphogenesis and homeostasis of the established epidermis, and the potential impact of p63 dysregulation on cancer development. (c) 2007 Wiley-Liss, Inc. C1 FDA Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, Bethesda, MD 20892 USA. RP Weinberg, WC (reprint author), FDA Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, HFD-123,29 Lincoln Dr,Bldg 4E04, Bethesda, MD 20892 USA. RI Weinberg, Wendy/A-8920-2009 NR 74 TC 28 Z9 28 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD AUG PY 2007 VL 46 IS 8 BP 716 EP 724 DI 10.1002/mc.20337 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 198YJ UT WOS:000248663100024 PM 17477357 ER PT J AU Volokhov, DV Neverov, AA George, J Kong, H Liu, SX Anderson, C Davidson, MK Chizhikov, V AF Volokhov, Dmitriy V. Neverov, Alexander A. George, Joseph Kong, Hyesuk Liu, Sue X. Anderson, Christine Davidson, Maureen K. Chizhikov, Vladimir TI Genetic analysis of housekeeping genes of members of the genus Acholeplasma: Phylogeny and complementary molecular markers to the 16S rRNA gene SO MOLECULAR PHYLOGENETICS AND EVOLUTION LA English DT Article DE Mollicutes; rpoB and gyrB genes; Mycoplasmas ID SEQUENCE DATA; SP-NOV; MOLLICUTES MYCOPLASMAS; COMPARATIVE METABOLISM; SPACER REGION; CLASSIFICATION; IDENTIFICATION; EVOLUTION; BACTERIA; DNA AB The partial nucleotide sequences of the rpoB and gyrB genes as well as the complete sequence of the 16S-23S rRNA intergenic transcribed spacer (ITS) were determined for all known Acholeplasma species. The same genes of Mesoplasma and Entomoplasma species were also sequenced and used to infer phylogenetic relationships among the species within the orders Entomoplasmatales and Acholeplasmatales. The comparison of the ITS, rpoB, and gyrB phylogenetic trees with the 16S rRNA phylogenctic tree revealed a similar branch topology suggesting that the ITS, rpoB, and gyrB could be useful complementary phylogenetic markers for investigation of evolutionary relationships among Acholeplasma species. Thus, the multilocus phylogenetic analysis of Acholeplasma multilocale sequence data (ATCC 49900 (T) = PN525 (NCTC 11723)) strongly indicated that this organism is most closely related to the genera Mesoplasma and Entomoplasma (family Entomoplasmataceae) and form the branch with Mesoplasma seiffertii, Mesoplasma syrphidae, and Mesoplasma) ia photuris. The closest genetic relatedness of this species to the order Entomoplasmatales was additionally supported by the finding that A. multilocale uses UGA as the tryptophan codon in its gyrB and gyrA sequences. Use of the UGA codon for encoding tryptophan was previously reported as a unique genetic feature of Entomoplasmatales and Mycoplasmatales but not of Acholeplasmatales. These data, as well as previously published data on metabolic features of A. multilocale, leads to the proposal to reclassify A. multilocale as a member of the family Entomplasmataceae. (c) 2006 Elsevier Inc. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Purdue Univ, Sch Vet Med, Dept Vet Pathobiol, W Lafayette, IN 47907 USA. RP Volokhov, DV (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM 470, Rockville, MD 20852 USA. EM dmitriy.volokhov@fda.hhs.gov NR 55 TC 18 Z9 20 U1 1 U2 8 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1055-7903 J9 MOL PHYLOGENET EVOL JI Mol. Phylogenet. Evol. PD AUG PY 2007 VL 44 IS 2 BP 699 EP 710 DI 10.1016/j.ympev.2006.12.001 PG 12 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 201UX UT WOS:000248859200014 PM 17267242 ER PT J AU Knudsen, JF Flowers, CM Kortepeter, C Awaad, Y AF Knudsen, James F. Flowers, Charlene M. Kortepeter, Cindy Awaad, Yasser TI Clinical profile of oxcarbazepine-related angioneurotic edema: Case report and review SO PEDIATRIC NEUROLOGY LA English DT Article ID INHIBITOR-INDUCED ANGIOEDEMA; ANGIOTENSIN; EXPERIENCE; MANAGEMENT AB Oxcarbazepine, a carbamazepine analog, was approved for use as an antiepileptic agent in the United States in 2000. A search of the United States Food and Drug Administration's Adverse Event Reporting System identified nine cases of oxcarbazepine-associated angioedema in pediatric patients aged 16 years and younger. We describe in detail the first U.S. case report, of a 41/2-year-old boy who experienced angioedema during treatment with oxcarbazepine. The reporting rate for angioedema was calculated to be 9.8 cases per 1,000,000 pediatric patients. Oxcarbazepine-associated angioedema manifested by swelling of the face, eyes, lips, or tongue or difficulty swallowing or breathing (or both) is a rare but potentially life-threatening reaction for which early recognition and management are vital. (c) 2007 by Elsevier Inc. All rights reserved. C1 US FDA, Off Drug Evaluat 1, Div Neurol Prod, Silver Spring, MD 20993 USA. US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. Oakwood Healthcare Syst, Pediat Neurol & Movement Disorders Program, Dearborn, MI USA. RP Knudsen, JF (reprint author), US FDA, Off Drug Evaluat 1, Div Neurol Prod, 10903 New Hampshire Ave,Bldg 22 Room 4336, Silver Spring, MD 20993 USA. EM james.knudsen@fda.hhs.gov NR 14 TC 7 Z9 9 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0887-8994 J9 PEDIATR NEUROL JI Pediatr. Neurol. PD AUG PY 2007 VL 37 IS 2 BP 134 EP 137 DI 10.1016/j.pediatrneurol.2007.03.010 PG 4 WC Clinical Neurology; Pediatrics SC Neurosciences & Neurology; Pediatrics GA 200YC UT WOS:000248797700010 PM 17675030 ER PT J AU Kaplan, S Staffa, JA Dal Pan, GJ AF Kaplan, Sigal Staffa, Judy A. Dal Pan, Gerald J. TI Duration of therapy with metoclopramide: a prescription claims data study SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article; Proceedings Paper CT 2nd North American Congress of Epidemiology CY JUN 21-24, 2006 CL Seattle, WA DE metoclopramide; prescription claims; episode of therapy; therapy duration; cumulative exposure; labeled recommendations ID INDUCED MOVEMENT-DISORDERS; TARDIVE-DYSKINESIA AB Purpose Metoclopramide-induced tardive dyskinesia is associated with cumulative drug exposure, which can result from prolonged use of the drug. We estimated therapy duration with metoclopramide, and measured the extent of therapy beyond the maximum time period of 12 weeks evaluated in the clinical trials and recommended in the label. Methods Prescription claims for metoclopramide from 2002 to 2004 were extracted for participants residing throughout the US and contained within the Caremark pharmacy benefit manager (PBM) database. An episode of therapy was defined as one or a series of consecutive claims with no more than a 30-day lag between the dispensing date of a new claim and the ending date of the preceding claim. Episode duration was calculated by subtracting the start date from the end date for each episode. Results During the study period, almost 80% of participants (total= 200907) had only one episode of therapy. The length of the longest episode for most patients (85%) varied from I to 90 days, yet 15% of the patients appeared to have received prescriptions for metoclopramide for a period longer than 90 days. Cumulative therapy for longer than 90 days was recorded for almost 20% of the patients. Conclusions These results suggest that despite the known risk of tardive dyskinesia and the labeled recommendations on duration of metoclopramide use, many patients appear to use the drug for relatively long time periods beyond the labeled recommendations. Physicians should carefully consider the risk-benefit profile of the drug and, if possible, avoid increased risk of tardive dyskinesia due to prolonged exposure. Published in 2007 by John Wiley & Sons, Ltd. C1 US FDA, Div Surveillance Res & Commun Support, Off Surveillance & Epidemiol, CDER, Silver Spring, MD 20993 USA. RP Kaplan, S (reprint author), US FDA, Div Surveillance Res & Commun Support, Off Surveillance & Epidemiol, CDER, 10903 New Hampshire Ave,BLDG 22,Mail Stop 4447, Silver Spring, MD 20993 USA. EM sigal.kaplan@fda.hhs.gov NR 9 TC 10 Z9 10 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 IS 8 BP 878 EP 881 DI 10.1002/pds.1397 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 200QA UT WOS:000248776700008 PM 17436356 ER PT J AU Ahmad, SR Swann, J AF Ahmad, Syed R. Swann, Joslyn TI Exenatide-associated acute pancreatitis SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, CDER, Off Surveillanc & Epidemiol, Div Drug Risk Evaluat, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 450 BP S213 EP S214 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200448 ER PT J AU Burwen, DR Ball, R Bryan, WW Izurieta, HS Voie, L Gibbs, N Kliman, R Braun, MM AF Burwen, Dale R. Ball, Robert Bryan, Wilson W. Izurieta, Hector S. La Voie, Lawrence Gibbs, Neville Kliman, Rebecca Braun, M. Miles TI Evaluation of occurrence of Guillain-Barre syndrome among recipients of influenza vaccine in 2000 and 2001 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Ctr Medicare, Baltimore, MD USA. Ctr Medicaid Sci, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 130 BP S62 EP S63 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200131 ER PT J AU Duggirala, HJ Yang, XH Van Manen, RP AF Duggirala, Hesha J. Yang, Xionghu Van Manen, Robbert P. TI Can disproportionality analysis play a role in monitoring medical device safety? SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Phase Forward, Lincoln Technol Drug Safety Div, Waltham, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 058 BP S28 EP S29 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200059 ER PT J AU Graham, DJ Singh, G Wang, H Mannalithara, A Lingala, V Mithal, A Triadafilopoulos, G AF Graham, David J. Singh, Gurkirpal Wang, H. Mannalithara, A. Lingala, V. Mithal, Alka Triadafilopoulos, George TI Risk of stroke in arthritis patients treated with cox-2 selective and non-selective NSAIDs SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. Stanford Univ, Sch Med, Dept Gastroenterol, Palo Alto, CA 94304 USA. ISPORE, Dept Outcomes Res, Palo Alto, CA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 139 BP S67 EP S67 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200140 ER PT J AU Haber, P Izurieta, H Patel, M Baggs, J Umesh, P AF Haber, Penina Izurieta, Hector Patel, Manish Baggs, James Umesh, Parashar TI Intussusception reports following RotaTeq (TM) vaccination: Vaccine adverse event reporting system (VAERS), 3/2006-02/2007 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 CDC, ISO, Atlanta, GA 30333 USA. US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 128 BP S61 EP S62 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200129 ER PT J AU Hammad, TA Kaplan, S Graham, DJ Staffa, JA Kornegay, CJ McCune, S Aly, H AF Hammad, Tarek A. Kaplan, Sigal Graham, David J. Staffa, Judy A. Kornegay, Cynthia J. McCune, Susan Aly, Hany TI Association between antidepressant drugs and persistent pulmonary hypertension in newborns in the UK-based general practice research database: A cohort study of mother-baby linked pairs SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. US FDA, Off Counterterrorism & Emergency Coordinat, Silver Spring, MD USA. George Washington Univ, Div Newborn Serv, Washington, DC 20052 USA. RI Research Datalink, Clinical Practice/H-2477-2013 NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 338 BP S160 EP S161 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200338 ER PT J AU McAdams, M Staffa, J Gerald, DP AF McAdams, Mara Staffa, Judy Gerald, Dal Pan TI Evaluation of a risk management plan to minimize concomitant use of ethinyl estradiol/dropirenone and potentially interacting drugs SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 378 BP S179 EP S180 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200378 ER PT J AU McAdams, M Staffa, J Dal Pan, G AF McAdams, Mara Staffa, Judy Dal Pan, Gerald TI Estimating the extent of adverse event reporting to the US food and drug administration: A case-study of the statin-associated rhabdomyolysis data SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 146 BP S70 EP S70 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200147 ER PT J AU McMahon, A Haber, P Belongia, E Pfeifer, D Caubel, P Shay, D Davis, R Braun, M AF McMahon, Ann Haber, Penina Belongia, Edward Pfeifer, Dina Caubel, Patrick Shay, David Davis, Robert Braun, Miles TI Tools for monitoring the safety and effectiveness of influenza vaccines during an influenza pandemic SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Div Epidemiol, Rockville, MD 20857 USA. Ctr Dis Control & Prevent, Immunizat Safety Off, Atlanta, GA USA. Marshfield Clin Res Fdn, Epidemiol Res Ctr, Marshfield, WI USA. WHO, CH-1211 Geneva, Switzerland. Sanofi Pasteur, Pharmacovigilance N Amer, Swiftwater, PA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 158 BP S76 EP S76 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200159 ER PT J AU Menis, M Burwen, DR O'Connell, K Anderson, SA AF Menis, Mikhail Burwen, Dale R. O'Connell, Kathryn Anderson, Steven A. TI Blood use by inpatient elderly population in the United States SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 Ctr Biol Evaluat & Res, Off Biostat Epidemiol, US FDA, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 433 BP S205 EP S205 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200431 ER PT J AU Mosholder, AD Pamer, C Kaplan, S Hammad, TA Willy, M AF Mosholder, Andrew D. Pamer, Carol Kaplan, Sigal Hammad, Tarek A. Willy, Mary TI Trends in US prescriptions for antidepressants in children, adolescents and young adults SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Off Surveillan & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 BP S128 EP S128 PG 1 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200269 ER PT J AU O'Connell, K Lindsey, K Wise, R AF O'Connell, Kathryn Lindsey, Kimberly Wise, Robert TI Biologic fibrin sealant safety surveillance SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Epidemiol, Rockville, MD USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 417 BP S198 EP + PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200417 ER PT J AU Willy, M Ahmad, SR Chang, YJ Nourjah, P Lee, L Avigan, MI AF Willy, Mary Ahmad, Syed R. Chang, Yoo Jung Nourjah, Parivash Lee, Lauren Avigan, Mark I. TI Recent trends in acetaminophen-associated overdoses in the United States, 2003 to 2005 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Meeting Abstract C1 FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD AUG PY 2007 VL 16 SU 2 MA 372 BP S176 EP S177 PG 2 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 201GT UT WOS:000248820200372 ER PT J AU Brennan, MJ Fruth, U Milstien, J Tiernan, R Nishioka, SDA Chocarro, L AF Brennan, Michael J. Fruth, Uli Milstien, Julie Tiernan, Rosemary Nishioka, Sergio de Andrade Chocarro, Liliana CA Developing Countries Vaccine Regul Ad Hoc Regulatory TB Expert Panel TI Development of new tuberculosis vaccines: A global perspective on regulatory issues SO PLOS MEDICINE LA English DT Editorial Material ID MYCOBACTERIUM-TUBERCULOSIS; CLINICAL-TRIALS; TB VACCINES; STRATEGIES; PROTEIN; PROTECTION; IMMUNITY; ESAT-6 C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Rockville, MD 20857 USA. WHO, Initiat Vaccine Res, CH-1211 Geneva, Switzerland. Univ Maryland, Sch Med, Dept Geograph Med, Montpellier, France. US FDA, Ctr Biol Evaluat & Res, Div Vaccines & Related Prod Applicat, Rockville, MD USA. Natl Hlth Surveillance Agcy ANVISA, Ctr Surveillance Adverse Events & Qual Deviat, Brasilia, DF, Brazil. WHO, CH-1211 Geneva, Switzerland. RP Brennan, MJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Rockville, MD 20857 USA. EM Michael.Brennan@fda.hhs.gov NR 19 TC 34 Z9 34 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1549-1277 J9 PLOS MED JI PLos Med. PD AUG PY 2007 VL 4 IS 8 BP 1299 EP 1302 AR e252 DI 10.1371/journal.pmed.0040252 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 205IT UT WOS:000249107900005 PM 17683198 ER PT J AU Piper, JT Gelderman, MP Vostal, JG AF Piper, John T. Gelderman, Monique P. Vostal, Jaroslau G. TI In vivo recovery of human platelets in severe combined immunodeficient mice as a measure of platelet damage SO TRANSFUSION LA English DT Article ID FLOW-CYTOMETRY; RABBIT MODEL; SURVIVAL; TRANSFUSION; VIABILITY; EFFICACY; QUALITY; STORAGE; FRESH AB BACKGROUND: Clinical performance of human platelet (PLT) products processed or stored under novel conditions is difficult to predict based on in vitro studies alone. Recovery and survival of radiolabeled PLTs in human subjects are used as surrogate markers for PLT efficacy in development of new products. Such experiments pose some risk to the participants, can be a financial burden on the sponsor, and may stifle innovation and development of new PLT products. Animal models for in vivo recovery and survival of human PLTs are limited by rapid, immune-mediated clearance of human cells. The severe combined immunodeficient (SCID) mice allowed prolonged circulation of human PLTs and were used to detect differences in recovery and survival between chemically damaged, aged PLTs, or normal PLTs. STUDY DESIGN AND METHODS: Human PLTs were transfused into SCID and wild-type (WT) mice, and the recoveries and survival times were detected in mouse whole blood by flow cytometry with an anti-human CD41-fluorescein isothiocyanate monoclonal antibody. Recoveries of damaged PLTs were compared to normal PLTS. RESULTS: Recoveries were significantly shorter in WT than in SCID mice at 4 hours after transfusion (WT, 20.8 +/- 5.4%, n = 12; SCID, 63.8 +/- 8.4%, n = 10) and with a t(1/2) estimate of 2 hours for WT and 7 hours for SCID mice. Human PLTs damaged either by chemical treatment or by improper storage exhibited decreased recoveries in SCID mice. CONCLUSION: The SCID mouse model can detect differences between damaged and control human PLTs and could be useful in evaluating novel PLT collection, processing, and storage technologies that may impact PLT quality. C1 US FDA, Lab Cellular Hematol, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Vostal, JG (reprint author), US FDA, Lab Cellular Hematol, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-335, Rockville, MD 20852 USA. EM vostal@cber.fda.gov NR 16 TC 15 Z9 17 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD AUG PY 2007 VL 47 IS 8 BP 1540 EP 1549 DI 10.1111/j.1537-2995.2007.01295.x PG 10 WC Hematology SC Hematology GA 197FN UT WOS:000248540100028 PM 17655600 ER PT J AU Kohl, KS Gidudu, J Bonhoeffer, J Braun, MM Buettcher, M Chen, RT Drammeh, B Duclos, P Heijbel, H Heininger, U Hummelman, E Jefferson, T Keller-Stanislawski, B Loupi, E Marcy, SM AF Kohl, Katrin S. Gidudu, Jane Bonhoeffer, Jan Braun, M. Miles Buettcher, Michael Chen, Robert T. Drammeh, Bakary Duclos, Philippe Heijbel, Harald Heininger, Ulrich Hummelman, Erik Jefferson, Thomas Keller-Stanislawski, Brigitte Loupi, Elisabeth Marcy, S. Michael TI The development of standardized case definitions and guidelines for adverse events following immunization SO VACCINE LA English DT Editorial Material ID HYPORESPONSIVE EPISODE HHE; VACCINE SAFETY DATA; DATA-COLLECTION; ACUTE INTUSSUSCEPTION; BRIGHTON COLLABORATION; RANDOMIZED-TRIALS; CONSORT STATEMENT; QUALITY; INFANTS C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Univ Childrens Hosp, Basel, Switzerland. US FDA, Rockville, MD 20857 USA. WHO, CH-1211 Geneva, Switzerland. Swedish Inst Infect Dis Control, Lund, Sweden. Cochrane Vaccines Field, Rome, Italy. Paul Ehrlich Inst, D-6070 Langen, Germany. Sanofi Pasteur, Lyon, France. Univ Calif Los Angeles, Kaiser Fdn Hosp, Ctr Vaccine Res, Panorama, CA USA. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. EM kkohl@cdc.gov RI Bonhoeffer, Jan/E-5903-2014 NR 26 TC 44 Z9 44 U1 1 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 AUG 1 PY 2007 VL 25 IS 31 BP 5671 EP 5674 DI 10.1016/j.vaccine.2007.02.063 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900001 PM 17400339 ER PT J AU Beigel, J Kohl, KS Khuri-Bulos, N Bravo, L Nell, P Marcy, SM Warschaw, K Ong-Lim, A Poerschke, G Weston, W Lindstrom, JA Stoltman, G Maurer, T AF Beigel, John Kohl, Katrin S. Khuri-Bulos, Najwa Bravo, Lulu Nell, Patricia Marcy, S. Michael Warschaw, Karen Ong-Lim, Anna Poerschke, Gabriele Weston, William Lindstrom, Jill A. Stoltman, Gillian Maurer, Toby CA Brighton Collaboration Rash TI Rash including mucosal involvement: Case definition and guidelines for collection, analysis, and presentation of immunization safety data SO VACCINE LA English DT Article DE rash; mucocutaneous; adverse event; immunization; guidelines; case definition ID STATEMENT; QUALITY; TRIALS C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Natl Inst Hlth, Bethesda, MD USA. Jordan Univ Hosp, Amman, Jordan. Univ Philippines, Manila, Philippines. USAF, Sturgeon Bay, WI USA. Univ So Calif, Panorama, CA USA. Univ Calif Los Angeles, Sch Med, Kaiser Fdn Hosp, Panorama, CA USA. Mayo Clin, Scottsdale, AZ USA. Merck Sharp & Dohme Asia Ltd, Hong Kong, Hong Kong, Peoples R China. Univ Colorado, Aurora, CO USA. US FDA, Rockville, MD 20857 USA. Michigan Dept Commun Hlth, Lansing, MI USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org RI Beigel, John/A-7111-2009 NR 10 TC 10 Z9 10 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 1 PY 2007 VL 25 IS 31 BP 5697 EP 5706 DI 10.1016/j.vaccine.2007.02.066 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900004 PM 17403561 ER PT J AU Jorch, G Tapiainen, T Bonhoeffer, J Fischer, TK Heininger, U Hoet, B Kohl, KS Lewis, EM Meyer, C Nelson, T Sandbu, S Schlaud, M Schwartz, A Varricchio, F Wise, RP AF Jorch, Gerhard Tapiainen, Terhi Bonhoeffer, Jan Fischer, Thea K. Heininger, Ulrich Hoet, Bernard Kohl, Katrin S. Lewis, E. M. Meyer, Christiane Nelson, Tony Sandbu, Synne Schlaud, Martin Schwartz, Ann Varricchio, Frederick Wise, Robert P. CA Brighton Collaboration Unexplained TI Unexplained sudden death, including sudden infant death syndrome (SIDS), in the first and second years of life: Case definition and guidelines for collection, analysis, and presentation of immunization safety data SO VACCINE LA English DT Article DE unexpected sudden death; unexplained sudden death; sudden infant death syndrome; adverse event; immunization; guidelines; case definition ID EVENT-REPORTING-SYSTEM; TETANUS-PERTUSSIS IMMUNIZATION; UNEXPECTED DEATH; RISK-FACTORS; DIPHTHERIA; VACCINE; TOXOIDS; EPIDEMIOLOGY; STATEMENT; QUALITY C1 Univ Childrens Hosp, Basel, Switzerland. Univ Magdeburg, D-39106 Magdeburg, Germany. Univ Oulu, Oulu, Finland. Ctr Dis Control & Prevent, Atlanta, GA USA. GlaxoSmithKline Biol, Rixensart, Belgium. Kaiser Permanente No Calif, Oakland, CA USA. Robert Koch Inst, D-1000 Berlin, Germany. Chinese Univ Hong Kong, Hong Kong, Hong Kong, Peoples R China. Prince Wales Hosp, Hong Kong, Hong Kong, Peoples R China. Inst Publ Hlth, Oslo, Norway. US FDA, Rockville, MD 20857 USA. RP Bonhoeffer, J (reprint author), Univ Childrens Hosp, Basel, Switzerland. EM secretariat@brightoncollaboration.org RI Bonhoeffer, Jan/E-5903-2014; OI Nelson, Edmund Anthony Severn/0000-0002-2521-3403; Fischer, Thea Kolsen/0000-0003-4812-980X NR 48 TC 12 Z9 12 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 AUG 1 PY 2007 VL 25 IS 31 BP 5707 EP 5716 DI 10.1016/j.vaccine.2007.02.068 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900005 PM 17408816 ER PT J AU Wise, RP Bonhoeffer, J Beeler, J Donato, H Downie, P Matthews, D Pool, V Riise-Bergsaker, M Tapiainen, T Varricchio, F AF Wise, Robert P. Bonhoeffer, Jan Beeler, Judy Donato, Hugo Downie, Peter Matthews, Dana Pool, Vitali Riise-Bergsaker, Marianne Tapiainen, Terhi Varricchio, Frederick CA Brighton Collaboration Thrombocyto TI Thrombocytopenia: Case definition and guidelines for collection, analysis, and presentation of immunization safety data SO VACCINE LA English DT Article DE thrombocytopenia; adverse event; immunization; guidelines; case definition ID PURPURA FOLLOWING MEASLES; HEPATITIS-B-VACCINE; MUMPS-RUBELLA VACCINATION; MEAN PLATELET VOLUME; ADVERSE EVENTS; REFERENCE INTERVALS; VARICELLA VACCINE; COUNT; SURVEILLANCE; CHILDREN C1 Univ Childrens Hosp, Basel, Switzerland. US FDA, Rockville, MD 20857 USA. Univ Oulu, Oulu, Finland. Hosp Ninos San Justo, Buenos Aires, DF, Argentina. Royal Childrens Hosp, Melbourne, Vic, Australia. Univ Washington, Seattle, WA 98195 USA. Childrens Hosp & Reg Med Ctr, Seattle, WA USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Norwegian Inst Publ Hlth, Oslo, Norway. RP Bonhoeffer, J (reprint author), Univ Childrens Hosp, Basel, Switzerland. EM secretariat@brightoncollaboration.org RI Bonhoeffer, Jan/E-5903-2014 NR 53 TC 12 Z9 12 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 1 PY 2007 VL 25 IS 31 BP 5717 EP 5724 DI 10.1016/j.vaccine.2007.02.067 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900006 PM 17493712 ER PT J AU Nell, P Kohl, KS Graham, PL LaRussa, PS Marcy, SM Fulginiti, VA Martin, B McMahon, A Norton, SA Trolin, I AF Nell, Patricia Kohl, Katrin S. Graham, Philip L. LaRussa, Philip S. Marcy, S. Michael Fulginiti, Vincent A. Martin, Bryan McMahon, Ann Norton, Scott A. Trolin, Ingrid CA Brighton Collaboration Vaccinia Vi TI Progressive vaccinia as an adverse event following exposure to vaccinia virus: Case definition and guidelines of data collection, analysis, and presentation of immunization safety data SO VACCINE LA English DT Article DE progressive vaccinia; adverse event; vaccinia virus; smallpox vaccine; immunization; guidelines; case definition ID SMALLPOX VACCINATION; UNITED-STATES; COMPLICATIONS; BIOTERRORISM; QUALITY; TRIALS; RISKS C1 Ctr Dis Control & Prevent, Off Chief Sci Officer, Immunizat Safety Off, Atlanta, GA 30333 USA. USAF, Sturgeon Bay, WI USA. Columbia Univ, New York Presbyterian Hosp, Coll Phys & Surg, Dept Pediat,Dept Epidemiol, New York, NY USA. Univ So Calif, Panorama, CA USA. Univ Calif Los Angeles, Kaiser Fdn Hosp, Sch Med, Panorama, CA USA. Univ Arizona, Dept Pediat, Tucson, AZ 85721 USA. Univ Colorado, Denver, CO 80202 USA. Walter Reed Army Med Ctr, Dept Allergy & Immunol, Washington, DC USA. US FDA, Vaccine Safety Branch, Rockville, MD 20857 USA. Walter Reed Army Med Ctr, Washington, DC USA. Med Prod Agcy, Uppsala, Sweden. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Off Chief Sci Officer, Immunizat Safety Off, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org NR 24 TC 7 Z9 10 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 AUG 1 PY 2007 VL 25 IS 31 BP 5735 EP 5744 DI 10.1016/j.vaccine.2007.02.088 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900008 PM 17540484 ER PT J AU Sejvar, JJ Kohl, KS Bilynsky, R Blumberg, D Cvetkovich, T Galama, J Gidudu, J Katikaneni, L Khuri-Bulos, N Oleske, J Tapiainen, T Wiznitzer, M AF Sejvar, James J. Kohl, Katrin S. Bilynsky, Roman Blumberg, Dean Cvetkovich, Therese Galama, Jochem Gidudu, Jane Katikaneni, Lakshmi Khuri-Bulos, Najwa Oleske, James Tapiainen, Terhi Wiznitzer, Max CA Brighton Collaboration Encephaliti TI Encephalitis, myelitis, and acute disseminated encephalomyelitis (ADEM): Case definitions and guidelines for collection, analysis, and presentation of immunization safety data SO VACCINE LA English DT Article DE encephalitis; ADEM; myelitis; encephalomyelitis; adverse event; immunization; guidelines; case definition ID NORMAL CEREBROSPINAL-FLUID; HERPES-SIMPLEX ENCEPHALITIS; NERVOUS-SYSTEM INFECTIONS; EVENT REPORTING SYSTEM; VIRAL ENCEPHALITIS; UNITED-STATES; CHILDREN; VACCINE; VALUES; EPIDEMIOLOGY C1 Ctr Dis Control & Prevent, Off Chief Sci Officer, Immunizat Safety Off, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Ctr Zoonot Vector Borne & Enter Dis, Div Vector Borne Infect Dis, Atlanta, GA USA. Ctr Dis Control & Prevent, Div Viral & Rickettsial Dis, Atlanta, GA USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Pediat, Winston Salem, NC 27103 USA. UC Davis Med Ctr, Dept Pediat, Sacramento, CA USA. US FDA, Ctr Biol Evaluat & Res, Div Vaccines & Related Prod, Rockville, MD 20857 USA. Univ Med Ctr Nijmegen, Dept Med Microbiol, Nijmegen, Netherlands. Univ S Carolina, Dept Pediat, Charleston, SC USA. New Jersery Med Sch, Div Pulmonary Allergy Immunol & Infect Dis, Newark, NJ 07101 USA. Univ Childrens Hosp, Basel, Switzerland. Univ Oulu, Dept Pediat, SF-90100 Oulu, Finland. Univ Hosp Cleveland, Dept Neurol, Cleveland, OH 44106 USA. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Off Chief Sci Officer, Immunizat Safety Off, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org NR 72 TC 61 Z9 62 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 AUG 1 PY 2007 VL 25 IS 31 BP 5771 EP 5792 DI 10.1016/j.vaccine.2007.04.060 PG 22 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900012 PM 17570566 ER PT J AU Tapiainen, T Prevots, R Izurieta, HS Abramson, J Bilynsky, R Bonhoeffer, J Bonnet, MC Center, K Galama, J Gillard, P Griot, M Hartmann, K Heininger, U Hudson, M Koller, A Khetsuriani, N Khuri-Bulos, N Marcy, SM Matulionyte, R Schondorf, I Sejvar, J Steele, R AF Tapiainen, Terhi Prevots, Rebecca Izurieta, Hector S. Abramson, Jon Bilynsky, Roman Bonhoeffer, Jan Bonnet, Marie-Claude Center, Kimberly Galama, Jochem Gillard, Paul Griot, Monika Hartmann, Katharina Heininger, Ulrich Hudson, Michael Koller, Annette Khetsuriani, Nino Khuri-Bulos, Najwa Marcy, S. Michael Matulionyte, Raimonda Schoendorf, Ines Sejvar, James Steele, Russell CA Brighton Collaboration Aseptic Men TI Aseptic meningitis: Case definition and guidelines for collection, analysis and presentation of immunization safety data SO VACCINE LA English DT Article DE aseptic meningitis; adverse event; immunization; guidelines; case definition ID MUMPS-RUBELLA VACCINATION; NORMAL CEREBROSPINAL-FLUID; C-REACTIVE PROTEIN; BACTERIAL-MENINGITIS; MASS VACCINATION; MMR VACCINE; VIRAL MENINGITIS; ADVERSE EVENTS; GRAM STAIN; WILD-TYPE C1 Univ Childrens Hosp, Basel, Switzerland. Univ Oulu, Dept Pediat, SF-90100 Oulu, Finland. Natl Inst Hlth, Natl Inst Allergy & Infect Dis, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Pediat, Winston Salem, NC 27103 USA. Patterson Army Hlth Ctr, Ft Monmouth, NJ USA. Aventis Pasteur, Lyon, France. Wyeth Pharmaceut, Collegeville, PA USA. Univ Med Ctr, Dept Med Microbiol, Nijmegen, Netherlands. GlaxoSmithKline Inc, Rixensart, Belgium. Berna Biotech, Kusnacht, Switzerland. Ctr Emergency Preparedness & Response, Hlth Protect Agcy, Salisbury, Wilts, England. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Div Viral & Rickettsial Dis, Atlanta, GA USA. Univ So Calif, Panorama, CA USA. Univ Calif Los Angeles, Kaiser Fdn Hosp, Sch Med, Panorama, CA USA. Vilnius State Univ, Dept Infect Dis, Vilnius, Lithuania. Novartis Vaccines, Marburg, Germany. LSU Med Sch, Dept Pediat, New Orleans, LA USA. RP Bonhoeffer, J (reprint author), Univ Childrens Hosp, Basel, Switzerland. EM secretariat@brightoncollaboration.org RI Bonhoeffer, Jan/E-5903-2014 NR 75 TC 24 Z9 24 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 AUG 1 PY 2007 VL 25 IS 31 BP 5793 EP 5802 DI 10.1016/j.vaccine.2007.04.058 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900013 PM 17574313 ER PT J AU Halperin, S Kohl, KS Gidudu, J Ball, L Hammer, SJ Heath, P Hennig, R Labadie, J Rothstein, E Schuind, A Varricchio, F Walop, W AF Halperin, Scott Kohl, Katrin S. Gidudu, Jane Ball, Leslie Hammer, Sandra Jo Heath, Paul Hennig, Renald Labadie, Jerry Rothstein, Edward Schuind, Anne Varricchio, Frederick Walop, Wikke CA Brighton Collaboration Local React TI Cellulitis at injection site: Case definition and guidelines for collection, analysis, and presentation of immunization safety data SO VACCINE LA English DT Article DE cellulitis; adverse event; immunization; guidelines; case definition ID EVENT FOLLOWING IMMUNIZATION; STATEMENT; QUALITY; TRIALS C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Dalhousie Univ, Halifax, NS, Canada. US FDA, Rockville, MD 20857 USA. Calif Dept Publ Hlth, Richmond, CA USA. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Novartis Vaccine, Marburg, Germany. Pennridge Pediat Associates, Sellersville, PA USA. GlaxoSmithKline Inc, King Of Prussia, PA USA. Publ Hlth Agcy Canada, Ottawa, ON, Canada. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org NR 20 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 1 PY 2007 VL 25 IS 31 BP 5803 EP 5820 DI 10.1016/j.vaccine.2007.04.059 PG 18 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900014 PM 17548135 ER PT J AU Kohl, KS Ball, L Gidudu, J Hammer, SJ Halperin, S Heath, P Hennig, R Labadie, J Rothstein, E Schuind, A Varricchio, F Walop, W AF Kohl, Katrin S. Ball, Leslie Gidudu, Jane Hammer, Sandra Jo Halperin, Scott Heath, Paul Hennig, Renald Labadie, Jerry Rothstein, Edward Schuind, Anne Varricchio, Frederick Walop, Wikke CA Brighton Collaboration Local React TI Abscess at injection site: Case definition and guidelines for collection, analysis, and presentation of immunization safety data SO VACCINE LA English DT Article DE abscess; adverse event; immunization; guidelines; case definition ID TOXOID-PERTUSSIS VACCINATION; EVENT FOLLOWING IMMUNIZATION; DIPHTHERIA; OUTBREAK; FEVER C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Rockville, MD USA. Calif Dept Publ Hlth, Richmond, CA USA. Dalhousie Univ, Halifax, NS, Canada. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Novartis Vaccine, Marburg, Germany. Pennridge Pediat Associates, Sellersville, PA USA. GlaxoSmithKline Inc, King Of Prussia, PA USA. Publ Hlth Agcy Canada, Ottawa, ON, Canada. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org NR 24 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 1 PY 2007 VL 25 IS 31 BP 5821 EP 5838 DI 10.1016/j.vaccine.2007.04.057 PG 18 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900015 PM 17540485 ER PT J AU Kohl, KS Walop, W Gidudu, J Ball, L Halperin, S Hammer, SJ Heath, P Hennig, R Rothstein, E Schuind, A Varricchio, F AF Kohl, Katrin S. Walop, Wikke Gidudu, Jane Ball, Leslie Halperin, Scott Hammer, Sandra Jo Heath, Paul Hennig, Renald Rothstein, Edward Schuind, Anne Varricchio, Frederick CA Brighton Collaboration Local React TI Induration at or near injection site: Case definition and guidelines for collection, analysis, and presentation of immunization safety data SO VACCINE LA English DT Article DE Induration; adverse event; immunization; guidelines; case definition ID DIPHTHERIA-TETANUS-PERTUSSIS; INFLUENZAE TYPE-B; HEPATITIS-A VACCINE; POLYSACCHARIDE VACCINE; COMPARATIVE TRIAL; RANDOMIZED-TRIAL; IMMUNOGENICITY; CHILDREN; INFANTS; CONJUGATE C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Publ Hlth Agcy Canada, Ottawa, ON, Canada. US FDA, Rockville, MD 20857 USA. Dalhousie Univ, Halifax, NS, Canada. Calif Dept Publ Hlth, Richmond, CA USA. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Novartis Vaccine, Marburg, Germany. Pennridge Pediat Associates, Sellersville, PA USA. GlaxoSmithKline Inc, King Of Prussia, PA USA. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org NR 32 TC 14 Z9 14 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 1 PY 2007 VL 25 IS 31 BP 5839 EP 5857 DI 10.1016/j.vaccine.2007.04.062 PG 19 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900016 PM 17553602 ER PT J AU Kohl, KS Walop, W Gidudu, J Ball, L Halperin, S Hammer, SJ Heath, P Varricchio, F Rothstein, E Schuind, A Hennig, R AF Kohl, Katrin S. Walop, Wikke Gidudu, Jane Ball, Leslie Halperin, Scott Hammer, Sandra Jo Heath, Paul Varricchio, Frederick Rothstein, Edward Schuind, Anne Hennig, Renald CA Brighton Collaboration Local React TI Swelling at or near injection site: Case definition and guidelines for collection, analysis and presentation of immunization safety data SO VACCINE LA English DT Article DE swelling; adverse event; immunization; guidelines; case definition ID CELL PERTUSSIS-VACCINE; ACELLULAR PERTUSSIS; CONJUGATE VACCINE; DIPHTHERIA; TETANUS; IMMUNOGENICITY; BOOSTER; INFANTS; REACTOGENICITY; STATEMENT C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Publ Hlth Agcy Canada, Ottawa, ON, Canada. US FDA, Rockville, MD 20857 USA. Dalhousie Univ, Halifax, NS, Canada. Calif Dept Publ Hlth, Richmond, CA USA. Univ London St Georges Hosp, Sch Med, London SW17 0RE, England. Pennridge Pediat Associates, Sellersville, PA USA. GlaxoSmithKline Inc, King Of Prussia, PA USA. Navartis Vaccine, Marburg, Germany. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org NR 27 TC 24 Z9 24 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD AUG 1 PY 2007 VL 25 IS 31 BP 5858 EP 5874 DI 10.1016/j.vaccine.2007.04.056 PG 17 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900017 PM 17548132 ER PT J AU Buettcher, M Heininger, U Braun, M Bonhoeffer, J Halperin, S Heijbel, H Martins, RD Vermeer-de Bondt, P AF Buettcher, Michael Heininger, Ulrich Braun, Miles Bonhoeffer, Jan Halperin, Scott Heijbel, Harald Martins, Reinaldo de Menezes Vermeer-de Bondt, Patricia CA Brighton Collaboration HHE Working TI Hypotonic-hyporesponsive episode (HHE) as an adverse event following immunization in early childhood: Case definition and guidelines for data collection, analysis, and presentation SO VACCINE LA English DT Article DE Hypotonic-hyporesponsive episode; adverse event; immunization; guidelines; case definition ID ACELLULAR PERTUSSIS VACCINES; WHOLE-CELL; CONTROLLED TRIAL; CHILDREN; VACCINATION; DIPHTHERIA; INFANTS; 2-COMPONENT; SEIZURES; COLLAPSE C1 Univ Childrens Hosp, Basel, Switzerland. US FDA, Rockville, MD 20857 USA. Dalhousie Univ, Halifax, NS, Canada. Swedish Inst Infect Dis Control, Lund, Sweden. Natl Inst Publ Hlth & Environm, Bilthoven, Netherlands. RP Heininger, U (reprint author), Univ Childrens Hosp, Basel, Switzerland. EM ulrich.heininger@ukbb.ch RI Bonhoeffer, Jan/E-5903-2014; Martins, Reinaldo/I-3413-2015 OI Martins, Reinaldo/0000-0002-0667-532X NR 24 TC 15 Z9 17 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 AUG 1 PY 2007 VL 25 IS 31 BP 5875 EP 5881 DI 10.1016/j.vaccine.2007.04.061 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 198QZ UT WOS:000248643900018 PM 17537554 ER PT J AU Melendez-Morales, L Konkle, BA Preiss, L Zhang, MD Mathew, P Eyster, ME Goedert, JJ AF Melendez-Morales, Lehida Konkle, Barbara A. Preiss, Liliana Zhang, Mingdong Mathew, Prasad Eyster, M. Elaine Goedert, James J. TI Chronic hepatitis B and other correlates of spontaneous clearance of hepatitis C virus among HIV-infected people with hemophilia SO AIDS LA English DT Article DE hemophilia; hepatitis B virus (HBV); hepatitis C virus (HCV) ID HUMAN-IMMUNODEFICIENCY-VIRUS; NATURAL-HISTORY; VIRAL CLEARANCE; LIVER-DISEASE; UNITED-STATES; POPULATION; PREVALENCE; LOAD AB Objective: To identify correlates of spontaneous hepatitis C virus (HCV) clearance among people with human immunodeficiency virus (HIV) co-infection. Design: Baseline (2001-2004) analysis of a cohort study of people with hemophilia. Methods: Detailed questionnaire data were used to identify dates of primary HCV and HIV infections and to categorize sex; race; alcohol use; interferon treatment; hepatitis B virus (HBV) status; and HIV/AIDS history, treatment and current status. Spontaneous HCV clearance was defined as nondetection of HCV RNA by polymerase chain reaction assay in paired annual plasma, excluding those treated with interferon. Chi-squared, Fisher exact test, and logistic regression were used to identify correlates of clearance. Results: Among 478 HIV-infected participants, 61 (12.8%) had cleared HCV. Among the 31 participants with chronic HBV (as well as HIV), 16 (51.6%) had cleared HCV. With chronic HBV, HCV clearance was increased 11.2-fold (95% confidence interval, 5.1-24.8), after adjusting for sex, race, and hemophilia severity. Excluding the participants with chronic HBV, the prevalence of HCV clearance was 10.1%; and it was significantly reduced among males (9.7%, P=0.05), blacks (1.6%, P=0.01), and participants with severe hemophilia (8.2%, P=0.02). HCV clearance was not associated with HIV RNA detection in plasma, CD4 cell count, anti-HIV therapy, AIDS history, ages at or years of HIV or HCV infection, or alcohol consumption. Conclusions: HCV clearance is unambiguously and markedly increased with chronic HBV infection among HIV co-infected people. (c) 2007 Lippincott Williams & Wilkins. C1 NCI, Viral Epidemiol Branch, DCEG, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Emerging Leaders Program, Natl Ctr HIV Hepatitis STD & TB Prevent, Atlanta, GA USA. Univ Penn, Dept Med, Div Hematol Oncol, Philadelphia, PA 19104 USA. Res Triangle Inst Int, Rockville, MD USA. FDA, CDRH, OSB, DPS,Epidemiol Branch, Rockville, MD USA. Univ New Mexico, Dept Pediat, Albuquerque, NM 87131 USA. Penn State Univ, Coll Med, Div Hematol & Oncol, Dept Med, Hershey, PA 17033 USA. RP Goedert, JJ (reprint author), NCI, Viral Epidemiol Branch, DCEG, 6120 Execut Blvd,Room 7066, Rockville, MD 20852 USA. EM goedertj@mail.nih.gov FU NCI NIH HHS [N01 CP 01004, N01 CO 12400] NR 17 TC 10 Z9 11 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD JUL 31 PY 2007 VL 21 IS 12 BP 1631 EP 1636 DI 10.1097/QAD.0b013e32826fb6d9 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 196PV UT WOS:000248495400017 PM 17630559 ER PT J AU Mills, K Ansah, TA Ali, SF Mukherjee, S Shockley, DC AF Mills, K. Ansah, T. A. Ali, S. F. Mukherjee, S. Shockley, D. C. TI Augmented behavioral response and enhanced synaptosomal calcium transport induced by repeated cocaine administration are decreased by calcium channel blockers SO LIFE SCIENCES LA English DT Article DE cocaine; sensitization; calcium channel blockers; motor activity; synaptosomes; rat ID VENTRAL TEGMENTAL AREA; INDUCED DOPAMINE RELEASE; NUCLEUS-ACCUMBENS; EXTRACELLULAR DOPAMINE; ANTAGONIST ISRADIPINE; LOCOMOTOR-ACTIVITY; MOTOR STIMULATION; CA2+ CHANNELS; SENSITIZATION; RATS AB Recent studies suggest that calcium influx via L-type calcium channels is necessary for psychostimulant-induced behavioral sensitization. In addition, chronic amphetamine upregulates subtype Cav1.2-containing L-type calcium channels. In the present studies, we assessed the effect of calcium channel blockers (CCBs) on cocaine-induced behavioral sensitization and determined whether the functional activity of L-type calcium channels is altered after repeated cocaine administration. Rats were administered daily intraperitoneal injections of either flunarizine (40 mg/kg), diltiazem (40 mg/kg) or cocaine (20 mg/kg) and the combination of the CCBs and cocaine for 30 days. Motor activities were monitored on Day 1, and every 6th day during the 30-day treatment period. Daily cocaine administration produced increased locomotor activity. Maximal augmentation of behavioral response to repeated cocaine administration was observed on Day 18. Flunarizine pretreatment abolished the augmented behavioral response to repeated cocaine administration while diltiazem was less effective. Measurement of tissue monoamine levels on Day 18 revealed cocaine-induced increases in DA and 5-HT in the nucleus accumbens. By contrast to behavioral response, diltiazem was more effective in attenuating increases in monoamine levels than flunarizine. Cocaine administration for 18 days produced increases in calcium uptake in synaptosomes prepared from the nucleus accumbens and frontal cortex. Increases in calcium uptake were abolished by flumarizine and diltiazem pretreatment. Taken together, the augmented cocaine-induced behavioral response on Day 18 may be due to increased calcium uptake in the nucleus accumbens leading to increased dopamine (DA) and scrotonin (5-HT) release. Flunarizine and diltiazem attenuated the behavioral response by decreasing calcium uptake and decreasing neurochemical release. (c) 2007 Elsevier Inc. All rights reserved. C1 Meharry Med Coll, Dept Pharmacol, Nashville, TN 37208 USA. US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Ansah, TA (reprint author), Meharry Med Coll, Dept Pharmacol, 1005 DB Todd Blvd, Nashville, TN 37208 USA. EM tansah@mmc.edu FU NHLBI NIH HHS [P32 HL07809, T32 HL007809]; NIDA NIH HHS [DA06686, R24 DA006686-03]; NIEHS NIH HHS [S11 ES014156]; NINDS NIH HHS [U01 NS041071, U54 NS041071, NS041071] NR 50 TC 9 Z9 9 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0024-3205 EI 1879-0631 J9 LIFE SCI JI Life Sci. PD JUL 26 PY 2007 VL 81 IS 7 BP 600 EP 608 DI 10.1016/j.lfs.2007.06.028 PG 9 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 208PS UT WOS:000249332300010 PM 17689567 ER PT J AU Karbiwnyk, CM Carr, LE Turnipseed, SB Andersen, WC Miller, KE AF Karbiwnyk, Christine M. Carr, Lori E. Turnipseed, Sherri B. Andersen, Wendy C. Miller, Keith E. TI Determination of quinolone residues in shrimp using liquid chromatography with fluorescence detection and residue confirmation by mass spectrometry SO ANALYTICA CHIMICA ACTA LA English DT Article DE quinolones; residue analysis; shrimp; fluorescence; mass spectrometry; confirmation ID OXOLINIC ACID RESIDUES; MULTIRESIDUE DETERMINATION; AQUACULTURED PRODUCTS; SALMON MUSCLE; DRUG RESIDUES; FLUMEQUINE; FISH; FLUOROQUINOLONES; VALIDATION; CATFISH AB The quinolones, oxolinic acid (OXO), flumequine (FLU), and nalidixic acid (NAL), are antibacterial drugs effective against Gram-negative bacteria. Quinolones are used in both human and veterinary medicine, but are currently not approved by the U.S. Food and Drug Administration for use in food fish. A liquid chromatography-fluorescence (LC-FL) method was developed to determine OXO, FLU, and NAL residues in shrimp. An additional liquid chromatography-mass spectrometry (LC-MS '') method was created to confirm these residues using the same sample extract. Samples were prepared with a simple ethyl acetate extraction followed by solvent exchange into 0.2% formic acid and cleaned-up with hexane. Reverse phase chromatography was used to separate the three compounds in both procedures. For the LC-FL determinative method, fluorescence emission was monitored at 369 nm with excitation at 327 nm. With electrospray ionization, the three most abundant ions from the MS' product ion spectrum were used to identify OXO, FLU, and NAL in the confirmation procedure. Shrimp samples fortified at levels ranging from 7.5 to 100 ng g. I were used to validate both methods. Published by Elsevier B.V. C1 US FDA, Anim Drugs Res Ctr, Denver, CO USA. US FDA, Denver Dist Lab, Denver, CO USA. Univ Denver, Denver, CO USA. RP Karbiwnyk, CM (reprint author), US FDA, Anim Drugs Res Ctr, Denver, CO USA. EM christine.karbiwnyk@fda.hhs.gov RI 志琴, 江/I-6431-2012 NR 40 TC 23 Z9 27 U1 1 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD JUL 23 PY 2007 VL 596 IS 2 BP 257 EP 263 DI 10.1016/j.aca.2007.06.018 PG 7 WC Chemistry, Analytical SC Chemistry GA 196GG UT WOS:000248469100009 PM 17631104 ER PT J AU Wu, AH Pike, MC Williams, LD Spicer, D Tseng, CC Churchwell, MI Doerge, DR AF Wu, Anna H. Pike, Malcolm C. Williams, Lee D. Spicer, Darcy Tseng, Chiu-Chen Churchwell, Mona I. Doerge, Daniel R. TI Tamoxifen, soy, and lifestyle factors in Asian American women with breast cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID SPRAGUE-DAWLEY RATS; METABOLITE CONCENTRATIONS; CYP2D6 GENOTYPE; MAMMARY-TUMORS; TRIAL; ISOFLAVONES; POPULATION; PREVENTION; INHIBITOR; SURVIVAL AB Purpose Soy foods have been a staple in Asia for centuries but the consumption of this food in the West is recent. Intake of soy among women at high risk for or with breast cancer has become a public health concern because genistein, a major component of soy, has weak estrogenic effects on breast epithelium, and has been found to negate the benefit of tamoxifen in some animal and in vitro studies. Patients and Methods We conducted a cross-sectional study in Asian Americans with breast cancer who were tamoxifen users ( n = 380) to investigate the association between soy intake and circulating levels of tamoxifen and its metabolites ( N-desmethyl tamoxifen [ N-DMT], 4-hydroxytamoxifen [ 4-OHT], and 4-hydroxy-N-desmethyl-tamoxifen [endoxifen]). Results Serum levels of tamoxifen or its metabolites were unrelated to self-reported intake of soy or serum levels of isoflavones. Blood levels of tamoxifen were 81% higher in postmenopausal women age 65 or older compared with premenopaual women age 45 or younger ( P =. 005); similar patterns of results were observed for the tamoxifen metabolites. Levels of N-DMT were 27% ( P = .03) lower among women in the highest tertile of body mass index ( BMI, > 24.4 kg/m(2)) compared with those in the lowest category ( BMI <= 21.5). Women who used hypertensive medications had higher levels of tamoxifen ( P = .02) and N-DMT ( P = .04) compared with nonusers. Conclusion We found no evidence that soy intake adversely affected levels of tamoxifen or its metabolites. However, age, menopausal status, BMI, and use of hypertensive medications significantly influenced circulating levels of tamoxifen and its metabolites in this population. C1 Univ So Calif, Dept Prevent Med, Los Angeles, CA 90033 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Wu, AH (reprint author), Univ So Calif, Dept Prevent Med, Hlth Sci Campus, Los Angeles, CA 90033 USA. EM annawu@usc.edu FU NCI NIH HHS [N01CN25403]; NIA NIH HHS [P01-AG024387]; PHS HHS [5P30 E207048] NR 30 TC 18 Z9 18 U1 1 U2 3 PU AMER SOC CLINICAL ONCOLOGY PI ALEXANDRIA PA 330 JOHN CARLYLE ST, STE 300, ALEXANDRIA, VA 22314 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUL 20 PY 2007 VL 25 IS 21 BP 3024 EP 3030 DI 10.1200/JCO.2006.10.5023 PG 7 WC Oncology SC Oncology GA 200DJ UT WOS:000248743800008 PM 17536081 ER PT J AU Zhao, S McDermott, PF White, DG Qaiyumi, S Friedman, SL Abbott, JW Glenn, A Ayers, SL Post, KW Fales, WH Wilson, RB Reggiardo, C Walker, RD AF Zhao, S. McDermott, P. F. White, D. G. Qaiyumi, S. Friedman, S. L. Abbott, J. W. Glenn, A. Ayers, S. L. Post, K. W. Fales, W. H. Wilson, R. B. Reggiardo, C. Walker, R. D. TI Characterization of multidrug resistant Salmonella recovered from diseased animals SO VETERINARY MICROBIOLOGY LA English DT Article DE Salmonella; antimicrobial resistance; diseased animals ID ENTERICA SUBSP ENTERICA; ESCHERICHIA-COLI; ANTIMICROBIAL RESISTANCE; FOOD ANIMALS; TYPHIMURIUM; SEROVARS; NEWPORT; OPERATION; GENETICS; TURKEYS AB Three hundred and eighty Salmonella isolates recovered from animal diagnostic samples obtained from four state veterinary diagnostic laboratories (AZ, NC, MO, and TN) between 2002 and 2003 were tested for antimicrobial susceptibilities and further characterized for bla(CMY) beta-lactamase genes, class 1 integrons and genetic relatedness using PFGE. Forty-seven serovars were identified, the most common being S. Typhimurium (26%), S. Heidelberg (9%), S, Dublin (8%), S. Newport (8%), S. Derby (7%), and S. Choleraesuis (7%). Three hundred and thirteen (82%) isolates were resistant to at least one antimicrobial, and 265 (70%) to three or more antimicrobials. Resistance was most often observed to tetracycline (78%), followed by streptomycin (73%), sulfamethoxazole (68%), and ampicillin (54%), and to a lesser extent chloramphenicol (37%), kanamycin (37%), amoxicillin-clavulanic acid (20%), and ceftiofur (17%). With regards to animal of origin, swine Salmonella isolates displayed the highest rate of resistance, being resistant to at least one antimicrobial (92%), followed by those recovered from turkey (91%), cattle (77%), chicken (68%), and equine (20%). Serovars commonly showing multidrug resistance (MDR) to >= 9 antimicrobials were S. Uganda (100%), S. Agona (79%), and S. Newport (62%), compared to S. Heidelberg (11%) and S. Typhimurium (7%). Class-1 integrons were detected in 43% of all isolates, and were found to contain aadA, aadB, dhfr, cmlA and sat] gene cassettes alone or in various combinations. All ceftiofur resistant isolates (n = 66) carried the bla(CMY) beta-lactamase gene. A total of 230 PFGE patterns were generated among the 380 isolates tested using XbaI, indicating extensive genetic diversity across recovered Salmonella serovars, however, several MDR clones were repeatedly recovered from different diseased animals. (C) 2007 Elsevier B.V. All rights reserved. C1 US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. Rollins Anim Dis Diagnost Lab, Raleigh, NC 27607 USA. Univ Missouri, VMDL, Columbia, MO 65205 USA. CE Kord Anim Dis Diagnost Lab, Tennessee Dept Agr, Nashville, TN 37204 USA. Univ Arizona, Arizona Vet Diagnost Lab, Tucson, AZ 85705 USA. RP Zhao, S (reprint author), US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. EM shaohua.zhao@FDA.HHS.GOV NR 29 TC 61 Z9 67 U1 0 U2 9 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD JUL 20 PY 2007 VL 123 IS 1-3 BP 122 EP 132 DI 10.1016/j.vetmic.2007.03.001 PG 11 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 189MY UT WOS:000247994200012 PM 17400409 ER PT J AU Malozowski, S Sahlroot, JT AF Malozowski, Saul Sahlroot, Jon Todd TI Interleukin-1-receptor antagonist in type 2 diabetes mellitus SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIDDKD, Bethesda, MD 20892 USA. Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Malozowski, S (reprint author), NIDDKD, Bethesda, MD 20892 USA. EM sm87j@nih.gov NR 1 TC 13 Z9 16 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 JUL 19 PY 2007 VL 357 IS 3 BP 302 EP 303 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 191FH UT WOS:000248115100018 PM 17634469 ER PT J AU Tran, HA Kang, E Becker, D AF Tran, Henry A. Kang, Eunice Becker, Daniel TI Omeprazole before endoscopy in patients with gastrointestinal bleeding SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 NIDDKD, Bethesda, MD 20892 USA. Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Tran, HA (reprint author), NIDDKD, Bethesda, MD 20892 USA. EM hat7e@hotmail.com NR 0 TC 1 Z9 1 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 19 PY 2007 VL 357 IS 3 BP 303 EP 304 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 191FH UT WOS:000248115100021 PM 17644833 ER PT J AU Klontz, KC Acheson, DW AF Klontz, Karl C. Acheson, David W. TI Dietary supplement-induced vitamin D intoxication SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, College Pk, MD 20740 USA. RP Klontz, KC (reprint author), US FDA, College Pk, MD 20740 USA. NR 2 TC 33 Z9 35 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 19 PY 2007 VL 357 IS 3 BP 308 EP 309 DI 10.1056/NEJMc063341 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 191FH UT WOS:000248115100027 PM 17634473 ER PT J AU Kavanaugh, CJ Trumbo, PR Ellwood, KC AF Kavanaugh, Claudine J. Trumbo, Paula R. Ellwood, Kathleen C. TI The US food and drug administration's evidence-based review for qualified health claims: Tomatoes, lycopene, and cancer SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Review ID CERVICAL INTRAEPITHELIAL NEOPLASIA; MULTICENTER CASE-CONTROL; HUMAN-PAPILLOMAVIRUS INFECTION; DIETARY BETA-CAROTENE; WESTERN NEW-YORK; PROSTATE-CANCER; LUNG-CANCER; BREAST-CANCER; GASTRIC-CANCER; SERUM CAROTENOIDS AB Several studies have reported an inverse association between tomato and/or lycopene intake and the risk of some types of cancer. In 2004, the U.S. Food and Drug Administration (FDA) received two petitions for qualified health claims regarding tomatoes, lycopene, and the risk reduction for some forms of cancer. Health claims that characterize the relationship between a food or food component and a disease or health-related condition require premarket approval by FDA to be included on the labels of conventional foods and dietary supplements. Here we describe FDA's review of the scientific data for tomato and/or lycopene intake with respect to risk reduction for certain forms of cancer. The FDA found no credible evidence to support an association between lycopene intake and a reduced risk of prostate, lung, colorectal, gastric, breast, ovarian, endometrial, or pancreatic cancer. The FDA also found no credible evidence for an assocaition between tomato consumption and a reduced risk of lung, colorectal, breast, cervical, or endometrial cancer. The FDA found very limited evidence to support an association between tomato consumption and reduced risks of prostate, ovarian, gastric, and pancreatic cancers. C1 USDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Kavanaugh, CJ (reprint author), USDA, Ctr Food Safety & Appl Nutr, HFS-830 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM claudine.kavanaugh@fda.hhs.gov NR 160 TC 87 Z9 91 U1 3 U2 12 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 18 PY 2007 VL 99 IS 14 BP 1074 EP 1085 DI 10.1093/jnci/djm037 PG 12 WC Oncology SC Oncology GA 200BD UT WOS:000248738000009 PM 17623802 ER PT J AU Kane, R AF Kane, Robert TI Re: When you look matters: The effect of assessment schedule on progression-free survival SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Letter C1 US FDA, Ctr Drug Evaluat, Div Drug Oncol Prod, Silver Spring, MD 20993 USA. RP Kane, R (reprint author), US FDA, Ctr Drug Evaluat, Div Drug Oncol Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM robert.kane@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD JUL 18 PY 2007 VL 99 IS 14 BP 1131 EP 1132 DI 10.1093/jnci.djm040 PG 2 WC Oncology SC Oncology GA 200BD UT WOS:000248738000016 PM 17623799 ER PT J AU Manger, R Woodle, D Berger, A Hungerford, J AF Manger, Ronald Woodle, Doug Berger, Andrew Hungerford, James TI Flow cytometric detection of saxitoxins using fluorescent voltage-sensitive dyes SO ANALYTICAL BIOCHEMISTRY LA English DT Article DE saxitoxins; flow cytometry; neuroblastoma; voltage-sensitive dyes ID PARALYTIC SHELLFISH TOXINS; RECEPTOR-BINDING ASSAY; POISONING PSP TOXINS; MOUSE BIOASSAY; SODIUM-CHANNELS; LIQUID-CHROMATOGRAPHY; CELL BIOASSAY; IN-VITRO; CYTOTOXICITY; BREVETOXINS AB By virtue of their ability to block depolarization of nerve cells, the saxitoxins exert the toxic effects associated with paralytic shellfish poisoning and allow for their detection through various methodologies. When veratridine-induced depolarization is followed using voltage-sensitive fluorescent dyes, the presence of these toxic blocking agents can be observed as a decrease in fluorescence of dye-treated nerve cells. Detection using flow cytometry provides for selection of the most responsive population of cultured mouse neuroblastoma (Neuro 2a) cells thereby enhancing assay sensitivity and this approach can be accomplished in real time. The method is demonstrated in preliminary studies using saxitoxin and crude shellfish extracts. (c) 2007 Elsevier Inc. All rights reserved. C1 Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98041 USA. RP Manger, R (reprint author), Fred Hutchinson Canc Res Ctr, Seattle, WA 98109 USA. EM rmanger@fhcrc.org NR 37 TC 11 Z9 11 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD JUL 15 PY 2007 VL 366 IS 2 BP 149 EP 155 DI 10.1016/j.ab.2007.04.010 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 187QL UT WOS:000247863000006 PM 17512490 ER PT J AU Sakamoto, N Tsuji, K Muul, LM Lawler, AM Petricoin, EF Candotti, F Metcalf, JA Tavel, JA Lane, HC Urba, WJ Fox, BA Varki, A Lunney, JK Rosenberg, AS AF Sakamoto, Norihisa Tsuji, Kazuhide Muul, Linda M. Lawler, Ann M. Petricoin, Emanuel F. Candotti, Fabio Metcalf, Julia A. Tavel, Jorge A. Lane, H. Clifford Urba, Walter J. Fox, Bernard A. Varki, Ajit Lunney, Joan K. Rosenberg, Amy S. TI Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in fetal calf serum in mice and humans SO BLOOD LA English DT Article ID EMBRYONIC STEM-CELLS; BREAST-CANCER; STROMAL CELLS; GENE-THERAPY; SIALIC-ACID; T-CELLS; ANTIBODIES; EXPANSION; IDENTIFICATION; VACCINATION AB Recent studies have demonstrated that cell populations intended for therapeutic purposes that are cultured in heterologous animal products can acquire xenoantigens, potentially limiting their utility. In investigations of the immune response to murine embryonic stem cells, we found that a strong antibody response was generated after the second infusion. Both polyclonal and monoclonal antibody responses, derived from immunized mice, were found to be specific for bovine apolipoprotein B-100, which binds to abundant low-density lipoprotein receptors on the cell surface and is internalized. Here we show that in the majority of patients administered 3 different types of cell-based therapies using cells grown in fetal calf serum-containing media, an antibody response to bovine apolipoprotein B-100 develops after the second infusion and is the dominant specificity. The known and potential clinical effects of such antibodies are discussed. C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. Okayama Univ, Sch Med & Dent & Pharmaceut Sci, Dept Dermatol, Okayama 7008530, Japan. NHGRI, Genet & Mol Biol Branch, NIH, Bethesda, MD USA. Johns Hopkins Univ, Sch Med, Transgen Mouse Facil, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Physiol, Baltimore, MD 21218 USA. George Mason Univ, Ctr Appl Proteom & Mol Med, Dept Mol & Microbiol, Manassas, VA 22030 USA. NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. Robert W Franz Canc Res Ctr, Lab Mol & Tumor Immunol, Earle Chiles Res Inst, Providence Portland Med Ctr, Portland, OR USA. Univ Calif San Diego, Glycobiol Res & Training Ctr, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Med, La Jolla, CA 92093 USA. Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA. USDA, Anim Parasit Dis Lab, ARS, Beltsville, MD 20705 USA. RP Rosenberg, AS (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. EM amy.rosenberg@fda.gov FU Intramural NIH HHS NR 35 TC 28 Z9 29 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUL 15 PY 2007 VL 110 IS 2 BP 501 EP 508 DI 10.1182/blood-2007-07-066522 PG 8 WC Hematology SC Hematology GA 191EH UT WOS:000248112400011 PM 17395779 ER PT J AU Rios, M Daniel, S Chancey, C Hewlett, IK Stramer, SL AF Rios, Maria Daniel, Sylvester Chancey, Caren Hewlett, Indira K. Stramer, Susan L. TI West Nile virus adheres to human red blood cells in whole blood SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; TRANSFUSION; HIV-1; RNA; TRANSMISSION; INFECTION; DISEASE; ASSAYS; DUFFY AB Background. West Nile virus ( WNV) is endemic in the United States. It is transmissible by blood transfusion, and the nation's blood supply is currently screened for WNV. Documented transmission of WNV infection through red blood cell ( RBC) units in which the plasma co-component had a low viral load could be explained, in at least 1 instance, by cell-association of WNV; in this case, the RBC unit was released as negative by minipool nucleic acid testing ( NAT) performed on plasma but was intermittently NAT-positive when subsequently tested as an individual sample. We hypothesized that a proportion of WNV bound to blood cells and was not measured by NAT performed on plasma samples. We have investigated whether WNV binds to RBCs, leading to reduction of WNV RNA detection by NAT performed on plasma samples. Methods. Equal volumes of leukoreduced RBCs and their corresponding plasma components from 20 blood donors with NAT results that were positive for WNV were tested in 5 replicates by reverse-transcriptase polymerase chain reaction TaqMan for WNV. In addition, aliquots from 8 of the RBC units were tested by infectivity assays using Vero cells. Results. The reverse-transcriptase polymerase chain reaction TaqMan assay showed that the viral load in the RBC components exceeded that in the corresponding plasma units by 1 order of magnitude. In addition, viruses associated with the RBCs were infectious in Vero cell cultures. Conclusions. These observations reinforce the notion that extraction of viral RNA from whole blood could improve assay sensitivity for blood donor screening and further reduce the residual risk of WNV transmission through transfusion. C1 US FDA, Lab Mol Virol, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Amer Red Cross, Gaithersburg, MD USA. RP Rios, M (reprint author), 8800 Rockville Pike,NIH Bldg 29,Rm 131, Bethesda, MD 20892 USA. EM Maria.Rios@fda.hhs.gov NR 26 TC 23 Z9 24 U1 0 U2 2 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JUL 15 PY 2007 VL 45 IS 2 BP 181 EP 186 DI 10.1086/518850 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 180EC UT WOS:000247343900006 PM 17578776 ER PT J AU Saha, S Takeshita, F Matsuda, T Jounai, N Kobiyama, K Matsumoto, T Sasaki, S Shida, AY Xin, KQ Klinman, DM Uematsu, S Ishii, KJ Akira, S Okuda, K AF Saha, Sukumar Takeshita, Fumihiko Matsuda, Tomoko Jounai, Nao Kobiyama, Kouji Matsumoto, Tetsuya Sasaki, Shin Shida, Atsushi Yo Xin, Ke-Qin Klinman, Dennis M. Uematsu, Satoshi Ishii, Ken J. Akira, Shizuo Okuda, Kenji TI Blocking of the TLR5 activation domain hampers protective potential of flagellin DNA vaccine SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTOR-5; PSEUDOMONAS-AERUGINOSA FLAGELLIN; BACTERIAL FLAGELLIN; IMMUNE-RESPONSES; INNATE IMMUNITY; PULMONARY INFLAMMATION; SALMONELLA FLAGELLIN; MUCOSAL IMMUNIZATION; GENE-EXPRESSION; CUTTING EDGE AB Flagellin is a key component of the flagella of many pathogens, including Pseudomonas aeruginosa. Flagellin is an attractive vaccine candidate because it is readily produced and manipulated as a recombinant protein and has intrinsic adjuvant activity mediated through TLR5. Although DNA vaccines encoding native Pseudomonas B-type (FliC) or A-type (FlaA) flagellin are strongly immunogenic, the resultant Ab response interferes with the interaction of homologous flagellin with TLR5. This reduces the ability of the host to clear homologous, but not heterologous, flagellin-expressing P. aeruginosa. To circumvent this problem, a DNA vaccine encoding a mutant FliC R90A flagellin was developed. The mutant Ag encoded by this vaccine was highly immunogenic, but its ability to interact with TLR5 was reduced by >100-fold. Vaccination with this flagellin mutant DNA vaccine induced cross-reactive Abs against both FliC and FlaA, but few Abs capable of interfering with TLR5 activation. The flagellin mutant DNA vaccine provided excellent protection against both FliC- and FlaA-expressing P. aeruginosa. These findings suggest that vaccines against flagellated pathogens should avoid inducing Abs against TLR5 and raise the possibility that flagellated bacteria evade host elimination by facilitating the production of Abs that reduce the host's ability to mount an innate immune response. C1 Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Kanazawa Ku, Yokohama, Kanagawa 236004, Japan. Tokyo Med Univ, Sch Med, Dept Microbiol, Tokyo, Japan. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. Res Inst Microbial Dis, Dept Host def, Osaka, Japan. Res Inst Microbial Dis, Dept Mol Protozool, Osaka, Japan. Japan Sci & Technol Agcy, Explorat Res Adv Technol, Akira Inate Immun Project, Osaka, Japan. RP Takeshita, F (reprint author), Yokohama City Univ, Grad Sch Med, Dept Mol Biodef Res, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 236004, Japan. EM takesita@yokohama-cu.ac.jp RI Akira, Shizuo/C-3134-2009; Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 43 TC 28 Z9 30 U1 1 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 JUL 15 PY 2007 VL 179 IS 2 BP 1147 EP 1154 PG 8 WC Immunology SC Immunology GA 186AS UT WOS:000247752100053 PM 17617608 ER PT J AU Moffit, JS Koza-Taylor, PH Holland, RD Thibodeau, MS Beger, RD Lawton, MP Manautou, JE AF Moffit, Jeffrey S. Koza-Taylor, Petra H. Holland, Ricky D. Thibodeau, Michael S. Beger, Richard D. Lawton, Michael P. Manautou, Jose E. TI Differential gene expression in mouse liver associated with the hepatoprotective effect of clofibrate SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the National-Society-of-Toxicology CY 2006 CL San Diego, CA SP Natl Soc Toxicol DE peroxisome proliferators; clofibrate; acetaminophen; vanin-1; hepatoprotection; cysteamine; cystamine; pantothenic acid; pantetheine ID INDUCED HEPATIC NECROSIS; MALE CD-1 MICE; ACETAMINOPHEN HEPATOTOXICITY; LIPID-PEROXIDATION; COVALENT BINDING; GLUTATHIONE; PROTECTION; MECHANISM; ALPHA; PRETREATMENT AB Pretreatment of mice with the peroxisome proliferator clofibrate (CFB) protects against acetaminophen (APAP)-induced hepatotoxicity. Previous studies have shown that activation of the nuclear peroxisome proliferator activated receptor-alpha (PPAR alpha) is required for this effect. The present study utilizes gene expression profile analysis to identify potential pathways contributing to PPAR alpha-mediated hepatoprotection. Gene expression profiles were compared between wild type and PPAR alpha-null mice pretreated with vehicle or CFB (500 mg/kg, i.p., daily for 10 days) and then challenged with APAP (400 mg/kg, p.o.). Total hepatic RNA was isolated 4 h after APAP treatment and hybridized to Affymetrix Mouse Genome MGU74 v2.0 GeneChips. Gene expression analysis was performed utilizing GeneSpring (R) software. Our analysis identified 53 genes of interest including vanin-1, cell cycle regulators, lipid-metabolizing enzymes, and aldehyde dehydrogenase 2, an acetaminophen binding protein. Vanin-1 could be important for CFB-mediated hepatoprotection because this protein is involved in the synthesis of cysteamine and cystamine. These are potent antioxidants capable of ameliorating APAP toxicity in rodents and humans. HPLC-ESI/MS/MS analysis of liver extracts indicates that enhanced vanin-1 gene expression results in elevated cystamine levels, which could be mechanistically associated with CFB-mediated hepatoprotection. (C) 2007 Elsevier Inc. All rights reserved. C1 Univ Connecticut, Sch Pharm, Dept Pharmaceut Sci, Toxicol Program, Storrs, CT 06269 USA. Pfizer Inc, Groton Labs, Mol & Invest Toxicol, Groton, CT 06340 USA. Natl Ctr Toxicol Res, Div Syst Technol, Jefferson, AR 72079 USA. RP Manautou, JE (reprint author), Univ Connecticut, Sch Pharm, Dept Pharmaceut Sci, Toxicol Program, 69 N Eagleville Rd Unit 3092, Storrs, CT 06269 USA. EM jose.manautou@uconn.edu FU NIDDK NIH HHS [R01 DK069557-01A1, DK069557, R01 DK069557] NR 46 TC 19 Z9 21 U1 1 U2 7 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 2007 VL 222 IS 2 BP 169 EP 179 DI 10.1016/j.taap.2007.04.008 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 195GR UT WOS:000248401000005 PM 17585979 ER PT J AU Azurmendi, HF Vionnet, J Wrightson, L Trinh, LB Shiloach, J Freedberg, DI AF Azurmendi, Hugo F. Vionnet, Justine Wrightson, Lauren Trinh, Loc B. Shiloach, Joseph Freedberg, Daron I. TI Extracellular structure of polysialic acid explored by on cell solution NMR SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE carbohydrate structure; isotopically labeled carbohydrates; in vivo kinetics; triple resonance NMR ID ESCHERICHIA-COLI K1; B MENINGOCOCCAL POLYSACCHARIDE; MENINGITIDIS GROUP-B; NEISSERIA-MENINGITIDIS; CAPSULAR POLYSACCHARIDE; SEROGROUP-B; SIALIC-ACID; ANTIBODY-RESPONSES; VACCINES; SPECTROSCOPY AB The capsular polysaccharide of the pathogens Neisseria meningitidis serogroup B and of Escherichia coli K1, alpha(2 -> 8) polysialic acid (PSA), is unusual, because when injected into adult humans, it generates little or no antibody. in contrast, people infected with these pathogens generate specific serum antibodies. A structural study on cells is used to address this anomaly by characterizing antigen structures in vivo. We introduce on cell multidimensional solution NMR spectroscopy for direct observation of PSA on E. coli bacteria. Using C-13,N-15-labeled PSA, we applied a combination of heteronuclear NMR methods, such as heteronuclear single quantum coherence, HNICA, and HNCO, in vivo. Analysis reveals that free and cell-bound PSA are structurally similar, indicating that the poor immunogenicity of PSA is not due to major structural differences between cells and purified IPSA. The C-13 linewidths of PSA on cells are 2 to 3 times larger than the corresponding ones in free PSA. The possible implications of the differences between free and on cell PSA are discussed. In addition, we demonstrate the suitability of the method for in vivo kinetic studies. C1 NIDDKD, Biotechnol Unit, MSC 5522, NIH, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res, Food & Drug Adm, Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA. RP Freedberg, DI (reprint author), NIDDKD, Biotechnol Unit, MSC 5522, NIH, Bethesda, MD 20892 USA. EM daron.freedberg@fda.hhs.gov NR 44 TC 29 Z9 30 U1 3 U2 14 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 10 PY 2007 VL 104 IS 28 BP 11557 EP 11561 DI 10.1073/pnas.0704404104 PG 5 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 190MQ UT WOS:000248063400010 PM 17609375 ER PT J AU Wysowski, DK Nourjah, P Swartz, L AF Wysowski, Diane K. Nourjah, Parivash Swartz, Lynette TI Bleeding complications with warfarin use - A prevalent adverse effect resulting in regulatory action SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID EMERGENCY-DEPARTMENT VISITS; DRUG EVENTS; VENOUS THROMBOEMBOLISM; NATIONAL SURVEILLANCE; UNITED-STATES; RISK INDEX; THERAPY; PREVENTION; PREDICTION AB Background: Warfarin sodium is widely used and causes bleeding; a review might suggest the need for regulatory action by the US Food and Drug Administration (FDA). Methods: We accessed warfarin prescriptions from the National Prescription Audit Plus database of IMS Health (Plymouth Meeting, Pennsylvania), adverse event reports submitted to the FDA, deaths due to therapeutic use of anticoagulants from vital statistics data, and warfarin bleeding complications from national hospital emergency department data. Results: The number of dispensed outpatient prescriptions for warfarin increased 45%, from 21 million in 1998 to nearly 31 million in 2004. The FDA's Adverse Event Reporting System indicated that warfarin is among the top 10 drugs with the largest number of serious adverse event reports submitted during the 1990 and 2000 decades. From US death certificates, anticoagulants ranked first in 2003 and 2004 in the number of total mentions of deaths for drugs causing "adverse effects in therapeutic use." Data from hospital emergency departments for 1999 through 2003 indicated that warfarin was associated with about 29 000 visits for bleeding complications per year, and it was among the drugs with the most visits. These data are consistent with literature reports of major bleeding frequencies for warfarin as high as 10% to 16%. Conclusions: Use of warfarin has increased, and bleeding from warfarin use is a prevalent reaction and an important cause of mortality. Consequently, a "black box" warning about warfarin's bleeding risk was added to the US product labeling in 2006. Physicians and nurses should tell patients to immediately report signs and symptoms of bleeding. A Medication Guide, which is required to be provided with each prescription, reinforces this message. C1 US FDA, Div Drug Risk Evaluat, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Wysowski, DK (reprint author), US FDA, Div Drug Risk Evaluat, Off Surveillance & Epidemiol, Bldg 22,Room 3424,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM diane.wysowski@fda.hhs.gov NR 34 TC 296 Z9 318 U1 0 U2 6 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD JUL 9 PY 2007 VL 167 IS 13 BP 1414 EP 1419 DI 10.1001/archinte.167.13.1414 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 188AT UT WOS:000247891500012 PM 17620536 ER PT J AU Woo, EJ Ball, R Braun, MM AF Woo, Emily Jane Ball, Robert Braun, M. Miles TI Varicella-zoster vaccine SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. RP Woo, EJ (reprint author), US FDA, Rockville, MD 20852 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUL 5 PY 2007 VL 357 IS 1 BP 88 EP 88 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 185OR UT WOS:000247720800029 PM 17611214 ER PT J AU Bi, LL Pan, G Atkinson, TP Zheng, LX Dale, JK Makris, C Reddy, V McDonald, JM Siegel, RM Puck, JM Lenardo, MJ Straus, SE AF Bi, Lilia L. Pan, George Atkinson, T. Prescott Zheng, Lixin Dale, Janet K. Makris, Christopher Reddy, Vishnu McDonald, Jay M. Siegel, Richard M. Puck, Jennifer M. Lenardo, Michael J. Straus, Stephen E. TI Dominant inhibition of Fas ligand-mediated apoptosis due to a heterozygous mutation associated with autoimmune lymphoproliferative syndrome (ALPS) Type Ib SO BMC MEDICAL GENETICS LA English DT Article ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; GENE POLYMORPHISMS; BREAST-CANCER; T-LYMPHOCYTES; DISEASE; DEFECTS; VARIANT; CELLS; CASPASE-10; FAMILIES AB Background: Autoimmune lymphoproliferative syndrome (ALPS) is a disorder of lymphocyte homeostasis and immunological tolerance due primarily to genetic defects in Fas (CD95/APO-1; TNFRSF6), a cell surface receptor that regulates apoptosis and its signaling apparatus. Methods: Fas ligand gene mutations from ALPS patients were identified through cDNA and genomic DNA sequencing. Molecular and biochemical assessment of these mutant Fas ligand proteins were carried out by expressing the mutant FasL cDNA in mammalian cells and analysis its effects on Fas- mediated programmed cell death. Results: We found an ALPS patient that harbored a heterozygous A530G mutation in the FasL gene that replaced Arg with Gly at position 156 in the protein's extracellular Fas-binding region. This produced a dominant-interfering FasL protein that bound to the wild-type FasL protein and prevented it from effectively inducing apoptosis. Conclusion: Our data explain how a naturally occurring heterozygous human FasL mutation can dominantly interfere with normal FasL apoptotic function and lead to an ALPS phenotype, designated Type Ib. C1 NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NIAID, Lab Clin Infect Dis, NIH, Bethesda, MD 20892 USA. NIAMS, Autoimmun Branch, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Pediat, San Francisco, CA 94143 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Pediat, Birmingham, AL 35294 USA. Birmingham Vet Adm Med Ctr, Birmingham, AL USA. RP Bi, LL (reprint author), NIAID, Immunol Lab, NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. EM bi@cber.fda.gov; gpan@uab.edu; PAtkinson@peds.uab.edu; LZHENG@niaid.nih.gov; JDALE@niaid.nih.gov; cmakris@uab.edu; vreddy@uab.edu; mcdonald@uab.edu; SiegelR@mail.nih.gov; puckj@peds.ucsf.edu; lenardo@nih.gov; LZHENG@niaid.nih.gov RI Siegel, Richard/C-7592-2009; OI Siegel, Richard/0000-0001-5953-9893; Reddy, Vishnu/0000-0001-5474-3289 FU Intramural NIH HHS NR 40 TC 36 Z9 36 U1 1 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2350 J9 BMC MED GENET JI BMC Med. Genet. PD JUL 2 PY 2007 VL 8 AR 41 DI 10.1186/1471-2350-8-41 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 196KF UT WOS:000248479500001 PM 17605793 ER PT J AU Chang, WT Shao, ZH Yin, JJ Mehendale, S Wang, CZ Qin, YM Li, J Chen, WJ Chien, CT Becker, LB Hoek, TLV Yuan, CS AF Chang, Wei-Tien Shao, Zuo-Hui Yin, Jun-Jie Mehendale, Sangeeta Wang, Chong-Zhi Qin, Yimin Li, Juan Chen, Wen-Jone Chien, Chiang-Ting Becker, Lance B. Hoek, Terry L. Vanden Yuan, Chun-Su TI Comparative effects of flavonoids on oxidant scavenging and ischemia-reperfusion injury in cardiomyocytes SO EUROPEAN JOURNAL OF PHARMACOLOGY LA English DT Article DE flavonoids; reperfusion injury; scavenging capacity; superoxide; hydroxyl radical ID CORONARY HEART-DISEASE; ANTIOXIDANT ACTIVITY; SIMULATED ISCHEMIA; CHICK CARDIOMYOCYTES; LIPID-PEROXIDATION; DNA-DAMAGE; CELL-DEATH; RECOVERY; GENERATION; PROTECTION AB Since flavonoids scavenge reactive oxygen species, they may potentially protect against ischemia/reperfusion injury. This study compared the scavenging capacity of specific flavonoids towards different reactive oxygen species. Whether the differential oxidant scavenging capacity correlated with their protective efficacy in ischemia/reperfusion injury of cardiomyocytes was determined. The free radical scavenging capacity of five flavonoids (wogonin, baicalin, baicalein, catechin and procyanidin B-2) was analyzed using electron spin resonance spectrometry for 3 radicals: 1, 1-diphenyl-2picrylhydrazyl (DPPH), superoxide and hydroxyl radical. A well-established chick cardiomyocyte model of ischemia (1 h)/reperfusion (3 h) was used to evaluate flavonoid-induced protection against ischemia/reperfusion injury in chronic treatment (pretreated 72 h and treated through ischemia/reperfusion) and acute treatment protocols (during ischemia/reperfusion or only at reperfusion). The cell viability was assessed by propidium iodide. The DPPH scavenging was most significant with catechin, followed by procyanidin B-2, baicalein, baicalin, and wogonin. The superoxide scavenging was, similarly, most significant with catechin, followed by baicalein, procyanidin B-2, and baicalin. For hydroxyl radical, only baicalein showed a significant scavenging capacity (> 50% reduction in ESR signal). For the cardiomyocyte studies, all flavonoids but wogonin showed protection against ischemia/reperfusion injury in the chronic treatment protocol. When flavonoids were administered only during ischemia/reperfusion, baicalein, procyanidin B-2, and catechin significantly reduced cell death. If flavonoids were administered just at reperfusion, only baicalein and procyanidin B-2 had protective effects, and the efficacy was less. Flavonoids possess specific but differential radical scavenging capacity, which, in conjunction with the timing of treatment, affects their protective efficacy in cardiomyocytes exposed to ischemia/reperfusion. (c) 2007 Elsevier B.V. All rights reserved. C1 Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. Univ Chicago, Emergency Resuscitat Ctr, Dept Med, Sect Emergency Med, Chicago, IL 60637 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Univ Chicago, Dept Anesthesia & Crit Care, Chicago, IL 60637 USA. Natl Taiwan Univ Hosp, Natl Taiwan Univ Coll Med, Dept Emergency Med, Taipei, Taiwan. Natl Taiwan Univ Hosp, Natl Taiwan Univ Coll Med, Dept Med Res, Taipei, Taiwan. RP Yuan, CS (reprint author), Univ Chicago, Dept Anesthesia & Crit Care, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM cyuan@airway.uchicago.edu RI Yin, Jun Jie /E-5619-2014; OI CHEN, WEN-JONE/0000-0002-2098-5922 FU NCCIH NIH HHS [AT002176, AT01575-01, R21 AT002176-02, R21 AT003255, AT003255, R21 AT001575, R21 AT002176, R21 AT003255-02]; NHLBI NIH HHS [HL68951, HL72734, U01 HL072734, R01 HL068951] NR 41 TC 64 Z9 69 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-2999 J9 EUR J PHARMACOL JI Eur. J. Pharmacol. PD JUL 2 PY 2007 VL 566 IS 1-3 BP 58 EP 66 DI 10.1016/j.ejphar.2007.03.037 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 179HY UT WOS:000247281600008 PM 17475241 ER PT J AU Powell, RLR Zhao, JQ Konings, FAJ Tang, SX Ewane, L Burda, S Urbanski, MM Saa, DR Hewlett, I Nyambi, PN AF Powell, Rebecca L. R. Zhao, Jiangqin Konings, Frank A. J. Tang, Shixing Ewane, Leonard Burda, Sherri Urbanski, Mateusz M. Saa, D. R. Hewlett, Indira Nyambi, Phillipe N. TI Circulating recombinant form (CRF) 37_cpx: An old strain in Cameroon composed of diverse, genetically distant lineages of subtypes A and G SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; EQUATORIAL RAIN-FORESTS; INTERSUBTYPE RECOMBINANT; SEQUENCE ALIGNMENT; RURAL VILLAGES; HIV-1; DYNAMICS; SUBSTITUTION; INFECTION; CRF02-AG AB HIV-1 in Cameroon is genetically diverse, but is predominated by the circulating recombinant form (CRF) 02_AG, which cocirculates among an array of other CRFs, unique recombinant forms (URFs), and all group M subtypes. In particular, our studies of HIV-1 diversity in the East Province found a high proportion of URFs and second generation recombinants (SGRs), suggesting this region of Cameroon may be a breading ground for new CRFs. Herein we present the full-length sequence analysis of one such CRF, composed primarily (66%) of unique, distant lineages of subtypes A and G in alternating regions throughout the genome. This CRF also combines segments in pol and env genes possessing intrasubtype distance (< 15%) to the CRF01_AE and CRF02_AG radiations. The genomic composition of this strain comprising gene segments of subtypes A and G as well as CRF01_AE and CRF02_AG defines this strain as a circulating SGR (CSGR), and the 37th CRF to be identified. Furthermore, more than half of CRF19_cpx, a CRF identified in Cuba, clusters with CRF37_cpx, and the clear genetic distance among the viruses in this cluster suggests this strain has been in circulation since the early days of the epidemic. The genetically distant segments comprising CRF37_cpx, which were found to cluster outside the crown groups of previously described viruses, may represent a link to very rare or extinct strains, and, potentially, to understanding the evolutionary history of HIV-1 in this region. C1 NYU, Sch Med, Dept Pathol, VA Med Ctr, New York, NY 10010 USA. NYU, Sch Med, Dept Microbiol, New York, NY 10010 USA. US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20014 USA. Lab Sante Hyg Mobile, Yaounde, Cameroon. Minist Publ Hlth, Yaounde, Cameroon. Vet Affairs New York Harbor Healtcare Syst, New York, NY USA. RP Nyambi, PN (reprint author), NYU, Sch Med, Dept Pathol, VA Med Ctr, 423 E 23rd St,Room 18124N, New York, NY 10010 USA. EM phillipe.nyambi@med.nyu.edu FU FIC NIH HHS [TW01254, TW01409]; NHLBI NIH HHS [BY1-HB-5026-01]; NIAID NIH HHS [AI027742-17, AI47053] NR 25 TC 25 Z9 26 U1 1 U2 1 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUL PY 2007 VL 23 IS 7 BP 923 EP 933 DI 10.1089/aid.2007.0040 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 197GG UT WOS:000248542000012 PM 17678477 ER PT J AU Wysowski, DK Pollock, ML AF Wysowski, Diane K. Pollock, Martin L. TI Propofol infusion syndrome: Is there any more information? - In reply SO ANESTHESIOLOGY LA English DT Letter C1 US FDA, Silver Spring, MD USA. RP Wysowski, DK (reprint author), US FDA, Silver Spring, MD USA. EM diane.wysowski@fda.hhs.gov NR 2 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-3022 J9 ANESTHESIOLOGY JI Anesthesiology PD JUL PY 2007 VL 107 IS 1 BP 176 EP 176 DI 10.1097/01.anes.0000268529.30494.07 PG 1 WC Anesthesiology SC Anesthesiology GA 184AK UT WOS:000247613300039 ER PT J AU Schaer, DJ Alayash, AI Buehler, PW AF Schaer, Dominik J. Alayash, Abdu I. Buehler, Paul W. TI Gating the radical hemoglobin to macrophages: The anti-inflammatory role of CD163, a scavenger receptor SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID GLUCOCORTICOID-INDUCIBLE MEMBER; CHEMICALLY-MODIFIED HEMOGLOBINS; CROSS-LINKED HEMOGLOBIN; CYSTEINE-RICH FAMILY; SICKLE-CELL-DISEASE; ENDOTHELIAL-CELLS; HUMAN MONOCYTES; HEME OXYGENASE; HAPTOGLOBIN; IDENTIFICATION AB Efficient extracellular hemoglobin (Hb) clearance is essential to prevent oxidative- and nitrosative-mediated toxicity. CD163 belongs to group B of the scavenger receptor cysteine-rich (SRCR) protein family found on the surface of monocytes and macrophages and is responsible for Hb-haptoglobin (Hp) complex uptake. Hb uptake by CD163 was thought to proceed exclusively through an Hp-dependent pathway. However, Hb can interact directly with CD163 via a low affinity binding when Hp is absent. As a result, a two-phase hypothesis of Hb clearance by monocytes/macrophages suggests that Hp-Hb binding to CD163 is the primary mechanism of plasma Hb clearance, while clearance of Hb by direct binding to CD163 is secondary to Hp depletion. The authors have considered the ligand specificity of CD163 in human macrophages and in a heterologous gene expression model to demonstrate that Hb is effectively endocytosed by CD163 in the absence of Hp. Additionally, the authors have considered Hb-based oxygen carriers (HBOCs) administration as a unique situation during which direct CD163 uptake may be relevant as a mechanism of clearance. However, the nature of chemical modifications introduced onto the Hb molecule and/or oxidative changes induced in the protein appear to influence the extent of CD163 interaction and cellular uptake. Here, an overview and novel insights into the role of CD163 in Hb redox inactivation and clearance are provided. C1 Univ Zurich, Med Clin B, Res Unit, CH-8006 Zurich, Switzerland. US FDA, Ctr Biol Evaluat & Res, Div Hematol, Lab Biochem & Vasc Biol, Bethesda, MD 20014 USA. RP Alayash, AI (reprint author), Univ Zurich, Med Clin B, Res Unit, CH-8006 Zurich, Switzerland. EM alayash@cber.fda.gov NR 50 TC 54 Z9 55 U1 0 U2 5 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUL PY 2007 VL 9 IS 7 BP 991 EP 999 DI 10.1089/ars.2007.1576 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 170EW UT WOS:000246646200018 PM 17508920 ER PT J AU Kothary, MH McCardell, BA Frazar, CD Deer, D Tall, BD AF Kothary, M. H. McCardell, B. A. Frazar, C. D. Deer, D. Tall, B. D. TI Characterization of the zinc-containing metalloprotease encoded by zpx and development of a species-specific detection method for Enterobacter sakazakii SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; VIBRIO-VULNIFICUS; CELLULAR LOCATION; ERWINIA-AMYLOVORA; PROTEASE; GENE; PURIFICATION; ENTEROTOXIN; IDENTIFICATION; ENVIRONMENTS AB Enterobacter sakazakii causes a severe form of neonatal meningitis that occurs as sporadic cases as well as outbreaks. The disease has been epidemiologically associated with consumption of reconstituted, dried infant formulas. Very little information is available regarding pathogenicity of the organism and production of virulence factors. Clinical and environmental strains were screened for production of factors which have activity against Chinese hamster ovary (CHO) cells in tissue culture. Polymyxin B lysate and sonicate preparations but not culture supernatants from the strains caused "rounding" of CHO cells. Subsequent studies showed that the CHO cell-rounding factor is a proteolytic enzyme that has activity against azocasein. The cell-bound protease was isolated by using a combination of polymyxin B lysis, followed by sonication of cells harvested from tryptone broth. The protease was purified to homogeneity by sequential ammonium sulfate precipitation, gel filtration chromatography with Sephadex G-100, hydrophobic interaction chromatography with phenyl-Sepharose CL-411, and a second gel filtration with Sephadex G-100. In addition to activity against azocasein, the purified protease also exhibits activity against azocoll and insoluble casein but not elastin. The protease has a molecular weight of 38,000 and an isoelectric point of 4.4. It is heat labile and for maximal activity against azocasein has an optimum temperature of 37 degrees C and a pH range of 5 to 7. Proteolytic activity is inhibited by ortho-phenanthroline and Zincov but is not affected by phenylmethylsulfonyl fluoride, N-ethylmaleimide, and trypsin inhibitors, which demonstrates that the protease is a zinc-containing metalloprotease. The metalloprotease does not hemagglutinate chicken or sheep erythrocytes. Twenty-three to 27 of the first 42 N-terminal amino acid residues of the metalloprotease are identical to proteases produced by Serratia proteamaculans, Pectobacterium carotovorum, and Anabaena sp. PCR analysis using primers designed from a consensus nucleotide sequence showed that 135 E. sakazakii strains possessed the metalloprotease gene, zpx, and 25 non-E. sakazakii strains did not. The cloned zpx gene of strain 29544 consists of 1,026 nucleotides, and the deduced amino acid sequence of the metalloprotease has 341 amino acid residues, which corresponds to a theoretical protein size of 37,782 with a theoretical pI of 5.23. The sequence possesses three well-characterized zinc-binding and active-site motifs present in other bacterial zinc metalloproteases. C1 US FDA, Ctr Food Safety & Appl Nutr, OARSA,Div Virulence Assessment, Virulence Mech Branch HFS025, Laurel, MD 20708 USA. RP Kothary, MH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, OARSA,Div Virulence Assessment, Virulence Mech Branch HFS025, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM mahendra.kothary@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629 NR 35 TC 51 Z9 54 U1 5 U2 15 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2007 VL 73 IS 13 BP 4142 EP 4151 DI 10.1128/AEM.02729-06 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 190PA UT WOS:000248070000007 PM 17483271 ER PT J AU Gelderman, MP Schiffmann, R Simak, J AF Gelderman, Monique P. Schiffmann, Raphael Simak, Jan TI Elevated endothelial microparticles in fabry children decreased after enzyme replacement therapy SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Letter ID DISEASE; TRIAL C1 FDA, CBER, Rockville, MD USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Gelderman, MP (reprint author), FDA, CBER, Rockville, MD USA. RI Simak, Jan/C-1153-2011 NR 6 TC 14 Z9 14 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUL PY 2007 VL 27 IS 7 BP E138 EP E139 DI 10.1161/ATVBAHA.107.143511 PG 2 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 180XN UT WOS:000247401400027 PM 17581828 ER PT J AU Woo, EJ Ball, R Landa, R Zimmerman, AW Braun, MM AF Woo, Emily Jane Ball, Robert Landa, Rebecca Zimmerman, Andrew W. Braun, M. Miles CA VAERS Working Grp TI Developmental regression and autism reported to the vaccine adverse event reporting system SO AUTISM LA English DT Article DE adverse event; autism; regression; vaccine ID RUBELLA VACCINATION; CAUSAL ASSOCIATION; THIMEROSAL EXPOSURE; UNITED-KINGDOM; DISORDERS; POPULATION; MEASLES; MUMPS; CHILDREN; INFANTS AB We report demographic and clinical characteristics of children reported to the US Vaccine Adverse Event Reporting System (VAERS) as having autism or another developmental disorder after vaccination. We completed 124 interviews with parents and reviewed medical records for 31 children whose records contained sufficient information to evaluate the child's developmental history. Medical record review indicated that 2 7 of 3 1 (87%) children had autism/ASD and 19 (61.3%) had evidence of developmental regression (loss of social, language, or motor skills). The proportion of VAERS cases of autism with regression was greater than that reported in population based studies, based on the subset of VAERS cases with medical record confirmation. This difference may reflect preferential reporting to VAERS of autism with regression. In other respects, the children in this study appear to be similar to other children with autism. Further research might determine whether the pathogenesis of autism with developmental regression differs from that of autism without regression. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Johns Hopkins Univ, Kennedy Krieger Inst, Baltimore, MD 21218 USA. RP Woo, EJ (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-222,1401 Rockville Pike, Rockville, MD 20852 USA. EM jane.woo@fda.hhs.gov NR 34 TC 4 Z9 4 U1 1 U2 7 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 1362-3613 J9 AUTISM JI Autism PD JUL PY 2007 VL 11 IS 4 BP 301 EP 310 DI 10.1177/1362361307078126 PG 10 WC Psychology, Developmental SC Psychology GA 201RJ UT WOS:000248850000002 PM 17656395 ER PT J AU Hanson, MA Ge, XD Kostov, Y Brorson, KA Moreira, AR Rao, G AF Hanson, Michael A. Ge, Xudong Kostov, Yordan Brorson, Kurt A. Moreira, Antonio R. Rao, Govind TI Comparisons of optical pH and dissolved oxygen sensors with traditional electrochemical probes during mammalian cell culture SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE optical sensor; electrochemical probe; mammalian; cell culture; process monitoring; scale-up ID ANTIBODY-PRODUCTION KINETICS; MONOCLONAL-ANTIBODY; CHO-CELLS; SHAKE FLASKS; GLYCOSYLATION; EXPRESSION; GROWTH; MICROBIOREACTOR; FERMENTATION; PROTEINS AB Small-scale upstream bioprocess development often occurs in flasks and multi-well plates. These culturing platforms are often not equipped to accurately monitor and control critical process parameters; thus they may not yield conditions representative of manufacturing. In response, we and others have developed optical sensors that enable small-scale process monitoring. Here we have compared two parameters critical to control in industrial cell culture, pH and dissolved oxygen (DO), measured with our optical sensors versus industrially accepted electrochemical probes. For both optical sensors, agreement with the corresponding electrochemical probe was excellent. The Pearson Correlations between the optical sensors and electrochemical probes were 98.7% and 99.7010, for DO and pH, respectively. Also, we have compared optical pH sensor performance in regular (320 mOsm/kg) and high-osmolality (450 mOsm/kg) cell culture media to simulate the increase in osmolality in pH-controlled cultures. Over a pH range of 6.38-7:98 the average difference in pH readings in the two media was 0.04 pH units. In summary, we have demonstrated that these optical sensors agree well with standard electrochemical probes. The accuracy of the optical probes demonstrates their ability to detect potential,parameter drift that could have significant impact. on growth, production kinetics, and protein product quality. We have also shown that an increase in osmolality that could result from controlling pH or operating the reactor in fed-batch mode has an insignificant impact on the functionality of the pH patches. Biotechnol. C1 Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Rockville, MD 20857 USA. RP Rao, G (reprint author), Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Dept Chem & Biochem Engn, 1000 Hilltop Citcle, Baltimore, MD 21250 USA. EM grao@umbc.edu NR 30 TC 58 Z9 59 U1 3 U2 24 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD JUL 1 PY 2007 VL 97 IS 4 BP 833 EP 841 DI 10.1002/bit.21320 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 177NC UT WOS:000247158800017 PM 17216654 ER PT J AU Anderson, KC Hannah, AL Pazdur, R Farrell, AT AF Anderson, Kenneth C. Hannah, Alison L. Pazdur, Richard Farrell, Ann T. TI A strategic framework for novel drug development in multiple myeloma SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Editorial Material DE multiple myeloma; accelerated approval; surrogate biomarker studies ID CLINICAL-TRIAL; PHASE-II; BORTEZOMIB; DEXAMETHASONE; ONCOLOGY; CANCER C1 Harvard Univ, Sch Med, Dept Med, Div Hematol Neoplasia,Dana Farber Canc Inst, Boston, MA 02115 USA. US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. US FDA, Div Drug Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Anderson, KC (reprint author), Harvard Univ, Sch Med, Dept Med, Div Hematol Neoplasia,Dana Farber Canc Inst, 44 Binney St,Mayer 557, Boston, MA 02115 USA. EM kenneth_anderson@dfci.harvard.edu NR 15 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD JUL PY 2007 VL 138 IS 2 BP 153 EP 159 DI 10.1111/j.1365-2141.2007.06641.x PG 7 WC Hematology SC Hematology GA 181ZV UT WOS:000247475800003 PM 17593022 ER PT J AU Slater, JE James, R Pongracic, JA Liu, AH Sarpong, S Sampson, HA Satinover, SM Woodfolk, JA Mitchell, HE Gergen, PJ Eggleston, PA AF Slater, J. E. James, R. Pongracic, J. A. Liu, A. H. Sarpong, S. Sampson, H. A. Satinover, S. M. Woodfolk, J. A. Mitchell, H. E. Gergen, P. J. Eggleston, P. A. TI Biological potency of German cockroach allergen extracts determined in an inner city population SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE allergen; asthma; cockroach; immunotherapy; standardization ID CHILDREN; ASTHMA; EXPOSURE; IGE AB Background Cockroach allergy is an important cause of inner city asthma. To perform valid studies on the diagnosis and treatment of cockroach allergy, biological potencies of test extracts need to be established, and a surrogate in vitro test for biological potency should be chosen. Methods Sixty-two cockroach-allergic adult subjects were recruited for quantitative skin testing with three commercial German cockroach extracts. The intradermal D50 values were determined using linear interpolation, and the biologic potencies were determined from D50 data. The extracts were also analysed for relative potency, using a competition ELISA, and for specific allergen content, using a two-site ELISA. Results Estimates of each extract's D50 were analysable in 48-55 subjects, with D50s between 10.3 and 11.8. All three extracts were bioequivalent using pre-set criteria. The biological potencies of the extracts were 1738-8570 bioequivalent allergy units (BAU)/mL (geometric mean=3300), and these relative potencies were similar to those estimated by competition ELISA and specific allergen content. IgE against cockroach allergens were detected in sera from 34 subjects with analysable D50s, and 17 subjects had IgE directed against specific cockroach allergens. Although the presence of anti-Bla g 5 correlated with the subjects' skin test responses for 2/3 extracts, no single allergen was immunodominant. Antibody responses among the subjects were heterogeneous. Conclusions Although commercial cockroach extracts are relatively low in potency, immunotherapeutic doses should be achievable. Biological potency may be estimated using D50 testing, a combination of specific allergen determinations, or by an overall potency assay such as the competition ELISA. Capsule Summary The biological potency of three German cockroach allergen extracts, determined in an inner city population, was 1738-8570 BAU/mL. No one allergen was immunodominant, and surrogate in vitro testing methods were examined. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Rho Inc, Chapel Hill, NC USA. Childrens Mem Hosp, Chicago, IL 60614 USA. Natl Jewish Med & Res Ctr, Denver, CO USA. Howard Univ, Washington, DC 20059 USA. Mt Sinai Sch Med, New York, NY USA. Univ Virginia, Hlth Syst, Charlottesville, VA 22903 USA. NIAID, NIH, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD 21218 USA. RP Slater, JE (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM jay.slater@fda.hhs.gov NR 20 TC 23 Z9 24 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD JUL PY 2007 VL 37 IS 7 BP 1033 EP 1039 DI 10.1111/j.1365-2222.2007.02751.x PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 180WQ UT WOS:000247398300009 PM 17581196 ER PT J AU Atrasheuskaya, AV Kulak, MV Rubin, S Ignatyev, GM AF Atrasheuskaya, A. V. Kulak, M. V. Rubin, S. Ignatyev, G. M. TI Mumps vaccine failure investigation in Novosibirsk, Russia, 2002-2004 SO CLINICAL MICROBIOLOGY AND INFECTION LA English DT Article DE genotyping; mumps virus; Russia; serology; vaccine failure ID SECONDARY IMMUNE-RESPONSES; IMMUNOGLOBULIN-G; MEASLES-VIRUS; IGG AVIDITY; POPULATION; OUTBREAK; CHILDREN; TRANSMISSION; SWITZERLAND; GENOTYPE AB The aims of this study were to estimate the importance of vaccine failure (VF) in cases of mumps during 2002-2004 in the city of Novosibirsk, Western Siberia, Russia, and to genotype the responsible virus strain. Mumps virus-specific RT-PCR testing of saliva was performed for 18 cases of mumps. Sera were tested for IgM and IgG, IgG avidity, and the ability to neutralise a panel of mumps viruses, including the Leningrad-3 mumps vaccine virus. Of the 12 patients for whom vaccination status was positively determined, 11 showed serological evidence of primary VF. Sequence analysis of virus RNA amplified from saliva revealed a genotype C2 virus in 2002, a genotype H2 virus in 2003, and both genotypes in 2004. Although several vaccinated patients were positive for mumps virus IgG at the time of first sampling, only nominal levels of neutralising antibody were detected, and these were effective in neutralising the vaccine strain, but not genotype C and H mumps virus strains. These results suggest that the majority of cases of mumps in vaccinees are caused by primary VF, defined as either a lack of seroconversion or a lack of IgG maturity, as based on avidity testing. The results also support the hypothesis that sera of low neutralising antibody titre have a limited ability to neutralise heterologous mumps virus strains, suggesting that antigenic differences between circulating and mumps vaccine virus strains may play a role in cases of breakthrough infection. Consistent with previous reports, mumps virus genotypes C and H continue to circulate in Novosibirsk. C1 State Res Ctr Virol & Biotechnol Vector, Lab Immunol Safety, Koltsov 630559, Novosibisrsk, Russia. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Atrasheuskaya, AV (reprint author), State Res Ctr Virol & Biotechnol Vector, Lab Immunol Safety, Koltsov 630559, Novosibisrsk, Russia. EM marburgman3@infonet.by NR 35 TC 15 Z9 19 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1198-743X J9 CLIN MICROBIOL INFEC JI Clin. Microbiol. Infect. PD JUL PY 2007 VL 13 IS 7 BP 670 EP 676 DI 10.1111/j.1469-0691.2007.01727.x PG 7 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 176VY UT WOS:000247114200004 PM 17484765 ER PT J AU Powell, JR Gobburu, JVS AF Powell, J. R. Gobburu, J. V. S. TI Pharmacometrics at FDA: Evolution and impact on decisions SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DRUG DEVELOPMENT; PHARMACOKINETICS AB Drug development and regulatory decisions are driven by information that is compiled primarily from clinical trials and other supportive experiments, but also through clinical experience in the post-market period. The wisdom of these decisions determines the efficiency of drug development, the decision to approve the drug, and the resultant drug product quality including guidance on how to use the product known as the label. Although the decisions are usually simple in nature (e.g., trial design and project progression at the company, product and labeling approval at the Food and Drug Administration (FDA)), the information informing the decision is complex and diverse. C1 US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Silver Spring, MD USA. US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Dept Pharmacometr, Silver Spring, MD USA. RP Powell, JR (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Silver Spring, MD USA. EM robert.powell@fda.hhs.gov NR 10 TC 24 Z9 30 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUL PY 2007 VL 82 IS 1 BP 97 EP 102 DI 10.1038/sj.clpt.6100234 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 179UU UT WOS:000247316400019 PM 17538553 ER PT J AU Katsenelson, N Kanswal, S Puig, M Mostowski, H Verthelyi, D Akkoyunlu, M AF Katsenelson, Nora Kanswal, Sunita Puig, Montserrat Mostowski, Howard Verthelyi, Daniela Akkoyunlu, Mustafa TI Synthetic CpG oligodeoxynucleotides augment BAFF- and APRIL-mediated immunoglobulin secretion SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE a proliferation; inducing ligand; BAFF; CpG; immunoglobulin; TACI ID CELL-ACTIVATING FACTOR; MEMORY B-CELLS; TNF FAMILY; T-CELL; AUTOIMMUNE-DISEASE; MATURATION ANTIGEN; IMMUNE-RESPONSE; RECEPTOR; TACI; DNA AB The B lymphocyte-activating factor belonging to TNF superfamily (BAFF) acts on B lymphocytes through BAFF receptor (BAFF-R), the transmembrane activator, calcium modulator, and cyclophilin ligand interactor (TACI), and the B cell maturation antigen (BCMA). Another cytokine, a proliferation-inducing ligand (APRIL), only binds to TACI and BCMA. In this study, we sought to determine the effect of Toll-like receptor agonists (TLR-A) on the expression of BAFF/APRIL receptors by murine splenic B lymphocytes. CpG oligodeoxynucleotides (ODN) and LPS strongly up-regulated TACI expression, while BAFF-R was only up-regulated by CpG ODN. CpG ODN pretreatment up-regulated TACI expression on follicular and marginal zone B lymphocytes and increased their responses to BAFF- and APRIL-mediated Ig secretion. TACI seemed to be playing a pivotal role in BAFF- or APRIL-induced Ig secretion because B lymphocytes from TACI-knockout mouse or the blocking of TACI with a neutralizing antibody resulted in total inhibition of IgA and IgG secretion in CpG ODN-pretreated and BAFF- or APRIL-stimulated B cells. Thus, CpG ODN-induced increase in TACI expression is likely to play an important role in Ig secretion following activation of B lymphocytes through TLR9. C1 US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Div Bacterial Parasit &Allergen Prod, Rockville, MD 20852 USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, Off Biotechnol Prod, Rockville, MD 20852 USA. RP Akkoyunlu, M (reprint author), US FDA, Lab Bacterial Polysaccharides, Ctr Biol Evaluat & Res, Div Bacterial Parasit &Allergen Prod, 1410 Rockville Pike,HFM-428, Rockville, MD 20852 USA. EM Mustafa.Akkoyunlu@fda.hhs.gov RI Akkoyunlu, Mustafa/I-5712-2012 NR 39 TC 73 Z9 76 U1 0 U2 2 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JUL PY 2007 VL 37 IS 7 BP 1785 EP 1795 DI 10.1002/eji.200636800 PG 11 WC Immunology SC Immunology GA 187DS UT WOS:000247828200011 PM 17557373 ER PT J AU Shabalina, SA Ogurtsov, AY Spiridonov, NA AF Shabalina, S. A. Ogurtsov, A. Y. Spiridonov, N. A. TI Periodic pattern of secondary structures in prokaryotic and eukaryotic mRNAs SO FEBS JOURNAL LA English DT Meeting Abstract CT 32nd Congress of the Federation-of-European-Biochemical-Societies (FEBS) CY JUL 07-12, 2007 CL Vienna, AUSTRIA SP Federat European Biochem Soc C1 [Shabalina, S. A.; Ogurtsov, A. Y.] NIH, Natl Lib Med, NCBI, Bethesda, MD 20892 USA. [Spiridonov, N. A.] FDA, Bethesda, MD USA. RP Shabalina, SA (reprint author), NIH, Natl Lib Med, NCBI, Bldg 10, Bethesda, MD 20892 USA. RI Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014 OI Shabalina, Svetlana/0000-0003-2272-7473; NR 0 TC 1 Z9 1 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1742-464X J9 FEBS J JI FEBS J. PD JUL PY 2007 VL 274 SU 1 BP 366 EP 366 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 264JO UT WOS:000253283801136 ER PT J AU D'Ovidio, KL Trucksess, MW Devries, JW Bean, G AF D'Ovidio, K. L. Trucksess, M. W. Devries, J. W. Bean, G. TI Effects of irradiation on fungi and famonisin B(1) in corn, and of microwave-popping on fumonisins in popcorn SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE fumonisins; popcorn; corn; irradiation; mycotoxins ID GAMMA-IRRADIATION; MAIZE; WHOLESOMENESS; STABILITY; STRAINS; FLAVUS; FOODS AB Fumonisins are metabolites produced in corn primarily by the fungus Fusariuni verticillioides (F moniliforme) and are toxic to humans and animals. Fumonisin B I (FBI) is the primary fumonisin produced and is found frequently in corn kernels, some of which may be used as food or food ingredients. A three-part study was conducted to determine the effects of gamma- and electron beam irradiation on the levels of fumonisins in naturally contaminated field corn, and the effects of microwave-popping on fumonisins in selected, naturally contaminated popcorn. To date, no effective means have been found to reduce consistently mycotoxin levels once foods are contaminated. Aqueous solutions of FBI at various concentrations, samples of whole corn, and samples of ground corn containing known levels of FBI were irradiated with various levels of cobalt and electron beam irradiation. Popcorn samples, taken from the reject streams of popcorn processing, were popped using normal microwave-popping conditions. FBI in aqueous solutions was reduced by 99.7% using a minimal level of irradiation (0.5 kGray). Gamma- and electron beam irradiation did not significantly reduce levels of FB(1) in whole and ground corn. Aspergillus sp., Penicillhan sp. and Fusariuni sp. fungi were totally eliminated at 30 kGray in ground corn and at 100 kGray in whole corn. The normal commercial cleaning processes for microwave popcorn before packaging reduced fumonisins to < 0.03 mu g g(-1) for the cleaned product stream. Microwave popping of popcorn from reject streams of the cleaning operation that contained fumonisins resulted in significant reduction of the mould toxin. C1 US FDA, College Pk, MD USA. Univ Maryland, College Pk, MD 20742 USA. Gen Mills Inc, Medall Labs, Minneapolis, MN USA. RP Trucksess, MW (reprint author), US FDA, College Pk, MD USA. EM mary.trucksess@fda.hhs.gov NR 32 TC 6 Z9 6 U1 2 U2 11 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1944-0049 J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PD JUL PY 2007 VL 24 IS 7 BP 735 EP 743 DI 10.1080/02652030701216453 PG 9 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 184ZO UT WOS:000247681300010 PM 17613059 ER PT J AU Vionnet, J Vann, WF AF Vionnet, Justine Vann, Willie F. TI Successive glycosyltransfer of sialic acid by Escherichia coli K92 polysialyltransferase in elongation of oligosialic acceptors SO GLYCOBIOLOGY LA English DT Article DE capsular polysaccharide; chain extension; polysialyltransferase; processivity; sialic acid ID PERFORMANCE LIQUID-CHROMATOGRAPHY; POLYSIALIC ACID; SERRATIA-MARCESCENS; ENZYMATIC-SYNTHESIS; COLOMINIC ACID; K1; SIALYLTRANSFERASE; EXPRESSION; MECHANISM; SUBSTRATE AB Escherichia coli K92 produces a capsular polysialic acid with alternating alpha 2,8 a2,9 NeuNAc linkages. This polysaccharide is cross-reactive with the neuroinvasive pathogen Neisseria meningitidis Group C. The K92 polysialyltransferase ( PST) catalyzes the synthesis of the polysialic acid with alternating linkages by the transfer of NeuNAc from CMP-NeuNAc to the nonreducing end of the growing polymer. We used afluorescent-based high-performance liquid chromatography assay to characterize the process of chain extension. The PST elongates the acceptor GT3-FCHASE in a biphasic fashion. The initial phase polymers are characterized by accumulation of product containing 1-8 additional sialic acid residues. This phase is followed by a very rapid formation of high-molecular weight (MW) polymer as the accumulated oligosaccharides containing 8-10 sialic acids are consumed. The high-MW polymer contains 90-100 sialic acids and is sensitive to degradation by periodate and K1-5 endoneuraminidase, suggesting that the polymer contains the alternating structure. The polymerization reaction does not appear to be strictly processive, since oligosaccharides of each intermediate size were detected before accumulation of high-molecular weight polymer. Synthesis can be blocked by CMP-9-azido-NeuNAc. These results suggest that the K92 PST forms both a2,8 and alpha 2,9 linkages in a successive and nonprocessive fashion. C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA. RP Vann, WF (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA. EM wvann@helix.nih.gov NR 31 TC 19 Z9 20 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 EI 1460-2423 J9 GLYCOBIOLOGY JI Glycobiology PD JUL PY 2007 VL 17 IS 7 BP 735 EP 743 DI 10.1093/glycob/cwm032 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 191RM UT WOS:000248148900008 PM 17384120 ER PT J AU McDiarmid, MA Engelhardt, SM Oliver, M Gucer, P Wilson, PD Kane, R Cernich, A Kaup, B Anderson, L Hoover, D Brown, L Albertini, R Gudi, R Jacobson-Kram, D Squibb, KS AF McDiarmid, M. A. Engelhardt, S. M. Oliver, M. Gucer, P. Wilson, P. D. Kane, R. Cernich, A. Kaup, B. Anderson, L. Hoover, D. Brown, L. Albertini, R. Gudi, R. Jacobson-Kram, D. Squibb, K. S. TI Health surveillance of gulf war I veterans exposed to depleted uranium: Updating the cohort SO HEALTH PHYSICS LA English DT Article DE exposure; cumulative; uranium; depleted; health effects; excretion; urinary ID CHINESE-HAMSTER OVARY; HUMAN OSTEOBLAST CELLS; DIOXIDE UO2 DUST; LUNG-CANCER RISK; URANYL ACETATE; CHROMOSOME-ABERRATIONS; 5-YEAR INHALATION; HPRT MUTATIONS; LEAD-EXPOSURE; FOLLOW-UP AB A cohort of seventy-four 1991 Gulf War soldiers with known exposure to depleted uranium (DU) resulting from their involvement in friendly-fire incidents with DU munitions is being followed by the Baltimore Veterans Affairs Medical Center. Biennial medical surveillance visits designed to identify uranium-related changes in health have been conducted since 1993. On-going systemic exposure to DU in veterans with embedded metal fragments is indicated by elevated urine uranium (U) excretion at concentrations up to 1,000-fold higher than that seen in the normal population. Health outcome results from the subcohort of this group of veterans attending the 2005 surveillance visit were examined based on two measures of U exposure. As in previous years, current U exposure is measured by determining urine U concentration at the time of their surveillance visit. A cumulative measure of U exposure was also calculated based on each veteran's past urine U concentrations since first exposure in 1991. Using either exposure metric, results continued to show no evidence of clinically significant DU-related health effects. Urine concentrations of retinol binding protein (RBP), a biomarker of renal proximal tubule function, were not significantly different between the low vs. high U groups based on either the current or cumulative exposure metric. Continued evidence of a weak genotoxic effect from the on-going DU exposure as measured at the HPRT (hypoxanthine-guanine phosphoribosyl transferase) locus and suggested by the fluorescent in-situ hybridization (FISH) results in peripheral blood recommends the need for continued surveillance of this population. C1 Univ Maryland, Sch Med, Dept Med, Baltimore, MD 21201 USA. Dept Vet Affairs Med Ctr, Baltimore, MD USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Psychiat, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Anat & Neurobiol, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Pathol, Baltimore, MD 21201 USA. Univ Vermont, Dept Pathol, Burlington, VT 05405 USA. Bioreliance, Rockville, MD USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Engelhardt, SM (reprint author), Occupat Hlth Program, 405 W Redwood St, Baltimore, MD 21201 USA. EM sengelha@medicine.umaryland.edu NR 67 TC 39 Z9 41 U1 0 U2 7 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 JUL PY 2007 VL 93 IS 1 BP 60 EP 73 DI 10.1097/01.HP.0000259850.66969.8c PG 14 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 179DQ UT WOS:000247270100006 PM 17563493 ER PT J AU Wear, KA AF Wear, Keith A. TI The effect of phase cancellation on estimates of calcaneal broadband ultrasound attenuation in vivo SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID BONE-MINERAL DENSITY; QUANTITATIVE HEEL ULTRASOUND; BOVINE CANCELLOUS BONE; HUMAN TRABECULAR BONE; CORTICAL END-PLATE; HIP FRACTURE RISK; MECHANICAL-PROPERTIES; FREQUENCY-DEPENDENCE; ELDERLY-WOMEN; OS CALCIS AB Broadband ultrasonic attenuation (BUA) is a clinically-accepted measurement for prediction of osteoporotic fracture risk. Typical clinical BUA measurements are performed with phase-sensitive receivers and, therefore, can be affected by phase cancellation. In order to separate the effects of conventional attenuation (absorption plus scattering) from phase cancellation, BUA was measured on phantoms with acrylic wedge phase aberrators and on 73 women using both phase sensitive (PS) and phase insensitive (PI) reception. A clinical bone sonometer with a two-dimensional (2-13) receiver array was used. PI BUA measurements on phantoms with acrylic wedge phase aberrators were found to be far more resistant to phase cancellation than PS BUA measurements. In data from 73 women, means and standard deviations for BUA measurements were 81.4 +/- 21.4 dB/MHz (PS) and 67.2 +/- 9.7 dB/MHz (PI). The magnitude of the discrepancy between PS BUA and PI BUA tended to increase with bone mineral density (BMD). C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. EM keith.wear@fda.hhs.gov NR 55 TC 24 Z9 25 U1 0 U2 1 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 EI 1525-8955 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD JUL PY 2007 VL 54 IS 7 BP 1352 EP 1359 DI 10.1109/TUFFC.2007.395 PG 8 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 183NE UT WOS:000247578700009 PM 17718324 ER PT J AU Poly, F Read, T Tribble, DR Baqar, S Lorenzo, M Guerry, P AF Poly, Frederic Read, Timothy Tribble, David R. Baqar, Shahida Lorenzo, Maria Guerry, Patricia TI Genome sequence of a clinical isolate of Campylobacter jejuni from Thailand SO INFECTION AND IMMUNITY LA English DT Article ID HELICOBACTER-PYLORI; DNA MICROARRAY; VIRULENCE; INFECTION; IDENTIFICATION; FLAGELLIN; BIOSYNTHESIS; PATHOGENESIS; DIVERSITY; RESPONSES AB Campylobacter jejuni CG8486, which belongs to the HS4 complex, was isolated from a patient with inflammatory diarrhea in Thailand. This strain caused a diarrheal disease in ferrets comparable to that caused by C. jejuni strain 81-176, but it was much less invasive for epithelial cells in vitro than 81-176. Complete genome sequencing of CG8486 revealed a 1.65-Mb genome that was very similar to the other two published genomes of clinical isolates of C. jejuni, the genomes of 81-176 and NCTC 11168, with a limited number of CG8486-specific genes mapping outside the hypervariable carbohydrate biosynthesis loci. These data suggest that the genes required for induction of inflammatory diarrhea are among the genes shared by CG8486 and 81-176 but that either major changes in the carbohydrate loci and/or more subtle changes in other genes may modulate virulence. C1 Enter Dis & Biol Def Res Directorate, Silver Spring, MD USA. US FDA, Beltsville, MD USA. RP Guerry, P (reprint author), Naval Med Res Ctr, Enter Dis Dept, 503 Robert Grant Ave, Silver Spring, MD 20906 USA. EM guertyp@nmrc.navy.mil RI Read, Timothy/E-6240-2011; Guerry, Patricia/A-8024-2011 NR 43 TC 60 Z9 60 U1 0 U2 5 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 JUL PY 2007 VL 75 IS 7 BP 3425 EP 3433 DI 10.1128/IAI.00050-07 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 185JP UT WOS:000247707600022 PM 17438034 ER PT J AU Machuca, A Tang, SX Hu, JJ Lee, S Wood, O Vockley, C Vutukuri, SG Deshmukh, R Awazi, B Hewlett, I AF Machuca, Ana Tang, Shixing Hu, Jinjie Lee, Sherwin Wood, Owen Vockley, Christopher Vutukuri, Suresh Gupta Deshmukh, Ranjana Awazi, Bih Hewlett, Indira TI Increased genetic diversity and intersubtype recombinants of HIV-1 in blood donors from urban Cameroon SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Letter ID TYPE-1; IDENTIFICATION; CRF02-AG; STRAINS; AFRICA C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Mol Virol Lab, Bethesda, MD 20014 USA. Haffkine Inst, Bombay, Maharashtra, India. Adm Hlth, Lab Sante, Mobile Lab Sanitat & Hyg, Yaounde, Cameroon. RP Machuca, A (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Mol Virol Lab, Bethesda, MD 20014 USA. NR 8 TC 14 Z9 14 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1525-4135 J9 JAIDS-J ACQ IMM DEF JI JAIDS PD JUL 1 PY 2007 VL 45 IS 3 BP 361 EP 363 DI 10.1097/QAI.0b013e318053754c PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 183KY UT WOS:000247572900018 PM 17592338 ER PT J AU Trucksess, MW Weaver, CM Oles, CJ Rump, LV White, KD Betz, JM Rader, JI AF Trucksess, Mary W. Weaver, Carol M. Oles, Carolyn J. Rump, Lydia V. White, Kevin D. Betz, Joseph M. Rader, Jeanne I. TI Use of multitoxin immunoaffinity columns for determination of aflatoxins and ochratoxin a in ginseng and ginger SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHY; MEDICINAL HERBS; TURKEY; CONTAMINATION; PERFORMANCE; MYCOTOXINS; EXTRACTS; CLEANUP; PLANTS; ROOTS AB Conditions were optimized for the simultaneous, alkaline, aqueous methanol extraction of aflatoxins (AFL), i.e., B-1 (AFB(1)), B-2 (AFB(2)), Gi (AFG(1)), and G(2) (AFG(2)), and ochratoxin A (OTA) with subsequent purification, isolation, and determination of the toxins in ginseng and ginger. Powdered roots were extracted with methanol-0.5% NaHCO3 solution (7 + 3). After shaking and centrifugation, the supernatant was diluted with 100 mM phosphate buffer containing 1 % Tween 20 and filtered through glass microfiber filter paper. The filtrate was then passed through an immunoaffinity column, and the toxins were eluted with methanol. The AFL were separated and determined by reversed-phase liquid chromatography (RPLC) with fluorescence detection after postcolumn UV photochemical derivatization. OTA was separated and determined by RPLC with fluorescence detection. Recoveries of AFL added at 2-16 ng/g and OTA added at 1-8 ng/g to ginseng were 72-80 and 86-95%, respectively. Recoveries of AFL and OTA added to ginger were similar to those for ginseng. A total of 39 commercially available ginger products from 6 manufacturers were analyzed. Twenty-six samples were found to be contaminated with AFL at 1-31 ng/g and 29 samples, with OTA at 1-10 ng/g. Ten samples contained no AFL or 07A. Ten ginseng finished products were also analyzed; 3 contained AFL at 0.1 ng/g and 4 contained CITA at levels ranging from 0.4 to 1.8 ng/g. LC/tandem mass spectrometry with multiple-reaction monitoring of 3 collisionally induced product ions from the protonated molecular ions of OTA, AFB(1), and AFG(1) was used to confirm the identities of the toxins in extracts of the finished products. C1 US FDA, College Pk, MD 20740 USA. Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Trucksess, MW (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mary.trucksess@fda.hhs.gov NR 16 TC 24 Z9 25 U1 1 U2 9 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2007 VL 90 IS 4 BP 1042 EP 1049 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 196YT UT WOS:000248520200025 PM 17760342 ER PT J AU Whitaker, TB Saltsman, JJ Ware, GM Slate, AB AF Whitaker, Thomas B. Saltsman, Joyce J. Ware, George M. Slate, Andrew B. TI Evaluating the performance of sampling plans to detect hypoglycin A in ackee fruit shipments imported into the United States SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TESTING SHELLED CORN; AFLATOXIN; VARIABILITY; LEVEL AB Hypoglycin A (HGA) is a toxic amino acid that is naturally produced in unripe ackee fruit. In 1973, the U.S. Food and Drug Administration (FDA) placed a worldwide import alert on ackee fruit, which banned the product from entering the United States. The FDA has considered establishing a regulatory limit for HGA and lifting the ban, which will require development of a monitoring program. The establishment of a regulatory limit for HGA requires the development of a scientifically based sampling plan to detect HGA in ackee fruit imported into the United States. Thirty-three lots of ackee fruit were sampled according to an experimental protocol in which 10 samples, i.e., ten 19 oz cans, were randomly taken from each lot and analyzed for HGA by using liquid chromatography. The total variance was partitioned into sampling and analytical variance components, which were found to be a function of the HGA concentration. Regression equations were developed to predict the total, sampling, and analytical variances as a function of HGA concentration. The observed HGA distribution among the test results for the 10 HGA samples was compared with the normal and lognormal distributions. A computer model based on the lognormal distribution was developed to predict the performance of sampling plan designs to detect HGA in ackee fruit shipments. The performance of several sampling plan designs was evaluated to demonstrate how to manipulate sample size and accept/reject limits to reduce misclassification of ackee fruit lots. C1 N Carolina State Univ, USDA, ARS, Raleigh, NC 27695 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Food Safety, College Pk, MD 20740 USA. US FDA, Atlanta, GA 30309 USA. N Carolina State Univ, Dept Agr & Biol Engn, Raleigh, NC 27695 USA. RP Whitaker, TB (reprint author), N Carolina State Univ, USDA, ARS, Box 7625, Raleigh, NC 27695 USA. EM Tom_Whitaker@ncsu.edu NR 20 TC 7 Z9 7 U1 1 U2 2 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JUL-AUG PY 2007 VL 90 IS 4 BP 1060 EP 1072 PG 13 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 196YT UT WOS:000248520200027 PM 17760344 ER PT J AU Kweon, O Kim, SJ Jones, RC Freeman, JP Adjei, MD Edmondson, RD Cerniglia, CE AF Kweon, Ohgew Kim, Seong-Jae Jones, Richard C. Freeman, James P. Adjei, Michael D. Edmondson, Ricky D. Cerniglia, Carl E. TI A polyomic approach to elucidate the fluoranthene-degradative pathway in Mycobacterium vanbaalenii PYR-1 SO JOURNAL OF BACTERIOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; SP STRAIN PYR-1; PYRENE-DEGRADING MYCOBACTERIUM; RING FISSION-PRODUCTS; MOLECULAR CHARACTERIZATION; CHLOROPHYLL FLUORESCENCE; MICROBIAL-METABOLISM; IDENTIFICATION; BACTERIUM; FLUORENE AB Mycobacterium vanbaalenii PYR-1 is capable of degrading a wide range of high-molecular-weight polycyclic aromatic hydrocarbons (PAHs), including fluoranthene. We used a combination of metabolomic, genomic, and proteomic technologies to investigate fluoranthene degradation in this strain. Thirty-seven fluoranthene metabolites including potential isomers were isolated from the culture medium and analyzed by high-performance liquid chromatography, gas chromatography-mass spectrometry, and LN-visible absorption. Total proteins were separated by one-dimensional gel and analyzed by liquid chromatography-tandem mass spectrometry in conjunction with the M. vanbaalenii PYR-1 genome sequence (http://jgi.doe.gov), which resulted in the identification of 1,122 proteins. Among them, 53 enzymes were determined to be likely involved in fluoranthene degradation. We integrated the metabolic information with the genomic and proteomic results and proposed pathways for the degradation of fluoranthene. According to our hypothesis, the oxidation of fluoranthene is initiated by dioxygenation at the C-1,2, C-2,3, and C-7,8 positions. The C-1,2 and C-2,3 dioxy. genation routes degrade fluoranthene via fluorene-type metabolites, whereas the C-7,8 routes oxidize fluoranthene via acenaphthylene-type metabolites. The major site of dioxygenation is the C-2,3 dioxygenation route, which consists of 18 enzymatic steps via 9-fluorenone-1-carboxylic acid and phthalate with the initial ring-hydroxylating oxygenase, NidA3B3, oxidizing fluoranthene to fluoranthene cis-2,3-dihydrodiol. Nonspecific monooxygenation of fluoranthene with subsequent 0 methylation of dihydroxyfluoranthene also occurs as a detoxification reaction. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Dept Publ Hlth, Norfolk, VA 23510 USA. US FDA, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Div Syst Toxicol, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM carl.cerniglia@fda.hhs.gov NR 65 TC 47 Z9 51 U1 1 U2 25 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 2007 VL 189 IS 13 BP 4635 EP 4647 DI 10.1128/JB.00128-07 PG 13 WC Microbiology SC Microbiology GA 183ZY UT WOS:000247612100010 PM 17449607 ER PT J AU Hunter, RP Short, CR Myers, MJ Farrell, DE McClure, JR Koch, CE Keowen, ML AF Hunter, Robert P. Short, Charles R. Myers, Michael J. Farrell, Dorothy E. McClure, James R. Koch, Catherine E. Keowen, Michael L. TI The effect of cimetidine and aminoguanidine on pro-inflammatory Cytokines in the horse SO JOURNAL OF EQUINE VETERINARY SCIENCE LA English DT Article DE cimetidine; cytokines; aminoguanidine; horse; inflammation ID NITRIC-OXIDE SYNTHASE; BLOOD MONONUCLEAR-CELLS; CHROMIUM PICOLINATE; LEUKOCYTE ADHESION; PROTEIN-SYNTHESIS; GENE-EXPRESSION; GROWTH-HORMONE; IN-VIVO; HISTAMINE; PHARMACOKINETICS AB In this study, six horses each had three subcutaneous tissue chambers. Each horse was pretreated with intravenous saline (control), cimetidine, or aminoguanidine with a 4-week washout period. On day 0, a carrageenan (NaCl inflamed) was instilled in I tissue chamber. Blood and all tissue chamber fluids were sampled on days -1 to 3 and measured for activity levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1, and lL-6. The T-max for all cytokines (TNF-alpha, IL-1, IL-6) was 0.5 and 1 day post-inflammation in tissue chamber fluid. 141 the tissue chamber fluid, NaCl inflamed (NaCl-I), cimetidine, and aminoguanidine groups showed significant increases in IL-1 production. In the NaCl-I and cimetidine, tissue chamber fluid IL-6 was significantly increased when compared with NaCl noninflamed (NaCl-N) for the periods of study -1 to 1 -1 to 2, and -1 to 3. The cimetidine tissue chamber fluid [TCF] appeared to have a delayed, but greater, IL-6 response than the NaCl-I treatment. Even with cimetidine and aminoguanidine pretreatment, the resulting decrease in NO production demonstrated in our previously reported results in these same animals appeared to be too late to decrease the early cytokine response. However, it may assist in preventing the subsequent NO-induced upregulation of pro-inflammatory cytokine production. C1 US FDA, Dept Vet Physiol, Laurel, MD USA. US FDA, Dept Pharmacol, Laurel, MD USA. US FDA, Dept Toxicol, Laurel, MD USA. US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD USA. Louisiana State Univ, Sch Vet Med, Baton Rouge, LA 70803 USA. RP Hunter, RP (reprint author), Div Eli Lilly & Co, Elanco Anim Hlth, 2001 W Main St, Greenfield, IN 46140 USA. RI Hunter, Robert/A-2306-2008 OI Hunter, Robert/0000-0003-1224-2376 NR 39 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0737-0806 J9 J EQUINE VET SCI JI J. Equine Vet. Sci. PD JUL PY 2007 VL 27 IS 7 BP 307 EP 312 DI 10.1016/j.jevs.2007.05.007 PG 6 WC Veterinary Sciences SC Veterinary Sciences GA 194ZA UT WOS:000248381100008 ER PT J AU De Martinis, ECP Duvall, RE Hitchins, AD AF Pereira De Martinis, Elaine Cristina Duvall, Robert E. Hitchins, Anthony D. TI Real-time PCR detection of 16S rRNA genes speeds most-probable-number enumeration of foodborne Listeria monocytogenes SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE-CHAIN-REACTION; MICROBIOLOGICAL QUALITY; DNA EXTRACTION; SMOKED SALMON; ENRICHMENT; PRODUCTS; FOODS; MEAT; QUANTIFICATION; SPECIFICITY AB Quantifying foodborne pathogens at concentrations of 0.1 to 1,000 CFU/g of food generally involves most-probablenumber (MPN) enumeration, which takes at least 4 days. A real-time PCR assay (RTi-PCR) was developed to accelerate MPN enumeration of foodborne Listeria monocytogenes. Foods were spiked from 70 to 110 CFU/g, and triplicate subportions from 0.0001 to 1g were selectively enriched for 48 h at 30 degrees C. For standard MPN enumeration, the enrichments were subcultured on Oxford agar (48 h at 35 degrees C) to isolate Listeria. For RTi-PCR MPN, the L. monocytogenes cells from the same enrichments were washed and resuspended in 2 ml of sterile water. DNA was extracted by boiling for 10 min. The DNA in the extract's supernatant was targeted with published oligonucleotide primers for amplifying an Lmo-specific sequence of 16S rRNA genes. Amplification was continuously monitored with SYBR Green. The resulting amplicon was characterized by its melting temperature. The L. monocytogenes specificity of the primers was confirmed by testing L. monocytogenes (15 strains), Listeria innocua (11 strains), and Listeria welshimeri, Listeria seeligeri, Listeria ivanovii, and Listeria grayi (1 strain each). Quantitatively spiked milk, lettuce, smoked salmon, Brie cheese, ice cream, pork pate, salami, ready-to-eat shrimp, raw ground beef, and fresh soft cheese were enumerated by both the standard and the PCR MPN method. The paired results from the two MPN methods agreed well, except for the fresh cheese. For some foods, 1-g samples required a decimal dilution for a positive test result, suggesting concentration-dependent food ingredient interference with the RTi-PCR. This RTi-PCR method reduced the time necessary for the MPN enumeration of foodborne L. monocytogenes from 4 to 2 days. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Sao Paulo, Fac Ciencias Farmaceut, BR-14040903 Ribeirao Preto, SP, Brazil. RP Hitchins, AD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM anthony.hitchins@fda.hhs.gov NR 50 TC 23 Z9 23 U1 2 U2 7 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUL PY 2007 VL 70 IS 7 BP 1650 EP 1655 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 187LT UT WOS:000247849900014 PM 17685338 ER PT J AU Wang, JH Roderiquez, G Jones, T McPhie, P Norcross, MA AF Wang, Jinhai Roderiquez, Gregory Jones, Taneishia McPhie, Peter Norcross, Michael A. TI Control of in vitro immune responses by regulatory oligodeoxynucleotides through inhibition of pIII promoter directed expression of MHC class II transactivator in human primary monocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERCELLULAR-ADHESION MOLECULE-1; COLONY-STIMULATING FACTOR; COMPLEX CLASS-I; SUPPRESSIVE OLIGODEOXYNUCLEOTIDES; BACTERIAL-DNA; CPG OLIGODEOXYNUCLEOTIDES; SCAVENGER RECEPTORS; BETA-CHEMOKINES; DENDRITIC CELLS; CCR5 EXPRESSION AB Ag presentation is a key step in the initiation of adaptive immune responses that depends on the expression of MHC Ags and costimulatory molecules. Immune-enhancing CpG and non-CPG oligodeoxynucleotides (ODNs) stimulate Ag presentation by stimulating the expression of these molecules and by promoting dendritic cell maturation. In this report, we identify immuno-regulatory orthophosphorothioate non-CpG molecules, referred to as regulatory ODNs (rODNs), by their ability to inhibit allogeneic monocyte-stimulated T cell responses and down-regulate HLA-DR in human primary monocytes. The rODNs promoted the survival of macrophages and were able to activate IL-8 secretion through a chloroquine-resistant pathway. Messenger RNAs for HLA-DR alpha and beta and the MHC CIITA were reduced by rODNs but not by stimulatory CpG ODN2006 and non-CpG ODN2006a. CIITA transcription in monocytes was controlled primarily by promoter III and not by promoter I or IV. rODNs blocked promoter III-directed transcription of CIITA in these cells. Under conditions that induced dendritic cell differentiation, rODNs also reduced HLA-DR expression. The activity of rODNs is phosphorothioate chemistry and G stretch dependent but TLR9 independent. G tetrads were detected by circular dichroism in active rODNs and associated with high m.w. multimers on non-denaturing gels. Heat treatment of rODNs disrupted G tetrads, the high m.w. aggregates, and the HLA-DR inhibitory activity of the ODNs. The inhibition of immune responses by regulatory oligodeoxynucleotides may be useful for the treatment of immune-mediated disorders including autoimmune diseases and graft rejection. C1 US FDA, NIH, Div Therapeut Proteins, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NIDDK, NIH, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), US FDA, NIH, Div Therapeut Proteins, Off Biotechnol Prod,Ctr Drug Evaluat & Res, Bldg 29B,Room 4E12,8800 Rockville Pike, Bethesda, MD 20892 USA. EM jinhai.wang@fda.hhs.gov NR 47 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2007 VL 179 IS 1 BP 45 EP 52 PG 8 WC Immunology SC Immunology GA 182IF UT WOS:000247497600009 PM 17579020 ER PT J AU Gao, ZM Moore, TW Smith, AP Doub, WH Westenberger, BJ AF Gao, Zongming Moore, Terry W. Smith, Anjanette P. Doub, William H. Westenberger, Benjamin J. TI Studies of variability in dissolution testing with USP apparatus 2 SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE dissolution test; gauge R&R; variability; f(1) and f(2) factors ID TABLETS AB In this study, gauge repeatability and reproducibility (gauge R&R) was used to analyze variability for USP apparatus 2 dissolution measurement systems. Experiments were designed to assess the variability due to apparatus, operator, and sample tablet. Since dissolution testing is a destructive test, a nested model was used for data analysis. Additionally, perturbation tests with both disintegrating and nondisintegrating tablets were performed to study the variability due to sample position within the dissolution vessel. For the gauge R&R study, two well-trained chemists used two mechanically calibrated USP apparatus 2 units. Six tests were performed by each operator on each apparatus. Evaluation of dissolution test results at 30 min using an internal DPA calibrator tablet NCDA#2 (10 mg prednisone) indicates that the main contribution to the total variance, approximately 70%, is due to the sample tablets, approximately 25% is from the apparatus and approximately 5% is due to the operators. There is no significant difference between operators and apparatuses as shown by the gauge R&R studies. In addition, dissolution results can be strongly affected by the position of the tablet within the vessel. Similarity (f(1)) and dissimilarity (f2) factors were calculated to statistically evaluate differences between perturbed and normal dissolution tests. (c) 2007 Wiley-Liss, Inc. C1 US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Gao, ZM (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM zongming.gao@fda.hhs.gov NR 22 TC 16 Z9 16 U1 2 U2 5 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUL PY 2007 VL 96 IS 7 BP 1794 EP 1801 DI 10.1002/jps.20839 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 185DO UT WOS:000247691800011 PM 17252609 ER PT J AU Wear, KA AF Wear, Keith A. TI The dependence of time-domain speed-of-sound measurements on center frequency, bandwidth, and transit-time marker in human calcaneus in vitro SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BOVINE CANCELLOUS BONE; QUANTITATIVE ULTRASOUND DEVICES; HUMAN TRABECULAR BONE; HUMAN FEMUR SPECIMENS; X-RAY ABSORPTIOMETRY; HIP FRACTURE; MECHANICAL-PROPERTIES; VELOCITY DISPERSION; ACOUSTIC PROPERTIES; HEEL ULTRASOUND AB Time-domain speed-of-sound (SOS) measurements in calcaneus are effective predictors of osteoporotic fracture risk. High attenuation and dispersion in bone, however, produce severe distortion of transmitted pulses that leads to ambiguity of time-domain SOS measurements. An equation to predict the effects of system parameters (center frequency and bandwidth), algorithm. parameters (pulse arrival-time marker), and bone properties (attenuation coefficient and thickness) on time-domain SOS estimates is derived for media with attenuation that varies linearly with frequency. The equation is validated using data from a bone-mimicking phantom and from 30 human calcaneus samples in vitro. The data suggest that the effects of dispersion are small compared with the effects of frequency-dependent attenuation. The equation can be used to retroactively compensate data. System-related variations in SOS are shown to decrease as the pulse-arrival-time marker is moved toward the pulse center. Therefore, compared with other time-domain measures of SOS, group velocity exhibits the minimum system dependence. (c) 2007 Acoustical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-140,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 55 TC 8 Z9 10 U1 1 U2 4 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2007 VL 122 IS 1 BP 636 EP 644 DI 10.1121/1.2735811 PG 9 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 191WA UT WOS:000248161500061 PM 17614520 ER PT J AU Song, FH AF Song, Fenhong TI A study of noncovalent protein complexes by matrix-assisted laser desorption/ionization SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID IONIZATION MASS-SPECTROMETRY; PEPTIDE COMPLEXES; MS AB A sample preparation method has been developed for detection of noncovalent protein-protein complexes by MALDI in this work. An aqueous solution of the matrix at pH 7 allows the reproducible detection of a protein dimer, a protein tetramer, and a heterodimer. The signals are stable under long irradiation and can be detected at wide ranges of concentrations and with different laser intensities. C1 Univ Maryland, Maryland Biotechnol Inst, Ctr Adv Res Biotechnol, Rockville, MD 20850 USA. RP Song, FH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM fenhong.song@fda.hhs.gov NR 24 TC 8 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JUL PY 2007 VL 18 IS 7 BP 1286 EP 1290 DI 10.1016/j.jasms.2007.03.026 PG 5 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 190MF UT WOS:000248062200014 PM 17512214 ER PT J AU Obias-Manno, D Scott, PE Kaczmarczyk, J Miller, M Pinnow, E Lee-Bishop, L Jones-London, M Chapman, K Kallgren, D Uhl, K AF Obias-Manno, Dulce Scott, Pamela E. Kaczmarczyk, Joseph Miller, Margaret Pinnow, Ellen Lee-Bishop, Lynda Jones-London, Michelle Chapman, Kennerly Kallgren, Deborah Uhl, Kathleen TI The food and drug administration office of Women's Health: Impact of science on regulatory policy SO JOURNAL OF WOMENS HEALTH LA English DT Article ID BREAST IMPLANT RUPTURE; TORSADES-DE-POINTES; CLINICAL-TRIALS; SEX-DIFFERENCES; QT INTERVAL; INDUCED PROLONGATION; GENDER DIFFERENCES; SILICONE; PHARMACOKINETICS; PHARMACODYNAMICS AB In 1994, the Food and Drug Administration Office of Women's Health (FDA-OWH) was created to provide leadership and policy direction for the Agency regarding issues of women's health. Within its first year, the FDA-OWH established a science program for women's health research, promoting the development of sound policy and regulation. In a little over a decade, the program has provided approximately $14 million to fund more than 100 women's health research studies covering a broad range of health topics affecting women across their lifespan. Some studies, such as those elucidating drug effects on QT prolongation in women and drug-dietary supplement interaction, have had significant influence on regulatory decisions. Other studies have provided sound scientific data on sex and gender differences supporting FDA guidelines to protect women's health. This paper describes the science program at the FDA-OWH, providing examples of how funded research impacts regulatory policy. C1 US FDA, OC, Off Womes Hlth, Rockville, MD 20857 USA. World Hlth Org, Dept Food Safety, Geneva, Switzerland. Hlth Resources & Serv Adm, Div Hlth Ctr Management, Dept Hlth & Human Serv, Bethesda, MD USA. Natl Inst Neurol Disorders & Stroke, Off Minor Hlth & Res, Bethesda, MD USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Scott, PE (reprint author), US FDA, OC, Off Womes Hlth, 5600 Fishers Lane,Room 16-65 HF-8, Rockville, MD 20857 USA. EM Pamela.Scott@FDA.hhs.gov NR 76 TC 6 Z9 6 U1 4 U2 6 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 JUL PY 2007 VL 16 IS 6 BP 807 EP 817 DI 10.1089/jwh.2006.0135 PG 11 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 197JR UT WOS:000248551600004 PM 17678451 ER PT J AU Scarzello, AJ Romero-Weaver, AL Maher, SG Veenstra, TD Zhou, M Qin, A Donnelly, RP Sheikh, F Gamero, AM AF Scarzello, Anthony J. Romero-Weaver, Ana L. Maher, Stephen G. Veenstra, Timothy D. Zhou, Ming Qin, Angel Donnelly, Raymond P. Sheikh, Faruk Gamero, Ana M. TI A mutation in the SH2 domain of STAT2 prolongs tyrosine phosphorylation of STAT1 and promotes type IIFN-induced apoptosis SO MOLECULAR BIOLOGY OF THE CELL LA English DT Article ID STIMULATED-GENE FACTOR-3; SERINE PHOSPHORYLATION; DNA-BINDING; INTERFERON-ALPHA; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; I INTERFERONS; CELL-LINES; GAMMA; ACTIVATION AB Type I interferons (IFN-alpha/beta) induce apoptosis in certain tumor cell lines but not others. Here we describe a mutation in STAT2 that confers an apoptotic effect in tumor cells in response to type I IFNs. This mutation was introduced in a conserved motif, PYTK, located in the STAT SH2 domain, which is shared by STAT1, STAT2, and STAT3. To test whether the tyrosine in this motif might be phosphorylated and affect signaling, Y631 of STAT2 was mutated to phenylalanine (Y631F). Although it was determined that Y631 was not phosphorylated, the Y631F mutation conferred sustained signaling and induction of IFN-stimulated genes. This prolonged IFN response was associated with sustained tyrosine phosphorylation of STAT1 and STAT2 and their mutual association as heterodimers, which resulted from resistance to dephosphorylation by the nuclear tyrosine phosphatase TcPTP. Finally, cells bearing the Y631F mutation in STAT2 underwent apoptosis after IFN-alpha stimulation compared with wild-type STAT2. Therefore, this mutation reveals that a prolonged response to IFN-alpha could account for one difference between tumor cell lines that undergo IFN-alpha-induced apoptosis compared with those that display an antiproliferative response but do not die. C1 NCI, Canc & Inflammat Program, Expt Immunol Lab, Canc Res Ctr,NIH, Frederick, MD 21702 USA. NCI, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. Ctr Drug Evaluat & Res, Div Therapeut Prot, Food & Drug Adm, Bethesda, MD 20892 USA. RP Gamero, AM (reprint author), NCI, Canc & Inflammat Program, Expt Immunol Lab, Canc Res Ctr,NIH, Frederick, MD 21702 USA. EM gameroa@ncifcrf.gov OI Maher, Stephen/0000-0003-0126-7906 FU Intramural NIH HHS; NCI NIH HHS [N01CO12400] NR 36 TC 16 Z9 16 U1 0 U2 2 PU AMER SOC CELL BIOLOGY PI BETHESDA PA 8120 WOODMONT AVE, STE 750, BETHESDA, MD 20814-2755 USA SN 1059-1524 J9 MOL BIOL CELL JI Mol. Biol. Cell PD JUL PY 2007 VL 18 IS 7 BP 2455 EP 2462 DI 10.1091/mbc.E06-09-0843 PG 8 WC Cell Biology SC Cell Biology GA 183WV UT WOS:000247604000007 PM 17442890 ER PT J AU Yang, YS Faustino, PJ Volpe, DA Elllison, CD Lyon, RC Yu, LX AF Yang, Yongsheng Faustino, Patrick J. Volpe, Donna A. Elllison, Christopher D. Lyon, Robbe C. Yu, Lawrence X. TI Biopharmaceutics classification of selected beta-blockers: Solubility and permeability class membership SO MOLECULAR PHARMACEUTICS LA English DT Article DE biopharmaceutics classification system; beta-blockers; caco-2; permeability; solubility ID CACO-2 CELL MONOLAYERS; APPARENT DRUG PERMEABILITY; IN-VITRO PERMEABILITY; INTESTINAL-ABSORPTION; LIQUID-CHROMATOGRAPHY; BLOCKING-AGENTS; TRANSPORT; MODEL; MEMBRANE; HUMANS AB The purpose of this study was to determine the permeability and solubility of seven beta-blockers (acebutolol, atenolol, labetalol, metoprolol, nadolol, sotalol, and timolol) and to classify them according to the Biopharmaceutics Classification System (BCS). Apparent permeability coefficients (P-app) were measured using the Caco-2 cell line, and the solubility was determined at 37 degrees C over a pH range of 1.0-7.5. The permeability coefficients ranged from 1.0 x 10(-7) to 4.8 x 10(-5) CM/S. On the basis of the in vitro permeability and solubility data observed in the study, labetolol, metoprolol, and timolol can be categorized as BCS Class I drugs, whereas acebutolol, atenolol, and nadolol belong to BCS Class III. The permeability coefficients in Caco-2 cells were consistent with the reported extent of intestinal absorption in humans for all drugs except sotalol. Sotalol displayed low permeability in the Caco-2 cell line, but the extent of intestinal absorption in humans is over 90%. The low permeability through the Caco-2 monolayers might be largely related to its low lipophilicity. In addition, the difference between the tightness of the intercellular junction in vivo and in vitro may partially contribute to this disparity in the sotalol permeability of in vivo and in vitro. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. RP Yu, LX (reprint author), 7500 Standish Pl,HFD-600, Rockville, MD 20855 USA. EM lawrence.yu@fda.hhs.gov NR 35 TC 39 Z9 39 U1 0 U2 15 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARM JI Mol. Pharm. PD JUL-AUG PY 2007 VL 4 IS 4 BP 608 EP 614 DI 10.1021/mp070028I PG 7 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 199HJ UT WOS:000248686500014 PM 17637014 ER PT J AU Darrah, PA Patel, DT De Luca, PM Lindsay, RWB Davey, DF Flynn, BJ Hoff, ST Andersen, P Reed, SG Morris, SL Roederer, M Seder, RA AF Darrah, Patricia A. Patel, Dipti T. De Luca, Paula M. Lindsay, Ross W. B. Davey, Dylan F. Flynn, Barbara J. Hoff, Soren T. Andersen, Peter Reed, Steven G. Morris, Sheldon L. Roederer, Mario Seder, Robert A. TI Multifunctional T(H)1 cells define a correlate of vaccine-mediated protection against Leishmania major SO NATURE MEDICINE LA English DT Article ID NECROSIS-FACTOR-ALPHA; CD8(+) T-CELLS; INTERFERON-GAMMA; MYCOBACTERIUM-TUBERCULOSIS; IMMUNE-RESPONSE; FLOW-CYTOMETRY; MEMORY CD4(+); NITRIC-OXIDE; IN-VIVO; INFECTION AB CD4(+) T cells have a crucial role in mediating protection against a variety of pathogens through production of specific cytokines. However, substantial heterogeneity in CD4(+) T-cell cytokine responses has limited the ability to define an immune correlate of protection after vaccination. Here, using multiparameter flow cytometry to assess the immune responses after immunization, we show that the degree of protection against Leishmania major infection in mice is predicted by the frequency of CD4(+) T cells simultaneously producing interferon-gamma, interleukin-2 and tumor necrosis factor. Notably, multifunctional effector cells generated by all vaccines tested are unique in their capacity to produce high amounts of interferon-gamma. These data show that the quality of a CD4(+) T-cell cytokine response can be a crucial determinant in whether a vaccine is protective, and may provide a new and useful prospective immune correlate of protection for vaccines based on T-helper type 1 (T(H)1) cells. C1 NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. Statens Serum Inst, Dept Infect Dis Immunol, DK-2300 Copenhagen S, Denmark. Infect Dis Res Inst, Seattle, WA 98104 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, ImmunoTechnol Sect, NIH, Bethesda, MD 20892 USA. RP Seder, RA (reprint author), NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, 40 Convent Dr, Bethesda, MD 20892 USA. EM rseder@mail.nih.gov RI Roederer, Mario/G-1887-2011 FU Intramural NIH HHS NR 49 TC 784 Z9 790 U1 0 U2 28 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD JUL PY 2007 VL 13 IS 7 BP 843 EP 850 DI 10.1038/nm1592 PG 8 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA 188EU UT WOS:000247902800031 PM 17558415 ER PT J AU Sampson, JH Raghavan, R Brady, ML Provenzale, JM Herndon, JE Croteau, D Friedman, AH Reardon, DA Coleman, RE Wong, T Bigner, DD Pastan, I Rodriguez-Ponce, MI Tanner, P Puri, R Pedain, C AF Sampson, John H. Raghavan, Raghu Brady, Martin L. Provenzale, James M. Herndon, James E., II Croteau, David Friedman, Allan H. Reardon, David A. Coleman, R. Edward Wong, Terence Bigner, Darell D. Pastan, Ira Rodriguez-Ponce, Maria Inmaculada Tanner, Philipp Puri, Raj Pedain, Christoph TI Clinical utility of a patient-specific algorithm for simulating intracerebral drug infusions SO NEURO-ONCOLOGY LA English DT Article DE brain neoplasms; computer simulation; convection; drug delivery systems; single-photon emission computed tomography ID CONVECTION-ENHANCED DELIVERY; RECURRENT MALIGNANT GLIOMA; IL4-PSEUDOMONAS EXOTOXIN NBI-3001; BRAIN-TUMORS; PSEUDOMONAS EXOTOXIN; RAT-BRAIN; TOXIN; MODEL; MOLECULES; EFFICACY AB Convection-enhanced delivery (CED) is a novel drug delivery technique that uses positive infusion pressure to deliver therapeutic agents directly into the interstitial spaces of the brain. Despite the promise of CED, clinical trials have demonstrated that target-tissue anatomy and patient-specific physiology play a major role in drug distribution using this technique. In this study, we retrospectively tested the ability of a software algorithm using MR diffusion tensor imaging to predict patient-specific drug distributions by CED. A tumor-targeted cytotoxin, cintredekin besudotox (interleukin 13-PE38QQR), was coinfused with iodine 123-labeled human serum albumin (I-123-HSA), in patients with recurrent malignant gliomas. The spatial distribution of 123I-HSA was then compared to a drug distribution simulation provided by the software algorithm. The algorithm had a high sensitivity (71.4%) and specificity (100%) for identifying the high proportion (7 of 14) of catheter trajectories that failed to deliver drug into the desired anatomical region (p = 0.021). This usually occurred when catheter trajectories crossed deep sulci, resulting in leak of the infusate into the subarachnoid cerebrospinal fluid space. The mean concordance of the volume of distribution at the 50% isodose level between the actual 123I-HSA distribution and simulation was 65.75% (95% confidence interval [CI], 52.0%-79.5%), and the mean maximal in plane deviation was less than 8.5 mm (95% CI, 4.0-13.0 mm). The use of this simulation algorithm was considered clinically useful in 84.6% of catheters. Routine use of this algorithm, and its further developments, should improve prospective selection of catheter trajectories, and thereby improve the efficacy of drugs delivered by this promising technique. C1 Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Pathol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Biostat & Bioinformat, Durham, NC 27710 USA. Therataxis LLC, Baltimore, MD 21210 USA. NeoPharm Inc, Waukegan, IL 60085 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. BrainLAB, D-85622 Feldkirchen, Germany. Univ Munich, Klinikum Grosshadern, Dept Neurosurg, D-81377 Munich, Germany. US FDA, CBER, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Sampson, JH (reprint author), Duke Univ, Med Ctr, Dept Surg, Div Neurosurg, Box 3050, Durham, NC 27710 USA. EM john.sampson@duke.edu RI Coleman, Ralph/A-7865-2009 FU Intramural NIH HHS; NCI NIH HHS [5P50-CA108786, P50 CA108786, R01 CA097611]; NCRR NIH HHS [K23 RR016065, K23 RR16065, S10 RR15697]; NINDS NIH HHS [2P50-NS20023, P50 NS020023] NR 44 TC 72 Z9 74 U1 0 U2 6 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD JUL PY 2007 VL 9 IS 3 BP 343 EP 353 DI 10.1215/15228517-2007-007 PG 11 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 189UL UT WOS:000248014000014 PM 17435179 ER PT J AU Wright, LKM Popke, EJ Allen, RR Pearson, EC Hammond, TG Paule, MG AF Wright, L. K. M. Popke, E. J. Allen, R. R. Pearson, E. C. Hammond, T. G. Paule, M. G. TI Effect of chronic MK-801 and/or phenytoin on the acquisition of complex behaviors in rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE MK-801; N-methyl-D-aspartate (NMDA) receptors; operant behavior; phenytoin; sodium channels ID NMDA RECEPTOR ANTAGONISTS; ANTIEPILEPTIC DRUGS; NONHUMAN-PRIMATES; SYNAPTIC DENSITY; SEX-DIFFERENCES; NERVOUS-SYSTEM; NA+ CHANNELS; NEUROTOXICITY; MEMORY; PERFORMANCE AB The purpose of the present experiment was to assess the effects of chronic MK-801 (an N-methyl-D-aspartate receptor antagonist) and/or phenytoin (a sodium channel blocker) treatment on behavioral acquisition and performance in rats. Learning, audio/visual discrimination and motivation were modeled using incremental repeated acquisition (IRA), audio/visual discrimination (AVD) and progressive ratio (PR) tasks, respectively. MK-801 and/or phenytoin were administered daily, 7 days/week by orogastric gavage beginning just after weaning on postnatal day (PND) 23 and continuing until PND 306. Monday through Friday behavioral assessments began on PND 27 and continued until PND 430. Throughout treatment, subjects in the high dose MK-801 (1.0 mg/kg/day) and the high dose drug combination (1.0 mg/kg/day MK-801 + 150 mg/ kg/day phenytoin) groups exhibited decreased body weight gains compared to control subjects. For these two affected groups, response rates were also decreased in all tasks. Task acquisition, as evidenced by an increase in response accuracy, was decreased for both these groups in the AVD task, but only for the high dose MK-801 group in the IRA task. The data suggest that chronic MK-801 treatment adversely affects the acquisition of IRA and AVD task performance and that the inclusion of phenytoin in the MK-801 dosing regimen blocks some of the adverse effects of chronic MK-801 treatment on IRA task acquisition. These findings are in marked contrast with those observed in nonhuman primates and suggest important species differences associated with chronic exposure to compounds that block NMDA receptors and/or sodium channels. Published by Elsevier Inc. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Peak Stat Serv, Evergreen, CO 80439 USA. AstraZeneca, Safety Assessment, Loughborough LE11 5RH, Leics, England. RP Wright, LKM (reprint author), Oklahoma State Univ, Coll Vet Hlth Sci, 165 McElroy Hall, Stillwater, OK 74078 USA. EM linnzi.wright@okstate.edu NR 35 TC 5 Z9 5 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 2007 VL 29 IS 4 BP 476 EP 491 DI 10.1016/j.ntt.2007.02.001 PG 16 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 190JY UT WOS:000248056300005 PM 17376648 ER PT J AU Bocchini, JA Baltimore, RS Bernstein, HH Bradley, JS Brady, MT Dennehy, PH Fisher, MC Frenck, RW Kimberlin, DW Long, SS McMillan, JA Rubin, LG Clover, RD Fischer, MA Gorman, RL Pratt, DR Schuchat, A Schwartz, B Starke, JR Swanson, J Pickering, LK Baker, CJ Ledbetter, EO Siwek, A AF Bocchini, Joseph A., Jr. Baltimore, Robert S. Bernstein, Henry H. Bradley, John S. Brady, Michael T. Dennehy, Penelope H. Fisher, Margaret C. Frenck, Robert W., Jr. Kimberlin, David W. Long, Sarah S. McMillan, Julia A. Rubin, Lorry G. Clover, Richard D. Fischer, Marc A. Gorman, Richard L. Pratt, Douglas R. Schuchat, Anne Schwartz, Benjamin Starke, Jeffrey R. Swanson, Jack Pickering, Larry K. Baker, Carol J. Ledbetter, Edgar O. Siwek, Alison CA Comm Infectious Dis TI Prevention of varicella: Recommendations for use of varicella vaccines in children, including a recommendation for a routine 2-dose varicella immunization schedule SO PEDIATRICS LA English DT Article DE chickenpox; varicella; immunization; Varivax; ProQuad ID HUMORAL IMMUNE-RESPONSES; ZOSTER VIRUS-INFECTIONS; HEALTH-CARE WORKERS; UNITED-STATES; HERPES-ZOSTER; ELEMENTARY-SCHOOL; ANTIBODY-RESPONSE; LONG-TERM; FOLLOW-UP; ADULTS AB National varicella immunization coverage using the current 1-dose immunization strategy has increased among vaccine-eligible children 19 through 35 months of age from 27% in 1997 to 88% by 2005. These high immunization rates have resulted in a 71% to 84% decrease in the reported number of varicella cases, an 88% decrease in varicella-related hospitalizations, a 59% decrease in varicella-related ambulatory care visits, and a 92% decrease in varicella-related deaths in 1- to 4-year-old children when compared with data from the prevaccine era. Despite this significant decrease, the number of reported cases of varicella has remained relatively constant during the past 5 to 6 years. Since vaccine effectiveness for prevention of disease of any severity has been 80% to 85%, a large number of cases of varicella continue to occur among people who already have received the vaccine ( breakthrough varicella), and outbreaks of varicella have been reported among highly immunized populations of schoolchildren. The peak age-specific incidence has shifted from 3- to 6-year-old children in the prevaccine era to 9- to 11-year-old children in the postvaccine era for cases in both immunized and unimmunized children during these outbreaks. Outbreaks of varicella are likely to continue with the current 1-dose immunization strategy. After administration of 2 doses of varicella vaccine in children, the immune response is markedly enhanced, with > 99% of children achieving an antibody concentration (determined by glycoprotein enzyme-linked immunosorbent assay) of >= 5 U/mL (an approximate correlate of protection) and a marked increase in geometric mean antibody titers after the second vaccine dose. The estimated vaccine efficacy over a 10-year observation period of 2 doses for prevention of any varicella disease is 98% (compared with 94% for 1 dose), with 100% efficacy for prevention of severe disease. Recipients of 2 doses of varicella vaccine are 3.3-fold less likely to have breakthrough varicella, compared with those who are given 1 dose, during the first 10 years after immunization. To achieve greater levels of immunity with fewer serosusceptible people, greater protection against breakthrough varicella disease, and reduction in the number of outbreaks that occur nationwide among school-aged populations, a 2-dose varicella immunization strategy is now recommended for children >= 12 months of age. C1 Ctr Dis Control & Prevent, Atlanta, GA USA. NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. OI Dennehy, Penelope/0000-0002-2259-5370 NR 79 TC 36 Z9 39 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUL PY 2007 VL 120 IS 1 BP 221 EP 231 DI 10.1542/peds.2007-1089 PG 11 WC Pediatrics SC Pediatrics GA 185OC UT WOS:000247719300028 ER PT J AU Wang, SJ O'Neill, RT Hung, HMJ AF Wang, Sue-Jane O'Neill, Robert T. Hung, H. M. James TI Approaches to evaluation of treatment effect in randomized clinical trials with genomic subset SO PHARMACEUTICAL STATISTICS LA English DT Article DE alpha allocation; genomic composite biomarker; adaptive design; futility; prevalence; effect size ratio ID BREAST-CANCER; SAMPLE-SIZE; DESIGNS; EFFICIENCY AB With the advances in human genomic/genetic studies, the clinical trial community gradually recognizes that phenotypically homogeneous patients may be heterogeneous at the genomic level. The genomic technology brings a possible avenue for developing a genomic (composite) biomarker to predict a genomically responsive patient subset that may have a (much) higher likelihood of benefiting from a treatment. Randomized controlled trial is the mainstay to provide scientifically convincing evidence of a purported effect a new treatment may demonstrate. In conventional clinical trials, the primary clinical hypothesis pertains to the therapeutic effect in all patients who are eligible for the study defined by the primary efficacy endpoint. The aspect of one-size-fits-all surrounding the conventional design has been challenged, particularly when the diseases may be heterogeneous due to observable clinical characteristics and/or unobservable underlying the genomic characteristics. Extension from the conventional single population design objective to an objective that encompasses two possible patient populations will allow more informative evaluation in the patients having different degrees of responsiveness to medication. Building in conventional clinical trials, an additional genomic objective can generate an appealing conceptual framework from the patient's perspective in addressing personalized medicine in well-controlled clinical trials. There are many perceived benefits of personalized medicine that are based on the notion of being genomically proactive in the identification of disease and prevention of disease or recurrence. In this paper, we show that an adaptive design approach can be constructed to study a clinical hypothesis of overall treatment effect and a hypothesis of treatment effect in a genomic subset more efficiently than the conventional nonadaptive approach. Published in 2007 by John Wiley & Sons, Ltd. C1 US FDA, Ctr Frug Evaluat & Res, Off Translat Sci, Off Biostat, Silver Spring, MD 20993 USA. US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Div Biometr, Silver Spring, MD USA. RP Wang, SJ (reprint author), US FDA, Ctr Frug Evaluat & Res, Off Translat Sci, Off Biostat, HFD-700,WO 22,Mail Stop 6105,10903 Hampshire Ave, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov NR 20 TC 126 Z9 126 U1 1 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1539-1604 J9 PHARM STAT JI Pharm. Stat. PD JUL-SEP PY 2007 VL 6 IS 3 BP 227 EP 244 DI 10.1002/pst.300 PG 18 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 210TA UT WOS:000249477300009 PM 17688238 ER PT J AU Burwen, DR La Voie, L Braun, MM Houck, P Ball, R AF Burwen, Dale R. La Voie, Lawrence Braun, M. Miles Houck, Peter Ball, Robert TI Evaluating adverse events after vaccination in the Medicare population SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article; Proceedings Paper CT 22nd International Conference on Pharmacoepidemiology and Therapeutic Risk Management CY AUG 24-27, 2006 CL Lisbon, PORTUGAL DE adverse effects; vaccines; pharmacoepidemiology; Medicare; influenza vaccines; pneumococcal vaccines ID PNEUMOCOCCAL POLYSACCHARIDE VACCINE; SAFETY INFORMATION; BENEFICIARIES; DESIGN; REVACCINATION AB Purpose Post-licensure observational studies using large linked databases can provide important data about whether adverse events are associated with vaccines, but databases that have been used may not have sufficient statistical power to examine rare events, and may underrepresent the elderly. We assessed the utility of Medicare data for evaluating adverse events after influenza and pneumococcal vaccines, by using an example involving selected clinical conditions, and evaluating aspects of data quality relevant to vaccine safety analyses. Methods We used 2001 data from the National Claims History File and Enrollment Database to determine if hospitalization for urinary tract infection (not likely associated with vaccination) or for cellulitis and abscess of the upper arm and forearm is associated with vaccination. Results For influenza vaccine, the 7-day period after vaccination did not demonstrate an elevation in hospitalization with cellulitis and abscess of the upper arm and forearm; for pneumococcal vaccine, a clear peak was evident. No increase in urinary tract infection was found after either influenza or pneumococcal vaccine. Having a prior Medicare claim for pneumococcal vaccine within 5 years was a risk factor for hospitalization with cellulitis and abscess of the upper arm and forearm (relative risk, 2.6; 95% confidence limits (CL), 1.3, 5.0). Conclusions Medicare data are a useful source for evaluating adverse events after vaccination. Screening analyses can be performed using administrative data, but medical record review to validate diagnoses will often be needed for rigorous study of vaccine-adverse event associations. Published in 2007 by John Wiley & Sons, Ltd. C1 US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Ctr Medicare & Medicaid Serv, Kansas City Reg Off, Kansas City, MO USA. Ctr Medicare & Medicaid Serv, Seattle Reg Off, Seattle, WA USA. RP Burwen, DR (reprint author), US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,Suite 200 S,HFM-222, Rockville, MD 20852 USA. EM dale.burwen@fda.hhs.gov NR 40 TC 24 Z9 24 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JUL PY 2007 VL 16 IS 7 BP 753 EP 761 DI 10.1002/pds.1390 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 197KH UT WOS:000248553400005 PM 17385786 ER PT J AU Adkins, S Mccollum, TG Albano, JP Kousik, CK Roberts, PD Baker, CA Webb, SE AF Adkins, S. Mccollum, T. G. Albano, J. P. Kousik, C. K. Roberts, P. D. Baker, C. A. Webb, S. E. TI Squash vein yellowing virus and its effects on watermelon SO PHYTOPATHOLOGY LA English DT Meeting Abstract C1 FDACS, Div Plant Ind, Gainesville, FL USA. USDA ARS, Charleston, SC USA. USDA ARS, Ft Pierce, FL USA. Univ Florida, Gainesville, FL USA. Univ Florida, Immokalee, FL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0031-949X J9 PHYTOPATHOLOGY JI Phytopathology PD JUL PY 2007 VL 97 IS 7 SU S BP S2 EP S2 PG 1 WC Plant Sciences SC Plant Sciences GA 181XP UT WOS:000247470000008 ER PT J AU Duan, Y Sun, X Gabriel, DW Gottwald, TR AF Duan, Y. Sun, X. Gabriel, D. W. Gottwald, T. R. TI Characterization of two new and emerging bacterial diseases of citrus in Florida SO PHYTOPATHOLOGY LA English DT Meeting Abstract C1 FDACS, Div Plant Ind, Gainesville, FL USA. USHRL, ARS, USDA, Ft Pierce, FL USA. Univ Florida, Gainesville, FL USA. NR 0 TC 0 Z9 0 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 JUL PY 2007 VL 97 IS 7 SU S BP S30 EP S30 PG 1 WC Plant Sciences SC Plant Sciences GA 181XP UT WOS:000247470000181 ER PT J AU Baker, CA Kamenova, I Raid, R Adkins, S AF Baker, C. A. Kamenova, I. Raid, R. Adkins, S. TI Bidens mottle virus identified in tropical soda apple in Florida. SO PLANT DISEASE LA English DT News Item ID SOLANUM-VIARUM C1 FDACS, Div Plant Ind, Gainesville, FL 32614 USA. USDA ARS, USHRL, Ft Pierce, FL 34945 USA. Univ Florida, Everglades Res & Educ Ctr, Belle Glade, FL 33430 USA. RP Baker, CA (reprint author), FDACS, Div Plant Ind, Gainesville, FL 32614 USA. NR 4 TC 4 Z9 5 U1 1 U2 2 PU AMER PHYTOPATHOLOGICAL SOC PI ST PAUL PA 3340 PILOT KNOB ROAD, ST PAUL, MN 55121 USA SN 0191-2917 J9 PLANT DIS JI PLANT DIS. PD JUL PY 2007 VL 91 IS 7 BP 905 EP 905 DI 10.1094/PDIS-91-7-0905A PG 1 WC Plant Sciences SC Plant Sciences GA 181DL UT WOS:000247417000021 ER PT J AU Alexander, GA Swartz, HM Amundson, SA Blakely, WF Buddemeier, B Gallez, B Dainiak, N Goans, RE Hayes, RB Lowry, PC Noska, MA Okunieff, P Salner, AL Schauer, DA Trompier, F Turteltaub, KW Voisin, P Wiley, AL Wilkins, R AF Alexander, George A. Swartz, Harold M. Amundson, Sally A. Blakely, William F. Buddemeier, Brooke Gallez, Bernard Dainiak, Nicholas Goans, Ronald E. Hayes, Robert B. Lowry, Patrick C. Noska, Michael A. Okunieff, Paul Salner, Andrew L. Schauer, David A. Trompier, Francois Turteltaub, Kenneth W. Voisin, Phillipe Wiley, Albert L., Jr. Wilkins, Ruth TI BiodosEPR-2006 Meeting: Acute dosimetry consensus committee recommendations on biodosimetry applications in events involving uses of radiation by terrorists and radiation accidents SO RADIATION MEASUREMENTS LA English DT Article; Proceedings Paper CT Joint Meeting of the 2nd International Conference on Biodosimetry/7th International Symposium on Electron Paramagnetic Resonance Dosimetry and Applications CY JUL 10-13, 2007 CL Bethesda, MD SP Uniformed Serv Univ DE acute dosimetry; radiological triage; dose assessment; electron paramagnetic resonance; cytogenetic biodosimetry; medical management of radiation casualties ID PREMATURE CHROMOSOME CONDENSATION; GENE-EXPRESSION CHANGES; ELECTRON-PARAMAGNETIC-RESONANCE; PERIPHERAL-BLOOD LYMPHOCYTES; TOTAL-BODY IRRADIATION; EARLY DOSE ASSESSMENT; VIVO EPR DOSIMETRY; BIOLOGICAL DOSIMETRY; IONIZING-RADIATION; MEDICAL-MANAGEMENT AB In the aftermath of a radiological terrorism incident or mass-casualty radiation accident, first responders and receivers require prior guidance and pre-positioned resources for assessment, triage and medical management of affected individuals [NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA]. Several recent articles [Dainiak, N., Waselenko, J.K., Armitage, J.O., MacVittie, T.J., Farese, A.M., 2003. The hematologist and radiation casualties. Hematology (Am. Soc. Hematol. Educ. Program) 473-496; Waselenko, J.K., MacVittie, T.J., Blakely, W.F., Pesik, N., Wiley, A.L., Dickerson, W.E., Tsu, H., Confer, D.L., Coleman, C.N., Seed, T., Lowry, P., Armitage, J.O., Dainiak, N., Strategic National Stockpile Radiation Working Group, 2004. Medical management of the acute radiation syndrome: recommendations of the Strategic National Stockpile Radiation Working Group. Ann. Intern. Med. 140(12), 1037-1051; Blakely, W.F., Salter, C.A., Prasanna, P.G., 2005. Early-response biological dosimetry-recommended countermeasure enhancements for mass-casualty radiological incidents and terrorism. Health Phys. 89(5), 494-504; Goans, R.E., Waselenko, J.K., 2005. Medical management of radiation casualties. Health Phys. 89(5), 505-512; Swartz, H.M., Iwasaki, A., Walczak, T., Demidenko, E., Salikhov, I., Lesniewski, P., Starewicz, P., Schauer, D., Romanyukha, A., 2005. Measurements of clinically significant doses of ionizing radiation using non-invasive in vivo EPR spectroscopy of teeth in situ. Appl. Radiat. Isot. 62, 293-299; Weisdorf, D., Chao, N., Waselenko, J.K., Dainiak, N., Armitage, J.O., McNiece, I., Confer, D., 2006. Acute radiation injury: contingency planning for triage, supportive care, and transplantation. Biol. Blood Marrow Transplant. 12(6), 672-682], national [National Council of Radiation Protection and Measurements (NCRP), 1994. Management of persons accidentally contaminated with radionuclides. NCRP Report No. 65, Bethesda, Maryland, USA; NCR-P, 2001. Management of terrorist events involving radioactive material. NCRP Report No. 138, Bethesda, Maryland, USA; NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA] and international [IAEA, 2005. Generic procedures for medical response during a nuclear or radiological emergency. EPR-Medical 2005, IAEA, Vienna, Austria] agencies have reviewed strategies for acute-phase biodosimetry. Consensus biodosimetric guidelines include: (a) clinical signs and symptoms, including peripheral blood counts, time to onset of nausea and vomiting and presence of impaired cognition and neurological deficits, (b) radioactivity assessment, (c) personal and area dosimetry, (d) cytogenetics, (e) in vivo electron paramagnetic resonance (EPR) and (f) other dosimetry approaches (i.e. blood protein assays, etc.). Emerging biodosimetric technologies may further refine triage and dose assessment strategies. However, guidance is needed regarding which biodosimetry techniques are most useful for different radiological scenarios and consensus protocols must be developed. The Local Organizing Committee for the Second International Conference on Biodosimetry and Seventh International Symposium on EPR Dosimetry and Applications (BiodosEPR-2006 Meeting) convened an Acute Dosimetry Consensus Committee composed of national and international experts to: (a) review the current literature for biodosimetry applications for acute-phase applications in raiological emergencies, (b) describe the strengths and weaknesses of each technique, (c) provide recommendations for the use of biodosimetry assays for selected defined radiation scenarios, and (d) develop protocols to apply these recommended biological dosimetry techniques with currently available supplies and equipment for first responders. The Acute Dosimetry Consensus Committee developed recommendations for use of a prioritized multiple-assay biodosimetric-based strategy, concluding that no single assay is sufficiently robust to address all of the potential radiation scenarios including management of mass casualties and diagnosis for early medical treatment. These recommendations may be used by first responders/first receivers that span time-windows of (i.e. 0-5 days) after the radiological incident for three radiological scenarios including: (a) radiation exposure device (RED), (b) radiological dispersal device (RDD), and (c) an improvised (or otherwise acquired) nuclear device (IND). Consensus protocols for various bioassays (i.e. signs and symptoms recording, bioassay sampling for radioactivity analysis, nail-clipping sampling for EPR analysis and blood collection for hematology, cytogenetics, and blood chemistry analyses) are presented as Appendix materials. As stated in NCRP Commentary No. 19 [NCRP, 2005. Key elements of preparing emergency responders for nuclear and radiological terrorism. NCRP Commentary No. 19, Bethesda, Maryland, USA], multi-parameter triage (i.e. time to vomiting, lymphocyte kinetics, and other biodosimetry indicators) offers the current best strategy for early assessment of absorbed dose. (c) 2007 Elsevier Ltd. All rights reserved. C1 Armed Forces Radiobiol Res Inst, Bethesda, MD 20889 USA. US Dept HHS, Off Preparedness & Emergency Operat, Washington, DC 20201 USA. Dartmouth Med Sch, Dept Radiol, Hanover, NH 03755 USA. Dartmouth Med Sch, Dept Physiol, Hanover, NH 03755 USA. Columbia Univ, Med Ctr, Ctr Radiol Res, New York, NY 10032 USA. US Dept Homeland Secur, Washington, DC 20528 USA. Univ Catholique Louvain, Biomed Magnet Resonance Unit, B-1200 Brussels, Belgium. Univ Catholique Louvain, Lab Med Chem & Radiopharm, B-1200 Brussels, Belgium. Bridgeport Hosp, Dept Med, Bridgeport, CT 06610 USA. MJW Corp, Clinton, TN 37716 USA. Remote Sensing Lab, Las Vegas, NV 89193 USA. Oak Ridge Associated Univ, Radiat Emergency Assitance Ctr Training Site, Oak Ridge, TN 37831 USA. US FDA, CDRH, Rockville, MD 20850 USA. Univ Rochester, Dept Radiat Oncol, Rochester, NY 14642 USA. Hartford Hosp, Helen & Harry Gray Canc Ctr, Ishikari, Hokkaido 06102, Japan. Natl Council Radiat Protect & Measurements, Bethesda, MD 20814 USA. Inst Radioprotect & Surete Nucl, Radiobiol & Epidemiol Dept, F-92262 Fontenay Aux Roses, France. Lawrence Livermore Natl Lab, Livermore, CA 94550 USA. Hlth Canada, Consumer & Clin Radiat Protect Bur, Ottawa, ON K1A 1C1, Canada. RP Blakely, WF (reprint author), Armed Forces Radiobiol Res Inst, 8901 Wisconsin Ave, Bethesda, MD 20889 USA. EM blakely@afrri.usuhs.mil OI TROMPIER, Francois/0000-0002-8776-6572 NR 131 TC 87 Z9 91 U1 1 U2 9 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1350-4487 J9 RADIAT MEAS JI Radiat. Meas. PD JUL-AUG PY 2007 VL 42 IS 6-7 SI SI BP 972 EP 996 DI 10.1016/j.radmeas.2007.05.035 PG 25 WC Nuclear Science & Technology SC Nuclear Science & Technology GA 224AH UT WOS:000250416900003 ER PT J AU Colman, E AF Colman, Eric TI Dinitrophenol and obesity: An early twentieth-century regulatory dilemma SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Editorial Material DE dinitrophenol; obesity; food and drug administration ID HEART AB In the early 1930s, the industrial chemical dinitrophenol found widespread favor as a weight-loss drug, due principally to the work of Maurice Tainter, a clinical pharmacologist from Stanford University. Unfortunately the compound's therapeutic index was razor thin and it was not until thousands of people suffered irreversible harm that mainstream physicians realized that dinitrophenol's risks outweighed its benefits and abandoned its use. Yet, it took passage of the Food, Drug, and Cosmetic Act in 1938 before federal regulators had the ability to stop patent medicine men from selling dinitrophenol to Americans lured by the promise of a drug that would safely melt one's fat away. Published by Elsevier Inc. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 2, Div Metab & Endocrinol Prod, Silver Spring, MD 20993 USA. RP Colman, E (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 2, Div Metab & Endocrinol Prod, 10903 New Hampshire Ave,Bldg 22,Room 3360, Silver Spring, MD 20993 USA. EM eric.colman@fda.hhs.gov NR 21 TC 47 Z9 50 U1 4 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUL PY 2007 VL 48 IS 2 BP 115 EP 117 DI 10.1016/j.yrtph.2007.03.006 PG 3 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 183CI UT WOS:000247549900001 PM 17475379 ER PT J AU Kauffman, JF Westenberger, BJ Robertson, JD Guthrie, J Jacobs, A Cummins, SK AF Kauffman, John F. Westenberger, Benjamin J. Robertson, J. David Guthrie, James Jacobs, Abigail Cummins, Susan K. TI Lead in pharmaceutical products and dietary supplements SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE ICP-MS; lead toxicity; lead exposure; pharmaceutical products; calcium supplements; vitamins; cGMP; USP lead limits ID ATOMIC-ABSORPTION-SPECTROMETRY; CALCIUM SUPPLEMENTS; INTELLECTUAL IMPAIRMENT; HEAVY-METALS; MEDICINE; EXPOSURE; CHILDREN; BRANDS AB The objective of this study is to determine lead concentrations in a variety of widely used pharmaceutical products, and to assess the risk of lead exposure from using these products. Lead concentrations of 45 products were measured with inductively-coupled plasma mass spectrometry. Six products had lead concentrations greater than 100 parts per billion (ppb), and the highest measured concentration was 500 ppb. The average mass of lead delivered to consumers by all products examined in this study when taken as directed was 0.22 micrograms per day, which is expected to increase the blood lead level of an adult by less than 1%. Five products were found to deliver more than 1 mu g of lead per day when used as directed. Current tolerable lead limits in pharmaceutical substances vary widely, and in some cases exceed 10,000 ppb. The products examined in this study have lead concentrations far below these levels. However, in light of recent research demonstrating adverse effects in both children and adults from low level lead exposure, current lead limits for pharmaceutical substances are unacceptably high. Uniform lead limits that reflect current manufacturing capabilities are needed to insure the lowest achievable exposure to lead from these products. (c) 2007 Elsevier Inc. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Pharmaceut Anal, St Louis, MO 63101 USA. Univ Missouri, Res Reactor Ctr, Columbia, MO 65211 USA. Univ Missouri, Dept Chem, Columbia, MO 65211 USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Silver Spring, MD USA. US FDA, Ctr Drug Evaluat & Res, Off Ctr Director, Silver Spring, MD USA. RP Kauffman, JF (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM John.Kauffman@fda.hhs.gov NR 32 TC 18 Z9 18 U1 2 U2 16 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 JUL PY 2007 VL 48 IS 2 BP 128 EP 134 DI 10.1016/j.yrtph.2007.03.001 PG 7 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 183CI UT WOS:000247549900003 PM 17467129 ER PT J AU Slikker, W Zou, XJ Hotchkiss, CE Divine, RL Sadovova, N Twaddle, NC Doerge, DR Scallet, AC Patterson, TA Hanig, JP Paule, MG Wang, C AF Slikker, William, Jr. Zou, Xiaoju Hotchkiss, Charlotte E. Divine, Rebecca L. Sadovova, Natalya Twaddle, Nathan C. Doerge, Daniel R. Scallet, Andrew C. Patterson, Tucker A. Hanig, Joseph P. Paule, Merle G. Wang, Cheng TI Ketamine-induced neuronal cell death in the perinatal rhesus monkey SO TOXICOLOGICAL SCIENCES LA English DT Article DE NMDA receptor; ketamine; neurotoxicology; apoptosis; development; anesthetic agents; nonhuman primate ID D-ASPARTATE RECEPTORS; INDUCED CORTICAL APOPTOSIS; NMDA RECEPTOR; UP-REGULATION; RAT-BRAIN; SUBUNIT IMMUNOREACTIVITY; DEVELOPMENTAL-CHANGES; CHRONIC PHENCYCLIDINE; ANESTHETIC AGENTS; MESSENGER-RNA AB Ketamine is widely used as a pediatric anesthetic. Studies in developing rodents have indicated that ketamine-induced anesthesia results in brain cell death. Additional studies are needed to determine if ketamine anesthesia results in brain cell death in the nonhuman primate and if so, to begin to define the stage of development and the duration of ketamine anesthesia necessary to produce brain cell death. Rhesus monkeys (N = 3 for each treatment and control group) at three stages of development (122 days of gestation and 5 and 35 postnatal days [PNDs]) were administered ketamine intravenously for 24 h to maintain a surgical anesthetic plane, followed by a 6-h withdrawal period. Similar studies were performed in PND 5 animals with 3 h of ketamine anesthesia. Animals were subsequently perfused and brain tissue processed for analyses. Ketamine (24-h infusion) produced a significant increase in the number of caspase 3-, Fluoro-Jade C- and silver stain-positive cells in the cortex of gestational and PND 5 animals but not in PND 35 animals. Electron microscopy indicated typical nuclear condensation and fragmentation in some neuronal cells, and cell body swelling was observed in others indicating that ketamine-induced neuronal cell death is most likely both apoptotic and necrotic in nature. Ketamine increased N-methyl-D-aspartate (NMDA) receptor NR1 subunit messenger RNA in the frontal cortex where enhanced cell death was apparent. Earlier developmental stages (122 days of gestation and 5 PNDs) appear more sensitive to ketamine-induced neuronal cell death than later in development (35 PNDs). However, a shorter duration of ketamine anesthesia (3 h) did not result in neuronal cell death in the 5-day-old monkey. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 1, Jefferson, AR 72079 USA. EM william.slikker@fda.hhs.gov NR 58 TC 240 Z9 250 U1 1 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2007 VL 98 IS 1 BP 145 EP 158 DI 10.1093/toxsci/kfm084 PG 14 WC Toxicology SC Toxicology GA 183VZ UT WOS:000247601800014 PM 17426105 ER PT J AU Gopee, NV Roberts, DW Webb, P Cozart, CR Siitonen, PH Warbritton, AR Yu, WW Colvin, VL Walker, NJ Howard, PC AF Gopee, Neera V. Roberts, Dean W. Webb, Peggy Cozart, Christy R. Siitonen, Paul H. Warbritton, Alan R. Yu, William W. Colvin, Vicki L. Walker, Nigel J. Howard, Paul C. TI Migration of intradermally injected quantum dots to sentinel organs in mice SO TOXICOLOGICAL SCIENCES LA English DT Article DE nanoparticles; nanoscale materials; quantum dots; sentinel organs; biodistribution ID TITANIUM-DIOXIDE; IN-VIVO; SEMICONDUCTOR PHOTOCATALYSIS; BACTERICIDAL ACTIVITY; NANOCRYSTALS; TIO2; SKIN; WATER; PENETRATION; PARTICLES AB Topical exposure to nanoscale materials is likely from a variety of sources including sunscreens and cosmetics. Because the in vivo disposition of nanoscale materials is not well understood, we have evaluated the distribution of quantum dots (QDs) following intradermal injection into female SKH-1 hairless mice as a model system for determining tissue localization following intradermal infiltration. The QD (CdSe core, US capped, poly[ethylene glycol] coated, 37 mn diameter, 621 nm fluorescence emission) were injected intradermally (ID) on the right dorsal flank. Within minutes following intradermal injection, the highly UV fluorescent QD could be observed moving from the injection sites apparently through the lymphatic duct system to regional lymph nodes. Residual fluorescent QD remained at the site of injection until necropsy at 24 h. Quantification of cadmium and selenium levels after 0, 4,8,12, or 24 h in multiple tissues, using inductively coupled plasma mass spectrometry (ICP-MS), showed a time-dependent loss of cadmium from the injection site, and accumulation in the liver, regional draining lymph nodes, kidney, spleen, and hepatic lymph node. Fluorescence microscopy corroborated the ICP-MS results regarding the tissue distribution of QD. The results indicated that (1) ID injected nanoscale QD remained as a deposit in skin and penetrated the surrounding viable subcutis, (2) QD were distributed to draining lymph nodes through the sc lymphatics and to the liver and other organs, and (3) sentinel organs are effective locations for monitoring transdermal penetration of nanoscale materials into animals. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Toxicol Program, Ctr Phototoxicol, Jefferson, AR 72079 USA. Toxicol Pathol Associates, Jefferson, AR 72079 USA. Rice Univ, Dept Chem, Houston, TX 77251 USA. Rice Univ, Ctr Biol & Environm Nanotechnol, Houston, TX 77251 USA. Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. Natl Inst Environm Hlth Sci, NIH, Res Triangle Pk, NC 27709 USA. RP Howard, PC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. EM paul.howard@fda.hhs.gov RI Walker, Nigel/D-6583-2012 OI Walker, Nigel/0000-0002-9111-6855 FU Intramural NIH HHS [Z99 ES999999]; NIEHS NIH HHS [Y01 ES001027-35] NR 59 TC 102 Z9 112 U1 0 U2 18 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2007 VL 98 IS 1 BP 249 EP 257 DI 10.1093/toxsci/kfm074 PG 9 WC Toxicology SC Toxicology GA 183VZ UT WOS:000247601800024 PM 17404394 ER PT J AU Wu, KM Farrelly, JG AF Wu, Kuei-Meng Farrelly, James G. TI Regulatory perspectives of Type II prodrug development and time-dependent toxicity management: Nonclinical Pharm/Tox analysis and the role of comparative toxicology SO TOXICOLOGY LA English DT Article; Proceedings Paper CT Annual Food and Drug Administration Science Forum CY APR 18, 2006 CL Washington, DC AB Many therapeutic agents are prepared in prodrug forms, which are classified into Type I, II and subtypes A, B based on their sites of conversion. Recently, an increasing number of INDs have appeared as Type II prodrugs that often contain dual tracks of toxicity profile exploration, one on the prodrug and another on the active drug. A comparative toxicology analysis is introduced here to assist reviewers to evaluate the dual toxicity profiles effectively. The analysis helps determine which toxicity is contributed by the prodrug itself, its intermediates, or the active drug itself. As prodrug INDs, or any other new molecular entity (NME) INDs progress into advanced phases of toxicology development, analysis of time-dependent component of toxicity expression, regarding the emergence of new target organs over time, becomes more significant. A strategy is developed to address Pharm/Tox issues such as what duration is required for a toxicity to emerge at the exposure level achieved or dose studied, how many animals in the group are affected, whether the toxicity is a cross-species phenomenon, and whether it is reversible, etc. In conclusion, dual-track comparative toxicology can be useful in the understanding of Type II prodrug's mechanism of toxicity, and that time-dependent toxicology analysis offers means to detecting new toxicity emergence over time. Both approaches could significantly facilitate secondary and tertiary review processes during IND development of a prodrug or NME. (c) 2007 Elsevier Ireland Ltd. All rights reserved. C1 Ctr Drug Evaluat & Res, Food & Drug Adm, Silver Spring, MD 20993 USA. RP Wu, KM (reprint author), Ctr Drug Evaluat & Res, Food & Drug Adm, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kueimeng.wu@fda.hhs.gov NR 7 TC 7 Z9 7 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD JUL 1 PY 2007 VL 236 IS 1-2 BP 1 EP 6 DI 10.1016/j.tox.2007.04.005 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 180IB UT WOS:000247355200001 PM 17507137 ER PT J AU Valerio, LG Arvidson, KB Chanderbhan, RF Contrera, JF AF Valerio, Luis G., Jr. Arvidson, Kirk B. Chanderbhan, Ronald F. Contrera, Joseph F. TI Prediction of rodent carcinogenic potential of naturally occurring chemicals in the human diet using high-throughput QSAR predictive modeling SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review DE carcinogenesis; rodent carcinogenicity; cancer; quantitative structure-activity relationship modeling; QSAR; SAR; predictive toxicology; computational toxicology; predictive toxicology; dietary chemical; natural product; phytochemical; risk assessment; safety assessment; food safety ID COMPOUND PROTOCATECHUIC ACID; NATIONAL-TOXICOLOGY-PROGRAM; CANCER-RISK ASSESSMENT; DNA ADDUCT FORMATION; E-STATE INDEXES; PYRROLIZIDINE ALKALOIDS; COLON CARCINOGENESIS; F344 RATS; FORESTOMACH CARCINOGENESIS; SYMPHYTUM-OFFICINALE AB Consistent with the U.S. Food and Drug Administration (FDA) Critical Path Initiative, predictive toxicology software programs employing quantitative Structure-activity relationship (QSAR) models are Currently under evaluation for regulatory risk assessment and scientific decision support for highly sensitive endpoints Such as carcinogenicity, mutagenicity and reproductive toxicity. At the FDA's Center for Food Safety and Applied Nutrition's Office of Food Additive Safety and the Center for Drug Evaluation and Research's Informatics and Computational Safety Analysis Staff (ICSAS), the use of computational SAR tools for both qualitative and quantitative risk assessment applications are being developed and evaluated. One tool Of Current interest is MDL-QSAR predictive discriminant analysis modeling of rodent carcinogenicity, which has been previously evaluated for pharmaceutical applications by the FDA ICSAS. The study described in this paper aims to evaluate the utility of this software to estimate the carcinogenic potential of small, organic, naturally occurring chemicals found in the human diet. In addition, a. group Of 19 known synthetic dietary constituents that were positive in rodent carcinogenicity studies served as a control group. In the test group of naturally occurring chemicals, 101 were found to be suitable for predictive modeling using this software's discriminant analysis modeling approach. Predictions performed on these compounds were compared to published experimental evidence of each compound's carcinogertic potential. Experimental evidence included relevant toxicological studies such as rodent cancer bioassays, rodent anti-carcinogenicity studies, genotoxic studies, and the presence of chemical structural alerts. Statistical indices of predictive performance were calculated to assess the utility of the predictive modeling method. Results revealed good predictive performance using this software's rodent carcinogenicity module of over 1200 chemicals, comprised primarily of pharmaceutical, industrial and some natural products developed under an FDA-MDL cooperative research and development agreement (CRADA). The predictive performance for this group of dietary natural products and the control group was 97% sensitivity and 80% concordance. Specificity was marginal at 53%. This study finds that the in silico QSAR analysis employing this software's rodent carcinogenicity database is capable of identifying the rodent carcinogenic potential of naturally occurring organic molecules found in the human diet with a high degree of sensitivity. It is the first study to demonstrate successful QSAR predictive modeling of naturally occurring carcinogens found in the human diet using an external validation test. Further test validation of this software and expansion of the training data set for dietary chemicals will help to support the future use of such QSAR methods for screening and prioritizing the risk of dietary chemicals when actual animal data are inadequate, equivocal, or absent. Published by Elsevier Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Addict Safety, Div Biotechnol & GRAS Notice Review,HFS 255, College Pk, MD 20740 USA. US FDA, Div Food Contact Notificat, Ctr Food Safety & Appl Nutr, Off Food Addict Safety,HFS 255, College Pk, MD 20740 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Informat & Computat Safety Anal Staff, College Pk, MD 20740 USA. RP Valerio, LG (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Addict Safety, Div Biotechnol & GRAS Notice Review,HFS 255, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM luis.valerio@FDA.HHS.gov NR 169 TC 45 Z9 45 U1 2 U2 13 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUL 1 PY 2007 VL 222 IS 1 BP 1 EP 16 DI 10.1016/j.taap.2007.03.012 PG 16 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 187NE UT WOS:000247853900001 PM 17482223 ER PT J AU Calabrese, EJ Bachmann, KA Bailer, AJ Bolger, PM Borak, J Cai, L Cedergreen, N Cherian, MG Chiueh, CC Clarkson, TW Cook, RR Diamond, DM Doolittle, DJ Dorato, MA Duke, SO Feinendegen, L Gardner, DE Hart, RW Hastings, KL Hayes, AW Hoffmann, GR Ives, JA Jaworowski, Z Johnson, TE Jonas, WB Kaminski, NE Keller, JG Klaunig, JE Knudsen, TB Kozumbo, WJ Lettleri, T Liu, SZ Maisseu, A Maynard, KI Masoro, EJ McClellan, RO Mehendale, HM Mothersill, C Newlin, DB Nigg, HN Oehme, FW Phalen, RF Philbert, MA Rattan, SIS Riviere, JE Rodricks, J Sapolsky, RM Scott, BR Seymour, C Sinclair, DA Smith-Sonneborn, J Snow, ET Spear, L Stevenson, DE Thomas, Y Tubiana, M Williams, GM Mattson, MP AF Calabrese, Edward J. Bachmann, Kenneth A. Bailer, A. John Bolger, P. Michael Borak, Jonathan Cai, Lu Cedergreen, Nina Cherian, M. George Chiueh, Chuang C. Clarkson, Thomas W. Cook, Ralph R. Diamond, David M. Doolittle, David J. Dorato, Michael A. Duke, Stephen O. Feinendegen, Ludwig Gardner, Donald E. Hart, Ronald W. Hastings, Kenneth L. Hayes, A. Wallace Hoffmann, George R. Ives, John A. Jaworowski, Zbigniew Johnson, Thomas E. Jonas, Wayne B. Kaminski, Norbert E. Keller, John G. Klaunig, James E. Knudsen, Thomas B. Kozumbo, Walter J. Lettleri, Teresa Liu, Shu-Zheng Maisseu, Andre Maynard, Kenneth I. Masoro, Edward J. McClellan, Roger O. Mehendale, Harlhara M. Mothersill, Carmel Newlin, David B. Nigg, Herbert N. Oehme, Frederick W. Phalen, Robert F. Philbert, Martin A. Rattan, Suresh I. S. Riviere, Jim E. Rodricks, Joseph Sapolsky, Robert M. Scott, Bobby R. Seymour, Colin Sinclair, David A. Smith-Sonneborn, Joan Snow, Elizabeth T. Spear, Linda Stevenson, Donald E. Thomas, Yolene Tubiana, Maurice Williams, Gary M. Mattson, Mark P. TI Biological stress response terminology: Integrating the concepts of adaptive response and preconditioning stress within a hormetic dose-response framework SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article ID RADIATION HORMESIS; HISTORICAL FOUNDATIONS; ALCOHOL-CONSUMPTION; ESCHERICHIA-COLI; DNA-REPAIR; HYPOTHESIS; MORTALITY AB Many biological subdisciplines that regularly assess dose-response relationships have identified an evolutionarily conserved process in which a low dose of a stressful stimulus activates an adaptive response that increases the resistance of the cell or organism to a moderate to severe level of stress. Due to a lack of frequent interaction among scientists in these many areas, there has emerged a broad range of terms that describe such dose-response relationships. This situation has become problematic because the different terms describe a family of similar biological responses (e.g., adaptive response, preconditioning, hormesis), adversely affecting interdisciplinary communication, and possibly even obscuring generalizable features and central biological concepts. With support from scientists in a broad range of disciplines, this article offers a set of recommendations we believe can achieve greater conceptual harmony in dose-response terminology, as well as better understanding and communication across the broad spectrum of biological disciplines. (c) 2007 Elsevier Inc. All rights reserved. C1 Univ Massachusetts, Sch Publ Hlth, Amherst, MA 01003 USA. Univ Toledo, Toledo, OH 43606 USA. Univ Miami, Coral Gables, FL 33124 USA. US FDA, Rockville, MD 20857 USA. Yale Univ, New Haven, CT 06520 USA. Univ Louisville, Sch Med, Louisville, KY 40292 USA. Univ Western Ontario, London, ON N6A 3K7, Canada. Taipei Med Univ, Taipei, Taiwan. Univ Rochester, Rochester, NY 14627 USA. RRC Consulting, Austin, TX 78727 USA. Univ S Florida, Tampa, FL 33620 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. USDA, ARS, Rockville, MD 20857 USA. Univ Dusseldorf, D-4000 Dusseldorf, Germany. Inhalat Toxicol Associates, Washington, DC 20006 USA. US FDA, NCTR, Rockville, MD 20857 USA. Harvard Univ, Boston, MA 02114 USA. Coll Holy Cross, Worcester, MA 01610 USA. Cent Lab Radiol Protect, Warsaw, Poland. Univ Colorado, Boulder, CO 80309 USA. Michigan State Univ, E Lansing, MI 48824 USA. RP Calabrese, EJ (reprint author), Univ Massachusetts, Sch Publ Hlth, Morill N344, Amherst, MA 01003 USA. EM edwardc@schoolpli.umass.edu RI Cai, Lu/A-6024-2008; Riviere, Jim/A-9210-2008; Mattson, Mark/F-6038-2012; Cedergreen, Nina/F-6731-2014; OI Riviere, Jim/0000-0001-8412-9650; Cedergreen, Nina/0000-0003-4724-9447; JOHNSON, THOMAS/0000-0001-7147-8237; Sinclair, David/0000-0002-9936-436X NR 27 TC 285 Z9 292 U1 5 U2 66 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 1 PY 2007 VL 222 IS 1 BP 122 EP 128 DI 10.1016/j.taap.2007.02.015 PG 7 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 187NE UT WOS:000247853900013 PM 17459441 ER PT J AU Kochman, SA AF Kochman, Sheryl A. TI Role of the Food and Drug Administration in the use of molecular techniques in immunohematology SO TRANSFUSION LA English DT Article; Proceedings Paper CT Workshop on Molecular Methods in Immunohematology CY SEP 25-26, 2006 CL Bethesda, MD SP FDA, CBER, DDHS OS Off Public Hlth & Sci, NIH, Nalt Heart, Lung & Blood Inst ID ACQUIRED B-ANTIGEN; REAGENTS C1 US FDA, Devices Review Branch, Div Blood Applicat, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Kochman, SA (reprint author), US FDA, Devices Review Branch, Div Blood Applicat, Off Blood Res & Review,Ctr Biol Evaluat & Res, HFM-390,1401 Rockeville Pike, Rockville, MD 20852 USA. EM sheryl.kochman@fda.hhs.gov NR 10 TC 5 Z9 5 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD JUL PY 2007 VL 47 IS 1 SU S BP 3S EP 9S DI 10.1111/j.1537-2995.2007.01303.x PG 7 WC Hematology SC Hematology GA 188IV UT WOS:000247914500002 PM 17593279 ER PT J AU Porter, CM Horvath-Arcidiacono, JA Singh, AK Horvath, KA Bloom, ET Mohiuddin, MM AF Porter, Cynthia M. Horvath-Arcidiacono, Judith A. Singh, Avneesh K. Horvath, Keith A. Bloom, Eda T. Mohiuddin, Muhammad M. TI Characterization and expansion of baboon CD4(+)CD25(+) Treg cells for potential use in a non-human primate xenotransplantation model SO XENOTRANSPLANTATION LA English DT Article DE baboon; immune tolerance; regulatory T cells; transplantation tolerance; xenotransplantation ID REGULATORY T-CELLS; TRANSPLANTATION TOLERANCE; IN-VITRO; CLINICAL XENOTRANSPLANTATION; CARDIAC XENOTRANSPLANTATION; INTERLEUKIN-2 PRODUCTION; B-CELLS; RAPAMYCIN; PIGS; XENOGRAFTS AB Background: It is well established that CD4(+)CD25(+) regulatory T (Treg) cells can modulate allogeneic immune responses. Xenotransplantation, proposed as a means to address the critical shortage of human organs, may also benefit from similar approaches to avert rejection. Baboons are a preferred preclinical animal model for xenogeneic organ transplantation experiments, and the characterization of baboon Treg cells will be beneficial to future tolerance studies in this animal model. Methods: We analyzed CD4(+) CD25(+) T cells from baboon lymph nodes, spleens, and blood by flow cytometry, then purified and expanded porcine antigen-specific baboon CD4(+) CD25(high) cells in vitro to evaluate their regulatory activity in the baboon anti-pig xenogeneic responses. Results: CD4(+) CD25(high) T cells were 1.7%, 3.1 %, and 1.9% of baboon splenic, lymph node, and blood T cells, respectively. The CD4(+) CD25(high) T cells expressed the Treg cell-associated transcription factor, FoxP3. Proliferation/suppression assays using irradiated pig peripheral blood mononuclear cells as stimulators showed that Treg cells suppressed the vigorous baboon CD4(+) CD25(-) T-cell anti-pig proliferation response and cytokine secretion. Expanded baboon Treg cells suppressed baboon anti-pig CD4(+) CD25(-) T-cell proliferation similar to 4- to 10-fold more than freshly isolated Treg cells. Expanded Treg cells suppressed proliferation to primary cells from the same pig used for expansion more effectively than proliferation to stimulators from a different strain of pig, suggesting a level of antigen specificity. Conclusion: We demonstrate that baboon Treg cells suppress immune responses to xenogeneic stimulation. These Studies suggest that adoptive transfer of expanded Treg cells into transplant recipients may provide an approach to prevent cell-mediated rejection of grafts and potentially induce tolerance in the pig to baboon xenotransplantation preclinical model. C1 US FDA, CBER, Div Cellular & Gene Therapy, Bethesda, MD 20892 USA. NIH, NHLBI, Cardiothorac Surg Res Program, Bethesda, MD 20892 USA. RP Porter, CM (reprint author), US FDA, CBER, Div Cellular & Gene Therapy, HFM-725,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Mohiuddin, Muhammad/M-4642-2013 OI Mohiuddin, Muhammad/0000-0003-4654-783X NR 49 TC 25 Z9 26 U1 1 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2007 VL 14 IS 4 BP 298 EP 308 DI 10.1111/j.1399-3089.2007.00416.x PG 11 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 201QI UT WOS:000248847300003 PM 17669171 ER PT J AU Levy, MF Argaw, T Wilson, CA Brooks, J Sandstrom, P Merks, H Logan, J Klintmalm, G AF Levy, Marlon F. Argaw, Takele Wilson, Carolyn A. Brooks, James Sandstrom, Paul Merks, Harriet Logan, John Klintmalm, Goran TI No evidence of PERV infection in healthcare workers exposed to transgenic porcine liver extracorporeal support SO XENOTRANSPLANTATION LA English DT Article DE disease transmission; healthcare workers; porcine endogenous retrovirus ID CROSS-SPECIES TRANSMISSION; ENDOGENOUS RETROVIRUS PERV; HUMAN-CELLS; ENDOTHELIAL-CELLS; HUMAN SERUM; XENOTRANSPLANTATION; PIGS; RECIPIENTS; INACTIVATION; XENOGRAFTS AB Background: Clinical xenotransplantation holds great promise by providing one solution to the shortage of human organs for transplantation, while also posing a potential public health threat by facilitating transmission of infectious disease from source animals to humans. One potential vector for infectious disease transmission is healthcare workers (HCW) who are involved in administering xenotransplantation procedures. Methods: In this study, we studied 49 healthcare workers involved in the care of two subjects who participated in a study of porcine liver perfusion as treatment of fulminant hepatic failure. We looked to,serologic and virologic evidence of transmission of porcine endogenous retrovirus, and found that HCW had no evidence of infection. Conclusions: Results of our survey demonstrate that application of standard precautions may be sufficient to prevent transmission of porcine endogenous retrovirus, an agent of concern in ex vivo xenotransplantation products. C1 Baylor All St Med Ctr, Ft Worth, TX 76104 USA. US FDA, CBER, Div Cellular & Gene Therapies, Bethesda, MD 20014 USA. Publ Hlth Agcy Canada, Ctr Infect Dis Prevent & Control, Natl HIV & Retrovirol Labs, Ottawa, ON, Canada. Baxter Healthcare Corp, McGaw Pk, IL USA. Baylor Univ, Med Ctr, Dallas, TX USA. RP Levy, MF (reprint author), Baylor All St Med Ctr, 1400 8th Ave, Ft Worth, TX 76104 USA. EM marlonl@baylorhealth.edu NR 35 TC 18 Z9 18 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2007 VL 14 IS 4 BP 309 EP 315 DI 10.1111/j.1399-308.2007.00408.x PG 7 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 201QI UT WOS:000248847300004 PM 17669172 ER PT J AU Bloom, ET AF Bloom, Eda T. TI National policies for xenotransplantation in the USA SO XENOTRANSPLANTATION LA English DT Editorial Material AB An overview of xenotransplantation regulatory policies in the USA was presented at the Satellite Symposium, "Xenotransplantation - Current Standards for Clinical Trials," held in conjunction with the World Transplant Congress, Boston, MA, USA 2006. This article summarizes that overview. C1 US FDA, Gene Transfer & Immunogen Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Rockville, MD 20852 USA. RP Bloom, ET (reprint author), US FDA, Gene Transfer & Immunogen Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, HFM-725,1401 Rockville Pike, Rockville, MD 20852 USA. EM eda.bloom@fda.hhs.gov NR 0 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD JUL PY 2007 VL 14 IS 4 BP 345 EP 346 DI 10.1111/j.1399-3089.2007.00396.x PG 2 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 201QI UT WOS:000248847300009 PM 17669177 ER PT J AU Hu, XJ Schroeder, RJ Wang, WC Boyett, JM AF Hu, X. Joan Schroeder, R. Jason Wang, Winfred C. Boyett, James M. TI Pseudoscore-based estimation from biased observations SO STATISTICS IN MEDICINE LA English DT Article DE auxiliary information; estimating function; missing data; non-ignorable non-response ID REGRESSION-MODELS; MISSING DATA; LOGISTIC-REGRESSION; COMPLEX SURVEYS; COVARIATE DATA AB There are many practical situations where observation of the primary variable Y for individuals in a population is incomplete and depends on some auxiliary variables X that are potentially correlated with Y. We consider parameter estimation for the distribution of Y with the incomplete data, without specifying the underlying association between Y and X. The approach is based on a class of pseudoscore functions using available information of X. We demonstrate the consistency and asymptotic normality of the estimators and study their finite-sample properties in various situations via simulation. The methodology is illustrated by an example involving kindergarten readiness skills in children with sickle cell disease. Copyright (C) 2006 John Wiley & Sons, Ltd. C1 Simon Fraser Univ, Dept Stat & Actuarial Sci, Burnaby, BC V5A 1S6, Canada. Food & Drug Adm, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20850 USA. St Jude Childrens Res Hosp, Dept Hematol, Memphis, TN 38105 USA. St Jude Childrens Res Hosp, Dept Biostat, Memphis, TN 38105 USA. RP Hu, XJ (reprint author), Simon Fraser Univ, Dept Stat & Actuarial Sci, Burnaby, BC V5A 1S6, Canada. EM joanh@stat.sfu.ca FU NIAID NIH HHS [R01 AI 56995] NR 21 TC 2 Z9 2 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0277-6715 J9 STAT MED JI Stat. Med. PD JUN 30 PY 2007 VL 26 IS 14 BP 2836 EP 2852 DI 10.1002/sim.2754 PG 17 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 176BU UT WOS:000247058500007 PM 17133648 ER PT J AU Meyer, RJ Hendeles, L Colice, GL AF Meyer, Robert J. Hendeles, Leslie Colice, Gene L. TI Albuterol inhalers - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Silver Spring, MD 20993 USA. Univ Florida, Gainesville, FL 32610 USA. Washington Hosp Ctr, Washington, DC 20010 USA. RP Meyer, RJ (reprint author), US FDA, Silver Spring, MD 20993 USA. EM hendeles@cop.ufl.edu NR 2 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 28 PY 2007 VL 356 IS 26 BP 2749 EP 2749 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 183HS UT WOS:000247564500029 ER PT J AU Straetemans, M Katz, LM Belson, M AF Straetemans, Masja Katz, Linda M. Belson, Martin TI Adverse reactions after permanent-makeup procedures SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Ctr Dis Control & Prevent, Chamblee, GA 30341 USA. US FDA, College Pk, MD 20740 USA. RP Straetemans, M (reprint author), Ctr Dis Control & Prevent, Chamblee, GA 30341 USA. EM straetemansm@rki.de NR 5 TC 6 Z9 6 U1 1 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 JUN 28 PY 2007 VL 356 IS 26 BP 2753 EP 2753 DI 10.1056/NEJMc063122 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 183HS UT WOS:000247564500034 PM 17596617 ER PT J AU Hariharan, P Myers, MR Banerjee, RK AF Hariharan, P. Myers, M. R. Banerjee, R. K. TI HIFU procedures at moderate intensities - effect of large blood vessels SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID FOCUSED ULTRASOUND SURGERY; LESION FORMATION; SOFT-TISSUE; IN-VIVO; MODEL; ATTENUATION; PROPAGATION; CAVITATION; ABLATION; BUBBLES AB A three- dimensional computational model is presented for studying the efficacy of high-intensity focused ultrasound (HIFU) procedures targeted near large blood vessels. The analysis applies to procedures performed at intensities below the threshold for cavitation, boiling and highly nonlinear propagation, but high enough to increase tissue temperature a few degrees per second. The model is based upon the linearized KZK equation and the bioheat equation in tissue. In the blood vessel the momentum and energy equations are satisfied. The model is first validated in a tissue phantom, to verify the absence of bubble formation and nonlinear effects. Temperature rise and lesion-volume calculations are then shown for different beam locations and orientations relative to a large vessel. Both single and multiple ablations are considered. Results show that when the vessel is located within about a beam width ( few mm) of the ultrasound beam, significant reduction in lesion volume is observed due to blood flow. However, for gaps larger than a beam width, blood flow has no major effect on the lesion formation. Under the clinically representative conditions considered, the lesion volume is reduced about 40% (relative to the no-flow case) when the beam is parallel to the blood vessel, compared to about 20% for a perpendicular orientation. Procedures involving multiple ablation sites are affected less by blood flow than single ablations. The model also suggests that optimally focused transducers can generate lesions that are significantly larger (> 2 times) than the ones produced by highly focused beams. C1 Univ Cincinnati, Dept Mech Ind & Nucl Engn, Cincinnati, OH 45221 USA. US FDA, Div Solid & Fluid Mech, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. Univ Cincinnati, Dept Biomed Engn, Cincinnati, OH USA. RP Hariharan, P (reprint author), Univ Cincinnati, Dept Mech Ind & Nucl Engn, Cincinnati, OH 45221 USA. EM matthew.myers@fda.hhs.gov NR 32 TC 40 Z9 43 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 2007 VL 52 IS 12 BP 3493 EP 3513 DI 10.1088/0031-9155/52/12/011 PG 21 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 175XR UT WOS:000247047800011 PM 17664556 ER PT J AU Reese, DH Ramos-Valle, M AF Reese, David H. Ramos-Valle, Moraima TI A high-throughput method for monitoring changes in homeobox gene expression SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE homeobox; Hox; P19 cells; EC cells; stem cells; pluripotent ID EMBRYONAL CARCINOMA-CELLS; RETINOIC ACID RECEPTOR; HOX GENES; MURINE; DIFFERENTIATION; AMPLIFICATION; TRANSCRIPTION; ORGANIZATION; PATTERN; ALPHA AB Members of the homeobox gene superfamily of transcription factors are essential determinants of cellular identity during development. Their regulation and downstream gene targets are not well understood, however. This is due, in part, to the large number of genes that need to be analyzed simultaneously. A method has been developed for the rapid and simultaneous detection of changes in the expression of homeobox-containing genes, including members of the developmentally important Hox gene family. The method selectively amplifies and labels homeobox-containing mRNAs using a 3'-RACE procedure in combination with a degenerate forward primer that targets a highly conserved region of the homeobox found in all vertebrate Hox genes and many non-Hox homeobox-containing genes. The amplified sequences are identified by hybridization to a membrane-based array of covalently bound Hox and non-Hox homeobox gene sequences of interest. The method has been used here to demonstrate previously undetected changes in the expression of homeobox genes during retinoic acid-induced nerve cell differentiation in mouse pluripotent P19 cells. Published by Elsevier Inc. C1 US FDA, Div Mol Biol, Laurel, MD 20708 USA. US FDA, Div Toxicol, Laurel, MD 20708 USA. RP Reese, DH (reprint author), US FDA, Div Mol Biol, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM david.reese@fda.hhs.gov NR 23 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD JUN 15 PY 2007 VL 357 IS 4 BP 882 EP 888 DI 10.1016/j.bbrc.2007.04.040 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 170FP UT WOS:000246648400011 PM 17459334 ER PT J AU Raveche, ES Salerno, E Scaglione, BJ Manohar, V Abbasi, F Lin, YC Fredrickson, T Landgraf, P Ramachandra, S Huppi, K Toro, JR Zenger, VE Metcalf, RA Marti, GE AF Raveche, Elizabeth S. Salerno, Erica Scaglione, Brian J. Manohar, Vijaya Abbasi, Fatima Lin, Yi-Chu Fredrickson, Torgny Landgraf, Pablo Ramachandra, Sumant Huppi, Konrad Toro, Jorge R. Zenger, Vincent E. Metcalf, Robert A. Marti, Gerald E. TI Abnormal microRNA-16 locus with synteny to human 13q14 linked to CLL in NZB mice SO BLOOD LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; MURINE MODEL; LYMPHOPROLIFERATIVE DISEASE; GENES; SEQUENCE; REGION; LUPUS; MOUSE; CELLS; SUSCEPTIBILITY AB New Zealand black (NZB) mice with autoimmune and B lymphoproliferative disease (B-LPD) are a model for human chronic lymphocytic leukemia (CLL). A genomewide linkage scan of the NZB loci associated with lymphoma was conducted in F1 backcrosses of NZB and a control strain, DBA/2. Of 202 mice phenotyped for the presence or absence of LPD, surface maker expression, DNA content, and microsatellite polymorphisms, 74 had disease. The CD5(+), IgM(+), B220(dim), hyperdiploid LPD was linked to 3 loci on chromosomes 14, 18, and 19 that are distinct from previously identified autoimmunity-associated loci. The region of synteny with mouse D14mit160 is the human 13q14 region, associated with human CLL, containing microRNAs mir-15a16-1. DNA sequencing of multiple NZB tissues identified a point mutation in the 3' flanking sequence of the identical microRNA, mir16-1, and this mutation was not present in other strains, including the nearest neighbor, NZW. Levels of miR-16 were decreased in NZB lymphoid tissue. Exogenous miR-16 delivered to an NZB malignant B-1 cell line resulted in cellcycle alterations and increased apoptosis. Linkage of the mir-15a/16-1 complex and the development of B-LPD in this spontaneous mouse model suggest that the altered expression of the mir-15a/16-1 is the molecular lesion in CLL. C1 Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol & Lab Med, Newark, NJ 07103 USA. Georgetown Univ, Med Ctr, Dept Physiol & Biophys, Washington, DC 20007 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIH, NIAID, Immunopathol Lab, Bethesda, MD 20892 USA. Natl Inst Hlth, Natl Canc Inst, Gene Silencing Sect, Ctr Adv Technol, Gaithersburg, MD USA. NIH, NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Rockville, MD USA. Rockefeller Univ, Howard Hughes Med Inst, Lab RNA Mol Biol, New York, NY 10021 USA. RP Marti, GE (reprint author), Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pathol & Lab Med, 185 S Orange Ave, Newark, NJ 07103 USA. EM gemarti@helix.nih.gov FU NIAID NIH HHS [CA/AI71478-07, F32 AI071478] NR 43 TC 178 Z9 193 U1 0 U2 8 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 15 PY 2007 VL 109 IS 12 BP 5079 EP 5086 DI 10.1182/blood-2007-02-071225 PG 8 WC Hematology SC Hematology GA 180JW UT WOS:000247360200012 PM 17351108 ER PT J AU Gaines, AR AF Gaines, Ann Reed TI Further examination of intravascular hemolysis (IVH) following intravenous anti-D for immune thrombocytopenic purpura (ITP) SO BLOOD LA English DT Letter ID GLOBULIN; HEMOGLOBINURIA C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol HFM 220, Rockville, MD 20852 USA. RP Gaines, AR (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol HFM 220, 1401 Rockville Pike, Rockville, MD 20852 USA. EM ann.gaines@fda.hhs.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD JUN 15 PY 2007 VL 109 IS 12 BP 5528 EP 5528 DI 10.1182/blood-2007-02-070706 PG 1 WC Hematology SC Hematology GA 180JW UT WOS:000247360200079 ER PT J AU Zhang, L Gao, LF Zhao, LJ Guo, BF Ji, K Tian, Y Wang, JG Yu, H Hu, JD Kalvakolanu, DV Kopecko, DJ Zhao, XJ Xu, DQ AF Zhang, Ling Gao, Lifang Zhao, Lijuan Guo, Baofeng Ji, Kun Tian, Yong Wang, Jinguo Yu, Hao Hu, Jiadi Kalvakolanu, Dhananjaya V. Kopecko, Dennis J. Zhao, Xuejian Xu, De-Qi TI Intratumoral delivery and suppression of prostate tumor growth by attenuated Salmonella enterica serovar typhimurium carrying plasmid-based small interfering RNAs SO CANCER RESEARCH LA English DT Article ID SIGNALING INDUCES APOPTOSIS; PROTEIN EXPRESSION THERAPY; STAT3 ACTIVITY; NUDE-MICE; MATRIX METALLOPROTEINASE-2; DOWN-REGULATION; IN-VIVO; CANCER; ACTIVATION; INHIBITION AB The facultative anaerobic, invasive Salmonella enterica serovar typhimurium (S. typhimurium) has been shown to retard the growth of established tumors. We wondered if a more effective antitumor response could be achieved in vivo if these bacteria were used as tools for delivering specific molecular antitumor therapeutics. Constitutively activated transcription factor signal transducer and activator of transcription 3 (STAT3) promotes the survival of a number of human tumors. In this study, we investigated the relative efficacies of attenuated S. typhimurium alone or combined with Stat3-specific small interfering RNA (siRNA) in terms of tumor growth and metastasis. The bacteria preferentially homed into tumors over normal liver and spleen tissues in vivo. S. typhimurium expressing plasmid-based Stat3-specific siRNAs significantly inhibited tumor growth, reduced the number of metastastic organs, and extended the life time for C57BL6 mice bearing an implanted prostate tumor, versus bacterial treatment alone. These results suggest that attenuated S. typhimurium combined with an RNA interference approach might be more effective for the treatment of primary as well as metastatic cancer. C1 Jilin Univ, Dept Pathophysiol, Sch Basic Med, Prostate Dis Prevent & Treatment Res Ctr, Changchun 130021, Peoples R China. Univ Maryland, Sch Med, Dept Microbiol & Immunol, Program Mol Biol,Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Maryland, Dept Diagnost Sci & Pathol, Baltimore, MD 21201 USA. US FDA, Ctr Biol Evaluat & Res, Lab Enter & Sexually Transmitted Dis, Bethesda, MD USA. RP Zhao, XJ (reprint author), Jilin Univ, Dept Pathophysiol, Sch Basic Med, Prostate Dis Prevent & Treatment Res Ctr, Xinmin St, Changchun 130021, Peoples R China. EM pro_2@jlu.edu; xud@cber.fda.gov FU NCI NIH HHS [CA105005, CA78282] NR 48 TC 73 Z9 88 U1 1 U2 12 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 JUN 15 PY 2007 VL 67 IS 12 BP 5859 EP 5864 DI 10.1158/0008-5472.CAN-07-0098 PG 6 WC Oncology SC Oncology GA 180JV UT WOS:000247360100037 PM 17575154 ER PT J AU Krucoff, MW Boam, A Schultz, DG AF Krucoff, Mitchell W. Boam, Ashley Schultz, Daniel G. TI Drug-eluting stents "deliver heartburn" - How do we spell relief going forward? SO CIRCULATION LA English DT Article ID BARE-METAL STENTS; CLINICAL END-POINTS; CORONARY STENTS; FDA PERSPECTIVE; TRIALS; THROMBOSIS; MORTALITY C1 Duke Univ, Med Ctr, Duke Clin Res Inst, Durham, NC 27705 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Krucoff, MW (reprint author), Duke Univ, Med Ctr, Duke Clin Res Inst, Room A3006,508 Fulton St, Durham, NC 27705 USA. EM kruco001@mc.duke.edu NR 18 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JUN 12 PY 2007 VL 115 IS 23 BP 2990 EP 2994 DI 10.1161/CIRCULATIONAHA.107.707778 PG 5 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 177KZ UT WOS:000247153300014 PM 17473280 ER PT J AU Atrasheuskaya, AV Blatun, EM Kulak, MV Atrasheuskaya, A Karpov, IA Rubin, S Ignatyev, GM AF Atrasheuskaya, Alena V. Blatun, Elena M. Kulak, Michail V. Atrasheuskaya, Alina Karpov, Igor A. Rubin, Steven Ignatyev, George M. TI Investigation of mumps vaccine failures in Minsk, Belarus, 2001-2003 SO VACCINE LA English DT Article DE Belarus; mumps genotyping; vaccine failure ID IMMUNOGLOBULIN-G AVIDITY; VIRUS GENOTYPES; MEASLES-VACCINE; IGG AVIDITY; MOLECULAR CHARACTERIZATION; AFFINITY MATURATION; ANTIBODY-RESPONSE; IDENTIFICATION; SECONDARY; POPULATION AB The purpose of this study was to investigate mumps vaccine failures (VF) in a highly vaccinated population of Minsk, Belarus, and to investigate a possible role for virus strain-specific immunity. During our 3-year study period, 22 adults were admitted to the Infectious Diseases Hospital in Minsk with a diagnosis of mumps. A genotype HI mumps virus (MuV) strain was identified in all patients. Of 15 patients from whom the paired sera were collected, 9 were confirmed to have been previously vaccinated. Serological examinations indicated primary VF in seven of these cases and secondary VF in two. Despite almost all vaccinated patients possessing MuV specific IgG, few possessed neutralizing antibody to the vaccine strain and titers were nominal. Importantly, none of the sera were able to neutralize a genotype H MuV strain. Our results demonstrate the importance of assaying for neutralizing antibody and support the assertion that antigenic differences between wild type and vaccine MuV strains may play a role in cases of breakthrough infection in vaccinees. @ 2007 Elsevier Ltd. All rights reserved. C1 State Res Ctr Virol & Biotechnol Vector, Lab Immunol Safety, Novosibirsk 630559, Russia. Hosp Infect Dis, Minsk 220050, Byelarus. State Med Univ, Dept Infect Dis, Minsk 220116, Byelarus. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Atrasheuskaya, AV (reprint author), State Res Ctr Virol & Biotechnol Vector, Lab Immunol Safety, Novosibirsk 630559, Russia. EM marburgman3@infonet.by; ignat@vector.nsc.ru NR 41 TC 15 Z9 18 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 JUN 11 PY 2007 VL 25 IS 24 BP 4651 EP 4658 DI 10.1016/j.vaccine.2007.04.020 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 181FU UT WOS:000247423200002 PM 17498853 ER PT J AU Mehta, JL Sanada, N Hu, CP Chen, JW Dandapat, A Sugawara, F Satoh, H Inoue, K Kawase, Y Jishage, K Suzuki, H Takeya, M Schnackenberg, L Beger, R Hermonat, PL Thomas, M Sawamura, T AF Mehta, Jawahar L. Sanada, Nobuhito Hu, Chang Ping Chen, Jiawei Dandapat, Abhijit Sugawara, Fumiaki Satoh, Hiroo Inoue, Kazuhiko Kawase, Yosuke Jishage, Kou-ichi Suzuki, Hiroshi Takeya, Motohiro Schnackenberg, Laura Beger, Richard Hermonat, Paul L. Thomas, Maria Sawamura, Tatsuya TI Deletion of LOX-1 reduces atherogenesis in LDLR knockout mice fed high cholesterol diet SO CIRCULATION RESEARCH LA English DT Article DE atherosclerosis; oxidative stress; inflammation; LOX-1 ID LOW-DENSITY-LIPOPROTEIN; VASCULAR ENDOTHELIAL-CELLS; FACTOR-KAPPA-B; LECTIN-LIKE; OXIDIZED LDL; RECEPTOR-1 LOX-1; OX-LDL; ATHEROSCLEROTIC LESION; INDUCIBLE EXPRESSION; SMOOTH-MUSCLE AB Atherosclerosis is associated with oxidative stress and inflammation, and upregulation of LOX-1, an endothelial receptor for oxidized LDL (oxLDL). Here, we describe generation of LOX-1 knockout (KO) mice in which binding of oxLDL to aortic endothelium was reduced and endothelium-dependent vasorelaxation preserved after treatment with oxLDL (P < 0.01 versus wild-type mice). To address whether endothelial functional preservation might lead to reduction in atherogenesis, we crossed LOX-1 KO mice with LDLR KO mice and fed these mice 4% cholesterol/ 10% cocoa butter diet for 18 weeks. Atherosclerosis was found to cover 61 +/- 2% of aorta in the LDLR KO mice, but only 36 +/- 3% of aorta in the double KO mice. Luminal obstruction and intima thickness were significantly reduced in the double KO mice (versus LDLR KO mice). Expression of redox-sensitive NF-kappa B and the inflammatory marker CD68 in LDLR KO mice was increased (P < 0.01 versus wild-type mice), but not in the double KO mice. On the other hand, antiinflammatory cytokine IL-10 expression and superoxide dismutase activity were low in the LDLR KO mice (P < 0.01 versus wild-type mice), but not in the double KO mice. Endothelial nitric oxide synthase expression was also preserved in the double KO mice. The proinflammatory signal MAPK P38 was activated in the LDLR KO mice, and LOX-1 deletion reduced this signal. In conclusion, LOX-1 deletion sustains endothelial function leading to a reduction in atherogenesis in association with reduction in proinflammatory and prooxidant signals. C1 Univ Arkansas Med Sci, Gene Therapy Program, Little Rock, AR 72205 USA. Natl Cardiovasc Ctr, Osaka, Japan. Kumamoto Univ, Kumamoto, Japan. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Mehta, JL (reprint author), Univ Arkansas Med Sci, Gene Therapy Program, Little Rock, AR 72205 USA. EM MehtaJL@uams.edu RI Sawamura, Tatsuya/E-7103-2010 NR 46 TC 232 Z9 244 U1 1 U2 16 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7330 J9 CIRC RES JI Circ.Res. PD JUN 8 PY 2007 VL 100 IS 11 BP 1634 EP 1642 DI 10.1161/CIRCRESAHA.107.149724 PG 9 WC Cardiac & Cardiovascular Systems; Hematology; Peripheral Vascular Disease SC Cardiovascular System & Cardiology; Hematology GA 176ID UT WOS:000247077300015 PM 17478727 ER PT J AU Li, AM Piccardo, P Barmada, SJ Ghetti, B Harris, DA AF Li, Aimin Piccardo, Pedro Barmada, Sami J. Ghetti, Bernardino Harris, David A. TI Prion protein with an octapeptide insertion has impaired neuroprotective activity in transgenic mice SO EMBO JOURNAL LA English DT Article DE mutation; neuroprotection; octapeptide; prion; transgenic ID INDUCED CELL-DEATH; NEURODEGENERATIVE DISEASE; CONFORMATIONAL CONVERSION; THERMODYNAMIC STABILITY; HUNTINGTONS-DISEASE; INFECTED MICE; HUMAN NEURONS; PRP; MUTATIONS; SCRAPIE AB Familial prion diseases are due to dominantly inherited, germline mutations in the PRNP gene that encodes the prion protein (PrP). The cellular mechanism underlying the pathogenic effect of these mutations remains uncertain. To investigate whether pathogenic mutations impair a normal, physiological activity of PrP, we have crossed Tg(PG14) mice, which express PrP with an octapeptide insertion associated with an inherited prion dementia, with Tg(PrP Delta 32-134) mice. Tg(PrP Delta 32-134) mice, which express an N-terminally truncated form of PrP, spontaneously develop a neurodegenerative phenotype that is stoichiometrically reversed by coexpression of wild-type PrP. We find that, at equivalent expression levels, PG14 PrP is significantly less efficient than wildtype PrP in suppressing the development of clinical symptoms and neuropathology in Tg(PrP Delta 32-134) mice. Thus, our results suggest that some features of the neurological illness associated with inherited PrP mutations may be attributable to a loss of PrP neuroprotective function. This mechanism stands in contrast to the toxic gain-of-function mechanisms that are usually invoked to explain the pathogenesis of dominantly inherited neurodegenerative disorders. C1 Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Indiana Univ, Sch Med, Div Neuropathol, Indianapolis, IN 46204 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Harris, DA (reprint author), Washington Univ, Sch Med, Dept Cell Biol & Physiol, 660 S Euclid Ave, St Louis, MO 63110 USA. EM dharris@wustl.edu FU NIA NIH HHS [P30 AG010133, P30 AG10133]; NIGMS NIH HHS [T32 GM007200, T32 GM07200]; NINDS NIH HHS [NS040975, R01 NS040975] NR 62 TC 28 Z9 28 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0261-4189 J9 EMBO J JI Embo J. PD JUN 6 PY 2007 VL 26 IS 11 BP 2777 EP 2785 DI 10.1038/sj.emboj.7601726 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 176KO UT WOS:000247084100015 PM 17510630 ER PT J AU Wagner, RF Metz, CE Campbell, G AF Wagner, Robert F. Metz, Charles E. Campbell, Gregory TI Assessment of medical imaging systems and computer aids: A tutorial review SO ACADEMIC RADIOLOGY LA English DT Review DE ROC analysis; multiple-reader multiple-case (MRMC) ROC analysis; assessment methodologies ID DORFMAN-BERBAUM-METZ; OPERATING CHARACTERISTIC ANALYSIS; CHARACTERISTIC ROC DATA; MONTE-CARLO VALIDATION; OBSERVER-PERFORMANCE; FREE-RESPONSE; EXPERIMENTAL-DESIGN; DIAGNOSTIC-TESTS; MRMC METHOD; MULTIPLE-ABNORMALITIES AB This article reviews the central issues that arise in the assessment of diagnostic imaging and computer-assist modalities. The paradigm of the receiver operating characteristic (ROC) curve-the dependence of the true-positive fraction versus the false-positive fraction as a function of the level of aggressiveness of the reader/radiologist toward a positive call-is essential to this field because diagnostic imaging systems are used in multiple settings, including controlled laboratory studies in which the prevalence of disease is different from that encountered in a study in the field. The basic equation of statistical decision theory is used to display how readers can vary their level of aggressiveness according to this diagnostic context. Most studies of diagnostic modalities in the last 15 years have demonstrated not only a range of levels of reader aggressiveness, but also a range of level of reader performance. These characteristics require a multivariate approach to ROC analysis that accounts for both the variation of case difficulty and the variation of reader skill in a study. The resulting paradigm is called the multiple-reader, multiple-case ROC paradigm. Highlights of historic as well as contemporary work in this field are reviewed. Many practical issues related to study design and resulting statistical power are included, together with recent developments and availability of analytical software. C1 US FDA, Off Sci, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. US FDA, Engn Labs, Rockville, MD 20850 USA. US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. RP Wagner, RF (reprint author), US FDA, Off Sci, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. EM robert.wagner@fda.hhs.gov FU NCI NIH HHS [R01-CA62362] NR 126 TC 83 Z9 86 U1 1 U2 12 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 EI 1878-4046 J9 ACAD RADIOL JI Acad. Radiol. PD JUN PY 2007 VL 14 IS 6 BP 723 EP 748 DI 10.1016/j.acra.2007.03.001 PG 26 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 173GK UT WOS:000246861300011 PM 17502262 ER PT J AU Sanders, GD Al-Khatib, SM Berliner, E Bigger, JT Buxton, AE Califf, RM Carlson, M Curtis, AB Curtis, JP Domanski, M Fain, E Gersh, BJ Gold, MR Goldberger, J Haghighi-Mood, A Hammill, SC Harder, J Healey, J Hlatky, MA Hohnloser, SH Lee, KL Mark, DB Mitchell, B Phurrough, S Prystowsky, E Smith, JM Stockbridge, N Temple, R AF Sanders, Gillian D. Al-Khatib, Sana M. Berliner, Elise Bigger, J. Thomas Buxton, Alfred E. Califf, Robert M. Carlson, Mark Curtis, Anne B. Curtis, Jeptha P. Domanski, Michael Fain, Eric Gersh, Bernard J. Gold, Michael R. Goldberger, Jeffrey Haghighi-Mood, Ali Hammill, Stephen C. Harder, Joel Healey, Jeffrey Hlatky, Mark A. Hohnloser, Stefan H. Lee, Kerry L. Mark, Daniel B. Mitchell, Brent Phurrough, Steve Prystowsky, Eric Smith, Joseph M. Stockbridge, Norman Temple, Robert TI Preventing tomorrow's sudden cardiac death today: Part 11: Translating sudden cardiac death risk assessment strategies into practice and policy SO AMERICAN HEART JOURNAL LA English DT Article ID IMPLANTABLE CARDIOVERTER-DEFIBRILLATOR; LEFT-VENTRICULAR DYSFUNCTION; COST-EFFECTIVENESS; MYOCARDIAL-INFARCTION; PROPHYLACTIC USE; HEART-FAILURE; RESYNCHRONIZATION THERAPY; DEVICE ADVISORIES; AMIODARONE; CARDIOMYOPATHY AB Although current evidence supporting a more precise strategy for identifying patients at highest risk for sudden cardiac death (SCD) is sparse, strategies for translating existing and future evidence into clinical practice and policy are needed today. A great many unanswered questions exist. Examples include the following: At what level of risk for SCD should we pursue further testing or therapy? How should clinical strategies ethically and economically balance alternative outcomes? How can we best translate optimal strategies into clinical practice so as to prevent tomorrow's SCDs? On July 20 and 2 1, 2006, a group of individuals with expertise in clinical cardiovascular medicine, biostatistics, economics, and health policy was joined by government (Food and Drug Administration; Centers for Medicare and Medicaid Services; National Heart, Lung, and Blood Institute; Agency for Healthcare Research and Quality), professional societies (Heart Rhythm Society), and industry to discuss strategies for risk assessment and prevention of SCD. The meeting was organized by the Duke Center for the Prevention of Sudden Cardiac Death and the Duke Clinical Research Institute. This article, the second of 2 documents, summarizes the policy discussions of that meeting, discusses an analytic framework for evaluating the risks and benefits associated with SCD prevention and risk stratification, and addresses the translation of SCD risk assessment strategies into practice and policy. C1 Duke Med Ctr, Duke Clin Res Inst, Durham, NC USA. Agcy Hlth Res & Qual, Rockville, MD USA. Columbia Univ, New York, NY USA. Rhode Isl Hosp, Providence, RI USA. St Jude Med, Sunnyvale, CA USA. Univ S Florida, Tampa, FL USA. Yale Univ, Sch Med, New Haven, CT USA. NHLBI, NIH, Bethesda, MD 20892 USA. Mayo Clin, New Rochelle, NY USA. Med Univ S Carolina, Charleston, SC 29425 USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. Cambridge Heart Inc, Bedford, MA USA. Heart Rhythm Soc, Washington, DC USA. McMaster Univ, Gen Hosp, Hamilton, ON, Canada. Sch Med, Stanford, CA USA. Univ Frankfurt, D-6000 Frankfurt, Germany. Libin Cardiovasc Inst Alberta, Albany, CA USA. Ctr Med, Medicoid Serv, Baltimore, MD USA. St Vincents Hosp, Indianapolis, IN USA. Boston Sci Inc, St Paul, MN USA. US FDA, Silver Spring, MD USA. RP Sanders, GD (reprint author), Duke Univ, Duke Clin Res Inst, PO Box 17969, Durham, NC 27715 USA. EM gillion.sanders@duke.edu NR 32 TC 10 Z9 10 U1 0 U2 1 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD JUN PY 2007 VL 153 IS 6 BP 951 EP 959 DI 10.1016/j.ahj.2007.03.002 PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 182YT UT WOS:000247540600009 PM 17540195 ER PT J AU Graham, D AF Graham, D. TI FDA's role in drug safety. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract CT 40th Annual Meeting of the Society-for-Epidemiologic-Research CY JUN 19-22, 2007 CL Boston, MA SP Soc Epidemiolog Res C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2007 VL 165 IS 11 SU S BP S93 EP S93 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 175SO UT WOS:000247034500372 ER PT J AU Cooper, WO Willy, ME Pont, SJ Ray, WA AF Cooper, William O. Willy, Mary E. Pont, Stephen J. Ray, Wayne A. TI Increasing use of antidepressants in pregnancy SO AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY LA English DT Article AB We quantified the rate of exposure to in a antidepressants during pregnancy large cohort of women enrolled in Tennessee Medicaid from 1999 through 2003. C1 Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. US FDA, Ctr Drug Evaluat & Res, Div Drug Risk Evaluat, Off Surveillance & Epidemiol, Silver Spring, MD USA. RP Cooper, WO (reprint author), Vanderbilt Univ, Sch Med, Dept Pediat, Nashville, TN 37212 USA. FU AHRQ HHS [HS-0384]; PHS HHS [HHSF223200510010C] NR 0 TC 169 Z9 172 U1 3 U2 11 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0002-9378 J9 AM J OBSTET GYNECOL JI Am. J. Obstet. Gynecol. PD JUN PY 2007 VL 196 IS 6 BP 544 EP 545 AR 544.e1 DI 10.1016/j.ajog.2007.01.033 PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 177EY UT WOS:000247137600018 PM 17547888 ER PT J AU Kanal, E Barkovich, AJ Bell, C Borgstede, JP Bradley, WG Froelich, JW Gilk, T Gimbel, JR Gosbee, J Kuhni-Kaminski, E Lester, JW Nyenhuis, J Parag, Y Schaefer, DJ Sebek-Scoumis, EA Weinreb, J Zaremba, LA Wilcox, P Lucey, L Sass, N AF Kanal, Emanuel Barkovich, A. James Bell, Charlotte Borgstede, James P. Bradley, William G., Jr. Froelich, Jerry W. Gilk, Tobias Gimbel, J. Rod Gosbee, John Kuhni-Kaminski, Ellisa Lester, James W., Jr. Nyenhuis, John Parag, Yoav Schaefer, Daniel J. Sebek-Scoumis, Elizabeth A. Weinreb, Jeffrey Zaremba, Loren A. Wilcox, Pamela Lucey, Leonard Sass, Nancy CA ACR Blue Ribbon Panel MR Safety TI ACR Guidance Document for Safe MR Practices: 2007 SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material DE MR contrast agents; MRI; safety ID NEPHROGENIC SYSTEMIC FIBROSIS; RADIOLOGY WHITE PAPER; PATIENT-MANAGEMENT; IMAGING SAFETY; GADODIAMIDE INJECTION; PEDIATRIC-PATIENTS; AMERICAN-COLLEGE; CONTRAST-MEDIA; GUIDELINES; GADOLINIUM C1 Amer Coll Radiol, Reston, VA USA. Univ Calif San Francisco, Neuroradiol Sect, San Francisco, CA 94143 USA. NYU, Sch Med, Dept Anesthesiol, New York, NY 10016 USA. Amer Soc Anesthesiologists, New York, NY USA. Colorado Springs Radiologists, Colorado Springs, CO USA. Univ Calif San Diego, Dept Radiol, San Diego, CA 92103 USA. Univ Minnesota, Dept Radiol, Minneapolis, MN 55455 USA. MRI Planning, Kansas City, MO USA. E Tennessee Heart Consultants, Lenoir City, TN USA. Univ Michigan Hlth Syst, Ann Arbor, MI USA. Red Forest Consulting, Ann Arbor, MI USA. Purdue Univ, Dept Elect & Comp Engn, W Lafayette, IN 47907 USA. GE Healthcare, MR Syst Engn, Milwaukee, WI USA. Yale Univ, Sch Med, New Haven, CT USA. US FDA, Rockville, MD 20857 USA. Univ Pittsburgh, Med Ctr, Dept Radiol, Pittsburgh, PA USA. RP Sass, N (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA USA. NR 74 TC 316 Z9 332 U1 2 U2 7 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 JUN PY 2007 VL 188 IS 6 BP 1447 EP 1474 DI 10.2214/AJR.06.1616 PG 28 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 170LV UT WOS:000246665800005 PM 17515363 ER PT J AU Rothmann, M Braun, MM Ng, TH AF Rothmann, Mark Braun, M. Miles Ng, Tie-Hua TI On the hazard ratios and corresponding confidence intervals that appear in Basran et al. (2006) SO ANESTHESIA AND ANALGESIA LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Rothmann, M (reprint author), US FDA, Rockville, MD 20857 USA. EM mark.rothmann@fda.hhs.gov NR 1 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JUN PY 2007 VL 104 IS 6 BP 1597 EP 1597 DI 10.1213/01.ane.0000260642.67261.5a PG 1 WC Anesthesiology SC Anesthesiology GA 172GB UT WOS:000246791000052 PM 17513665 ER PT J AU Trigona, WL Porter, CM Horvath-Arcidiacono, JA Majumdar, AS Bloom, ET AF Trigona, Wendy L. Porter, Cynthia M. Horvath-Arcidiacono, Judith A. Majumdar, Anish S. Bloom, Eda T. TI Could heme-oxygenase-1 have a role in modulating the recipient immune response to embryonic stem cells? SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID HEME OXYGENASE-1; CARBON-MONOXIDE; ALLOGRAFT SURVIVAL; REPERFUSION INJURY; RAT LIVERS; TRANSPLANTATION; BILIVERDIN; EXPRESSION; INDUCTION; TOLERANCE AB Pluripotent human embryonic stem cells (hESCs) may provide a potential source of cellular therapies, but as allogeneic cells may require evading the recipient's immune response. Using an NIH-registry hESC line, it was found that undifferentiated hESCs induce a reduced proliferative response compared to PBMC and demonstrate that this diminished response correlates with the activity of heme oxygenase-1 (HO-1). Inhibition of HO-1 significantly increases T cell proliferation against hESC, indicating the potential suppression of these cells during transplantation of allogeneic hESC. These data suggest the hypothesis that HO-1 provides a mechanism for protecting hESCs in vivo. C1 US FDA, CBER, OCTGT, DCGT GTIB, Bethesda, MD 20892 USA. Geron Corp, Menlo Pk, CA USA. RP Bloom, ET (reprint author), US FDA, CBER, OCTGT, DCGT GTIB, HFM-725,8800 Rockville Pike, Bethesda, MD 20892 USA. EM eda.bloom@fda.hhs.gov NR 33 TC 11 Z9 11 U1 0 U2 11 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD JUN PY 2007 VL 9 IS 6 BP 751 EP 756 DI 10.1089/ars.2007.1602 PG 6 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 170EU UT WOS:000246646000013 PM 17511591 ER PT J AU Johnson, TJ Wannemuehler, YM Johnson, SJ Logue, CM White, DG Doetkott, C Nolan, LK AF Johnson, Timothy J. Wannemuehler, Yvonne M. Johnson, Sara J. Logue, Catherine M. White, David G. Doetkott, Curt Nolan, Lisa K. TI Plasmid replicon typing of commensal and pathogenic types of Escherichia coli isolates (vol 73, pg 1976, 2007) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Correction C1 Iowa State Univ, Dept Vet Microbiol & Prevent Med, Coll Vet Med, Ames, IA 50011 USA. US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. N Dakota State Univ, Informat Technol Serv, Fargo, ND 58105 USA. RP Johnson, TJ (reprint author), Iowa State Univ, Dept Vet Microbiol & Prevent Med, Coll Vet Med, 1802 Elwood Dr,VMRI 2, Ames, IA 50011 USA. NR 1 TC 0 Z9 0 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 JUN PY 2007 VL 73 IS 11 BP 3768 EP 3768 DI 10.1128/AEM.00760-07 PG 1 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 175MB UT WOS:000247016600043 ER PT J AU Bhattacharjee, A Pal, S Feldman, GM Cathcart, MK AF Bhattacharjee, Ashish Pal, Sralbani Feldman, Gerald M. Cathcart, Martha K. TI The role of Src kinase in regulating 15-lipoxygenase expression in primary human monocytes SO ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY LA English DT Meeting Abstract CT Annual Conference on Arteriosclerosis, Thrombosis, and Vascular Biology CY APR 19-21, 2007 CL Chicago, IL SP Amer Heart Assoc Council Arterioscleros, Thrombos, & Vascular Biol, Council Nutr, Phys Activity, & Metabolism, Natl Heart, Lung, & Blood Inst C1 Cleveland Clin, Lerner Res Inst, Cleveland, OH USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1079-5642 J9 ARTERIOSCL THROM VAS JI Arterioscler. Thromb. Vasc. Biol. PD JUN PY 2007 VL 27 IS 6 BP E117 EP E117 PG 1 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 171DH UT WOS:000246714600466 ER PT J AU Metz, B Brunel, F Chamberlin, C van der Gun, J Halder, M Jiskoot, W Kersten, G van Opstal, O Petersen, JW Ravetkar, SD Redhead, K Schwanig, M Wilhelmsen, ES Vann, WF Hendriksen, C AF Metz, Bernard Brunel, Florence Chamberlin, Catherine van der Gun, Johan Halder, Marlies Jiskoot, Wim Kersten, Gideon van Opstal, Omer Petersen, Jesper W. Ravetkar, Satish D. Redhead, Keith Schwanig, Michael Wilhelmsen, Ellen Sloth Vann, Willie F. Hendriksen, Coenraad TI The potential of physicochemical and immunochemical assays to replace animal tests in the quality control of toxoid vaccines - The report and recommendations of ECVAM workshop 61(a) SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article ID DIPHTHERIA; FORMALDEHYDE; ADJUVANTS; IMMUNOGENICITY; TETANUS; ANTIGEN; TOXIN; REACTOGENICITY; ADSORPTION; STABILITY C1 Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM, I-21020 Ispra, VA, Italy. Netherlands Vaccine Inst, Bilthoven, Netherlands. Sanofi Pasteur, Marcy Letoile, France. Council Europe, European Directorate Qual Med, Strasbourg, France. Leiden Univ, Leiden Amsterdam Ctr Drug Res, Leiden, Netherlands. GlaxoSmithKline Biol, Rixensart, Belgium. Statens Serum Inst, DK-2300 Copenhagen, Denmark. Serum Inst India Ltd, Pune, Maharashtra, India. Intervet UK Ltd, Milton Keynes, Bucks, England. Paul Ehrlich Inst, D-6070 Langen, Germany. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Univ Utrecht, Netherlands Ctr Alternat Anim Use, Utrecht, Netherlands. RP Metz, B (reprint author), Commiss European Communities, Joint Res Ctr, Inst Hlth & Consumer Protect, ECVAM, I-21020 Ispra, VA, Italy. EM bernard.metz@nvi-vaccin.nl; marlies.halder@jrc.it RI Jiskoot, Wim/A-6877-2016 OI Jiskoot, Wim/0000-0002-1012-3456 NR 29 TC 12 Z9 12 U1 0 U2 1 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD JUN PY 2007 VL 35 IS 3 BP 323 EP 331 PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 195GW UT WOS:000248401500012 PM 17650951 ER PT J AU Perez-Losada, M Crandall, KA Bash, MC Dan, M Zenilman, J Viscidi, RP AF Perez-Losada, Marcos Crandall, Keith A. Bash, Margaret C. Dan, Michael Zenilman, Jonathan Viscidi, Raphael P. TI Distinguishing importation from diversification of quinolone-resistant Neisseria gonorrhoeae by molecular evolutionary analysis SO BMC EVOLUTIONARY BIOLOGY LA English DT Article ID AMINO-ACID SITES; LEVEL CIPROFLOXACIN RESISTANCE; POPULATION-GENETICS; DECREASED SUSCEPTIBILITY; HOUSEKEEPING GENES; HIGH-PREVALENCE; SELECTION; EPIDEMIOLOGY; MUTATIONS; INFERENCE AB Background: Distinguishing the recent introduction of quinolone resistant gonococci into a population from diversification of resistant strains already in the population is important for planning effective infection control strategies. We applied molecular evolutionary analyses to DNA sequences from 9 housekeeping genes and gyrA, parC and porB of 24 quinolone resistant N. gonorrhoeae ( QRNG) and 24 quinolone sensitive isolates collected in Israel during 2000 - 2001. Results: Phylogenetic and eBURST analyses and estimates of divergence time indicated QRNG were introduced on 3 separate occasions and underwent limited diversification by mutation, deletion and horizontal gene transfer. Reconstruction of N. gonorrhoeae demography showed a slowly declining effective strain population size from 1976 to 1993, rapid decline between 1994 and 1999, and an increase from 1999 to 2001. This is partially attributable to declining gonorrhea case rates from 1973 to 1994. Additional contributing factors are selective sweeps of antibiotic resistant gonococci and increased transmission from sex workers. The abrupt decline in the mid- 1990s heralded an increased incidence of gonorrhea from 1997 to the present. The subsequent increase in effective strain population size since 1999 reflects the increased gonococcal census population and introduction of quinolone resistance strains. Conclusion: Our study demonstrates the effective use of population genetic approaches to assess recent and historical population dynamics of N. gonorrhoeae. C1 Brigham Young Univ, Dept Integrat Biol, Provo, UT 84602 USA. Brigham Young Univ, Dept Microbiol & Mol Biol, Provo, UT 84602 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20014 USA. Edith Wolf Hosp, Infect Dis Unit, Tel Aviv, Israel. Johns Hopkins Univ, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21218 USA. Johns Hopkins Univ, Sch Med, Dept Pediat, Stanley Div, Baltimore, MD 21218 USA. RP Viscidi, RP (reprint author), Brigham Young Univ, Dept Integrat Biol, Provo, UT 84602 USA. EM mlosada@genoma-llc.com; keith_crandall@byu.edu; Bash@cber.FDA.go; midan@post.tau.ac.il; jzenilm1@jhmi.edu; rviscid1@jhmi.edu RI Perez-Losada, Marcos/I-4407-2013; OI Perez-Losada, Marcos/0000-0002-2585-4657; Crandall, Keith/0000-0002-0836-3389 FU NIAID NIH HHS [R01 AI050217, R01-AI-50217] NR 44 TC 8 Z9 8 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2148 J9 BMC EVOL BIOL JI BMC Evol. Biol. PD JUN 1 PY 2007 VL 7 AR 84 DI 10.1186/1471-2148-7-84 PG 10 WC Evolutionary Biology; Genetics & Heredity SC Evolutionary Biology; Genetics & Heredity GA 186AP UT WOS:000247751800001 PM 17543117 ER PT J AU Honjo, Y Bian, YS Kawakami, K Molinolo, A Longenecker, G Boppana, R Larsson, J Karlsson, S Gutkind, JS Puri, RK Kulkarni, AB AF Honjo, Yasuyuki Bian, Yansong Kawakami, Koji Molinolo, Alfredo Longenecker, Glenn Boppana, Ramanamurthy Larsson, Jonas Karlsson, Stefan Gutkind, J. Silvio Puri, Raj K. Kulkarni, Ashok B. TI TGF-beta receptor I conditional knockout mice develop spontaneous squamous cell carcinoma SO CELL CYCLE LA English DT Article DE TGF-beta receptor I; squamous cell carcinoma; IL-13; Cre-lox P system; TGF-beta; cytotoxin; head and neck cancer ID GROWTH-FACTOR-BETA; TARGETED CANCER-THERAPY; PSEUDOMONAS EXOTOXIN; IL-13 RECEPTOR; NECK-CANCER; TUMOR IMMUNOSURVEILLANCE; APOPTOTIC PATHWAYS; ALPHA-2 CHAIN; COLON-CANCER; MERKEL CELL AB We generated a mouse model with a conditional deletion of TGF-beta signaling in the neurons by crossing TGF-beta receptor I (T beta RI) floxed mice with neurofilament-H (NF-H) Cre mice. 35% of F1 conditional knockout (COKO) mice developed spontaneous squamous cell carcinomas (SCCs) in periorbital and/ or perianal regions. Transplantation of these tumors into athymic nude mice resulted in 62% tumorigenicity. To determine whether evasion of the immune response plays any role in this tumorigenesis, we analyzed the expression levels of receptors for interleukin-13 (mIL-13R), a key negative regulator of tumor immunosurveillance, and found that 33% of COKO tumors expressed the IL-13R alpha 2 chain. Primary cultures of the SCCs expressing IL-13R alpha 2 were sensitive to the cytotoxic effect of IL-13R-directed cytotoxin treatment. This is the first demonstration that loss of T beta RI can lead to spontaneous tumor formation. These mice can serve as a unique mouse model of SCC to evaluate the tumorigenicity and effect of anti-cancer therapeutics. C1 NIDCR, LCDB, NIH, Funct Genom Sect, Bethesda, MD 20892 USA. NIDCR, Gene Targeting Facil, NIH, Bethesda, MD USA. NIDCR, Oral & Pharyngeal Canc Branch, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. Univ Lund Hosp, Inst Lab Med, Dept Mol Med & Gene Therapy, S-22185 Lund, Sweden. RP Kulkarni, AB (reprint author), NIDCR, LCDB, NIH, Funct Genom Sect, 30 Convent Dr,Bldg 30,Room 130,MSC 4395, Bethesda, MD 20892 USA. EM ak40m@nih.gov RI Gutkind, J. Silvio/A-1053-2009 NR 56 TC 18 Z9 19 U1 0 U2 0 PU LANDES BIOSCIENCE PI GEORGETOWN PA 810 SOUTH CHURCH STREET, GEORGETOWN, TX 78626 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD JUN 1 PY 2007 VL 6 IS 11 BP 1360 EP 1366 PG 7 WC Cell Biology SC Cell Biology GA 190SZ UT WOS:000248081700016 PM 17534148 ER PT J AU Derrick, SC Morris, SL AF Derrick, Steven C. Morris, Sheldon L. TI The ESAT6 protein of Mycobacterium tuberculosis induces apoptosis of macrophages by activating caspase expression SO CELLULAR MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; DENDRITIC CELLS; BCG VACCINES; VIRULENCE; ANTIGENS; INFECTION; INDUCTION; MECHANISM; IMMUNITY; ONCOSIS AB The secreted Mycobacterium tuberculosis protein, ESAT6, has been studied extensively in pathogenicity and vaccine experiments. Despite these studies little is known about the function of this protein. In this report, we demonstrate that ESAT6 induces apoptosis in THP-1 human macrophages using fluorescein isothiocyanate-Annexin V and intracellular caspase staining. We show that the induction of apoptosis by ESAT6 is dependent on the dose of the protein and the expression of caspase genes. Using real-time RT-PCR, we found that expression of caspase-1, -3, -5, -7 and -8 genes was upregulated in cells treated with ESAT6 relative to untreated cells. Furthermore, we show that while infection of THP-1 cells with wild-type M. tuberculosis strain H37Rv resulted in significant apoptosis 48 h post infection, a deletion mutant that does not express ESAT6 failed to induce significant apoptosis. Finally, experimental results using a cell impermeable fluorescent stain suggests that the formation of membrane pores may be a primary mechanism by which ESAT6 evokes an apoptotic response. C1 United States Food & Drug Adm, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. RP Derrick, SC (reprint author), United States Food & Drug Adm, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. EM steven.derrick@fda.hhs.gov NR 42 TC 111 Z9 125 U1 0 U2 8 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD JUN PY 2007 VL 9 IS 6 BP 1547 EP 1555 DI 10.1111/j.1462-5822.2007.00892.x PG 9 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 169FF UT WOS:000246577400016 PM 17298391 ER PT J AU Lesko, LJ AF Lesko, L. J. TI Personalized medicine: Elusive dream or imminent reality? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID DRUG DEVELOPMENT; WARFARIN AB The market for molecular diagnostic tests is predicted to grow at extraordinary rates over the next 10 years, fueled by pharmacogenetics and the elusive dream of personalized medicine. The challenge is managing the expectations of the medical community and the public at large that have already been set by speculation, promises, and the repeated exposure to headlines about genetic discoveries. Personalized medicine is a paradigm that exists more in conceptual terms than in reality, with only a few marketed drug-test companion products and not very many actual clinical practices set up to personalize medicine in the way that supporters have intended. Nevertheless, the reality of personalized medicine has become more imminent because of the increased awareness of the shortcomings in the delivery of drugs with adequate benefit/risk to patients, a better molecular understanding of how to optimize drug selection and dosing, and an increased demand for integrating more clinically relevant genetic information into the drug development process to improve both innovation and productivity. This paper focuses on personalized medicine by (1) looking at some converging changes taking place in the health-care landscape that are creating a scientific and social infrastructure to enable personalized medicine, (2) considering challenges that need to be addressed with regard to clinical evidence standards for validating genotype-phenotype associations, and (3) considering how clinical pharmacology can help construct a rational personalized medicine framework. As therapeutic experts, clinical pharmacologists can work to assure that '' good therapeutics follows good diagnostics ''. They are well equipped to provide timely genetic education to others and to interpret genetic data so that actionable decisions, especially about drug dosing in individual patients, can be implemented in clinical practice. C1 US FDA, Off Clin Pharmacol, Silver Spring, MD USA. RP Lesko, LJ (reprint author), US FDA, Off Clin Pharmacol, Silver Spring, MD USA. EM lawrence.lesko@fda.hhs.gov NR 11 TC 87 Z9 95 U1 1 U2 21 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JUN PY 2007 VL 81 IS 6 BP 807 EP 816 DI 10.1038/sj.clpt.6100204 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 168QT UT WOS:000246539800007 PM 17505496 ER PT J AU Rafii, F Jackson, LD Ross, I Heinze, TM Lewis, SM Aidoo, A Lyn-Cook, L Manjanathas, M AF Rafii, Fatemeh Jackson, Leslie D. Ross, Ian Heinze, Thomas M. Lewis, Sherry M. Aidoo, Anane Lyn-Cook, Lascelles Manjanathas, Mugimane TI Metabolism of daidzein by fecal bacteria in rats SO COMPARATIVE MEDICINE LA English DT Article ID DIETARY SOY PHYTOESTROGENS; INTESTINAL BACTERIA; GUT MICROFLORA; ISOFLAVONOID DAIDZEIN; URINARY METABOLITES; OVARIECTOMIZED RATS; CYNOMOLGUS MONKEYS; REPRODUCTIVE-TRACT; C-RING; EQUOL AB Daidzein (4',7-dihydroxyisoflavone), a soy phytoestrogen, is a weakly estrogenic compound that may have potential health benefits. Biotransformation of daidzein by the human gut microflora after ingestion converts it to either the highly estrogenic metabolite equol or to nonestrogenic metabolites. We investigated the metabolism of daidzein by colonic microflora of rats. Fecal samples, obtained before and after rats were exposed to daidzein at 250 or 1000 parts per million, were incubated in brain-heart infusion (BHD broth with daidzein under anaerobic conditions. Samples were removed from the cultures daily and analyzed by high-performance liquid chromatography (HPLC) and mass spectrometry. The fecal bacteria of all rats, regardless of prior daidzein exposure, metabolized the added daidzein to dihydrodaidzein. Both compounds disappeared rapidly from BHI cultures incubated for more than 24 h, but no other daidzein metabolites were detected. Only daidzein and dihydrodaidzein were found in a direct analysis of the feces of rats that had consumed daidzein in their diets. Unlike the fecal bacteria of humans and monkeys, the rat flora rapidly metabolized daidzein to aliphatic compounds that could not be detected by HPLC or mass spectral analysis. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Reprod Toxicol, Jefferson, AR 72079 USA. RP Rafii, F (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM Fatemeh.Rafii@fda.hhs.gov NR 43 TC 16 Z9 17 U1 2 U2 7 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 2007 VL 57 IS 3 BP 282 EP 286 PG 5 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 180UJ UT WOS:000247391300006 PM 17605343 ER PT J AU Schmid, I Lambert, C Ambrozak, D Marti, GE Moss, DM Perfetto, SP AF Schmid, Ingrid Lambert, Claude Ambrozak, David Marti, Gerald E. Moss, Delynn M. Perfetto, Stephen P. TI International society for analytical cytology biosafety standard for sorting of unfixed cells SO CYTOMETRY PART A LA English DT Article DE flow cytometry; occupational health; bio-hazards; cell sorting; biosafety; aerosol containment ID HUMAN-IMMUNODEFICIENCY-VIRUS; FLOW-CYTOMETRY; POSTEXPOSURE PROPHYLAXIS; HEALTH-CARE; INFECTIONS; AEROSOL; CANCER; INACTIVATION; EXPOSURES; SURVIVAL AB Background: Cell sorting of viable biological specimens has become very prevalent in laboratories involved in basic and clinical research. As these samples can contain infectious agents, precautions to protect instrument operators and the environment from hazards arising from the use of sorters are paramount. To this end the International Society of Analytical Cytology (ISAC) took a lead in establishing biosafety guidelines for sorting of unfixed cells (Schmid et al., Cytometry 1997;28:99-117). During the time period these recommendations have been available, they have become recognized worldwide as the standard practices and safety precautions for laboratories performing viable cell sorting experiments. However, the field of cytometry has progressed since 1997, and the document requires an update. Methods: Initially, suggestions about the document format and content were discussed among members of the ISAC Biosafety Committee and were incorporated into a draft version that was sent to all committee members for review. Comments were collected, carefully considered, and incorporated as appropriate into a draft document that was posted on the ISAC web site to invite comments from the flow cytometry community at large. The revised document was then submitted to ISAC Council for review. Simultaneously, further comments were sought from newly-appointed ISAC Biosafety committee members. Results: This safety standard for performing viable cell sorting experiments was recently generated. The document contains background information on the biohazard potential of sorting and the hazard classification of infectious agents as well as recommendations on (1) sample handling, (2) operator training and personal protection, (3) laboratory design, (4) cell sorter set-up, maintenance, and decontamination, and (5) testing the instrument for the efficiency of aerosol containment. Conclusions: This standard constitutes an updated and expanded revision of the 1997 biosafety guideline document. It is intended to provide laboratories involved in cell sorting with safety practices that take into account the enhanced hazard potential of high-speed sorting. Most importantly; it states that droplet-based sorting of infectious or hazardous biological material requires a higher level of containment than the one recommended for the risk group classification of the pathogen. The document also provides information on safety features of novel instrumentation, new options for personal protective equipment, and recently developed methods for testing the efficiency of aerosol containment. Published 2007 Wdey-Liss, Inc(dagger). C1 Univ Calif Los Angeles, David Geffen Sch Med, Dept Hematol Oncol, Los Angeles, CA 90095 USA. Univ Hosp St Etienne, Immunol Lab, St Etienne, France. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIH, CBER FDA, Lab Med & Mol Genet, Flow & Image Cytometry Sect,Div Cell & Gene Thera, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Schmid, I (reprint author), Univ Calif Los Angeles, David Geffen Sch Med, Dept Hematol Oncol, 12-236 Factor Bldg, Los Angeles, CA 90095 USA. EM schmid@mednet.ucla.edu FU NCI NIH HHS [CA-16042]; NIAID NIH HHS [AI-28697] NR 60 TC 26 Z9 27 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4922 J9 CYTOM PART A JI Cytom. Part A PD JUN PY 2007 VL 71A IS 6 BP 414 EP 437 DI 10.1002/cyto.a.20390 PG 24 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 171EQ UT WOS:000246718100010 PM 17385740 ER PT J AU Dearfield, KL Fuscoe, JC AF Dearfield, Kerry L. Fuscoe, James C. TI Impact of Genomic Technologies on Regulatory Policies - Presentations at the 37th Annual Meeting of the Environmental Mutagen Society SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material C1 USDA, Food Safety & Inspect Serv, Off Publ Hlth Sci, Washington, DC 20250 USA. US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Dearfield, KL (reprint author), USDA, Food Safety & Inspect Serv, Off Publ Hlth Sci, Washington, DC 20250 USA. EM kerry.dearfield@fsis.usda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUN PY 2007 VL 48 IS 5 BP 347 EP 348 DI 10.1002/em.20311 PG 2 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 182ED UT WOS:000247487000002 ER PT J AU Fuscoe, JC Tong, W Shi, L AF Fuscoe, James C. Tong, Weida Shi, Leming TI QA/QC issues to aid regulatory acceptance of microarray gene expression data SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc DE FDA critical path; MAQC; regulatory decision-making ID CONTROL MAQC PROJECT; QUALITY-CONTROL; PHARMACEUTICAL-INDUSTRY; PLATFORMS; PERFORMANCE; CONSISTENCY; GENOMICS; ARRAYS AB The U.S. Food and Drug Administration is responsible for (1) promoting and protecting public health by assuring the safety and effectiveness of medicines and medical devices and (2) advancing public health by helping to speed innovations that make medicines and foods safer, more effective, and more affordable. The genomics revolution has dramatically increased our knowledge of basic biology but this has not resulted in the expected acceleration of new medical product development. The Agency's Critical Path to New Medical Products stresses that new tools are needed to address this pipeline problem. Microarray technology is one of these promising tools although questions have risen about the reproducibility of measurements. The Microarray Quality Control (MAQC) Project was initiated by FDA scientists to address this issue. This large project, which evaluated reference RNA samples on seven microarray platforms, found good intralaboratory repeatability and interlaboratory reproducibility. In addition, there was high cross-platform consistency. All data are available free of cost and the reference RNA samples are available for proficiency testing. Thus, current microarray technology appears to provide both reliability and consistency for regulatory submissions. C1 US FDA, Natl Ctr Toxicol Res, Ctr Funct Genom, Div Syst Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Toxicoinformat, Jefferson, AR 72079 USA. RP Fuscoe, JC (reprint author), US FDA, Natl Ctr Toxicol Res, Ctr Funct Genom, Div Syst Toxicol, 3900 NCTR RD,HFT-130, Jefferson, AR 72079 USA. EM james.fuscoe@fda.hhs.gov NR 18 TC 9 Z9 9 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUN PY 2007 VL 48 IS 5 BP 349 EP 353 DI 10.1002/em.20293 PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 182ED UT WOS:000247487000003 PM 17567852 ER PT J AU Goodsaid, F Frueh, FW AF Goodsaid, Federico Frueh, Felix W. TI Implementing the US FDA Guidance on Pharmacogenomic Data Submissions SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT 37th Annual Meeting of the Environmental-Mutagen-Society CY SEP 16-20, 2006 CL Vancouver, CANADA SP Environm Mutagen Soc DE genomic; biomarker; regulatory AB The FDA Guidance for Industry: Pharmacogenomics Data Submissions was issued in 2005. This guidance document covers a broad area associated with how and when to submit genomic data to the FDA. Additional tasks associated with genomic data submissions include the implementation of genomic data submissions; the process for qualification of exploratory biomarkers into valid biomarkers; and technical recommendations for the generation and submission of genomic data to the FDA. These tasks have been addressed throughout the past 2 years by a number of initiatives. These initiatives have included the development of the Interdisciplinary Pharmacogenomics Review Group for review of pharmacogenomic data submissions, the pilot process for qualification of biomarkers, and the concept paper on recommendations for the generation and submission of genomic data. These initiatives have contributed to the effective implementation of the Pharmacogenomics Guidance at the FDA. C1 US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol,Genom Grp, Silver Spring, MD 20903 USA. RP Goodsaid, F (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Clin Pharmacol,Genom Grp, 10903 New Hampshire Ave,Bldg 21,Room 3663, Silver Spring, MD 20903 USA. EM federico.goodsaid@fda.hhs.gov NR 5 TC 31 Z9 33 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD JUN PY 2007 VL 48 IS 5 BP 354 EP 358 DI 10.1002/em.20294 PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 182ED UT WOS:000247487000004 PM 17567848 ER PT J AU Ilev, IK AF Ilev, I. K. TI A simple confocal fibre-optic laser method for intraocular lens power measurement SO EYE LA English DT Article DE intraocular lens dioptric power confocal fibre-optic laser method; single-mode fibre coupler ID EFFECTIVE FOCAL LENGTHS; OPTICAL-ELEMENTS AB Purpose To develop novel confocal fibre-optic laser method ( CFOLM) for accurate and objective measuring of the dioptric power of both positive and negative intraocular lenses ( IOLs). Methods The CFOLM principle of operation is based on a simple apertureless single-mode fibre laser confocal design. The key element is a single-mode fibre coupler that serves simultaneously as a point light source ( 3-5 mu m fibre diameter) used for the formation of a collimated Gaussian beam, and as a confocal point receiver that is highly sensitive to spatial displacements of the focused backreflectance laser emission. The basic CFOLM systems include IOL testing set-ups for the measurement of both positive and negative IOLs. Results The CFOLM designs provide high accuracy ( <= 1 mu m) in spatially locating the IOL focal point and in measuring the focal length in a broad range of both positive and negative powers including high-magnification IOLs with power greater than 720 D. We have tested various IOL samples with both positive ( +5 to +30 D) and negative ( -5 to -20 D) powers and we have obtained high levels of power testing repeatability estimated by a SD in the interval of 0.004-0.06/0.003-0.013D and a relative error in the interval of 0.015-0.3/0.02-0.16%, for positive/negative IOLs, respectively. Conclusions The presented IOL power testing method offers a simple, accurate, objective, quick, and relatively inexpensive approach for dioptric power measurement of positive and negative IOLs. It provides an independent source of IOL power measurement data and information for evaluating the effectiveness and safety of novel IOL products. C1 US FDA, Div Phys, Off Sci & Engn Labs, Ctr Device & Radiol Hlth, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Div Phys, Off Sci & Engn Labs, Ctr Device & Radiol Hlth, HFZ-130,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. EM ilko.ilev@fda.hhs.gov NR 14 TC 11 Z9 11 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-222X J9 EYE JI Eye PD JUN PY 2007 VL 21 IS 6 BP 819 EP 823 DI 10.1038/sj.eye.6702406 PG 5 WC Ophthalmology SC Ophthalmology GA 176WR UT WOS:000247116100024 PM 16710435 ER PT J AU Loving, CL Kennett, M Lee, GM Grippe, VK Merkel, TJ AF Loving, Crystal L. Kennett, Mary Lee, Gloria M. Grippe, Vanessa K. Merkel, Tod J. TI Murine aerosol challenge model of anthrax SO INFECTION AND IMMUNITY LA English DT Article ID EXPERIMENTAL INHALATION ANTHRAX; NECROSIS-FACTOR-ALPHA; BACILLUS-ANTHRACIS; INTRATRACHEAL INSTILLATION; ALVEOLAR MACROPHAGES; PULMONARY ANTHRAX; STERNE STRAIN; SPORES; MICE; PATHOGENESIS AB The availability of relevant and useful animal models is critical for progress in the development of effective vaccines and therapeutics. The infection of rabbits and non-human primates with fully virulent Bacillus anthracis spores provides two excellent models of anthrax disease. However, the high cost of procuring and housing these animals and the specialized facilities required to deliver fully virulent spores limit their practical use in early stages of product development. Conversely, the small size and low cost associated with using mice makes this animal model more practical for conducting experiments in which large numbers of animals are required. In addition, the availability of knockout strains and well-characterized immunological reagents makes it possible to perform studies in mice that cannot be performed easily in other species. Although we, along with others, have used the mouse aerosol challenge model to examine the outcome of B. anthracis infection, a detailed characterization of the disease is lacking. The current study utilizes a murine aerosol challenge model to investigate disease progression, innate cytokine responses, and histological changes during the course of anthrax after challenge with aerosolized spores. Our results show that anthrax disease progression in a complement-deficient mouse after challenge with aerosolized Sterne spores is similar to that described for other species, including rabbits and non-human primates, challenged with fully virulent B. anthracis. Thus, the murine aerosol challenge model is both useful and relevant and provides a means to further investigate the host response and mechanisms of B. anthracis pathogenesis. C1 CBER, Lab Resp & Special Pathogens, DBPAP, FDA, Bethesda, MD 20892 USA. Penn State Univ, Dept Vet & Bimed Sci, State Coll, PA 16804 USA. RP Merkel, TJ (reprint author), CBER, Lab Resp & Special Pathogens, DBPAP, FDA, Bld 29,Room 418,29 Lindoln Dr,880 Rockville Pike, Bethesda, MD 20892 USA. EM merkel@cber.fda.gov FU NIAID NIH HHS [U54 AI 50804, K08 AI050804] NR 51 TC 47 Z9 48 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2007 VL 75 IS 6 BP 2689 EP 2698 DI 10.1128/IAI.01875-06 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 172SN UT WOS:000246824500006 PM 17353290 ER PT J AU Raffoul, JJ Banerjee, S Che, MX Knoll, ZE Doerge, DR Abrams, J Kucuk, O Sarkar, FH Hillman, GG AF Raffoul, Julian J. Banerjee, Sanjeev Che, Mingxin Knoll, Zvi E. Doerge, Daniel R. Abrams, Judith Kucuk, Omer Sarkar, Fazlul H. Hillman, Gilda G. TI Soy isoflavones enhance radiotherapy in a metastatic prostate cancer model SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE prostate cancer; soy isoflavones; genistein; radiation ID GENISTEIN IN-VITRO; ORTHOTOPIC MODEL; TUMOR-MODEL; RADIATION; GROWTH; MICE; VIVO; PHYTOESTROGENS; INHIBITION; CARCINOMA AB We previously reported that genistein, the bioactive isoflavone of soybeans, acts as a radiosensitizer for prostate cancer. Pretreatment of tumor cells with genistein potentiated radiation-induced killing in vitro and in orthotopic models in vivo. However, pure genistein promoted increased lymph node metastasis, when administered alone in vivo. We investigated in vitro and in vivo the effects of soy isoflavones (genistein, daidzein and glycitein) as soy pills of similar composition are used in human interventions but not pure genistein. Soy isoflavones inhibited cell survival and potentiated radiation cell killing in PC-3 tumor cells, in vitro. Increased cell killing correlated with inhibition of antiapoptotic molecules Bcl-xL and survivin, upregulation of proapoptotic Bax molecule and PARP cleavage, suggesting activation of apoptotic pathways. In vivo, using the PC-3 orthotopic metastatic mouse model, soy isoflavones and prostate tumor irradiation led to enhanced control of primary tumor growth and metastasis, as observed with pure genistein and radiation. Interestingly, treatment with soy isoflavones did not increase metastasis to para-aortic lymph nodes in contrast to the consistent increase caused by pure genistein. Histologically prostate tumors, treated with soy isoflavones and radiation, showed tumor destruction and in situ tissue alterations, comparable with genistein and radiation effects. However, genistein, but not soy isoflavones, caused induction of HIF1-alpha in prostate tumors, suggesting that induction of hypoxia by pure genistein could contribute to increased metastasis. Our studies demonstrate the safety and potential role of soy isoflavones for enhancing the therapeutic effect of radiotherapy in prostate cancer. (c) 2007 Wiley-Liss, Inc. C1 Wayne State Univ, Dept Radiat Oncol, Barbara Ann Karmanos Canc Inst, Sch Med, Detroit, MI 48201 USA. Wayne State Univ, Dept Pathol, Barbara Ann Karmanos Canc Inst, Sch Med, Detroit, MI 48201 USA. Wayne State Univ, Dept Integrated Biostat, Barbara Ann Karmanos Canc Inst, Sch Med, Detroit, MI 48201 USA. Wayne State Univ, Dept Internal Med, Barbara Ann Karmanos Canc Inst, Sch Med, Detroit, MI 48201 USA. US FDA, Div Biochem Toxicol, Jefferson, AR USA. RP Hillman, GG (reprint author), Wayne State Univ, Dept Radiat Oncol, Barbara Ann Karmanos Canc Inst, Sch Med, 515 HWCRC,4100 John R, Detroit, MI 48201 USA. EM hillmang@karmanos.org NR 23 TC 44 Z9 45 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD JUN 1 PY 2007 VL 120 IS 11 BP 2491 EP 2498 DI 10.1002/ijc.22548 PG 8 WC Oncology SC Oncology GA 156XV UT WOS:000245684100028 PM 17304503 ER PT J AU Edwards, MC Gardner, ES Chelonis, JJ Schulz, EG Flake, RA Diaz, PF AF Edwards, Mark C. Gardner, Eunice S. Chelonis, John J. Schulz, Eldon G. Flake, Rebecca A. Diaz, Pamela F. TI Estimates of the validity and utility of the Conners' continuous performance test in the assessment of inattentive and/or hyperactive-impulsive behaviors in children SO JOURNAL OF ABNORMAL CHILD PSYCHOLOGY LA English DT Article DE CPT; ADHD; Conner's continuous performance task; assessment; children ID ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; DEFICIT DISORDER; SUSTAINED ATTENTION; ADHD; DIAGNOSIS; TASK; PSYCHOPATHOLOGY; SYMPTOMS; BOYS; TOOL AB This study evaluated the validity and classification utility of the Conners' Continuous Performance Test (CCPT) in the assessment of inattentive and hyperactive-impulsive behaviors in children. Significant, positive correlations between the CCPT parameters and behavioral ratings of ADHD behaviors were hypothesized. In addition, it was hypothesized that the CCPT parameters would perform better than a random test (chance) and show fair to moderate utility of classification across the different indices. Participants were 104 children between 6 and 12 years of age who were referred for evaluation of attention problems. The first hypothesis was not supported. There were no significant, positive correlations between the CCPT parameters and parent and teacher ratings of inattentive and hyperactive-impulsive behaviors. The second hypothesis was only partially supported. The CCPT Overall Index and the Omission Errors (84th percentile cutoff) performed better than a random test; however, the utility of the CCPT Overall Index only ranged from poor to slight. Receiver operating characteristic analyses showed the accuracy of the CCPT to be low. The implications and limitations of this study and future research directions are discussed. C1 Arkansas Childrens Hosp, Little Rock, AR 72202 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72202 USA. Univ Arkansas, Dept Res & Sponsored Programs, Little Rock, AR 72701 USA. Natl Ctr Toxicol Res, Jefferson, AR USA. Univ Kentucky, Dept Psychol, Lexington, KY 40506 USA. Idaho State Univ, Dept Psychol, Pocatello, ID 83209 USA. RP Edwards, MC (reprint author), Arkansas Childrens Hosp, 800 Marshall St,Slot 512-21, Little Rock, AR 72202 USA. EM edwardsmark@uams.edu NR 50 TC 32 Z9 35 U1 1 U2 7 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0091-0627 J9 J ABNORM CHILD PSYCH JI J. Abnorm. Child Psychol. PD JUN PY 2007 VL 35 IS 3 BP 393 EP 404 DI 10.1007/s10802-007-9098-3 PG 12 WC Psychology, Clinical; Psychology, Developmental SC Psychology GA 171KG UT WOS:000246734200006 PM 17295064 ER PT J AU Vierk, KA Koehler, KM Fein, SB Street, DA AF Vierk, Katherine A. Koehler, Kathleen M. Fein, Sara B. Street, Debra A. TI Prevalence of self-reported food allergy in American adults and use of food labels SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE food allergy; food labeling; prevalence ID TELEPHONE SURVEY; POPULATION AB Background: Few population-based studies in the United States have determined the prevalence of food allergy in adults and the problems these individuals might have with reading food labels. Objective: The objectives of this study are to report the prevalence of self-reported food allergy, to identify the characteristics of food allergy reactions, and to describe the use of labels among adults with food allergy. Methods: Questions from the US Food and Drug Administration's 2001 Food Safety Survey were analyzed to determine the prevalence of food allergy and opinions about food labels in the management of food allergy. Results: The prevalence of self-reported food allergy is 9.1% among all survey respondents, with 5.3% of all respondents reporting a doctor-diagnosed food allergy. The prevalence of food allergy to the 8 most common allergens (peanut, tree nuts, egg, milk, wheat, soybeans, fish, and crustacean shellfish) is self-reported as 2.7% among respondents with doctors' diagnoses. Several label issues, such as words on some ingredient lists being too technical or hard to understand and food labels not always alerting persons to new ingredients, were reported as serious or very serious obstacles for managing an allergy. Conclusion: The prevalence of self-reported doctor-diagnosed food allergy among US adults is 5.3%, and a large portion of adults with food allergy found certain label issues a serious problem for managing their food allergy. Clinical implications: The findings provide a needed source of population-based prevalence data of food allergy among US adults. Label issues identified are useful in understanding the difficulties of managing a food allergy. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Vierk, KA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 728, College Pk, MD 20740 USA. EM katherine.vierk@fda.hhs.gov NR 17 TC 92 Z9 95 U1 3 U2 17 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUN PY 2007 VL 119 IS 6 BP 1504 EP 1510 DI 10.1016/j.jaci.2007.03.011 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 178PO UT WOS:000247232800028 PM 17451802 ER PT J AU Hariharan, P Chang, I Myers, MR Banerjee, RK AF Hariharan, Prasanna Chang, Isaac Myers, Matthew R. Banerjee, Rupak K. TI Radio-frequency ablation in a realistic reconstructed hepatic tissue SO JOURNAL OF BIOMECHANICAL ENGINEERING-TRANSACTIONS OF THE ASME LA English DT Article ID HEAT-TRANSFER; TUMOR ABLATION; EQUATION; PERFUSION; MODEL AB This study uses a reconstructed vascular geometry to evaluate the thermal response of tissue during a three-dimensional radiofrequency (rf) tumor ablation. MRI images of a sectioned liver tissue containing arterial vessels are processed and converted into a finite-element mesh. A rf heat source in the form of a spherically symmetric Gaussian distribution, fit from a previously computed profile, is employed. Convective cooling within large blood vessels is treated using direct physical modeling of the heat and momentum transfer within the vessel. Calculations of temperature rise and thermal dose are performed for transient rf procedures in cases where the tumor is located at three different locations near the bifurcation point of a reconstructed artery. Results demonstrate a significant dependence of tissue temperature profile on the reconstructed vasculature and the tumor location. Heat convection through the arteries reduced the steady-state temperature rise, relative to the no-flow case, by up to 70% in the targeted volume. Blood flow also reduced the thermal dose value, which quantifies the extent of cell damage, from similar to 3600 min, for the no-flow condition, to 10 min for basal flow (13.8 cm/s). Reduction of thermal dose below the threshold value of 240 min indicates ablation procedures that may inadequately elevate the temperature in some regions, thereby permitting possible tumor recursion. These variations are caused by vasculature tortuosity that are patient specific and can be captured only by the reconstruction of the realistic geometry. C1 Univ Cincinnati, Dept Mech Engn, Cincinnati, OH 45221 USA. US FDA, Ctr Devices & Radiol Hlth, Div Solid & Fluid Mech, Silver Spring, MD 20993 USA. US FDA, Ctr Devices & Radiol Hlth, Div Phys, Silver Spring, MD 20993 USA. Univ Cincinnati, Dept Mech Engn, Cincinnati, OH 45221 USA. RP Banerjee, RK (reprint author), Univ Cincinnati, Dept Mech Engn, 688 Rhodes Hall,POB 210072, Cincinnati, OH 45221 USA. EM rupak.banerjee@uc.edu NR 33 TC 10 Z9 11 U1 0 U2 3 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 JUN PY 2007 VL 129 IS 3 BP 354 EP 364 DI 10.1115/1.2720912 PG 11 WC Biophysics; Engineering, Biomedical SC Biophysics; Engineering GA 178KL UT WOS:000247219500007 PM 17536902 ER PT J AU Brinker, A Mosholder, A Schech, SD Burgess, M Avigan, M AF Brinker, Allen Mosholder, Andrew Schech, Stephanie D. Burgess, Margaret Avigan, Mark TI Indication and use of drug products used to treat attention-deficit/hyperactivity disorder: A cross-sectional study with inference on the likelihood of treatment in adulthood SO JOURNAL OF CHILD AND ADOLESCENT PSYCHOPHARMACOLOGY LA English DT Article ID PATTERNS AB Introduction: Published literature suggests that attention-deficit/hyperactivity disorder (ADHD) affects 4% of adults and that as many as 60% of children with a diagnosis of ADHD will continue to have problems with inattention and impulsivity in adulthood. We analyzed cross-sectional prescription claims data and data from a national survey of office-based physicians for further inference on the likelihood of treatment with ADHD medications into adulthood. Methods: This study used data from a proprietary, national survey of office- based physicians (the IMS Health National Disease and Therapeutic Index, NDTI (TM)) to describe the indication associated with office visits with mention of common stimulant medications and atomoxetine. Enrollment and prescription claims data maintained by a large national health-care company were analyzed for age-specific utilization of these same agents. Results: Data from the NDTI (TM) suggest that the vast majority of visits associated with a stimulant medication or atomoxetine was coded with a diagnosis consistent with a mental health condition and not obesity/weight loss. The health plans included in this study processed 222,096 prescriptions for stimulant medications and atomoxetine among 43,175 unique patients aged 1-64 years during the calendar year 2004. Analyses of pharmacy claims data showed a steep increase in use through age 11 (prevalence = 70.3 per 1,000 covered lives) followed by a marked decrease and plateau from age 25 through age 64 years (prevalence = 5 to 10 per 1,000 covered lives). Conclusions: On the basis of comparison of the prevalence rate peak of 70 per 1,000 around age 11 years to a plateau of 7 per 1,000 during the early career years, our results are consistent with a prediction that at least one child in 10 placed on an ADHD medication in childhood will receive treatment into adulthood. The decrease in the prevalence of use of these medications with advancing age as seen in this cross-sectional study may reflect upon several clinical and secular factors. C1 US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD USA. Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN USA. RP Brinker, A (reprint author), FDA White Oak Campus,Room 3412,Bldg 22,10903 New, Silver Spring, MD 20993 USA. EM allen.brinker@fda.hhs.gov FU FDA HHS [FD-U-002067-03, FD-U-002067-02] NR 8 TC 7 Z9 7 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1044-5463 J9 J CHILD ADOL PSYCHOP JI J. Child Adolesc. Psychopharmacol. PD JUN PY 2007 VL 17 IS 3 BP 328 EP 333 DI 10.1089/cap.2006.0062 PG 6 WC Pediatrics; Pharmacology & Pharmacy; Psychiatry SC Pediatrics; Pharmacology & Pharmacy; Psychiatry GA 190CE UT WOS:000248034700010 PM 17630866 ER PT J AU Weisz, A Idina, A Ben-Ari, J Karni, M Mandelbaum, A Ito, Y AF Weisz, Adrian Idina, Ana Ben-Ari, Julius Karni, Miriam Mandelbaum, Asher Ito, Yoichiro TI Preparative separation of isomeric and stereoisomeric dicarboxylic acids by pH-zone-refining counter-current chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 4th International Conference on Countercurrent Chromatography CY AUG 08-11, 2006 CL NIH, Bethesda, MD HO NIH DE pH-zone-refining counter-current chromatography; dicarboxylic acids; separation of stereoisomers; dimerization energies; pK(a); mechanism ID LIQUID PARTITION CHROMATOGRAPHY; SOLID SUPPORT; DISSOCIATION; EQUILIBRIA; COMPONENTS AB This work involves the preparative separation of some isomeric dicarboxylic acids using pH-zone-refining counter-current chromatography (CCC), a relatively new preparative technique for the separation of ionizable compounds. The paper concentrates especially on the separation of a synthetic mixture of closely related cis and trans pairs of 1-methyl- and 1,3-dimethyl-1,3-cyclohexanedicarboxylic acids. The elution sequence of the isomers is discussed in terms of their relative acidities (pK(a) values) in solution and gas phase, hydrophobicities, and steric configuration. Two possible explanations are suggested for the mechanism of separation. They both involve the amount of retainer acid used, as it affects the separation and plays a role in the chemohydrodynamic equilibrium of the dicarboxylic acids in the column. (C) 2007 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. Technion Israel Inst Technol, Dept Chem, IL-32000 Haifa, Israel. Technion Israel Inst Technol, Lise Meitner Minerva Ctr Computat Quantum Chem, IL-32000 Haifa, Israel. NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Cosmet & Colors, College Pk, MD 20740 USA. EM adrian.weisz@fda.hhs.gov NR 29 TC 18 Z9 18 U1 1 U2 15 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 JUN 1 PY 2007 VL 1151 IS 1-2 BP 82 EP 90 DI 10.1016/j.chroma.2007.03.085 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 175YH UT WOS:000247049400013 PM 17433339 ER PT J AU Ito, Y Qi, L Powell, J Sharpnack, F Metger, H Host, J Cao, XL Dong, YM Huo, LS Zhu, XP Li, T AF Ito, Yoichiro Qi, Lin Powell, Jimmie Sharpnack, Frank Metger, Howard Host, James Cao, Xue-Li Dong, Yin-Mao Huo, Liang-Sheng Zhu, Xiao-Ping Li, Ting TI Mixer-settler counter-current chromatography with a barricaded spiral disk assembly with glass beads SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 4th International Conference on Countercurrent Chromatography CY AUG 08-11, 2006 CL NIH, Bethesda, MD HO NIH DE mixer-settler counter-current chromatography; barricaded spiral disk; assembly; coil planet centrifuge; purification of biopolymers AB A novel spiral disk is designed by placing barricades at 6 mm intervals in the middle of the spiral channel to divide the channel into multiple sections. Glass beads are placed in every other section so that the planetary motion produces repetitive mixing and settling of polymer phase systems. Performance of this mixer-settler spiral disk assembly was examined for separation of lysozyme and myoglobin with a polymer phase system. The best results were obtained with a spiral disk equipped with barricades with openings ranging from 1.2 to 0.4 mm on each side at a high revolution speed up to 1200 rpm. (C) 2006 Elsevier B.V. All rights reserved. C1 NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. US FDA, OPS, CDER, Off New Drug Qual Assessment, Silver Spring, MD 20993 USA. NIH, Machine Instrumentat Design & Fabricat, Bethesda, MD 20892 USA. NIST, Shady Grove, MD 20982 USA. Beijing Technol & Business Univ, Coll Chem & Environm Engn, Beijing Key Lab Plant Resource Res, Beijing 100037, Peoples R China. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, NIH, Bldg 50,Room 3334,50 S Dr, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov NR 7 TC 21 Z9 22 U1 2 U2 11 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 JUN 1 PY 2007 VL 1151 IS 1-2 BP 108 EP 114 DI 10.1016/j.chroma.2006.11.078 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 175YH UT WOS:000247049400017 PM 17316660 ER PT J AU Qi, L Ito, Y AF Qi, Lin Ito, Yoichiro TI Immunoaffinity centrifugal precipitation chromatography SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 4th International Conference on Countercurrent Chromatography CY AUG 08-11, 2006 CL NIH, Bethesda, MD HO NIH DE immunoaffinity centrifugal precipitation chromatography; antibody; HSA (human serum albumin); human plasma; ammonium sufate ID AMMONIUM-SULFATE; DIALYSIS MEMBRANE; PLASMID DNA; FRACTIONATION; PROTEIN; SEPARATION; SOLUBILITY; RNA AB Purification of proteins based on immunoaffinity has been performed using a solid support coated with antibody against the target proteins. The method requires immobilizing the antibody onto the solid support using protein A or G, and has a risk of adsorptive loss of target proteins onto the solid support. Centrifugal precipitation chromatography has been successfully used to purify enzymes, such as ketosteroid isomerase and hyaluronidase without the use of solid support. The purpose of this study is to demonstrate that immunoaffinity centrifugal precipitation chromatography is capable of isolating an antigen by exploiting antigen-antibody binding. The separation was initiated by filling both channels with 40% saturated ammonium sulfate (AS) of pH 4-4.5 followed by loading 20 RI of human plasma (National Institutes of Health blood bank) mixed with 2 mg of rabbit anti-HSA (human serum protein) antibody (Sigma). Then, the sample channel was eluted with water at 0.03 ml/min and AS channel with 40% AS solution of pH 4-1.5 at 1 ml/min until all non-binding components were eluted. Then, the releasing reagent (50% AS solution containing 0.5 M glycine and 10% ammonium hydroxide at pH 10) was introduced through the AS channel to release the target protein (HSA). The retained antibody was recovered by eluting the sample channel with water at 1 ml/min. A hollow fiber membrane device at the outlet (MicroKros, Spectrum, New Brunswick, NJ, USA) was provided on-line dialysis of the eluent before fractions were collected, so that the fractions could be analyzed by SDS-PAGE (sodium dodecyl sulfate - polyacrylamide gel electrophoresis) without further dialysis. The current method does not require immobilizing the antibody onto a matrix, which is used by the conventional immunoaffinity chromatography. This method ensures full recovery of the antigen and antibody, and it may be applied to purification of other proteins. (C) 2007 Elsevier B.V. All rights reserved. C1 NHLBI, Ctr Biochem & Biophys, NIH, Bethesda, MD 20892 USA. US FDA, OPS, CDER, Off New Drug Qual Assessment, Silver Spring, MD 20993 USA. RP Ito, Y (reprint author), NHLBI, Ctr Biochem & Biophys, NIH, Bldg 50,Room 3334,50 S Dr, Bethesda, MD 20892 USA. EM itoy2@mail.nih.gov NR 17 TC 2 Z9 2 U1 0 U2 7 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 JUN 1 PY 2007 VL 1151 IS 1-2 BP 121 EP 125 DI 10.1016/j.chroma.2007.02.119 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 175YH UT WOS:000247049400019 PM 17416378 ER PT J AU Miller, RA Reimschuessel, R Carson, MC AF Miller, Ron A. Reimschuessel, Renate Carson, Mary C. TI Determination of oxytetracycline levels in rainbow trout serum on a biphenyl column using high-performance liquid chromatography SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE oxytetracycline; HPLC; high-performance liquid chromatography; riboflavin; fish; aquaculture; rainbow trout ID SINGLE INTRAMUSCULAR INJECTION; LONG-ACTING PREPARATION; PHARMACOKINETICS; RESIDUES; FISH; BIOAVAILABILITY; TISSUE; FEED AB We developed a simple and sensitive high-performance liquid chromatography method on a biphenyl column to determine oxytetracycline (OTC) levels in rainbow trout serum. The assay used deproteination, filtration, and subsequent separation on a reverse-phase biphenyl column, with UV detection at 355 nm. OTC (7.8-7.9 min) was completely resolved from structurally similar riboflavin (10.4-10.5 min), a common feed supplement. Estimated limits of detection and quantitation of OTC were 0.01 and 0.04 mu g/mL, respectively. The average recovery for OTC was 102% with a R.S.D. of 8.34%. Calibration standards were linear from 0.01 to 10 mu g/mL. (c) 2007 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Miller, RA (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM Ron.Miller@fda.hhs.gov NR 17 TC 4 Z9 4 U1 1 U2 2 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 1 PY 2007 VL 852 IS 1-2 BP 655 EP 658 DI 10.1016/j.jchromb.2007.01.040 PG 4 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 179JV UT WOS:000247286700092 PM 17301001 ER PT J AU Coleman, J Singh, A Pinto, P Phillips, J Pritchard, W Wray-Cahen, D Wood, BJ AF Coleman, Jonathan Singh, Amar Pinto, Peter Phillips, John Pritchard, William Wray-Cahen, Diane Wood, Bradford J. TI Radiofrequency-assisted laparoscopic partial nephrectomy: Clinical and histologic results SO JOURNAL OF ENDOUROLOGY LA English DT Article ID RADIO-FREQUENCY ABLATION; RENAL-CELL CARCINOMA; SPARING SURGERY; EXPERIENCE; DEVICE; TUMORS; MASSES; MODEL AB Purpose: To evaluate a surface conductive radiofrequency (RF) coagulation instrument (Tissuelink FB3.0) in laparoscopic and open partial nephrectomy (PN) in hereditary kidney cancer. The lesion depth and viability in the pathologic specimens from a surgical series and an acute porcine model were characterized under conditions of vascular perfusion and occlusion. Materials and Methods: A total of 19 patients underwent 20 laparoscopic and open procedures with the device. Data were acquired on tumor number, size, operative time, blood loss, length of stay, renal function, complications, pathologic diagnosis, and surgical-margin status. Renal lesions were created in pigs with the device, ultrasonic shears, and a standard electrocautery for specified time intervals and operative energy settings. These lesions were analyzed for depth, diameter, and tissue viability. Results: In 20 separate (14 laparoscopic; 6 open) procedures in 19 patients, a total of 112 tumors were removed (range 1-31 tumors per procedure). The median operative time, blood loss, and length of stay were 310 minutes, 250 mL, and 4 days, respectively. There were no positive surgical margins. Median preoperative and postoperative creatinine concentrations were similar (1.0 v 1.0 mg/dL). The average treatment margin depth was 3 mm. In the porcine experiments, the treatment depth in the unclamped vascular model was significantly less in than the clamped model (4.0 +/- 1.7 mm v 7.0 +/- 1.6 mm; P < 0.05). Lesion depth and diameter increased with treatment time. Viability depth correlated well with the depth of the visible thermal lesions (Pearson correlation 0.989). Conclusions: This RF energy device can provided adequate and uniform hemostatic control without hilar clamping during laparoscopic and open PN for hereditary renal tumors. Gross measures of renal function after surgery appeared clinically unchanged. Coagulation depth is dependent on both tissue perfusion and time in the porcine model. C1 NIH, Urol Oncol Branch, Bethesda, MD 20892 USA. NIH, Dept Diagnost Radiol, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. RP Coleman, J (reprint author), NIH, Urol Oncol Branch, Bldg 10, Bethesda, MD 20892 USA. EM colemanj@mail.nih.gov OI Coleman, Jonathan/0000-0002-6428-7835 FU Intramural NIH HHS [Z99 CL999999] NR 21 TC 15 Z9 15 U1 0 U2 2 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0892-7790 J9 J ENDOUROL JI J. Endourol. PD JUN PY 2007 VL 21 IS 6 BP 600 EP 605 DI 10.1089/end.2006.0223 PG 6 WC Urology & Nephrology SC Urology & Nephrology GA 190SM UT WOS:000248079700006 PM 17638553 ER PT J AU Kiessling, CR Jackson, M Watts, KA Loftis, MH Kiessling, WM Buen, MB Laster, EW Sofos, JN AF Kiessling, Connie R. Jackson, Marc Watts, Kathleen A. Loftis, Mercedes H. Kiessling, William M. Buen, Marie B. Laster, Ebony W. Sofos, John N. TI Antimicrobial susceptibility of Salmonella isolated from various products, from 1999 to 2003 SO JOURNAL OF FOOD PROTECTION LA English DT Article ID RESISTANT SALMONELLA; FOOD-BORNE; ANTIBIOTIC-RESISTANCE; IMPORTED FOODS; CHICKENS; ANIMALS; STRAINS; GENTAMICIN; SEROVARS; ENGLAND AB Foodborne salmonellosis continues to be a major health concern worldwide; thus, detection and tracking of antimicrobial resistance in Salmonella isolates is of interest. The U.S. Food and Drug Administration initiated antimicrobial sensitivity screening of Salmonella isolates from food and related samples in 1999. This paper summarizes the antimicrobial resistance data for Salmonella isolates obtained from 1999 to 2003. A total of 22,231 imported and domestic samples were analyzed for Salmonella, of which 1,319 (5.9%) yielded the pathogen. Since more than one culture was isolated from some samples, the total number of isolates obtained and tested for antimicrobial sensitivity was 1,382. Antimicrobial sensitivity screening was performed with the disc diffusion assay on 11 antimicrobial agents. Of the 1, 108 food isolates screened, 42.1% (n = 467) were serotypes Weltevreden, Newport, Lexington, Senftenberg, Typhimurium, Saint Paul, Paratyphi, Enteritidis, Thompson, and Bareilly. A total of 249 (18.0%) isolates from all sources were resistant to two or more antimicrobials. Resistance to sulfisoxazole, streptomycin, and tetracycline was most common, whereas resistance to ciprofloxacin was least common. Weltevreden (n = 148) was the most common serotype isolated from food, but only nine (6.1%) of these isolates were resistant to two or more antimicrobials. In contrast, although Derby was recovered only 19 times, 11 (57.9%) of these isolates were resistant to two or more antimicrobials. Of the 274 isolates from animal feed, dog treats and environmental swabs, 49.6% (n = 136) belonged to serotypes Infantis, Mbandaka, Anatum, Senftenberg, Typhimurium, Montevideo, Cerro, Enteritidis, and Bredeney, with 76 (27.7%) of these isolates resistant to two or more antimicrobials. Only limited trends in antimicrobial resistance were observed over time, with resistance to sulfisoxazole increasing, resistance to tetracycline decreasing, and resistance to streptomycin fluctuating. C1 US FDA, Denver Dist Lab, Denver Fed Ctr, Denver, CO 80225 USA. Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. RP Kiessling, CR (reprint author), US FDA, Denver Dist Lab, Denver Fed Ctr, Denver, CO 80225 USA. EM connie.kiessling@fda.hhs.gov NR 25 TC 3 Z9 4 U1 2 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 2007 VL 70 IS 6 BP 1334 EP 1338 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 176MY UT WOS:000247090600003 PM 17612060 ER PT J AU Laassri, M Meseda, CA Williams, O Merchlinsky, M Weir, JP Chumakov, K AF Laassri, Majid Meseda, Clement A. Williams, Ollie Merchlinsky, Michael Weir, Jerry P. Chumakov, Konstantin TI Microarray assay for evaluation of the genetic stability of modified vaccinia virus ankara B5R gene SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE smallpox vaccines; MVA strain; oligonucleotide microarray; mutations; vaccinia virus identification ID EXTRACELLULAR ENVELOPED VIRUS; ACTIN TAIL FORMATION; OLIGONUCLEOTIDE MICROARRAY; SMALLPOX VACCINE; PLAQUE SIZE; PROTEIN B5R; MEMBRANE; NEUTRALIZATION; DISSEMINATION; ANTIBODIES AB Adverse events associated with the use of live smallpox vaccines have led to the development of a new generation of attenuated smallpox vaccines that are prepared in cultured cells as alternatives. The inability to conduct direct clinical evaluation of their efficacy in humans demands that licensure be based on animal studies and exhaustive evaluation of their in vitro properties. One of the most important characteristics of live viral vaccines is their genetic stability, including reversion of the vaccine strain to more virulent forms, recombination with other viral sequences to produce potentially pathogenic viruses, and genetic drift that can result in decrease of immunogenicity and efficacy. To study genetic stability of an immunoessential vaccinia virus gene in a new generation smallpox vaccine, an advanced oligonucleotide microchip was developed and used to assay for mutations that could emerge in B5R gene, a vaccinia virus gene encoding for a protein that contains very important neutralizing epitopes. This microarray contained overlapping oligonucleoticles covering the 13513 gene of modified vaccinia virus Ankara (MVA), a well-studied candidate smallpox vaccine. The microarray assay was shown to be able to detect even a single point mutation, and to differentiate between vaccinia strains. At the same time, it could detect newly emerged mutations in clones of vaccinia strains. In the work described here, it was shown that MVA B5R gene was stable after 34 passages in Vero and MRC-5 cells that were proposed for use as cell substrates for vaccine manufacture. Potentially, the proposed method could be used as an identity test and could be extended for the entire viral genome and used to monitor consistency of vaccine production. J. Med. Virol. 79:791-802, 2007. (C) 2007 Wiley-Liss, Inc. C1 US FDA, CBER, Rockville, MD 20852 USA. RP Laassri, M (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA. EM majid.laassri@fda.hhs.gov NR 37 TC 8 Z9 9 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD JUN PY 2007 VL 79 IS 6 BP 791 EP 802 DI 10.1002/jmv.20889 PG 12 WC Virology SC Virology GA 163MM UT WOS:000246164000019 PM 17457926 ER PT J AU Cohen, ED AF Cohen, Ethan D. TI Prosthetic interfaces with the visual system: biological issues SO JOURNAL OF NEURAL ENGINEERING LA English DT Review ID RETINAL GANGLION-CELLS; LATERAL GENICULATE-NUCLEUS; OPTIC-NERVE STIMULATION; TRANSRETINAL ELECTRICAL-STIMULATION; MULTICHANNEL ELECTRODE ARRAY; ARTIFICIAL SYNAPSE CHIP; SOURCE-DENSITY ANALYSIS; SACCADIC EYE-MOVEMENTS; HUMAN OCCIPITAL CORTEX; FIBER LAYER THICKNESS AB The design of effective visual prostheses for the blind represents a challenge for biomedical engineers and neuroscientists. Significant progress has been made in the miniaturization and processing power of prosthesis electronics; however development lags in the design and construction of effective machine-brain interfaces with visual system neurons. This review summarizes what has been learned about stimulating neurons in the human and primate retina, lateral geniculate nucleus and visual cortex. Each level of the visual system presents unique challenges for neural interface design. Blind patients with the retinal degenerative disease retinitis pigmentosa (RP) are a common population in clinical trials of visual prostheses. The visual performance abilities of normals and RP patients are compared. To generate pattern vision in blind patients, the visual prosthetic interface must effectively stimulate the retinotopically organized neurons in the central visual field to elicit patterned visual percepts. The development of more biologically compatible methods of stimulating visual system neurons is critical to the development of finer spatial percepts. Prosthesis electrode arrays need to adapt to different optimal stimulus locations, stimulus patterns, and patient disease states. C1 Ctr Devices & Radiol Hlth, Div Phys, Off Sci, Rockville, MD 20852 USA. Ctr Devices & Radiol Hlth, Engn Labs, Rockville, MD 20852 USA. RP Cohen, ED (reprint author), Ctr Devices & Radiol Hlth, Div Phys, Off Sci, HFZ130,12725 Twinbrook Pkwy, Rockville, MD 20852 USA. EM ethan.cohen@fda.hhs.gov NR 210 TC 35 Z9 35 U1 3 U2 18 PU IOP PUBLISHING LTD PI BRISTOL PA DIRAC HOUSE, TEMPLE BACK, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 J9 J NEURAL ENG JI J. Neural Eng. PD JUN PY 2007 VL 4 IS 2 BP R14 EP R31 DI 10.1088/1741-2560/4/2/R02 PG 18 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA 188VL UT WOS:000247947300002 PM 17409473 ER PT J AU Snorek, SM Bauer, JF Chidambaram, N Doub, WH Duffy, EP Etzler, FM Kelly, RN Lane, JJ Mueller, RL Prasanna, HR Pujara, CP Reif, VD Scarlett, B Stowell, JG Toma, PH AF Snorek, Sharon M. Bauer, John F. Chidambaram, Nallaperumal Doub, William H. Duffy, Eric P. Etzler, Frank M. Kelly, Richard N. Lane, Justin J. Mueller, Ronald L. Prasanna, Hullahalli R. Pujara, Chetan P. Reif, Van D. Scarlett, Brian Stowell, Joseph G. Toma, Pascal H. TI PQRI recommendations on particle-size analysis of drug substances used in oral dosage forms SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Review DE particle size; morphology; microscopy; analysis; image analysis; light-scattering ID LASER DIFFRACTION AB This document provides information for the Pharmaceutical Industry and the Federal Drug Administration (FDA) regarding the selection of suitable particle-size analysis techniques, development and validation of particle-size methods, and the establishment of acceptance criteria for the particle size of drug substances used in oral solid-dosage forms. The document is intended for analysts knowledgeable in the techniques necessary to conduct particle-size characterization (a table of acronyms is provided at the end of the document). It is acknowledged that each drug substance, formulation, and manufacturing process is unique and that multiple techniques and instruments are available to the analyst. (C) 2007 Wiley-Liss, Inc. C1 Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Abbott Labs, Abbott Pk, IL 60064 USA. US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Analysis, St Louis, MO 63101 USA. US FDA, CDER, Rockville, MD 20857 USA. GlaxoSmithKline Inc, King Of Prussia, PA 19406 USA. GlaxoSmithKline Inc, Res Triangle Pk, NC 27709 USA. Johnson & Johnson Pharmaceut Res & Dev LLC, King Of Prussia, PA 19406 USA. Schering Plough Corp, Inst Res, Kenilworth, NJ 07033 USA. Chao Ctr, W Lafayette, IN 47906 USA. Univ Florida, Gainesville, FL 32608 USA. US Pharmacopeia & Natl Formulary, Rockville, MD 20852 USA. RP Snorek, SM (reprint author), Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. EM snorek_sharon_m@lilly.com NR 30 TC 3 Z9 3 U1 2 U2 6 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JUN PY 2007 VL 96 IS 6 BP 1451 EP 1467 DI 10.1002/jps.20822 PG 17 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 174HB UT WOS:000246931700003 PM 17238204 ER PT J AU Woodworth, T Furst, DE Alten, R Bingham, C Yocum, D Sloan, V Tsuji, W Stevens, R Fries, J Witter, J Johnson, K Lassere, M Brooks, P AF Woodworth, Thasia Furst, Daniel E. Alten, Rieke Bingham, Clifton Yocum, David Sloan, Victor Tsuji, Wayne Stevens, Randall Fries, James Witter, James Johnson, Kent Lassere, Marissa Brooks, Peter TI Standardizing assessment and reporting of adverse effects in rheumatology clinical trials II: the rheumatology common toxicity criteria v.2.0 SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 8th International Consensus Conference on Outcome Measures in Rheumatology Clinical Trails (OMERACT 8) CY MAY 10-14, 2006 CL St Julians Bay, MALTA DE drug safety; adverse event reporting; safety profiles ID DRUG EVENTS; SAFETY; CHEMOTHERAPY; SYMPTOMS; INDEX AB Objective. The OMERACT Drug Safety Working Group focuses on standardization of assessment and reporting of adverse events in clinical trials and longitudinal and observational studies in rheumatology. This group developed the Rheumatology Common Toxicity Criteria (RCTC) in 1999, building on the Oncology Common Toxicity Criteria. At OMERACT 8, a workshop group reviewed the use of the RCTC and other instruments in rheumatology clinical trials to date, to revise and to stimulate its implementation. Methods. The Working Group drafted a revision of the RCTC after an iterative examination of its contents, terms, and definitions. The RCTC were compared with the Oncology Common Toxicity Criteria (CTC v.2.0), and the Common Terminology Criteria for Adverse Events (CTCAE v.3.0). In addition a pharmaceutical company focus group met to clarify the challenges of application of RCTC terms and definitions, relative to the standard in pharmaceutical clinical trials, i.e., verbatim recording of adverse events followed by mapping to Medical Dictionary of Drug Regulatory Activities (MedDRA) terms. The workshop focused on the proposed revision of RCTC to version 2.0 and oil the research agenda, including a validation of the RCTC in future trials. Results. At OMERACT 8, breakout groups amended the contents of the 4 current and 2 new categories of adverse event terms within the draft RCTC v.2.0. Participants recognized the need to standardize the definitions for disease flares, infection, malignancy, and certain syndromes such as drug hypersensitivity and infusion reactions. Moderate consensus (62%) was reached in the final plenary session that the amended RCTC v.2.0 should be promulgated and tested in available trials of anti-tumor necrosis factor agents. Conclusion. The RCTC has face validity and construct validity. However, documentation of discrimination and feasibility (the other elements of the OMERACT filter) is needed. Collaboration with drug safety working groups in rheumatology professional organizations is necessary to enable this project. C1 Roche Pharmaceut, Welwyn Garden City, Herts, England. Univ Calif Los Angeles, Los Angeles, CA USA. Schlosspark Klin, Berlin, Germany. Johns Hopkins Univ, Baltimore, MD USA. Amgen Inc, Seattle, WA USA. Roche Pharmaceut, Nutley, NJ USA. Stanford Univ, Med Ctr, Palo Alto, CA 94304 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Newcastle, Newcastle, NSW 2308, Australia. Gen Hosp St Georg, Kogarah, NSW, Australia. Univ Queensland, Brisbane, Qld, Australia. RP Woodworth, T (reprint author), Roche Pharmaceut, 6 Falcon Way, Welwyn Garden City, Herts, England. EM thasia.woodworth@roche.com RI Fries, James/F-6271-2011 NR 20 TC 25 Z9 26 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD JUN PY 2007 VL 34 IS 6 BP 1401 EP 1414 PG 14 WC Rheumatology SC Rheumatology GA 176WW UT WOS:000247116600032 PM 17552067 ER PT J AU Vogel, R Saha, A Chakrabarti, K Badano, A AF Vogel, Rebecca Saha, Anindita Chakrabarti, Kish Badano, Aldo TI Evaluation of high-resolution and mobile display systems for digital radiology in dark and bright environments using human and computational observers SO JOURNAL OF THE SOCIETY FOR INFORMATION DISPLAY LA English DT Article DE medical displays; mobile displays; image quality AB As digital display systems replace film traditionally used for reading radiographic images, resource-intensive acceptance testing must be performed to ensure that quality meets and maintains desired specifications. If machine observers can replace human readers, whose performances are highly variable, the results will be more consistent and less costly. To be effective, however, the automated observers must track human performance. An approach for a model observer, validated with human readers, for the evaluation of the visibility of low-contrast small targets in high-resolution and mobile displays under different ambient illumination, will be described. The displays were tested using CDMAM-like digital phantoms containing disks of varying diameters and contrasts on a flat background. For this task, we find the best indicator of display performance to be the display's ability to represent small luminance contrast, not resolution or pixel size. The results confirm that high-resolution systems perform better under low illumination while illuminance has a minor impact on the mobile-display performance. Finally, the results show that the machine observer tracks the performance of human readers. Machine observers with proper validation can replace humans in the acceptance testing procedures, saving the testers both time and money. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Vogel, R (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,WO 62-3116, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 10 TC 6 Z9 6 U1 0 U2 2 PU SOC INFORMATION DISPLAY PI CAMPBELL PA 1475 S BASCOM AVE, STE 114, CAMPBELL, CA 95008 USA SN 1071-0922 J9 J SOC INF DISPLAY JI J. Soc. Inf. Disp. PD JUN PY 2007 VL 15 IS 6 BP 357 EP 365 DI 10.1889/1.2749321 PG 9 WC Engineering, Electrical & Electronic; Materials Science, Multidisciplinary; Optics; Physics, Applied SC Engineering; Materials Science; Optics; Physics GA 178VH UT WOS:000247247700004 ER PT J AU Bertke, AS Patel, A Krause, PR AF Bertke, Andrea S. Patel, Amita Krause, Philip R. TI Herpes simplex virus latency-associated transcript sequence downstream of the promoter influences type-specific reactivation and viral neurotropism SO JOURNAL OF VIROLOGY LA English DT Article ID GENITAL HERPES; IN-VIVO; PREGANGLIONIC NEURONS; 5 END; APOPTOSIS; REGION; EXPRESSION; INFECTION; HSV-1; GENOME AB Herpes simplex virus (HSV) establishes latency in sensory nerve ganglia during acute infection and may later periodically reactivate to cause recurrent disease. HSV type 1 (HSV-1) reactivates more efficiently than HSV-2 from trigeminal ganglia while HSV-2 reactivates more efficiently than HSV-1 from lumbosacral dorsal root ganglia (DRG) to cause recurrent orofacial and genital herpes, respectively. In a previous study, a chimeric HSV-2 that expressed the latency-associated transcript (LAT) from HSV-1 reactivated similarly to wild-type HSV-1, suggesting that the LAT influences the type-specific reactivation phenotype of HSV-2. To further define the LAT region essential for type-specific reactivation, we constructed additional chimeric HSV-2 viruses by replacing the HSV-2 LAT promoter (HSV2-LAT-P1) or 2.5 kb of the HSV-2 LAT sequence (HSV2-LAT-S1) with the corresponding regions from HSV-1. HSV2-LAT-S1 was impaired for reactivation in the guinea pig genital model, while its rescuant and HSV2-LAT-P1 reactivated with a wild-type HSV-2 phenotype. Moreover, recurrences of HSV-2-LAT-S1 were frequently fatal, in contrast to the relatively mild recurrences of the other viruses. During recurrences, HSV2-LAT-S1 DNA increased more in the sacral cord compared to its rescuant or HSV-2. Thus, the LAT sequence region, not the LAT promoter region, provides essential elements for type-specific reactivation of HSV-2 and also plays a role in viral neurotropism. HSV-1 DNA, as quantified by real-time PCR, was more abundant in the lumbar spinal cord, while HSV-2 DNA was more abundant in the sacral spinal cord, which may provide insights into the mechanism for type-specific reactivation and different patterns of central nervous system infection of HSV-1 and HSV-2. C1 CBER, FDA, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Krause, PR (reprint author), CBER, FDA, HFM-457,29 Lincoln Dr, Bethesda, MD 20892 USA. EM philip.krause@fda.hhs.gov OI Krause, Philip/0000-0002-1045-7536 NR 38 TC 18 Z9 18 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2007 VL 81 IS 12 BP 6605 EP 6613 DI 10.1128/JVI.02701-06 PG 9 WC Virology SC Virology GA 175BP UT WOS:000246987500042 PM 17409161 ER PT J AU Keely, A Kyprianou, I Jennings, R Myers, K Gilat-Schmidt, T AF Keely, A. Kyprianou, I. Jennings, R. Myers, K. Gilat-Schmidt, T. TI Phantom development for artifact reduction in cone-beam CT SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Marquette Univ, Milwaukee, WI 53233 USA. US FDA, Ctr Device & Radiol Hlth, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2340 EP 2340 DI 10.1118/1.2760389 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600104 ER PT J AU Nemmers, S Mitchell, C Thomas, J Chakrabarti, K Kaczmarek, R Romanyhukha, A AF Nemmers, S. Mitchell, C. Thomas, J. Chakrabarti, K. Kaczmarek, R. Romanyhukha, A. TI Effect of room setting on object dectectability for two different AMLCD displays SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. US FDA, CDRH, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2347 EP 2347 DI 10.1118/1.2760418 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479600132 ER PT J AU Kyprianou, I AF Kyprianou, I. TI Personalized coronary imaging with a virtual catheterization laboratory SO MEDICAL PHYSICS LA English DT Meeting Abstract CT 49th Annual Meeting of the American-Association-of-Physicists-in-Medicine CY JUL 22-26, 2007 CL Minneapolis, MN SP Amer Assoc Physicists Med C1 US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2007 VL 34 IS 6 BP 2647 EP 2647 DI 10.1118/1.2761746 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 182BH UT WOS:000247479601352 ER PT J AU Schnackenberg, LK Dragan, YP Reily, MD Robertson, DG Beger, RD AF Schnackenberg, Laura K. Dragan, Yvonne P. Reily, Michael D. Robertson, Donald G. Beger, Richard D. TI Evaluation of NMR spectral data of urine in conjunction with measured clinical chemistry and histopathology parameters to assess the effects of liver and kidney toxicants SO METABOLOMICS LA English DT Article DE metabonomics; metabolic trajectory; NMR; renal toxicity; hepatotoxicity ID PATTERN-RECOGNITION; METABOLIC-RESPONSES; TOXICITY CLASSIFICATION; H-1-NMR SPECTROSCOPY; D-GALACTOSAMINE; RAT-LIVER; METABONOMICS; MODEL; NEPHROTOXICITY; INJURY AB Single low and high doses of several compounds with known renal toxic effects (para-aminophenol, puromycin aminonucleoside, sodium chromate, and hexachlorobutadiene,) or known liver toxic effects (galactosam line, allyl alcohol, and thioacetamide) were administered to male Wistar rats in groups of 4 or 8 for each compound. Predose urine samples (Day 0) and samples from post-closing (Days 1-4) were collected for each rat and monitored by ID H-1 NMR. Principal component analysis (PCA) of the NMR spectra was used to investigate differences between dose levels for each compound individually. The findings from PCA at both dose levels for each compound were examined in the context of the corresponding clinical chemistry and pathology data collected during the study. The PCA clustering of NMR spectra from rats dosed with each individual compound were shown to be associated with the measured levels of creatinine, BUN, AST, ALT and histopathology findings. Finally, scaled-to-maximum, aligned, and reduced trajectories (SMART) analysis was applied to compare the temporal metabolic trajectories obtained for each animal at each dose level of the administered compounds. By day 4, the SMART trajectories for allyl alcohol and hexachlorobutadiene had returned to predose levels indicating a recovery response, however, the high dose SMART trajectories for para-aminophenol, puromycin aminonucleoside, sodium chromate, and galactosamine did not appear to return to predose levels indicating a prolonged toxic effect. C1 US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. Pfizer Global Res & Dev, Metabon Evaluat Grp, Ann Arbor, MI 48105 USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM berger@fda.hhs.gov OI Reily, Michael/0000-0003-1179-1525 NR 34 TC 15 Z9 15 U1 0 U2 7 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1573-3882 EI 1573-3890 J9 METABOLOMICS JI Metabolomics PD JUN PY 2007 VL 3 IS 2 BP 87 EP 100 DI 10.1007/s11306-006-0046-y PG 14 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 176JX UT WOS:000247082200002 ER PT J AU Kotewicz, ML Jackson, SA LeClerc, JE Cebula, TA AF Kotewicz, Michael L. Jackson, Scott A. LeClerc, J. Eugene Cebula, Thomas A. TI Optical maps distinguish individual strains of Escherichia coli O157 : H7 SO MICROBIOLOGY-SGM LA English DT Article ID TOXIN-ENCODING BACTERIOPHAGES; FIELD GEL-ELECTROPHORESIS; SINGLE-NUCLEOTIDE POLYMORPHISMS; SHIGA-TOXIN; GENOMIC DIVERSITY; BACTERIAL PATHOGENS; HEMORRHAGIC COLITIS; SALMONELLA; EVOLUTION; SEQUENCE AB Optical maps of 11 Escherichia coli O157 : H 7 strains have been generated by the assembly of contiguous sets of restriction fragments across their entire 5.3 to 5.6 Mbp chromosomes. Each strain showed a distinct, highly individual configuration of 500-700 BamHI fragments, yielding a map resembling a DNA 'bar code'. The accuracy of optical mapping was assessed by comparing directly the in silico restriction maps of two wholly sequenced reference genomes of E. coli O157 : H7, i.e. EDL933 and the Sakai isolate (RIMD 0509952), with the optical maps of the same strains. The optical maps of nine other E coli O157 : H7 strains were compared similarly, using the sequence-based maps of the Sakai and EDL933 strains as references. A total of 91 changes at 28 loci were positioned and sized; these included complex chromosomal inversions, insertions, deletions, substitutions, as well as a number of simple IRFLPs. The optical maps defined unique genome landmarks in each of the strains and demonstrated the ability of optical mapping to distinguish and differentiate, at the individual level, strains of this important pathogen. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. EM Thomas.Cebula@fda.hhs.gov NR 44 TC 31 Z9 31 U1 1 U2 4 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD JUN PY 2007 VL 153 BP 1720 EP 1733 DI 10.1099/mic.0.2006/004507-0 PG 14 WC Microbiology SC Microbiology GA 179QM UT WOS:000247304900005 PM 17526830 ER PT J AU Pogribny, IP Tryndyak, VP Boyko, A Rodriguez-Juarez, R Beland, FA Kovalchuk, O AF Pogribny, Igor P. Tryndyak, Volodymyr P. Boyko, Alex Rodriguez-Juarez, Rocio Beland, Frederick A. Kovalchuk, Olga TI Induction of microRNAome deregulation in rat liver by long-term tamoxifen exposure SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE MiRNAs; tamoxifen; rat; hepatocarcinogenesis ID HEPATOCELLULAR-CARCINOMA; FUNCTIONAL GENOMICS; EXPRESSION PATTERNS; CELL-PROLIFERATION; GENE-EXPRESSION; DOWN-REGULATION; CANCER; HEPATOCARCINOGENESIS; APOPTOSIS; CHROMATIN AB Micro RNAs (miRNAs) are small non-coding RNA molecules that function as negative regulators of gene expression. They play a crucial role in the regulation of genes involved in the control of development, cell proliferation, apoptosis, and stress response. Although miRNA levels are substantially altered in tumors, their role in carcinogenesis, specifically at the early pre-cancerous stages, has not been established. Here we report that exposure of Fisher 344 rats to tamoxifen, a potent hepatocarcinogen in rats, for 24 weeks leads to substantial changes in the expression of miRNA genes in the liver. We noted a significant up-regulation of known oncogenic miRNAs, such as the 17-92 cluster, miR-106a, and miR-34. Furthermore, we confirmed the corresponding changes in the expression of proteins targeted by these miRNAs, which include important cell cycle regulators, chromatin modifiers, and expression regulators implicated in carcinogenesis. All these miRNA changes correspond to previously reported alterations in full-fledged tumors, including hepatocellular carcinomas. Thus, our findings indicate that miRNA changes occur prior to tumor formation and are not merely a consequence of a transformed state. (c) 2007 Elsevier B.V. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov; olga.kovalchuk@uleth.ca NR 44 TC 100 Z9 117 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD JUN 1 PY 2007 VL 619 IS 1-2 BP 30 EP 37 DI 10.1016/j.mrfmmm.2006.12.006 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 170MP UT WOS:000246667800004 PM 17343880 ER PT J AU Woodcock, J Griffin, J Behrman, R Cherney, B Crescenzi, T Fraser, B Hixon, D Joneckis, C Kozlowski, S Rosenberg, A Schrager, L Shacter, E Temple, R Webber, K Winkle, H AF Woodcock, Janet Griffin, Joseph Behrman, Rachel Cherney, Barry Crescenzi, Terrie Fraser, Blair Hixon, Dena Joneckis, Christopher Kozlowski, Steven Rosenberg, Amy Schrager, Lewis Shacter, Emily Temple, Robert Webber, Keith Winkle, Helen TI Opinion - The FDA's assessment of follow-on protein products: a historical perspective SO NATURE REVIEWS DRUG DISCOVERY LA English DT Article AB The scientific and regulatory issues that are associated with the possible introduction of 'follow-on' versions of protein drug products are the topic of considerable debate at present. Because of the differences between protein drug products and small-molecule drugs, the development of follow-on versions of protein products presents more complex scientific challenges than those presented by the development of generic versions of small-molecule drugs. Here, with a view to illustrating the Food and Drug Administration's (FDA's) scientific reasoning and experience in this area, we discuss past examples of the FDA's actions involving the evaluation of various types of follow-on and second-generation protein products and within-product manufacturing changes. The FDA believes its evaluation of the safety and effectiveness of follow-on protein products will evolve as scientific and technological advances in product characterization and manufacturing continue to reduce some of the complexity and uncertainty that are inherent in the manufacturing of protein products. C1 US FDA, Working Grp Follow Prot, Rockville, MD 20857 USA. RP Woodcock, J (reprint author), US FDA, Working Grp Follow Prot, 5600 Fishers Lane, Rockville, MD 20857 USA. EM janet.woodcock@fda.hhs.gov NR 4 TC 99 Z9 102 U1 0 U2 8 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-1776 J9 NAT REV DRUG DISCOV JI Nat. Rev. Drug Discov. PD JUN PY 2007 VL 6 IS 6 BP 437 EP 442 DI 10.1038/nrd2307 PG 6 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 175DE UT WOS:000246992000012 PM 17633790 ER PT J AU Li, J Feuers, RJ Desai, VG Lewis, SM Duffy, PH Mayhugh, MA Cowan, G Buffington, CK AF Li, Jing Feuers, Ritchie J. Desai, Varsha G. Lewis, Sherry M. Duffy, Peter H. Mayhugh, Martha A. Cowan, George, Jr. Buffington, Cynthia K. TI Surgical caloric restriction ameliorates mitochondrial electron transport dysfunction in obese females SO OBESITY SURGERY LA English DT Article DE electron transport system; caloric restriction; morbid obesity; lymphocytes; mitochondria; obesity surgery ID GASTRIC BYPASS-SURGERY; RESPIRATORY-CHAIN FUNCTION; TYPE-2 DIABETES-MELLITUS; HUMAN SKELETAL-MUSCLE; MORBID-OBESITY; DIETARY RESTRICTION; OXIDATIVE STRESS; AGE; DECLINE; IMPACT AB Background: The authors examine the mitochondrial electron transport system (ETS) with regard to caloric restriction and body size in humans. Methods: The study population included 59 morbidly obese (MO) female subjects with mean body mass index (BMI) 49.6 +/- 1.7 and 40 age-matched previously morbidly obese patients with surgically-induced caloric restriction (SCR) and mean BMI 28.9 +/- 1.1. ETS function in the 2 study groups were made by measuring their lymphocyte mitochondrial ETS complexes I=IV activities and complex III binding kinetics. Linear regression analyses were used to analyze the interactions between ETS function and BMI, energy intake, and metabolic status. Results: The MO, as compared to SCR, subjects had significantly (P < 0.01) higher ETS complexes II-IV activities (complex II = 20.4 +/- 1.9 vs 15.3 +/- 1.1, complex III = 129.4 +/- 10.1 vs 72.3 +/- 4.9, complex IV = 3.1 +/- 0.3 vs 1.4 +/- 0.1 nmol/mg/min for the MO vs SCR, respectively). ETS complexes activities were positively and significantly correlated with subjects' BMI, carbohydrate caloric intake, and fasting plasma insulin levels. Michaelis-Menten kinetic analysis showed that the Km for ubiquinol-2 in complex III of MO patients was 2-fold greater than SCR values, reflecting an apparent reduction in substrate binding capacities producing a resistance to electron flow in the MO population. Caloric consumption, carbohydrate calories, insulin levels, and BMI were also each significantly (P < 0.05) and positively correlated with the Km of Complex Ill. Conclusions: ETS function and efficiency are compromised by increasing BMI and caloric consumption in morbidly obese women, and caloric restriction may reduce the potential for excessive oxidative free radical generation via the ETS. C1 Florida Hosp Celebrat Hlth, Celebration, FL 34747 USA. Guangzhou Inst Resp Dis, Guangzhou, Peoples R China. Natl Ctr Toxicol Res, Div Vet Med, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Sci Coordinat, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Bionet, Jefferson, AR USA. Univ Tennessee, Dept Surg, Memphis, TN USA. RP Buffington, CK (reprint author), Florida Hosp Celebrat Hlth, 400 Celebrat Pl,Rm A250, Celebration, FL 34747 USA. EM cynthia.buffington@flhosp.org NR 47 TC 3 Z9 3 U1 0 U2 1 PU F D-COMMUNICATIONS INC PI TORONTO PA 3100 BAYVIEW AVE, UNIT 4, TORONTO, ONTARIO M2N 5L3, CANADA SN 0960-8923 J9 OBES SURG JI Obes. Surg. PD JUN PY 2007 VL 17 IS 6 BP 800 EP 808 DI 10.1007/s11695-007-9146-7 PG 9 WC Surgery SC Surgery GA 173ZU UT WOS:000246911800017 PM 17879581 ER PT J AU Dreyer, Z Dondorf, P Sather, H Steuber, C Carroll, W Hilden, J Camitta, B AF Dreyer, Z. Dondorf, P. Sather, H. Steuber, C. Carroll, W. Hilden, J. Camitta, B. TI Shortened, intensified therapy in infant ALL: A pediatric oncology group study SO PEDIATRIC BLOOD & CANCER LA English DT Meeting Abstract C1 US FDA, Silver Spring, MD USA. COG, Stat Off, Arcadia, CA USA. New York Med Ctr, New York, NY USA. Cleveland Clin, Cleveland, OH 44106 USA. Midwest Ca Ctr, Milwaukee, WI USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1545-5009 J9 PEDIATR BLOOD CANCER JI Pediatr. Blood Cancer PD JUN 1 PY 2007 VL 48 IS 6 BP 605 EP 605 PG 1 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 161KN UT WOS:000246013900020 ER PT J AU McMahon, AW Zinderman, C Ball, R Gupta, G Braun, MM AF McMahon, A. W. Zinderman, C. Ball, R. Gupta, G. Braun, M. M. TI Comparison of military and civilian reporting rates for smallpox vaccine adverse events SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE adverse events; smallpox vaccine; reporting rates ID SURVEILLANCE; SYSTEM AB Introduction US smallpox vaccination (SMA) started most recently in December 2002. Military and civilian personnel report adverse events (AEs) to the Vaccine Adverse Event Reporting System (VAERS), a surveillance system that relies on spontaneous reports. Although reported rates of probable myo/pericarditis after SMA in the literature are similar between military personnel and civilian healthcare workers, some civilian AE reporting rates after SMA appeared higher than those in the military. Objective Determine if SMA-associated reporting rates are different in civilians than in the military, considering age, sex, seriousness, and expectedness of the AE, as well as self-reporting. Methods Numerators were SMA reports in VAERS from 12/12/02 to 3/1/04. Limitations of VAERS include underreporting and lack of diagnostic confirmation. Denominators were number of military and civilian vaccinees. Results Reporting rates stratified by age and sex of serious and non-serious AEs were significantly higher in civilian than military personnel ages <55 years (rate ratios 4-27). These rate ratios decreased with increasing age. Conclusions Reporting rates in VAERS differed significantly and substantially in civilians compared to military personnel <55 years of age. Differences in stimulated passive surveillance systems, and AE reporting practices, including the 'threshold' for reporting most likely explain these findings. These results suggest that in the case of smallpox vaccine AEs, there may be systematic differences in reporting completeness between the civilian and military sectors, and that passive surveillance data should be interpreted with caution. Copyright (C) 2006 John Wiley & Sons, Ltd. C1 US FDA, Off Biostat & Epidemiol, Rockville, MD 20857 USA. RP McMahon, AW (reprint author), 1401 Rockville Pike,HFM-220, Rockville, MD 20852 USA. EM ann.mcmahon@fda.hhs.gov NR 14 TC 10 Z9 10 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JUN PY 2007 VL 16 IS 6 BP 597 EP 604 DI 10.1002/pds.1349 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 185WC UT WOS:000247740100001 PM 17154344 ER PT J AU Sauna, ZE Kimchi-Sarfaty, C Ambudkar, SV Gottesman, MM AF Sauna, Zuben E. Kimchi-Sarfaty, Chava Ambudkar, Suresh V. Gottesman, Michael M. TI The sounds of silence: synonymous mutations affect function SO PHARMACOGENOMICS LA English DT Editorial Material ID CODON USAGE; P-GLYCOPROTEIN; MDR1 GENE; PROTEIN EXPRESSION; POLYMORPHISMS; TRANSLATION; HAPLOTYPES; EVOLUTION; DISEASE; GENOME C1 NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Gottesman, MM (reprint author), NCI, Cell Biol Lab, Canc Res Ctr, NIH, Bldg 37, Bethesda, MD 20892 USA. EM mgottesman@nih.gov FU Intramural NIH HHS NR 41 TC 32 Z9 35 U1 0 U2 4 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JUN PY 2007 VL 8 IS 6 BP 527 EP 532 DI 10.2217/14622416.8.6.527 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 183QD UT WOS:000247586400001 PM 17559340 ER PT J AU Chen, JJ Wang, SJ Tsai, CA Lin, CJ AF Chen, J. J. Wang, S-J Tsai, C-A Lin, C-J TI Selection of differentially expressed genes in microarray data analysis SO PHARMACOGENOMICS JOURNAL LA English DT Article DE fold-change; gene ranking; P-value; permutation test; volcano plot ID PLATFORMS; DISCOVERY; CANCER AB One common objective in microarray experiments is to identify a subset of genes that express differentially among different experimental conditions, for example, between drug treatment and no drug treatment. Often, the goal is to determine the underlying relationship between poor versus good gene signatures for identifying biological functions or predicting specific therapeutic outcomes. Because of the complexity in studying hundreds or thousands of genes in an experiment, selection of a subset of genes to enhance relationships among the underlying biological structures or to improve prediction accuracy of clinical outcomes has been an important issue in microarray data analysis. Selection of differentially expressed genes is a two-step process. The first step is to select an appropriate test statistic and compute the P-value. The genes are ranked according to their P-values as evidence of differential expression. The second step is to assign a significance level, that is, to determine a cutoff threshold from the P-values in accordance with the study objective. In this paper, we consider four commonly used statistics, t-, S- (SAM), U-(Mann-Whitney) and M-statistics to compute the P-values for gene ranking. We consider the family-wise error and false discovery rate false-positive error-controlled procedures to select a limited number of genes, and a receiver-operating characteristic (ROC) approach to select a larger number of genes for assigning the significance level. The ROC approach is particularly useful in genomic/genetic profiling studies. The well-known colon cancer data containing 22 normal and 40 tumor tissues are used to illustrate different gene ranking and significance level assignment methods for applications to genomic/genetic profiling studies. The P-values computed from the t-, U- and M-statistics are very similar. We discuss the common practice that uses the P-value, false-positive error probability, as the primary criterion, and then uses the fold-change as a surrogate measure of biological significance for gene selection. The P-value and the fold-change can be pictorially shown simultaneously in a volcano plot. We also address several issues on gene selection. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, Silver Spring, MD USA. Acad Sinica, Inst Stat Sci, Taipei 115, Taiwan. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT-20, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov OI Tsai, Chen-An/0000-0002-7490-4331 NR 21 TC 45 Z9 46 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PD JUN PY 2007 VL 7 IS 3 BP 212 EP 220 DI 10.1038/sj.tpj.6500412 PG 9 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 172PI UT WOS:000246815900005 PM 16940966 ER PT J AU Chen, JJ Moon, H Kodell, RL AF Chen, James J. Moon, Hojin Kodell, Ralph L. TI A probabilistic framework for non-cancer risk assessment SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE benchmark dose; distribution of exposure; hierarchical model; interspecies and intraspecies uncertainties; point of departure ID MODEL; FORMALDEHYDE; UNCERTAINTY; CHLORIDE; RFD AB Risk assessment involves an analysis of the relationship between exposure and health related outcomes to derive an allowable exposure level or to estimate a low-dose risk. Acceptable levels of human exposure for non-cancer effects generally are derived by dividing an experimental no-observed-adverse-effect-level or a lower confidence limit benchmark dose by a product of several uncertainty factors. This paper presents a hierarchical modeling framework for a probabilistic approach to non-cancer risk assessment. The hierarchical model integrates the distributions of uncertainty factors and the distribution of the actual exposure level to construct the dose-response model for the proportion of population at risk and the dose-response model for the expected proportion of population at risk for a given exposure distribution. The proposed approach is based on the use of the BMDL (lower confidence limit on the benchmark dose) as a POD (point of departure) for risk assessment of non-cancer effects. Published by Elsevier Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov NR 23 TC 5 Z9 5 U1 1 U2 5 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 2007 VL 48 IS 1 BP 45 EP 50 DI 10.1016/j.yrtph.2006.10.008 PG 6 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 183CG UT WOS:000247549700006 PM 17166641 ER PT J AU Pena, C Li, K Felten, R Ogden, N Melkerson, M AF Pena, Carlos Li, Khan Felten, Richard Ogden, Neil Melkerson, Mark TI An example of US food and drug administration device regulation - Medical devices indicated for use in acute ischemic stroke SO STROKE LA English DT Article DE acute stroke; stroke; treatment ID RANDOMIZED CONTROLLED-TRIAL; PLASMINOGEN-ACTIVATOR; CLOT RETRIEVER; ALTEPLASE; ECASS AB The Food and Drug Administration has established requirements for protecting the public health by assuring the safety and effectiveness of a variety of medical products including drugs, devices, and biological products, and for promoting public health by expediting the approval of treatments that are safe and effective. The Center for Devices and Radiological Health is the center within the agency that is responsible for pre- and postmarket regulation of medical devices. In this article, we review current regulation of medical devices, research and development programs, pre- and postmarket perspectives, and future considerations of medical devices, particularly as they relate to devices targeting acute ischemic stroke as an example of the process. We also review the Center for Devices and Radiological Health's historical perspective of acute ischemic stroke trials and clinical trial design considerations used in prior studies that have led to US market clearance as they are related to currently marketed devices indicated for acute ischemic stroke. C1 US FDA, Ctr Devices & Radiol Hlth, Div Gen Restorat & Neurol Devices, Off Device Evaluat, Rockville, MD 20857 USA. RP Pena, C (reprint author), US FDA, HHS, Off Sci & Hlth Coordinat, 5600 Fishers Lane,HF-33 Rm 14B08, Rockville, MD 20857 USA. EM carlos.pena@fda.hhs.gov NR 9 TC 4 Z9 4 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD JUN PY 2007 VL 38 IS 6 BP 1988 EP 1992 DI 10.1161/STROKEAHA.106.473918 PG 5 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 172TK UT WOS:000246827100053 PM 17478744 ER PT J AU Mahmood, I AF Mahmood, Iftekhar TI Prediction of drug clearance in children: Impact of allometric exponents, body weight, and age SO THERAPEUTIC DRUG MONITORING LA English DT Article DE allometric scaling; exponents; children; clearance; root mean square error ID PHARMACOKINETICS; INFANTS; ADULTS; MASS; ONTOGENY; PATHWAYS; RISKS; SIZE AB In recent years, with the advent of pediatric exclusivity and requirements for conducting clinical studies involving children, emphasis has been placed on finding safe and efficacious doses of drugs for children. It has been suggested that one can predict the clearance (CL) of a drug in children according to this equation: CL in the child = Adult CL * (Weight of the child/70)(0.75). In light of the controversy surrounding the exponent of 0.75 for the prediction of clearance, the objectives of the study were as follows: (1) to develop allometric equations based on body weight or age to predict clearance of a drug in children; (2) to determine if the fixed exponent of 0.75 is a suitable exponent for the prediction of clearance in children from adult data, as compared with the allometric exponent generated for individual drugs; (3) to determine if the allometric equation generated on the basis of age predicts clearance in children better or worse than the allometric equation generated on the basis of body weight; and (4) to propose a new approach based on the findings of the current evaluation. Five methods were used to predict drug clearance in children. Six drugs were used in the evaluation, and drug clearance in each child was predicted for a given drug. Besides evaluating the exponent of 0.75, allometric equations were developed using double log plots of clearance versus body weight or age. The exponents of the allometric equations were then used to predict drug clearance by replacement of 0.75 in the aforementioned equation. The results of the study indicate that 0.75 is not the best exponent for prediction of drug clearance in children, and a more suitable approach is to develop an allometric relationship for a given drug in children. For all 6 drugs, there were 77 children in whom the clearance was predicted. There were 48 observations for which error in the predicted clearance was 50% or more with use of the exponent 0.75, whereas there were only 13 observations with prediction error >= 50% when 0.75 was replaced by an allometric exponent developed for a given drug. In order to predict drug clearance in children with reasonable accuracy, an allometric equation should be developed for every drug and the exponent 0.75 should be replaced by the exponent of the allometric equation developed for that drug. C1 US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Mahmood, I (reprint author), US FDA, Off Blood Review & Res, Ctr Biol Evaluat & Res, 1451 Rockville Pike, Rockville, MD 20857 USA. EM Iftekhar.mahmood@fda.hhs.gov NR 24 TC 43 Z9 49 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD JUN PY 2007 VL 29 IS 3 BP 271 EP 278 DI 10.1097/FTD.0b013e318042d3c4 PG 8 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 173OL UT WOS:000246882300002 PM 17529882 ER PT J AU Ball, D Blanchard, J Jacobson-Kram, D McClellan, RO McGovern, T Norwood, DL Vogel, WM Wolff, R Nagao, L AF Ball, Douglas Blanchard, James Jacobson-Kram, David McClellan, Roger O. McGovern, Timothy Norwood, Daniel L. Vogel, W. Mark Wolff, Ron Nagao, Lee TI Development of safety qualification thresholds and their use in orally inhaled and nasal drug product evaluation SO TOXICOLOGICAL SCIENCES LA English DT Article DE qualification threshold; safety concern threshold; leachables; extractables; inhalation; nasal; PQRI ID NATIONAL-TOXICOLOGY-PROGRAM; CARCINOGENIC POTENCY; CHEMICAL-STRUCTURE; UNCERTAINTY FACTOR; ASTHMATIC-PATIENTS; SUBSTANCES PRESENT; HUMAN VARIABILITY; NITROGEN-DIOXIDE; RISK-ASSESSMENT; MUTAGENICITY AB Safety thresholds for chemical impurities and leachables in consumer products such as foods and drugs have helped to ensure public health while establishing scientifically sound limits for identification and risk assessment of these compounds. The Product Quality Research Institute (PQRI) Leachables and Extractables Working Group, a collaboration of chemists and toxicologists from the U.S. Food and Drug Administration (FDA), industry, and academia, has developed safety thresholds for leachables and extractables in orally inhaled and nasal drug products (OINDP), for application in United States pharmaceutical submissions. The PQRI safety concern threshold (SCT) is 0.15 mu g/day, and the qualification threshold is 5 mu g/day. OINDP are important in the treatment of lung diseases such as asthma and chronic bronchitis, as well as systemic diseases such as diabetes. Analysis of extractables and minimization of leachables in OINDP are vital to ensuring the quality and safety of the final product. It is expected that the thresholds developed by the PQRI Leachables and Extractables Working Group will be used by both industry and regulators to ensure and assess such quality and safety in OINDP applications. In this article, we describe the importance of the PQRI safety thresholds in the OINDP pharmaceutical development process; the background and context of safety thresholds for consumer products; how these safety thresholds were developed using well-established, robust databases and quantitative risk assessment approaches; and how these thresholds can be applied in a pharmaceutical safety qualification process, including FDA regulatory perspectives on the use of safety thresholds for OINDP. C1 Pfizer Global Res & Dev, Groton Labs, Safety Sci, Groton, CT 06340 USA. Aradigm Corp, Hayward, CA 94545 USA. US FDA, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Univ New Mexico, Hlth Sci Ctr, Albuquerque, NM 87111 USA. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. Pfizer Global Res & Dev, Safety Sci, Ann Arbor, MI 48105 USA. Nektar Therapeut, San Carlos, CA 94070 USA. Drinker Biddle & Reath LLP, Washington, DC 20005 USA. RP Ball, D (reprint author), Pfizer Global Res & Dev, Groton Labs, Safety Sci, Eastern Point Rd,MS 8274-1215, Groton, CT 06340 USA. EM douglas.j.ball@pfizer.com NR 44 TC 25 Z9 29 U1 3 U2 10 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 2007 VL 97 IS 2 BP 226 EP 236 DI 10.1093/toxsci/kfm058 PG 11 WC Toxicology SC Toxicology GA 177UO UT WOS:000247178200002 PM 17369604 ER PT J AU Eichelberger, MC AF Eichelberger, Maryna C. TI The cotton rat as a model to study influenza pathogenesis and immunity SO VIRAL IMMUNOLOGY LA English DT Article; Proceedings Paper CT Keystone Symposium on Immunologic Memory CY MAR 03-08, 2007 CL Santa Fe, NM ID A VIRUS-INFECTION; HETEROSUBTYPIC IMMUNITY; TRANSMISSION MODEL; GENE-EXPRESSION; ANIMAL-MODEL; MX PROTEINS; T-CELLS; B-CELLS; MICE; PROTECTION AB Influenza viruses continue to cause significant morbidity and mortality worldwide. With the threat of the emergence of a pandemic influenza strain, there is an urgency to develop new vaccine strategies that offer broad protection. The rational basis for the design of such vaccines comes from the use of animal models. Cotton rats are a helpful tool to study influenza disease pathogenesis and immunity because adaptation of human influenza strains is not required for virus replication in the lower respiratory tract and subsequent disease signs. This review describes innate and adaptive responses to influenza in infected cotton rats, and points out immune mechanisms that contribute to protection against disease. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20014 USA. RP Eichelberger, MC (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20014 USA. EM Maryna.Eichelberger@fda.hhs.gov NR 43 TC 22 Z9 23 U1 0 U2 3 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 0882-8245 J9 VIRAL IMMUNOL JI Viral Immunol. PD JUN PY 2007 VL 20 IS 2 BP 243 EP 249 DI 10.1089/vim.2007.0017 PG 7 WC Immunology; Virology SC Immunology; Virology GA 185NG UT WOS:000247717100003 PM 17603841 ER PT J AU Chan-Tack, KM Truffa, MM Struble, KA Birnkrant, DB AF Chan-Tack, Kirk M. Truffa, Melissa M. Struble, Kimberly A. Birnkrant, Debra B. TI Atazanavir-associated nephrolithiasis: cases from the US food and drug administration's adverse event reporting system SO AIDS LA English DT Article AB The risk of nephrolithiasis associated with atazanavir is not well characterized. The US Food and Drug Administration's Adverse Event Reporting System was searched for reports of nephrolithiasis in HIV-infected patients taking an atazanavir-based regimen. Thirty cases were identified. Many patients required hospitalization for management, including lithotripsy, ureteral stent insertion, or endoscopic stone removal. Some cases of nephrolithiasis resulted in atazanavir discontinuation. Healthcare professionals and patients should be informed that nephrolithiasis is a possible adverse event with atazanavir. C1 US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Chan-Tack, KM (reprint author), US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 5 TC 61 Z9 63 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 31 PY 2007 VL 21 IS 9 BP 1215 EP 1218 DI 10.1097/QAD.0b013e32813aee35 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 175VY UT WOS:000247043300019 PM 17502736 ER PT J AU Whittaker, P Keys, CE Brown, EW Fry, FS AF Whittaker, Paul Keys, Christine E. Brown, Eric W. Fry, Frederick S. TI Differentiation of Enterobacter sakazakii from closely related Enterobacter and Citrobacter species using fatty acid profiles SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE gas chromatography; fatty acids; Enterobacter sakazakii ID INFANT FORMULA; PCR ASSAY; PATHOGEN AB Capillary gas chromatography with flame ionization detection (GC-FID) was used to determine the cellular fatty acid (CFA) profiles of 134 Enterobacter sakazakii strains, and these were compared to the CFA profiles of other closely related Enterobacter and Citrobacter species. For GC-FID analysis, whole cell fatty acid methyl esters (FAMEs) from cells cultured on brain heart infusion (BHI) agar at 37 degrees C for 24 h were obtained by saponification, methylation, and extraction into hexane/methyl tert-butyl ether. A database for E. sakazakii was prepared using fatty acid profiles from the 134 strains. Major fatty acids of E. sakazakii strains evaluated in this study were straight-chain 12:0, 14:0, and 16:0, unsaturated 18:1 omega 7c, and 17:0 omega cyclo 7-8. Principal component analysis (PCA) based on CFA profiles for E. sakazakii strains shows separation of E. sakazakii subgroups A and B. The CFA profiles for E. sakazakii and Enterobacter cloacae show that there are several fatty acids, 14:0, 17:0 omega cyclo 7-8, 18:1 omega 7c, and summed 16:1 omega 6c/16:1 omega 7c, that differ significantly between these two species. A PCA model based on CFA profiles for E. sakazakii strains clearly shows separation of E. sakazakii from closely related Enterobacter and Citrobacter species. Analysis of FAMEs from E. sakazakii strains grown on BHI agar by a rapid GC-FID method can provide a sensitive procedure for the identification of this organism, and this analytical method provides a confirmatory procedure for the differentiation of E. sakazakii strains from closely related Enterobacter and Citrobacter species. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM paul.whittaker@fda.hhs.gov NR 20 TC 9 Z9 9 U1 0 U2 1 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 30 PY 2007 VL 55 IS 11 BP 4617 EP 4623 DI 10.1021/jf070193a PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 170PB UT WOS:000246674800045 PM 17472390 ER PT J AU Kim, DH Kang, JU Ilev, IK AF Kim, D. H. Kang, J. U. Ilev, I. K. TI Advanced confocal microscope using single hollow-core photonic bandgap fibre design SO ELECTRONICS LETTERS LA English DT Article ID CRYSTAL FIBER AB A simple confocal microscope design based on a single hollow-core fibre approach has been developed and experimentally analysed. Key optical components are the use of a hollow-core photonic bandgap fibre and a holed-mirror beam-splitter, both of which provide significant reduction of Fresnel back-reflections at the fibre tips and total background level resulting in increased resolving confocal laser power. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. RP Kim, DH (reprint author), US FDA, Ctr Devices & Radiol Hlth, Bldg 62,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM do-hyun.kim@fda.hhs.gov RI Kim, Do-Hyun/C-5311-2009; Kang, Jin/A-3228-2010 NR 6 TC 5 Z9 5 U1 0 U2 1 PU INST ENGINEERING TECHNOLOGY-IET PI HERTFORD PA MICHAEL FARADAY HOUSE SIX HILLS WAY STEVENAGE, HERTFORD SG1 2AY, ENGLAND SN 0013-5194 J9 ELECTRON LETT JI Electron. Lett. PD MAY 24 PY 2007 VL 43 IS 11 BP 608 EP 609 DI 10.1049/el:20070951 PG 2 WC Engineering, Electrical & Electronic SC Engineering GA 216YI UT WOS:000249914500007 ER PT J AU Jackson, SA Mammel, MK Patel, IR Mays, T Albert, TJ LeClerc, JE Cebula, TA AF Jackson, Scott A. Mammel, Mark K. Patel, Isha R. Mays, Tammy Albert, Thomas J. LeClerc, J. Eugene Cebula, Thomas A. TI Interrogating genornic diversity of E-coli O157 : H7 using DNA tiling arrays SO FORENSIC SCIENCE INTERNATIONAL LA English DT Article DE tiling DNA microarray; Escherichia coli O157 : H7; single nucleotide polymorphism ID SINGLE-NUCLEOTIDE POLYMORPHISMS; HEMOLYTIC UREMIC SYNDROME; COMPLETE GENOME SEQUENCE; TELLURITE-RESISTANCE; MICROBIAL FORENSICS; HEMORRHAGIC COLITIS; EVOLUTION; STRAINS; IDENTIFICATION; SEROTYPE AB Here, we describe a novel microarray-based approach for investigating the genomic diversity of Escherichia coli O157:H7 in a semi-high throughput manner using a high density, oligonucleotide-based microarray. This microarray, designed to detect polymorphisms at each of 60,000 base-pair (bp) positions within an E. coli genome, is composed of overlapping 29-mer oligonucleotides specific for 60 equally spaced, 1000-bp loci of the E. coli O157:H7 strain EDL933 chromosome. By use of a novel 12-well microarray that permitted the simultaneous investigation of 12 strains, the genomes of 44 individual isolates of E. coli O157:H7 were interrogated. These analyses revealed more than 150 single nucleotide polymorphisms (SNPs) and several deletions and amplifications in the test strains. Pyrosequencing was used to confirm the usefulness of the novel SNPs by determining their allelic frequency among a collection of diverse isolates of E. coli O157:H7. The tiling DNA microarray system would be useful for the tracking and identification of individual strains of E. coli O157:H7 needed for forensic investigations. (C) 2006 Elsevier Ireland Ltd. All rights reserved.. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Mol Biol, Laurel, MD 20708 USA. NimbleGen Syst Inc, Madison, WI 53711 USA. RP Cebula, TA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Mol Biol, Laurel, MD 20708 USA. EM Thomas.Cebula@fda.hhs.gov NR 32 TC 17 Z9 17 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0379-0738 J9 FORENSIC SCI INT JI Forensic Sci.Int. PD MAY 24 PY 2007 VL 168 IS 2-3 BP 183 EP 199 DI 10.1016/j.forsciint.2006.06.079 PG 17 WC Medicine, Legal SC Legal Medicine GA 171IK UT WOS:000246729200016 PM 16934953 ER PT J AU Irony, I Parks, MH Meyer, RJ AF Irony, Ilan Parks, Mary H. Meyer, Robert J. TI New treatments for diabetes SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Silver Spring, MD 20993 USA. RP Irony, I (reprint author), US FDA, Silver Spring, MD 20993 USA. EM ilan.irony@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 24 PY 2007 VL 356 IS 21 BP 2221 EP 2221 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 170ON UT WOS:000246673100033 PM 17526095 ER PT J AU Chen, Q Espey, MG Sun, AY Lee, JH Krishna, MC Shacter, E Choyke, PL Pooput, C Kirk, KL Buettner, GR Levine, M AF Chen, Qi Espey, Michael Graham Sun, Andrew Y. Lee, Je-Hyuk Krishna, Murali C. Shacter, Emily Choyke, Peter L. Pooput, Chaya Kirk, Kenneth L. Buettner, Garry R. Levine, Mark TI Ascorbate in pharmacologic concentrations selectively generates ascorbate radical and hydrogen peroxide in extracellular fluid in vivo SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE ascorbic acid; cancer; vitamin C; pharmacokinetics ID RECOMMENDED DIETARY ALLOWANCE; VITAMIN-C PHARMACOKINETICS; TERMINAL HUMAN CANCER; SUPPLEMENTAL ASCORBATE; SUPPORTIVE TREATMENT; OXIDATIVE STRESS; SURVIVAL TIMES; CELLS; ACID; APOPTOSIS AB Ascorbate (ascorbic acid, vitamin C) in pharmacologic concentrations easily achieved in humans by i.v. administration, selectively kills some cancer cells but not normal cells. We proposed that pharmacologic ascorbate is a prodrug for preferential steady-state formation of ascorbate radical (Asc(.-)) and H2O2 in the extracellular space compared with blood. Here we test this hypothesis in vivo. Rats were administered parenteral (i.v. or i.p.) or oral ascorbate in typical human pharmacologic doses (approximate to 0.25-0.5 mg per gram of body weight). After i.v. injection, ascorbate baseline concentrations of 50-100 mu M in blood and extracellular fluid increased to peaks of > 8 mM. After i.p. injection, peaks approached 3 mM in both fluids. By gavage, the same doses produced ascorbate concentrations of < 150 mu M in both fluids. In blood, Asc(.-)concentrations measured by EPR were undetectable with oral administration and always < 50 nM with parenteral administration, even when corresponding ascorbate concentrations were > 8 mM. After parenteral dosing, Asc(.-) concentrations in extracellular fluid were 4- to 12-fold higher than those in blood, were as high as 250 nM, and were a function of ascorbate concentrations. By using the synthesized probe peroxyxanthone, H2O2 in extracellular fluid was detected only after parenteral administration of ascorbate and when Asc(.-) concentrations in extracellular fluid exceeded 100 nM. The data show that pharmacologic ascorbate is a prodrug for preferential steady-state formation of Asc- and H2O2 in the extracellular space but not blood. These data provide a foundation for pursuing pharmacologic ascorbate as a prooxidant therapeutic agent in cancer and infections. C1 NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. NIDDK, Lab Bioorgan Chem, NIH, Bethesda, MD 20892 USA. NCI, Radiat Biol Branch, Bethesda, MD 20892 USA. NCI, Mol Imaging Program, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Biochem Lab, Bethesda, MD 20892 USA. Univ Iowa, Free Rad & Radiat Biol Program, Iowa City, IA 52242 USA. RP Levine, M (reprint author), NIDDK, Mol & Clin Nutr Sect, NIH, Bethesda, MD 20892 USA. EM markL@mail.nih.gov RI Chen, Qi/D-8278-2015; OI Chen, Qi/0000-0002-7173-8411; Buettner, Garry/0000-0002-5594-1903 FU NIDDK NIH HHS [Z01 DK054506, Z01 DK54506] NR 42 TC 224 Z9 234 U1 3 U2 18 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 22 PY 2007 VL 104 IS 21 BP 8749 EP 8754 DI 10.1073/pnas.0702854104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 173DM UT WOS:000246853700015 PM 17502596 ER PT J AU Dobardzic, A Izurieta, H Woo, EJ Iskander, J Shadomy, S Rupprecht, C Ball, R Braun, MM AF Dobardzic, Azra Izurieta, Hector Woo, Emily Jane Iskander, John Shadomy, Sean Rupprecht, Charles Ball, Robert Braun, M. Miles TI Safety review of the purified chick embryo cell rabies vaccine: Data from the Vaccine Adverse Event Reporting System (VAERS), 1997-2005 SO VACCINE LA English DT Review DE RabAvert; PCEC vaccine; rabies; adverse events ID IMMUNIZATION; EPIDEMIOLOGY; CHILDREN AB On October 20, 1997, the U.S. Food and Drug Administration (FDA) licensed Purified Chick Embryo Cell (PCEC, RabAvert (R)) vaccine against rabies in humans following clinical trials demonstrating safety and efficacy. From October 1997 through December 2005, the Vaccine Adverse Event Reporting System (VAERS) received 336 reports of adverse events (AEs) following vaccination with PCEC vaccine in the U.S.; there were no death reports. Serious events, including 20 hospitalizations and 13 neurological events, were described in 24 (7%) reports. There was no pattern among the 13 neurological AEs suggesting a plausible relationship to vaccination. A total of 20 AEs, 3 serious, were classified as possible anaphylaxis. There were 312 non-serious AEs (93%). Nineteen reports (6%) described that the vaccination series was discontinued because of non-serious AEs. Most reported AEs are non-serious and consistent with pre-licensure safety data. The rabies risk must be carefully considered before vaccine discontinuation. (c) 2007 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. RP Dobardzic, A (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM azra.dobardzic@fda.hhs.gov NR 30 TC 23 Z9 25 U1 1 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 MAY 22 PY 2007 VL 25 IS 21 BP 4244 EP 4251 DI 10.1016/j.vaccine.2007.02.075 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 184KS UT WOS:000247640900015 PM 17382435 ER PT J AU Hsia, CC Chlzhikov, VE Yang, AX Selvapandiyan, A Hewlett, I Duncan, R Puri, RK Nakhasi, HL Kaplan, GG AF Hsia, Chu Chieh Chlzhikov, Vladimir E. Yang, Amy X. Selvapandiyan, Angamuthu Hewlett, Indira Duncan, Robert Puri, Raj K. Nakhasi, Hira L. Kaplan, Gerardo G. TI Microarray multiplex assay for the simultaneous detection and discrimination of hepatitis B, hepatitis C, and human immunodeficiency type-1 viruses in human blood samples SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE microarray technology; human immunodeficiency virus type-1 (HIV-1); hepatitis C virus (HCV); hepatitis B virus (HBV); multiplex detection and discrimination; PCR; blood-borne virus ID RNA; PATHOGENS; DNA; HYBRIDIZATION; TECHNOLOGY; INFECTIONS; PREVALENCE; RISK AB Hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus type-1 (HIV-1) are transfusion-transmitted human pathogens that have a major impact oil blood safety and public health worldwide. We developed a microarray multiplex assay for the simultaneous detection and discrimination of these three viruses. The microarray consists of 16 oligonucleotide probes, immobilized on a silylated glass slide. Amplicons from multiplex PCR were labeled with Cy-5 and hybridized to the microarray. The assay detected 1 International Unit (IU), 10 IU, 20 IU of HBV, HCV, and HIV-1, respectively, in a single multiplex reaction. The assay also detected and discriminated the presence of two or three of these viruses in a single sample. Our data represent a proof-of-concept for the possible use of highly sensitive multiplex microarray assay to screen and confirm the presence of these viruses in blood donors and patients. Published by Elsevier Inc. C1 US FDA, Ctr Biol Evaluat & Review, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Review, Div Viral Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Review, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Hsia, CC (reprint author), US FDA, Ctr Biol Evaluat & Review, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. EM chuchieh.hsia@fda.hhs.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 24 TC 18 Z9 20 U1 0 U2 5 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 MAY 18 PY 2007 VL 356 IS 4 BP 1017 EP 1023 DI 10.1016/j.bbrc.2007.03.087 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 158ZD UT WOS:000245833500031 PM 17407765 ER PT J AU Inoue, S Scott, D Golding, B Leitner, WW AF Inoue, Satoshi Scott, Dorothy Golding, Basil Leitner, Wolfgang W. TI Regulatory B cells inhibit antitumor immunity SO CANCER RESEARCH LA English DT Letter C1 US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. RP Inoue, S (reprint author), US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RI Leitner, Wolfgang/F-5741-2011 OI Leitner, Wolfgang/0000-0003-3125-5922 NR 4 TC 0 Z9 2 U1 0 U2 1 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 2007 VL 67 IS 10 BP 5059 EP 5059 DI 10.1158/0008-5472.CAN-06-4780 PG 1 WC Oncology SC Oncology GA 172BG UT WOS:000246778500066 ER PT J AU Zhang, P Wu, CG Mihalik, K Virata-Theimer, ML Yu, MYW Alter, HJ Feinstone, SM AF Zhang, Pei Wu, Charles G. Mihalik, Kathleen Virata-Theimer, Maria Luisa Yu, Mei-Ying W. Alter, Harvey J. Feinstone, Stephen M. TI Hepatitis C virus epitope-specific neutralizing antibodies in Igs prepared from human plasma SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE anti-hepatitis C virus-positive plasma; Ig intravenous ID HUMAN MONOCLONAL-ANTIBODIES; LIVER-TRANSPLANTATION; ENVELOPE GLYCOPROTEIN; IMMUNE GLOBULIN; CELL-CULTURE; IN-VITRO; HCV; INFECTION; PROTEIN; PSEUDOPARTICLES AB Neutralizing antibodies directed against hepatitis C virus (HCV) are present in Igs made from anti-HCV-positive plasma. However, these HCV-specific Igs are largely ineffective in vivo. The mechanism for the poor effectiveness is currently unknown. We hypothesize that the presence of nonneutralizing antibodies in HCV-specific Igs interferes with the function of neutralizing antibodies, resulting in the reduction or blockage of their effect. In the present study, we identified at least two epitopes at amino acid residues 412-419 (epitope I) and 434-446 (epitope II), located downstream of the hypervariable region I within the HCV E2 protein. We demonstrated that epitope I, but not epitope II, was implicated in HCV neutralization and that binding of a nonneutralizing antibody to epitope II completely disrupted virus neutralization mediated by antibody binding at epitope I. The dynamic interaction between nonneutralizing and neutralizing antibodies may thus play a key role in determining the outcomes of HCV infection. Further exploration of this interplay should lead to a better understanding of the mechanisms of neutralization and immune escape and may indicate pathways for the manufacture of an effective HCV-specific Ig product for immune prophylaxis of HCV infection. C1 US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Gastroenterol Prodl, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NIH, Dept Transfus Med, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Zhang, P (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM pei.zhang@fda.hhs.gov; halter@dtm.cc.nih.gov NR 27 TC 84 Z9 87 U1 0 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 15 PY 2007 VL 104 IS 20 BP 8449 EP 8454 DI 10.1073/pnas.0703039104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 169NW UT WOS:000246599900047 PM 17494735 ER PT J AU Schmeisser, F Weir, JP AF Schmeisser, Falko Weir, Jerry P. TI Incorporation of a lambda phage recombination system and EGFP detection to simplify mutagenesis of Herpes simplex virus bacterial artificial chromosomes SO BMC BIOTECHNOLOGY LA English DT Article ID LENGTH INFECTIOUS CLONE; HUMAN CYTOMEGALOVIRUS; ESCHERICHIA-COLI; GLYCOPROTEIN-B; IN-VIVO; GENOME; CONSTRUCTION; VECTOR; DNA; MANIPULATION AB Background: Targeted mutagenesis of the herpesvirus genomes has been facilitated by the use of bacterial artificial chromosome ( BAC) technology. Such modified genomes have potential uses in understanding viral pathogenesis, gene identification and characterization, and the development of new viral vectors and vaccines. We have previously described the construction of a herpes simplex virus 2 ( HSV- 2) BAC and the use of an allele replacement strategy to construct HSV- 2 recombinants. While the BAC mutagenesis procedure is a powerful method to generate HSV- 2 recombinants, particularly in the absence of selective marker in eukaryotic culture, the mutagenesis procedure is still difficult and cumbersome. Results: Here we describe the incorporation of a phage lambda recombination system into an allele replacement vector. This strategy enables any DNA fragment containing the phage alpha ttL recombination sites to be efficiently inserted into the alpha ttR sites of the allele replacement vector using phage lambda clonase. We also describe how the incorporation of EGFP into the allele replacement vector can facilitate the selection of the desired cross-over recombinant BACs when the allele replacement reaction is a viral gene deletion. Finally, we incorporate the lambda phage recombination sites directly into an HSV- 2 BAC vector for direct recombination of gene cassettes using the phage lambda clonase-driven recombination reaction. Conclusion: Together, these improvements to the techniques of HSV BAC mutagenesis will facilitate the construction of recombinant herpes simplex viruses and viral vectors. C1 US FDA, Lab DNA Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Schmeisser, F (reprint author), US FDA, Lab DNA Viruses, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM falko.schmeisser@fda.hhs.gov; jerry.weir@fda.hhs.gov NR 30 TC 7 Z9 7 U1 2 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1472-6750 J9 BMC BIOTECHNOL JI BMC Biotechnol. PD MAY 14 PY 2007 VL 7 AR 22 DI 10.1186/1472-6750-7-22 PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 174XR UT WOS:000246976700001 PM 17501993 ER PT J AU Belongia, E Izurieta, H Braun, MM Ball, R Haber, P Baggs, J Weintraub, E Gargiullo, P Vellozzi, C Iskander, J Patel, M Parashar, U Cortese, M Gentsch, J Wallace, G Bartlett, D AF Belongia, E. Izurieta, H. Braun, M. M. Ball, R. Haber, P. Baggs, J. Weintraub, E. Gargiullo, P. Vellozzi, C. Iskander, J. Patel, M. Parashar, U. Cortese, M. Gentsch, J. Wallace, G. Bartlett, D. CA CDC TI Postmarketing monitoring of intussusception after RotaTeq (TM) vaccination - United States, February 1, 2006-February 15, 2007 (Reprinted from MMWR, vol 56, pg 218-222, 2007) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. CDC, Immunizat Safety Off, Off Chief Sci Officer, Atlanta, GA 30333 USA. CDC, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. RP Belongia, E (reprint author), Marshfield Clin Fdn Med Res & Educ, Marshfield, WI 54449 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 9 PY 2007 VL 297 IS 18 BP 1972 EP + PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 165JM UT WOS:000246301800009 ER PT J AU Moore, DF Gelderman, MP Ferreira, PA Fuhrmann, SR Yi, HQ Elkahloun, A Lix, LM Brady, RO Schiffmann, R Goldin, E AF Moore, David F. Gelderman, Monique P. Ferreira, Paulo A. Fuhrmann, Steven R. Yi, Haiqing Elkahloun, Abdel Lix, Lisa M. Brady, Roscoe O. Schiffmann, Raphael Goldin, Ehud TI Genomic abnormalities of the murine model of Fabry disease after disease-related perturbation, a systems biology approach SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE glycolipids; growth factor; lysosomal; reactive oxygen species ID ALPHA-GALACTOSIDASE; ENZYME REPLACEMENT; SUBCELLULAR-LOCALIZATION; CEREBRAL HYPERPERFUSION; MICE; DEFICIENCY; PROTEOLYSIS; THROMBOSIS; PROTEINS; REVERSAL AB Fabry disease is a disorder of alpha-D-galactosyl-containing glycolipids resulting from a deficiency of alpha-galactosidase A. Patients have a poorly understood vascular dysregulation. We hypothesized that disease-related perturbation by using enzyme replacement therapy in the murine model of Fabry disease would provide insight into abnormal biological processes in Fabry disease. Gene expression analyses of the heart, aorta, and liver of male alpha-galactosidase A knockout mice 28 weeks of age were compared with that of WT mice. Microarray analyses were performed before and after six weekly injections of a-galactosidase A. Alteration of Rpgrip1 ranked highest statistically in all three organs when knockout mice were compared with WT, and its splice variants responded in a unique way to alpha-galactosidase A. Enzyme replacement therapy tended to not only normalize gene expression, e.g., reduce the overexpression of securin, but also specifically modified gene expression in each tissue examined. Following multiple comparison analysis, gene expression correlation graphs were constructed, and a priori hypotheses were examined by using structural equation modeling. This systems biology approach demonstrated multiple and complex parallel cellular abnormalities in Fabry disease. These abnormalities form the basis for informed, in a Bayesian sense, sequential, hypothesis-driven research that can be subsequently tested experimentally. C1 Univ Manitoba, Neurol Sect, Winnipeg, MB R3T 2N2, Canada. Univ Manitoba, Dept Community Hlth Sci, Winnipeg, MB R3T 2N2, Canada. US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Rockville, MD 20857 USA. IOMAI Corp, Gaithersburg, MD 20878 USA. Duke Univ, Med Ctr, Dept Ophthalmol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 USA. Natl Inst Neurol Disorders & Strokes, Microarray Core Facil, Bethesda, MD 20892 USA. Natl Inst Neurol Disorders & Strokea, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. RP Goldin, E (reprint author), Univ Manitoba, Neurol Sect, Winnipeg, MB R3T 2N2, Canada. EM rb57v@nih.gov RI Ferreira, Paulo/A-3893-2008; Ferreira, Paulo/S-4209-2016 OI Ferreira, Paulo/0000-0003-4585-1717 FU Intramural NIH HHS; NEI NIH HHS [2P30-EY 005722-21, EY 11993, P30 EY005722, R01 EY011993, R01 EY012665] NR 46 TC 11 Z9 11 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD MAY 8 PY 2007 VL 104 IS 19 BP 8065 EP 8070 DI 10.1073/pnas.0701991104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 167OR UT WOS:000246461500060 PM 17470787 ER PT J AU Padavattan, S Schirmer, T Schmidt, M Akdis, C Valenta, R Mittermann, I Soldatova, L Slater, J Mueller, U Markovic-Housley, Z AF Padavattan, Sivaraman Schirmer, Tilman Schmidt, Margit Akdis, Cezmi Valenta, Rudolf Mittermann, Irene Soldatova, Lyudmila Slater, Jay Mueller, Ulrich Markovic-Housley, Zora TI Identification of a B-cell epitope of hyaluronidase, a major bee venom allergen, from its crystal structure in complex with a specific fab SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE hyaluronidase; bee venom allergen; B-cell epitope; hyaluronidase/Fab complex; X-ray structure ID SITE-DIRECTED MUTAGENESIS; ANTIBODY-ANTIGEN COMPLEX; YELLOW JACKET VENOM; HYMENOPTERA VENOM; GLYCOSYL HYDROLASES; ANGSTROM RESOLUTION; IMMUNE-RESPONSES; PROTEIN ANTIGENS; WATER-MOLECULES; COMBINING SITE AB The major allergens of honeybee venom, hyaluronidase (Hyal) and phospholipase A2, can induce life-threatening IgE-mediated allergic reactions in humans. Although conventional immunotherapy is effective, up to 40% of patients develop allergic side effects including anaphylaxis and thus, there is a need for an improved immunotherapy. A murine monoclonal anti-Hyal IgG1 antibody (mAb 21E11), that competed for Hyal binding with lgEs from sera of bee venom allergic patients, was raised. The fragment of these IgG antibodies which bind to antigen (Fab) was produced and complexed (1:1) with Hyal. The crystal structure determination of Hyal/Fab 21E11 complex (2.6 angstrom) enabled the identification of the Hyal-IgG interface which provides indirect information on the Hyal-IgE interaction (B-cell epitope). The epitope is composed of a linear array of nine residues (Arg138, His141-Arg148) located at the tip of a helix-turn-helix motive which protrudes away, from the globular core and fits tightly into the deep surface pocket formed by the residues from the six complementarity determining regions (CDRs) of the Fab. The epitope is continuous and yet its conformation appears to be essential for Ab recognition, since the synthetic 15-mer peptide comprising the entire epitope (Arg138-Glu152) is neither recognized by mAb 21E11 nor by human IgEs. The structure of the complex provides the basis for the rational design of Hyal derivatives with reduced allergenic activity, which could be used in the development of safer allergen-specific immunotherapy. (c) 2007 Elsevier Ltd. All rights reserved. C1 Univ Basel, Biozentrum, Div Struct Biol, CH-4056 Basel, Switzerland. E Carolina Univ, Dept Biol, Greenville, NC 27858 USA. Swiss Inst Allergy & Asthma Res, Dept Cellular Allergol Immunol, CH-7270 Davos, Switzerland. Med Univ Vienna, Dept Pathophysiol, Div Immunopathol, Christian Doppler Lab Allergy Res, A-1090 Vienna, Austria. US FDA, OPS ONDQA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. SpitalBern, CH-3001 Bern, Switzerland. RP Markovic-Housley, Z (reprint author), Univ Basel, Biozentrum, Div Struct Biol, CH-4056 Basel, Switzerland. EM zora.housley@unibas.ch RI Mueller, Uwe/B-6293-2013 NR 60 TC 42 Z9 46 U1 1 U2 7 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 MAY 4 PY 2007 VL 368 IS 3 BP 742 EP 752 DI 10.1016/j.jmb.2007.02.036 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 162BB UT WOS:000246060200011 PM 17374540 ER PT J AU Cheng, ZH Zhou, HP Yin, JJ Yu, LL AF Cheng, Zhihong Zhou, Huiping Yin, Junjie Yu, Liangli TI Electron spin resonance estimation of hydroxyl radical scavenging capacity for lipophilic antioxidants SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE hydroxyl radical; lipophilic antioxidant; ESR; Fenton reaction; solvent effect ID CANCER PREVENTION; BETA-CYCLODEXTRIN; ASSAY; VEGETABLES; FRUIT AB Hydroxyl radical scavenging capacity estimation for lipophilic antioxidants is a challenge due to their poor solubility in aqueous radical generating and measuring systems. In this study, an electron spin resonance (ESR) method was developed and validated for its application in estimating the relative hydroxyl radical (HO center dot) scavenging capacity for lipophilic antioxidants under physiological pH using a Fenton Fe2+/H2O2 system for radical generation and acetonitrile as a solvent. The Fenton Fe2+/H2O2 system generates a constant flux of pure HO center dot under the assay conditions. The method was validated by linearity, precision, and reproducibility using selected known lipophilic antioxidants including alpha-tocopherol, lutein, beta-carotene, and BHT. The potential effects of commonly used water-miscible and water-immiscible organic solvents on the Fenton Fe2+/H2O2 HO center dot generating system as well as their possible interactions with the fluorescent and spectroscopic probes were also reported. In addition, the limitation of the ESR assay was described. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Virginia Commonwealth Univ, Sch Med, Dept Microbiol & Immunol, Richmond, VA 23298 USA. US FDA, CFSAN, Instrumentat & Biophys Branch, College Pk, MD 20740 USA. RP Yu, LL (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM lyu5@umd.edu RI Yin, Jun Jie /E-5619-2014 NR 23 TC 24 Z9 25 U1 1 U2 11 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 2 PY 2007 VL 55 IS 9 BP 3325 EP 3333 DI 10.1021/jf0634808 PG 9 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 160MQ UT WOS:000245946300013 PM 17381117 ER PT J AU Hellmich, B Flossmann, O Gross, WL Bacon, P Cohen-Tervaert, JW Guillevin, L Jayne, D Mahr, A Merkel, PA Raspe, H Scott, DGI Witter, J Yazici, H Luqmani, RA AF Hellmich, Bernhard Flossmann, Oliver Gross, Wolfgang L. Bacon, Paul Cohen-Tervaert, Jan Willem Guillevin, Loic Jayne, David Mahr, Alfred Merkel, Peter A. Raspe, Heiner Scott, David G. I. Witter, James Yazici, Hasan Luqmani, Raashid A. CA European Vasculitis Study Grp TI EULAR recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis: focus on anti-neutrophil cytoplasm antibody-associated vasculitis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID CHURG-STRAUSS-SYNDROME; ANCA-ASSOCIATED VASCULITIS; GIANT-CELL ARTERITIS; TERM-FOLLOW-UP; REFRACTORY WEGENERS-GRANULOMATOSIS; PLACEBO-CONTROLLED TRIAL; TNF-ALPHA BLOCKADE; OPEN-LABEL TRIAL; QUALITY-OF-LIFE; POLYARTERITIS-NODOSA AB Objectives: To develop the European League Against Rheumatism (EULAR) recommendations for conducting clinical studies and/or clinical trials in systemic vasculitis. Methods: An expert consensus group was formed consisting of rheumatologists, nephrologists and specialists in internal medicine representing five European countries and the USA, a clinical epidemiologist and representatives from regulatory agencies. Using an evidence-based and expert opinion-based approach in accordance with the standardised EULAR operating procedures, the group identified nine topics for a systematic literature search through a modified Delphi technique. On the basis of research questions posed by the group, recommendations were derived for conducting clinical studies and/or clinical trials in systemic vasculitis. Results: Based on the results of the literature research, the expert committee concluded that sufficient evidence to formulate guidelines on conducting clinical trials was available only for anti-neutrophil cytoplasm antibody-associated vasculitides (AAV). It was therefore decided to focus the recommendations on these diseases. Recommendations for conducting clinical trials in AAV were elaborated and are presented in this summary document. It was decided to consider vasculitis-specific issues rather than general issues of trial methodology. The recommendations deal with the following areas related to clinical studies of vasculitis: definitions of disease, activity states, outcome measures, eligibility criteria, trial design including relevant end points, and biomarkers. A number of aspects of trial methodology were deemed important for future research. Conclusions: On the basis of expert opinion, recommendations for conducting clinical trials in AAV were formulated. Furthermore, the expert committee identified a strong need for well-designed research in non-AAV systemic vasculitides. C1 Univ Oxford, Botnar Res Ctr, Oxford OX3 7LD, England. Nuffield Orthopaed Ctr, Dept Rheumatol, Oxford OX3 7LD, England. Univ Hosp Schleswig Holstein, Dept Rheumatol, Lubeck, Germany. Addenbrookes Hosp, Dept Nephrol, Cambridge, England. Univ Birmingham, Dept Rheumatol, Birmingham, W Midlands, England. Maastricht Univ, Div Clin & Expt Immunol, Maastricht, Netherlands. Univ Paris 05, Cochin Hosp, Dept Internal Med, Paris, France. Boston Univ, Sch Med, Vasculitis Ctr, Rheumatol Sect, Boston, MA 02215 USA. Boston Univ, Sch Med, Clin Epidemiol Unit, Boston, MA 02215 USA. Univ Hosp Schleswig Holstein, Inst Social Med, Lubeck, Germany. Univ E Anglia, Norfolk Hosp, Dept Rheumatol, Norwich NR4 7TJ, Norfolk, England. US FDA, Rockville, MD 20857 USA. Istanbul Univ, Cerrahpasa Med Fac, Div Rheumatol, Dept Med, Istanbul, Turkey. RP Luqmani, RA (reprint author), Nuffield Orthopaed Ctr, Dept Rheumatol, Oxford OX3 7LD, England. EM raashid.luqmani@ndos.ox.ac.uk RI Raspe, Heiner /E-3612-2010; Gross, Wolfgang Ludwig/C-8733-2011; OI Luqmani, Raashid/0000-0002-4446-5841 NR 86 TC 260 Z9 267 U1 1 U2 8 PU BMJ PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 EI 1468-2060 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAY 1 PY 2007 VL 66 IS 5 BP 605 EP 617 DI 10.1136/ard.2006.062711 PG 13 WC Rheumatology SC Rheumatology GA 161LZ UT WOS:000246018000006 PM 17170053 ER PT J AU Wright, LKM Paule, MG AF Wright, L. K. M. Paule, M. G. TI Response sequence difficulty in an incremental repeated acquisition (learning) procedure SO BEHAVIOURAL PROCESSES LA English DT Article DE incremental repeated acquisition; learning; rat ID BEHAVIORAL CHAINS; PAPIO-PAPIO; RAT; TRANSITION AB Incremental repeated acquisition (IRA) procedures require subjects to learn a different sequence of behavioral responses during each experimental session with required response sequences increasing incrementally in length as subjects demonstrate mastery of shorter response chains. The purpose of this study was to investigate whether some response sequences are more or less difficult to acquire than others. If true, then sequcnce difficulty must be considered as a potential confound when attempting to assess the effects of drugs and other experimental manipulations on learning. Accuracy for each response sequence was assessed using control data from two large rodent studies, and each sequence was classified as easy, moderate or hard. Sequences that required responses on adjacent levers were easier (characterized by higher accuracies) to acquire than those that required responses on non-adjacent levers. In addition, sequences that required responses on only two of three response levels were easier to acquire than those that required responses on all three levers. These results provide strong evidence for differing levels of response sequence difficulty in IRA procedures with sequence difficulty seeming to be dependent on whether or not responses are required on adjacent levers. (c) 2007 Published by Elsevier B.V. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci Hosp, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. RP Wright, LKM (reprint author), Oklahoma State Univ, Ctr Vet Hlth Sci, 165 McElroy Hall, Stillwater, OK 74078 USA. EM linnzi.wright@okstate.edu NR 14 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0376-6357 J9 BEHAV PROCESS JI Behav. Processes PD MAY PY 2007 VL 75 IS 1 BP 81 EP 84 DI 10.1016/j.beproc.2007.01.007 PG 4 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA 159RU UT WOS:000245884800010 PM 17324533 ER PT J AU Slikker, W Zou, X Sadovova, N Divine, B Hotchkiss, C Patterson, T Ali, S Hanig, J Paule, M Wang, C AF Slikker, Jr. W. Zou, X. Sadovova, N. Divine, B. Hotchkiss, C. Patterson, T. Ali, S. Hanig, J. Paule, M. Wang, C. TI Brain cell death induced by a combination of inhalation anesthetics in the developing at and protection from this effect by L-carnitine SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 US FDA, NCTR, Jefferson, AR USA. Toxicol Pathol Assoc, Jefferson, AR USA. Bionet, Jefferson, AR USA. US FDA, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2007 VL 79 IS 5 MA 43 BP 374 EP 374 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 167BO UT WOS:000246425800044 ER PT J AU Hansen, DK AF Hansen, D. K. TI Examples of associations between polymorphisms and birth defects: Folic acid and retinoic acid SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2007 VL 79 IS 5 MA S24 BP 394 EP 394 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 167BO UT WOS:000246425800079 ER PT J AU Slikker, W AF Slikker, Jr. W. TI Susceptability to the developmental neurotoxicity of anesthetics: Studies on neuroprotection SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2007 VL 79 IS 5 MA S25 BP 394 EP 394 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 167BO UT WOS:000246425800080 ER PT J AU Delclos, KB Weis, CC Newbold, RR AF Delclos, K. B. Weis, C. C. Newbold, R. R. TI Reproductive and developmental toxicity of phytoestrogens SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD MAY PY 2007 VL 79 IS 5 MA W12 BP 402 EP 402 PG 1 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 167BO UT WOS:000246425800092 ER PT J AU Panicker, G Vickery, MCL Bej, AK AF Panicker, Gitika Vickery, Michael C. L. Bej, Asim K. TI Multiplex PCR detection of clinical and environmental strains of Vibrio vulnificus in shellfish (vol 50, pg 911, 2004) SO CANADIAN JOURNAL OF MICROBIOLOGY LA English DT Correction C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Univ Alabama, Dept Biol, Birmingham, AL 35294 USA. RP Bej, AK (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville, PO Box 158, Dauphin Isl, AL 36528 USA. EM abej@uab.edu NR 1 TC 0 Z9 0 U1 0 U2 1 PU NATL RESEARCH COUNCIL CANADA-N R C RESEARCH PRESS PI OTTAWA PA BUILDING M 55, OTTAWA, ON K1A 0R6, CANADA SN 0008-4166 J9 CAN J MICROBIOL JI Can. J. Microbiol. PD MAY PY 2007 VL 53 IS 5 BP 671 EP 671 DI 10.1139/W07-058 PG 1 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Immunology; Microbiology GA 199FV UT WOS:000248682500015 ER PT J AU Goode, J Sapirstein, W Zuckerman, B AF Goode, Jennifer Sapirstein, Wolf Zuckerman, Bram TI FDA perspective on clinical trial design for femoropopliteal stent correction of peripheral vascular insufficiency cardiovascular devices - Editorial comment SO CATHETERIZATION AND CARDIOVASCULAR INTERVENTIONS LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20857 USA. RP Goode, J (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20857 USA. EM Jennifer.Goode@fda.hhs.gov NR 2 TC 4 Z9 4 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1522-1946 J9 CATHETER CARDIO INTE JI Catheter. Cardiovasc. Interv. PD MAY 1 PY 2007 VL 69 IS 6 BP 920 EP 921 DI 10.1002/ccd.21209 PG 2 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 164UJ UT WOS:000246259800026 PM 17455345 ER PT J AU Kocabas, C Katsenelson, N Kanswal, S Kennedy, MN Cui, XL Blake, MS Segal, DM Akkoyunlu, M AF Kocabas, Can Katsenelson, Nora Kanswal, Sunita Kennedy, Margaret N. Cui, Xinle Blake, Milan S. Segal, David M. Akkoyunlu, Mustafa TI Neisseria meningitidis type C capsular polysaccharide inhibits lipooligosaccharide-induced cell activation by binding to CD14 SO CELLULAR MICROBIOLOGY LA English DT Article ID HUMAN DENDRITIC CELLS; TOLL-LIKE RECEPTOR-4; BACTERIAL LIPOPOLYSACCHARIDE; IMMUNE-RESPONSES; ENDOTOXIN; PROTEIN; MACROPHAGES; EXPRESSION; LIGAND; LPS AB Encapsulated Neisseria meningitidis can invade mucosal barriers and cause systemic diseases. Activation of the innate immune system by conserved meningococcal molecules such as lipooligosaccharides (LOS) is essential for the generation of an effective host immune response. Here we show that the type C capsular polysaccharide of N. meningitidis (MCPS) inhibited LOS-induced interleukin-6 and TNF-alpha secretion from monocytes, and blocked the maturation of dendritic cells induced by LOS, while the capsular polysaccharide from group B streptococcus type III and t(4-hydroxy-3-nitrophenyl) acetyl (NP)-Ficoll had no such effect. MCPS also inhibited the LOS-induced NF-kappa B activation and phosphorylation of signalling molecules such as ERK1/2, p38 and Jun N-terminal kinase. In a direct binding assay, MCPS manifested a concentration-dependent binding to recombinant lipoprotein binding protein and CD14, the two members of the LOS receptor complex. In addition, the binding of LOS to CD14 and lipopolysaccharide binding protein was inhibited by MCPS. We established that MCPS binding to CD14 is responsible for the inhibition of LOS-mediated cell activation because MCPS inhibition of LOS was reversed when access amounts of CD14 were added to culture media of HEK293 cells expressing TLR4 and MD-2, and the magnitude of recovery in LOS stimulation correlated with the increase in CD14 concentration. These results suggest a new virulence property of meningococcal capsular polysaccharides. C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Rockville, MD 20852 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Akkoyunlu, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Rockville, MD 20852 USA. EM Mustafa.Akkoyunlu@fda.hhs.gov RI Akkoyunlu, Mustafa/I-5712-2012 NR 38 TC 15 Z9 15 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1462-5814 J9 CELL MICROBIOL JI Cell Microbiol. PD MAY PY 2007 VL 9 IS 5 BP 1297 EP 1310 DI 10.1111/j.1462-5822.2006.00872.x PG 14 WC Cell Biology; Microbiology SC Cell Biology; Microbiology GA 154KO UT WOS:000245506100019 PM 17250593 ER PT J AU Cutlip, DE Windecker, S Mehran, R Boam, A Cohen, DJ van Es, GA Steg, PG Morel, MA Mauri, L Vranckx, P McFadden, E Lansky, A Hamon, M Krucoff, MW Serruys, PW AF Cutlip, Donald E. Windecker, Stephan Mehran, Roxana Boam, Ashley Cohen, David J. van Es, Gerrit-Anne Steg, P. Gabriel Morel, Marie-angele Mauri, Laura Vranckx, Pascal McFadden, Eugene Lansky, Alexandra Hamon, Martial Krucoff, Mitchell W. Serruys, Patrick W. CA Acad Res Consortium TI Clinical end points in coronary stent trials - A case for standardized definitions SO CIRCULATION LA English DT Article DE restenosis; stents; thrombosis; clinical trials ID DRUG-ELUTING STENTS; JOINT EUROPEAN-SOCIETY; ANGIOGRAPHIC FOLLOW-UP; CREATINE KINASE-MB; MYOCARDIAL-INFARCTION; ARTERY-DISEASE; BARE-METAL; TROPONIN-T; CARDIOLOGY/AMERICAN COLLEGE; INTRACORONARY BRACHYTHERAPY AB Background - Although most clinical trials of coronary stents have measured nominally identical safety and effectiveness end points, differences in definitions and timing of assessment have created confusion in interpretation. Methods and Results - The Academic Research Consortium is an informal collaboration between academic research organizations in the United States and Europe. Two meetings, in Washington, DC, in January 2006 and in Dublin, Ireland, in June 2006, sponsored by the Academic Research Consortium and including representatives of the US Food and Drug Administration and all device manufacturers who were working with the Food and Drug Administration on drug-eluting stent clinical trial programs, were focused on consensus end point definitions for drug-eluting stent evaluations. The effort was pursued with the objective to establish consistency among end point definitions and provide consensus recommendations. On the basis of considerations from historical legacy to key pathophysiological mechanisms and relevance to clinical interpretability, criteria for assessment of death, myocardial infarction, repeat revascularization, and stent thrombosis were developed. The broadly based consensus end point definitions in this document may be usefully applied or recognized for regulatory and clinical trial purposes. Conclusion - Although consensus criteria will inevitably include certain arbitrary features, consensus criteria for clinical end points provide consistency across studies that can facilitate the evaluation of safety and effectiveness of these devices. C1 Harvard Univ, Sch Med, Harvard Clin Res Inst, Boston, MA 02215 USA. Univ Hosp Bern, CH-3010 Bern, Switzerland. Columbia Univ, Cardiovasc Res Fdn, New York, NY USA. US FDA, Rockville, MD 20857 USA. Cardialysis, Rotterdam, Netherlands. CHU Bichat, Paris, France. Hosp Virga Jesse, Hasselt, Belgium. Univ Hosp Cork, Cork, Ireland. CHU Caen, Normandy, France. Duke Univ, Duke Clin Res Inst, Durham, NC USA. Erasmus Univ, Thoraxctr, Med Ctr, NL-3000 DR Rotterdam, Netherlands. RP Cutlip, DE (reprint author), Harvard Univ, Sch Med, Harvard Clin Res Inst, 930 Commonwealth Ave, Boston, MA 02215 USA. EM dcutlip@bidmc.harvard.edu NR 44 TC 2563 Z9 2685 U1 31 U2 131 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD MAY 1 PY 2007 VL 115 IS 17 BP 2344 EP 2351 DI 10.1161/CIRCULATIONAHA.106.685313 PG 8 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 162XK UT WOS:000246122600014 PM 17470709 ER PT J AU Hassantoufighi, A Oglesbee, M Richter, BWM Prince, GA Hemming, V Niewiesk, S Eichelberger, MC AF Hassantoufighi, A. Oglesbee, M. Richter, B. W. M. Prince, G. A. Hemming, V. Niewiesk, S. Eichelberger, M. C. TI Respiratory syncytial virus replication is prolonged by a concomitant allergic response SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE fungus; virus; allergy; lung; IFN-gamma ID INDUCED AIRWAY HYPERRESPONSIVENESS; COTTON RAT; HYPERSENSITIVITY PNEUMONITIS; CYTOKINE PRODUCTION; INTERFERON-GAMMA; INFECTION; MICE; PATHOGENESIS; INFLAMMATION; CHILDREN AB Epidemiological studies show an association between early exposure to respiratory syncytial virus (RSV) and the development or exacerbation of asthma. This idea is supported by studies in mice that demonstrate worsened airway hyper-reactivity (AHR) when RSV-infected animals are exposed to allergen. The effect of allergen on RSV disease, however, has not been reported. Cotton rats (Sigmodon hispidus) that have been used as a model to study RSV pathogenesis were sensitized to extracts of Aspergillus fumigatus (Af), a common household mould. The allergic response to Af included eosinophilia, formation of granulomas and induction of Th2 type cytokines. RSV infection prior to allergen challenge resulted in exacerbation of the inflammatory response as well as increased airway responsiveness to methacholine. The exacerbated response was indeed dependent on virus replication. Virus replication in turn was influenced by the allergic response, with persistence in the noses for 2 days longer in animals challenged with allergen. This diminished clearance corresponded to decreased induction of mRNA for IFN-gamma, a Th1-type cytokine that is characteristic of viral infection. Treatment of RSV-infected Af-challenged animals with recombinant IFN-gamma reduced the allergic inflammatory response as well as the relative levels of Th1 and Th2 cytokine mRNA. However, this treatment did not reduce airway reactivity, showing that these pathologic and physiologic measures of exacerbated disease are independent. We speculate that the reciprocal effect of the allergic response on viral immunity may benefit the host by limiting exacerbation of physiologic responses that are IFN-gamma-dependent. C1 Virion Syst Inc, Rockville, MD USA. Ohio State Univ, Dept Vet Biosci, Columbus, OH USA. RP Eichelberger, MC (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29B Room 1 N N-15,8800 Rockville Pike, Rockville, MD 20852 USA. EM Maryna.Eichelberger@fda.hhs.gov FU PHS HHS [R25 G063993-02] NR 34 TC 14 Z9 15 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD MAY PY 2007 VL 148 IS 2 BP 218 EP 229 DI 10.1111/j.1365-2249.2007.03341.x PG 12 WC Immunology SC Immunology GA 155UL UT WOS:000245603800004 PM 17335559 ER PT J AU Tsai, CA Chen, JJ AF Tsai, Chen-An Chen, James J. TI Kernel estimation for adjusted p-values in multiple testing SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE family-wise error rate (FWER); kernel density estimation; maximal test-statistic; minimal p-values; permutation test AB Multiple testing procedures are frequently applied to biomedical and genomic research, for instance, identification of differentially expressed genes in microarray experiments. Resampling methods are commonly used to compute adjusted p-values in multiple hypothesis testing problems. Importantly, the resampling-based multiple testing procedures are sensitive to the number of permutations, especially for the MinP adjustment procedure. The single-step MinP adjusted p-values are derived from the distribution of the minimum of the p-values. Because of computational complexity, the adjusted p-values are often computed using the distribution of the maximum of the test statistics (MaxT). This paper proposes an approach based on the kernel density estimation (KDE) technique to reduce the number of permutations for implementing the single-step MinP adjustment. Simulation studies are conducted to demonstrate that the KDE method is more powerful than the MinP adjustment method under independent and correlated models. The three resampling-based single-step adjustment procedures, MaxT, MinP, and KDE, are applied to two published microarray data sets, the colon tumor data set consisting of 40 tumor and 22 normal colon tissue samples on 2000 human genes (endpoints) and the leukemia data set consisting of 27 acute lymphoblastic leukemia and 11 acute myeloid leukemia samples on 3051 genes. The MaxT adjusted p-values are very robust to the number of permutations. The MaxT adjusted p-values are stable with 10,000 permutations, while the MinP adjusted p-values are step functions. As the number of permutations increases, the number of ties decrease. The adjusted p-values are stable with 500,000 permutations. For the KDE method, the adjusted p-values are stable at 50,000 permutations. At 1000,000 permutations, the three procedures have similar adjusted p-values. (c) Published by Elsevier B.V. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Acad Sinica, Inst Stat Sci, Taipei 11529, Taiwan. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov OI Tsai, Chen-An/0000-0002-7490-4331 NR 10 TC 1 Z9 1 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD MAY 1 PY 2007 VL 51 IS 8 BP 3885 EP 3897 DI 10.1016/j.csda.2006.03.007 PG 13 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 162ZQ UT WOS:000246128500020 ER PT J AU Aarestrup, FM Hendriksen, RS Lockett, J Gay, K Teates, K McDermott, PF White, DG Hasman, H Sorensen, G Bangtrakulnonth, A Pornreongwong, S Pulsrikarn, C Angulo, FJ Gerner-Smidt, P AF Aarestrup, Frank M. Hendriksen, Rene S. Lockett, Jana Gay, Katie Teates, Kathryn McDermott, Patrick F. White, David G. Hasman, Henrik Sorensen, Gitte Bangtrakulnonth, Aroon Pornreongwong, Srirat Pulsrikarn, Chaiwat Angulo, Frederick J. Gerner-Smidt, Peter TI International spread of multidrug-resistant Salmonella Schwarzengrund in food products SO EMERGING INFECTIOUS DISEASES LA English DT Article ID ENTERICA SEROTYPE CHOLERAESUIS; UNITED-STATES; ANTIMICROBIAL RESISTANCE; FLUOROQUINOLONE RESISTANCE; QUINOLONE RESISTANCE; TYPHIMURIUM; HUMANS; INFECTION; OUTBREAK; ENGLAND AB We compared 581 Salmonella enterica serotype Schwarzengrund isolates from persons, food, and food animals in Denmark, Thailand, and the United States by antimicrobial drug susceptibility and pulsed-field gel electrophoresis (PFGE) typing. Resistance, including resistance to nalidixic acid, was frequent among isolates from persons and chickens in Thailand, persons in the United States, and food imported from Thailand to Denmark and the United States. A total of 183 PFGE patterns were observed, and 136 (23.4%) isolates had the 3 most common patterns. Seven of 14 isolates from persons in Denmark had patterns found in persons and chicken meat in Thailand; 22 of 390 human isolates from the United States had patterns found in Denmark and Thailand. This study suggests spread of multidrug-resistant S. Schwarzengrund from chickens to persons in Thailand, and from imported Thai food products to persons in Denmark and the United States. C1 Natl Food Inst, Copenhagen, Denmark. Ctr Dis Control & Prevent, Atlanta, GA USA. Atlanta Res & Educ Fdn, Atlanta, GA USA. US FDA, Laurel, MD USA. Minist Publ Hlth, Bangkok, Thailand. State Serum Inst, Copenhagen, Denmark. RP Aarestrup, FM (reprint author), Tech Univ Denmark, Natl Food Inst, Bulowsvej 27, DK-1790 Copenhagen V, Denmark. EM faa@food.dtu.dk NR 38 TC 67 Z9 74 U1 1 U2 5 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAY PY 2007 VL 13 IS 5 BP 726 EP 731 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 164DD UT WOS:000246212400008 PM 17553251 ER PT J AU Bough, KJ Paquet, M Pare, JF Hassel, B Smith, Y Hall, RA Dingledine, R AF Bough, Kristopher J. Paquet, Maryse Pare, Jean-Francois Hassel, Bjornar Smith, Yoland Hall, Randy A. Dingledine, Raymond TI Evidence against enhanced glutamate transport in the anticonvulsant mechanism of the ketogenic diet SO EPILEPSY RESEARCH LA English DT Article DE ketogenic diet; glutamate; GLT-1; GLAST; EAAC1; epilepsy ID AMINO-ACID-METABOLISM; DENTATE GYRUS; RAT; EXPRESSION; SEIZURES; EPILEPSY; BRAIN; MODEL AB Excessive glutamatergic neurotransmission is considered an underlying factor of epilepsy. Energy-dependent glutamate transporters clear extracellular glutamate to limit neuronal excitability. Evidence suggests that reduced expression and/or activity of glutamate transporters contribute to hyperexcitability and progressive seizure activity in rats. By comparison, treatment with the anticonvulsant ketogenic diet (KD) results in increased mRNA expression of the neuronal glutamate transporter EAAC1, elevated energy reserves, and an increased resistance to seizures in rats. The goal of the current study was to determine whether the expression and/or re-uptake activity of glutamate transporters were elevated in hippocampal tissue of rats after KD treatment. Rats were fed either a ketogenic- or control diet for 4-5 weeks. Western blot analysis showed that protein levels of EAAC1, GLT-1 and GLAST glutamate transporters were not changed in hippocampus, cerebral cortex, or cerebellum after KID. Electron microscopic evidence indicated that the KD did not affect hippocampal EAAC1 distribution. In addition, the re-uptake activity of H-3-glutamate into hippocampal proteoliposomes was similar in both KID and control tissue extracts. These multiple studies suggest that the anticonvulsant nature of the KID does not stem from enhanced glutamate re-uptake. (C) 2007 Elsevier B.V. All rights reserved. C1 Emory Univ, Dept Pharmacol, Atlanta, GA 30322 USA. Emory Univ, Yerkes Natl Reg Primate Res Ctr, Atlanta, GA 30322 USA. Robarts Res Inst, London, ON N6A 5C1, Canada. Norwegian Def Res Estab, N-2007 Kjeller, Norway. RP Bough, KJ (reprint author), US FDA, MPN 1,Room 1345,7520 Standish Pl, Rockville, MD 20855 USA. EM kbough96@yahoo.com RI dingledine, Ray/F-5173-2011; OI Hall, Randy/0000-0002-8318-8728 NR 18 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0920-1211 J9 EPILEPSY RES JI Epilepsy Res. PD MAY PY 2007 VL 74 IS 2-3 BP 232 EP 236 DI 10.1016/j.eplepsyres.2007.03.002 PG 5 WC Clinical Neurology SC Neurosciences & Neurology GA 172WX UT WOS:000246836300021 PM 17416486 ER PT J AU Alayash, AI D'Agnillo, F Buehler, PW AF Alayash, Abdu I. D'Agnillo, Felice Buehler, Paul W. TI First-generation blood substitutes: what have we learned? Biochemical and physiological perspectives SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE blood substitutes; free radicals; hemoglobin; nitric oxide; vascular effects ID CROSS-LINKED HEMOGLOBIN; CELL-FREE HEMOGLOBIN; SUPEROXIDE-DISMUTASE CATALASE; ENDOTHELIAL-CELLS; HEMORRHAGIC-SHOCK; OXIDATIVE-STRESS; PROTEIN EXPRESSION; HYDROGEN-PEROXIDE; OXYGEN CARRIER; IN-VITRO AB Chemically modified or recombinant hemoglobin (Hb)-based oxygen carriers (HBOCs) have been developed as oxygen therapeutics or 'blood substitutes' for use in a variety of clinical settings. Oxidative and nitrosative reactions of acellular Hb can limit the effectiveness and compromise the safety of HBOCs. The reactions between Hb and biologically relevant redox active molecules may also perturb redox sensitive signaling pathways. In recent years, systematic in vitro and in vivo structural and functional evaluation of several HBOCs has been carried out and, in some cases, delineated the 'structural' origin of their toxicity. This enables potential protective strategies against Hb-mediated side reactions to be rationally suggested. Here the authors provide an overview of their research experiences, novel insights into the molecular basis of toxicities of these products and some lessons learned. C1 US FDA, CBER, Lab Biochem & vasc Biol, Div Hematol, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, CBER, Lab Biochem & vasc Biol, Div Hematol, NIH Campus,8800 Rockville Pike,Bldg 29,Room 112, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov NR 66 TC 30 Z9 30 U1 2 U2 8 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD MAY PY 2007 VL 7 IS 5 BP 665 EP 675 DI 10.1517/14712598.7.5.665 PG 11 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 163KW UT WOS:000246159600010 PM 17477804 ER PT J AU von Eschenbach, AC AF von Eschenbach, Andrew C. TI Eliminating error-prone notations in medical communications SO EXPERT OPINION ON DRUG SAFETY LA English DT Editorial Material DE abbreviation; dose designation; medical notation; medication error; symbol AB Three decades advocating the elimination of ambiguous medical notations, one of the most common, but preventable causes of medication errors, came into sharp focus in 2006 when the FDA and the Institute for Safe Medication Practices launched a comprehensive educational campaign against medical mistakes rooted in unclear abbreviations, symbols and dose designations. Acting out of a joint effort to promote safe healthcare practices, FDA and the Institute for Safe Medication Practices determined that eliminating the use of potentially confusing notations in all forms of medical communication is one way to increase awareness about this important issue, and is one area in which education could help save lives. Still, the frequency of preventable medication-related injuries represents and remains a very serious cause for concern. C1 US FDA, Rockville, MD 20857 USA. RP von Eschenbach, AC (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 2 Z9 2 U1 0 U2 1 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1474-0338 J9 EXPERT OPIN DRUG SAF JI Expert Opin. Drug Saf. PD MAY PY 2007 VL 6 IS 3 BP 233 EP 234 DI 10.1517/14740338.6.3.233 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 166NQ UT WOS:000246386100002 PM 17480172 ER PT J AU Schnackenberg, LK AF Schnackenberg, Laura K. TI Global metabolic profiling and its role in systems biology to advance personalized medicine in the 21st Century SO EXPERT REVIEW OF MOLECULAR DIAGNOSTICS LA English DT Review DE drug toxicity; global metabolic profiling; metabolomics; metabonomics; personalized medicine; systems biology ID MAGNETIC-RESONANCE-SPECTROSCOPY; SPINNING H-1-NMR SPECTROSCOPY; PERFORMANCE LIQUID-CHROMATOGRAPHY; MULTIVARIATE STATISTICAL-ANALYSIS; PATTERN-RECOGNITION ANALYSIS; NMR-BASED METABONOMICS; TOF MASS-SPECTROMETRY; FATTY-ACID SYNTHESIS; DRUG DISCOVERY; INBORN-ERRORS AB Systems biology attempts to elucidate the complex interaction between genes, proteins and metabolites to provide a mechanistic understanding of cellular function and how this function is affected by disease processes, drug toxicity or drug efficacy effects. Global metabolic profiling is an important component of systems biology that can be applied in both preclinical and clinical settings for drug discovery and development, and to study disease mechanisms. The metabolic profile encodes the phenotype, which is composed of the genotype and environmental factors. The phenotypic profile can be used to make decisions about the best course of treatment for an individual patient. Understanding the combined effects of genetics and environment through a systems biology framework will enable the advancement of personalized medicine. C1 US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Schnackenberg, LK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM laura.schnackenberg@fda.hhs.gov NR 141 TC 23 Z9 26 U1 0 U2 6 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1473-7159 J9 EXPERT REV MOL DIAGN JI Expert Rev. Mol. Diagn. PD MAY PY 2007 VL 7 IS 3 BP 247 EP 259 DI 10.1586/14737159.7.3.247 PG 13 WC Pathology SC Pathology GA 169SZ UT WOS:000246613300004 PM 17489732 ER PT J AU Doull, J Borzelleca, JF Becker, R Daston, G DeSesso, J Fan, A Fenner-Crisp, P Holsapple, M Holson, J Llewellyn, GC MacGregor, J Seed, J Walls, I Woo, YT Olin, S AF Doull, John Borzelleca, Joseph F. Becker, Richard Daston, George DeSesso, John Fan, Anna Fenner-Crisp, Penelope Holsapple, Michael Holson, Joseph Llewellyn, G. Craig MacGregor, James Seed, Jennifer Walls, Isabel Woo, Yin-tak Olin, Stephen TI Framework for use of toxicity screening tools in context-based decision-making SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Review DE toxicity testing; decision tree; structure-activity relationships; endocrine disrupter; carcinogenicity; immunotoxicity ID LYMPH-NODE ASSAY; FECAL-OCCULT-BLOOD; PREDICTIVE TOXICOLOGY CHALLENGE; TERM BIOASSAY SYSTEM; RAT-LIVER BIOASSAY; CHO-HGPRT SYSTEM; RISK-ASSESSMENT; RODENT CARCINOGENICITY; GENETIC TOXICITY; AVAILABLE DATA AB One of the principal applications of toxicology data is to inform risk assessments and support risk management decisions that are protective of human health. Ideally, a risk assessor would have available all of the relevant information on (a) the toxicity profile of the agent of interest; (b) its interactions with living systems; and (c) the known or projected exposure scenarios: to whom, how much, by which route(s), and how often. In practice, however, complete information is seldom available. Nonetheless, decisions still must be made. Screening-level assays and tools can provide support for many aspects of the risk assessment process, as long as the limitations of the tools are understood and to the extent that the added uncertainty the tools introduce into the process can be characterized and managed. Use of these tools for decision-making may be an end in itself for risk assessment and decision-making or a preliminary step to more extensive data collection and evaluation before assessments are undertaken or completed and risk management decisions made. This paper describes a framework for the application of screening tools for human health decision-making, although with some modest modification, it could be made applicable to environmental settings as well. The framework consists of problem formulation, development of a screening strategy based on an assessment of critical data needs, and a data analysis phase that employs weight-of-evidence criteria and uncertainty analyses, and leads to context-based decisions. Criteria for determining the appropriate screening tool(s) have been identified. The choice and use of the tool(s) will depend on the question and the level of uncertainty that may be appropriate for the context in which the decision is being made. The framework is iterative, in that users may refine the question(s) as they proceed. Several case studies illustrate how the framework may be used effectively to address specific questions for any endpoint of toxicity. (c) 2006 Elsevier Ltd. All rights reserved. C1 ILSI Res Fdn, Risk Sci Inst, Washington, DC 20005 USA. Univ Kansas, Lawrence, KS 66045 USA. Virginia Commonwealth Univ, Richmond, VA 23284 USA. Procter & Gamble Co, Cincinnati, OH 45202 USA. US FDA, Rockville, MD 20857 USA. RP Olin, S (reprint author), ILSI Res Fdn, Risk Sci Inst, 1 Thomas Circle NW,Suite 900, Washington, DC 20005 USA. EM solin@ilsi.org OI Walls, Isabel/0000-0002-9643-8845 NR 192 TC 11 Z9 11 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD MAY PY 2007 VL 45 IS 5 BP 759 EP 796 DI 10.1016/j.fct.2006.10.025 PG 38 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 164DR UT WOS:000246213800009 PM 17215066 ER PT J AU Gammell, PM Maruvada, S Harris, GR AF Gammell, Paul M. Maruvada, Subha Harris, Gerald R. TI An ultrasonic time-delay spectrometry system employing digital processing SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID HYDROPHONE PROBES; 100 MHZ; CALIBRATION; AMPLITUDE AB Time-delay spectrometry (TDS) is a swept-frequency technique that has proven useful in several ultrasonic applications. Commercial TDS systems are available, but only in the audio frequency range. Several ultrasonic research TDS systems have been constructed, and they have been used effectively for substitution calibration of hydrophones and for measurement of attenuation and sound velocity in materials. Unfortunately these systems depend on features of commercial equipment no longer manufactured, so a new system has been designed using modern equipment and straightforward signal processing. This system requires a frequency source with a reasonably linear sweep of frequency versus time, audio frequency filters, a standard double-balanced mixer, a power splitter, a waveform digitizer capable of handling audio frequency signals, and a personal computer. An optional implementation that shifts the signal to a lower frequency for more convenient digitization and easier velocity measurements additionally requires an audio frequency oscillator and an audio-range analog multiplier. The processing steps are performed with standard signal processing software. To demonstrate the operation of the system, substitution calibration measurements of hydrophones as well as attenuation measurements on a tissue mimicking material were obtained and compared to a custom TDS system previously described by the authors. The data from these two TDS systems agree to within +/- 0.5 dB in the 1-10 MHz frequency range used. Higher frequency source transducers could be used to extend this range. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Gammell, PM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM pgammell@ieee.org NR 19 TC 14 Z9 14 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD MAY PY 2007 VL 54 IS 5 BP 1036 EP 1044 DI 10.1109/TUFFC.2007.349 PG 9 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 163VY UT WOS:000246192500016 PM 17523568 ER PT J AU Verma, A Burns, DL AF Verma, Anita Burns, Drusilla L. TI Requirements for assembly of PtlH with the pertussis toxin transporter apparatus of Bordetella pertussis SO INFECTION AND IMMUNITY LA English DT Article ID ISLET-ACTIVATING PROTEIN; NUCLEOTIDE-BINDING SITE; IV SECRETION; ADENYLATE-CYCLASE; SUBCELLULAR-LOCALIZATION; ENVELOPE PROTEINS; MEMBRANE-PROTEIN; GENE; SYSTEM; VIRB11 AB PtlH is an essential component of the Ptl system, the type IV transporter responsible for secretion of pertussis toxin (PT) across the outer membrane of Bordetella pertussis. The nine Ptl proteins are believed to interact to form a membrane-spanning apparatus through which the toxin is secreted. In this study, we monitored the subcellular localization of PtlH in strains of B. pertussis lacking PT, lacking other Ptl proteins, or from which ATP has been depleted in order to gain insight into the requirements for assembly of PtlH with the remainder of the Ptl transporter complex that is thought to be tightly embedded in the membrane. We found that PtlH is exclusively localized to the inner membrane fraction of the cell in a wild-type strain of B. pertussis. In contrast, PtlH localized to both the cytoplasmic and inner membrane fractions of a mutant strain of B. pertussis that does not produce PT. In comparison to how it localized in wild-type strains of B. pertussis, PtlH exhibited aberrant localization in strains lacking PtlD, PtlE, PtlF, and PtlG. We also found that localization of PtlH was perturbed in B. pertussis strains that were treated with carbonyl cyanide m-chlorophenylhydrazone and sodium arsenate, which are capable of depleting cellular ATP levels, and in strains of B. pertussis that produce an altered form of PtlH that lacks ATPase activity. When taken together, these results indicate that tight association of PtlH with the membrane, likely through interactions with components of the transporter-PT complex, requires the toxin substrate, a specific subset of the Ptl proteins, and ATP. Based on these data, a model for the assembly of the Ptl transporter-PT complex is presented. C1 FDA, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP Burns, DL (reprint author), FDA, CBER, HFM 434, Bldg 29,Room 130,8800 Rockville Pike, Bethesda, MD 20892 USA. EM drusilla.burns@fda.hhs.gov NR 42 TC 13 Z9 14 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 MAY PY 2007 VL 75 IS 5 BP 2297 EP 2306 DI 10.1128/IAI.00008-07 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 165YY UT WOS:000246345000025 PM 17339350 ER PT J AU Bibb, LA Kunkle, CA Schmitt, MP AF Bibb, Lori A. Kunkle, Carey A. Schmitt, Michael P. TI The ChrA-ChrS and HrrA-HrrS signal transduction systems are required for activation of the hmuO promoter and repression of the hemA promoter in Corynebacterium diphtheriae SO INFECTION AND IMMUNITY LA English DT Article ID IRON TRANSPORT-SYSTEM; FUNCTION SIGMA-FACTOR; ESCHERICHIA-COLI; RESPONSE REGULATOR; BORDETELLA-AVIUM; GENE-EXPRESSION; 2-COMPONENT SYSTEMS; DTXR REGULON; CROSS-TALK; IDENTIFICATION AB Transcription of the Corynebacterium diphtheriae hmuO gene, which encodes a heme oxygenase involved in heme iron utilization, is activated in a heme- or hemoglobin-dependent manner in part by the two-component system ChrA-ChrS. Mutation of either the chrA or the chrS gene resulted in a marked reduction of hemoglobin-dependent activation at the hmuO promoter in C. diphtheriae; however, it was observed that significant levels of hemoglobin-dependent expression were maintained in the mutants, suggesting that an additional activator is involved in regulation. A BLAST search of the C. diphtheriae genome sequence revealed a second two-component system, encoded by DIP2268 and DIP2267, that shares similarity with ChrS and ChrA, respectively; we have designated these genes hrrS (DIP2268) and hrrA (DIP2267). Analysis of hmuO promoter expression demonstrated that hemoglobin-dependent activity was fully abolished in strains from which both the chrA-chrS and the hrrA-hrrS two-component systems were deleted. Similarly, deletion of the sensor kinase genes chrS and hrrS or the genes encoding both of the response regulators chrA and hrrA also eliminated hemoglobin-dependent activation at the hmuO promoter. We also show that the regulators ChrA-ChrS and HrrA-HrrS are involved in the hemoglobin-dependent repression of the promoter upstream of hemA, which encodes a heme biosynthesis enzyme. Evidence for cross talk between the ChrA-ChrS and HrrA-HrrS systems is presented. In conclusion, these findings demonstrate that the ChrA-ChrS and HrrA-HrrS regulatory systems are critical for full hemoglobin-dependent activation at the hmuO promoter and also suggest that these two-component systems are involved in the complex mechanism of the regulation of heme homeostasis in C. diphtheriae. C1 DBPAP, CBER, FDA, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), DBPAP, CBER, FDA, Lab Resp & Special Pathogens, Bldg 29,Room 108,8800 Rockville Pike, Bethesda, MD 20892 USA. EM michael.schmitt@fda.hhs.gov NR 61 TC 37 Z9 39 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAY PY 2007 VL 75 IS 5 BP 2421 EP 2431 DI 10.1128/IAI.01821-06 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 165YY UT WOS:000246345000040 PM 17353293 ER PT J AU Marks, HS AF Marks, Heidi S. TI Rapid gas chromatography/mass spectrometry determination and confirmation of patulin in apple juice SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PHASE EXTRACTION METHOD AB A gas chromatography/mass spectrometry (GC/MS) method was developed for the quantitative determination and confirmation of patulin extracted from apple juice. Juice is alkalized and extracted with ethyl acetate-hexane, a portion concentrated under NZ then resolubilized in acetonitrile for simple derivatization with bis(trimethylsilyl)trifluoracetamide. Patulin was determined by GUMS using an electron-impact source and selected ion monitoring of characteristic ions. Spike levels of 20-100 mu g/L gave an average recovery of 86%, and 6 ions of sample and standard spectra matched within 10% absolute for confirmation. The limits of quantitation and detection were 10 and 3 mu g/L, respectively. C1 US FDA, Pacific Reg Lab, Bothell, WA 98021 USA. RP Marks, HS (reprint author), US FDA, Pacific Reg Lab, Bothell, WA 98021 USA. EM heidi.marks@fda.hhs.gov NR 7 TC 17 Z9 21 U1 2 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2007 VL 90 IS 3 BP 879 EP 883 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 174HK UT WOS:000246932600032 PM 17580643 ER PT J AU Slikker, W Paule, MG Wright, LKM Patterson, TA Wang, C AF Slikker, William, Jr. Paule, Merle G. Wright, Linnzi K. M. Patterson, Tucker A. Wang, Cheng TI Systems biology approaches for toxicology SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Review DE development; NMDA receptor antagonist; anesthetic agents; neurodegeneration; DNA repair; gene expression; ArrayTrack ID D-ASPARTATE RECEPTOR; FACTOR-KAPPA-B; INDUCED CORTICAL APOPTOSIS; NMDA RECEPTOR; UP-REGULATION; MOLECULAR-CLONING; RAT HIPPOCAMPUS; MESSENGER-RNA; BASAL GANGLIA; GLUTAMATE NEUROTOXICITY AB Systems biology/toxicology involves the iterative and integrative study of perturbations by chemicals and other stressors of gene and protein expression that are linked firmly to toxicological outcome. In this review, the value of systems biology to enhance the understanding of complex biological processes such as neurodegeneration in the developing brain is explored. Exposure of the developing mammal to NMDA (N-methyl-D-aspartate) receptor antagonists perturbs the endogenous NMDA receptor system and results in enhanced neuronal cell death. It is proposed that continuous blockade of NMDA receptors in the developing brain by NMDA antagonists such as ketamine (a dissociative anesthetic) causes a compensatory up-regulation of NMDA receptors, which makes the neurons bearing these receptors subsequently more vulnerable (e.g. after ketamine washout), to the excitotoxic effects of endogenous glutamate: the up-regulation of NMDA receptors allows for the accumulation of toxic levels of intracellular Ca2+ under normal physiological conditions. Systems biology, as applied to toxicology, provides a framework in which information can be arranged in the form of a biological model. In our ketamine model, for example, blockade of NMDA receptor up-regulation by the co-administration of antisense oligonucleotides that specifically target NMDA receptor NR1 subunit mRNA, dramatically diminishes ketamine-induced cell death. Preliminary gene expression data support the role of apoptosis as a mode of action of ketamine-induced neurotoxicity. In addition, ketamine-induced cell death is also prevented by the inhibition of NF-kappa B translocation into the nucleus. This process is known to respond to changes in the redox state of the cytoplasm and has been shown to respond to NMDA-induced cellular stress. Although comprehensive gene expression/proteomic studies and mathematical modeling remain to be carried out, biological models have been established in an iterative manner to allow for the confirmation of biological pathways underlying NMDA antagonist-induced cell death in the developing nonhuman primate and rodent. Published in 2007 John Wiley & Sons, Ltd. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM william.slikker@fda.hhs.gov NR 86 TC 38 Z9 42 U1 1 U2 7 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD MAY-JUN PY 2007 VL 27 IS 3 BP 201 EP 217 DI 10.1002/jat.1207 PG 17 WC Toxicology SC Toxicology GA 160SN UT WOS:000245962700001 PM 17265419 ER PT J AU Kunkle, CA Schmitt, MP AF Kunkle, Carey A. Schmitt, Michael P. TI Comparative analysis of hmuO function and expression in Corynebacterium species SO JOURNAL OF BACTERIOLOGY LA English DT Article ID HEME-DEGRADING ENZYMES; SIGNAL-TRANSDUCTION SYSTEM; DIPHTHERIA-TOXIN; STAPHYLOCOCCUS-AUREUS; IRON ACQUISITION; GENE; DTXR; SIDEROPHORE; IDENTIFICATION; OXYGENASE AB We have constructed defined deletions in the hmuO gene from Corynebacterium diphtheriae and Corynebacterium ulcerans and show that the C. ulcerans hmuO mutation results in a significant reduction in hemoglobin-iron utilization, whereas in C. diphtheriae strains, deletion of hmuO caused no or only partial reduction in the utilization of heme as an iron source. We also show that expression from the C. ulcerans hmuO promoter exhibits minimal regulation by iron and heme whereas transcription from the C. diphtheriae hmuO promoter shows both significant iron repression and heme-dependent activation. These findings indicate that variability in HmuO function and expression exists among Corynebacterium species. C1 US FDA, DBPAP, CBER, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), US FDA, DBPAP, CBER, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. EM michael.schmitt@fda.hhs.gov NR 33 TC 13 Z9 14 U1 1 U2 5 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 MAY PY 2007 VL 189 IS 9 BP 3650 EP 3654 DI 10.1128/JB.00056-07 PG 5 WC Microbiology SC Microbiology GA 161PS UT WOS:000246028400035 PM 17322319 ER PT J AU Chaurasia, CS Muller, M Bashaw, ED Benfeldt, E Bolinder, J Bullock, R Bungay, PM DeLange, ECM Derendorf, H Elmquist, WF Hammarlund-Udenaes, M Joukhadar, C Kellogg, DL Lunte, CE Nordstrom, CH Rollema, H Sawchuk, RJ Cheung, BWY Shah, VP Stahle, L Ungerstedt, U Welty, DF Yeo, H AF Chaurasia, Chandra S. Muller, Markus Bashaw, Edward D. Benfeldt, Eva Bolinder, Jan Bullock, Ross Bungay, Peter M. DeLange, Elizabeth C. M. Derendorf, Hartmut Elmquist, William F. Hammarlund-Udenaes, Margareta Joukhadar, Christian Kellogg, Dean L., Jr. Lunte, Craig E. Nordstrom, Carl Henrik Rollema, Hans Sawchuk, Ronald J. Cheung, Belinda W. Y. Shah, Vinod P. Stahle, Lars Ungerstedt, Urban Welty, Devin F. Yeo, Helen TI AAPS-FDA workshop white paper: Microdialysis principles, application, and regulatory perspectives SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE microdialysis; regulatory aspects; tissue pharmacokinetics ID IN-VIVO MICRODIALYSIS; BLOOD-BRAIN-BARRIER; ZERO-NET-FLUX; CEREBROSPINAL-FLUID; DIABETIC-PATIENTS; SKELETAL-MUSCLE; DRUG-DELIVERY; PHARMACOKINETICS; TRANSPORT; DOPAMINE C1 US FDA, Div Bioequivalence, Off Gener Drugs, Rockville, MD 20857 USA. Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria. US FDA, Div Clin Pharmacol 3, Off Clin Pharmacol, Silver Spring, MD USA. Univ Copenhagen, Dept Dermatol, Copenhagen NV, Denmark. Karolinska Univ, Huddinge Hosp, Dept Med, Stockholm, Sweden. Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA USA. NIH, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. LACDR, Leiden, Netherlands. Univ Florida, Dept Pharmaceut, Gainesville, FL USA. Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden. Med Univ Vienna, Dept Clin Pathol, Vienna, Austria. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Kansas, Dept Chem, Lawrence, KS 66045 USA. Univ Lund Hosp, Dept Neurosurg, S-22185 Lund, Sweden. Pfizer Global Res, Dept Neurosci, Groton, CT USA. Astra Zeneca, Sodertalje, Sweden. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. Allergan Pharmaceut Inc, Pharmacokinet & Drug Metab, Irvine, CA USA. Roche Palo Alto, Dept Drug Metab & Pharmokinet, Palo Alto, CA USA. RP Chaurasia, CS (reprint author), US FDA, Div Bioequivalence, Off Gener Drugs, Rockville, MD 20857 USA. EM chandra.chaurasia@fda.hhs.gov RI Derendorf, Hartmut/B-4628-2012 OI Derendorf, Hartmut/0000-0003-4016-1370 NR 58 TC 44 Z9 46 U1 2 U2 10 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 2007 VL 47 IS 5 BP 589 EP 603 DI 10.1177/0091270006299091 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 163IT UT WOS:000246154000005 PM 17442685 ER PT J AU Yourick, JJ Sasik, CT Bronaugh, RL AF Yourick, Jeffrey J. Sasik, Camille T. Bronaugh, Robert L. TI In vitro dermal absorption and metabolism of D&C red no. 17 in human and porcine skin SO JOURNAL OF COSMETIC SCIENCE LA English DT Article; Proceedings Paper CT 34th SCCM Congress CY JAN, 2005 CL Phoenix, AZ SP SCCM ID INVITRO PERCUTANEOUS-ABSORPTION AB D&C red no. 17 is approved for use in externally applied drug and cosmetic applications, in amounts consistent with good manufacturing practice. Concerns about the safety of the color additive (1-[4phenylazophenylazo]-2-napthol (PAN) is the primary color constituent) have been raised due to potential metabolic cleavage of PAN to yield 4-aminoazobenzene. C-14-PAN was applied in a commercially available suntan vehicle containing D&C red no. 17 to viable porcine and non-viable (cadaver) human skin in flow-through diffusion cells. At the end of 24 h, unabsorbed material was removed from the skin and some cells were allowed to continue for an additional 48 h. In human skin, 0.07% and 0.17% of the applied dose were absorbed into the receptor fluid after 24 and 72 h, respectively. At the end of 24 h, 12.5% of the applied dose remained in the skin, which did not decrease at 72 h. When PAN was applied to viable porcine skin for 24 h, 0.3% of the applied dose was absorbed and 12.7% remained in the skin. Additional studies to simulate short-term exposure were completed with PAN applied to the skin for only 15 min, and absorption was determined for 24 and 72 h. These studies in human cadaver skin found 0.02% and 0.08% of the applied dose in the receptor fluid after 24 and 72 h, respectively. Viable porcine skin studies with the 15-min application resulted in receptor fluid values of 0.1% of the applied dose after 24 h. Lipophilic receptor fluids composed of the non-ionic surfactant Volpo 20 at wt% concentrations of 1%, 3%, or 6% in water did not increase partitioning of PAN from the skin into the receptor fluid. No metabolism of PAN was found in viable porcine skin when examined by HPLC. In conclusion, skin absorption of PAN from a commercially available suntan product was low. C1 [Yourick, Jeffrey J.; Sasik, Camille T.; Bronaugh, Robert L.] US FDA, Off Cosmet & Colors, College Pk, MD 20740 USA. RP Yourick, JJ (reprint author), US FDA, Off Cosmet & Colors, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 9 TC 1 Z9 1 U1 0 U2 5 PU SOC COSMETIC CHEMISTS PI NEW YORK PA 120 WALL STREET, SUITE 2400, NEW YORK, NY 10005-4088 USA SN 1525-7886 J9 J COSMET SCI JI J. Cosmet. Sci. PD MAY-JUN PY 2007 VL 58 IS 3 BP 255 EP 266 PG 12 WC Chemistry, Applied; Dermatology SC Chemistry; Dermatology GA 250VD UT WOS:000252328500005 PM 17598027 ER PT J AU Perfield, JW Lock, AL Griinari, JM Saebo, A Delmonte, P Dwyer, DA Bauman, DE AF Perfield, J. W., II Lock, A. L. Griinari, J. M. Saebo, A. Delmonte, P. Dwyer, D. A. Bauman, D. E. TI Trans-9, cis-11 conjugated linoleic acid reduces milk fat synthesis in lactating dairy cows SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE conjugated linoleic acid; milk fat depression; lactation; cow ID DIETARY SUPPLEMENTATION; COMPOSITION RESPONSES; ABOMASAL INFUSIONS; SUNFLOWER OIL; FISH-OIL; CLA; ISOMERS; DELTA(9)-DESATURASE; PERSISTENCY; CONCENTRATE AB Under certain dietary situations, rumen biohydrogenation results in the production of unique fatty acids that inhibit milk fat synthesis. The first of these to be identified was trans-10, cis-12 conjugated linoleic acid (CLA), but others are postulated to contribute to diet-induced milk fat depression (MFD). Our objective was to examine the potential role of trans-9, cis-11 CLA in the regulation of milk fat. In a preliminary study, we used gas-liquid and high-performance liquid chromatography techniques to examine milk fat samples from a diet-induced MFD study and found that an increase in trans-9, cis-11 CLA corresponded to the decrease in milk fat yield. We investigated this further using a CLA enrichment of 9, 11 isomers to examine the biological effect of trans-9, cis-11 CLA on milk fat synthesis. Four rumen-fistulated Holstein cows were randomly assigned in a 4 x 4 Latin square experiment involving 5d treatment periods and abomasal infusion of 1) ethanol (control), 2) a 9, 11 CLA mix (containing 32% trans-9, cis-11, 29% cis-9, trans-11, and 17% trans-9, trans-11), 3) a trans-9, trans-11 CLA supplement, and 4) a trans-10, cis-12 CLA supplement (positive control). The trans-9, trans-11 CLA and trans-10, cis-12 CLA supplements were of high purity (> 90%), and all supplements were infused at a rate to provide 5 g/d of the CLA isomer of interest. Milk yield and dry matter intake did not differ among treatments. Compared with the control treatment, milk fat yield was reduced by 15% for the 9, 11 CLA mixture and by 27% for the trans-10, cis-12 CLA treatment. We also found that trans-9, trans-11 CLA had no effect on milk fat yield, and previous research has shown that milk fat yield is unaltered when cows are infused with cis-9, trans-11 CLA. When all treatments were considered, results suggested that trans-9, cis-11 was the CLA isomer in the 9, 11 CLA mix responsible for the reduction in milk fat synthesis, although the magnitude was less than that observed for trans-10, cis-12 CLA. Interestingly, trans-9, trans-11 CLA altered the milk fat desaturase index, further demonstrating that alterations in desaturase can occur independently of effects on milk fat synthesis. Overall, our investigations identified that an increase in milk fat content of trans-9, cis-11 CLA was associated with diet-induced MFD and provided evidence of a role for this isomer in MFD based on the 15% reduction in milk fat yield with abomasal infusion of a CLA enrichment that supplied 5 g/d of trans-9, cis-11 CLA. C1 Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. Univ Helsinki, Dept Anim Sci, Helsinki, Finland. Nat ASA, Hovdebygda, Norway. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Bauman, DE (reprint author), Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. EM deb6@cornell.edu NR 34 TC 91 Z9 97 U1 0 U2 15 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD MAY PY 2007 VL 90 IS 5 BP 2211 EP 2218 DI 10.3168/jds.2006-745 PG 8 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 156MC UT WOS:000245651700015 PM 17430919 ER PT J AU Khan, AT Graham, TC Ogden, L Ali, S Thompson, SSJ Shireen, KF Mahboob, M AF Khan, Abu T. Graham, Thomas C. Ogden, L. Ali, S. Thompson, Salwa Sherylee J. Shireen, Kaniz F. Mahboob, Mohd TI A two-generational reproductive toxicity study of zinc in rats SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART B-PESTICIDES FOOD CONTAMINANTS AND AGRICULTURAL WASTES LA English DT Article DE rats; zinc; reproduction; fertility; pup viability ID RANDOMIZED CONTROLLED-TRIAL; DIETARY ZINC; SUPPLEMENTATION; CHOLESTEROL; DEFICIENCY; PREGNANCY; INFANTS; MICE AB A two-generation reproductive toxicity study of zinc chloride (ZnCl2) was conducted in rats. F-o male and female rats were administered 0.00 (control), 7.50 (low), 15.00 (mid) and 30.00 (high) mg/kg/day of ZnCl2. Selected F-1 male and female rats were exposed to the same doses received by their parents (Fo). Exposure of Fo parental rats to ZnCl2 showed significant reduction in fertility, viability (days 0 and 4), and the body weight of F-1 pups from the high-dose group but caused no effects on litter size, weaning index, and sex ratio. Similarly, the continued exposure of F-1 parental rats to ZnCl2 also reduced fertility, liter size, viability (day 0), and the body weight of F-2 pups within the high-dose group but caused no effects on weaning index and sex ratio. Exposure of ZnCl2 to F-0 and F-1 parental males resulted in a significant reduction in their body weights, and the F-0 and F-1 parental females did not show any significant difference in their body weights compared to their control groups. However, the postpartum dam weights of both F-0 and F-1 female rats were significantly reduced compared to their controls. Exposure of ZnCl2 to F-0 and F-1 generation parental rats did not produce any significant change of their clinical signs as well as their clinical pathology parameters, except the alkaline phosphotase (ALK) level, which showed an upward trend in both sexes of both generations. Exposure of ZnCl2 to F-0 rats resulted in a reduction of brain, liver, kidney, spleen and seminal vesicles weights of males and in the spleen and uterus of females. Similarly, exposure of F, rats to ZnCl2 also resulted in reduction of brain, liver, kidney, adrenal, spleen, prostate and seminal vesicles weights of males and in spleen and uterus of females. ZnCl2 exposure resulted in grossly observed gastro-intestianla (GI) tract, lymphoreticular/hematopoietic, and reproductive tract lesions in parental rats in both generations. Reduced body fat was also recorded in F, parental rats. C1 Tuskegee Univ, Coll Vet Med Nursing & Allied Hlth, Tuskegee, AL 36088 USA. RP Khan, AT (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-265, College Pk, MD 20740 USA. EM abu.khan@fda.hhs.gov NR 37 TC 7 Z9 7 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0360-1234 J9 J ENVIRON SCI HEAL B JI J. Environ. Sci. Health Part B-Pestic. Contam. Agric. Wastes PD MAY PY 2007 VL 42 IS 4 BP 403 EP 415 DI 10.1080/03601230701312795 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA 173XN UT WOS:000246905900009 PM 17474020 ER PT J AU Mossoba, MM Al-Khaldi, SF Curtis, SK Battrell, CF Fry, FS AF Mossoba, M. M. Al-Khaldi, S. F. Curtis, S. K. Battrell, C. F. Fry, F. S. TI Application of a novel hydrophilic infrared-transparent membrane to the differentiation between microcolonies of Enterobacter sakazakii and Klebsiella pneumoniae SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POWDERED INFANT FORMULA; VIBRATIONAL SPECTROSCOPY; IDENTIFICATION; MICROORGANISMS; INFECTIONS; BACTERIA; MILK AB A proof-of-concept study is reported for the differentiation between microcolonies of Enterobacter sakazakii and Klebsiella pneumoniae by means of a novel sample preparation for infrared (IR) analysis. A disposable, IR-transparent, microporous (0.2-mu m pores), hydrophobic, polyethylene (PE) membrane (51 mu m thick) was plasma treated under an oxygen atmosphere and used to (i) filter (or print microarrays of) dilute aqueous foodborne bacterial suspensions and (ii) subsequently grow bacterial microcolonies when the treated, hydrophilic PE membrane was placed over brain heart infusion agar medium and incubated. Because this unique membrane is transparent to IR light, isolated microcolonies (200 mu m) of bacterial cells grown on this PE substrate for the first time could be directly fingerprinted by IR microspectroscopy in the transmission mode. Hence, time-consuming bacterial cell transfer from culture plates to an IR sample holder for subsequent measurement by IR spectroscopy was eliminated. Multivariate analysis of the observed IR spectra for microcolonies allowed the rapid differentiation between E. sakazakii and K. pneumoniae. C1 US FDA, Div Analyt Chem, College Pk, MD 20740 USA. US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Micronics Inc, Redmond, WA 98052 USA. RP Mossoba, MM (reprint author), US FDA, Div Analyt Chem, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov NR 17 TC 1 Z9 1 U1 1 U2 2 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 2007 VL 70 IS 5 BP 1241 EP 1245 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 164OT UT WOS:000246244100026 PM 17536686 ER PT J AU Samuel, MC Vugia, DJ Koehler, KM Marcus, R Deneen, V Damaske, B Shiferaw, B Hadler, J Henao, OL Angulo, FJ AF Samuel, Michael C. Vugia, Duc J. Koehler, Kathleen M. Marcus, Ruthanne Deneen, Valerie Damaske, Barbara Shiferaw, Beletshachew Hadler, James Henao, Olga L. Angulo, Frederick J. TI Consumption of risky foods among adults at high risk for severe foodborne diseases: Room for improved targeted prevention messages SO JOURNAL OF FOOD SAFETY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SALMONELLA-ENTERITIDIS; MULTISTATE SURVEY; UNITED-STATES; EPIDEMIOLOGY; LISTERIOSIS; INFECTIONS; PATHOGENS; ILLNESS AB Foodborne disease is of particular concern in populations at risk for severe consequences, including the elderly and persons with immune-compromising conditions. Using data from the Foodborne Diseases Active Surveillance Network (FoodNet) Population Survey, we examined the association of risky food consumption with gender, age, immune status, income and education. Gender age and immune status were associated with consumption of risky foods. More males than females ate at least one risky,food while persons aged >= 65 years were less likely than those 18-44 to eat risky foods. In the 18-44 group, those with immunosuppressive conditions were more likely to eat risky foods (P < 0. 001). In the >= 65 group, those taking immunosuppressive drugs were more likely than healthy persons to eat risky foods (P < 0.001). Our findings suggest that young adults with immune-compromising conditions and elderly persons who take immunosuppressive drugs report eating more risky foods than their healthy counterparts. C1 CA DHS STD Control Branch, Calif Emerging Infect Program, Richmond, CA 94804 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. Connecticut Emerging Infect Program, New Haven, CT USA. Minnesota Emerging Infect Program, St Paul, MN USA. New York Emerging Infect Program, Albany, NY USA. Oregon Dept Human Serv, Portland, OR USA. Atlanta Res & Educ Fdn, Atlanta, GA USA. RP Samuel, MC (reprint author), CA DHS STD Control Branch, Calif Emerging Infect Program, 850 Marina Bay Pkwy,Bldg P,2nd Floor, Richmond, CA 94804 USA. EM msamuel@dhs.ca.gov NR 24 TC 6 Z9 7 U1 2 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD MAY PY 2007 VL 27 IS 2 BP 219 EP 232 DI 10.1111/j.1745-4565.2007.00074.x PG 14 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 160ZP UT WOS:000245984400010 ER PT J AU Lando, AM Labiner-Wolfe, J AF Lando, Amy M. Labiner-Wolfe, Judith TI Helping consumers make more healthful food choices: Consumer views on modifying food labels and providing point-of-purchase nutrition information at quick-service restaurants SO JOURNAL OF NUTRITION EDUCATION AND BEHAVIOR LA English DT Article DE nutrition policy; food labeling; food industry; focus groups AB Objectives: To understand consumer (1) interest in nutrition information on food labels and quick-service restaurant menu boards and (2) reactions to modifying this information to help highlight calories and more healthful choices. Design: Eight consumer focus groups, using a guide and stimuli. Setting: Focus group discussions in 4 US cities. Participants: A total of 68 consumers, with 7 to 10 per focus group. Analysis: Authors prepared detailed summaries of discussions based on observation. Video recordings and transcripts were used to cross-check summaries. Data were systematically reviewed, synthesized, and analyzed. Phenomenon of Interest: Consumer views on alternative presentations of nutrition information on packaged food items and quick-service restaurant menu boards. Results: Participants (1) were interested in having nutrition information available, but would not use it at every eating occasion; (2) thought that food products typically consumed at 1 eating occasion should be labeled as a single serving; and (3) indicated that an icon on labels and menu boards that signaled more healthful options could be helpful. Conclusions and implications: Findings provide a basis for the development of more systematic studies to better understand whether alternative presentations of nutrition information would help consumers. C1 [Lando, Amy M.; Labiner-Wolfe, Judith] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Lando, AM (reprint author), 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM amy.lando@fda.hhs.gov NR 18 TC 47 Z9 49 U1 0 U2 18 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1499-4046 J9 J NUTR EDUC BEHAV JI J. Nutr. Educ. Behav. PD MAY-JUN PY 2007 VL 39 IS 3 BP 157 EP 163 DI 10.1016/j.jneb.2006.12.010 PG 7 WC Education, Scientific Disciplines; Nutrition & Dietetics SC Education & Educational Research; Nutrition & Dietetics GA 258JX UT WOS:000252865300009 PM 17493566 ER PT J AU Shah, RB Tawakkul, MA Khan, MA AF Shah, Rakh B. Tawakkul, Mobin A. Khan, Mansoor A. TI Process analytical technology: Chemometric analysis of Raman and near infra-red spectroscopic data for predicting physical properties of extended release matrix tablets SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE image analysis; compression; porosity; hardness; sensor technology ID HYDROCHLORIDE; HARDNESS AB The purpose of this work was to develop a correlation between pharmaceutical properties such as hardness, porosity, and content with prediction models employed using Raman and near infrared (NIR) spectroscopic methods. Metoprolol tartrate tablets were prepared by direct compression and wet granulation methods. NIR spectroscopy and chemical imaging, and Raman spectra were collected, and hardness, porosity, and dissolution were measured. The NIR PLS model showed a validated correlation coefficient of > 0.90 for the predicted versus measured porosity, hardness, and amount of drug with raw and second derivative NIR spectra. Raman spectra correlated porosity of the tablets using raw data for directly compressed tablets and wet granulated tablets (r(2) > 0.90). A very close root-mean square error of calibration (RMSEC) and root-mean square error of prediction (RMSEP) values were found in all the cases indicating validity of the calibration models. Raman spectroscopy was used for the first time to predict physical quality attribute such as porosity successfully. Chemical imaging utilizing NIR detector also demonstrated to show physical changes due to compression differences. In conclusion, sensor technologies can be potentially used to predict physical parameters of the matrix tablets. (c) 2007 Wiley-Liss, Inc. and the American Pharmacists Association. C1 US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Silver Spring, MD USA. RP Khan, MA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Silver Spring, MD USA. EM Mansoor.khan@fda.hhs.gov NR 24 TC 44 Z9 45 U1 1 U2 12 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD MAY PY 2007 VL 96 IS 5 BP 1356 EP 1365 DI 10.1002/jps.20931 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 163BF UT WOS:000246132800033 PM 17455359 ER PT J AU Carraway, J Witt, W AF Carraway, Jeff Witt, William TI IACUC complacency SO LAB ANIMAL LA English DT Editorial Material C1 Natl Ctr Toxicol Res, Div Vet Serv, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates Inc, Jefferson, AR 72079 USA. RP Carraway, J (reprint author), Natl Ctr Toxicol Res, Div Vet Serv, Jefferson, AR 72079 USA. NR 2 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD MAY PY 2007 VL 36 IS 5 BP 14 EP 14 DI 10.1038/laban0507-14a PG 1 WC Veterinary Sciences SC Veterinary Sciences GA 164IZ UT WOS:000246228400003 PM 17450163 ER PT J AU Wright, LKM Pearson, EC Hammond, TG Paule, MG AF Wright, L. K. M. Pearson, E. C. Hammond, T. G. Paule, M. G. TI Behavioral effects associated with chronic ketamine or remacemide exposure in rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE ketamine; N-methyl-D-aspartate (NMDA) receptors; operant behavior; sodium channels; remacemide ID NMDA RECEPTOR ANTAGONISTS; NONHUMAN-PRIMATES; NERVOUS-SYSTEM; NEUROTOXICITY; PERFORMANCE; DOPAMINE; RELEASE; SLICES; CELLS; SEX AB The effects of chronic exposure to ketamine or remacemide on the acquisition and performance of food-reinforced operant behaviors was assessed in female Sprague-Dawley rats. Ketamine is an anesthetic N-methyl-D-aspartate (NMDA) receptor antagonist, whereas remacemide is an active central nervous system compound with both NMDA receptor antagonist and sodium channel blocking properties. Learning, audio/visual discrimination and motivation were modeled using incremental repeated acquisition (IRA), audio/visual discrimination (AVD) and progressive ratio (PR) tasks, respectively. Ketamine (10 or 100 mg/kg/day), remacemide (100 or 150 mg/kg/day) or water was administered daily (7 days/ week) via orogastric gavage beginning on postnatal day (PND) 23 and continuing until PND 257. Monday through Friday behavioral assessments began on PND 27 and continued until PND 383. Chronic treatment with the high dose of ketamine decreased response rate in all tasks suggesting decreased motivation or motoric capabilities. Chronic treatment with ketamine or remacemide had no effect on the acquisition of IRA task performance at any dose tested. While chronic treatment with either high-dose ketamine or low-dose remacemide only delayed the acquisition of AVD task performance for a brief period midway through treatment, chronic treatment with high-dose remacemide delayed the acquisition of AVD task performance until late in treatment. The findings for ketamine are quite different from those of MK-801 (the prototypic NMDA receptor antagonist) in a previous rat study in which MK-801 severely disrupted the acquisition of both IRA and AVD task performances. These observations suggest important differences in the mechanism of action between ketamine and MK-801. For example, ketamine has a much lower binding affinity than MK-801 for the NMDA receptor, the dopamine transporter and the dopamine D2 receptor. In addition, the findings for remacemide observed in rats are in marked contrast with those seen in monkeys where chronic remacemide had profound disruptive effects on the acquisition of both IRA and AVD task performances and suggest important species differences. Published by Elsevier Inc. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. AstraZeneca, Safety Assessment, Loughborough LE11 5RH, Leics, England. RP Paule, MG (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM merle.paule@fda.hhs.gov NR 28 TC 4 Z9 4 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 MAY-JUN PY 2007 VL 29 IS 3 BP 348 EP 359 DI 10.1016/j.ntt.2006.12.004 PG 12 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 185YS UT WOS:000247746900004 PM 17291718 ER PT J AU Ferguson, SA Smith, ME Garey, JD Paule, MG AF Ferguson, S. A. Smith, M. E. Garey, J. D. Paule, M. G. TI Long-term locomotor activity assessments appear insensitive to acrylamide treatment in young adult rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the Neurobehavioral-Teratology-Society CY JUN 23-27, 2007 CL Pittsburg, PA SP Neurobehav Teratol Soc C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 1 TC 2 Z9 2 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2007 VL 29 IS 3 BP 404 EP 404 DI 10.1016/j.ntt.2007.03.032 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 185YS UT WOS:000247746900037 ER PT J AU Smith, ME Paule, MG Garey, JD Ferguson, SA AF Smith, M. E. Paule, M. G. Garey, J. D. Ferguson, S. A. TI Morris water maze and dry-land complex maze performance appear insensitive to acrylamide treatment in young adult rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the Neurobehavioral-Teratology-Society CY JUN 23-27, 2007 CL Pittsburg, PA SP Neurobehav Teratol Soc C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 1 TC 3 Z9 3 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2007 VL 29 IS 3 BP 404 EP 405 DI 10.1016/j.ntt.2007.03.033 PG 2 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 185YS UT WOS:000247746900038 ER PT J AU Garey, J Paule, MG AF Garey, J. Paule, M. G. TI Chronic low-dose acrylamide exposure reduces appetitive motivation in Fischer 344 rats SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the Neurobehavioral-Teratology-Society CY JUN 23-27, 2007 CL Pittsburg, PA SP Neurobehav Teratol Soc C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2007 VL 29 IS 3 BP 407 EP 407 DI 10.1016/j.ntt.2007.03.040 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 185YS UT WOS:000247746900045 ER PT J AU Paule, MG Garey, J AF Paule, M. G. Garey, J. TI Effects of chronic oral acrylamide exposure on incremental repeated acquisition (learning) performance in Fischer 344 rats through eight months of age SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Meeting Abstract CT 31st Annual Meeting of the Neurobehavioral-Teratology-Society CY JUN 23-27, 2007 CL Pittsburg, PA SP Neurobehav Teratol Soc C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2007 VL 29 IS 3 BP 407 EP 407 DI 10.1016/j.ntt.2007.03.041 PG 1 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 185YS UT WOS:000247746900046 ER PT J AU Doub, WH Adams, WP Spencer, JA Buhse, LF Nelson, MP Treado, PJ AF Doub, William H. Adams, Wallace P. Spencer, John A. Buhse, Lucinda F. Nelson, Matthew P. Treado, Patrick J. TI Raman chemical imaging for ingredient-specific particle size characterization of aqueous suspension nasal spray formulations: A progress report SO PHARMACEUTICAL RESEARCH LA English DT Article DE drug delivery; nasal; image analysis; spectroscopy; Raman ID COMPOSITES; MICROSCOPY; SURFACE; GLASS AB Purpose. This study was conducted to evaluate the feasibility of using Raman chemical imaging (i.e., Raman imaging microspectroscopy) to establish chemical identity, particle size and particle size distribution (PSD) for a representative corticosteroid in aqueous nasal spray suspension formulations. Materials and Methods. The Raman imaging PSD protocol was validated using polystyrene (PS) microsphere size standards (NIST-traceable). A Raman spectral library was developed for the active and inactive compounds in the formulation. Four nasal sprays formulated with beclomethasone dipropionate (BDP) ranging in size from 1.4 to 8.3 mu m were imaged by both Raman and brightfield techniques. The Raman images were then processed to calculate the PSD for each formulation. Results. Within each region examined, active pharmaceutical ingredient (API) particles are unambiguously identified and the total number of those particles, particle size and PSD of API free of excipients and PSD of API particles adhered to other excipients are reported. Conclusions. Good statistical agreement is obtained between the reported and measured sizes of the PS microspheres. BDP particles were clearly distinguishable from those of excipients. Raman chemical imaging (RCI) is able to differentiate between and identify the chemical makeup of multiple components in complex BDP sample and placebo mixtures. The Raman chemical imaging method (coupled Raman and optical imaging) shows promise as a method for characterizing particle size and shape of corticosteroid in aqueous nasal spray suspension formulations. However, rigorous validation of RCI for PSD analysis is incomplete and requires additional research effort. Some specific areas of concern are discussed. C1 CDER, OPS, Div Pharmaceut Anal Food & Drug Adm, St Louis, MO USA. US FDA, CDER, OPS, Off Gener Drugs, Rockville, MD 20857 USA. ChemImage Corp, Pittsburgh, PA 15208 USA. US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Doub, WH (reprint author), CDER, OPS, Div Pharmaceut Anal Food & Drug Adm, St Louis, MO USA. EM william.doub@fda.hhs.gov NR 19 TC 44 Z9 44 U1 2 U2 21 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD MAY PY 2007 VL 24 IS 5 BP 934 EP 945 DI 10.1007/s11095-006-9211-2 PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 162TL UT WOS:000246112300010 PM 17372686 ER PT J AU Chaurasia, CS Muller, M Bashaw, ED Benfeldt, E Bolinder, J Bullock, R Bungay, PM DeLange, ECM Derendorf, H Elmquist, WF Hammarlund-Udenaes, M Joukhadar, C Kellogg, DL Lunte, CE Nordstrom, CH Rollema, H Sawchuk, RJ Cheung, BWY Shah, VP Stahle, L Ungerstedt, U Welty, DF Yeo, H AF Chaurasia, Chandra S. Mueller, Markus Bashaw, Edward D. Benfeldt, Eva Bolinder, Jan Bullock, Ross Bungay, Peter M. DeLange, Elizabeth C. M. Derendorf, Hartmut Elmquist, William F. Hammarlund-Udenaes, Margareta Joukhadar, Christian Kellogg, Dean L., Jr. Lunte, Craig E. Nordstrom, Carl Henrik Rollema, Hans Sawchuk, Ronald J. Cheung, Belinda W. Y. Shah, Vinod P. Stahle, Lars Ungerstedt, Urban Welty, Devin F. Yeo, Helen TI AAPS-FDA workshop white paper: Microdialysis principles, application and regulatory perspectives SO PHARMACEUTICAL RESEARCH LA English DT Article DE clinical pharmacology; microdialysis; recovery; regulatory aspects ID IN-VIVO MICRODIALYSIS; BLOOD-BRAIN-BARRIER; ZERO-NET-FLUX; CEREBROSPINAL-FLUID; DIABETIC-PATIENTS; SKELETAL-MUSCLE; DRUG-DELIVERY; PHARMACOKINETICS; TRANSPORT; DOPAMINE AB Many decisions in drug development and medical practice are based on measuring blood concentrations of endogenous and exogenous molecules. Yet most biochemical and pharmacological events take place in the tissues. Also, most drugs with few notable exceptions exert their effects not within the bloodstream, but in defined target tissues into which drugs have to distribute from the central compartment. Assessing tissue drug chemistry has, thus, for long been viewed as a more rational way to provide clinically meaningful data rather than gaining information from blood samples. More specifically, it is often the extracellular (interstitial) tissue space that is most closely related to the site of action (biophase) of the drug. Currently microdialysis (mu D) is the only tool available that explicitly provides data on the extracellular space. Although mu D as a preclinical and clinical tool has been available for two decades, there is still uncertainty about the use of mu D in drug research and development, both from a methodological and a regulatory point of view. In an attempt to reduce this uncertainty and to provide an overview of the principles and applications of mu D in preclinical and clinical settings, an AAPS-FDA workshop took place in November 2005 in Nashville, TN, USA. Stakeholders from academia, industry and regulatory agencies presented their views on mu D as a tool in drug research and development. C1 US FDA, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20857 USA. Med Univ Vienna, Dept Clin Pharmacol, Vienna, Austria. US FDA, Off Clin Pharmacol, Div Clin Pharmacol 3, Silver Spring, MD USA. Univ Copenhagen, Dept Dermatol, Copenhagen, Denmark. Karolinska Univ Hosp Huddinge, Karolinska Inst, Dept Med, Stockholm, Sweden. Virginia Commonwealth Univ Med Coll Virginia, Richmond, VA USA. Off Res Serv, Div Bioengn & Phys Sci, NIH, Bethesda, MD USA. LACDR, Leiden, Netherlands. Univ Florida, Dept Pharmaceut, Gainesville, FL USA. Univ Minnesota, Dept Pharmaceut, Minneapolis, MN 55455 USA. Uppsala Univ, Dept Pharmaceut Biosci, Uppsala, Sweden. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Univ Kansas, Dept Chem, Lawrence, KS 66045 USA. Univ Hosp, Dept Neurosurg, Lund, Sweden. Pfizer Global Res, Dept Neurosci, Groton, CT USA. Pharmaceut Federat, N Potomac, MD USA. Astra Zeneca, Sodertalje, Sweden. Karolinska Inst, Dept Physiol & Pharmacol, Stockholm, Sweden. Allergan Pharmaceut Inc, Irvine, CA USA. Dept Drug Metab & Pharmacokinet, Palo Alto, CA USA. RP Chaurasia, CS (reprint author), US FDA, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20857 USA. EM chandra.chaurasia@fda.hhs.gov RI Derendorf, Hartmut/B-4628-2012 OI Derendorf, Hartmut/0000-0003-4016-1370 NR 63 TC 110 Z9 116 U1 1 U2 18 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD MAY PY 2007 VL 24 IS 5 BP 1014 EP 1025 DI 10.1007/s11095-006-9206-z PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 162TL UT WOS:000246112300019 PM 17458685 ER PT J AU Kelly, WN Arellano, FM Barnes, J Bergman, U Edwards, IR Fernandez, AM Freedman, SB Goldsmith, DI Huang, K Jones, JK McLeay, R Moore, N Stather, RH Trenque, T Troutman, WG van Puijenbroek, E Williams, F Wise, RP AF Kelly, William N. Arellano, Felix M. Barnes, Joanne Bergman, Ulf Edwards, I. Ralph Fernandez, Alina M. Freedman, Stephen B. Goldsmith, David I. Huang, Kui Jones, Judith K. McLeay, Rachel Moore, Nicholas Stather, Rosie H. Trenque, Thierry Troutman, William G. van Puijenbroek, Eugene Williams, Frank Wise, Robert P. TI Guidelines for submitting adverse event reports for publication SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material ID DRUG-REACTIONS; PHARMACOVIGILANCE; ANECDOTES; STANDARDS; CRITERIA; QUALITY AB Publication of case reports describing suspected adverse effects of drugs and medical products that include herbal and complementary medicines, vaccines, and other biologicals and devices is important for postmarketing surveillance. Publication lends credence to important signals raised in these adverse event reports. Unfortunately, deficiencies in vital information in published cases can often limit the value of such reports by failing to provide sufficient details for either (i) a differential diagnosis or provisional assessment of cause-effect association, or (ii) a reasonable pharmacological or biological explanation. Properly described, a published report of one or more adverse events can provide a useful signal of possible risks associated with the use of a drug or medical product which might warrant further exploration. A review conducted by the Task Force authors found that many major journals have minimal requirements for publishing adverse event reports, and some have none at all. Based on a literature review and our collective experience in reviewing adverse event case reports in regulatory, academic, and industry settings, we have identified information that we propose should always be considered for inclusion in a report submitted for publication. These guidelines have been endorsed by the International Society for Pharmacoepidemiology (ISPE) and the International Society of Pharmacovigilance (ISoP) and are freely available on the societies' web sites. Their widespread distribution is encouraged. ISPE and ISoP urge biomedical journals to adopt these guidelines and apply them to case reports submitted for publication. They also encourage schools of medicine, pharmacy, and nursing to incorporate them into the relevant curricula that address the detection, evaluation, and reporting of suspected drug or other medical product adverse events. Copyright (c) 2007 Kelly et al. Reproduced with permission by John Wiley & Sons, Ltd. C1 William N Kelly Consulting Inc, Oldsmar, FL 34677 USA. Risk Management Resources, Bridgewater, NY USA. Univ Auckland, Auckland 1, New Zealand. Karolinska Inst, S-10401 Stockholm, Sweden. Uppsala Monitoring Ctr, Uppsala, Sweden. TAP Pharmaceut Prod Inc, Lake Forest, IL USA. Hosp Sick Children, Toronto, ON M5G 1X8, Canada. Goldsmith Pharmacovigilance & Syst, New York, NY USA. Pfizer Pharmaceut Inc, New York, NY USA. Degge Grp Ltd, Arlington, VA USA. Wolters Kluwer Hlth, Auckland, New Zealand. Univ Victor Segalen, Bordeaux, France. Univ Reims, Ctr Hosp, F-51100 Reims, France. Univ New Mexico, Albuquerque, NM 87131 USA. Netherlands Pharmacovigilance Ctr, sHertogenbosch, Netherlands. USN, Bethesda, MD 20084 USA. US FDA, Rockville, MD 20857 USA. RP Kelly, WN (reprint author), William N Kelly Consulting Inc, 2147 Warwick Dr, Oldsmar, FL 34677 USA. EM wnkelly@earthlink.net RI Moore, nicholas/B-2368-2013; Freedman, Saul/C-1625-2013; OI Bergman, Ulf/0000-0003-4654-2211 NR 20 TC 27 Z9 31 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAY PY 2007 VL 16 IS 5 BP 581 EP 587 DI 10.1002/pds.1399 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 168YP UT WOS:000246560200014 PM 17471601 ER PT J AU Chen, JJ AF Chen, James J. TI Key aspects of analyzing microarray gene-expression data SO PHARMACOGENOMICS LA English DT Review DE class comparison; class prediction; cross validation; gene class testing; gene selection; multiple selection criteria; multiple testing; significance analysis ID FALSE DISCOVERY RATES; B-CELL LYMPHOMA; VARIANCE-COMPONENTS; ARRAY DATA; CANCER; CLASSIFICATION; SELECTION; PREDICTION; NORMALIZATION; CLASSIFIERS AB One major challenge with the use of microarray technology is the analysis of massive amounts of gene-expression data for various applications. This review addresses the key aspects of the microarray gene-expression data analysis for the two most common objectives: class comparison and class prediction. Class comparison mainly aims to select which genes are differentially expressed across experimental conditions. Gene selection is separated into two steps: gene ranking and assigning a significance level. Class prediction uses expression profiling analysis to develop a prediction model for patient selection, diagnostic prediction or prognostic classification. Development of a prediction model involves two components: model building and performance assessment. It also describes two additional data analysis methods: gene-class testing and multiple ordering criteria. 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 57 TC 25 Z9 26 U1 0 U2 5 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 MAY PY 2007 VL 8 IS 5 BP 473 EP 482 DI 10.2217/14622416.8.5.473 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 167PY UT WOS:000246464800011 PM 17465711 ER PT J AU Huang, A Roy, DA Summers, RM Franaszek, M Petrick, N Choi, JR Pickhardt, PJ AF Huang, Adam Roy, Dave A. Summers, Ronald M. Franaszek, Marek Petrick, Nicholas Choi, J. Richard Pickhardt, Perry J. TI Teniae coli-based circumferential localization system for CT colonography: Feasibility study SO RADIOLOGY LA English DT Article ID COMPUTED-TOMOGRAPHY COLONOGRAPHY; VIRTUAL COLONOSCOPY; POLYP DETECTION; SUPINE AB This HIPAA-compliant study, with institutional review board approval and informed patient consent, was conducted to retrospectively develop a teniae coli-based circumferential localization method for guiding virtual colon navigation and colonic polyp registration. Colonic surfaces (n = 72) were depicted at computed tomographic (CT) colonography performed in 36 patients (26 men, 10 women; age range, 47-72 years) in the supine and prone positions. For 70 (97%) colonic surfaces, the tenia omentalis (TO), the most visible of the three teniae coli on a well-distended colonic surface, was manually extracted from the cecum to the descending colon. By virtually dissecting and flattening the colon along the TO, the authors developed a localization system involving 12 grid lines to estimate the circumferential positions of polyps. A sessile polyp would most likely (at 95% confidence level) be found within +/- 1.2 grid lines (one grid line equals 1/12 the circumference) with use of the proposed method. By orienting and positioning the virtual cameras with use of the new localization system, synchronized prone and supine navigation was achieved. The teniae coli are extractable landmarks, and the teniae coli-based circumferential localization system helps guide virtual navigation and polyp registration at CT colonography. (c) RSNA, 2007. C1 NIH, Dept Diagnost Radiol, Clin Ctr, Bethesda, MD 20892 USA. US FDA, Joint Lab Assessment Med Imaging Syst, CDRH, NIBIB, Rockville, MD 20857 USA. Uniformed Serv Univ hlth Sci, Bethesda, MD USA. Walter Reed Army Med Ctr, Washington, DC 20307 USA. Natl Naval Med Ctr, Bethesda, MD USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Clin Ctr, 10 Ctr Dr,MSC 1182,bldg 10,Room 1C351, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS NR 17 TC 25 Z9 25 U1 0 U2 1 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2007 VL 243 IS 2 BP 551 EP 560 DI 10.1148/radiol.2432060353 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 170UP UT WOS:000246691500031 PM 17456877 ER PT J AU Bellack, AS Green, MF Cook, JA Fenton, W Harvey, PD Heaton, RK Laughren, T Leon, AC Mayo, DJ Patrick, DL Patterson, TL Rose, A Stover, E Wykes, T AF Bellack, Alan S. Green, Michael F. Cook, Judith A. Fenton, Wayne Harvey, Philip D. Heaton, Robert K. Laughren, Thomas Leon, Andrew C. Mayo, Donna J. Patrick, Donald L. Patterson, Thomas L. Rose, Andrew Stover, Ellen Wykes, Til TI Assessment of community functioning in people with schizophrenia and other severe mental illnesses: A white paper based on an NIMH-sponsored workshop SO SCHIZOPHRENIA BULLETIN LA English DT Article DE schizophrenia; assessment; outcomes ID QUALITY-OF-LIFE; PSYCHIATRIC-PATIENTS; RATING-SCALE; PSYCHOSOCIAL REHABILITATION; NEUROCOGNITIVE DEFICITS; SOCIAL-ADJUSTMENT; NEGATIVE SYMPTOMS; PERFORMANCE; VALIDATION; OUTCOMES AB People with schizophrenia frequently have significant problems in community functioning. Progress in developing effective interventions to ameliorate these problems has been slowed by the absence of reliable and valid measures that are suitable for use in clinical trials. The National Institute of Mental Health convened a workgroup in September 2005 to examine this issue and make recommendations to the field that would foster research in this area. This article reports on issues raised at the meeting. Many instruments have been developed to assess community functioning, but overall insufficient attention has been paid to psychometric issues and many instruments are not suitable for use in clinical trials. Consumer self-report, informant report, ratings by clinicians and trained raters, and behavioral assessment all can provide useful and valid information in some circumstances and may he practical for use in clinical trials. However, insufficient attention has been paid to when and how different forms of assessment and sources of information are useful or how to understand inconsistencies. A major limiting factor in development of reliable and valid instruments is failure to develop a suitable model of functioning and its primary mediators and moderators. Several examples that can guide thinking are presented. Finally, the field is limited by the absence of an objective gold standard of community functioning. Hence, outcomes must be evaluated in part by "clinical significance." This criterion is problematic because different observers and constituencies often have different opinions about what types of change are clinically important and how much change is significant. C1 Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Univ Illinois, Chicago, IL 60680 USA. Mt Sinai Sch Med, New York, NY 10029 USA. Univ Calif San Diego, San Diego, CA 92103 USA. US FDA, Div Psychiat Prod, Rockville, MD 20857 USA. Cornell Univ, Weill Med Coll, Ithaca, NY 14853 USA. NIMH, Bethesda, MD 20892 USA. Kings Coll London, Inst Psychiat, London WC2R 2LS, England. RP Bellack, AS (reprint author), Univ Maryland, Sch Med, 737 Lombard St,Suite 551, Baltimore, MD 21201 USA. EM abellack@psych.umaryland.edu RI Wykes, Til/B-7894-2008; Wykes, Til/B-3812-2011; Cook, Judith/B-9107-2013 OI Wykes, Til/0000-0002-5881-8003; NR 95 TC 94 Z9 96 U1 4 U2 14 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0586-7614 J9 SCHIZOPHRENIA BULL JI Schizophr. Bull. PD MAY PY 2007 VL 33 IS 3 BP 805 EP 822 DI 10.1093/schbul/sbl035 PG 18 WC Psychiatry SC Psychiatry GA 178SZ UT WOS:000247241700028 PM 16931542 ER PT J AU Geng, YS Wu, CG Bhattacharyya, SP Tan, D Guo, ZP Yu, MYW AF Geng, Yansheng Wu, Chuan-ging Bhattacharyya, Siba P. Tan, De Guo, Zheng-Ping Yu, Mei-ying W. TI Parvovirus B19 DNA in Factor VIII concentrates: effects of manufacturing procedures and B19 screening by nucleic acid testing SO TRANSFUSION LA English DT Article ID BLOOD-PRODUCTS; PLASMA POOLS; HIGH-PURITY; TRANSMISSION; INFECTION; PREVALENCE; PCR; FRACTIONATION; CONTAMINATION; TECHNOLOGY AB BACKGROUND: Parvovirus B19 (B19) is a common contaminant, especially in coagulation factors. Because of B19 transmission by pooled plasma, solvent/detergent treated in 1999, some fractionators initiated minipool nucleic acid testing (NAT) to limit the B19 load in manufacturing pools. In this study, the extent of B19 DNA contamination in commercial Factor VIII concentrates, that is, antihemophilic factor (human) (AHF), manufactured before and after B19 NAT screening was implemented, was determined. STUDY DESIGN AND METHODS: A total of 284 lots representing six AHF products made during 1993 to 1998 and 2001 to 2004 were assayed for B19 DNA by an in-house NAT procedure. Anti-B19 immunoglobulin G (IgG) was also measured. RESULTS: Most lots made during 1993 to 1998 had detectable B19 DNA. The prevalence ranged from 56 to 100 percent and appeared to differ between manufacturers. The highest level of B19 DNA found was 10(6) genome equivalents (geq or international units [IU]) per mL. Forty percent of the lots tested contained 10(3) geq (IU) per mL. In comparison, both prevalence and levels in source plasma-derived AHF products made in 2001 to 2004 were lower. Both, however, remained unchanged in the recovered plasma-derived product because B19 NAT screening had not been implemented. Only an intermediate-purity AHF product was positive for the presence of anti-B19 IgG. CONCLUSION: The prevalence and levels of B19 DNA in AHF prepared from B19 NAT unscreened plasma were high but varied among products with different manufacturing procedures. B19 NAT screening of plasma effectively lowered the B19 DNA level in the final products and in the majority of cases rendered it undetectable and hence potentially reduced the risk of B19 transmission. C1 US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Yu, MYW (reprint author), US FDA, Div Hematol, Ctr Biol Evaluat & Res, Room 303,29 Lincoln Dr, Bethesda, MD 20892 USA. EM mei-ying.yu@fda.hhs.gov NR 37 TC 20 Z9 23 U1 0 U2 0 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAY PY 2007 VL 47 IS 5 BP 883 EP 889 DI 10.1111/j.1537-2995.2007.01205.x PG 7 WC Hematology SC Hematology GA 161CU UT WOS:000245992700020 PM 17465954 ER PT J AU Soreth, J Cox, E Kweder, S Jenkins, J Galson, S AF Soreth, Janice Cox, Edward Kweder, Sandra Jenkins, John Galson, Steven TI Ketek - The FDA perspective SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Soreth, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 1 TC 17 Z9 17 U1 1 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 19 PY 2007 VL 356 IS 16 BP 1675 EP 1676 DI 10.1056/NEJMc076135 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 158AB UT WOS:000245762000013 PM 17442912 ER PT J AU Loyo-Berrios, NI Irizarry, R Hennessey, JG Tao, XGG Matanoski, G AF Loyo-Berrios, Nilsa I. Irizarry, Rafael Hennessey, Joseph G. Tao, Xuguang Grant Matanoski, Genevieve TI Air pollution sources and childhood asthma attacks in Catano, Puerto Rico SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE air pollution; asthma; child ID RESPIRATORY-DISEASES; ONTARIO HOSPITALS; CHILDREN; ASSOCIATION; ADMISSIONS; HEALTH; PARTICULATE; BARCELONA; SEATTLE; VISITS AB Asthma prevalence in the Catano Air Basin of Puerto Rico is 27% for children aged 13-14 years and 45% for children aged 5-6 years. There is concern that these rates are related to air pollution. The authors conducted a nested case-control study to evaluate whether proximity to air pollution point sources was associated with increased risk of asthma attacks. For 1997-2001, 1,382 asthma-related medical visits (International Classification of Diseases, Ninth Revision, codes 493 and 493.9) in children under 17 were identified through health insurance claims. Controls were children with no asthma attacks who were randomly selected from enrollees in two health insurance companies by incidence density sampling (1:5) and matched to cases on gender, age, insurance company, and event date. The distance from a point source to the subject's residence area represented a surrogate exposure measurement. Odds ratios for a 1-km decrease in distance were obtained by conditional logistic regression. Risk of asthma attack was associated with residing near a grain mill (odds ratio (OR) 1.35), petroleum refinery (OR 1.44), asphalt plant (OR 1.23), or power plant (OR 1.28) (all p's < 0.05). Residence near major air emissions sources (> 100 tons/year) increased asthma attack risk by 108% (p < 0.05). These results showed that proximity to some air pollution sources is associated with increased risks of asthma attacks. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, US Dept HHS, Rockville, MD 20850 USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA. Johns Hopkins Univ, Whiting Sch Engn, Ctr Imaging Sci, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Dept Psychiat, Baltimore, MD USA. Johns Hopkins Univ, Sch Med, Div Environm & Occupat Hlth, Baltimore, MD USA. Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA. Dist Columbia Hlth Dept, Dist Columbia Canc Registry, Washington, DC USA. RP Loyo-Berrios, NI (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, US Dept HHS, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. EM nilsa.loyo-berrrios@fda.hhs.gov NR 28 TC 21 Z9 21 U1 2 U2 10 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD APR 15 PY 2007 VL 165 IS 8 BP 927 EP 935 DI 10.1093/aje/kwk088 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 152GI UT WOS:000245349100011 PM 17308332 ER PT J AU Mann, BS Johnson, JR He, K Sridhara, R Abraham, S Booth, BP Verbois, L Morse, DE Jee, JM Pope, S Harapanhalli, RS Dagher, R Farrell, A Justice, R Pazdur, R AF Mann, Bhupinder S. Johnson, John R. He, Kun Sridhara, Rajeshwari Abraham, Sophia Booth, Brian P. Verbois, Leigh Morse, David E. Jee, Josephine M. Pope, Sarah Harapanhalli, Ravi S. Dagher, Ramzi Farrell, Ann Justice, Robert Pazdur, Richard TI Vorinostat for treatment of cutaneous manifestations of advanced primary cutaneous T-cell lymphoma SO CLINICAL CANCER RESEARCH LA English DT Article AB Purpose: To discuss vorinostat approval for treatment of cutaneous manifestations of advanced cutaneous T-cell lymphoma (CTCL). Experimental Design: Data from 1 single-arm, open-label, multicenter pivotal trial and 11 other trials submitted to support the new drug application for vorinostat in the treatment of advanced primary CTCL were reviewed. The pivotal trial assessed responses by changes in overall skin disease score using a severity-weighted assessment tool (SWAT). Vorinostat could be considered active in CTCL if observed response rate was at least 20% and the lower bound of the corresponding 95% confidence interval (95% Cl) excluded 5%. Patients reported pruritis relief using a questionnaire and a visual analogue scale. Results: The pivotal trial enrolled 74 patients with stage IB or higher CTCL. Median number of prior treatments Was 3, and 61 patients (82%) had stage IIB or higher disease. The objective response rate in the skin disease assessed by change in the overall SWAT score from the baseline was 30% (95% Cl, 18.5 to 42.6) in patients with stage IIB or higher disease. Median response duration (end of response defined by 50% increase in SWAT score from the nadir) was 168 days. Median time to tumor progression was 148 days for overall population and 169 days for patients with stage IIB or higher disease. Assessment of pruritis relief was considered unreliable. Conclusions: Vorinostat showed activity in CTCL, and skin responses were a clinical benefit. Vorinostat was approved for treatment of cutaneous manifestations of CTCL. A nonblinded, single-arm trial did not allow a reliable assessment of pruritis relief. C1 US FDA, Silver Spring, MD 20993 USA. RP Mann, BS (reprint author), US FDA, Room 2103,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM bhupinder.mann@fda.hhs.gov NR 6 TC 125 Z9 129 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 APR 15 PY 2007 VL 13 IS 8 BP 2318 EP 2322 DI 10.1158/1078-0432.CCR-06-2672 PG 5 WC Oncology SC Oncology GA 159RK UT WOS:000245883800004 PM 17438089 ER PT J AU Fogg, CN Americo, JL Lustig, S Huggins, JW Smith, SK Damon, I Resch, W Earl, PL Klinman, DM Moss, B AF Fogg, Christiana N. Americo, Jeffrey L. Lustig, Shlomo Huggins, John W. Smith, Scott K. Damon, Inger Resch, Wolfgang Earl, Patricia L. Klinman, Dennis M. Moss, Bernard TI Adjuvant-enhanced antibody responses to recombinant proteins correlates with protection of mice and monkeys to orthopoxvirus challenges SO VACCINE LA English DT Article DE smallpox; monkeypox; vaccinia virus ID EXTRACELLULAR ENVELOPED VIRUS; T-LYMPHOCYTE RESPONSES; MONOPHOSPHORYL-LIPID-A; VACCINIA VIRUS; SMALLPOX VACCINE; IMMUNE-RESPONSES; SAPONIN ADJUVANT; POXVIRUS INFECTION; NONHUMAN-PRIMATES; CPG MOTIFS AB Recombinant proteins are being evaluated as smallpox and monkeypox vaccines because of their perceived safety compared to live vaccinia virus. Previously, we demonstrated that three or more injections of a Ribi-type adjuvant with a combination of three proteins from the outer membranes of intracellular (L1 protein) and extracellular (A33 and B5 proteins) forms of vaccinia virus protected mice against a lethal intranasal challenge with vaccinia virus. Here, we compared several adjuvants and found that QS-21 and to a lesser extent alum+CpG oligodeoxynucleotides accelerated and enhanced neutralizing antibody responses to a mixture of L1 and A33 proteins, provided the highest ratio of IgG2a to IgG1 isotype response, and protected mice against disease and death after only two immunizations 3 weeks apart. In addition, monkeys immunized with recombinant vaccinia virus proteins and QS-21 developed neutralizing antibody to monkeypox virus and had reduced virus load, skin lesions, and morbidity compared to the non-immunized group following monkeypox virus challenge. (c) 2007 Elsevier Ltd. All rights reserved. C1 NIAID, NIH, Viral Dis Lab, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. Ctr Dis Control & Prevent, Poxvirus & Rabies Branch, Atlanta, GA 30333 USA. FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Moss, B (reprint author), NIAID, NIH, Viral Dis Lab, 33 N Dr MSC3210,Bldg 33,Room 1E13C-1, Bethesda, MD 20892 USA. EM bmoss@nih.gov FU Intramural NIH HHS; NIAID NIH HHS [U54 AI057168, RCE-U54-AI57168, Z01 AI000979-01] NR 63 TC 39 Z9 40 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 12 PY 2007 VL 25 IS 15 BP 2787 EP 2799 DI 10.1016/j.vaccine.2006.12.037 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 158WL UT WOS:000245825800007 PM 17229505 ER PT J AU Reepmeyer, JC Woodruff, JT d'Avignon, DA AF Reepmeyer, John C. Woodruff, Jeffrey T. d'Avignon, D. Andre TI Structure elucidation of a novel analogue of sildenafil detected as an adulterant in an herbal dietary supplement SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE dietary supplements; sildenafil analogue; methisosildenafil; liquid chromatography-mass spectrometry (LC-MS); nuclear magnetic resonance (NMR) ID SYNTHETIC PHOSPHODIESTERASE-5 INHIBITORS; MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; ERECTILE DYSFUNCTION; DESIGNER DRUG; IDENTIFICATION; VARDENAFIL; TADALAFIL; PRODUCTS; MATRICES AB A new analogue of sildenafil was detected in an herbal dietary supplement, which was sold over the internet and promoted as a product for the enhancement of sexual performance. The structure of the compound was established using LC-MS, UV spectroscopy, MS-MS, and NMR. In addition, the compound was cleaved at its sulfonamide S-N bond yielding a sulfonic acid and an amine, which were independently characterized using LC-MS, GC-MS, and derivatization. The compound, named methisosildenafil, is a novel synthetic analogue of sildenafil in which the N-methylpiperazine moiety has been replaced with 2,6-dimethylpiperazine. (c) 2006 Elsevier B.V. All rights reserved. C1 US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. Washington Univ, Dept Chem, St Louis, MO 63130 USA. RP Reepmeyer, JC (reprint author), US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM john.reepmeyer@fda.hhs.gov NR 15 TC 57 Z9 59 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 11 PY 2007 VL 43 IS 5 BP 1615 EP 1621 DI 10.1016/j.jpba.2006.11.037 PG 7 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 161IO UT WOS:000246008300004 PM 17207601 ER PT J AU Ciavarella, AB Gupta, A Sayeed, VA Khan, MA Faustino, PJ AF Ciavarella, Anthony B. Gupta, Abhay Sayeed, Vilayat A. Khan, Mansoor A. Faustino, Patrick J. TI Development and application of a validated HPLC method for the determination of gabapentin and its major degradation impurity in drug products SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE gabapentin; HPLC; impurity; degradation; lactam; drug products ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SOLID-PHASE EXTRACTION; HUMAN PLASMA; MASS-SPECTROMETRY; CAPILLARY-ELECTROPHORESIS; FLUORESCENCE DETECTION; ULTRAVIOLET DETECTION; SERUM; DERIVATIZATION; QUANTIFICATION AB A simple isocratic reversed-phase HPLC method for the determination of gabapentin and its major degradation impurity, 3,3-pentamethylene-4-butyrolactam, was developed and validated for use in the analysis of pharmaceutical tablets and capsules. Separation was achieved on a Brownlee Spheri-5 Cyano column using an acetonitrile-10 mM KH2PO4/10 mM K2HPO4 (pH 6.2) (8:92, v/v) mobile phase. The compounds were eluted isocratically at a flow rate of 1 mL/min. Both compounds were analyzed with UV detection at 210 nm. The method was validated according to USP Category I requirements for gabapentin and USP Category II for 3,3-pentamethylene-4-butyrolactam. The validation characteristics included accuracy, precision, linearity, range, specificity, limit of quantitation and robustness. Validation acceptance criteria were met in all cases. This method was used successfully for the quality assessment of four gabapentin drug products. Published by Elsevier B.V. C1 US FDA, Div Prod Qual Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. US FDA, Off Gener Drugs, Rockville, MD 20855 USA. RP Faustino, PJ (reprint author), US FDA, Div Prod Qual Res, Off Pharmaceut Sci, Life Sci Bldg 64,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM patrick.faustino@fda.hhs.gov NR 22 TC 27 Z9 28 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 11 PY 2007 VL 43 IS 5 BP 1647 EP 1653 DI 10.1016/j.jpba.2006.12.020 PG 7 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 161IO UT WOS:000246008300008 PM 17275240 ER PT J AU Jiao, Y Su, MM Chen, MJ Jia, W Chou, YQ Huang, ZY Yang, NL Tong, WD AF Jiao, Yang Su, Mingming Chen, Minjun Jia, Wei Chou, Yiqun Huang, Zhongyi Yang, Nanlin Tong, Weida TI LC/ESI-MS method for the determination of trimetazidine in human plasma: Application to a bioequivalence study on Chinese volunteers SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE trimetazidine; LC/ESI-MS; pharmacokinetics; bioequivalence; Chinese population AB A rapid liquid chromatography electrospray ionization mass spectrometry (LC/ESI-MS) method with good sensitivity and specificity has been developed and validated for the identification and quantification of trimetazidine in human plasma. Trimetazidine and lidocaine (internal standard) were isolated from plasma samples by protein precipitation with methanol. The chromatographic separation was accomplished on a Xterra MS C-18 Column (150 mm x 4.6 mm, 5 mu m particle size) with the mobile phase consisting of methanol and water (40:60, v/v) (pH 2.0, adjusted with trifluoroacetic acid), and the flow rate was set at 0.6 mL/min. Detection was performed on a single quadruple mass spectrometer by selected ion monitoring (SIM) mode (m/z 267.0 for trimetazidine and m/z 235.0 for lidocaine) with the retention time at about 3.47 and 5.05 min, respectively. The calibration curve for trimetazidine was satisfactory with regression coefficient 0.9995 over the range of 2.5-100 ng/mL in the plasma. The LOQ (S/N = 10) was accordingly 2.5 ng/mL. The intra-day and inter-day precision expressed as relative standard deviation was 2.83-6.10% and 4.83-5.82%. The method was successfully applied to investigate the bioequivalence between two kinds of tablets (test versus reference product) in 19 healthy male Chinese volunteers. After a single 20 mg dose for the test and reference product, the resulting mean of major phannacokinetic parameters such as AUC(0-24), AUC(0-infinity), C-max, T-max and t(1/2) of trimetazidine were (673.1 +/- 117.6 ng h mL(-1) versus 652.3 +/- 121.9 ng h mL(-1)), (717.1 +/- 120.9 ng h mL(-1) versus 692 +/- 128.6 ng h mL(-1)), (74.85 +/- 12.13 ng mL(-1) versus 71.93 +/- 14.32 ng mL(-1)), (2.312 +/- 0.663 h versus 2.211 +/- 0.608 h) and (4.785 +/- 0.919 h versus 4.740 +/- 0.823 h), respectively, indicating that these two kinds of tablets were bioequivalent in the Chinese population. (c) 2007 Elsevier B.V. All rights reserved. C1 Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200030, Peoples R China. Shanghai Jing An Cent Hosp, Shanghai 200040, Peoples R China. Jiangsu WuZhong Chinese Tradit Med R&D Co Ltd, Suzhou 215000, Peoples R China. US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Chen, MJ (reprint author), Shanghai Jiao Tong Univ, Sch Pharm, Shanghai 200030, Peoples R China. EM minjunchen@gmail.com RI Su, Mingming/B-2162-2012 OI Su, Mingming/0000-0002-9996-9094 NR 8 TC 17 Z9 20 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 11 PY 2007 VL 43 IS 5 BP 1804 EP 1807 DI 10.1016/j.jpba.2006.11.040 PG 4 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 161IO UT WOS:000246008300030 PM 17208404 ER PT J AU Asafu-Adjaye, EB Faustino, PJ Tawakkul, MA Anderson, LW Yu, LX Kwon, H Volpe, DA AF Asafu-Adjaye, Ebenezer B. Faustino, Patrick J. Tawakkul, Mobin A. Anderson, Lawrence W. Yu, Lawrence X. Kwon, Hyojong Volpe, Donna A. TI Validation and application of a stability-indicating HPLC method for the in vitro determination of gastric and intestinal stability of venlafaxine SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE venlafaxine; in vitro; stability; gastric; intestinal; dehydro-venlafaxine ID TANDEM MASS-SPECTROMETRY; O-DESMETHYLVENLAFAXINE; LIQUID-CHROMATOGRAPHY; HUMAN PLASMA; HUMAN SERUM; ANTIDEPRESSANT; QUANTIFICATION; WY-45,030 AB Gastrointestinal stability of venlafaxine was evaluated in vitro in simulated gastric (SGF) and intestinal (SIF) fluids using a stability indicating HPLC method. The method was validated using a 5 mu m Ascentis (R) C-18 column (150 mm x 4.6 mm) and mobile phase consisting of 30% acetonitrile in 20 mM potassium phosphate buffer (pH 6.5) delivered isocratically at a flow rate of 1 mL/min with UV detection at 228 nm. Venlafaxine in USP simulated gastric and intestinal fluids (0.4 mg/mL) was incubated at 37 degrees C in a shaking water bath. The gastric stability study samples were assayed at 0, 15, 30 and 60 min intervals while sampling for the intestinal stability study was at 0, 1, 2 and 3 h. System suitability determinations gave R.S.D.s of 0.68, 0.5 and 3.9% for retention factor (V), peak area and tailing factor, respectively. The method was shown to be accurate, precise, specific, and linear over the analytical range. Intra- and inter-day precision was < 5.3%. Forced degradation studies of drug substance in basic media at 70 degrees C as well as in H2O2 for 1 h and ultra-violet photostability studies at 255 and 365 nm for 24 h did not produce any detectable degradation products. Forced degradation studies of drug substance in acidic media at 70 degrees C for 1 h produced the dehydro-venlafaxine degradant. Venlafaxine was stable in SGF (pH similar to 1.2) for the 1-h incubation period and in SIF (pH 6.8) up to 3 h with < 1.5% relative difference (RD) between the amount of drug added and that found for all time points. This stability experiment in simulated gastric and intestinal fluids suggests that drug loss in the gastrointestinal tract takes place by membrane permeation rather than a degradation process. Published by Elsevier B.V. C1 US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA. US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. US FDA, Ctr Drug Evaluat & Res, Lab Clin Pharmacol, Silver Spring, MD 20993 USA. RP Faustino, PJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA. EM patrick.faustino@fda.hhs.gov NR 23 TC 25 Z9 28 U1 0 U2 12 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD APR 11 PY 2007 VL 43 IS 5 BP 1854 EP 1859 DI 10.1016/j.jpba.2006.12.035 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 161IO UT WOS:000246008300038 PM 17300896 ER PT J AU Gupta, S Indelicato, SR Jethwa, V Kawabata, T Kelley, M Mire-Sluis, AR Richards, SM Rup, B Shores, E Swanson, SJ Wakshull, E AF Gupta, Shalini Indelicato, Stephen R. Jethwa, Vijay Kawabata, Thomas Kelley, Marian Mire-Sluis, Anthony R. Richards, Susan M. Rup, Bonita Shores, Elizabeth Swanson, Steven J. Wakshull, Eric TI Recommendations for the design, optimization, and qualification of cell-based assays used for the detection of neutralizing antibody responses elicited to biological therapeutics SO JOURNAL OF IMMUNOLOGICAL METHODS LA English DT Review DE neutralizing antibody bioassay; cell-based assay; serum-based bioassay; immunogenicity assay; NAb assay ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; GROWTH-FACTOR; PROTEIN-A; RECEPTOR; VALIDATION; ACTIVATION; EXPRESSION; GREEN; BETA AB The administration of biological therapeutics can evoke some level of immune response to the drug product in the receiving subjects. An immune response comprised of neutralizing antibodies can lead to loss of efficacy or potentially more serious clinical sequelae. Therefore, it is important to monitor the immunogenicity of biological therapeutics throughout the drug product development cycle. Immunoassays are typically used to screen for the presence and development of anti-drug product antibodies. However, in-vitro cell-based assays prove extremely useful for the characterization of immunoassay-positive samples to determine if the detected antibodies have neutralizing properties. This document provides scientific recommendations based on the experience of the authors for the development of cell-based assays for the detection of neutralizing antibodies in non-clinical and clinical studies. (c) 2006 Elsevier B.V. All rights reserved. C1 Amgen Inc, Thousand Oaks, CA 91320 USA. Schering Plough Res Inst, Pharmsci Qual Qual Syst Improvement Off, Kenilworth, NJ 07033 USA. Biogen Idec, Res Triangle Pk, NC 27709 USA. Pfizer Global Res & Dev, Groton, CT 06340 USA. Centocor R&D Inc, Radnor, PA 19087 USA. Genzyme Corp, Framingham, MA 01701 USA. Wyeth Ayerst Res, Andover, MA 01810 USA. Ctr Drug Evaluat & Res, Div Therapeut Prot, Off Biotechnol Prod, Bethesda, MD 20892 USA. Biogen Idnc, Cambridge, MA 02142 USA. RP Gupta, S (reprint author), Amgen Inc, Thousand Oaks, CA 91320 USA. EM shalinig@amgen.com NR 35 TC 132 Z9 138 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0022-1759 J9 J IMMUNOL METHODS JI J. Immunol. Methods PD APR 10 PY 2007 VL 321 IS 1-2 BP 1 EP 18 DI 10.1016/j.jim.2006.12.004 PG 18 WC Biochemical Research Methods; Immunology SC Biochemistry & Molecular Biology; Immunology GA 158MD UT WOS:000245794700001 PM 17307199 ER PT J AU Probst, C Njapau, H Cotty, PJ AF Probst, Claudia Njapau, Henry Cotty, Peter J. TI Outbreak of an acute aflatoxicosis in Kenya in 2004: Identification of the causal agent SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ASPERGILLUS-SECTION FLAVI; SOUTH TEXAS; ATOXIGENIC STRAIN; COTTON; CONTAMINATION; COMMUNITIES; SCLEROTIA; FUNGI; SOILS AB Maize contaminated with aflatoxins has been implicated in deadly epidemics in Kenya three times since 1981, but the fungi contaminating the maize with aflatoxins have not been characterized. Here we associate the S strain of Aspergillus flavus with lethal aflatoxicoses that took more than 125 lives in 2004. C1 Univ Arizona, USDA ARS, Dept Plant Sci, Tucson, AZ 85721 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Cotty, PJ (reprint author), Univ Arizona, USDA ARS, Dept Plant Sci, POB 210036, Tucson, AZ 85721 USA. EM pjcotty@email.arizona.edu NR 28 TC 113 Z9 119 U1 3 U2 21 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 2007 VL 73 IS 8 BP 2762 EP 2764 DI 10.1128/AEM.02370-06 PG 3 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 168RT UT WOS:000246542400044 PM 17308181 ER PT J AU Il Kim, P Jung, MY Chang, YH Kim, S Kim, SJ Park, YH AF Il Kim, Pyoung Jung, Min Young Chang, Young-Hyo Kim, Saehun Kim, Seong-Jae Park, Yong-Ha TI Probiotic properties of Lactobacillus and Bifidobacterium strains isolated from porcine gastrointestinal tract SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE Lactobacillus amylovorus; Lactobacillus reuteri; Lactobacillus salivarius; Bifidobacterium thermacidophilum; antagonistic effect; Clostridium perfringens ID LACTIC-ACID BACTERIA; INTESTINAL EPITHELIAL-CELLS; IN-VITRO; CLOSTRIDIUM-PERFRINGENS; SURFACE PROTEIN; CACO-2 CELLS; ACIDOPHILUS; ADHESION; MUCUS; COLONIZATION AB One strain of Lactobacillus salivarius, two strains of Lactobacillus reuteri and Lactobacillus amylovorus, and two strains of Bifidobacterium thermacidophilum with antagonistic effect against Clostridium perfringens were isolated from porcine gastrointestinal tract. Isolates were assayed for their ability to survive in synthetic gastric juice at pH 2.5 and were examined for their ability to grow on agar plate containing porcine bile extract. There was a large variation in the survival of the isolates in gastric juice and growth in the medium containing 0.3% (w/v) bile. L. salivarius G11 and L. amylovorus S6 adhered to the HT-29 epithelial cell line. Cell-free supernatant of L. amylovorus S6 showed higher antagonistic activity as effective as the antibiotics such as neomycin, chlortetracycline, and oxytetracycline against bacterial pathogens including C. perfringens, Salmonella typhimurium, Staphylococcus aureus, Vibrio cholerae, Edwardsiella tarda, and Aeromonas salmonicida subsp. salmonicida. C1 Yeungnam Univ, Dept Appl Microbiol, Gyongsan, South Korea. Korea Res Inst Biosci & Biotechnol, Taejon 305333, South Korea. Korea Univ, Div Food Sci, Seoul 136701, South Korea. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Park, YH (reprint author), Yeungnam Univ, Dept Appl Microbiol, Gyongsan, South Korea. EM peter@yumail.ac.kr NR 60 TC 30 Z9 34 U1 1 U2 5 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD APR PY 2007 VL 74 IS 5 BP 1103 EP 1111 DI 10.1007/s00253-006-0741-7 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 147IJ UT WOS:000244996300019 PM 17136367 ER PT J AU Petricoin, EF Espina, V Araujo, RP Midura, B Yeung, C Wan, XL Eichler, GS Johann, DJ Qualman, S Tsokos, M Krishnan, K Helman, LJ Liotta, LA AF Petricoin, Emanuel F., III Espina, Virginia Araujo, Robyn P. Midura, Brieanne Yeung, Choh Wan, Xiaolin Eichler, Gabriel S. Johann, Donald J., Jr. Qualman, Stephen Tsokos, Maria Krishnan, Kartik Helman, Lee J. Liotta, Lance A. TI Phosphoprotein pathway mapping: Akt/mammalian target of rapamycin activation is negatively associated with childhood rhabdomyosarcoma survival SO CANCER RESEARCH LA English DT Article ID CHILDRENS-ONCOLOGY-GROUP; MAMMALIAN TARGET; PROTEIN MICROARRAYS; ALVEOLAR RHABDOMYOSARCOMA; KINASE; TRANSLATION; INHIBITION; GROWTH; PHOSPHORYLATION; DIFFERENTIATION AB Mapping of protein signaling networks within tumors can identify new targets for therapy and provide a means to stratify patients for individualized therapy. Despite advances in combination chemotherapy, the overall survival for childhood rhabdomyosarcoma remains similar to 60%. A critical goal is to identify, functionally important protein signaling defects associated with treatment failure for the 40% nonresponder cohort. Here, we show, by phosphoproteomic network analysis of microdissected tumor cells, that interlinked components of the Akt/mammalian target of rapamycin (mTOR) pathway exhibited increased levels of phosphorylation for tumors of patients with short-term survival. Specimens (n = 59) were obtained from the Children's Oncology Group Intergroup Rhabdomyosarcoma Study (IRS) TV, D9502 and D9803, with 12-year follow-up. High phosphorylation levels were associated with poor overall and poor disease-free survival: Akt Ser 473 (overall survival P < 0.001, recurrence-free survival P < 0.0009), 4EBPI Thr 37/46 (overall survival P < 0.0110, recurrence-free survival P < 0.0106), eIF4G Ser(1108) (overall survival P < 0.0017, recurrence-free survival P < 0.0072), and p70S6 Thr(389) (overall survival P < 0.0085, recurrence-free survival P < 0.0296). Moreover, the findings support an altered interrelationship between the insulin receptor substrate (IRS-1) and Akt/mTOR path-way proteins (P < 0.0027) for tumors from patients with poor survival. The functional significance of this pathway was tested using CCI-779 in a mouse xenograft model. CCI-779 suppressed phosphorylation of mTOR downstream proteins and greatly reduced the growth of two different rhabdomyosarcoma (RD embryonal P = 0.00008; Rh30 alveolar P = 0.0002) cell lines compared with controls. These results suggest that phosphoprotein mapping of the Akt/mTOR pathway should be studied further as a means to select patients to receive mTOR/IRS pathway inhibitors before administration of chemotherapy. C1 NCI, NIH, US FDA, Ctr Biol Evaluat & Res,Off Cellular & Gene Therap, Bethesda, MD 20892 USA. NCI, NIH, Pathol Lab, Bethesda, MD 20892 USA. NCI, NIH, Dept Pediat Oncol, Bethesda, MD 20892 USA. NCI, NIH, Genom & Bioinformat Grp, Mol Pharmacol Lab,Ctr Canc Res, Bethesda, MD 20892 USA. Columbus Childrens Hosp, Dept Pathol, Columbus, OH USA. RP Espina, V (reprint author), George Mason Univ, Ctr Appl Proteom & Mol Med, 10900 Univ Blvd MS 1A9, Manassas, VA 20110 USA. EM vespina@gmu.edu OI Espina, Virginia/0000-0001-5080-5972 FU Intramural NIH HHS NR 44 TC 140 Z9 146 U1 0 U2 1 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 APR 1 PY 2007 VL 67 IS 7 BP 3431 EP 3440 DI 10.1158/0008-5472.CAN-06-1344 PG 10 WC Oncology SC Oncology GA 156BM UT WOS:000245622900064 PM 17409454 ER PT J AU Uhl, K Parekh, A Kweder, S AF Uhl, K. Parekh, A. Kweder, S. TI Females in clinical studies: Where are we going? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article AB Historically females of all ages have been underrepresented in clinical research. Reasons for this exclusion are multifactorial and may possibly have their origins in regulation that forbid the participation of females of childbearing potential in the earliest phase clinical studies that support drug approval. Decades of female underrepresentation in clinical studies has resulted in inequality in the understanding, diagnosis, and treatment of disease between the sexes. Adequate numbers of both sexes is one approach which is likely to present overwhelming financial constraints. Advances in study design, statistical methodologies, and the promise of evolving technologies will lead to new tools that can foster a better understanding of the biology that governs sex and gender differences. C1 US FDA, Off Womens Hlth, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Uhl, K (reprint author), US FDA, Off Womens Hlth, Rockville, MD 20857 USA. EM kathleen.uhl@fda.hhs.gov NR 6 TC 22 Z9 24 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD APR PY 2007 VL 81 IS 4 BP 600 EP 602 DI 10.1038/sj.clpt.6100112 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 153LJ UT WOS:000245435900020 PM 17314925 ER PT J AU Cai, S Singh, BR Sharma, S AF Cai, Shuowei Singh, Bal Ram Sharma, Shashi TI Botulism diagnostics: From clinical symptoms to in vitro assays SO CRITICAL REVIEWS IN MICROBIOLOGY LA English DT Review DE botulinum neurotoxin; botulism; diagnostics; mouse bioassay; ELISA; electrochemiluminescence; immunopolymerase; chain reaction; biosensor; endopoeptidase activity assay; mass spectrometry; lateral flow test; protein microarray; rolling circle amplification; aptamer; nanoparticle ID LINKED-IMMUNOSORBENT-ASSAY; NEUROTOXIN LIGHT-CHAIN; COLORIMETRIC CAPTURE ELISAS; NUCLEIC-ACID AMPLIFICATION; CLOSTRIDIUM-BOTULINUM; B NEUROTOXIN; NEUROTRANSMITTER RELEASE; TOXIN-A; MOUSE BIOASSAY; SEROTYPE-A AB Botulinum neurotoxin (BoNT), which cause the deadly neuroparalytic disease, botulism, is the most toxic substance known to man. BoNT can be used as potential bioterrorism agents, and therefore, pose great threat to national security and public health. Rapid and sensitive detection of BoNTs using molecular and biochemical techniques is an essential component in the diagnosis of botulism, and is yet to be achieved. The most sensitive and widely accepted assay method for BoNTs is mouse bioassay, which takes 4 days to complete. This clearly can not meet the need for clinical diagnosis of botulism, botulinum detection in field conditions, and screening of large scale samples. Consequently, the clinical diagnosis of botulism relies on the clinical symptom development, thus limiting the effectiveness of antitoxin treatment. In response to this critical need, many in vitro methods for BoNT detection are under development. This review is focused on recently developed in vitro detection methods for BoNTs, and emerging new technologies with potential for sensitive and rapid in vitro diagnostics for botulism. C1 Univ Massachusetts, Dept Chem & Biochem, N Dartmouth, MA 02747 USA. Univ Massachusetts, Botulinum Res Ctr, N Dartmouth, MA 02747 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Cai, S (reprint author), Univ Massachusetts, Dept Chem & Biochem, 285 Old Westport Rd, N Dartmouth, MA 02747 USA. EM scai@umassd.edu NR 138 TC 66 Z9 68 U1 3 U2 31 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1040-841X J9 CRIT REV MICROBIOL JI Crit. Rev. Microbiol. PD APR-JUN PY 2007 VL 33 IS 2 BP 109 EP 125 DI 10.1080/10408410701364562 PG 17 WC Microbiology SC Microbiology GA 185SK UT WOS:000247730500002 PM 17558660 ER PT J AU Lee, H Stultz, BG Hursh, DA AF Lee, Heuijung Stultz, Brian G. Hursh, Deborah A. TI The Zic family member, odd-paired, regulates the Drosophila BMP, decapentaplegic, during adult head development SO DEVELOPMENT LA English DT Article DE decapentaplegic; BMP; odd-paired; Zic; peripodial; adult head ID ANTENNA IMAGINAL DISK; FOREBRAIN DEVELOPMENT; EYE DEVELOPMENT; JNK PATHWAY; GENE FAMILY; MORPHOGENESIS; EXPRESSION; HEDGEHOG; SPECIFICATION; MUTATIONS AB The eye/antennal discs of Drosophila form most of the adult head capsule. We are analyzing the role of the BMP family member decapentaplegic (dpp) in the process of head formation, as we have identified a class of cis-regulatory dpp mutations (dpp(s-hc)) that specifically disrupts expression in the lateral peripodial epithelium of eye/antennal discs and is required for ventral head formation. Here we describe the recovery of mutations in odd-paired (opa), a zinc finger transcription factor related to the vertebrate Zic family, as dominant enhancers of this dpp head mutation. A single loss-of-function opa allele in combination with a single copy of a dpp(s-hc) produces defects in the ventral adult head. Furthermore, postembryonic loss of opa expression alone causes head defects identical to loss of dpp(s-hc)/dpp(s-hc), and dpp(hc)/+;opa/+ mutant combinations. opa is required for dpp expression in the lateral peripodial epithelium, but not other areas of the eye/antennal disc. Thus a pathway that includes opa and dpp expression in the peripodial epithelium is crucial to the formation of the ventral adult head. Zic proteins and members of the BMP pathway are crucial for vertebrate head development, as mutations in them are associated with midline defects of the head. The interaction of these genes in the morphogenesis of the fruitfly head suggests that the regulation of head formation may be conserved across metazoans. C1 US FDA, Div Cell & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Hursh, DA (reprint author), US FDA, Div Cell & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM deborah.hursh@fda.hhs.gov NR 56 TC 14 Z9 14 U1 0 U2 3 PU COMPANY OF BIOLOGISTS LTD PI CAMBRIDGE PA BIDDER BUILDING CAMBRIDGE COMMERCIAL PARK COWLEY RD, CAMBRIDGE CB4 4DL, CAMBS, ENGLAND SN 0950-1991 J9 DEVELOPMENT JI Development PD APR 1 PY 2007 VL 134 IS 7 BP 1301 EP 1310 DI 10.1242/dev.02807 PG 10 WC Developmental Biology SC Developmental Biology GA 144YM UT WOS:000244832500007 PM 17329368 ER PT J AU Wang, JY Chen, T Honma, M Chen, L Moore, MM AF Wang, Jianyong Chen, Tao Honma, Masamitsu Chen, Ling Moore, Martha M. TI 3 '-azido-3 '-deoxythymidine induces deletions in L5178Y mouse lymphoma cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE 3 '-azido-3 '-deoxythymidine; mouse lymphoma assay; loss of heterozygosity; copy number; mutation spectrum ID HUMAN-LYMPHOBLASTOID-CELLS; DOUBLE-STRAND BREAKS; THYMIDINE KINASE GENE; TRIFLUOROTHYMIDINE-RESISTANT; ILLEGITIMATE RECOMBINATION; DNA INCORPORATION; MUTANT FREQUENCY; SOMATIC-CELLS; ALLELIC LOSS; APRT LOCUS AB 3'-Azido-3'-deoxythymidine (AZT), a nucleoside analogue used for the treatment of acquired immunodeficiency syndrome (AIDS), induced a significant dose-related increase in the thymidine kinase (Tk) mutant frequency (MF) in L5178Y/Tk(+/-) 3.7.2C mouse lymphoma cells. Treatment with 1 mg/ml (3,742 mu M) AZT for 24 hr resulted in a MF of 407 X 10(-6) compared to a control MF of 84 x 10(-6). The MFs of the large and small colony mutants resulting from AZT exposure were 142 X 10-6 and 265 X 10-6, respectively. One hundred and fifty mutants from the 1 mg/ml (3,742 mu M) AZT-treated culture and sixty-nine mutants from independent untreated cultures were isolated and analyzed. LOH analysis using a heteromorphic microsatellite locus located in the Tk gene was performed to determine the presence or absence of the TV allele. Eight other microsatellite markers spanning the entire mouse chromosome 11 also were examined for heterozygosity to determine the extent of LOH. In addition, Tk gene dosage analysis was conducted using Real-Time PCR in those mutants showing LOH at the Tk locus. The presence of only one Tk allele based on Real-Time PCR indicated that the mutant resulted from deletion while the presence of two alleles was consistent with a recombination event. More mutants from the AZT-treated culture showed Tk LOH than did independent mutants from the untreated cultures (91% vs. 64%) and the induced mutants also showed distinct chromosome 11 LOH patterns. The mutation spectrum of mutants from AZT-treated cells was also significantly different from that of spontaneous mutants. More deletions and fewer intragenic mutations were observed in the mutants from the AZTtreated culture than independent mutants from the untreated control. Our data indicate that AZT primarily induced LOH mutations in L5178Y mouse lymphoma cells and a large number of LOH mutations resulted from deletions. Environ. Mal. Mutagen. 48:248-257, 2007. Published 2007 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, FDA, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 158, Japan. Shanghai Jiao Tong Univ, Coll Life Sci & Technol, Shanghai 200030, Peoples R China. RP Wang, JY (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, FDA, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jianyong.wang@fda.hhs.gov NR 58 TC 10 Z9 11 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR-MAY PY 2007 VL 48 IS 3-4 BP 248 EP 257 DI 10.1002/em.20263 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100011 PM 17358034 ER PT J AU Von Tungeln, LS Williams, LD Doerge, DR Shaddock, JG McGarrity, LJ Morris, SM Mittelstaedt, RA Heflich, RH Beland, FA AF Von Tungeln, Linda S. Williams, Lee D. Doerge, Daniel R. Shaddock, Joseph G. McGarrity, Lynda J. Morris, Suzanne M. Mittelstaedt, Roberta A. Heflich, Robert H. Beland, Frederick A. TI Transplacental drug transfer and frequency of Tk and Hprt lymphocyte mutants and peripheral blood micronuclei in mice treated transplacentally with zidovudine and lamivudine SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE metabolism; thymidine kinase; hypoxanthine-guanine phosphoribosyltransferase; loss of heterozygosity; pharmacokinetics ID HUMAN-IMMUNODEFICIENCY-VIRUS; BONE-MARROW MICRONUCLEI; ETHYL-N-NITROSOUREA; EXPOSED IN-UTERO; 3'-AZIDO-3'-DEOXYTHYMIDINE AZT; MITOCHONDRIAL TOXICITY; MUTATIONAL SPECTRA; UNINFECTED INFANTS; OXIDATIVE DAMAGE; PREGNANT BABOON AB In previous studies, we have shown that zidovudine (3'-azido-3'-deoxythymidine; AZT), but not lamivudine [(-)2',3'-dideoxy-3'-thiacytidine; 3TC], is genotoxic when administered to neonatal mice, and that 3TC when coadministered with AZT does not alter the responses observed with AZT alone (Von Tungeln et al. [20021 Carcinogenesis 23:1427-1432). We now have investigated the transplacental transfer of these drugs and the induction of mutants and micronuclei in the neonatal offspring. From gestational day 12 until parturition, female C57BL/6N and C57BL/6N/Tk(+/-) mice, which had been mated to male C3H/HeNMTV mice, were treated daily by gavage with AZT, 3TC, or a combination of AZT and 3TC. In both dams and fetuses, AZT was found at much higher levels than its metabolites, AZT 5'-glucuronide and 3'-azido-3'-deoxythymidine. In the neonates, AZT and the mixture of AZT and 3TC caused a decrease in the percentage of reticulocytes (RETs) and an increase in the percentage of micronucleated RETs and micronucleated normochromatic erythrocytes. When assessed 3 weeks after birth, AZT and the combination of AZT and 3TC increased the thymidine kinase (Tk) mutant frequency in male mice; at 5 weeks, 3TC increased the Tk mutant frequency in female mice. The increase in Tk mutants in mice treated with AZT and the mixture of AZT and 3TC was associated with loss of the wild-type (Tk) allele (loss of heterozygosity; LOH) and a pattern of discontinuous LOH. These data indicate that AZT, 3TC, and the combination of AZT and 3TC are transplacental mutagens and that the increase in mutants resulting from AZT is due mainly to largescale genetic alterations. Environ. Mal. Mutagen. 48:258-269, 2007. Published 2006 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM frederick.beland@fda.hhs.gov FU PHS HHS [224-93-001] NR 46 TC 26 Z9 26 U1 0 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD APR-MAY PY 2007 VL 48 IS 3-4 BP 258 EP 269 DI 10.1002/em.20237 PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100012 PM 16850453 ER PT J AU Dobrovolsky, VN Shaddock, JG Mittelstaedt, RA Bishop, ME Lewis, SM Lee, FW Aidoo, A Leakey, JEA Dunnick, JK Heflich, RH AF Dobrovolsky, Vasily N. Shaddock, Joseph G. Mittelstaedt, Roberta A. Bishop, Michelle E. Lewis, Sherry M. Lee, Fei W. Aidoo, Anane Leakey, Julian E. A. Dunnick, June K. Heflich, Robert H. TI Frequency of Hprt mutant lymphocytes and micronucleated erythrocytes in p53-haplodeficient mice treated perinatally with AZT and AZT in combination with 3TC SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE nucleoside analog reverse transcriptase inhibitors; reticulocytes; normochromatic erythrocytes; transplacental exposure; neonatal exposure ID IMMUNODEFICIENCY-VIRUS TYPE-1; MATERNAL-INFANT TRANSMISSION; TRANSGENIC MOUSE MODELS; ETHYL-N-NITROSOUREA; REVERSE-TRANSCRIPTASE; DNA-POLYMERASE; 3'-AZIDO-3'-DEOXYTHYMIDINE AZT; MITOCHONDRIAL TOXICITY; NUCLEOSIDE ANALOG; TK(+/-) MICE AB Azidothymidine (AZT) is a nucleoside reverse transcriptase inhibitor (NRTI) that is used for reducing mother-to-child transmission of human immunodeficiency virus 1. Combinations of AZT and 3'-thiacyticline (3TC) are even more effective than AZT alone. AZT, however, is a mutagen and carcinogen in rodent models and 3TC can increase the genotoxicity of AZT. Since p53 plays a key role in human and mouse tumorigenesis, p53-haplodeficient mice are currently being evaluated as a model for assessing the carcinogenicity of perinatal exposure to NRTIs. In the present study, male C57BL/6 p53(+/+) and p53(-/-) mice were mated with C3H p53(+/+) females; the pregnant females were treated on gestation day 12 through parturition with 40, 80, and 160 mg/kg of AZT or a combination of 160 mg/kg AZT and 100 mg/kg 3TC (AZT-3TC); the p53(+/+) and p53(+/-) offspring were treated daily after birth through postnatal day (PND) 28. The frequencies of micronucleated reticulocytes (MN-RETs) and micronucleated normochromatic erythrocytes (MN-NCEs) were determined on PNDI, PND 10, and PND28; the frequency of Hprt mutant lymphocytes was measured on PND28. The frequencies of MN-RETs and MN-NCEs were increased in treated animals at all time points; there were no differences in the responses of p53(+/+) and p53(+/-) animals treated with identical doses of NRTIs. After correction for clonal expansion, both AZT and AZT-3TC treatments induced small but significant increases in the frequency of Hprt mutant lymphocytes in p53(+/-) mice, but not in p53(+/+) mice. The data indicatethatp53 haplodeficiency affects the genotoxicity of NRTIs; thus, p53(+/-) mice may be a sensitive model for evaluating the carcinogenicity of perinatal exposure to NRTIs. Environ. Mol. Mutagen. 48:270-282, 2007. Published 2007 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, US FDA, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Off Sci Coordinat, Jefferson, AR 72079 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Dobrovolsky, VN (reprint author), Natl Ctr Toxicol Res, US FDA, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT 120, Jefferson, AR 72079 USA. EM vasily.dobrovolsky@fda.hhs.gov NR 50 TC 11 Z9 11 U1 0 U2 1 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-MAY PY 2007 VL 48 IS 3-4 BP 270 EP 282 DI 10.1002/em.20280 PG 13 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 151VE UT WOS:000245318100013 PM 17358030 ER PT J AU Shields, AF Briston, DA Chandupatla, S Douglas, KA Lawhorn-Crews, J Collins, JM Mangner, TJ Heilbrun, LK Muzik, O AF Shields, Anthony F. Briston, David A. Chandupatla, Samatha Douglas, Kirk A. Lawhorn-Crews, Jawana Collins, Jerry M. Mangner, Thomas J. Heilbrun, Lance K. Muzik, Otto TI A simplified analysis of [F-18]3 '-deoxy-3 '-fluorothymidine metabolism and retention (vol 32, pg 1269, 2005) SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Correction C1 Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Dept Internal Med, Detroit, MI 48202 USA. US FDA, Rockville, MD 20857 USA. Wayne State Univ, Dept Radiol, Detroit, MI USA. Wayne State Univ, Dept Pediat, Detroit, MI USA. RP Shields, AF (reprint author), Karmanos Canc Inst, 4100 John R St,4 HWCRC, Detroit, MI 48201 USA. EM shieldsa@karmanos.org NR 1 TC 0 Z9 0 U1 2 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD APR PY 2007 VL 34 IS 4 BP 613 EP 613 DI 10.1007/s00259-006-0335-8 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 146RE UT WOS:000244951300028 ER PT J AU Ellwood, K Shimakawa, T Brandt, M AF Ellwood, Kathleen Shimakawa, Tomoko Brandt, Mary TI Sources and intakes of added sugars in the United States SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 FDA CFSAN, Nutr Program & Labeling, College Pk, MD 20740 USA. FDA CFSAN, Res & Appl Technol, College Pk, MD 20740 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR PY 2007 VL 21 IS 5 BP A307 EP A308 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708502327 ER PT J AU Kirsch, SB Morris, D Humphrey, B AF Kirsch, Sandra Beth Morris, Diane Humphrey, Brooke TI Characterization of chicken cationic amino acid transporter-2 isoform tissue distribution, promoter usage and cellular localization SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. US FDA, Ctr Allergy & Infect Dis, Bethesda, MD 20892 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 2007 VL 21 IS 5 BP A531 EP A531 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708504298 ER PT J AU Miller, TJ Knapton, A Adeyemo, O Noory, LS Weaver, JL Hanig, JP Honchel, R Zhang, J Espandiari, P Benedick, MF Umbreit, TH Tomazic-Jezic, VJ Sadrieh, N AF Miller, Terry J. Knapton, Alan Adeyemo, Oluwafunke Noory, Laila S. Weaver, James L. Hanig, Joseph P. Honchel, Ronald Zhang, Jun Espandiari, Parvaneh Benedick, Matthew F. Umbreit, Thomas H. Tomazic-Jezic, Vesna J. Sadrieh, Nakissa TI Toxicology of Titanium Dioxide (TiO2) Nanoparticles: In vitro and in vivo evaluation of macrophage uptake of TiO2 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 US FDA, CDER, Silver Spring, MD 20993 USA. US FDA, CDRH, Silver Spring, MD 20993 USA. NR 0 TC 1 Z9 1 U1 1 U2 6 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 2007 VL 21 IS 6 BP A812 EP A812 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708700360 ER PT J AU Mitra, MS Donthamsetty, S Latendresse, JR Mehendale, HM AF Mitra, Mayurranjan S. Donthamsetty, Shishikiran Latendresse, John R. Mehendale, Harihara M. TI Nuclear factor PPAR-alpha induction in the heart plays a pivotal role in determining the final outcome of doxorubicin-induced cardiotoxicity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Louisiana Monroe, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Latendresse, John/A-9215-2009 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 2007 VL 21 IS 6 BP A799 EP A799 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708700304 ER PT J AU Pfeiffer, CM Johnson, CL Jain, RB Yetley, EA Picciano, MF Rader, JI Fisher, KD Mulinare, J Osterloh, JD AF Pfeiffer, Christine M. Johnson, Clifford L. Jain, Ram B. Yetley, Elizabeth A. Picciano, Mary Frances Rader, Jeanne I. Fisher, Ken D. Mulinare, Joe Osterloh, John D. TI Trends in blood folate levels in the United States, 1988-2004 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Ctr Dis Control & Prevent, Atlanta, GA 30341 USA. Ctr Dis Control & Prevent, HYAT Bldg 4, Hyattsville, MD USA. NIH, Rockville, MD 20892 USA. Food & Drug Adm, CPK1, College Pk, MD USA. Ctr Dis Control & Prevent, EXPK Bldg 12, Atlanta, GA 30329 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 2007 VL 21 IS 5 BP A104 EP A104 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708500500 ER PT J AU Shahab-Ferdows, S Anaya, M Rosado, J Pogribny, I Tryndyak, V Allen, LH AF Shahab-Ferdows, Setareh Anaya, Miriam Rosado, Jorge Pogribny, Igor Tryndyak, Volodymyr Allen, Lindsay H. TI Biochemical, hemtological, bone and DNA methylation responses to B 12 supplementation in deficient Mexican women SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Calif Davis, Dept Nutr, Davis, CA 95616 USA. Univ Autonoam, Queretaro, Mexico. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Calif Davis, Western Human Nutr Res Ctr, USDA ARS, Davis, CA 95616 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 2007 VL 21 IS 5 BP A679 EP A679 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505404 ER PT J AU Tsai, P Cao, GL Merkel, T Rosen, G AF Tsai, Pei Cao, Guan-Liang Merkel, Todd Rosen, Gerald TI A novel approach toward in vivo EPR imaging of B. anthracis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. Univ Maryland, Sch Pharm, Ctr EPR Imaging In Vivo Physiol, Baltimore, MD 21201 USA. Univ Maryland, Ctr Med Biotechnol, Inst Biotechnol, Baltimore, MD 21201 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20812 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 2007 VL 21 IS 5 BP A633 EP A633 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HD UT WOS:000245708505177 ER PT J AU Zhang, P Li, D Ray, R Singh, BR Keller, JE Adler, M Ray, P AF Zhang, Peng Li, Dan Ray, Radharaman Singh, Bal Ram Keller, James E. Adler, Michael Ray, Prabhati TI Targeted therapeutic peptide delivery to synaptic junctions as botulism countermeasure SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2007 Annual Meeting CY APR 28-MAY 02, 2007 CL Washington, DC C1 Walter Reed Army Inst Res, Silver Spring, MD 20910 USA. USA, Med Res Inst Chem Def, Aberdeen Proving Ground, MD 21010 USA. Univ Massachusetts, N Dartmouth, MA 02747 USA. US FDA, Bethesda, MD 20892 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 2007 VL 21 IS 6 BP A1001 EP A1001 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 157HF UT WOS:000245708702153 ER PT J AU Daly, KT Tracy, AC Malik, M Wang, T Francke-Carroll, S Magnuson, BA AF Daly, K. T. Tracy, A. C. Malik, M. Wang, T. Francke-Carroll, S. Magnuson, B. A. TI Enhanced estrogenic responses and sensitivity to azoxymethane following dietary soy isoflavone supplementation in older female rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE soy isoflavones; aberrant crypt foci; gastrointestinal; estradiol ID ABERRANT CRYPT FOCI; NORMAL COLONIC-MUCOSA; FED CHOLIC-ACID; POSTMENOPAUSAL WOMEN; CONTROLLED TRIAL; FISCHER-344 RAT; RECEPTOR-BETA; F344 RATS; ER-BETA; CANCER AB Soy isoflavones are popular supplements among middle-aged and older women based on their potential protection against cancer and their use as alternative hormone replacement therapy. The purpose of this study was to investigate the effects of dietary soy isoflavones on early stage colon cancer in various ages of female rats. Young (1 month), mature (11 month) and old (22 month) female Fisher 344 rats were fed either the control diet or a diet containing 0.4%, soy isoflavone isolate for 1 week, injected once with 20 mg/kg azoxymethane (AOM) and maintained on the diets for another 15 weeks. The concentration of isoflavones in the diet was 2 g/kg diet, composed of 1.2 g/kg genistin, 0.7 g/kg daidzin and 0.1 g/kg other isoflavones including glycitin, acetylgenistin, acetyldaidzin, genistein, daidzein, and glycitein. There was no difference over all ages in the development of preneoplastic colonic aberrant crypt foci between rats fed the soy compared to the control diet, indicating that the soy diet did not provide protection against early stage colonic carcinogenesis. On the contrary, several adverse effects of soy supplementation in female AOM-treated rats were observed. Soy-supplemented rats had greater weight loss and a slower recovery of body weight following the AOM injection compared to rats fed the control diet and these changes increased with age. Five of the 21 rats fed the soy supplement died before the end of the experiment while all animals on the control diet survived to term. The density of normal crypts lining the colonic mucosa was reduced in rats fed the soy compared to control diet, indicating gastrointestinal damage. Uterine weights, serum estradiol and serum isoflavone levels were increased in mature and old female rats fed the soy-supplemented diets compared to age-matched controls, suggesting an increasing estrogenic response with age to isoflavone supplementation. These adverse effects of soy isoflavones in aged female animals need further examination because women, and particularly older women, are the prime target population for consumption of soy supplements. (c) 2006 Elsevier Ltd. All rights reserved. C1 Univ Maryland, College Pk, MD 20742 USA. USDA, Phytonutrients Lab, Beltsville, MD 20705 USA. US FDA, CFSAN, Pathol Branch, College Pk, MD USA. USUHS, OBG, Bethesda, MD USA. RP Magnuson, BA (reprint author), Univ Maryland, College Pk, MD 20742 USA. EM bmagnuso@umd.edu NR 52 TC 7 Z9 8 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD APR PY 2007 VL 45 IS 4 BP 628 EP 637 DI 10.1016/j.fct.2006.10.021 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 157YR UT WOS:000245758000014 PM 17157426 ER PT J AU Hoofnagle, JH Doo, E Liang, TJ Fleischer, R Lok, ASF AF Hoofnagle, Jay H. Doo, Edward Liang, T. Jake Fleischer, Russell Lok, Anna S. F. TI Management of hepatitis B: Summary of a clinical research workshop SO HEPATOLOGY LA English DT Review ID TENOFOVIR DISOPROXIL FUMARATE; E-ANTIGEN SEROCONVERSION; TERM-FOLLOW-UP; HUMAN-IMMUNODEFICIENCY-VIRUS; LAMIVUDINE-RESISTANT PATIENTS; BONE-MARROW-TRANSPLANTATION; ADEFOVIR DIPIVOXIL THERAPY; HBEAG(+) CHRONIC HEPATITIS; ALPHA-INTERFERON TREATMENT; HIV-INFECTED PATIENTS AB Chronic hepatitis B is caused by persistent infection with the hepatitis B virus (HBV), a unique DNA vim that replicates through an RNA intermediate produced from a stable covalently dosed circular DNA molecule. Viral persistence appears to be due to inadequate innate and adaptive immune responses. Chronic infection has a variable course after several decades resulting in cirrhosis in up to one-third of patients and liver cancer in a proportion of those with cirrhosis. Sensitive assays for HBV DNA levels in serum have been developed that provide important insights into pathogenesis and natural history. Therapy of hepatitis B is evolving. Peginterferon induces long-term remissions in disease in one-third of patients with typical hepatitis B e antigen (HBeAg) positive chronic hepatitis B, but a lesser proportion of those without HBeAg. Several oral nucleoside analogues with activity against HBV have been shown to be effective in suppressing viral levels and improving biochemical and histological features of disease in a high proportion of patients with and without HBeAg, at least in the short term. What is uncertain is which agent or combination of agents is most effective, how long therapy should last, and which criteria should be used to start, continue, switch or stop therapy. Long-term therapy with nucleoside analogues may be the most appropriate approach to treatment, but the expense and lack of data on long-term safety and efficacy make recommendations difficult. Clearly, many basic and clinical research challenges remain in defining optimal means of management of chronic hepatitis B. C1 NIDDK, Liver Dis Res Branch, NIH, Bethesda, MD 20892 USA. NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. US FDA, Div Antiviral Prod, Silver Spring, MD USA. Univ Michigan, Med Ctr, Div Gastroenterol, Ann Arbor, MI 48109 USA. RP Hoofnagle, JH (reprint author), NIDDK, Liver Dis Res Branch, NIH, Bldg 31,Room 9A27,31 Ctr Dr, Bethesda, MD 20892 USA. EM HoofnagleJ@extra.niddk.nih.gov RI Lok, Anna /B-8292-2009; OI Yang, Shuman/0000-0002-9638-0890 FU Intramural NIH HHS NR 187 TC 352 Z9 413 U1 5 U2 33 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2007 VL 45 IS 4 BP 1056 EP 1075 DI 10.1002/hep.21627 PG 20 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 154MS UT WOS:000245512300026 PM 17393513 ER PT J AU Bassen, H Seidman, S Rogul, J Desta, AB Wolfgang, S AF Bassen, Howard Seidman, Seth Rogul, Jonathan Desta, Abiy B. Wolfgang, Steven TI AN EXPOSURE SYSTEM FOR EVALUATING POSSIBLE EFFECTS OF RFID ON VARIOUS FORMULATIONS OF DRUG PRODUCTS SO IEEE COMMUNICATIONS MAGAZINE LA English DT Article AB We developed hardware and software to perform exposure studies of the effects of certain RF electromagnetic fields on solid and liquid pharmaceuticals and biologics. The RF fields generated by our systems are similar to those emitted by RFID readers operating in the U. S. licensed HF and UHF bands (13.56 and 915 MHz, respectively). Our systems can expose drug samples (pharmaceuticals and biologics) to uniform electric (E) and/or magnetic (H) fields at levels that are much higher than those experienced by drugs near "worstcase" readers at a distance of 20 cm. Worst-case readers are defined as those that emit the highest allowable field strengths. Maximum field strengths near these readers were identified by measurements and computations of fields from commercial readers, and are extrapolated to the maximum allowable effective isotropic radiated power or field strength dictated by the U. S. Federal Communications Commission. The UHF system we developed included a commercially available circularly polarized antenna, a microwave generator with pulse modulation, a high-power amplifier, a plastic foam enclosure, and fiber optic temperature monitoring probes placed in the drugs and the surrounding air. The HF system we developed included a specially designed Helmholtz coil pair, an HF signal generator with pulse modulation, an HF amplifier, an RF impedance matching device, and the same enclosure, and thermometry system as in the UHF system. Exposures can be performed for each drug in both its retail primary package (the smallest container produced with an RFID tag on it, e. g., bottle) and in 54 mm diameter culture dishes. The containers are suitable for exposing a wide variety of formulations of drugs (tablets, liquids, powers, capsules, creams, etc.). Exposures of drugs in culture dishes ensure uniform induced electric fields and currents. In contrast, exposures in the primary containers (e. g., vials) allow studies that account for the interactions of RF fields with the packaging materials and container geometry. In our UHF system we can expose drugs to over 20 W effective isotropic radiated power, over five times the FCC limits. We evaluated H fields emitted by commercially available RFID readers. In our HF system we can expose drugs to at least five times the H field they produce at 20 cm from the reader. We can expose samples to 5 A/m in primary packaging or in special organ culture dishes with an outer concentric ring. The ring has inner and outer diameters of 32 mm and 55 mm, respectively. Computer monitoring of power, drug temperature, and air temperature can be performed continuously during exposure. Surrounding air temperature is monitored at all times while in our laboratory (storage and exposure) and while shipped to drug laboratories for analysis. C1 [Bassen, Howard] US FDA, Wireless & Electromagnet Lab, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Seidman, Seth] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Rogul, Jonathan; Wolfgang, Steven] US FDA, Rockville, MD 20857 USA. [Desta, Abiy B.] US FDA, Radiat Biol Lab, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Bassen, H (reprint author), US FDA, Wireless & Electromagnet Lab, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM howard.bassen@fda.hhs.gov; jonathan.rogul@gmail.com NR 7 TC 3 Z9 3 U1 2 U2 3 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0163-6804 EI 1558-1896 J9 IEEE COMMUN MAG JI IEEE Commun. Mag. PD APR PY 2007 VL 45 IS 4 SU S BP 17 EP 23 DI 10.1109/MCOM.2007.348673 PG 7 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA V32TW UT WOS:000208974500006 ER PT J AU Oakley, MSM Kumar, S Anantharaman, V Zheng, H Mahajan, B Haynes, JD Moch, JK Fairhurst, R McCutchan, TF Aravind, L AF Oakley, Miranda S. M. Kumar, Sanjai Anantharaman, Vivek Zheng, Hong Mahajan, Babita Haynes, J. David Moch, J. Kathleen Fairhurst, Rick McCutchan, Thomas F. Aravind, L. TI Molecular factors and biochemical pathways induced by febrile temperature in intraerythrocytic Plasmodium falciparum parasites SO INFECTION AND IMMUNITY LA English DT Article ID HEAT-SHOCK PROTEINS; MULTIPLE SEQUENCE ALIGNMENT; INFECTED ERYTHROCYTES; ANTIGENIC VARIATION; GROWTH-INHIBITION; MALARIA PARASITES; MOSQUITO MIDGUT; HEMOGLOBIN-C; IN-VITRO; APOPTOSIS AB Intermittent episodes of febrile illness are the most benign and recognized symptom of infection with malaria parasites, although the effects on parasite survival and virulence remain unclear. In this study, we identified the molecular factors altered in response to febrile temperature by measuring differential expression levels of individual genes using high-density oligonucleotide microarray technology and by performing biological assays in asexual-stage Plasmodiuntfalciparurn parasite cultures incubated at 37 degrees C and 41 degrees C (an elevated temperature that is equivalent to malaria-induced febrile illness in the host). Elevated temperature had a profound influence on expression of individual genes; 336 of approximately 5,300 genes (6.3% of the genome) had altered expression profiles. Of these, 163 genes (49%) were upregulated by twofold or greater, and 173 genes (51%) were downregulated by twofold or greater. In-depth sensitive sequence profile analysis revealed that febrile temperature-induced responses caused significant alterations in the major parasite biologic networks and pathways and that these changes are well coordinated and intricately linked. One of the most notable transcriptional changes occurs in genes encoding proteins containing the predicted Pexel motifs that are exported into the host cytoplasm or inserted into the host cell membrane and are likely to be associated with erythrocyte remodeling and parasite sequestration functions. Using our sensitive computational analysis, we were also able to assign biochemical or biologic functional predictions for at least 100 distinct genes previously annotated as "hypothetical." We find that cultivation of P.falciparum parasites at 41 degrees C leads to parasite death in a time-dependent manner. The presence of the "crisis forms" and the terminal deoxynucleotidyltransferase-mediated dUTP-biotin nick end labeling-positive parasites following heat treatment strongly support the notion that an apoptosis-like cell death mechanism might be induced in response to febrile temperatures. These studies enhance the possibility of designing vaccines and drugs on the basis of disruption in molecules and pathways of parasite survival and virulence activated in response to febrile temperatures. C1 US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. NIAID, Lab Malaria & Vector Res, NIH, Rockville, MD USA. Uniformed Serv Univ Hlth Sci, Emerging Infect Dis Program, Bethesda, MD 20814 USA. Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD USA. Walter Reed Army Inst Res, Silver Spring, MD USA. USN, Med Res Ctr, Silver Spring, MD USA. RP Kumar, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD 20892 USA. EM Sanjai.kumar@fda.hhs.gov OI Anantharaman, Vivek/0000-0001-8395-0009 FU Intramural NIH HHS NR 52 TC 69 Z9 70 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 APR PY 2007 VL 75 IS 4 BP 2012 EP 2025 DI 10.1128/IAI.01236-06 PG 14 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 153GY UT WOS:000245421400054 PM 17283083 ER PT J AU Smith, MJ Garrett, RH AF Smith, M. J. Garrett, R. H. TI Part II. Eosinophilia-Myalgia Syndrome: further correlations between compromised histamine degradation, eosinophilias and myopathies SO INFLAMMATION RESEARCH LA English DT Article; Proceedings Paper CT 35th Meeting of the European-Histamine-Research-Society CY MAY 10-13, 2006 CL Delphi, GREECE SP European Histamine Res Soc ID METABOLISM; RAT C1 US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, College Pk, MD 20740 USA. Univ Virginia, Dept Biol, Charlottesville, VA 22904 USA. RP Smith, MJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mitchell.smith@cfsan.fda.gov NR 8 TC 1 Z9 1 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 APR PY 2007 VL 56 BP S7 EP S8 DI 10.1007/s00011-006-0503-0 PG 2 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 163XI UT WOS:000246196100004 PM 17806156 ER PT J AU Phillips, AMB DePaola, A Bowers, J Ladner, S Grimes, DJ AF Phillips, A. M. B. DePaola, A. Bowers, J. Ladner, S. Grimes, D. J. TI An evaluation of the use of remotely sensed parameters for prediction of incidence and risk associated with Vibrio parahaemolyticus in Gulf Coast oysters (Crassostrea virginica) SO JOURNAL OF FOOD PROTECTION LA English DT Article ID UNITED-STATES; WATERS; GENE AB The U.S. Food and Drug Administration recently published a Vibrio parahaemol.y'ticus risk assessment for consumption of raw oysters that predicts V. parahaemolyticus densities at harvest based on water temperature. We retrospectively compared archived remotely sensed measurements (sea surface temperature, chlorophyll, and turbidity) with previously published data from an environmental study of V. parahaemolyticus in Alabama oysters to assess the utility of the former data for predicting V. parahaemolyticus densities in oysters. Remotely sensed sea surface temperature correlated well with previous in situ measurements (R-2 = 0.86) of bottom water temperature, supporting the notion that remotely sensed sea surface temperature data are a sufficiently accurate substitute for direct measurement. Turbidity and chlorophyll levels were not determined in the previous study, but in comparison with the V. parahaemolyticus data, remotely sensed values for these parameters may explain some of the variation in V. parahaemolyticus levels. More accurate determination of these effects and the temporal and spatial variability of these parameters may further improve the accuracy of prediction models. To illustrate the utility of remotely sensed data as a basis for risk management, predictions based on the U.S. Food and Drug Administration V. parahaemolyticus risk assessment model were integrated with remotely sensed sea surface temperature data to display graphically variations in V. parahaemolyticus density in oysters associated with spatial variations in water temperature. We believe images such as these could be posted in near real time, and that the availability of such information in a user-friendly format could be the basis for timely and informed risk management decisions. C1 Univ So Mississippi, Gulf Coast Res Lab, Ocean Springs, MS 39564 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. Planning Syst Inc, Stennis Space Ctr, MS 39529 USA. US FDA, College Pk, MD USA. RP Grimes, DJ (reprint author), Univ So Mississippi, Gulf Coast Res Lab, Ocean Springs, MS 39564 USA. EM jay.grimes@usm.edu NR 34 TC 23 Z9 24 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 APR PY 2007 VL 70 IS 4 BP 879 EP 884 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 154RK UT WOS:000245525000010 PM 17477256 ER PT J AU Brzezinski, JL AF Brzezinski, Jennifer L. TI Detection of sesame seed DNA in foods using real-time PCR SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MAJOR ALLERGEN; 2S ALBUMIN; IDENTIFICATION; CHILDREN; INFANTS; SENSITIZATION; ANAPHYLAXIS; EXPRESSION; PROTEINS; HAZELNUT AB The detection of potentially allergenic foods, Such as sesame seeds, in food products is a major concern for the food-processing industry. A real-time PCR method was designed to determine if sesame seed DNA is present in food products. The PCR reaction amplifies a 66-bp fragment of the sesame seed 2S albumin gene, which is detected with a sesame-specific, dual-labeled TaqMan probe. This reaction will not amplify DNA derived from other seeds present in baked goods, such as pumpkin, poppy, and sunflower seeds. Additionally, this assay will not cross-react with DNA from several tree nut species, such as almond, Brazil nut, cashew, hazelnut, and walnut, as well as four varieties of peanut. This assay is sensitive enough to detect 5 pg of purified sesame seed DNA, as well as sesame seed DNA in a spiked wheat cracker sample. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Brzezinski, JL (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM jennifer.brzezinski@fda.gov NR 30 TC 20 Z9 22 U1 2 U2 8 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 2007 VL 70 IS 4 BP 1033 EP 1036 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 154RK UT WOS:000245525000035 PM 17477281 ER PT J AU Akkoyunlu, M Kanswal, S Katsenelson, N AF Akkoyunlu, Mustafa Kanswal, Sunita Katsenelson, Nora TI Severely reduced B cell TACI expression in newborn mice lead to impaired BAFF or APRIL induced immunoglobulin secretion SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Akkoyunlu, Mustafa; Kanswal, Sunita; Katsenelson, Nora] US FDA, Div Bacterial Parasit & Allergen Prod, CBER, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 95.13 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758202311 ER PT J AU Farber, JM Song, KM Zhang, HWH Rabin, RL Hill, BJ Sereti, I Prussin, C Siegel, RM Douek, DC Roederer, M AF Farber, Joshua M. Song, Kaimei Zhang, Hongwei H. Rabin, Ronald L. Hill, Brenna J. Sereti, Irini Prussin, Colman Siegel, Richard M. Douek, Daniel C. Roederer, Mario TI CCR2 identifies first responders among human CD4+memory T cells: long-lived, apoptosis-resistant, antigen-responsive cells with enhanced migration potential, a low threshold for activation, and immediate effector capabilities SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Farber, Joshua M.; Song, Kaimei; Zhang, Hongwei H.; Hill, Brenna J.; Sereti, Irini; Prussin, Colman; Douek, Daniel C.; Roederer, Mario] NIAID, Bethesda, MD USA. [Rabin, Ronald L.] US FDA, Bethesda, MD USA. [Siegel, Richard M.] NIAMS, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 85.5 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758202145 ER PT J AU Loving, CL Chaplin, DD Iwakura, Y Merkel, TJ AF Loving, Crystal Lynn Chaplin, David D. Iwakura, Yoichiro Merkel, Tod J. TI Differential role for IL-1 dependent on anthrax infection route SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Loving, Crystal Lynn; Merkel, Tod J.] US FDA, Lab Resp & Special Pathogens, CBER, Bethesda, MD 20892 USA. [Chaplin, David D.] Univ Alabama Birmingham, Dept Microbiol, Birmingham, AL 35294 USA. [Iwakura, Yoichiro] Univ Tokyo, Ctr Med Expt, Minato Ku, Tokyo 1088639, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA B176 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758201132 ER PT J AU Sakamoto, N Tuji, K Muul, LM Lawler, AM Candotti, F Metcalf, JA Tayel, JA Lane, HC Urba, WJ Fox, BA Varki, AP Lunney, JK Rosenberg, AS AF Sakamoto, Norihisa Tuji, Kuzuhide Muul, Linda M. Lawler, Ann M. Candotti, Fabio Metcalf, Julia A. Tayel, Jorge A. Lane, H. Clifford Urba, Walter J. Fox, Bernard A. Varki, Ajit P. Lunney, Joan K. Rosenberg, Amy S. TI Bovine apolipoprotein B-100 is a dominant immunogen in therapeutic cell populations cultured in FCS in mice and humans SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Sakamoto, Norihisa; Rosenberg, Amy S.] US FDA, CDER, Bethesda, MD 20892 USA. [Tuji, Kuzuhide] Okayama Univ, Okayama 7008558, Japan. [Muul, Linda M.; Candotti, Fabio] NHGRI, NIH, Bethesda, MD 20892 USA. [Lawler, Ann M.] Johns Hopkins Univ, Sch Med, Baltimore, MD 21205 USA. [Metcalf, Julia A.; Tayel, Jorge A.; Lane, H. Clifford] NIAID, NIH, Bethesda, MD 20892 USA. [Urba, Walter J.; Fox, Bernard A.] Providence Portland Med Ctr, Providence Portland Medi, Earle A Chiles Res Inst, Robert W Franz Canc Res Ctr, Portland, OR 97213 USA. [Varki, Ajit P.] Univ Calif San Diego, La Jolla, CA 92093 USA. [Lunney, Joan K.] ARS, USDA, Beltsville, MD 20705 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 88.29 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758202113 ER PT J AU Shin, EC Seifert, U Urban, S Truong, KT Feinstone, SM Rice, CM Kloetzel, PM Rehermann, B AF Shin, Eui-Cheol Seifert, Ulrike Urban, Sabrina Truong, Kim-Thuy Feinstone, Stephen M. Rice, Charles M. Kloetzel, Peter-M Rehermann, Barbara TI Proteasome activator and antigen-processing aminopeptidases are regulated by virus induced type I interferon in the hepatitis C virus-infected liver SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Shin, Eui-Cheol; Truong, Kim-Thuy; Rehermann, Barbara] NIDDK, Immunol Sect, LDB, NIH, Bethesda, MD 20892 USA. [Seifert, Ulrike; Urban, Sabrina; Kloetzel, Peter-M] Humboldt Univ, Charite, Inst Biochem, D-10117 Berlin, Germany. [Feinstone, Stephen M.] US FDA, Lab Hepatitis Viruses, CBER, Bethesda, MD 20892 USA. [Rice, Charles M.] Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 44.39 PG 1 WC Immunology SC Immunology GA V44OL UT WOS:000209758201348 ER PT J AU Zhu, Q Belyakov, IM Klinman, DM Berzofsky, JA AF Zhu, Qing Belyakov, Igor M. Klinman, Dennis M. Berzofsky, Jay A. TI In vivo synergy of TLR ligands through activation of distinct signaling pathways in dendritic cells SO JOURNAL OF IMMUNOLOGY LA English DT Meeting Abstract C1 [Zhu, Qing; Belyakov, Igor M.; Berzofsky, Jay A.] NCI, Vaccine Branch, NIH, Bethesda, MD 20892 USA. [Klinman, Dennis M.] US FDA, Sect Retroviral Res, CBER, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 EI 1550-6606 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 2007 VL 178 SU 1 MA 52.1 PG 2 WC Immunology SC Immunology GA V44OL UT WOS:000209758200300 ER PT J AU Boekhoudt, GH Frazier-Jessen, MR Feldman, GM AF Boekhoudt, Gunther H. Frazier-Jessen, Michelle R. Feldman, Gerald M. TI Immune complexes suppress IFN-gamma signaling by activation of the Fc-gamma RI pathway SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE monocytes; Jak/STAT; cytokine signaling; Fc receptors ID INTERFERON-GAMMA; MYCOBACTERIAL INFECTION; INDUCED TRANSCRIPTION; ANTIVIRAL DEFENSE; RECEPTORS; GENE; PHOSPHATASE; EXPRESSION; KINASE; MICE AB Antigen-driven immune responses are modulated by immune complexes (ICs), in part through their ability to inhibit IFN-gamma-dependent MHC Class 11 expression. We have demonstrated previously that ICs dramatically inhibit IFN-gamma-induced activation of human monocytes through the suppression of the JAK/STAT signaling pathway. In the current study, we further explore the mechanisms by which ICs regulate IFN-gamma activation of human monocytes. Consistent with previous studies in monocytes pretreated with ICs, there was a reduction in steady-state levels of RNA by real-time RT-PCR of the IFN-inducible protein 10 gene as well as the Fc gamma RI gene. Pull-down assays confirm that IC pretreatment inhibits IFN-gamma-induced STAT1 phosphorylation without affecting the ability of STAT1 to bind to the STAT1-binding domain of the IFN-gamma receptor. In addition, the inhibitory function of ICs was reduced when cells from the FcR common gamma-chain knockout mice were used, supporting the role of the Fc gamma RI in this inhibitory pathway. It is unexpected that ICs also require the phosphatase Src homology-2-containing tyrosine phosphatase 1 (SHP-1) to inhibit IFN-gamma induction, as demonstrated by studies with cells from the SHP-1 knockout (motheaten) mice. These data suggest a mechanism of IC-mediated inhibition of IFN-gamma signaling, which requires the ITAM-containing Fc gamma RI, as well as the ITIM-dependent phosphatase SHP-1, ultimately resulting in the suppression of STAT1 phosphorylation. C1 CDER, OPS, Food & Drug Adm,Off Pharmaceut Sci,Ctr Drug Evalu, Div Monoclonal Antibodies,Off Biotechnol Prod, Bethesda, MD 20892 USA. RP Feldman, GM (reprint author), CDER, OPS, Food & Drug Adm,Off Pharmaceut Sci,Ctr Drug Evalu, Div Monoclonal Antibodies,Off Biotechnol Prod, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM gerald.feldman@fda.hhs.gov NR 34 TC 13 Z9 13 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 APR PY 2007 VL 81 IS 4 BP 1086 EP 1092 DI 10.1189/jlb.0906543 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 153TL UT WOS:000245458000026 PM 17227821 ER PT J AU Midha, KK Shah, VP Singh, GJP Patnaik, R AF Midha, Kamal K. Shah, Vinod P. Singh, Gur Jai Pal Patnaik, Rabi TI Conference report: Bio-international 2005 SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Editorial Material DE bioequivalence; bioavailability; Biopharmaceutics Classification System; regulatory science; transdermal ID HIGHLY-VARIABLE DRUGS; IN-VIVO; BIOEQUIVALENCY ASSESSMENT; TOPICAL TERBINAFINE; PRODUCTS; BIOAVAILABILITY; METABOLITES; CLASSIFICATION; AVAILABILITY; ASTHMA AB This is a summary report of the International Pharmaceutical Federation/Board of Pharmaceutical Sciences (FIP/BPS) international conference, Bio-International 2005, which was held October 24-26, 2005 at the Royal Pharmaceutical Society, in London, UK. Bioequivalence (BE) issues related to multisource locally delivered topical dosage forms, oral inhalation drug products, highly variable drug products (HVDP), and endogenously occurring drugs were discussed. The conference also focused on alternate approaches to assess BE for some of these drug products. Pharmacokinetic (PK) approaches like, dermatopharmacokinetics (DPK) for dermatological topical dosage forms, scaled average BE (s-ABE) where within-subject variability is considered for estimation of 90% confidence intervals to document BE for highly variable drugs (HVD) were recommended. In addition, issues and difficulties related to the BE assessment of oral inhalation products, role, and appropriateness of metabolites in BE assessment, importance of base line correction in BE assessment of endogenously occurring drugs, and waiver of BE study requirements for certain drugs based on a Biopharmaceuties Classification System (BCS), were also discussed. C1 Univ Saskatchewan, Coll Pharm & Med, Saskatoon, SK S7N 0W0, Canada. Pharmalyt Inc, Saskatoon, SK, Canada. FIP Sci Secretary, N Potomac, MD USA. US FDA, Div Bioequivalence, Rockville, MD USA. Watson Labs, Corona, CA USA. RP Midha, KK (reprint author), Univ Saskatchewan, Coll Pharm & Med, Saskatoon, SK S7N 0W0, Canada. EM midha@pharmalytics.ca NR 36 TC 19 Z9 21 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD APR PY 2007 VL 96 IS 4 BP 747 EP 754 DI 10.1002/jps.20786 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 153IW UT WOS:000245426900003 PM 17094144 ER PT J AU Wear, KA AF Wear, Keith A. TI Group velocity, phase velocity, and dispersion in human calcaneus in vivo SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID BOVINE CANCELLOUS BONE; QUANTITATIVE ULTRASOUND MEASUREMENTS; TRABECULAR BONE; HIP FRACTURE; MINERAL-CONTENT; ACOUSTIC-WAVES; OS CALCIS; POWER-LAW; ATTENUATION; DENSITY AB Commercial bone sonometers measure broadband ultrasonic attenuation and/or speed of sound (SOS) in order to assess bone status. Phase velocity, which is usually measured in frequency domain, is a fundamental material property of bone that is related to SOS, which is usually measured in time domain. Four previous in vitro studies indicate that phase velocity in human cancellous bone decreases with frequency (i.e., negative dispersion). In order to investigate frequency-dependent phase velocity in vivo, through-transmission measurements were performed in 73 women using a GE Lunar Achilles Insight (R) commercial bone sonometer. Average phase velocity at 500 kHz was 1489 +/- 55 m/s (mean standard deviation). Average dispersion rate was -59 +/- 52 m/sMHz. Group velocity was usually lower than phase velocity, as is expected for negatively dispersive media. Using a stratified model to represent cancellous bone, the reductions in phase velocity and dispersion rate in vivo as opposed to in vitro can be explained by (1) the presence of marrow instead of water as a fluid filler, and (2) the decreased porosity of bones of living (compared with deceased) subjects. (c) 2007 Acoustical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-142 12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 58 TC 27 Z9 28 U1 1 U2 4 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 APR PY 2007 VL 121 IS 4 BP 2431 EP 2437 DI 10.1121/1.2697436 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 156ZE UT WOS:000245687600056 PM 17471754 ER PT J AU Mossoba, MM Kramer, JKG Milosevic, V Milosevic, M Azizian, H AF Mossoba, M. M. Kramer, J. K. G. Milosevic, V. Milosevic, M. Azizian, H. TI Interference of saturated fats in the determination of low levels of trans fats (below 0.5%) by infrared spectroscopy SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article ID RAPID-DETERMINATION AB The mandate to label food products with the content of total trans fatty acids has led to an increase in demand for sensitive and accurate methodologies for the rapid quantitation of trans fats. Unfortunately, the latest official infrared (IR) spectroscopic method lacks the required sensitivity. A more sensitive IR procedure that requires the measurement of the height of the second derivative (2D) of the trans absorption band at 966 cm(-1) was recently proposed; however, a reported inconsistency at low trans levels between GC (0% of total fat) and IR (1.2% of total fat) results for a fully hydrogenated vegetable oil could not be reconciled, and triggered further investigations. For the first time, we recognize and report the presence of weak interference bands (962-956 cm(-1)) attributed to saturated fats in the IR spectra of trans fats; these interference bands have an adverse impact on the sensitivity and accuracy of the IR determination at low trans levels (<= 0.5% of total fat). Therefore, weak spectral features observed at energies below the one expected for trans bands (966 cm(-1)) in test samples high in saturated fat (coconut oil and cocoa butter) must not be mistaken for trans bands. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Agr & Agri Food Canada, Guelph, ON, Canada. MeV Photon, Westport, CT USA. NIR Technol, Oakville, ON, Canada. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Mail Stop HFS-717,Room BE-012,5100 Paint Branch P, College Pk, MD 20740 USA. EM magdi.mossoba@fda.hhs.gov NR 7 TC 17 Z9 18 U1 0 U2 8 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD APR PY 2007 VL 84 IS 4 BP 339 EP 342 DI 10.1007/s11746-007-1038-4 PG 4 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 154HD UT WOS:000245496600004 ER PT J AU Park, S Gallas, BD Badano, A Petrick, NA Myers, KJ AF Park, Subok Gallas, Bradon D. Badano, Aldo Petrick, Nicholas A. Myers, Kyle J. TI Efficiency of the human observer for detecting a Gaussian signal at a known location in non-Gaussian distributed lumpy backgrounds SO JOURNAL OF THE OPTICAL SOCIETY OF AMERICA A-OPTICS IMAGE SCIENCE AND VISION LA English DT Article ID MODEL OBSERVERS; DETECTION TASKS; IMAGE QUALITY; PERFORMANCE; NOISE; MAMMOGRAMS AB A previous study [J. Opt. Soc. Am. A 22, 3 (2005)] has shown that human efficiency for detecting a Gaussian signal at a known location in non-Gaussian distributed lumpy backgrounds is approximately 4%. This human efficiency is much less than the reported 40% efficiency that has been documented for Gaussian-distributed lumpy backgrounds [J. Opt. Soc. Am. A 16, 694 (1999) and J. Opt. Soc. Am. A 18, 473 (2001)]. We conducted a psychophysical study with a number of changes, specifically in display-device calibration and data scaling, from the design of the aforementioned study. Human efficiency relative to the ideal observer was found again to be approximately 5%. Our variance analysis indicates that neither scaling nor display made a statistically significant difference. in human performance for the task. We conclude that the non-Gaussian distributed lumpy background is a major factor in our low human-efficiency results. (c) 2007 Optical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math,Lab Assessment Med Imagin, Natl Inst Biomed Imaging & Bioengn, Rockville, MD 20852 USA. RP Park, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Imaging & Appl Math,Lab Assessment Med Imagin, Natl Inst Biomed Imaging & Bioengn, Rockville, MD 20852 USA. EM subok.park@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 FU Intramural NIH HHS NR 26 TC 10 Z9 10 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1084-7529 J9 J OPT SOC AM A JI J. Opt. Soc. Am. A-Opt. Image Sci. Vis. PD APR PY 2007 VL 24 IS 4 BP 911 EP 921 DI 10.1364/JOSAA.24.000911 PG 11 WC Optics SC Optics GA 152EL UT WOS:000245343600002 PM 17361278 ER PT J AU Tami, C Silberstein, E Manangeeswaran, M Freeman, GJ Umetsu, SE DeKruyff, RH Umetsu, DT Kaplan, GG AF Tami, Cecilia Silberstein, Erica Manangeeswaran, Mohanraj Freeman, Gordon J. Umetsu, Sarah E. DeKruyff, Rosemarie H. Umetsu, Dale T. Kaplan, Gerardo G. TI Immunoglobulin A (IgA) is a natural ligand of hepatitis A virus cellular receptor 1 (HAVCR1), and the association of IgA with HAVCR1 enhances virus-receptor interactions SO JOURNAL OF VIROLOGY LA English DT Article ID T-CELL-ACTIVATION; TIM GENE FAMILY; MONOCLONAL-ANTIBODY 190/4; KIDNEY INJURY MOLECULE-1; NECROSIS-FACTOR-ALPHA; HEPATITIS-A; PERIPHERAL TOLERANCE; HUMAN MONOCYTES; MUCIN-DOMAIN; RICH REGION AB The hepatitis A virus cellular receptor 1 (HAVCR1/TIM1), a member of the T-cell immunoglobulin mucin (TIM) family, is an important atopy susceptibility gene in humans. The exact natural function of HAVCR1/ TIM1 and the inverse association between HAV infection and prevention of atopy are not well understood. To identify natural ligands of human HAVCR1/TIM1, we used an expression cloning strategy based on the binding of dog cells transfected with a human lymph node cDNA library to a RAVCR1/TIM1 Fc fusion protein. The transfected cells that bound to the human HAVCR1/TIM1 Fc contained cDNA of human immunoglobulin alpha 1 heavy (Ig alpha 1) and lambda light (Ig lambda) chain and secreted human IgA1 lambda antibody that bound to the cell surface. Cotransfection of the isolated Ig alpha 1 and Ig lambda cDNAs to naive dog cells resulted in the secretion of IgA1 lambda that bound to HAVCR1/TIM1 Fc but not to a poliovirus receptor Fc fusion protein in a capture enzyme-linked immunosorbent assay. The interaction of HAVCR1/TIM1 with IgA was inhibited by monoclonal antibodies (MAbs) against Ig alpha 1 and Ig lambda, excess IgA1 lambda, or anti-HAVCR1/TIM1 MAN IgA did not inhibit HAV infection of African green monkey cells, suggesting that the IgA and the virus binding sites are in different epitopes on HAVCR1/TIM1. IgA enhanced significantly the neutralization of HAV by HAVCR1/TIM1 Fc. Our results indicate that IgA1 lambda is a specific ligand of HAVCR1/TIM1 and that their association has a synergistic effect in virus-receptor interactions. C1 US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA. Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA. Northwestern Univ, Feinberg Sch Med, Dept Immunol Microbiol, Chicago, IL 60611 USA. Harvard Univ, Childrens Hosp, Sch Med, Karp Labs,Div Immunol, Boston, MA 02115 USA. RP Kaplan, GG (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis & Related Emerging Agents, Bethesda, MD 20892 USA. EM GK@helix.nih.gov FU NIAID NIH HHS [P01 AI 54456, P01 AI054456] NR 53 TC 25 Z9 28 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 APR PY 2007 VL 81 IS 7 BP 3437 EP 3446 DI 10.1128/JVI.01585-06 PG 10 WC Virology SC Virology GA 147FF UT WOS:000244988100039 PM 17229699 ER PT J AU Bowers, DC McNeil, DE Liu, Y Leisenring, W Stovall, M Gurney, JG Robison, LL Packer, RJ Oeffinger, KC AF Bowers, D. C. McNeil, D. E. Liu, Y. Leisenring, W. Stovall, M. Gurney, J. G. Robison, L. L. Packer, R. J. Oeffinger, K. C. TI Risk of stroke among long-term survivors of childhood brain tumors: A report from the childhood cancer survivor study SO NEURO-ONCOLOGY LA English DT Meeting Abstract CT 12th International Symposium on Pediatric Neuro-Oncology CY JUL 06-09, 2006 CL Nara, JAPAN C1 Univ Texas SW, Med Ctr, Dallas, TX USA. US FDA, Rockville, MD USA. Fred Hutchinson Canc Res Ctr, Seattle, WA 98104 USA. Univ Texas, MD Anderson Canc Ctr, Houston, TX 77030 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Univ Minnesota, Minneapolis, MN USA. St Jude Childrens Hosp, Memphis, TN 38105 USA. Childrens Natl Med Ctr, Washington, DC USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 1522-8517 J9 NEURO-ONCOLOGY JI Neuro-Oncology PD APR PY 2007 VL 9 IS 2 BP 170 EP 171 PG 2 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 154EJ UT WOS:000245489300015 ER PT J AU Wyeth, J Green, L Avigan, M AF Wyeth, Jo Green, Lanh Avigan, Mark TI US Food and Drug Administration analysis of strokes associated with raloxifene SO OBSTETRICS AND GYNECOLOGY LA English DT Letter ID BREAST-CANCER; TAMOXIFEN; METAANALYSIS; EVENTS; RISK C1 US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Wyeth, J (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 4 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD APR PY 2007 VL 109 IS 4 BP 999 EP 999 DI 10.1097/01.AOG.0000260152.10941.f6 PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 195AI UT WOS:000248384500028 PM 17400869 ER PT J AU Chang, S Begier, EM Schech, SD Venus, P Shatin, D Braun, MM Ball, R AF Chang, Soju Begier, Elizabeth M. Schech, Stephanie D. Venus, Patricia Shatin, Deborah Braun, M. Miles Ball, Robert TI Perinatal hepatitis B transmission and vaccination timing in a managed care cohort - Assessment of the temporary delay in newborn hepatitis B vaccination due to thimerosal content SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE perinatal hepatitis B transmission; childhood immunization; thimerosal ID JOINT STATEMENT; INFANTS BORN; RECOMMENDATIONS; IMPACT; POPULATION; VACCINES; COVERAGE; SURVEILLANCE; HOSPITALS; WOMEN AB Background: From July to September 1999, due to a concern of toxicity from exposure to thimerosal-containing vaccines, the American Academy of Pediatrics and U.S. Public Health Service temporarily recommended delaying the administration of first dose of hepatitis B vaccine until the age of 2-6 months for infants born to hepatitis B surface antigen negative mothers. Our objectives were to determine whether the recommendation affected the rate of perinatal hepatitis B infection in a multistate managed care population; to describe neonatal and early childhood cases of hepatitis B infection and to evaluate a possible role of the recommendation; and to assess the timeliness. with respect to the U.S. childhood immunization schedule. of vaccinations during the first 2 years of life. Methods: We identified 3 cohorts of infants born before (July 1998 to June 1999). during (July 1999 to September 1999) and after (October 1999 to September 2000) the recommendation period. We used automated claims data to identify possible neonatal and early childhood hepatitis B cases using specific ICD-9 diagnosis and CPT procedure codes and validated cases through medical record review. Using Health Plan Employer Data and Information Set (HEDIS) data, we calculated vaccination coverage for the first dose of hepatitis B vaccine at 3-month intervals from January 1999 to September 2000. Results: The eligible populations in the "before" "during" and "after" cohorts were 29,347, 7791 and 29,215 infants, respectively. Of 41 possible hepatitis B cases identified in the 3 cohorts, we confirmed 1 case in the after cohort with medical record review. Despite receiving the first dose of hepatitis B vaccine and hepatitis B immunoglobulin within 12-24 hours of birth, the infant was diagnosed with laboratory-confirmed chronic hepatitis B at age of 9 months. An analysis of HEDIS data showed that vaccination coverage for the first dose of hepatitis B vaccine was 98% (January to March 1999) and 96% (April to June 1999) for the "before" cohort and 66% for the "during" cohort. For the "after" cohort the coverage was 72% (October to December 1999), 83% (January to March 2000), 91% (April to June 2000) and 95% (July to September 2000). Conclusions: This study did not identify any perinatal hepatitis B transmission among health plan enrollees associated with the 1999 recommendation. The recommendation did result in a delay of hepatitis B birth dose in the "during" cohort as intended for infants born to hepatitis B surface antigen negative mothers. Six months after the recommendation was rescinded there was still a delay in the timing of first dose of hepatitis B vaccine, but the timing had returned to the prerecommendation level after 9-12 months. C1 US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN USA. RP Ball, R (reprint author), US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 222, Rockville, MD 20852 USA. EM robert.ball@fda.hhs.gov NR 31 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD APR PY 2007 VL 26 IS 4 BP 329 EP 333 DI 10.1097/01.inf.0000258616.12752.51 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 151JV UT WOS:000245287200011 PM 17414397 ER PT J AU Miller, SA Coelho, SG Zmudzka, BZ Beer, JZ AF Miller, S. A. Coelho, S. G. Zmudzka, B. Z. Beer, J. Z. TI Criticism of FDA pilot study unfounded (response to R. M. Sayre and J. C. Dowdy) (vol 23, pg 59, 2007) SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Correction C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Miller, SA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy,HFZ-130, Rockville, MD 20850 USA. EM sharona.miller@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD APR-JUN PY 2007 VL 23 IS 2-3 BP 103 EP 103 PG 1 WC Dermatology SC Dermatology GA 167JW UT WOS:000246449000010 ER PT J AU Wu, KM Farrelly, JG Upton, R Chen, J AF Wu, K. M. Farrelly, J. G. Upton, R. Chen, J. TI Complexities of the herbal nomenclature system in traditional Chinese medicine (TCM): Lessons learned from the misuse of Aristolochia-related species and the importance of the pharmaceutical name during botanical drug product development SO PHYTOMEDICINE LA English DT Article DE misuse of Aristolochia-related species; nomenclature in traditional chinese medicine (TCM); pharmaceutical name required AB Herbs used in traditional Chinese medicine (TCM) have diverse cultural/historical backgrounds and are described based on complex nomenclature systems. Using the family Aristolochiaceae as an example, at least three categories of nomenclature could be identified: (1) one-to-one (one plant part from one species): the herb guan mutong refers to the root of Aristolochia manshuriensis; (2) multiple-to-one (multiple plant parts from the same species serve as different herbs): three herbs, madouling, qingmuxiang and tianxianteng, derived respectively from the fruit, root and stem of Aristolochia debilis; and (3) one-to-multiple (one herb refers to multiple species): the herb fangji refers to the root of either Aristolochia fangchi, Stephania tetrandra or Cocculus trilobus; in this case, the first belongs to a different family (Aristolochiaceae) than the latter two (Menispermaceae), and only the first contains aristolochic acid (AA), as demonstrated by independent analytical data provided in this article. Further, mutong (Akebia quinata) is allowed in TCM herbal medicine practice to be substituted with either guan mutong (Aristolochia manshuriensis) or chuan mutong (Clematis armandii); and mu fangji (Cocculus trilobus) by guang fanchi (Aristolochia fangchi) or hanzhong fangji (Aristolochia heterophylla), thereby increasing the risk of exposing renotoxic AA-containing Aristolochia species to patients. To avoid these and other confusions, we wish to emphasize the importance of a pharmaceutical name, which defines the species name, the plant part, and sometimes the special process performed on the herb, including cultivating conditions. The pharmaceutical name as referred to in this article is defined, and is limited to those botanicals that are intended to be used as drug. It is hoped that by following the pharmaceutical name, toxic herbs can be effectively identified and substitution or adulteration avoided. (c) 2006 Elsevier GmbH. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Amer Herbal Pharmacopoeia, Scotts Valley, CA 95067 USA. Chengdu Univ TCM, Chengdu, Sichuan, Peoples R China. RP Wu, KM (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kueimeng.wu@fda.hhs.gov NR 9 TC 41 Z9 41 U1 1 U2 8 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 APR PY 2007 VL 14 IS 4 BP 273 EP 279 DI 10.1016/j.phymed.2006.05.009 PG 7 WC Plant Sciences; Chemistry, Medicinal; Integrative & Complementary Medicine; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy; Integrative & Complementary Medicine GA 163BV UT WOS:000246134400006 PM 16863692 ER PT J AU Kodell, RL Chen, JJ AF Kodell, Ralph L. Chen, James J. TI On the use of hierarchical probabilistic models for characterizing and managing uncertainty in risk/safety assessment SO RISK ANALYSIS LA English DT Article DE ADI; Bayesian; empirical distribution; Monte Carlo; RfD; unitary factor ID REFERENCE DOSE RFD; RISK-ASSESSMENT; CANCER AB A general probabilistically-based approach is proposed for both cancer and noncancer risk/safety assessments. The familiar framework of the original ADI/RfD formulation is used, substituting in the numerator a benchmark dose derived from a hierarchical pharmacokinetic/pharmacodynamic model and in the denominator a unitary uncertainty factor derived from a hierarchical animal/average human/sensitive human model. The empirical probability distributions of the numerator and denominator can be combined to produce an empirical human-equivalent distribution for an animal-derived benchmark dose in external-exposure units. C1 Univ Arkansas Med Sci, Dept Biostat, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Biometry Branch, Jefferson, AR 72079 USA. RP Kodell, RL (reprint author), Univ Arkansas Med Sci, Dept Biostat, 4301 W Markham St,781, Little Rock, AR 72205 USA. EM rlkodell@uams.edu NR 17 TC 6 Z9 6 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD APR PY 2007 VL 27 IS 2 BP 433 EP 437 DI 10.1111/j.1539-6924.2007.00895.x PG 5 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 169XO UT WOS:000246625600014 PM 17511709 ER PT J AU Anderson, SA Menis, M O'Connell, K Burwen, DR AF Anderson, Steven A. Menis, Mikhail O'Connell, Kathryn Burwen, Dale R. TI Blood use by inpatient elderly population in the United States SO TRANSFUSION LA English DT Article ID CRITICALLY-ILL; TRANSFUSION; HOSPITALS; SURVIVAL; ANEMIA AB BACKGROUND: Our objective was to characterize inpatient blood use by the US elderly population during 2001. As the US population ages the demand for blood is expected to grow. There have been no comprehensive studies, however, detailing blood use by the elderly in the United States. STUDY DESIGN AND METHODS: A descriptive cross-sectional study of blood utilization was conducted with the 5 percent Medicare Provider Analysis and Review (MedPAR) data file obtained from the Centers for Medicare and Medicaid Services (CMS). Each record of the file represented a billing record of an inpatient stay. Blood use was identified by either a nonzero blood pints furnished quantity or a procedure code for transfusion of whole blood or red blood cells (RBCs). RESULTS: Among 635,700 stays, 43,220 (6.8%) recorded transfusion of whole blood or RBCs. Blood use prevalence was approximately 4.5 times higher for stays with at least one medical procedure compared to stays without procedures. Of 15,579 stays with number of blood pints furnished recorded, the top 20 principal procedures with the largest quantities of blood accounted for about 56 percent of total blood pints furnished; however, these procedures represented only about 19 percent of all stays. CONCLUSION: Our study shows a strong association between medical procedures and blood use among inpatient stays for the elderly. Some of the highest blood utilization occurred with surgical procedures. More precise information on blood utilization may serve as the basis for estimating risks associated with blood transfusion and may inform decisions that maintain an adequate supply of blood. C1 US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Anderson, SA (reprint author), US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. EM steven.anderson@fda.hhs.gov NR 34 TC 24 Z9 25 U1 0 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2007 VL 47 IS 4 BP 582 EP 592 DI 10.1111/j.1537-2995.2007.01159.x PG 11 WC Hematology SC Hematology GA 154ZC UT WOS:000245546300008 PM 17381615 ER PT J AU Tesfamariam, B DeFelice, AF AF Tesfamariam, Belay DeFelice, Albert F. TI Endothelial injury in the initiation and progression of vascular disorders SO VASCULAR PHARMACOLOGY LA English DT Review DE endothelium; biomarkers; drugs; vasculitis; immune reactions; adhesion molecules; free radicals ID ANTIENDOTHELIAL CELL ANTIBODIES; WEGENERS-GRANULOMATOSIS; POLYARTERITIS-NODOSA; RECEPTOR ANTAGONIST; CD40 LIGAND; T-CELLS; EXPRESSION; ADHESION; DOGS; DYSFUNCTION AB Endothelial cell dysfunction is considered to be an early event which subsequently leads to vascular wall disorders. Ultrastructural studies indicate that the endothelial cell changes involve membrane damage, increased permeability, swelling and necrosis. The endothelial cell loss of function could be as a result of changes in hemodynamic forces (shear and/or hoop stress), direct drug-induced cytotoxicity, mechanical device implant-induced injury and/or immune-mediated mechanisms. Drugs may perturb endothelial cell integrity by directly triggering inflammatory signaling cascades, enhancing expression of cellular adhesion molecules, activation of cytotoxic T cells and/or autoantibodies directed against endothelial cell membranes. Local release of inflammatory cytokines and chemokines activate endothelial cells to upregulate soluble adhesion molecules, activate neutrophils and generate reactive oxygen species which serve to amplify the initial inflammation leading to dysregulated apoptosis, secondary necrosis and overt vascular injury lesions. Considering the role of the endothelium in the initiation and propagation of vascular wall injury, there is a need for the discovery of validated biomarkers to serve as a predictor of activation of inflammatory cascades in the development of vascular injury. This article reviews some aspects of the multifaceted mechanisms that lead to the initial endothelial cell disruption and subsequent vascular wall injury. (c) 2007 Elsevier Inc. All rights reserved. C1 US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Tesfamariam, B (reprint author), US FDA, Div Cardiovasc & Renal Prod, Ctr Drug Evaluat & Res, Bldg 22,Rm 4176,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM belay.tesfamariam@fda.hhs.gov NR 47 TC 76 Z9 91 U1 1 U2 8 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1537-1891 J9 VASC PHARMACOL JI Vasc. Pharmacol. PD APR PY 2007 VL 46 IS 4 BP 229 EP 237 DI 10.1016/j.vph.2006.11.005 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 138ZL UT WOS:000244401700001 PM 17218160 ER PT J AU Walker, RI Steele, D Aguado, T AF Walker, Richard I. Steele, Duncan Aguado, Teresa CA Ad Hoc ETEC Technical Expert Comm TI Analysis of strategies to successfully vaccinate infants in developing countries against enterotoxigenic E-coli (ETEC) disease SO VACCINE LA English DT Review DE enterotoxigenic Escherichia coli; vaccine; diarrhoeal disease ID HEAT-LABILE ENTEROTOXIN; COLONIZATION FACTOR ANTIGENS; ORAL CHOLERA VACCINE; WHOLE-CELL VACCINE; TOXIN B-SUBUNIT; IMMUNE-RESPONSES; VIBRIO-CHOLERAE; DIARRHEAL DISEASES; SHIGELLA VACCINE; BIODEGRADABLE MICROSPHERES AB Enterotoxigenic Escherichia coli (ETEC) is the most common bacterial cause of diarrhoea in the world,annually affecting up to 400,000,000 children under 5 years of age living in developing countries (DCs). Although ETEC possesses numerous antigens, the relatively conserved colonization factor (CF) antigens and the heat labile enterotoxin (LT) have been associated with protection and most vaccine candidates have exploited these antigens. A cafe and effective vaccine against ETEC is a feasible goal as supported by the acquisition of protective immunity. The success of an ETEC vaccine targeting infants and children in DCs will depend on a combination of maximally antigenic vaccine preparations and regimens for their delivery which will produce optimal immune responses to these antigens. Vaccine candidates having a high priority for accelerated development and clinical testing for eventual use in infants would include inactivated ETEC or Shigella hybrids expressing FTEC antigens as well as attenuated ETEC strains which express the major CF antigens and LT toxin B-subunit, as well as attenuated Shigella, Vibrio cholerae and Salmonella typhi hybrids engineered to deliver antigens of ETEC. Candidates for an ETEC vaccine would have to meet the minimal requirement of providing at least 50% protection against severe disease in DCs during the first 2 years of life. The critical roadblock to achieving, this goal has not been the science as much as the lack of a sufficiently funded and focused effort to bring it to realization. However, a Product Development Partnership to overcome this hurdle Could accelerate the time lines towards when control of ETEC disease in DCS is Substantially closer. (c) 2006 Elsevier Ltd. All rights reserved. C1 Ctr Biol Evaluat & Res, Div Bacterial Parasit & allergen Prod, Rockville, MD 20851 USA. WHO, Dept Immunizat Vaccines & Biol, IVR, BAC, CH-1211 Geneva 27, Switzerland. RP Walker, RI (reprint author), Ctr Biol Evaluat & Res, Div Bacterial Parasit & allergen Prod, 1401 Rockville Pike, Rockville, MD 20851 USA. EM walkerri@cber.fda.gov NR 141 TC 76 Z9 80 U1 0 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAR 30 PY 2007 VL 25 IS 14 BP 2545 EP 2566 DI 10.1016/j.vaccine.2006.12.028 PG 22 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 157PO UT WOS:000245732700004 PM 17224212 ER PT J AU Hendeles, L Colice, GL Meyer, RJ AF Hendeles, Leslie Colice, Gene L. Meyer, Robert J. TI Current concepts - Withdrawal of albuterol inhalers containing chlorofluorocarbon propellants SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Review ID METERED-DOSE INHALER; EXERCISE-INDUCED BRONCHOCONSTRICTION; HYDROFLUOROALKANE-134A HFA ALBUTEROL; TO-MODERATE ASTHMATICS; CFC ALBUTEROL; PROVENTIL HFA; SALBUTAMOL SULFATE; ELECTROSTATIC CHARGE; PLASTIC SPACERS; REGULAR USE C1 Univ Florida, Coll Pharm, Gainesville, FL 32610 USA. Univ Florida, Pediat Pulm Div, Gainesville, FL 32610 USA. George Washington Univ, Sch Med, Washington, DC USA. Washington Hosp Ctr, Washington, DC 20010 USA. US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Hendeles, L (reprint author), Univ Florida, Coll Pharm, Box 100486, Gainesville, FL 32610 USA. EM hendeles@cop.ufl.edu NR 49 TC 39 Z9 40 U1 0 U2 5 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 29 PY 2007 VL 356 IS 13 BP 1344 EP 1351 DI 10.1056/NEJMra050380 PG 8 WC Medicine, General & Internal SC General & Internal Medicine GA 150MN UT WOS:000245221000008 PM 17392304 ER PT J AU Heiserman, WM Limm, W Begley, TH Walker, RA AF Heiserman, Wendy M. Limm, William Begley, Timothy H. Walker, Robert A. TI AGFD 87-Migration and diffusion of common antioxidant additives from and through food contact polymers SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Walker, Robert A.] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Limm, William] Div Chem Res & Environm Review Food & Drug Adm, College Pk, MD 20740 USA. [Begley, Timothy H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM wendyh@umd.edu; rawalker@umd.edu NR 0 TC 0 Z9 0 U1 1 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 25 PY 2007 VL 233 MA 87-AGFD BP 124 EP 124 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V14GL UT WOS:000207722800122 ER PT J AU Kim, YH Cerniglia, CE AF Kim, Yong-Hak Cerniglia, Carl E. TI AGRO 57-Evaluation of the fate of erythromycin A in aquaculture sediments SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 [Kim, Yong-Hak] Seoul Natl Univ, Sch Biol Sci, Seoul, South Korea. [Cerniglia, Carl E.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. EM yhkim660628@hotmail.com; carl.cerniglia@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 25 PY 2007 VL 233 MA 57-AGRO BP 261 EP 261 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA V14GL UT WOS:000207722800236 ER PT J AU de Jager, LS Perfetti, GA Diachenko, GW AF de Jager, Lowri S. Perfetti, Gracia A. Diachenko, Gregory W. TI Determination of coumarin, vanillin, and ethyl vanillin in vanilla extract products: liquid chromatography mass spectrometry method development and validation studies SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE coumarin; mass spectrometry; vanillin; vanilla extracts; LC-MS ID SOLID-PHASE MICROEXTRACTION; GAS-CHROMATOGRAPHY AB A LC-MS method was developed for the determination of coumarin, vanillin, and ethyl vanillin in vanilla products. Samples were analyzed using LC-electrospray ionization (ESI)-MS in the positive ionization mode. Limits of detection for the method ranged from 0.051 to 0.073 mu g mL(-1). Using the optimized method, 24 vanilla products were analyzed. All samples tested negative for coumarin. Concentrations ranged from 0.38 to 8.59 mg mL(-1) ((x) over bar = 3.73) for vanillin and 0.33 to 2.27 mg mL(-1) ((x) over bar = 1.03) for ethyl vanillin. The measured concentrations are compared to values calculated using UV monitoring and to results reported in a similar survey in 1988. Analytical results, method precision, and accuracy data are presented. Published by Elsevier B.V. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP de Jager, LS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD USA. EM lowri.dejager@fda.hhs.gov; gracia.perfetti@fda.hhs.gov; gregory.diachenko@fda.hhs.gov NR 13 TC 32 Z9 32 U1 5 U2 27 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 MAR 23 PY 2007 VL 1145 IS 1-2 BP 83 EP 88 DI 10.1016/j.chroma.2007.01.039 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 151OG UT WOS:000245299400005 PM 17250844 ER PT J AU Philip, BK Mumtaz, MM Latendresse, JR Mehendale, HM AF Philip, Binu K. Mumtaz, Moiz M. Latendresse, John R. Mehendale, Harihara M. TI Impact of repeated exposure on toxicity of perchloroethylene in Swiss Webster mice SO TOXICOLOGY LA English DT Article DE kidney injury; liver injury; perchloroethylene (Perc); subchronic toxicity; tissue repair ID TISSUE-REPAIR RESPONSE; LIVER-INJURY; IN-VITRO; PEROXISOME PROLIFERATION; GLUTATHIONE CONJUGATION; DEPENDENT DIFFERENCES; TRICHLOROACETIC-ACID; MEDIATES PROGRESSION; DICHLOROACETIC ACID; RATS AB The aim was to study the subchronic toxicity of perchloroethylene (Perc) by measuring injury and repair in liver and kidney in relation to disposition of Perc and its major metabolites. Male SW mice (25-29 g) were given three dose levels of Perc (150, 500, and 1000 mg/kg day) via aqueous gavage for 30 days. Tissue injury was measured during the dosing regimen (0, 1, 7, 14, and 30 days) and over a time course of 24-96 h after the last dose (30 days). Perc produced significant liver injury (ALT) after single day exposure to all three doses. Liver injury was mild to moderate and regressed following repeated exposure for 30 days. Subchronic Perc exposure induced neither kidney injury nor dysfunction during the entire time course as evidenced by normal renal histology and BLIN. TCA was the major metabolite detected in blood, liver, and kidney. Traces of DCA were also detected in blood at initial time points after single day exposure. With single day exposure, metabolism of Perc to TCA was saturated with all three doses. AUC/dose ratio for TCA was significantly decreased with a concomitant increase in AUC/dose of Perc levels in liver and kidney after 30 days as compared to I day exposures, indicating inhibition of metabolism upon repeated exposure to Perc. Hepatic CYP2E1 expression and activity were unchanged indicating that CYP2E1 is not the critical enzyme inhibited. Hepatic CYNA expression, measured as a marker of peroxisome proliferation was increased transiently only on day 7 with the high dose, but was unchanged at later time points. Liver tissue repair peaked at 7 days, with all three doses and was sustained after medium and high dose exposure for 14 days. These data indicate that subchronic Perc exposure via aqueous gavage does not induce nephrotoxicity and sustained hepatotoxicity suggesting adaptive hepatic repair mechanisms. Enzymes other than CYP2E], involved in the metabolism of Perc may play a critical role in the metabolism of Perc upon subehronic exposure in SW mice. Liver injury decreased during repeated exposure due to inhibition of metabolism and possibly due to adaptive tissue repair mechanisms. (c) 2006 Elsevier Ireland Ltd. All rights reserved. C1 Univ Louisiana, Dept Toxicol, Coll Pharm, Monroe, LA 71209 USA. ATSDR, Dept Hlth & Human Serv, Atlanta, GA 30333 USA. Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana, Dept Toxicol, Coll Pharm, 700 Univ Ave,Sugar Hall 306, Monroe, LA 71209 USA. EM mehendale@ulm.edu RI Latendresse, John/A-9215-2009 NR 53 TC 9 Z9 9 U1 0 U2 2 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 MAR 22 PY 2007 VL 232 IS 1-2 BP 1 EP 14 DI 10.1016/j.tox.2006.12.018 PG 14 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 152EZ UT WOS:000245345200001 PM 17267091 ER PT J AU Chu, PS Lopez, MI AF Chu, Pak-Sin Lopez, Mayda I. TI Determination of nitrofuran residues in milk of dairy cows using liquid chromatography-tandem mass spectrometry SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE nitrofurans; milk; LC-MS/MS; method; residues ID BOUND RESIDUES; FURAZOLIDONE; METABOLITES; TISSUE; SEMICARBAZIDE; CONTAMINATION; PRODUCTS AB An analytical method has been developed for the determination of total bound and extractable residues of the nitrofuran drugs furazolidone, nitrofurazone, furaltadone, and nitrofurantoin in milk of dairy cows. The method involves overnight acid hydrolysis and simultaneous derivatization of the released side chains with 2-nitrobenzaldehyde. During hydrolysis, the bound metabolites are hydrolyzed to the side chains. After pH adjustment and solid-phase extraction cleanup, the derivatives are detected and quantitated using a liquid chromatography-tandem mass spectrometry system with an atmospheric pressure chemical ionization interface. Validation of the method is accomplished by fortifying control milk with a mixture of side chains at 1, 2, and 4 ng/g. Internal standards are added at the beginning of the procedure to compensate for matrix effects and recovery losses. Method accuracies range from 83 to 104% with coefficients of variation less than 13% for all four analytes. The limits of detection are <= 0.2 ng/g for the side chains. In the milk of a dosed cow, nitrofurantoin exhibits the lowest level of residues among the four nitrofurans. Seventy-two hours after dosing, side-chain residue levels in milk drop below 0.2 ng/g. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Chu, PS (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM pak.chu@fda.hhs.gov NR 24 TC 31 Z9 36 U1 4 U2 22 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 MAR 21 PY 2007 VL 55 IS 6 BP 2129 EP 2135 DI 10.1021/jf063391v PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 145LT UT WOS:000244867300012 PM 17326656 ER PT J AU Mattei, E Triventi, M Calcagnini, G Censi, F Kainz, W Bassen, HI Bartolini, P AF Mattei, E. Triventi, M. Calcagnini, G. Censi, F. Kainz, W. Bassen, H. I. Bartolini, P. TI Temperature and SAR measurement errors in the evaluation of metallic linear structures heating during MRI using fluoroptic (R) probes SO PHYSICS IN MEDICINE AND BIOLOGY LA English DT Article ID RADIOLOGY WHITE PAPER; MAGNETIC-RESONANCE; IN-VITRO; RADIOFREQUENCY ABLATION; CARDIAC-PACEMAKERS; ABSORPTION RATE; CATHETER; SAFETY; INTERFERENCE; ELECTRODE AB The purpose of this work is to evaluate the error associated with temperature and SAR measurements using fluoroptic (R) temperature probes on pacemaker ( PM) leads during magnetic resonance imaging (MRI). We performed temperature measurements on pacemaker leads, excited with a 25, 64, and 128 MHz current. The PM lead tip heating was measured with a fluoroptic (R) thermometer (Luxtron, Model 3100, USA). Different contact configurations between the pigmented portion of the temperature probe and the PM lead tip were investigated to find the contact position minimizing the temperature and SAR underestimation. A computer model was used to estimate the error made by fluoroptic (R) probes in temperature and SAR measurement. The transversal contact of the pigmented portion of the temperature probe and the PM lead tip minimizes the underestimation for temperature and SAR. This contact position also has the lowest temperature and SAR error. For other contact positions, the maximum temperature error can be as high as -45%, whereas the maximum SAR error can be as high as -54%. MRI heating evaluations with temperature probes should use a contact positionminimizing the maximum error, need to be accompanied by a thorough uncertainty budget and the temperature and SAR errors should be specified. C1 Italian Natl Inst Hlth, Dept Technol & Hlth, Rome, Italy. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Mattei, E (reprint author), Italian Natl Inst Hlth, Dept Technol & Hlth, Rome, Italy. EM eugenio.mattei@iss.it RI CALCAGNINI, GIOVANNI/E-3711-2015; CENSI, FEDERICA/E-3712-2015; TRIVENTI, MICHELE/E-4624-2015; MATTEI, EUGENIO/E-4623-2015 OI TRIVENTI, MICHELE/0000-0003-2120-6959; MATTEI, EUGENIO/0000-0002-6494-9456 NR 24 TC 38 Z9 38 U1 1 U2 5 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 MAR 21 PY 2007 VL 52 IS 6 BP 1633 EP 1646 DI 10.1088/0031-9155/52/6/006 PG 14 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA 143IP UT WOS:000244714300007 PM 17327653 ER PT J AU Welch, TJ Fricke, WF McDermott, PF White, DG Rosso, ML Rasko, DA Mammel, MK Eppinger, M Rosovitz, MJ Wagner, D Rahalison, L LeClerc, JE Hinshaw, JM Lindler, LE Cebula, TA Carniel, E Ravel, J AF Welch, Timothy J. Fricke, W. Florian McDermott, Patrick F. White, David G. Rosso, Marie-Laure Rasko, David A. Mammel, Mark K. Eppinger, Mark Rosovitz, M. J. Wagner, David Rahalison, Lila LeClerc, J. Eugene Hinshaw, Jeffrey M. Lindler, Luther E. Cebula, Thomas A. Carniel, Elisabeth Ravel, Jacques TI Multiple Antimicrobial Resistance in Plague: An Emerging Public Health Risk SO PLOS ONE LA English DT Article AB Antimicrobial resistance in Yersinia pestis is rare, yet constitutes a significant international public health and biodefense threat. In 1995, the first multidrug resistant (MDR) isolate of Y. pestis (strain IP275) was identified, and was shown to contain a self-transmissible plasmid (pIP1202) that conferred resistance to many of the antimicrobials recommended for plague treatment and prophylaxis. Comparative analysis of the DNA sequence of Y. pestis plasmid pIP1202 revealed a near identical IncA/C plasmid backbone that is shared by MDR plasmids isolated from Salmonella enterica serotype Newport SL254 and the fish pathogen Yersinia ruckeri YR71. The high degree of sequence identity and gene synteny between the plasmid backbones suggests recent acquisition of these plasmids from a common ancestor. In addition, the Y. pestis pIP1202-like plasmid backbone was detected in numerous MDR enterobacterial pathogens isolated from retail meat samples collected between 2002 and 2005 in the United States. Plasmid-positive strains were isolated from beef, chicken, turkey and pork, and were found in samples from the following states: California, Colorado, Connecticut, Georgia, Maryland, Minnesota, New Mexico, New York and Oregon. Our studies reveal that this common plasmid backbone is broadly disseminated among MDR zoonotic pathogens associated with agriculture. This reservoir of mobile resistance determinants has the potential to disseminate to Y. pestis and other human and zoonotic bacterial pathogens and therefore represents a significant public health concern. C1 [Fricke, W. Florian; Rasko, David A.; Eppinger, Mark; Rosovitz, M. J.; Ravel, Jacques] Inst Genom Res, Rockville, MD USA. [Welch, Timothy J.] ARS, Natl Ctr Cool & Cold Water Aquaculture, USDA, Kearneysville, WV USA. [McDermott, Patrick F.; White, David G.] US FDA, Res Off, Ctr Vet Med, Laurel, MD USA. [Rosso, Marie-Laure; Carniel, Elisabeth] Inst Pasteur, Yersinia Res Unit, Paris, France. [Rasko, David A.] Univ Texas SW Med Ctr Dallas, Dallas, TX 75390 USA. [Mammel, Mark K.; LeClerc, J. Eugene; Cebula, Thomas A.] US FDA, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD USA. [Wagner, David] No Arizona Univ, Flagstaff, AZ 86011 USA. [Rahalison, Lila] Inst Pasteur, Antananarivo, Madagascar. [Hinshaw, Jeffrey M.] N Carolina State Univ, Dept Zool, Fletcher, NC USA. [Lindler, Luther E.] DoD GEIS, Publ Hlth Lab Serv, Silver Spring, MD USA. RP Ravel, J (reprint author), Inst Genom Res, Rockville, MD USA. EM jravel@tigr.org RI Wagner, David/A-5125-2010; OI Ravel, Jacques/0000-0002-0851-2233; David, Rasko/0000-0002-7337-7154 FU National Institute of Allergy and Infectious Diseases, NIH, DHHS [N01-AI-30071]; ARS [1930-31000-002] FX This research was supported by Federal funds from the National Institute of Allergy and Infectious Diseases, NIH, DHHS, under Contract No. N01-AI-30071 and by ARS CRIS project 1930-31000-002. NR 18 TC 204 Z9 214 U1 0 U2 23 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 21 PY 2007 VL 2 IS 3 AR e309 DI 10.1371/journal.pone.0000309 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA V10DQ UT WOS:000207445100011 PM 17375195 ER PT J AU Wong, HC Liu, SH Chiou, CS Nishibuchi, M Lee, BK Suthienkul, O Nair, GB Kaysner, CA Taniguchi, H AF Wong, Hin-chung Liu, Shu-Hui Chiou, Chien-Shun Nishibuchi, Mitsuaki Lee, Bok-Kwon Suthienkul, Orasa Nair, Gopinath Balakrish Kaysner, Charles A. Taniguchi, Hatsumi TI A pulsed-field gel electrophoresis typing scheme for Vibrio parahaemolyticus isolates from fifteen countries SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Vibrio parahaemolyticus; pulsed-field gel electrophoresis; typing scheme ID FOOD POISONING OUTBREAKS; FOODBORNE ILLNESS; CLINICAL STRAINS; PANDEMIC SPREAD; O3-K6 STRAINS; TAIWAN; CLONE; EMERGENCE; PCR; PREVALENCE AB Vibrio parahaemolyticus is an important foodbome pathogen in Taiwan and many other maritime Asian countries where seafood is frequently consumed. A total of 535 strains of V. parahaemolyticus were recovered mostly (97%) from clinical samples obtained in Taiwan or in 14 other countries. These strains were typed by pulsed-field get electrophoresis following fil digestion and a typing scheme was generated. The 115 different patterns identified were grouped into 13 types with dissimilarity values less than 15, plus 16 miscellaneous patterns not grouped into any of the types. Types I, A, D and J contained the most patterns, with the numbers of patterns being 17, 13, 12, and 11, respectively. However, types I, B, D, A, H and C contained the most strains, with the numbers of strains being 204, 73, 71, 54, 29 and 25, respectively. Type I consisted exclusively of the pandemic 03:K6 strains and genetically closely related strains. This PFGE typing scheme for V. parahaemolyticus could be used for the characterization of pathogenic isolates. (C) 2006 Elsevier B.V. All rights reserved. C1 Soochow Univ, Dept Microbiol, Taipei 111, Taiwan. Branch Off 3, Ctr Dis Control, Taichung 408, Taiwan. Kyoto Univ, Ctr SE Asian Studies, Kyoto 6068501, Japan. NIH, Dept Microbiol, Lab Enter Infect, Seoul, South Korea. Mahidol Univ, Fac Publ Hlth, Dept Microbiol, Bangkok 10400, Thailand. Natl Inst Cholera & Enter Dis, Kolkata 700010, W Bengal, India. Food & Drug Adm, Seafood Prod Res Ctr, Bothell, WA 98041 USA. Univ OCCUP, Dept Microbiol, Kitakyushu, Fukuoka 8078555, Japan. Univiron Hlth Sci Med Yahatauishi, Kitakyushu, Fukuoka 8078555, Japan. RP Wong, HC (reprint author), Soochow Univ, Dept Microbiol, Taipei 111, Taiwan. EM wonghc@scu.edu.tw NR 33 TC 22 Z9 24 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 EI 1879-3460 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD MAR 20 PY 2007 VL 114 IS 3 BP 280 EP 287 DI 10.1016/j.ijfoodmicro.2006.09.024 PG 8 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 167CW UT WOS:000246429500004 PM 17161487 ER PT J AU Curtis, JR Martin, C Saag, KG Patkar, NM Kramer, J Shatin, D Allison, J Braun, MM AF Curtis, J. R. Martin, C. Saag, K. G. Patkar, N. M. Kramer, J. Shatin, D. Allison, J. Braun, M. M. TI Confirmation of administrative claims-identified opportunistic infections and other serious potential adverse events associated with tumor necrosis factor alpha antagonists and disease-modifying antirheumatic drugs SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID CARINII-PNEUMONIA; CROHNS-DISEASE; PHARMACY; INFLIXIMAB; THERAPY; PATIENT; RECORDS C1 Univ Alabama Birmingham, Birmingham, AL 35294 USA. Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN USA. Duke Univ, Med Ctr, Durham, NC 27706 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Curtis, JR (reprint author), Univ Alabama Birmingham, 510 20th St S,FOT 840, Birmingham, AL 35294 USA. OI Allison, Jeroan/0000-0003-4472-2112 FU AHRQ HHS [HS-10389]; NIAMS NIH HHS [K24-AR-052361-01, T32-AR-47512-03]; PHS HHS [223-02-1420] NR 13 TC 17 Z9 17 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 EI 1529-0131 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD MAR 15 PY 2007 VL 57 IS 2 BP 343 EP 346 DI 10.1002/art.22544 PG 4 WC Rheumatology SC Rheumatology GA 145RF UT WOS:000244881500023 PM 17330283 ER PT J AU Karnaukhova, E AF Karnaukhova, Elena TI Interactions of human serum albumin with retinoic acid, retinal and retinyl acetate SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE human serum albumin; retinoic acid; retinal; retinyl acetate; circular dichroism; protein-induced chirality ID CIRCULAR-DICHROISM; BINDING PROPERTIES; FATTY-ACIDS; HUMAN SKIN; CHEMOPREVENTION; PROTEINS; REVEALS; CANCER; CHAIN AB Human serum albumin (HSA), a major plasma protein and plasma-derived therapeutic, interacts with a wide variety of drugs and native plasma metabolites. In this study the interactions between HSA and small lipophilic molecules all-trans retinoic acid (RA), all-trans retinaldehyde (retinal, RAL) and all-trans retinyl acetate (RAC) were investigated by UV-vis absorption spectroscopy, fluorescence spectroscopy and circular dichroism (CD). This paper focuses on investigation of the interactions between HSA and RA by the visible CD. RAL and RAC were used in this study due to their structural identity to RA to elucidate the importance of the end functional group for the complex formation. Our data demonstrate that RA specifically binds to HSA in a stable non-covalent complex at least at two internal binding sites with close but distinct affinities. Upon titration of HSA with RA, visible CD spectra clearly demonstrate the appearance of a well-defined induced positive Cotton Effect (CE) around 350 nm. Beyond ligand-to-protein ratio of 0.8 and up to saturation (2.0), CD exhibits two major bands of opposite signs, suggesting exciton coupling between the chromophore molecules in the protein interior. The fluorescence quenching data suggest proximity of the primary RA binding site to tryptophan (W-214). RAC shows a weak association with HSA with stoichiometry close to that of RA, while interactions of RAL with HSA proceed non-specifically at multiple sites. Contrary to RA, the adducts of HSA with RAC and RAL do not show any induced chirality, thus indicating that despite their high structural similarity to RA, both compounds do not appear to occupy the internal binding sites, but associate with the protein exterior. Published by Elsevier Inc. C1 Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, Food & Drug Adm, Bethesda, MD 20892 USA. RP Karnaukhova, E (reprint author), Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Div Hematol, Food & Drug Adm, Bethesda, MD 20892 USA. EM elena.karnaukhova@fda.hhs.gov NR 46 TC 38 Z9 39 U1 2 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 15 PY 2007 VL 73 IS 6 BP 901 EP 910 DI 10.1016/j.bcp.2006.11.023 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144TY UT WOS:000244820400017 PM 17217919 ER PT J AU Bialek, SR George, PA Xia, GL Glatzer, MB Motes, ML Veazey, JE Hammond, RM Jones, T Shieh, YC Wamnes, J Vaughan, G Khudyakov, Y Fiore, AE AF Bialek, Stephanie R. George, Prethiba A. Xia, Guo-Liang Glatzer, Marc B. Motes, Miles L. Veazey, John E. Hammond, Roberta M. Jones, Timothy Shieh, Y. Carol Wamnes, Janet Vaughan, Gilberto Khudyakov, Yury Fiore, Anthony E. TI Use of molecular epidemiology to confirm a multistate outbreak of hepatitis A caused by consumption of oysters SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID UNITED-STATES AB The 39 oyster consumption-related cases of hepatitis A reported in 2005 represent the first large outbreak of hepatitis A associated with shellfish consumption in the United States in > 15 years. This is the first outbreak investigation in which an identical hepatitis A virus sequence was obtained from both the implicated food product and case patients. C1 Ctr Dis Control & Prevent, Div Viral Hepatitis, Atlanta, GA 30333 USA. US FDA, Tallahassee, FL USA. Florida Dept Hlth, Bur Community Environm Hlth, Tallahassee, FL USA. Florida Dept Hlth, Ft Pierce, FL USA. US FDA, Mobile, AL USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. US FDA, Baton Rouge, LA USA. Tennessee Dept Hlth, Nashville, TN USA. RP Bialek, SR (reprint author), Ctr Dis Control & Prevent, Div Viral Hepatitis, Mailstop G-37,1600 Clifton Rd NE, Atlanta, GA 30333 USA. EM sbialek@cdc.gov NR 11 TC 21 Z9 21 U1 0 U2 5 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2007 VL 44 IS 6 BP 838 EP 840 DI 10.1086/511874 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 136RT UT WOS:000244242500013 PM 17304457 ER PT J AU Piccardo, P Manson, JC King, D Ghetti, B Barron, RM AF Piccardo, Pedro Manson, Jean C. King, Declan Ghetti, Bernardino Barron, Rona M. TI Accumulation of prion protein in the brain that is not associated with transmissible disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE amyloid; Gerstmann-Straussler-Scheinker; transmissible spongiform encephalopathy; neurodegeneration ID STRAUSSLER-SCHEINKER-DISEASE; CREUTZFELDT-JAKOB-DISEASE; SINGLE AMINO-ACID; SPONGIFORM ENCEPHALOPATHY; SCRAPIE INFECTIVITY; TRANSGENIC MICE; INCUBATION-TIME; N-TERMINUS; PRP; STRAINS AB Prion diseases or transmissible spongiform encephalopathies are characterized histopathologically by the accumulation of prion protein (PrP) ranging from diffuse deposits to amyloid plaques. Moreover, pathologic PrP isoforms (PrPSc) are detected by immunoblot analysis and used both as diagnostic markers of disease and as indicators of the presence of infectivity in tissues. It is not known which forms of PrP are associated with infectivity. To address this question, we performed bioassays using human brain extracts from two cases with phenotypically distinct forms of familial prion disease (Gerstmann-Straussler-Scheinker P102L). Both cases had PrP accumulations in the brain, but each had different PrPSc isoforms. Only one of the brains had spongiform degeneration. Tissue from this case transmitted disease efficiently to transgenic mice (Tg PrP101LL), resulting in spongiform encephalopathy. In contrast, inoculation of tissue from the case with no spongiform degeneration resulted in almost complete absence of disease transmission but elicited striking PrP-amyloid deposition in several recipient mouse brains. Brains of these mice failed to transmit any neurological disease on passage, but PrP-amyloid deposition was again observed in the brains of recipient mice. These data suggest the possible isolation of an infectious agent that promotes PrP amyloidogenesis in the absence of a spongiform encephalopathy. Alternatively, the infectious agent may be rendered nonpathogenic by sequestration in amyloid plaques, or PrP amyloid can seed amyloid accumulation in the brain, causing a proteinopathy that is unrelated to prion disease. Formation of PrP amyloid may therefore not necessarily be a reliable marker of transmissible spongiform encephalopathy infectivity. C1 Inst Anim Hlth, Neuropathogenesis Unit, Edinburgh EH9 3JF, Midlothian, Scotland. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Div Neuropathol, Indianapolis, IN 46202 USA. RP Barron, RM (reprint author), Inst Anim Hlth, Neuropathogenesis Unit, Ogston Bldg,W Mains Rd, Edinburgh EH9 3JF, Midlothian, Scotland. EM rona.barron@bbsrc.ac.uk RI Barron, Rona/C-7703-2013; OI Barron, Rona/0000-0003-4512-9177 FU Biotechnology and Biological Sciences Research Council [BBS/E/A/00001650]; NIA NIH HHS [P30 AG010133, P30 AG 10133] NR 33 TC 109 Z9 111 U1 0 U2 7 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 13 PY 2007 VL 104 IS 11 BP 4712 EP 4717 DI 10.1073/pnas.0609241104 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 146ZH UT WOS:000244972700083 PM 17360589 ER PT J AU Yang, Y Brownell, CR Sadrieh, N May, JC Del Grosso, AV Lyon, RC Faustino, PJ AF Yang, Yongsheng Brownell, Charles R. Sadrieh, Nakissa May, Joan C. Del Grosso, Alfred V. Lyon, Robbe C. Faustino, Patrick J. TI Validation of an in vitro method for the determination of cyanide release from ferric-hexacyanoferrate: Prussian blue SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE cyanide; Prussian blue; spectroquant cyanide-test kit; method validation ID EFFECTIVE ANTIDOTE; RADIOCESIUM; ACCIDENT; BLOOD; AFCF AB Prussian blue (PB), ferric hexacyanoferrate, Fe-4[Fe(CN)(6)](3) is indicated for the treatment of known or suspected internal contamination with radioactive cesium, radioactive thallium, or non-radioactive thallium. Owing to the molecular properties, cyanide is likely dissociated from PB under physiologically relevant pH conditions, thus raising a concern for the safety of the product. The objective of this study was to calibrate and validate a cyanide assay over a wide pH range (from 0.5 to 12) on the basis of Spectroquant cyanide test method (Merck). Merck's photometric method requires that the measurement solution be within pH 5.5-6.0, hence samples and standards need to be adjusted to this pH range. Since the process of pH adjustment may have significant impact on the determination of cyanide, the analysis method needs to be optimized, calibrated and validated under each pH condition in the study. The validation characteristics included accuracy, precision, quantification limit, linearity, and stability. The intra-day accuracy ranged from 90% to 109% for the deionized water and solutions of pH 0.5-12. The intra-day precision (R.S.D.) ranged from 2.4% to 8.1% for the deionized water and solutions of pH 0.5-12. The analytical range was linear from 0.05 to 0.5 ppm (mg/L). The R-2 ranged from 0.9925 to 0.9998. This validated method was successfully implemented to determine cyanide release from PB under various pH conditions (from 1.0 to 12) at different time-points (from I to 24 h). C1 Ctr Drug Evaluat & Res, Div Prod Qual Res, Food & Drug Adm, Silver Spring, MD 20993 USA. Ctr Drug Evaluat & Res, Off Pharmacuet Sci, Food & Drug Adm, Silver Spring, MD 20993 USA. Ctr Biol Evaluat & Res, Food & Drug Adm, Off Vaccines Res & Review, Lab Analyt Chem, Kensington, MD 20895 USA. RP Faustino, PJ (reprint author), Ctr Drug Evaluat & Res, Div Prod Qual Res, Food & Drug Adm, 10903 New Hamshire Ave, Silver Spring, MD 20993 USA. EM patrick.faustino@fda.hhs.gov NR 22 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 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD MAR 12 PY 2007 VL 43 IS 4 BP 1358 EP 1363 DI 10.1016/j.jpba.2006.11.010 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 151BC UT WOS:000245262300023 PM 17174056 ER PT J AU Farb, A Boam, AB AF Farb, Andrew Boam, Ashley B. TI Stent thrombosis redux - The FDA perspective SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Intervent Cardiol Devices Branch, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Farb, A (reprint author), US FDA, Intervent Cardiol Devices Branch, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 5 TC 185 Z9 195 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 MAR 8 PY 2007 VL 356 IS 10 BP 984 EP 987 DI 10.1056/NEJMp068304 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 143DC UT WOS:000244699200002 PM 17296827 ER PT J AU Zidan, AS Sammour, OA Hammad, MA Megrab, NA Habib, MJ Khan, MA AF Zidan, Ahmed S. Sammour, Omaima A. Hammad, Mohammed A. Megrab, Nagia A. Habib, Muhammad J. Khan, Mansoor A. TI Quality by design: Understanding the formulation variables of a cyclosporine A self-nanoemulsified drug delivery systems by Box-Behnken design and desirability function SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE quality by design; cyclosporine; self-nanoemulsification; Box-Behnken; optimization ID IN-WATER EMULSIONS; BIOAVAILABILITY; NANOPARTICLES; OPTIMIZATION; GLYCERIDES; SEDDS AB Quality by design (QBD) refers to the achievement of certain predictable quality with desired and predetermined specifications. A very useful component of the QBD is the understanding of factors and their interaction effects by a desired set of experiments. The present project deals with a case study to understand the effect of formulation variables of nanoemulsified particles of a model drug, cyclosporine A (CyA). A three-factor, three-level design of experiment (DOE) with response surface methodology (RSM) was run to evaluate the main and interaction effect of several independent formulation variables that included amounts of Emulphor EI-620 (X-1), Capmul MCM-C8 (X-2) and 20% (w/w) CyA in sweet orange oil (X-3). The dependent variables included nanodroplets size (Y-1), nanoemulsions turbidity (Y-2), amounts released after 5 and 10 min (Y-3, Y-4), emulsification rate (Y-5) and lag time (Y-6). A desirability function was used to minimize lag time and to maximize the other dependent variables. A mathematical relationship, Y-5 = 9.09 - 0.37X(1) + 0.37X(2) - 0.45X(3) + 0.732X(1)X(2) - 0.62X(1)X(3) + 0.3X(2)X(3) + 0.02X(1)(2) -0.28X(2)(2) + 0.471X(3)(2) (r(2) = 0.92), was obtained to explain the effect of all factors and their colinearities on the emulsification rate. The optimized nanodroplets were predicted to yield Y-1, Y-2, Y-3, Y-4, Y-5 and Y-6 values of 42.1 nm, 50.6 NTU, 56.7, 107.2, 9.3%/min and 3.5 min, respectively, when X-1, X-2, and X-3 values were 36.4, 70 and 10 mg, respectively. A new batch was prepared with these levels of the independent variables to yield Y-1-Y-6 values that were remarkably close to the predicted values. In conclusion, this investigation demonstrated the potential of QBD in understanding the effect of the formulation variables on the quality of CyA self-nanoemulsified formulations. (c) 2006 Published by Elsevier B.V. C1 US FDA, Div Prod Qual Res, Rockville, MD 20857 USA. Zagazig Univ, Fac Pharm, Zagazig, Egypt. Howard Univ, Sch Pharm, Washington, DC 20059 USA. RP Khan, MA (reprint author), US FDA, Div Prod Qual Res, Rockville, MD 20857 USA. EM Mansoor.Khan@fda.hhs.gov RI Zidan, Ahmed/I-1147-2012 NR 19 TC 62 Z9 67 U1 1 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-5173 J9 INT J PHARM JI Int. J. Pharm. PD MAR 6 PY 2007 VL 332 IS 1-2 BP 55 EP 63 DI 10.1016/j.ijpharm.2006.09.060 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144OU UT WOS:000244806500007 PM 17169518 ER PT J AU Chen, JJ Tsai, CA Tzeng, SL Chen, CH AF Chen, James J. Tsai, Chen-An Tzeng, ShengLi Chen, Chun-Houh TI Gene selection with multiple ordering criteria SO BMC BIOINFORMATICS LA English DT Article ID EXPRESSION DATA; CLASSIFICATION; SAMPLE; MICROARRAYS; TUMOR; BIAS AB Background: A microarray study may select different differentially expressed gene sets because of different selection criteria. For example, the fold-change and p-value are two commonly known criteria to select differentially expressed genes under two experimental conditions. These two selection criteria often result in incompatible selected gene sets. Also, in a two-factor, say, treatment by time experiment, the investigator may be interested in one gene list that responds to both treatment and time effects. Results: We propose three layer ranking algorithms, point-admissible, line-admissible (convex), and Pareto, to provide a preference gene list from multiple gene lists generated by different ranking criteria. Using the public colon data as an example, the layer ranking algorithms are applied to the three univariate ranking criteria, fold-change, p-value, and frequency of selections by the SVM-RFE classifier. A simulation experiment shows that for experiments with small or moderate sample sizes (less than 20 per group) and detecting a 4-fold change or less, the two-dimensional (p-value and fold-change) convex layer ranking selects differentially expressed genes with generally lower FDR and higher power than the standard p-value ranking. Three applications are presented. The first application illustrates a use of the layer rankings to potentially improve predictive accuracy. The second application illustrates an application to a two-factor experiment involving two dose levels and two time points. The layer rankings are applied to selecting differentially expressed genes relating to the dose and time effects. In the third application, the layer rankings are applied to a benchmark data set consisting of three dilution concentrations to provide a ranking system from a long list of differentially expressed genes generated from the three dilution concentrations. Conclusion: The layer ranking algorithms are useful to help investigators in selecting the most promising genes from multiple gene lists generated by different filter, normalization, or analysis methods for various objectives. C1 Acad Sinica, Inst Stat Sci, Taipei 115, Taiwan. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, CH (reprint author), Acad Sinica, Inst Stat Sci, 128 Acad Rd,Sec 2, Taipei 115, Taiwan. EM jamesJ.chen@fda.hhs.gov; catsai@stat.sinica.edu.tw; h0h1@stat.sinica.edu.tw; cchen@stat.sinica.edu.tw NR 23 TC 20 Z9 21 U1 0 U2 2 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PD MAR 5 PY 2007 VL 8 AR 74 DI 10.1186/1471-2105/8/74 PG 17 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 148ZQ UT WOS:000245116300003 PM 17338815 ER PT J AU Kelloff, GJ Sullivan, DM Wilson, W Cheson, B Juweid, M Mills, GQ Zelenetz, AD Horning, SJ Weber, W Sargent, DJ Dodd, L Korn, E Armitage, J Schilsky, R Christian, M O'Connor, OA Wang, SJ Farrell, AT Pazdur, R Graham, M Wahl, RL Larson, SM Kostakoglu, L Daube-Witherspoon, M Gastonis, C Siegel, BA Shankar, LK Lee, DB Higley, HR Sigman, CC Carucci, D Timko, D Degennaro, LJ Sigal, E Barker, A Woodcock, J AF Kelloff, Gary J. Sullivan, Daniel M. Wilson, Wyndham Cheson, Bruce Juweid, Malik Mills, George Q. Zelenetz, Andrew D. Horning, Sandra J. Weber, Wolfgang Sargent, Daniel J. Dodd, Lori Korn, Edward Armitage, James Schilsky, Richard Christian, Michaele O'Connor, Owen A. Wang, Sue Jane Farrell, Ann T. Pazdur, Richard Graham, Michael Wahl, Richard L. Larson, Steven M. Kostakoglu, Lale Daube-Witherspoon, Margaret Gastonis, Constantine Siegel, Barry A. Shankar, Lalitha K. Lee, David B. Higley, Howard R. Sigman, Caroline C. Carucci, Daniel Timko, David deGennaro, Louis J. Sigal, Ellen Barker, Anna Woodcock, Janet TI FDG-PET lymphoma demonstration project invitational workshop SO ACADEMIC RADIOLOGY LA English DT Article DE FDG-PET; lymphoma; imaging biomarker; chemotherapy response; drug development ID POSITRON-EMISSION-TOMOGRAPHY; NON-HODGKINS-LYMPHOMA; INTERNATIONAL WORKSHOP; AGGRESSIVE LYMPHOMA; TREATMENT FAILURE; PROGRESSION-FREE; CANCER-THERAPY; CHEMOTHERAPY; CYCLES; SURVIVAL AB The proceedings of a workshop focusing on a project to evaluate the use of fluorodeoxyglucose-positron emission tomography (FDG-PET) as a tool to measure treatment response in non-Hodgkin lymphoma (NHL) are described. Sponsored by the Leukemia & Lymphoma Society, the Foundation of the National Institutes of Health, and the National Cancer Institute, and attended by representatives of the Food and Drug Administration, the Centers for Medicare and Medicaid Services, and scientists and clinical researchers from academia and the pharmaceutical and medical imaging industries, the workshop reviewed the etiology and current standards of care for NHL and proposed the development of a clinical trial to validate FDG-PET imaging techniques as a predictive biomarker for cancer therapy response. As organized under the auspices of the Oncology Biomarker Qualification Initiative, the three federal health agencies and their private sector and nonprofit/advocacy group partners believe that FDG-PET not only demonstrates the potential to be used for the diagnosis and staging of many cancers but in particular can provide an early indication of therapeutic response that is well correlated with clinical outcomes for chemotherapy for this common form of lymphoma. The development of standardized criteria for FDG-PET imaging and establishment of procedures for transmission, storage, quality assurance, and analysis of PET images afforded by this demonstration project could streamline clinical trials of new treatments for more intractable forms of lymphoma and other cancers and, hence, accelerate new drug approvals. C1 CCS Associates, Mountain View, CA USA. NCI, DCTC, Canc Imaging Program, NIH, Bethesda, MD 20892 USA. NCI, Ctr Canc Res, Metab Branch, NIH, Bethesda, MD 20892 USA. NCI, DCTC, Biometr Res Branch, NIH, Bethesda, MD 20892 USA. NCI, Off Director, NIH, Bethesda, MD 20892 USA. Lombardi Comprehens Canc Ctr, Washington, DC USA. Univ Iowa, Coll Med, Iowa City, IA USA. US FDA, Rockville, MD 20857 USA. Mem Sloan Kettering Canc Ctr, New York, NY 10021 USA. Stanford Univ, Stanford, CA 94305 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. Mayo Clin & Coll Med, Rochester, MN USA. Univ Nebraska, Omaha, NE 68182 USA. Univ Chicago, Canc & Leukemia Grp B, Chicago, IL 60637 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Mt Sinai Med Ctr, New York, NY 10029 USA. Univ Penn, Philadelphia, PA 19104 USA. Brock Univ, St Catharines, ON L2S 3A1, Canada. Washington Univ, Sch Med, St Louis, MO 63130 USA. Fdn Natl Inst Hlth, Bethesda, MD USA. Leukemia & Lymphoma Soc, White Plains, NY USA. RP Higley, HR (reprint author), CCS Associates, Mountain View, CA USA. EM hhigley@ccsain.com OI Sargent, Daniel/0000-0002-2684-4741 NR 22 TC 22 Z9 22 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD MAR PY 2007 VL 14 IS 3 BP 330 EP 339 DI 10.1016/j.acra.2006.12.003 PG 10 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 173GI UT WOS:000246861100011 PM 17307666 ER PT J AU Soldatova, LN Tsai, C Dobrovolskaia, E Markovic-Housley, Z Slater, JE AF Soldatova, Lyudmila N. Tsai, Chaoming Dobrovolskaia, Ekaterina Markovic-Housley, Zora Slater, Jay E. TI Characterization of the N-glycans of recombinant bee venom hyaluronidase (Api m 2) expressed in insect cells SO ALLERGY AND ASTHMA PROCEEDINGS LA English DT Article DE allergen; bee venom allergy; honeybee; hymenoptera; hyaluronidase; recombinant ID HIGH-LEVEL EXPRESSION; DUST MITE ALLERGEN; OLE E 1; ESCHERICHIA-COLI; PICHIA-PASTORIS; HONEY-BEE; GLYCOSYLATION; CARBOHYDRATE; PURIFICATION; IGE AB Honeybee venom hyaluronidase (Api m 2) is a major glycoprotein allergen. Previous studies have indicated that recombinant Api m 2 expressed in insect cells has enzyme activity and IgE binding comparable with that Of native Api m 2. In contrast, Api m 2 expressed in Escherichia coli does not. In this study, we characterized the carbohydrate side chains of Api m 2 expressed in insect cells, and compared our data with the established carbohydrate structure of native Api m 2. We assessed both the monosaccharide and the oligosaccharide content of recombinant Api m 2 using fluorophore-assisted carbohydrate electrophoresis and HPLC. To identify the amino acid residues at which glycosylation occurs, we digested recombinant Api m 2 with endoproteinase Glu-C and identified the fragments that contained carbohydrate by specific staining. Recombinant Api m 2 expressed in insect cells contains N-acetylglucosamine, mannose, and fucose, as well as trace amounts of glucose and galactose, and the oligosaccharide analysis is consistent with heterogeneous oligosaccharide chains consisting of two to seven monosaccharides. No sialic acid or N-acetylgalactosamine were detected. These results are similar to published data for native Api m 2, although some monosaccharide components appear to be absent in the recombinant protein. Analysis of proteolytic digests indicates that of the four candidate N-glycosylation sites, carbohydrate chains are attached at asparagines 115 and 263. Recombinant Api m 2 expressed in insect cells has enzymic activity and IgE binding comparable with the native protein, and its carbohydrate composition is very similar. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Univ Basel, Dept Struct Biol, Biozentrum, CH-4003 Basel, Switzerland. RP Slater, JE (reprint author), US FDA, Lab Immunobiochem, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 422, Rockville, MD 20852 USA. EM jay.slater@fda.hhs.gov NR 24 TC 9 Z9 10 U1 1 U2 2 PU OCEAN SIDE PUBLICATIONS INC PI PROVIDENCE PA 95 PITMAN ST, PROVIDENCE, RI 02906 USA SN 1088-5412 J9 ALLERGY ASTHMA PROC JI Allergy Asthma Proc. PD MAR-APR PY 2007 VL 28 IS 2 BP 210 EP 215 DI 10.2500/aap.2007.28.2947 PG 6 WC Allergy SC Allergy GA 160IO UT WOS:000245934300016 PM 17479607 ER PT J AU Sampson, JH Raghavan, R Provenzale, JM Croteau, D Reardon, DA Coleman, RE Ponce, IR Pastan, I Puri, RK Pedain, C AF Sampson, John H. Raghavan, Raghu Provenzale, James M. Croteau, David Reardon, David A. Coleman, R. Edward Ponce, Inmaculada Rodriguez Pastan, Ira Puri, Raj K. Pedain, Christoph TI Induction of hyperintense signal on T2-weighted MR images correlates with infusion distribution from intracerebral convection-enhanced delivery of a tumor-targeted cytotoxin SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article DE brain; convection-enhanced delivery; drug delivery; glioma; MRI; oncology ID RECURRENT MALIGNANT GLIOMA; IL4-PSEUDOMONAS EXOTOXIN NBI-3001; NEUROTROPHIC FACTOR; BRAIN-TUMORS; MICROINFUSION; EFFICACY; PATIENT; PROTEIN; SAFETY; MODEL AB OBJECTIVE. Convection-enhanced delivery is a promising approach to intracerebral drug delivery in which a fluid pressure gradient is used to infuse therapeutic macromolecules through an indwelling catheter into the interstitial spaces of the brain. Our purpose was to test the hypothesis that hyperintense signal changes on T2-weighted images produced by such infusions can be used to track drug distribution. SUBJECTS AND METHODS. Seven adults with recurrent malignant glioma underwent concurrent intracerebral infusions of the tumor-targeted cytotoxin cintredekin besudotox and I-123-labeled human serum albumin. The agents were administered through a total of 18 catheters among the seven patients. Adequacy of distribution of drug was determined by evidence of distribution of I-123-labeled human serum albumin on SPECT images coregistered with MR images. Qualitative analysis was performed by three blinded observers. Quantitative analysis also was performed. RESULTS. Infusions into 12 catheters produced intraparenchymal distribution as seen on SPECT images, but infusions into six catheters did not. At qualitative assessment of signal changes on MR images, reviewers correctly predicted which catheters would produce extraparenchymal distribution and which catheters would produce parenchymal distribution. Of the 12 infusions that produced intraparenchymal distribution, four catheters had been placed in regions of relatively normal signal intensity and produced regions of newly increased signal intensity, the volume of which highly correlated with the volume and geometry of distribution on SPECT (r(2) = 0.9502). Eight infusions that produced intraparenchymal distribution were performed in regions of preexisting hyperintense signal. In these brains, additional signal changes were always produced, but quantitative correlations between areas of newly increased signal intensity and the volume and geometry of distribution on SPECT could not be established. CONCLUSION. Convection-enhanced infusions frequently do not provide intraparenchymal drug distribution, and these failures can be identified with MRI soon after infusion. When infusions are performed into regions of normal signal intensity, development of hyperintense signal change strongly correlates with the volume and geometry of distribution of infusate. C1 Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Surg, Durham, NC 27710 USA. Therataxis Inc, Baltimore, MD 21218 USA. NeoPharm Inc, Waukegan, IL 60085 USA. Brain LAB AG, Feldkirchen, Germany. NCI, Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Provenzale, JM (reprint author), Duke Univ, Med Ctr, Dept Radiol, Box 3808, Durham, NC 27710 USA. EM prove001@mc.duke.edu RI Coleman, Ralph/A-7865-2009 FU Intramural NIH HHS; NCI NIH HHS [5P50-CA108786, R01 CA97611]; NCRR NIH HHS [K23 RR16065, S10 RR15697]; NINDS NIH HHS [2P50-NS20023] NR 35 TC 48 Z9 49 U1 0 U2 0 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 2007 VL 188 IS 3 BP 703 EP 709 DI 10.2214/AJR.06.0428 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 156QE UT WOS:000245663300016 PM 17312057 ER PT J AU Mengel, M Chapman, JR Cosio, FG Cavaille-Coll, MW Haller, H Halloran, PF Kirk, AD Mihatsch, MJ Nankivell, BJ Racusen, LC Roberts, IS Rush, DN Schwarz, A Seron, D Stegall, MD Colvin, RB AF Mengel, M. Chapman, J. R. Cosio, F. G. Cavaille-Coll, M. W. Haller, H. Halloran, P. F. Kirk, A. D. Mihatsch, M. J. Nankivell, B. J. Racusen, L. C. Roberts, I. S. Rush, D. N. Schwarz, A. Seron, D. Stegall, M. D. Colvin, R. B. TI Protocol biopsies in renal transplantation: Insights into patient management and pathogenesis SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Editorial Material DE biopsy; kidney; protocol; rejection; subclinical; surrogate ID CHRONIC ALLOGRAFT NEPHROPATHY; EARLY CYCLOSPORINE WITHDRAWAL; SUBCLINICAL REJECTION; KIDNEY-TRANSPLANTATION; DIAGNOSIS; CRITERIA; INJURY; CELLS AB A 1-day symposium on the application of protocol biopsies in renal transplantation was held in Boston, 21 July 2006. Representatives from centers with extensive experience in the use of protocol biopsies for routine patient care and research reported results on the pathological findings and their value in patient management. The consensus was that protocol biopsies, in experienced hands, are a safe and valuable means of detecting subclinical disease that can benefit from modification of therapy. Furthermore, molecular studies reveal evidence of activity or progression not readily appreciated by histological techniques. Wider application is expected in multicenter clinical trials to predict and validate outcomes. The principal barrier to wider use of protocol biopsies is knowledge of the benefits of intervention. C1 Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Hannover Med Sch, Inst Pathol, D-3000 Hannover, Germany. Westmead Hosp, Ctr Transplant Res & Renal Res, Sydney, NSW, Australia. Mayo Clin & Mayo Fdn, Div Nephrol & Hypertens, Rochester, MN 55905 USA. US FDA, CDER, Div Special Pathogen & Transplantat Prod, Rockville, MD 20857 USA. Hannover Med Sch, Dept Nephrol, D-3000 Hannover, Germany. Univ Alberta, Alberta Transplant Appl Genom Ctr, Edmonton, AB, Canada. Natl Inst Digest & Kidney Dis, Transplantat Branch, NIH, Bethesda, MD USA. Univ Basel, Inst Pathol, CH-4003 Basel, Switzerland. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Oxford Radcliffe Hosp, Dept Pathol, Oxford, England. Univ Manitoba, Dept Nephrol, Winnipeg, MB, Canada. Univ Bellvitge, Dept Nephrol, Hosp, Barcelona, Spain. Mayo Clin & Mayo Fdn, Dept Surg, Rochester, MN 55905 USA. RP Colvin, RB (reprint author), Harvard Univ, Sch Med, Dept Pathol, Boston, MA 02115 USA. EM Colvin@helix.mgh.harvard.edu RI Kirk, Allan/B-6905-2012; Halloran, Philip/J-1390-2012 OI Halloran, Philip/0000-0003-1371-1947 NR 26 TC 64 Z9 66 U1 0 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PD MAR PY 2007 VL 7 IS 3 BP 512 EP 517 DI 10.1111/j.1600-6143.2006.01677.x PG 6 WC Surgery; Transplantation SC Surgery; Transplantation GA 143JD UT WOS:000244715800006 PM 17250556 ER PT J AU Schultheis, LW Rappaport, BA AF Schultheis, Lex W. Rappaport, Bob A. TI The food and drug administration perspective: Use of an investigational drug in a medical emergency SO ANESTHESIA AND ANALGESIA LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Div Anesthesia Analgesia & Rheumatol Prod, Off Drug Evaluat 2, Silver Spring, MD 20993 USA. RP Rappaport, BA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Anesthesia Analgesia & Rheumatol Prod, Off Drug Evaluat 2, 10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM bob.rappaport@fda.hhs.gov NR 1 TC 6 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAR PY 2007 VL 104 IS 3 BP 479 EP 480 DI 10.1213/01.ane.0000257291.34935.ad PG 2 WC Anesthesiology SC Anesthesiology GA 139KU UT WOS:000244431500002 PM 17312189 ER PT J AU Mellon, RD Simone, AF Rappaport, BA AF Mellon, R. Daniel Simone, Arthur F. Rappaport, Bob A. TI Use of anesthetic agents in neonates and young children SO ANESTHESIA AND ANALGESIA LA English DT Article ID D-ASPARTATE RECEPTORS; DEVELOPING RAT-BRAIN; INDUCED APOPTOTIC NEURODEGENERATION; GATED ION CHANNELS; NEURONAL DEGENERATION; GENERAL-ANESTHETICS; MK-801 PROTECTS; KETAMINE; NEUROTOXICITY; INHIBITION AB BACKGROUND: Some drugs used for sedation and anesthesia produce histopathologic central nervous system changes in juvenile animal models. These observations have raised concerns regarding the use of these drugs in pediatric patients. We summarized the findings in developing animals and describe the steps that the Food and Drug Administration (FDA) and others are taking to assess potential risks in pediatric patients. The FDA views this communication as opening a dialog with the anesthesia community to address this issue. METHODS: We reviewed the available animal studies literature examining the potential neurotoxic effects of commonly used anesthetic drugs on the developing brain. The search strategy involved crossing the keywords neurotoxic and neuroapoptosis with the following general and specific terms: anesthetic, N-methyl-D-aspartate (NMDA), ketamine, midazolam, lorazepam, fentanyl, methadone, morphine, meperidine, isoflurane, nitrous oxide, sevoflurane, halothane, enflurane, desflurane, propofol, etomidate, barbiturate, methoxyflurane, and chloral hydrate. We summarized several studies sponsored by the FDA in rats and monkeys, initially examining the potential for ketamine, as a prototypical agent, to induce neurodegeneration in the developing brain. RESULTS: Numerous animal studies in rodents indicate that NMDA receptor antagonists, including ketamine, induce neurodegeneration in the developing brain. The effects of ketamine are dose dependent. The data suggest that limiting exposure limits the potential for neurodegeneration. There is also evidence that other general anesthetics, such as isoflurane, can induce neurodegeneration in rodent models, which may be exacerbated by concurrent administration of midazolam or nitrous oxide. There are very few studies that have examined the potential functional consequences of the neurodegeneration noted in the animal models. However, the studies that have been reported suggest subtle, but prolonged, behavioral changes in rodents. Although the doses and durations of ketamine exposure that resulted in neurodegeneration were slightly larger than those used in the clinical setting, those associated with isoflurane were not. There are insufficient human data to either support or refute the clinical applicability of these findings. CONCLUSIONS: Animal studies suggest that neurodegeneration, with possible cognitive sequelae, is a potential long-term risk of anesthetics in neonatal and young pediatric patients. The existing nonclinical data implicate not only NMDA-receptor antagonists, but also drugs that potentiate gamma-aminobutyric acid signal transduction, as potentially neurotoxic to the developing brain. The potential for the combination of drugs that have activity at both receptor systems or that can induce more or less neurotoxicity is not clear, however, recent nonclinical data suggest that some combinations may be more neurotoxic than the individual components. The lack of information to date precludes the ability to designate any one anesthetic agent or regimen as safer than any other. Ongoing studies in juvenile animals should provide additional information regarding the risks. The FDA anticipates working with the anesthesia community and pharmaceutical industry to develop strategies for further assessing the safety of anesthetics in neonates and young children, and for providing data to guide clinicians in making the most informed decisions possible when choosing anesthetic regimens for their pediatric patients. C1 US FDA, Ctr Drug Evaluat & Res, Div Anesthesia Analgesia & Rheumatol Prod, Off Drug Evaluat 2,Dept Hlth & Human Serv, Silver Spring, MD 20993 USA. RP Rappaport, BA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Anesthesia Analgesia & Rheumatol Prod, Off Drug Evaluat 2,Dept Hlth & Human Serv, Silver Spring, MD 20993 USA. NR 41 TC 173 Z9 197 U1 2 U2 24 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD MAR PY 2007 VL 104 IS 3 BP 509 EP 520 DI 10.1213/01.ane.0000255729.96438.b0 PG 12 WC Anesthesiology SC Anesthesiology GA 139KU UT WOS:000244431500013 PM 17312200 ER PT J AU Lories, RJU Peeters, J Bakker, A Tylzanowski, P Derese, I Schrooten, J Thomas, JT Luyten, FP AF Lories, R. J. U. Peeters, J. Bakker, A. Tylzanowski, P. Derese, I. Schrooten, J. Thomas, J. T. Luyten, F. P. TI FRZB, a molecular basis for an inverse relationship between osteoarthritis and osteoporosis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Meeting Abstract CT 27th European Workshop for Rheumatology Research CY FEB 22-24, 2007 CL Florence, ITALY C1 Katholieke Univ Leuven, Lab Skeletal Dev & Joint Disorders, Louvain, Belgium. Katholieke Univ Leuven, Dept Met & Mat Engn, Louvain, Belgium. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RI Tylzanowski, Przemko/G-8881-2013 NR 0 TC 0 Z9 0 U1 0 U2 1 PU B M J PUBLISHING GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0003-4967 J9 ANN RHEUM DIS JI Ann. Rheum. Dis. PD MAR 1 PY 2007 VL 66 SU 1 MA 070 BP A28 EP A28 PG 1 WC Rheumatology SC Rheumatology GA 138BN UT WOS:000244337600086 ER PT J AU Elkins, CA Mullis, LB AF Elkins, Christopher A. Mullis, Lisa B. TI Substrate competition studies using whole-cell accumulation assays with the major tripartite multidrug efflux pumps of Escherichia coli SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID LARGE PERIPLASMIC LOOPS; GRAM-NEGATIVE BACTERIA; PSEUDOMONAS-AERUGINOSA; RND-TYPE; RESISTANCE; ACRB; SPECIFICITY; TRANSPORTER; MECHANISM; BINDING AB AcrAB-ToIC is the major, constitutively expressed tripartite multidrug efflux system in Escherichia coli that recognizes various structurally unrelated molecules, including many antibiotics, dyes, and steroids. The AcrB inner membrane pump portion of the efflux system has been shown in recent structural studies to bind substrates at multiple sites, suggesting that particular substrate "sets" may compete for efflux by interfering with a certain binding site(s). However, our data indicate that the general structural class does not appear to dictate a particular substrate binding site that can be competitively inhibited in whole cells. In our study, substrate competition failed to increase cell-associated levels of steroids or dyes to levels characteristic of AcrB- or AcrB/EmrAB-deficient genomic mutants or achieved with the pump inhibitor carbonyl cyanide m-chlorophenylhydrazone. In addition, this general observation was sustained even with (i) a cocktail containing seven-pump substrates supplied slightly below their respective wild-type MIC levels, (ii) competing drug substrates of the same structural class (steroids or macrolides), and (iii) hyper-MIC levels of the exogenously supplied agents. Thus, this pump system (and possibly EmrAB-ToIC) may have an extraordinary capacity to simultaneously handle multiple-drug substrates that is not necessarily reflected in MIC analyses. In addition, our study has extended the range of substrates recognized by the AcrAB- and EmrAB-ToIC systems. C1 Natl Ctr Toxicol Res, Div Microbiol, US FDA, Jefferson, AR 72079 USA. RP Elkins, CA (reprint author), Natl Ctr Toxicol Res, Div Microbiol, US FDA, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM chris.elkins@fda.hhs.gov NR 39 TC 31 Z9 32 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2007 VL 51 IS 3 BP 923 EP 929 DI 10.1128/AAC.01048-06 PG 7 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 142QT UT WOS:000244665500018 PM 17210767 ER PT J AU Volokhov, DV Duperrier, S Neverov, AA George, J Buchrieser, C Hitchins, AD AF Volokhov, Dmitriy V. Duperrier, Sandra Neverov, Alexander A. George, Joseph Buchrieser, Carmen Hitchins, Anthony D. TI The presence of the internalin gene in natural atypically hemolytic Listetia innocua strains suggests descent from L. monocytogenes SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID SUBTYPING LISTERIA-MONOCYTOGENES; FIELD GEL-ELECTROPHORESIS; COMPARATIVE GENOMICS; MAMMALIAN-CELLS; VIRULENCE; PRFA; EVOLUTION; IDENTIFICATION; EXPRESSION; PHYLOGENY AB The atypical hemolytic Listeria innocua strains PR-L/NW 15B95 and J1-023 were previously shown to contain gene clusters analogous to the pathogenicity island (LIPI-1) present in the related foodborne gram-positive facultative intracellular pathogen Listeria monocytogenes, which causes listeriosis. LIPI-1 includes the hemolysin gene, thus explaining the hemolytic activity of the atypical L. innocua strains. No other L. monocytogenes-specific virulence genes were found to be present. In order to investigate whether any other specific L. monocytogenes genes could be identified, a global approach using a Listeria biodiversity DNA array was applied. According to the hybridization results, the isolates were defined as L. innocua strains containing LIPI-1. Surprisingly, evidence for the presence of the L. monocytogenes-specific inlA gene, previously thought to be absent, was obtained. The inlA gene codes for the InlA protein which enables bacterial entry into some nonprofessional phagocytic cells. PCR and sequence analysis of this region revealed that the flanking genes of the inlA gene at the upstream, 5'-end region were similar to genes found in L. monocytogenes serotype 4b isolates, whereas the organization of the downstream, Y-end region was similar to that typical of L. innocua. Sequencing of the inlA region identified a small stretch reminiscent of the inlB gene of L. monocytogenes. The presence of two clusters of L. monocytogenes-specific genes makes it unlikely that PRL/NW 15B95 and J1-023 are L. innocua strains altered by horizontal transfer. It is more likely that they are distinct relics of the evolution of L. innocua from an ancestral L. monocytogenes, as postulated by others. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20895 USA. Inst Pasteur, Lab Genom Microorganismes Pathogenes, F-75724 Paris, France. RP Hitchins, AD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Anthony.Hitchins@fda.hhs.gov NR 43 TC 33 Z9 36 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAR PY 2007 VL 73 IS 6 BP 1928 EP 1939 DI 10.1128/AEM.01796-06 PG 12 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 149OR UT WOS:000245156800030 PM 17220266 ER PT J AU Johnson, TJ Wannemuehler, YM Johnson, SJ Logue, CM White, DG Doetkott, C Nolan, LK AF Johnson, Timothy J. Wannemuehler, Yvonne M. Johnson, Sara J. Logue, Catherine M. White, David G. Doetkott, Curt Nolan, Lisa K. TI Plasmid replicon typing of commensal and pathogenic Escherichia coli isolates SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID COMPLETE DNA-SEQUENCE; COMPARATIVE GENOMICS; R-PLASMID; RESISTANCE; SALMONELLA; TYPHIMURIUM; INTEGRON; STRAINS; INCFI; GENE AB Despite the critical role of plasmids in horizontal gene transfer, few studies have characterized plasmid relatedness among different bacterial populations. Recently, a multiplex PCR replicon typing protocol was developed for classification of plasmids occurring in members of the Enterobacteriaceae. Here, a simplified version of this replicon typing procedure which requires only three multiplex panels to identify 18 plasmid replicons is described. This method was used to screen 1,015 Escherichia coli isolates of avian, human, and poultry meat origin for plasmid replicon types. Additionally, the isolates were assessed for their content of several colicin-associated genes. Overall, a high degree of plasmid variability was observed, with 221 different profiles occurring among the 1,015 isolates examined. IncFIB plasmids were the most common type identified, regardless of the source type of E. coli. IncFIB plasmids occurred significantly more often in avian pathogenic E. coli (APEC) and retail poultry E. coli (RPEC) than in uropathogenic E. coli (UPEC) and avian and human fecal commensal E. coli isolates (AFEC and HFEC, respectively). APEC and RPEC were also significantly more likely than UPEC, HFEC, and AFEC to possess the colicin-associated genes cvaC, cbi, and/or cma in conjunction with one or more plasmid replicons. The results suggest that E. coli isolates contaminating retail poultry are notably similar to APEC with regard to plasmid profiles, with both generally containing multiple plasmid replicon types in conjunction with colicin-related genes. In contrast, UPEC and human and avian commensal E. coli isolates generally lack the plasmid replicons and colicin-related genes seen in APEC and RPEC, suggesting limited dissemination of such plasmids among these bacterial populations. C1 Iowa State Univ, Coll Vet Med, Dept Vet Microbiol & Prevent Med, Ames, IA 50011 USA. US FDA, Ctr Vet Med, Off Res, Laurel, MD 20708 USA. N Dakota State Univ, Informt Technol Serv, Fargo, ND 58105 USA. RP Nolan, LK (reprint author), Iowa State Univ, Coll Vet Med, Dept Vet Microbiol & Prevent Med, 1802 elwood Dr,VMRI 2, Ames, IA 50011 USA. EM lknolan@iastate.edu FU NIAID NIH HHS [U24 AI 50139] NR 39 TC 149 Z9 152 U1 2 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD MAR PY 2007 VL 73 IS 6 BP 1976 EP 1983 DI 10.1128/AEM.02171-06 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 149OR UT WOS:000245156800035 PM 17277222 ER PT J AU LeBaron, CW Beeler, J Sullivan, BJ Forghani, B Bi, DL Beck, C Audet, S Gargiullo, P AF LeBaron, Charles W. Beeler, Judith Sullivan, Bradley J. Forghani, Bagher Bi, Daoling Beck, Carol Audet, Susette Gargiullo, Paul TI Persistence of measles antibodies after 2 doses of measles vaccine in a postelimination environment SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article ID PLAQUE-NEUTRALIZATION TEST; MUMPS-RUBELLA VACCINE; UNITED-STATES; IMMUNE-RESPONSES; FOLLOW-UP; ELIMINATION; OUTBREAK; CHILDREN; REVACCINATION; TRANSMISSION AB Objective: To evaluate the persistence of measles antibodies after 2 doses of measles vaccine in a setting where exposure to wild- type measles was unlikely. Measles was declared eliminated from the United States in 2000, an achievement attributed to effective implementation of a routine 2- dose vaccination policy. Some have questioned whether measles transmission could resume if immunity wanes in the absence of boosting from wild- type measles. Design: Prospective, observational, volunteer cohort study. Setting: Rural Wisconsin health maintenance organization. Participants: Children who received the second measles vaccine dose at kindergarten ( aged 4- 6 years) or middle school ( aged 10- 12 years) in 1994 or 1995. Serum samples were collected periodically during a 10- year period for the kindergarten group and a 5- year period for the middle school group. Intervention: Second dose of measles vaccine. Main Outcome Measure: Measles antibody levels were assessed by plaque- reduction neutralization: titers less than 8 mIU/ mL were considered seronegative and suggestive of susceptibility to measles, and titers of 120 mIU/ mL or less were considered low and suggestive of potential susceptibility. Results: During the study period, no measles was reported in the study area. Voluntary attrition reduced the study population from 621 at enrollment to 364 ( 58.6%) by study end. Before the second dose, 3.1% ( 19/ 621) had low titers, of whom 74% ( 14/ 19) were antibodynegative, with geometric mean titers being significantly higher in kindergarteners ( 1559 mIU/ mL) than in middle schoolers ( 757 mIU/ mL) and rates of negativity significantly lower ( 1.0% [ 3/ 312] vs 3.6% [ 11/ 309]). One month after the second dose, 0.2% ( 1/ 612) had low titers and none was seronegative, with geometric mean titers being significantly higher in kindergarteners ( 2814 mIU/ mL) than in middle schoolers ( 1672 mIU/ mL). By study end, 4.9% ( 18/ 364) had low titers and none was seronegative, with no significant difference in geometric mean titers between kindergarteners ( 641 mIU/ mL) and middle schoolers ( 737 mIU/ mL) when both groups were aged 15 years. Projections suggest that the proportion of persons with low antibody levels may increase over time. Conclusions: Measles antibody persisted in all vaccinees available for follow- up 10 years after a second dose of vaccine, with no seronegative results detected. Declining titers suggest the need for vigilance in ensuring disease protection for the vaccinated population. C1 Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. US FDA, Div Viral Prod, Bethesda, MD 20014 USA. Marshfield Clin Med Res Fdn, Marshfield, WI USA. Calif Dept Hlth Serv, Viral & Rickettsial Dis Lab Branch, Div Communicable Dis Control, Richmond, CA USA. RP LeBaron, CW (reprint author), Ctr Dis Control & Prevent, Div Viral Dis, Natl Ctr Immunizat & Resp Dis, Mail Stop A-47, Atlanta, GA 30333 USA. EM clebaron@cdc.gov NR 47 TC 41 Z9 43 U1 0 U2 5 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD MAR PY 2007 VL 161 IS 3 BP 294 EP 301 DI 10.1001/archpedi.161.3.294 PG 8 WC Pediatrics SC Pediatrics GA 142LC UT WOS:000244650300011 PM 17339511 ER PT J AU Appelbaum, FR Rosenblum, D Arceci, RJ Carroll, WL Breitfeld, PP Forman, SJ Larson, RA Lee, SJ Murphy, SB O'Brien, S Radich, J Scher, NS Smith, FO Stone, RM Tallman, MS AF Appelbaum, Frederick R. Rosenblum, Daniel Arceci, Robert J. Carroll, William L. Breitfeld, Philip P. Forman, Stephen J. Larson, Richard A. Lee, Stephanie J. Murphy, Sharon B. O'Brien, Susan Radich, Jerald Scher, Nancy S. Smith, Franklin O. Stone, Richard M. Tallman, Martin S. TI End points to establish the efficacy of new agents in the treatment of acute leukemia SO BLOOD LA English DT Article ID ACUTE-MYELOID-LEUKEMIA; ACUTE LYMPHOBLASTIC-LEUKEMIA; MINIMAL RESIDUAL DISEASE; BONE-MARROW-TRANSPLANTATION; ACUTE MYELOGENOUS LEUKEMIA; QUALITY-OF-LIFE; STEM-CELL TRANSPLANTATION; ONCOLOGY-GROUP; RETROSPECTIVE ANALYSIS; GEMTUZUMAB OZOGAMICIN AB Federal regulations provide 2 pathways for approval of new agents for the treatment of acute leukemia, regular and accelerated approval. Regular approval requires evidence of clinical benefit, which is generally defined as either prolongation of life or improved quality of life, or an effect on an end point established as a surrogate for clinical benefit. Accelerated approval can be obtained based on demonstration of an effect on a surrogate measure "reasonably likely" to predict clinical benefit, but requires demonstration of clinical benefit after approval as well. The acute leukemias are a heterogeneous and relatively uncommon group of diseases. The design and execution of prospective randomized clinical trials demonstrating prolongation of life or improved quality of life for patients with these disorders can be difficult and costly and require lengthy follow-up. Thus, the development of novel trial design and inclusion of validated surrogate markers for clinical benefit are needed. To explore some of the issues pertinent to the choice of end points for drug approval in acute leukemia, the Food and Drug Administration invited the American Society of Hematology to participate in the organization and conduct of a joint workshop. In this report, we present the results of that effort. C1 Fred Hutchinson Canc Res Ctr, Div Clin Res, Seattle, WA 98109 USA. NIH, Bethesda, MD 20892 USA. Johns Hopkins, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD USA. Mt Sinai Sch Med, Sch Med, New York, NY USA. NYU, Sch Med, New York, NY USA. Duke Univ, Sch Med, Durham, NC USA. City Hope Natl Med Ctr, Duarte, CA 91010 USA. Univ Chicago, Med Ctr, Chicago, IL 60637 USA. Dana Farber Canc Inst, Boston, MA 02115 USA. Univ Texas, Hlth Sci Ctr, Childrens Canc Res Inst, San Antonio, TX 78285 USA. MD Anderson Canc Ctr, Houston, TX USA. US FDA, Rockville, MD 20857 USA. Cincinnati Childrens Hosp, Med Ctr, Cincinnati, OH USA. Northwestern Univ, Sch Med, Chicago, IL 60611 USA. RP Appelbaum, FR (reprint author), Fred Hutchinson Canc Res Ctr, Div Clin Res, 1100 Fairview Ave N,D5-310,POB 19024, Seattle, WA 98109 USA. EM fappelba@fhcrc.org OI Larson, Richard/0000-0001-9168-3203 NR 41 TC 47 Z9 50 U1 0 U2 2 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 1 PY 2007 VL 109 IS 5 BP 1810 EP 1816 DI 10.1182/blood-2006-08-041152 PG 7 WC Hematology SC Hematology GA 142HW UT WOS:000244641100011 PM 17095617 ER PT J AU Cokic, VP Bhattacharya, B Smith, RD Beleslin-Cokic, BB Noguchi, CT Puri, RK Schechter, AN AF Cokic, Vladan P. Bhattacharya, Bhaskar Smith, Reginald D. Beleslin-Cokic, Bojana B. Noguchi, Constance T. Puri, Raj K. Schechter, Alan N. TI Gene expression profiling in fetal and adult definitive erythropoiesis SO BLOOD CELLS MOLECULES AND DISEASES LA English DT Meeting Abstract CT 15th Conference on Hemoglobin Switching CY SEP 14-18, 2006 CL St Johns Coll, Oxford, ENGLAND HO St Johns Coll C1 Inst Med Res, Lab Expt Hematol, Belgrade, Serbia. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Tumor Vaccines & Biotechnol Branch, Bethesda, MD USA. GE Global Res Ctr, Biosci Technol, Niskayuna, NY USA. Inst Endocrinol Diabetes & Dis Metab, Belgrade, Serbia. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1079-9796 J9 BLOOD CELL MOL DIS JI Blood Cells Mol. Dis. PD MAR-APR PY 2007 VL 38 IS 2 MA 20 BP 131 EP 132 DI 10.1016/j.bcmd.2006.10.031 PG 2 WC Hematology SC Hematology GA 140OB UT WOS:000244513900030 ER PT J AU Young, JF Luecke, RH Doerge, DR AF Young, John F. Luecke, Richard H. Doerge, Daniel R. TI Physiologically based pharmacokinetic/pharmacodynamic model for acrylamide and its metabolites in mice, rats, and humans SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HEMOGLOBIN ADDUCT FORMATION; FISCHER-344 RATS; B6C3F(1) MICE; GLYCIDAMIDE; TOXICOKINETICS; EXPOSURE; BIOMARKERS; GENOTOXICITY AB A physiologically based pharmacokinetic model was developed for acrylamide (AA) and three of its metabolites: glycidamide (GA) and the glutathione conjugates of acrylamide (AA-GS) and glycidamide (GA-GS). Liver GA-DNA adducts and hemoglobin (Hb) adducts with AA and GA were included as pharmacodynamic components of the model. Serum AA and GA concentrations combined with urinary elimination levels for all four components from male and female mice and rats were simulated from iv and oral administration of 0.1 mg/kg AA or 0.12 mg/kg GA. Adduct formation and decay rates were determined from a 6 week exposure to approximately 1 mg/kg AA in the drinking water and subsequent 6 week nonexposure period. Human urinary excretion data and Hb adduct data were utilized to extrapolate to a human model. The steady-state human liver GA-DNA adduct level from exposure to background levels of AA in the diet was predicted to be between 0.06 and 0.26 adducts per 10(8) nucleotides. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Risk Assessment & Biochem Toxicol, Jefferson, AR 72079 USA. Univ Missouri, Dept Chem Engn, Columbia, MO 65211 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry, Jefferson, AR 72079 USA. EM Daniel.Doerge@fda.hhs.gov NR 26 TC 28 Z9 28 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 2007 VL 20 IS 3 BP 388 EP 399 DI 10.1021/tx600287w PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 146TU UT WOS:000244958400006 PM 17323977 ER PT J AU Turesky, RJ Goodenough, AK Ni, WJ McNaughton, L LeMaster, DM Holland, RD Wu, RW Felton, JS AF Turesky, Robert J. Goodenough, Angela K. Ni, Weijuan McNaughton, Lynn LeMaster, David M. Holland, Ricky D. Wu, Rebekah W. Felton, James S. TI Identification of 2-amino-1,7-dimethylimidazo[4,5-g]quinoxaline: An abundant mutagenic heterocyclic aromatic amine formed in cooked beef SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID TANDEM MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; SALMONELLA-TYPHIMURIUM; COLORECTAL-CANCER; DNA-ADDUCTS; FOOD MUTAGENS; HUMAN TISSUES; RISK; MEAT; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE AB A previously unknown isomer of the carcinogenic heterocyclic aromatic amine (HAA) 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) was recently discovered in the urine of meat eaters and subsequently detected in cooked ground beef (Holland, R.D., et al. (2004) Chem. Res. Toxicol. 17, 1121-1136). In this current investigation, the identity of the analyte was determined through a comparison of its chromatographic t(R) by HPLC and through UV and mass spectral comparisons to the synthesized isomers of 8-MeIQx. Angular tricyclic isomers of 8-MeIQx were excluded as potential structures of the newly discovered HAA, on the basis of dissimilar t(R) and product ion mass spectral data. The linear tricyclic isomers 2-amino-1,6-dimethylimidazo[4,5-g]quinoxaline (6-MeIgQx) and 2-amino-1,7-dimethylimidazo[4,5-g]quinoxaline (7-MeIgQx) were postulated as plausible structures. Both compounds were synthesized from 4-fluoro-5-nitro-benzene-1,2-diamine in five steps. The structure of the analyte was proven to be 7-MeIgQx, on the basis of co-injection of the compound with the synthetic isomers, and corroborated by comparisons of the UV and mass spectral data of the analyte and MeIgQx isomers. 7-MeIgQx induced 348 revertants/mu g in the S. typhimurium tester strain YG1024, when liver S-9 homogenate of rats pretreated with polychlorinated biphenyls (PCBs) was used for bioactivation. This newly discovered 7-MeIgQx molecule is one of the most abundant HAAs formed in cooked ground beef patties and pan-fried scrapings. The human health risk of 7-MeIgQx requires investigation. C1 New York State Dept Hlth, Wadsworth Ctr, Div Environm Dis Prevent, Albany, NY 12201 USA. New York State Dept Hlth, Wadsworth Ctr, Div Mol Med, Albany, NY 12201 USA. US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. Lawrence Livermore Natl Lab, Chem Mat & Life Sci Directorate, Livermore, CA 94551 USA. RP Turesky, RJ (reprint author), New York State Dept Hlth, Wadsworth Ctr, Div Environm Dis Prevent, Albany, NY 12201 USA. EM rturesky@wadsworth.org RI yang, min/G-3030-2011 FU NCI NIH HHS [CA55861, P01 CA055861-089001, P01 CA055861] NR 45 TC 20 Z9 21 U1 1 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 2007 VL 20 IS 3 BP 520 EP 530 DI 10.1021/tx600317r PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 146TU UT WOS:000244958400020 PM 17316027 ER PT J AU Goodman, VL Rock, EP Dagher, R Ramchandani, RP Abraham, S Gobburu, JVS Booth, BP Verbois, SL Morse, DE Liang, CY Chiclambaram, N Jiang, JX Tang, S Mahjoob, K Justice, R Pazdur, R AF Goodman, Vicki L. Rock, Edwin P. Dagher, Ramzi Ramchandani, Roshni P. Abraham, Sophia Gobburu, Jogarao V. S. Booth, Brian P. Verbois, S. Leigh Morse, David E. Liang, Cheng Yi Chiclambaram, Nallaperumal Jiang, Janet X. Tang, Shenghui Mahjoob, Kooros Justice, Robert Pazdur, Richard TI Approval summary: Sunitinib for the treatment of imatinib refractory or intolerant gastrointestinal stromal tumors and advanced renal cell carcinoma SO CLINICAL CANCER RESEARCH LA English DT Article ID INTERFERON ALFA-2A; SURVIVAL; INTERLEUKIN-2; TRIAL; MESYLATE AB Purpose: To describe the Food and Drug Administration (FDA) review and approval of sunitinib malate (Sutent). Sunitinib received regular approval for the treatment of gastrointestinal stromal tumor (GIST) after disease progression or intolerance to imatinib mesylate (Gleevec). Additionally, sunitinib received accelerated approval for the treatment of advanced renal cell carcinoma. Experimental Design: For the GIST indication, FDA reviewed data from a randomized, placebo-controlled trial with supportive evidence from a single-arm study. For the advanced renal cell carcinoma indication, FDA reviewed data from two single-arm studies of patients with cytokine-refractory metastatic renal cell carcinoma. Results: In patients with imatinib refractory or intolerant GIST, time-to-tumor progression of sunitinib-treated patients was superior to that of placebo-treated patients. Median time-to-tumor progression of sunitinib-treated patients was 27.3 weeks, compared with 6.4 weeks for placebo-treated patients (P < 0.0001). Partial responses were observed in 6.8% of sunitinib-treated patients. In patients with metastatic renal cell carcinoma, partial responses were observed in 25.5% (95% confidence interval, 17.5, 34.9) and 36.5% (95% confidence interval, 24.7, 49.6) of patients treated with sunitinib. Median response durations were 27.1 and 54 weeks. The most common adverse events attributed to sunitinib included diarrhea, mucositis, skin abnormalities, and altered taste. Reductions in left ventricular ejection fraction and severe hypertension were also more common in sunitinib-treated patients. Conclusions: On January 26, 2006, the FDA approved sunitinib for the treatment of patients with imatinib refractory or intolerant GIST Accelerated approval was granted for the treatment of advanced renal cell carcinoma. C1 US FDA, Div Drug Oncol Prod, Silver Spring, MD 20903 USA. US FDA, Div Clin Pharmacol, Off Clin Pharmacol, Silver Spring, MD 20903 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmceut Sci, Silver Spring, MD 20903 USA. US FDA, Ctr Drug Evaluat & Res, Off Biostat, Silver Spring, MD 20903 USA. US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD 20903 USA. RP Goodman, VL (reprint author), US FDA, Div Drug Oncol Prod, Room 2139,Bldg 22,10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM vicki.goodman@fda.hhs.gov NR 19 TC 251 Z9 271 U1 1 U2 20 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 MAR 1 PY 2007 VL 13 IS 5 BP 1367 EP 1373 DI 10.1158/1078-0432.CCR-06-2328 PG 7 WC Oncology SC Oncology GA 144CL UT WOS:000244772800004 PM 17332278 ER PT J AU Averbuch, M Katzper, M AF Averbuch, M. Katzper, M. TI Evidence based regulatory guidance, to flare or not to flare in the osteoarthritis pain model. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 21-24, 2007 CL Anaheim, CA SP Amer Soc Clin Pharmacol & Therapeut C1 Tel Aviv Univ, Ctr Med, IL-69978 Tel Aviv, Israel. CDER, US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2007 VL 81 SU 1 BP S12 EP S12 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144FW UT WOS:000244782900034 ER PT J AU Kim, M Huang, S Frueh, F Rahman, A Burckart, GJ Thummel, KE Lesko, LJ AF Kim, M. Huang, S. Frueh, F. Rahman, A. Burckart, G. J. Thummel, K. E. Lesko, L. J. TI Knowledge of CYP2C9 and VKORC1 genotype can improve dosing of warfarin. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 21-24, 2007 CL Anaheim, CA SP Amer Soc Clin Pharmacol & Therapeut C1 Univ So Calif, US FDA, Silver Spring, MD USA. Washington Univ, US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2007 VL 81 SU 1 BP S18 EP S18 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144FW UT WOS:000244782900049 ER PT J AU Pinnow, E Scott, P Derbis, J Toigo, T Uhl, K AF Pinnow, E. Scott, P. Derbis, J. Toigo, T. Uhl, K. TI Risk management during drug development: Pregnancy prevention strategies employed in clinical trials submitted to the FDA. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 21-24, 2007 CL Anaheim, CA SP Amer Soc Clin Pharmacol & Therapeut C1 US FDA, Off Womens Hlth, Rockville, MD 20857 USA. US FDA, Off Special Hlth Issues, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2007 VL 81 SU 1 BP S9 EP S9 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144FW UT WOS:000244782900025 ER PT J AU Thummel, K Chung, S Nallani, S Reynolds, K Strong, J Yasuda, S Zhang, L Huang, S AF Thummel, K. Chung, S. Nallani, S. Reynolds, K. Strong, J. Yasuda, S. Zhang, L. Huang, S. TI When is a multiple-inhibitor study necessary SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 21-24, 2007 CL Anaheim, CA SP Amer Soc Clin Pharmacol & Therapeut C1 Univ Washington, Seattle, WA 98195 USA. CDER, OCP, FDA, OTR, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2007 VL 81 SU 1 BP S74 EP S74 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144FW UT WOS:000244782900215 ER PT J AU Uhl, K Pinnow, E Hollinger, K AF Uhl, K. Pinnow, E. Hollinger, K. TI Demographic data on sex in ASCPT posters: Discrimination or not? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT Annual Meeting of American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 21-24, 2007 CL Anaheim, CA SP Amer Soc Clin Pharmacol & Therapeut C1 US FDA, Off Womens Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD MAR PY 2007 VL 81 SU 1 BP S66 EP S67 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 144FW UT WOS:000244782900194 ER PT J AU Tompkins, SM Zhao, ZS Lo, CY Misplon, JA Liu, T Ye, ZP Hogan, RJ Wu, ZQ Benton, KA Tumpey, TM Epstein, SL AF Tompkins, Stephen Mark Zhao, Zi-Shan Lo, Chia-Yun Misplon, Julia A. Liu, Teresa Ye, Zhiping Hogan, Robert J. Wu, Zhengqi Benton, Kimberly A. Tumpey, Terrence M. Epstein, Suzanne L. TI Matrix protein 2 vaccination and protection against influenza viruses, including subtype H5N1 SO EMERGING INFECTIOUS DISEASES LA English DT Article ID A VIRUS; EXTRACELLULAR DOMAIN; M2 PROTEIN; T-CELLS; MICE; CHALLENGE; IMMUNITY; IMMUNIZATION; INFECTION; VACCINES AB Changes in influenza viruses require regular reformulation of strain-specific influenza vaccines. Vaccines based on conserved antigens provide broader protection. Influenza matrix protein 2 (M2) is highly conserved across influenza A subtypes. To evaluate its efficacy as a vaccine candidate, we vaccinated mice with M2 peptide of a widely shared consensus sequence. This vaccination induced antibodies that cross-reacted with divergent M2 peptide from an H5N1 subtype. A DNA vaccine expressing full-length consensus-sequence M2 (M2-DNA) induced M2-specific antibody responses and protected against challenge with lethal influenza. Mice primed with M2-DNA and then boosted with recombinant adenovirus expressing M2 (M2-Ad) had enhanced antibody responses that cross-reacted with human and avian M2 sequences and produced T-cell responses. This M2 prime-boost vaccination conferred broad protection against challenge with lethal influenza A, including an H5N1 strain. Vaccination with M2, with key sequences represented, may provide broad protection against influenza A. C1 Univ Georgia, Dept Infect Dis, Athens, GA 30602 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Bethesda, MD 20014 USA. RP Tompkins, SM (reprint author), Univ Georgia, Dept Infect Dis, 111 Carlton St, Athens, GA 30602 USA. EM tompkins@vet.uga.edu RI Tompkins, Stephen/A-3317-2008 OI Tompkins, Stephen/0000-0002-1523-5588 NR 22 TC 177 Z9 197 U1 2 U2 11 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD MAR PY 2007 VL 13 IS 3 BP 426 EP 435 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 144MQ UT WOS:000244800900009 PM 17552096 ER PT J AU Knechtges, PL Sprando, RL Porter, KL Brennan, LM Miller, MF Kumsher, DM Dennis, WE Brown, CC Clegg, ED AF Knechtges, Paul L. Sprando, Robert L. Porter, Karen L. Brennan, Linda M. Miller, Mark F. Kumsher, David M. Dennis, William E. Brown, Charles C. Clegg, Eric D. TI A novel amphibian tier 2 testing protocol: A 30-week exposure of Xenopus tropicalis to the antiandrogen flutamide SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE endocrine disruption; amphibian; flutamide; Xenopus tropicalis ID SEXUAL-DIFFERENTIATION; LAEVIS; FROGS; ATRAZINE; REPLICATION; RESPONSES; ANIMALS; EMBRYO; ASSAY AB In 1996, the U.S. Congress mandated the development of a screening program for endocrine-disrupting chemicals (EDCs) using validated test systems. Subsequently, the Endocrine Disruptor Screening and Testing Advisory Committee recommended the development of a standardized amphibian assay for tier 2 testing of EDCs. For that reason, a tier 2 testing protocol using Xenopus (Silurana) tropicalis and a 30-week, flow-through exposure to the antiandrogen flutamide from stage 46 tadpoles through sexually mature adult frogs were developed and evaluated in this pilot study. The endpoints for this study included measurements of frog body lengths and weights, liver weights, ovary/egg mass weights, testicular and ovarian histopathology, plasma vitellogenin levels, and notes on any abnormalities observed at necropsy. Increasing exposure concentrations to flutamide caused significant increases in frogs with no recognizable gonadal tissue and increased body and liver weights in male frogs, whereas the body lengths and weights decreased significantly in female frogs. Important issues must be resolved before a tier 2 amphibian assay can be further developed and validated, including the establishment of baseline values in the controls for the parameters under study; the maintenance, measurement, and timing of exposure concentrations; and the development of additional biomolecular markers of effect. This study demonstrated the feasibility of conducting long-term EDC exposure studies using X. tropicalis. C1 USA, Ctr Environm Hlth Res, Sci Applicat Int Corp, Ft Detrick, MD 21702 USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. Univ Michigan, Dept Mol Cellular & Dev Biol, Rockville, MD 20853 USA. RP Porter, KL (reprint author), USA, Ctr Environm Hlth Res, Sci Applicat Int Corp, 568 Doughten Dr, Ft Detrick, MD 21702 USA. EM karen.porter@amedd.army.mil RI Porter, Karen/A-9591-2009 NR 34 TC 5 Z9 7 U1 1 U2 7 PU SOCIETY ENVIRONMENTAL TOXICOLOGY & CHEMISTRY-SETAC PI PENSACOLA PA 1010 NORTH 12TH AVE, PENSACOLA, FL 32501-3367 USA SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD MAR PY 2007 VL 26 IS 3 BP 555 EP 564 DI 10.1897/06-210R.1 PG 10 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 136RK UT WOS:000244241600023 PM 17373522 ER EF