FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Rao, G Moreira, A Brorson, K AF Rao, Govind Moreira, Antonio Brorson, Kurt TI Disposable Bioprocessing: The Future Has Arrived SO BIOTECHNOLOGY AND BIOENGINEERING LA English DT Article DE disposable technology; PAT; QbD; process consistency and validation; sensors; scale-up ID MICROBIOREACTOR AB Increasing cost pressures are driving the rapid adoption of disposables in bioprocessing. While well ensconced in lab-scale operations, the lower operating/ validation costs at larger scale and relative ease of use are leading to these systems entering all stages and operations of a typical biopharmaceutical manufacturing process. Here, we focus on progress made in the incorporation of disposable equipment with sensor technology in bioprocessing throughout the development cycle. We note that sensor patch technology is mostly being adapted to disposable cell culture devices, but future adaptation to downstream steps is conceivable. Lastly, regulatory requirements are also briefly assessed in the context of disposables and the Process Analytical Technologies (PAT) and Quality by Design (QbD) initiatives. C1 [Rao, Govind; Moreira, Antonio] UMBC, TRC, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Brorson, Kurt] US FDA, Ctr Drug Evaluat & Res, Off Biotech Prod, Div Monoclonal Antibodies, Silver Spring, MD 20903 USA. RP Rao, G (reprint author), UMBC, TRC, Dept Chem & Biochem Engn, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. EM grao@umbc.edu FU NSF; NIH; (Artisan, Baxter, DuPont, Fluorometrix, Genentech, Grace, Merck, Pfizer, Sartorius-Stedim Biotech) FX The authors think Scott Lute, George Miesegaes, and Maik Jornitz for insightful comments. Funding over the years from NSF, NIH and various corporations (Artisan, Baxter, DuPont, Fluorometrix, Genentech, Grace, Merck, Pfizer, Sartorius-Stedim Biotech) over the years is gratefully acknowledged. GR has an equity Position in Flurometrix. BioProcessors and SartOriLIS-Stedim Biotechnology are sub-licensees of Fluorometrix. We thank Michael Hanson, Jose Vallejos, Yordan Kostov, Seth Rodgers, and Pat Stancati for providing the figures and pictures. Views expressed in this article are those of the authors and not necessarily those of the US FDA or the US government. Discussion of individual Cell Culture devices does not constitute an endorsement by the US FDA or US Government. We dedicate this paper to Prof. Arthur E. Humphrey on the occasion of his 81st birthday. Art pioneered the development of modern biochemical engineering and taught all his students that "it is better to be approximately right than exactly wrong" and strongly encouraged monitoring of bioprocesses by all possible means. NR 21 TC 51 Z9 51 U1 1 U2 21 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0006-3592 J9 BIOTECHNOL BIOENG JI Biotechnol. Bioeng. PD FEB 1 PY 2009 VL 102 IS 2 BP 348 EP 356 DI 10.1002/bit.22192 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 395RD UT WOS:000262540300003 PM 19090536 ER PT J AU Rao, VA Klein, SR Agama, KK Toyoda, E Adachi, N Pommier, Y Shacter, EB AF Rao, V. Ashutosh Klein, Sarah R. Agama, Keli K. Toyoda, Eriko Adachi, Noritaka Pommier, Yves Shacter, Emily B. TI The Iron Chelator Dp44mT Causes DNA Damage and Selective Inhibition of Topoisomerase II alpha in Breast Cancer Cells SO CANCER RESEARCH LA English DT Article ID DOUBLE-STRAND BREAKS; 3-AMINOPYRIDINE-2-CARBOXALDEHYDE THIOSEMICARBAZONE 3-AP; POTENT ANTITUMOR-ACTIVITY; RIBONUCLEOTIDE REDUCTASE; ISONICOTINOYL HYDRAZONE; CYCLE ARREST; TUMOR-GROWTH; DEXRAZOXANE; DOXORUBICIN; GAMMA-H2AX AB Di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone (Dp44mT) is being developed as an iron chelator with selective anticancer activity. We investigated the mechanism whereby Dp44mT kills breast cancer cells, both as a single agent and in combination with doxorubicin. Dp44mT alone induced selective cell killing in the breast cancer cell line MDA-MB-231 when compared with healthy mammary epithelial cells (MCF-12A). It induces G(1) cell cycle arrest and reduces cancer cell clonogenic growth at nanomolar concentrations. Dp44mT, but not the iron chelator desferal, induces DNA double-strand breaks quantified as S139 phosphorylated historic foci (gamma-H2AX) and Comet tails induced in MDA-MB-231 cells. Doxorubicin-induced cytotoxicity and DNA damage were both enhanced significantly in the presence of low concentrations of Dp44mT. The chelator caused selective poisoning of DNA topoisomerase II alpha (top2 alpha) as measured by an in vitro DNA cleavage assay and cellular topoisomerase-DNA complex formation. Heterozygous Nalm-6 top2 alpha knockout cells (top2 alpha(+/-)) were partially resistant to Dp44mT-induced cytotoxicity compared with isogenic top2 alpha(+/+) or top2 beta(-/-) cells. Specificity for top2 alpha was confirmed using top2 alpha and top2 beta small interfering RNA knockdown in HeLa cells. The results show that Dp44mT is cytotoxic to breast cancer cells, at least in part, due to selective inhibition of top2 alpha. Thus, Dp44mT may serve as a mechanistically unique treatment for cancer due to its dual ability to chelate iron and inhibit top2 alpha activity. [Cancer Res 2009;69(3):948-57] C1 [Rao, V. Ashutosh] NCI, Food & Drug Adm, Interagency Oncol Task Force Program, Bethesda, MD 20892 USA. [Agama, Keli K.; Pommier, Yves] NCI, Mol Pharmacol Lab, Ctr Canc Res, US Dept HHS, Bethesda, MD 20892 USA. [Toyoda, Eriko; Adachi, Noritaka] Yokohama City Univ, Yokohama, Kanagawa 232, Japan. RP Rao, VA (reprint author), 29 Lincoln Dr,Bldg 29A,Room 2A-11,HFD-122, Bethesda, MD 20892 USA. EM ashutosh.rao@fda.hhs.gov; emily.shacter@fda.hhs.gov FU Intramural Research Program; Center for Cancer Research; National Cancer Institute; NIH FX Intramural Research Program, Center for Cancer Research, National Cancer Institute, NIH. NR 50 TC 77 Z9 77 U1 1 U2 11 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 FEB 1 PY 2009 VL 69 IS 3 BP 948 EP 957 DI 10.1158/0008-5472.CAN-08-1437 PG 10 WC Oncology SC Oncology GA 402YJ UT WOS:000263048700030 PM 19176392 ER PT J AU Haas, DM Renbarger, JL Denne, S Ahmed, MS Easterling, T Feibus, K Meslin, EM Koren, G Zajicek, A Snodgrass, WR Flockhart, DA AF Haas, David M. Renbarger, Jamie L. Denne, Scott Ahmed, Mahmoud S. Easterling, Thomas Feibus, Karen Meslin, Eric M. Koren, Gideon Zajicek, Anne Snodgrass, Wayne R. Flockhart, David A. TI Pharmacotherapy and Pregnancy HIGHLIGHTS FROM THE FIRST INTERNATIONAL CONFERENCE FOR INDIVIDUALIZED PHARMACOTHERAPY IN PREGNANCY SO CTS-CLINICAL AND TRANSLATIONAL SCIENCE LA English DT Editorial Material ID WOMEN; DEPRESSION C1 [Haas, David M.; Renbarger, Jamie L.; Denne, Scott; Meslin, Eric M.; Flockhart, David A.] Indiana Univ, Sch Med, PREGMED, Ctr Pharmacogenet & Therapeut Res Maternal & Chil, Indianapolis, IN 46204 USA. [Ahmed, Mahmoud S.; Snodgrass, Wayne R.] Univ Texas Med Branch Galveston, Galveston, TX USA. [Easterling, Thomas] Univ Washington, Sch Med, Seattle, WA USA. [Feibus, Karen] US FDA, Washington, DC 20204 USA. [Meslin, Eric M.] Indiana Univ, Ctr Bioeth, Indianapolis, IN 46204 USA. [Koren, Gideon] SickKids Hosp, Toronto, ON, Canada. [Zajicek, Anne] NICHHD, Washington, DC USA. RP Haas, DM (reprint author), Indiana Univ, Sch Med, PREGMED, Ctr Pharmacogenet & Therapeut Res Maternal & Chil, Indianapolis, IN 46204 USA. EM dahaas@iupui.edu FU NICHD NIH HHS [U10 HD063094] NR 17 TC 3 Z9 4 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1752-8054 J9 CTS-CLIN TRANSL SCI JI CTS-Clin. Transl. Sci. PD FEB PY 2009 VL 2 IS 1 BP 11 EP 14 DI 10.1111/j.1752-8062.2009.00079.x PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 532RW UT WOS:000272768200009 PM 20443863 ER PT J AU He, Z AF He, Zhen TI Fluorogold Induces Persistent Neurological Deficits and Circling Behavior in Mice Over-Expressing Human Mutant Tau SO CURRENT NEUROVASCULAR RESEARCH LA English DT Article DE Amygdala; apoptosis; circling behavior; fluorogold; nanospecie; neurological deficit; human mutant tau; mouse ID MOUSE MODEL; CEREBRAL-ISCHEMIA; GLOBAL-ISCHEMIA; CELL-DEATH; HIPPOCAMPAL; NEURONS; RATS; VISUALIZATION; TAUOPATHY; IMPROVES AB An increasing number of applications use nanospecie-fluorescent labeling technology; however, no established guidelines are available to warrant their safety for potential clinical use. Here, rTg4510 transgenic mice and their littermate controls were injected with fluorogold, a nanospecie tracer, or phosphate buffered saline ( PBS) targeted to the right amygdala. No significant abnormal behavior was detected in any mice injected with PBS. After fluorogold injection, however, rTg4510 mice displayed persistent left-sided neurological deficits and left circling behavior for up to 14 days post-injection, while control mice demonstrated a transient syndrome. Mortality occurred only in rTg4510 mice and statistically significant differences appeared independent of age. An immunofluorescent study revealed TUNEL positive cells that were heavily and extensively distributed in the periamygdalar region that overlapped with the fluorogold deposit region in rTg4510 mice, whereas control mice showed only sporadic distribution of TUNEL-positive cells. Co-localization of TUNEL and caspase-3 active peptide immunoreactivity was identified in a subset of the cells, indicating an involvement of caspase-dependent apoptotic mechanisms. In conclusion, fluorogold induces damage in the central nervous system most noticeably in mice over-expressing human mutant tau. C1 [He, Zhen] US FDA, Div Neurotoxicol, NCTR, Jacksonville, FL USA. [He, Zhen] Mayo Clin, Dept Neurosci, Jacksonville, FL USA. RP He, Z (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Zhen.He@fda.hhs.gov FU Mayo Foundation FX This work was supported in part by the Mayo Foundation. The author wishes to thank Drs. Merle Paule and Sherry Ferguson for manuscript review and revision. NR 27 TC 8 Z9 8 U1 0 U2 3 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1567-2026 J9 CURR NEUROVASC RES JI Curr. Neurovasc. Res. PD FEB PY 2009 VL 6 IS 1 BP 54 EP 61 PG 8 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA 415SH UT WOS:000263954500006 PM 19355926 ER PT J AU Harth, E Matsuda, L Hernandez, C Rioseco, ML Romero, J Gonzalez-Escalona, N Martinez-Urtaza, J Espejo, RT AF Harth, Erika Matsuda, Luis Hernandez, Cristina Rioseco, Maria L. Romero, Jaime Gonzalez-Escalona, Narjol Martinez-Urtaza, Jaime Espejo, Romilio T. TI Epidemiology of Vibrio parahaemolyticus Outbreaks, Southern Chile SO EMERGING INFECTIOUS DISEASES LA English DT Article ID DIRECT HEMOLYSIN GENE; RIBOSOMAL-RNA GENES; SECRETION SYSTEMS; STRAINS; SEQUENCE; O3-K6; DIARRHEA; CLONE; PCR; EMERGENCE AB Disease outbreaks caused by Vibrio parahaemolyticus in Puerto Montt, Chile, began in 2004 and reached a peak in 2005 at 3,600 clinical cases. Until 2006, every analyzed case was caused by the serovar O3:K6 pandemic strain. In the summer of 2007, only 475 cases were reported; 73% corresponded to the pandemic strain. This decrease was associated with a change in serotype of many pandemic isolates to O3:K59 and the emergence of new clinical strains. One of these strains, associated with 11% of the cases, was genotypically different from the pandemic strain but contained genes that were identical to those found on its pathogenicity island. These findings suggest that pathogenicity-related genes were laterally transferred from the pandemic strain to one of the different V parahaemolyticus groups comprising the diverse and shifting bacterial population in shellfish in this region. C1 [Espejo, Romilio T.] Univ Chile, Inst Nutr & Tecnol Alimentos, Santiago 6903625, Chile. [Hernandez, Cristina] Secretaria Reg Ministerial Salud, Puerto Montt, Chile. [Rioseco, Maria L.] Hosp Reg Puerto Montt, Puerto Montt, Chile. [Gonzalez-Escalona, Narjol] US FDA, College Pk, MD USA. [Martinez-Urtaza, Jaime] Univ Santiago de Compostela, Santiago De Compostela, Spain. RP Espejo, RT (reprint author), Univ Chile, Inst Nutr & Tecnol Alimentos, El Libano 5524, Santiago 6903625, Chile. EM respejo@inta.cl RI Gonzalez-Escalona, Narjol/A-7598-2009; Romero, Jaime/I-2816-2013; Martinez-Urtaza, Jaime/A-5528-2015; Espejo, Romilio/J-3183-2015; OI Romero, Jaime/0000-0001-9614-2393; Espejo, Romilio/0000-0003-0495-4576; Gonzalez-Escalona, Narjol/0000-0003-4568-0022 FU Fondo Nacional de Desarrollo Cientifico Technologico [1040875, 1070658]; Deutscher Akademischer Austausch Diemst. FX This Study was Supported in part by grants from Fondo Nacional de Desarrollo Cientifico Technologico (nos. 1040875 and 1070658). E.H. was supported by a scholarship from Deutscher Akademischer Austausch Diemst. NR 29 TC 51 Z9 54 U1 0 U2 5 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD FEB PY 2009 VL 15 IS 2 BP 163 EP 168 DI 10.3201/eid1502.071269 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 405NE UT WOS:000263230700003 PM 19193258 ER PT J AU Guo, L Li, QZ Xia, QS Dial, S Chan, PC Fu, P AF Guo, Lei Li, Quanzhen Xia, Qingsu Dial, Stacey Chan, Po-Chuen Fu, Peter TI Analysis of gene expression changes of drug metabolizing enzymes in the livers of F344 rats following oral treatment with kava extract SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Drug metabolizing enzyme; Drug metabolizing gene; Gene expression; Kava extract; Microarray; TaqMan assay ID ST-JOHNS-WORT; DIETARY-SUPPLEMENTS; PIPER-METHYSTICUM; PYRROLIZIDINE ALKALOIDS; GINKGO-BILOBA; IN-VIVO; CYTOCHROME-P450; KAVALACTONES; TOXICITY; PHARMACOKINETICS AB The association of kava product use with liver-related risks has prompted regulatory action in many countries. We studied the changes in gene expression of drug metabolizing enzymes in the livers of Fischer 344 male rats administered kava extract by gavage for 14 weeks. Analysis of 22,226 genes revealed that there were 14, 41, 110, 386, and 916 genes significantly changed in the 0.125, 0.25, 0.5, 1.0, and 2.0 g/kg treatment groups, respectively. There were 16 drug metabolizing genes altered in all three high-dose treatment groups, among which seven genes belong to cytochrome P450 isozymes. While gene expression of Cyp1a1, 1a2, 26, 3a1, and 3a3 increased: Cyp 2c23 and 2c40 decreased, all in a dose-dependent manner. Real-time PCR analyses of several genes verified these results. Our results indicate that kava extract can significantly modulate drug metabolizing enzymes, particularly the CYP isozymes, which could cause herb-drug interactions and may potentially lead to hepatotoxicity. Published by Elsevier Ltd. C1 [Guo, Lei; Dial, Stacey] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Li, Quanzhen] Univ Texas SW Med Ctr Dallas, Microarray Core Facil, Dallas, TX 75390 USA. [Xia, Qingsu; Fu, Peter] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Chan, Po-Chuen] NIEHS, Res Triangle Pk, NC 27709 USA. RP Guo, L (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM lei.guo@fda.hhs.gov; peter.fu@fda.hhs.gov RI Guo, Lei/E-9232-2011 NR 52 TC 33 Z9 33 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 EI 1873-6351 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD FEB PY 2009 VL 47 IS 2 BP 433 EP 442 DI 10.1016/j.fct.2008.11.037 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 408IX UT WOS:000263429800026 PM 19100306 ER PT J AU Madsen, CB Hattersley, S Buck, J Gendel, SM Houben, GF Hourihane, JO Mackie, A Mills, ENC Norhede, P Taylor, SL Crevel, RWR AF Madsen, C. B. Hattersley, S. Buck, J. Gendel, S. M. Houben, G. F. Hourihane, J. O'B. Mackie, A. Mills, E. N. C. Norhede, P. Taylor, S. L. Crevel, R. W. R. TI Approaches to risk assessment in food allergy: Report from a workshop "developing a framework for assessing the risk from allergenic foods" SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE Risk assessment; Food allergy; Uncertainty factors; Margin of Exposure; Probabilistic ID HYPERSENSITIVITY REACTIONS; PEANUT ALLERGY; DOUBLE-BLIND; THRESHOLD; CHILDREN; SENSITIVITY; TOXICITY; MODEL AB A workshop was organised to investigate whether risk assessment strategies and methodologies used in classical/conventional toxicology may be used for risk assessment of allergenic foods. to discuss the advantages and limitations of different approaches and to determine the research needed to move the area forward. Three possible approaches to safety assessment and risk assessment for allergenic foods were presented and discussed: safety assessment using NOAEL/LOAEL and uncertainty factors, safety assessment using Benchmark Dose and Margin of Exposure (MoE), and risk assessment using probabilistic models. The workshop concluded that all the three approaches to safety and risk assessment of allergenic foods should continue to be considered. A particular strength of the MoE and probabilistic approaches is that they do not rely on low-dose extrapolations with its inherent issues. Probabilistic modelling is considered to be the most promising approach for use in population risk assessment (which is a particular focus for risk managers). For all approaches, further improvement of input data is desirable, particularly data on consumption patterns/food choices in food allergic consumers, data on minimum eliciting doses and data that can be used to evaluate whether the whole population at risk has been modelled accurately. Specific research topics were identified. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Madsen, C. B.; Norhede, P.] Tech Univ Denmark, Natl Food Inst, Dept Toxicol & Risk Assessment, Res Leader, DK-2860 Soborg, Denmark. [Hattersley, S.; Buck, J.] Food Stand Agcy, London, England. [Gendel, S. M.] US FDA, Rockville, MD 20857 USA. [Houben, G. F.] TNO, Qual Life, Zeist, Netherlands. [Hourihane, J. O'B.] Univ Coll Cork, Dept Paediat & Child Hlth, Cork, Ireland. [Mackie, A.; Mills, E. N. C.] Inst Food Res, Inst Food Res, Norwich NR4 7UA, Norfolk, England. [Taylor, S. L.] Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. [Crevel, R. W. R.] Unilever Colworth, Safety & Environm Assurance Ctr, Sharnbrook, Beds, England. RP Madsen, CB (reprint author), Tech Univ Denmark, Natl Food Inst, Dept Toxicol & Risk Assessment, Res Leader, 19 Morkhoj Bygade, DK-2860 Soborg, Denmark. EM charm@food.dtu.dk FU European Commission [514000] FX The workshop was funded by the European Commission contract no. 514000 EuroPrevall "The Prevalence, Cost and Basis of Food Allergy across Europe" and by the UK Food Standards Agency, and organised in collaboration with the ILSI-Europe Food Allergy Task Force. NR 24 TC 47 Z9 48 U1 1 U2 10 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 FEB PY 2009 VL 47 IS 2 BP 480 EP 489 DI 10.1016/j.fct.2008.12.001 PG 10 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 408IX UT WOS:000263429800032 PM 19101602 ER PT J AU Yang, BW Zheng, J Brown, EW Zhao, SH Meng, JH AF Yang, Baowei Zheng, Jie Brown, Eric W. Zhao, Shaohua Meng, Jianghong TI Characterisation of antimicrobial resistance-associated integrons and mismatch repair gene mutations in Salmonella serotypes SO INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS LA English DT Article DE Salmonella; Antimicrobial resistance; Integron; Mutation ID ESCHERICHIA-COLI; TYPHIMURIUM DT104; ACQUISITION; DNA AB In this study, we examined the presence of integrons and Salmonella genomic island 1 (SGI1) and assessed their contribution to antimicrobial resistance as well as determining the extent of the mutator phenotype in Salmonella isolates. A total of 81 Salmonella enterica serotype Typhimurium isolates were examined for the presence of integrons and SGI1 and for hypermutators using polymerase chain reaction (PCR) and the mutator assay, respectively. An additional 336 Salmonella isolates were also used to screen for hypermutators. Fourteen S. Typhimurium isolates carried class 1 integrons, of which six were shown to possess SGI1. Five putative mutators, S. Typhimurium ST20751, S. enterica serotype Heidelberg 22396 and S. enterica serotype Enteritidis 17929, 17929N and 17929R, were identified among the 417 Salmonella isolates. Complementation analysis with the wild-type mutH, mutL, mutS and uvrD genes indicated that none of the five mutators contained defective mismatch repair (MMR) system alleles. DNA sequence analysis revealed that single point mutations resulting in aspartic acid (codon 87) substitution in the gyrA gene conferred resistance to nalidixic acid and/or other fluoroquinolone drugs (ciprofloxacin and enrofloxacin) among four isolates. Our findings indicated that integrons and SGI1 play an important role in multidrug resistance in Salmonella. The incidence of hypermutators owing to defective MMR in Salmonella appears to be rare. (C) 2008 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved. C1 [Yang, Baowei] NW A&F Univ, Coll Food Sci & Engn, Yangling 712100, Shaanxi, Peoples R China. [Zheng, Jie; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Brown, Eric W.] US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods, Div Microbiol Studies, College Pk, MD USA. [Zhao, Shaohua] US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM jmeng@umd.edu FU Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland; US Food and Drug Administration FX This study was made possible by funding from the Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland and the US Food and Drug Administration. NR 25 TC 7 Z9 11 U1 1 U2 5 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 FEB PY 2009 VL 33 IS 2 BP 120 EP 124 DI 10.1016/j.ijantimicag.2008.08.016 PG 5 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 397II UT WOS:000262655700004 PM 19013057 ER PT J AU deVore, NC Huynh, S Slater, JE AF deVore, N. C. Huynh, S. Slater, J. E. TI Multiplex Microbead Measurements of Cat Allergen Extract Potency SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [deVore, N. C.; Huynh, S.; Slater, J. E.] US FDA, CBER, OVRR, DBPAP, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2009 VL 123 IS 2 MA 825 BP S215 EP S215 DI 10.1016/j.jaci.2008.12.823 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596301301 ER PT J AU Valerio, C Arlian, LG Slater, JE AF Valerio, C. Arlian, L. G. Slater, J. E. TI Bacterial DNA Sequences Isolated from Standardized Dust Mite Extracts and Wild Mites SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 65th Annual Meeting of the American-Academy-of-Allergy-Asthma-and-Immunology CY MAR 13-17, 2009 CL Washington, DC SP Amer Acad Allergy, Asthma & Immunol C1 [Valerio, C.; Slater, J. E.] US FDA, CBER, OVRR, DBPAP, Rockville, MD 20857 USA. [Arlian, L. G.] Wright State Univ, Dayton, OH 45435 USA. NR 0 TC 1 Z9 1 U1 0 U2 3 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2009 VL 123 IS 2 MA 832 BP S216 EP S216 DI 10.1016/j.jaci.2008.12.826 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 410RR UT WOS:000263596301304 ER PT J AU Jung, CM Heinze, TM Strakosha, R Elkins, CA Sutherland, JB AF Jung, C. M. Heinze, T. M. Strakosha, R. Elkins, C. A. Sutherland, J. B. TI Acetylation of fluoroquinolone antimicrobial agents by an Escherichia coli strain isolated from a municipal wastewater treatment plant SO JOURNAL OF APPLIED MICROBIOLOGY LA English DT Article DE acetylation; antimicrobial agents; Escherichia coli; fluoroquinolones; quinolone-resistance determining regions; resistance; transformation; wastewater ID QUINOLONE RESISTANCE GENE; SEWAGE-TREATMENT PLANTS; SOLID-PHASE EXTRACTION; ANTIBACTERIAL AGENTS; TRANSFERABLE PLASMID; EMERGING MECHANISMS; MASS-SPECTROMETRY; MODIFYING ENZYME; DRUG-RESISTANCE; SP NOV. AB To isolate environmental bacteria capable of transforming fluoroquinolones to inactive molecules. Bacteria were isolated from the aerobic liquor of a wastewater treatment plant on a medium containing norfloxacin (100 mg l(-1)). Twenty-two isolates were highly resistant (minimal inhibitory concentration: 6.25-200 mu g ml(-1)) to five fluoroquinolones and six of them were positive by PCR amplification for the aminoglycoside resistance gene aac(6')-Ib. Of these, only Escherichia coli strain LR09 had the ciprofloxacin-acetylating variant gene aac(6')-Ib-cr; HPLC and mass spectrometry showed that this strain transformed both ciprofloxacin and norfloxacin by N-acetylation. This bacterium also had mutations in the quinolone-resistance determining regions of the gyrA and parC genes. An E. coli isolate from wastewater, which possessed at least two distinct fluoroquinolone resistance mechanisms, inactivated ciprofloxacin and norfloxacin by N-acetylation. This is the first report of N-acetylation of fluoroquinolones by an aac(6')-Ib-cr-containing bacterium from an environmental source. C1 [Jung, C. M.; Strakosha, R.; Elkins, C. A.; Sutherland, J. B.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Heinze, T. M.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov FU Postgraduate Research Fellowship Program; National Centre for Toxicological Research; Oak Ridge Institute for Science and Education; U.S. Department of Energy and the U.S. Food and Drug Administration FX We thank G.A. Jacoby for kindly providing reference strains, A.J. Williams, L.B. Mullis, A.A. Khan, F. Rafii and R.S. Steele for technical advice, and C.E. Cerniglia for research support. We also thank the Little Rock Wastewater Utility for access to their facilities. This work was supported in part by appointments to the Postgraduate Research Fellowship Program (C.M.J.) and the Summer Student Research Program (R.S.) at the National Centre for Toxicological Research, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 59 TC 23 Z9 24 U1 0 U2 18 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1364-5072 EI 1365-2672 J9 J APPL MICROBIOL JI J. Appl. Microbiol. PD FEB PY 2009 VL 106 IS 2 BP 564 EP 571 DI 10.1111/j.1365-2672.2008.04026.x PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 395IA UT WOS:000262516600022 PM 19200322 ER PT J AU Scaglione, BJ Salerno, E Gala, K Pan, M Langer, JA Mostowski, HS Bauer, S Marti, G Li, Y Tsiagbe, VK Raveche, ES AF Scaglione, Brian J. Salerno, Erica Gala, Kinisha Pan, Manjing Langer, Jerome A. Mostowski, Howard S. Bauer, Steven Marti, Gerald Li, Yu Tsiagbe, Vincent K. Raveche, Elizabeth S. TI Regulatory T cells as central regulators of both autoimmunity and B cell malignancy in New Zealand Black mice SO JOURNAL OF AUTOIMMUNITY LA English DT Article DE Autoimmunity; Regulatory T cells; Tumor immunity ID CHRONIC LYMPHOCYTIC-LEUKEMIA; SYSTEMIC-LUPUS-ERYTHEMATOSUS; IMMUNOLOGICAL SELF-TOLERANCE; AUTO-IMMUNE DISEASE; NZB MICE; INTERFERON-ALPHA; MURINE LUPUS; LYMPHOPROLIFERATIVE DISEASE; AUTOANTIBODY PRODUCTION; LEUKOCYTE INTERFERONS AB Regulatory T cells (Tregs) play an important role in protection against autoimmune disease and are also known to be potent inhibitors of anti-tumor immune responses. The New Zealand Black (NZB) mouse is a murine model for both autoimmune diseases, since high levels of autoantibodies are present, and human CLL, due to the expansion of malignant B-1 cells. In this study, we examined the functional role of CD4(+)CD25(+) Foxp3(+) Tregs in these different manifestations. Flow cytometric analysis showed increased levels of Tregs in NZB mice compared to healthy C57Bl/6 controls. Aged NZB mice that have developed a B-1 cell malignancy identified as IgM(+)CD5(+), have the most pronounced increase in Tregs. Ex vivo treatment of splenocytes from NZB mice with IFN-alpha resulted in a decrease in the frequency of Tregs and malignant B-1 cells. In vivo treatment of both NZB and C57Bl/6 mice with poly (I:C), a potent inducer of IFN-alpha, also led to a decrease in the levels of Tregs and malignant B-1 cells (NZB only) while amplifying autoimmune manifestations. These results indicate that while high levels of Tregs found in NZB mice might suppress a more severe autoimmune disease, they may also contribute to the development of the B cell malignancy. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Salerno, Erica; Gala, Kinisha; Tsiagbe, Vincent K.; Raveche, Elizabeth S.] Univ Med & Dent, New Jersey Med Sch, Newark, NJ 07103 USA. [Pan, Manjing; Langer, Jerome A.] Univ Med & Dent, Robert Wood Johnson Med Sch, Piscataway, NJ 08854 USA. [Mostowski, Howard S.; Bauer, Steven; Marti, Gerald] US FDA, Ctr Biol Evaluat, NIH, Bethesda, MD 20892 USA. [Tsiagbe, Vincent K.] Univ Med & Dent, New Jersey Dent Sch, Newark, NJ 07103 USA. RP Raveche, ES (reprint author), Univ Med & Dent, New Jersey Med Sch, MSB C512,185 S Orange Ave, Newark, NJ 07103 USA. EM raveches@umdnj.edu OI Bauer, Steven/0000-0003-2831-846X; Langer, Jerome/0000-0002-4617-3260 NR 68 TC 8 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0896-8411 J9 J AUTOIMMUN JI J. Autoimmun. PD FEB PY 2009 VL 32 IS 1 BP 14 EP 23 DI 10.1016/j.jaut.2008.10.001 PG 10 WC Immunology SC Immunology GA 413BT UT WOS:000263768600003 PM 19022624 ER PT J AU Janda, M Buch, B AF Janda, Michel Buch, Barbara TI The Challenges of Clinical Validation of Emerging Technologies: Computer-Assisted Devices for Surgery SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Orthopaedic-Surgeons/Orthopaedic-Research-Society CY MAY 15-17, 2008 CL Providence, RI SP Amer Acad Orhopaed Surg, Orthopaed Res Soc ID MINIMALLY INVASIVE SURGERY; ARTHROPLASTY AB Over the last decade, the use of computers and robotics in medicine has increased commensurate with emergent advances in technology. This article largely focuses on the challenges that the U.S. Food and Drug Administration faces when evaluating new technologies for entry into the market. How different categories of devices are categorized and what types of data have been used for regulatory approval or clearance are described. These are compared with expectations that the clinical community may have for these devices. A brief discussion of current regulatory thinking about these types of devices is also included. C1 [Janda, Michel; Buch, Barbara] US FDA, Ctr Devices & Radiol Hlth, Div Gen Restorat & Neurol Devices, Rockville, MD 20850 USA. RP Janda, M (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Gen Restorat & Neurol Devices, 9200 Corp Blvd,HFZ-410, Rockville, MD 20850 USA. NR 10 TC 6 Z9 6 U1 0 U2 5 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD FEB PY 2009 VL 91A BP 17 EP 21 DI 10.2106/JBJS.H.01337 PG 5 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 405RX UT WOS:000263243000006 PM 19182016 ER PT J AU Kim, MJ Huang, SM Meyer, UA Rahman, A Lesko, LJ AF Kim, Myong-Jin Huang, Shiew-Mei Meyer, Urs A. Rahman, Atiqur Lesko, Lawrence J. TI A Regulatory Science Perspective on Warfarin Therapy: A Pharmacogenetic Opportunity SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE Warfarin; pharmacogenetics; CYP2C9; VKORC1 ID K EPOXIDE REDUCTASE; GAMMA-GLUTAMYL-CARBOXYLASE; ATRIAL-FIBRILLATION; CYTOCHROME P4502C9; BLEEDING COMPLICATIONS; DOSE REQUIREMENTS; CYP2C9 GENOTYPES; GENE VARIANTS; FACTOR-VII; POLYMORPHISMS AB Warfarin is a challenging drug to accurately dose both initially and for maintenance, because of its narrow therapeutic range, wide interpatient variability, and long list of factors that can influence dosing. Two million people in the United States are initiated on warfarin therapy annually, and this number is steadily increasing because of the increase in number of eligible patients. Recently, warfarin was reported to be the fourth leading cause of adverse events. The U.S. Food and Drug Administration recognizes that the adverse event rate of warfarin can be improved through better initial dosing, because many of the serious adverse events of warfarin occur soon after starting treatment. A substantial number of studies demonstrate that common variants of two genes, VKORC1 and CYP2C9 along with other nongenetic factors, correlate significantly with warfarin dosing. The genotypes of VKORC1 and CYP2C9 alone account for nearly 3 times more of the variability (similar to 30%) in warfarin dosing than do age, weight, gender, and other clinical factors combined (similar to 12%). Therefore, the purpose of this report is to review the current recommendations for warfarin therapy that involve genetic testing. C1 [Kim, Myong-Jin; Huang, Shiew-Mei; Meyer, Urs A.; Rahman, Atiqur; Lesko, Lawrence J.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Huang, SM (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Rm 3188,Bldg 51,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM shiewmei.huang@fda.hhs.gov NR 51 TC 41 Z9 42 U1 0 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD FEB PY 2009 VL 49 IS 2 BP 138 EP 146 DI 10.1177/0091270008328098 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 401XN UT WOS:000262976400002 PM 19179293 ER PT J AU Cao, Y Calafat, AM Doerge, DR Umbach, DM Bernbaum, JC Twaddle, NC Ye, XY Rogan, WJ AF Cao, Yang Calafat, Antonia M. Doerge, Daniel R. Umbach, David M. Bernbaum, Judy C. Twaddle, Nathan C. Ye, Xiaoyun Rogan, Walter J. TI Isoflavones in urine, saliva, and blood of infants: data from a pilot study on the estrogenic activity of soy formula SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE phytoestrogen; isoflavone; genistein; daidzein; infant feeding; soy formula ID HUMAN-MILK; PHYTOESTROGENS; GENISTEIN; DAIDZEIN; PHARMACOKINETICS; CONSUMPTION; EXCRETION; EXPOSURE; PROTEIN; PLASMA AB In the United States, about 25% of infant formula sold is based on soy protein, which is an important source of estrogenic isoflavones in the human food supply. Nevertheless, few studies report isoflavone levels in infants. We did a partly cross-sectional and partly longitudinal pilot study to examine children's exposure to isoflavones from different feeding methods. A total of 166 full-term infants between birth and 1 year of age were recruited into soy formula, cow milk formula, or breast milk regimens according to their feeding histories. A total of 381 urine, 361 saliva, and 88 blood samples were collected at 382 visits. We used automated online solid-phase extraction coupled to high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) for measuring three isoflavones ( daidzein, genistein, and equol) in urine, and used similar LC/MS/MS techniques for saliva and blood spots. Concentrations of daidzein and genistein were undetectable in most blood or saliva samples from children fed breast milk or cow milk formula. The proportion of non-detectable values was somewhat lower in urine than in the other matrices. Concentrations of equol were detectable only in a few urine samples. For both daidzein and genistein, urine contained the highest median concentrations, followed by blood and then saliva. Urinary concentrations of genistein and daidzein were about 500 times higher in the soy formula-fed infants than in the cow milk formula-fed infants. The correlations between matrices for either analyte were strikingly lower than the correlation between the two analytes in any single matrix. We did not find significant correlations between isoflavone concentrations and the levels of certain hormones in children fed soy formula. Our results, based on much larger numbers of infants, strongly confirm previous reports, but whether phytoestrogens in soy formula are biologically active in infants is still an open question. We plan further longitudinal studies focusing on physical and developmental findings reflecting the effects of estrogen exposure. C1 [Cao, Yang; Rogan, Walter J.] NIEHS, Epidemiol Branch, Res Triangle Pk, NC 27709 USA. [Calafat, Antonia M.; Ye, Xiaoyun] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Atlanta, GA 30341 USA. [Doerge, Daniel R.; Twaddle, Nathan C.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Umbach, David M.] NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. [Bernbaum, Judy C.] Univ Penn, Sch Med, Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. RP Rogan, WJ (reprint author), NIEHS, Epidemiol Branch, POB 12233,Mail Drop A3-05,FedEx UPS 111 TW Alexa, Res Triangle Pk, NC 27709 USA. EM rogan@niehs.nih.gov RI Rogan, Walter/I-6034-2012 OI Rogan, Walter/0000-0002-9302-0160 FU Intramural NIH HHS [Z99 ES999999] NR 31 TC 65 Z9 70 U1 8 U2 22 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1559-0631 J9 J EXPO SCI ENV EPID JI J. Expo. Sci. Environ. Epidemiol. PD FEB PY 2009 VL 19 IS 2 BP 223 EP 234 DI 10.1038/jes.2008.44 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 395CT UT WOS:000262500600007 PM 18665197 ER PT J AU Hellinger, FJ AF Hellinger, Fred Joseph TI Tax-Exempt Hospitals and Community Benefits: A Review of State Reporting Requirements SO JOURNAL OF HEALTH POLITICS POLICY AND LAW LA English DT Article ID FOR-PROFIT HOSPITALS; CARE; MORTALITY AB In June 2007 the Internal Revenue Service proposed a major overhaul of its reporting requirements for tax-exempt hospitals and released draft Form 990 (the IRS form filed by tax-exempt organizations each year). In December 2007 the IRS promulgated the final Form 990 after incorporating some of the recommendations made in the almost seven hundred public comments on the discussion draft. One recommendation adopted in the final Form 990 is the postponement until tax year 2009 (returns filed in 2010) of the requirement for hospitals to submit detailed information on the percentage of total expenses attributable to charity care, unreimbursed Medicaid costs, and community-health improvement programs (the discussion draft required this information for tax year 2007). Although the IRS will not require tax-exempt hospitals to provide detailed information about community benefits until the 2009 tax year, sixteen states have laws requiring tax-exempt hospitals to enumerate the benefits that they provide to the community. Information about the impact of these laws on the provision of community benefits (e.g., charity and uncompensated care) is examined in this study whose primary purpose is to highlight information policy makers may glean from states that have adopted community-benefit reporting laws. C1 [Hellinger, Fred Joseph] US FDA, Off Commissioner, Rockville, MD 20857 USA. [Hellinger, Fred Joseph] US Hlth Care Financing Adm, Off Res & Demonstrat, Baltimore, MD 21207 USA. NR 44 TC 14 Z9 14 U1 0 U2 2 PU DUKE UNIV PRESS PI DURHAM PA 905 W MAIN ST, STE 18-B, DURHAM, NC 27701 USA SN 0361-6878 J9 J HEALTH POLIT POLIC JI J. Health Polit. Policy Law PD FEB PY 2009 VL 34 IS 1 BP 37 EP 61 DI 10.1215/03616878-2008-991 PG 25 WC Health Care Sciences & Services; Health Policy & Services; Medicine, Legal; Social Issues; Social Sciences, Biomedical SC Health Care Sciences & Services; Legal Medicine; Social Issues; Biomedical Social Sciences GA 411YN UT WOS:000263690500003 PM 19234293 ER PT J AU Girnita, DM Brooks, MM Webber, SA Burckart, GJ Ferrell, R Girnita, AL Chinnock, R Canter, C Addonizio, L Bernstein, D Kirklin, JK Naftel, D Zeevi, A AF Girnita, D. M. Brooks, M. M. Webber, S. A. Burckart, G. J. Ferrell, R. Girnita, A. L. Chinnock, R. Canter, C. Addonizio, L. Bernstein, D. Kirklin, J. K. Naftel, D. Zeevi, A. TI Genetic Polymorphisms Impact the Risk of Infection in Pediatric Heart Transplantation - A Multi-center Study SO JOURNAL OF HEART AND LUNG TRANSPLANTATION LA English DT Meeting Abstract CT 29th Annual Meeting and Scientific Session of the International-Society-for-Heart-and-Lung-Transplantation CY APR 22-25, 2009 CL Paris, FRANCE SP Int Soc Heart & Lung Transplantat C1 [Girnita, D. M.; Brooks, M. M.; Webber, S. A.; Ferrell, R.; Girnita, A. L.; Zeevi, A.] Univ Pittsburgh, Pittsburgh, PA USA. [Burckart, G. J.] US FDA, Silver Spring, MD USA. [Chinnock, R.] Loma Linda Univ, Loma Linda, CA 92350 USA. [Canter, C.] Washington Univ, St Louis, MO USA. [Addonizio, L.] Columbia Univ, New York, NY USA. [Bernstein, D.] Stanford Univ, Palo Alto, CA 94304 USA. [Kirklin, J. K.; Naftel, D.] Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1053-2498 J9 J HEART LUNG TRANSPL JI J. Heart Lung Transplant. PD FEB PY 2009 VL 28 IS 2 MA 532 BP S251 EP S251 PG 1 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery; Transplantation SC Cardiovascular System & Cardiology; Respiratory System; Surgery; Transplantation GA 409XT UT WOS:000263539800528 ER PT J AU Zhang, YT Van Hook, J AF Zhang, Yuanting Van Hook, Jennifer TI Marital Dissolution Among Interracial Couples SO JOURNAL OF MARRIAGE AND FAMILY LA English DT Article DE culture; dissolution; ethnicity; interracial; marriage; race; stability ID EDUCATIONAL HOMOGAMY; MEXICAN-AMERICANS; UNITED-STATES; TRENDS; DIVORCE; MARRIAGE; BLACK; INTERMARRIAGE; PATTERNS; CONVERGENCE AB Increases in interracial marriage have been interpreted as reflecting reduced social distance among racial and ethnic groups, but little is known about the stability of interracial marriages. Using six panels of Survey of Income and Program Participation (N = 23,139 married couples), we found that interracial marriages are less stable than endogamous marriages, but these findings did not hold up consistently. After controlling for couple characteristics, the risk of divorce or separation among interracial couples was similar to the more-divorce-prone origin group. Although marital dissolution was found to be strongly associated with race or ethnicity, the results failed to provide evidence that interracial marriage per se is associated with an elevated risk of marital dissolution. C1 [Zhang, Yuanting] US FDA, Rockville, MD 20857 USA. [Van Hook, Jennifer] Penn State Univ, University Pk, PA 16802 USA. RP Zhang, YT (reprint author), US FDA, Rockville, MD 20857 USA. EM zhangyuant@gmail.com FU NICHD NIH HHS [R24 HD041025] NR 41 TC 41 Z9 42 U1 1 U2 24 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0022-2445 EI 1741-3737 J9 J MARRIAGE FAM JI J. Marriage Fam. PD FEB PY 2009 VL 71 IS 1 BP 95 EP 107 DI 10.1111/j.1741-3737.2008.00582.x PG 13 WC Family Studies; Sociology SC Family Studies; Sociology GA 399EA UT WOS:000262782000007 PM 25284887 ER PT J AU Deeds, J AF Deeds, J. TI THE EVOLVING STORY OF GYMNODINIUM GALATHEANUM = KARLODINIUM MICRUM = KARLODINIUM VENEFICUM. A TEN YEAR PERSPECTIVE SO JOURNAL OF PHYCOLOGY LA English DT Meeting Abstract C1 [Deeds, J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3646 J9 J PHYCOL JI J. Phycol. PD FEB PY 2009 VL 45 MA 3 BP 1 EP 2 PG 2 WC Plant Sciences; Marine & Freshwater Biology SC Plant Sciences; Marine & Freshwater Biology GA 415BW UT WOS:000263910300004 ER PT J AU Wear, KA AF Wear, Keith A. TI The dependencies of phase velocity and dispersion on volume fraction in cancellous-bone-mimicking phantoms SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID HUMAN TRABECULAR BONE; QUANTITATIVE ULTRASOUND; HUMAN CALCANEUS; NEGATIVE DISPERSION; STRATIFIED MODEL; HIP FRACTURE; WAVE-PROPAGATION; ELDERLY-WOMEN; OS CALCIS; IN-VIVO AB Frequency-dependent phase velocity was measured in eight cancellous-bone-mimicking phantoms consisting of suspensions of randomly oriented nylon filaments (simulating trabeculae) in a soft-tissue-mimicking medium (simulating marrow). Trabecular thicknesses ranged from 152 to 356 mu m. Volume fractions of nylon filament material ranged from 0% to 10%. Phase velocity varied approximately linearly with frequency over the range from 300 to 700 kHz. The increase in phase velocity (compared with phase velocity in a phantom containing no filaments) at 500 kHz was approximately proportional to volume fraction occupied by nylon filaments. The derivative of phase velocity with respect to frequency was negative and exhibited nonlinear, monotonically decreasing dependence on volume fraction. The dependencies of phase velocity and its derivative on volume fraction in these phantoms were similar to those reported in previous studies on (1) human cancellous bone and (2) phantoms consisting of parallel nylon wires immersed in water. [DOI:10.1121/1.3050310] 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 keith.wear@fda.hhs.gov NR 47 TC 10 Z9 10 U1 0 U2 1 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 FEB PY 2009 VL 125 IS 2 BP 1197 EP 1201 DI 10.1121/1.3050310 PG 5 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 417TE UT WOS:000264100600061 PM 19206892 ER PT J AU Tang, S Patel, A Krause, PR AF Tang, Shuang Patel, Amita Krause, Philip R. TI Novel Less-Abundant Viral MicroRNAs Encoded by Herpes Simplex Virus 2 Latency-Associated Transcript and Their Roles in Regulating ICP34.5 and ICP0 mRNAs SO JOURNAL OF VIROLOGY LA English DT Article ID READING FRAME P; TYPE-1 LATENCY; GENE-EXPRESSION; IN-VIVO; GAMMA(1)34.5 PROTEIN; MALIGNANT GLIOMA; INFECTED NEURONS; EYE MODEL; REACTIVATION; REPLICATION AB We recently identified an acutely and latently expressed viral microRNA (miRNA), miR-I, encoded by herpes simplex virus 2 (HSV-2) latency-associated transcript (LAT) through small RNA cloning and two miRNAs encoded by HSV-1 LAT through prediction. We now report the use of high-throughput sequencing technology to identify two additional relatively less-abundant viral miRNAs, miR-II and miR-III, encoded by HSV-2 LAT exon 2. miR-II includes two miRNAs, miR-II-5p and miR-II-3p, which are processed from the same miRNA precursor. miR-II and miR-III map antisense to the 5' untranslated region of ICP34.5 and to the coding region of ICP0 exon 3, respectively. These novel miRNAs are conserved in different HSV-2 strains, and their presence in infected- and transfected-cell cultures was confirmed by Northern hybridization. All three HSV-2 LAT-encoded miRNAs map to genome locations similar to those of three out of four identified HSV-1 LAT-encoded miRNAs, but the sequences of these miRNAs are not conserved. The expression of LAT-encoded miRNAs is negatively regulated by ICP4, the major viral transactivator. We further show that, similar to miR-I, miR-II is able to efficiently silence the expression of ICP34.5, a key viral neurovirulence factor, and that miR-III is able to silence the expression of ICP0, a key viral transactivator. All these data suggest that LAT sequences likely contribute to HSV latency and reactivation through tight control of these LAT-encoded miRNAs and their viral targets. C1 [Tang, Shuang; Patel, Amita; Krause, Philip R.] US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, HFM 457,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Philip.krause@fda.hhs.gov RI Tang, Shuang/F-9115-2014; OI Tang, Shuang/0000-0002-3084-0903; Krause, Philip/0000-0002-1045-7536 FU Intramural NIH HHS NR 50 TC 82 Z9 93 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB 1 PY 2009 VL 83 IS 3 BP 1433 EP 1442 DI 10.1128/JVI.01723-08 PG 10 WC Virology SC Virology GA 392TR UT WOS:000262325600026 PM 19019961 ER PT J AU Cote, TR Sobin, LH AF Cote, Timothy R. Sobin, Leslie H. TI Primary melanomas of the esophagus and anorectum: epidemiologic comparison with melanoma of the skin SO MELANOMA RESEARCH LA English DT Article DE epidemiology; gastrointestinal; melanoma ID PRIMARY MALIGNANT-MELANOMA; CANCER; RADIATION; RECTUM; MEN; SEX AB The objective of this study was to use recently available data to describe the epidemiology of melanomas of the esophagus and the anorectum in contrast to melanoma of the skin. The methods used include descriptive epidemiology using cases reported to the Surveillance Epidemiology and End Results registry, 1973-2003. All rates were age adjusted. We found 46759 cutaneous melanomas, 170 anorectal melanomas and 20 esophageal melanomas, corresponding to age-adjusted rates of 70.1, 0.27, and 0.03 per million population, respectively. Median age of patients with melanoma of the skin was less than those with melanoma of the anorectum or esophagus (55 years vs. 71 years and 69 years, respectively). Rates of melanoma of the skin were 1.5-fold higher for men than for women (87.1 vs. 58.1 per 10(6)); in contrast, rates of anorectal melanoma were 1.6-fold higher for women than for men (0.324 vs. 0.199 per 10(6)). Rates of cutaneous melanoma for whites were 13-fold higher than for blacks (80.6 vs. 6.1 per 10(6), P<0.001), whereas the rates of anorectal melanoma were 1.7-fold higher among whites than blacks (0.273 vs. 0.173 per 10(6)). Comparing the period 1973-1987 with 1988-2003, the rate of cutaneous melanoma increased 1.4-fold (56.0-80.1 per 10(6)), whereas the rate of anorectal melanoma similarly increased 1.8-fold (0.182 to 0.329 per 10(6)). In conclusion, anorectal melanomas, and especially, esophageal melanomas remain rare malignancies. This is the first report where temporal trends in anorectal melanoma are following the increased incidence of cutaneous melanomas, but it is unclear whether immunohistochemical diagnostic practices have influenced this trend. As gastrointestinal melanomas represent melanocytic transformation in the absence of sunlight, their epidemiology may provide etiologic clues to alternative or systemic transformative factors also operant in cutaneous melanoma. Melanoma Res 19:58-60 (C) 2009 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins. C1 [Cote, Timothy R.] US FDA, Rockville, MD 20857 USA. [Sobin, Leslie H.] Armed Forces Inst Pathol, Columbia, DC USA. RP Cote, TR (reprint author), OOPD FDA, 5600 Fishers Lane,6A-55, Rockville, MD 20857 USA. EM timothy.cote@fda.hhs.gov NR 23 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-8931 J9 MELANOMA RES JI Melanoma Res. PD FEB PY 2009 VL 19 IS 1 BP 58 EP 60 DI 10.1097/CMR.0b013e32831ef262 PG 3 WC Oncology; Dermatology; Medicine, Research & Experimental SC Oncology; Dermatology; Research & Experimental Medicine GA 407EO UT WOS:000263346600009 PM 19430407 ER PT J AU Desai, VG Lee, T Moland, CL Branham, WS Von Tungeln, LS Beland, FA Fuscoe, JC AF Desai, Varsha G. Lee, Taewon Moland, Carrie L. Branham, William S. Von Tungeln, Linda S. Beland, Frederick A. Fuscoe, James C. TI Effect of short-term exposure to zidovudine (AZT) on the expression of mitochondria-related genes in skeletal muscle of neonatal mice SO MITOCHONDRION LA English DT Article DE Zidovudine (AZT); Infant B6C3F(1) mouse; Skeletal muscle; Mitochondrial functions ID ANTIRETROVIRAL THERAPY; PHOSPHORYL TRANSFER; HIV-1 TRANSMISSION; PERINATAL EXPOSURE; ADENYLATE KINASE; CELL-DEATH; LONG-TERM; IN-UTERO; TOXICITY; MYOPATHY AB Zidovudine (3'-azido-3'-deoxythymidine; AZT) is the main anti-retroviral drug given to HIV-1-infected pregnant women during pregnancy and to their infants after birth to reduce mother-to-child transmission of the virus. In animal studies, however, a significant mitochondrial morphological damage has been reported in skeletal muscle as a consequence of transplacental or perinatal exposure to AZT. Because proper muscle function is highly dependent on efficient mitochondrial function and information on AZT-induced mitochondrial toxicity during neonatal exposure is limited, we investigated the effect of AZT on the expression of 542 mitochondria-related genes encoded by both nuclear and mitochondrial DNA in the skeletal muscle of infant male and female mice using microarray technology. Animals were treated orally by gavage with AZT at 0, 10, 50, 100, and 200 mg/kg body weight/day from postnatal day (PND) 1 through 8 and were sacrificed at 1- and 2-h following the last dose on PND 8. These doses in mice correspond to 0, 1.1, 5.5, 11.0, and 22.0 mg/kg AZT in human infants [Center for Drug Evaluation and Research (CDER) 2005. Pharmacology and Toxicology, Guidance for industry. Estimating the maximum safe dose in initial clinical trials for therapeutics in adult healthy volunteers, p. 7. http://www.fda.gov/cder/guidance/index.htm.]. Microarray data were analyzed for effects of time, sex, treatment, and their interactions using a fixed effect linear model. The results showed modest, but significant, dose-related responses in the expression level of genes associated with apoptosis, fatty acid metabolism, mitochondrial DNA maintenance, and various mitochondrial membrane transporters. The transcription levels were not significantly different at both time points and were not sex dependent. The results suggest that changes in expression of mitochondria-related genes in skeletal muscle may be an initial response to short-term AZT exposure in infant mice. Published by Elsevier B.V. on behalf of Mitochondria Research Society. C1 [Desai, Varsha G.; Moland, Carrie L.; Branham, William S.; Fuscoe, James C.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Funct Genom, Jefferson, AR 72079 USA. [Lee, Taewon] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Von Tungeln, Linda S.; Beland, Frederick A.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Desai, VG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Ctr Funct Genom, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM varsha.desai@fda.hhs.gov FU National Center for Toxicological Research/Food and Drug Administration and the National Institute for Environmental Health Sciences/National Toxicology Program [224-07-007] FX We greatly appreciate Prof. Robert Delongchamp, Department of Epidemiology, the University of Arkansas for Medical Sciences, Little Rock, AR for critical review of statistical analyses and providing his valuable input during preparation of the manuscript. The authors also wish to thank Dr. Robert Heflich and Dr. Eden Tareke for their critical review of the manuscript. This research was supported by Interagency Agreement No. 224-07-007 between the National Center for Toxicological Research/Food and Drug Administration and the National Institute for Environmental Health Sciences/National Toxicology Program. NR 44 TC 12 Z9 12 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 FEB PY 2009 VL 9 IS 1 BP 9 EP 16 DI 10.1016/j.mito.2008.09.002 PG 8 WC Cell Biology; Genetics & Heredity SC Cell Biology; Genetics & Heredity GA 416IN UT WOS:000263999500002 PM 18824140 ER PT J AU Tyner, KM Wokovich, AM Doub, WH Buhse, LF Sung, LP Watson, SS Sadrieh, N AF Tyner, Katherine M. Wokovich, Anna M. Doub, William H. Buhse, Lucinda F. Sung, Li-Piin Watson, Stephanie S. Sadrieh, Nakissa TI Comparing methods for detecting and characterizing metal oxide nanoparticles in unmodified commercial sunscreens SO NANOMEDICINE LA English DT Article DE formulated products; nano-methods; nanotechnology; sunscreen; TiO(2); unmodified analysis; ZnO ID TITANIUM-DIOXIDE; SIZE; NANOTECHNOLOGY AB Aims: To determine if commercial sunscreens contain distinct nanoparticles and to evaluate analytical methods for their ability to detect and characterize nanoparticles in unmodified topical products using commercial sunscreens as a model. Methods: A total of 20 methods were evaluated for their ability to detect and characterize nanoparticles in unmodified commercial sunscreens. Results: Variable-pressure scanning-electron microscopy, atomic-force microscopy, laser-scanning confocal microscopy and X-ray diffraction were found to be viable and complementary methods for detecting and characterizing nanoparticles in sunscreens. Conclusions: it was determined that several of the commercial sunscreens contained distinct nanciparticles. No one method was able to completely characterize nanciparticles in the unmodified products but the viable methods provided complementary information regarding the nanoparticles and how they were interacting with the sunscreen matrix. C1 [Tyner, Katherine M.; Sadrieh, Nakissa] FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Wokovich, Anna M.; Doub, William H.; Buhse, Lucinda F.] FDA, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. [Sung, Li-Piin; Watson, Stephanie S.] Natl Inst Stand & Technol, Bldg & Fire Res Lab, Gaithersburg, MD 20899 USA. RP Sadrieh, N (reprint author), FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM nakissa.sadrieh@fda.hhs.gov NR 27 TC 21 Z9 21 U1 1 U2 18 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1743-5889 J9 NANOMEDICINE-UK JI Nanomedicine PD FEB PY 2009 VL 4 IS 2 BP 145 EP 159 DI 10.2217/17435889.4.2.145 PG 15 WC Biotechnology & Applied Microbiology; Nanoscience & Nanotechnology SC Biotechnology & Applied Microbiology; Science & Technology - Other Topics GA 411BA UT WOS:000263621200011 PM 19193182 ER PT J AU Wu, WJ Hirsch, DS AF Wu, Wen Jin Hirsch, Dianne S. TI Mechanism of E-cadherin lysosomal degradation SO NATURE REVIEWS CANCER LA English DT Letter ID ENDOCYTOSIS C1 [Wu, Wen Jin; Hirsch, Dianne S.] US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Wu, WJ (reprint author), US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM wen.wu@fda.hhs.gov NR 5 TC 5 Z9 5 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1474-175X J9 NAT REV CANCER JI Nat. Rev. Cancer PD FEB PY 2009 VL 9 IS 2 BP 145 EP 145 DI 10.1038/nrc2521-c1 PG 1 WC Oncology SC Oncology GA 404VK UT WOS:000263180900018 PM 19148182 ER PT J AU Mosholder, AD Gelperin, K Hammad, TA Phelan, K Johann-Liang, R AF Mosholder, Andrew D. Gelperin, Kate Hammad, Tarek A. Phelan, Kathleen Johann-Liang, Rosemary TI Hallucinations and Other Psychotic Symptoms Associated With the Use of Attention-Deficit/Hyperactivity Disorder Drugs in Children SO PEDIATRICS LA English DT Article DE ADHD; adverse drug reactions; drug safety; psychiatric issues in primary care ID METHYLPHENIDATE; HYPERACTIVITY AB OBJECTIVES. To gain a better understanding of the capacity of psychostimulant medications to induce adverse psychiatric reactions and determine the frequency of such reactions, we analyzed postmarketing surveillance data and clinical trial data for drugs, either approved or under development, for the treatment of attention-deficit/hyperactivity disorder. METHODS. The US Food and Drug Administration requested manufacturers of drugs approved for attention-deficit/hyperactivity disorder or with active clinical development programs for that indication to search their electronic clinical trial databases for cases of psychosis or mania using prespecified search terms. The manufacturers supplied descriptions of clinical trials, numbers of patients exposed to study drug, and duration of exposure to permit calculations of incidence rates. Independently, cases of psychosis or mania in children and adults for drugs used to treat attention-deficit/hyperactivity disorder from the Food and Drug Administration Adverse Event Reporting System safety database were analyzed. Manufacturers were asked to conduct similar analyses of their postmarketing surveillance databases. RESULTS. We analyzed data from 49 randomized, controlled clinical trials in the pediatric development programs for these products. A total of 11 psychosis/mania adverse events occurred during 743 person-years of double-blind treatment with these drugs, and no comparable adverse events occurred in a total of 420 person-years of placebo exposure in the same trials. The rate per 100 person-years in the pooled active drug group was 1.48. The analysis of spontaneous postmarketing reports yielded >800 reports of adverse events related to psychosis or mania. In similar to 90% of the cases, there was no reported history of a similar psychiatric condition. Hallucinations involving visual and/or tactile sensations of insects, snakes, or worms were common in cases in children. CONCLUSIONS. Patients and physicians should be aware that psychosis or mania arising during drug treatment of attention-deficit/hyperactivity disorder may represent adverse drug reactions. Pediatrics 2009; 123: 611-616 C1 [Mosholder, Andrew D.; Gelperin, Kate; Hammad, Tarek A.; Phelan, Kathleen] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. [Johann-Liang, Rosemary] US Hlth Resources & Serv Adm, Dept Hlth & Human Serv, Rockville, MD 20857 USA. RP Gelperin, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, 10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM kate.gelperin@fda.hhs.gov NR 19 TC 33 Z9 35 U1 0 U2 15 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 FEB PY 2009 VL 123 IS 2 BP 611 EP 616 DI 10.1542/peds.2008-0185 PG 6 WC Pediatrics SC Pediatrics GA 397RB UT WOS:000262678700030 PM 19171629 ER PT J AU Chang, CYC Sachs, HC Lee, CE AF Chang, Christina Yu-Ching Sachs, Hari C. Lee, Charles E. TI Unexpected Infant Deaths Associated With Use of Cough and Cold Medications SO PEDIATRICS LA English DT Letter C1 [Chang, Christina Yu-Ching] US FDA, Div Nonprescrip Clin Evaluat, Off Nonprescript Prod, Off New Drugs, Silver Spring, MD USA. [Sachs, Hari C.] US FDA, Pediat & Maternal Hlth Staff, Off New Drugs, Silver Spring, MD USA. [Lee, Charles E.] US FDA, Ctr Drug Evaluat & Res, Div New Drugs & Labeling Compliance, Off Compliance, Silver Spring, MD USA. RP Chang, CYC (reprint author), US FDA, Div Nonprescrip Clin Evaluat, Off Nonprescript Prod, Off New Drugs, Silver Spring, MD USA. NR 1 TC 2 Z9 2 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 2009 VL 123 IS 2 BP E358 EP E359 DI 10.1542/peds.2008-3424 PG 11 WC Pediatrics SC Pediatrics GA 397RB UT WOS:000262678700083 PM 19171592 ER PT J AU Shephard, GS Berthiller, F Dorner, J Krska, R Lombaert, GA Malone, B Maragos, C Sabino, M Solfrizzo, M Trucksess, MW van Egmond, HP Whitaker, TB AF Shephard, G. S. Berthiller, F. Dorner, J. Krska, R. Lombaert, G. A. Malone, B. Maragos, C. Sabino, M. Solfrizzo, M. Trucksess, M. W. van Egmond, H. P. Whitaker, T. B. TI Developments in mycotoxin analysis: an update for 2007-2008 SO WORLD MYCOTOXIN JOURNAL LA English DT Article DE aflatoxin; Alternaria toxins; cyclopiazonic acid; ergot; fumonisin; ochratoxin; patulin; trichothecenes; zearalenone; sampling ID TANDEM MASS-SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; IMMUNOAFFINITY COLUMN CLEANUP; MACROCYCLIC LACTONE MYCOTOXINS; SOLID-PHASE MICROEXTRACTION; NOVASIL CLAY INTERVENTION; ISOTOPE DILUTION ANALYSIS; APPLE-BASED PRODUCTS; MAIZE FLOUR SAMPLES; CORN-BASED FOOD AB This review highlights developments in mycotoxin analysis and sampling over a period between mid-2007 and mid-2008. It covers the major mycotoxins: aflatoxins, Alternaria toxins, cyclopiazonic acid, fumonisins, ochratoxin, patulin, trichothecenes, and zearalenone. Some aspects of natural occurrence, particularly if linked to novel aspects of analytical methods, are also included. The review demonstrates the rise of LC-MS methods, the continuing interest in developing alternative and rapid methods and the modification of well-established mycotoxin analytical methods by individual laboratories to meet their own requirements. C1 [Shephard, G. S.] MRC, PROMEC Unit, ZA-7505 Tygerberg, South Africa. [Berthiller, F.; Krska, R.] Univ Bodenkultur Wien, Ctr Analyt Chem, Dept Agrobiotechnol IFA Tulln, Christian Doppler Lab Mycotoxin Res, A-3430 Tulln, Austria. [Dorner, J.] ARS, USDA, Natl Peanut Res Lab, Dawson, GA 31742 USA. [Lombaert, G. A.] Hlth Canada, Winnipeg, MB R2J 3Y1, Canada. [Malone, B.] Tril Analyt Lab, Washington, MO 63090 USA. [Maragos, C.] ARS, USDA, Natl Ctr Agr Utilizat Res, Peoria, IL 61604 USA. [Sabino, M.] Adolfo Lutz Inst, BR-01246902 Sao Paulo, Brazil. [Solfrizzo, M.] CNR, Inst Sci Food Prod, I-700126 Bari, Italy. [Trucksess, M. W.] US FDA, College Pk, MD 20740 USA. [van Egmond, H. P.] Natl Inst Publ Hlth & Environm, Lab Food & Residue Anal ARO, NL-3720 BA Bilthoven, Netherlands. [Whitaker, T. B.] N Carolina State Univ, ARS, USDA, Raleigh, NC 27695 USA. RP Shephard, GS (reprint author), MRC, PROMEC Unit, POB 19070, ZA-7505 Tygerberg, South Africa. EM gordon.shephard@mrc.ac.za OI Shephard, Gordon Seymour/0000-0002-1267-9036 NR 178 TC 16 Z9 17 U1 4 U2 20 PU WAGENINGEN ACADEMIC PUBLISHERS PI WAGENINGEN PA PO BOX 220, WAGENINGEN, 6700 AE, NETHERLANDS SN 1875-0710 EI 1875-0796 J9 WORLD MYCOTOXIN J JI World Mycotoxin J. PD FEB PY 2009 VL 2 IS 1 BP 3 EP 21 DI 10.3920/WMJ2008.1095 PG 19 WC Food Science & Technology; Mycology; Toxicology SC Food Science & Technology; Mycology; Toxicology GA 664WT UT WOS:000282995300002 ER PT J AU Xia, XD Zhao, SH Smith, A McEvoy, J Meng, JH Bhagwat, AA AF Xia, Xiaodong Zhao, Shaohua Smith, Allen McEvoy, James Meng, Jianghong Bhagwat, Arvind A. TI Characterization of Salmonella isolates from retail foods based on serotyping, pulse field gel electrophoresis, antibiotic resistance and other phenotypic properties SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE Salmonella; Pulse field gel electrophoresis (PFGE); DNA fingerprinting; Food-borne pathogens ID ESCHERICHIA-COLI STRAINS; ACID RESISTANCE; ENTERITIDIS; CELLS; TOLERANCE; VIRULENT; RPOS AB Sixteen Salmonella strains isolated from a variety of foods during 2000 and 2003 by the Florida State Department of Agriculture were characterized by various genotypic and phenotypic tests. Among 16 isolates, 15 different serotypes were identified. Pulse-field gel electrophoresis (PFGE) fingerprinting profiles obtained using restriction endonucleases XbaI and BlnI revealed that 16 Salmonella isolates were genetically diverse with 16 unique PFGE patterns. The PFGE pattern of eight isolates matched with the CDC/FDA data base of previous outbreaks and clinical isolates indicating their potential to cause disease. With the exception of isolates obtained from alligator meat (tetracycline resistant) and orange juice (chloramphenicol and sulfisoxazole resistant), the remainder of the isolates were susceptible to the panel of 15 antimicrobials tested. Molecular subtyping was further complimented by a variety of phenotypic tests such as acid-tolerance, Caco-2 cell invasion and biofilm formation which have often been used as a gauge of virulence and infection potential of Salmonella isolates. The induced acid tolerance level of the isolate obtained from orange juice was not significantly different from the laboratory reference strain S. enterica serovar Typhimurium SL1344. Six isolates exhibited very low levels of constitutive acid-tolerance, of which four isolates failed to infect differentiated Caco-2 cells. Although all isolates formed biofilms, there was no clear relation between the ability to form biofilms, infect differentiated Caco-2 cells and induce acid-tolerance. This study indicated that different serotypes of Salmonella were present in a variety of retail foods and exhibited diverse phenotypic characteristics. Published by Elsevier B.V. C1 [Xia, Xiaodong; McEvoy, James; Bhagwat, Arvind A.] ARS, Prod Qual & Safety Lab, USDA, BARC W, Beltsville, MD 20705 USA. [Smith, Allen] ARS, Diet Genom & Immunol Lab, Henry A Wallace Beltsville Agr Res Ctr, USDA, Beltsville, MD 20705 USA. [Zhao, Shaohua] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Xia, Xiaodong; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Bhagwat, AA (reprint author), ARS, Prod Qual & Safety Lab, USDA, BARC W, 10300 Baltimore Ave,Bldg 002, Beltsville, MD 20705 USA. EM arvind.bhagwat@ars.usda.gov NR 25 TC 14 Z9 14 U1 0 U2 18 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 JAN 31 PY 2009 VL 129 IS 1 BP 93 EP 98 DI 10.1016/j.ijfoodmicro.2008.11.007 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 404IW UT WOS:000263146000016 PM 19068272 ER PT J AU Lee, CH Kuo, WC Beri, S Kapre, S Joshi, JS Bouveret, N LaForce, FM Frasch, CE AF Lee, Che-Hung Kuo, Wen-Chun Beri, Suresh Kapre, Subash Joshi, Jayant S. Bouveret, Nancy LaForce, F. Marc Frasch, Carl E. TI Preparation and characterization of an immunogenic meningococcal group A conjugate vaccine for use in Africa SO VACCINE LA English DT Article DE Vaccine; Conjugate; Polysaccharide ID NEISSERIA-MENINGITIDIS SEROGROUP; SUB-SAHARAN AFRICA; CAPSULAR POLYSACCHARIDE; O-ACETYLATION; GROUP-B; ANTIBODY; IMMUNIZATION; PERSISTENCE; PREVENTION; EPIDEMIC AB Periodic epidemics of group A meningococcal (Mn A) meningitis continue to occur in sub-Saharan Africa. For its prevention, a Mn A polysaccharide (PS)-tetanus toxoid (TT) conjugate vaccine was developed using reductive amination of polysaccharicle aldehydes and toxoid hydrazides. In mouse immunization studies, a schedule of three bi-weekly s.c. immunizations of 0.1 or 1 mu g of the conjugate (PS content) without an adjuvant induced serum antibody levels of >10,000 units/mL measured by enzyme-linked immunosorbent assay (ELISA) as compared to similar to 100 units/mL in PS control mice. The elicited antibodies were active in bactericidal assays using either baby rabbit or human complement (titers >1500 compared to similar to 200 for the PS control group). The synthesis process is reproducible and scalable, and has been successfully used for manufacturing a Mn A PS-TT conjugate vaccine based on a paradigm of shared manufacturing with transfer of new technology [Jodar L, LaForce FM, Ceccarini C, Aguado T, Granoff DM. Meningococcal conjugate vaccine for Africa: a model for development of new vaccine for the poorest countries. Lancet 2003, 361:1092-4]. A phase 1 clinical trial of the manufactured Men A-TT conjugate vaccine has been successfully carried out in adults in India, and a phase 2 clinical trial in young children is currently underway in Africa. Published by Elsevier Ltd. C1 [Frasch, Carl E.] US FDA, Lab Bacterial Polysaccharides, HFM 428, DBPAP,OVRR,CBER,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Beri, Suresh; Kapre, Subash; Joshi, Jayant S.] Serum Inst India Ltd, Pune, Maharashtra, India. [Bouveret, Nancy; LaForce, F. Marc] Meningitis Vaccine Project, Ferney Voltaire, France. RP Lee, CH (reprint author), US FDA, Lab Bacterial Polysaccharides, HFM 428, DBPAP,OVRR,CBER,Ctr Biol Evaluat & Res, NIH Campus,Bldg 29,Room 404,29 Lincoln Ave, Bethesda, MD 20892 USA. EM robert.lee@fda.hhs.gov FU CRADA FX The authors are grateful to Dr. Dan Granoff and his laboratory for performing bactericidal assay with human complement. We thank Ms. Britany Bowen for her technical support, Mr. Scot Noris for recording the NMR spectra of native and activated Mn A PS, and Drs. Margaret Bash, Chao-Ming Tsai and Willie Vann for their review and comments of this manuscript. This research is supported in part by a CRADA between CBER and PATH. NR 35 TC 39 Z9 43 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X EI 1873-2518 J9 VACCINE JI Vaccine PD JAN 29 PY 2009 VL 27 IS 5 BP 726 EP 732 DI 10.1016/j.vaccine.2008.11.065 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 405II UT WOS:000263216100019 PM 19063929 ER PT J AU Trucksess, MW Whitaker, TB Weaver, CM Slate, A Giesbrecht, FG Rader, JI Betz, JM AF Trucksess, Mary W. Whitaker, Thomas B. Weaver, Carol M. Slate, Andrew Giesbrecht, Francis G. Rader, Jeanne I. Betz, Joseph M. TI Sampling and Analytical Variability Associated with the Determination of Total Aflatoxins and Ochratoxin A in Powdered Ginger Sold As a Dietary Supplement in Capsules SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Sampling; analytical uncertainty; aflatoxins; ochratoxin A; ginger capsules; dietary supplements ID PART I; MYCOTOXINS; GINSENG; FOODS AB The U.S. Food and Drug Administration is studying the need to monitor dietary supplements for mycotoxins such as total aflatoxins and ochratoxin A. An effective mycotoxin-monitoring program requires knowledge of the sampling and analytical variability associated with the determination of total aflatoxins (AF) and ochratoxin A (OTA) in dietary supplements. Three lots of ginger sold as a powder in capsule form and packaged in individual bottles were analyzed for both AF and OTA. The total variability associated with measuring AF and OTA in powdered ginger was partitioned into bottle-to-bottle, within bottle, and analytical variances. The variances were estimated using a nested design. For AF and OTA, the within-bottle variance associated with the 5 g laboratory sample size was the largest component of variability accounting for about 43% and 85% of the total variance, respectively; the analytical variance accounted for about 34% and 9% of the total variability, respectively; and the bottle-to-bottle variance accounted for about 23% and 7% of the total variance, respectively. When the total variance is converted into the coefficient of variation (CV or standard deviation relative to the mean concentration), the CV is lower for AF (16.9%) than OTA (24.7%). C1 [Trucksess, Mary W.; Weaver, Carol M.; Rader, Jeanne I.] US FDA, College Pk, MD USA. [Whitaker, Thomas B.] N Carolina State Univ, USDA, Raleigh, NC 27695 USA. [Slate, Andrew] N Carolina State Univ, Dept Biol & Agr Engn, Raleigh, NC 27695 USA. [Giesbrecht, Francis G.] N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. [Betz, Joseph M.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Trucksess, MW (reprint author), US FDA, College Pk, MD USA. NR 12 TC 11 Z9 11 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 JAN 28 PY 2009 VL 57 IS 2 BP 321 EP 325 DI 10.1021/jf8017854 PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 397LU UT WOS:000262665000001 PM 19105639 ER PT J AU Brinker, AD AF Brinker, Allen D. TI Allopurinol and the Role of Uric Acid in Hypertension SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 [Brinker, Allen D.] US FDA, Ctr Drug Evaluat & Res, Div Epidemiol, Off Surveillance & Epidemiol, Silver Spring, MD USA. RP Brinker, AD (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Epidemiol, Off Surveillance & Epidemiol, Silver Spring, MD USA. EM allen.brinker@fda.hhs.gov NR 4 TC 3 Z9 3 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610-0946 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 21 PY 2009 VL 301 IS 3 BP 270 EP 270 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 395IV UT WOS:000262518700006 PM 19155448 ER PT J AU Tryndyak, VP Beland, FA Pogribny, IP AF Tryndyak, V. P. Beland, F. A. Pogribny, I. P. TI Inhibition of E-cadherin is associated with down-regulation of members of the miR-200 family but not with promoter methylation in human breast cancer cell lines SO CANCER RESEARCH LA English DT Meeting Abstract CT 31st Annual San Antonio Breast Cancer Symposium CY DEC 10-14, 2008 CL San Antonio, TX C1 [Tryndyak, V. P.; Beland, F. A.; Pogribny, I. P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 2009 VL 69 IS 2 BP 352S EP 353S PG 2 WC Oncology SC Oncology GA 396HQ UT WOS:000262583201491 ER PT J AU Li, H Smith, ML Chiesa, OA Kijak, PJ AF Li, Hui Smith, Michelle L. Chiesa, O. Alberto Kijak, Philip J. TI Determination of sulfadimethoxine and N-4-acetylsulfadimethoxine in bovine plasma, urine, oral fluid, and kidney and liver biopsy samples obtained surgically from standing animals by LC/MS/MS SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE Sulfadimethoxine; N-4-acetylsulfadimethoxine; Liquid chromatography/tandem mass; spectrometry; Veterinary drug residue; Quantitation; Bovine; Plasma; Urine; Oral fluid; Kidney; Liver ID LIQUID-CHROMATOGRAPHIC DETERMINATION; PHARMACOLOGIC PROPERTIES; PHARMACOKINETIC MODEL; FROZEN STORAGE; COUNTY FAIRS; DAIRY FARMS; SULFONAMIDES; CATTLE; RESIDUES; TISSUE AB A quantitative method was developed and validated to measure the concentration of sulfadimethoxine (SDM) and its major metabolite, N-4-acetylsulfadimethoxine (AcSDM), in bovine tissues and body fluids. Liquid chromatography/tandem mass spectrometry (LC/MS/MS) gave quantitative results for these two analytes in extracts from bovine plasma, urine, oral fluid, kidney, and liver, using SDM-d(4) as internal standard (I.S.). The lower limit of quantitation (LLOQ) for both analytes in these matrices was validated at 2, 100, and 5 ng/mL in plasma, urine, and oral fluid respectively, and 10 ng/g in both kidney (cortex) and liver. The overall accuracy (average of 4 levels) is, for plasma, 104% (SDM) and 95% (AcSDM), with standard deviation of 9% (SDM) and 15% (AcSDM); for urine, 100% (SDM)and 106% (AcSDM), with standard deviation of 5% (SDM) and 6% (AcSDM): for oral fluid, 103% (SDM) and 103% (AcSDM), with standard deviation of 4% (SDM) and 4% (AcSDM); for kidney, 101% (SDM) and 111% (AcSDM), with standard deviation of 7% (SDM) and 6% (AcSDM): and for liver, 99% (SDM) and 115% (AcSDM), with standard deviation of 11% (SDM) and 9% (AcSDM). C18 SPE cartridges were used to clean-up these matrices, except for urine which was diluted directly with buffer before analysis by LC/MS/MS. Published by Elsevier B.V. C1 [Li, Hui; Smith, Michelle L.; Chiesa, O. Alberto; Kijak, Philip J.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Li, H (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM hui.li@fda.hhs.gov NR 27 TC 6 Z9 6 U1 0 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 JAN 15 PY 2009 VL 877 IS 3 BP 237 EP 246 DI 10.1016/j.jchromb.2008.12.015 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 400OJ UT WOS:000262877500019 PM 19124282 ER PT J AU Sulub, Y Wabuyele, B Gargiulo, P Pazdan, J Cheney, J Berry, J Gupta, A Shah, R Wu, HQ Khan, M AF Sulub, Yusuf Wabuyele, Busolo Gargiulo, Paul Pazdan, James Cheney, James Berry, Joseph Gupta, Abhay Shah, Rakhi Wu, Huiquan Khan, Mansoor TI Real-time on-line blend uniformity monitoring using near-infrared reflectance spectrometry: A noninvasive off-line calibration approach SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Pharmaceutical; Blend uniformity; Near-infrared; Partial least-squares; Off-line calibration ID ANALYTICAL TECHNOLOGY APPROACH; PART II; SPECTROSCOPY; HOMOGENEITY; PREDICTION; PROBE AB A robust, noninvasive, real-time, on-line near-infrared (NIR) quantitative method is described for blend uniformity monitoring of a pharmaceutical solid dosage form containing 29.4% (w/w) drug load with three major excipients (crospovidone, lactose, and microcrystalline cellulose). A set of 21 off-line. static calibration samples were used to develop a multivariate partial least-squares (PLS) calibration model for on-line prediction of the API content during the blending process. The concentrations of the API and the three major excipients were varied randomly to minimize correlations between the components. A micro electrical-mechanical system (MEMS) based portable, battery operated NIR spectrometer was used for this study. To minimize spectral differences between the static and dynamic measurement modes, the acquired NIR spectra were preprocessed using standard normal variate (SNV) followed by second derivative Savitzky-Golay using 21 points. The performance of the off-line PLS calibration model were evaluated in real-time on 16 laboratory scale (30 L bin size) blend experiments conducted over 3 months. To challenge the robustness of the off-line calibration model, several blend experiments were conducted using a different bin size, faster revolution speed and variations in the potency of the API. Employing the PLS calibration model developed using the off-line calibration approach, the real-time API NIR (%) predictions for all experiments were all within 90-110%. These results were confirmed using the conventional thief sampling of the final blend followed by high performance liquid chromatography (HPLC) analysis. Further confirmation was established through content uniformity by HPLC of manufactured tablets. Finally, the optimized off-line PLS method was successfully transferred to a production site which involved using a secondary NIR instrument with a 15-fold scale-up in bin size from development. (c) 2008 Elsevier B.V. All rights reserved. C1 [Sulub, Yusuf; Wabuyele, Busolo; Gargiulo, Paul; Pazdan, James] Novartis Pharmaceut, Pharmaceut & Analyt Dev, E Hanover, NJ 07936 USA. [Cheney, James] Novartis Pharmaceut, Global Qual Operat, E Hanover, NJ 07936 USA. [Berry, Joseph] QRxPharma Inc, Somerset, NJ USA. [Gupta, Abhay; Shah, Rakhi; Wu, Huiquan; Khan, Mansoor] US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Sulub, Y (reprint author), Novartis Pharmaceut, Pharmaceut & Analyt Dev, E Hanover, NJ 07936 USA. EM yusuf.sulub@novartis.com NR 18 TC 44 Z9 46 U1 1 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 JAN 15 PY 2009 VL 49 IS 1 BP 48 EP 54 DI 10.1016/j.jpba.2008.10.001 PG 7 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 403MZ UT WOS:000263088000007 PM 19027256 ER PT J AU Reepmeyer, JC d'Avignon, DA AF Reepmeyer, John C. d'Avignon, D. Andre TI Structure elucidation of thioketone analogues of sildenafil detected as adulterants in herbal aphrodisiacs SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Dietary supplements; Sildenafil analogue; Thiomethisosildenafil; Liquid chromatography-mass spectrometry (LC-MS); Nuclear magnetic resonance (NMR) ID SYNTHETIC PHOSPHODIESTERASE-5 INHIBITORS; PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; DIETARY-SUPPLEMENT; ERECTILE DYSFUNCTION; IDENTIFICATION; PRODUCTS; VARDENAFIL; TADALAFIL; DRINKS AB Two analogues of sildenafil were detected in herbal dietary supplements marketed as aphrodisiacs. Both compounds were identified as thioketone analogues or sildenafil in which the carbonyl group in the pyrimidine ring of sildenafil was substituted with a thiocarbonyl group. The first compound was identified as thiosildenafil, a compound that has recently been reported as an adulterant in health supplements. The structure of the second compound was established using LC-MS, UV spectroscopy, ESI-MS(n). NMR and a hydrolytic process. A detailed study of the hydrolysis products of sildenafil, thiosildenafil, and the second unknown Compound proved that the second compound, named thiomethisosildenafil, had a structure analogous to sildenafil in which the N-methylpiperazine moiety had been replaced with 2,6-dimethylpiperazine and the oxygen atom of the carbonyl group in the heterocyclic ring had been replaced with a sulfur atom. Under the hydrolytic reaction conditions employed in this study, thioketones hydrolyze to ketones (e.g., thiosildenafil -> sildenafil), making this a valuable technique for the structure elucidation of thiosildenafil analogues. Ten herbal dietary supplements, each as a capsule dosage form, were found to contain 8-151 mg of thiomethisosildenafil per capsule, and one herbal dietary supplement was found to contain 35 mg of thiosildenafil per capsule. Published by Elsevier B.V. C1 [Reepmeyer, John C.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. [d'Avignon, D. Andre] Washington Univ, Dept Chem, St Louis, MO 63130 USA. RP Reepmeyer, JC (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM john.reepmeyer@fda.hhs.gov NR 18 TC 37 Z9 41 U1 2 U2 9 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 JAN 15 PY 2009 VL 49 IS 1 BP 145 EP 150 DI 10.1016/j.jpba.2008.10.007 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 403MZ UT WOS:000263088000021 PM 19042103 ER PT J AU Alosh, M Huque, MF AF Alosh, Mohamed Huque, Mohammad F. TI A flexible strategy for testing subgroups and overall population SO STATISTICS IN MEDICINE LA English DT Article DE subgroup analysis; study power; dependence; significance levels for the subgroup analysis ID PIOGLITAZONE CLINICAL-TRIAL; MULTIPLE END-POINTS; MACROVASCULAR EVENTS; ADJUSTMENT AB Subgroup analyses in addition to the total study population analysis are common in clinical trials. However, it is well recognized that findings from subgroup analyses do not provide confirmatory evidence for subgroup treatment effects without placing a priori criteria for ensuring that their findings are scientifically we address some of the common pitfalls of subgroup analyses. Subgroups analyses sound. In this paper inherently have low power for detecting treatment effects. We investigate the power interplay for a Subgroup analysis and that for the total study population and list factors that impact the power of a subgroup analysis. Then we introduce a flexible statistical strategy for testing a pre-specified sequence of hypotheses for both the overall and a subgroup. The proposed method strongly controls the familywise Type I error rate and enjoys higher power than other traditional methods. This testing strategy allows testing for a subgroup once a pre-specified degree of consistency in the efficacy findings between the subgroup and the overall study population is met. In addition, it accounts for the dependency between test statistics for the subgroup and the overall study population. We discuss the power performance of this new method and provide significance levels for Subgroup analysis. Finally, we illustrate its application through retrospective analysis of data from three published clinical trials. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Alosh, Mohamed] FDA, CDER, OTS, Off Biostat,Div Biometr 3, Silver Spring, MD 20993 USA. [Huque, Mohammad F.] FDA, CDER, OTS,OB, Div Biometr 4, Silver Spring, MD 20993 USA. [Huque, Mohammad F.] Georgia So Univ, Adjunct Fac, Jiann Ping Hsu Coll Publ Hlth, Statesboro, GA 30460 USA. RP Alosh, M (reprint author), FDA, CDER, OTS, Off Biostat,Div Biometr 3, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mohamed.Alosh@fda.hhs.gov NR 21 TC 36 Z9 36 U1 0 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 15 PY 2009 VL 28 IS 1 BP 3 EP 23 DI 10.1002/sim.3461 PG 21 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 391ZC UT WOS:000262271700002 PM 18985704 ER PT J AU De Alwis, GKH Needham, LL Barr, DB AF De Alwis, G. K. Hemakanthi Needham, Larry L. Barr, Dana B. TI Automated solid phase extraction, on-support derivatization and isotope dilution-GC/MS method for the detection of urinary dialkyl phosphates in humans SO TALANTA LA English DT Article DE Organophosphorous pesticides; Dialkyl phosphate metabolites; Extractive-derivatization ID TANDEM MASS-SPECTROMETRY; GAS-CHROMATOGRAPHIC DETERMINATION; ORGANOPHOSPHORUS PESTICIDES; SAMPLE PREPARATION; ALKYL PHOSPHATES; HUMAN EXPOSURE; METABOLITES; INSECTICIDES; SENSITIVITY; CARBONYLS AB We developed an analytical method based on solid phase extraction, on-support derivatization and isotope dilution-GC/MS for the detection of dialkyl phosphate (DAP) metabolites, dimethyl thiophosphate, diethyl thiophosphate. dimethyl dithiophosphate, and diethyl dithiophosphate in human urine. The sample preparative procedure is simple and fully automated. In this method, the analytes were extracted from the urinary matrix onto a styrene-divinyl benzene polymer-based solid phase extraction cartridge and derivatized on-column with pentafluorobenzyl bromide. The ester conjugated analytes are eluted from the column with acetonitrile, concentrated and analyzed. Compared to extraction-post extraction derivatization methods for the analysis of DAP metabolites, this on-support derivatization is fast, efficient, and less labor-intensive. Furthermore. it has fewer steps in the sample preparation, uses less solvent and produces less interference. The method is highly sensitive with limits of detection for the analytes ranging from 0.1 to 0.3 ng/mL. The recoveries were high and comparable with those of our previous method. Relative standard deviation, indicative of the repeatability and precision of the method, was 1-17% for the metabolites. Published by Elsevier B.V. C1 [De Alwis, G. K. Hemakanthi; Needham, Larry L.; Barr, Dana B.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA. RP De Alwis, GKH (reprint author), US FDA, FDA Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM hemakanthi.dealwis@fda.hhs.gov RI Needham, Larry/E-4930-2011; Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013 FU National Center for Environmental Health, Division of Laboratory Sciences FX This work was supported in part by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention (CDC), National Center for Environmental Health, Division of Laboratory Sciences, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC. NR 34 TC 8 Z9 8 U1 0 U2 15 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 J9 TALANTA JI Talanta PD JAN 15 PY 2009 VL 77 IS 3 BP 1063 EP 1067 DI 10.1016/j.talanta.2008.08.007 PG 5 WC Chemistry, Analytical SC Chemistry GA 398WD UT WOS:000262761300021 PM 19064092 ER PT J AU Gerecke, DR Chen, M Isukapalli, SS Gordon, MK Chang, YC Tong, W Androulakis, IP Georgopoulos, PG AF Gerecke, Donald R. Chen, Minjun Isukapalli, Sastry S. Gordon, Marion K. Chang, Yoke-Chen Tong, Weida Androulakis, Ioannis P. Georgopoulos, Panos G. TI Differential gene expression profiling of mouse skin after sulfur mustard exposure: Extended time response and inhibitor effect SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Vesicant; Sulfur mustard; Microarray; Alkylating agent; Skin; MMP inhibitor; MMP; Matrix metalloproteinase ID MICROARRAY ANALYSIS; SULFIDE AB Sulfur mustard (HD, SM), is a chemical warfare agent that within hours causes extensive blistering at the dermal-epidermal junction of skin. To better understand the progression of SM-induced blistering, gene expression profiling for mouse skin was performed after a single high dose of SM exposure. Punch biopsies of mouse ears were collected at both early and late time periods following SM exposure (previous studies only considered early time periods). The biopsies were examined for pathological disturbances and the samples further assayed for gene expression profiling using the Affymetrix microarray analysis system. Principal component analysis and hierarchical cluster analysis of the differently expressed genes, performed with ArrayTrack showed clear separation of the various groups. Pathway analysis employing the KEGG library and Ingenuity Pathway Analysis (IPA) indicated that cytokine-cytokine receptor interaction, cell adhesion molecules (CAMS), and hematopoietic cell lineage are common pathways affected at different time points. Gene ontology analysis identified the most significantly altered biological processes as the immune response, inflammatory response, and chemotaxis; these findings are consistent with other reported results for shorter time periods. Selected genes were chosen for RT-PCR verification and showed correlations in the general trends for the microarrays. Interleukin 1 beta was checked for biological analysis to confirm the presence of protein correlated to the corresponding microarray data. The impact of a matrix metalloproteinase inhibitor, MMP-2/MMP-9 inhibitor 1, against SM exposure was assessed. These results can help in understanding the molecular mechanism of SM-induced blistering, as well as to test the efficacy of different inhibitors. (C) 2008 Elsevier Inc. All rights reserved. C1 [Gerecke, Donald R.; Chen, Minjun; Isukapalli, Sastry S.; Gordon, Marion K.; Chang, Yoke-Chen; Georgopoulos, Panos G.] Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, EOHSI, Piscataway, NJ 08854 USA. [Gerecke, Donald R.; Chen, Minjun; Isukapalli, Sastry S.; Gordon, Marion K.; Chang, Yoke-Chen; Georgopoulos, Panos G.] Rutgers State Univ, Piscataway, NJ 08854 USA. [Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Androulakis, Ioannis P.] State Univ New Jersey, Dept Biomed Engn, Piscataway, NJ USA. RP Gerecke, DR (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, EOHSI, Piscataway, NJ 08854 USA. EM gerecke@eohsi.rutgers.edu FU NIEHS; NIH/NIEHS [ES004738]; NIH/NEI [EY09056]; NIH [NIAMS U54AR055073]; USEPA STAR [GAD R 832721-010]; [NIEHS P30ES005022] FX This research was supported in part by the following grants: NIEHS sponsored UMDNJ Center for Environmental Exposures and Disease (Grant # NIEHS P30ES005022); NIH/NIEHS funded Training in Environmental Toxicology (ES004738); NIH/NEI funded Expression of Specialized Collagens in Cornea (EY09056); NIH funded CounterACT Program (NIAMS U54AR055073); and USEPA STAR Grant funded Environmental Bioinformatics and Computational Toxicology Center (GAD R 832721-010). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the funding agencies including NIH, USFDA, and USEPA. Appreciation is extended to Linda Everett of EOHSI for editorial assistance. NR 16 TC 17 Z9 19 U1 0 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JAN 15 PY 2009 VL 234 IS 2 BP 156 EP 165 DI 10.1016/j.taap.2008.09.020 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 398WG UT WOS:000262761600002 PM 18955075 ER PT J AU Marcucci, KT Argaw, T Wilson, CA Salomon, DR AF Marcucci, Katherine T. Argaw, Takele Wilson, Carolyn A. Salomon, Daniel R. TI Identification of two distinct structural regions in a human porcine endogenous retrovirus receptor, HuPAR2, contributing to function for viral entry SO RETROVIROLOGY LA English DT Article ID APE LEUKEMIA-VIRUS; AMINO-ACID TRANSPORTER; CELL-SURFACE RECEPTOR; ECOTROPIC MURINE RETROVIRUSES; LIVER SUPPORT-SYSTEM; NO EVIDENCE; BIOARTIFICIAL LIVER; EXTRACELLULAR DOMAIN; PHOSPHATE TRANSPORTERS; MINIATURE SWINE AB Background: Of the three subclasses of Porcine Endogenous Retrovirus (PERV), PERV-A is able to infect human cells via one of two receptors, HuPAR1 or HuPAR2. Characterizing the structure-function relationships of the two HuPAR receptors in PERV-A binding and entry is important in understanding receptor-mediated gammaretroviral entry and contributes to evaluating the risk of zoonosis in xenotransplantation. Results: Chimeras of the non-permissive murine PAR and the permissive HuPAR2, which scanned the entire molecule, revealed that the first 135 amino acids of HuPAR2 are critical for PERV-A entry. Within this critical region, eighteen single residue differences exist. Site-directed mutagenesis used to map single residues confirmed the previously identified L109 as a binding and infectivity determinant. In addition, we identified seven residues contributing to the efficiency of PERV-A entry without affecting envelope binding, located in multiple predicted structural motifs (intracellular, extracellular and transmembrane). We also show that expression of HuPAR2 in a non-permissive cell line results in an average 11-fold higher infectivity titer for PERV-A compared to equal expression of HuPAR1, although PERV-A envelope binding is similar. Chimeras between HuPAR-1 and -2 revealed that the region spanning amino acids 152-285 is responsible for the increase of HuPAR2. Fine mapping of this region revealed that the increased receptor function required the full sequence rather than one or more specific residues. Conclusion: HuPAR2 has two distinct structural regions. In one region, a single residue determines binding; however, in both regions, multiple residues influence receptor function for PERV-A entry. C1 [Marcucci, Katherine T.; Salomon, Daniel R.] Scripps Res Inst, Dept Mol & Expt Med, La Jolla, CA 92037 USA. [Argaw, Takele; Wilson, Carolyn A.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Marcucci, Katherine T.] Childrens Hosp Philadelphia, Dept Pediat, Philadelphia, PA 19104 USA. RP Salomon, DR (reprint author), Scripps Res Inst, Dept Mol & Expt Med, 10666 N Torrey Pines Rd, La Jolla, CA 92037 USA. EM marcuccik@email.chop.edu; takele.argaw@fda.hhs.gov; carolyn.wilson@fda.hhs.gov; dsalomon@scripps.edu RI Salomon, Daniel/E-9380-2012 FU NIAID NIH HHS [R01 AI52349, R01 AI052349] NR 67 TC 4 Z9 4 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD JAN 14 PY 2009 VL 6 AR 3 DI 10.1186/1742-4690-6-3 PG 15 WC Virology SC Virology GA 412OO UT WOS:000263734300001 PM 19144196 ER PT J AU Mendelsohn, NJ Messinger, YH Rosenberg, AS Kishnani, PS AF Mendelsohn, Nancy J. Messinger, Yoav H. Rosenberg, Amy S. Kishnani, Priya S. TI Elimination of Antibodies to Recombinant Enzyme in Pompe's Disease SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID ACID ALPHA-GLUCOSIDASE; REPLACEMENT THERAPY C1 [Mendelsohn, Nancy J.; Messinger, Yoav H.] Childrens Hosp & Clin Minnesota, Minneapolis, MN 55404 USA. [Rosenberg, Amy S.] US FDA, Bethesda, MD 20892 USA. [Kishnani, Priya S.] Duke Univ, Med Ctr, Durham, NC 27710 USA. RP Mendelsohn, NJ (reprint author), Childrens Hosp & Clin Minnesota, Minneapolis, MN 55404 USA. EM nancy.mendelsohn@childrensmn.org NR 4 TC 75 Z9 75 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 JAN 8 PY 2009 VL 360 IS 2 BP 194 EP 195 DI 10.1056/NEJMc0806809 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 391UG UT WOS:000262258300032 PM 19129538 ER PT J AU Niu, MT Ball, R Woo, EJ Burwen, DR Knippen, M Braun, MM AF Niu, Manette T. Ball, Robert Woo, Emily Jane Burwen, Dale R. Knippen, Maureen Braun, M. Miles CA VAERS Working Grp TI Adverse events after anthrax vaccination reported to the Vaccine Adverse Event Reporting System (VAERS), 1990-2007 SO VACCINE LA English DT Article DE Anthrax vaccine; Post-marketing surveillance; VAERS ID AMYOTROPHIC-LATERAL-SCLEROSIS; GULF-WAR VETERANS; UNITED-STATES; THROMBOCYTOPENIC PURPURA; RHEUMATOID-ARTHRITIS; PSORIATIC-ARTHRITIS; AUTOIMMUNE-DISEASES; CLINICAL-FEATURES; ROTAVIRUS VACCINE; MILITARY SERVICE AB During the period March 1, 1998 to January 14, 2007, approximately 6 million doses of Anthrax vaccine adsorbed (AVA) vaccine were administered. As of January 16, 2007, 4753 reports of adverse events following receipt of AVA vaccination had been submitted to the Vaccine Adverse Event Reporting System (VAERS). Taken together, reports to VAERS did not definitively link any serious unexpected risk to this vaccine, and review of death and serious reports did not show a distinctive pattern indicative of a causal relationship to AVA vaccination. Continued monitoring of VAERS and analysis of potential associations between AVA vaccination and rare, serious events is warranted. Published by Elsevier Ltd. C1 [Niu, Manette T.; Ball, Robert; Woo, Emily Jane; Burwen, Dale R.; Braun, M. Miles] US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol,Vaccine Safety Branch, Rockville, MD 20852 USA. [Knippen, Maureen] Off Compliance & Biol Qual, Rockville, MD 20852 USA. RP Niu, MT (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol,Vaccine Safety Branch, 1401 Rockville Pike,HFM-220, Rockville, MD 20852 USA. EM manette.niu@fda.hhs.gov NR 67 TC 14 Z9 15 U1 0 U2 5 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 7 PY 2009 VL 27 IS 2 BP 290 EP 297 DI 10.1016/j.vaccine.2008.10.044 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 399DM UT WOS:000262780600018 PM 18992783 ER PT S AU Tibbelin, S Badano, A Danielsson, M AF Tibbelin, Sandra Badano, Aldo Danielsson, Mats GP IEEE TI Feasibility Study for Photon Counting Detector for High Resolution Pre Clinical SPECT SO 2008 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (2008 NSS/MIC), VOLS 1-9 SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference CY OCT 19-25, 2008 CL Dresden, GERMANY SP IEEE Nucl & Plasma Sci Soc, Natl Nucl Secur Adm, US Def Threat Reduct Agcy, ICx Radiat GmbH, ORTEC, Hamamatsu, European Phys Journal, Hilger Crystals, SAFC Hitech, ATOMTEX, Canberra, SensL, ASP, Brookhaven Natl Lab, CEA, CERN, DESY, Forschungszentrum Julich GmbH, Int Atom Energy Agcy, Lawrence Livermore Natl Lab ID X-RAY AB We plan to integrate a photon counting, large area, high spatial resolution, high efficiency detector in a system for pre-clinical SPECT. We are aiming for a high spatial resolution for the detector of around 20 mu m. The agent for radiolabelling is assumed to be I-125, with an emission peak at 27 keV, since it is readily available. The aim of this feasibility study was to optimize the scintillator and electronics. We consider a complementary metal-oxide-semiconductor (CMOS) circuit together with a columnar CsI scintillator. In our case CMOS is advantageous over CCD due to a more flexible readout and an opportunity for data processing and trigger logic at the pixel level. The position of the x-ray interaction in the scintillator can be estimated with high accuracy by fitting a two-dimensional Gaussian curve to the pixel hit-map. The goal of this study is to determine optimal scintillator thickness, pixel size, readout rate and the corresponding achievable spatial resolution. Results for a CA thickness of 600 mu m show a detection efficiency close to 90 % and a spatial resolution in the range of 20 mu m. Optimum pixel size for this application is between 40 - 60 mu m and as long as the readout speed exceeds 750 Hz the noise from the dark current will not be significant. C1 [Tibbelin, Sandra; Danielsson, Mats] Royal Inst Technol, Dept Phys, S-10044 Stockholm, Sweden. [Badano, Aldo] US FDA, Ctr Devices & Radiolog Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math,NIBIB CDRH Lab Assessment, Silver Spring, MD USA. RP Tibbelin, S (reprint author), Royal Inst Technol, Dept Phys, S-10044 Stockholm, Sweden. EM sandra.tibbelin@mi.physics.kth.se NR 4 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4244-2714-7 J9 IEEE NUCL SCI CONF R PY 2009 BP 3250 EP + PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BKN17 UT WOS:000268656001281 ER PT S AU Caucci, L Kupinski, MA Freed, M Furenlid, LR Wilson, DW Barrett, HH AF Caucci, Luca Kupinski, Matthew A. Freed, Melanie Furenlid, Lars R. Wilson, Donald W. Barrett, Harrison H. GP IEEE TI Adaptive SPECT for Tumor Necrosis Detection SO 2008 IEEE NUCLEAR SCIENCE SYMPOSIUM AND MEDICAL IMAGING CONFERENCE (2008 NSS/MIC), VOLS 1-9 SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium/Medical Imaging Conference CY OCT 19-25, 2008 CL Dresden, GERMANY SP IEEE Nucl & Plasma Sci Soc, Natl Nucl Secur Adm, US Def Threat Reduct Agcy, ICx Radiat GmbH, ORTEC, Hamamatsu, European Phys Journal, Hilger Crystals, SAFC Hitech, ATOMTEX, Canberra, SensL, ASP, Brookhaven Natl Lab, CEA, CERN, DESY, Forschungszentrum Julich GmbH, Int Atom Energy Agcy, Lawrence Livermore Natl Lab DE SPECT; adaptive imaging; multimodality imaging; tumor necrosis; assessment of image quality; human observer; detection; channelized Hotelling observer; MLEM reconstruction; ROC curve ID OBSERVER; PERFORMANCE; RADIOLOGY; MODEL AB In this paper, we consider a prototype of an adaptive SPECT system, and we use simulation to objectively assess the system's performance with respect to a conventional, non-adaptive SPECT system. Objective performance assessment is investigated for a clinically relevant task: the detection of tumor necrosis at a known location and in a random lumpy background. The iterative maximum-likelihood expectation-maximization (MLEM) algorithm is used to perform image reconstruction. We carried out human observer studies on the reconstructed images and compared the probability of correct detection when the data are generated with the adaptive system as opposed to the non-adaptive system. Task performance is also assessed by using a channelized Hotelling observer, and the area under the receiver operating characteristic curve is the figure of merit for the detection task. Our results show a large performance improvement of adaptive systems versus non-adaptive systems and motivate further research in adaptive medical imaging. C1 [Caucci, Luca; Kupinski, Matthew A.; Furenlid, Lars R.; Barrett, Harrison H.] Univ Arizona, Coll Opt Sci, 1630 E Univ Blvd, Tucson, AZ 85721 USA. [Caucci, Luca; Kupinski, Matthew A.; Furenlid, Lars R.; Wilson, Donald W.; Barrett, Harrison H.] Univ Arizona, Ctr Gamma Ray Imaging, Tucson, AZ 85719 USA. [Freed, Melanie] US FDA, Silver Spring 20993, MD USA. RP Caucci, L (reprint author), Univ Arizona, Coll Opt Sci, 1630 E Univ Blvd, Tucson, AZ 85721 USA. FU NIH [P41EB002035, R37EBOOO803] FX This work was supported by NIH grants P41EB002035 and R37EBOOO803. NR 16 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4244-2714-7 J9 IEEE NUCL SCI CONF R PY 2009 BP 4821 EP + PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BKN17 UT WOS:000268656002216 ER PT J AU King, A Procter, S Andresen, D Hatcliff, J Warren, S Spees, W Jetley, R Jones, P Weininger, S AF King, Andrew Procter, Sam Andresen, Dan Hatcliff, John Warren, Steve Spees, William Jetley, Raoul Jones, Paul Weininger, Sandy GP IEEE TI An Open Test Bed for Medical Device Integration and Coordination SO 2009 31ST INTERNATIONAL CONFERENCE ON SOFTWARE ENGINEERING, COMPANION VOLUME SE International Conference on Software Engineering LA English DT Proceedings Paper CT 31st International Conference on Software Engineering (ICSE 2009) CY MAY 16-27, 2009 CL Vancouver, CANADA SP ACM, IEEE, IEEE Comp Soc, SIGSOFT ID INTEROPERABILITY AB Medical devices historically have been monolithic units - developed, validated, and approved by regulatory authorities as stand-alone entities. Modern medical devices increasing incorporate connectivity mechanisms that offer the potential to stream device data into electronic health records, integrate information from multiple devices into single customizable displays, and coordinate the actions of groups of cooperating devices to realize "closed loop" scenarios and automate clinical workflows. However, it is not clear what middleware and integration architectures may be best suited for these possibly numerous scenarios. More troubling, current verification and validation techniques used it? the device industry are not targeted to assuring groups of integrated devices. In this paper we propose a publish-subscribe architecture for medical device integration based on the Java Messaging Service, and we report at? our experience with this architecture in multiple scenarios that we believe represent the types of deployments that will benefit from rapid device integration. This implementation and the experiments presented in this paper are offered as an open test bed for exploring development, quality assurance, and regulatory issues related to medical device coordination. C1 [King, Andrew; Procter, Sam; Andresen, Dan; Hatcliff, John; Warren, Steve] Kansas State Univ, Manhattan, KS 66506 USA. [Spees, William; Jetley, Raoul; Jones, Paul; Weininger, Sandy] US FDA, Silver Spring, MD USA. RP Hatcliff, J (reprint author), Kansas State Univ, Manhattan, KS 66506 USA. EM aking@ksu.edu; samue13@ksu.edu; dan@ksu.edu; hatcliff@ksu.edu; swarren@ksu.edu; William.Spees@fda.hhs.gov; Raoul.Jetley@fda.hhs.gov; PaulL.Jones@fda.hhs.gov; Sandy.Weininger@fda.hhs.gov FU National Science Foundation [0454348, 0734204]; Air Force Office of Scientific Research FX This material is based upon work supported by the National Science Foundation under Grants # 0454348 and 0734204 and by the Air Force Office of Scientific Research. NR 19 TC 13 Z9 13 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0270-5257 J9 PROC INT CONF SOFTW PY 2009 BP 141 EP + DI 10.1109/ICSE-COMPANION.2009.5070972 PG 2 WC Computer Science, Software Engineering SC Computer Science GA BLU95 UT WOS:000271113800014 ER PT J AU King, A Procter, S Andresen, D Hatcliffl, J Warren, S Spees, W Jetley, R Jones, P Weininger, S AF King, Andrew Procter, Sam Andresen, Dan Hatcliffl, John Warren, Steve Spees, William Jetley, Raoul Jones, Paul Weininger, Sandy GP IEEE TI Demonstration of a Medical Device Integration and Coordination Framework SO 2009 31ST INTERNATIONAL CONFERENCE ON SOFTWARE ENGINEERING, COMPANION VOLUME SE International Conference on Software Engineering LA English DT Proceedings Paper CT 31st International Conference on Software Engineering (ICSE 2009) CY MAY 16-27, 2009 CL Vancouver, CANADA SP ACM, IEEE, IEEE Comp Soc, SIGSOFT AB This tool demonstration presents a framework for integrating and coordinating the activities of medical devices. The framework uses a publish-subscribe framework for communicating with and controlling devices and a model-driven component-based development environment for rapid implementation of device coordination tasks. A multi-faceted graphical user interface supports activities such as device/driver registering and installation, model-based development of device integrations, and monitoring system activities/performance. The framework also includes a control/display environment that clinicians would use to (a) display integrated information pulled from multiple devices and (b) launch and interact with device coordinations that automate clinical workflows. The distribution of the framework includes a collection of mock medical devices, and instructions for integrating real devices. The codebase is freely available under an open source license. C1 [King, Andrew; Procter, Sam; Andresen, Dan; Hatcliffl, John; Warren, Steve] Kansas State Univ, Manhattan, KS 66506 USA. [Spees, William; Jetley, Raoul; Jones, Paul; Weininger, Sandy] US FDA, Montgomery, AL 36101 USA. RP King, A (reprint author), Kansas State Univ, Manhattan, KS 66506 USA. EM aking@ksu.edu; samuel3@ksu.edu; dan@ksu.edu; hatcliff@ksu.edu; swarren@ksu.edu; William.Spees@fda.hhs.gov; Raoul.Jetley@fda.hhs.gov; PaulL.Jones@fda.hhs.gov; Sandy.Weininger@fda.hhs.gov FU National Science Foundation [0454348, 0734204]; Air Force Office of Scientific Research FX This material is based upon work supported by the National Science Foundation under Grants # 0454348 and 0734204 and by the Air Force Office of Scientific Research. NR 3 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0270-5257 J9 PROC INT CONF SOFTW PY 2009 BP 433 EP + DI 10.1109/ICSE-COMPANION.2009.5071048 PG 2 WC Computer Science, Software Engineering SC Computer Science GA BLU95 UT WOS:000271113800089 ER PT S AU Wang, SJ Yao, JH Liu, JM Petrick, N Summers, RM AF Wang, Shijun Yao, Jianhua Liu, Jiamin Petrick, Nicholas Summers, Ronald M. GP IEEE TI Registration of Prone and Supine CT Colonography Scans Based on Correlation Optimized Warping and Canonical Correlation Analysis SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc AB In this paper, we propose an automated method for colon registration from supine and prone scans. Four anatomical salient points on the colon are distinguished first. Then correlation optimized warping (COW) method is applied to the segments defined by the anatomical landmarks to find better global registration based on local correlation of segments. To utilize more features along the colon centerline, we extended the COW method by embedding canonical correlation analysis into it for correlation calculation of colon segments. To verify the effectiveness of the proposed method, we tested the algorithm on a CTC dataset of 19 patients with 23 polyps. Experimental results show that by using our method, the estimation error of polyp location could be reduced 68.5% (from 41.6mm to 13.1mm on average) compared to a traditional dynamic warping algorithm. C1 [Wang, Shijun; Yao, Jianhua; Liu, Jiamin; Summers, Ronald M.] NIH, Imaging Biomarkers & Comp Aided Diag Lab, Bldg 10,Room B2S-231 MSC 1182, Bethesda, MD 20892 USA. [Petrick, Nicholas] US FDA, NIBIB CDRH Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), NIH, Imaging Biomarkers & Comp Aided Diag Lab, Bldg 10,Room B2S-231 MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU NIH Clinical Center FX This research was supported by the Intramural Research Program of the NIH Clinical Center. We thank Drs. Perry Pickhardt, J. Richard Choi and William Schindler for providing CT colonography data. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 81 EP + DI 10.1109/IEMBS.2009.5334691 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543600022 ER PT S AU Harris, GR AF Harris, Gerald R. GP IEEE TI FDA Regulation of Clinical High Intensity Focused Ultrasound (HIFU) Devices SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc ID CALIBRATION; MODEL AB In the U. S., medical devices are regulated under the authority of the 1976 Medical Device Amendments to the Food, Drug, and Cosmetic Act, with the Food and Drug Administration's Center for Devices and Radiological Health having primary responsibility. The Act defines several regulatory paths to market depending on the complexity of the device and indications for use. For most high intensity focused ultrasound (HIFU) devices the premarket submissions include both pre-clinical and clinical data. Pre-clinical testing generally comprises ultrasound power measurements and field characterization, in vitro and in vivo temperature measurements, thermal computational modeling, and demonstrating the accuracy for targeting the region of interest and monitoring treatment progress. Protocols for clinical trials are developed by the device sponsor in conjunction with FDA medical and scientific staff. Currently there are no recognized guidance or standards documents for HIFU testing that could be used in the regulatory review process, but such work is underway within the International Electrotechnical Commission. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20992 USA. RP Harris, GR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20992 USA. EM gerald.harris@fda.hhs.gov NR 25 TC 8 Z9 8 U1 1 U2 3 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 145 EP 148 DI 10.1109/IEMBS.2009.5332444 PG 4 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543600038 ER PT S AU Hazra, P Myklebust, J Winters, J AF Hazra, Promita Myklebust, Joel Winters, Jack GP IEEE TI Evaluation of Applied Forces and EMG of the Young, Aged & Stroke Population in a 3D Arm Workspace SO 2009 ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOLS 1-20 SE IEEE Engineering in Medicine and Biology Society Conference Proceedings LA English DT Proceedings Paper CT Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY SEP 03-06, 2009 CL Minneapolis, MN SP IEEE Engn Med & Biol Soc AB The objectives of this study were to evaluate 11 muscle electromyograms (EMGs) while performing force application tasks in a 3D workspace, and to identify challenging regions within the workspace in which subjects had difficultly generating forces in desired directions. Each subject (4 young healthy adults, 4 older with stroke-induced disability, 4 age-matched older) applied forces (8 lbs desired) in 6 directions at 19 locations spatially distributed in the workspace. The normals could meet the force threshold levels except for the 2 female aged participants for the Right force direction. The stroke group had common difficult directions of Up and Right. The muscle activations were dependent upon the applied force direction, with Up force being associated with maximum EMGs. Maximum variation in the EMGs was in the right and far region for the young adults and in far and low region for the older adults. The stroke subjects' shoulder-arm EMGs showed less directional variability in the regions of workspace, and considerable compensatory trunk movement, unlike the normals. C1 [Hazra, Promita; Winters, Jack] Marquette Univ, Milwaukee, WI 53233 USA. [Myklebust, Joel] Food & Drug Adm, Silver Spring, MD USA. RP Hazra, P (reprint author), Marquette Univ, Milwaukee, WI 53233 USA. OI Myklebust, Joel/0000-0002-8709-9706 FU National Institute on Disability and Rehabilitation Research; U.S. Department of Education [H133E020729]; Office of Science and Engineering Laboratories of the Center for Devices and Radiological Health of the Food and Drug Administration (FDA) FX Authors thank: Rehabilitation Engineering Research Center on Accessible Medical Instrumentation (RERC), funded by the National Institute on Disability and Rehabilitation Research, U.S. Department of Education Grant #H133E020729; and the Office of Science and Engineering Laboratories of the Center for Devices and Radiological Health of the Food and Drug Administration (FDA). NR 8 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1557-170X BN 978-1-4244-3295-0 J9 IEEE ENG MED BIO PY 2009 BP 3971 EP + DI 10.1109/IEMBS.2009.5333779 PG 2 WC Engineering, Biomedical SC Engineering GA BQB05 UT WOS:000280543603085 ER PT B AU Tata, DB Waynant, RW AF Tata, Darrell B. Waynant, Ronald W. GP IEEE TI Red He-Ne laser exposure enhances Hydrogen Peroxide production and induces the "by-stander" effect and modulations in metabolic activity in malignant human brain cancer SO 2009 CONFERENCE ON LASERS AND ELECTRO-OPTICS AND QUANTUM ELECTRONICS AND LASER SCIENCE CONFERENCE (CLEO/QELS 2009), VOLS 1-5 LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics/Quantum Electronics and Laser Science Conference (CLEO/QELS 2009) CY JUN 02-04, 2009 CL Baltimore, MD AB Enhanced generation of H(2)O(2), modulations in metabolic activity, and the "by-stander" effect from malignant human brain cancer cells due to red He-Ne laser exposures have been quantified and found to be light exposure dose dependent. The findings herein support evidence for an important role for light induced H(2)O(2) to mediate biomodulations. (C) 2009 Optical Society of America C1 [Tata, Darrell B.; Waynant, Ronald W.] US FDA, Ctr Devices & Radiol Hlth, Div Phys, Silver Spring, MD 20993 USA. RP Tata, DB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Phys, 10903 New Hampshire Ave,Bldg 62, Silver Spring, MD 20993 USA. EM darayash.tata@fda.hhs.gov; Ronald.waynant@fda.hhs.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-5184-5 PY 2009 BP 572 EP 573 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BNJ62 UT WOS:000274751300288 ER PT B AU Benkler, S Kainz, W Guag, J Victor, K Myklebust, J Isaac, C Chavannes, N Kim, JH Sarntinoranont, M Kuster, N AF Benkler, Stefan Kainz, Wolfgang Guag, Joshua Victor, Krauthamer Myklebust, Joel Isaac, Chang Chavannes, Nicolas Kim, Jung Hwan Sarntinoranont, Malisa Kuster, Niels GP IEEE TI Development of a magneto-hydrodynamic solver for anatomical models SO 2009 IEEE ANTENNAS AND PROPAGATION SOCIETY INTERNATIONAL SYMPOSIUM AND USNC/URSI NATIONAL RADIO SCIENCE MEETING, VOLS 1-6 LA English DT Proceedings Paper CT IEEE Antennas and Propagation International Symposium /USNC/URSI National Radio Science Meeting CY JUN 01-05, 2009 CL N Charleston, SC SP IEEE, USNC, URSI ID BLOOD-FLOW; FIELDS C1 [Benkler, Stefan] Schmid & Partner Engn AG, Zurich, Switzerland. [Kainz, Wolfgang; Guag, Joshua; Victor, Krauthamer; Myklebust, Joel; Isaac, Chang] United States Food & Drug Adm, Silver Spring, MD 20902 USA. [Chavannes, Nicolas; Kuster, Niels] ITIS, Zurich, Switzerland. [Kim, Jung Hwan; Sarntinoranont, Malisa] Univ Florida, Dept Mech & Aerospace Engn, Soft Tissue Mech & Drug Delivery Lab, Gainesville, FL 32611 USA. RP Benkler, S (reprint author), Schmid & Partner Engn AG, Zurich, Switzerland. EM benkler@speag.com NR 5 TC 0 Z9 0 U1 0 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3646-0 PY 2009 BP 1804 EP + PG 3 WC Engineering, Electrical & Electronic; Telecommunications SC Engineering; Telecommunications GA BON71 UT WOS:000277085400453 ER PT B AU Krefting, I AF Krefting, Ira GP IEEE TI FDA Perspective on Ultrasound Contrast Agents Safety and Development SO 2009 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING: FROM NANO TO MACRO, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE Internaional Symposium on Biomedical Imaging - From Nano to Macro CY JUN 28-JUL 01, 2009 CL Boston, MA SP IEEE C1 US FDA, Silver Spring, MD USA. RP Krefting, I (reprint author), US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-3931-7 PY 2009 BP 754 EP 754 DI 10.1109/ISBI.2009.5193158 PG 1 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BLO57 UT WOS:000270678400190 ER PT B AU Ilev, IK AF Ilev, Ilko K. GP IEEE TI From Biophotonics toward Nanobiophotonics: Breaking the Diffraction Barrier in the Subwavelength Nanoscale SO 2009 IEEE/NIH LIFE SCIENCE SYSTEMS AND APPLICATIONS WORKSHOP LA English DT Proceedings Paper CT IEEE/NIH Life Science Systems and Applications Workshop CY APR 09-10, 2009 CL Bethesda, MD SP IEEE, NIH ID SCANNING OPTICAL MICROSCOPY AB We present fundamental principals and features of novel approaches in biophotonics and nanobiophotonics field for biomedical applications with spatial resolution beyond the diffraction barrier in the subwavelength (below 100 nm) nanoscale range. C1 US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Ilev, IK (reprint author), US FDA, Div Phys, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ilko.ilev@fda.hhs.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-4292-8 PY 2009 BP 25 EP 28 DI 10.1109/LISSA.2009.4906700 PG 4 WC Engineering, Biomedical SC Engineering GA BKH13 UT WOS:000268062300007 ER PT B AU Tata, DB Waynant, RW AF Tata, Darrell B. Waynant, Ronald W. GP IEEE TI He-Ne laser enhanced cellular hydrogen peroxide production and induced modulations in metabolic activity in malignant human brain cancer: Evidence for a "by-stander" effect SO 2009 IEEE/NIH LIFE SCIENCE SYSTEMS AND APPLICATIONS WORKSHOP LA English DT Proceedings Paper CT IEEE/NIH Life Science Systems and Applications Workshop CY APR 09-10, 2009 CL Bethesda, MD SP IEEE, NIH AB Continuous-wave He-Ne laser exposures (Intensity=35 mW/cm(2), lambda=632.8nm, Fluence range: 1J/cm(2) to 50 J/cm(2)) on non-confluent and actively dividing human malignant glioblastoma cells was found to increase the cellular production levels of H(2)O(2). Modulations in the cellular metabolic activity were detected (through the NITS assay) three days after laser irradiation. The metabolic activity was found to be dependent on the laser dose of exposure (i.e., fluence). In addition, three days after the laser exposure, the potential laser induced "bystander" effect was tested through the transfer of growth media from laser irradiated cells onto non-irradiated cells. After two additional days of incubation (5 days post exposure), the non-laser irradiated cells were found to have a significant increase in their metabolic activities. Modulations in the metabolic activities in the non-irradiated cells were found to be fluence dependent from the initial laser exposed cells treatment conditions. The results herein support the hypothesis of an important functional role for light enhanced cellular H(2)O(2) generation to yield bio-modulatory effects locally and at a distance. The classical "bi-phasic" modulation response of cells to light irradiation is hypothesized to depend upon the quantity of light-enhanced H(2)O(2) molecules generated from the mitochondria and the number of cells which interact with the H(2)O(2) molecules. C1 [Tata, Darrell B.; Waynant, Ronald W.] US FDA, CDRH, Div Phys, Silver Spring, MD 20993 USA. RP Tata, DB (reprint author), US FDA, CDRH, Div Phys, 10903 New Hampshire Ave,Bldg 62, Silver Spring, MD 20993 USA. EM Darayash.Tata@fda.hhs.gov; Ronald.Waynant@fda.hhs.gov NR 4 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 978-1-4244-4292-8 PY 2009 BP 141 EP 142 DI 10.1109/LISSA.2009.4906729 PG 2 WC Engineering, Biomedical SC Engineering GA BKH13 UT WOS:000268062300036 ER PT S AU Badal, A Badano, A AF Badal, Andreu Badano, Aldo BE Yu, B TI Monte Carlo Simulation of X-Ray Imaging Using a Graphics Processing Unit SO 2009 IEEE NUCLEAR SCIENCE SYMPOSIUM CONFERENCE RECORD, VOLS 1-5 SE IEEE Nuclear Science Symposium Conference Record LA English DT Proceedings Paper CT IEEE Nuclear Science Symposium Conference 2009 CY OCT 25-31, 2009 CL Orlando, FL SP IEEE, Nucl Plasma Sci Sect, IEEE ID PHOTON; CODE AB A code for Monte Carlo simulations of radiation transport using a Graphics Processing Unit (GPU) is introduced. The code has been developed using the CUDA (TM) programming model, an extension to the C language that allows the execution of general purpose computations on the new generation of GPUs from NVIDIA. The accurate Compton and Rayleigh interaction models and interaction mean free paths from the PENELOPE package, and a generic voxelized geometry model, have been implemented in the new code. The secondary particles generated by Compton, photoelectric and pair-production events are not transported. An ideal x-ray detector and a cone beam source can be defined to reproduce an imaging system and facilitate the simulations of medical imaging applications. A 24-fold speed up factor with the GPU compared to the CPU is reported for a radiographic projection of a detailed anthropomorphic female phantom. A description of the simulation algorithm and the technical implementation in the GPU are provided. This work shows that GPUs are already a good alternative to CPUs for Monte Carlo simulation of x-ray transport. C1 [Badal, Andreu; Badano, Aldo] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Badal, A (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM Andreu.Badal-Soler@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 12 TC 9 Z9 9 U1 0 U2 2 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1082-3654 BN 978-1-4244-3961-4 J9 IEEE NUCL SCI CONF R PY 2009 BP 4081 EP 4084 DI 10.1109/NSSMIC.2009.5402382 PG 4 WC Engineering, Electrical & Electronic; Nuclear Science & Technology SC Engineering; Nuclear Science & Technology GA BQA51 UT WOS:000280505102152 ER PT B AU Badano, A Guarnieri, G Ramponi, G Albani, L AF Badano, Aldo Guarnieri, Gabriele Ramponi, Giovanni Albani, Luigi BE Morreale, J TI Quantization in Medical Imaging Displays - Initial Observer Results for a High-Luminance-Range, Dual-Layer LCD SO 2009 SID INTERNATIONAL SYMPOSIUM DIGEST OF TECHNICAL PAPERS, VOL XL, BOOKS I - III LA English DT Proceedings Paper CT 47th Annual Symposium of the Society-for-Information-Display CY MAY 31-JUN 05, 2009 CL San Antonio, TX SP Soc Informat Display ID CLUSTERED LUMPY BACKGROUNDS; TEXTURE SYNTHESIS; PERFORMANCE; ALGORITHM; IMAGES; NOISE AB We studied the effect of image quantization by comparing observer detection performance with 8- and 16-bit grayscale presentation. Eight readers evaluated 532 image pairs using a two-alternative forced choice experimental design. The image set consisted of synthetic backgrounds generated using the mammography-like cluster lumpy background (CLB) technique with a dual-layer approach with parameter values that have been shown to replicate the correlation structure found in digital mammography. The image pairs were reviewed in a display device prototype with one million pixels capable of processing and displaying 16-bit images (up to 65536 luminance values). These image pairs were presented either as non-quantized (full range) images in a 16-bit presentation scale, or as quantized, 8-bit images, with a perceptual mapping of gray levels to luminance. The difference in reader performance between reads on quantized image pairs and reads on non-quantized image pairs were derived using fraction of correct decisions. The variance of our measurements was estimated using a multi-reader, multi-case analysis. Average reader performance difference between 16- and 8-bit quantization was 0.065 with an associated standard deviation of 0.048. Our study showed that image quantization is an important factor in visual detection task, that is, a quantization from 16- to 8-bit significantly reduces reader detection performance. C1 [Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU SOC INFORMATION DISPLAY PI CAMPBELL PA 1475 S BASCOM AVE, STE 114, CAMPBELL, CA 95008 USA PY 2009 BP 923 EP 926 PG 4 WC Engineering, Electrical & Electronic; Optics; Imaging Science & Photographic Technology SC Engineering; Optics; Imaging Science & Photographic Technology GA BMN94 UT WOS:000272997600239 ER PT S AU Reed, JL Avendano, L Velozo, L Welliver, RC AF Reed, Jennifer L. Avendano, Luis Velozo, Luis Welliver, Robert C., Sr. BE Spier, R TI Desired immune response characteristics in an RSV vaccine: What infants tell us SO 2ND GLOBAL CONGRESS ON VACCINES SE Procedia in Vaccinology LA English DT Proceedings Paper CT 2nd Global Congress on Vaccines CY DEC 07-09, 2008 CL Boston, MA DE respiratory syncytial virus; innate immunity; BAFF; mucosal antibody AB Respiratory syncytial virus (RSV) represents an important target for vaccine development. The design of an effective vaccine for infants is hindered by a lack of knowledge of the nature of the protective immune response to RSV infection in this age group. To understand immune mechanisms in the infant lung, we examined respiratory samples from infants 0-6 months with severe RSV LRI, and compared these to uninfected infants. At the peak of RSV infection (but not in controls), activated macrophages (CD14+, CD16+, CD68+) and B lymphocytes (CD20+, IgA+, IgM+, IgG+) are prominent while dendritic cells (MHCII+), T lymphocytes and T cell associated cytokines (Welliver et al, 2007 J. Infect. Dis. 195: 1126) are not. In nasopharyngeal secretions, polyreactive IgG, IgM and IgA recognizing RSV virions and apoptotic debris were readily detected. The presence of polyspecific local antibodies strongly correlated with mucosal expression of BAFF, a T-independent, B-cell activating cytokine, which localized in lung tissue to RSV-infected and apoptotic respiratory epithelium. Polyspecific local antibodies were associated with better oxygenation at presentation. In vitro, products of RSV infected epithelium, such as BAFF, TLR7 ligand, and type I IFN synergistically elicited Ig and cytokine production from cultured B lymphocytes, while virions alone had no such effect. Our data suggest that in infants, innate immune factors released from RSV infected epithelium elicit T independent, polyspecific B cell responses which have modest protective effects. Perhaps the lack of antigen presentation via dendritic cells in infant respiratory tissue impedes the development of T-dependent responses and contributes to severe disease susceptibility in this age group. RSV vaccine strategies tailored for infants should recruit and mature lung-associated macrophages and dendritic cells, in order to deliver antigen to elicit long-lasting, T-cell dependent immunity. Alternatively, an RSV vaccine that promotes local innate B lymphocyte responses might elicit short-term protection, bridging the gap between maternal antibody protection and the development of mature immune responses found in older children. (C) 2009 Elsevier B. V. All rights reserved C1 [Reed, Jennifer L.] US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. [Avendano, Luis] Univ Chile, Santiago 1027, Chile. [Velozo, Luis] Roberto Rio Childrens Hosp, Santiago 1085, Chile. [Welliver, Robert C., Sr.] SUNY Buffalo, Women & Childrens Hosp, Buffalo, NY 14222 USA. RP Reed, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM jennifer.reed@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1877-282X J9 PROCEDIA VACCINOL JI Procedia Vaccinol. PY 2009 VL 1 IS 1 BP 45 EP 48 DI 10.1016/j.provac.2009.07.009 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA BOF33 UT WOS:000276449200008 ER PT S AU Soneson, JE AF Soneson, Joshua E. BE Ebbini, ES TI A User-Friendly Software Package for HIFU Simulation SO 8TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 8th International Symposium on Therapeutic Ultras CY SEP 10-13, 2008 CL Minneapolis, MN SP Int Soc Therapeut Ultrasound, Imasonic, SuperSonic Imagine, Onda Corp, EDAP, JJA Instruments, Philips, Focused Ultrasound Surg Fdn, China Med Technologies DE Software; nonlinear acoustics; numerical methods AB A freely-distributed, MATLAB (The Mathworks, Inc., Natick, MA)-based software package for simulating axisymmetric high-intensity focused ultrasound (HIFU) beams and their heating effects is discussed. ne package (HIFU-Simulator) consists of a propagation module which solves the Khokhlov-Zabolotskaya-Kuznetsov (KZK) equation and a heating module which solves Pennes' bioheat transfer (BHT) equation. The pressure. intensity. heating rate, temperature, and thermal dose fields are computed, plotted, the output is released to the MATLAB workspace for further user analysis or postprocessing. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Soneson, JE (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM joshua.soneson@fda.hhs.gov NR 10 TC 14 Z9 14 U1 0 U2 2 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0650-6 J9 AIP CONF PROC PY 2009 VL 1113 BP 165 EP 169 PG 5 WC Acoustics; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BJJ44 UT WOS:000266425300031 ER PT S AU Maruvada, S Liu, YB Herman, BA Harris, GR AF Maruvada, Subha Liu, Yunbo Herman, Bruce A. Harris, Gerald R. BE Ebbini, ES TI Temperature Measurements in Tissue-Mimicking Material during HIFU Exposure SO 8TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 8th International Symposium on Therapeutic Ultras CY SEP 10-13, 2008 CL Minneapolis, MN SP Int Soc Therapeut Ultrasound, Imasonic, SuperSonic Imagine, Onda Corp, EDAP, JJA Instruments, Philips, Focused Ultrasound Surg Fdn, China Med Technologies DE HIFU; Cavitation; Tissue-mimicking material AB Cavitation in high intensity focused ultrasound (HIFU) procedures can yield unpredictable results, particularly when the same location is targeted for more than several seconds. To study this effect, temperature rise was measured in tissue mimicking material TMM) during HIFU exposures. A 50 urn thin wire thermocouple (TC) was embedded in (fie center of a hydrogel-based TMM that was previously developed for HIFU applications. HIFU at 825 kHz was Focused at the TC junction. Thirty second HIFU exposures of increasing pressure front 1-7 MPa were applied and the temperature rise and decay during and after sonication were recorded. B-mode imaging was used to monitor any cavitation activity during sonication. If cavitation was noted during the sonication, the sonication was repeated at the same pressure level two more times at 20 minute intervals in order to characterize the repeatability given that cavitation had occurred. The cavitation threshold of the TMM was determined to be approximately 3 MPa at 825 kHz. Temperature traces obtained at various pressure levels demonstrated a wide range of-heating profiles in the TMM due to the occurrence of cavitation. C1 [Maruvada, Subha; Liu, Yunbo; Herman, Bruce A.; Harris, Gerald R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Maruvada, S (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 4 TC 2 Z9 2 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0650-6 J9 AIP CONF PROC PY 2009 VL 1113 BP 286 EP 290 PG 5 WC Acoustics; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BJJ44 UT WOS:000266425300055 ER PT S AU Liu, YB Maruvada, S King, RL Herman, BA Wear, KA AF Liu, Yunbo Maruvada, Subha King, Randy L. Herman, Bruce A. Wear, Keith A. BE Ebbini, ES TI Temperature-dependent Physical Properties of a HIFU Blood Mimicking Fluid SO 8TH INTERNATIONAL SYMPOSIUM ON THERAPEUTIC ULTRASOUND SE AIP Conference Proceedings LA English DT Proceedings Paper CT 8th International Symposium on Therapeutic Ultras CY SEP 10-13, 2008 CL Minneapolis, MN SP Int Soc Therapeut Ultrasound, Imasonic, SuperSonic Imagine, Onda Corp, EDAP, JJA Instruments, Philips, Focused Ultrasound Surg Fdn, China Med Technologies DE HIFU; blood mimicking fluid; ultrasound characterization; thermal ablation ID INTENSITY FOCUSED ULTRASOUND AB A blood mimicking fluid (BMF) has been developed and characterized in a temperature dependent manner for high intensity focused ultrasound (HIFU) ablation devices. The BMF is based oil a degassed and de-ionized water solution dispersed with low density polyethylene micro-spheres, nylon particles, gellan gum and glycerol. A broad range of physical parameters, including frequency dependent ultrasound attenuation, speed of sound, viscosity, thermal conductivity and diffusivity were characterized as a function of temperature (20 degrees C to 70 degrees C). The nonlinear parameter B/A and backscatter coefficient were also measured at room temperature. The attenuation coefficient is linearly proportional to the frequency (2 MHz - 8 MHz) with a slope of about 0.2 dB cm(-1)MHz(-1) in the 20 degrees C to 70 degrees C range as has been reported for human blood. All the other temperature dependent physical parameters are also close to the reported values in human blood. These properties make the BMF a useful HIFU research toot for developing standardized exposimetry techniques, validating numerical models, and determining the satiety and efficacy of HIFU ablation devices. C1 [Liu, Yunbo; Maruvada, Subha; Herman, Bruce A.; Wear, Keith A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [King, Randy L.] Stanford Univ, Dept Bioengn, Stanford, CA 94305 USA. RP Liu, YB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. FU Defense Advanced Research Projects Agency (DARPA) through IAG [224-05-6016] FX This research was supported by the Defense Advanced Research Projects Agency (DARPA) through IAG # 224-05-6016. Note: The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the Department of Health and Human Services. NR 7 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 978-0-7354-0650-6 J9 AIP CONF PROC PY 2009 VL 1113 BP 291 EP + PG 2 WC Acoustics; Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BJJ44 UT WOS:000266425300056 ER PT J AU Summers, RM Frentz, SM Liu, JM Yao, JH Brown, L Louie, A Barlow, DS Jensen, DW Dwyer, AJ Pickhardt, PJ Petrick, N AF Summers, Ronald M. Frentz, Suzanne M. Liu, Jiamin Yao, Jianhua Brown, Linda Louie, Adeline Barlow, Duncan S. Jensen, Donald W. Dwyer, Andrew J. Pickhardt, Perry J. Petrick, Nicholas TI Conspicuity of Colorectal Polyps at CT Colonography: Visual Assessment, CAD Performance, and the Important Role of Polyp Height SO ACADEMIC RADIOLOGY LA English DT Article DE CT; colon; colon cancer; conspicuity ID COMPUTED-TOMOGRAPHIC COLONOGRAPHY; VIRTUAL COLONOSCOPY; ASYMPTOMATIC ADULTS; STRUCTURED NOISE; AIDED DETECTION; MISSED LESIONS; FLAT; FEATURES; NODULES; SEARCH AB Rationale and Objectives. The factors that influence the conspicuity of polyps on computed tomographic (CT) colonography (CTC) are poorly understood. The aim of this study is to compare radiologists' visual assessment of polyp conspicuity to quantitative image features and show the relationship between Visual conspicuity and the detection of colonic polyps by computer-aided detection (CAD) on CTC. Methods. One polyp (size range 6-10 mm) was selected from the CTC examination of each of 29 patients from a larger cohort. All patients underwent oral contrast-enhanced CTC with same-day optical colonoscopy with segmental unblinding. The polyps were analyzed by a previously validated CAD system and placed into one of two groups (detected [n = 12] or not detected [n = 171 by CAD). The study population was intentionally enriched with polyps that were not detected by the CAD system. Four board-certified radiologists, blinded to the CAD results, reviewed two- and three-dimensional CTC images of the polyps and scored the conspicuity of the polyps using a 4-point scale (0 = least conspicuous, 3 = most conspicuous). Polyp height and width were measured by a trained observer. A t-test (two-tailed, unpaired equal variance) was done to determine statistical significance. Intra- and interobserver variabilities of the conspicuity scores were assessed using the weighted kappa test. Regression analysis was used to investigate the relationship of conspicuity to polyp height and width. Results. A statistically significant difference was found between the average conspicuity scores for polyps that were detected by CAD compared to those that were not (2.3 +/- 0.6 vs. 1.4 +/- 0.8) (P = .004). There was moderate intraobserver agreement of the conspicuity scores (weighted kappa 0.57 +/- 0.09). Interobserver agreement was fair (average weighted kappa for six pair-wise comparisons, 0.38 +/- 0.15). Conspicuity was correlated with manual measurement of polyp height (r(2) = 0.38-0.56 P < .001). Conclusions. This CAD system tends to detect 6-10 mm polyps that are more visually conspicuous. Polyp height is a major determinant of visual conspicuity. The generalizability of these findings to other CAD systems is currently unknown. Nevertheless, CAD developers may need to specifically target flatter and less conspicuous polyps for CAD to better assist the radiologist to find polyps in this clinically important size category. C1 [Summers, Ronald M.; Frentz, Suzanne M.; Liu, Jiamin; Yao, Jianhua; Brown, Linda; Louie, Adeline; Dwyer, Andrew J.] NIH, Dept Diagnost Radiol, Ctr Clin, Bethesda, MD 20892 USA. [Barlow, Duncan S.; Jensen, Donald W.] Natl Naval Med Ctr, Colon Hlth Initiat, Bethesda, MD USA. [Pickhardt, Perry J.] Univ Wisconsin, Sch Med, Dept Radiol, Madison, WI USA. [Petrick, Nicholas] FDA CDRH OSEL, LAMIS Image Anal Lab, Silver Spring, MD USA. RP Summers, RM (reprint author), NIH, Dept Diagnost Radiol, Ctr Clin, Bldg 10,Room 1C368X,MSC 1182, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural Research Programs of the NIH Clinical Center; National Institute of Biomedical Imaging and Bioengineering FX This research was supported in part by the Intramural Research Programs of the NIH Clinical Center and the National Institute of Biomedical Imaging and Bioengineering. NR 25 TC 12 Z9 12 U1 0 U2 2 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 JAN PY 2009 VL 16 IS 1 BP 4 EP 14 DI 10.1016/j.acra.2008.06.007 PG 11 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 388LP UT WOS:000262021600002 PM 19064206 ER PT J AU Guo, F Kothary, MH Wang, Y Yu, XP Howard, AJ Fu, TJ Zhang, YZ AF Guo, Feng Kothary, Mahendra H. Wang, Yang Yu, Xiaoping Howard, Andrew J. Fu, Tong-Jen Zhang, Yu-Zhu TI Purification and crystallization of Cor a 9, a major hazelnut allergen SO ACTA CRYSTALLOGRAPHICA SECTION F-STRUCTURAL BIOLOGY AND CRYSTALLIZATION COMMUNICATIONS LA English DT Article ID CORYLUS-AVELLANA L.; INITIAL CRYSTALLOGRAPHIC CHARACTERIZATION; CROSS-REACTIVITY; 11S GLOBULIN; DOUBLE-BLIND; BRAZIL-NUT; IDENTIFICATION; ANAPHYLAXIS; ANTIOXIDANT; GLYCININ AB Hazelnut (Corylus avellana) is one of the food sources that induce allergic reaction in a subpopulation of people with food allergy. The 11S legumin-like seed-storage protein from hazelnut has been identified as one of the major hazelnut allergens and named Cor a 9. In this study, Cor a 9 was extracted from hazelnut kernels using a high-salt solution and was purified by desalting out and FPLC to a highly purified state. Diffraction-quality single crystals were obtained using the hanging-drop vapour-diffusion method. Diffraction data were collected and a structure solution has been obtained by molecular-replacement calculations. Further refinement of the structure is currently in progress. C1 [Guo, Feng; Wang, Yang; Yu, Xiaoping; Howard, Andrew J.; Zhang, Yu-Zhu] IIT, Dept Biol Chem & Phys Sci, Chicago, IL 60616 USA. [Kothary, Mahendra H.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Fu, Tong-Jen] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Zhang, Yu-Zhu] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Zhang, YZ (reprint author), IIT, Dept Biol Chem & Phys Sci, Chicago, IL 60616 USA. EM zhangy@iit.edu RI Zhang, Yuzhu/A-7109-2009 OI Zhang, Yuzhu/0000-0001-7882-5692 FU US Food and Drug Administration; National Center for Food Safety and Technology [FD-0004331]; Illinois Institute of Technology; US Department of Energy, Office of Science, Office of Basic Energy Sciences [W-31-109-Eng-38] FX This work was supported by a cooperative agreement between the US Food and Drug Administration and the National Center for Food Safety and Technology (FD-0004331) and a fund from Illinois Institute of Technology. X-ray diffraction data were collected on Southeast Regional Collaborative Access Team (SER-CAT) 22-ID beamline at the APS, Argonne National Laboratory. Use of the APS was supported by the US Department of Energy, Office of Science, Office of Basic Energy Sciences under Contract W-31-109-Eng-38. NR 26 TC 6 Z9 6 U1 0 U2 8 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1744-3091 J9 ACTA CRYSTALLOGR F JI Acta Crystallogr. F-Struct. Biol. Cryst. Commun. PD JAN PY 2009 VL 65 BP 42 EP 46 DI 10.1107/S1744309108039894 PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biophysics; Crystallography SC Biochemistry & Molecular Biology; Biophysics; Crystallography GA 390PE UT WOS:000262175400011 PM 19153454 ER PT J AU Ortiz, PG Hansen, SH Shah, VP Menne, T Benfeldt, E AF Ortiz, Patricia Garcia Hansen, Steen H. Shah, Vinod P. Menne, Torkil Benfeldt, Eva TI Impact of Adult Atopic Dermatitis on Topical Drug Penetration: Assessment by Cutaneous Microdialysis and Tape Stripping SO ACTA DERMATO-VENEREOLOGICA LA English DT Article DE atopic dermatitis; dermatopharmacokinetics; metronidazole; microdialysis; skin penetration; tape stripping; topical formulations ID WATER-VAPOR LOSS; PERCUTANEOUS-ABSORPTION; DERMATOPHARMACOKINETIC METHOD; BARRIER FUNCTION; UNINVOLVED SKIN; HYDROCORTISONE; CHILDREN; HUMANS; STANDARDIZATION; BIOEQUIVALENCE AB Appropriate methodologies for the determination of drug penetration in diseased skin have not yet been established. The aim of this study was to determine the cutaneous penetration of a metronidazole cream formulation in atopic dermatitis, employing dermal microdialysis and tape strip sampling techniques. Non-invasive measuring methods were used for the quantification of the severity of the dermatitis. Skin thickness and the depth of the microdialysis probes in the skin were measured by 20 MHz ultrasound scanning. Metronidazole concentration, sampled by microdialysis, was 2.4-fold higher in the atopic dermatitis compared with uninvolved skin (p<0.001). Tape stripping methodology did not disclose this difference in penetration. Thus, the skin layer of interest and the integrity of the skin barrier should be considered when selecting sampling methodology. Microdialysis sampling is the method of choice whenever the dermis is the target tissue for topical treatment and a skin disease affecting the barrier function is present. C1 [Ortiz, Patricia Garcia; Menne, Torkil; Benfeldt, Eva] Univ Copenhagen, Gentofte Hosp, Dept Dermatol, DK-2900 Hellerup, Denmark. [Hansen, Steen H.] Univ Copenhagen, Pharmaceut Fac, Dept Pharmaceut & Analyt Chem, Copenhagen, Denmark. [Shah, Vinod P.] US FDA, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Ortiz, PG (reprint author), Univ Copenhagen, Gentofte Hosp, Dept Dermatol, Niels Andersens Vej 65, DK-2900 Hellerup, Denmark. EM patriciagarcia@dadlnet.dk FU Aage Bang's Foundation; Hans and Nora Buchard's Foundation; Danish Hospital Foundation for Medical Research; Greenland Foundation; Leo Foundation; Mrs Liv Brylin's Foundation; Danish Psoriasis Foundation; Foundation for Scientific Research without Animal Experiments FX This study was conducted in the Phase I Unit at Gentofte Hospital, and we thank ChiefPhysician Jesper Sonne for his hospitality. Aage Volund, PhD, is thanked for statistical Support, and laboratory technicians Kirsten Andersen and Eva Tiedemann for excellent technical assistance. Consultant Dermatologist Tove Agner is also thanked for lending us access to the Evaporimeter, Minolta Chromameter and Dermascan.; Financial support for this study was provided by Aage Bang's Foundation, Hans and Nora Buchard's Foundation, the Danish Hospital Foundation for Medical Research, Region of Copenhagen, The Faeroe Islands and Greenland Foundation, The Leo Foundation, Mrs Liv Brylin's Foundation, The Danish Psoriasis Foundation and the Foundation for Scientific Research without Animal Experiments. NR 23 TC 21 Z9 21 U1 1 U2 11 PU ACTA DERMATO-VENEREOLOGICA PI UPPSALA PA TRADGARDSGATAN 14, UPPSALA, SE-753 09, SWEDEN SN 0001-5555 J9 ACTA DERM-VENEREOL JI Acta Derm.-Venereol. PY 2009 VL 89 IS 1 BP 33 EP 38 DI 10.2340/00015555-0562 PG 6 WC Dermatology SC Dermatology GA 396AF UT WOS:000262563900007 ER PT J AU Duan, SJ Gu, LZ Wang, YY Zheng, RB Lu, JF Yin, JJ Guli, LW Ball, M AF Duan, Shaojin Gu, Lizhen Wang, Yanyun Zheng, Rongbo Lu, Jingfen Yin, Junjie Guli, Laowa Ball, Michele TI Regulation of Influenza Virus-Caused Oxidative Stress by Kegan Liyan Oral Prescription, as Monitored by Ascorbyl Radical ESR Signals SO AMERICAN JOURNAL OF CHINESE MEDICINE LA English DT Article DE Oxidative Stress; Influenza Virus; Antioxidant; Kegan Liyan; Flos Lonicerae; Radix; Scutellariae; Radix Glycyrrhizae ID NITRIC-OXIDE; A VIRUS; NUTRIENT MIXTURE; VIRAL-INFECTION; OXYGEN RADICALS; CELLS; PATHOGENESIS; ANTIOXIDANT; EXTRACT; ACID AB To study the oxidative stress level of the influenza virus A FM1 subset-infected mouse in intranasal inhalation as a model, we employ an ascorbyl radical's ESR (electron spin resonance) spectrum as an oxidative stress biomarker. These infected mice were pretreated with Ribavirin, ascorbic acid, superoxide dismutase (SOD) or Kegan Liyan oral prescription (KGLY, proprietary Chinese medicine for influenza and common cold) in the stomach tube for 3 days, and then followed by the virus-infecting for 4 days. On the 4th day, samples were collected. It is recognized the strength of ascorbyl radical's ESR signal (A(-.)) (aH(4) = 0.177 Gauss, g = 2.00517) denotes oxidative stress level in vivo and in vitro. The magnitude of ESR spectrum (28.65 +/- 10.71 AU) in mice infected with influenza virus was significantly higher than those of healthy control mice (19.10 +/- 3.61 AU). Serum A(-.) in mice treated with Ribavirin, ascorbic acid, SOD and KGLY declined to 19.70 +/- 6.05, 18.50 +/- 2.93 and 16.25 +/- 3.59, 18.40 +/- 2.14 AU respectively. It is close to A(-.) signal height in healthy controls via down-regulation of the influenza virus-caused oxidative stress level getting decline in the lung index of pneumonia as compare to those of untreated healthy and the influenza virus infected mice pneumonia. It is well known that SOD can prevent the influenza virus pneumonia enhancing mouse survival rate; Ribavirin can treat viral diseases. Data from this study suggested that KGLY may indirectly relieve influenza virus-infected pneumonia via down-regulation of virus caused oxidative stress coupled with a redox reaction cascade as ribavirin, ascorbic acid and SOD. C1 [Duan, Shaojin] China Acad Chinese Med Sci, Inst Med Clin 2, Guang An Men Hosp, Dept Basic Med, Beijing 100053, Peoples R China. [Ball, Michele] China Acad Chinese Med Sci, Grad Sch, Beijing 100053, Peoples R China. [Lu, Jingfen; Guli, Laowa] Peking Univ, Hlth Sci Ctr, Natl Lab Nat & Biomimet Drugs, Beijing 100083, Peoples R China. [Zheng, Rongbo] Guangzhou WangLaoJi Pharmaceut Co Ltd, Guangzhou 510450, Guangdong, Peoples R China. [Yin, Junjie] FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Duan, SJ (reprint author), China Acad Chinese Med Sci, Inst Med Clin 2, Guang An Men Hosp, Dept Basic Med, Beijing 100053, Peoples R China. EM shaojduan@yahoo.com RI Yin, Jun Jie /E-5619-2014 FU Ministry of Public Health; People's Republic of China [94-1-070] FX This investigation was supported by a grant from the foundation of the Ministry of Public Health, the People's Republic of China (No. 94-1-070). Our thanks to our colleagues, T. J. Li, Z. Chen, S. Z. Chen, J. H. Pan for their contribution in the model of influenza virus-infected mice and making figures and editing. NR 41 TC 6 Z9 8 U1 0 U2 3 PU WORLD SCIENTIFIC PUBL CO PTE LTD PI SINGAPORE PA 5 TOH TUCK LINK, SINGAPORE 596224, SINGAPORE SN 0192-415X J9 AM J CHINESE MED JI Am. J. Chin. Med. PY 2009 VL 37 IS 6 BP 1167 EP 1177 DI 10.1142/S0192415X09007570 PG 11 WC Integrative & Complementary Medicine; Medicine, General & Internal SC Integrative & Complementary Medicine; General & Internal Medicine GA 523SA UT WOS:000272093600013 PM 19938224 ER PT J AU Forshee, RA Storey, ML Anderson, PA AF Forshee, Richard A. Storey, Maureen L. Anderson, Patricia A. TI Sugar-sweetened beverages and BMI in children and adolescents: reanalyses of a meta-analysis Reply SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Letter ID BODY-MASS INDEX; CONSUMPTION; WEIGHT C1 [Forshee, Richard A.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Storey, Maureen L.; Anderson, Patricia A.] Amer Beverage Assoc, Washington, DC 20036 USA. RP Forshee, RA (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM mstorey@ameribev.org NR 9 TC 3 Z9 3 U1 1 U2 5 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 JAN 1 PY 2009 VL 89 IS 1 BP 439 EP 440 DI 10.3945/ajcn.2008.27089 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 391VM UT WOS:000262262300058 ER PT J AU Brazeau, GA Meyer, SM Belsey, M Bednarczyk, EM Bilic, S Bullock, J DeLander, GE Fiese, EF Giroux, SL McNatty, D Nemire, R Prescott, WA Traynor, AP AF Brazeau, Gayle A. Meyer, Susan M. Belsey, Michele Bednarczyk, Edward M. Bilic, Sanela Bullock, Julie DeLander, Gary E. Fiese, E. F. Giroux, Stephen L. McNatty, Danny Nemire, Ruth Prescott, William A., Jr. Traynor, Andrew P. TI Preparing Pharmacy Graduates for Traditional and Emerging Career Opportunities SO AMERICAN JOURNAL OF PHARMACEUTICAL EDUCATION LA English DT Article ID SUPPLY-AND-DEMAND; CLINICAL-PHARMACY; AMERICAN-COLLEGE; RESEARCH AGENDA; PROGRAM; INVESTIGATOR; SIMULATIONS; STUDENTS; SKILLS AB Educational programs in pharmacy must focus on educating pharmacists of the future who are prepared to serve as competent and confident health care "providers" whose "practice" can occur in any number of current and future settings; and whose expertise is essential to an interprofessional health care team. Graduates must be able to incorporate a scholarly approach to their practice in identifying patient care problems; practicing in an evidence-based manner; and ensuring safe, effective, and appropriate use of medications. It is time for colleges and schools of pharmacy to implement contemporary teaching and assessment strategies that facilitate effective and efficient student learning that is focused at the graduate professional level, to evolve the content around which the curriculum is organized, and clearly articulate the abilities graduates must have to function effectively in the myriad professional roles in which they may find themselves. C1 [Brazeau, Gayle A.; Bednarczyk, Edward M.; Prescott, William A., Jr.] SUNY Buffalo, Sch Pharm & Pharmaceut Sci, Buffalo, NY USA. [Meyer, Susan M.] Univ Pittsburgh, Sch Pharm, Pittsburgh, PA 15260 USA. [Belsey, Michele] Rite Aid Corp, Camp Hill, PA USA. [Bilic, Sanela] Nova Pharmaceut Corp, Florham Pk, NJ USA. [Bullock, Julie] US FDA, Silver Spring, MD USA. [DeLander, Gary E.] Oregon State Univ, Coll Pharm, Corvallis, OR 97331 USA. [Fiese, E. F.] Pfizer Inc, Groton, CT 06340 USA. [Giroux, Stephen L.] Modem Giroux Inc, Middleport Family Hlth Ctr, New York, NY USA. [McNatty, Danny] Midwestern Univ, Coll Pharm, Downers Grove, IL 60515 USA. [Nemire, Ruth] Touro Coll Pharm, New York, NY USA. [Traynor, Andrew P.] Univ Minnesota, Coll Pharm, Duluth, MN 55812 USA. RP Brazeau, GA (reprint author), SUNY Buffalo, Sch Pharm, Buffalo, NY USA. EM gbrazeau@buffalo.edu NR 53 TC 9 Z9 10 U1 0 U2 5 PU AMER ASSOC COLL PHARMACY PI ALEXANDRIA PA 1426 PRINCE STREET, ALEXANDRIA, VA 22314-2815 USA SN 0002-9459 EI 1553-6467 J9 AM J PHARM EDUC JI Am. J. Pharm. Educ. PY 2009 VL 73 IS 8 AR 157 PG 12 WC Education, Scientific Disciplines; Pharmacology & Pharmacy SC Education & Educational Research; Pharmacology & Pharmacy GA 535FV UT WOS:000272953600022 PM 20221350 ER PT J AU Cunningham, JE Sheehan, AH AF Cunningham, Jean Ellen Sheehan, Amy Heck TI Proposed Guidelines for Uniformity of Postgraduate Industry-Affiliated Fellowships SO AMERICAN JOURNAL OF PHARMACEUTICAL EDUCATION LA English DT Letter C1 [Cunningham, Jean Ellen; Sheehan, Amy Heck] Purdue Univ, Sch Pharm & Pharmaceut Sci, W Lafayette, IN 47907 USA. [Cunningham, Jean Ellen] Eli Lilly & Co, Indianapolis, IN USA. [Cunningham, Jean Ellen] US FDA, Rockville, MD 20857 USA. RP Cunningham, JE (reprint author), Univ Findlay, Coll Pharm, Findlay, OH 45840 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC COLL PHARMACY PI ALEXANDRIA PA 1426 PRINCE STREET, ALEXANDRIA, VA 22314-2815 USA SN 0002-9459 J9 AM J PHARM EDUC JI Am. J. Pharm. Educ. PY 2009 VL 73 IS 5 PG 1 WC Education, Scientific Disciplines; Pharmacology & Pharmacy SC Education & Educational Research; Pharmacology & Pharmacy GA 489RY UT WOS:000269441200016 ER PT J AU Guglani, L Reed, JL Hintz, KH Welliver, RC AF Guglani, L. Reed, J. L. Hintz, K. H. Welliver, R. C. TI Appropriate Timing of Innate Immune Responses Is Crucial to Optimal Recovery from Respiratory Syncytial Virus (RSV) Bronchiolitis in Human Infants. SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Guglani, L.] Women & Childens Hosp Buffalo, Dept Pediat, Buffalo, NY USA. [Reed, J. L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Hintz, K. H.; Welliver, R. C.] Women & Childens Hosp Buffalo, Div Infect Dis, Buffalo, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2009 VL 179 MA A5169 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733104633 ER PT J AU Penn, AL Rouse, RL Perveen, Z AF Penn, A. L. Rouse, R. L. Perveen, Z. TI Adult Lung Gene Expression Changes Following Ovalbumin Exposure Are Magnified in Mice Exposed to Environmental Tobacco Smoke (ETS) In Utero SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Penn, A. L.; Perveen, Z.] LSU SVM, Baton Rouge, LA USA. [Rouse, R. L.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2009 VL 179 MA A1669 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733100669 ER PT J AU Reed, JL Avendano, L Velozo, L Scott, DE Welliver, RC AF Reed, J. L. Avendano, L. Velozo, L. Scott, D. E. Welliver, R. C. TI Local Regulation of Alpha-1 Proteinase Inhibitor during Severe Respiratory Syncytial Virus Infection in Infants SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Meeting Abstract C1 [Reed, J. L.; Scott, D. E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Avendano, L.] Univ Chile, Dept Virol, Santiago, Chile. [Velozo, L.] Roberto del Rio Childrens Hosp, Santiago, Chile. [Welliver, R. C.] SUNY Buffalo, Women & Childrens Hosp, Buffalo, NY USA. EM jennifer.reed@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PY 2009 VL 179 MA A3508 PG 1 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA V29FA UT WOS:000208733102742 ER PT J AU Girnita, DM Brooks, M Webber, S Burckart, G Ferrell, R Chinnock, R Canter, C Addonizio, L Bernstein, D Kirklin, J Naftel, D Girnita, AL Zeevi, A AF Girnita, D. M. Brooks, M. Webber, S. Burckart, G. Ferrell, R. Chinnock, R. Canter, C. Addonizio, L. Bernstein, D. Kirklin, J. Naftel, D. Girnita, A. L. Zeevi, A. TI Bacterial and Viral Infections Are Impacted by Different Genetic Polymorphisms - A Multicenter Pediatric Heart Transplant Study. SO AMERICAN JOURNAL OF TRANSPLANTATION LA English DT Meeting Abstract CT 9th Joint Meeting of the American-Society-of-Transplant-Surgeon/American-Society-of-Transplantati on CY MAY 30-JUN 03, 2009 CL Boston, MA SP Amer Soc Transplant Surg, Amer Soc Transplantat C1 [Girnita, D. M.; Brooks, M.; Webber, S.; Ferrell, R.; Girnita, A. L.; Zeevi, A.] Univ Pittsburgh, Pittsburgh, PA 15260 USA. [Burckart, G.] US FDA, Rockville, MD 20857 USA. [Chinnock, R.] Loma Linda Univ, Loma Linda, CA 92350 USA. [Canter, C.] Washington Univ, St Louis, MO 63130 USA. [Addonizio, L.] Columbia Univ, New York, NY 10027 USA. [Bernstein, D.] Stanford Univ, Stanford, CA 94305 USA. [Kirklin, J.; Naftel, D.] Univ Alabama, Birmingham, AL USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1600-6135 J9 AM J TRANSPLANT JI Am. J. Transplant. PY 2009 VL 9 BP 196 EP 196 PG 1 WC Surgery; Transplantation SC Surgery; Transplantation GA 431NQ UT WOS:000265068800020 ER PT J AU Modric, T Mergia, A AF Modric, Tomislav Mergia, Ayalew TI THE USE OF VIRAL VECTORS IN INTRODUCING GENES INTO AGRICULTURAL ANIMAL SPECIES SO ANIMAL BIOTECHNOLOGY LA English DT Article ID PANTROPIC RETROVIRAL VECTORS; RECOMBINANT ADENOASSOCIATED VIRUS; GREEN FLUORESCENT PROTEIN; GERM-LINE TRANSMISSION; HIGH-LEVEL EXPRESSION; EMBRYONIC STEM-CELLS; HUMAN GROWTH-HORMONE; FC FUSION PROTEIN; LIVE-BEARING FISH; TRANSGENIC CHICKENS AB The use of viral vectors is a method for introducing foreign genes into various animal species. Vectors based on retro-, adeno-, flavi-, and parvoviruses have been used for research in animal species of agricultural importance, such as chickens, quail, swine, cows, goats, sheep, fish, crustaceans, and mollusks. Viral vectors allow for efficient transgenic integration into host genome or for transient expression of the transgenic construct in somatic tissues. Because of that, viral vectors are important tools for research and potentially other biotechnology applications such as improving animal production qualities and introducing disease resistance, thus improving food quality and safety. Other uses may include generating animal models of human diseases and using animals as bioreactors for production of therapeutic proteins. Each vector type provides a unique set of advantages and limitations, which are in some cases specific to an animal species or a method of introduction. This article discusses viral vector characteristics and potential applications in agriculturally important animal species. It discusses advantages and disadvantages of using viral vectors in genetic engineering of agricultural animals. C1 [Modric, Tomislav] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. [Mergia, Ayalew] Univ Florida, Coll Vet Med, Dept Infect Dis & Pathol, Gainesville, FL USA. RP Modric, T (reprint author), US FDA, Ctr Vet Med, 7519 Standish Pl,MPN 4, Rockville, MD 20855 USA. EM tomislav.modric@fda.hhs.gov NR 92 TC 1 Z9 1 U1 1 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1049-5398 J9 ANIM BIOTECHNOL JI Anim. Biotechnol. PY 2009 VL 20 IS 4 BP 216 EP 230 DI 10.1080/10495390903196380 PG 15 WC Agriculture, Dairy & Animal Science; Biotechnology & Applied Microbiology SC Agriculture; Biotechnology & Applied Microbiology GA 500PE UT WOS:000270314800003 PM 19937496 ER PT J AU Halbert, SE Corsini, D Wiebe, M Vaughn, SF AF Halbert, S. E. Corsini, D. Wiebe, M. Vaughn, S. F. TI Plant-derived compounds and extracts with potential as aphid repellents SO ANNALS OF APPLIED BIOLOGY LA English DT Article DE Aphididae; Homoptera; plant volatiles; repellent ID MYZUS-PERSICAE; MONOTERPENES; OIL; HOMOPTERA; VULGARIS; ROSEMARY; VIRUS AB We devised a method for screening various Substances for possible aphid repellency . Corn leaf aphids (Rhopalosiphum maidis) were released in an arena and allowed to select paired green tiles coated with petroleum jelly alone or pctroleuni Jelly containing 1% of file substance being tested. Aphids adhering to tiles were Counted 24 h later. 11 significantly fewer aphids landed on treated tiles, file Substance was considered to have potential for repelling aphids. Fifty-five substances were tested. Most showed no activity, but several including beta-citronellol, farnesol, geraniol, linalool, oils distilled from several species of Artemisia and Achillea millefolia (yarrow) oil showed sonic promise. C1 [Halbert, S. E.; Corsini, D.; Wiebe, M.; Vaughn, S. F.] Univ Idaho, Dept Plant Soil & Agr Sci, Aberdeen Res & Extens Ctr, Aberdeen, ID USA. [Vaughn, S. F.] USDA ARS, New Crops Proc & Technol Res Unit, Natl Ctr Agr Utilizat Res, Peoria, IL USA. RP Halbert, SE (reprint author), FDACS, Div Plant Ind, POB 147100, Gainesville, FL 32614 USA. EM halbers@doacs.state.fl.us NR 18 TC 23 Z9 23 U1 1 U2 16 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0003-4746 J9 ANN APPL BIOL JI Ann. Appl. Biol. PY 2009 VL 154 IS 2 BP 303 EP 307 DI 10.1111/j.1744-7348.2008.00300.x PG 5 WC Agriculture, Multidisciplinary SC Agriculture GA 452OE UT WOS:000266549700015 ER PT S AU Gobburu, JVS Lesko, LJ AF Gobburu, Jogarao V. S. Lesko, Lawrence J. TI Quantitative Disease, Drug, and Trial Models SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY SE Annual Review of Pharmacology and Toxicology LA English DT Review; Book Chapter DE model-based drug development; regulatory decisions; simulation; drug development; exposure response; trial design ID PROGRESSION; PLACEBO; IMPACT; PHARMACOMETRICS; DECISIONS; RATES; TIME; FDA AB Quantitative disease-drug-trial models allow learning from prior experience and summarize the knowledge in a ready to apply format. Employing these models to plan future development is proposed as a powerful solution to improve pharmaceutical RED productivity. The disease and trial models are, to a large extent, independent of the product, but the drug model is not. The goals are to apply the disease and trial models to future development and regulatory decisions, and publicly share them. We propose working definitions of these models, describe the various subcomponents, provide examples, and discuss the challenges and potential solutions for developing such models. Building useful disease-drug-trial models is a challenging task and cannot be achieved by any single organization. It requires a consorted effort by industry, academic, and regulatory scientists. We also describe the strategic goals of the FDA Pharmacometrics group. C1 [Gobburu, Jogarao V. S.; Lesko, Lawrence J.] US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Gobburu, JVS (reprint author), US FDA, Off Clin Pharmacol, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jogarao.gobburu@fda.hhs.gov NR 38 TC 57 Z9 63 U1 0 U2 5 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 BN 978-0-8243-0448-5 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2009 VL 49 BP 291 EP 301 DI 10.1146/annurev.pharmtox.011008.145613 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 410GQ UT WOS:000263565900013 PM 18851702 ER PT B AU Bash, MC McKnew, DL Tapsall, JW AF Bash, Margaret C. McKnew, Durrie L. Tapsall, John W. BE Mayers, DL TI Antibiotic Resistance in Neisseria SO ANTIMICROBIAL DRUG RESISTANCE, VOL 2: CLINICAL AND EPIDEMIOLOGICAL ASPECTS SE Infectious Disease LA English DT Article; Book Chapter ID SEXUALLY-TRANSMITTED-DISEASES; PENICILLIN-BINDING PROTEIN-2; PELVIC-INFLAMMATORY-DISEASE; CHROMOSOMALLY MEDIATED RESISTANCE; SHOWING DECREASED SUSCEPTIBILITY; BETA-LACTAM ANTIBIOTICS; MTRRCDE EFFLUX SYSTEM; LOW-LEVEL RESISTANCE; NEW-ZEALAND EPIDEMIC; MENINGOCOCCAL-DISEASE C1 [Bash, Margaret C.] US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA. [Tapsall, John W.] Prince Wales Hosp, WHO, Collaborating Ctr STD & HIV, Sydney, NSW, Australia. RP Bash, MC (reprint author), US FDA, Ctr Biol Evaluat & Res, Silver Spring, MD USA. EM margaret.bash@fda.hhs.gov NR 206 TC 0 Z9 0 U1 0 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-594-1 J9 INFECT DIS PY 2009 BP 763 EP 782 DI 10.1007/978-1-60327-595-8_52 D2 10.1007/978-1-60327-595-8 PG 20 WC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology SC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology GA BKN89 UT WOS:000268730200006 ER PT B AU McDermott, PF Simala-Grant, JL Taylor, DE AF McDermott, Patrick F. Simala-Grant, Joanne L. Taylor, Diane E. BE Mayers, DL TI Antimicrobial Resistance in Helicobacter and Campylobacter SO ANTIMICROBIAL DRUG RESISTANCE, VOL 2: CLINICAL AND EPIDEMIOLOGICAL ASPECTS SE Infectious Disease LA English DT Article; Book Chapter ID 23S RIBOSOMAL-RNA; REAL-TIME PCR; GASTRIC BIOPSY SPECIMENS; MULTIDRUG EFFLUX PUMP; IN-SITU HYBRIDIZATION; JEJUNI SUBSP JEJUNI; LEVEL METRONIDAZOLE RESISTANCE; POLYMERASE-CHAIN-REACTION; QUALITY-CONTROL RANGES; AGAR DILUTION METHODS C1 [McDermott, Patrick F.] US FDA, Div Anim & Foor Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. [Simala-Grant, Joanne L.] Univ Alberta, Fac Med & Dent, Edmonton, AB, Canada. [Taylor, Diane E.] Univ Alberta, Dept Med Microbiol & Immunol, Edmonton, AB, Canada. RP McDermott, PF (reprint author), US FDA, Div Anim & Foor Microbiol, Res Off, Ctr Vet Med, Laurel, MD USA. EM Patrick.McDermott@fda.hhs.gov NR 253 TC 2 Z9 2 U1 0 U2 0 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA BN 978-1-60327-594-1 J9 INFECT DIS PY 2009 BP 847 EP 863 DI 10.1007/978-1-60327-595-8_59 D2 10.1007/978-1-60327-595-8 PG 17 WC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology SC Public, Environmental & Occupational Health; Infectious Diseases; Microbiology GA BKN89 UT WOS:000268730200013 ER PT J AU Xiang, D Lobrutto, R Cheney, J Wabuyele, BW Berry, J Lyon, R Wu, HQ Khan, MA Hussain, AS AF Xiang, Dong Lobrutto, Rosario Cheney, James Wabuyele, Busolo Wa Berry, Joseph Lyon, Robbe Wu, Huiquan Khan, Mansoor A. Hussain, Ajaz S. TI Evaluation of Transmission and Reflection Modalities for Measuring Content Uniformity of Pharmaceutical Tablets with Near-Infrared Spectroscopy SO APPLIED SPECTROSCOPY LA English DT Article DE Near-infrared spectroscopy; NIR spectroscopy; Transmission; Diffuse reflection; Pharmaceutical tablets; Content uniformity; Partial least squares; PLS regression ID INTACT TABLETS; AQUEOUS-SOLUTIONS; ACTIVE-SUBSTANCE; QUALITY-CONTROL; DOSAGE FORMS; ASSAY; VALIDATION; QUANTITATION; TRANSMITTANCE; QUANTIFICATION AB This paper examines how one may assess spectral changes with instrument configuration (or composition), in combination with the spectral changes in the measurement that are caused by experimental effects, and subsequently select an appropriate measurement modality for tablet content uniformity determination with near-infrared (NIR) spectroscopy. Two NIR spectrometers furnished with three configurations in the sample measurement interface were evaluated. One spectrometer, Broker MPA (multiple purpose analyzer), was equipped with two measurement modalities, diffuse transmission (DT) and diffuse reflection based on integrating sphere optics (DR/IS). The other spectrometer, Broker StepOne, was equipped only with diffuse reflection mode based on a fiber-optic probe (DR/FO). The data were collected with each of the configurations for the tablets associated with two dosage strengths differing significantly in diameter and thickness. Spectral diagnosis was performed in terms of sensitivity and selectivity. The signal-to-noise ratio computed for the data collected with the DT and DR/IS spectrometers was approximately an order of magnitude greater than that computed for the DR/FO spectrometer. The net-analyte-signal-based selectivity analysis of NIR spectra associated with the sample tablet and the placebo tablet indicated that both transmission and reflection mode provided similar selectivity when the optimal spectral range was chosen. A partial least squares (PLS) calibration model was developed for each data set. The overall standard error of calibration for each DT and DR/IS measurement was approximately 0.3% in weight for each strength, significantly better than the value of 1.0% in weight produced by the DR/FO measurement. This result was consistent with the sensitivity analysis based on spectral noise characterization. The poor analytical performance of the DR/FO spectrometer was attributed to the small illumination spot size of the reflection probe and thus the sensitivity of the measurements to the tablet engraving. The PLS analysis and spectral diagnostics both showed that transmission and reflection modes based on the Bruker MPA provided similar measurement accuracy for each strength. However, the robustness study clearly revealed that the transmission mode would be more robust than the reflection mode when there is considerable variability in the chemical composition and physical properties of tablets. C1 [Xiang, Dong; Lobrutto, Rosario; Cheney, James; Wabuyele, Busolo Wa] Nova Pharmaceut Corp, Pharmaceut & Analyt Dev, E Hanover, NJ 07936 USA. [Berry, Joseph] QRxPharma Inc, Tech Operat, Bedminster, NJ 07921 USA. [Lyon, Robbe; Wu, Huiquan; Khan, Mansoor A.] OTR, OPS, CDER, FDA,Div Prod Qual Res, Silver Spring, MD 20993 USA. [Hussain, Ajaz S.] Phillip Morris Int Res & Dev, Philip Morris Prod SA, CH-2000 Neuchatel, Switzerland. RP Xiang, D (reprint author), Nova Pharmaceut Corp, Pharmaceut & Analyt Dev, E Hanover, NJ 07936 USA. EM dong.xiang@novartis.com NR 38 TC 12 Z9 12 U1 1 U2 10 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD JAN PY 2009 VL 63 IS 1 BP 33 EP 47 PG 15 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 395RZ UT WOS:000262542500007 PM 19146717 ER PT J AU Peng, SC Lu, N Chatterjee, M AF Peng, Shu-Chen Lu, Nelson Chatterjee, Monita TI Effects of Cooperating and Conflicting Cues on Speech Intonation Recognition by Cochlear Implant Users and Normal Hearing Listeners SO AUDIOLOGY AND NEURO-OTOLOGY LA English DT Article DE Cochlear implants; Intonation; Speech; Perception ID TEMPORAL CUES; PERCEPTION; INFORMATION; FREQUENCY; TONES; NOISE; PITCH; CHILDREN AB Cochlear implant (CI) recipients have only limited access to fundamental frequency (F0) information, and thus exhibit deficits in speech intonation recognition. For speech intonation, F0 serves as the primary cue, and other potential acoustic cues (e. g. intensity properties) may also contribute. This study examined the effects of cooperating or conflicting acoustic cues on speech intonation recognition by adult CI and normal hearing (NH) listeners with full-spectrum and spectrally degraded speech stimuli. Identification of speech intonation that signifies question and statement contrasts was measured in 13 CI recipients and 4 NH listeners, using resynthesized bi-syllabic words, where F0 and intensity properties were systematically manipulated. The stimulus set was comprised of tokens whose acoustic cues (i.e. F0 contour and intensity patterns) were either cooperating or conflicting. Subjects identified if each stimulus is a 'statement' or a 'question' in a single-interval, 2-alternative forced-choice (2AFC) paradigm. Logistic models were fitted to the data, and estimated coefficients were compared under cooperating and conflicting conditions, between the subject groups (CI vs. NH), and under full-spectrum and spectrally degraded conditions for NH listeners. The results indicated that CI listeners' intonation recognition was enhanced by co-operating F0 contour and intensity cues, but was adversely affected by these cues being conflicting. On the other hand, with full-spectrum stimuli, NH listeners' intonation recognition was not affected by cues being cooperating or conflicting. The effects of cues being cooperating or conflicting were comparable between the CI group and NH listeners with spectrally degraded stimuli. These findings suggest the importance of taking multiple acoustic sources for speech recognition into consideration in aural rehabilitation for CI recipients. Copyright (C) 2009 S. Karger AG, Basel C1 [Peng, Shu-Chen; Chatterjee, Monita] Univ Maryland, Cochlear Implants & Psychophys Lab, Dept Hearing & Speech Sci, College Pk, MD 20742 USA. [Peng, Shu-Chen; Lu, Nelson] US FDA, Ctr Device & Radiol Hlth, Rockville, MD 20857 USA. RP Peng, SC (reprint author), Univ Maryland, Cochlear Implants & Psychophys Lab, Dept Hearing & Speech Sci, College Pk, MD 20742 USA. EM speng@hesp.umd.edu FU NIDCD NIH HHS [R01 DC004786, R01 DC004786-06, R01 DC004786-07A2, R01DC04786] NR 20 TC 24 Z9 24 U1 0 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1420-3030 J9 AUDIOL NEURO-OTOL JI Audiol. Neuro-Otol. PY 2009 VL 14 IS 5 BP 327 EP 337 DI 10.1159/000212112 PG 11 WC Audiology & Speech-Language Pathology; Neurosciences; Otorhinolaryngology SC Audiology & Speech-Language Pathology; Neurosciences & Neurology; Otorhinolaryngology GA 472DB UT WOS:000268108300008 PM 19372651 ER PT J AU Ferguson, SA Gopee, NV Paule, MG Howard, PC AF Ferguson, Sherry A. Gopee, Neera V. Paule, Merle G. Howard, Paul C. TI Female mini-pig performance of temporal response differentiation, incremental repeated acquisition, and progressive ratio operant tasks SO BEHAVIOURAL PROCESSES LA English DT Article DE Learning; Motivation; Operant behavior; Progressive ratio; Time estimation; Timing ID BEHAVIORAL-TEST BATTERY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; COMPLEX BRAIN-FUNCTION; GOTTINGEN MINIPIG; RHESUS-MONKEYS; POSTNATAL-DEVELOPMENT; D-AMPHETAMINE; CHILDREN; CEREBELLAR; PIGS AB Increased knowledge of the cognitive abilities of mini-pigs is needed due to their increasing use in behavioral neuroscience research. Here, six female Yucatan mini-pigs performed tasks thought to measure timing behavior (temporal response differentiation, TRD), learning (incremental repeated acquisition, IRA), and motivation (progressive ratio, PR). Daily 30-min sessions for food reinforcers required a lever press be maintained for at least 10 but no longer than 14 s (TRD), learning a new sequence of lever presses each test day (IRA) or an escalating number of presses for subsequent reinforcers (PR). All animals performed PR two days/week while three performed TRD five days/week and the other three performed IRA five days/week. Over the four test weeks, no animal completed TRD training and only one appeared to progress. For this task, lever press maintenance appeared difficult since by choice, the pigs used a front hoof, rather than the snout, to press the lever. IRA subjects showed gradually increasing performance with response rates comparable to those of rats but below those of children and monkeys and accuracy below that for rats. PR response rates were higher than those typically reported for rats, but lower than for adult rhesus monkeys or children. Physical differences in the way that each species responds likely account for these differences. Published by Elsevier B.V. C1 [Ferguson, Sherry A.; Paule, Merle G.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Gopee, Neera V.; Howard, Paul C.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132, Jefferson, AR 72079 USA. EM Sherry.Ferguson@fda.hhs.gov NR 51 TC 13 Z9 13 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0376-6357 J9 BEHAV PROCESS JI Behav. Processes PD JAN PY 2009 VL 80 IS 1 BP 28 EP 34 DI 10.1016/j.beproc.2008.08.006 PG 7 WC Psychology, Biological; Behavioral Sciences; Zoology SC Psychology; Behavioral Sciences; Zoology GA 395TR UT WOS:000262546900005 PM 18804519 ER PT J AU Cochran, CJ Hoyer, PB Zirkin, BR AF Cochran, Chiissy J. Hoyer, Patricia B. Zirkin, Barry R. TI Ovarian Steroidogenesis in the Brown Norway Rat with Age SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract CT 42nd Annual Meeting of the Society-for-the-Study-of-Reproduction CY JUL 18-22, 2009 CL Pittsburgh, PA SP Soc Study Reproduct, David L Lawrence Convent Ctr C1 US FDA, Rockville, MD 20857 USA. Univ Arizona, Tucson, AZ USA. Johns Hopkins Univ, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 2009 SU S MA 480 BP 156 EP 156 PG 1 WC Reproductive Biology SC Reproductive Biology GA 543UY UT WOS:000273605500458 ER PT J AU Tang, R Muller, HG AF Tang, Rong Mueller, Hans-Georg TI Time-synchronized clustering of gene expression trajectories SO BIOSTATISTICS LA English DT Article ID B-SPLINES; OPTIMIZATION; ONTOLOGY; SAMPLE AB Current clustering methods are routinely applied to gene expression time course data to find genes with similar activation patterns and ultimately to understand the dynamics of biological processes. As the dynamic unfolding of a biological process often involves the activation of genes at different rates, successful clustering in this context requires dealing with varying time and shape patterns simultaneously. This motivates the combination of a novel pairwise warping with a suitable clustering method to discover expression shape clusters. We develop a novel clustering method that combines an initial pairwise curve alignment to adjust for time variation within likely clusters. The cluster-specific time synchronization method shows excellent performance over standard clustering methods in terms of cluster quality measures in simulations and for yeast and human fibroblast data sets. In the yeast example, the discovered clusters have high concordance with the known biological processes. C1 [Tang, Rong] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. [Mueller, Hans-Georg] Univ Calif Davis, Dept Stat, Davis, CA 95616 USA. RP Tang, R (reprint author), US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. EM rong.tang@fda.hhs.gov FU National Science Foundation [DMS03-54448, DMS05-05537] FX National Science Foundation (DMS03-54448, DMS05-05537). NR 29 TC 20 Z9 20 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1465-4644 J9 BIOSTATISTICS JI Biostatistics PD JAN PY 2009 VL 10 IS 1 BP 32 EP 45 DI 10.1093/biostatistics/kxn011 PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 383MU UT WOS:000261678500004 PM 18502728 ER PT J AU Li, ZG Su, ZQ Wen, ZN Shi, LM Chen, T AF Li, Zhiguang Su, Zhenqiang Wen, Zhining Shi, Leming Chen, Tao TI Microarray platform consistency is revealed by biologically functional analysis of gene expression profiles SO BMC BIOINFORMATICS LA English DT Article CT 6th Annual Conference of the MidSouth-Computational-Biology-and-Bioinformatics-Society CY FEB 20-21, 2009 CL Mississippi State Univ, Starkville, MS SP MidSouth Computat Biol & Bioinformat Soc HO Mississippi State Univ ID CHINESE HERBS NEPHROPATHY; ARISTOLOCHIC ACID; CARCINOMA; KIDNEY; RATS; INDUCTION; LIVER AB Background: Several different microarray platforms are available for measuring gene expression. There are disagreements within the microarray scientific community for intra-and inter-platform consistency of these platforms. Both high and low consistencies were demonstrated across different platforms in terms of genes with significantly differential expression. Array studies for gene expression are used to explore biological causes and effects. Therefore, consistency should eventually be evaluated in a biological setting to reveal the functional differences between the examined samples, not just a list of differentially expressed genes (DEG). In this study, we investigated whether different platforms had a high consistency from the biologically functional perspective. Results: DEG data without filtering the different probes in microarrays from different platforms generated from kidney samples of rats treated with the kidney carcinogen, aristolochic acid, in five test sites using microarrays from Affymetrix, Applied Biosystems, Agilent, and GE health platforms (two sites using Affymetrix for intra-platform comparison) were input into the Ingenuity Pathway Analysis (IPA) system for functional analysis. The functions of the DEG lists determined by IPA were compared across the four different platforms and two test sites for Affymetrix platform. Analysis results showed that there is a very high level of consistency between the two test sites using the same platform or among different platforms. The top functions determined by the different platforms were very similar and reflected carcinogenicity and toxicity of aristolochic acid in the rat kidney. Conclusion: Our results demonstrate that highly consistent biological information can be generated from different microarray platforms. C1 [Li, Zhiguang; Chen, Tao] US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Su, Zhenqiang; Wen, Zhining; Shi, Leming] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, T (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM zhiguang.li@fda.hhs.gov; zhenqiang.su@fda.hhs.gov; zhining.wen@fda.hhs.gov; leming.shi@fda.hhs.gov; tao.chen@fda.hhs.gov RI Su, Zhenqiang/H-3914-2012 NR 19 TC 13 Z9 13 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2105 J9 BMC BIOINFORMATICS JI BMC Bioinformatics PY 2009 VL 10 AR S12 DI 10.1186/1471-2105-10-S11-S12 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Mathematical & Computational Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Mathematical & Computational Biology GA 509YY UT WOS:000271056400012 PM 19811677 ER PT J AU Chiesa, OA von Bredow, J Li, H Smith, M AF Chiesa, O. Alberto von Bredow, Jurgen Li, Hui Smith, Michelle TI Isobaric (gasless) laparoscopic liver and kidney biopsy in standing steers SO CANADIAN JOURNAL OF VETERINARY RESEARCH-REVUE CANADIENNE DE RECHERCHE VETERINAIRE LA English DT Article ID CARBON-DIOXIDE INSUFFLATION; UTERINE MYOMECTOMY; BOVINE KIDNEY; RENAL BIOPSY; SURGERY; PNEUMOPERITONEUM; DOGS; CARDIOPULMONARY; HORSES; BLOOD AB The purpose of the current study was to investigate the suitability of an isobaric laparoscopic procedure, using a single port, for obtaining serial kidney and liver biopsy samples from standing steers. The samples were used in support of a pharmacokinetic tissue-fluid correlation study. Laparoscopic access was performed 3 times in each of 8 healthy Holstein steers, alternating from the right side to the left side and then to the right side again. The surgery was performed in standing stocks after the animals were given 3 doses of sulfadimethoxine sulfate intravenously and fasted for at least 18 h. Sedation and analgesia were achieved with acepromazine and xylazine. Lidocaine 2% was injected at the center of the paralumbar fossa (left or right), and an incision was made for introduction of a trocar-cannula assembly. Room air was allowed to enter the abdomen through the cannula at the time of insertion. Once the peritoneal cavity was reached, an operating endoscope was inserted. No pressurized insufflation was performed. A biopsy forceps was introduced into the operating channel of the endoscope to obtain a 100-mg kidney or liver sample. No complications were encountered. The 24 laparoscopic procedures provided 24 kidney and 16 liver samples. The results suggest that the isobaric (gasless) single-port laparoscopic technique is feasible for kidney and liver biopsy on standing steers. The procedure can be performed in a reliable and efficient manner in the sedated standing bovine. C1 [Chiesa, O. Alberto] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biol,Lab Cardiovasc & Intervent Therapeut, Laurel, MD 20708 USA. [von Bredow, Jurgen; Li, Hui; Smith, Michelle] US FDA, Ctr Vet Med, Res Off, Div Residue Chem, Laurel, MD 20708 USA. RP Chiesa, OA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Biol,Lab Cardiovasc & Intervent Therapeut, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM oscar.chiesa@fda.gov NR 38 TC 7 Z9 7 U1 0 U2 0 PU CANADIAN VET MED ASSOC PI OTTAWA PA 339 BOOTH ST ATTN: KIMBERLY ALLEN-MCGILL, OTTAWA, ONTARIO K1R 7K1, CANADA SN 0830-9000 J9 CAN J VET RES JI Can. J. Vet. Res.-Rev. Can. Rech. Vet. PD JAN PY 2009 VL 73 IS 1 BP 42 EP 48 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA 401BH UT WOS:000262912600008 PM 19337395 ER PT J AU Martin, PJ Przepiorka, D Lee, SJ AF Martin, Paul J. Przepiorka, Donna Lee, Stephanie J. BE Vogelsang, GB Pavletic, SZ TI DESIGN OF CLINICAL TRIALS TESTING TREATMENT FOR CHRONIC GRAFT VERSUS HOST DISEASE SO CHRONIC GRAFT VERSUS HOST DISEASE: INTERDISCIPLINARY MANAGEMENT LA English DT Article; Book Chapter ID CONSENSUS DEVELOPMENT PROJECT; WORKING GROUP-REPORT; CRITERIA; THALIDOMIDE; DIAGNOSIS; THERAPY C1 [Martin, Paul J.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Dept Med, Seattle, WA 98195 USA. [Martin, Paul J.] Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Dept Pediat, Seattle, WA 98195 USA. [Przepiorka, Donna] US FDA, Ctr Biol, Rockville, MD 20857 USA. RP Martin, PJ (reprint author), Univ Washington, Fred Hutchinson Canc Res Ctr, Div Clin Res, Dept Med, Seattle, WA 98195 USA. NR 16 TC 0 Z9 0 U1 0 U2 0 PU CAMBRIDGE UNIV PRESS PI CAMBRIDGE PA THE PITT BUILDING, TRUMPINGTON ST, CAMBRIDGE CB2 1RP, CAMBS, ENGLAND BN 978-0-521-88423-5 PY 2009 BP 351 EP 359 DI 10.1017/CBO9780511576751.032 D2 10.1017/CBO9780511576751 PG 9 WC Transplantation SC Transplantation GA BDG89 UT WOS:000313180800032 ER PT S AU Jin, K Stockbridge, N AF Jin, K. Stockbridge, N. BE Murray, A TI Smoothing and Discriminating MAP Data SO CINC: 2009 36TH ANNUAL COMPUTERS IN CARDIOLOGY CONFERENCE SE Computers in Cardiology Series LA English DT Proceedings Paper CT 36th Annual Computers in Cardiology Conference (CinC 2009) CY SEP 13-16, 2009 CL Pk City, UT SP EMB, IEEE, Medtron, CareFus, Biosense Webster, Mortara Instrument, Vitamin Water, Coca-Cola, IBM, GE Healthcare, Forest Pharmaceut Inc, St Jude Med, IOP Publishing, Zoll, Philips Healthcare, SCI - Univ Utah AB Cubic B-Splines are used to approximate mean ambulatory blood pressure data and the fitted coefficients serve as discretization of the curves. A rank based method is proposed to predict Test Set A. A double cross validation approach is proposed to predict Test Set B. C1 FDA, 10903 New Hampshire Ave,Bldg 21,RM 4622, Silver Spring, MD 20993 USA. [Jin, K.; Stockbridge, N.] US FDA, CDER, White Oak, MD USA. RP Jin, K (reprint author), FDA, 10903 New Hampshire Ave,Bldg 21,RM 4622, Silver Spring, MD 20993 USA. EM kun.jin@fda.hhs.gov NR 3 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 0276-6574 BN 978-1-4244-7281-9 J9 COMPUT CARDIOL PY 2009 BP 633 EP + PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA BPM81 UT WOS:000279344300159 ER PT B AU Joffe, HV Parks, MH AF Joffe, Hylton V. Parks, Mary H. BE Robertson, D Williams, GH TI Regulatory Environment SO CLINICAL AND TRANSLATIONAL SCIENCE: PRINCIPLES OF HUMAN RESEARCH LA English DT Article; Book Chapter C1 [Joffe, Hylton V.] US FDA, Diabet Drug Grp, Div Metab & Endocrinol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Parks, Mary H.] US FDA, Div Metab & Endocrinol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Joffe, HV (reprint author), US FDA, Diabet Drug Grp, Div Metab & Endocrinol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092019-1; 978-0-12-373639-0 PY 2009 BP 401 EP 414 DI 10.1016/B978-0-12-373639-0.00027-3 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA BHL23 UT WOS:000325772400029 ER PT J AU Lim, J Derrick, SC Kolibab, K Yang, AL Porcelli, S Jacobs, WR Morris, SL AF Lim, JaeHyun Derrick, Steven C. Kolibab, Kristopher Yang, Amy Li Porcelli, Steven Jacobs, William R. Morris, Sheldon L. TI Early Pulmonary Cytokine and Chemokine Responses in Mice Immunized with Three Different Vaccines against Mycobacterium tuberculosis Determined by PCR Array SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID T-CELLS; PROTECTIVE IMMUNITY; BCG; INFECTION; VACCINATION; EXPRESSION; IMMUNOLOGY; IL-23; MODEL; IL-17 AB In this study, the early pulmonary cytokine and chemokine responses in mice immunized with either BCG vaccine, a Delta secA2 mutant of Mycobacterium tuberculosis, or a DNA vaccine expressing an ESAT6-antigen 85B fusion protein and then aerogenically challenged with a low dose of M. tuberculosis were evaluated by PCR array. The cellular immune responses at day 10 postchallenge were essentially equivalent in the lungs of mice immunized with either the highly immunogenic BCG vaccine or the Delta secA2 M. tuberculosis mutant strain. Specifically, 12 immune biomolecules (including gamma interferon [IFN-gamma], interleukin-21 [IL-21], IL-27, IL-17f, CXCL9, CXCL10, and CXCL11) were differentially regulated, relative to the levels for naive controls, in the lungs of vaccinated mice at this time point. Although the vaccine-related immune responses evoked in mice immunized with the DNA vaccine were relatively limited at 10 days postinfection, upregulation of IFN-gamma RNA synthesis as well as increased expression levels of CXCL9, CXCL10, and CXCL11 chemokines were detected. C1 [Lim, JaeHyun; Derrick, Steven C.; Kolibab, Kristopher; Yang, Amy Li; Morris, Sheldon L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Jacobs, William R.] Albert Einstein Coll Med, Dept Microbiol & Immunol, Dept Genet, Bronx, NY 10467 USA. [Porcelli, Steven] Albert Einstein Coll Med, Dept Med, Bronx, NY 10467 USA. [Jacobs, William R.] Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10467 USA. RP Morris, SL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. EM sheldon.morris@fda.hhs.gov NR 29 TC 19 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD JAN PY 2009 VL 16 IS 1 BP 122 EP 126 DI 10.1128/CVI.00359-08 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 390IM UT WOS:000262157500016 PM 19038785 ER PT J AU Gubernot, DM Lucey, CT Lee, KC Conley, GB Holness, LG Wise, RP AF Gubernot, Diane M. Lucey, Charles T. Lee, Karen C. Conley, Gilliam B. Holness, Leslie G. Wise, Robert P. TI Babesia Infection through Blood Transfusions: Reports Received by the US Food and Drug Administration, 1997-2007 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID LYME-DISEASE; PARASITEMIA; PREVENTION; RISK AB Background. Human babesiosis is an illness with clinical manifestations that range from asymptomatic to fatal. Although babesiosis is not nationally notifiable, the US incidence appears to be increasing. Babesia infection is a transfusion-transmissable disease. An estimated 70 cases were reported during 1979-2007; most of these cases were reported during the past decade. Methods. We queried the 3 following US Food and Drug Administration safety surveillance systems to assess trends in babesiosis reporting since 1997: fatality reports for blood donors and transfusion recipients, the Adverse Event Reporting System (which includes MedWatch), and the Biological Product Deviations Reporting system. We analyzed fatality reports for time frames, clinical presentations, and patient and donor demographic characteristics. Results. Eight of 9 deaths due to transfusion-transmitted babesiosis that were reported since 1997 occurred within the past 3 years (2005-2007). Four implicated donors and 5 patients lived in areas where Babesia infection is not endemic. Increasing numbers of Biological Product Deviations Reports were submitted to the US Food and Drug Administration over the past decade; the Adverse Event Reporting System received no reports. Conclusions. After nearly a decade with no reported death due to transfusion-transmitted babesiosis, the US Food and Drug Administration received 8 reports from November 2005 onward. The increased numbers of deaths reported and Biological Product Deviations Reports suggest an increasing incidence of transfusion-transmitted babesiosis. Physicians should consider babesiosis in the differential diagnosis in immunocompromised, febrile patients with a history of recent transfusion, even in areas where Babesia infection is not endemic. Accurate and timely reporting of babesiosis-related donor and transfusion events assists the US Food and Drug Administration in developing appropriate public health-control measures. C1 [Gubernot, Diane M.; Lucey, Charles T.; Holness, Leslie G.] US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20857 USA. [Lee, Karen C.; Wise, Robert P.] US PHS, Rockville, MD USA. [Lee, Karen C.; Wise, Robert P.] Off Biostat & Epidemiol, Rockville, MD USA. [Conley, Gilliam B.] Off Compliance & Biol Qual, Rockville, MD USA. RP Gubernot, DM (reprint author), 1401 Rockville Pike,HFM 394, Rockville, MD 20852 USA. EM diane.gubernot@fda.hhs.gov NR 26 TC 57 Z9 64 U1 1 U2 3 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 JAN PY 2009 VL 48 IS 1 BP 25 EP 30 DI 10.1086/595010 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 381OW UT WOS:000261546800004 PM 19035776 ER PT J AU Amur, SG Mummaneni, P Arasappan, D Tong, W Siegel, J Men, A Nallani, S Dawisha, S Frueh, F Burckart, G AF Amur, S. G. Mummaneni, P. Arasappan, D. Tong, W. Siegel, J. Men, A. Nallani, S. Dawisha, S. Frueh, F. Burckart, G. TI GENE EXPRESSION SIGNATURES AND PATHWAYS ASSOCIATED WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): A META-ANALYSIS STUDY. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 18-21, 2009 CL National Harbor, MD SP Amer Soc Clin Pharmacol & Therapeut C1 [Amur, S. G.; Mummaneni, P.; Men, A.; Nallani, S.; Burckart, G.] OCP OTS CDER FDA, Silver Spring, MD USA. [Arasappan, D.] Z Tech Corp, Silver Spring, MD USA. [Tong, W.] NCTR FDA, Silver Spring, MD USA. [Siegel, J.] OND CDER FDA, Silver Spring, MD USA. [Dawisha, S.] OIVD DCTD CDRH, Silver Spring, MD USA. [Frueh, F.] MEDCO, Franklin Lakes, NJ USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2009 VL 85 BP S76 EP S76 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 399RH UT WOS:000262816500243 ER PT J AU Brinker, AD Wu, Y Kaplan, S Mehta, H Mosholder, AD Gelperin, K AF Brinker, A. D. Wu, Y. Kaplan, S. Mehta, H. Mosholder, A. D. Gelperin, K. TI TRENDS IN USE OF MEDICATIONS FOR ATTENTION DEFICIT/HYPERACTIVITY DISORDER BEFORE AND AFTER PUBLIC FDA ADVISORY MEETINGS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 18-21, 2009 CL National Harbor, MD SP Amer Soc Clin Pharmacol & Therapeut C1 [Brinker, A. D.; Wu, Y.; Kaplan, S.; Mehta, H.; Mosholder, A. D.; Gelperin, K.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2009 VL 85 BP S18 EP S18 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 399RH UT WOS:000262816500055 ER PT J AU Fisher, J Knudsen, J Sokol, GH AF Fisher, J. Knudsen, J. Sokol, G. H. TI TERATOGENIC RISK OF TOPIRAMATE USE DURING PREGNANCY SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 18-21, 2009 CL National Harbor, MD SP Amer Soc Clin Pharmacol & Therapeut C1 [Fisher, J.; Knudsen, J.] US FDA, Silver Spring, MD USA. [Sokol, G. H.] Univ S Florida, H Lee Moffitt Canc Ctr, Tampa, FL 33682 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2009 VL 85 BP S68 EP S68 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 399RH UT WOS:000262816500217 ER PT J AU Li, F Lee, P Gobburu, J Tornoe, C AF Li, F. Lee, P. Gobburu, J. Tornoe, C. TI IMPLEMENTATION OF COMPUTER CLUSTER FOR PHARMACOMETRICS ANALYSES AT FDA SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 18-21, 2009 CL National Harbor, MD SP Amer Soc Clin Pharmacol & Therapeut C1 [Li, F.; Lee, P.; Gobburu, J.; Tornoe, C.] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2009 VL 85 BP S26 EP S26 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 399RH UT WOS:000262816500081 ER PT J AU Mummaneni, P Amur, S Frueh, F Burckart, G Huang, S Lesko, LJ AF Mummaneni, P. Amur, S. Frueh, F. Burckart, G. Huang, S. Lesko, L. J. TI GENETICS AND ETHINICITY BASED RECOMMENDATIONS FOR TESTING CYTOCHROME P450POLYMORPHIC ALLELES IN CLINICAL TRIALS. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 18-21, 2009 CL National Harbor, MD SP Amer Soc Clin Pharmacol & Therapeut C1 [Mummaneni, P.; Amur, S.; Burckart, G.; Huang, S.; Lesko, L. J.] US FDA, Silver Spring, MD USA. [Frueh, F.] Medco, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2009 VL 85 BP S78 EP S79 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 399RH UT WOS:000262816500250 ER PT J AU Wagner, JA Vassileva, M Ghosh, S Kochan, J Prince, MJ Schneider, B Velasquez, J Wang, M Wright, E Ennis, M AF Wagner, J. A. Vassileva, M. Ghosh, S. Kochan, J. Prince, M. J. Schneider, B. Velasquez, J. Wang, M. Wright, E. Ennis, M. TI EVALUATION OF THE UTILITY OF ADIPONECTIN AS A BIOMARKER PREDICTIVE OF GLYCEMIC EFFICACY BY POOLING EXISTING CLINICAL TRIAL DATA FROM PREVIOUSLY CONDUCTED STUDIES SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics (ASCPT) CY MAR 18-21, 2009 CL Natl Harbor, MD SP Amer Soc Clin Pharmacol & Therapeut (ASCPT) C1 [Wagner, J. A.] Merck & Co Inc, Rahway, NJ 07065 USA. [Vassileva, M.] Fdn NIH, Bethesda, MD USA. [Ghosh, S.] GlaxoSmithKline, Res Triangle Pk, NC USA. [Kochan, J.] Hoffmann La Roche Inc, Nutley, NJ 07110 USA. [Prince, M. J.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Schneider, B.] US FDA, Rockville, MD 20857 USA. [Velasquez, J.] NIAAA, Bethesda, MD USA. [Wang, M.] Eli Lilly & Co, Indianapolis, IN 46285 USA. [Wright, E.] NIDDK, Bethesda, MD USA. [Ennis, M.] Quintiles, Austin, TX USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2009 VL 85 SU 1 BP S20 EP S20 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 399RH UT WOS:000262816500061 ER PT J AU Wang, D Zhang, S Zhao, H Men, A Parivar, K AF Wang, D. Zhang, S. Zhao, H. Men, A. Parivar, K. TI FIXED DOSING VERSUS BW/BSA-BASED DOSING FOR MONOCLONAL ANTIBODY THERAPEUTICS SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 18-21, 2009 CL National Harbor, MD SP Amer Soc Clin Pharmacol & Therapeut C1 [Wang, D.; Zhang, S.; Parivar, K.] Pfizer, San Diego, CA USA. [Zhao, H.; Men, A.] US FDA, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2009 VL 85 BP S64 EP S64 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 399RH UT WOS:000262816500205 ER PT J AU Zhang, L Vgontzas, A Doddapaneni, S Feibus, KB Fields, E Hertz, S Huang, S Kim, M Lee, D Nallani, SC AF Zhang, L. Vgontzas, A. Doddapaneni, S. Feibus, K. B. Fields, E. Hertz, S. Huang, S. Kim, M. Lee, D. Nallani, S. C. TI NARCOTIC METABOLISM AND POTENCY INFORMATION MAY INDICATE STRATEGIES FOR SAFER USE OF NARCOTICS IN PREGNANT AND LACTATING WOMEN SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 18-21, 2009 CL National Harbor, MD SP Amer Soc Clin Pharmacol & Therapeut C1 [Zhang, L.; Vgontzas, A.; Doddapaneni, S.; Huang, S.; Kim, M.; Lee, D.; Nallani, S. C.] US FDA, Off Clin Pharmacol, Off Translat Sci, CDER, Silver Spring, MD USA. [Feibus, K. B.] US FDA, OND, CDER, Silver Spring, MD USA. [Fields, E.; Hertz, S.] US FDA, DAARP, Off Drug Evaluat 2, ON,CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2009 VL 85 BP S81 EP S81 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 399RH UT WOS:000262816500259 ER PT J AU Zhao, P Ragueneau-Majlessi, I Zhang, L Strong, JM Reynolds, KS Levy, RH Thummel, KE Huang, S AF Zhao, P. Ragueneau-Majlessi, I. Zhang, L. Strong, J. M. Reynolds, K. S. Levy, R. H. Thummel, K. E. Huang, S. TI EVALUATION OF SINGLE DOSE KETOCONAZOLE TO OBTAIN MAXIMAL CYP3A INHIBITION SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 18-21, 2009 CL National Harbor, MD SP Amer Soc Clin Pharmacol & Therapeut C1 [Zhao, P.; Zhang, L.; Strong, J. M.; Reynolds, K. S.; Huang, S.] US FDA, Silver Spring, MD USA. [Ragueneau-Majlessi, I.; Levy, R. H.; Thummel, K. E.] Univ Washington, Seattle, WA 98195 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2009 VL 85 BP S65 EP S65 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 399RH UT WOS:000262816500206 ER PT J AU Zhu, H Wang, Y Garnett, C Gobburu, J AF Zhu, H. Wang, Y. Garnett, C. Gobburu, J. TI CONCENTRATION-QT ANALYSIS IN THE PRESENCE OF PHARMACOKINETIC AND/OR PHARMACODYNAMIC INTERACTION SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 110th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 18-21, 2009 CL National Harbor, MD SP Amer Soc Clin Pharmacol & Therapeut C1 [Zhu, H.; Wang, Y.; Garnett, C.; Gobburu, J.] US FDA, OCP, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD JAN PY 2009 VL 85 BP S31 EP S31 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 399RH UT WOS:000262816500097 ER PT J AU Luo, J Huang, L Hachey, M Tiwari, R AF Luo, Jun Huang, Lan Hachey, Mark Tiwari, Ram TI Adjacency Method for Finding Connected Subsets of a Graph: An Application of Graph Theory to Spatial Statistics SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION LA English DT Article DE Adjacency method; Cluster detection; Connected subset; Edge; Flexible shaped spatial scan statistic; Graph; Spatial scan statistic; Vertex ID RARE DISEASES; CLUSTERS; TESTS AB This article proposes the adjacency method for generating all connected subsets of a graph without generating any disconnected subset. The motivation for the method is an algorithm for finding all candidate clusters of cancer cases in a specified geographic region. Tango and Takahashi (2005) suggested the ergodic method to find all candidate clusters for flexibly shaped spatial scan statistics. The adjacency method is an improvement of the ergodic method. A slight modification of the adjacency method can also be used to determine the connectivity of a graph. A recursive algorithm for finding all connected subsets is proposed in this article. Given a graph with n vertices, the cost of storage of the algorithm is O(n(2)) and the cost of the calculation is bounded by vertical bar Omega vertical bar * O(n(2)), where Omega is the collection of all connected subsets and vertical bar Omega vertical bar is the cardinality of Omega. In some situations, vertical bar Omega vertical bar is far less than 2(n), the number of all subsets of the graph. For example, for a string with length n, vertical bar Omega vertical bar/2(n) = o((1/2 + delta)(n)), where delta > 0. C1 [Luo, Jun] Informat Management Serv Inc, Silver Spring Off, Silver Spring, MD 20904 USA. [Huang, Lan] Natl Canc Inst, Div Canc Control & Populat Sci, Rockville, MD USA. [Tiwari, Ram] FDA, CDER, Silver Spring, MD USA. RP Luo, J (reprint author), Informat Management Serv Inc, Silver Spring Off, 12501 Prosper Dr,Suite 200, Silver Spring, MD 20904 USA. EM luoj@imsweb.com FU National Cancer Institute; NIH FX Most of Ram Tiwari work was done while he was at the National Cancer Institute, NIH. The views expressed in this article do not necessarily represent those of the US Food and Drug Administration, and of the National Cancer Institute. NR 15 TC 1 Z9 1 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0918 J9 COMMUN STAT-SIMUL C JI Commun. Stat.-Simul. Comput. PY 2009 VL 38 IS 5 BP 1136 EP 1151 DI 10.1080/03610910902807854 PG 16 WC Statistics & Probability SC Mathematics GA 423XG UT WOS:000264529500005 ER PT J AU Zhang, ZW AF Zhang, Zhiwei TI Estimating a Marginal Causal Odds Ratio Subject to Confounding SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE Causal inference; Collapsibility; Confounding; Logistic regression; Odds ratio ID PROPENSITY SCORE METHODS; MISSING DATA; INFERENCE; MODELS; BIAS AB Odds ratios are frequently used to describe the relationship between a binary treatment or exposure and a binary outcome. An odds ratio can be interpreted as a causal effect or a measure of association, depending on whether it involves potential outcomes or the actual outcome. An odds ratio can also be characterized as marginal versus conditional, depending on whether it involves conditioning on covariates. This article proposes a method for estimating a marginal causal odds ratio subject to confounding. The proposed method is based on a logistic regression model relating the outcome to the treatment indicator and potential confounders. Simulation results show that the proposed method performs reasonably well in moderate-sized samples and may even offer an efficiency gain over the direct method based on the sample odds ratio in the absence of confounding. The method is illustrated with a real example concerning coronary heart disease. C1 US FDA, Div Biostat, OSB, CDRH, Rockville, MD 20850 USA. RP Zhang, ZW (reprint author), US FDA, Div Biostat, OSB, CDRH, HFZ-550, Rockville, MD 20850 USA. EM zhiwei.zhang@fda.hhs.gov NR 16 TC 5 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2009 VL 38 IS 3 BP 309 EP 321 AR PII 907053386 DI 10.1080/03610920802200076 PG 13 WC Statistics & Probability SC Mathematics GA 386HS UT WOS:000261873800001 ER PT J AU Gallas, BD Bandos, A Samuelson, FW Wagner, RF AF Gallas, Brandon D. Bandos, Andriy Samuelson, Frank W. Wagner, Robert F. TI A Framework for Random-Effects ROC Analysis: Biases with the Bootstrap and Other Variance Estimators SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE Bias; Multi-reader Multi-case (MRMC); Nonparametric AUC; ROC analysis; Three-way bootstrap; Wilcoxon-Mann-Whitney statistic ID OPERATING CHARACTERISTIC ANALYSIS; DORFMAN-BERBAUM-METZ; MRMC METHOD; PROBABILISTIC MODEL; MULTIREADER; VALIDATION; READERS AB In this article, we analyze the three-way bootstrap estimate of the variance of the reader-averaged nonparametric area under the receiver operating characteristic (ROC) curve. The setting for this work is medical imaging, and the experimental design involves sampling from three distributions: a set of normal and diseased cases ( patients), and a set of readers ( doctors). The experiment we consider is fully crossed in that each reader reads each case. A reading generates a score that indicates the reader's level of suspicion that the patient is diseased. The distribution of scores for the normal patients is compared to the distribution of scores for the diseased patients via an ROC curve, and the area under the ROC curve (AUC) summarizes the reader's diagnostic ability to separate the normal patients from the diseased ones. We find that the bootstrap estimate of the variance of the reader-averaged AUC is biased, and we represent this bias in terms of moments of success outcomes. This representation helps unify and improve several current methods for multi-reader multi-case (MRMC) ROC analysis. C1 [Gallas, Brandon D.; Samuelson, Frank W.; Wagner, Robert F.] NIBIB CDRH, Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. [Bandos, Andriy] Univ Pittsburgh, Dept Biostat, Pittsburgh, PA 15261 USA. RP Gallas, BD (reprint author), NIBIB CDRH, Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. EM brandon.gallas@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620 FU National Institute for Biomedical Imaging and Bioengineering [EB002106, EB001694]; National Institutes of Health; Department of Health and Human Services FX The authors would like to thank Dr. Yulei Jiang for providing us with his high-quality dataset comparing radiologists with and without a computer aid to classify microcalcification clusters. We'd also like to thank the many colleagues at each institution that have contributed their time and expertise in discussions related to this work. This work is supported in part by grants # EB002106 and EB001694 to the University of Pittsburgh from the National Institute for Biomedical Imaging and Bioengineering, National Institutes of Health, Department of Health and Human Services. NR 27 TC 11 Z9 11 U1 0 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0361-0926 EI 1532-415X J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2009 VL 38 IS 15 BP 2586 EP 2603 DI 10.1080/03610920802610084 PG 18 WC Statistics & Probability SC Mathematics GA 485TH UT WOS:000269146700012 ER PT B AU Evancho, GM Tortorelli, S Scott, VN AF Evancho, George M. Tortorelli, Suzanne Scott, Virginia N. BE Sperber, WH Doyle, MP TI Microbiological Spoilage of Canned Foods SO COMPENDIUM OF THE MICROBIOLOGICAL SPOILAGE OF FOODS AND BEVERAGES SE Food Microbiology and Food Safety LA English DT Article; Book Chapter ID MESOPHILIC ANAEROBIC SPOREFORMERS; CLOSTRIDIUM-BOTULINUM; THERMOPHILIC ORGANISMS; TOXIN PRODUCTION; COOLING WATER; TOMATO JUICE; BUTYRICUM; PRODUCTS; SULFIDE; GROWTH C1 [Scott, Virginia N.] US FDA, College Pk, MD 20740 USA. [Tortorelli, Suzanne] Campbell Soup Co, Camden, NJ 08103 USA. RP Evancho, GM (reprint author), 19693 Marimar Court, Lewes, DE 19958 USA. EM george_evancho@verizon.net; suzanne_tortorelli@campbellsoup.com; jennyscott@verizon.net NR 54 TC 2 Z9 2 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-1-4419-0825-4 J9 FOOD MICROBIOL FOOD PY 2009 BP 185 EP 221 DI 10.1007/978-1-4419-0826-1_7 PG 37 WC Food Science & Technology SC Food Science & Technology GA BLU11 UT WOS:000271016100007 ER PT J AU Taylor, SL Gendel, SM Houben, GF Julien, E AF Taylor, Steve L. Gendel, Steven M. Houben, Geert F. Julien, Elizabeth TI The Key Events Dose-Response Framework: A Foundation for Examining Variability in Elicitation Thresholds for Food Allergens SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review DE Low dose dose-response; food allergy; thresholds; minimal eliciting dose; Key Events Dose-Response Framework ID NATURAL-HISTORY; RISK-ASSESSMENT; ADVERSE-REACTIONS; MILK ALLERGY; DOUBLE-BLIND; CHILDREN; MODEL; HYPERSENSITIVITY; ANAPHYLAXIS; REACTIVITY AB Food allergies are caused by immunological reactions in individuals sensitized to normal protein components of foods. For any given sensitized individual, the severity of a reaction is generally assumed to be proportional to the dose of allergenic protein. There is substantial clinical evidence that othresholdo doses exist for the elicitation of an allergic reaction; however, the threshold (i.e., lowest dose that elicits a reaction) varies substantially across the sensitized population. Current approaches to protecting sensitized individuals from exposure to food allergens are highly qualitative (i.e., they rely on food avoidance). The Key Events Dose-Response Framework is an analytical approach for refining understanding of the biological basis of the dose-response. Application of this approach to food allergy provides a foundation for a more rigorous quantitative understanding of variability in allergic response. This study reviews the allergic disease process and the current approaches to identifying thresholds for food allergens. The pathway of key biological events occurring between food intake and allergic response is considered, along with factors that may determine the nature and severity of response to food allergens. Data needs, as well as implications for identifying thresholds, and for characterizing variability in thresholds, are also discussed. C1 [Julien, Elizabeth] ILSI Res Fdn, Washington, DC 20005 USA. [Taylor, Steve L.] Univ Nebraska, Dept Food Sci & Technol, Food Allergy Res & Resource Program, Lincoln, NE 68583 USA. [Gendel, Steven M.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Houben, Geert F.] TNO, NL-3700 AJ Zeist, Netherlands. RP Julien, E (reprint author), ILSI Res Fdn, 1156 Fifteenth St NW,2nd Floor, Washington, DC 20005 USA. EM bjulien@ilsi.org FU ILSI Research Foundation; Health Canada; Ajinomoto; Coca-Cola Company; Groupe Danone; Kellogg Company; Kraft Foods, Inc.; Mars, Inc.; Mead Johnson Nutritionals; Monsanto Company; Nestle; PepsiCo, Inc.; Procter Gamble Company; Syngenta Ltd.; Flavor Extract Manufacturers Association; Grocery Manufacturers Association FX Financial support for this project from the following sources is gratefully acknowledged: ILSI Research Foundation, Health Canada, Ajinomoto, Coca-Cola Company, Groupe Danone, Kellogg Company, Kraft Foods, Inc., Mars, Inc., Mead Johnson Nutritionals, Monsanto Company, Nestle, PepsiCo, Inc., The Procter & Gamble Company, Syngenta Ltd., Flavor Extract Manufacturers Association, and Grocery Manufacturers Association. Assistance from Ms. Julie Fitzpatrick with coordination of the final preparation of these papers is also gratefully acknowledged. NR 50 TC 15 Z9 15 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8398 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2009 VL 49 IS 8 BP 729 EP 739 AR PII 914017328 DI 10.1080/10408390903098707 PG 11 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 485CX UT WOS:000269099500006 PM 19690998 ER PT S AU Donnelly, RP Young, HA Rosenberg, AS AF Donnelly, Raymond P. Young, Howard A. Rosenberg, Amy S. BE Donnelly, RP TI An Overview of Cytokines and Cytokine Antagonists as Therapeutic Agents SO CYTOKINE THERAPIES: NOVEL APPROACHES FOR CLINICAL INDICATIONS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Cytokine Therapies - Novel Approaches for Clinical Indications CY MAR 26-27, 2009 CL New York Acad Sci, New York, NY SP US FDA, BioLegend, Invitrogen, PBL InterferonSource HO New York Acad Sci DE cytokines; inflammation; interferons; interleukins; receptors ID INTERFERON-GAMMA; INTERLEUKIN-10; AUTOIMMUNITY; DISEASES; COMPLEX; ALPHA AB Cytokine-based therapies have the potential to provide novel treatments for cancer, autoimmune diseases, and many types of infectious disease. However, to date, the full clinical potential of cytokines as drugs has been limited by a number of factors. To discuss these limitations and explore ways to overcome them, the FDA partnered with the New York Academy of Sciences in March 2009 to host a two-day forum to discuss more effective ways to harness the clinical potential of cytokines and cytokine antagonists as therapeutic agents. The first day was focused primarily on the use of recombinant cytokines as therapeutic agents for treatment of human diseases. The second day focused largely on the use of cytokine antagonists as therapeutic agents for treatment of human diseases. This issue of the Annals includes more than a dozen papers that summarize much of the information that was presented during this very informative two-day conference. C1 [Donnelly, Raymond P.; Rosenberg, Amy S.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Young, Howard A.] NCI, Expt Immunol Lab, Ctr Canc Res, Frederick, MD 21701 USA. RP Donnelly, RP (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bldg 29A,Room 3B-15,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Raymond.Donnelly@fda.hhs.gov; Raymond.Donnelly@fda.hhs.gov NR 30 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-783-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1182 BP 1 EP 13 DI 10.1111/j.1749-6632.2009.05382.x PG 13 WC Immunology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Immunology; Research & Experimental Medicine; Science & Technology - Other Topics GA BOV08 UT WOS:000277730400001 PM 20074270 ER PT S AU Kozlowski, S Cherney, B Donnelly, RP AF Kozlowski, Steven Cherney, Barry Donnelly, Raymond P. BE Donnelly, RP TI Hurdles and Leaps for Protein Therapeutics Cytokines and Inflammation SO CYTOKINE THERAPIES: NOVEL APPROACHES FOR CLINICAL INDICATIONS SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Cytokine Therapies - Novel Approaches for Clinical Indications CY MAR 26-27, 2009 CL New York Acad Sci, New York, NY SP US FDA, BioLegend, Invitrogen, PBL InterferonSource HO New York Acad Sci DE cytokines; biotechnology; inflammation; pharmaceutical development; manufacturing ID MASTER REGULATOR; INTERLEUKIN-2 THERAPY; PERIODIC SYNDROMES; RECOMBINANT DNA; PHASE-II; CELL; DISEASE; CANCER; BIOLOGY; INTERFERONS AB Cytokines encompass a wide variety of proteins that can trigger many cellular activities. An important set of cytokines modulate inflammatory responses (inflammatory cytokines). These molecules have potent biological activities and have been a major focus for protein drug development. There have been both successes and failures in this area. Initial hurdles, such as limited manufacturing capacity, have now been largely overcome. However clinical development remains a challenge. On the basis of the history of cytokine therapeutics, a number of strategies for future drug development are considered. C1 [Kozlowski, Steven] US FDA, Off Biotechnol Prod, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Cherney, Barry; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Kozlowski, S (reprint author), US FDA, Off Biotechnol Prod, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, White Oak Bldg 21 Room 1510,10903 New Hampshire A, Silver Spring, MD 20993 USA. EM steven.kozlowski@fda.hhs.gov NR 85 TC 3 Z9 3 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 0077-8923 BN 978-1-57331-783-2 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2009 VL 1182 BP 146 EP 160 DI 10.1111/j.1749-6632.2009.05158.x PG 15 WC Immunology; Medicine, Research & Experimental; Multidisciplinary Sciences SC Immunology; Research & Experimental Medicine; Science & Technology - Other Topics GA BOV08 UT WOS:000277730400014 PM 20074283 ER PT S AU Wang, QZ Agrawal, A Wang, NS Pfefer, J AF Wang, Quanzeng Agrawal, Anant Wang, Nam Sun Pfefer, Josh BE Raghavachari, R Liang, R TI Evaluation of a reflectance-based approach for optical property determination in layered tissue SO DESIGN AND QUALITY FOR BIOMEDICAL TECHNOLOGIES II SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Design and Quality for Biomedical Technologies II CY JAN 26, 2009 CL San Jose, CA SP SPIE DE fiberoptic; optical properties; neural network; Monte Carlo; reflectance; multi-layer tissue ID EPITHELIAL TISSUE; SPECTRA; ULTRAVIOLET; MODEL AB In order to elucidate light propagation mechanisms involved in optical spectroscopy devices, the optical properties of layered mucosal tissues at ultraviolet and visible wavelengths are needed. Previous approaches to measuring this data have typically been based on spatially-resolved reflectance. However, these approaches have limitations, some of which are not well understood. Therefore, the objectives of this study were (1) to elucidate the relationship between spatially-resolved reflectance distributions and optical properties in two-layer tissue models and (2) introduce and assess an unconstrained approach to optical property measurement. The first part of this study involved calculating reflectance from two-layer tissue for a wide variety of optical property combinations (mu(a) = 1-22.5, mu(s)' = 5-42.5 cm(-1)) using a Monte Carlo scaling technique. In the second part, a neural network inverse model trained with the aforementioned results was evaluated using simulated reflectance data. This relationship between optical properties and reflectance provides fundamental insights into the strengths, weaknesses and potential limitations of strategies for optical property measurement based on spatially-resolved reflectance. The neural network approach estimated optical property values with a degree of accuracy that depended on the probe geometry (5-, 6-, 10- and 11-fiber probes were simulated). The average error in determination of mu(a) ranged from 15 to 51% and average error for mu(s)' ranged from 8 to 32%. While computationally expensive to develop, neural network models calibrated with simulation data may prove to be a highly effective approach for rapid, unconstrained estimation of the optical properties of two-layer tissues. C1 [Wang, Quanzeng; Agrawal, Anant; Pfefer, Josh] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wang, QZ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM quanzeng_wang@yahoo.com NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7416-2 J9 P SOC PHOTO-OPT INS PY 2009 VL 7170 AR 71700I DI 10.1117/12.813847 PG 11 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BSS50 UT WOS:000285710000012 ER PT J AU Yang, YS Yu, LX AF Yang, Yongsheng Yu, Lawrence X. BE Qiu, Y Chen, Y Zhang, GGZ TI Oral Drug Absorption, Evaluation, and Prediction SO DEVELOPING SOLID ORAL DOSAGE FORMS: PHARMACEUTICAL THEORY AND PRACTICE LA English DT Article; Book Chapter ID MOLECULAR-SURFACE PROPERTIES; BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; SMALL-INTESTINAL ABSORPTION; EPITHELIAL CACO-2 CELLS; LOW-PERMEABILITY DRUGS; IN-VITRO PERMEABILITY; P-GLYCOPROTEIN; HUMAN JEJUNUM; MEMBRANE-PERMEABILITY; TIME DISTRIBUTION C1 [Yang, Yongsheng] US FDA, Silver Spring, MD USA. [Yu, Lawrence X.] US FDA, Rockville, MD 20857 USA. RP Yang, YS (reprint author), US FDA, Silver Spring, MD USA. NR 94 TC 2 Z9 2 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-093272-9 PY 2009 BP 289 EP 308 DI 10.1016/B978-0-444-53242-8.00012-6 PG 20 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCP47 UT WOS:000310963200013 ER PT J AU Jiang, WL Yu, LX AF Jiang, Wenlei Yu, Lawrence X. BE Qiu, Y Chen, Y Zhang, GGZ TI Modern Pharmaceutical Quality Regulations: Question-based Review SO DEVELOPING SOLID ORAL DOSAGE FORMS: PHARMACEUTICAL THEORY AND PRACTICE LA English DT Review; Book Chapter ID SOLID POLYMORPHISM; DRUG APPLICATIONS; COMPATIBILITY C1 [Jiang, Wenlei; Yu, Lawrence X.] US FDA, Rockville, MD 20857 USA. RP Jiang, WL (reprint author), US FDA, Rockville, MD 20857 USA. NR 43 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-093272-9 PY 2009 BP 885 EP 901 DI 10.1016/B978-0-444-53242-8.00038-2 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCP47 UT WOS:000310963200039 ER PT B AU Naum, M Bell, R Mammel, M Zheng, J Brown, EW AF Naum, M. Bell, R. Mammel, M. Zheng, J. Brown, E. W. BE Ovesen, K Matthiesen, U TI DNA Sequencing: Methods, Strategies and Protocols SO DNA: FINGERPRINTING, SEQUENCING AND CHIPS SE DNA Properties and Modifications Functions and Interactions Recombination and Applications LA English DT Article; Book Chapter ID NUCLEOTIDE POLYMORPHISM ANALYSIS; FIELD GEL-ELECTROPHORESIS; ENTERICA SEROVAR TYPHIMURIUM; HIGH-THROUGHPUT; EVOLUTIONARY RELATIONSHIPS; BACTERIAL PATHOGENS; MASS-SPECTROMETRY; SUSPENSION ARRAY; SALMONELLA; IDENTIFICATION AB DNA sequencing is a common and requisite practice for molecular biologists today working in all areas of biology, including microbiology. A number of nucleotide and amino acid-based sequence typing methods are now widely recognized and have transformed the way in which complex evolutionary and epidemiological relationships are elucidated among bacterial strains. Recent advances in DNA sequencing underpin a vast array of bacterial subtyping methods and have become an integral component to traceback investigations of foodborne outbreaks caused by specific bacterial pathogenic strains. Direct DNA sequence-based approaches include multi-locus sequence analysis (MLSA), which simultaneously analyzes the nucleotide substitutions found within concatenated sequence alignments from multiple housekeeping genes. This collective and simultaneous analysis of nascent single nucleotide polymorphisms (SNPs) is effective in differentiating highly homogeneous strain clusters including the closely related strains and serovars of Salmonella enterica. In addition to the extraordinary power this approach offers in molecular evolution/epidemiology, the study of concatenated gene sequences has been instrumental in defining a new paradigm for horizontal gene transfer in the genetic structure of many bacterial species. Facile variations of MLSA are now being developed that rely on the culling of SNP-based targets from relatively uncharted and under-exploited regions of the bacterial genome. As an example, SNPs that reside in the selectively neutral intergenic non-transcribed spacer regions of the genome hold great promise in resolving bacterial strains down to a level of epidemiological relevance. In parallel with these advances in nucleotide sequence analysis, the development of rapid and highly accurate SNP discovery and detection tools is and includes methods such as Pyrosequencing, Luminex probe recognition technology, and single-basepair primer extension assays to name but a few. Together, these successes clearly position DNA sequence-based strategies at the helm for future discoveries in the genetics, evolution, and epidemiology of bacterial strains and species. C1 [Naum, M.; Bell, R.; Zheng, J.; Brown, E. W.] US FDA, Div Microbiol, College Pk, MD USA. [Mammel, M.] US FDA, Div Mol Biol, Laurel, MD USA. RP Naum, M (reprint author), US FDA, Div Microbiol, 5100 Paint Branch Pkwy,HFS-712, College Pk, MD USA. NR 57 TC 0 Z9 0 U1 1 U2 1 PU NOVA SCIENCE PUBLISHERS, INC PI HAUPPAUGE PA 400 OSER AVE, STE 1600, HAUPPAUGE, NY 11788-3635 USA BN 978-1-60741-814-6 J9 DNA PROP MODIF FUNCT PY 2009 BP 55 EP 72 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA BOB49 UT WOS:000276105000003 ER PT J AU Moore, T Smith, A Ye, W Toler, DY Westenberger, BJ Lionberger, R Raw, A Yu, L Buhse, LF AF Moore, Terry Smith, Anjanette Ye, Wei Toler, Duckhee Y. Westenberger, Benjamin J. Lionberger, Robert Raw, Andre Yu, Lawrence Buhse, Lucinda F. TI Generic omeprazole delayed-release capsules: in vitro performance evaluations SO DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY LA English DT Article DE Delayed-release capsules; dissolution; generics; omeprazole; stability AB Background: After the patent on omeprazole delayed-release capsules expired, Food and Drug Administration (FDA) approved several generic omeprazole delayed-release capsule applications. FDA has received some complaints concerning a lack of therapeutic effect of the generic omeprazole delayed-release capsules. Aim: To investigate the quality of five different marketed generic omeprazole delayed-release capsules. Method: The dissolution characteristics of these generic omeprazole delayed-release capsules were determined according to the United States Pharmacopeia (USP). Additional dissolution studies under simulated in vivo physiological conditions were also conducted to determine whether generic omeprazole capsules would perform similarly under these conditions. Results: The experimental data show that all the generic omeprazole delayed-release capsules met the USP standards. The in vitro dissolution of generic drugs is similar to that of the brand omeprazole product. Conclusions: There is no scientific evidence to support the claims that the generic omeprazole delayed-release capsules perform differently from the brand omeprazole product in vitro. C1 [Moore, Terry; Smith, Anjanette; Ye, Wei; Toler, Duckhee Y.; Westenberger, Benjamin J.; Buhse, Lucinda F.] US FDA, Off Testing & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Lionberger, Robert; Raw, Andre; Yu, Lawrence] US FDA, Off Gener Drugs, Rockville, MD 20857 USA. RP Moore, T (reprint author), US FDA, Off Testing & Res, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM terry.moore@fda.hhs.gov NR 3 TC 3 Z9 4 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0363-9045 J9 DRUG DEV IND PHARM JI Drug Dev. Ind. Pharm. PY 2009 VL 35 IS 8 BP 917 EP 921 DI 10.1080/03639040802698802 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 482IO UT WOS:000268879400003 PM 19555236 ER PT J AU Wokovich, A Tyner, K Doub, W Sadrieh, N Buhse, LF AF Wokovich, Anna Tyner, Katherine Doub, William Sadrieh, Nakissa Buhse, Lucinda F. TI Particle size determination of sunscreens formulated with various forms of titanium dioxide SO DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY LA English DT Article DE Laser scanning confocal microscopy; nanoparticle; scanning electron microscopy; titanium dioxide ID RESEARCH STRATEGIES; SAFETY EVALUATION; NANOMATERIALS; NANOPARTICLES AB Background: There has been some apprehension expressed in the scientific literature that nanometersized titanium dioxide (TiO2) and other nanoparticles, if able to penetrate the skin, may cause cytotoxicity. In light of a lack of data regarding dermal penetration of titanium dioxide from sunscreen formulations, the Food and Drug Administration Center for Drug Evaluation and Research initiated a study in collaboration with the National Center for Toxicology Research using minipigs to determine whether nanoscale TiO2 in sunscreen products can penetrate intact skin. Four sunscreen products were manufactured. Method: The particle size distribution of three TiO2 raw materials, a sunscreen blank (no TiO2) and three sunscreen formulations containing uncoated nanometer-sized TiO2, coated nanometer-sized TiO2 or sub-micron TiO2 were analyzed using scanning electron microscopy (SEM), laser scanning confocal microscopy (LSCM), and X-ray diffraction (XRD) to determine whether the formulation process caused a change in the size distributions (e. g., agglomeration or deagglomeration) of the TiO2. Results: SEM and XRD of the formulated sunscreens containing nanometer TiO2 show the TiO2 particles to have the same size as that observed for the raw materials. This suggests that the formulation process did not affect the size or shape of the TiO2 particles. Conclusion: Because of the resolution limit of optical microscopy, nanoparticles could not be accurately sized using LSCM, which allows for detection but not sizing of the particles. LSCM allows observation of dispersion profiles throughout the sample; therefore, LSCM can be used to verify that results observed from SEM experiments are not solely surface effects. C1 [Wokovich, Anna; Doub, William; Buhse, Lucinda F.] US FDA, Ctr Drug Evaluat & Res, St Louis, MO 63101 USA. [Tyner, Katherine; Sadrieh, Nakissa] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Wokovich, A (reprint author), US FDA, Ctr Drug Evaluat & Res, 1114 Market St, St Louis, MO 63101 USA. EM anna.wokovich@fda.hhs.gov NR 32 TC 18 Z9 18 U1 0 U2 13 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 2-4 PARK SQUARE, MILTON PARK, ABINGDON OR14 4RN, OXON, ENGLAND SN 0363-9045 EI 1520-5762 J9 DRUG DEV IND PHARM JI Drug Dev. Ind. Pharm. PY 2009 VL 35 IS 10 BP 1180 EP 1189 DI 10.1080/03639040902838043 PG 10 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 511SM UT WOS:000271187400003 PM 19555241 ER PT J AU Shah, RB Tawakkul, MA Sayeed, VA Khan, MA AF Shah, Rakhi B. Tawakkul, Mobin A. sayeed, Vilayat A. Khan, Mansoor A. TI Complexation between risperidone and amberlite resin by various methods of preparation and binding study SO DRUG DEVELOPMENT AND INDUSTRIAL PHARMACY LA English DT Article DE Amberlite; binding; complexation; freeze drying; granulation; risperidone ID BETA-CYCLODEXTRIN AB Purpose: The purpose of this work was to investigate the effect of preparation methods and the drug-to-resin ratio on complex formation between risperidone and amberlite resin. Methods:The existence of such resin complex may provide taste-masking properties to the dosage forms. It is important to determine when and how the complex forms. Therefore, in this study, the complexes of risperidone and amberlite resin were prepared by granulation, solution, and freeze-drying methods at various drug-to-resin ratios. The physical mixtures of drug-resin were used to compare the results of complexes prepared by granulation, solution, and freeze drying. The complexes were evaluated by various methods of characterization including differential scanning calorimetry, X-ray diffraction, spectroscopy (near infrared, Fourier transform infrared, and Raman), drug release, and binding studies. Results:Complexation between risperidone and amberlite was investigated for various preparation methods. It was found that complexation occurred at lower amounts of amberlite resin (drug-to-resin ratios of 1:1 and 1:2) when solution form of drug was contacted with the resin as in the case of solution and freeze-drying techniques compared with granulation (drug-to-resin ratios of 1:4 and 1:6). Characterization studies such as differential scanning calorimetry, X-ray diffraction, spectroscopic techniques, and drug release studies differentiated complexes from the physical mixtures. Binding studies between them revealed that the binding was linear with solubility of the drug limiting the adsorption capacity. Conclusions: Results of the study highlighted the importance of the preparation methodologies to formulate complexes. When the drug and the resin were simply mixed physically, no complexation occurred. Thus, a careful evaluation of manufacturing procedure would indicate the nature and extent of complexation. C1 [Shah, Rakhi B.; Tawakkul, Mobin A.; Khan, Mansoor A.] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Prod Qual Res,Off Testing Res, Silver Spring, MD 20993 USA. [sayeed, Vilayat A.] US FDA, Off Gener Drugs, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Khan, MA (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Prod Qual Res,Off Testing Res, 10903 New Hampshire Ave,LS Bldg 64, Silver Spring, MD 20993 USA. EM mansoor.khan@fda.hhs.gov NR 12 TC 8 Z9 8 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0363-9045 J9 DRUG DEV IND PHARM JI Drug Dev. Ind. Pharm. PY 2009 VL 35 IS 12 BP 1409 EP 1418 DI 10.3109/03639040902939247 PG 10 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 529YD UT WOS:000272554400001 PM 19929200 ER PT J AU Wang, SJ AF Wang, Sue-Jane TI Bridging Study Versus Prespecified Regions Nested in Global Trials SO DRUG INFORMATION JOURNAL LA English DT Article DE Nested region; Noninferiority; Pharmacogenomics; Subgroup; Two-stage adaptive test ID CLINICAL-TRIALS; STATISTICAL-METHODS AB Ethnic sensitivity to drug treatment has received worldwide attention since the development of the ICH E-5 guidance. The concept of a bridging study was first introduced in the 1990s. The informativeness of statistical inference from small bridging clinical trials with a study size as small as 40 patients is often questionable. In addition, statistical metrics for evaluating the consistency of region-specific treatment effects to global treatment effects have been controversial. Since 1998, the evolution of the approaches to ethnic sensitivity of a drug effect has ranged from criteria to accept foreign clinical data to Partnership in harmonization for global drug development. We consider and compare an indirect method and a direct method to evaluate the treatment effect in a bridging study by borrowing the strength of effect observed in the foreign trial. When a multiregional clinical trial is the drug development approach, we consider a prospectively planned evaluation of global treatment effect without sacrificing the opportunity to also evaluate a prespecified region-specific treatment effect that has a reasonable number of patients and under the same common protocol. We discuss the similarities and the differences between the bridging study problem and the noninferiority study problem. Concerns with extrapolating the results of the study to other regions are raised in regard to the bridging approach that prompts consideration of streamlining clinical trials. When the intrinsic versus extrinsic factors may not be well understood, one approach to addressing heterogeneity issues is a two-stage adaptive test that not only builds in an additional region-specific treatment effect hypothesis, but also addresses potential ethnic sensitivity to overall multiregional treatment effects. The two-stage adaptive test provides flexibility to assess variance using the blinded data at the late stage of the trial, and thus has the potential to withdraw the region-specific hypothesis due to large variability. in the clinical endpoint, eliminating an uninformative region-specific effect assessment. C1 US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, HFD-700,WO 21,Mailstop Room 3562,10903 New Hampshi, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov FU Center for Drug Evaluation and Research, US Food and Drug Administration [02-06, 04-06, 05-2, 05-14, 08-48] FX We thank Dr. Herng-Der Chern of the Center for Drug Evaluation, Taiwan, for the kind invitation, and thank Dr. H. M. James Hung and Dr. Robert O'Neill of the US FDA for insightful comments. The research work was supported by RSR funds #02-06, #04-06, #05-2, #05-14, and #08-48 awarded by the Center for Drug Evaluation and Research, US Food and Drug Administration. NR 17 TC 7 Z9 7 U1 0 U2 0 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2009 VL 43 IS 1 BP 27 EP 34 PG 8 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 392ZI UT WOS:000262340300006 ER PT J AU van der Loan, JW Forster, R Ledwith, B Gruber, M Gould, S Segal, L Penninks, A AF van der Laan, Jan Willem Forster, Roy Ledwith, Brian Gruber, Marion Gould, Sarah Segal, Lawrence Penninks, Andre TI Nonclinical Testing of Vaccines: Report From a Workshop SO DRUG INFORMATION JOURNAL LA English DT Article DE Vaccines; Nonclinical evaluation; Safety testing; Developmental and reproductive toxicology; Adjuvants; DNA vaccines; Therapeutic vaccines ID RESPONSIVENESS; CELL AB Vaccine research and development is a heterogeneous and intensely active area, encompassing the development of many different kinds of novel preventive and therapeutic vaccines (eg, against infectious, allergic, and autoimmune diseases, cancer, etc). Included in this is the development of different types of vaccines (eg, DNA vaccines, novel routes of administration, novel adjuvants, and immune system modulation). This poses challenges regarding approaches to preclinical evaluation of these products. Published regulatory guidance has not always kept up with scientific advances and innovation in this area and, at the same time, many vaccine developers are interested in better understanding and meeting regulatory expectations. It was in this context that in June 2007 a workshop was organized and held in Amsterdam (DIA International Workshop on Nonclinical Testing of Vaccines) to discuss the nonclinical aspects of vaccine development. This article provides a short historical overview of preclinical testing of vaccines and reviews and summarizes the discussions held during the June 2007 meeting. C1 [van der Laan, Jan Willem] Natl Inst Publ Hlth & Environm, Ctr Biol Med & Med Technol, NL-3720 BA Bilthoven, Netherlands. [Ledwith, Brian] Merck Res Labs, West Point, PA USA. [Gruber, Marion] US FDA, Rockville, MD 20857 USA. [Segal, Lawrence] GSK Biologicals, Wavre, Belgium. [Penninks, Andre] TNO Pharma, Zeist, Netherlands. RP van der Loan, JW (reprint author), Natl Inst Publ Hlth & Environm, Ctr Biol Med & Med Technol, POB 1, NL-3720 BA Bilthoven, Netherlands. EM jan-willem.van.der.laan@rivm.nl NR 14 TC 2 Z9 2 U1 0 U2 1 PU DRUG INFORMATION ASSOC PI HORSHAM PA 800 ENTERPRISE ROAD, SUITE 200, HORSHAM, PA 19044-3595 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PY 2009 VL 43 IS 1 BP 97 EP 107 PG 11 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 392ZI UT WOS:000262340300015 ER PT B AU Fang, H Perkins, R Shi, LM Sheehan, DM Tong, WD AF Fang, Hong Perkins, Roger Shi, Leming Sheehan, Daniel M. Tong, Weida BE Devillers, J TI The US Food and Drug Administration's (FDA) Endocrine Disruptor Knowledge Base (EDKB) Lessons Learned in QSAR Modeling and Applications SO ENDOCRINE DISRUPTION MODELING SE QSAR in Environmental and Health Sciences LA English DT Article; Book Chapter DE Applicability domain; Chance correlation; Comparative molecular field analysis (CoMFA); Decision Forest; Endocrine Disruptor Knowledge Base (EDKB); EDKB datasets; EDKB Web database; Four-phase approach; Model validation; Structure-Activity Relationship/Quantitative Structure-Activity Relationship (SAR/QSAR) ID ESTROGEN-RECEPTOR-BINDING; LARGE DIVERSE SET; STRUCTURE-PROPERTY RELATIONSHIP; FIELD ANALYSIS COMFA; POLYCHLORINATED HYDROXYBIPHENYLS; ENVIRONMENTAL ESTROGENS; VARIABLE SELECTION; ANDROGEN RECEPTOR; RISK-ASSESSMENT; BETA SUBTYPES AB Considerable scientific, regulatory, and popular press attention has been devoted to the endocrine disrupting chemicals (EDCs). A larger number of potential estrogenic EDCs are associated with products regulated by the Food and Drug Administration (FDA), including plastics used in food packaging, phytoestrogens, food additives, pharmaceuticals, and cosmetics. Given the huge number of chemicals, many commercially important, and the expense of testing, Structure-Activity Relationship/Quantitative Structure-Activity Relationship (SAR/QSAR) has been considered to be an important priority setting strategy for subsequent experimentation. At the U.S. FDA's National Center for Toxicological Research (NCTR), we conducted the Endocrine Disruptor Knowledge Base (EDKB) project, of which SAR/QSARs is a major component. We developed predictive models for estrogen and androgen receptor binding. The strengths and weaknesses of various QSAR methods were assessed to select those most appropriate for regulatory priority setting. This chapter, rather than presenting the work and results of the EDKB program in an exhaustive manner, selectively discusses salient concepts, issues, and challenges, endeavoring to achieve a tutorial outcome. In particular, concepts such as designing training sets, living models, use of QSARs in a regulatory context, predictive model validation, QSAR applicability domain, and prediction confidence estimates are among topics the authors have chosen to highlight. The concepts are presented and discussed using EDKB program results to provide qualitative and quantitative illustrations and examples. We believe the experience and lessons learned in the EDKB program will prove valuable to practitioners of QSAR should they endeavor to extend predictive systems to real-world regulatory implementations. C1 [Fang, Hong; Perkins, Roger] US FDA, Natl Ctr Toxicol Res, Z Tech Corp, Jefferson, AR 72079 USA. [Shi, Leming; Sheehan, Daniel M.; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Fang, H (reprint author), US FDA, Natl Ctr Toxicol Res, Z Tech Corp, Jefferson, AR 72079 USA. NR 74 TC 0 Z9 0 U1 0 U2 2 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4200-7635-6 J9 QSAR ENVIRON HEALTH PY 2009 BP 143 EP 171 D2 10.1201/9781420076363 PG 29 WC Toxicology SC Toxicology GA BKB80 UT WOS:000267704800006 ER PT B AU Beger, RD Buzatu, DA Wilkes, JG AF Beger, Richard D. Buzatu, Dan A. Wilkes, Jon G. BE Devillers, J TI Quantitative Spectrometric Data-Activity Relationships (QSDAR) Models of Endocrine Disruptor Binding Activities SO ENDOCRINE DISRUPTION MODELING SE QSAR in Environmental and Health Sciences LA English DT Article; Book Chapter DE Comparative spectral analysis (CoSA); Comparative structural connectivity spectral analysis (CoSCoSA); Estrogen receptor ID NUCLEAR-MAGNETIC-RESONANCE; AUTOMATED STRUCTURE EVALUATION; ARYL-HYDROCARBON RECEPTOR; ANALYSIS COSCOSA MODELS; FIELD ANALYSIS COMFA; LARGE DIVERSE SET; ESTROGEN-RECEPTOR; C-13 NMR; POLYCHLORINATED DIBENZODIOXINS; ENVIRONMENTAL CHEMICALS AB This chapter covers a strategy for model building known as Spectrometric Data-Activity Relationships (SDARs). SDAR models are based on the correlation between the spectral and activity leg of the triangular structure-spectra-activity relationship, whereas traditional three-dimensional Quantitative Structure-Activity Relationship (3D-QSAR) models are based on the structure-activity relationship. This chapter covers one-dimensional (1D) comparative spectral analysis (CoSA) and two-dimensional (2D) comparative structural connectivity spectral analysis (CoSCoSA) modeling methods for endocrine disruptors. A qualitative ID CoSA model segregated 108 compounds into 20 strong, 15 medium, and 73 weak relative binding affinity (RBA) classifications to the estrogen receptor, based on C-13 NMR (nuclear magnetic resonance) data alone and gave a leave-one-out (LOO) cross-validation of 75.0%. A CoSA model, based on a composite of C-13 NMR and electron ionization mass spectra (EI MS) data, gave a LOO cross-validation of 82.4%. Most of the compounds classified by the SDAR models incorrectly were between those exhibiting weak and medium RBAs. A quantitative 2D CoSCoSA model of 130 diverse compounds binding to the estrogen receptor employed 16 bins selected from the C-13-C-13 COSY spectral data and had an r(2) of 0.827 and a leave-13-out cross-validation average (q(13)(2)) of 0.78. Another CoSCoSA model of estrogen receptor binding that used 15 bins plus one additional distance-related 3D constraint had an r(2) of 0.833 and an average q(13)(2) of 0.78. CoSCoSA modeling is based on chemical shifts and electrostostatic properties like that used in QSAR models along with added structural atom-to-atom distance information in order to produce a more powerful modeling method. Our results show that CoSA and CoSCoSA models can be used to build computationally rugged, objective, and predictive models of endocrine disruptor activity. C1 [Beger, Richard D.; Buzatu, Dan A.; Wilkes, Jon G.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. NR 51 TC 0 Z9 0 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-1-4200-7635-6 J9 QSAR ENVIRON HEALTH PY 2009 BP 235 EP 258 D2 10.1201/9781420076363 PG 24 WC Toxicology SC Toxicology GA BKB80 UT WOS:000267704800009 ER PT J AU Joffe, HV Emerson, CH Braverman, LE AF Joffe, Hylton V. Emerson, Charles H. Braverman, Lewis E. TI Dr. Robert David ("Bob") Utiger, 1931-2008 In Memoriam SO ENDOCRINE PRACTICE LA English DT Biographical-Item C1 [Joffe, Hylton V.] US FDA, Div Metab & Endocrinol Prod, Rockville, MD 20857 USA. [Emerson, Charles H.] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. [Braverman, Lewis E.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Joffe, HV (reprint author), US FDA, Div Metab & Endocrinol Prod, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC CLIN ENDOCRINOL PI JACKSONVILLE PA 1000 RIVERSIDE AVE, STE 205, JACKSONVILLE, FL 32204 USA SN 1530-891X J9 ENDOCR PRACT JI Endocr. Pract. PD JAN-FEB PY 2009 VL 15 IS 1 BP 83 EP 84 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 437NO UT WOS:000265494400019 ER PT J AU Schoeb, TR McConnell, EE Juliana, MM Davis, JK Davidson, MK Lindsey, JR AF Schoeb, Trenton R. McConnell, Ernest E. Juliana, M. Margaret Davis, Jerry K. Davidson, Maureen K. Lindsey, J. Russell TI Mycoplasma pulmonis and Lymphoma SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Letter ID SPRAGUE-DAWLEY RATS; RESPIRATORY MYCOPLASMOSIS; SPONTANEOUS TUMORS; NEOPLASMS; ASPARTAME C1 [Schoeb, Trenton R.; Juliana, M. Margaret] Univ Alabama, Dept Genet, Birmingham, AL USA. [McConnell, Ernest E.] ToxPath Inc, Raleigh, NC USA. [Davis, Jerry K.] Purdue Univ, Dept Comparat Pathobiol, W Lafayette, IN 47907 USA. [Davidson, Maureen K.] US FDA, Silver Spring, MD USA. RP Schoeb, TR (reprint author), Univ Alabama, Dept Genet, Birmingham, AL USA. NR 27 TC 4 Z9 4 U1 1 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 JAN PY 2009 VL 50 IS 1 BP 1 EP 3 DI 10.1002/em.20465 PG 3 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 396AO UT WOS:000262564800001 PM 19107899 ER PT J AU Sutherland, JB Heinze, TM Pearce, MG Deck, J Williams, AJ Freeman, JP AF Sutherland, John B. Heinze, Thomas M. Pearce, Mason G. Deck, Joanna Williams, Anna J. Freeman, James P. TI BIOTRANSFORMATION OF ACRIDINE BY MYCOBACTERIUM VANBAALENII SO ENVIRONMENTAL TOXICOLOGY AND CHEMISTRY LA English DT Article DE Acridine; Azaarenes; Biotransformation; Mycobacterium vanbaalenii ID AZA-ARENES; DEGRADATION; METABOLISM; PHENANTHRENE; AZAARENES; TRANSFORMATION; ANTHRACENE; TOXICITY; PYR-1; CYTOCHROME-P450 AB Cultures of Mycobacterium vanbaalenii strain PYR-1 in a liquid medium were exposed to the toxic environmental contaminant acridine (260 mu M). After incubation for 7 d, the cultures were extracted with ethyl acetate. Metabolites were purified using high-performance liquid chromatography and analyzed by mass spectrometry and (1)H nuclear magnetic resonance spectroscopy. Four metabolites, 9,10-dihydroacridine, 4-hydroxyacridine, acridine cis-1,2-dihydrodiol, and acridin-9(10H)-one, were identified. C1 [Sutherland, John B.; Pearce, Mason G.; Deck, Joanna; Williams, Anna J.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Heinze, Thomas M.; Freeman, James P.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov FU Summer Student Research Program at the National Center; U.S. Department of Energy; U.S. Food and Drug Administration FX We thank C.E. Cerniglia. The present study was supported in part by the appointment of M.G. Pearce to the Summer Student Research Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 35 TC 3 Z9 3 U1 0 U2 4 PU SETAC PRESS PI PENSACOLA PA 1010 N 12TH AVE, PENSACOLA, FL 32501-3367 USA SN 0730-7268 J9 ENVIRON TOXICOL CHEM JI Environ. Toxicol. Chem. PD JAN PY 2009 VL 28 IS 1 BP 61 EP 64 DI 10.1897/08-206.1 PG 4 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA 393UU UT WOS:000262399700008 PM 18717621 ER PT J AU Fink, DW Bauer, SR AF Fink, Donald W. Bauer, Steven R. BE Lanza, R Gearhart, J Hogan, B Melton, D Pedersen, R Thomas, ED Thomson, J Wilmut, I TI Stem Cell-based Therapies: Food and Drug Administration Product and Pre-Clinical Regulatory Considerations SO ESSENTIALS OF STEM CELL BIOLOGY, 2ND EDITION LA English DT Article; Book Chapter AB The expectation that cellular biologic therapies either consisting of or derived from embryonic, fetal or adult stem cells (stem cell-based products) will provide effective treatments for a variety of current unmet medical requiring replacement, restoration, repair, or regeneration of damaged or diseased tissues and organ systems continues to drive expanding research efforts. Previously limited primarily to the domain of stem cells isolated from bone marrow or peripheral blood used for reconstitution of the hematopoietic and lymphopoietic systems following myeloablative and immunosuppressive treatments, the phenotypes, anatomic sources and potential clinical indications for stem-cell based products has expanded considerably in recent years. Beyond the promise of direct therapeutic efficacy achieved through seeding and repopulating or promulgation of bystander effects that provide trophic support of endogenous cells in areas ravaged by trauma, stem cells are projected to serve as biologic vehicles that may be engineered to deliver functional genes and gene products to discrete target sites where degenerative damage and disease is the consequence of genetic anomalies. Moreover, there is growing recognition that tissue-specific in vitro differentiation of stem cells could result in generation of important new model systems suited for investigating the underlying biological basis of disease as well as provide critical testing paradigms to screen potential lead candidate pharmaceuticals for toxicological safety and putative therapeutic efficacy. The scientific underpinnings necessary to support initiation of clinical safety trials in humans involving stem cell-based products have been buttressed by important research findings generated over the past several years. Sustaining ongoing science-driven efforts to identify and critically assess issues pertaining to stem cell safety is key to achieving the ultimate goal of producing novel cellular products that are both safe and effective. The challenge of drawing upon the spectrum of scientific evidence available to assess and guage the safety of biologics produced from stem cells is the responsibility of the Center for Biologics Evaluation and Research (CBER) within the Food and Drug Administration (FDA). Detailed information pertaining to the safety and efficacy of investigational stem cell-based products is reviewed by staff within the Office of Cellular, Tissue, and Gene C1 [Fink, Donald W.] US FDA, Cell Therapy Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Rockville, MD 20857 USA. [Bauer, Steven R.] US FDA, Lab Stem Cell Biol, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Rockville, MD 20857 USA. RP Fink, DW (reprint author), US FDA, Cell Therapy Branch, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eva, Rockville, MD 20857 USA. OI Bauer, Steven/0000-0003-2831-846X NR 14 TC 4 Z9 4 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 978-0-08-088497-4 PY 2009 BP 619 EP 630 DI 10.1016/B978-0-12-374729-7.00068-8 PG 12 WC Cell & Tissue Engineering; Cell Biology SC Cell Biology GA BCR48 UT WOS:000311099200073 ER PT B AU Badano, A Sharma, D Guarnieri, G Ramponi, G Albani, L AF Badano, Aldo Sharma, Diksha Guarnieri, Gabriele Ramponi, Giovanni Albani, Luigi GP GALAAD EDIZONI TI Effect of case variability on the measurement of reader performance when comparing medical display technologies: application to the study of high-luminance-range displays SO EURODISPLAY 2009 LA English DT Proceedings Paper CT 29th International Display Research Conference (EURODISPLAY-2009) CY SEP 14-17, 2009 CL Univ Romw, Rome, ITALY SP Soc Informat Display, Mid Europe Chapter, Consiglio Nazl Ricer, Univ Roma, HOLOEYE, NOKIA HO Univ Romw ID CLUSTERED LUMPY BACKGROUNDS; TEXTURE SYNTHESIS; ALGORITHM AB We studied the effect of case variability on the measured reader performance for a high-luminance-range (HLR) display device based on dual-layer LCD technology. The reader studies consisted of two-alternative-forced-choice experiments using a database of 532 images of synthetic clustered lumpy backgrounds and a Gaussian signal. In one experiment, the readers were asked to repeat three times the experiment using the same sorting of images that resulted in identical image pairs and identical selection of the signal-present and signal-absent images. In the second experiment, we let the selection of image pairs to be random. We analyze the image sets using the difference in mean gray level in a ROI positioned at the center of the image (where the signal is to be found) between the image pairs. We round that in addition to the well known, intra-reader variability, the selection of cases has a significant effect on performance measurements for a HLR medical display. C1 [Badano, Aldo; Sharma, Diksha] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Badano, A (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave Bldg 62,Room 3116, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov NR 8 TC 0 Z9 0 U1 0 U2 1 PU GALAAD EDIZIONI PI GIULIANOVA PA VIA MARCOZZI, 4, CASELLA POSTALE 60, GIULIANOVA, TERAMO 64021, ITALY PY 2009 BP 54 EP 57 PG 4 WC Materials Science, Multidisciplinary; Optics; Physics, Applied SC Materials Science; Optics; Physics GA BQR67 UT WOS:000281650300010 ER PT J AU Kanungo, J AF Kanungo, J. TI Gradual Loss of DNA-PK Activity from the Cytoplasm Is Coincident with the Nuclear Translocation of Its Activator Ku during Early Development of Xenopus laevis SO FOLIA BIOLOGICA LA English DT Article DE Ku; DNA-PK; gastrulation; Xenopus ID DEPENDENT PROTEIN-KINASE; STRAND BREAK REPAIR; PHOSPHORYLATION ACTIVITY; AUTOANTIGEN KU; CELLS; DIFFERENTIATION; ARBACIA; GENE; RECOMBINATION; OOCYTES AB DNA-dependent protein kinase is a serine/threonine kinase consisting of a catalytic subunit, p460, and a regulatory subunit called Ku (p80/p70). DNA-dependent protein kinase plays a role in transcription, non-homologous recombination, and DNA repair. Previous data have shown the presence of DNA-dependent protein kinase in Xenopus oocytes and changes in its activity during vitellogenesis. Metabolic labelling studies have shown that the increased enzyme activity in vitellogenic oocytes correlates with increased levels of Ku protein, and compared to the pre- and early-vitellogenic oocytes, vitellogenic and post-vitellogenic oocytes show an increased level of DNA-dependent protein kinase activity. Whether DNA-dependent protein kinase activity is altered during early embryogenesis in Xenopus is not known. The present study demonstrates that DNA-dependent protein kinase activity is gradually lost from the cytoplasm in the early embryonic cells of blastulae and gastrulae. The gradual loss of DNA-dependent protein kinase activity during post-fertilization early embryogenesis in Xenopus is consistent with the reports on Arbacia punctulata. Immunohistochemistry of the oocytes at various stages and early embryos (gastrulae) shows that Ku70, a regulatory subunit of DNA-dependent protein kinase, is present both in the cytoplasm and nucleus in the pre-vitellogenic oocytes, full-grown post-vitellogenic oocytes and in the gastrula cells. However, Ku70 appears to accumulate in higher concentrations in the nuclei of gastrula cells. These results suggest that gradual loss of DNA-dependent protein kinase activity from the cytoplasm of the early embryos could be the consequence of Ku translocating to the nuclei that may be necessary for post-zygotic transcription followed by cellular differentiation. C1 [Kanungo, J.] Med Coll Georgia, Inst Mol Med & Genet, Augusta, GA 30912 USA. RP Kanungo, J (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd,Bldg 53D,Rm 3020, Jefferson, AR 72079 USA. EM jyo-tshnabala.kanungo@fda.hhs.gov FU Mason Trust FX This work was supported by funding from the Mason Trust. NR 25 TC 1 Z9 1 U1 0 U2 0 PU CHARLES UNIV PRAGUE, FIRST FACULTY MEDICINE PI PRAGUE 6 PA FLEMINGOVO NAM. 2, PRAGUE 6 166 37, CZECH REPUBLIC SN 0015-5500 J9 FOLIA BIOL-PRAGUE JI Folia Biol.-Prague PY 2009 VL 55 IS 6 BP 218 EP 223 PG 6 WC Biochemistry & Molecular Biology; Biology; Oncology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Oncology; Cell Biology GA 549HX UT WOS:000274039700003 PM 20163770 ER PT J AU Iha, MH Trucksess, MW Tournas, VH AF Iha, M. H. Trucksess, M. W. Tournas, V. H. TI Effect of processing on ochratoxin A content in dried beans SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article DE processing HPLC; immunoaffinity columns; mycotoxins; ochratoxin A; beans ID PHASEOLUS-VULGARIS L.; CONTAMINATION; MYCOFLORA; CROATIA; FRUITS; GRAPES; WHEAT; WINE; RATS AB Dried pink beans naturally contaminated with ochratoxin A (OTA) and dried carioca beans artificially contaminated with OTA by inoculation with Aspergillus ochraceus (ATCC 22947) were tested for ochratoxin A levels as follows: dried beans were washed with water for 2, 60 or 120 min, soaked in water for 60, 120 min or 10 h, and cooked for 60 or 120 min. At each step, test water and beans were separated. Test water, raw beans and cooked beans were analyzed for OTA. The amount of OTA partitioned into water and in residual beans was determined by methanol-sodium bicarbonate extraction, buffer dilution, immunoaffinity column cleanup, liquid chromatographic separation and fluorescence detection. The results demonstrated that the distribution of OTA in processing water and beans depends on the method of preparation. All treatments (washing, soaking and cooking) when applied individually reduced the amounts of OTA retained in bean flour and whole beans. Higher amounts of OTA remained in whole beans than in bean flour after removing the processing water. The combination of the three treatments eliminated about 50% of the toxin from whole beans. This study provides evidence that discarding the washing, soaking and cooking water leads to a significant reduction in OTA contamination in dried beans. C1 [Iha, M. H.] Inst Adolfo Lutz Registro, Lab Ribeirao Preto, BR-14085410 Ribeirao Preto, Brazil. [Trucksess, M. W.; Tournas, V. H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Iha, MH (reprint author), Inst Adolfo Lutz Registro, Lab Ribeirao Preto, BR-14085410 Ribeirao Preto, Brazil. EM mhiha@ial.sp.gov.br FU Oak Ridge Institute for Science and Education FX This project was supported in part by the appointment of MH Iha to the Research Participation Program at the Center for Food Safety and Applied Nutrition administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and US Food and Drug Administration. The equipment used in part of this project was provided by Fundacao de Amparo a Pesquisa do Estado de Sao Paulo. NR 20 TC 4 Z9 4 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PY 2009 VL 26 IS 10 BP 1389 EP 1395 AR PII 914031237 DI 10.1080/02652030903013286 PG 7 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 492WQ UT WOS:000269693700007 PM 19693718 ER PT J AU Ackerman, LK Noonan, GO Begley, TH AF Ackerman, L. K. Noonan, G. O. Begley, T. H. TI Assessing direct analysis in real-time-mass spectrometry (DART-MS) for the rapid identification of additives in food packaging SO FOOD ADDITIVES AND CONTAMINANTS PART A-CHEMISTRY ANALYSIS CONTROL EXPOSURE & RISK ASSESSMENT LA English DT Article; Proceedings Paper CT 4th International Symposium on Food Packaging CY NOV 19-21, 2008 CL Prague, CZECH REPUBLIC SP Int Life Sci Inst, European Branch DE in-house validation; screening assays; food-contact materials; packaging additives; paper; plastics ID POLYMER ADDITIVES; LASER-DESORPTION; INDUCED DISSOCIATION; IONIZATION; EXTRACTION; SURFACE; ION; CHROMATOGRAPHY; POLYSTYRENE; MIGRATION AB The ambient ionization technique direct analysis in real time (DART) was characterized and evaluated for the screening of food packaging for the presence of packaging additives using a benchtop mass spectrometer (MS). Approximate optimum conditions were determined for 13 common food-packaging additives, including plasticizers, anti-oxidants, colorants, grease-proofers, and ultraviolet light stabilizers. Method sensitivity and linearity were evaluated using solutions and characterized polymer samples. Additionally, the response of a model additive (di-ethyl-hexyl-phthalate) was examined across a range of sample positions, DART, and MS conditions (temperature, voltage and helium flow). Under optimal conditions, molecular ion (M+H+) was the major ion for most additives. Additive responses were highly sensitive to sample and DART source orientation, as well as to DART flow rates, temperatures, and MS inlet voltages, respectively. DART-MS response was neither consistently linear nor quantitative in this setting, and sensitivity varied by additive. All additives studied were rapidly identified in multiple food-packaging materials by DART-MS/MS, suggesting this technique can be used to screen food packaging rapidly. However, method sensitivity and quantitation requires further study and improvement. C1 [Ackerman, L. K.; Noonan, G. O.; Begley, T. H.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Ackerman, LK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM Luke.Ackerman@fda.hhs.gov RI Ackerman, Luke/E-4597-2011 OI Ackerman, Luke/0000-0001-6626-3039 NR 30 TC 47 Z9 51 U1 3 U2 53 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM A JI Food Addit. Contam. Part A-Chem. PY 2009 VL 26 IS 12 BP 1611 EP 1618 AR PII 914865031 DI 10.1080/02652030903232753 PG 8 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 522DD UT WOS:000271977000010 PM 19753496 ER PT J AU Heitkemper, DT Kubachka, KM Halpin, PR Allen, MN Shockey, NV AF Heitkemper, D. T. Kubachka, K. M. Halpin, P. R. Allen, M. N. Shockey, N. V. TI Survey of total arsenic and arsenic speciation in US-produced rice as a reference point for evaluating change and future trends SO FOOD ADDITIVES & CONTAMINANTS PART B-SURVEILLANCE LA English DT Article DE inductively coupled plasma mass spectrometry (ICP/MS); environmental contaminants; rice; arsenic; arsenic speciation ID ORYZA-SATIVA L.; PLASMA-MASS SPECTROMETRY; MARKET BASKET SURVEY; UNITED-STATES; ICP-MS; ION CHROMATOGRAPHY; DIETARY EXPOSURE; FOOD COMPOSITES; WEST-BENGAL; COOKED RICE AB Rice generally contains higher levels of arsenic than most terrestrial-based foods. Studies related to dietary intake of arsenic from rice must take into account arsenic speciation due to toxicity differences in arsenic species. In this study, microwave-assisted extraction with trifluoroacetic acid was used to prepare rice samples for arsenic speciation analysis by high-performance liquid chromatography-inductively coupled plasma mass spectrometry. Fifty-three samples collected directly from the fields in four major rice-producing states in 1980 and 1981 were analysed for total and speciated arsenic and the results were compared with each other and with results for several more recently collected samples from local markets. The average content of total arsenic was 210 +/- 190 ng As g(-1). This study demonstrates that US rice samples with higher levels of total arsenic have higher levels of dimethylarsinic acid; however, inorganic arsenic levels, regardless of the total arsenic content, rarely exceed 150 ng As g(-1) dry weight. These data are consistent with more recent findings, thus establishing trends that arsenic content in US-grown rice has been relatively constant throughout the last 30 years. To the authors' knowledge, the presented data are unique in that they provide a historical reference point for arsenic distribution in US-produced rice. These data would be invaluable for several applications including long-term arsenic exposure studies, environmental clean-up assessments, and to establish models for future trends in arsenic contribution in total diet studies. C1 [Heitkemper, D. T.; Kubachka, K. M.; Halpin, P. R.; Allen, M. N.; Shockey, N. V.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Heitkemper, DT (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. EM douglas.heitkemper@fda.hhs.gov FU USFDA; USEPA [DW-75939361, DW-7592171501] FX This work was sponsored by the USFDA and USEPA under Interagency Agreement Numbers IAG DW-75939361 and DW-7592171501 and by appointments to the Research Fellowship Program at the USFDA administered by Oak Ridge Associated Universities through a contract with the USFDA. NR 41 TC 20 Z9 21 U1 1 U2 23 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1939-3210 J9 FOOD ADDIT CONTAM B JI Food Addit. Contam. Part B-Surveill. PY 2009 VL 2 IS 2 BP 112 EP 120 DI 10.1080/02652030903148298 PG 9 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 532LZ UT WOS:000272750900003 PM 24785173 ER PT J AU Kelly, JJ David, M AF Kelly, Jeremiah J. David, Michael TI No Longer "If," But "When": The Coming Abbreviated Approval Pathway for Follow-on Biologics SO FOOD AND DRUG LAW JOURNAL LA English DT Article ID POLICY-MAKING C1 [Kelly, Jeremiah J.; David, Michael] Whiteford Taylor & Preston LLP, Baltimore, MD USA. [Kelly, Jeremiah J.] US FDA, Rockville, MD 20857 USA. RP Kelly, JJ (reprint author), Whiteford Taylor & Preston LLP, Baltimore, MD USA. NR 53 TC 3 Z9 3 U1 1 U2 1 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2009 VL 64 IS 1 BP 115 EP 148 PG 34 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 413WG UT WOS:000263822700005 PM 19998743 ER PT J AU Bleicher, EWB AF Bleicher, Esther W. B. TI Encouraging Research and Development of Pediatric Medical Devices Through Legislative and Regulatory Action: The Pediatric Medical Device Safety and Improvement Act of 2007 in Context SO FOOD AND DRUG LAW JOURNAL LA English DT Article ID CHILDREN C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Bleicher, EWB (reprint author), US FDA, Off Commissioner, Rockville, MD 20857 USA. NR 23 TC 5 Z9 5 U1 1 U2 2 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2009 VL 64 IS 3 BP 531 EP 564 PG 34 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 495VJ UT WOS:000269922900006 PM 19999642 ER PT J AU White, DG McDermott, PF AF White, David G. McDermott, Patrick F. BE Jaykus, LA Wang, HH Schlesinger, LS TI ANTIMICROBIAL RESISTANCE IN FOOD-BORNE PATHOGENS SO FOOD-BORNE MICROBES: SHAPING THE HOST ECOSYSTEM LA English DT Article; Book Chapter ID ESCHERICHIA-COLI O157-H7; SALMONELLA-TYPHIMURIUM DT104; SPECTRUM-CEPHALOSPORIN RESISTANCE; AMPC BETA-LACTAMASE; CAMPYLOBACTER-JEJUNI INFECTIONS; NORTHEASTERN UNITED-STATES; HUMAN HEALTH CONSEQUENCES; URINARY-TRACT-INFECTIONS; CLASS 1 INTEGRONS; ANTIBIOTIC-RESISTANCE C1 [White, David G.] US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP White, DG (reprint author), US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. NR 221 TC 0 Z9 0 U1 2 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA PY 2009 BP 231 EP 265 PG 35 WC Gastroenterology & Hepatology; Microbiology SC Gastroenterology & Hepatology; Microbiology GA BOY54 UT WOS:000278065800014 ER PT S AU Sapsford, KE Sun, S Francis, J Kostov, Y Rasooly, A Farrell, D Mattoussi, H Medintze, IL AF Sapsford, Kim E. Sun, Steven Francis, Jesse Kostov, Yordan Rasooly, Avraham Farrell, Dorothy Mattoussi, Hedi Medintze, Igor L. BE Fauchet, PM TI Energy Transfer-Based Biosensing of Protease Activity Measured Using an Electroluminescent Platform SO FRONTIERS IN PATHOGEN DETECTION: FROM NANOSENSORS TO SYSTEMS SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference On Frontiers in Pathogen Detection - From Nanosensors to Systems CY JAN 24-26, 2009 CL San Jose, CA SP SPIE DE Electroluminescent excitation; CCD; FRET; Quantum Dots; Peptides; Proteases; Biosensor; Trypsin; botulinum neurotoxin A ID POLYMERASE-CHAIN-REACTION; QUANTUM-DOT FLUOROPHORES; BOTULINUM NEUROTOXIN; NANOCRYSTALLITES; MICROSTRUCTURES; LIGANDS; SYSTEMS; CANCER AB We present a biosensing platform that uses spatial electroluminescent (EL) illumination combined with charge-coupled device (CCD)-based detection for fluorescence measurements. The resulting EL-CCD detector platform was used to monitor different protease activities with substrates labeled for fluorescence resonance energy transfer (FRET)-based assays. The first uses a commercial FITC/DABCYL-SNAP-25 peptide substrate to monitor the activity of the light chain derivative (LcA) of botulinum neurotoxin A, achieving a limit of detection (LOD) of 1.25 nM (62 ng/ml). The second protease activity assay measured trypsin proteolysis using peptide substrates immobilized onto semiconductor quantum dot (QD) nanoparticles with a LOD of 6.2 nM trypsin (140 ng/ml). The specific ovomucoid inhibition of trypsin activity was also monitored. The highlighted studies clearly demonstrate the utility of the EL-CCD detector platform for monitoring fluorescent-based protease activity assays with potential healthcare applications, including point-of-care diagnostics. C1 [Sapsford, Kim E.; Sun, Steven; Francis, Jesse; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Sapsford, KE (reprint author), US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. EM kim.sapsford@fda.hhs.gov NR 36 TC 0 Z9 0 U1 1 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7413-1 J9 P SOC PHOTO-OPT INS PY 2009 VL 7167 AR 71670X DI 10.1117/12.809301 PG 10 WC Engineering, Biomedical; Nanoscience & Nanotechnology; Remote Sensing; Optics SC Engineering; Science & Technology - Other Topics; Remote Sensing; Optics GA BSU91 UT WOS:000285842500023 ER PT J AU Myklebust, JB Lovett, EG Myklebust, BM Reynolds, N Milkowski, L Prieto, TE AF Myklebust, J. B. Lovett, E. G. Myklebust, B. M. Reynolds, N. Milkowski, L. Prieto, T. E. TI Two-dimensional coherence for measurement of asymmetry in postural steadiness SO GAIT & POSTURE LA English DT Article DE Balance; Postural steadiness; Asymmetry; Signal processing; Huntington's Disease ID SPECTRAL ESTIMATION; STANDING BALANCE; WEIGHT-BEARING; SWAY ACTIVITY; STROKE; HEMIPARESIS; RELIABILITY; STABILITY; PRESSURE; DYNAMICS AB Two-dimensional magnitude squared coherence (2D-MSC) is developed to compare the two-valued time series which represent the center of pressure (COP) under each foot. A sinusoidal Multiple taper spectral estimator is used to reduce bias and improve spectral resolution. The measure is applied to evaluate symmetry in the dual-plate postural steadiness time series obtained from healthy young and elderly volunteers, and patients with Huntington's Disease (HD), a group in which asymmetries in postural steadiness are anticipated. The results demonstrate that the 2D-MSC is a robust measure of inter-limb coordination that may be of value in studies of aging and neurologic disease. Published by Elsevier B.V. C1 [Myklebust, J. B.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Lovett, E. G.] CVRx Inc, Minneapolis, MN USA. [Myklebust, B. M.] George Washington Univ, Sch Engn & Appl Sci, Washington, DC 20052 USA. [Reynolds, N.; Prieto, T. E.] Med Coll Wisconsin, Dept Neurol, Milwaukee, WI USA. [Milkowski, L.] Milwaukee Sch Engn, Dept EECS, Milwaukee, WI USA. RP Myklebust, JB (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. EM Joel.Myklebust@fda.hhs.gov OI Myklebust, Joel/0000-0002-8709-9706 NR 29 TC 8 Z9 9 U1 1 U2 3 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0966-6362 J9 GAIT POSTURE JI Gait Posture PD JAN PY 2009 VL 29 IS 1 BP 1 EP 5 DI 10.1016/j.gaitpost.2008.05.011 PG 5 WC Neurosciences; Orthopedics; Sport Sciences SC Neurosciences & Neurology; Orthopedics; Sport Sciences GA 396LC UT WOS:000262592200001 PM 18603428 ER PT B AU Woodcock, J AF Woodcock, Janet BE Willard, HF Ginsburg, GS TI Federal Regulation of Genomic Medicine SO GENOMIC AND PERSONALIZED MEDICINE, VOL 1 LA English DT Article; Book Chapter ID PHARMACOGENOMICS; OVERSIGHT C1 US FDA, Rockville, MD 20857 USA. RP Woodcock, J (reprint author), US FDA, Rockville, MD 20857 USA. NR 18 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-12-370888-5 PY 2009 BP 414 EP 423 PG 10 WC Genetics & Heredity; Medicine, Research & Experimental SC Genetics & Heredity; Research & Experimental Medicine GA BCX27 UT WOS:000311822400037 ER PT J AU Nichols, WL Hultln, MB James, AH Manco-Johnson, MJ Montgomery, RR Ortel, TL Rick, ME Sadler, JE Weinstein, M Yawn, BP AF Nichols, W. L. Hultln, M. B. James, A. H. Manco-Johnson, M. J. Montgomery, R. R. Ortel, T. L. Rick, M. E. Sadler, J. E. Weinstein, M. Yawn, B. P. TI von Willebrand factor content in Alphanate((R)) (Laurence J. Logan) - reply SO HAEMOPHILIA LA English DT Letter ID FACTOR CONCENTRATE; DISEASE C1 [Nichols, W. L.] Mayo Clin, Special Coagulat Lab, Coll Med, Div Hematopathol,Dept Lab Med & Pathol, Rochester, MN 55905 USA. [Nichols, W. L.] Mayo Clin, Coagulat Clin, Coll Med, Rochester, MN 55905 USA. [Nichols, W. L.] Mayo Clin, Comprehens Hemophilia Ctr, Coll Med, Div Hematol & Internal Med, Rochester, MN 55905 USA. [Hultln, M. B.] SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. [James, A. H.] Duke Univ, Med Ctr, Dept Obstet & Gynecol, Durham, NC 27710 USA. [Manco-Johnson, M. J.] Univ Colorado Denver, Dept Pediat, Aurora, CO USA. [Manco-Johnson, M. J.] Childrens Hosp, Ctr Canc & Blood Disorders, Denver, CO 80218 USA. [Montgomery, R. R.] Med Coll Wisconsin, BloodCtr Wisconsin, Blood Res Inst, Milwaukee, WI 53226 USA. [Montgomery, R. R.] Med Coll Wisconsin, Sect Pediat Hematol, Dept Pediat, Milwaukee, WI 53226 USA. [Ortel, T. L.] Duke Univ, Med Ctr, Dept Pathol, Clin Coagulat Lab, Durham, NC 27710 USA. [Ortel, T. L.] Duke Univ, Dept Med, Div Hematol, Durham, NC 27710 USA. [Rick, M. E.] NIH, Warren G Magnuson Clin Ctr, Hematol Serv, Bethesda, MD 20892 USA. [Sadler, J. E.] Washington Univ, Dept Med, St Louis, MO USA. [Weinstein, M.] US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Yawn, B. P.] Univ Minnesota, Dept Family & Community Med, Minneapolis, MN USA. [Yawn, B. P.] Olmsted Med Ctr, Dept Res, Rochester, MN USA. RP Nichols, WL (reprint author), Mayo Clin, Special Coagulat Lab, Coll Med, Div Hematopathol,Dept Lab Med & Pathol, Hilton 200, Rochester, MN 55905 USA. EM nichols.william@mayo.edu RI Sadler, Evan/D-8556-2011; OI Sadler, J. Evan/0000-0001-5705-469X NR 4 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PD JAN PY 2009 VL 15 IS 1 BP 370 EP 371 DI 10.1111/j.1365-2516.2008.01903.x PG 2 WC Hematology SC Hematology GA 394TK UT WOS:000262470600053 ER PT J AU Kina, SH Wosinska, M AF Kina, Samuel H. Wosinska, Marta BE Rao, VR TI Pharmaceutical pricing SO HANDBOOK OF PRICING RESEARCH IN MARKETING LA English DT Article; Book Chapter ID DRUG DEVELOPMENT COSTS; PRESCRIPTION DRUGS; INDUSTRY; ENTRY; COMPETITION; PRICES; MARKETS; DEMAND; PRODUCTS; DYNAMICS AB In this chapter, we discuss the multiple institutional characteristics that affect prescription drug pricing. We organize our discussion around the 5Cs that define the prescription drug industry: companies (the innovative process), competitors (the limits of patent protections), customers (how insurance markets affect pricing), collaborators (roles played by physicians and various channel players), and context (government regulation of pricing). We conclude the chapter with implications for drug pricing research. We categorize areas for future research in three distinct areas. First, future research should continue to clarify the nature of the current market. Second, we believe that more research is needed on how to optimize the current system. Finally, given the dynamic nature of the regulatory and institutional environment that defines the pharmaceutical industry, continued research on how these changes influence pricing will be needed as the industry continues to evolve. C1 [Kina, Samuel H.; Wosinska, Marta] Harvard Univ, Sch Business, Boston, MA 02115 USA. [Wosinska, Marta] US FDA, Off Planning & Informat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Wosinska, Marta] Columbia Business Sch, New York, NY USA. RP Kina, SH (reprint author), Harvard Univ, Sch Business, Boston, MA 02115 USA. NR 59 TC 0 Z9 0 U1 1 U2 4 PU EDWARD ELGAR PUBLISHING LTD PI CHELTENHAM PA GLENSANDA HOUSE, MONTPELLIER PARADE, CHELTENHAM GL50 1UA, GLOS, ENGLAND BN 978-1-84720-240-6 PY 2009 BP 488 EP 511 PG 24 WC Business; Economics SC Business & Economics GA BZF92 UT WOS:000301444800025 ER PT J AU Anadon, A Martinez-Larranaga, MR Valerio, LG AF Anadon, Arturo Rosa Martinez-Larranaga, Maria Valerio, Luis G., Jr. BE Gupta, RC TI Onchidal and Fasciculins SO HANDBOOK OF TOXICOLOGY OF CHEMICAL WARFARE AGENTS LA English DT Article; Book Chapter ID BLACK MAMBA VENOM; E-STATE INDEXES; MDL-QSAR; GENETIC TOXICITY; SNAKE-VENOM; ACETYLCHOLINESTERASE; TOXINS; CHEMICALS; MECHANISM; DESCRIPTORS AB This research report is not an official US Food and Drug Administration guidance or policy statement. No official support or endorsement by the US Food and Drug Administration is intended or should be inferred. C1 [Anadon, Arturo; Rosa Martinez-Larranaga, Maria] Univ Complutense Madrid, Fac Vet, Dept Farmacol & Toxicol, E-28040 Madrid, Spain. [Valerio, Luis G., Jr.] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Anadon, A (reprint author), Univ Complutense Madrid, Fac Vet, Dept Farmacol & Toxicol, E-28040 Madrid, Spain. NR 48 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 9780-0-80-92273-7 PY 2009 BP 143 EP 152 DI 10.1016/B978-0-12-374484-5.00011-0 PG 10 WC Toxicology SC Toxicology GA BFT95 UT WOS:000321306800012 ER PT J AU Han, J Kioi, M Chu, WS Kasperbauer, JL Strome, SE Puri, RK AF Han, Jing Kioi, Mitomu Chu, Wei-Sing Kasperbauer, Jan L. Strome, Scott E. Puri, Raj K. TI Identification of potential therapeutic targets in human head & neck squamous cell carcinoma SO HEAD & NECK ONCOLOGY LA English DT Article AB Background: Human head and neck squamous cell carcinoma (HNSCC) is an aggressive and recurrent malignancy. Identification of unique or overexpressed cell-associated or cell surface antigens is critical for diagnosis and development of cancer vaccines and targeted therapies for HNSCC. We have used high throughput microarray technology to search for candidate targets in HNSCC. Methods: Gene expression profiling in 17 HNSCC tumors and 3 normal tonsil tissues was performed by microarray. QRT-PCR analysis was performed to validate the microarray results. The five candidate genes were further characterized by immunohistochemical technique in surgical samples and tissue arrays. Results: A total of 192 up-regulated genes at statistical significance of p < 0.01 and log2 ratio >= 1 were identified in HNSCC tumors compared to normal tissues. These genes belong to immune response, cell growth, cell cycle regulation, oncogenes, metabolism and others. Five potential novel target genes (FABP5, CD24, CD44, CD74, and HSP27) were identified, which were highly expressed in HNSCC tumor samples and tissue arrays. CD24, CD44, and CD74 proteins were expressed on the cell surface, and FABP5 and HSP27 proteins were predominantly expressed in the cytoplasm of HNSCC. Conclusion: Five genes and their products may serve as a diagnostic biomarker or therapeutic target for HNSCC. While additional work is needed to elucidate the biological significance of these proteins, CD24 and CD74 expressed only in small proportion of cells indicating tumor heterogeneity and subtypes of tumor initiating cells (CD24+/CD44+) present in HNSCC. C1 [Han, Jing; Kioi, Mitomu; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Chu, Wei-Sing] Armed Forces Inst Pathol, Dept Sci Labs, Washington, DC 20306 USA. [Kasperbauer, Jan L.] Mayo Clin, Ctr Canc, Rochester, MN 55905 USA. [Strome, Scott E.] Univ Maryland, Sch Med, Dept Otorhinolaryngol Head & Neck Surg, Baltimore, MD 21201 USA. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM jing.han@fda.hhs.gov; mitomuk@stanford.edu; chuzhu@yahoo.com; kasperbauer.jan@mayo.edu; sstrome@smail.umaryland.edu; raj.puri@fda.hhs.gov NR 45 TC 28 Z9 31 U1 0 U2 5 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1758-3284 J9 HEAD NECK ONCOL JI Head Neck Oncol. PY 2009 VL 1 AR 27 DI 10.1186/1758-3284-1-27 PG 9 WC Oncology SC Oncology GA V19YF UT WOS:000208107000026 PM 19602232 ER PT J AU Brinker, AD Wassel, RT Lyndly, J Serrano, J Avigan, M Lee, WM Seeff, LB AF Brinker, Allen D. Wassel, Ronald T. Lyndly, Jenna Serrano, Jose Avigan, Mark Lee, William M. Seeff, Leonard B. TI Telithromycin-Associated Hepatotoxicity: Clinical Spectrum and Causality Assessment of 42 Cases SO HEPATOLOGY LA English DT Article ID FULMINANT HEPATIC-FAILURE; INDUCED LIVER-INJURY; ADVERSE REACTIONS; CLARITHROMYCIN; THERAPY; DISEASE; DRUGS AB Telithromycin is the first of a new class of ketolide antibiotics with increased activity against penicillin-resistant and erythromycin-resistant pneumococci. This agent received approval by the United States Food and Drug Administration (FDA) in 2004 for treatment of upper and lower respiratory infections. Following market introduction, spontaneous reports of telithromycin-associated hepatotoxicity, including frank liver failure, were received. To address these reports, an ad hoc group with expertise in spontaneous adverse events reporting and experience in evaluating drug-induced liver injury was formed, including members of the FDA, other federal agencies, and academia. The primary objective of this group was to adjudicate case reports of hepatic toxicity for causal attribution to telithromycin. After an initial screening of all cases of liver injury associated with telithromycin reported to FDA as of April 2006 by one of the authors, 42 cases were comprehensively reviewed and adjudicated. Five cases included a severe outcome of either death (n = 4) or liver transplantation (n = 1); more than half were considered highly likely or probable in their causal association with telithromycin. Typical clinical features were: short latency (median, 10 days) and abrupt onset of fever, abdominal pain, and jaundice, sometimes with the presence of ascites; even in cases that resolved. Concurrence in assignment of causality increased after agreement on definitions of categories and interactive discussions. Conclusion: Telithromycin is a rare cause of drug-induced liver injury that may have a distinctive clinical signature and associated high mortality rate. Consensus for attribution of liver injury to a selected drug exposure by individual experts can be aided by careful definition of terminology and discussion. (HEPATOLOGY 2009;49:250-257.) C1 [Brinker, Allen D.; Wassel, Ronald T.; Lyndly, Jenna; Avigan, Mark] US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. [Serrano, Jose; Seeff, Leonard B.] NIDDKD, NIH, Liver Dis Res Branch, Div Digest Dis & Nutr, Bethesda, MD 20892 USA. [Lee, William M.] Univ Texas SW Med Ctr Dallas, Meredith Mosley Chair Liver Dis, Dallas, TX 75390 USA. RP Brinker, AD (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Surveillance & Epidemiol, 10903 New Hampshire Ave,Bldg 22, Silver Spring, MD 20993 USA. EM allen.brinker@fda.hhs.gov NR 44 TC 55 Z9 60 U1 2 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD JAN PY 2009 VL 49 IS 1 BP 250 EP 257 DI 10.1002/hep.22620 PG 8 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 389WX UT WOS:000262127400029 PM 19085949 ER PT J AU Rivkees, SA Szarfman, A AF Rivkees, Scott A. Szarfman, Ana TI Dissimilar hepatotoxicity of propylthiouracil and methimazole in pediatric patients SO HORMONE RESEARCH LA English DT Meeting Abstract C1 [Rivkees, Scott A.] Yale Univ, Yale Pediat Thyroid Ctr, New Haven, CT USA. [Szarfman, Ana] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0301-0163 J9 HORM RES JI Horm. Res. PY 2009 VL 72 BP 61 EP 61 PG 1 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 502WB UT WOS:000270489900185 ER PT J AU Mendoza, MCB Burns, TL Jones, MP AF Mendoza, Maria C. B. Burns, Trudy L. Jones, Michael P. TI Case-Deletion Diagnostics for Maximum Likelihood Multipoint Quantitative Trait Locus Linkage Analysis SO HUMAN HEREDITY LA English DT Article DE Case-deletion diagnostics; Empirical influence function; Influential observation; Outlier AB Objectives: Case-deletion diagnostic methods are tools that allow identification of influential observations that may affect parameter estimates and model fitting conclusions. The goal of this paper was to develop two case-deletion diagnostics, the exact case deletion (ECD) and the empirical influence function (EIF), for detecting outliers that can affect results of sib-pair maximum likelihood quantitative trait locus (QTL) linkage analysis. Methods: Subroutines to compute the ECD and EIF were incorporated into the maximum likelihood QTL variance estimation components of the linkage analysis program MAPMAKER/SIBS. Performance of the diagnostics was compared in simulation studies that evaluated the proportion of outliers correctly identified (sensitivity), and the proportion of non-outliers correctly identified (specificity). Results: Simulations involving nuclear family data sets with one outlier showed EIF sensitivities approximated ECD sensitivities well for outlier-affected parameters. Sensitivities were high, indicating the outlier was identified a high proportion of the time. Simulations also showed the enormous computational time advantage of the EIF. Diagnostics applied to body mass index in nuclear families detected observations influential on the lod score and model parameter estimates. Conclusions: The EIF is a practical diagnostic tool that has the advantages of high sensitivity and quick computation. Copyright (C) 2009 S. Karger AG, Basel C1 [Mendoza, Maria C. B.] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Mendoza, Maria C. B.; Jones, Michael P.] Univ Iowa, Dept Biostat, Iowa City, IA USA. [Burns, Trudy L.] Univ Iowa, Dept Epidemiol, Iowa City, IA USA. RP Mendoza, MCB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, 3900 NCTR Rd,Bldg 15,Room 114D, Jefferson, AR 72079 USA. EM maria.mendoza@fda.hhs.gov FU NIH [HD029569] FX This dissertation research of M. C. B. Mendoza was supported by NIH grant HD029569 which also supported the recruitment and examination of the Muscatine nuclear families. NR 12 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0001-5652 J9 HUM HERED JI Hum. Hered. PY 2009 VL 67 IS 4 BP 276 EP 286 DI 10.1159/000194980 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 428QR UT WOS:000264864500006 PM 19172086 ER PT S AU Chang, IA Pfefer, TJ AF Chang, Isaac A. Pfefer, T. Joshua BE Vaezy, S Zderic, V TI Modeling of Image-Guided Therapy SO IMAGE-GUIDED THERAPY SYSTEMS SE Engineering in Medicine and Biology LA English DT Article; Book Chapter ID 3-DIMENSIONAL FINITE-ELEMENT; OPTICAL COHERENCE TOMOGRAPHY; RADIOFREQUENCY-CATHETER ABLATION; FOCUSED ULTRASOUND SURGERY; MONTE-CARLO CODE; BREAST-CANCER; LEFT ATRIUM; IN-VIVO; DIELECTRIC-PROPERTIES; CARDIAC ABLATION C1 [Chang, Isaac A.; Pfefer, T. Joshua] US FDA, Silver Spring, MD 20993 USA. RP Chang, IA (reprint author), US FDA, 10903 New Hampshire Ave,Bldg 62,Room 1108, Silver Spring, MD 20993 USA. EM isaac.chang@fda.hhs.gov; joshua.pfefer@fda.hhs.gov NR 61 TC 0 Z9 0 U1 1 U2 2 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA SN 0278-0054 BN 978-1-59693-109-1 J9 ENG MED BIOL JI Eng. Med. Biol. PY 2009 BP 367 EP 399 PG 33 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BKL87 UT WOS:000268458600018 ER PT J AU Damsker, JM Okwumabua, I Pushkarsky, T Arora, K Bukrinsky, MI Constant, SL AF Damsker, Jesse M. Okwumabua, Ifeanyi Pushkarsky, Tatiana Arora, Kamalpreet Bukrinsky, Michael I. Constant, Stephanie L. TI Targeting the chemotactic function of CD147 reduces collagen-induced arthritis SO IMMUNOLOGY LA English DT Article DE autoimmunity; chemokines; collagen-induced arthritis; inflammation; rheumatoid arthritis ID MATRIX-METALLOPROTEINASE INDUCER; RHEUMATOID-ARTHRITIS; T-CELLS; CYCLOPHILIN; INFLAMMATION; DISEASE; SYNOVIOCYTES; PROGRESSION; EXPRESSION; SYNOVIUM AB CD147 is a type I transmembrane glycoprotein expressed on a wide variety of cell types, including all leucocytes. While CD147 is best known as a potent inducer of matrix metalloproteinases, it can also function as a regulator of leucocyte migration through its cell surface interaction with chemotactic extracellular cyclophilins. A potential role for CD147-cyclophilin interactions during inflammatory diseases, including rheumatoid arthritis (RA), is suggested from several studies. For example, CD147 expression is increased on reactive leucocytes in the synovial fluid and tissues of patients with arthritis. In addition, the synovial fluid of patients with RA contains high levels of extracellular cyclophilin A. In the current studies we investigated the contribution of the chemotactic function of CD147-cyclophilin interactions to joint inflammation using the mouse model of collagen-induced arthritis. Our data demonstrate that proinflammatory leucocytes, specifically neutrophils, monocytes and activated CD4(+) T cells, lose their ability to migrate in response to cyclophilin A in vitro when treated with anti-CD147 monoclonal antibody. Furthermore, in vivo treatment with anti-CD147 monoclonal antibody can reduce the development of collagen-induced arthritis in mice by > 75%. Such findings suggest that CD147-cyclophilin interactions might contribute to the pathogenesis of RA by promoting the recruitment of leucocytes into joint tissues. C1 [Damsker, Jesse M.; Okwumabua, Ifeanyi; Pushkarsky, Tatiana; Bukrinsky, Michael I.; Constant, Stephanie L.] George Washington Univ, Dept Microbiol Immunol & Trop Med, Washington, DC 20037 USA. [Arora, Kamalpreet] US FDA, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Constant, SL (reprint author), George Washington Univ, Dept Microbiol Immunol & Trop Med, Ross Hall 738,2300 Eye St NW, Washington, DC 20037 USA. EM mtmslc@gwumc.edu FU National Institutes of Health [R21-AI60720]; AHA [0615392U] FX These studies were funded by National Institutes of Health grant R21-AI60720, and AHA predoctoral fellowship 0615392U (JMD). NR 31 TC 54 Z9 58 U1 0 U2 4 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0019-2805 J9 IMMUNOLOGY JI Immunology PD JAN PY 2009 VL 126 IS 1 BP 55 EP 62 DI 10.1111/j.1365-2567.2008.02877.x PG 8 WC Immunology SC Immunology GA 381ID UT WOS:000261528300007 PM 18557953 ER PT J AU Grande, KK Meysick, KC Rasmussen, SB O'Brien, AD AF Grande, Kerian K. Meysick, Karen C. Rasmussen, Susan B. O'Brien, Alison D. TI Cytotoxic Necrotizing Factor Type 1-Neutralizing Monoclonal Antibody NG8 Recognizes Three Amino Acids in a C-Terminal Region of the Toxin and Reduces Toxin Binding to HEp-2 Cells SO INFECTION AND IMMUNITY LA English DT Article ID UROPATHOGENIC ESCHERICHIA-COLI; BACTERIAL PROTEIN TOXINS; RHO-GTPASES; YERSINIA-PSEUDOTUBERCULOSIS; DEAMIDATION; ACTIVATION; TISSUE; DOMAIN; PURIFICATION; VIRULENCE AB Cytotoxic necrotizing factor type 1 (CNF1) and CNF2 are toxins of pathogenic Escherichia coli that share 85% identity over 1,014 amino acids. Although both of these toxins modify GTPases, CNF1 is a more potent inducer of multinucleation in HEp-2 cells, binds more efficiently to HEp-2 cells, and, despite the conservation of amino acids (C866 and H881) required for enzymatic activity of the toxins, deamidates RhoA and Cdc42 better than CNF2. Here we exploited the differences between CNF1 and CNF2 to define the epitope on CNF1 to which the CNF1-specific neutralizing monoclonal antibody (MAb) (MAb NG8) binds and to determine the mechanism by which MAb NG8 neutralizes CNF1 activity on HEp-2 cells. For these purposes, we generated a panel of 21 site-directed mutants in which amino acids in CNF1 were exchanged for the amino acids in CNF2 between amino acids 546 and 869 and vice versa. This region of CNF1 not only is recognized by MAb NG8 but also is involved in binding of this toxin to HEp-2 cells. All the mutants retained the capacity to induce multinucleation of HEp-2 cells. However, the CNF1 double mutant with D591E and F593L mutations (CNF1 D591E F593L) and the CNF1(H661Q) single mutant displayed drastically reduced reactivity with MAb NG8. A reverse chimeric triple mutant, CNF1(E591D) (L593F) (Q661H), imparted MAb NG8 reactivity to CNF2. MAb NG8 neutralized CNF2(E591D) (L593F) (Q661H) activity in a dose-dependent manner and reduced the binding of this chimeric toxin to HEp-2 cells. Taken together, these results pinpoint three amino acids in CNF1 that are key amino acids for recognition by neutralizing MAb NG8 and further help define a region in CNF1 that is critical for full toxin binding to HEp-2 cells. C1 [Grande, Kerian K.; Rasmussen, Susan B.; O'Brien, Alison D.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Meysick, Karen C.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP O'Brien, AD (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM aobrien@usuhs.mil OI O'Brien, Alison/0000-0002-1315-3204 FU National Institutes of Health [AI38281] FX This work was supported by grant AI38281 from the National Institutes of Health. NR 34 TC 4 Z9 4 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 JAN PY 2009 VL 77 IS 1 BP 170 EP 179 DI 10.1128/IAI.00943-08 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 399BT UT WOS:000262776100016 PM 18955470 ER PT J AU Loving, CL Khurana, T Osorio, M Lee, GM Kelly, VK Stibitz, S Merkel, TJ AF Loving, Crystal L. Khurana, Taruna Osorio, Manuel Lee, Gloria M. Kelly, Vanessa K. Stibitz, Scott Merkel, Tod J. TI Role of Anthrax Toxins in Dissemination, Disease Progression, and Induction of Protective Adaptive Immunity in the Mouse Aerosol Challenge Model SO INFECTION AND IMMUNITY LA English DT Article ID NECROSIS-FACTOR-ALPHA; IN-VITRO CORRELATE; BACILLUS-ANTHRACIS; LETHAL TOXIN; INHALATIONAL ANTHRAX; ALVEOLAR MACROPHAGES; CYTOKINE RESPONSE; RHESUS MACAQUES; DENDRITIC CELLS; GUINEA-PIGS AB Anthrax toxins significantly contribute to anthrax disease pathogenesis, and mechanisms by which the toxins affect host cellular responses have been identified with purified toxins. However, the contribution of anthrax toxin proteins to dissemination, disease progression, and subsequent immunity after aerosol infection with spores has not been clearly elucidated. To better understand the role of anthrax toxins in pathogenesis in vivo and to investigate the contribution of antibody to toxin proteins in protection, we completed a series of in vivo experiments using a murine aerosol challenge model and a collection of in-frame deletion mutants lacking toxin components. Our data show that after aerosol exposure to Bacillus anthracis spores, anthrax lethal toxin was required for outgrowth of bacilli in the draining lymph nodes and subsequent progression of infection beyond the lymph nodes to establish disseminated disease. After pulmonary exposure to anthrax spores, toxin expression was required for the development of protective immunity to a subsequent lethal challenge. However, immunoglobulin (immunoglobulin G) titers to toxin proteins, prior to secondary challenge, did not correlate with the protection observed upon secondary challenge with wild-type spores. A correlation was observed between survival after secondary challenge and rapid anamnestic responses directed against toxin proteins. Taken together, these studies indicate that anthrax toxins are required for dissemination of bacteria beyond the draining lymphoid tissue, leading to full virulence in the mouse aerosol challenge model, and that primary and anamnestic immune responses to toxin proteins provide protection against subsequent lethal challenge. These results provide support for the utility of the mouse aerosol challenge model for the study of inhalational anthrax. C1 [Merkel, Tod J.] US FDA, Lab Resp & Special Pathogens, DBPAP, CBER, Bethesda, MD 20892 USA. [Osorio, Manuel; Stibitz, Scott] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), US FDA, Lab Resp & Special Pathogens, DBPAP, CBER, Bldg 29,Rm 418,29 Lincoln Dr, Bethesda, MD 20892 USA. EM merkel@cber.fda.gov FU National Institute of Allergy and Infectious Diseases; National Institutes of Health; Department of Health and Human Services [IAAY1-A1-6153-01] FX This project has been funded in whole or in part with Federal funds from the National Institute of Allergy and Infectious Diseases, National Institutes of Health, Department of Health and Human Services, under IAAY1-A1-6153-01. NR 65 TC 31 Z9 31 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 JAN PY 2009 VL 77 IS 1 BP 255 EP 265 DI 10.1128/IAI.00633-08 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 399BT UT WOS:000262776100024 PM 18955474 ER PT J AU Cybulski, RJ Sanz, P Alem, F Stibitz, S Bull, RL O'Brien, AD AF Cybulski, Robert J., Jr. Sanz, Patrick Alem, Farhang Stibitz, Scott Bull, Robert L. O'Brien, Alison D. TI Four Superoxide Dismutases Contribute to Bacillus anthracis Virulence and Provide Spores with Redundant Protection from Oxidative Stress SO INFECTION AND IMMUNITY LA English DT Article ID MURINE MACROPHAGES; MOUSE MODEL; IN-VIVO; MYCOBACTERIUM-TUBERCULOSIS; HYDROGEN-PEROXIDE; GERMINATION; SUBTILIS; COAT; EXOSPORIUM; PROTEINS AB The Bacillus anthracis genome encodes four superoxide dismutases (SODs), enzymes capable of detoxifying oxygen radicals. That two of these SODs, SOD15 and SODA1, are present in the outermost layers of the B. anthracis spore is indicated by previous proteomic analyses of the exosporium. Given the requirement that spores must survive interactions with reactive oxygen species generated by cells such as macrophages during infection, we hypothesized that SOD15 and SODA1 protect the spore from oxidative stress and contribute to the pathogenicity of B. anthracis. To test these theories, we constructed a double-knockout (Delta sod15 Delta sodA1) mutant of B. anthracis Sterne strain 34F2 and assessed its lethality in an A/J mouse intranasal infection model. The 50% lethal dose of the Delta sod15 Delta sodA1 strain was similar to that of the wild type (34F2), but surprisingly, measurable whole-spore SOD activity was greater than that in 34F2. A quadruple-knockout strain (Delta sod15 Delta sodA1 Delta sodC Delta sodA2) was then generated, and as anticipated, spore-associated SOD activity was diminished. Moreover, the quadruple-knockout strain, compared to the wild type, was attenuated more than 40-fold upon intranasal challenge of mice. Spore resistance to exogenously generated oxidative stress and to macrophage-mediated killing correlated with virulence in A/J mice. Allelic exchange that restored sod15 and sodA1 to their wild-type state restored wild-type characteristics. We conclude that SOD molecules within the spore afford B. anthracis protection against oxidative stress and enhance the pathogenicity of B. anthracis in the lung. We also surmise that the presence of four SOD alleles within the genome provides functional redundancy for this key enzyme. C1 [Cybulski, Robert J., Jr.; Sanz, Patrick; Alem, Farhang; O'Brien, Alison D.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Stibitz, Scott] US FDA, CBER, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. [Bull, Robert L.] USN, Med Res Ctr, Silver Spring, MD 20910 USA. RP O'Brien, AD (reprint author), Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM aobrien@usuhs.mil OI O'Brien, Alison/0000-0002-1315-3204 FU NIH/NIAID Middle Atlantic Regional Center of Excellence [U54 AI057168]; U. S. Navy through Uniformed Services University [G173HS] FX This work was supported by NIH/NIAID Middle Atlantic Regional Center of Excellence grant U54 AI057168 and research funds from the U. S. Navy through Uniformed Services University grant G173HS. We also give special thanks to the U. S. Army Long-Term Health Education and Training Program for support of R. Cybulski. NR 56 TC 46 Z9 46 U1 0 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2009 VL 77 IS 1 BP 274 EP 285 DI 10.1128/IAI.00515-08 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 399BT UT WOS:000262776100026 PM 18955476 ER PT S AU Rios, M AF Rios, M. GP ISBT TI Climate change and vector-borne viral diseases potentially transmitted by transfusion SO ISBT SCIENCE SERIES, VOL 4, NO 1, STATE OF THE ART PRESENTATIONS SE ISBT Science Series LA English DT Proceedings Paper CT 19th Regional Congress of the International-Society-of-Blood-Transfusion CY MAR 21-25, 2009 CL Cairo, EGYPT SP Int Soc Blood Transfus ID AEDES-ALBOPICTUS; HEALTH; TRANSMISSION AB Vector-borne diseases occur when infectious agents (virus, protozoa, bacteria, or helminthes) are transmitted to their hosts by a carrier organism. Climate conditions and their changes play a role in the inter-relationship between these agents, the vectors and the host (or hosts). This review is focused on arthropod-borne viruses (Arboviruses). These viruses are transmitted between susceptible vertebrate hosts by blood-feeding arthropods, and may be transmitted by blood transfusion, tissue and organ transplantation and breast feeding. The lifecycle of arboviruses is influenced by changes in temperature, rainfall, humidity, length of day, average daily solar radiation and/or storm patterns, as well as changes in the frequency or rare events such as floods or droughts. A plethora of studies have suggested that climate changes, particularly temperature changes, are likely to be induced by increase in the amount of greenhouse gases, such as methane, carbon dioxide (CO(2)) and chlorofluorocarbons, which deplete ozone in the atmosphere leading to an increase in ultraviolet radiation. Current models predict that ambient temperature will increase by 3-5 degrees C on average with a doubling in CO(2) concentration in the atmosphere. Vectors, pathogens and hosts each survive and reproduce within a range of optimal climatic conditions: temperature and precipitation being most important, while sea level elevation, wind and daylight duration are also important. Climate changes may affect important determinants of vector-borne disease transmission including (i) vector survival and reproduction, (ii) the vector's biting rate, and (iii) the pathogen's incubation rate within the vector organism. Droughts can increase the dissemination of arboviral diseases in urban areas by allowing a boost in the population of mosquitoes in foul water concentrated in catch basins where they breed. Furthermore, eggs can be vertically infected with arboviruses and heat waves speed up the maturation of the mosquitoes and of the viruses within mosquitoes. Droughts also cause a decline in mosquito predators like frogs, darning needles and dragonflies. In addition, birds congregate around shrinking water sites, enhancing circulation of viruses among birds and mosquitoes. In conclusion, the seriousness of some of the recent epidemics like West Nile virus and Dengue appear to has been influenced by climate change. As most of the arboviral infections are asymptomatic in humans, there is an increased opportunity for blood, organ and tissue donations by infected individuals during the viraemic period, resulting in an increased risk of transmission of arboviruses. C1 US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Rios, M (reprint author), US FDA, Mol Virol Lab, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM maria.rios@fda.hhs.gov NR 25 TC 5 Z9 5 U1 5 U2 15 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXEN, ENGLAND SN 1751-2816 J9 ISBT SCI SERIES PY 2009 VL 4 IS 1 BP 87 EP 94 PG 8 WC Hematology SC Hematology GA BJD60 UT WOS:000265020700016 ER PT J AU Johnson, RC Zhou, Y Statler, K Thomas, J Cox, F Hall, S Barr, JR AF Johnson, Rudolph C. Zhou, Yingtao Statler, Kristen Thomas, Jerry Cox, Frederick Hall, Sherwood Barr, John R. TI Quantification of Saxitoxin and Neosaxitoxin in Human Urine Utilizing Isotope Dilution Tandem Mass Spectrometry SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID PARALYTIC SHELLFISH POISON; ELECTROSPRAY IONIZATION; CYANOBACTERIAL TOXINS; POSTMORTEM ANALYSIS; IDENTIFICATION; ELIMINATION; SAMPLES; TISSUE; RAT C1 [Johnson, Rudolph C.; Zhou, Yingtao; Statler, Kristen; Thomas, Jerry; Barr, John R.] Ctr Dis Control & Prevent, Div Sci Lab, Atlanta, GA 30341 USA. [Cox, Frederick] Battelle Eastern Sci & Technol Ctr, Aberdeen, MD 21001 USA. [Hall, Sherwood] US FDA, Off Regulatory Sci HFS 716, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Johnson, RC (reprint author), Ctr Dis Control & Prevent, Div Sci Lab, 4770 Buford Highway,MS F44, Atlanta, GA 30341 USA. NR 32 TC 17 Z9 18 U1 1 U2 8 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0146-4760 EI 1945-2403 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD JAN-FEB PY 2009 VL 33 IS 1 BP 8 EP 14 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 400OD UT WOS:000262876800002 PM 19161664 ER PT J AU Zheng, J Cui, SH Meng, JH AF Zheng, Jie Cui, Shenghui Meng, Jianghong TI Effect of transcriptional activators RamA and SoxS on expression of multidrug efflux pumps AcrAB and AcrEF in fluoroquinolone-resistant Salmonella Typhimurium SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article ID ENTERICA SEROVAR TYPHIMURIUM; MULTIPLE-ANTIBIOTIC-RESISTANCE; ESCHERICHIA-COLI; DECREASED SUSCEPTIBILITY; KLEBSIELLA-PNEUMONIAE; CHROMOSOMAL GENES; DRUG-RESISTANCE; REGULATORY GENE; STRESS REGULON; GYRA GENE AB Multidrug resistance (MDR) including fluoroquinolone resistance in Salmonella Typhimurium can result from overexpression of efflux pumps. We examined the mechanisms of fluoroquinolone resistance among in vitro-induced ciprofloxacin-resistant Salmonella Typhimurium mutants, LTL and LTH, derived from laboratory strain LT2. Deletion mutation and RT-PCR techniques were employed to study the role of efflux pumps in fluoroquinolone resistance and their regulation cascades. In addition to point mutations in DNA gyrase (gyrA, gyrB) and topoisomerase IV (parC, parE) genes, increased expression of efflux pump genes, such as acrAB and acrEF, was observed in fluoroquinolone-resistant Salmonella strains. Constitutive expression of ramA containing a 9 bp deletion in the promoter region was directly associated with the overexpression of acrAB and acrEF and conferred an MDR phenotype in LTL. Inactivation of ramA increased the antimicrobial susceptibility of LTL, whereas complementation with the mutant allele induced an MDR phenotype in drug-susceptible Salmonella Typhimurium LT2, as demonstrated by 2- to 64-fold increases in resistance to fluoroquinolones, tetracycline and chloramphenicol. On the other hand, inactivation of mutant soxRS resulted in a slight increase in the susceptibility of LTH to several fluoroquinolone drugs, and the introduction of the mutant allele had no effect on antimicrobial susceptibility of LT2, indicating that constitutive expression of soxRS played a minimum role in fluoroquinolone resistance. Mutations in the promoter region of ramA appear to play a role in the up-regulation of RamA and AcrAB, and RamA is an activator of the MDR regulation cascade in Salmonella Typhimurium. C1 [Zheng, Jie; Cui, Shenghui; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Zheng, Jie; Meng, Jianghong] Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM jmeng@umd.edu FU Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland; U. S. Food & Drug Administration FX This study was supported in part by the Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland and the U. S. Food & Drug Administration. NR 52 TC 40 Z9 45 U1 0 U2 1 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 JAN PY 2009 VL 63 IS 1 BP 95 EP 102 DI 10.1093/jac/dkn448 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 383NT UT WOS:000261681000016 PM 18984645 ER PT J AU McClure, FD Lee, JK AF McClure, Foster D. Lee, Jung. K. TI On Using a Normal Approximation for the Noncentral t-Distribution in Determining Upper Limits for Future Sample Relative Repeatability and Reproducibility Standard Deviations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Formulas, based on a normal approximation for the noncentral t-distribution, were developed to compute 100p% one-tailed upper limits for future sample relative repeatability and relative reproducibility standard deviations (RSD(r),% and RSD(R),%) collaboratively obtained under a completely randomized model. The accuracy of the formulas for obtaining a one-tailed upper limit for the future sample RSD(r),% was assessed by comparing the computed noncentral t-distribution-based upper limits with the one-tailed upper limits based on a normal approximation for the noncentral t-distribution. The accuracy of the normal approximation formula for obtaining a one-tailed upper limit for a future sample RSD(R),% was assessed by comparing the formula-based one-tailed upper limits with those obtained in a Monte Carlo simulation study. C1 [McClure, Foster D.; Lee, Jung. K.] US FDA, Ctr Food Safety & Appl Nutr, Dept Hlth & Human Serv,Div Publ Hlth & Biostat, Off Food Def Commun & Emergency Response, College Pk, MD 20740 USA. RP McClure, FD (reprint author), POB 413, Frederick, MD 21705 USA. EM fdmc5100@yahoo.com NR 8 TC 0 Z9 0 U1 0 U2 0 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2009 VL 92 IS 1 BP 320 EP 328 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 418DJ UT WOS:000264127100040 PM 19396976 ER PT J AU Choi, J Zhang, Q Reipa, V Wang, NS Stratmeyer, ME Hitchins, VM Goering, PL AF Choi, Jonghoon Zhang, Qin Reipa, Vytas Wang, Nam Sun Stratmeyer, Melvin E. Hitchins, Victoria M. Goering, Peter L. TI Comparison of cytotoxic and inflammatory responses of photoluminescent silicon nanoparticles with silicon micron-sized particles in RAW 264.7 macrophages SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE silicon; nanoparticles; macrophages; cytokines; tumor necrosis factor-alpha; interleukin-6; cytotoxicity ID QUANTUM DOTS; ULTRAFINE PARTICLES; CARBON NANOTUBES; CELLULAR UPTAKE; IN-VITRO; TOXICITY; CELLS; LUNG; EXPRESSION; CHALLENGES AB Photoluminescent silicon nanoparticles have a bright and stable fluorescence and are promising candidates for bio-imaging, cell staining and drug delivery. With increasing development of nanotechnology applications for biomedicine, an understanding of the potential toxicity of nanoparticles is needed to assess safety concerns for clinical applications. The objective of this study was to compare biological responses of silicon nanoparticles (SNs, 3 nm diameter) with silicon microparticles (SMs, similar to 100-3000 nm diameter) in cultured murine macrophages (RAW 264.7) using standard protocols for assessing cytotoxicity/cell viability and inflammatory responses developed for micron-sized particles. SNs and SMs were exposed to macrophages with and without addition of endotoxin lipopolysaccharide (LIPS), a positive inducer of tumor necrosis factor-alpha (TNF-alpha), interleukin 6 (IL-6), and nitric oxide (NO). Cytotoxicity was assayed using the dye exclusion and MTT assays. Cell supernatants were assayed for production TNF-alpha, IL-6 and NO. SNs at concentrations <= 20 mu g ml(-1) exhibited no cytotoxicity or inflammatory responses; however, SNs and SMs > 20 and 200 mu g ml(-1), respectively, increased cytotoxicity compared with controls. SMs induced concentration-related increases in TNF-alpha and IL-6 production; in contrast, the production of these cytokines was shown to decrease with increasing concentrations of SNs. NO production was not induced by SNs or SMs alone. Fluorescence microscopy demonstrated that SNs were associated with the macrophages, either internalized or attached to cell membranes. In conclusion, evaluating differences in biological responses for nanoparticles compared with microparticles of the same material may help improve tests to assess biological responses of nanoparticles that may be used in biomedical applications. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Choi, Jonghoon; Zhang, Qin; Stratmeyer, Melvin E.; Hitchins, Victoria M.; Goering, Peter L.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Choi, Jonghoon; Wang, Nam Sun] Univ Maryland, Dept Chem & Biomol Engn, College Pk, MD 20742 USA. [Choi, Jonghoon; Reipa, Vytas] Natl Inst Stand & Technol, Div Biochem Sci, Gaithersburg, MD 20899 USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Bldg 64,Rm 4064, Silver Spring, MD 20993 USA. EM nsw@umd.edu; nsw@umd.edu RI Choi, Jonghoon/A-7693-2011; Wang, Nam Sun/E-4253-2016 OI Choi, Jonghoon/0000-0003-3554-7033; FU NIST-UMD; ORISE (FDA) FX This work was supported by a NIST-UMD research grant and an ORISE (FDA) grant. The authors would like to thank Dr Jayne B. Morrow (NIST), Dr David Kaplan (FDA) and Dr Wen-An Chiou (UMD) for valuable discussions and assistance with fluorescent and electron microscopy measurements. NR 41 TC 56 Z9 58 U1 1 U2 26 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD JAN PY 2009 VL 29 IS 1 BP 52 EP 60 DI 10.1002/jat.1382 PG 9 WC Toxicology SC Toxicology GA 391YV UT WOS:000262271000008 PM 18785685 ER PT J AU Wokovich, AM Brown, SA Shen, M Doub, WH Cai, B Sadrieh, N Chen, ML Machado, S Buhse, LF AF Wokovich, Anna M. Brown, Stanley A. Shen, Meiyu Doub, William H. Cai, Bing Sadrieh, Nakissa Chen, Mei Ling Machado, Stella Buhse, Lucinda F. TI Evaluation of Substrates for 90 degrees Peel Adhesion-A Collaborative Study. II. Transdermal Drug Delivery Systems SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE adhesion; peel; transdermal system; patch; skin AB In a previous study on peel adhesion for medical tapes, it was shown that a stainless steel (SS) substrate better discriminated among medical tapes than a high-density polyethylene (HDPE) substrate. The objective of this study was to determine if a SS substrate would also better distinguish among transdermal drug delivery systems (TDDSs). Five TDDSs (Vivelle Dot (R), Climara (R), Catapres-TTS (R), Duragesic (R)), and Mylan Fentanyl) were evaluated on three different substrates (SS, HDPE, and human cadaver skin). All measurements were made using a dwell time of similar to 3 min, a peel angle of 90 degrees, and a peel speed of 300 mm/min. Differences among TDDSs were greater for SS than for HDPE, using the F statistic for testing for differences among TDDSs means as a measure of heterogeneity, thereby indicating greater discrimination by SS. (c) 2008 Wiley Periodicals, Inc.*J Biomed Maier Res Part B: Appl Biomater 88B: 61-65, 2009 C1 [Wokovich, Anna M.; Doub, William H.; Buhse, Lucinda F.] US FDA, Ctr Drug Evaluat & Res, St Louis, MO USA. [Brown, Stanley A.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Shen, Meiyu; Sadrieh, Nakissa; Chen, Mei Ling; Machado, Stella] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Cai, Bing] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Wokovich, AM (reprint author), US FDA, Ctr Drug Evaluat & Res, St Louis, MO USA. EM anna.wokovich@fda.hhs.gov NR 12 TC 6 Z9 6 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD JAN PY 2009 VL 88B IS 1 BP 61 EP 65 DI 10.1002/jbm.b.31149 PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 386PO UT WOS:000261895300007 PM 18546200 ER PT J AU Hung, HMJ Wang, SJ AF Hung, H. M. James Wang, Sue-Jane TI Some Controversial Multiple Testing Problems in Regulatory Applications SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Composite endpoint; Group-sequential; Intersection-union; Noninferiority; Sequential gate keeping; Studywise; Superiority; Union-intersection ID PRIMARY END-POINTS; CLINICAL-TRIALS AB Multiple testing problems in regulatory applications are often more challenging than the problems of handling a set of mathematical symbols representing multiple null hypotheses under testing. In the union-intersection setting, it is important to define a family of null hypotheses relevant to the clinical questions at issue. The distinction between primary endpoint and secondary endpoint needs to be considered properly in different clinical applications. Without proper consideration, the widely used sequential gate keeping strategies often impose too many logical restrictions to make sense, particularly to deal with the problem of testing multiple doses and multiple endpoints, the problem of testing a composite endpoint and its component endpoints, and the problem of testing superiority and noninferiority in the presence of multiple endpoints. Partitioning the null hypotheses involved in closed testing into clinical relevant orderings or sets can be a viable alternative to resolving the illogical problems requiring more attention from clinical trialists in defining the clinical hypotheses or clinical question(s) at the design stage. In the intersection-union setting there is little room for alleviating the stringency of the requirement that each endpoint must meet the same intended alpha level, unless the parameter space under the null hypothesis can be substantially restricted. Such restriction often requires insurmountable justification and usually cannot be supported by the internal data. Thus, a possible remedial approach to alleviate the possible conservatism as a result of this requirement is a group-sequential design strategy that starts with a conservative sample size planning and then utilizes an alpha spending function to possibly reach the conclusion early. C1 [Hung, H. M. James] US FDA, OB ITS CDER, Div Biometr 1, Silver Spring, MD 20993 USA. [Wang, Sue-Jane] US FDA, OTS CDER, Off Biostat, Silver Spring, MD 20993 USA. RP Hung, HMJ (reprint author), US FDA, OB ITS CDER, Div Biometr 1, 10903 New Hampshire Ave,Bldg 21 Room 4616,HFD-71, Silver Spring, MD 20993 USA. EM hsienming.hung@fda.hhs.gov NR 15 TC 35 Z9 35 U1 0 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 EI 1520-5711 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 1 BP 1 EP 11 AR PII 907426452 DI 10.1080/10543400802541693 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 391QN UT WOS:000262247900001 PM 19127460 ER PT J AU Siddiqui, O Hung, HMJ O'Neill, R AF Siddiqui, Ohidul Hung, H. M. James O'Neill, Robert TI MMRM vs. LOCF: A Comprehensive Comparison Based on Simulation Study and 25 NDA Datasets SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Ignorable missing data; Last observation carried forward; Missing at random; Missing completely at random; Missing not at random ID LONGITUDINAL CLINICAL-TRIALS; PATTERN-MIXTURE MODELS; MISSING DATA; DROP-OUT; INCOMPLETE DATA AB In recent years, the use of the last observation carried forward (LOCF) approach in imputing missing data in clinical trials has been greatly criticized, and several likelihood-based modeling approaches are proposed to analyze such incomplete data. One of the proposed likelihood-based methods is the Mixed-Effect Model Repeated Measure (MMRM) model. To compare the performance of LOCF and MMRM approaches in analyzing incomplete data, two extensive simulation studies are conducted, and the empirical bias and Type I error rates associated with estimators and tests of treatment effects under three missing data paradigms are evaluated. The simulation studies demonstrate that LOCF analysis can lead to substantial biases in estimators of treatment effects and can greatly inflate Type I error rates of the statistical tests, whereas MMRM analysis on the available data leads to estimators with comparatively small bias, and controls Type I error rates at a nominal level in the presence of missing completely at random (MCAR) or missing at random (MAR) and some possibility of missing not at random (MNAR) data. In a sensitivity analysis of 48 clinical trial datasets obtained from 25 New Drug Applications (NDA) submissions of neurological and psychiatric drug products, MMRM analysis appears to be a superior approach in controlling Type I error rates and minimizing biases, as compared to LOCF ANCOVA analysis. In the exploratory analyses of the datasets, no clear evidence of the presence of MNAR missingness is found. C1 [Siddiqui, Ohidul; Hung, H. M. James; O'Neill, Robert] US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Siddiqui, O (reprint author), US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Av, Silver Spring, MD 20993 USA. EM ohidul.siddiqui@fda.hhs.gov NR 28 TC 142 Z9 146 U1 1 U2 6 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 2 BP 227 EP 246 AR PII 908658805 DI 10.1080/10543400802609797 PG 20 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 406JS UT WOS:000263291400001 PM 19212876 ER PT J AU Siddiqui, O AF Siddiqui, Ohidul TI STATISTICAL METHODS TO ANALYZE ADVERSE EVENTS DATA OF RANDOMIZED CLINICAL TRIALS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Adverse events; AEs; Gender; ISS; MCF ID DRUG SAFETY AB The adverse events data of randomized clinical trials are often analyzed based on either crude incidence rates or exposure-adjusted incidence rates. These rates do not adequately account for an individual patient's profile of adverse events over the study period when an individual may remain in the trial after experiencing one or more events (i.e., occurrence of multiple events of the same kind or different kinds). Moreover, the required statistical assumptions (e. g., constant hazard rate over time) for valid estimates of incidence rates are not likely to be met in practice by adverse events data of clinical trials. A nonparametric approach called the mean cumulative function (MCF) provides a valid statistical inference on recurrent adverse event profiles of drugs in randomized clinical trials. The estimate involves no assumptions about the form of MCF. To demonstrate the applicability and utility of the MCF approach in clinical trial datasets, an adverse event dataset obtained from a clinical trial is analyzed in this article. As compared to the crude or exposure-adjusted incidence rates of adverse events, the MCF estimates facilitate more understanding of safety profiles of a drug in a randomized clinical trial. C1 US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, Silver Spring, MD 20993 USA. RP Siddiqui, O (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Translat Sci, Off Biostat, 10903 New Hampshire Ave,Room 4606, Silver Spring, MD 20993 USA. EM ohidul.siddiqui@fda.hhs.gov NR 11 TC 15 Z9 15 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 5 BP 889 EP 899 DI 10.1080/10543400903105463 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 544AJ UT WOS:000273623200010 PM 20183450 ER PT J AU Soon, GX AF Soon, Guoxing (Greg) TI MISSING DATA-PREVENTION AND ANALYSIS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Editorial Material C1 US FDA, Div Biometr 4, Off Biostat, CDER, Silver Spring, MD USA. RP Soon, GX (reprint author), US FDA, Div Biometr 4, Off Biostat, CDER, Silver Spring, MD USA. NR 0 TC 1 Z9 3 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 6 BP 941 EP 944 DI 10.1080/10543400903331226 PG 4 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 544DW UT WOS:000273633700001 PM 20183456 ER PT J AU Walton, MK AF Walton, Marc K. TI ADDRESSING AND ADVANCING THE PROBLEM OF MISSING DATA SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Missing data; Imputation; Prevention; Sensitivity analysis ID MULTIPLE IMPUTATION; TRIAL AB Missing data can pose substantial risk of reaching incorrect conclusions from clinical studies. Imputation for the missing values is common, but can supply only an approximate result desired to be "close enough" to the intended true result. Prevention optimally addresses the issue. Knowledge of the effective techniques to minimize the problem, likely to vary with clinical setting, is presently inadequate. Formal evaluation of preventative methods should be encouraged and lead to publication of the assessments. Designers of clinical trials should also plan for study analysis where missing values occur. Simple imputation methods have been used and may be sufficient in some settings, but have potential to introduce bias and inaccuracy into the statistical analysis. More complex methods such as multiple imputation potentially offer reduced risk of bias. Multiple imputation also offers the potential for study designers to include some auxiliary outcome assessments that may substantially improve the quality of the imputation with limited added burden to the study. In all cases, sensitivity analyses examining the importance of the specific preferred method as compared to methods with different underlying assumptions is essential to assessing how adequately the missing data issue has been addressed. C1 US FDA, Off Translat Sci, CDER, Silver Spring, MD 20993 USA. RP Walton, MK (reprint author), US FDA, Off Translat Sci, CDER, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Marc.walton@fda.hhs.gov NR 18 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 6 BP 945 EP 956 DI 10.1080/10543400903238959 PG 12 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 544DW UT WOS:000273633700002 PM 20183457 ER PT J AU Kong, FH Chen, YF Jin, K AF Kong, Fanhui Chen, Yeh-Fong Jin, Kun TI A BIAS CORRECTION IN TESTING TREATMENT EFFICACY UNDER INFORMATIVE DROPOUT IN CLINICAL TRIALS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Grouping method; Linear mixed effects model; LOCF; MMRM; Non-ignorable (informative) dropout; Treatment efficacy ID LINEAR-MODEL; MISSINGNESS; OUTS AB In clinical trials of drug development, patients are often followed for a certain period of time, and the outcome variables are measured at scheduled time intervals. The main interest of the trial is the treatment efficacy at a prespecified time point, which is often the last visit. In such trials, patient dropout is often the major source for missing data. With possible informative patient dropout, the missing information often causes biases in the inference of treatment efficacy. In this article, for a time-saturated treatment effect model and an informative dropout scheme that depends on the unobserved outcomes only through the random coefficients, we propose a grouping method to correct the biases in the estimation of treatment effect. The asymptotic variance estimator is also obtained for statistical inference. In a simulation study, we compare the new method with the traditional methods of the observed case (OC) analysis, the last observation carried forward (LOCF) analysis, and the mixed model repeated measurement (MMRM) approach, and find it improves the current methods and gives more stable results in the treatment efficacy inferences. C1 [Kong, Fanhui; Chen, Yeh-Fong; Jin, Kun] US FDA, Div Biometr 1, Silver Spring, MD 20993 USA. RP Kong, FH (reprint author), US FDA, Div Biometr 1, HFD 710,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM fanhui.kong@fda.hhs.gov FU U.S. Food and Drug Administration [RSR-04-09, RSR-05-04] FX This research was sponsored by the Regulatory Science and Review Enhancement Fund RSR-04-09 and RSR-05-04 of the U.S. Food and Drug Administration. The authors thank Dr. Hsien Ming Hung for his continuing encouragement and insightful comments and suggestions. They also thank two referees and the guest editor for their helpful comments and suggestions that improved the presentation of this article. NR 15 TC 2 Z9 2 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 6 BP 980 EP 1000 DI 10.1080/10543400903242753 PG 21 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 544DW UT WOS:000273633700005 PM 20183460 ER PT J AU Alosh, M AF Alosh, Mohamed TI THE IMPACT OF MISSING DATA IN A GENERALIZED INTEGER-VALUED AUTOREGRESSION MODEL FOR COUNT DATA SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Dropouts; Integer-valued autoregressive model; Longitudinal count data; Marginal and conditional models ID REGRESSION-MODELS AB The impact of the missing data mechanism on estimates of model parameters for continuous data has been extensively investigated in the literature. In comparison, minimal research has been carried out for the impact of missing count data. The focus of this article is to investigate the impact of missing data on a transition model, termed the generalized autoregressive model of order 1 for longitudinal count data. The model has several features, including modeling dependence and accounting for overdispersion in the data, that make it appealing for the clinical trial setting. Furthermore, the model can be viewed as a natural extension of the commonly used log-linear model. Following introduction of the model and discussion of its estimation we investigate the impact of different missing data mechanisms on estimates of the model parameters through a simulation experiment. The findings of the simulation experiment show that, as in the case of normally distributed data, estimates under the missing completely at random (MCAR) and missing at random (MAR) mechanisms are close to their analogue for the full dataset and that the missing not at random (MNAR) mechanism has the greatest bias. Furthermore, estimates based on imputing the last observed value carried forward (LOCF) for missing data under the MAR assumption are similar to those of the MAR. This latter finding might be attributed to the Markov property underlying the model and to the high level of dependence among successive observations used in the simulation experiment. Finally, we consider an application of the generalized autoregressive model to a longitudinal epilepsy dataset analyzed in the literature. C1 US FDA, Div Biometr 3, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Alosh, M (reprint author), US FDA, Div Biometr 3, Ctr Drug Evaluat & Res, Bldg 21,Room 3626,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Mohamed.Alosh@fda.hhs.gov FU Center for Drug Evaluation and Research, Food and Drug Administration (CDER/FDA) [09-49] FX I thank the editor and two anonymous referees for a thorough review and helpful comments that improved the presentation of the material of the article. This research was supported by the Center for Drug Evaluation and Research, Food and Drug Administration (CDER/FDA) grant RSR # 09-49. NR 22 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 6 BP 1039 EP 1054 DI 10.1080/10543400903242787 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 544DW UT WOS:000273633700008 PM 20183463 ER PT J AU Rothmann, MD Koti, K Lee, KY Lu, HL Shen, YL AF Rothmann, Mark D. Koti, Kallappa Lee, Kyung Yul Lu, Hong Laura Shen, Yuan Li TI MISSING DATA IN BIOLOGIC ONCOLOGY PRODUCTS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Disease-free survival; Intent-to-treat principle; Loss to follow-up; Overall survival; Progression-free survival ID PROGRESSION-FREE SURVIVAL; TRIALS AB The intent-to-treat principle requires analyses according to the treatment groups to which patients were randomized and that patients be followed to the occurrence of the endpoint or the end of study. This provides unbiased comparisons with valid p values. For many trials the limitations of the data will not be known until the data are analyzed. In this article, the loss-to-follow-up with respect to the intent-to-treat principle on the most important efficacy endpoints was evaluated for clinical trials of anticancer biologic products submitted to the FDA from August 2005 to October 2008. We provide recommendations in light of the results. C1 [Rothmann, Mark D.; Koti, Kallappa; Lee, Kyung Yul; Lu, Hong Laura; Shen, Yuan Li] US FDA, Div Biometr 5, Silver Spring, MD 20993 USA. RP Rothmann, MD (reprint author), US FDA, Div Biometr 5, 10903 New Hampshire Ave,HFD 711,Bldg 21, Silver Spring, MD 20993 USA. EM Mark.Rothmann@fda.hhs.gov NR 9 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 6 BP 1074 EP 1084 DI 10.1080/10543400903242993 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 544DW UT WOS:000273633700010 PM 20183465 ER PT J AU Yan, X Lee, S Li, N AF Yan, Xu Lee, Shiowjen Li, Ning TI MISSING DATA HANDLING METHODS IN MEDICAL DEVICE CLINICAL TRIALS SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Clinical trials; Dropout; Imputation methods; Missing data; Missing data mechanism; Tipping-point analysis AB One of the major problems in the analysis of clinical trials is missing data caused by patients dropping out before study completion. The issue of missing data can result in biased treatment comparisons and can impact the interpretation of study results. Since the missing data mechanism is unknown and unverifiable in most situations, regulatory agencies often request various sensitivity analyses for handling missing data to evaluate the robustness of study results. This article discusses methods used to handle missing data in medical device clinical trials, focusing on tipping-point analysis as a general approach for the assessment of missing data impact. Tipping points are outcomes that result in a change of study conclusion. Such outcomes can be conveyed to clinical reviewers to determine if they are implausibly unfavorable. The analysis aids clinical reviewers in making judgment regarding treatment effect in the study. Three examples with a reasonably representative range of missing data rate are included to illustrate the methods referred. C1 [Yan, Xu; Lee, Shiowjen; Li, Ning] US FDA, Silver Spring, MD 20993 USA. RP Li, N (reprint author), US FDA, 10903 New Hampshire Ave,Rm 66-2120, Silver Spring, MD 20993 USA. EM ericylee1@gmail.com NR 10 TC 18 Z9 19 U1 0 U2 11 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 6 BP 1085 EP 1098 DI 10.1080/10543400903243009 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 544DW UT WOS:000273633700011 PM 20183466 ER PT J AU Nie, L Chu, H Cheng, Y Spurney, C Nagaraju, K Chen, J AF Nie, L. Chu, H. Cheng, Y. Spurney, C. Nagaraju, K. Chen, J. TI MARGINAL AND CONDITIONAL APPROACHES TO MULTIVARIATE VARIABLES SUBJECT TO LIMIT OF DETECTION SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE Limit of detection; Marginal approach; Maximum likelihood estimate; Variance-component mixed effect model ID MIXTURE DISTRIBUTIONS; CENSORED-DATA; SAMPLE-SIZE; 2-PART MODELS; INTERVENTIONS; CONTEXT; POWER; ASSAYS; ZEROS AB A marginal approach and a variance-component mixed effect model approach (here called a conditional approach) are commonly used to analyze variables that are subject to limit of detection. We examine the theoretical relationship and investigate the numerical performance of these two approaches. We make some recommendations based on our results. The marginal approach is recommended for bivariate normal variables, and the variance-component mixed effect model is preferable for other multivariate analysis in most circumstances. Two approaches are illustrated through one case study from a preclinical experiment. C1 [Nie, L.] US FDA, Div Biometr 4, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. [Chu, H.] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. [Chu, H.] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Cheng, Y.; Spurney, C.; Nagaraju, K.] Childrens Natl Med Ctr, Res Ctr Genet Med, Childrens Natl Heart Inst, Washington, DC 20010 USA. [Chen, J.] Abbott Labs, Abbott Pk, IL 60064 USA. RP Nie, L (reprint author), US FDA, Div Biometr 4, Off Biostat, OTS,CDER, Silver Spring, MD 20993 USA. EM lei.nie@fda.hhs.gov RI Chu, Haitao /J-7576-2012; OI Chu, Haitao/0000-0003-0932-598X FU U.S. National Cancer Institute [CA16086]; U.S. National Institutes of Health [P30-AI-50410] FX We thank the editor and two referees for their very insightful and constructive comments, which have greatly improved the quality of the article. Dr. Chu was supported in part by the Lineberger Cancer Center Core Grant CA16086 from the U.S. National Cancer Institute and P30-AI-50410 from the U.S. National Institutes of Health. NR 22 TC 4 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2009 VL 19 IS 6 BP 1151 EP 1161 DI 10.1080/10543400903243033 PG 11 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 544DW UT WOS:000273633700014 PM 20183469 ER PT J AU Scherr, D Dalal, D Cheema, A Nazarian, S Almasry, I Bilchick, K Cheng, A Henrikson, CA Spragg, D Marine, JE Berger, RD Calkins, H Dong, J AF Scherr, Daniel Dalal, Darshan Cheema, Aamir Nazarian, Saman Almasry, Ibrahim Bilchick, Kenneth Cheng, Alan Henrikson, Charles A. Spragg, David Marine, Joseph E. Berger, Ronald D. Calkins, Hugh Dong, Jun TI Long- and Short-Term Temporal Stability of Complex Fractionated Atrial Electrograms in Human Left Atrium During Atrial Fibrillation SO JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY LA English DT Article DE atrial fibrillation; complex atrial electrogram; atrium; mapping; ablation ID CATHETER ABLATION; AUTOMATED DETECTION; SUBSTRATE ABLATION; PULMONARY VEINS; TERMINATION; SITES; HEART AB Background: Complex fractionated atrial electrograms (CFAEs) have been reported as targets for catheter ablation of atrial fibrillation (AF). However, the temporal stability of CFAE sites remains poorly defined. Methods and Results: The study consisted of two phases. In the initial phase, two automated software algorithms, namely the interval confidence level (ICL) and the average interpotential interval (AIPI) were assessed for their diagnostic accuracy for automated CFAE detection. The AIPI was found to be superior to the ICL, and an AIPI of <= 100 ms was associated with a sensitivity and specificity of both 92% for detection of CFAEs. In the second phase of the study, 12 patients (2 females, mean age 54 +/- 12 years) who underwent catheter ablation for persistent AF were studied to investigate the temporal stability of CFAEs. Two consecutive left atrial (LA) three-dimensional CFAE maps coded with AIPI readings were reconstructed during ongoing AF in each study patient, with a mean time difference of 34.3 +/- 8.7 minutes between the two maps. Among a total of 149 CFAE sites and 238 non-CFAE sites on the first CFAE map that were precisely revisited during the repeat mapping process, 135 (90.6%) and 225 (94.5%) remained as CFAE sites and non-CFAE sites, respectively. RF ablation at the selected stable CFAE sites significantly prolonged AF cycle length (181 +/- 26 ms to 199 +/- 29 ms, P < 0.0001). Conclusion: CFAEs recorded in the LA during AF display high temporal stability in patients with persistent AF. The clinical significance of our findings warrants further investigation. (J Cardiovasc Electrophysiol, Vol. 20, pp. 13-21, January 2009). C1 [Dong, Jun] US FDA, Div Cardiovasc Devices, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. [Scherr, Daniel; Dalal, Darshan; Cheema, Aamir; Nazarian, Saman; Almasry, Ibrahim; Bilchick, Kenneth; Cheng, Alan; Henrikson, Charles A.; Spragg, David; Marine, Joseph E.; Berger, Ronald D.; Calkins, Hugh; Dong, Jun] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Scherr, Daniel] Med Univ Graz, Dept Med, Div Cardiol, Graz, Austria. RP Dong, J (reprint author), US FDA, Div Cardiovasc Devices, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-450, Rockville, MD 20850 USA. EM jun.dong@fda.hhs.gov FU FWF Austrian Science Fund; The Norbert and Louise Grunwald Cardiac Arrhythmia Research Fund FX Dr. Daniel Scherr is supported by a research grant of the FWF Austrian Science Fund. Dr. Jun Dong was supported by The Norbert and Louise Grunwald Cardiac Arrhythmia Research Fund. NR 30 TC 26 Z9 27 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1045-3873 J9 J CARDIOVASC ELECTR JI J. Cardiovasc. Electrophysiol. PD JAN PY 2009 VL 20 IS 1 BP 13 EP 21 DI 10.1111/j.1540-8167.2008.01278.x PG 9 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 388WE UT WOS:000262049900003 PM 18775047 ER PT J AU Sun, JC Schnackenberg, LK Holland, RD Schmitt, TC Cantor, GH Dragan, YR Beger, RD AF Sun, Jinchun Schnackenberg, Laura K. Holland, Ricky D. Schmitt, Thomas C. Cantor, Glenn H. Dragan, Yvonne R. Beger, Richard D. TI Metabonomics evaluation of urine from rats given acute and chronic doses of acetaminophen using NMR and UPLC/MS (vol 871, pg 328, 2008) SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Correction C1 [Sun, Jinchun; Schnackenberg, Laura K.; Holland, Ricky D.; Schmitt, Thomas C.; Dragan, Yvonne R.; Beger, Richard D.] US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Cantor, Glenn H.] Pharmacia Corp, Invest Toxicol, Kalamazoo, MI 49001 USA. RP Beger, RD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM Richard.Beger@fda.hhs.gov NR 1 TC 0 Z9 0 U1 2 U2 13 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 JAN 1 PY 2009 VL 877 IS 1-2 BP 105 EP 105 DI 10.1016/j.jchromb.2008.11.019 PG 1 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 396VB UT WOS:000262618200018 ER PT J AU Hong, HX Hong, QL Perkins, R Shi, LM Fang, H Su, ZQ Dragan, Y Fuscoe, JC Tong, WD AF Hong, Huixiao Hong, Qilong Perkins, Roger Shi, Leming Fang, Hong Su, Zhenqiang Dragan, Yvonne Fuscoe, James C. Tong, Weida TI The Accurate Prediction of Protein Family from Amino Acid Sequence by Measuring Features of Sequence Fragments SO JOURNAL OF COMPUTATIONAL BIOLOGY LA English DT Article DE prediction; protein family; protein feature; recognition; sequence ID HIDDEN MARKOV-MODELS; SUPPORT VECTOR MACHINES; COUPLED RECEPTORS; CLASSIFICATION; MULTICLASS; INFORMATION AB The rapid advances in proteomic analyses coupled with the completion of multiple genomes have led to an increased demand for determining protein functions. The first step is classification or prediction into families. A method was developed for the prediction of protein family based only on protein sequence using support vector machine (SVM) models. In these models, the amino acids were classified into three categories (apolar, polar, and charged). Consecutive fragments ranging from one to five were annotated by amino acid type to define the protein features of each protein. SVM models were constructed based on the protein features of a training set of proteins and then examined with an independent set of proteins. The approach was tested for 20 protein families from the iProClass database of Protein Information Resources (PIR). For two-class SVM models, an average prediction accuracy of 0.9985 was achieved, while for multi-class SVM models an accuracy of 0.9941 was achieved. This study demonstrates that SVM based methods can accurately recognize and predict the protein family to which a sequence belongs based solely on its primary amino acid sequence. C1 [Hong, Huixiao; Shi, Leming; Su, Zhenqiang; Dragan, Yvonne; Fuscoe, James C.; Tong, Weida] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Hong, Qilong] Univ Arkansas, Dept Mech Engn, Fayetteville, AR 72701 USA. [Perkins, Roger; Fang, Hong] US FDA, Div Bioinformat, ICF Int Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Hong, HX (reprint author), US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Huixiao.Hong@fda.hhs.gov RI Su, Zhenqiang/H-3914-2012 NR 21 TC 7 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1066-5277 J9 J COMPUT BIOL JI J. Comput. Biol. PY 2009 VL 16 IS 12 BP 1671 EP 1688 DI 10.1089/cmb.2008.0115 PG 18 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 545CG UT WOS:000273709400004 PM 20047490 ER PT J AU Ray, PC Yu, HT Fu, PP AF Ray, Paresh Chandra Yu, Hongtao Fu, Peter P. TI Toxicity and Environmental Risks of Nanomaterials: Challenges and Future Needs SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Nanomaterials; silver; gold; carbon; metal oxides; toxicity; environmental impact ID TITANIUM-DIOXIDE NANOPARTICLES; HUMAN EPIDERMAL-KERATINOCYTES; SEMICONDUCTOR QUANTUM DOTS; RESONANCE ENERGY-TRANSFER; WALL CARBON NANOTUBES; METAL-ENHANCED FLUORESCENCE; DNA HYBRIDIZATION DETECTION; SURFACE-PLASMON RESONANCE; GOLD NANOPARTICLES; ULTRAFINE-PARTICLES AB Nanotechnology has gained a great deal of public interest because of the needs and applications of nanomaterials in many areas of human endeavors including industry, agriculture, business, medicine, and public health. Environmental exposure to nanomaterials is inevitable as nanomaterials become part of our daily life, and, as a result, nanotoxicity research is gaining attention. This review presents a summary of recent research efforts on fate, behavior, and toxicity of different classes of nanomaterials in the environment. A critical evaluation of challenges and future needs for the safe environmental nanotechnology are discussed. C1 [Ray, Paresh Chandra; Yu, Hongtao] Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. [Fu, Peter P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Ray, PC (reprint author), Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. EM paresh.c.ray@jsums.edu FU NCRR NIH HHS [G12 RR013459-078175]; NIGMS NIH HHS [S06 GM008047] NR 192 TC 97 Z9 101 U1 16 U2 91 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2009 VL 27 IS 1 BP 1 EP 35 AR PII 908589297 DI 10.1080/10590500802708267 PG 35 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 405DY UT WOS:000263204100001 PM 19204862 ER PT J AU Benfenati, E Benigni, R DeMarini, DM Helma, C Kirkland, D Martin, TM Mazzatorta, P Ouedraogo-Arras, G Richard, AM Schilter, B Schoonen, WGEJ Snyder, R Yang, C AF Benfenati, E. Benigni, R. DeMarini, D. M. Helma, C. Kirkland, D. Martin, T. M. Mazzatorta, P. Ouedraogo-Arras, G. Richard, A. M. Schilter, B. Schoonen, W. G. E. J. Snyder, R. D. Yang, C. TI Predictive Models for Carcinogenicity and Mutagenicity: Frameworks, State-of-the-Art, and Perspectives SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Carcinogenicity; mutagenicity; QSAR; in silico; predictive methods ID FOLLOW-UP; SACCHAROMYCES-CEREVISIAE; TOXICITY DATABASES; GENOTOXICITY ASSAY; CANCER MORTALITY; AROMATIC-AMINES; QSAR MODELS; TOXICOLOGY; CHEMICALS; REPAIR AB Mutagenicity and carcinogenicity are endpoints of major environmental and regulatory concern. These endpoints are also important targets for development of alternative methods for screening and prediction due to the large number of chemicals of potential concern and the tremendous cost (in time, money, animals) of rodent carcinogenicity bioassays. Both mutagenicity and carcinogenicity involve complex, cellular processes that are only partially understood. Advances in technologies and generation of new data will permit a much deeper understanding. In silico methods for predicting mutagenicity and rodent carcinogenicity based on chemical structural features, along with current mutagenicity and carcinogenicity data sets, have performed well for local prediction (i.e., within specific chemical classes), but are less successful for global prediction (i.e., for a broad range of chemicals). The predictivity of in silico methods can be improved by improving the quality of the data base and endpoints used for modelling. In particular, in vitro assays for clastogenicity need to be improved to reduce false positives (relative to rodent carcinogenicity) and to detect compounds that do not interact directly with DNA or have epigenetic activities. New assays emerging to complement or replace some of the standard assays include Vitotox, GreenScreenGC, and RadarScreen. The needs of industry and regulators to assess thousands of compounds necessitate the development of high-throughput assays combined with innovative data-mining and in silico methods. Various initiatives in this regard have begun, including CAESAR, OSIRIS, CHEMOMENTUM, CHEMPREDICT, OpenTox, EPAA, and ToxCast. In silico methods can be used for priority setting, mechanistic studies, and to estimate potency. Ultimately, such efforts should lead to improvements in application of in silico methods for predicting carcinogenicity to assist industry and regulators and to enhance protection of public health. C1 [Benfenati, E.] Ist Ric Farmacol Mario Negri, Lab Environm & Chem Toxicol, I-20156 Milan, Italy. [Benigni, R.] Ist Super Sanita, Environm & Hlth Dept, I-00161 Rome, Italy. [DeMarini, D. M.] US EPA, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. [Helma, C.] Silico Toxicol, Basel, Switzerland. [Kirkland, D.] Covance Labs Ltd, Harrogate, England. [Martin, T. M.] US EPA, Sustainable Technol Div, Natl Risk Management Res Lab, Cincinnati, OH 45268 USA. [Mazzatorta, P.; Schilter, B.] Nestle Res Ctr, Qual & Safety Dept, CH-1000 Lausanne, Switzerland. [Ouedraogo-Arras, G.] LOreal, Safety Res Dept, Aulnay Sous Bois, France. [Richard, A. M.] US EPA, Natl Ctr Computat Toxicol, Res Triangle Pk, NC 27711 USA. [Schoonen, W. G. E. J.] Schering Plough Res Inst, Oss, Netherlands. [Snyder, R. D.] Schering Plough Res Inst, Summit, NJ USA. [Yang, C.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Benfenati, E (reprint author), Ist Ric Farmacol Mario Negri, Lab Environm & Chem Toxicol, Via Masa 19, I-20156 Milan, Italy. EM benfenati@marionegri.it RI Embrett, Mark/H-4466-2014 OI Embrett, Mark/0000-0002-3969-0219 FU European Commission [SP5A-CT-2007-044166] FX We acknowledge the financial support of the European Commission, project SCARLET, contract no. SP5A-CT-2007-044166. This manuscript has been reviewed by the National Health and Environmental Effects Research Laboratory and National Center for Computational Toxicology, U. S. Environmental Protection Agency, and is approved for publication. Approval does not signify that the contents reflect the views of the Agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use. NR 78 TC 57 Z9 57 U1 3 U2 31 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1059-0501 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2009 VL 27 IS 2 BP 57 EP 90 AR PII 910915395 DI 10.1080/10590500902885593 PG 34 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 439UV UT WOS:000265653700001 PM 19412856 ER PT J AU Fu, PP Chiang, HM Xia, QS Chen, T Chen, BH Yin, JJ Wen, KC Lin, G Yu, HT AF Fu, Peter P. Chiang, Hsiu-Mei Xia, Qingsu Chen, Tao Chen, Bai Hsiun Yin, Jue-Jie Wen, Kuo-Ching Lin, Ge Yu, Hongtao TI Quality Assurance and Safety of Herbal Dietary Supplements SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE Herbal dietary supplements; Chinese traditional herbs; quality assurance; toxicological effects ID DNA ADDUCT FORMATION; CHINESE MEDICINAL HERBS; FORMATION IN-VIVO; ARISTOLOCHIC ACID; PYRROLIZIDINE ALKALOIDS; METABOLIC-ACTIVATION; GINKGO-BILOBA; LIGUSTICUM-CHUANXIONG; KAVA EXTRACT; INFRARED-SPECTROSCOPY AB Since the U.S. Congress passed the Dietary Supplement Health and Education Act (DSHEA) in 1994, use of herbal products has been growing rapidly worldwide. To ensure consumer health protection, the quality and safety of herbal plants, particularly those used for dietary supplement preparations, must be determined. To date, toxicological data on the identification of genotoxic and tumorigenic ingredients in many raw herbs and their mechanisms of action are lacking. Thus, identification of carcinogenic components in herbal plants is timely and important. In this review, the issues of quality control and safety evaluation of raw herbs and herbal dietary supplements are discussed. Two examples of tumorigenicity and mechanism of tumor induction are discussed: aristolochic acid and riddelliine, both of which have been detected in Chinese herbal plants. It is proposed that an organized effort with international participation on cancer risk assessment should be actively pursued so that the safety of commercial herbal plants and herbal dietary supplements can be ensured. C1 [Fu, Peter P.; Xia, Qingsu; Chen, Tao] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chiang, Hsiu-Mei; Wen, Kuo-Ching] China Med Univ, Dept Cosmeceut, Taichung, Taiwan. [Chen, Bai Hsiun] Kaohsiung Med Univ, Coll Med, Kaohsiung, Taiwan. [Yin, Jue-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Lin, Ge] Chinese Univ Hong Kong, Dept Pharmacol, Hong Kong, Hong Kong, Peoples R China. [Yu, Hongtao] Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM peter.fu@fda.hhs.gov RI Chiang, Hsiu-Mei/L-8150-2013; Yin, Jun Jie /E-5619-2014 NR 117 TC 37 Z9 37 U1 1 U2 23 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 530 WALNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1059-0501 EI 1532-4095 J9 J ENVIRON SCI HEAL C JI J. Environ. Sci. Health Pt. C-Environ. Carcinog. Ecotoxicol. Rev. PY 2009 VL 27 IS 2 BP 91 EP 119 AR PII 910916326 DI 10.1080/10590500902885676 PG 29 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 439UV UT WOS:000265653700002 PM 19412857 ER PT J AU Schlesser, JE Parisi, B AF Schlesser, Joseph E. Parisi, Brian TI Inactivation of Yersinia pseudotuberculosis 197 and Francisella tularensis LVS in Beverages by High Pressure Processing SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI; FRUIT JUICES AB In 2003, the U.S. Department of Health and Human Services announced a new research program to develop technologies and strategies to prevent and minimize potential food safety and security threats. The threat of terrorist attacks against the nation's food supplies has created the need to study microorganisms not typically associated with foodborne illness. High-pressure processing has been proposed as a treatment to reduce Yersinia pestis and Francisella tularensis LVS levels in beverages. The objectives of this work were to determine the pressure resistance of Y. pseudotuberculosis 197 (surrogate for Y. pestis) and F. tularensis LVS (vaccine strain). For each bacterium, samples of ultrahigh-temperature pasteurized skim milk and pasteurized reduced-acid orange juice (pH ca. 4.2) were inoculated at a minimum level of 5 log CFU/ml. Ten-milliliter samples of the inoculated product were vacuum sealed in polyester pouches and subjected to pressures of 300 and 500 MPa for holding times ranging from 30 s to 6 min. One set of trials was performed at an initial temperature of 10 degrees C and another at 25 degrees C. Processed samples were immediately plated and enumerated. A pressure treatment of 300 MPa at 25 degrees C for less than 6 min was not sufficient to achieve a 5-log reduction of Y. pseudotuberculosis 197 or F. tularensis LVS in milk. However, a pressure treatment of 500 MPa was effective at hold times as low as 30 s. Overall, F. tularensis LVS demonstrated less pressure resistance than Y. pseudotuberculosis 197. Based on these findings, a high-pressure process designed to inactivate 5 log CFU of Y. pseudotuberculosis 197 per ml and F. tularensis LVS in orange juice or milk should be set at or above 500 MPa with a hold time of 2 min or greater. C1 [Schlesser, Joseph E.] US FDA, Rockville, MD 20857 USA. [Parisi, Brian] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Schlesser, JE (reprint author), US FDA, Rockville, MD 20857 USA. EM joseph.schlesser@fda.hhs.gov FU U.S. Food and Drug Administration [FD-000431]; National Center for Food Safety and Technology FX This research was supported by Cooperative Agreement No. FD-000431 from the U.S. Food and Drug Administration and the National Center for Food Safety and Technology. The contents of this article are solely the opinions of the authors and do not necessarily represent the official view of the FDA. The authors acknowledge the Staff of NCFST and CFSAN for their help and guidance in this research. NR 13 TC 3 Z9 3 U1 1 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 JAN PY 2009 VL 72 IS 1 BP 165 EP 168 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 393BO UT WOS:000262346100024 PM 19205479 ER PT J AU Piccotti, JR Lebrec, HN Evans, E Herzyk, DJ Hastings, KL Burns-Naas, LA Gourley, IS Wierda, D Kawabata, TT AF Piccotti, Joseph R. Lebrec, Herve N. Evans, Ellen Herzyk, Danuta J. Hastings, Kenneth L. Burns-Naas, Leigh Ann Gourley, Ian S. Wierda, Daniel Kawabata, Thomas T. TI Summary of a workshop on nonclinical and clinical immunotoxicity assessment of immunomodulatory drugs SO JOURNAL OF IMMUNOTOXICOLOGY LA English DT Editorial Material DE Immunomodulators; immunotoxicity; ITC; Workshop; anti-inflammatory ID NECROSIS-FACTOR-ALPHA; MONOCLONAL-ANTIBODY AB The number of anti-inflammatory and immunomodulatory drugs being developed in the pharmaceutical industry has increased considerably in the past decade. This increase in research and development has been paralleled by questions from both regulatory agencies and industry on how best to assess decreased host resistance to infections or adverse immunostimulation caused by immunomodulatory agents such as anti-cytokine antibodies (e.g., the tumor necrosis factor-alpha inhibitors), anti-adhesion molecule antibodies (e.g., anti-alpha-4 integrin inhibitors) and immunostimulatory molecules (e.g., anti-CD28 antibodies). Although several methods have been developed for nonclinical assessment of immunotoxicity, highly publicized adverse events have brought to light significant gaps in the application of nonclinical immunotoxicity testing in assessing potential risk in humans. Confounding this problem is inconsistent application of immunotoxicology methods for risk assessment within the scientific community, limited understanding of appropriate immunotoxicity testing strategy for immunomodulators and inconsistent testing requests by regulatory agencies. To address these concerns, The Immunotoxicology Technical Committee (ITC) of the International Life Science Institute (ILSI) Health and Environmental Sciences Institute (HESI) organized a workshop on Immunomodulators and Clinical Immunotoxicology in May 2007. The Workshop was convened to identify key gaps in nonclinical and clinical immunotoxicity testing of anti-inflammatory and immunomodulatory agents and to begin to develop consistent approaches for immunotoxicity testing and risk assessment. This paper summarizes the outcome of the HESI ITC Immunomodulators and Clinical Immunotoxicology Workshop. Topics not discussed at the Workshop were outside the scope of this report. Although more work is needed to develop consistent approaches for immunotoxicity assessment of immunomodulators, this Workshop provided the foundation for future discussion. C1 [Piccotti, Joseph R.; Evans, Ellen] Schering Plough Res Inst, Summit, NJ 07901 USA. [Piccotti, Joseph R.; Evans, Ellen] Schering Plough Res Inst, Lafayette, NJ USA. [Lebrec, Herve N.] Amgen Inc, Toxicol, Seattle, WA USA. [Herzyk, Danuta J.] Merck & Co Inc, Dept Safety Assessment, West Point, PA USA. [Hastings, Kenneth L.] United States Food & Drug Adm, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Burns-Naas, Leigh Ann; Kawabata, Thomas T.] Pfizer Global Res & Dev, Drug Safety Res & Dev, San Diego, CA USA. [Burns-Naas, Leigh Ann; Kawabata, Thomas T.] Pfizer Global Res & Dev, Drug Safety Res & Dev, Groton, CT USA. [Gourley, Ian S.] Wyeth Res, Early Dev & Clin Pharmacol, Collegeville, PA USA. [Wierda, Daniel] Eli Lilly & Co, Immunotoxicol, Greenfield, IN USA. RP Piccotti, JR (reprint author), Schering Plough Res Inst, 556 Morris Ave, Summit, NJ 07901 USA. EM joseph.piccotti@spcorp.com NR 14 TC 8 Z9 9 U1 0 U2 0 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1547-691X J9 J IMMUNOTOXICOL JI J. Immunotoxicol. PY 2009 VL 6 IS 1 BP 1 EP 10 DI 10.1080/15476910802656440 PG 10 WC Toxicology SC Toxicology GA 481HE UT WOS:000268797500001 PM 19519157 ER PT J AU Link, JM Anderson, L Collins, J AF Link, J. M. Anderson, L. Collins, J. TI SYNTHESIS OF [C-11]-DOXORUBICIN SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Meeting Abstract C1 [Link, J. M.] Univ Washington, Dept Radiol, Div Nucl Med, Seattle, WA 98195 USA. [Anderson, L.] US FDA, Lab Clin Pharmacol, Silver Spring, MD USA. [Collins, J.] NCI, NIH, Dev Therapeut Program, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PY 2009 VL 52 BP S430 EP S430 PG 1 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 480HQ UT WOS:000268724900431 ER PT J AU Shah, D Vidal, S Link, MA Rubin, SA Wright, KE AF Shah, Dion Vidal, Silvia Link, Malen A. Rubin, Steven A. Wright, Kathryn E. TI Identification of Genetic Mutations Associated With Attenuation and Changes in Tropism of Urabe Mumps Virus SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE Mumps virus; attenuation; vaccine; mutations ID HEMAGGLUTININ-NEURAMINIDASE PROTEIN; RECOMBINANT VACCINIA VIRUS; SIALIC-ACID-BINDING; MEASLES-VIRUS; NUCLEOTIDE-SEQUENCE; POLYMERASE PROTEIN; PHOSPHOPROTEIN-P; RNA-POLYMERASE; SENDAI-VIRUS; F-GENE AB Although several effective mumps virus vaccines have been developed, almost nothing is known about the genetic changes responsible for loss of virulence. One vaccine, Urabe AM9, was withdrawn from the market because of insufficient attenuation. The vaccine was found to contain a mixture of viruses that could be distinguished based on the sequence of the hemagglutinin-neuraminidase gene (HN). Viruses containing lysine at HN amino acid position 335 were isolated from cases of post-vaccination parotitis or meningitis whereas viruses containing glutamic acid at this position were not associated with post-vaccination disease. Using a rat based model of mumps neurovirulence, we demonstrate that this latter virus is significantly attenuated compared to a virus isolated from a patient with post-vaccination meningitis. Complete sequence analysis of the genomes of the two viruses identified sixteen genetic differences, some or all of which must be responsible for differences in virulence. These same genetic differences also account for changes in tropism in cell culture. J. Med. Virol. 81:130-138, 2009. (c) 2008 Wiley-Liss, Inc. C1 [Shah, Dion; Wright, Kathryn E.] Univ Ottawa, Dept Biochem Microbiol & Immunol, Ottawa, ON, Canada. [Vidal, Silvia] McGill Univ, Dept Human Genet, Montreal, PQ, Canada. [Link, Malen A.; Rubin, Steven A.] US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Wright, KE (reprint author), BMI, 451 Smyth Rd, Ottawa, ON K1H 8M5, Canada. EM kwright@uottawa.ca FU Natural Sciences and Engineering Research Council of Canada; NSERC; Canadian Foundation for Innovation, CFI; Premier's Research Excellence Award FX Grant sponsor: Natural Sciences and Engineering Research Council of Canada (partial support), NSERC (to K.W.); Grant sponsor: Canadian Foundation for Innovation, CFI (to S.V.); Grant sponsor: Premier's Research Excellence Award (PREA) (to S.V.). NR 54 TC 8 Z9 8 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 JAN PY 2009 VL 81 IS 1 BP 130 EP 138 DI 10.1002/jmv.21381 PG 9 WC Virology SC Virology GA 377QU UT WOS:000261266500017 PM 19031463 ER PT J AU Kazeminy, A Hashemi, S Williams, RL Ritchie, GE Rubinovitz, R Sen, S AF Kazeminy, Assad Hashemi, Saeed Williams, Roger L. Ritchie, Gary E. Rubinovitz, Ronad Sen, Sumit TI A comparison of near infrared method development approaches using a drug product on different spectrophotometers and chemometric software algorithms SO JOURNAL OF NEAR INFRARED SPECTROSCOPY LA English DT Article DE near infrared (NIR) spectroscopy; instrument variability; chemometric software algorithms; multivariate discriminant analysis; PCA ID STANDARD PRACTICE; SPECTROSCOPY; MULTIVARIATE AB It is welt known that spectral variability in near infrared (NIR) spectroscopy can be attributed to the analyst, sample, sample positioning, instrument configuration and software (in both algorithm formats and structures used as welt as in the execution of data pre-treatment and anatysis). It is often acknowledged that the single largest factor impacting NIR results is sample presentation. However, what is obvious but not often acknowledged is that there are instrumental and software differences as well. These differences, evident in the quality of the spectra, may impact the chemometrics that are subsequently performed and, possibly, the results obtained from the multivariate statistical models. In order to investigate just what are these sources of variability, and just how much these variations may impact the results of the multivariate models for predicting the identification of pharmaceutical dosage forms, a study has been conducted. To the authors' knowledge, no other systematic study of this kind has been published. In this study, we are interested in learning what variability, if any, the choices for instrument and software have on the development of a NIR method for the identification of pharmaceutical dosage forms. Furthermore, we would Like to learn what and how do the choices made early on in the experimental design impact the final quality of the spectra and the resulting multivariate models obtained from these spectra. A study protocol was designed, using a common data set consisting of four formulations of Ibuprofen, involving three investigating parties, namely, US FDA. USP and Irvine Pharmaceutical Services and using three NIR instruments, namely (listed in alphabetical order), a Bruker spectrometer, a Buchi spectrometer and a Foss spectrometer. Based on the results and despite differences in instrument configuration [dispersive or Fourier Transform (FT)], number of spectral data points, principal components analysis (PCA) or factorisation algorithms, and validation modelling approach, exact and accurate spectroscopic results can be achieved using NIR spectroscopy for discriminate analysis. More importantly, this study shows that the same NIR method spectral range and pre-treatment parameters can be used, and that nearly the same multivariate models can be obtained, despite instrumental and software differences, to accurately predict the identity of pharmaceutical dosage forms. C1 [Sen, Sumit] US FDA, Irvine, CA 92612 USA. [Kazeminy, Assad; Hashemi, Saeed] Irvine Pharmaceut Serv Inc, Irvine, CA 92618 USA. [Williams, Roger L.; Ritchie, Gary E.] United States Pharmacopeial Convent, Rockville, MD 20852 USA. [Rubinovitz, Ronad] Buchi Corp, New Castle, DE 19720 USA. RP Sen, S (reprint author), US FDA, 19701 Fairchild, Irvine, CA 92612 USA. EM sumit_sen@hotmail.com NR 12 TC 3 Z9 3 U1 0 U2 3 PU N I R PUBLICATIONS PI CHICHESTER PA 6 CHARLTON MILL, CHARLTON, CHICHESTER PO18 0HY, WEST SUSSEX, ENGLAND SN 0967-0335 J9 J NEAR INFRARED SPEC JI J. Near Infrared Spectrosc. PY 2009 VL 17 IS 5 BP 233 EP 245 DI 10.1255/jnirs.854 PG 13 WC Chemistry, Applied; Spectroscopy SC Chemistry; Spectroscopy GA 523VA UT WOS:000272101500001 ER PT J AU Mohan, KVK Zhang, CX Atreya, CD AF Mohan, Ketha V. K. Zhang, Cheryl X. Atreya, Chintamani D. TI The proteoglycan bamacan is a host cellular ligand of vaccinia virus neurovirulence factor N1L SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE chondroitin sulfate; CSPG6; GFP; poxvirus; SMC3; WR strain ID SURFACE HEPARAN-SULFATE; CHONDROITIN-SULFATE; PROTEIN BINDS; CDNA CLONING; IN-VITRO; SMALLPOX; BRAIN; CELLS; GENE; OVEREXPRESSION AB Neurovirulence is one of the pathological complications associated with vaccinia virus (VV) infection/vaccination. Although the viral N1L protein has been identified as the neurovirulence factor, none of the host N1L-interacting factors have been identified so far. In the present study, we identified N1L-interacting proteins by screening a human brain cDNA expression library with N1L as a bait protein in a yeast two-hybrid analysis. The analysis revealed that N1L interacts with human brain-originated cellular basement membrane-associated chondroitin sulfate proteoglycan ( bamacan). The N1L-binding domain of bamacan was mapped to its C-terminal 227 amino acids. The N1L-bamacan interaction was further confirmed in both VV-infected and N1L-transfected mammalian cells. Following the confirmation of the protein interactions by coimmunoprecipitation experiments, confocal microscopic analysis revealed that N1L colocalizes with bamacan both in VV-infected B-SC-1 cells as well as in mice neuronal tissue. Furthermore, a human neural cell line, which expresses bamacan to moderately elevated levels relative to a non-neural cell line, supported enhanced viral growth. Overall, these studies clearly suggest that bamacan interacts with the VV-N1L and such interactions seem to play a positive role in promoting the viral growth and perhaps contribute to the virulence of VV in neural cells. Journal of NeuroVirology (2009) 15, 229-237. C1 [Mohan, Ketha V. K.; Zhang, Cheryl X.] US FDA, CBER, Div Viral Prod, Bethesda, MD 20892 USA. [Mohan, Ketha V. K.; Atreya, Chintamani D.] US FDA, Div Hematol, Lab Cellular Hematol, Sect Cell Biol, Bethesda, MD 20892 USA. RP Mohan, KVK (reprint author), US FDA, CBER, Div Viral Prod, Bldg 29A,Room 2C-15,HFM-335,NIH Campus,8800 Rockv, Bethesda, MD 20892 USA. EM krishna.ketha391534@fda.hhs.gov FU CBER; FDA CounterTerrorism (CT) Unmet Needs FX The authors gratefully acknowledge Dr. Bernard Moss and Norman Cooper, NIAID, for kind gift of WR strain; Dr. Geoffrey Smith, University of Oxford, UK, for anti-N1L antibody; and Dr. Dorothy Scott, CBER, for VIG serum. Manuscript review by Drs. Ronald Lundquist and Zhiping Ye, DVP, CBER, FDA, is duly acknowledged. Funds from CBER and FDA CounterTerrorism (CT) Unmet Needs in the past partly supported this study. NR 30 TC 3 Z9 4 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2009 VL 15 IS 3 BP 229 EP 237 DI 10.1080/13550280902913636 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 479SJ UT WOS:000268680900003 PM 19444697 ER PT J AU Ghosh, K Tiwari, RC AF Ghosh, Kaushik Tiwari, Ram C. TI A unified approach to variations of ranked set sampling with applications SO JOURNAL OF NONPARAMETRIC STATISTICS LA English DT Article DE extreme ranked set sample; empirical process; Q-Q plot; P-P plot; Wilcoxon-Mann-Whitney test; control percentile test AB In this article, we develop a general theory of inference using data collected from different variations of ranked set sampling. Such variations include balanced and unbalanced ranked set sampling, balanced and unbalanced k-tuple ranked set sampling, nomination sampling, simple random sampling, as well as a combination of them. We provide methods of estimating the underlying distribution function as well as its functionals and establish the asymptotic properties of the resulting estimators. The results so obtained can be used to develop nonparametric procedures for one- and two-sample problems. Some investigation of the small-sample properties of these estimators is also provided. We conclude with an application to a real-life example. C1 [Ghosh, Kaushik] Univ Nevada, Dept Math Sci, Las Vegas, NV 89154 USA. [Tiwari, Ram C.] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Ghosh, K (reprint author), Univ Nevada, Dept Math Sci, Las Vegas, NV 89154 USA. EM kaushik.ghosh@unlv.edu NR 20 TC 4 Z9 4 U1 0 U2 3 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1048-5252 J9 J NONPARAMETR STAT JI J. Nonparametr. Stat. PY 2009 VL 21 IS 4 BP 471 EP 485 AR PII 908137641 DI 10.1080/10485250802652077 PG 15 WC Statistics & Probability SC Mathematics GA 435HY UT WOS:000265336200010 ER PT J AU Thompson, KL AF Thompson, Karol L. TI Toxicogenomic Concepts Applicable to Studies of the Genomic Effects of Dietary Components SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Thompson, Karol L.] US FDA, Ctr Drug Evaluat & Res, US Dept Hlth & Human Serv, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2009 VL 2 IS 4-5 BP 199 EP 199 PG 1 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 610BD UT WOS:000278703300026 ER PT J AU Pogribny, IP Starlard-Davenport, A Tryndyak, V Beland, FA AF Pogribny, I. P. Starlard-Davenport, A. Tryndyak, V. Beland, F. A. TI Dietary Methyl Deficiency, microRNA Expression, and Susceptibility to Liver Carcinogenesis SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Pogribny, I. P.; Starlard-Davenport, A.; Tryndyak, V.; Beland, F. A.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2009 VL 2 IS 4-5 BP 200 EP 200 PG 1 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 610BD UT WOS:000278703300029 ER PT J AU Kavanaugh, CJ AF Kavanaugh, Claudine J. TI Opportunities and Challenges for the US Food And Drug Administration SO JOURNAL OF NUTRIGENETICS AND NUTRIGENOMICS LA English DT Meeting Abstract C1 [Kavanaugh, Claudine J.] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1661-6499 J9 J NUTRIGENET NUTRIGE JI J. Nutrigenet. Nutrigenomics PY 2009 VL 2 IS 4-5 BP 203 EP 203 PG 1 WC Genetics & Heredity; Nutrition & Dietetics SC Genetics & Heredity; Nutrition & Dietetics GA 610BD UT WOS:000278703300035 ER PT J AU Saylor, DM Kim, CS Patwardhan, DV Warren, JA AF Saylor, David M. Kim, Chang-Soo Patwardhan, Dinesh V. Warren, James A. TI Modeling Microstructure Development and Release Kinetics in Controlled Drug Release Coatings SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE controlled release/delivery; thermodynamics; dissolution; diffusion; in silico modeling; mathematical model; solubility; biodegradable polymers ID POLYMER-SOLVENT SYSTEMS; DIFFUSION-COEFFICIENTS; MACROPOROUS POLYMERS; ELUTING STENTS; SOLUBILITY; DELIVERY; MATRICES AB In recent years, controlled release coatings, comprised of drug-polymer composites, have been integrated with medical devices, improving device functionality and performance. However, relationships between material properties, manufacturing environment, composite (micro)structure, and subsequent release kinetics are not well established. We apply a thermodynamically consistent model to probe the influence of drug-polymer chemistry (phobicity), drug loading, and evaporation rate on microstructure development during fabrication. For these structures, we compute release profiles for exposure to polymer-insoluble media and media in which the polymer readily dissolves. We find that with increasing drug-polymer phobicity, structural heterogeneities form at lower loadings and more rapid rates. The heterogeneities remain isolated and compact at low loadings and become interconnected as the drug to polymer ratio approaches 1.0. Release into polymer-insoluble media was dramatically enhanced by heterogeneities, resulting in up to a fourfold increase in drug release. In polymer-soluble media, however, heterogeneities diminished release. Although reductions of only 30% were typically observed, the absolute changes were much larger than observed in polymer-insoluble media. Our results suggest that improved comprehension and quantification of the pbysico-chemical properties in controlled release systems will enable the microstructure to be tailored to achieve desired responses that are insensitive to manufacturing variations. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:169-186, 2009 C1 [Saylor, David M.; Kim, Chang-Soo; Patwardhan, Dinesh V.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20903 USA. [Warren, James A.] Natl Inst Stand & Technol, Mat Sci & Engn Labs, Div Met, Gaithersburg, MD 20899 USA. RP Saylor, DM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20903 USA. EM david.saylor@fda.hhs.gov RI Warren, James/B-1698-2008 OI Warren, James/0000-0001-6887-1206 NR 31 TC 10 Z9 10 U1 1 U2 10 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JAN PY 2009 VL 98 IS 1 BP 169 EP 186 DI 10.1002/jps.21416 PG 18 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 391JC UT WOS:000262228600015 PM 18481310 ER PT J AU Gao, ZM Moore, TW Buhse, LF Doub, WH AF Gao, Zongming Moore, Terry W. Buhse, Lucinda F. Doub, William H. TI The Random Vibration Effects on Dissolution Testing with USP Apparatus 2 SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE dissolution testing; random vibration; USP apparatus 2; disintegrating tablet; prednisone tablet ID VARIABILITY; REPRODUCIBILITY AB Dissolution testing is of primary importance for optimization of drug formulation and quality control, but test results typically show large variability. Vibration is one of the factors that can increase variability of dissolution testing. In this study, a Distek USP Apparatus 2 was used to perform dissolution testing using disintegrating 10 mg prednisone tablets at 50 rpm in 500 mL of 37 degrees C degassed water medium. A controllable vertical random vibration was applied to the dissolution apparatus during the dissolution testing. Real-time vibration waveforms were recorded using accelerometers placed at various locations on the vessel plate and on the dissolution vessels. Preliminary results showed a strong correlation between induced vibration and dissolution results. The vibration measured on the vessel plate correlates well with that measured within nearby vessels. The observed dissolution profiles suggest that vibration affects the disintegration and dissolving processes by different mechanisms, leading to high or low results depending upon during which phase of the dissolution process the vibration occurs. This study also presents a method capable of measuring vibration in a meaningful manner and bow to determine where best to measure it. (C) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 98:297-306, 2009 C1 [Gao, Zongming; Moore, Terry W.; Buhse, Lucinda F.; Doub, William H.] Ctr Drug Evaluat & Res, US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. RP Gao, ZM (reprint author), Ctr Drug Evaluat & Res, US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. EM zongming.gao@fda.hhs.gov NR 19 TC 2 Z9 2 U1 0 U2 3 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD JAN PY 2009 VL 98 IS 1 BP 297 EP 306 DI 10.1002/jps.21402 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 391JC UT WOS:000262228600025 PM 18399543 ER PT J AU Stewart, G Jiao, YG Valente, EJ Fu, PP Li, TQ Hu, ZZ Yu, HT AF Stewart, Gernerique Jiao, Yuguo Valente, Edward J. Fu, Peter P. Li, Tianqiao Hu, Zhenzhong Yu, Hongtao TI Photochemical reaction of 9-nitro-substituted anthracene-like molecules 9-methyl-10-nitroanthracene and 12-methyl-7-nitrobenz[a]anthracene SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY LA English DT Article DE Photoreaction; 9-Methyl-10-nitroanthracene; 7-Nitrobenz[a]anthracene; 12-Methyl-7-nitrobenz[a]anthracene; Nitro-rearrangement ID POLYCYCLIC AROMATIC-HYDROCARBONS; STEADY-STATE PHOTOLYSIS; ATMOSPHERIC REACTIONS; LASER PHOTOLYSIS; NITRO-PAHS; 1-NITROPYRENE; MUTAGENICITY; 9-NITROANTHRACENE; DERIVATIVES; 9-BENZOYL-10-NITROANTHRACENE AB Photolysis of 9-methyl-10-nitroanthracene in chloroform or methanol produces mainly two products 9-methyl-9-nitrosoanthracen-10-one and 9,10-anthraquinone in about 4:1 ratio under ambient air. The formation of 9-methyl-9-nitrosoanthracen-10-one confirms the proposed excited state rearrangement reaction of the nitro group peri to two hydrogens and perpendicular to the aromatic rings. The nitro group rearranges to a nitrite, followed by breaking of the N-O bond producing NO radical. The NO radical further forms a bond with the carbon on the opposite site of the benzene ring through radical recombination. Photolysis of 12-methyl-7-nitrobenz[a]anthracene produced several nitroso ketone-like compounds which further convert to an aldehyde. Photolysis of the desmethyl nitro compounds, 9-nitroanthracene and 7-nitrobenz[a]anthracene, produced the respective quinones. Published by Elsevier B.V. C1 [Stewart, Gernerique; Jiao, Yuguo; Yu, Hongtao] Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. [Jiao, Yuguo; Li, Tianqiao; Hu, Zhenzhong] Cent Univ Nationalities, Coll Life & Environm Sci, Beijing 100081, Peoples R China. [Valente, Edward J.] Mississippi Coll, Dept Chem & Biochem, Clinton, MS 39058 USA. [Fu, Peter P.] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yu, HT (reprint author), Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. EM yu@jsums.edu FU National Institutes of Health [NIH-RCMI G12 RR13459]; US Department of Education [P031 B040101-07] FX This research has been supported by the National Institutes of Health through a generous grant: NIH-RCMI G12 RR13459. This research has also been supported by the "211" program of Central University for nationalities of China. G.S. wishes to thank the US Department of Education for stipend support through the Title III grant: P031 B040101-07. The authors wish to thank Mr. Kui Zeng for assistance in the mass spectroscopic analysis. NR 35 TC 8 Z9 8 U1 0 U2 8 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1010-6030 J9 J PHOTOCH PHOTOBIO A JI J. Photochem. Photobiol. A-Chem. PD JAN 1 PY 2009 VL 201 IS 1 BP 39 EP 44 DI 10.1016/j.jphotochem.2008.09.016 PG 6 WC Chemistry, Physical SC Chemistry GA 398WV UT WOS:000262763100006 PM 20046227 ER PT J AU Wang, SG Wang, L Yin, JJ Wang, Z Fu, PP Yu, HT AF Wang, Shuguang Wang, Lei Yin, Jun-Jie Wang, Zheng Fu, Peter P. Yu, Hongtao TI Light-induced toxic effects of tamoxifen: A chemotherapeutic and chemopreventive agent SO JOURNAL OF PHOTOCHEMISTRY AND PHOTOBIOLOGY A-CHEMISTRY LA English DT Article DE Tamoxifen; Phototoxicity; HaCaT keratinocytes; Salmonella TA102; DNA damage; Lipid peroxidation ID POLYCYCLIC AROMATIC-HYDROCARBONS; PERFORMANCE LIQUID-CHROMATOGRAPHY; LAMBDA/LACI TRANSGENIC RATS; PRIORITY POLLUTANT LIST; BREAST-CANCER PATIENTS; DNA-ADDUCTS; FLUORESCENCE DETECTION; RETINYL PALMITATE; SINGLET OXYGEN; CELLS AB Tamoxifen is a powerful drug used to treat breast cancer patients, and more than 500,000 women in the U.S. are being treated with this drug. In our study, tamoxifen is found to be photomutagenic in Salmonella typhimurium TA102 at concentrations as low as 0.08 mu M and reaches maximum photomutagenicity at 0.4 mu M under a light dose equivalent to 20 min sunlight. These concentrations are comparable to the plasma tamoxifen concentration of 0.4-3 mu M for patients undergoing tamoxifen therapy. The toxicity seems to be the result of DNA damage and/or lipid peroxidation caused by light irradiation of tamoxifen. The DNA damage caused by irradiation of Phi X174 DNA in the presence of tamoxifen appears to be formation of DNA-tamoxifen covalent adducts, not single strand/double strand cleavages, and there is no oxygen involvement. This is confirmed by EPR experiments that carbon-centerd radicals are formed by light irradiation of tamoxifen and there is no singlet oxygen formation. Although superoxide radical is formed, it is not involved in DNA damage. Published by Elsevier B.V. C1 [Wang, Shuguang; Wang, Lei; Wang, Zheng; Yu, Hongtao] Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Yu, HT (reprint author), Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. EM hongtao.yu@jsums.edu RI Yin, Jun Jie /E-5619-2014 FU National Institutes of Health [NIH SCORE S06 GM08047] FX This research was in part supported by the National Institutes of Health: NIH SCORE S06 GM08047. We thank NIH-RCMI for Core Molecular and Cellular Biology Facility and Analytical Chemistry Facility established at JSU. NR 54 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE SA PI LAUSANNE PA PO BOX 564, 1001 LAUSANNE, SWITZERLAND SN 1010-6030 J9 J PHOTOCH PHOTOBIO A JI J. Photochem. Photobiol. A-Chem. PD JAN 1 PY 2009 VL 201 IS 1 BP 50 EP 56 DI 10.1016/j.jphotochem.2008.09.013 PG 7 WC Chemistry, Physical SC Chemistry GA 398WV UT WOS:000262763100008 PM 20046228 ER PT J AU Schier, JG Rubin, CS Miller, D Barr, D McGeehin, MA AF Schier, Joshua G. Rubin, Carol S. Miller, Dorothy Barr, Dana McGeehin, Michael A. TI Medication-associated diethylene glycol mass poisoning: A review and discussion on the origin of contamination SO JOURNAL OF PUBLIC HEALTH POLICY LA English DT Article DE diethylene glycol; mass poisoning; poisoning ID SACCHAROMYCES-CEREVISIAE; GLYCEROL PRODUCTION; FERMENTATION; INTOXICATION; EPIDEMIC; CHILDREN; DEATHS AB Diethylene glycol (DEG), an extremely toxic chemical, has been implicated as the etiologic agent in at least 12 medication-associated mass poisonings over the last 70 years. Why DEG mass poisonings occur remains unclear. Most reports do not contain detailed reports of trace-back investigations into the etiology. The authors, therefore, conducted a systematic literature review on potential etiologies of these mass poisonings. The current available evidence suggests that substitution of DEG or DEG-containing compounds for pharmaceutical ingredients results from: (1) deception as to the true nature of certain ingredients by persons at some point in the pharmaceutical manufacturing process, and (2) failure to adhere to standardized quality control procedures in manufacturing pharmaceutical products intended for consumers. We discuss existing guidelines and new recommendations for prevention of these incidents. Journal of Public Health Policy (2009) 30, 127-143. doi:10.1057/jphp.2009.2 C1 [Schier, Joshua G.; Rubin, Carol S.] Ctr Dis Control & Prevent, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Hlth Studies Branch, Atlanta, GA 30333 USA. [Miller, Dorothy] US FDA, Off Crisis Management, Rockville, MD 20857 USA. [Barr, Dana] Ctr Dis Control & Prevent, Div Sci Lab, Natl Ctr Environm Hlth, Pesticide Lab, Atlanta, GA USA. RP Schier, JG (reprint author), Ctr Dis Control & Prevent, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Hlth Studies Branch, Atlanta, GA 30333 USA. EM jschier@cdc.gov RI Schier, Joshua/F-9861-2013 NR 47 TC 15 Z9 16 U1 0 U2 6 PU PALGRAVE MACMILLAN LTD PI BASINGSTOKE PA BRUNEL RD BLDG, HOUNDMILLS, BASINGSTOKE RG21 6XS, HANTS, ENGLAND SN 0197-5897 J9 J PUBLIC HEALTH POL JI J. Public Health Policy PY 2009 VL 30 IS 2 BP 127 EP 143 DI 10.1057/jphp.2009.2 PG 17 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 469OK UT WOS:000267909000001 PM 19597445 ER PT J AU Wu, M Long, SY Frutos, AG Eichelberger, M Li, M Fang, Y AF Wu, Meng Long, Shunyou Frutos, Anthony G. Eichelberger, Maryna Li, Min Fang, Ye TI Interrogation of phosphor-specific interaction on a high-throughput label-free optical biosensor system-Epic (R) system SO JOURNAL OF RECEPTORS AND SIGNAL TRANSDUCTION LA English DT Article; Proceedings Paper CT 1st Label-Free Summit 2008 CY OCT 06-07, 2008 CL Corning, NY DE Label free; phosphor-specific; Epic (R); 14-3-3; kinase ID 14-3-3 PROTEINS; KINASE ASSAYS; FLUORESCENCE; BINDING; SITE; 14-3-3-PROTEINS; SURFACE; LIGAND; ZETA AB The Epic(R) system, a high-throughput label-free optical biosensor system, is applied for the biochemical interrogation of phosphor-specific interactions of the 14-3-3 protein and its substrates. It has shown the capability not only for high-throughput characterization of binding rank and affinity but also for the exploration of potential interacting kinases for the substrates. A perspective of biochemical applications for diagnostics and biomarker discovery, as well as cell-based applications for endogenous receptors and viral infection characterization, are also provided. C1 [Wu, Meng; Long, Shunyou; Li, Min] Johns Hopkins Univ, Sch Med, Dept Neurosci, High Throughput Biol Ctr, Baltimore, MD 21205 USA. [Wu, Meng; Long, Shunyou; Li, Min] Johns Hopkins Univ, Sch Med, Johns Hopkins Ion Channel Ctr, Baltimore, MD 21205 USA. [Frutos, Anthony G.; Fang, Ye] Corning Inc, Div Sci & Technol, Corning, NY 14831 USA. [Eichelberger, Maryna] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Li, M (reprint author), Johns Hopkins Univ, Sch Med, Dept Neurosci, High Throughput Biol Ctr, 733 N Broadway,BRB311, Baltimore, MD 21205 USA. EM minli@jhmi.edu RI Wu, Meng/F-3958-2010 FU NIGMS NIH HHS [R01 GM078579]; NIMH NIH HHS [U54 MH084691] NR 28 TC 5 Z9 5 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1079-9893 J9 J RECEPT SIG TRANSD JI J. Recept. Signal Transduct. PY 2009 VL 29 IS 3-4 BP 202 EP 210 DI 10.1080/10799890903068474 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 491ZZ UT WOS:000269624400011 PM 19640222 ER PT J AU Young, JF Luecke, RH Pearce, BA Lee, T Ahn, H Baek, S Moon, H Dye, DW Davis, TM Taylor, SJ AF Young, John F. Luecke, Richard H. Pearce, Bruce A. Lee, Taewon Ahn, Hongshik Baek, Songjoon Moon, Hojin Dye, Daniel W. Davis, Thomas M. Taylor, Susan J. TI Human Organ/Tissue Growth Algorithms that Include Obese Individuals and Black/White Population Organ Weight Similarities from Autopsy Data SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID SKELETAL-MUSCLE MASS; X-RAY ABSORPTIOMETRY; ADIPOSE-TISSUE DISTRIBUTION; BLACK-AND-WHITE; FAT-FREE MASS; BODY-COMPOSITION; CARDIAC-OUTPUT; STROKE VOLUME; ELDERLY SUBJECTS; WOMEN AB Physiologically based pharmacokinetic (PBPK) models need the correct organ/tissue weights to match various total body weights in order to be applied to children and the obese individual. Baseline data from Reference Man for the growth of human organs (adrenals, brain, heart, kidneys, liver, lungs, pancreas, spleen, thymus, and thyroid) were augmented with autopsy data to extend the describing polynomials to include the morbidly obese individual (up to 250 kg). Additional literature data similarly extends the growth curves for blood volume, muscle, skin, and adipose tissue. Collectively these polynomials were used to calculate blood/organ/tissue weights for males and females from birth to 250 kg, which can be directly used to help parameterize PBPK models. In contrast to other black/white anthropomorphic measurements, the data demonstrated no observable or statistical difference in weights for any organ/tissue between individuals identified as black or white in the autopsy reports. C1 [Young, John F.; Lee, Taewon; Baek, Songjoon; Taylor, Susan J.] Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [Luecke, Richard H.] Univ Missouri, Dept Chem Engn, Columbia, MO 65211 USA. [Ahn, Hongshik] SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. [Moon, Hojin] Calif State Univ Long Beach, Dept Math & Stat, Long Beach, CA 90840 USA. [Dye, Daniel W.; Davis, Thomas M.] Univ Arkansas Med Sci, Dept Pathol, Little Rock, AR 72205 USA. RP Young, JF (reprint author), Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. EM johnfyoung@aristotle.net NR 43 TC 29 Z9 29 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PY 2009 VL 72 IS 8 BP 527 EP 540 AR PII 909289646 DI 10.1080/15287390802647203 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 415JR UT WOS:000263930600003 PM 19267313 ER PT J AU Il'yasova, D McCarthy, BJ Erdal, S Shimek, J Goldstein, J Doerge, DR Myers, SR Vineis, P Wishnok, JS Swenberg, JA Bigner, DD Davis, FG AF Il'yasova, Dora McCarthy, Bridget J. Erdal, Serap Shimek, Joanna Goldstein, Jennifer Doerge, Daniel R. Myers, Steven R. Vineis, Paolo Wishnok, John S. Swenberg, James A. Bigner, Darell D. Davis, Faith G. TI HUMAN EXPOSURE TO SELECTED ANIMAL NEUROCARCINOGENS: A BIOMARKER-BASED ASSESSMENT AND IMPLICATIONS FOR BRAIN TUMOR EPIDEMIOLOGY SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART B-CRITICAL REVIEWS LA English DT Review ID POLYCYCLIC AROMATIC-HYDROCARBONS; N-NITROSO COMPOUNDS; HEMOGLOBIN ADDUCT LEVELS; PUBLIC WATER-SUPPLIES; SEMUSTINE METHYL-CCNU; PAH O-QUINONES; FISCHER-344 RATS; MORTALITY PATTERNS; REACTIVE OXYGEN; BLADDER-CANCER AB This review is based on the proceedings from the Second Lebow Conference, held in Chicago in 2007. The conference concentrated on developing a framework for innovative studies in the epidemiology of environmental exposures, focusing specifically on the potential relationship with brain tumors. Researchers with different perspectives, including toxicology, pharmacokinetics, and epidemiological exposure assessment, exchanged information and ideas on the use of biomarkers of exposure in molecular epidemiology studies and summarized the current knowledge on methods and approaches for biomarker-based exposure assessment. This report presents the state of science regarding biomarker-based exposure assessment of the four most common neurocarcinogens: acrylamide, 1,3-butadiene, N-nitroso compounds, and polycyclic aromatic hydrocarbons. Importantly, these chemicals are also carcinogenic in other organs; therefore, this discussion is useful for environmental epidemiologists studying all cancer types. C1 [Il'yasova, Dora] Duke Univ, Med Ctr, Canc Control & Prevent Program, Dept Community & Family Med,Div Prevent Res, Durham, NC 27710 USA. [Il'yasova, Dora; Bigner, Darell D.] Duke Univ, Med Ctr, Preston Robert Tisch Brain Tumor Ctr Duke, Durham, NC 27710 USA. [McCarthy, Bridget J.; Davis, Faith G.] Univ Illinois, Sch Publ Hlth, Div Epidemiol & Biostat, Chicago, IL USA. [Erdal, Serap; Shimek, Joanna] Univ Illinois, Sch Publ Hlth, Div Environm & Occupat Sci, Chicago, IL USA. [Goldstein, Jennifer] Duke Univ, Med Ctr, Dept Pediat, Durham, NC 27710 USA. [Doerge, Daniel R.] US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. [Myers, Steven R.] Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. [Vineis, Paolo] Univ London Imperial Coll Sci Technol & Med, London, England. [Wishnok, John S.] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Swenberg, James A.] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC USA. [Swenberg, James A.] Univ N Carolina, Dept Nutr, Chapel Hill, NC USA. [Swenberg, James A.] Univ N Carolina, Dept Pathol & Lab Med, Chapel Hill, NC USA. [Swenberg, James A.] Univ N Carolina, Ctr Environm Hlth & Susceptibil, Chapel Hill, NC USA. [Bigner, Darell D.] Duke Univ, Med Ctr, Pediat Brain Tumor Fdn Inst Duke, Dept Pathol, Durham, NC 27710 USA. RP Il'yasova, D (reprint author), Duke Univ, Med Ctr, Canc Control & Prevent Program, Dept Community & Family Med,Div Prevent Res, 2424 Erwin Rd,Hock Bldg,Ste 602,Box 2949, Durham, NC 27710 USA. EM dora.ilyasova@duke.edu FU NINDS [5P50 NS20023-25]; NIH SPORE [5P50 CA108786-4]; NIH Merit [R37 CA011898-38] FX The authors are grateful for the generosity of the LeBow family for sponsoring this conference and for the invaluable administrative support of Naomi Berkowitz, Executive Director of the American Brain Tumor Association. We also thank the other speakers and moderators, Dr. Francis Ali-Osman, Dr. Paul Kleihues, Dr. Beatrice Malmer, and Dr. Hiroko Ohgaki, for their important contribution. This review was funded by NINDS grant 5P50 NS20023-25, NIH SPORE grant 5P50 CA108786-4, and NIH Merit Award R37 CA011898-38. NR 105 TC 2 Z9 2 U1 0 U2 7 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1093-7404 EI 1521-6950 J9 J TOXICOL ENV HEAL B JI J. Toxicol. Env. Health-Pt b-Crit. Rev. PY 2009 VL 12 IS 3 BP 175 EP 187 DI 10.1080/10937400902894152 PG 13 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 483GT UT WOS:000268951700001 PM 19466671 ER PT J AU Fayer, R Orlandi, P Perdue, ML AF Fayer, Ronald Orlandi, Palmer Perdue, Michael L. TI Virulence factor activity relationships for hepatitis E and Cryptosporidium SO JOURNAL OF WATER AND HEALTH LA English DT Article CT Workshop on Virulence Factor Activity Relationships CY OCT, 2004 CL US Environm Protect Agcy, Washington, DC SP Natl Acad Sci, Natl Res Council HO US Environm Protect Agcy DE cryptosporidiosis; epidemiology; hepatitis; molecular; proteins; taxonomy ID NON-B HEPATITIS; ACUTE VIRAL-HEPATITIS; POLYMERASE-CHAIN-REACTION; E VIRUS; MOLECULAR CHARACTERIZATION; NON-A; SPORADIC ACUTE; ZOONOTIC TRANSMISSION; FULMINANT-HEPATITIS; ENZYME-IMMUNOASSAY AB The hepatitis E virus and Cryptosporidium are waterborne pathogens, each consisting of distinct taxa, genotypes and isolates that infect humans, nonhuman animal species or both. Some are associated with disease, others are not. Factors contributing to disease are extremely complicated, possibly involving differences in one or more traits associated with an organism's taxon, genotype or isolate and its infectious dose, and age or condition, as well as the host's physiology and immune status. Potential virulence factors have not yet been identified for HEV. Putative virulence factors for Cryptosporidium might be found in recently recognized genes involved in processes such as excystation, adherence to host cells, invasion, intracellular maintenance and host cell destruction. C1 [Fayer, Ronald] USDA, Anim & Nat Resources Inst, Environm Microbial Safety Lab, Beltsville, MD 20705 USA. [Orlandi, Palmer] US FDA, ORA, Div Field Sci, Rockville, MD 20857 USA. [Perdue, Michael L.] US Dept Hlth & Human Sci, Div Influenza & Emerging Dis Biomed Adv Res & Dev, Off Assistant Secretary Preparedness & Response, Washington, DC 20201 USA. RP Fayer, R (reprint author), USDA, Anim & Nat Resources Inst, Environm Microbial Safety Lab, Beltsville, MD 20705 USA. EM ronald.fayer@ars.usda.gov NR 75 TC 2 Z9 4 U1 0 U2 3 PU I W A PUBLISHING PI LONDON PA ALLIANCE HOUSE, 12 CAXTON ST, LONDON SW1H0QS, ENGLAND SN 1477-8920 J9 J WATER HEALTH JI J. Water Health PY 2009 VL 7 BP S55 EP S63 DI 10.2166/wh.2009.044 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Microbiology; Water Resources SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Microbiology; Water Resources GA 492BL UT WOS:000269629000005 PM 19717931 ER PT J AU Sun, S Ossandon, M Kostov, Y Rasooly, A AF Sun, Steven Ossandon, Miguel Kostov, Yordan Rasooly, Avraham TI Lab-on-a-chip for botulinum neurotoxin a (BoNT-A) activity analysis SO LAB ON A CHIP LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; ARRAY BIOSENSOR; NEUROTRANSMITTER RELEASE; FLUORESCENCE DETECTION; PROTEOLYTIC CLEAVAGE; SENSITIVE DETECTION; MASS-SPECTROMETRY; MEMBRANE-PROTEIN; RAPID DETECTION; MOUSE BIOASSAY AB A Lab-on-a-chip (LOC) was designed, fabricated and tested for the in vitro detection of botulinum neurotoxin serotype A (BoNT-A) activity using an assay that measures cleavage of a fluorophore-tagged peptide substrate specific for BoNT-A (SNAP-25) by the toxin light chain (LcA). LcA cleavage was detected by Forster Resonance Energy Transfer (FRET) fluorescence. FRET fluorescence was measured by a newly developed portable charge-coupled device (CCD) fluorescent detector equipped with multi-wavelength light-emitting diodes (LED) illumination. An eight V-junction microchannel device for BoNTs activity assays was constructed using Laminated Object Manufacturing (LOM) technology. The six-layer device was fabricated with a Poly(methyl methacrylate (PMMA) core and five polycarbonate (PC) layers micromachined by CO(2) laser. The LOC is operated by syringe and is equipped with reagents, sample wells, reaction wells, diffusion traps (to avoid cross contamination among channels) and waste reservoirs. The system was detected LcA at concentrations as low as 0.5 nM, which is the reported sensitivity of the SNAP-25 in vitro cleavage assay. Combined with our CCD detector, the simple point of care system enables the detection of BoNTs activity and may be useful for the performance of other complex medical assays without a laboratory. This approach may realize the potential to enhance the quality of health care delivery for underserved populations. C1 [Sun, Steven; Rasooly, Avraham] NCI, Div Biol, Off Sci & Engn Labs, FDA,NIH, Silver Spring, MD 20993 USA. [Sun, Steven; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Ossandon, Miguel; Rasooly, Avraham] Natl Canc Inst, Canc Diag Program, Rockville, MD 20892 USA. RP Rasooly, A (reprint author), NCI, Div Biol, Off Sci & Engn Labs, FDA,NIH, Silver Spring, MD 20993 USA. EM rasoolya@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 54 TC 36 Z9 36 U1 3 U2 18 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 1473-0197 J9 LAB CHIP JI Lab Chip PY 2009 VL 9 IS 22 BP 3275 EP 3281 DI 10.1039/b912097a PG 7 WC Biochemical Research Methods; Chemistry, Multidisciplinary; Nanoscience & Nanotechnology SC Biochemistry & Molecular Biology; Chemistry; Science & Technology - Other Topics GA 512JH UT WOS:000271243600014 PM 19865736 ER PT J AU Waynant, R Tata, D AF Waynant, Ronald Tata, Darrell TI LOW LEVEL LIGHT INDUCED BIOMODULATIONS AND THE BYSTANDER EFFECT: EVIDENCE FOR ENHANCED GENERATION OF HYDROGEN PEROXIDE IN VITRO SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 29th Annual Conference of the American-Society-for-Laser-Medicine and Surgery CY APR 01-05, 2009 CL National Harbor, MD SP Amer Soc Laser Med & Surg C1 [Waynant, Ronald; Tata, Darrell] US FDA, Silver Spring, MD 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 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PY 2009 BP 59 EP 59 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 464RV UT WOS:000267524700171 ER PT J AU Kozlowski, S Behrman, R AF Kozlowski, Steven Behrman, Rachel TI Biosimilars: considerations for an abbreviated pathway SO LEUKEMIA & LYMPHOMA LA English DT Editorial Material ID PERSPECTIVE; PRODUCTS C1 [Kozlowski, Steven] US FDA, Off Biotechnol Prod, Silver Spring, MD 20993 USA. RP Kozlowski, S (reprint author), US FDA, Off Biotechnol Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM steven.kozlowski@fda.hhs.gov NR 10 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 1042-8194 J9 LEUKEMIA LYMPHOMA JI Leuk. Lymphoma PY 2009 VL 50 IS 4 BP 527 EP 528 AR PII 910513126 DI 10.1080/10428190902853151 PG 2 WC Oncology; Hematology SC Oncology; Hematology GA 435RR UT WOS:000265361500006 PM 19373649 ER PT B AU Yin, JJ Fu, PP AF Yin, J. J. Fu, P. P. BE Guojonsdottir, M Belton, P Webb, G TI APPLICATION OF ELECTRON SPIN RESONANCE TO STUDY FOOD ANITOXIDATIVE AND PROOXIDATIVE ACTIVITIES SO MAGNETIC RESONANCE IN FOOD SCIENCE: CHALLENGES IN A CHANGING WORLD LA English DT Proceedings Paper CT 9th International Conference on Applications of Magnetic Resonance in Food Science CY SEP 15-17, 2008 CL Nordic House, Reykjavik, ICELAND HO Nordic House ID CONJUGATED LINOLEIC-ACID; SINGLET OXYGEN; LIPID-PEROXIDATION; LATERAL DIFFUSION; FUMONISIN B-1; UVA PHOTOIRRADIATION; FREE-RADICALS; LABEL PAIRS; MEMBRANES; ELDOR C1 [Yin, J. J.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM junjie.yin@fda.hhs.gov NR 31 TC 7 Z9 7 U1 1 U2 1 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, CAMBRIDGE CB4 4WF, CAMBS, ENGLAND BN 978-0-85404-117-6 PY 2009 BP 213 EP 221 PG 9 WC Food Science & Technology SC Food Science & Technology GA BKA37 UT WOS:000267586900025 ER PT S AU Tata, DB Waynant, RW AF Tata, Darrell B. Waynant, Ronald W. BE Hamblin, MR Waynant, RW Anders, J TI A Comparative Study on Non-confluent and Confluent Human Malignant Brain Cancer Metabolic Response to He-Ne Laser Exposures: Evidence for Laser Enhanced Cellular Production of H(2)O(2) and Laser induced "Bystander" Effect SO MECHANISMS FOR LOW-LIGHT THERAPY IV SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Mechanisms for Low-Light Therapy IV CY JAN 24, 2009 CL San Jose, CA SP SPIE ID HYDROGEN-PEROXIDE; CELLS AB Continuous wave He-Ne laser exposures (Intensity = 35 mW/cm(2), lambda= 632.8nm, Fluence range: 1J/cm(2) to 50 J/cm(2)) on non-confluent and fully confluent human malignant glioblastoma cells was found to increase the cellular production levels of H(2)O(2). Modulations in the cellular metabolic activity were detected (through the MTS assay) three days after the laser irradiation. The metabolic activity was found to be dependent on the laser fluence for both cell growth conditions. Furthermore, three days after the laser exposure, the potential laser induced "bystander" effect was tested through the transfer of growth media from laser irradiated cells onto non-irradiated cells. After two additional days of incubation (5 days post exposure), the non-laser irradiated cells grown under the non-confluent condition were found to have a significant increase in their metabolic activities, whereas minimal to null response was found for the fully confluent condition. For cells grown under the non-confluent conditions, modulations in the metabolic activities in the non-irradiated cells were found to be laser fluence dependent from the initial laser exposed cells treatment conditions. The results herein support the hypothesis of an important role for light enhanced cellular H(2)O(2) generation to yield bio-modulatory effects locally and at a distance. The classical "bi-phasic" modulation response of cells to light irradiation is hypothesized to depend upon the quantity of light enhanced H(2)O(2) molecules generated from the mitochondria and the number of cells which interact with the H(2)O(2) molecules. C1 [Tata, Darrell B.; Waynant, Ronald W.] US FDA, Silver Spring, MD USA. RP Tata, DB (reprint author), US FDA, Silver Spring, MD USA. EM Darayash.Tata@fda.hhs.gov; Ronald.Waynant@fda.hhs.gov; Ronald.Waynant@fda.hhs.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7411-7 J9 P SOC PHOTO-OPT INS PY 2009 VL 7165 AR 716508 DI 10.1117/12.813409 PG 12 WC Engineering, Biomedical; Optics; Physics, Applied SC Engineering; Optics; Physics GA BSS59 UT WOS:000285712700005 ER PT S AU Brown, DG AF Brown, David G. BE Sahiner, B Manning, DJ TI Bob's first decade: In at the beginning SO MEDICAL IMAGING 2009: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 11-12, 2009 CL CAD, Lake Buena Vista, FL SP SPIE HO CAD DE Robert Wagner; imaging performance; medical imaging ID IMAGING-SYSTEMS AB Arriving at the Bureau of Radiological Health in 1972, Bob Wagner was thrust into the Bureau's quandary over how to quantify the imaging benefit associated with the radiation dose cost of medical imaging procedures. In short order he had set up the framework for FDA imaging research for the next 36 years. Bob played a key role in these early years in assisting in the founding of the SPIE Medical Imaging series of meetings, in measuring and organizing round robin comparisons of imaging measurements of the fundamental physical quantities required for performance evaluation, and in developing the framework for how these measurements could be combined to provide meaningful assessment figures of merit. He worked assiduously to counter both those who claimed that radiology was an art not a science and those who made extravagant claims for the dose reduction/image quality benefits of their particular variety of image capture/image processing system. In the process he became one of the founding fathers and key participants in the medical image performance assessment community as represented today at SPIE Medical Imaging 2009. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Brown, DG (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Rm 4118, Silver Spring, MD 20993 USA. EM david.brown@fda.hhs.gov NR 18 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7514-5 J9 PROC SPIE PY 2009 VL 7263 AR 72630D DI 10.1117/12.817797 PG 9 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ41 UT WOS:000306174400012 ER PT S AU Chen, WJ Wagner, RF Yousef, WA Gallas, BD AF Chen, Weijie Wagner, Robert F. Yousef, Waleed A. Gallas, Brandon D. BE Sahiner, B Manning, DJ TI Comparison of classifier performance estimators: a simulation study SO MEDICAL IMAGING 2009: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 11-12, 2009 CL CAD, Lake Buena Vista, FL SP SPIE HO CAD DE bias-variance trade-off; training variability; classification; AUC; bootstrap; resampling; cross-validation ID ROC CURVE; AREA AB We aim to compare resampling-based estimators of the area under the ROC curve (AUC) of a classifier with a Monte Carlo simulation study. The comparison is in terms of bias, variance, and mean square error. We also examine the corresponding variance estimators of these AUC estimators. We compared three AUC estimators: the hold-out (HO) estimator, the leave-one-out cross validation (LOOCV) estimator, and the leave-pair-out bootstrap (LPOB) estimator. Each performance estimator has its own variability estimator. In our simulations, in terms of the mean square error, HO is always the worst and the ranking of the other two estimators depends on the interplay of sample size, dimensionality, and the population separability. In terms of estimators variability, the LPOB is the least variable estimator and the HO is the most variable estimator. The results also show that the estimation of the variance of LPOB using the influence function approach with a finite data set is unbiased or conservatively biased whereas the estimation of the variance of the LOOCV or the HO is downwardly (i.e., anti-consevatively) biased. C1 [Chen, Weijie; Wagner, Robert F.; Yousef, Waleed A.; Gallas, Brandon D.] US FDA, NIBIB CDRH Joint Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, OSEL,CDRH, Silver Spring, MD 20993 USA. RP Chen, WJ (reprint author), US FDA, NIBIB CDRH Joint Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, OSEL,CDRH, Silver Spring, MD 20993 USA. EM weijie.chen@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620 NR 9 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7514-5 J9 PROC SPIE PY 2009 VL 7263 AR 72630X DI 10.1117/12.811584 PG 11 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ41 UT WOS:000306174400032 ER PT S AU Gallas, BD Pesce, LL AF Gallas, Brandon D. Pesce, Lorenzo L. BE Sahiner, B Manning, DJ TI Comparison of ROC methods for partially-paired data SO MEDICAL IMAGING 2009: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 11-12, 2009 CL CAD, Lake Buena Vista, FL SP SPIE HO CAD DE Receiver Operating Characteristic (ROC); AUC; missing data; partially-paired data; ROCKIT; bootstrap ID OPERATING CHARACTERISTIC CURVES; AREA AB In this work we investigate ROC methods that compare the difference in AUCs (area under the ROC curve) from two modalities given partially paired data. Such methods are needed to accommodate the real world situations, where every case cannot be imaged or interpreted using both modalities. We compare variance estimation of the bivariate binormal-model based method ROCKIT of Metz et al., as well as several different non-parametric methods, including the bootstrap and U-statistics. This comparison explores different ROC curves, study designs (pairing structure of the data), sample sizes, case mix, and modality effect sizes. C1 [Gallas, Brandon D.] US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Rm 3124, Silver Spring, MD 20993 USA. [Pesce, Lorenzo L.] Univ Chicago, Chicago, IL 60637 USA. RP Gallas, BD (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave,Bldg 62,Rm 3124, Silver Spring, MD 20993 USA. EM brandon.gallas@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620 FU cluster and the time of Lorenzo Pesce [HHSN267200700039C]; NIH/NIAAA FX We would like to thank Robert Nishikawa for sponsoring Brandon Gallas to work on the University of Chicago Scientific Image Recontstruction and Analysis Facility, C. Chan (cluster administrator) and the grants that support this cluster and the time of Lorenzo Pesce: HHSN267200700039C (Charlies Metz PI) contract with NIH/NIAAA. We would also like to thank the FDA scientific cluster adminstrators for allowing Lorenzo Pesce to have a workspace there and assisting with installation of software. NR 20 TC 0 Z9 0 U1 0 U2 1 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7514-5 J9 PROC SPIE PY 2009 VL 7263 AR 72630V DI 10.1117/12.813688 PG 12 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ41 UT WOS:000306174400030 ER PT S AU Myers, KJ AF Myers, Kyle J. BE Sahiner, B Manning, DJ TI Finding order in complexity: Themes from the career of Dr. Robert F. Wagner SO MEDICAL IMAGING 2009: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 11-12, 2009 CL CAD, Lake Buena Vista, FL SP SPIE HO CAD DE RF Wagner; image evaluation; objective assessment; decision theory; CAD ID OPERATING CHARACTERISTIC ANALYSIS; COMPUTER-AIDED DIAGNOSIS; MEDICAL IMAGING-SYSTEMS; OF-VARIANCE MODELS; ROC ANALYSIS; ASSIST SYSTEMS; CLASSIFIERS; COMPONENTS; SAMPLE; MODALITIES AB Over the course of his long and productive career, Dr. Robert F. Wagner built a framework for the evaluation of imaging systems based on a task-based, decision theoretic approach. His most recent contributions involved the consideration of the random effects associated with multiple readers of medical images and the logical extension of this work to the problem of the evaluation of multiple competing classifiers in statistical pattern recognition. This contemporary work expanded on familiar themes from Bob's many SPIE presentations in earlier years. It was driven by the need for practical solutions to current problems facing FDA'S Center for Devices and Radiological Health and the medical imaging community regarding the assessment of new computer-aided diagnosis tools and Bob's unique ability to unify concepts across a range of disciplines as he gave order to increasingly complex problems in our field. C1 US FDA, Div Imaging & Appl Math, OSEL, CDRH, Silver Spring, MD 20993 USA. RP Myers, KJ (reprint author), US FDA, Div Imaging & Appl Math, OSEL, CDRH, WO62-3118,10993 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kyle.myers@fda.hhs.gov NR 41 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7514-5 J9 PROC SPIE PY 2009 VL 7263 AR 72630H DI 10.1117/12.817794 PG 9 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ41 UT WOS:000306174400016 ER PT S AU Paquerault, S Samuelson, FW Myers, KJ Smith, RC AF Paquerault, Sophie Samuelson, Frank W. Myers, Kyle J. Smith, Robert C. BE Sahiner, B Manning, DJ TI Non-Localization and Localization ROC Analyses Using Clinically-Based Scoring SO MEDICAL IMAGING 2009: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 11-12, 2009 CL CAD, Lake Buena Vista, FL SP SPIE HO CAD DE Multiple reader multiple case (MRMC) analysis; location-specific and non-location-specific receiver operating characteristic; Computer-aided detection ID IMAGING-SYSTEMS; PERFORMANCE AB We are investigating the potential for differences in study conclusions when assessing the estimated impact of a computer-aided detection (CAD) system on readers' performance. The data utilized in this investigation were derived from a multi-reader multi-case observer study involving one hundred mammographic background images to which fixed-size and fixed-intensity Gaussian signals were added, generating a low-and high-intensity signal sets. The study setting allowed CAD assessment in two situations: when CAD sensitivity was 1) superior or 2) lower than the average reader. Seven readers were asked to review each set in the unaided and CAD-aided reading modes, mark and rate their findings. Using this data, we studied the effect on study conclusion of three clinically-based receiver operating characteristic (ROC) scoring definitions. These scoring definitions included both location-specific and non-location-specific rules. The results showed agreement in the estimated impact of CAD on the overall reader performance. In the study setting where CAD sensitivity is superior to the average reader, the mean difference in AUC between the CAD-aided read and unaided read was 0.049 (95% CIs: -0.027; 0.130) for the image scoring definition that is based on non-location-specific rules, and 0.104 (95% CIs: 0.036; 0.174) and 0.090 (95% CIs: 0.031; 0.155) for image scoring definitions that are based on location-specific rules. The increases in AUC were statistically significant for the location-specific scoring definitions. It was further observed that the variance on these estimates was reduced when using the location-specific scoring definitions compared to that using a non-location-specific scoring definition. In the study setting where CAD sensitivity is equivalent or lower than the average reader, the mean differences in AUC are slightly above 0.01 for all image scoring definitions. These increases in AUC were not statistical significant for any of the image scoring definitions. The results on the variance analysis differed from those observed in the other study setting. This investigation furthers our understanding of the relationships between non-localization-specific and localization-specific ROC assessment methodologies and their relevance to clinical practice. C1 [Paquerault, Sophie; Samuelson, Frank W.; Myers, Kyle J.; Smith, Robert C.] CDRH NIBIB, Lab Assessment Med Imaging Syst, Food & Drug Adm, Rockville, MD 20852 USA. RP Paquerault, S (reprint author), CDRH NIBIB, Lab Assessment Med Imaging Syst, Food & Drug Adm, Rockville, MD 20852 USA. NR 9 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7514-5 J9 PROC SPIE PY 2009 VL 7263 AR 72630U DI 10.1117/12.813761 PG 9 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ41 UT WOS:000306174400029 ER PT S AU Witten, JM Park, S Myers, KJ AF Witten, Joel M. Park, Subok Myers, Kyle J. BE Sahiner, B Manning, DJ TI Using partial least squares to compute efficient channels for the Bayesian ideal observer SO MEDICAL IMAGING 2009: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Medical Imaging - Image Perception, Observer Performance, and Technology Assessment CY FEB 11-12, 2009 CL CAD, Lake Buena Vista, FL SP SPIE HO CAD DE Bayesian ideal observer; Hotelling observer; channelized ideal observer; partial least squares; efficient channels; non-Gaussian lumpy backgrounds AB We define image quality by how accurately an observer, human or otherwise, can perform a given task, such as determining to which class an image belongs. For detection tasks, the Bayesian ideal observer(1) is the best observer, in that it sets an upper bound for observer performance, summarized by the area under the receiver operating characteristic curve.(2) However, the use of this observer is frequently infeasible because of unknown image statistics, whose estimation is computationally costly. As a result, a channelized ideal observer(3) (CIO) was investigated to reduce the dimensionality of the data, yet approximate the performance of the ideal observer. Previously investigated channels include Laguerre Gauss (LG) channels(3) and channels via the singular value decomposition of the given linear system(4) (SVD). Though both types are highly efficient for the ideal observer, they nevertheless have the weakness that they may not be as efficient for general detection tasks involving complex/realistic images; the former is particular to the signal and background shape, and the latter is particular to the system operator. In this work, we attempt to develop channels that can be applied to a system with any signal and background type and without knowledge of any characteristics of the system. The method used is a partial least squares algorithm(5) (PLS), in which channels are chosen to maximize the squared covariance between images and their classes. Preliminary results show that the CIO with PLS channels outperforms one with either the LG or SVD channels and very closely approximates ideal-observer performance. C1 [Witten, Joel M.] Univ Maryland, College Pk, MD 20742 USA. [Witten, Joel M.; Park, Subok; Myers, Kyle J.] NIBIB CDRH Joint Lab Assessment Med Imaging Syst, OSEL CDRH FDA, Div Imaging & Appl Math, Bethesda, MD 20892 USA. RP Witten, JM (reprint author), Univ Maryland, College Pk, MD 20742 USA. EM subok.park@fda.hhs.gov FU Center for Biologics Evaluation and Research; U.S. Department of Energy; U.S. Food and Drug Administration; FDA's Office of Women's Health; National Science Foundation FX This project was supported in part by an appointment to the Research Participation Program at the Center for Biologics Evaluation and Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and the U.S. Food and Drug Administration. The project is also in part supported by the FDA's Office of Women's Health and by the National Science Foundation's VIGRE grant NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7514-5 J9 PROC SPIE PY 2009 VL 7263 AR 72630Q DI 10.1117/12.813550 PG 8 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BAZ41 UT WOS:000306174400025 ER PT J AU Li, J Huang, A Yao, J Liu, JM Van Uitert, RL Petrick, N Summers, RM AF Li, Jiang Huang, Adam Yao, Jack Liu, Jiamin Van Uitert, Robert L. Petrick, Nicholas Summers, Ronald M. TI Optimizing computer-aided colonic polyp detection for CT colonography by evolving the Pareto front SO MEDICAL PHYSICS LA English DT Article; Proceedings Paper CT European Congress of Radiology CY 2007 CL Vienna, AUSTRIA DE computer-aided detection; pattern recognition; statistical methods; multiobjective evolution; genetic algorithm ID TOMOGRAPHIC VIRTUAL COLONOSCOPY; FALSE POSITIVES; REDUCTION; OPTIMIZATION; METAANALYSIS; ALGORITHM; FEATURES; CANCER; SCHEME; CAD AB A multiobjective genetic algorithm is designed to optimize a computer-aided detection (CAD) system for identifying colonic polyps. Colonic polyps appear as elliptical protrusions on the inner surface of the colon. Curvature-based features for colonic polyp detection have proved to be successful in several CT colonography (CTC) CAD systems. Our CTC CAD program uses a sequential classifier to form initial polyp detections on the colon surface. The classifier utilizes a set of thresholds on curvature-based features to cluster suspicious colon surface regions into polyp candidates. The thresholds were previously chosen experimentally by using feature histograms. The chosen thresholds were effective for detecting polyps sized 10 mm or larger in diameter. However, many medium-sized polyps, 6-9 mm in diameter, were missed in the initial detection procedure. In this paper, the task of finding optimal thresholds as a multiobjective optimization problem was formulated, and a genetic algorithm to solve it was utilized by evolving the Pareto front of the Pareto optimal set. The new CTC CAD system was tested on 792 patients. The sensitivities of the optimized system improved significantly, from 61.68% to 74.71% with an increase of 13.03% (95% CI [6.57%, 19.5%], p = 7.78 X 10(-5) ) for the size category of 6-9 mm polyps, from 65.02% to 77.4% with an increase of 12.38% (95% CI [6.23%, 18.53%], p = 7.95 X 10(-5) ) for polyps 6 mm or larger, and from 82.2% to 90.58% with an increase of 8.38% (95% CI [0.75%, 16%], p = 0.03) for polyps 8 mm or larger at comparable false positive rates. The sensitivities of the optimized system are nearly equivalent to those of expert radiologists. (C) 2009 American Association of Physicists in Medicine. [DOI: 10.1118/1.3040177] C1 [Li, Jiang; Huang, Adam; Yao, Jack; Liu, Jiamin; Van Uitert, Robert L.; Summers, Ronald M.] NIH, Ctr Clin, Bethesda, MD 20892 USA. [Li, Jiang] Old Dominion Univ, Dept Elect & Comp Engn, VMASC, Norfolk, VA 23529 USA. [Petrick, Nicholas] FDA CDRH OSEL, Div Imaging & Appl Math, LAMIS Image Anal Lab, Silver Spring, MD 20993 USA. RP Summers, RM (reprint author), NIH, Ctr Clin, Bethesda, MD 20892 USA. EM rms@nih.gov FU Intramural NIH HHS [Z01 CL040003-05] NR 40 TC 12 Z9 13 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 JAN PY 2009 VL 36 IS 1 BP 201 EP 212 DI 10.1118/1.3040177 PG 12 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 389OU UT WOS:000262105200023 PM 19235388 ER PT B AU Dair, BJ Tyner, K Sapsford, KE AF Dair, Benita J. Tyner, Katherine Sapsford, Kim E. BE Rege, K Medintz, IL TI Techniques for the Characterization of Nanoparticle-Bioconjugates SO METHODS IN BIOENGINEERING: NANOSCALE BIOENGINEERING AND NANOMEDICINE SE Artech House Methods in Bioengineering Series LA English DT Article; Book Chapter DE review; nanoparticle; biomolecule; bioconjugation; separation; microscopy; spectroscopic; mass spectroscopy; thermal ID FIELD-FLOW FRACTIONATION; RESONANCE ENERGY-TRANSFER; FLUORESCENCE CORRELATION SPECTROSCOPY; DYNAMIC LIGHT-SCATTERING; ATOMIC-FORCE MICROSCOPY; WALLED CARBON NANOTUBES; MONOLAYER-PROTECTED NANOPARTICLES; CIRCULAR-DICHROISM SPECTROSCOPY; SINGLE-MOLECULE FLUORESCENCE; PROTEIN SECONDARY STRUCTURE AB There are a variety of well-developed analytical tools that have been successfully applied to unmodified/native nanoparticle (NP) characterization. The question addressed here is whether these same technologies can be used for the analysis of NP-bioconjugates, given the added complexity of their composite structure, and if they can provide the additional information sought by the user. The short answer is, of course, yes, but as found with unmodified NP analysis, it is fair to say that no one technique can provide a complete characterization of engineered NP-bioconjugates. Rather, a combination of techniques must be used to characterize the many metrics associated with the NP scaffold itself and also the overall NP-bioconjugate assembly. The aim of this chapter is to provide the reader with an overview of the general principles and potential information available from each technology, along with some pertinent examples which highlight both the potential advantages and/or drawbacks of each particular technique. C1 [Sapsford, Kim E.] US FDA, Div Biol, Off Sci & Engn, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Tyner, Katherine] US FDA, Div Appl Pharmacol Res, Off Testing & Res, Off Pharmaceut Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Dair, Benita J.] US FDA, Div Chem & Mat Sci, Off Sci & Engn, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Sapsford, KE (reprint author), US FDA, Div Biol, Off Sci & Engn, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kim.sapsford@fda.hhs.gov NR 243 TC 2 Z9 2 U1 0 U2 9 PU ARTECH HOUSE PI NORWOOD PA 685 CANTON ST, NORWOOD, MA 02062 USA BN 978-1-59693-410-8 J9 ARTECH HSE METH BIOE JI Art. Hse. Meth. Bioengr. Ser. PY 2009 BP 293 EP 331 PG 39 WC Engineering, Biomedical; Nanoscience & Nanotechnology SC Engineering; Science & Technology - Other Topics GA BKZ87 UT WOS:000269709900015 ER PT J AU Rodriguez, JS Paule, MG AF Rodriguez, Jesse S. Paule, Merle G. BE Buccafusco, JJ TI Working Memory Delayed Response Tasks in Monkeys SO METHODS OF BEHAVIOR ANALYSIS IN NEUROSCIENCE, SECOND EDITION SE Frontiers in Neuroscience LA English DT Article; Book Chapter ID OPERANT TEST BATTERY; ATTENTION-DEFICIT/HYPERACTIVITY DISORDER; IMPAIRED RECOGNITION MEMORY; RHESUS-MONKEYS; NONHUMAN-PRIMATES; MATCHING PERFORMANCE; PREFRONTAL CORTEX; AGED MONKEYS; TO-SAMPLE; CALORIC RESTRICTION C1 [Rodriguez, Jesse S.; Paule, Merle G.] Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Rodriguez, JS (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NR 67 TC 12 Z9 12 U1 2 U2 3 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA J9 FRONT NEUROSCI JI Front. Neurosci. PY 2009 SI 2nd BP 247 EP 265 PG 19 WC Neurosciences SC Neurosciences & Neurology GA BKW98 UT WOS:000269503500012 ER PT B AU Shi, LM Perkins, RG Tong, WD AF Shi, Leming Perkins, Roger G. Tong, Weida BE Dill, K Liu, RH Grodzinski, P TI The Current Status of DNA Microarrays SO MICROARRAYS: PREPARATION, MICROFLUIDICS, DETECTION METHODS, AND BIOLOGICAL APPLICATIONS SE Integrated Analytical Systems LA English DT Article; Book Chapter DE DNA microarray; fabrication; gene expression; microarray experimental process; reproducibility; data analysis; clinical applications; regulatory decision-making ID GENE-EXPRESSION MEASUREMENTS; CONTROL MAQC PROJECT; QUALITY-CONTROL; OLIGONUCLEOTIDE ARRAYS; PLATFORMS; CANCER; PERFORMANCE; CONSISTENCY; VALIDATION; NOISE AB DNA microarray technology that allows simultaneous assay of thousands of genes in a single experiment has steadily advanced to become a mainstream method used in research, and has reached a stage that envisions its use in medical applications and personalized medicine. Many different strategies have been developed for manufacturing DNA microarrays. In this chapter, we discuss the manufacturing characteristics of seven microarray platforms that were used in a recently completed large study by the MicroArray Quality Control (MAQC) consortium, which evaluated the concordance of results across these platforms. The platforms can be grouped into three categories: (1) in situ synthesis of oligonucleotide probes on microarrays (Affymetrix GeneChip (R) arrays based on photolithography synthesis and Agilent's arrays based on inkjet synthesis); (2) spotting of presynthesized oligonucleotide probes on microarrays (GE Healthcare's CodeLink system, Applied Biosystems' Genome Survey Microarrays, and the custom microarrays printed with Operon's oligonucleotide set); and (3) deposition of presynthesized oligonucleotide probes on bead-based microarrays (Illumina's BeadChip microarrays). We conclude this chapter with our views on the challenges and opportunities toward acceptance of DNA microarray data in clinical and regulatory settings. C1 [Shi, Leming; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Perkins, Roger G.] Z Tech Corp, Jefferson, AR 72079 USA. RP Shi, LM (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Leming.Shi@fda.hhs.gov NR 41 TC 4 Z9 4 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES BN 978-0-387-72716-5 J9 INTEGR ANAL SYST PY 2009 BP 3 EP 24 DI 10.1007/978-0-387-72719-6_1 D2 10.1007/978-0-387-72719-6 PG 22 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Genetics & Heredity SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Genetics & Heredity GA BJY42 UT WOS:000267419200001 ER PT J AU Elkins, KL Colombini, SM Krieg, AM De Pascalis, R AF Elkins, Karen L. Colombini, Susan M. Krieg, Arthur M. De Pascalis, Roberto TI NK cells activated in vivo by bacterial DNA control the intracellular growth of Francisella tularensis LVS SO MICROBES AND INFECTION LA English DT Article DE Francisella; Natural killer cells; B cells; Macrophages; Bacterial DNA ID LIVE VACCINE STRAIN; CPG OLIGODEOXYNUCLEOTIDES; DENDRITIC CELLS; PROTECTIVE IMMUNITY; INTERFERON-GAMMA; INFECTION; MICE; RESPONSES; INNATE; RESISTANCE AB We demonstrated previously that mice treated with bacterial or oligonucleotide DNA containing unmethylated CpG motifs are transiently protected against lethal parenteral challenge with the intracellular bacterium Francisella tularensis Live Vaccine Strain (LVS). Here we explore the cellular basis of this protection. Wild-type mice that were treated with CpG oligonucleotide DNA and challenged with a lethal dose of LVS survived, while mice lacking TLR9 did not. In vitro, treatment of LVS-infected macrophages and/or naive splenocytes with oligo DNA had no impact on intracellular bacterial replication. In contrast, in vitro co-culture of LVS-infected macrophages with splenocytes obtained from mice treated with oligo DNA in vivo resulted in control of intracellular LVS growth. Control was reversed by antibodies to interferon-gamma or to tumor necrosis factor-alpha and by inhibition of nitric oxide, and to a lesser degree by antibodies to Interleukin-12. Further, splenocytes from DNA-primed normal, T cell KO, B cell KO, lymphocyte-deficient scid, or perforin KO mice all controlled intra-macrophage LVS growth. Enriched DNA-primed natural killer cells, but not B cells, clearly controlled intracellular LVS growth. Thus, NK cells contribute to DNA-mediated protection by production of cytokines including IFN-gamma and TNF-alpha, resulting in nitric oxide production and control of intracellular Francisella replication. Published by Elsevier Masson SAS. C1 [Elkins, Karen L.; Colombini, Susan M.; Krieg, Arthur M.; De Pascalis, Roberto] CBER FDA, Div Bacterial Parasit & Allergen Prod, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20852 USA. RP Elkins, KL (reprint author), CBER FDA, Div Bacterial Parasit & Allergen Prod, Lab Mycobacterial Dis & Cellular Immunol, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. EM karen.elkins@fda.hhs.gov NR 30 TC 13 Z9 14 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JAN PY 2009 VL 11 IS 1 BP 49 EP 56 DI 10.1016/j.micinf.2008.10.005 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 408IK UT WOS:000263428500007 PM 18992838 ER PT J AU Bhagwat, AA Jun, W Liu, L Kannan, P Dharne, M Pheh, B Tall, BD Kothary, MH Gross, KC Angle, S Meng, JH Smith, A AF Bhagwat, Arvind A. Jun, Won Liu, Liu Kannan, Porteen Dharne, Mahesh Pheh, Benedict Tall, Ben D. Kothary, Mahendra H. Gross, Kenneth C. Angle, Scott Meng, Jianghong Smith, Allen TI Osmoregulated periplasmic glucans of Salmonella enterica serovar Typhimurium are required for optimal virulence in mice SO MICROBIOLOGY-SGM LA English DT Article ID MEMBRANE-DERIVED OLIGOSACCHARIDES; COMPLETE GENOME SEQUENCE; ESCHERICHIA-COLI; BRADYRHIZOBIUM-JAPONICUM; PSEUDOMONAS-AERUGINOSA; INTRACELLULAR SURVIVAL; CYCLIC BETA-1,2-GLUCAN; ERWINIA-CHRYSANTHEMI; ACID RESISTANCE; LOCUS AB We purified osmoregulated periplasmic glucans (OPGs) from Salmonella enterica serovar Typhimurium and found them to be composed of 100% glucose with 2-linked glucose as the most abundant residue, with terminal glucose, 2,3-linked and 2,6-linked glucose also present in high quantities. The two structural genes for OPG biosynthesis, opgG and opgH, form a bicistronic operon, and insertion of a kanamycin resistance gene cassette into this operon resulted in a strain devoid of OPGs. The opgGH mutant strain was impaired in motility and growth under low osmolarity conditions. The opgGH mutation also resulted in a 2 log increase in the LD(50) in mice compared to the wild-type strain SL1344. Inability to synthesize OPGs had no significant impact on the organism's lipopolysaccharide pattern or its ability to survive antimicrobial peptides-, detergent-, pH- and nutrient-stress conditions. We observed that the opgGH-defective strain respired at a reduced rate under acidic growth conditions (pH 5.0) and had lower ATP levels compared to the wild-type strain. These data indicate that OPGs; of S. Typhimurium contribute towards mouse virulence as well as growth and motility under low osmolarity growth conditions. C1 [Bhagwat, Arvind A.; Jun, Won; Liu, Liu; Kannan, Porteen; Dharne, Mahesh; Pheh, Benedict; Gross, Kenneth C.] USDA ARS, Produce Qual & Safety Lab, Henry A Wallace Beltsville Agr Res Ctr, BARC W, Beltsville, MD 20705 USA. [Smith, Allen] USDA ARS, Diet Genom & Immunol Lab, Henry A Wallace Beltsville Agr Res Ctr, BARC W, Beltsville, MD 20705 USA. [Tall, Ben D.; Kothary, Mahendra H.] US FDA, Div Virulence Assessment, Laurel, MD 20708 USA. [Jun, Won] Univ Maryland, Dept Plant Sci & Landscape Architecture, College Pk, MD 20742 USA. [Angle, Scott] Univ Maryland, Coll Agr, College Pk, MD 20742 USA. [Meng, Jianghong] Univ Maryland, Dept Food Sci & Nutr, College Pk, MD 20742 USA. [Liu, Liu] NW A&F Univ, Yangling, Peoples R China. [Tall, Ben D.] Ngee Ann Polytech, Sch Life Sci & Chem Technol, Singapore 599489, Singapore. RP Bhagwat, AA (reprint author), USDA ARS, Produce Qual & Safety Lab, Henry A Wallace Beltsville Agr Res Ctr, BARC W, 10300 Baltimore Ave,Bldg 002, Beltsville, MD 20705 USA. EM arvind.bhagwat@ars.usda.gov RI Dharne, Mahesh/K-3541-2012; OI Tall, Ben/0000-0003-0399-3629; Kannan, Porteen/0000-0002-6925-328X FU China Scholarship Council; Ministry of Education, China; overseas Industrial Attachment Program of the School of Life Sciences and Chemical Technology, Ngee Ann Polytechnic, Singapore FX We thank Dr Brian Vinyard, Biometric Consulting Section, USDA-ARS, Beltsville, MD, USA, for his help in statistical analysis. The study was supported in part by the China Scholarship Council, Ministry of Education, China (L.L.) and the overseas Industrial Attachment Program of the School of Life Sciences and Chemical Technology, Ngee Ann Polytechnic, Singapore (B. P.). NR 46 TC 21 Z9 21 U1 0 U2 0 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 JAN PY 2009 VL 155 BP 229 EP 237 DI 10.1099/mic.0.023747-0 PG 9 WC Microbiology SC Microbiology GA 398KG UT WOS:000262730400024 PM 19118363 ER PT S AU Tettelin, H Feldblyum, T AF Tettelin, Herve Feldblyum, Tamara BE Caugant, DA TI Bacterial Genome Sequencing SO MOLECULAR EPIDEMIOLOGY OF MICROORGANISMS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Bacteria; diversity; genome; pathogen; sequencing technology ID SEROGROUP-B MENINGOCOCCUS; MICROBIAL PAN-GENOME; VACCINE CANDIDATES; PROTEIN FAMILIES; DNA-POLYMERASE; IDENTIFICATION; DATABASE; GENERATION; EVOLUTION; BIOLOGY AB For over 30 yr, the Sanger method has been the standard for DNA sequencing. Instruments have been developed and improved over time to increase throughput, but they always relied on the same technology Today, we are facing a revolution in DNA sequencing with many drastically different platforms that have become or will soon become available on the market. We review a number of sequencing technologies and provide examples of applications. We also discuss the impact genomics and new DNA sequencing approaches have had on various fields of biological research. C1 [Tettelin, Herve] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Inst Genome Sci, Baltimore, MD 21201 USA. [Feldblyum, Tamara] US FDA, Ctr Devices & Radiol Hlth, Off In Vitro Diagnost Devices Evaluat & Safety, Rockville, MD 20857 USA. RP Tettelin, H (reprint author), Univ Maryland, Sch Med, Dept Microbiol & Immunol, Inst Genome Sci, Baltimore, MD 21201 USA. NR 50 TC 14 Z9 14 U1 1 U2 3 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-998-7 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 551 BP 231 EP 247 DI 10.1007/978-1-60327-999-4_18 D2 10.1007/978-1-60327-999-4 PG 17 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKJ96 UT WOS:000268335900018 PM 19521879 ER PT J AU Griggs, RC Batshaw, M Dunkle, M Gopal-Srivastava, R Kaye, E Krischer, J Nguyen, T Paulus, K Merkel, PA AF Griggs, Robert C. Batshaw, Mark Dunkle, Mary Gopal-Srivastava, Rashmi Kaye, Edward Krischer, Jeffrey Nguyen, Tan Paulus, Kathleen Merkel, Peter A. CA Rare Dis Clinical Res Network TI Clinical research for rare disease: Opportunities, challenges, and solutions SO MOLECULAR GENETICS AND METABOLISM LA English DT Article DE Rare diseases; Research training; Clinical trials; Patient advocacy groups (PAGs) ID RANDOMIZED-TRIALS; CONDUCT; DESIGN AB Over 7000 rare diseases, each <200,000 US residents, affect nearly 30 million people in the United States. Furthermore, for the 10% of people with a rare disease and for their families, these disorders no longer seem rare. Molecular genetics have characterized the cause of many rare diseases and provide unprecedented opportunities for identifying patients, determining phenotypes, and devising treatments to prevent, stabilize, or improve each disease. Rare disease research poses challenges to investigators requiring specific approaches to: (1) the design of clinical studies; (2) the funding of research programs; (3) the discovery, testing, and approval of new treatments, and (4) the training of clinical scientists. Rigorous, statistically-valid, natural history-controlled, cross-over, and n-of-1 trials can establish efficacy and support regulatory approval of new treatments for rare diseases. The U.S. Orphan Drug Act of the U.S. FDA has stimulated industry investment in clinical trials to develop treatments for rare diseases. For trainees interested in finding a treatment for a rare disease, a commitment to longitudinal care of patients provides a base for the characterization of phenotype and natural history, a stimulus for innovation, a target population for research and helps fund training and research. The scientific methodology, financial resources, and logistics of clinical research for rare diseases have changed dramatically in the past two decades resulting in increased understanding of the pathophysiology of these disorders and direct benefit to patients. (C) 2008 Elsevier Inc. All rights reserved. C1 [Griggs, Robert C.] Univ Rochester, Dept Neurol, Rochester, NY 14620 USA. [Batshaw, Mark] Childrens Natl Med Ctr, Washington, DC 20010 USA. [Dunkle, Mary] NORD, Danbury, CT 06813 USA. [Gopal-Srivastava, Rashmi] NIH, Off Rare Dis, Bethesda, MD 20892 USA. [Kaye, Edward] Genzyme Corp, Cambridge, MA 02142 USA. [Krischer, Jeffrey; Paulus, Kathleen] Univ S Florida, Data Technol Coordinat Off, Tampa, FL 33612 USA. [Nguyen, Tan] US FDA, Off Vitro Diagnost, Rockville, MD 20857 USA. [Merkel, Peter A.] Boston Univ, Sch Med, Rheumatol Sect, Boston, MA 02118 USA. [Merkel, Peter A.] Boston Univ, Sch Med, Clin Epidemiol Unit, Vasculitis Ctr E5, Boston, MA 02118 USA. RP Griggs, RC (reprint author), Univ Rochester, Dept Neurol, 1351 Mt Hope Ave,Suite 203, Rochester, NY 14620 USA. EM Robert_griggs@urmc.rochester.edu FU NIH [R13 RR024337, U54 NS059065, U54 RR019497, U54-RR019453, U54-RR019478, U54-RR019480, U54-RR019397, U54-RR019484, U54-RR019498, U54-RR019259, U54-HL077878, U54-DK078377] FX R13 RR024337 Merkel, Peter A., Boston University, Boston, MA.; U54 NS059065 Griggs, Robert C., University of Rochester, Rochester, NY.; U54 RR019497 Merkel, Peter, Boston University, Boston, MA.; U54-RR019453 Batshaw, Mark, National Children's Hospital, Washington, DC.; U54-RR019478 Beaudet, Arthur, Baylor College of Medicine, Houston, TX.; U54-RR019480 Knowles, Michael, University of North Carolina, Chapel Hill, NC.; U54-RR019397 Maciejewski, Jaroslaw, Cleveland Clinic College of Medicine-CWRU, Cleveland, OH.; U54-RR019484 New, Maria, Mount Sinai School of Medicine, New York, NY.; U54-RR019498 Trapnell, Bruce, Children's Hospital, Cincinnati, OH.; U54-RR019259 Krischer, Jeff, University of South Florida,Tampa, FL.; U54-HL077878 Ortel, Thomas, Duke University Medical Center, Durham, NC.; U54-DK078377 Sokol, Ronald, Children's Hospital, Denver, CO.; The Rare Diseases Clinical Research Network (RDCRN) Steering Committee includes the following: Barbara Alving, MD, Mark L. Batshaw, MD, Elaine Collier, MD, Robert C. Griggs, MD, Stephen Groft, PharmD, Michael R. Knowles, MD, Peter A. Merkel, MD, MPH, Maria 1. New, MD, Thomas L. Ortel, MD, Ph.D., Alan K. Percy, MD, Ronald J. Sokol, MD, Bruce C. Trapnell, MD, PK Burnette, Ph.D. NR 20 TC 98 Z9 99 U1 0 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 J9 MOL GENET METAB JI Mol. Genet. Metab. PD JAN PY 2009 VL 96 IS 1 BP 20 EP 26 DI 10.1016/j.ymgme.2008.10.003 PG 7 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 398KV UT WOS:000262731900004 PM 19013090 ER PT J AU Chen, ML Yu, L AF Chen, Mei-Ling Yu, Lawrence TI The Use of Drug Metabolism for Prediction of Intestinal Permeability SO MOLECULAR PHARMACEUTICS LA English DT Article DE Biopharmaceutics Classification System; BCS; Biopharmaceutics Drug Disposition Classification System; BDDCS; drug permeability ID BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; OBSTRUCTIVE PULMONARY-DISEASE; CLINICAL PHARMACOKINETICS; PHOSPHODIESTERASE-4 INHIBITOR; ABSOLUTE BIOAVAILABILITY; CACO-2 CELLS; IN-VIVO; ABSORPTION; HUMANS; SOTALOL AB The Biopharmaceutics Classification System (BCS), based on the aqueous solubility and intestinal permeability of a drug substance, has been widely used to predict the extent of drug absorption during the course of pharmaceutical development. Combined with product dissolution data, this system has gained a prominent role in regulatory process to determine if a drug formulated in an immediate release solid oral dosage form qualifies for waiver of in vivo bioequivalence studies. In parallel, the Biopharmaceutics Drug Disposition Classification System (BDDCS), using aqueous solubility and drug metabolism, takes on another venue to predict overall drug disposition. It has been suggested that the matrix of drug metabolism in BDDCS can be used to substantiate the classification of permeability by BCS. A total of 51 drugs were compiled in this study to examine the use of drug metabolism for predicting permeability. All compounds were classified as high permeability based on BCS, but only 73% of the compounds were found to exhibit extensive metabolism. Lipophilicity accounts for significant metabolism of many highly permeable drugs. Fourteen (14) out of 51 drugs have poor metabolism, suggesting that high permeability as defined by BCS does not necessarily dictate extensive metabolism. The drugs that have high permeability but poor metabolism are generally hydrophilic molecules with low molecular weight and are likely to be absorbed by active transport mechanisms. Based on the present data and literature information, it seems logical to predict that the extent of absorption is mostly complete (or >= 90%) if the drug is subject to a high degree of metabolism (e.g., >= 90%). The extent of drug metabolism may be useful in supporting permeability classification under certain circumstances. C1 [Chen, Mei-Ling] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Off Gener Drugs, Silver Spring, MD 20993 USA. RP Chen, ML (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Off Gener Drugs, 10903 New Hampshire Ave,Bldg 51,Rm 4108, Silver Spring, MD 20993 USA. EM meiling.chen@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 68 TC 33 Z9 36 U1 1 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1543-8384 J9 MOL PHARMACEUT JI Mol. Pharm. PD JAN-FEB PY 2009 VL 6 IS 1 BP 74 EP 81 DI 10.1021/mp8001864 PG 8 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 402TC UT WOS:000263035000009 PM 19132929 ER PT J AU Arlt, VM Stiborova, M Martinek, V Da Costa, GG Phillips, DH Reynisson, J AF Arlt, Volker M. Stiborova, Marie Martinek, Vaclav Da Costa, Goncalo Gamboa Phillips, David H. Reynisson, Johannes TI Mutagenic potential of nitrenium ions of nitrobenzanthrones: correlation between theory and experiment SO MUTAGENESIS LA English DT Meeting Abstract C1 [Reynisson, Johannes] Nottingham Trent Univ, Sch Sci & Technol, Nottingham NG11 8NS, England. [Da Costa, Goncalo Gamboa] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Arlt, Volker M.; Phillips, David H.] Inst Canc Res, Sutton SM2 5NG, Surrey, England. [Stiborova, Marie; Martinek, Vaclav] Charles Univ Prague, Fac Sci, Dept Biochem, Prague 12840 2, Czech Republic. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD JAN PY 2009 VL 24 IS 1 MA 28 BP 106 EP 106 PG 1 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 388CK UT WOS:000261997700040 ER PT S AU Trucksess, MW Whitaker, TB AF Trucksess, Mary W. Whitaker, Thomas B. BE Appell, M Kendra, DF Trucksess, MW TI Sampling Plans of Mycotoxins in Foods and Dietary Supplements (Ginger Capsules) SO MYCOTOXIN PREVENTION AND CONTROL IN AGRICULTURE SE ACS Symposium Series LA English DT Proceedings Paper CT Symposium Mycotoxin Prevention and Control in Agriculture CY APR 06-10, 2008 CL New Orleans, LA SP Amer Chem Soc, Div Agr & Food Chem ID TESTING SHELLED CORN; OCHRATOXIN-A; PART I; AFLATOXIN; VARIABILITY; PEANUTS; GINSENG; DESIGN; LOTS; SIZE AB Detection and quantitation of mycotoxins in foods and feeds are important to human and animal health. Regulatory decisions for edible quality of imported and domestic foods depend on the classification of the bulk lot as acceptable or unacceptable. The classification is made by comparing the measured mycotoxin concentration in a test sample taken from the bulk lot to a legal limit. The assumption is that the lot concentration is the same as the test sample concentration. If the test sample concentration does not represent the lot concentration then the lot may be misclassified. Some good lots may be rejected by the sampling plan (seller's risk) and some bad lots may be accepted by the sampling plan (buyer's risk). The results will be either economic loss or adverse health impacts. Because of the large variability among sample test results taken from the same lot, it is difficult to obtain a precise and accurate estimate of the true contaminant concentration of a bulk lot when using small test samples. Proper sampling plans must be developed according to "suitable for purpose" principle. Some of the sampling plans for grains and nuts will be covered. Recent research on sampling and analytical variability associated with determination of aflatoxins and ochratoxin A in dietary supplement ginger capsules is presented to illustrate the development of sampling plans. C1 [Trucksess, Mary W.] US FDA, College Pk, MD 20740 USA. RP Trucksess, MW (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 22 TC 0 Z9 0 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 978-0-8412-6990-3 J9 ACS SYM SER JI ACS Symp. Ser. PY 2009 VL 1031 BP 207 EP 221 PG 15 WC Agriculture, Multidisciplinary; Biotechnology & Applied Microbiology; Food Science & Technology; Mycology SC Agriculture; Biotechnology & Applied Microbiology; Food Science & Technology; Mycology GA BVW21 UT WOS:000292954300014 ER PT J AU Rathore, AS Winkle, H AF Rathore, Anurag S. Winkle, Helen TI Quality by design for biopharmaceuticals SO NATURE BIOTECHNOLOGY LA English DT Article ID PROCESS ANALYTICAL TECHNOLOGY; MULTIVARIATE DATA-ANALYSIS; BIOTECH PRODUCTS; PAT; RECOMMENDATIONS; FERMENTATION; OPTIMIZATION; ANTIBODIES; ASSAYS; SPACE C1 [Rathore, Anurag S.] Proc Dev, Thousand Oaks, CA 91320 USA. [Winkle, Helen] Off Pharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Rathore, AS (reprint author), Proc Dev, M-S 30-2-A,1 Amgen Ctr Dr, Thousand Oaks, CA 91320 USA. EM asrathore@yahoo.com NR 28 TC 267 Z9 270 U1 8 U2 90 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD JAN PY 2009 VL 27 IS 1 BP 26 EP 34 DI 10.1038/nbt0109-26 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 394TP UT WOS:000262471200018 PM 19131992 ER PT J AU Kutner, RH Zhang, XY Reiser, J AF Kutner, Robert H. Zhang, Xian-Yang Reiser, Jakob TI Production, concentration and titration of pseudotyped HIV-1-based lentiviral vectors SO NATURE PROTOCOLS LA English DT Article ID VESICULAR STOMATITIS-VIRUS; MESENCHYMAL STEM-CELLS; NONDIVIDING CELLS; GENE-TRANSFER; ENVELOPE GLYCOPROTEINS; TRANSGENE EXPRESSION; TRANSDUCTION; TITER; PROMOTERS; GENERATION AB Over the past decade, lentiviral vectors have emerged as powerful tools for transgene delivery. The use of lentiviral vectors has become commonplace and applications in the fields of neuroscience, hematology, developmental biology, stem cell biology and transgenesis are rapidly emerging. Also, lentiviral vectors are at present being explored in the context of human clinical trials. Here we describe improved protocols to generate highly concentrated lentiviral vector pseudotypes involving different envelope glycoproteins. In this protocol, vector stocks are prepared by transient transfection using standard cell culture media or serum-free media. Such stocks are then concentrated by ultracentrifugation and/or ion exchange chromatography, or by precipitation using polyethylene glycol 6000, resulting in vector titers of up to 10(10) transducing units per milliliter and above. We also provide reliable real-time PCR protocols to titrate lentiviral vectors based on proviral DNA copies present in genomic DNA extracted from transduced cells or on vector RNA. These production/concentration methods result in high-titer vector preparations that show reduced toxicity compared with lentiviral vectors produced using standard protocols involving ultracentrifugation-based methods. The vector production and titration protocol described here can be completed within 8 d. C1 [Kutner, Robert H.; Zhang, Xian-Yang; Reiser, Jakob] Louisiana State Univ, Hlth Sci Ctr, Dept Med, Gene Therapy Program, New Orleans, LA 70112 USA. [Reiser, Jakob] US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. RP Reiser, J (reprint author), Louisiana State Univ, Hlth Sci Ctr, Dept Med, Gene Therapy Program, 533 Bolivar St, New Orleans, LA 70112 USA. EM Jakob.Reiser@fda.hhs.gov FU NIH [NS044832] FX This work was supported by NIH grant NS044832. NR 26 TC 226 Z9 233 U1 4 U2 29 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1754-2189 J9 NAT PROTOC JI Nat. Protoc. PY 2009 VL 4 IS 4 BP 495 EP 505 DI 10.1038/nprot.2009.22 PG 11 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 441PV UT WOS:000265782100006 PM 19300443 ER PT J AU Schultz, DG AF Schultz, Daniel G. TI Possible Malfunction of Electronic Medical Devices Caused by Computed Tomography Scanning SO NEUROMODULATION LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Schultz, DG (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. OI Krames, Elliot/0000-0001-5374-022X NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1094-7159 J9 NEUROMODULATION JI Neuromodulation PD JAN PY 2009 VL 12 IS 1 BP 5 EP 7 DI 10.1111/j.1525-1403.2009.00193.x PG 3 WC Medicine, Research & Experimental; Clinical Neurology SC Research & Experimental Medicine; Neurosciences & Neurology GA 394VM UT WOS:000262479500002 ER PT J AU Boctor, SY Ferguson, SA AF Boctor, Sherin Y. Ferguson, Sherry A. TI Neonatal NMDA receptor antagonist treatments have no effects on prepulse inhibition of postnatal day 25 Sprague-Dawley rats SO NEUROTOXICOLOGY LA English DT Article DE Ketamine; Phencyclidine; Prepulse inhibition; Body weight; Sensorimotor gating ID PHENCYCLIDINE; KETAMINE; SCHIZOPHRENIA; NEUROTOXICITY; PERFORMANCE; APOPTOSIS; SYMPTOMS; BLOCKADE; DEFICITS; MK-801 AB Glutamate activation of the NMDA receptor is essential for neuronal differentiation, migration, and survival. Treatment with NMDA receptor antagonists, such as ketamine (KET) or phencyclidine (PCP), can trigger apoptosis in neonatal rats. However, L-carnitine (LC) treatment appears to prevent glutamate-induced toxicity in the developing CNS. Previously, we described altered preweaning behaviors (i.e., abnormal home cage, slant board and forelimb hang behaviors) resulting from neonatal PCP and KET treatment. Those adverse effects of KET were somewhat ameliorated by LC [Boctor SY, Wang C, Ferguson SA. Neonatal PCP is more potent than ketamine at modifying preweaning behaviors of Sprague-Dawley rats. Toxicol Sci 2008;106:172-9]. Here, a portion of those subjects were evaluated for prepulse inhibition (PPI) of the acoustic startle response at postnatal day (PND) 25 since previous reports described PCP-induced effects on this response. Rats were subcutaneously treated with: saline; 10 mg/kg PCP (1 x/day) on PNDs 7, 9 and 11; 20 mg/kg KET (6 injections every 2 h on PND 7); or a similar regimen of ketamine and 250 mg/kg LC on PND 7, with a single injection of 250 mg/kg LC on PNDs 8-11 (KLC). Male and female rats were assessed using a standard PPI paradigm with prepulses of 68, 78 and 82 dB. Body weight was decreased 17-21% and whole brain weight was decreased 10% in PCP-treated rats. Specifically, cerebellar weight was significantly less in PCP-treated rats relative to control. Despite the magnitude of those PCP-induced changes, startle response in normal pulse only trials and percent of PPI in PCP-, KET-, and KLC-treated groups were comparable to controls. Average latency to maximum startle was 2.6 ms less in females than males (p < 0.007); there were no other significant sex effects. The lack of neonatal PCP treatment on later PPI is similar to that reported by Rasmussen et al. [Rasmussen BA, O'Neil J, Manaye KF, Perry DC, Tizabi Y. Long-term effects of developmental PCP administration on sensorimotor gating in male and female rats. Psychopharmacology (Berl) 2007; 190: 43-9.], and indicates that neonatal PCP-induced effects on PPI [Wang C, McInnis J, Ross-Sanchez M, Shinnick-Gallagher P, Wiley JL, Johnson KM. Long-term behavioral and neurodegenerative effects of perinatal phencyclidine administration: implications for schizophrenia. Neuroscience 2001; 107: 535-50.] appear difficult to replicate. Published by Elsevier Inc. C1 [Boctor, Sherin Y.; Ferguson, Sherry A.] Natl Ctr Toxicol Res FDA, Div Neurotoxicol, Jefferson, AR 72079 USA. [Boctor, Sherin Y.; Ferguson, Sherry A.] Univ Arkansas Med Sci, Dept Interdisciplinary Biomed Sci, Little Rock, AR 72205 USA. RP Ferguson, SA (reprint author), Natl Ctr Toxicol Res FDA, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM Sherin.Boctor@fda.hhs.gov; Sherry.Ferguson@fda.hhs.gov FU PHS HHS [224-93-0001] NR 25 TC 14 Z9 14 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JAN PY 2009 VL 30 IS 1 BP 151 EP 154 DI 10.1016/j.neuro.2008.10.011 PG 4 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 402XW UT WOS:000263047400020 PM 19038286 ER PT S AU Arias, HR Santamaria, A Ali, SF AF Arias, Hugo R. Santamaria, Abel Ali, Syed F. BE Sharma, HS TI PHARMACOLOGICAL AND NEUROTOXICOLOGICAL ACTIONS MEDIATED BY BUPROPION AND DIETHYLPROPION SO NEW CONCEPTS OF PSYCHOSTIMULANTS INDUCED NEUROTOXICITY SE International Review of Neurobiology LA English DT Review; Book Chapter ID NICOTINIC ACETYLCHOLINE-RECEPTOR; DIFFERENT CONFORMATIONAL STATES; BIOGENIC-AMINE TRANSPORTERS; HUMAN DOPAMINE TRANSPORTER; ANTAGONIST BINDING-SITES; IN-VIVO; MOLECULAR-MECHANISMS; ION-CHANNEL; TRICYCLIC ANTIDEPRESSANTS; MONOAMINE TRANSPORTERS AB The antiappetite agent diethylpropion (DEP), and the antidepressant and antismoking aid compound bupropion (BP), not only share the same structural motif but. also present similar mechanisms of action fit the CNS. For example, both drugs induce the release as well as inhibit the reuptake of neurotranstmitters such as a dopamine (DA) and norepinephrine (NE). In general, they produce mild side effects, including reversible psychomotor alterations mostly in geriatric patients (by BP), or moderate changes in neurotransmitter contents linked to oxidative damage (by DEP). Therefore, attention must be paid during any therapeutic use of these agents. Regarding the interaction of BP with the DA transporter, residues S359, located in the middle of TM7, and A279, located close to the extracellular end of TM5, contribute to the binding and blockade of translocation mediated by BP, respectively. Additional mechanisms of action have also been determined for each Compound. For example, BP is a noncompetitive antagonist (NCA) of several nicotinic acetylcholine receptors (AChRs). Based on this evidence, the dual antidepressant and antinicotinic activity of BP IS Currently considered to be mediated by its stimulatory action on DA and NE systems as well as its inhibitory action on AChRs. Considering the results obtained in the archetypical mouse muscle AChR, a sequential mechanism can be hypothesized to explain the inhibitory action of BP on neuronal AChRs: (1) BP first binds to AChRs in the resting state, decreasing the probability of ion channel opening, (2) the remnant fraction of open ion channels is subsequently decreased by accelerating the desensitization process, and finally (3) BP interacts with a binding domain located between the serine (position 9') and valine (Position 13') rings that is shared with the NCA phencyclidine and other tricyclic antidepressants. The homologous location in the alpha 3 beta 4 AChR is between the serine and valine/phenylalanine rings. This new evidence opens a window for further investigation using AChRs as targets for the action of safer antidepressants and novel antiaddictive compounds. C1 [Arias, Hugo R.] Midwestern Univ, Dept Pharmaceut Sci, Coll Pharmacy, Glendale, AZ 85308 USA. [Santamaria, Abel] Lab Aminoacidos Excitadores, Inst Natl Neurol & Neurocirugia, Mexico City, DF, Mexico. [Ali, Syed F.] Natl Ctr Toxicol Res Food & Drug Adm, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Arias, HR (reprint author), Midwestern Univ, Dept Pharmaceut Sci, Coll Pharmacy, Glendale, AZ 85308 USA. NR 104 TC 13 Z9 13 U1 1 U2 3 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0074-7742 BN 978-0-12-374504-0 J9 INT REV NEUROBIOL JI Int. Rev. Neurobiol. PY 2009 VL 88 BP 223 EP + DI 10.1016/S0074-7742(09)88009-4 PG 34 WC Neurosciences SC Neurosciences & Neurology GA BMI37 UT WOS:000272436800010 PM 19897080 ER PT J AU Wysowski, DK AF Wysowski, Diane K. TI Reports of Esophageal Cancer with Oral Bisphosphonate Use SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID ALENDRONATE; FEATURES C1 [Wysowski, Diane K.] US FDA, Silver Spring, MD 20993 USA. RP Wysowski, DK (reprint author), US FDA, Silver Spring, MD 20993 USA. EM diane.wysowski@fda.hhs.gov NR 5 TC 101 Z9 106 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 JAN 1 PY 2009 VL 360 IS 1 BP 89 EP 90 DI 10.1056/NEJMc0808738 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 389MI UT WOS:000262096800023 PM 19118315 ER PT J AU Kavanaugh, CJ Trumbo, PR Ellwood, KC AF Kavanaugh, Claudine J. Trumbo, Paula R. Ellwood, Kathleen C. TI Qualified Health Claims for Calcium and Colorectal, Breast, and Prostate Cancers: The US Food and Drug Administration's Evidence-Based Review SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Review ID II-NUTRITION-COHORT; VITAMIN-D; DAIRY-PRODUCTS; UNITED-STATES; COLON-CANCER; ADENOMA RECURRENCE; SUPPLEMENT USE; RANDOMIZED-TRIAL; DIETARY FACTORS; REDUCED RISK AB In 2003, the United States Food and Drug Administration (FDA) received a health claim petition for calcium supplements and reduced risk of colorectal, breast, and prostate cancers. Health claims characterize the relationship between a substance (food or food component) and disease (e.g., cancer or cardiovascular disease) or health-related condition (e.g., hypertension) and require premarket approval for the labeling of conventional foods and dietary supplements by the FDA. This review describes how the FDA used the evidence-based review system to evaluate the scientific evidence for these proposed health claims. FDA found no credible evidence to support health claims for calcium and a reduced risk of breast and prostate cancers. The agency did find limited evidence for the relationship between calcium intake and colorectal cancer risk. C1 [Kavanaugh, Claudine J.; Trumbo, Paula R.; Ellwood, Kathleen C.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Kavanaugh, CJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 830,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM claudine.kavanaugh@fda.hhs.gov NR 51 TC 3 Z9 3 U1 1 U2 3 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2009 VL 61 IS 2 BP 157 EP 164 AR PII 908886084 DI 10.1080/01635580802395741 PG 8 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 411KL UT WOS:000263648400001 PM 19235032 ER PT J AU Kane, RC Farrell, AT Madabushi, R Booth, B Chattopadhyay, S Sridhara, R Justice, R Pazdur, R AF Kane, Robert C. Farrell, Ann T. Madabushi, Rajanikanth Booth, Brian Chattopadhyay, Somesh Sridhara, Rajeshwari Justice, Robert Pazdur, Richard TI Sorafenib for the Treatment of Unresectable Hepatocellular Carcinoma SO ONCOLOGIST LA English DT Article DE Sorafenib; Hepatocellular carcinoma; Regular approval AB Purpose. To describe the U. S. Food and Drug Administration (FDA) review and approval of sorafenib (Nexavar (R); Bayer Pharmaceuticals Corp., Montville, NJ, and Onyx Pharmaceuticals Corp., Emeryville, CA), an oral kinase inhibitor, for the treatment of patients with unresectable hepatocellular carcinoma (HCC). Experimental Design. The FDA independently analyzed an international, double-blind, placebo-controlled trial comparing the effect of best supportive care plus sorafenib or matching placebo on overall survival. Eligible patients had unresectable, biopsy-proven HCC and had not received prior systemic therapy. Results. Among the 602 randomized patients (placebo, 303; sorafenib, 299), baseline characteristics were well balanced, and 97% were Child-Pugh score A. HCC was "advanced" in 70% overall, as defined by extrahepatic metastases or by tumor radiographically visible in venous structures outside the liver. Underlying liver diseases included hepatitis B (18%), hepatitis C (28%), and alcohol-related (26%). The trial was stopped following a prespecified second interim analysis showing a statistically significant survival advantage for sorafenib [median, 10.7 vs 7.9 months; hazard ratio, 0.69 (95% confidence interval, (0.55, 0.87)), p = 0.00058]. Adverse events in sorafenib-treated patients included diarrhea in 55%(grade 3, 10%), hand-foot syndrome in 21% (grade 3, 8%), rash in 19% (grade 3, 1%), and cardiac ischemia or infarction in 2.7% (versus 1.3% for placebo). On sorafenib, treatment-emergent hypertension occurred in 9% of patients (placebo, 4%) and was grade 3 in 4% (placebo, 1%); elevated serum lipase occurred in 40% (placebo, 37%); hypophosphatemia occurred in 35% (placebo, 11%). Conclusions. Sorafenib is the first systemic therapy to demonstrate a survival benefit in a randomized trial for unresectable HCC and has received FDA approval for this indication. The Oncologist 2009; 14: 95-100 C1 [Kane, Robert C.; Farrell, Ann T.; Madabushi, Rajanikanth; Booth, Brian; Chattopadhyay, Somesh; Sridhara, Rajeshwari; Justice, Robert; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Kane, RC (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 2109, Silver Spring, MD 20993 USA. EM robert.kane@fda.hhs.gov NR 2 TC 89 Z9 96 U1 0 U2 3 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD JAN PY 2009 VL 14 IS 1 BP 95 EP 100 DI 10.1634/theoncologist.2008-0185 PG 6 WC Oncology SC Oncology GA 407MJ UT WOS:000263368100013 PM 19144678 ER PT J AU Cohen, MH Farrell, A Justice, R Pazdur, R AF Cohen, Martin H. Farrell, Ann Justice, Robert Pazdur, Richard TI Approval Summary: Imatinib Mesylate in the Treatment of Metastatic and/or Unresectable Malignant Gastrointestinal Stromal Tumors SO ONCOLOGIST LA English DT Article DE Imatinib; Gleevec; KIT; CD117; Gastrointestinal stromal tumors ID TYROSINE KINASE; C-KIT; MUTATIONS; GIST AB The purpose of the present application was to fulfill a postmarketing commitment to provide long-term efficacy and safety data on treatment with imatinib mesylate (Gleevec(R); Novartis Pharmaceuticals, East Hanover, NJ) in patients with CD117(+) unresectable and/or metastatic malignant gastrointestinal stromal tumors (GISTs). In addition, this application also provides evidence to support a change in the label to allow for an escalation of imatinib dosing to 800 mg/day for patients with progressive disease on a lower dose. Two open-label, controlled, multicenter, intergroup, international, randomized phase III studies were submitted-one conducted by the European Organization for Research and Treatment of Cancer (n = 946) and the other by the Southwest Oncology Group ( n = 746). These studies compared 400 mg/day of imatinib with 800 mg/day of imatinib. A combined analysis of the two studies was prospectively defined and agreed to by both groups. Both protocols allowed patients randomized to the 400-mg/day imatinib arm to cross over to 800 mg/day imatinib at progression. Objective responses were achieved in > 50% of patients receiving either imatinib dose. The median progression-free survival time was approximately 20 months and the median overall survival (OS) time was approximately 49 months. In the combined analysis, 347 patients crossed over to 800 mg/day imatinib at the time of progression. The median OS time after crossover was 14.3 months. The most common adverse events (AEs) were fluid retention, nausea, fatigue, skin rash, gastrointestinal complaints, and myalgia. The most common laboratory abnormality was anemia. Most often the AEs were of mild-to-moderate severity. Fluid retention events and skin rash were numerically reported more often in the 800-mg/day treatment cohort of patients. The Oncologist 2009; 14: 174-180 C1 [Cohen, Martin H.; Farrell, Ann; Justice, Robert; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. RP Cohen, MH (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, White Oak Campus,10903 New Hampshire Ave,Bldg 22,, Silver Spring, MD 20993 USA. EM martin.cohen@fda.hhs.gov NR 11 TC 24 Z9 27 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 2 BP 174 EP 180 DI 10.1634/theoncologist.2008-0255 PG 7 WC Oncology SC Oncology GA 417ZD UT WOS:000264116100010 PM 19193781 ER PT J AU Giusti, RM Cohen, MH Keegan, P Pazdur, R AF Giusti, Ruthann M. Cohen, Martin H. Keegan, Patricia Pazdur, Richard TI FDA Review of a Panitumumab (Vectibix (TM)) Clinical Trial for First-Line Treatment of Metastatic Colorectal Cancer SO ONCOLOGIST LA English DT Article DE Panitumumab; Colorectal cancer; FDA drug review ID SIMPLIFIED BIMONTHLY LEUCOVORIN; PHASE-III TRIAL; 5-FLUOROURACIL REGIMEN; RANDOMIZED-TRIAL; 2ND-LINE THERAPY; DOSE LEUCOVORIN; FLUOROURACIL; OXALIPLATIN; IRINOTECAN; PLUS AB On September 27, 2006, the U. S. Food and Drug Administration granted accelerated approval to panitumumab (Vectibix (TM); Amgen, Inc., Thousand Oaks, CA) for the treatment of patients with epidermal growth factor receptor-expressing, metastatic colorectal carcinoma with disease progression on or following fluoropyrimidine-, oxaliplatin-, and irinotecan-containing chemotherapy regimens. Accelerated approval was based on demonstration of a beneficial effect on progression-free survival (PFS). The present submission summarizes a second clinical trial, to be included in the panitumumab package insert in June 2008, of chemotherapy and bevacizumab with and without panitumumab in the first-line treatment of patients with metastatic colorectal cancer. The study was closed when inferior PFS and greater toxicity were demonstrated at the time of the planned interim efficacy analysis. Patients receiving panitumumab in combination with bevacizumab and chemotherapy experienced a higher incidence of death (9% versus 4%) and a higher risk for grade 3 and 4 toxicities than patients receiving bevacizumab and chemotherapy alone. The incidences of any Common Terminology Criteria for Adverse Events grade 3 and 4 adverse events (AEs) were 87% and 72% in the panitumumab and control groups, respectively. Grade 3 and 4 AEs occurring more commonly in panitumumab-treated patients included rash/acneiform dermatitis, diarrhea, dehydration, primarily resulting from diarrhea, hypokalemia, stomatitis/mucositis, and pulmonary embolism. The addition of panitumumab to bevacizumab and chemotherapy for the first-line treatment of metastatic colorectal cancer was harmful when compared with bevacizumab and chemotherapy alone. The use of panitumumab in this setting cannot be recommended. The Oncologist 2009; 14: 284-290 C1 [Giusti, Ruthann M.; Cohen, Martin H.; Keegan, Patricia; Pazdur, Richard] US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Giusti, RM (reprint author), US FDA, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ruthann.giusti@fda.hhs.gov NR 23 TC 23 Z9 28 U1 0 U2 1 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 3 BP 284 EP 290 DI 10.1634/theoncologist.2008-0254 PG 7 WC Oncology SC Oncology GA 429SM UT WOS:000264940400011 PM 19282350 ER PT J AU Cohen, MH Justice, R Pazdur, R AF Cohen, Martin H. Justice, Robert Pazdur, Richard TI Approval Summary: Pemetrexed in the Initial Treatment of Advanced/Metastatic Non-Small Cell Lung Cancer SO ONCOLOGIST LA English DT Article DE Pemetrexed; Non-small cell lung cancer; First-line treatment ID VINORELBINE PLUS CISPLATIN; RANDOMIZED PHASE-III; THYMIDYLATE SYNTHASE; CHEMOTHERAPY; GEMCITABINE; TRIAL AB On September 26, 2008, the U. S. Food and Drug Administration approved pemetrexed injection (Alimta (R) Injection; Eli Lilly and Company, Indianapolis, IN) for use in combination with cisplatin for the initial treatment of patients with stage IIIB/IV nonsquamous non-small cell lung cancer (NSCLC). A randomized, phase III, open-label study was conducted in 1,725 patients. Patients were randomly assigned to receive 21-day cycles of pemetrexed plus cisplatin (AC) or gemcitabine plus cisplatin ( GC). The primary objective was overall survival. The median survival time was 10.3 months in both the AC arm and the GC arm ( adjusted hazard ratio [HR], 0.94; 95% confidence interval [CI], 0.84-1.05). The median progression-free survival times were 4.8 and 5.1 months for the AC and GC arms, respectively ( adjusted HR, 1.04; 95% CI, 0.94-1.15). The overall response rates were 27.1% and 24.7% for the AC and GC arms, respectively. A prespecified analysis of the impact of NSCLC histology on overall survival was conducted. In the nonsquamous NSCLC subgroup, the median survival times were 11.0 and 10.1 months in the AC and GC groups, respectively (unadjusted HR, 0.84; 95% CI, 0.74-0.96). However, in the squamous cell histology subgroup, the median survival times were 9.4 versus 10.8 months in the AC and GC groups, respectively (unadjusted HR, 1.22; 95% CI, 0.99-1.50). This unfavorable effect of squamous histology on overall survival was also noted in a retrospective analysis of a trial that compared pemetrexed with docetaxel in NSCLC patients who received prior chemotherapy. No new pemetrexed safety signals were observed. The Oncologist 2009; 14: 930-935 C1 [Cohen, Martin H.; Justice, Robert; Pazdur, Richard] US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, Silver Spring, MD 20993 USA. RP Cohen, MH (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Oncol Drug Prod, White Oak Campus,10903 New Hampshire Ave,Bldg 22,, Silver Spring, MD 20993 USA. EM martin.cohen@fda.hhs.gov FU U. S. Food and Drug Administration FX The views expressed are the result of independent work and do not necessarily represent the views and findings of the U. S. Food and Drug Administration. NR 14 TC 31 Z9 31 U1 0 U2 2 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 9 BP 930 EP 935 DI 10.1634/theoncologist.2009-0092 PG 6 WC Oncology SC Oncology GA 497FJ UT WOS:000270042200008 PM 19737998 ER PT J AU Cohen, MH Shen, YL Keegan, P Pazdur, R AF Cohen, Martin H. Shen, Yuan Li Keegan, Patricia Pazdur, Richard TI FDA Drug Approval Summary: Bevacizumab (Avastin (R)) as Treatment of Recurrent Glioblastoma Multiforme SO ONCOLOGIST LA English DT Article DE Bevacizumab; Avastin (R); Glioblastoma multiforme; Recurrent disease; Phase II trial ID HIGH-GRADE GLIOMAS; PHASE-II; MALIGNANT GLIOMA; RADIATION NECROSIS; PLUS IRINOTECAN; CLINICAL-TRIALS; CHEMOTHERAPY; TEMOZOLOMIDE; CARMUSTINE; EFFICACY AB On May 5, 2009, the U. S. Food and Drug Administration granted accelerated approval to bevacizumab injection (Avastin (R); Genentech, Inc., South San Francisco, CA) as a single agent for patients with glioblastoma multiforme (GBM) with progressive disease following prior therapy. The approval was based on durable objective responses (independent radiologic review with stable or decreasing corticosteroid use). Two trials evaluating bevacizumab, 10 mg/kg by i.v. infusion every 2 weeks, were submitted. One trial also randomized patients to bevacizumab plus irinotecan treatment. All patients had received prior surgery, radiotherapy, and temozolomide. Patients with active brain hemorrhage were excluded. One trial enrolled 78 independently confirmed GBM patients. Partial responses were observed in 25.9% (95% confidence interval [CI], 17.0%-36.1%) of the patients. The median response duration was 4.2 months (95% CI, 3.0-5.7 months). The second trial enrolled 56 GBM patients. Partial responses were observed in 19.6% (95% CI, 10.9%-31.3%) of the patients. The median response duration was 3.9 months (95% CI, 2.4-17.4 months). Safety data were provided for the first study. The most frequently reported bevacizumab adverse events of any grade were infection, fatigue, headache, hypertension, epistaxis, and diarrhea. Grade 3-5 bevacizumab-related adverse events included bleeding/hemorrhage, central nervous system (CNS) hemorrhage, hypertension, venous and arterial thromboembolic events, wound-healing complications, proteinuria, gastrointestinal perforation, and reversible posterior leukoencephalopathy. The attribution of certain adverse events (e.g., CNS hemorrhage, wound-healing complications, and thromboembolic events) to either bevacizumab, underlying disease, or both could not be determined because of the single-arm, noncomparative study design. The Oncologist 2009;14:1131-1138 C1 [Cohen, Martin H.; Shen, Yuan Li; Keegan, Patricia; Pazdur, Richard] US FDA, Div Biol Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Cohen, MH (reprint author), US FDA, Div Biol Oncol Prod, Off Oncol Drug Prod, Ctr Drug Evaluat & Res, White Oak Campus,10903 New Hampshire Ave,Bldg 22,, Silver Spring, MD 20993 USA. EM martin.cohen@fda.hhs.gov NR 29 TC 221 Z9 224 U1 2 U2 11 PU ALPHAMED PRESS PI DURHAM PA 318 BLACKWELL ST, STE 260, DURHAM, NC 27701-2884 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PY 2009 VL 14 IS 11 BP 1131 EP 1138 DI 10.1634/theoncologist.2009-0121 PG 8 WC Oncology SC Oncology GA 524TS UT WOS:000272166800009 PM 19897538 ER PT S AU Kim, DH Kang, JU Ilev, IK AF Kim, Do-Hyun Kang, Jin U. Ilev, Ilko K. BE Gannot, I TI Advanced Confocal Fiber-Optic Imaging and Sensing Approaches SO OPTICAL FIBERS AND SENSORS FOR MEDICAL DIAGNOSTICS AND TREATMENT APPLICATIONS IX SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications IX CY JAN 24-25, 2009 CL San Jose, CA SP SPIE DE confocal microscopy; photonic bandgap fiber; confocal interference microscopy; upconversion fluorescence ID PHOTONIC CRYSTAL FIBER; AXIAL RESOLUTION; MICROSCOPE AB Fiber-optic-based confocal microscopy has been extensively used as an effective imaging and sensor technology due to its submicron spatial resolution, flexible beam delivery, and scanning potential. Recent research efforts in confocal microscopy have been focused on improving the resolution, increasing the imaging speed, and adapting multi-photon modalities. Here, we present our recent research studies on various advanced confocal fiber-optic imaging and sensing approaches using the following novel confocal methods. First, we investigated an all-fiber-optic confocal interference microscope approach using a low-coherence near-infrared (1310 nm) light source. A signal-to-noise ratio (SNR) enhancement of 3.38 dB compared to a reflection-mode confocal microscope was observed. The use of a low-coherence light source reduced the interference effects between various optical components, and an all-fiber-optic, robust and compact confocal setup could be designed. Second, we experimentally investigated a single-fiber confocal microscope approach using a hollow-core photonic bandgap fiber. The single-fiber hollow-core structure reduced the back-reflection by 85% which enhanced the SNR. The measured lateral resolution was as high as or better than 0.78 mu m when a 532-nm laser source was used. Third, we explored a novel upconversion confocal microscope approach utilizing a continuous-wave near-infrared (1550 nm) pump light source. An Erbium-doped glass powder was used as an upconversion phosphor medium that emits an upconverted signal at 660 nm. Using this upconversion fiber-optic confocal microscope method, high resolution images with a lateral resolution close to theoretical limits were obtained. C1 [Kim, Do-Hyun; Ilev, Ilko K.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Kim, DH (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. RI Kang, Jin/A-3228-2010 NR 15 TC 0 Z9 0 U1 0 U2 3 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7419-3 J9 PROC SPIE PY 2009 VL 7173 AR 71730B DI 10.1117/12.816537 PG 7 WC Optics; Physics, Applied SC Optics; Physics GA BSL17 UT WOS:000284821100008 ER PT J AU Zhang, XC Hashemi, SS Yousefi, M Gao, CL Sheng, J Ni, JS Wang, W Mason, J Man, YG AF Zhang, Xichen Hashemi, Shahreyar Shar Yousefi, Morvarid Gao, Chunling Sheng, Joy Ni, Jinsong Wang, Wan Mason, Jeffrey Man, Yan-gao TI Atypical E-cadherin expression in cell clusters overlying focally disrupted mammary myoepithelial cell layers: Implications for tumor cell motility and invasion SO PATHOLOGY RESEARCH AND PRACTICE LA English DT Article DE E-cadherin; Breast cancer invasion; Myoepithelial cell layer disruption; Epithelial-stromal-interaction; Double immunohistochemistry ID CARCINOMA IN-SITU; TERM FOLLOW-UP; BREAST-CANCER; EPITHELIAL-CELLS; STROMAL INTERACTIONS; GENETIC ALTERATIONS; BASEMENT-MEMBRANE; GROWTH-FACTOR; PROGRESSION; DIFFERENTIATION AB Our recent studies showed that cell clusters overlying focal myoepithelial cell layer disruptions (FMCLD) had a significantly higher rate of ER negativity, genetic instabilities, and expression of invasion-related genes than adjacent cells within the same duct. This study attempted to determine if these cells would show aberrant E-cadherin expression, which imparts greater propensity for cell motility and invasion. Consecutive sections from breast tumors with a high frequency of FMCLD were double-immunostained for E-cadherin and a panel of related markers. The E-cadherin mRNA levels in cells overlying FMCLD and adjacent cells within the same duct were compared using real-time PCR. Nearly all the cell clusters overlying FMCLD were strongly immunoreactive for E-cadherin, whereas their adjacent counterparts within the same duct were largely negative. Cell clusters overlying FMCLD were generally arranged as tongue-like projections, "puncturing" deep into the stroma or tube-like structures that often contained red blood cells. The sub-cellular localization of E-cadherin in the above structures, however, was primarily cytoplasmic. The mRNA level of E-cadherin in cell clusters overlying FMCLD was significantly higher than that in adjacent cells within the same duct. These findings suggest that aberrant expression of E-cadherin may contribute to cell motility and invasion. Published by Elsevier GmbH. C1 [Man, Yan-gao] Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, Washington, DC 20306 USA. [Zhang, Xichen] Jilin Univ, Coll Anim Sci & Vet Med, Changchun 130023, Jilin, Peoples R China. [Hashemi, Shahreyar Shar; Yousefi, Morvarid] Staten Isl Univ Hosp, Dept Surg & Internal Med, Staten Isl, NY USA. [Gao, Chunling] US FDA, Div Monoclonal Antibodies, Bethesda, MD 20014 USA. [Sheng, Joy] Appl Biosyst Inc, Real Time PCR Tech Support Dept, Foster City, CA 94404 USA. [Wang, Wan] China Japan Union Hosp, Breast & Thyroid Surg Dept, Changchun, Jilin, Peoples R China. [Ni, Jinsong] Jilin Univ, Norman Bethune Coll Med Sci, Changchun 130023, Jilin, Peoples R China. [Mason, Jeffrey] Armed Forces Inst Pathol, Dept Biophys, Rockville, MD USA. RP Man, YG (reprint author), Armed Forces Inst Pathol, Dept Gynecol & Breast Pathol, 6825,16th St NW, Washington, DC 20306 USA. EM man@afip.osd.mil FU Ministry of Chinese Science and Technology Department [2006CB910505]; US Congressionally Directed Medical Research Programs [DAMD 17-01-1-0129, DAMD17-01-1-0130, PC051308]; The Susan G. Komen Breast Cancer Foundation [BCTR0706983]; AFIP/ARP [05AA] FX This study was supported in part by Grant 2006CB910505 from the Ministry of Chinese Science and Technology Department to Drs. Xichen Zhang and Yan-gao Man, and also by Grants DAMD 17-01-1-0129, DAMD17-01-1-0130, and PC051308 from the US Congressionally Directed Medical Research Programs, Grant BCTR0706983 from The Susan G. Komen Breast Cancer Foundation, and Grant 05AA from the AFIP/ARP joint research initiative project to Dr. Yan-gao Man. NR 63 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER GMBH, URBAN & FISCHER VERLAG PI JENA PA OFFICE JENA, P O BOX 100537, 07705 JENA, GERMANY SN 0344-0338 J9 PATHOL RES PRACT JI Pathol. Res. Pract. PY 2009 VL 205 IS 6 BP 375 EP 385 DI 10.1016/j.prp.2008.08.009 PG 11 WC Pathology SC Pathology GA 446PA UT WOS:000266132400001 PM 19395181 ER PT J AU Avigan, MI AF Avigan, Mark I. TI Pharmacogenomic biomarkers of susceptibility to adverse drug reactions: just around the corner or pie in the sky? SO Personalized Medicine LA English DT Article DE adverse drug reactions (ADRs); ADR phenotyping; genome-wide association studies; pharmacogenomic biomarkers; targeted gene analysis ID COMPLEX TRAITS; HUMAN-GENOME; HYPERSENSITIVITY; POLYMORPHISM; DEFICIENCY; HEPATITIS; TOXICITY; GENOTYPE; WARFARIN; ABACAVIR AB Two overarching goals tied to a futuristic vision of personalized medicine are to maximize individually derived benefits from available therapeutic drugs or biological agents and identify a reliable set of predictors of toxic outcomes to optimally manage a patient's treatment-related risk. This article will primarily address the second of these goals with a specific focus on challenges faced in the development of pharmacogenomic markers that would be used by practitioners to predict individual susceptibility to serious adverse drug reactions. The potential complexity of polygenic modifiers of risk for certain adverse drug reactions and demographic diversity in the prevalence of genomic variants pose significant challenges in the development of useful predictive biomarkers. Implementing rigorous scientific and logistical strategies to address these will be crucial in order to achieve meaningful success. C1 US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Avigan, MI (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, WO22 Room 3478,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mark.avigan@fda.nhs.gov NR 42 TC 10 Z9 10 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1741-0541 J9 PERS MED JI Pers. Med. PD JAN PY 2009 VL 6 IS 1 BP 67 EP 78 DI 10.2217/17410541.6.1.67 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 395KT UT WOS:000262523700012 ER PT J AU Kaput, J AF Kaput, Jim TI DEVELOPING A RESEARCH STRATEGY FOR PERSONALIZING NUTRITION AND MEDICINE SO PHARMACEUTICAL BIOLOGY LA English DT Meeting Abstract C1 [Kaput, Jim] FDA Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72201 USA. EM James.Kaput@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2009 VL 47 BP 2 EP 2 PG 1 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 403OZ UT WOS:000263093200005 ER PT J AU Betz, JM Saldanha, LG Fisher, KD Coates, PM Klein, M Engel, J Pho, AN Sharpless, KE Sander, LC Wise, SA Rimmer, CA Phinney, K AF Betz, J. M. Saldanha, L. G. Fisher, K. D. Coates, P. M. Klein, M. Engel, J. Pho, A. Nguyen Sharpless, K. E. Sander, L. C. Wise, S. A. Rimmer, C. A. Phinney, K. TI THE NIH/ODS ANALYTICAL METHODS AND REFERENCE MATERIALS PROGRAM FOR DIETARY SUPPLEMENTS: FIVE-YEAR ACCOMPLISHMENTS AND FUTURE DIRECTIONS SO PHARMACEUTICAL BIOLOGY LA English DT Meeting Abstract C1 [Betz, J. M.; Saldanha, L. G.; Fisher, K. D.; Coates, P. M.; Klein, M.; Engel, J.] NIH, Off Dietary Supplements, Bethesda, MD 20892 USA. [Pho, A. Nguyen] US FDA, Silver Spring, MD 20993 USA. [Sharpless, K. E.; Sander, L. C.; Wise, S. A.; Rimmer, C. A.; Phinney, K.] Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. EM betzj@od.nih.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1388-0209 J9 PHARM BIOL JI Pharm. Biol. PY 2009 VL 47 BP 29 EP 29 PG 1 WC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy SC Plant Sciences; Medical Laboratory Technology; Pharmacology & Pharmacy GA 403OZ UT WOS:000263093200079 ER PT J AU Johann-Liang, R Wyeth, J Chen, M Cope, JU AF Johann-Liang, Rosemary Wyeth, Jo Chen, Min Cope, Judith U. TI Pediatric drug surveillance and the food and drug administration's adverse event reporting system: an overview of reports, 2003-2007 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE pediatric; children; drug safety; drug surveillance; adverse events; reporting AB Purpose Our objective was to examine the numbers and characteristics of US pediatric adverse events (AEs) reported to the Food and Drug Administration (FDA)'s adverse event reporting system (AERS) for 5 years following implementation of the Best Pharmaceuticals for Children Act (BPCA) in 2002. Methods We analyzed reports in AERS received by FDA from January 1, 2003 to January 1, 2008 for overall numbers, age, gender, and seriousness of outcome in children and adults. Pediatric and adult age groups (<2, 2-10, 11-17, 18-50, and >50 years of age) were further evaluated for most frequently reported suspect drug classes and AEs. Results Seventy-two percent of 815 267 crude count reports had specified age information. Six percent of the total reports with age information reported age <18 years. Numbers of AEs being reported for children have remained steady, while those for adults have increased. The proportion of serious AEs reported was similar for pediatrics as compared to adults. Frequently reported suspect drug classes noted in pediatric age groups that were not observed in adults included anticonvulsants, attention deficit hyperactivity disorder (ADHD), anti-acne, and respiratory medications. Conclusions This overview highlights the need for strengthening the passive drug surveillance system from a pediatric perspective, as well as investing in more active surveillance systems. Drug safety initiatives to better capture risk information in order to balance the risk/benefit of drug use in children. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Johann-Liang, Rosemary] US Dept HHS, Natl Vaccine Injury Compensat Program, US Hlth Resources & Serv Adm, Rockville, MD 20857 USA. [Wyeth, Jo; Chen, Min] US FDA, Div Adverse Event Anal, Off Surveillance & Epidemiol, Silver Spring, MD USA. [Cope, Judith U.] US FDA, Off Pediat Therapeut, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Johann-Liang, R (reprint author), US Dept HHS, Natl Vaccine Injury Compensat Program, US Hlth Resources & Serv Adm, 5600 Fishers Lane,11C-03, Rockville, MD 20857 USA. EM Rjohann-liang@hrsa.gov NR 12 TC 26 Z9 27 U1 1 U2 3 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD JAN PY 2009 VL 18 IS 1 BP 24 EP 27 DI 10.1002/pds.1679 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 405EX UT WOS:000263206700004 PM 19009550 ER PT J AU Frueh, FW Salerno, RA Lesko, LJ Hockett, RD AF Frueh, Felix W. Salerno, Ronald A. Lesko, Lawrence J. Hockett, Richard D. TI 4th US FDA-Drug Information Association pharmacogenomics workshop, held 10-12 December, 2007 SO PHARMACOGENOMICS LA English DT Article DE biomarkers; drug development; regulatory decision making AB The 4th US FDA/Industry workshop, in a series on Pharmacogenomics, was on 'Biomarkers and Pharmacogenomics in Drug Development and Regulatory Decision Making' and was held on December 10-12, 2007 in Bethesda, MD, USA, with clear objectives to continue the dialogue that began in 2002 for enabling the use of biomarkers and pharmacogenomics in drug development and regulatory decision-making. This brief commentary will highlight the major topics and outcomes discussed at this meeting that was jointly sponsored by the FDA, The Pharmacogenomics Working Group (PWG), The Pharmaceutical Research and Manufacturers of America (PhRMA), The Biotechnology industry Organization (BIO) and The Drug Information Association (DIA). C1 [Frueh, Felix W.] Medco Hlth Solut Inc, Gaithersburg, MD 20878 USA. [Frueh, Felix W.; Lesko, Lawrence J.] US FDA, Off Clin Pharmacol, Silver Spring, MD USA. [Salerno, Ronald A.] Biol Consulting Grp Inc, Alexandria, VA USA. [Hockett, Richard D.] Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Frueh, FW (reprint author), Medco Hlth Solut Inc, 14401 Falling Leaf Dr, Gaithersburg, MD 20878 USA. EM felix_frueh@medco.com NR 0 TC 4 Z9 5 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2009 VL 10 IS 1 BP 111 EP 115 DI 10.2217/14622416.10.1.111 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 396BR UT WOS:000262567700016 PM 19102720 ER PT J AU Armstrong, M Bromley, C Cohen, N Hunt, CM O'Neil, R Power, A AF Armstrong, Martin Bromley, Christina Cohen, Nadine Hunt, Christine M. O'Neil, Robert Power, Aidan TI Developing the evidence base for applying pharmacogenomics: proceeds from DIA Workshop IV - Breakout Session 1 SO PHARMACOGENOMICS LA English DT Article DE biomarkers; drug development; genetics; pharmacogenomics; polymorphisms ID DIABETES PREVENTION PROGRAM; ABACAVIR HYPERSENSITIVITY; MISSENSE POLYMORPHISMS; SCHIZOPHRENIA; NEPHROPATHY; METFORMIN; HLA-B-ASTERISK-5701; PARAOXONASE-2; PROGRESSION; GENETICS AB The 4th Drug Information Association Workshop in a series of workshops on Pharmacogenomics: 'Biomarkers and Pharmacogenomics in Drug Development and Regulatory Decision Making' took place on December 10-12, 2007 in Bethesda, MD, USA. A number of breakout sessions were conducted to focus on different aspects of the development of biomarkers. Breakout Session 1 considered the evidence base for the development of pharmacogenomic markers from both safety and efficacy perspectives, with a view to understanding the challenges in the design of appropriate clinical studies during drug development. Case studies based on data generated during all stages of drug development were used to stimulate discussion and refine considerations for what constitutes a sufficient evidence base to support the effective use of novel, pharmacogenomic biomarkers. The discussions were open and lively, and some broad principles were drawn from the discussion. In this article, we summarize the case studies presented and develop key discussion points that arose out of the meeting. These case studies help to illustrate the current state of the art in the application of pharmacogenomics in drug development and the challenges being faced in the development of pharmacogenomics from interesting, exploratory associations into predictive biomarkers with clinical utility. We hope that this will serve as a stimulus to consideration of the critical issues facing the implementation of pharmacogenomics into drug development. C1 [Armstrong, Martin] AstraZeneca, R&D, Macclesfield, Cheshire, England. [O'Neil, Robert] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Power, Aidan] Pfizer Global Res & Dev, New London, CT 06320 USA. RP Armstrong, M (reprint author), AstraZeneca, R&D, Macclesfield, Cheshire, England. EM aidan.c.power@pfizer.com NR 27 TC 0 Z9 0 U1 1 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2009 VL 10 IS 1 BP 117 EP 125 DI 10.2217/14622416.10.1.117 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 396BR UT WOS:000262567700017 PM 19102721 ER PT J AU Hinma, L Spear, B Tsuchihashi, Z Kelly, J Bross, P Goodsaid, F Kalush, F AF Hinma, Lois Spear, Brain Tsuchihashi, Zenta Kelly, James Bross, Peter Goodsaid, Federico Kalush, Francis TI Drug-diagnostic codevelopment strategies: FDA and industry dialog at the 4th FDA/DIA/PhRMA/PWG/BIO Pharmacogenomics Workshop SO PHARMACOGENOMICS LA English DT Article DE biomarkers; companion diagnostics; drug/diagnostic codevelopment; pharmacogenomics AB The 4th US FDA/Industry Workshop on Pharmacogenomics in Drug Development and Regulatory Decision Making, was held in MD, USA, on December 10-12, 2007. One of the breakout sessions of the workshop focused on the regulatory issues around codevelopment of drugs and companion diagnostics. This session used hypothetical case studies as focal points for discussion of current thought and critical issues for both industry and the FDA in this evolving field. The panel and the audience discussed the evolution of the FDA's thinking on the regulatory path for companion diagnostics since the release of the April 2005 draft Drug Test Codevelopment Concept Paper and the issues faced by industry in attempting codevelopment efforts. This session provided an opportunity to allow an exchange of ideas between the FDA and industry and to identify critical issues that need further discussion in this important and evolving field. C1 [Hinma, Lois] Novartis Pharmaceut, E Hanover, NJ 07939 USA. [Spear, Brain] Abbott Labs, Abbott Pk, IL 60064 USA. [Tsuchihashi, Zenta] Bristol Myers Squibb Co, New York, NY 10154 USA. [Goodsaid, Federico] US FDA, Off Clin Pharmacol, CDER, Rockville, MD 20857 USA. RP Hinma, L (reprint author), Novartis Pharmaceut, 1 Hlth Pl, E Hanover, NJ 07939 USA. NR 5 TC 10 Z9 11 U1 0 U2 2 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2009 VL 10 IS 1 BP 127 EP 136 DI 10.2217/14622416.10.1.127 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 396BR UT WOS:000262567700018 PM 19102722 ER PT J AU Surh, LC Lesko, LJ Hobbs, S Gutman, S Minasian, LM Della Pasqua, OE Austin, MJF Lu, K AF Surh, Linda C. Lesko, Lawrence J. Hobbs, Stuart Gutman, Steve Minasian, Lori M. Della Pasqua, Oscar E. Austin, M. J. Finley Lu, Kan TI Fit-for-purpose pharmacogenomic biomarkers in drug development: a project team case study with 'what-ifs' SO PHARMACOGENOMICS LA English DT Article DE biomarkers; drug development; pharmacogenetics; pharmacogenomics; Product Label; SPC; Summary of Product Characteristics; USPI; US Prescribing Information AB Over the past four years, the annual US FDA-DIA pharmacogenomic workshops have brought together attendees with wide-ranging expertise spanning industry, regulatory authorities and academia. This special report summarizes a breakout session using a novel, interactive case format as a way to engage participants, raise awareness and share diverse learnings via 'real life' decisions that project teams might face in developing a new medicine. This case was situated just prior to approval by a Regulatory Authority as a project team is finalizing a new medicine label. To effectively integrate new biomarkers such as pharmacogenomics into developing new medicines, this session highlighted the importance in considering medical practice implications as relevant (or not) to information or actions by a prescriber; progressing validation beyond assay to clinical; and fitting pharmacogenomics into context with other evidence often built over decades during a drug's development. All converge onto a label that must communicate evidence-based use of a new medicine that is effective and safe. C1 [Surh, Linda C.] GlaxoSmithKline Inc, CEDD, Global Regulatory Affairs Neurol & Pharmacogenet, Greenford UB6 0HE, Middx, England. [Lesko, Lawrence J.] US FDA, Off Clin Pharmacol, CDER, Rockville, MD 20857 USA. [Hobbs, Stuart; Lu, Kan] GlaxoSmithKline Inc, Strateg Prod Labelling, Res Triangle Pk, NC USA. [Gutman, Steve] US FDA, Off In Vitro Diagonost, CDRH, Rockville, MD 20857 USA. [Minasian, Lori M.] NCI, NIH, Bethesda, MD 20892 USA. [Della Pasqua, Oscar E.] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. RP Surh, LC (reprint author), GlaxoSmithKline Inc, CEDD, Global Regulatory Affairs Neurol & Pharmacogenet, Greenford Rd, Greenford UB6 0HE, Middx, England. EM lcs29779@gsk.com NR 4 TC 4 Z9 5 U1 0 U2 0 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD JAN PY 2009 VL 10 IS 1 BP 137 EP 147 DI 10.2217/14622416.10.1.137 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 396BR UT WOS:000262567700019 PM 19102723 ER PT S AU Katz, E Kim, DH Ilev, I Krauthamer, V AF Katz, Elizabeth Kim, Do-Hyun Ilev, Ilko Krauthamer, Victor BE MahadevanJansen, A Jansen, ED TI Effects of optical irradiation parameters on safe peripheral nerve stimulation with infrared light SO PHOTONS AND NEURONS SE Proceedings of SPIE-The International Society for Optical Engineering LA English DT Proceedings Paper CT Conference on Photons and Neurons CY JAN 25-26, 2009 CL San Jose, CA SP SPIE DE optical stimulation; sciatic nerve; compound action potentials; safety parameters ID LASER; THERAPY; PULSE AB Optical stimulation (OS) is a relatively novel approach for restoring function to the damaged nervous system. The effectiveness and safety of OS is dependent upon selecting the appropriate stimulation parameters. This involves stimulating neurons to their activation threshold while preventing laser-induced tissue injury. Although significant advances have been made in studying the efficacy of OS, safety parameters are still being developed. We have employed electrophysiological techniques to determine salient experimental parameters of safety that can be used to optimize OS. Extracellular recordings of compound nerve potentials were obtained from excised adult rat sciatic nerves. OS was accomplished with infrared pulsed Nd:YAG, Er:YAG and diode lasers that had peak wavelength emissions at 1.064 mu m, 2.94 mu m and 1.85 mu m, respectively. Electrically evoked compound action potentials (E-CAPs) were assayed before and after laser irradiation to determine if OS affected E-CAPs. Injurious laser irradiation doses were observed at levels 2-3 fold greater than optical threshold, producing tissue hyalinization and decreases in the peak amplitude of E-CAPs. However, effects on electrical threshold and conduction velocity were negligible. At laser irradiation doses near optical threshold, low repetition rates of laser pulses produced a gradual increase in laser evoked CAP (L-CAP) amplitudes, suggesting a cumulative effect in the interactions between light and tissue. Higher repetition rates (5-10 Hz) at laser irradiation doses 2-3 fold above optical threshold produced a decrement in L-CAP and E-CAP amplitudes. These results suggest that laser pulse parameters have a direct impact on optical stimulation and damage thresholds. C1 [Katz, Elizabeth; Kim, Do-Hyun; Ilev, Ilko; Krauthamer, Victor] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. RP Katz, E (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. NR 20 TC 0 Z9 0 U1 2 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 978-0-8194-7426-1 J9 P SOC PHOTO-OPT INS PY 2009 VL 7180 AR 71800P DI 10.1117/12.816718 PG 8 WC Engineering, Biomedical; Optics SC Engineering; Optics GA BSS62 UT WOS:000285713100011 ER PT J AU Kannan, M Ahmad, F Yadav, BK Anand, M Jain, P Kumar, R Saxena, R AF Kannan, Meganathan Ahmad, Firdos Yadav, Birendra Kumar Anand, Mona Jain, Paresh Kumar, Rajive Saxena, Renu TI Glanzmann's thrombasthenia in North Indians: Sub classification and carrier detection by flow cytometry SO PLATELETS LA English DT Article DE Glanzmann's Thrombasthenia; flow cytometry; carrier detection; North India ID IRAQI-JEWISH; GLYCOPROTEIN-IIIA; ARAB; MUTATIONS; INSIGHTS; SUBUNIT; ISRAEL AB Thirty-three patients of Glanzmann's thrombasthenia (GT) and their families were assessed for the expression of IIb3 on platelet surface, by flow cytometry, to determine the common subtypes in North Indians as well as to assess the carrier status in family members of GT patients. GT was diagnosed in patients with bleeding manifestations accompanied by absent/reduced platelet aggregation, secondary to adenosine-di-phosphate, adrenaline, arachidonic acid and collagen. Based on IIb3 levels, 21 patients (64%) were classified as type I (as IIb3 was absent), 4 patients (12%) as type II and 8 patients (24%) as type III. Eight out of 20 fathers, 10 out of 20 mothers and 20 out of 31 siblings were found to have reduced IIb3 levels. Reduced IIb3 expression was seen in 63% of parents and 65% of siblings. It is possible that low IIb3 levels in family members may reflect their carrier status. It is postulated that flow cytometry estimation of IIb3 in parents/siblings may detect carrier status in GT. It is also revealed that type I GT is the commonest subtype in North Indians. C1 [Kannan, Meganathan; Ahmad, Firdos; Yadav, Birendra Kumar; Saxena, Renu] All India Inst Med Sci, Dept Haematol, New Delhi 110029, India. [Anand, Mona; Jain, Paresh; Kumar, Rajive] All India Inst Med Sci, IRCH, Lab Oncol Unit, New Delhi 110029, India. [Kannan, Meganathan] US FDA, CBER, Div Hematol, Bethesda, MD 20014 USA. RP Saxena, R (reprint author), All India Inst Med Sci, Dept Haematol, IRCH Bldg 1st Floor, New Delhi 110029, India. EM renusax@hotmail.com RI Ahmad, Firdos/G-6664-2015 NR 14 TC 5 Z9 6 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0953-7104 J9 PLATELETS JI Platelets PY 2009 VL 20 IS 1 BP 12 EP 15 AR PII 908191554 DI 10.1080/09537100802434853 PG 4 WC Cell Biology; Hematology SC Cell Biology; Hematology GA 399HC UT WOS:000262790000003 PM 19172516 ER PT B AU Farrar, J Guzewich, J AF Farrar, Jeff Guzewich, Jack BE Sapers, GM Solomon, EB Matthews, KR TI Identification of the Source of Contamination SO PRODUCE CONTAMINATION PROBLEM: CAUSES AND SOLUTIONS SE Food Science and Technology-International Series LA English DT Article; Book Chapter C1 [Farrar, Jeff] Calif Dept Publ Hlth, Food & Drug Branch, Sacramento, CA 95814 USA. [Guzewich, Jack] USDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Farrar, J (reprint author), Calif Dept Publ Hlth, Food & Drug Branch, Sacramento, CA 95814 USA. NR 4 TC 4 Z9 4 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092111-2; 978-0-12-374186-8 J9 FOOD SCI TECH-INT SE PY 2009 BP 49 EP 77 DI 10.1016/B978-0-12-374186-8.00003-3 PG 29 WC Agricultural Engineering; Agronomy; Food Science & Technology SC Agriculture; Food Science & Technology GA BA4PH UT WOS:000336095200004 ER PT B AU Keller, SE AF Keller, Susanne E. BE Sapers, GM Solomon, EB Matthews, KR TI Tree Fruits and Nuts: Outbreaks, Contamination Sources, Prevention, and Remediation SO PRODUCE CONTAMINATION PROBLEM: CAUSES AND SOLUTIONS SE Food Science and Technology-International Series LA English DT Article; Book Chapter ID ESCHERICHIA-COLI O157-H7; UNPASTEURIZED APPLE CIDER; GOLDEN-DELICIOUS APPLES; SALMONELLA-TYPHIMURIUM DT104; ENTERITIDIS PHAGE TYPE-30; LISTERIA-MONOCYTOGENES; ACID TOLERANCE; FRESH PRODUCE; ORANGE JUICE; SHIGELLA-FLEXNERI C1 Natl Ctr Food Safety & Technol, FDA CFSAN, Summit Argo, IL 60501 USA. RP Keller, SE (reprint author), Natl Ctr Food Safety & Technol, FDA CFSAN, Summit Argo, IL 60501 USA. NR 117 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-092111-2; 978-0-12-374186-8 J9 FOOD SCI TECH-INT SE PY 2009 BP 249 EP 269 DI 10.1016/B978-0-12-374186-8.00011-2 PG 21 WC Agricultural Engineering; Agronomy; Food Science & Technology SC Agriculture; Food Science & Technology GA BA4PH UT WOS:000336095200012 ER PT S AU Fang, H Harris, SC Su, ZJ Chen, MJ Qian, F Shi, LM Perkins, R Tong, WD AF Fang, Hong Harris, Stephen C. Su, Zhenjiang Chen, Minjun Qian, Feng Shi, Leming Perkins, Roger Tong, Weida BE Nikolsky, Y Bryant, J TI ArrayTrack: An FDA and Public Genomic Tool SO PROTEIN NETWORKS AND PATHWAY ANALYSIS SE Methods in Molecular Biology LA English DT Article; Book Chapter DE ArrayTrack; bioinformatics; MAQC; pharmacogenomics; VGDS; microarray; toxicogenomics; systems toxicology; database; genomics ID MICROARRAY DATA; TOXICOGENOMICS; TOXICOLOGY; QUALITY AB A robust bioinformatics capability is widely acknowledged as central to realizing the promises of toxicogenomics. Successful application of toxicogenomic approaches, such as DNA microarrays, inextricably relics on appropriate data management, the ability to extract knowledge from massive amounts of data, and the availability of functional information for data interpretation. At the FDA's National Center for Toxicological Research (NCTR), we are developing a public microarray data management and analysis software, called ArrayTrack, that is also used in the routine review., of genomic data submitted to the FDA. ArrayTrack stores a hill range of information related to DNA microarrays and clinical and non-clinical Studies as well as the digested data derived from proteomics and metabonomics experiments. In addition, ArrayTrack provides a rich collection of functional information about genes, proteins, and pathways drawn from various public biological databases for Facilitating data interpretation. Many data analysis and visualization tools are available with ArrayTrack for individual platform data analysis, multiple omics; data integration, and integrated analysis of omics data with study data. Importantly, gene expression data, functional information,and analysis methods are hilly integrated so that the data analysis and interpretation process is simplified and enhanced. Using ArrayTrack, users can select an analysis method from the ArrayTrack tool box, apply the method to selected microarray data, and the analysis of results can be directly linked to individual gene, pathway, and Gene Ontology analysis. ArrayTrack is publicly available online (http://www.fda.gov/nctr/science/centers/toxicoinformatics/ArrayTrack/index.htm) and the prospective user can also request a local instillation version by contacting the authors. C1 [Fang, Hong; Qian, Feng] Z Tech Corp, Jefferson, AR USA. [Harris, Stephen C.; Su, Zhenjiang; Chen, Minjun; Shi, Leming; Perkins, Roger; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Fang, H (reprint author), Z Tech Corp, Jefferson, AR USA. NR 18 TC 43 Z9 44 U1 1 U2 4 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60761-174-5 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 563 BP 379 EP 398 DI 10.1007/978-1-60761-175-2_20 D2 10.1007/978-1-60761-175-2 PG 20 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA BKY50 UT WOS:000269615300020 PM 19597796 ER PT J AU Hambali, AS Ng, KH Abdullah, BJJ Wang, HB Jamal, N Spelic, DC Suleiman, OH AF Hambali, Ahmad Shariff Ng, Kwan-Hoong Abdullah, Basri Johan Jeet Wang, Hwee-Beng Jamal, Noriah Spelic, David C. Suleiman, Orhan H. TI Entrance surface dose and image quality: comparison of adult chest and abdominal X-ray examinations in general practitioner clinics, public and private hospitals in Malaysia SO RADIATION PROTECTION DOSIMETRY LA English DT Article ID DIAGNOSTIC-RADIOLOGY; RADIOGRAPHY; REDUCTION; ABDOMEN AB This study was undertaken to compare the entrance surface dose (ESD) and image quality of adult chest and abdominal X-ray examinations conducted at general practitioner (GP) clinics, and public and private hospitals in Malaysia. The surveyed facilities were randomly selected within a given category (28 GP clinics, 20 public hospitals and 15 private hospitals). Only departmental X-ray units were involved in the survey. Chest examinations were done at all facilities, while only hospitals performed abdominal examinations. This study used the x-ray attenuation phantoms and protocols developed for the Nationwide Evaluation of X-ray Trends (NEXT) survey program in the United States. The ESD was calculated from measurements of exposure and clinical geometry. An image quality test tool was used to evaluate the low-contrast detectability and high-contrast detail performance under typical clinical conditions. The median ESD value for the adult chest X-ray examination was the highest (0.25 mGy) at GP clinics, followed by private hospitals (0.22 mGy) and public hospitals (0.17 mGy). The median ESD for the adult abdominal X-ray examination at public hospitals (3.35 mGy) was higher than that for private hospitals (2.81 mGy). Results of image quality assessment for the chest X-ray examination show that all facility types have a similar median spatial resolution and low-contrast detectability. For the abdominal X-ray examination, public hospitals have a similar median spatial resolution but larger low-contrast detectability compared with private hospitals. The results of this survey clearly show that there is room for further improvement in performing chest and abdominal X-ray examinations in Malaysia. C1 [Ng, Kwan-Hoong; Abdullah, Basri Johan Jeet] Univ Malaya, Dept Biomed Imaging, Kuala Lumpur 50603, Malaysia. [Hambali, Ahmad Shariff; Wang, Hwee-Beng] Fed Govt Adm Ctr, Engn Serv Div, Minist Hlth Malaysia, Putrajaya 62590, Malaysia. [Jamal, Noriah] Malaysian Nucl Agcy, Med Technol Div, Kajang 43000, Malaysia. [Spelic, David C.; Suleiman, Orhan H.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20903 USA. RP Ng, KH (reprint author), Univ Malaya, Dept Biomed Imaging, Kuala Lumpur 50603, Malaysia. EM ngkh@um.edu.my RI Ng, Kwan-Hoong/D-2231-2009 NR 23 TC 1 Z9 1 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0144-8420 J9 RADIAT PROT DOSIM JI Radiat. Prot. Dosim. PD JAN PY 2009 VL 133 IS 1 BP 25 EP 34 DI 10.1093/rpd/ncp007 PG 10 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 410VM UT WOS:000263606400005 PM 19223292 ER PT J AU Khurana, S Norris, PJ Busch, MP Mlisana, K Salim, AK Hunter, E Golding, H AF Khurana, S. Norris, P. J. Busch, M. P. Mlisana, K. Salim, A. K. Hunter, E. Golding, H. TI HIV-SELECTEST EIA and rapid test: a novel assay for differential diagnosis of HIV infections in the face of vaccine-generated antibodies SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Khurana, S.; Golding, H.] US FDA, CBER, Bethesda, MD 20014 USA. [Norris, P. J.; Busch, M. P.] Blood Syst Res Inst, San Francisco, CA USA. [Mlisana, K.; Salim, A. K.] Ctr AIDS Programme Res S Africa, Durban, South Africa. [Hunter, E.] Emory Vaccine Res Ctr, Atlanta, GA USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PY 2009 VL 6 AR P192 PG 2 WC Virology SC Virology GA 509KL UT WOS:000271015300243 ER PT B AU Lorenz, BD Donnenberg, MS AF Lorenz, Benjamin D. Donnenberg, Michael S. BE Fratamico, PM Smith, JL Brogden, KA TI Escherichia coli: Enteric and Extraintestinal Infections SO SEQUELAE AND LONG-TERM CONSEQUENCES OF INFECTIOUS DISEASES LA English DT Article; Book Chapter ID HEMOLYTIC-UREMIC SYNDROME; IRRITABLE-BOWEL-SYNDROME; URINARY-TRACT-INFECTIONS; MICROVASCULAR ENDOTHELIAL-CELLS; INTESTINAL EPITHELIAL-CELLS; EMERGING FOODBORNE DISEASES; GRAM-NEGATIVE BACILLI; MEMBRANE PROTEIN-A; TRAVELERS DIARRHEA; SHIGA TOXIN C1 [Lorenz, Benjamin D.] US FDA, Ctr Drug Evaluat Res, Div Antiinfect & Ophthalmol Prod, Silver Spring, MD 20933 USA. [Lorenz, Benjamin D.; Donnenberg, Michael S.] Univ Maryland, Sch Med, Dept Med, Div Infect Dis, Baltimore, MD 21201 USA. [Donnenberg, Michael S.] Univ Maryland, Sch Med, Dept Microbiol & Immunol, Baltimore, MD 21201 USA. RP Lorenz, BD (reprint author), US FDA, Ctr Drug Evaluat Res, Div Antiinfect & Ophthalmol Prod, Silver Spring, MD 20933 USA. NR 203 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N STREET NW, WASHINGTON, DC 20036-2904 USA BN 978-1-55581-430-4 PY 2009 BP 69 EP 85 PG 17 WC Infectious Diseases SC Infectious Diseases GA BKK70 UT WOS:000268393800005 ER PT B AU Cheng, WC AF Cheng, Wei-Chung GP IS&T TI Evaluating Display Quality with Electroencephalography SO SEVENTEENTH COLOR IMAGING CONFERENCE - COLOR SCIENCE AND ENGINEERING SYSTEMS, TECHNOLOGIES, AND APPLICATIONS LA English DT Proceedings Paper CT 17th Color Imaging Conference on Color Science and Engineering Systems, Technologies, and Applications CY NOV 09-13, 2009 CL Albuquerque, NM SP Mitsubishi Elect Res Lab, Adobe, Canon, Kodak, Hewlett Packard, Lexmark, OCE, Xerox AB The observer's brain activities recorded by electroencephalograph (EEG) were used to evaluate the chromatic flicker on field sequential displays. The EEG signals retrieved near the visual cortex VI indicate the annoying degree and can be used to assess the image quality in terms of ergonomic comfort. C1 US FDA, Silver Spring, MD 20993 USA. RP Cheng, WC (reprint author), US FDA, Silver Spring, MD 20993 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU SOC IMAGING SCIENCE & TECHNOLOGY PI SPRINGFIELD PA 7003 KILWORTH LANE, SPRINGFIELD, VA 22151 USA BN 978-0-89208-288-9 PY 2009 BP 32 EP 34 PG 3 WC Imaging Science & Photographic Technology SC Imaging Science & Photographic Technology GA BUQ38 UT WOS:000290064200007 ER PT B AU Cheng, WC Chen, HMP Huang, JF AF Cheng, Wei-Chung Chen, Huang-Ming P. Huang, Jih-Fon GP IS&T TI Color Management for Flexible Cholesteric-LCD under LED Illumination SO SEVENTEENTH COLOR IMAGING CONFERENCE - COLOR SCIENCE AND ENGINEERING SYSTEMS, TECHNOLOGIES, AND APPLICATIONS LA English DT Proceedings Paper CT 17th Color Imaging Conference on Color Science and Engineering Systems, Technologies, and Applications CY NOV 09-13, 2009 CL Albuquerque, NM SP Mitsubishi Elect Res Lab, Adobe, Canon, Kodak, Hewlett Packard, Lexmark, OCE, Xerox AB The reflective cholesteric liquid crystal display suffers from voltage-induced color shift and viewing angle-dependent color shift. In this paper, three solutions are presented to overcome these problems. First, four types of cholesteric liquid crystals were synthesized and characterized to find the best mixture with the lowest voltage-induced color shift and reflectance reduction. Secondly, 5-primary (red, yellow, green, cyan and blue) cholesteric liquid crystals were synthesized such that the color gamut and reflectance were enhanced. Finally, the viewing angle-dependent color shift was characterized and then compensated by adjusting the chromaticity of the red/green/blue LED light sources. C1 [Cheng, Wei-Chung] US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Cheng, WC (reprint author), US FDA, Div Imaging & Appl Math, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU SOC IMAGING SCIENCE & TECHNOLOGY PI SPRINGFIELD PA 7003 KILWORTH LANE, SPRINGFIELD, VA 22151 USA BN 978-0-89208-288-9 PY 2009 BP 254 EP 259 PG 6 WC Imaging Science & Photographic Technology SC Imaging Science & Photographic Technology GA BUQ38 UT WOS:000290064200047 ER PT S AU Hunt, R Sauna, ZE Ambudkar, SV Gottesman, MM Kimchi-Sarfaty, C AF Hunt, Ryan Sauna, Zuben E. Ambudkar, Suresh V. Gottesman, Michael M. Kimchi-Sarfaty, Chava BE Komar, AA TI Silent (Synonymous) SNPs: Should We Care About Them? SO SINGLE NUCLEOTIDE POLYMORPHISMS: METHODS AND PROTOCOLS, SECOND EDITION SE Methods in Molecular Biology LA English DT Article; Book Chapter DE Single nucleotide polymorphism; messenger RNA splicing; messenger RNA stability; messenger RNA structure; protein folding; synonymous mutations; nonsynonymous mutations; codon frequency; codon usage ID SINGLE-NUCLEOTIDE POLYMORPHISMS; MESSENGER-RNA STABILITY; SEQUENCE EVOLUTION; CODON USAGE; PROTEIN; GENE; MUTATIONS; SCHIZOPHRENIA; POPULATION; EXPRESSION AB One of the surprising findings of the Human Genome Project was that single nucleotide polymorphisms (SNPs), which, by definition, have a minor allele frequency greater than 1%, occur at higher rates than previously suspected. When occurring in the gene coding regions, SNPs can be synonymous (i.e., not causing a change in the amino acid) or nonsynonymous (when the amino acid is altered). It has long been assumed that synonymous SNPs arc inconsequential, as the primary sequence of the protein is retained. A number of studies have questioned this assumption over the last decade, shoving that synonymous mutations arc also under evolutionary pressure and they can be implicated in disease. More importantly, several of the mechanisms by which synonymous mutations alter the structure, function, and expression level of proteins are now being elucidated. Studies have demonstrated that synonymous polymorphisms can affect messenger RNA splicing, stability, and structure as well as protein folding. These changes can have a significant effect on the function of proteins, change cellular response to therapeutic targets, and often explain the different responses of individual patients to a certain medication. C1 [Hunt, Ryan; Sauna, Zuben E.; Kimchi-Sarfaty, Chava] US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Ambudkar, Suresh V.; Gottesman, Michael M.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. RP Hunt, R (reprint author), US FDA, Lab Hemostasis, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. FU Intramural NIH HHS NR 56 TC 88 Z9 96 U1 0 U2 6 PU HUMANA PRESS INC PI TOTOWA PA 999 RIVERVIEW DR, STE 208, TOTOWA, NJ 07512-1165 USA SN 1064-3745 BN 978-1-60327-410-4 J9 METHODS MOL BIOL JI Methods Mol. Biol. PY 2009 VL 578 BP 23 EP 39 DI 10.1007/978-1-60327-411-1_2 D2 10.1007/978-1-60327-411-1 PG 17 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BNM36 UT WOS:000274946200002 PM 19768585 ER PT J AU Farkas, V Gomercic, T Sindicic, M Slijepcevic, V Huber, D Frkovic, A Modric, S AF Farkas, Vladimir Gomercic, Tomislav Sindicic, Magda Slijepcevic, Vedran Huber, Duro Frkovic, Alojzije Modric, Sanja TI CRANIOMETRICAL ANALYSIS AND DETERMINATION OF SEXUAL DIMORPHISM IN BROWN BEAR (Ursus arctos L.) FROM CROATIA SO SUMARSKI LIST LA Croatian DT Article DE brown bear; Ursus arctos; craniometry; sex dimorphism; skull; Croatia ID SPELAEUS; SKULL AB Family of bears (Ursidae) have a potential to exhibit various characteristics under the influence of environment and nutrition. The goal of this paper was to analyze craniometrical measurements of brown bear (Ursus arctos L.) population from Croatia with objectives to define them, as well as to determinate differences between sexes. A total of 34 skulls have been studied, out of which 13 (38,24 %) belonged to female animals, 20 (58,83 %) to males, while sex was not identified for one (2,93 %) skull. All skulls belonged to adult animals, with the average age of 8,4 years (range 3 to 20 years). A total of 49 measurements were taken on each skull with the 0,1 mm precision, so totally 829 craniometrical measurements have been statistically analyzed. Statistically significant difference between the sexes has been observed in 42 (85,72 %) craniometrical measurements, while for totally 16 (32,65 %) measurements it has been observed that males are absolutely bigger than the female bears (meaning that the smallest males were bigger than the biggest females). For those 16 measures we have defined border values that could help in sex determination. Correlation and equation of regression were calculated for total length of skull and zygomatic breadth. Corelation was r = 0,7961 for male bears and r = 0,6812 for females, while equaton of regression for calculation of zygomatic width using total skull length was: for males - zygomatic width = 0,8365 total skull length - 79,105; for females - zygomatic width = 0,6867 total skull length - 31,247. In comparison of skull features of bears from Croatia with the ones from Slovakia we have found that male bears were almost the same while Croatian females were smaller Bears in Croatia were smaller than the ones in Romania but the differences among males were smaller while the females were significantly larger in Romania. C1 [Gomercic, Tomislav; Sindicic, Magda; Huber, Duro] Veterinarski Fak Sveucilista Zagrebu, Zagreb 10000, Croatia. [Modric, Sanja] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Farkas, V (reprint author), Kralja Zvonimira 12, Vladislavci 31404, Croatia. EM vfarkas@vef.hr; tomislav.gomercic@vef.hr; magda.sindicic@vef.hr; vedran.slijepcevic@gmail.com; huber@vef.hr; alojzije.frkovic@ri.htnet.hr; sanja.modric@fda.hhs.gov RI Huber, Djuro/P-3493-2016 NR 35 TC 1 Z9 1 U1 1 U2 1 PU CROATIAN FORESTRY SOC PI ZAGREB PA TRG MAZURANICA 11, ZAGREB, 00000, CROATIA SN 0373-1332 J9 SUMAR LIST JI Sumar. List PY 2009 VL 133 IS 9-10 BP 527 EP 537 PG 11 WC Forestry SC Forestry GA 525OG UT WOS:000272225100006 ER PT J AU Joffe, HV Emerson, CH Braverman, LE AF Joffe, Hylton V. Emerson, Charles H. Braverman, Lewis E. TI Dr. Robert David ("Bob'') Utiger, 1931-2008 In Memoriam SO THYROID LA English DT Biographical-Item C1 [Joffe, Hylton V.] US FDA, Div Metab & Endocrinol Prod, Rockville, MD 20857 USA. [Emerson, Charles H.] Univ Massachusetts, Sch Med, Amherst, MA 01003 USA. [Braverman, Lewis E.] Boston Univ, Sch Med, Boston, MA 02215 USA. RP Joffe, HV (reprint author), US FDA, Div Metab & Endocrinol Prod, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1050-7256 J9 THYROID JI Thyroid PD JAN PY 2009 VL 19 IS 1 BP 81 EP 82 DI 10.1089/thy.2008.1562 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 390IB UT WOS:000262156400017 PM 19119984 ER PT J AU McBurney, RN Hines, WM Von Tungeln, LS Schnackenberg, LK Beger, RD Moland, CL Han, T Fuscoe, JC Chang, CW Chen, JJ Su, ZQ Fan, XH Tong, WD Booth, SA Balasubramanian, R Courchesne, PL Campbell, JM Graber, A Guo, Y Juhasz, PJ Li, TY Lynch, MD Morel, NM Plasterer, TN Takach, EJ Zeng, CH Beland, FA AF McBurney, Robert N. Hines, Wade M. Von Tungeln, Linda S. Schnackenberg, Laura K. Beger, Richard D. Moland, Carrie L. Han, Tao Fuscoe, James C. Chang, Ching-Wei Chen, James J. Su, Zhenqiang Fan, Xiao-Hui Tong, Weida Booth, Shelagh A. Balasubramanian, Raji Courchesne, Paul L. Campbell, Jennifer M. Graber, Armin Guo, Yu Juhasz, Peter J. Li, Tricin Y. Lynch, Moira D. Morel, Nicole M. Plasterer, Thomas N. Takach, Edward J. Zeng, Chenhui Beland, Frederick A. TI The Liver Toxicity Biomarker Study: Phase I Design and Preliminary Results SO TOXICOLOGIC PATHOLOGY LA English DT Article DE liver toxicity; biomarker; entacapone; tolcapone ID O-METHYLTRANSFERASE INHIBITORS; PARKINSONS-DISEASE; TOLCAPONE; ENTACAPONE; SAFETY; HEPATOTOXICITY; PARAMETERS; DRUGS; RATS AB Drug-induced liver injury (DILI) is the primary adverse event that results in withdrawal of drugs from the market and a frequent reason for the failure of drug candidates in development. The Liver Toxicity Biomarker Study (LTBS) is an innovative approach to investigate DILI because it compares molecular events produced in vivo by compound pairs that ( a) are similar in structure and mechanism of action, (b) are associated with few or no signs of liver toxicity in preclinical studies, and ( c) show marked differences in hepatotoxic potential. The LTBS is a collaborative preclinical research effort in molecular systems toxicology between the National Center for Toxicological Research and BG Medicine, Inc., and is supported by seven pharmaceutical companies and three technology providers. In phase I of the LTBS, entacapone and tolcapone were studied in rats to provide results and information that will form the foundation for the design and implementation of phase II. Molecular analysis of the rat liver and plasma samples combined with statistical analyses of the resulting datasets yielded marker analytes, illustrating the value of the broad-spectrum, molecular systems analysis approach to studying pharmacological or toxicological effects. C1 [McBurney, Robert N.; Hines, Wade M.; Booth, Shelagh A.; Balasubramanian, Raji; Courchesne, Paul L.; Campbell, Jennifer M.; Graber, Armin; Guo, Yu; Juhasz, Peter J.; Li, Tricin Y.; Lynch, Moira D.; Morel, Nicole M.; Plasterer, Thomas N.; Takach, Edward J.; Zeng, Chenhui] BG Med Inc, Waltham, MA USA. [Von Tungeln, Linda S.; Schnackenberg, Laura K.; Beger, Richard D.; Moland, Carrie L.; Han, Tao; Fuscoe, James C.; Chang, Ching-Wei; Chen, James J.; Su, Zhenqiang; Fan, Xiao-Hui; Tong, Weida] US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP McBurney, RN (reprint author), 610 N Lincoln St, Waltham, MA 02451 USA. EM rmcburney@bg-medicine.com RI Su, Zhenqiang/H-3914-2012 NR 31 TC 39 Z9 39 U1 1 U2 7 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2009 VL 37 IS 1 BP 52 EP 64 DI 10.1177/0192623308329287 PG 13 WC Pathology; Toxicology SC Pathology; Toxicology GA 463XE UT WOS:000267466500008 PM 19171931 ER PT J AU Miller, T Honchel, R Rosenzweig, B Pine, PS Weaver, J Knapton, A Thompson, K AF Miller, Terry Honchel, Ronald Rosenzweig, Barry Pine, P. Scott Weaver, James Knapton, Alan Thompson, Karol TI Characterization of Phospholipidosis in Skeletal Muscle Induced in the Rat by Chronic Exposure to Chloroquine SO TOXICOLOGIC PATHOLOGY LA English DT Meeting Abstract C1 [Miller, Terry; Honchel, Ronald; Rosenzweig, Barry; Pine, P. Scott; Weaver, James; Knapton, Alan; Thompson, Karol] US FDA, CDER, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD JAN PY 2009 VL 37 IS 1 MA P62 BP 142 EP 142 PG 1 WC Pathology; Toxicology SC Pathology; Toxicology GA 463XE UT WOS:000267466500075 ER PT J AU Kauffman, J AF Kauffman, John TI Raman chemical imaging advances SO TRAC-TRENDS IN ANALYTICAL CHEMISTRY LA English DT News Item C1 US FDA, Div Pharmaceut Anal, St Louis, MO USA. RP Kauffman, J (reprint author), US FDA, Div Pharmaceut Anal, St Louis, MO USA. EM john.Kauffman@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0165-9936 J9 TRAC-TREND ANAL CHEM JI Trac-Trends Anal. Chem. PD JAN PY 2009 VL 28 IS 1 BP IV EP V PG 2 WC Chemistry, Analytical SC Chemistry GA 404HB UT WOS:000263141000004 ER PT J AU Garra, BS Locher, M Felker, S Wear, KA AF Garra, Brian S. Locher, Melanie Felker, Steven Wear, Keith A. TI MEASUREMENTS OF ULTRASONIC BACKSCATTERED SPECTRAL CENTROID SHIFT FROM SPINE IN VIVO: METHODOLOGY AND PRELIMINARY RESULTS SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE Bone; Vertebra; Backscatter ID ATTENUATION AB Ultrasonic backscatter measurements from vertebral bodies (1,3 and 1,4) in nine women were performed using a clinical ultrasonic imaging system. Measurements were made through the abdomen. The location of a vertebra was identified from the bright specular reflection from the vertebral anterior surface. Backscattered signals were gated to isolate signal emanating from the cancellous interiors of vertebrae. The spectral centroid shift of the backscattered signal, which has previously been shown to correlate highly with bone mineral density (BMD) in human calcaneus in vitro, was measured. BMD was also measured in the nine subjects' vertebrae using a clinical bone densitometer. The correlation coefficient between centroid shift and BMD was r = -0.61. The slope of the linear fit was -160 kHz / (g/cm(2)). The negative slope was expected because the attenuation coefficient (and therefore magnitude of the centroid downshift) is known from previous studies to increase with BNID. The centroid shift may be a useful parameter for characterizing bone in vivo. C1 [Wear, Keith A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Garra, Brian S.; Locher, Melanie; Felker, Steven] Univ Vermont, Dept Radiol, Burlington, VT USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Bldg 62 Room 3108, Silver Spring, MD 20993 USA. EM keith.wear@fda.hhs.gov FU NCRR NIH HHS [RR 00109] NR 9 TC 19 Z9 20 U1 1 U2 4 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-5629 EI 1879-291X J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD JAN PY 2009 VL 35 IS 1 BP 165 EP 168 DI 10.1016/j.ultrasmedbio.2008.06.004 PG 4 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 390DN UT WOS:000262144600020 PM 18723270 ER PT J AU Krause, PR AF Krause, Philip R. BE Barrett, ADT Stanberry, LR TI US Regulatory Issues Related to Vaccines against Emerging Infectious Diseases SO VACCINES FOR BIODEFENSE AND EMERGING AND NEGLECTED DISEASES LA English DT Article; Book Chapter ID CHALLENGES; SAFETY; IMMUNIZATION; HISTORY; LIVE AB The primary goal of the U.S. vaccine regulatory process is to provide assurance that vaccines are consistently safe and effective. This chapter summarizes the issues and regulatory process for development and licensure of vaccines in the United States, with particular emphasis on emerging infectious diseases. As is the case for all vaccines, vaccines to prevent emerging infectious diseases must fulfill the science-based regulatory requirements for safety and efficacy, but the special nature of these infections can make vaccine development more challenging, both from scientific and regulatory standpoints. Regulatory requirements are generally organized by phase of clinical development, with emphasis on safety throughout the development process, and on efficacy and immunogenicity later in development. Specific issues associated with assays and cell substrates must be considered throughout development. Frequent reference to the underlying regulations and sources of guidance is useful to assure that important issues are addressed. Regulatory processes that may have particular relevance to emerging infectious diseases include the Orphan Drug Program, Accelerated Approval, the Animal Rule, the Fast Track Program, Priority Review, Treatment IND, and Emergency Use Authorizations. C1 US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Krause, PR (reprint author), US FDA, Div Viral Prod, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 56 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-091902-7 PY 2009 BP 191 EP 210 DI 10.1016/B978-0-12-369408-9.00014-7 PG 20 WC Public, Environmental & Occupational Health; Immunology; Infectious Diseases SC Public, Environmental & Occupational Health; Immunology; Infectious Diseases GA BCR60 UT WOS:000311106000016 ER PT S AU Baylor, NW Houn, F AF Baylor, Norman W. Houn, Florence BE Compans, RW Orenstein, WA TI Considerations for Licensure of Influenza Vaccines with Pandemic and Prepandemic Indications SO VACCINES FOR PANDEMIC INFLUENZA SE Current Topics in Microbiology and Immunology LA English DT Article; Book Chapter ID H5N1 VACCINE; VIRUS; IMMUNOGENICITY; TRIVALENT; ANTIBODY; SAFETY; ADULTS; SERUM AB With over 409 human cases of avian influenza and over 256 deaths worldwide resulting from infection with avian influenza (H5N1), an influenza pandemic is still a real threat, especially with H5N1 continuing to evolve into antigenically distinct clades. The Food and Drug Administration (FDA) along with other national regulatory authorities (NRAs) recognize the important role that safe and effective vaccines will play in protecting the public health from the threat of an influenza pandemic. The challenges to the FDA and other NRAs are significant as regulatory agencies pursue the development of new scientific and regulatory criteria to evaluate vaccines against pandemic influenza strains for licensure. To this end, the FDA is actively utilizing current regulatory processes such as accelerated approval and priority review as well as developing the regulatory pathways needed to speed the availability of vaccines against pandemic influenza. In May of 2007, the FDA issued two final guidance documents, one describing the clinical data recommended to support the licensure of annual influenza vaccines, and the other describing the clinical data recommended to support the licensure of pandemic influenza vaccines. These guidances contain specific approaches outlined by the FDA to assist manufacturers in developing new vaccines to increase the supply of safe and effective influenza vaccines for both annual and pandemic use. In this article we define the nomenclature "pandemic" and "prepandemic," describe the regulatory pathway for licensing new influenza vaccines for pandemic and prepandemic use, and outline considerations for evaluating pandemic/prepandemic vaccines that have been formulated using new approaches such as cell culture and non-aluminum salt adjuvants. C1 [Baylor, Norman W.; Houn, Florence] US FDA, CBER, OVRR, Rockville, MD 20852 USA. RP Baylor, NW (reprint author), US FDA, CBER, OVRR, HFM-405,1401 Rockville Pike, Rockville, MD 20852 USA. EM norman.baylor@fda.hhs.gov; florence.houn@fda.hhs.gov NR 15 TC 7 Z9 7 U1 0 U2 0 PU SPRINGER-VERLAG BERLIN PI BERLIN PA HEIDELBERGER PLATZ 3, D-14197 BERLIN, GERMANY SN 0070-217X BN 978-3-540-92164-6 J9 CURR TOP MICROBIOL JI Curr.Top.Microbiol.Immunol. PY 2009 VL 333 BP 453 EP 470 DI 10.1007/978-3-540-92165-3_22 D2 10.1007/978-3-540-92165-3 PG 18 WC Biotechnology & Applied Microbiology; Immunology; Microbiology SC Biotechnology & Applied Microbiology; Immunology; Microbiology GA BKY26 UT WOS:000269608300022 PM 19768419 ER PT J AU Fletcher, J Franz, D LeClerc, JE AF Fletcher, Jacqueline Franz, David LeClerc, J. Eugene TI Healthy plants: necessary for a balanced 'One Health' concept SO VETERINARIA ITALIANA LA English DT Article DE Animal; Disease; Health; Human; One Health; Pathology; Plant; Public health ID ESCHERICHIA-COLI O157-H7; UNITED-STATES; PATHOGENICITY; MYCOTOXINS; INFECTION; OUTBREAKS; SEROTYPE; REVEALS; PRODUCE; TOXINS AB All life forms depend ultimately upon Sunlight to create the energy 'currency' required for the functions of living. Green plants can make that conversion directly but the rest Of LIS would perish without access to foods derived, directly or indirectly, from plants. We also require their fibre which We use for clothing, building and other purposes. However, plants, just as humans and animals, are attacked by pathogens that cause a myriad of symptoms that can lead to reduced yields, lower quality products and diminished nutritional value. Plant pathogens share many features With their human and animal counterparts. Some pathogens - whether of humans, animals, or plants - have nimble genomes or the ability to pirate genes from other organisms via mobile elements. Some have developed the ability to cross kingdoms in their host ranges. Many others share virulence factors, such as the type III secretion system (T3SS) or mechanisms for sensing population density, that work equally well in all kingdoms. Certain pathogens of hosts in all kingdoms rely upon insect vectors and use similar mechanisms to ensure dispersal (and sometimes survival) in this way. Plant-pathogen interactions have more direct consequence for humans when the microbes are human pathogens such as Escherichia coli O157:H7 and Salmonella spp., which can contaminate fresh produce or when they produce metabolites, such as mycotoxins, which are harmful when consumed. Finally, national biosecurity concerns and the need for prevention, preparedness and forensic capabilities cross all kingdom barriers. Thus, our communities that focus on one of these kingdoms have much to learn from one another and a complete and balanced 'One Health' initiative Must be tripartite, embracing the essential components of healthy plants, healthy animals and healthy people. C1 [Fletcher, Jacqueline] Oklahoma State Univ, Natl Inst Microbial Forens & Food & Agr Biosecur, Stillwater, OK 74078 USA. [Franz, David] Midwest Res Inst, Frederick, MD 21701 USA. [LeClerc, J. Eugene] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Fletcher, J (reprint author), Oklahoma State Univ, Natl Inst Microbial Forens & Food & Agr Biosecur, Stillwater, OK 74078 USA. EM jacqueline.fletcher@okstate.edu NR 45 TC 4 Z9 5 U1 0 U2 6 PU IST ZOOPROFILATTICO SPERIMENTALE ABRUZZO & MOLISE G CAPORALE-IZS A&M PI TERAMO PA CAMPO BOARIO, TERAMO, 64100, ITALY SN 0505-401X J9 VET ITAL JI Vet. Ital. PD JAN-MAR PY 2009 VL 45 IS 1 BP 79 EP 95 PG 17 WC Veterinary Sciences SC Veterinary Sciences GA 476JQ UT WOS:000268436700008 PM 20391392 ER PT B AU Suttie, JW AF Suttie, John W. BE Suttie, JW TI Historical Background SO VITAMIN K IN HEALTH AND DISEASE LA English DT Article; Book Chapter ID DIETARY HEMORRHAGIC-DISEASE; VITAMIN-K DEFICIENCY; SCURVY-LIKE DISEASE; ANTIHEMORRHAGIC VITAMIN; CHEMICAL NATURE; CHICK DISEASE; BABY CHICKS; PROTHROMBIN; PURIFICATION; DISCOVERY C1 [Suttie, John W.] Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. [Suttie, John W.] Univ Wisconsin, Dept Nutr Sci, Madison, WI 53706 USA. [Suttie, John W.] US FDA, Blood Prod Advisory Comm, Rockville, MD 20857 USA. [Suttie, John W.] USDA, Amer Soc Biochem & Mol Biol, NAREEE Advisory Board, ILSI,Food Nutr & Safety Comm, Washington, DC 20250 USA. RP Suttie, JW (reprint author), Univ Wisconsin, Dept Biochem, Madison, WI 53706 USA. NR 72 TC 30 Z9 30 U1 0 U2 0 PU CRC PRESS-TAYLOR & FRANCIS GROUP PI BOCA RATON PA 6000 BROKEN SOUND PARKWAY NW, STE 300, BOCA RATON, FL 33487-2742 USA BN 978-0-8493-3392-7 PY 2009 BP 1 EP 12 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA BKK15 UT WOS:000268358500001 ER PT J AU Thorpe, SJ Fox, B Sharp, G Heath, AB Behr-Gross, ME Terao, E Virata-Theimer, ML Yu, MW AF Thorpe, S. J. Fox, B. Sharp, G. Heath, A. B. Behr-Gross, M. -E. Terao, E. Virata-Theimer, M. L. Yu, M. W. TI International collaborative study to evaluate candidate reference reagents to standardize haemagglutination testing for anti-A and anti-B in normal intravenous immunoglobulin products SO VOX SANGUINIS LA English DT Article DE blood group antibodies; haemagglutination; IVIG; isoagglutinins A and B; reference method; specification ID RH-D ACTIVITY; GAMMA-GLOBULIN; RECIPIENTS; HEMOLYSIS; BATCHES AB Background and Objectives The aim of the study was to evaluate, in an international collaboration, three lyophilized intravenous immunoglobulin (IVIG) preparations for their suitability to standardize and control haemagglutination testing for anti-A and anti-B in IVIG products. Materials and Methods Twenty-three laboratories tested candidate IVIG reference reagents consisting of a Positive control (07/306), a Negative control (07/308), and a specifically formulated Limit preparation (07/310) to define the maximum (e.g. pharmacopoeial) limits of anti-A and anti-B in IVIG products, where limits are applicable. Laboratories performed direct haemagglutination using papain-treated erythrocytes and/or indirect antiglobulin tests. Results For both methods, there was up to 16-fold variation in anti-A and anti-B titres, although there was good agreement over a two-fold titre range for anti-A and anti-B between laboratories for both 07/306 and 07/310 using the direct method. Comparative titration data for 07/306 and 07/310 indicated that the use of a 'Limit' reference reagent would facilitate identification of higher titre batches when the direct haemagglutination method is used. Conclusions The establishment of preparations 07/306, 07/308 and 07/310 as reference reagents by the World Health Organization will facilitate global standardization of haemagglutination tests for anti-A and anti-B, ensure that such tests are sufficiently sensitive and specific, and facilitate identification of batches that exceed maximum recommended levels of anti-A and anti-B. The Commission of the European Pharmacopoeia and the United States Food and Drug Administration have adopted the same reference reagents including the maximal specifications defined by preparation 07/310. C1 [Thorpe, S. J.] Natl Inst Biol Stand & Controls, Biotherapeut Grp, Potters Bar EN6 3QG, Herts, England. [Behr-Gross, M. -E.; Terao, E.] Council Europe, European Directorate Qual Med & HealthCare, Strasbourg, France. [Virata-Theimer, M. L.; Yu, M. W.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Thorpe, SJ (reprint author), Natl Inst Biol Stand & Controls, Biotherapeut Grp, Blanche Lane,S Mimms, Potters Bar EN6 3QG, Herts, England. EM susan.thorpe@nibsc.hpa.org.uk RI Thorpe, Susan/E-1808-2013; Fox, Bernard/E-2523-2013 NR 16 TC 12 Z9 12 U1 0 U2 0 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0042-9007 J9 VOX SANG JI Vox Sang. PY 2009 VL 97 IS 2 BP 160 EP 168 DI 10.1111/j.1423-0410.2009.01194.x PG 9 WC Hematology SC Hematology GA 469HC UT WOS:000267886100009 PM 19402856 ER PT S AU de las Heras, H Tischenko, O Xu, Y Schlattl, H Hoeschen, C AF de las Heras, H. Tischenko, O. Xu, Y. Schlattl, H. Hoeschen, C. BE Dossel, O Schlegel, WC TI Efficient data acquisition in CT: dual optimal reading SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, VOL 25, PT 2 - DIAGNOSTIC IMAGING SE IFMBE Proceedings LA English DT Proceedings Paper CT 11th International Congress of the IUPESM/World Congress on Medical Physics and Biomedical Engineering CY SEP 07-12, 2009 CL Munich, GERMANY SP IUPESM, Int Org Med Phys (IOMP) DE Computed Tomography; reconstruction; dose reduction; rebinning; CT-devices ID RECONSTRUCTION AB The sampling geometry of CT-scanners plays an important role for the reconstruction process of the images. We have previously reported elsewhere a new system that can collect parallel sets of Radon data directly through appropriate collimation of the conventional fan-beam. These data can be efficiently treated with series expansion algorithms (for example, OPED), without significant loss of image quality. Preliminary results with a test device have shown the feasibility of the idea. In this contribution, we stress the potential of the idea showing results with an optimized set-up. At the end, we discuss two technical difficulties of the proposed system, which have motivated future work in our group. C1 [de las Heras, H.; Tischenko, O.; Schlattl, H.; Hoeschen, C.] Helmholtz Zentrum Muenchen, Med Phys Grp, Neuherberg, Germany. [de las Heras, H.] US FDA, Div Imaging & Appl Math, Silver Spring, MD USA. [Xu, Y.] Univ Oregon, Dept Math, Eugene, OR USA. RP de las Heras, H (reprint author), Helmholtz Zentrum Muenchen, Med Phys Grp, Neuherberg, Germany. EM hugo.heras@daad-alumni.de; oleg.tischenko@helmholtz-muenchen.de FU Helmholtz-DAAD; ORISE FX The work of the first author was funded in part by a Helmholtz-DAAD fellowship. His current work is funded by an ORISE research appointment NR 13 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1680-0737 BN 978-3-642-03878-5; 978-3-642-03879-2 J9 IFMBE PROC PY 2009 VL 25 BP 575 EP 578 PN 2 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BAY37 UT WOS:000306060900161 ER PT S AU de las Heras, H Beatson, R Castell, WZ Tischenko, O Xu, Y Hoeschen, C AF de las Heras, H. Beatson, R. Castell, W. Zu Tischenko, O. Xu, Y. Hoeschen, C. BE Dossel, O Schlegel, WC TI CT with Dual Optimal Reading: compatibility of the two data sets and interpolation issues SO WORLD CONGRESS ON MEDICAL PHYSICS AND BIOMEDICAL ENGINEERING, VOL 25, PT 2 - DIAGNOSTIC IMAGING SE IFMBE Proceedings LA English DT Proceedings Paper CT 11th International Congress of the IUPESM/World Congress on Medical Physics and Biomedical Engineering CY SEP 07-12, 2009 CL Munich, GERMANY SP IUPESM, Int Org Med Phys (IOMP) DE Computed Tomography; reconstruction; interpolation; scanning geometry; devices ID RECONSTRUCTION AB The geometry of CT d'Or (Dual Optimal Reading), presented in another abstract for this conference, acquires data for two independent but complementary reconstructions using a special mask to collimate the fan beam. However, 25 % of the pixels in the sinogram must be calculated through interpolation. In this contribution, we explain the structure of the data and thus the need for that interpolation. We compare experimental results of both kind of reconstructions, obtained with a simplified test-device. Additionally, we show the potential of new 2D-interpolation methods within the reconstruction algorithm OPED (Orthogonal Polynomial Expansion on Disc), for which the geometry of CT d'Or is optimally suited. C1 [de las Heras, H.; Tischenko, O.; Hoeschen, C.] Helmholtz Zentrum Muenchen, Med Phys Grp, Neuherberg, Germany. [de las Heras, H.] US FDA, Div Imaging Appl Math, Silver Spring, MD USA. [Beatson, R.] Univ Canterbury, Dept Math & Stat, Christchurch, New Zealand. [Castell, W. Zu] Helmholtz Zentrum Muenchen, Inst Biomath & Biometry, Neuherberg, Germany. [Xu, Y.] Univ Oregon, Dept Math, Eugene, OR USA. RP de las Heras, H (reprint author), Helmholtz Zentrum Muenchen, Med Phys Grp, Neuherberg, Germany. EM hugo.heras@daad-alumni.de; oleg.tischenko@helmholtz-muenchen.de FU Helmholtz-DAAD; ORISE FX The work of the first author was funded in part by a Helmholtz-DAAD fellowship. His current work is funded by an ORISE research appointment NR 9 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 1680-0737 BN 978-3-642-03878-5; 978-3-642-03879-2 J9 IFMBE PROC PY 2009 VL 25 BP 579 EP 582 PN 2 PG 4 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BAY37 UT WOS:000306060900162 ER PT J AU An, SSA Barletta, T Constantine, N AF An, Seong Soo A. Barletta, Tanet Constantine, Neil TI Differential Epitope-Mapping of the Two Forms of the Prion Protein: Alterations at the C-Terminus SO BULLETIN OF THE KOREAN CHEMICAL SOCIETY LA English DT Article DE Prion; Epitope; Conformation specific antibody ID MONOCLONAL-ANTIBODIES; CYCLIC AMPLIFICATION; AMYLOID FIBRILS; SCRAPIE; DISEASE; PRP; ISOFORM; PEPTIDE; BLOOD; PANEL AB Most of the diagnostic methods for transmissible spongiform encephalopathies are based on the detection of the abnormal protease-resistant conformers of the. prion protein (PrPSc), when the normal protease-sensitive conformers (PrPC) are also present. A selective immune detection of PrPSc with high sensitivity is hampered by the absence of sufficient knowledge about the structure of PrPSc. An economical and rapid mapping approach is used here for the identification of epitopes that are exposed differently oil PrPSc and PrPC. This approach revealed remarkable differences in the conformation/accessibility of the two long helical segments between the two prion forms. This result is not in harmony with recent models of PrPSc. C1 [An, Seong Soo A.] Kyungwon Univ, Dept Bionano Technol, Gyeonggi 401761, South Korea. [Barletta, Tanet] US FDA, CDER OPS Microbiol, Rockville, MD 20857 USA. [Constantine, Neil] Univ Maryland, Sch Med, Inst Human Virol, Baltimore, MD 21201 USA. RP An, SSA (reprint author), Kyungwon Univ, Dept Bionano Technol, Gyeonggi 401761, South Korea. EM seongaan@kyungwon.ac.kr FU Institute of Biochemistry and Institute of Enzymology, Biological Research Center of the Hungarian Academy FX Authors would like to thank Dr. Ervin Welker from Institute of Biochemistry and Institute of Enzymology, Biological Research Center of the Hungarian Academy for his supports in reviewing the manuscript, and scientific discussions and suggestions. NR 39 TC 0 Z9 0 U1 0 U2 1 PU KOREAN CHEMICAL SOC PI SEOUL PA 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 0253-2964 J9 B KOREAN CHEM SOC JI Bull. Korean Chem. Soc. PD DEC 20 PY 2008 VL 29 IS 12 BP 2403 EP 2406 PG 4 WC Chemistry, Multidisciplinary SC Chemistry GA 393UB UT WOS:000262397500020 ER PT J AU Delmonte, P Hu, Q Kia, ARF Rader, JI AF Delmonte, Pierluigi Hu, Qing Kia, Ali-Reza Fardin Rader, Jeanne I. TI Preparation, chromatographic separation and relative retention times of cis/trans heptadecaenoic (17:1) fatty acids SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Fatty acids; Trans fat; Lipids; Heptadecenoic acid ID PERFORMANCE LIQUID-CHROMATOGRAPHY; TANDEM MASS-SPECTROMETRY; REFLECTION INFRARED-SPECTROSCOPY; METHYL-ESTERS; TRANS FAT; GEOMETRICAL-ISOMERS; RAPID-DETERMINATION; GAS-CHROMATOGRAPHY; MILK-FAT; IDENTIFICATION AB In recent years, several countries have implemented new regulations regarding limitations or labeling of the trans fatty acid (tFA) content in foods. In order to comply with the new requirements, gas chromatographic methods for fatty acid (FA) analysis have been refined toward the quantitation of a larger number of FAs. Increased attention is also being paid to those present in lower quantities. This article describes a simple procedure for obtaining, pure or in mixtures, geometric and positional isomers of a commercially available monounsaturated FA. cis 10-17:1 Fatty acid methyl ester (FAME) was isomerized into its positional/geometrical isomers by repeated hydrobromination/dehydrobromination of its double bond. Reaction products were fractionated into cis and trans geometric isomers by silver ion HPLC. Pure cis-17:1 FAME positional isomers were obtained by reversed-phase HPLC fractionation and identified by gas chromatography-covalent adduct chemical ionization MS/MS using acetonitrile as the reacting gas. The isomerization with p-toluenesulfinic acid of the purified FAME yielded the corresponding trans isomers: these products were analyzed by GC with flame ionization detection using a Supelco 2560 capillary column in order to determine their elution order and retention times (t(R)). A novel procedure was developed to determine t(r) for 17:1 FAME positional/geometrical isomers relative to that of the commercially available cis 10-17:1 FAME. (c) Published by Elsevier B.V. C1 [Delmonte, Pierluigi; Kia, Ali-Reza Fardin; Rader, Jeanne I.] US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Hu, Qing] Shanghai Inst Food & Drug Control, Shanghai 201203, Peoples R China. RP Delmonte, P (reprint author), US FDA, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 717, College Pk, MD 20740 USA. EM Pierluigi.delmonte@fda.hhs.gov NR 37 TC 22 Z9 23 U1 2 U2 18 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 DEC 19 PY 2008 VL 1214 IS 1-2 BP 30 EP 36 DI 10.1016/j.chroma.2008.10.086 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 385LU UT WOS:000261816500005 PM 19004449 ER PT J AU Guo, CN Stine, KJ Kauffman, JF Doub, WH AF Guo, Changning Stine, Keith J. Kauffman, John F. Doub, William H. TI Assessment of the influence factors on in vitro testing of nasal sprays using Box-Behnken experimental design SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Nasal drug delivery; In vitro testing; Automated actuation; Shot weight; Spray pattern; Plume geometry; Droplet size distribution; Viscosity; Surface tension; Box-Behnken experimental design ID DEPOSITION; PARAMETERS; PUMPS; SIZE AB The purpose of the research was to investigate the influences of actuation parameters and formulation physical properties on nasal spray delivery performance using design of experiment (DOE) methodology. A 3-level, 4-factor Box-Behnken design with a total of 27 experimental runs was used in this study. Nine simulated aqueous formulations with different viscosities and surface tensions were prepared using carboxymethylcellulose sodium (CMC, gelling agent) and Tween80 (surfactant) each at three concentration levels. Four factors, actuation stroke length, actuation velocity, concentration of gelling agent, and concentration of surfactant were investigated for their influences on measured responses of shot weight, spray pattern, plume geometry and droplet size distribution (DSD). The models based on data from the DOE were then optimized by eliminating insignificant terms. Pfeiffer nasal spray pump units filled with the simulated formulations were used in the study. Nasal pump actuation stroke length exerts a strong, independent influence on shot weight, and also slightly affects spray pattern and plume geometry. Actuation velocity and concentration of gelling agent have significant effects on spray pattern, plume geometry and DSD, in a complicated manner through interaction terms. Concentration of surfactant has little, if any, influence on nasal spray characteristics. Results were fitted to quadratic models describing the inherent relationships between the four factors evaluated and nasal spray performance. The DOE study helped us to identify the source of variability in nasal spray product performance, and obtained better understanding in how to control the variability. Moreover, the quadratic models developed from the DOE study quantitatively describe the inherent relationships between the factors and nasal spray performance characteristics. With the assistance of the response surfaces developed from the DOE model, the time and labor in designing a nasal spray product to achieve desired product performance characteristics can be reduced. Published by Elsevier B.V. C1 [Guo, Changning; Kauffman, John F.; Doub, William H.] US FDA, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Stine, Keith J.] Univ Missouri, Dept Chem & Biochem, St Louis, MO 63121 USA. [Stine, Keith J.] Univ Missouri, Ctr Nanosci, St Louis, MO 63121 USA. RP Guo, CN (reprint author), US FDA, Div Pharmaceut Anal, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM changning.guo@fda.hhs.gov NR 8 TC 30 Z9 34 U1 0 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD DEC 18 PY 2008 VL 35 IS 5 BP 417 EP 426 DI 10.1016/j.ejps.2008.09.001 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 384QU UT WOS:000261760100005 PM 18832029 ER PT J AU Sarin, H Kanevsky, AS Wu, HT Brimacombe, KR Fung, SH Sousa, AA Auh, S Wilson, CM Sharma, K Aronova, MA Leapman, RD Griffiths, GL Hall, MD AF Sarin, Hemant Kanevsky, Ariel S. Wu, Haitao Brimacombe, Kyle R. Fung, Steve H. Sousa, Alioscka A. Auh, Sungyoung Wilson, Colin M. Sharma, Kamal Aronova, Maria A. Leapman, Richard D. Griffiths, Gary L. Hall, Matthew D. TI Effective transvascular delivery of nanoparticles across the blood-brain tumor barrier into malignant glioma cells SO JOURNAL OF TRANSLATIONAL MEDICINE LA English DT Article ID IRON-OXIDE NANOPARTICLES; IMAGING CONTRAST AGENTS; DRUG-DELIVERY; CHEMICAL-PROPERTIES; RECURRENT GLIOMAS; MOLECULAR-SIZE; CHEMOTHERAPY; MODEL; PERMEABILITY; DENDRIMERS AB Background: Effective transvascular delivery of nanoparticle-based chemotherapeutics across the blood-brain tumor barrier of malignant gliomas remains a challenge. This is due to our limited understanding of nanoparticle properties in relation to the physiologic size of pores within the blood-brain tumor barrier. Polyamidoamine dendrimers are particularly small multigenerational nanoparticles with uniform sizes within each generation. Dendrimer sizes increase by only 1 to 2 nm with each successive generation. Using functionalized polyamidoamine dendrimer generations 1 through 8, we investigated how nanoparticle size influences particle accumulation within malignant glioma cells. Methods: Magnetic resonance and fluorescence imaging probes were conjugated to the dendrimer terminal amines. Functionalized dendrimers were administered intravenously to rodents with orthotopically grown malignant gliomas. Transvascular transport and accumulation of the nanoparticles in brain tumor tissue was measured in vivo with dynamic contrast-enhanced magnetic resonance imaging. Localization of the nanoparticles within glioma cells was confirmed ex vivo with fluorescence imaging. Results: We found that the intravenously administered functionalized dendrimers less than approximately 11.7 to 11.9 nm in diameter were able to traverse pores of the blood-brain tumor barrier of RG-2 malignant gliomas, while larger ones could not. Of the permeable functionalized dendrimer generations, those that possessed long blood half-lives could accumulate within glioma cells. Conclusion: The therapeutically relevant upper limit of blood-brain tumor barrier pore size is approximately 11.7 to 11.9 nm. Therefore, effective transvascular drug delivery into malignant glioma cells can be accomplished by using nanoparticles that are smaller than 11.7 to 11.9 nm in diameter and possess long blood half-lives. C1 [Sarin, Hemant; Sousa, Alioscka A.; Aronova, Maria A.; Leapman, Richard D.] Natl Inst Biomed Imaging & Bioengn, Natl Inst Hlth, Bethesda, MD 20892 USA. [Sarin, Hemant; Kanevsky, Ariel S.] Natl Inst Hlth, Ctr Clin, Dept Diagnost Radiol, Bethesda, MD 20892 USA. [Wu, Haitao; Wilson, Colin M.; Griffiths, Gary L.] NHLBI, Imaging Probe Dev Ctr, Natl Inst Hlth, Bethesda, MD 20892 USA. [Brimacombe, Kyle R.; Hall, Matthew D.] NCI, Cell Biol Lab, Natl Inst Hlth, Bethesda, MD 20892 USA. [Fung, Steve H.] Massachusetts Gen Hosp, Dept Neuroradiol, Boston, MA 02114 USA. [Auh, Sungyoung] Natl Inst Neurol Disorders & Stroke, Natl Inst Hlth, Bethesda, MD 20892 USA. [Sharma, Kamal] Natl Canc Inst, Metab Branch, Natl Inst Hlth, Bethesda, MD 20892 USA. [Sharma, Kamal] US FDA, Div Biol Drug Prod, Off Oncol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Sarin, H (reprint author), Natl Inst Biomed Imaging & Bioengn, Natl Inst Hlth, Bethesda, MD 20892 USA. EM sarinh@mail.nih.gov; kanevskya@mail.nih.gov; wuh3@mail.nih.gov; brimacombek@mail.nih.gov; sfung@partners.org; sousaali@mail.nih.gov; auhs@mail.nih.gov; wilsoncm@mail.nih.gov; kamal.sharma@fda.hhs.gov; aronovaa@mail.nih.gov; leapmanr@mail.nih.gov; griffithsgl@mail.nih.gov; hallma@mail.nih.gov RI Hall, Matthew/B-2132-2010; OI Fung, Steve/0000-0002-1177-682X FU National Institute of Biomedical Imaging Bioengineering (NIBIB); National Cancer Institute (NCI); Radiology and Imaging Sciences Program (CC) FX This study was funded by the National Institute of Biomedical Imaging Bioengineering (NIBIB), National Cancer Institute (NCI), and the Radiology and Imaging Sciences Program (CC). We thank Guofeng Zhang of the Laboratory of Bioengineering and Physical Science (NIBIB) and Yide Mi of the Radiology and Imaging Sciences Program (CC) for technical assistance. We thank Daniel Glen and Rick Reynolds of the Scientific and Statistical Computing Core (National Institute of Mental Health [ NIMH]) for their assistance during our use of the Analysis of Functional NeuroImages (AFNI) software suite for data analyses. NR 71 TC 116 Z9 118 U1 2 U2 38 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1479-5876 J9 J TRANSL MED JI J. Transl. Med. PD DEC 18 PY 2008 VL 6 AR 80 DI 10.1186/1479-5876-6-80 PG 15 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 409WS UT WOS:000263537100001 PM 19094226 ER PT J AU Blossom, DB Kallen, AJ Patel, PR Elward, A Robinson, L Gao, GP Langer, R Perkins, KM Jaeger, JL Kurkjian, KM Jones, M Schillie, SF Shehab, N Ketterer, D Venkataraman, G Kishimoto, TK Shriver, Z McMahon, AW Austen, KF Kozlowski, S Srinivasan, A Turabelidze, G Gould, CV Arduino, MJ Sasisekharan, R AF Blossom, David B. Kallen, Alexander J. Patel, Priti R. Elward, Alexis Robinson, Luke Gao, Ganpan Langer, Robert Perkins, Kiran M. Jaeger, Jennifer L. Kurkjian, Katie M. Jones, Marilyn Schillie, Sarah F. Shehab, Nadine Ketterer, Daniel Venkataraman, Ganesh Kishimoto, Takashi Kei Shriver, Zachary McMahon, Ann W. Austen, K. Frank Kozlowski, Steven Srinivasan, Arjun Turabelidze, George Gould, Carolyn V. Arduino, Matthew J. Sasisekharan, Ram TI Outbreak of Adverse Reactions Associated with Contaminated Heparin SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Article ID ANAPHYLACTOID REACTIONS; CLINICAL EVENTS; HEMODIALYSIS AB Background: In January 2008, the Centers for Disease Control and Prevention began a nationwide investigation of severe adverse reactions that were first detected in a single hemodialysis facility. Preliminary findings suggested that heparin was a possible cause of the reactions. Methods: Information on clinical manifestations and on exposure was collected for patients who had signs and symptoms that were consistent with an allergic-type reaction after November 1, 2007. Twenty-one dialysis facilities that reported reactions and 23 facilities that reported no reactions were included in a case-control study to identify facility-level risk factors. Unopened heparin vials from facilities that reported reactions were tested for contaminants. Results: A total of 152 adverse reactions associated with heparin were identified in 113 patients from 13 states from November 19, 2007, through January 31, 2008. The use of heparin manufactured by Baxter Healthcare was the factor most strongly associated with reactions (present in 100.0% of case facilities vs. 4.3% of control facilities, P<0.001). Vials of heparin manufactured by Baxter from facilities that reported reactions contained a contaminant identified as oversulfated chondroitin sulfate (OSCS). Adverse reactions to the OSCS-contaminated heparin were often characterized by hypotension, nausea, and shortness of breath occurring within 30 minutes after administration. Of 130 reactions for which information on the heparin lot was available, 128 (98.5%) occurred in a facility that had OSCS-contaminated heparin on the premises. Of 54 reactions for which the lot number of administered heparin was known, 52 (96.3%) occurred after the administration of OSCS-contaminated heparin. Conclusions: Heparin contaminated with OSCS was epidemiologically linked to adverse reactions in this nationwide outbreak. The reported clinical features of many of the cases further support the conclusion that contamination of heparin with OSCS was the cause of the outbreak. C1 [Blossom, David B.; Kallen, Alexander J.; Patel, Priti R.; Schillie, Sarah F.; Shehab, Nadine; Srinivasan, Arjun; Gould, Carolyn V.; Arduino, Matthew J.] Ctr Dis Control & Prevent, Div Healthcare Qual Promot, Atlanta, GA 30333 USA. [Blossom, David B.; Kallen, Alexander J.; Jaeger, Jennifer L.; Kurkjian, Katie M.; Schillie, Sarah F.] Ctr Dis Control & Prevent, Epidem Intelligence Serv Program, Atlanta, GA 30333 USA. [Blossom, David B.; Kallen, Alexander J.; Perkins, Kiran M.; Jaeger, Jennifer L.; Kurkjian, Katie M.; Schillie, Sarah F.; Ketterer, Daniel] Ctr Dis Control & Prevent, Off Workforce & Career Dev, Atlanta, GA 30333 USA. [Elward, Alexis] St Louis Childrens Hosp, St Louis, MO 63178 USA. [Jones, Marilyn] BJC Healthcare, St Louis, MO USA. [Turabelidze, George] Missouri Dept Hlth & Senior Serv, St Louis, MO USA. [Robinson, Luke; Gao, Ganpan; Langer, Robert; Sasisekharan, Ram] MIT, Dept Biol Engn, Cambridge, MA 02139 USA. [Langer, Robert] MIT, Dept Chem Engn, Cambridge, MA 02139 USA. [Langer, Robert; Sasisekharan, Ram] MIT, Harvard Mit Div Hlth Sci & Technol, Cambridge, MA 02139 USA. [Robinson, Luke; Gao, Ganpan; Langer, Robert; Sasisekharan, Ram] MIT, Koch Inst Integrat Canc Res, Cambridge, MA 02139 USA. [Venkataraman, Ganesh; Kishimoto, Takashi Kei; Shriver, Zachary] Momenta Pharmaceut, Cambridge, MA USA. [McMahon, Ann W.; Kozlowski, Steven] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Austen, K. Frank] Brigham & Womens Hosp, Boston, MA 02115 USA. [Austen, K. Frank] Harvard Univ, Sch Med, Boston, MA 02115 USA. RP Patel, PR (reprint author), Ctr Dis Control & Prevent, Div Healthcare Qual Promot, 1600 Clifton Rd,MS-A31, Atlanta, GA 30333 USA. EM ppatel@cdc.gov RI Arduino, Matthew/C-1461-2012 OI Arduino, Matthew/0000-0001-7072-538X FU National Institutes of Health [GM57073, HL080279]; Momenta Pharmaceuticals and Scientific Protein; Momenta Pharmaceuticals; SAGE Products; Pfizer; Lilly; Monsanto; Walgreens; General Electric; Abbott FX The CDC investigation had no external funding. The laboratory analysis was supported in part by grants from the National Institutes of Health (GM57073 and HL080279, to Dr. Sasisekharan).; Dr. Venkataraman reports being an employee of Momenta Pharmaceuticals and holding equity in the company, which performs the analysis and characterization of complex mixtures, including heparin, and being an inventor on patent applications for Momenta Pharmaceuticals; Dr. Kishimoto, being an employee of, holding equity in, and being an inventor on patent applications for Momenta Pharmaceuticals; Dr. Langer, receiving consulting fees from Momenta Pharmaceuticals and Scientific Protein, having equity in Momenta Pharmaceuticals, and serving on a paid board of Momenta Pharmaceuticals; Dr. Shriver, being an employee of Momenta Pharmaceuticals and holding equity in the company; Dr. Sasisekharan, holding equity in Momenta Pharmaceuticals and receiving consulting fees or serving on a paid board of Momenta Pharmaceuticals and Scientific Protein Labs; Dr. Austen, receiving consulting fees from Momenta Pharmaceuticals; Dr. Elward, receiving consulting fees or serving on a paid advisory board for Trinity and receiving grant support from SAGE Products; and Dr. Schillie, holding equity in Pfizer, Lilly, Monsanto, Walgreens, General Electric, and Abbott. No other potential conflict of interest relevant to this article was reported.; The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention. Use of trade names and commercial sources is for identification only and does not imply endorsement by the U. S. Department of Health and Human Services.; We thank the many health care professionals at facilities at which adverse events occurred for reporting to public health authorities and for sending heparin vials for laboratory testing; the state epidemiologists and representatives of the End Stage Renal Disease Network for their assistance in facilitating contact between facilities with adverse events and the CDC; Laura Governale ( IMS Health), Gary Warns ( Gambro), and Bill Singley ( Minntech) for the timely information they provided; and representatives of the FDA for their close collaboration, especially in the early stages of this outbreak investigation, in particular, Karen Deasy and Tarun Mallick, who served as important links between the FDA and the CDC and furthered our collective efforts. NR 22 TC 134 Z9 138 U1 3 U2 7 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 18 PY 2008 VL 359 IS 25 BP 2674 EP 2684 DI 10.1056/NEJMoa0806450 PG 11 WC Medicine, General & Internal SC General & Internal Medicine GA 384PS UT WOS:000261757300007 PM 19052120 ER PT J AU Konduru, K Virata-Theimer, ML Yu, MYW Kaplan, GG AF Konduru, Krishnamurthy Virata-Theimer, Maria Luisa Yu, Mei-ying W. Kaplan, Gerardo G. TI A simple and rapid Hepatitis A Virus (HAV) titration assay based on antibiotic resistance of infected cells: evaluation of the HAV neutralization potency of human immune globulin preparations SO Virology Journal LA English DT Article ID MULTISTATE OUTBREAK; PLAQUE-ASSAY; IMMUNOGLOBULIN; PROPHYLAXIS; GROWTH; ANTIBODY; CULTURE; VACCINE AB Background: Hepatitis A virus (HAV), the causative agent of acute hepatitis in humans, is an atypical Picornaviridae that grows poorly in cell culture. HAV titrations are laborious and time-consuming because the virus in general does not cause cytopathic effect and is detected by immunochemical or molecular probes. Simple HAV titration assays could be developed using currently available viral construct containing selectable markers. Results: We developed an antibiotic resistance titration assay (ARTA) based on the infection of human hepatoma cells with a wild type HAV construct containing a blasticidin (Bsd) resistance gene. Human hepatoma cells infected with the HAV-Bsd construct survived selection with 2 mu g/ml of blasticidin whereas uninfected cells died within a few days. At 8 days postinfection, the color of the pH indicator phenol red in cell culture media correlated with the presence of HAV-Bsd-infected blasticidin-resistant cells: an orange-to-yellow color indicated the presence of growing cells whereas a pink-to-purple color indicated that the cells were dead. HAV-Bsd titers were determined by an endpoint dilution assay based on the color of the cell culture medium scoring orange-to-yellow wells as positive and pink-to-purple wells as negative for HAV. As a proof-of-concept, we used the ARTA to evaluate the HAV neutralization potency of two commercially available human immune globulin (IG) preparations and a WHO International Standard for anti-HAV. The three IG preparations contained comparable levels of anti-HAV antibodies that neutralized approximately 1.5 log of HAV-Bsd. Similar neutralization results were obtained in the absence of blasticidin by an endpoint dilution ELISA at 2 weeks postinfection. Conclusion: The ARTA is a simple and rapid method to determine HAV titers without using HAV-specific probes. We determined the HAV neutralization potency of human IG preparations in 8 days by ARTA compared to the 14 days required by the endpoint dilution ELISA. The ARTA reduced the labour, time, and cost of HAV titrations making it suitable for high throughput screening of sera and antivirals, determination of anti-HAV antibodies in human immune globulin preparations, and research applications that involve the routine evaluation of HAV titers. C1 [Konduru, Krishnamurthy; Kaplan, Gerardo G.] US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Virata-Theimer, Maria Luisa; Yu, Mei-ying W.] US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kaplan, GG (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM Krishnamurthy.konduru@fda.hhs.gov; marialuisa.virata@fda.hhs.gov; mei-ying.yu@fda.hhs.gov; gk@helix.nih.gov FU FDA FX We thank K. V. K Mohan K. V. K., and the NIH Fellows Editorial Board for critical review of the manuscript. The work was supported by FDA intramural funds to MYY and GGK. NR 27 TC 7 Z9 8 U1 0 U2 1 PU BIOMED CENTRAL LTD PI LONDON PA CURRENT SCIENCE GROUP, MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD DEC 18 PY 2008 VL 5 AR 155 DI 10.1186/1743-422X-5-155 PG 9 WC Virology SC Virology GA 395MY UT WOS:000262529400002 PM 19094229 ER PT J AU Gupta, A Hunt, RL Khan, MA AF Gupta, Abhay Hunt, Robert L. Khan, Mansoor A. TI Influence of tablet characteristics on weight variability and weight loss in split tablets SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Letter ID ACCURACY C1 [Gupta, Abhay; Hunt, Robert L.; Khan, Mansoor A.] US FDA, Div Product Qual Res, Off Pharmaceut Sci, Silver Spring, MD 20993 USA. RP Gupta, A (reprint author), US FDA, Div Product Qual Res, Off Pharmaceut Sci, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mansoor.khan@fda.hhs.gov NR 4 TC 1 Z9 3 U1 0 U2 3 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD DEC 15 PY 2008 VL 65 IS 24 BP 2326 EP + DI 10.2146/ajhp080371 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 380SS UT WOS:000261486100010 PM 19052274 ER PT J AU Chumakov, K Ehrenfeld, E AF Chumakov, Konstantin Ehrenfeld, Ellie TI New Generation of Inactivated Poliovirus Vaccines for Universal Immunization after Eradication of Poliomyelitis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID SYNONYMOUS CODON USAGE; ATTENUATED POLIOVIRUS; PROTECTIVE PROPERTIES; SABIN STRAINS; UNITED-STATES; VIRUS; IMMUNOGENICITY; VACCINATION; CELLS; DEOPTIMIZATION AB Twenty years of global polio eradication efforts may soon eliminate the transmission of wild-type poliovirus. However, new information that has been learned about poliovirus, as well as the political realities of a modern world, demand that universal immunity against poliomyelitis be maintained, even after wild-type poliovirus is eradicated. Although 2 excellent vaccines have proven to be highly effective in the past, neither the live-attenuated vaccine nor the currently used inactivated vaccine are optimal for use in the posteradication era. Therefore, concerted efforts are urgently needed to develop a new generation of vaccine that is risk-free and affordable and can be produced on a global scale. Here, we discuss the desired properties of a vaccine and methods to create a new polio vaccine. C1 [Chumakov, Konstantin] US FDA, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Ehrenfeld, Ellie] NIAID, NIH, Bethesda, MD 20892 USA. RP Chumakov, K (reprint author), US FDA, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM-470, Rockville, MD 20852 USA. EM konstantin.chumakov@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases, National Institutes of Health; US Food and Drug Administration; US Department of Health and Human Services FX National Institute of Allergy and Infectious Diseases, National Institutes of Health; US Food and Drug Administration; and US Department of Health and Human Services. NR 57 TC 29 Z9 32 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 15 PY 2008 VL 47 IS 12 BP 1587 EP 1592 DI 10.1086/593310 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 376DO UT WOS:000261163600020 PM 18990066 ER PT J AU Bluhm, E McNeil, DE Cnattingius, S Gridley, G El Ghormli, L Fraumeni, JF AF Bluhm, Elizabeth McNeil, Dawn Elizabeth Cnattingius, Sven Gridley, Gloria El ghormli, Laure Fraumeni, Joseph F., Jr. TI Prenatal and perinatal risk factors for neuroblastoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE neuroblastoma; prenatal; delayed effects; prenatal exposure; anemia; case-control study ID CHILDHOOD-CANCER; NEURO-BLASTOMA; BIRTH CHARACTERISTICS; MEDICATION USE; CONGENITAL-ANOMALIES; YOUNG-CHILDREN; BRAIN-TUMORS; PREGNANCY; ASSOCIATION; DEFECTS AB Neuroblastoma is a rare embryonal tumor of childhood for which risk factors are not well known. Using a nested case-control design, we investigated prenatal, perinatal and neonatal risk factors in detail by linking 245 pediatric neuroblastoma cases identified in the Swedish Cancer Register diagnosed in the year 1973-1995 with the Swedish Medical Birth Register. Five living controls per case were randomly selected from the birth registry, matched by gender and age. Increased risks were associated with maternal anemia during pregnancy (odds ratio (OR) = 2.95, 95% confidence interval (CI): 1.53, 5.69), neonatal respiratory distress (OR = 3.61, 95% CI: 1.41, 9.24) and low (below or equal to 7) 1-min Apgar score (OR = 2.23, 95% CI: 1.41, 3.52). Increased risks were limited to cases diagnosed before 1 year of age. Markers of prenatal, perinatal and neonatal distress may be associated with neuroblastoma in infancy, but not with diagnoses at 1 year or above. Published 2008 Wiley-Liss, Inc. C1 [Bluhm, Elizabeth] Washington Hosp Ctr, Gen Internal Med Sect, Washington, DC 20010 USA. [Bluhm, Elizabeth] NCI, Radiat Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [McNeil, Dawn Elizabeth] US FDA, Div Neurol Drug Prod, Silver Spring, MD USA. [Cnattingius, Sven] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden. [Gridley, Gloria] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. [El ghormli, Laure] George Washington Univ, Ctr Biostat, Rockville, MD USA. [Fraumeni, Joseph F., Jr.] NCI, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. RP Bluhm, E (reprint author), Washington Hosp Ctr, Gen Internal Med Sect, POB 1A-50,110 Irving St NW, Washington, DC 20010 USA. EM elizabeth.c.bluhm@medstar.net FU Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics FX Grant sponsor: Intramural Research Program of the NIH, National Cancer Institute, Division of Cancer Epidemiology and Genetics. NR 53 TC 14 Z9 14 U1 1 U2 5 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 DEC 15 PY 2008 VL 123 IS 12 BP 2885 EP 2890 DI 10.1002/ijc.23847 PG 6 WC Oncology SC Oncology GA 375KO UT WOS:000261112900021 PM 18798548 ER PT J AU Ishige, K Shoda, J Kawamoto, T Matsuda, S Ueda, T Hyodo, I Ohkohchi, N Puri, RK Kawakami, K AF Ishige, Kazunori Shoda, Junichi Kawamoto, Toru Matsuda, Sachiko Ueda, Tetsuya Hyodo, Ichinosuke Ohkohchi, Nobuhiro Puri, Raj K. Kawakami, Koji TI Potent in vitro and in vivo antitumor activity of interleukin-4-conjugated Pseudomonas exotoxin against human biliary tract carcinoma SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE biotherapy; cytotoxin; cytokine receptor; gallbladder carcinoma; cholangiocarcinoma ID CANCER CELLS; INTERLEUKIN-4-PSEUDOMONAS EXOTOXIN; INTRAHEPATIC CHOLANGIOCARCINOMA; CHOLANGIOCELLULAR CARCINOMA; GALLBLADDER CANCER; CYTOTOXIN THERAPY; IL-4 RECEPTOR; PHASE-II; PROTEIN; GEMCITABINE AB Targeting cytotoxins or immunotoxins to tumor cell surface receptors represents a new approach for the treatment of cancers. We tested the antitumor activity of a cytotoxin (IL-4-PE) composed of an interleukin-4 (IL-4) targeting moiety and a truncated form of Pseudomonas exotoxin A against human biliary tract carcinoma (BTC). Immunohistochemical analysis showed that cultured BTC cell lines and cancerous epithelia in BTC tissue (e.g., gallbladder carcinoma, extraheaptic cholangiocarcinoma, and intrahepatic cholangiocarcinoma) expressed receptors for IL-4 in situ at high densities. However, normal epithelial cells in gallbladder and bile duct tissues did not express these IL-4 receptors. Eight BTC cell lines; expressed IL-4R on the cell surface as determined by radiolabeled ligand binding assays. When these cells were treated with IL-4-PE, significant cytotoxicity was observed as determined by the inhibition of protein synthesis. The concentration of agent causing 50% inhibition of protein synthesis (IC50) was found to be less than 10 ng/mL in 4 of the 8 BTC cell lines studied. The antitumor activity of IL-4-PE was assessed for human BTC cells implanted subcutaneously in immunodeficient mice. By intratumoral injection of IL-4-PE, complete disappearance of the estabfished tumors was observed in 40% of animals. Intraperitoneal administration of IL-4. PE at tolerated doses to animals with peritoneally disseminated BTC exhibited significantly prolonged survival compared to untreated animals (>14 weeks vs, 5 weeks in treated and untreated mice, respectively). These results indicate that IL-4 receptor-targeted cytotoxin is a potent agent that may provide a new therapeutic option for BTC. (C) 2008 Wiley-Liss, Inc. C1 [Kawakami, Koji] Kyoto Univ, Grad Sch Med & Publ Hlth, Dept Pharmacoepidemiol, Sakyo Ku, Kyoto 6068501, Japan. [Ishige, Kazunori; Shoda, Junichi; Hyodo, Ichinosuke] Univ Tsukuba, Grad Sch Comprehens Human Sci, Inst Clin Med, Dept Gastroenterol, Tsukuba, Ibaraki, Japan. [Ishige, Kazunori; Matsuda, Sachiko; Kawakami, Koji] Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Bunkyo Ku, Tokyo, Japan. [Kawamoto, Toru] Univ Texas MD Anderson Canc Ctr, Dept Med Oncol, Houston, TX 77030 USA. [Ueda, Tetsuya] Mitsubishi Chem Medience Corp, Medichem Business Segment, Pharmacodynam Grp, Drug Dev Serv Div,Itabashi Ku, Tokyo, Japan. [Ohkohchi, Nobuhiro] Univ Tsukuba, Grad Sch Comprehens Human Sci, Inst Clin Med, Dept Surg, Tsukuba, Ibaraki, Japan. [Puri, Raj K.] US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Tumor Vaccines & Biotechnol Branch, Bethesda, MD 20014 USA. RP Kawakami, K (reprint author), Kyoto Univ, Grad Sch Med & Publ Hlth, Dept Pharmacoepidemiol, Sakyo Ku, Kyoto 6068501, Japan. EM kawakami-k@pbh.med.kyoto-u.ac.jp FU Ministry of Education, Culture, Sports, Science and Technology. Japan [20390339] FX Grant sponsors: Ministry of Education, Culture, Sports, Science and Technology. Japan; Grant number: 20390339. NR 39 TC 6 Z9 8 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD DEC 15 PY 2008 VL 123 IS 12 BP 2915 EP 2922 DI 10.1002/ijc.23965 PG 8 WC Oncology SC Oncology GA 375KO UT WOS:000261112900026 PM 18798553 ER PT J AU Robertson, SM Maldarelli, F Natarajan, V Formentini, E Alfaro, RM Penzak, SR AF Robertson, Sarah M. Maldarelli, Frank Natarajan, Ven Formentini, Elizabeth Alfaro, Raul M. Penzak, Scott R. TI Efavirenz Induces CYP2B6-Mediated Hydroxylation of Bupropion in Healthy Subjects SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article DE efavirenz; bupropion; metabolism; CYP2B6; drug interaction; induction ID CYTOCHROME P4502B6 ACTIVITY; POTENTIAL-DRUG INTERACTIONS; IN-VITRO; HUMAN LIVER; POPULATION PHARMACOKINETICS; CATALYTIC-ACTIVITY; CYP2B6; METABOLISM; POLYMORPHISM; SUBSTRATE AB Objective: To characterize the effect of efavirenz on bupropion hydroxylation as a marker of cytochrome P450 (CYP) 2136 activity in healthy subjects. Methods: Thirteen subjects received a single oral dose of bupropion SR 150 mg before and after 2 weeks of efavirenz administration for comparison of bupropion and hydroxybupropion pharmacokinetics. Efavirenz plasma concentrations were also assessed. Subjects were genotyped for CYP2B6 (G516T, C1459T, and A785G), CYP3A4 (A-392G), CYP3A5 (A6986G), and multidrug resistance protein 1 (C3435T). Results: The area under the concentration vs. time curve ratio of hydroxybupropion: bupropion increased 2.3-fold after efavirenz administration (P = 0.0001). Bupropion area under the concentration vs. time curve and C(max) decreased by 55% and 34%, respectively (P < 0.002). None of the CYP2B6 or CYP3A genotypes evaluated were associated with a difference in bupropion or efavirenz clearance. The 2 individuals homozygous for multidrug resistance protein 1 3435-T/T had 2.5- and 1.8-fold greater bupropion and efavirenz clearance, respectively, relative to C/C and C/T individuals (P < 0.05). Conclusions: Our results confirm that efavirenz induces CYP2B6 enzyme activity in vivo, as demonstrated by an increase in bupropion hydroxylation after 2 weeks of efavirenz administration. C1 [Robertson, Sarah M.] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Maldarelli, Frank] Natl Canc Inst, HIV Drug Resistance Program, Frederick, MD USA. [Natarajan, Ven] Natl Canc Inst, SAIC Frederick, Mol Cell Biol Lab, Frederick, MD USA. [Formentini, Elizabeth] NIH, Dept Crit Care Med, Bethesda, MD 20892 USA. [Alfaro, Raul M.; Penzak, Scott R.] NIH, Clin Res Ctr, Dept Pharm, Bethesda, MD 20892 USA. RP Robertson, SM (reprint author), US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Bldg 21,Room 4653,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sarah.robertson@fda.hhs.gov FU Society of Infectious Diseases Pharmacists/Pfizer Award; Research in Infectious Disease Phamacotherapy FX Supported by the Society of Infectious Diseases Pharmacists/Pfizer Award for Research in Infectious Disease Phamacotherapy; awarded December 2005. NR 39 TC 37 Z9 37 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 DEC 15 PY 2008 VL 49 IS 5 BP 513 EP 519 DI 10.1097/QAI.0b013e318183a425 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 376YN UT WOS:000261219000008 PM 18989234 ER PT J AU Reed, JL Brewah, YA Delaney, T Welliver, T Burwell, T Benjamin, E Kuta, E Kozhich, A McKinney, L Suzich, J Kiener, PA Avendano, L Velozo, L Humbles, A Welliver, RC Coyle, AJ AF Reed, Jennifer L. Brewah, Yambasu A. Delaney, Tracy Welliver, Timothy Burwell, Timothy Benjamin, Ebony Kuta, Ellen Kozhich, Alexander McKinney, LuAnn Suzich, JoAnn Kiener, Peter A. Avendano, Luis Velozo, Luis Humbles, Alison Welliver, Robert C., Sr. Coyle, Anthony J. TI Macrophage Impairment Underlies Airway Occlusion in Primary Respiratory Syncytial Virus Bronchiolitis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 6th International Respiratory Syncytial Virus Symposium CY OCT 25-28, 2007 CL Marco Isl, FL ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; RABBIT ALVEOLAR MACROPHAGE; MARGINAL ZONE MACROPHAGES; TOLL-LIKE RECEPTOR-4; ANIMAL DEVELOPMENT; LUNG INFLAMMATION; APOPTOTIC CELLS; INNATE IMMUNITY; PRONE MICE; INFECTION AB Although respiratory syncytial virus (RSV) infection is the most important cause of bronchiolitis in infants, the pathogenesis of RSV disease is poorly described. We studied histopathologic changes in a panel of lung tissue specimens obtained from infants with fatal cases of primary RSV infection. In these tissues, airway occlusion with accumulations of infected, apoptotic cellular debris and serum protein was consistently observed. Similar observations were found after RSV infection in New Zealand black (NZB) mice, which have constitutive deficiencies in macrophage function, but not in BALB/c mice. A deficiency in the number of alveolar macrophages in NZB mice appears to be central to enhanced disease, because depletion of alveolar macrophages in BALB/c mice before RSV exposure resulted in airway occlusion. In mice with insufficient numbers of macrophages, RSV infection yielded an increased viral load and enhanced expression of type I interferon-associated genes at the height of disease. Together, our data suggest that innate, rather than adaptive, immune responses are critical determinants of the severity of RSV bronchiolitis. C1 [Reed, Jennifer L.; Brewah, Yambasu A.; Delaney, Tracy; Welliver, Timothy; Burwell, Timothy; Benjamin, Ebony; Kuta, Ellen; Kozhich, Alexander; McKinney, LuAnn; Suzich, JoAnn; Kiener, Peter A.; Humbles, Alison; Coyle, Anthony J.] Resp Inflammat & Autoimmun Grp, Gaithersburg, MD USA. [Welliver, Robert C., Sr.] SUNY Buffalo, Womens & Childrens Hosp, Dept Pediat, Buffalo, NY 14260 USA. [Avendano, Luis] Univ Chile, Programa Virol, Santiago, Chile. [Velozo, Luis] Roberto del Rio Childrens Hosp, Dept Anat Patol, Santiago, Chile. RP Reed, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike HFM-345, Bethesda, MD 20892 USA. EM jennifer.reed@fda.hhs.gov NR 50 TC 41 Z9 41 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD DEC 15 PY 2008 VL 198 IS 12 BP 1783 EP 1793 DI 10.1086/593173 PG 11 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 376QB UT WOS:000261197000005 PM 18980502 ER PT J AU Shankar, G Devanarayan, V Amaravadi, L Barrett, YC Bowsher, R Finco-Kent, D Fiscella, M Gorovits, B Kirschner, S Moxness, M Parish, T Quarmby, V Smith, H Smith, W Zuckerman, LA Koren, E AF Shankar, Gopi Devanarayan, Viswanath Amaravadi, Lakshmi Barrett, Yu Chen Bowsher, Ronald Finco-Kent, Deborah Fiscella, Michele Gorovits, Boris Kirschner, Susan Moxness, Michael Parish, Thomas Quarmby, Valerie Smith, Holly Smith, Wendell Zuckerman, Linda A. Koren, Eugen TI Recommendations for the validation of immunoassays used for detection of host antibodies against biotechnology products SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Review DE Method validation; Immunogenicity; Immunoassay; Anti-drug antibody ID IMMUNOGENICITY; RESPONSES; OPTIMIZATION; STRATEGIES; DESIGN; ASSAYS AB Most biological drug products elicit some level of anti-drug antibody (ADA) response. This antibody response can, in some cases, lead to potentially serious side effects and/or loss of efficacy. In humans, ADA often causes no detectable clinical effects, but in the instances of some therapeutic proteins these antibodies have been shown to cause a variety of clinical consequences ranging from relatively mild to serious adverse events. In nonclinical (preclinical) studies, ADA can affect drug exposure, complicating the interpretation of the toxicity, pharmacokinetic (PK) and pharmacodynamic (PD) data. Therefore, the immunogenicity of therapeutic proteins is a concern forclinicians, manufacturers and regulatory agencies. In order to assess the immunogenic potential of biological drug molecules, and be able to correlate laboratory results with clinical events, it is important to develop reliable laboratory test methods that provide valid assessments of antibody responses in both nonclinical and clinical studies. For this, method validation is considered important, and is a necessary bioanalytical component of drug marketing authorization applications. Existing regulatory guidance documents dealing with the validation of methods address immunoassays in a limited manner, and in particular lack information on the validation of immunogenicity methods. Hence this article provides scientific recommendations for the validation of ADA immunoassays. Unique validation performance characteristics are addressed in addition to those provided in existing regulatory documents pertaining to bioanalyses. The authors recommend experimental and statistical approaches for the validation of immunoassay performance characteristics; these recommendations should be considered as examples of best practice and are intended to foster a more unified approach to antibody testing across the biopharmaceutical industry. (C) 2008 Elsevier B.V. All rights reserved. C1 [Koren, Eugen] Abbott Vasc Inc, Bioanalyt R&D, Santa Clara, CA 95054 USA. [Shankar, Gopi] Centocor Res & Dev Inc, Clin Pharmacol Sci, Radnor, PA 19087 USA. [Devanarayan, Viswanath] Abbott Labs, Parsippany, NJ 07054 USA. [Amaravadi, Lakshmi] Biogen Inc, Preclin & Clin Dev Sci, Cambridge, MA 02142 USA. [Barrett, Yu Chen] Bristol Myers Squibb Co, Clin Discovery, Princeton, NJ 08543 USA. [Bowsher, Ronald] Millipore Corp, BioPharma Serv Div, St Charles, MO 63304 USA. [Bowsher, Ronald] B2S Consulting, Beech Grove, IN 46107 USA. [Finco-Kent, Deborah] Pfizer, Drug Safety Res & Dev, Groton, CT 06340 USA. [Fiscella, Michele] Human Genome Sci, Rockville, MD 20850 USA. [Gorovits, Boris] Wyeth, Drug Safety & Metab, Pearl River, NY 10965 USA. [Kirschner, Susan] Food & Drug Adm, CDER, Off Biotechnol Prod, Bethesda, MD 20892 USA. [Moxness, Michael] Amgen Inc, Med Sci, Clin Immunol, Thousand Oaks, CA 91320 USA. [Parish, Thomas] Procter & Gamble Pharmaceut, Dept Analyt Sci, Norwich, NY 13815 USA. [Quarmby, Valerie] Genentech Inc, BioAnalyt Res &Dev, San Francisco, CA 94080 USA. [Smith, Holly] Eli Lilly & Co, Investigat Toxicol, Greenfield, IN 46140 USA. [Smith, Wendell] B2S Consulting, Greenfield, IN 46140 USA. [Zuckerman, Linda A.] Zymogenet Inc, PreClin Dev Dept, Seattle, WA 98102 USA. RP Koren, E (reprint author), Abbott Vasc Inc, Bioanalyt R&D, Santa Clara, CA 95054 USA. EM eugen.koren@av.abbott.com NR 29 TC 211 Z9 216 U1 3 U2 26 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 DEC 15 PY 2008 VL 48 IS 5 BP 1267 EP 1281 DI 10.1016/j.jpba.2008.09.020 PG 15 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 401DZ UT WOS:000262920800001 PM 18993008 ER PT J AU Kauffman, JF Batykefer, LM Tuschel, DD AF Kauffman, John F. Batykefer, Linda M. Tuschel, David D. TI Raman detected differential scanning calorimetry of polymorphic transformations in acetaminophen SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Raman spectroscopy; Differential scanning calorimetry; Polymorphism; Acetaminophen ID SINTERED-LIKE CRYSTALS; DIRECT COMPRESSION; PURE PARACETAMOL; MECHANICAL-PROPERTIES; FORM-III; FT-IR; MIXTURES; BEHAVIOR AB Acetaminophen is known to crystallize in three polymorphic forms. Thermally induced transformations between the crystalline forms and the super-cooled liquid have been observed by differential scanning calorimetry (DSC), but the assignment of calorimetric transitions to specific polymorphic transformations remains challenging, because the transition temperatures for several transformations are close to one another, and the characteristics of the observed transitions depend on experimental variables that are often poorly controlled. This paper demonstrates the simultaneous application of DSC and Raman microscopy for the observation of thermally driven transitions between polymorphs of pharmaceutical materials. Raman detected differential scanning calorimetry (RD-DSC) has been used to monitor the DSC thermograms of super-cooled liquid acetaminophen and confirms the assignment of two exothermic transitions to specific polymorphic transformations. Principal component analysis of the Raman spectra have been used to determine the number of independent components that participate in the phase transformations, and multivariate regression has been used to determine transition temperatures from the spectral data. The influence of the laser excitation source on measured DSC thermograms has also been investigated, and it has been demonstrated that a baseline shift occurs in RD-DSC when a polymorphic transformation occurs between crystalline and amorphous forms. RD-DSC has been used to examine the influence of sample aging and sample pan configuration on the observed polymorphic transformations, and both of these variables were found to influence the thermal behavior of the sample. The results demonstrate the advantage of simultaneous Raman spectroscopy and differential scanning calorimetry for the unambiguous assignment of thermally driven polymorphic transformations. Published by Elsevier B.V. C1 [Kauffman, John F.] US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, St Louis, MO 63101 USA. [Batykefer, Linda M.; Tuschel, David D.] ChemImage Corp, Pittsburgh, PA USA. RP Kauffman, JF (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, 1114 Market St, St Louis, MO 63101 USA. EM John.Kauffman@fda.hhs.gov NR 20 TC 24 Z9 25 U1 2 U2 32 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 DEC 15 PY 2008 VL 48 IS 5 BP 1310 EP 1315 DI 10.1016/j.jpba.2008.09.008 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 401DZ UT WOS:000262920800005 PM 18930622 ER PT J AU Shein, MJ Schultz, DG AF Shein, Mitchell J. Schultz, Daniel G. TI Testing New ICD Technology SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Shein, Mitchell J.; Schultz, Daniel G.] US FDA, Rockville, MD 20857 USA. RP Shein, MJ (reprint author), US FDA, Rockville, MD 20857 USA. NR 2 TC 5 Z9 5 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 DEC 11 PY 2008 VL 359 IS 24 BP 2610 EP 2610 DI 10.1056/NEJMc086467 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 381KG UT WOS:000261534200017 PM 19073982 ER PT J AU Ilev, IK Faaland, RW Kim, DH James, RH Calogero, D AF Ilev, Iko K. Faaland, Robert W. Kim, Do-Hyun James, Robert H. Calogero, Don TI Innovative confocal laser method for exact dioptric power measurement of intraocular lens implants SO CHINESE OPTICS LETTERS LA English DT Article ID FOCAL LENGTH AB We present a novel confocal laser method (CLM) for precise testing of the dioptric power of both positive and negative intraocular lens (IOL) implants. The CLM principle is based on a simple fiber-optic confocal laser design including a single-mode fiber coupler that serves simultaneously as a point light source used for formation of a collimated Gaussian laser beam, and as a highly sensitive confocal point receiver. The CLM approach provides art accurate, repeatable, objective; and fast method for IOL dioptric power measurement over the range from 0 D to greater than +/- 30 D under both dry and in-situ simulated conditions. C1 [Ilev, Iko K.; Faaland, Robert W.; Kim, Do-Hyun; James, Robert H.] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Calogero, Don] US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20850 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM ilko.ilev@fda.hhs.gov RI Kim, Do-Hyun/C-5311-2009 NR 10 TC 6 Z9 6 U1 0 U2 1 PU CHINESE LASER PRESS PI SHANGHAI PA PO BOX 800-211, SHANGHAI, 201800, PEOPLES R CHINA SN 1671-7694 J9 CHIN OPT LETT JI Chin. Opt. Lett. PD DEC 10 PY 2008 VL 6 IS 12 BP 876 EP 878 DI 10.3788/COL20080612.0876 PG 3 WC Optics SC Optics GA 389UV UT WOS:000262120900002 ER PT J AU Liu, X Li, XL Kim, DH Ilev, I Kang, JU AF Liu, Xuan Li, Xiaolu Kim, Do-Hyun Ilev, Ilko Kang, Jin U. TI Fiber-optic Fourier-domain common-path OCT SO CHINESE OPTICS LETTERS LA English DT Article ID OPTICAL COHERENCE TOMOGRAPHY; INTERFEROMETER AB We experimentally and theoretically investigated the performance of a fiber-optic based Fourier-domain common-path optical coherence tomography (OCT). The fiber-optic common-path OCT operated at the 840-nm center wavelength. The resolution of the system was 8.8 mu m (in air) and the working depth using a bare fiber probe was approximately 1.5 mm. The signal-to-noise ratio (SNR) of the system was analyzed. OCT images obtained by the system were also presented. C1 [Liu, Xuan; Li, Xiaolu; Kang, Jin U.] Johns Hopkins Univ, Dept Elect & Comp Engn, Baltimore, MD 21218 USA. [Kim, Do-Hyun; Ilev, Ilko] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Liu, X (reprint author), Johns Hopkins Univ, Dept Elect & Comp Engn, 3400 N Charles St, Baltimore, MD 21218 USA. EM xliu35@jhu.edu RI Kim, Do-Hyun/C-5311-2009; Kang, Jin/A-3228-2010 NR 9 TC 23 Z9 23 U1 0 U2 1 PU CHINESE OPTICS LETTERS MANUSCRIPT OFFICE PI SHANGHAI PA PO BOX 800-211, SHANGHAI, 201800, PEOPLES R CHINA SN 1671-7694 J9 CHIN OPT LETT JI Chin. Opt. Lett. PD DEC 10 PY 2008 VL 6 IS 12 BP 899 EP 901 DI 10.3788/COL20080612.0899 PG 3 WC Optics SC Optics GA 389UV UT WOS:000262120900009 ER PT J AU Parveen, S Hettiarachchi, KA Bowers, JC Jones, JL Tamplin, ML Mckay, R Beatty, W Brohawn, K DaSilva, LV DePaola, A AF Parveen, Salina Hettiarachchi, Kumidini A. Bowers, John C. Jones, Jessica L. Tamplin, Mark L. McKay, Rusty Beatty, William Brohawn, Kathy DaSilva, Ligia V. DePaola, Angelo TI Seasonal distribution of total and pathogenic Vibrio parahaemolyticus in Chesapeake Bay oysters and waters SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE V. parahaemolyticus; Seasonal distribution; Chesapeake Bay ID REAL-TIME PCR; UNITED-STATES; COASTAL WATERS; VULNIFICUS; BACTERIA; ECOLOGY; ENVIRONMENT; DENSITIES; HEMOLYSIN; ABUNDANCE AB The objectives of this study were to investigate the seasonal distribution of total and pathogenic Vibrio parahaemolyticus in the Chesapeake Bay oysters and waters, and to determine the degree of association between V. parahaemolyticus densities and selected environmental parameters. Oyster and water samples were collected monthly from three sites in Chesapeake Bay, Maryland from November 2004 through October 2005. During collection of samples, water temperature, salinity, turbidity, dissolved oxygen, pH, chlorophyll a, and fecal coliform levels in oysters were also determined. V. parahaemolyticus levels were enumerated by a quantitative direct-plating method followed by DNA colony hybridization; presence/absence was further determined by overnight broth enrichment followed by either standard colony isolation or real-time PCR. The thermolabile hemolysin (tlh) gene and thermostable direct hemolysin (tdh) gene were targeted for detection of total and pathogenic V parahaemolyticus, respectively, for both direct plating and enrichment. The thermostable related hemolysin (trh) gene, which is a presumptive pathogenicity marker, was targeted only for the enrichment approach. By direct plating. colonies producing tlh signals were detected in 79% of oyster samples at densities ranging from 1.5 x 10(1) to 6.0 x 10(2) CFU/g. Pathogenic V. parahaemolyticus (tdh+) was detected in 3% (level was 10 CFU/g) of oyster samples while no V. parahaemolyticus was detected in water samples. By the enrichment approach with standard colony isolation, 67% of oyster and 55% of water samples (n = 33) were positive for total V parahaemolyticus, and all samples were negative for pathogenic V parahaemolyticus. In contrast, enrichment followed by real-time PCR detected tlh, tdh and trh in 100%. 20% and 40% of oyster and 100%, 13% and 40% of water enrichments collected from June to October 2005, respectively. V parahaemolyticus densities in oysters varied seasonally and were found to be positively correlated with water temperature, turbidity, and dissolved oxygen. (C) 2008 Elsevier B.V. All rights reserved. C1 [Parveen, Salina; Hettiarachchi, Kumidini A.; DaSilva, Ligia V.] Univ Maryland Eastern Shore, Food Sci & Technol Ph D Program, Dept Agr Food & Resource Sci, Princess Anne, MD 21853 USA. [Bowers, John C.] US FDA, Div Publ Hlth & Biostat, College Pk, MD 20740 USA. [Jones, Jessica L.] US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. [Tamplin, Mark L.] Univ Tasmania, Food Safety Ctr, Hobart, Tas 7001, Australia. [Beatty, William; Brohawn, Kathy; DePaola, Angelo] Maryland Dept Environm, Baltimore, MD 21230 USA. RP Parveen, S (reprint author), Univ Maryland Eastern Shore, Food Sci & Technol Ph D Program, Dept Agr Food & Resource Sci, 2116 Ctr Food Sci & Technol, Princess Anne, MD 21853 USA. EM sparveen@umes.edu FU U.S. Department of Education; Title III; National Research Initiative of the United States Department of Agriculture, Cooperative State Research, Education and Extension Service [2006-35201-16644] FX We appreciate the assistance of Mathew Whittiker and Jeffry RLIttO in sample processing. We thank Elizabeth Haskins for providing the map, Carolyn Brooks, Jurgen Schwarz and Tom Rippen for helpful suggestions, and Madhumi Mitra for allowing us to use YSI 6600 multiparameter unit. This project was supported by U.S. Department of Education, Title III and the National Research Initiative of the United States Department of Agriculture, Cooperative State Research, Education and Extension Service, grant # 2006-35201-16644. NR 41 TC 70 Z9 77 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD DEC 10 PY 2008 VL 128 IS 2 BP 354 EP 361 DI 10.1016/j.ijfoodmicro.2008.09.019 PG 8 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 383IU UT WOS:000261668100024 PM 18963158 ER PT J AU Gidudu, J Kohl, KS Halperin, S Harnmer, SJ Heath, PT Hennig, R Hoet, B Rothstein, E Schuind, A Varricchioi, F Walop, W AF Gidudu, Jane Kohl, Katrin S. Halperin, Scott Harnmer, Sandra Jo Heath, Paul T. Hennig, Renald Hoet, Bernard Rothstein, Edward Schuind, Anne Varricchioi, Frederick Walop, Wikke CA A Local Reaction near Injection TI A local reaction 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 A local reaction; Adverse event; Immunization; Guidelines; Case definition ID ACELLULAR PERTUSSIS-VACCINE; BCG VACCINATION; CONJUGATE VACCINE; DIPHTHERIA; TETANUS; INFANTS; IMMUNOGENICITY; REACTOGENICITY; METAANALYSIS; STATEMENT AB The need for developing a case definition and guidelines for a local reaction at or near the injection site, methods for the development of the case definition and guidelines as an adverse event following immunization as well as the rationale for selected decisions about the case definition for a local reaction at or near the injection site are explained in the Preamble section. The case definition is structured in 2 levels of diagnostic certainty: level I includes any description of morphological OF physiological change at OF near the injection site that is described or identified by a healthcare provider. Level 2 is any description of morphological or physiological change at or near injection site that is described by any other person. In Guidelines section, the working group recommends to enable meaningful and standardized data collection, analysis, and presentation of information about a local reaction at or near the injection site. However, implementation of all guidelines might not be possible in all settings. The availability of information may vary depending upon resources, geographic region, and whether the Source of information is a prospectively designed clinical trial, a post-marketing surveillance or epidemiologic study, or ail individual report of a local reaction at injection site. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Gidudu, Jane; Kohl, Katrin S.] Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. [Halperin, Scott] Dalhousie Univ, Halifax, NS, Canada. [Harnmer, Sandra Jo] Calif Dept Publ Hlth, Richmond, CA USA. [Heath, Paul T.] St Georges Univ, London, England. [Hennig, Renald] Scratch GbR, Pharmacovigilance Serv, Butzbach, Germany. [Hoet, Bernard] GlaxoSmithKline Biol, Rixensart, Belgium. [Rothstein, Edward] Pennridge Pediat Associates, Sellersville, PA USA. [Schuind, Anne] GlaxoSmithKline Inc, King Of Prussia, PA USA. [Varricchioi, Frederick] US FDA, Rockville, MD 20857 USA. [Walop, Wikke] Publ Hlth Agcy Canada, Ottawa, ON, Canada. RP Gidudu, J (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd NE,Mailstop D-26, Atlanta, GA 30333 USA. EM secretariat@brightoncollaboration.org FU Brighton Collaboration Steering Committee FX The authors are grateful for the support and helpful comments from members of the Brighton Collaboration Steering Committee (S. Michael Marcy, Ulrich Heininger, Miles Braun, Brigitte Keller Stanislawski, Michael Blum, and Odile Leroy), and participants in the Reference Group: Jose-Maria Bayas, Silvia Berardi, Arthur Brown, Gayle Burns, Daniela Burroni, Arani Chatterjee, Christopher da Costa, Iris de Bruijn, Jean-Luc Grenier, Mathew Hohenboken, John Iskander, Lisajackson, Ali Khamesipour, Alasdair King, Andrew Kroger, Dale N Lawrence, David Nalin, Thomas Nisslein, Hanne Nokleby,James M Oleske, Francoise Sillan, Robert Sparks, Lina Tao, Anna Vilella, Beverly Warden, Virginia Wong, Giovanna Zanoni, and juergen Zorn as well as the medical illustrator Patty Chen, the Brighton General Manager April Compingbutra for her help with the working group, and Onnalee Gomez for conducting the literature searches. NR 46 TC 22 Z9 22 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 DEC 9 PY 2008 VL 26 IS 52 BP 6800 EP 6813 DI 10.1016/j.vaccine.2008.10.006 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 386QT UT WOS:000261898400013 PM 18950670 ER PT J AU Chiesa, R Piccardo, P Biasini, E Ghetti, B Harris, DA AF Chiesa, Roberto Piccardo, Pedro Biasini, Emiliano Ghetti, Bernardino Harris, David A. TI Aggregated, Wild-Type Prion Protein Causes Neurological Dysfunction and Synaptic Abnormalities SO JOURNAL OF NEUROSCIENCE LA English DT Article DE prion; transgenic; protein aggregation; synapse; wild-type; neurodegeneration ID TRANSGENIC MICE; INSERTIONAL MUTATION; PRIMARY MYOPATHY; DISEASE; PRP; SCRAPIE; NEURODEGENERATION; ACCUMULATION; DEGENERATION; OLIGOMERS AB The neurotoxic forms of the prion protein (PrP) that cause neurodegeneration in prion diseases remain to be conclusively identified. Considerable evidence points to the importance of noninfectious oligomers of PrP in the pathogenic process. In this study, we describe lines of Tg(WT) transgenic mice that over-express wild-type PrP by either similar to 5-fold or similar to 10-fold (depending on whether the transgene array is, respectively, hemizygous or homozygous). Homozygous but not hemizygous Tg( WT) mice develop a spontaneous neurodegenerative illness characterized clinically by tremor and paresis. Both kinds of mice accumulate large numbers of punctate PrP deposits in the molecular layer of the cerebellum as well as in several other brain regions, and they display abnormally enlarged synaptic terminals accompanied by a dramatic proliferation of membranous structures. The over-expressed PrP in Tg(WT) mice assembles into an insoluble form that is mildly protease-resistant and is recognizable by aggregation-specific antibodies, but that is not infectious in transmission experiments. Together, our results demonstrate that noninfectious aggregates of wild-type PrP are neurotoxic, particularly to synapses, and they suggest common pathogenic mechanisms shared by prion diseases and nontransmissible neurodegenerative disorders associated with protein misfolding. C1 [Chiesa, Roberto; Biasini, Emiliano] Ist Ric Farmacol Mario Negri, Dulbecco Telethon Inst, I-20156 Milan, Italy. [Chiesa, Roberto; Biasini, Emiliano] Ist Ric Farmacol Mario Negri, Dept Neurosci, I-20156 Milan, Italy. [Piccardo, Pedro; Ghetti, Bernardino] Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Indianapolis, IN 46202 USA. [Piccardo, Pedro] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Biasini, Emiliano; Harris, David A.] Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. RP Chiesa, R (reprint author), Ist Ric Farmacol Mario Negri, Dulbecco Telethon Inst, Via G La Masa 19, I-20156 Milan, Italy. EM chiesa@marionegri.it; dharris@wustl.edu RI Biasini, Emiliano/A-3147-2011 OI Biasini, Emiliano/0000-0002-3927-6341 FU National Institutes of Health [NS040975, P30 AG010133]; Telethon-Italy [TCR05006, GFP04007] FX This work was supported by grants from the National Institutes of Health to D. A. H. (NS040975) and B. G. (P30 AG010133); and from Telethon-Italy to R. C. (TCR05006) and E. B. ( Fellowship GFP04007). R. C. is an Assistant Telethon Scientist (Dulbecco Telethon Institute, Fondazione Telethon). The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. We thank Richard Kascsak for 3F4 and 6D11 antibodies, Man-Sun Sy for 8H4 antibody, and Alex Raeber and Bruno Oesch from Prionics ( Zurich, Switzerland) for 15B3 antibody. We are grateful to Assunta Senatore for help with Western blot quantification; Cheryl Adles and Su Deng for mouse colony maintenance and genotyping; and Rose Richardson and Constance Alyea for preparation of histological specimens. NR 52 TC 36 Z9 36 U1 0 U2 2 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD DEC 3 PY 2008 VL 28 IS 49 BP 13258 EP 13267 DI 10.1523/JNEUROSCI.3109-08.2008 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 379DZ UT WOS:000261378100025 PM 19052217 ER PT J AU Gilhooly, CH Das, SK Golden, JK McCrory, MA Rochon, J DeLany, JP Freed, AM Fuss, PJ Dallal, GE Saltzman, E Roberts, SB AF Gilhooly, Cheryl H. Das, Sai Krupa Golden, Julie K. McCrory, Megan A. Rochon, James DeLany, James P. Freed, Alicia M. Fuss, Paul J. Dallal, Gerard E. Saltzman, Edward Roberts, Susan B. TI Use of cereal fiber to facilitate adherence to a human caloric restriction program SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE Caloric restriction; dietary fiber; dietary satisfaction; weight loss ID ENERGY-EXPENDITURE; DIETARY FIBER; BODY-COMPOSITION; SERUM-LIPIDS; WHEAT FIBER; WEIGHT; WOMEN; MEN; SUPPLEMENTATION; SATIETY AB Background and aims: Caloric restriction (CR) attenuates biological aging in animal models but there is little information on the feasibility and efficacy of CR regimens in humans. We examined the effects of consuming an insoluble cereal fiber supplement on ability to sustain CR over 1 year in healthy overweight adults. Methods: In 34 healthy overweight women and men (BMI 25-30 kg/m(2), age 20-42 yr), a 30% CR regimen meeting national recommendations for dietary fiber was provided for 24 weeks, and for an additional 24 weeks subjects were counseled to prepare the same regimen at home. During 5-10 weeks of CR, subjects were randomized to consume an extra 20 g/day of dietary fiber from a high fiber cereal (+F) or to not consume additional fiber (F). After this time, all subjects were encouraged to consume the extra fiber. Outcomes included adherence to the provided and self-prepared CR regimens (energy intake determined using doubly labeled water), changes in body weight, and self-reported satisfaction with the amount of consumed food. Results: During 5-10 weeks of CR when all food was provided, both +F and -F groups were highly adherent to the CR regimen and there was no significant difference between groups in energy intake (p=0.51), weight change (p=0.96), or satisfaction with amount of provided food (p=0.08). During self-prepared CR from 25 to 48 weeks, mean adherence was lower than during the food-provided phase and there was a significant association between fiber intake and % CR (r=0.69, p<0.001), decreased BMI (r=0.38, p=0.04) and satisfaction with the amount of consumed food (r=0.59, p=0.002). Conclusions: A high fiber cereal intake may facilitate CR in humans self-selecting their own food; longer-term intervention studies are needed to confirm these findings. C1 [Roberts, Susan B.] Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr, Energy Metab Lab, Boston, MA 02111 USA. [Golden, Julie K.] US FDA, Silver Spring, MD USA. [McCrory, Megan A.] Purdue Univ, Dept Foods & Nutr, W Lafayette, IN 47907 USA. [Rochon, James] Duke Clin Res Inst, Durham, NC USA. [DeLany, James P.] Univ Pittsburgh, Coll Med, Pittsburgh, PA USA. RP Roberts, SB (reprint author), Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr, Energy Metab Lab, Room 1312,711 Washington St, Boston, MA 02111 USA. EM susan.roberts@tufts.edu FU National Institutes of Health [U01-AG20480]; U.S. Department of Agriculture [58-1950-4-401]; Boston Obesity Nutrition Research Center [H15001] FX Supported by the National Institutes of Health grant U01-AG20480, the U.S. Department of Agriculture, under agreement No. 58-1950-4-401, and Boston Obesity Nutrition Research Center H15001. Any opinions, findings, conclusions, or recommendations expressed in this publication are those of the authors adn do not necessarily reflect the view of the U.S. Department of Agriculture or the U.S. Food and Drug Administration. NR 32 TC 6 Z9 6 U1 1 U2 4 PU EDITRICE KURTIS S R L PI MILAN PA VIA LUIGI ZOJA 30, 20153 MILAN, ITALY SN 1594-0667 J9 AGING CLIN EXP RES JI Aging Clin. Exp. Res. PD DEC PY 2008 VL 20 IS 6 BP 513 EP 520 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 404BW UT WOS:000263126700005 PM 19179834 ER PT J AU Hof, I Arbab-Zadeh, A Dong, J Scherr, D Chilukuri, K Calkins, H AF Hof, Irene Arbab-Zadeh, Armin Dong, Jun Scherr, Daniel Chilukuri, Karuna Calkins, Hugh TI Validation of a Simplified Method to Determine Left Atrial Volume by Computed Tomography in Patients With Atrial Fibrillation SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID CATHETER ABLATION; SIZE; ANATOMY AB The success of catheter ablation of atrial fibrillation (AF) is highly dependent on a preprocedural assessment of the size and shape of the left atrium. The most precise method to determine left atrial (LA) volume using computed tomography requires manually tracing the LA area of each cross-sectional image. This is a labor-intensive and time-consuming technique. The purpose of this study was to compare LA volume derived using the "gold-standard" multiple-slice technique with LA volume estimated using 3 orthogonal LA dimensions in patients with AF. The patient population was composed of 100 patients referred for catheter ablation of AF (87 men, mean age 57 +/- 12 years). AF was paroxysmal in 49 patients and persistent in 51. Each patient underwent computed tomography before catheter ablation, and LA volume was measured using the 2 methods. The mean LA volume measured using the multiple-slice technique was 1.36 +/- 46 ml. According to the simpler estimation approach, the mean LA volume was 112 +/- 41 ml. A close correlation was noted between atrial volumes determined using the 2 methods (r = 0.91, p < 0.001). There was a mean underestimation of LA volume by the estimation technique of 17 +/- 13%. In conclusion, the results of this study reveal that LA volume determined using an estimation approach correlates closely with true LA volume as determined using the gold-standard multiple-slice approach. This estimation approach underestimates true LA volume by approximately 20%. (c) 2008 Elsevier Inc. All rights reserved. (Am J Cardiol 2008;102:1567-1570) C1 [Arbab-Zadeh, Armin; Dong, Jun; Scherr, Daniel; Chilukuri, Karuna; Calkins, Hugh] Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. [Hof, Irene] Univ Med Ctr, Div Heart & Lungs, Dept Cardiol, Utrecht, Netherlands. [Dong, Jun] US FDA, Div Cardiovasc Devices, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Scherr, Daniel] Med Univ Graz, Div Cardiol, Dept Med, Graz, Austria. RP Calkins, H (reprint author), Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA. EM hcalkins@jhmi.edu NR 12 TC 15 Z9 16 U1 0 U2 0 PU EXCERPTA MEDICA INC-ELSEVIER SCIENCE INC PI BRIDGEWATER PA 685 ROUTE 202-206 STE 3, BRIDGEWATER, NJ 08807 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD DEC 1 PY 2008 VL 102 IS 11 BP 1567 EP 1570 DI 10.1016/j.amjcard.2008.07.048 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 382DQ UT WOS:000261585700027 PM 19026316 ER PT J AU Nagarkatti, R Jani, D Beatty, W Angel, R Slebodnick, C Andersen, J Kumar, S Rathore, D AF Nagarkatti, Rana Jani, Dewal Beatty, Wandy Angel, Ross Slebodnick, Carla Andersen, John Kumar, Sanjai Rathore, Dharmendar TI HDP- A NOVEL HEME DETOXIFICATION PROTEIN IN THE MALARIA PARASITE SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Nagarkatti, Rana; Jani, Dewal; Rathore, Dharmendar] Virginia Bioinformat Inst, Blacksburg, VA USA. [Beatty, Wandy] Washington Univ, Sch Med, St Louis, MO USA. [Beatty, Wandy] Virginia Polytech Inst & State Univ, Blacksburg, VA 24061 USA. [Andersen, John] NIH, Lab Malaria & Vector Res, Rockville, MD USA. [Kumar, Sanjai] US FDA, Bethesda, MD 20014 USA. RI Angel, Ross/K-9924-2015 OI Angel, Ross/0000-0003-0861-398X NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2008 VL 79 IS 6 MA 811 BP 239 EP 240 PG 2 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601176 ER PT J AU Peters, NC Egen, JG Secundino, N Debrabant, A Kimblin, N Kamhawi, S Lawyer, P Germain, RN Sacks, D AF Peters, Nathan C. Egen, Jackson G. Secundino, Naglia Debrabant, Alain Kimblin, Nicola Kamhawi, Shaden Lawyer, Phillip Germain, Ronald N. Sacks, David TI NEUTROPHILS ARE THE PREDOMINANT INITIAL HOST CELL FOR LEISHMANIA MAJOR AND ARE ESSENTIAL FOR THE ESTABLISHMENT OF SAND FLY TRANSMITTED INFECTION SO AMERICAN JOURNAL OF TROPICAL MEDICINE AND HYGIENE LA English DT Meeting Abstract CT 57th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 07-11, 2008 CL New Orleans, LA SP Amer Soc Trop Med & Hyg C1 [Peters, Nathan C.; Secundino, Naglia; Kimblin, Nicola; Kamhawi, Shaden; Lawyer, Phillip; Sacks, David] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Egen, Jackson G.; Germain, Ronald N.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Debrabant, Alain] US FDA, Div Emerging & Transfus Transmitted Dis, OBRR, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TROP MED & HYGIENE PI MCLEAN PA 8000 WESTPARK DR, STE 130, MCLEAN, VA 22101 USA SN 0002-9637 J9 AM J TROP MED HYG JI Am. J. Trop. Med. Hyg. PD DEC PY 2008 VL 79 IS 6 MA 1241 BP 365 EP 365 PG 1 WC Public, Environmental & Occupational Health; Tropical Medicine SC Public, Environmental & Occupational Health; Tropical Medicine GA 382ZT UT WOS:000261644601604 ER PT J AU Mohan, K Muller, J Atreya, C AF Mohan, Ketha V. Muller, Jacqueline Atreya, Chintamani D. TI Defective rotavirus particle assembly in lovastatin-treated MA104 cells SO ARCHIVES OF VIROLOGY LA English DT Article ID HUMAN VACCINE; VIRUS; CHOLESTEROL; PROTEIN; INFECTION; PATHWAY; STRAIN; IDENTIFICATION; REPLICATION; MUTATIONS AB Rotavirus is a non-enveloped virus that depends on cellular lipids for cell entry and associates with lipid rafts during assembly. However, the effects of cellular lipids on rotavirus assembly are still not fully understood. The present study analyzes the effects of lovastatin, an inhibitor of cholesterol biosynthesis, during rotavirus infection in MA104 cells with regard to viral growth and particle assembly. Following viral infection, a 2-log relative reduction of viral titers was observed in drug-treated cells, while viral mRNA levels in infected cells remained unaltered in both groups. Furthermore, the levels of some viral proteins in drug-treated cells were elevated. The observed discordance between the viral RNA and protein levels and the decrease in infectivity titers of viral progeny in the drug-treated cells suggested that the drug affects viral assembly, the viral proteins not being properly incorporated into virions. Transmission electron microscopic (TEM) analysis revealed that in drug-treated cells there was an increase in "empty-looking" rotavirus particles devoid of an electron-dense core as compared to the normal, electron-dense particles seen in untreated infected cells. The present study thus provides visual evidence of defective rotavirus particle assembly as a result of cholesterol depletion. C1 [Muller, Jacqueline] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Vector Borne Viral Dis, Bethesda, MD 20892 USA. [Mohan, Ketha V.; Atreya, Chintamani D.] US FDA, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. RP Mohan, K (reprint author), US FDA, CBER, Bldg 29A,Room 2C-15,NIH Campus,8800 Rockville Pik, Bethesda, MD 20892 USA. EM krishna.ketha@fda.hhs.gov NR 36 TC 13 Z9 13 U1 0 U2 1 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 DEC PY 2008 VL 153 IS 12 BP 2283 EP 2290 DI 10.1007/s00705-008-0261-0 PG 8 WC Virology SC Virology GA 391KJ UT WOS:000262231900012 PM 19030953 ER PT J AU Tami, C Puig, M Reepmeyer, JC Ye, HP D'Avignon, DA Buhse, L Verthelyi, D AF Tami, Cecilia Puig, Montserrat Reepmeyer, John C. Ye, Hongping D'Avignon, D. Andre Buhse, Lucinda Verthelyi, Daniela TI Inhibition of Taq polymerase as a method for screening heparin for oversulfated contaminants SO BIOMATERIALS LA English DT Article DE Heparin; Oversulfated chondroitin sulfate; Glycosaminoglycan; Taq polymerase; PCR; Safety ID CHONDROITIN SULFATE; THROMBOCYTOPENIA; AMPLIFICATION; RNA; PCR AB Heparin and low molecular heparins are extensively used in the treatment of a wide range of diseases in addition to their classic anticoagulant activity and can be found coating medical devices Such as catheters, stents and filters. Early in 2008, a sharp increase in heparin-associated severe adverse events, including over 80 deaths, was linked to the presence of a contaminant identified as hypersulfated chondroitin sulfate (OS-CS). OS-CS is one of several oversulfated glycosaminoglycans (GAGs) of different origins that can potentially Cause similar clinical problems underscoring the need to develop robust screening methods for contaminants in existing and future lots of heparin. This study demonstrates that oversulfated GAGs block the activity of Taq polymerase used for real time PCR. Based on this finding we developed a simple, rapid, sensitive and high throughput screening method to detect and quantify oversulfated chondroitin sulfate (OS-CS) and other potential oversulfated contaminants in commercial lots of heparin. This method requires less than 100 miliUnits (mU) of heparin as starting material, therefore avoiding the need to lyophilize and concentrate samples, and has a limit of detection of < 1 ng for all oversulfated GAGs tested. Published by Elsevier Ltd. C1 [Tami, Cecilia; Puig, Montserrat; Verthelyi, Daniela] US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Lab Immunol,Div Therapeut Prod, Bethesda, MD 20892 USA. [Reepmeyer, John C.; Ye, Hongping; Buhse, Lucinda] US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Anal, Bethesda, MD 20892 USA. [D'Avignon, D. Andre] Washington Univ, Dept Chem, St Louis, MO 63130 USA. RP Verthelyi, D (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biotechnol Prod, Lab Immunol,Div Therapeut Prod, Bldg 29A,Room 3B19,8800 Rockville Pike, Bethesda, MD 20892 USA. EM daniela.verthelyi@fda.hhs.gov NR 18 TC 31 Z9 33 U1 1 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0142-9612 J9 BIOMATERIALS JI Biomaterials PD DEC PY 2008 VL 29 IS 36 BP 4808 EP 4814 DI 10.1016/j.biomaterials.2008.08.024 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 372YV UT WOS:000260939100011 PM 18801571 ER PT J AU Tang, R Muller, HG AF Tang, Rong Mueller, Hans-Georg TI Pairwise curve synchronization for functional data SO BIOMETRIKA LA English DT Article ID MAXIMUM-LIKELIHOOD-ESTIMATION; REGRESSION; SAMPLE; ALIGNMENT AB Data collected by scientists are increasingly in the form of trajectories or curves. Often these can be viewed as realizations of a composite process driven by both amplitude and time variation. We consider the situation in which functional variation is dominated by time variation, and develop a curve-synchronization method that uses every trajectory in the sample as a reference to obtain pairwise warping functions in the first step. These initial pairwise warping functions are then used to create improved estimators of the underlying individual warping functions in the second step. A truncated averaging process is used to obtain robust estimation of individual warping functions. The method compares well with other available time-synchronization approaches and is illustrated with Berkeley growth data and gene expression data for multiple sclerosis. C1 [Tang, Rong] US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20850 USA. [Mueller, Hans-Georg] Univ Calif Davis, Dept Stat, Davis, CA 95616 USA. RP Tang, R (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20850 USA. EM rong.tang@fda.hhs.gov; mueller@wald.ucdavis.edu FU U.S. National Science Foundation FX Thanks are due to Professor D.M. Titterington, the associate editor and two anonymous referees for helpful remarks. This research was supported in part by the U.S. National Science Foundation. NR 27 TC 29 Z9 30 U1 1 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0006-3444 J9 BIOMETRIKA JI Biometrika PD DEC PY 2008 VL 95 IS 4 BP 875 EP 889 DI 10.1093/biomet/asn047 PG 15 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 377VN UT WOS:000261279900007 ER PT J AU Sapsford, KE Sun, S Francis, J Sharma, S Kostov, Y Rasooly, A AF Sapsford, Kim E. Sun, Steven Francis, Jesse Sharma, Shashi Kostov, Yordan Rasooly, Avraham TI A fluorescence detection platform using spatial electroluminescent excitation for measuring botulinum neurotoxin A activity SO BIOSENSORS & BIOELECTRONICS LA English DT Article DE Electroluminescent excitation; CCD; Fluorescence; Forster resonance energy transfer (FRET); Botulinum neurotoxin A; Biodetection; Point of care ID LINKED-IMMUNOSORBENT-ASSAY; POLYMERASE-CHAIN-REACTION; ARRAY BIOSENSOR; NEUROTRANSMITTER RELEASE; PROTEOLYTIC CLEAVAGE; SENSITIVE DETECTION; MASS-SPECTROMETRY; RAPID DETECTION; B NEUROTOXIN; SENSOR ARRAY AB Current biodetection illumination technologies (laser. LED, tungsten lamp, etc.) are based on spot illumination with additional optics required when spatial excitation is required. Herein we describe a new approach of spatial illumination based on electroluminescence (EL) semiconductor strips available in several wavelengths, greatly simplifying the biosensor design by eliminating the need for additional optics. This work combines EL excitation with charge-coupled device (CCD) based detection (EL-CCD detector) of fluorescence for developing a simple portable detector for botulinum neurotoxin A (BoTN-A) activity analysis. A Forster Resonance Energy Transfer (FRET) activity assay for BoTN-A was used to both characterize and optimize the EL-CCD detector. The system consists of two modules: (1) the detection module which houses the CCD camera and emission filters, and (2) the excitation and sample module, containing the EL strip, the excitation filter and the 9-well sample chip. The FRET activity assay used in this study utilized a FITC/DABCYL-SNAP-25 peptide substrate in which cleavage of the substrate by BoTN-A, or its light chain derivative (LcA), produced an increase in fluorescence emission. EL-CCD detector measured limits of detection (LODs) were similar to those measured using a standard fluorescent plate reader with valves between 0.625 and 1.25 nM (31-62 ng/ml) for LcA and 0.313 nM (45 ng/ml) for the full toxin, BoTN-A. As far as the authors are aware this is the first demonstration of phosphor-based EL strips being used for the spatial illumination/excitation of a surface, coupled with CCD for point of care detection. Published by Elsevier B.V. C1 [Sapsford, Kim E.; Sun, Steven; Francis, Jesse; Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn Labs, Silver Spring, MD 20993 USA. [Sun, Steven; Francis, Jesse; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Sharma, Shashi] US FDA, Div Microbiol, Off Regulatory Sci, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Rasooly, Avraham] NCI, Rockville, MD 20892 USA. RP Rasooly, A (reprint author), NCI, NIH, 6130 Execut Blvd,EPN Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov FU Office of Public Health emergency Preparedness (OPHEP) [IAG 224-05-655]; FDA [HHSF223200610765P] FX We would like to thank Dr. Nikolay Sergeev and Mr. Sean Wilson for their technical assistance. This work was supported in part by the Office of Public Health emergency Preparedness (OPHEP) IAG 224-05-655 (to A. Rasooly) and by FDA contract HHSF223200610765P (to Dr. Yordan Kostov). NR 52 TC 31 Z9 31 U1 1 U2 20 PU ELSEVIER ADVANCED TECHNOLOGY PI OXFORD PA OXFORD FULFILLMENT CENTRE THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-5663 J9 BIOSENS BIOELECTRON JI Biosens. Bioelectron. PD DEC 1 PY 2008 VL 24 IS 4 BP 618 EP 625 DI 10.1016/j.bios.2008.06.018 PG 8 WC Biophysics; Biotechnology & Applied Microbiology; Chemistry, Analytical; Electrochemistry; Nanoscience & Nanotechnology SC Biophysics; Biotechnology & Applied Microbiology; Chemistry; Electrochemistry; Science & Technology - Other Topics GA 377PB UT WOS:000261262000018 PM 18644709 ER PT J AU Paz, MM Ladwa, S Champeil, E Liu, Y Rockwell, S Boamah, EK Bargonetti, J Callahan, J Roach, J Tomasz, M AF Paz, Manuel M. Ladwa, Sweta Champeil, Elise Liu, Yanfeng Rockwell, Sara Boamah, Ernest K. Bargonetti, Jill Callahan, John Roach, John Tomasz, Maria TI Mapping DNA Adducts of Mitomycin C and Decarbamoyl Mitomycin C in Cell Lines Using Liquid Chromatography/Electrospray Tandem Mass Spectrometry SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID INTERSTRAND CROSS-LINKS; MAMMARY-TUMOR CELLS; IN-VIVO; METABOLITE 2,7-DIAMINOMITOSENE; HAMSTER-CELLS; CANCER CELLS; REPAIR; EMT6; REMOVAL; CROSSLINKING AB The antitumor antibiotic and cancer chemotherapeutic agent mitomycin C (MC) alkylates and cross-links DNA, forming six major MC-deoxyguanosine adducts of known structures in vitro and in vivo. Two of these adducts are derived from 2,7-diaminomitosene (2,7-DAM), a nontoxic reductive metabolite of MC formed in cells in situ. Several methods have been used for the analysis of MC-DNA adducts in the past; however, a need exists for a safer, more comprehensive and direct assay of the six-adduct complex. Development of an assay, based on mass spectrometry, is described. DNA from EMT6 mouse mammary tumor cells, Fanconi Anemia-A fibroblasts, normal human fibroblasts, and MCF-7 human breast cancer cells was isolated after MC or 10-decarbamoyl mitomycin C (DMC) treatment of the cells, digested to nucleosides, and submitted to liquid chromatography electrospray-tandem mass spectrometry. Two fragments of each parent ion were monitored ("multiple reaction monitoring"). Identification and quantitative analysis were based on a standard mixture of six adducts, the preparation of which is described here in detail. The lower limit of detection of adducts is estimated as 0.25 pmol. Three initial applications of this method are reported as follows: (i) differential kinetics of adduct repair in EMT6 cells, (ii) analysis of adducts in MC- or DMC-treated Fanconi Anemia cells, and (iii) comparison of the adducts generated by treatment of MCF-7 breast cancer cells with MC and DMC. Notable results are the following: Repair removal of the DNA interstrand cross-link and of the two adducts of 2,7-DAM is relatively slow; both MC and DMC generate DNA interstrand cross-links in human fibroblasts, Fanconi Anemia-A fibroblasts, and MCF-7 cells as well as EMT6 cells; and DMC shows a stereochemical preference of linkage to the guanine-2-amino group opposite from that of MC. C1 [Paz, Manuel M.; Ladwa, Sweta; Tomasz, Maria] CUNY, Hunter Coll, Dept Chem, New York, NY 10021 USA. [Boamah, Ernest K.; Bargonetti, Jill] CUNY, Hunter Coll, Dept Biol Sci, New York, NY 10021 USA. [Champeil, Elise] CUNY, John Jay Coll, Dept Sci, New York, NY 10019 USA. [Callahan, John; Roach, John] US FDA, Ctr Food Safety, College Pk, MD 20740 USA. [Liu, Yanfeng; Rockwell, Sara] Yale Univ, Sch Med, Dept Therapeut Radiol, New Haven, CT 06520 USA. RP Tomasz, M (reprint author), CUNY, Hunter Coll, Dept Chem, New York, NY 10021 USA. EM mtomasz@hunter.cuny.edu RI Rockwell, Sara/B-8458-2009; Paz, Manuel/F-2732-2011 OI Paz, Manuel/0000-0002-5734-1266 FU National Institutes of Health (NIH) [CA28681, S06 GM60654, CA 129186]; National Center for Research Resources [RR03037]; Minority Biomedical Research Initiative in Science Enhancement [GM60665]; PSC-CUNY Research Award [60035-3738] FX This research was supported by National Institutes of Health (NIH) Grants CA28681 (M.T.), S06 GM60654 (J.B.), CA28681, and CA 129186 (S.R.); a National Center for Research Resources, Award RR03037, to support the research infrastructure at Hunter College; and a Minority Biomedical Research Initiative in Science Enhancement, Grant GM60665 (E.B.). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or NCRR. This work was also supported by a PSC-CUNY Research Award 60035-3738 (E.C.). NR 44 TC 15 Z9 15 U1 0 U2 6 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 DEC PY 2008 VL 21 IS 12 BP 2370 EP 2378 DI 10.1021/tx8002615 PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 384HU UT WOS:000261736700017 PM 19053323 ER PT J AU Xia, QS Guo, L Dial, S Li, Q Chan, PC Fu, PP AF Xia, Qingsu Guo, Lei Dial, Stacey Li, Quan Chan, Po-Chuen Fu, Peter P. TI Analysis of Gene Expression Changes of Drug Metabolizing Enzymes in the Livers of F344 Rats Following Oral Treatment with Kava Extract SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 236th National Meeting of the Division of Chemical Toxicology of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc, Div Chem Toxicol C1 [Xia, Qingsu; Fu, Peter P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Guo, Lei; Dial, Stacey] Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Li, Quan] Microarray Core Facil UTSW Med Ctr, Dallas, TX 75390 USA. [Chan, Po-Chuen] Natl Inst Environm Hlth Sci Res, Res Triangle Pk, NC 27709 USA. EM qingsu.xia@fda.hhs.gov; lei.guo@fda.hhs.gov; stacey.dial@fda.hhs.gov; Quan.Li@UTSouthwestem.edu; chanp@niehs.nih.gov; peter.fu@fdahhs.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 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD DEC PY 2008 VL 21 IS 12 MA 41 BP 2440 EP 2440 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 384HU UT WOS:000261736700062 ER PT J AU Marques, MM Martins, I Antunes, AMM Santos, PP da Costa, GG Beland, FA AF Marques, M. Matilde Martins, Ines Antunes, Alexandra M. M. Santos, Pedro P. da Costa, Goncalo Gamboa Beland, Frederick A. TI Synthesis and Characterization of Amino Acid Adducts from the HIV Reverse Transcriptase Inhibitor Nevirapine SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Meeting Abstract CT 236th National Meeting of the American-Chemical-Society CY AUG 17-21, 2008 CL Philadelphia, PA SP Amer Chem Soc C1 [Marques, M. Matilde; Santos, Pedro P.] Univ Tecn Lisboa, Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal. [Martins, Ines; Antunes, Alexandra M. M.] Univ Nova Lisboa, Dept Quim, Fac Ciencias & Tecnol, P-2829516 Caparica, Portugal. [da Costa, Goncalo Gamboa; Beland, Frederick A.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM matilde.marques@ist.utl.pt; amma@dq.fct.unl.pt; pepesantos@ist.utl.pt; goncalo.gamboa@fda.hhs.gov; frederick.beland@.fda.hhs.gov RI Marques, M. Matilde/E-2535-2012; PTMS, RNEM/C-1589-2014; Antunes, Alexandra/B-7871-2009 OI Marques, M. Matilde/0000-0002-7526-4962; Antunes, Alexandra/0000-0003-1827-7369 NR 0 TC 1 Z9 1 U1 0 U2 4 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 DEC PY 2008 VL 21 IS 12 MA 105 BP 2453 EP 2453 PG 1 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 384HU UT WOS:000261736700122 ER PT J AU Dayan, GH Rubin, S AF Dayan, Gustavo H. Rubin, Steven TI Mumps Outbreaks in Vaccinated Populations: Are Available Mumps Vaccines Effective Enough to Prevent Outbreaks? SO CLINICAL INFECTIOUS DISEASES LA English DT Review ID LONG-TERM PERSISTENCE; COMBINED LIVE MEASLES; RUBELLA VACCINE; VARICELLA VACCINE; HEALTHY-CHILDREN; YOUNG-CHILDREN; VIRUS STRAINS; UNITED-STATES; JERYL-LYNN; FOLLOW-UP AB Increased reports of mumps in vaccinated populations prompted a review of the performance of mumps vaccines. The effectiveness of prior vaccination with 1 dose of vaccine ranged from 72.8% to 91% for the Jeryl Lynn strain, from 54.4% to 93% for the Urabe strain, and from 0% to 33% for the Rubini strain. Vaccine effectiveness after 2 doses of mumps vaccine was reported in 3 outbreaks and ranged from 91% to 94.6%. There was evidence of waning immunity, which is a likely factor in mumps outbreaks, aggravated by possible antigenic differences between the vaccine strain and outbreak strains. Inadequate vaccine coverage or use of the Rubini vaccine strain accounted for the majority of outbreaks reviewed; however, some outbreaks could not be prevented, despite high vaccination coverage with 2 doses of the Jeryl Lynn vaccine strain. Our findings indicate the need for more-effective mumps vaccines and/or for review of current vaccination policies to prevent future outbreaks. C1 [Rubin, Steven] US FDA, Ctr Biol Evaluat & Res, Div Virol Prod, Bethesda, MD 20892 USA. [Dayan, Gustavo H.] Sanofi Pasteur, Clin Dept, Swiftwater, PA USA. RP Rubin, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Virol Prod, Bldg 29A,Rm 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Steven.Rubin@fda.hhs.gov FU Oak Ridge Institute for Science and Education; US Department of Energy; US Food and Drug Administration FX National Vaccine Program Office administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the US Department of Energy and the US Food and Drug Administration. NR 107 TC 69 Z9 76 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 EI 1537-6591 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD DEC 1 PY 2008 VL 47 IS 11 BP 1458 EP 1467 DI 10.1086/591196 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 369UT UT WOS:000260720100015 PM 18959494 ER PT J AU Higgins, K Singer, M Valappil, T Nambiar, S Lin, D Cox, E AF Higgins, K. Singer, M. Valappil, T. Nambiar, S. Lin, D. Cox, E. TI Overview of Recent Studies of Community-Acquired Pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Workshop on Issues in the Design and Conduct of Clinical Trials of Antibacterial Drugs in the Treatment of Community-Acquired Pneumonia CY JAN 17-18, 2008 CL Silver Spring, MD SP FDA, Infect Dis Soc Amer ID EQUIVALENCE RANDOMIZED-TRIALS; NONINFERIORITY TRIALS AB All recent studies of antibacterial drugs for the indication of community-acquired pneumonia submitted to the US Food and Drug Administration have been designed as noninferiority studies. We provide a summary of results of 7 recent clinical studies of oral antibacterial drugs for treatment of community-acquired pneumonia. In these 7 studies, the majority of patients enrolled had Pneumonia Patient Outcomes Research Team scores of I or II. The percentage of randomized subjects with pathogens identified at baseline ranged from 47% to 76%, and the percentage of subjects with Streptoccocus pneumoniae isolated at baseline ranged from similar to 6% to 20%. The primary end point in these studies was clinical cure, assessed 7-21 days after completion of therapy. Clinical cure rates were >80% in the intent-to-treat populations and >90% in the per-protocol populations. We also briefly summarize the results from several recently submitted clinical studies of intravenously administered antibacterial drugs for treatment of community-acquired pneumonia, in which we found similar results. C1 [Higgins, K.; Singer, M.; Valappil, T.; Nambiar, S.; Lin, D.; Cox, E.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Higgins, K (reprint author), US FDA, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM karen.higgins@fda.hhs.gov NR 13 TC 7 Z9 7 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 DEC 1 PY 2008 VL 47 SU 3 BP S150 EP S156 DI 10.1086/591397 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 368XI UT WOS:000260655900009 PM 18986282 ER PT J AU Singer, M Nambiar, S Valappil, T Higgins, K Gitterman, S AF Singer, M. Nambiar, S. Valappil, T. Higgins, K. Gitterman, S. TI Historical and Regulatory Perspectives on the Treatment Effect of Antibacterial Drugs for Community-Acquired Pneumonia SO CLINICAL INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Workshop on Issues in the Design and Conduct of Clinical Trials of Antibacterial Drugs in the Treatment of Community-Acquired Pneumonia CY JAN 17-18, 2008 CL Silver Spring, MD SP FDA, Infect Dis Soc Amer ID LOBAR PNEUMONIA; PNEUMOCOCCAL PNEUMONIA; HOSPITALIZED ADULTS; ESPECIAL REFERENCE; SERUM; VACCINATION; INFECTIONS; BACTEREMIA; THERAPY; HORSE AB A noninferiority margin based on the treatment effect of antibacterial drugs is required for noninferiority studies of community-acquired pneumonia. A quantitative estimate of treatment effect is generally determined from placebo-controlled trials, but, since the mid-to-late 1930s, no studies have compared outcomes for patients who received placebo (or no specific therapy) with those for patients who received an antibacterial drug for treatment of community-acquired pneumonia. In this article, early controlled studies, as well as observational data, are reviewed, and the beneficial effect of antibacterial drugs on mortality rates among patients with pneumococcal pneumonia is demonstrated. However, because these data were obtained in the early 20th century, several important factors have changed, including patient populations, the etiological agents of pneumonia, and medical standards of care. Thus, the applicability of these studies to the determination of a noninferiority margin for contemporary trials for community-acquired pneumonia remains in question. C1 [Singer, M.; Nambiar, S.; Valappil, T.; Higgins, K.; Gitterman, S.] US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Antimicrobial Prod, Silver Spring, MD 20993 USA. RP Singer, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Off Antimicrobial Prod, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mary.singer@fda.hhs.gov NR 33 TC 13 Z9 13 U1 1 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 DEC 1 PY 2008 VL 47 SU 3 BP S216 EP S224 DI 10.1086/591407 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 368XI UT WOS:000260655900020 PM 18986293 ER PT J AU Mei, N Guo, L Tseng, J Dial, SL Liao, W Manjanatha, MG AF Mei, Nan Guo, Lei Tseng, Jo Dial, Stacey L. Liao, Wayne Manjanatha, Mugimane G. TI Gene Expression Changes Associated with Xenobiotic Metabolism Pathways in Mice Exposed to Acrylamide SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE acrylamide; gene expression; metabolism pathway ID MAILLARD REACTION; DRINKING-WATER; DNA; GLYCIDAMIDE; RATS; CARCINOGENICITY; ACRYLONITRILE; ONCOGENICITY; MECHANISMS; MICROARRAY AB The discovery of acrylamide (AA) in a variety of fried foods has raised public health concerns. In this study, groups of male mice were administered 500 mg/L AA in drinking water for 3 weeks, and gene expression changes were evaluated in the livers of AA-treated mice within 24 hr of the last treatment. When a two-fold cutoff value and a P-value less than 0.05 were selected, 696 genes (233 up-regulated and 463 down-regulated) were identified as differentially expressed genes in AA-treated mice when compared with the controls. Gene ontology analysis revealed that the principle pathways affected by AA were xenobiotic metabolism by cytochrome P450 (CYPs) and glutathione metabolism, suggesting that drug and/or xenobiotic metabolism is most affected by exposure. The results provide more information about AA metabolism and further insight into the molecular mechanisms involved in AA-induced toxicity. Environ. Mol. Mutagen. 49:741-745, 2008. Published 2008 Wiley-Liss, Inc. C1 [Mei, Nan; Manjanatha, Mugimane G.] Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Guo, Lei; Dial, Stacey L.] Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. [Tseng, Jo; Liao, Wayne] PhalanxBio Inc, Palo Alto, CA USA. RP Mei, N (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM nan.mai@fda.hhs.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 20 TC 15 Z9 15 U1 1 U2 9 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 DEC PY 2008 VL 49 IS 9 BP 741 EP 745 DI 10.1002/em.20429 PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 384EA UT WOS:000261725900009 PM 18800343 ER PT J AU Uhlenhaut, C Sierra-Honigmann, AM Nanda, S Tang, S Krause, PR AF Uhlenhaut, C. Sierra-Honigmann, A. M. Nanda, S. Tang, S. Krause, P. R. TI Universal Virus Detection SO INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES LA English DT Meeting Abstract C1 [Uhlenhaut, C.; Sierra-Honigmann, A. M.; Nanda, S.; Tang, S.; Krause, P. R.] FDA CBER, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1201-9712 J9 INT J INFECT DIS JI Int. J. Infect. Dis. PD DEC PY 2008 VL 12 BP E473 EP E474 DI 10.1016/j.ijid.2008.05.1337 PG 2 WC Infectious Diseases SC Infectious Diseases GA 406II UT WOS:000263287801187 ER PT J AU Li, JX Shefcheck, K Callahan, J Fenselau, C AF Li, Jinxi Shefcheck, Kevin Callahan, John Fenselau, Catherine TI Extension of microwave-accelerated residue-specific acid cleavage to proteins with carbohydrate side chains and disulfide linkages SO INTERNATIONAL JOURNAL OF MASS SPECTROMETRY LA English DT Article DE Chemical proteolysis; Glycoprotein; Disulfide linkages; Heterogeneity ID CHEMICAL CLEAVAGE AB This laboratory has introduced a chemical method for residue-specific protein cleavage and has provided a preliminary assessment of the suitability of microwave-accelerated acid cleavage as a proteomic tool. This report is a continuing assessment of the fate of common protein modifications in microwave-accelerated acid cleavage. We have examined the cleavage of ribonuclease A and the related N-linked glycoprotein ribonuclease B, and the O-linked glycoprotein alpha crystallin A chain, using MALIDI-TOF and LC-ESI-MS to identify the peptide products. RNase A and B each contains four disulfide bonds, and the addition of a reducing reagent, such as dithiothreitol, was found to be required to achieve efficient acidic proteolysis. The linkage of the glycosidic group to the asparagine side chain in ribonuclease B was found not to be cleaved by brief microwave treatment in 12.5% acetic acid. The distribution of the heterogeneous carbohydrate side chain in the glycopeptide products of acid cleavage was compared to that of the glycopeptide products of tryptic digestion. Hydrolysis within the carbohydrate chain itself is minimal under the conditions used. The O-linked side chain on alpha crystalline A was found to be cleaved during acid cleavage of the protein. (c) 2008 Elsevier B.V. All rights reserved. C1 [Li, Jinxi; Fenselau, Catherine] Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. [Shefcheck, Kevin; Callahan, John] US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. RP Fenselau, C (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. EM fenselau@umd.edu FU NIGMS NIH HHS [R01 GM021248-31, R01 GM021248] NR 8 TC 15 Z9 15 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1387-3806 J9 INT J MASS SPECTROM JI Int. J. Mass Spectrom. PD DEC 1 PY 2008 VL 278 IS 2-3 BP 109 EP 113 DI 10.1016/j.ijms.2008.04.030 PG 5 WC Physics, Atomic, Molecular & Chemical; Spectroscopy SC Physics; Spectroscopy GA 378EM UT WOS:000261304000003 PM 19956338 ER PT J AU Rolland, J Badano, A Menegaz, G Wang, YT Itoh, M AF Rolland, Jannick Badano, Aldo Menegaz, Gloria Wang, Yongtian Itoh, Masahide TI Guest Editorial-Special Issue on Medical Display SO JOURNAL OF DISPLAY TECHNOLOGY LA English DT Editorial Material C1 [Rolland, Jannick] Univ Cent Florida, CREOL, Coll Opt & Photon, Orlando, FL 32816 USA. [Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Menegaz, Gloria] Univ Verona, Dept Comp Sci, I-37134 Verona, Italy. [Wang, Yongtian] Ctr Res Optoelect Technol & Informat Syst, Beijing 100081, Peoples R China. [Itoh, Masahide] Univ Tsukuba, Ibaraki 3058573, Japan. RP Rolland, J (reprint author), Univ Cent Florida, CREOL, Coll Opt & Photon, Orlando, FL 32816 USA. RI Menegaz, Gloria/D-3365-2013; OI Menegaz, Gloria/0000-0002-6889-3461; badano, aldo/0000-0003-3712-6670 NR 0 TC 2 Z9 2 U1 0 U2 6 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1551-319X J9 J DISP TECHNOL JI J. Disp. Technol. PD DEC PY 2008 VL 4 IS 4 BP 354 EP 355 DI 10.1109/JDT.2008.2006874 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 376YR UT WOS:000261219400002 ER PT J AU Saha, A Liang, HY Vogel, R Badano, A AF Saha, Anindita Liang, Hongye Vogel, Rebecca Badano, Aldo TI Assessment of Mobile Technologies for Displaying Medical Images SO JOURNAL OF DISPLAY TECHNOLOGY LA English DT Article DE Displays; medical display; radiology; mobile display; portable display ID LIQUID-CRYSTAL DISPLAYS AB We compared the characteristics of state-of-the-art mobile display systems based on reflective and transmissive liquid crystal displays (LCDs) and an organic light-emitting display with respect to physical characterization metrics and observer studies. Physical performance factors provided information on the differences among display technologies. Observer studies resulted in different system ranking between the task-based performance and user-preference approaches. The results of the physical characterization and preference study showed that the reflective LCD ranked lower. We also found that ambient illumination played a lesser role than previously seen in large-format workstation displays. The methodology developed in this study provides an initial insight into the comparison of alternative technologies for display of diagnostic images in small portable devices. C1 [Saha, Anindita; Liang, Hongye; Vogel, Rebecca; Badano, Aldo] US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math,CDRH NIBIB Lab Assessment, Silver Spring, MD 20993 USA. RP Saha, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Imaging & Appl Math,CDRH NIBIB Lab Assessment, Silver Spring, MD 20993 USA. EM aldo.badano@fda.hhs.gov OI badano, aldo/0000-0003-3712-6670 NR 14 TC 2 Z9 2 U1 4 U2 9 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 1551-319X J9 J DISP TECHNOL JI J. Disp. Technol. PD DEC PY 2008 VL 4 IS 4 BP 415 EP 423 DI 10.1109/JDT.2008.924157 PG 9 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA 376YR UT WOS:000261219400010 ER PT J AU Cheng, CM Lin, W Van, KT Phan, L Tran, NN Farmer, D AF Cheng, Chorng-Ming Lin, Wen Van, Khanh Thien Phan, Lieuchi Tran, Nelly N. Farmer, Doris TI Rapid Detection of Salmonella in Foods Using Real-Time PCR SO JOURNAL OF FOOD PROTECTION LA English DT Article ID POLYMERASE-CHAIN-REACTION; REACTION ASSAY; GENE SEQUENCE; HILA GENE; AMPLIFICATION; TYPHIMURIUM; SAMPLES; INVA; PATHOGENS; PRODUCTS AB Conventional methods for detection of Salmonella serovars; in foods are generally time-consuming and labor intensive. A real-time PCR method has been developed with custom designed primers and a TaqMan probe to detect the presence of a 262-bp fragment of the Salmonella-specific invA gene. The method has been tested with a total of 384 field-isolated Salmonella serovars and non-Salmonella stock strains, as well as 420 U.S. Food and Drug Administration food samples, comprising a variety of food matrices. The method was highly specific in detecting Salmonella in spiked chili powder and shrimp samples, with a sensitivity of 0.04 CFU`/g. In addition, the method is faster, more accurate, and less costly than the traditional U.S. Food and Drug Administration's Bacteriological Analytical Manual cell-culturing and the AOAC International-approved VIDAS methods to detect Salmonella in foods. C1 [Cheng, Chorng-Ming; Lin, Wen; Van, Khanh Thien; Phan, Lieuchi; Tran, Nelly N.] US FDA, Pacific Reg Lab SW, Irvine, CA 92612 USA. [Farmer, Doris] US FDA, Denver Dist Lab, Denver, CO 80225 USA. RP Cheng, CM (reprint author), US FDA, Pacific Reg Lab SW, Irvine, CA 92612 USA. EM chorng-ming.cheng@fda.hhs.gov NR 33 TC 50 Z9 51 U1 5 U2 15 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 DEC PY 2008 VL 71 IS 12 BP 2436 EP 2441 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 380NR UT WOS:000261472900009 PM 19256088 ER PT J AU Hamad, ML Gupta, A Shah, RB Lyon, RC Sayeed, VA Khan, MA AF Hamad, Mazen L. Gupta, Abhay Shah, Rakhi B. Lyon, Robbie C. Sayeed, Vilayat A. Khan, Mansoor A. TI Functionality of Magnesium Stearate Derived from Bovine and Vegetable Sources: Dry Granulated Tablets SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE functionality; lubricant efficiency; physical mixture; slugging; characterization ID LUBRICANT PROPERTIES; DISSOLUTION RATE; COMPRESSION; FORMS AB Magnesium stearate is a functional excipient used to ensure efficient ejection of tablets. This study compares the functionality of a vegetable and bovine grade of magnesium stearate. Tablets were prepared by direct compression and dry granulation of a model formulation. Physical and chemical tests were performed on bulk powders, granule intermediates, and finished tablets to provide a comprehensive comparison of the two grades of magnesium stearates. Raw material characterization of the two grades showed no difference in particle size, surface area, true density, and total moisture content. However, significant differences in fatty acid composition, surface tension, and zeta potential were detected. Tablet ejection force for the physical mixture formulations was variable, showing similar ejection force for the two grades of magnesium stearate at some concentrations and different ejection forces at other concentrations. The dry granulated formulation containing vegetable-based magnesium stearate showed a lower ejection force than the formulation containing bovine-based magnesium stearate. There was no difference between the dissolution profiles of the tablets containing the two grades of magnesium stearate prepared by both methods. The results indicated that magnesium stearate interchangeability with respect to lubricant efficiency depends upon the level in which it is used and the manufacturing method. (c) 2008 Wiley-Liss, Inc. and the American Pharmacists Association J Pharm Sci 97:5328-5340, 2008 C1 [Hamad, Mazen L.; Gupta, Abhay; Shah, Rakhi B.; Lyon, Robbie C.; Khan, Mansoor A.] US FDA, Off Pharmaceut Sci, Div Product Qual Res, Silver Spring, MD 20993 USA. [Sayeed, Vilayat A.] US FDA, Off Gener Drugs, Div Chem 3, Rockville, MD 20855 USA. RP Khan, MA (reprint author), US FDA, Off Pharmaceut Sci, Div Product Qual Res, Life Sci Bldg 64,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM mansoor.khan@fda.hhs.gov NR 19 TC 7 Z9 7 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 DEC PY 2008 VL 97 IS 12 BP 5328 EP 5340 DI 10.1002/jps.21381 PG 13 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 378IA UT WOS:000261313200025 PM 18351597 ER PT J AU Bennett, RW AF Bennett, Reginald W. TI AN ANTIBODY MODIFIED AUTOMATED ENZYME-LINKED IMMUNOSORBENT ASSAY-BASED METHOD FOR DETECTION OF STAPHYLOCOCCAL ENTEROTOXIN SO JOURNAL OF RAPID METHODS AND AUTOMATION IN MICROBIOLOGY LA English DT Article AB Studies were conducted with an automated enzyme-linked immunosorbent assay (ELISA)-based method (Vidas, Staph enterotoxin-II [SET-II]), exhibiting an antibody capture that had undergone modification by removal of the F(c) fragment on the antibody. Raw liquid or shell eggs containing a nontoxin component with an attraction to the staphylococcal antienterotoxins were studied. Prior to ELISA testing, the eggs were homogenized and extracts collected by centrifugation. Studies showed that regardless of the ELISA-based method used that utilized the unmodified antibodies with both the F(ab)(1) + F(c) fragments intact, positive (false positive) ELISA responses occurred with fertilized egg yolks and fertilized whole liquid or whole shell eggs. Conversely, when modified (F(ab)(1)) antibodies were used, the automated SET-II enzyme-linked fluorescent immunoassay was negative. C1 US FDA, College Pk, MD 20740 USA. RP Bennett, RW (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM reginald.bennett@fda.hhs.gov NR 12 TC 3 Z9 3 U1 2 U2 5 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1060-3999 J9 J RAPID METH AUT MIC JI J Rapid Methods Autom. Microbiol. PD DEC PY 2008 VL 16 IS 4 BP 320 EP 329 DI 10.1111/j.1745-4581.2008.00138.x PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 378ZZ UT WOS:000261365100005 ER PT J AU Liu, DY Lawrence, ML Hitchins, AD AF Liu, Dongyou Lawrence, Mark L. Hitchins, Anthony D. TI MOLECULAR CHARACTERIZATION OF LISTERIA MONOCYTOGENES STRAINS HARBORING LISTERIA INNOCUA PUTATIVE TRANSCRIPTIONAL REGULATOR GENE LIN0464 SO JOURNAL OF RAPID METHODS AND AUTOMATION IN MICROBIOLOGY LA English DT Article ID MULTIPLEX PCR; VIRULENCE; IDENTIFICATION; PROTEIN; SPP. AB The genus Listeria comprises six closely related bacterial species that share considerable morphological, ecological, biochemical and molecular similarities. In this study, through examination of a large collection (n = 84) of Listeria monocytogenes strains, we identified four serovar 4c strains (i.e., RM3894, RM3899, RM3901 and RM3905) that cross-reacted with Listeria innocua putative transcriptional regulator gene lin0464 primers. We then investigated these four unusual strains by polymerase chain reaction (PCR) with primers for several L. monocytogenes species-, virulence- and group-specific genes and a newly identified L. innocua-specific transcriptional regulator lin2455 gene. The fact that the four strains were recognized by L. monocytogenes inlA, lmo0733, inlJ, lmo2672 and lmo1134 primers but undetected by L. innocua-specific lin2455 primers suggests their L. monocytogenes species identity, and this was confirmed by their testing positive for the presence of L. monocytogenes specific rRNA. As these strains displayed a reaction pattern with L. monocytogenes-specific primers that is typical of lineage subgroup IIIA serovar 4c strains (ATCC 19116, RM3030 and FSL-F2-458), they are likely of serovar 4c in the lineage subgroup IIIA in spite of their possession of L. innocua putative transcriptional regulator gene lin0464. It is clear from this and other published examples that the close relatedness of the Listeria species even extends to the occasional possession by one species of gene(s) normally regarded as specific to another species. C1 [Liu, Dongyou; Lawrence, Mark L.] Mississippi State Univ, Coll Vet Med, Mississippi State, MS 39762 USA. [Hitchins, Anthony D.] US FDA, College Pk, MD USA. RP Liu, DY (reprint author), Mississippi State Univ, Coll Vet Med, POB 6100, Mississippi State, MS 39762 USA. EM liu@cvm.msstate.edu NR 26 TC 3 Z9 3 U1 0 U2 3 PU WILEY-BLACKWELL PUBLISHING, INC PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 1060-3999 J9 J RAPID METH AUT MIC JI J Rapid Methods Autom. Microbiol. PD DEC PY 2008 VL 16 IS 4 BP 412 EP 427 DI 10.1111/j.1745-4581.2008.00145.x PG 16 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 378ZZ UT WOS:000261365100012 ER PT J AU Wear, KA AF Wear, Keith A. TI Ultrasonic attenuation in parallel-nylon-wire cancellous-bone-mimicking phantoms SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID HUMAN TRABECULAR BONE; HIP FRACTURE RISK; QUANTITATIVE ULTRASOUND; WAVE-PROPAGATION; FREQUENCY-DEPENDENCE; HUMAN CALCANEUS; ELDERLY-WOMEN; IN-VITRO; 2 MHZ; PREDICTION AB Attenuation coefficients between 1.5 and 3.5 MHz were measured on four parallel-nylon-wire arrays (simulating cancellous bone) with four different wire diameters (150, 200, 250, and 300 mu m). Interwire spacing was 800 Am for all four parallel-nylon-wire arrays. The measured frequency dependencies of attenuation were consistent. with theoretical predications based on Faran's theory, which considers the component of attenuation due to scattering of longitudinal waves. [DOI: 10.1121/1.2998784] C1 US FDA, Silver Spring, MD 20993 USA. RP Wear, KA (reprint author), US FDA, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM keith.wear@fda.hhs.gov FU US FDA Office of Women's Health FX Funding from the US FDA Office of Women's Health and assistance in phantom design/development from Heather Pierce, Computerized Imaging Reference Systems, Norfolk, VA, is greatly appreciated. NR 37 TC 4 Z9 4 U1 0 U2 3 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD DEC PY 2008 VL 124 IS 6 BP 4042 EP 4046 DI 10.1121/1.2998784 PG 5 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 398XS UT WOS:000262765600064 PM 19206826 ER PT J AU Chu, HT Nie, L AF Chu, Haitao Nie, Lei TI A Few Remarks on "A Capture-Recapture Approach for Screening Using Two Diagnostic Tests With Availability of Disease Status for the Test Positives Only" by Bohning and Patilea SO JOURNAL OF THE AMERICAN STATISTICAL ASSOCIATION LA English DT Article ID EXPOSURE C1 [Chu, Haitao] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27516 USA. [Chu, Haitao] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27516 USA. [Nie, Lei] US FDA, Off Biostat, Silver Spring, MD 20993 USA. RP Chu, HT (reprint author), Univ N Carolina, Dept Biostat, Chapel Hill, NC 27516 USA. EM hchu@bios.unc.edu; lei.nie@fda.hhs.gov RI Chu, Haitao /J-7576-2012; OI Chu, Haitao/0000-0003-0932-598X FU NCI NIH HHS [P30 CA016086, P30 CA016086-28] NR 5 TC 2 Z9 2 U1 0 U2 4 PU AMER STATISTICAL ASSOC PI ALEXANDRIA PA 1429 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0162-1459 J9 J AM STAT ASSOC JI J. Am. Stat. Assoc. PD DEC PY 2008 VL 103 IS 484 BP 1518 EP 1519 DI 10.1198/016214508000000940 PG 2 WC Statistics & Probability SC Mathematics GA 402JB UT WOS:000263008900019 PM 20539836 ER PT J AU Hung, HMJ AF Hung, H. M. James TI Considerations in Adapting Clinical Trial Design SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Review DE adaptive design; alpha spending; fixed design; group sequential design; logistics; trial conduct ID VIEW AB The concept of adaptation of trial design during the course of a clinical trial has recently drawn much interest from the pharmaceutical industry. The interest arises partly because statistical decision trees employed to address multiple complex clinical hypotheses within a clinical trial are increasingly complex, and the statistical information generated from learning data prior to designing the trial is often insufficient to provide informative guidance for planning a pivotal trial. While the conventional fixed designs, which usually permit no modification influenced by the internal trial data of key design specifications, often cannot cover the range of complex statistical decision trees that must be prespecified in the study protocol, it seems natural to consider modifications of trial design at some point in the trial. In regulatory practice, some adjustments to study protocols are mostly made known to regulatory agencies in the form of so-called protocol amendments. However, such design modifications may demand careful consideration in dealing with any biases that may be caused by the adaptation, and may impede the interpretability of trial results. [J Formos Med Assoc 2008;107(12 Suppl):S14-S18] C1 [Hung, H. M. James] US FDA, Div Biometr 1, Off Biostat, Rockville, MD 20857 USA. [Hung, H. M. James] US FDA, Off Translat Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hung, HMJ (reprint author), US FDA, Div Biometr 1, OB OTS, CDER, 10903 New Hampshire Ave,W021,Room 4616, Silver Spring, MD 20994 USA. EM hsienming.hung@fda.hhs.gov NR 10 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SINGAPORE PTE LTD PI SINGAPORE PA 3 KILLINEY ROAD 08-01, WINSLAND HOUSE 1, SINGAPORE, 239519, SINGAPORE SN 0929-6646 J9 J FORMOS MED ASSOC JI J. Formos. Med. Assoc. PD DEC PY 2008 VL 107 IS 12 BP S14 EP S18 PG 5 WC Medicine, General & Internal SC General & Internal Medicine GA 394EE UT WOS:000262427700004 ER PT J AU Wang, SJ AF Wang, Sue-Jane TI Utility of Adaptive Strategy and Adaptive Design for Biomarker-facilitated Patient Selection in Pharmacogenomic or Pharmacogenetic Clinical Development Program SO JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION LA English DT Article DE genomic biomarker; patient adaptation; personalized medicine; prospective/retrospective study; study design; treatment effect ID GENE SELECTION; BREAST-CANCER; SIGNATURE; TRIALS AB In the early to late phases of conventional clinical trials, improvement of disease status at study baseline is the anchor of;in effective treatment measured by therapeutic response. These population-based clinical trials do not formally account for disease-associated marker genotype or genome-associated therapeutic response. We discuss alternative study designs in pharmacogenomic or pharmacogenetic clinical trials for genomic or genetic biomarker development, and for formally assessing the clinical utility of genomic or genetic (composite) biomarkers. A two-stage adaptive strategy from completed, ongoing or prospectively planned pharmacogenomic or pharmacogenetic clinical trials is described for development of a genomic or genetic biomarker. We present two types of adaptive design: (I) the genomic biomarker is developed external to the clinical trial, which is designed for treatment effect inference; and (2) first-stage data are used to explore a genomic biomarker, but statistical inference of treatment effect in the genomically or genetically defined biomarker subset is only performed at the second stage of the same trial. When the null hypothesis of no treatment effect in all randomized patients and the genomic patient subset are prospectively specified, we compare the statistical power between fixed and adaptive designs. We also compare the two types of adaptive design. Results from simulation studies showed that adaptive design is more powerful than fixed design for those genomic or genetic biomarkers whose clinical utility is predictive of treatment effect. Pursuit of adaptive design gains at least 20% to more than 30% genomic patient subset power when the genomic biomarker status is readily usable at study initiation, in comparison to when it is explored using the first-stage data of the same clinical trial. In exploratory studies, adaptive strategy provides wide flexibility in the process of genomic or genetic biomarker development. In contrast, an adaptive design trial that employs limited flexibility, and is an adequate and well-controlled investigation, has a greater power gain than a fixed design trial, in which the genomic biomarker is capable of predicting treatment effects that pertain only to the prespecified genomic or genetic patient subset. [J Formos Med Assoc 2008;107(12 Suppl): S19-S27] C1 US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, Off Translat Sci, Ctr Drug Evaluat & Res, HFD-700,WO 21,Mail Stop Room 3562,10903 New Hamps, Silver Spring, MD 20993 USA. EM suejane.wang@fda.hhs.gov FU Center for Drug Evaluation and Research [02-06, 04-06, 05-2, 05-14, 08-48]; LIS Food and Drug Administration FX The author thanks Dr Chin-Fu Hsiao of the National Health Research Institutes, Taiwan, for the invitation to make this contribution. This research work was supported by the regulatory science research grants #02-06, #04-06, #05-2, #05-14, #08-48 awarded by the Center for Drug Evaluation and Research, LIS Food and Drug Administration. The research views expressed in this article are the author's professional views and are not necessarily those of the US Food and Drug Administration. NR 15 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SINGAPORE PTE LTD PI SINGAPORE PA 3 KILLINEY ROAD 08-01, WINSLAND HOUSE 1, SINGAPORE, 239519, SINGAPORE SN 0929-6646 J9 J FORMOS MED ASSOC JI J. Formos. Med. Assoc. PD DEC PY 2008 VL 107 IS 12 BP S19 EP S27 PG 9 WC Medicine, General & Internal SC General & Internal Medicine GA 394EE UT WOS:000262427700005 ER PT J AU Grinev, A Daniel, S Laassri, M Chumakov, K Chizhikov, V Rios, M AF Grinev, Andriyan Daniel, Sylvester Laassri, Majid Chumakov, Konstantin Chizhikov, Vladimir Rios, Maria TI Microarray-based assay for the detection of genetic variations of structural genes of West Nile virus SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Mosquito-borne virus; Flavivirus; Microarray technology; PCR; Mutations; Genetic variability ID OLIGONUCLEOTIDE MICROARRAY; UNITED-STATES; PHYLOGENETIC ANALYSIS; DNA MICROARRAY; BLOOD-DONORS; NEW-YORK; HYBRIDIZATION; STRAINS; DISCRIMINATION; IDENTIFICATION AB Adaptation through fixation of spontaneous mutations in the viral genome is considered to be one of the important factors that enable recurrent West Nile virus (WNV) outbreaks in the U.S. Genetic variations can alter viral phenotype and virulence, and degrade the performance of diagnostic and screening assays, vaccines, and potential therapeutic agents. A microarray assay was developed and optimized for the simultaneous detection of any nucleotide mutations in the entire structural region of WNV in order to facilitate public health surveillance of genetic variation of WNV, The DNA microarray consists of 263 oligonucleotide probes overlapping at half of their lengths which have been immobilized on an amine-binding glass slide. The assay was validated using 23 WNV isolates from the 2002-2005 U.S. epidemics. Oligonucleotide-based WNV arrays detected unambiguously all mutations in the structural region of each one of the isolates identified previously by sequencing analysis, serving as a rapid and effective approach for the identification of mutations in the WNV genome. Published by Elsevier B.V. C1 [Grinev, Andriyan; Daniel, Sylvester; Rios, Maria] Div Emerging & Transfus Transmitted Dis, Mol Virol Lab, Rockville, MD 20852 USA. [Laassri, Majid; Chumakov, Konstantin; Chizhikov, Vladimir] US FDA, Lab Methods Dev, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Grinev, A (reprint author), 8800 Rockville Pike,NIH Bldg 29,Room B18, Bethesda, MD 20892 USA. EM Andriyan.Grinev@fda.hhs.gov; Maria.Rios@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases Trans National Institutes of Health/FDA Intramural Biodefense Program [FY06-08] FX We thank Caren Chancey and Robert Duncan for helpful discussion and review of the manuscript, and Dmitriy Volokhov for technical assistance. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. This study was supported by the FY06-08 National Institute of Allergy and Infectious Diseases Trans National Institutes of Health/FDA Intramural Biodefense Program. NR 42 TC 7 Z9 8 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD DEC PY 2008 VL 154 IS 1-2 BP 27 EP 40 DI 10.1016/j.jviromet.2008.09.015 PG 14 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 385UJ UT WOS:000261838800005 PM 18930080 ER PT J AU Xu, ZL Tian, J Smith, JS Byrnes, AP AF Xu, Zhili Tian, Jie Smith, Jeffrey S. Byrnes, Andrew P. TI Clearance of Adenovirus by Kupffer Cells Is Mediated by Scavenger Receptors, Natural Antibodies, and Complement SO JOURNAL OF VIROLOGY LA English DT Article ID INNATE IMMUNE-RESPONSES; VECTORS IN-VIVO; GENE-TRANSFER; INTRAVENOUS-INJECTION; TRANSGENE EXPRESSION; ENDOTHELIAL-CELLS; INFLUENZA-VIRUS; IGM ANTIBODIES; HEPATIC-UPTAKE; CAR-BINDING AB Kupffer cells (KCs) rapidly remove intravenously injected adenovirus (Ad) vectors from the circulation. A better understanding of the mechanisms involved could suggest strategies to improve Ad gene delivery by suppressing or evading KC uptake. We recently showed that clearance of Ad type 5 vectors by KCs does not involve the interaction of Ad with the well-established Ad receptors, namely, integrins or the coxsackievirus and Ad receptor (J.S. Smith, Z.Xu, J.Tian, S.C.Stevenson, and A. P. Byrnes, Hum. Gene Ther. 19: 547-554, 2008). In the current study, we systematically quantified the contributions of various receptors and plasma proteins to the clearance of Ad by KCs. We found that scavenger receptors are a predominant mechanism for the clearance of Ad by KCs. In addition, we found that Ad is opsonized by natural immunoglobulin M antibodies and complement and that these opsonins play a contributory role in the clearance of Ad by KCs. We also examined additional mechanisms that have been postulated to be involved in the clearance of Ad, including the binding of Ad to platelets and vitamin K-dependent coagulation factors, but we found that neither of these were required for the clearance of Ad by KCs. C1 [Xu, Zhili; Tian, Jie; Smith, Jeffrey S.; Byrnes, Andrew P.] US FDA, CBER, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Byrnes, AP (reprint author), US FDA, CBER, Div Cellular & Gene Therapies, HFM-725,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Andrew.Byrnes@fda.hhs.gov RI Byrnes, Andrew/D-2808-2013 OI Byrnes, Andrew/0000-0003-1135-2629 FU FDA; Critical Path Program FX This research was supported by the FDA, including support from the Critical Path Program.; We thank Mike Havert and Takele Argaw for helpful reviews of the manuscript. NR 70 TC 96 Z9 98 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD DEC PY 2008 VL 82 IS 23 BP 11705 EP 11713 DI 10.1128/JVI.01320-08 PG 9 WC Virology SC Virology GA 370UX UT WOS:000260789700021 PM 18815305 ER PT J AU Zhang, YQ Zhang, BL AF Zhang, Yaqin Zhang, Baolin TI TRAIL Resistance of Breast Cancer Cells Is Associated with Constitutive Endocytosis of Death Receptors 4 and 5 SO MOLECULAR CANCER RESEARCH LA English DT Article ID APOPTOSIS-INDUCING LIGAND; MEDIATED ENDOCYTOSIS; LIPID RAFTS; SELECTIVE MUTANTS; DECOY RECEPTORS; THERAPY; SIGNAL; PROTEIN; DR5; APO2L/TRAIL AB Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and its agnostic antibodies, which are being evaluated clinically as anticancer therapies, selectively kill cancer cells through the death receptors DR4 and DR5. However, their therapeutic potential is limited by occurring resistance in tumor cells. Here, we compared the apoptotic response of a panel of six human breast cancer cell lines with recombinant human TRAIL and antibodies to DR4 or DR5. Despite their total mRNA and protein expression, TRAIL death receptors, with a higher frequency in DR4, are absent on cell surface in some cell lines. Loss of cell surface expression of DR4 or DR5 accounts for resistance to their corresponding antibody and, importantly, correlates with a decreased sensitivity to TRAIL. TRAIL resistance occurs when both receptors are absent on cell surface regardless of alterations in Bcl-2 family proteins or caspases. Furthermore, inhibition of endocytosis by pharmacologic inhibitors or disruption of clathrin-dependent endocytosis signaling components (adaptor protein 2 and clathrin) restores cell surface expression of the death receptors and sensitize TRAIL-resistant cells to TRAIL-induced apoptosis. DR4 endocytosis appears to be mediated by its cytoplasmic domain EAQC(337)LL. The results show that TRAIL death receptors undergo constitutive endocytosis in some breast cancer cells. Loss of cell surface expression of DR4 and DR5 could be evaluated as a biomarker for TRAIL resistance in breast tumors. Moreover, the clathrin-mediated endocytosis pathway could be a potential target for therapeutics to overcome tumor resistance to TRAIL receptor-targeted therapies. (Mol Cancer Res 2008;6(12):1861-71) C1 [Zhang, Yaqin; Zhang, Baolin] USDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Zhang, BL (reprint author), USDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, 29 Lincoln Dr,Bldg 29A,Room 2A01,HFD-122, Bethesda, MD 20892 USA. EM Baolin.zhang@fda.hhs.gov FU Food and Drug Administration Critical Path Fund FX Grant support: Food and Drug Administration Critical Path Fund. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. NR 44 TC 117 Z9 122 U1 0 U2 9 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1541-7786 J9 MOL CANCER RES JI Mol. Cancer Res. PD DEC PY 2008 VL 6 IS 12 BP 1861 EP 1871 DI 10.1158/1541-7786.MCR-08-0313 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 385OZ UT WOS:000261824800007 PM 19074831 ER PT J AU Prow, TW Bhutto, I Kim, SY Grebe, R Merges, C McLeod, DS Uno, K Mennon, M Rodriguez, L Leong, K Lutty, GA AF Prow, Tarl W. Bhutto, Imran Kim, Sahng Y. Grebe, Rhonda Merges, Carol McLeod, D. Scott Uno, Koichi Mennon, Mohamed Rodriguez, Li Leong, Kam Lutty, Gerard A. TI Ocular nanoparticle toxicity and transfection of the retina and retinal pigment epithelium SO NANOMEDICINE-NANOTECHNOLOGY BIOLOGY AND MEDICINE LA English DT Article DE Chitosan; Magnetic nanoparticle; Gene delivery; Retina; Toxicity ID GENE DELIVERY; CHITOSAN NANOPARTICLES; IN-VIVO; LOCALIZATION; EFFICIENCY; DISEASES; SYSTEM; CELLS; LIVER AB Chitosan, PCEP (poly{[(cholesteryl oxocarbonylamido ethyl) methyl bis(ethylene) ammonium iodide] ethyl phosphate}), and magnetic nanoparticles (MNPs) were evaluated for the safe delivery of genes in the eye. Rabbits were injected with nanoparticles either intravitreally (IV) or subretinally (SR) and sacrificed 7 days later. Eyes were grossly evaluated for retinal pigment epithelium abnormalities, retinal degeneration, and inflammation. All eyes were cryopreserved and sectioned for analysis of toxicity and expression of either enhanced green or red fluorescent proteins. All of the nanoparticles were able to transfect cells in vitro and in vivo. IV chitosan showed inflammation in 12/13 eyes, whereas IV PCEP and IV MNPs were not inflammatory and did not induce retinal pathology. SR PCEP was nontoxic in the majority of cases but yielded poor transfection, whereas SR MNPs were nontoxic and yielded good transfection. Therefore, we conclude that the best nanoparticle evaluated in vivo was the least toxic nanoparticle tested, the MNP. (c) 2008 Elsevier Inc. All rights reserved. C1 [Lutty, Gerard A.] Johns Hopkins Univ, Wilmer Ophthalmol Inst, Sch Med, Baltimore, MD 21287 USA. [Rodriguez, Li] US FDA, Rockville, MD 20857 USA. [Leong, Kam] Duke Univ, Durham, NC USA. RP Lutty, GA (reprint author), Johns Hopkins Univ, Wilmer Ophthalmol Inst, Sch Med, Baltimore, MD 21287 USA. EM glutty@jhmi.edu RI Prow, Tarl/A-4764-2010; OI Prow, Tarl/0000-0003-2892-6238; Leong, Kam/0000-0002-8133-4955 FU NEI NIH HHS [L40 EY016943-01, EY01765, P30 EY001765, R01 EY009357, R01 EY009357-12A1, R01 EY009357-13, R01 EY009357-14, R01 EY016151, R01 EY016151-01A2, R01 EY016151-02, R01 EY016151-03, R01EY09357, R03 EY013744, R03 EY013744-01, R03 EY013744-02, R03 EY013744-03, R03EY013744]; NHLBI NIH HHS [T32 HL007525, T32HL007525] NR 17 TC 50 Z9 51 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1549-9634 J9 NANOMED-NANOTECHNOL JI Nanomed.-Nanotechnol. Biol. Med. PD DEC PY 2008 VL 4 IS 4 BP 340 EP 349 DI 10.1016/j.nano.2008.06.003 PG 10 WC Nanoscience & Nanotechnology; Medicine, Research & Experimental SC Science & Technology - Other Topics; Research & Experimental Medicine GA 397NE UT WOS:000262668600009 PM 18640079 ER PT J AU Farrell, AT Pazdur, R von Eschenbach, AC AF Farrell, Ann T. Pazdur, Richard von Eschenbach, Andrew C. TI Expediting the availability of drugs for US patients with cancer SO NATURE CLINICAL PRACTICE UROLOGY LA English DT Editorial Material ID APPROVAL C1 [von Eschenbach, Andrew C.] US FDA, Rockville, MD 20847 USA. RP von Eschenbach, AC (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20847 USA. EM avonesch@fda.gov NR 12 TC 1 Z9 1 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 1743-4270 J9 NAT CLIN PRACT UROL JI Nat. Clin. Pract. Urol. PD DEC PY 2008 VL 5 IS 12 BP 654 EP 656 DI 10.1038/ncpuro1255 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 379GF UT WOS:000261384000008 PM 19050708 ER PT J AU McCabe-Sellers, B Lovera, D Nuss, H Wise, C Ning, B Teitel, C Clark, BS Toennessen, T Green, B Bogle, ML Kaput, J AF McCabe-Sellers, Beverly Lovera, Dalia Nuss, Henry Wise, Carolyn Ning, Baitang Teitel, Candee Clark, Beatrice Shelby Toennessen, Terri Green, Bridgett Bogle, Margaret L. Kaput, Jim TI Personalizing Nutrigenomics Research through Community Based Participatory Research and Omics Technologies SO OMICS-A JOURNAL OF INTEGRATIVE BIOLOGY LA English DT Article ID LOWER MISSISSIPPI DELTA; INTERNATIONAL HAPMAP PROJECT; DIETARY-INTAKE; MYOCARDIAL-INFARCTION; FOOD INSECURITY; HEALTH; NUTRITION; POPULATION; MEDICINE; GENOME AB Personal and public health information are often obtained from studies of large population groups. Risk factors for nutrients, toxins, genetic variation, and more recently, nutrient-gene interactions are statistical estimates of the percentage reduction in disease in the population if the risk were to be avoided or the gene variant were not present. Because individuals differ in genetic makeup, lifestyle, and dietary patterns than those individuals in the study population, these risk factors are valuable guidelines, but may not apply to individuals. Intervention studies are likewise limited by small sample sizes, short time frames to assess physiological changes, and variable experimental designs that often preclude comparative or consensus analyses. A fundamental challenge for nutrigenomics will be to develop a means to sort individuals into metabolic groups, and eventually, develop risk factors for individuals. To reach the goal of personalizing medicine and nutrition, new experimental strategies are needed for human study designs. A promising approach for more complete analyses of the interaction of genetic makeups and environment relies on community-based participatory research (CBPR) methodologies. CBPR's central focus is developing a partnership among researchers and individuals in a community that allows for more in depth lifestyle analyses but also translational research that simultaneously helps improve the health of individuals and communities. The USDA-ARS Delta Nutrition Intervention Research program exemplifies CBPR providing a foundation for expanded personalized nutrition and medicine research for communities and individuals. C1 [Wise, Carolyn; Ning, Baitang; Teitel, Candee; Toennessen, Terri; Green, Bridgett; Kaput, Jim] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [McCabe-Sellers, Beverly; Lovera, Dalia; Nuss, Henry; Bogle, Margaret L.] USDA ARS, Delta NIRI, Little Rock, AR 72211 USA. [Clark, Beatrice Shelby] Boys Girls & Adults Community Dev Center, Marvell, AR 72366 USA. RP Kaput, J (reprint author), US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM James.Kaput@fda.hhs.gov FU USDA; ARS [6251-53000-004-00D]; FDA National Center for Toxicological Research; Division of Personalized Nutrition and Medicine FX We are indebted to members of the Lower Delta Mississippi communities who collaborate with us. This research is supported in part by USDA, ARS# 6251-53000-004-00D, and the FDA National Center for Toxicological Research, Division of Personalized Nutrition and Medicine. This manuscript was written by Jim Kaput, Beverly McCabe-Sellers, Margaret Bogle, and edited by Carolyn Wise and Dalia Lovera. Henry Nuss, Candee Teitel, Bridgett Green, Baitang Ning, Terri Toennessen, and Beatrice Clark Shelby contributed to discussions on implementation and conducting biomedical research projects through CBPR activities. This work includes contributions from, and was reviewed by, the FDA. This work has been approved for publication by this agency but it does not necessarily reflect official agency policy. NR 92 TC 18 Z9 19 U1 1 U2 4 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1536-2310 J9 OMICS JI OMICS PD DEC PY 2008 VL 12 IS 4 BP 263 EP 272 DI 10.1089/omi.2008.0041 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity SC Biotechnology & Applied Microbiology; Genetics & Heredity GA 384KU UT WOS:000261744500006 PM 19040372 ER PT J AU Chen, ML Lee, VH AF Chen, Mei-Ling Lee, Vincent H. L. TI Equivalence-by-Design: Targeting In Vivo Drug Delivery Profile SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material DE bioequivalence; in vivo drug delivery profile; pharmaceutical equivalence; quality by design; therapeutic equivalence ID P-GLYCOPROTEIN; PHARMACEUTICAL EXCIPIENTS; BIOEQUIVALENCY ASSESSMENT; GASTROINTESTINAL TRANSIT; LINEAR PHARMACOKINETICS; MEMBRANE TRANSPORTERS; ORAL BIOAVAILABILITY; GAMMA-SCINTIGRAPHY; DOSAGE FORMS; ABSORPTION AB In the United States (U.S.), drug products are considered therapeutically equivalent if they meet regulatory criteria of pharmaceutical equivalence and bioequivalence. These requirements can be traced back to 1977 when the U.S. Food and Drug Administration (FDA) published the regulations on bioavailability and bioequivalence. Over the years, to keep up with the advancement in science and technology, the FDA has been constantly updating the regulatory approaches to assessing and ensuring equivalence. In view of the recent growth in novel pharmaceutical dosage forms and delivery systems, this paper examines the current framework for documentation of therapeutic equivalence and explores the opportunities of further advancing equivalence methods for complex drug products. It is proposed that equivalence may be established by matching the in vivo drug delivery profile (iDDP) between drug products in comparison. This can be achieved by characterizing the iDDP of the reference formulation with application of an equivalence-by-design approach for pharmaceutical development. Critical variables can be identified to serve as in vitro markers or biomarkers for mapping the desired drug delivery profile in vivo. A multidisciplinary approach may be necessary to develop these markers for characterization of iDDPs. C1 [Chen, Mei-Ling] US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Lee, Vincent H. L.] Chinese Univ Hong Kong, Fac Med, Sch Pharm, Shatin, Hong Kong, Peoples R China. RP Chen, ML (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM meiling.chen@fda.hhs.gov RI Lee, Vincent/A-9439-2008 OI Lee, Vincent/0000-0001-7708-6269 NR 89 TC 3 Z9 4 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORD JI Pharm. Res. PD DEC PY 2008 VL 25 IS 12 BP 2723 EP 2730 DI 10.1007/s11095-008-9743-8 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 378SF UT WOS:000261343500004 PM 18956142 ER PT J AU Moore, KM Duddy, A Braun, MM Platt, R Brown, JS AF Moore, Kristen M. Duddy, April Braun, M. Miles Platt, Richard Brown, Jeffrey S. TI Potential population-based electronic data sources for rapid pandemic influenza vaccine adverse event detection: a survey of health plans SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE pandemic influenza vaccine; adverse event detection; distributed data network ID PUBLIC-HEALTH; SURVEILLANCE; SYSTEM; SAFETY AB Purpose A vaccine against pandemic influenza may be rapidly and widely distributed, and could be used in populations with little prior exposure to influenza vaccines. Under such conditions, it will be important to gain timely information about the rates of vaccine adverse events, ideally by using electronic data from large populations. Many public and private health plans and payers have such information. Methods Between May and September 2007, we conducted a decision maker interview and technical assessment with several health plans in the United States. The interview and survey evaluated technical capability, organizational capacity, and willingness to participate in a coordinated program of rapid safety research targeting pandemic and other influenza vaccines. Results Eleven health plans (eight private, three public) participated in the decision maker interview. Most interviewees were medical directors or held similar positions within their organizations. Participating plans provided coverage and/or care for approximately 150 million members in the U.S. Nine health plans completed a technical assessment survey. Most decision makers indicated interest and willingness to participate in a coordinated rapid safety surveillance program, and all reported the necessary claims data analysis experience. Respondents noted legal, procedural, budgetary, and technical barriers to participation. Conclusions Senior decision makers representing private and public health plans were willing and asserted the ability of their organizations to participate in pandemic influenza vaccine safety monitoring. Developing working relationships, negotiating contracts, and obtaining necessary regulatory and legal approvals were identified as key barriers. These findings may be generalizable to other vaccines and pharmaceutical products. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Moore, Kristen M.; Duddy, April; Platt, Richard; Brown, Jeffrey S.] Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02215 USA. [Moore, Kristen M.; Duddy, April; Platt, Richard; Brown, Jeffrey S.] Harvard Pilgrim Hlth Care, Boston, MA USA. [Moore, Kristen M.; Duddy, April; Platt, Richard; Brown, Jeffrey S.] HMO Res Network, Ctr Educ & Res Therapeut, Boston, MA USA. [Braun, M. Miles] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Brown, JS (reprint author), Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, 133 Brookline Ave,6th Floor, Boston, MA 02215 USA. EM jeff_brown@harvardpilgrim.org FU FDA [200-2002-00732] FX We thank Robert Ball, Dale Burwen, Hector Izurieta, and Sukhminder Sandhu from FDA, and Meredith Chace from DACP for their participation in study design, input on survey methods, and thoughtful comments on this manuscript. This study was funded by FDA contract no. 200-2002-00732. NR 14 TC 9 Z9 9 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD DEC PY 2008 VL 17 IS 12 BP 1137 EP 1141 DI 10.1002/pds.1642 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 386WB UT WOS:000261912200002 PM 18763248 ER PT J AU Hammad, TA McAdams, MA Feight, A Iyasu, S Dal Pan, GJ AF Hammad, Tarek A. McAdams, Mara A. Feight, Andrea Iyasu, Solomon Dal Pan, Gerald J. TI Determining the predictive value of Read/OXMIS codes to identify incident acute myocardial infarction in the General Practice Research Database SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE validation of incident acute myocardial infarction; Read/OXMIS codes; General Practice Research Database ID VALIDATION; RISK; HYPERTENSION; DRUGS AB Purpose To determine (1) the positive predictive value (PPV) of multiple Read/OXMIS codes to identify incident acute myocardial infarction (AMI) cases in General Practice Research Database (GPRD); (2) the ability to capture the correct timing of the clinical event. Methods A random sample of 238 records (from 155 general practitioner (GP) practices) with AMI codes, between 1 January 1997 and 31 December 2004, was selected from GPRD. Questionnaires were sent to the GPs to verify the diagnosis and timing of code-identified incident AMI events and collect supporting information. We calculated the PPV of the AMI codes as the proportion of code-identified AMIs that the GPs confirmed as AMI cases. Two physicians from Food and Drug administration (FDA), blinded to the GP response, reviewed the supporting hospital records returned by GPs for 98 AMI cases. Results A total of 217 questionnaires were completed (91% response rate). The PPV of the AMI codes was 93% (201/217). Thirty one (15%) cases had a different event date than the one recorded in the electronic medical records (EMR); 28 (90%) of the dates were within 15 days. One GP indicated that a patient had a previous AMI, I 10 days before the codes that captured the AMI diagnosis. A total of 159 (79%) AMI cases were hospitalized; hospital records were provided for 98 patients. Physician review of the hospital records found that 96% of these records had enough information for classification, but not independent diagnosis, of AMI. Conclusions Information in GPRD is sufficient to identify incident AMI cases and determine the event date with reasonable accuracy. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Hammad, Tarek A.; McAdams, Mara A.; Feight, Andrea; Iyasu, Solomon; Dal Pan, Gerald J.] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. RP Hammad, TA (reprint author), 10903 New Hampshire Ave Bldg 22,Room 4474,Mail St, Silver Spring, MD 20993 USA. EM tarek.hammad@fda.hhs.gov RI Research Datalink, Clinical Practice/H-2477-2013; CPRD, CPRD/B-9594-2017; OI McAdams-DeMarco, Mara/0000-0003-3013-925X FU Center for Drug Evaluation and Research at the US Food and Drug Administration FX This work was sponsored by the Center for Drug Evaluation and Research at the US Food and Drug Administration. NR 13 TC 38 Z9 38 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD DEC PY 2008 VL 17 IS 12 BP 1197 EP 1201 DI 10.1002/pds.1672 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 386WB UT WOS:000261912200009 PM 18985705 ER PT J AU Goodsaid, FM AF Goodsaid, Federico M. TI Modulation of Clopidogrel Pharmacodynamic Response SO PHARMACOTHERAPY LA English DT Editorial Material DE clopidogrel; prasugrel; thienopyridines; drug-drug interactions; platelet aggregation; pharmacodynamics; pharmacogenomics ID OF-FUNCTION POLYMORPHISM; HEALTHY-SUBJECTS; RESPONSIVENESS; PRASUGREL; VARIABILITY; CYP2C19 C1 [Goodsaid, Federico M.] US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Goodsaid, FM (reprint author), 10903 New Hampshire Ave,Bldg 51,Room 2148, Silver Spring, MD 20903 USA. EM federico.goodsaid@fda.hhs.gov NR 11 TC 0 Z9 0 U1 0 U2 2 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD DEC PY 2008 VL 28 IS 12 BP 1423 EP 1424 DI 10.1592/phco.28.12.1423 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 380RF UT WOS:000261482200001 PM 19025421 ER PT J AU Teramoto, T Kohno, Y Mattoo, P Markoff, L Falgout, B Padmanabhan, R AF Teramoto, Tadahisa Kohno, Yukari Mattoo, Pravina Markoff, Lewis Falgout, Barry Padmanabhan, Radhakrishnan TI Genome 3 '-end repair in dengue virus type 2 SO RNA-A PUBLICATION OF THE RNA SOCIETY LA English DT Article DE RNA virus; RNA replication; RNA-dependent RNA polymerase; quasi-species; RNA structure ID DEPENDENT RNA-POLYMERASE; DE-NOVO SYNTHESIS; WEST-NILE-VIRUS; IN-VITRO; FLAVIVIRUS RNA; VIRAL-RNA; 3'-UNTRANSLATED REGION; CYCLIZATION SEQUENCES; 3'-TERMINAL REGIONS; SECONDARY STRUCTURE AB Genomes of RNA viruses encounter a continual threat from host cellular ribonucleases. Therefore, viruses have evolved mechanisms to protect the integrity of their genomes. To study the mechanism of 3'-end repair in dengue virus-2 in mammalian cells, a series of 3'-end deletions in the genome were evaluated for virus replication by detection of viral antigen NS1 and by sequence analysis. Limited deletions did not cause any delay in the detection of NS1 within 5 d. However, deletions of 7-10 nucleotides caused a delay of 9 d in the detection of NS1. Sequence analysis of RNAs from recovered viruses showed that at early times, virus progenies evolved through RNA molecules of heterogeneous lengths and nucleotide sequences at the 39 end, suggesting a possible role for terminal nucleotidyl transferase activity of the viral polymerase (NS5). However, this diversity gradually diminished and consensus sequences emerged. Template activities of 3'-end mutants in the synthesis of negative-strand RNA in vitro by purified NS5 correlate well with the abilities of mutant RNAs to repair and produce virus progenies. Using the Mfold program for RNA structure prediction, we show that if the 3' stem-loop (3' SL) structure was abrogated by mutations, viruses eventually restored the 39 SL structure. Taken together, these results favor a two-step repair process: non-template-based nucleotide addition followed by evolutionary selection of 3'-end sequences based on the best-fit RNA structure that can support viral replication. C1 [Teramoto, Tadahisa; Mattoo, Pravina; Markoff, Lewis; Falgout, Barry] US FDA, Lab Vector Borne Virus Dis, Ctr Biol Evaluat & Review, Bethesda, MD 20892 USA. [Kohno, Yukari; Padmanabhan, Radhakrishnan] Georgetown Univ, Med Ctr, Dept Microbiol & Immunol, Washington, DC 20057 USA. RP Falgout, B (reprint author), US FDA, Lab Vector Borne Virus Dis, Ctr Biol Evaluat & Review, Bethesda, MD 20892 USA. EM Barry.Falgout@fda.hhs.gov; rp55@georgetown.edu FU NIAID [AI54776, AI 070791]; ORISE FX We thank Mike Klutch for excellent technical support in sequence analysis. The work was supported by grants from NIAID, AI54776, and AI 070791 and an ORISE grant. NR 45 TC 22 Z9 22 U1 0 U2 2 PU COLD SPRING HARBOR LAB PRESS, PUBLICATIONS DEPT PI WOODBURY PA 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2924 USA SN 1355-8382 J9 RNA JI RNA-Publ. RNA Soc. PD DEC PY 2008 VL 14 IS 12 BP 2645 EP 2656 DI 10.1261/rna.1051208 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 379LT UT WOS:000261398400020 PM 18974278 ER PT J AU Taitt, CR Shriver-Lake, LC Ngundi, MM Ligler, FS AF Taitt, Chris Rowe Shriver-Lake, Lisa C. Ngundi, Miriam M. Ligler, Frances S. TI Array Biosensor for Toxin Detection: Continued Advances SO SENSORS LA English DT Review DE toxin; detection; biosensor; multi-analyte; multiplex; food; clinical diagnostics ID SURFACE-PLASMON RESONANCE; STAPHYLOCOCCAL-ENTEROTOXIN-B; PROSTATE-SPECIFIC ANTIGEN; CHOLERA-TOXIN; ANTIMICROBIAL PEPTIDES; SERUM ANTIBODIES; RECOGNITION MOLECULES; BOTULINUM NEUROTOXIN; ESCHERICHIA-COLI; IN-VITRO AB The following review focuses on progress made in the last five years with the NRL Array Biosensor, a portable instrument for rapid and simultaneous detection of multiple targets. Since 2003, the Array Biosensor has been automated and miniaturized for operation at the point-of-use. The Array Biosensor has also been used to demonstrate (1) quantitative immunoassays against an expanded number of toxins and toxin indicators in food and clinical fluids, and (2) the efficacy of semi-selective molecules as alternative recognition moieties. Blind trials, with unknown samples in a variety of matrices, have demonstrated the versatility, sensitivity, and reliability of the automated system. C1 [Taitt, Chris Rowe; Shriver-Lake, Lisa C.; Ligler, Frances S.] USN, Res Lab, Ctr Biomol Sci & Engn, Washington, DC 20375 USA. [Ngundi, Miriam M.] US FDA, Bethesda, MD 20892 USA. RP Taitt, CR (reprint author), USN, Res Lab, Ctr Biomol Sci & Engn, Code 6900, Washington, DC 20375 USA. EM chris.taitt@nrl.navy.mil; lisa.shriverlake@nrl.navy.mil; Miriam.Ngundi@fda.hhs.gov; frances.ligler@nrl.navy.mil FU NIH/NIAID [UO1 AI075489]; Defense Threat Reduction Agency FX This work was supported by NIH/NIAID partnership grant UO1 AI075489 and the Defense Threat Reduction Agency. The views are those of the authors and do not reflect opinion or policy of the NRL, US Navy, Department of Defense, NIH or Department of Health and Human Services. NR 64 TC 30 Z9 30 U1 4 U2 39 PU MOLECULAR DIVERSITY PRESERVATION INTERNATIONAL-MDPI PI BASEL PA KANDERERSTRASSE 25, CH-4057 BASEL, SWITZERLAND SN 1424-8220 J9 SENSORS-BASEL JI Sensors PD DEC PY 2008 VL 8 IS 12 BP 8361 EP 8377 DI 10.3390/s8128361 PG 17 WC Chemistry, Analytical; Electrochemistry; Instruments & Instrumentation SC Chemistry; Electrochemistry; Instruments & Instrumentation GA 387JJ UT WOS:000261948200047 PM 27873991 ER PT J AU Chan-Tack, KM Struble, KA Morgensztejn, N Murray, JS Gulick, R Cheng, B Weller, I Miller, V AF Chan-Tack, Kirk M. Struble, Kimberly A. Morgensztejn, Nathalie Murray, Jeffrey S. Gulick, Roy Cheng, Ben Weller, Ian Miller, Veronica TI HIV clinical trial design for antiretroviral development: moving forward SO AIDS LA English DT Review DE antiretroviral therapy; clinical trial design; HIV-1; noninferiority; optimized background regimen; salvage therapy; treatment-experienced; treatment-naive ID EXPERIENCED HIV-1-INFECTED PATIENTS; OPTIMIZED BACKGROUND REGIMEN; PLACEBO-CONTROLLED TRIAL; TMC125 ETRAVIRINE; DURABLE EFFICACY; DOUBLE-BLIND; INFECTION; SAFETY; RITONAVIR; RALTEGRAVIR C1 [Cheng, Ben; Miller, Veronica] George Washington Univ, Forum Collaborat HIV Res, Washington, DC 20037 USA. [Chan-Tack, Kirk M.; Struble, Kimberly A.; Murray, Jeffrey S.] US FDA, Div Antiviral Prod, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Morgensztejn, Nathalie] EMEA, Representat European Med Agcy, London, England. [Weller, Ian] UCL, Ctr Sexual Hlth & HIV Res, London, England. [Gulick, Roy] Weill Cornel Med Coll, New York, NY USA. RP Miller, V (reprint author), George Washington Univ, Forum Collaborat HIV Res, 2175 K St NW,Suite 700, Washington, DC 20037 USA. EM vmiller@gwu.edu FU NIAID NIH HHS [AI-51966 (K24)] NR 37 TC 10 Z9 10 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 NOV 30 PY 2008 VL 22 IS 18 BP 2419 EP 2427 DI 10.1097/QAD.0b013e32831692e6 PG 9 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 384VM UT WOS:000261772300002 PM 19005265 ER PT J AU Asher, DM AF Asher, David M. TI Kuru: memories of the NIH years SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES LA English DT Editorial Material ID CREUTZFELDT-JAKOB-DISEASE; TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHIES; CENTRAL-NERVOUS-SYSTEM; SCRAPIE AGENT; PERSON TRANSMISSION; SPIDER MONKEY; VIRUS-LIKE; INFECTIVITY; INACTIVATION; BLOOD C1 US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis,HFM 313, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Asher, DM (reprint author), US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis,HFM 313, Off Blood Res & Review,Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM david.asher@fda.hhs.gov NR 59 TC 4 Z9 4 U1 0 U2 1 PU ROYAL SOC PI LONDON PA 6-9 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 0962-8436 J9 PHILOS T R SOC B JI Philos. Trans. R. Soc. B-Biol. Sci. PD NOV 27 PY 2008 VL 363 IS 1510 BP 3618 EP 3625 DI 10.1098/rstb.2008.4002 PG 8 WC Biology SC Life Sciences & Biomedicine - Other Topics GA 371WX UT WOS:000260864500005 PM 18849246 ER PT J AU Kohl, KS Magnus, M Ball, R Halsey, N Shadomy, S Farley, TA AF Kohl, Katrin S. Magnus, Manya Ball, Robert Halsey, Neal Shadomy, Sean Farley, Thomas A. TI Applicability, reliability, sensitivity, and specificity of six Brighton Collaboration standardized case definitions for adverse events following immunization SO VACCINE LA English DT Article DE Adverse events following immunization; Case definitions; Evaluation methodology; Fever; Persistent crying; Hypotonic-hyporesponsive episode; Intussusception; Nodule at injection site; Generalized convulsive seizure ID HYPORESPONSIVE EPISODE HHE; DATA-COLLECTION; ACUTE INTUSSUSCEPTION; VACCINE SAFETY; GUIDELINES; SURVEILLANCE; ENCEPHALITIS; CHILDREN; INFANTS; FEVER AB We evaluated the applicability, reliability, sensitivity, and specificity of six standardized case definitions for adverse events following immunization (AEFI) (for fever, generalized Convulsive seizure, hypotonic-hyporesponsive episode, intussusception, nodule, and persistent crying) developed by the Brighton Collaboration using the U.S. Vaccine Adverse Event Reporting System (VAERS). The evaluation included: (a) the development of codified search strings using standardized coding terminology, and (b) for sensitivity and specificity analyses, the development of a "gold standard" for case determination by clinical expert reviews, and its comparison against the application of the definitions to VAERS reports by nonclinicians. Application of the case definitions in an automated approach proved to be valid, feasible, and unlikely to miss confirmed cases of the reported clinical event. The definitions had variable but generally high sensitivity and specificity compared to clinician review, which in itself yielded inconsistent case determination. The study demonstrated the need for the developed standardized definitions for AEFI and their usefulness in passive surveillance. (c) 2008 Elsevier Ltd. All rights reserved. C1 [Kohl, Katrin S.; Shadomy, Sean] Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Natl Ctr Preparedness Detect & Control Infect Dis, Immunizat Safety Off,Off Chief Sci Officer, Atlanta, GA 30333 USA. [Magnus, Manya] George Washington Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Washington, DC USA. [Ball, Robert] US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. [Halsey, Neal] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Int Hlth, Baltimore, MD USA. [Farley, Thomas A.] Tulane Univ, Sch Publ Hlth & Trop Med, Dept Community Hlth Sci, New Orleans, LA USA. RP Kohl, KS (reprint author), Ctr Dis Control & Prevent, Div Global Migrat & Quarantine, Natl Ctr Preparedness Detect & Control Infect Dis, Immunizat Safety Off,Off Chief Sci Officer, Mailstop E-61, Atlanta, GA 30333 USA. EM kfk0@cdc.gov NR 27 TC 12 Z9 12 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 25 PY 2008 VL 26 IS 50 BP 6349 EP 6360 DI 10.1016/j.vaccine.2008.09.002 PG 12 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 385OE UT WOS:000261822700010 PM 18805456 ER PT J AU Watford, WT Hissong, BD Durant, LR Yamane, H Muul, LM Kanno, Y Tato, CM Ramos, HL Berger, AE Mielke, L Pesu, M Solomon, B Frucht, DM Paul, WE Sher, A Jankovic, D Tsichlis, PN O'Shea, JJ AF Watford, Wendy T. Hissong, Bruce D. Durant, Lydia R. Yamane, Hidehiro Muul, Linda M. Kanno, Yuka Tato, Cristina M. Ramos, Haydee L. Berger, Alan E. Mielke, Lisa Pesu, Marko Solomon, Benjamin Frucht, David M. Paul, William E. Sher, Alan Jankovic, Dragana Tsichlis, Philip N. O'Shea, John J. TI Tpl2 kinase regulates T cell interferon-gamma production and host resistance to Toxoplasma gondii SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ACTIVATED PROTEIN-KINASE; NF-KAPPA-B; TNF-ALPHA PRODUCTION; SIGNALING PATHWAYS; IFN-GAMMA; EXPRESSION; STAT4; IL-12; CYTOKINE; MICE AB Tpl2 (Tumor progression locus 2), also known as Cot/MAP3K8, is a hematopoietically expressed serine-threonine kinase. Tpl2 is known to have critical functions in innate immunity in regulating tumor necrosis factor-alpha, Toll-like receptor, and G protein-coupled receptor signaling; however, our understanding of its physiological role in T cells is limited. We investigated the potential roles of Tpl2 in T cells and found that it was induced by interleukin-12 in human and mouse T cells in a Stat4-dependent manner. Deficiency of Tpl2 was associated with impaired interferon (IFN)-gamma production. Accordingly, Tpl2(-/-) mice had impaired host defense against Toxoplasma gondii with reduced parasite clearance and decreased IFN-gamma production. Furthermore, reconstitution of Rag2(-/-) mice with Tpl2-deficient T cells followed by T. gondii infection recapitulated the IFN-gamma defect seen in the Tpl2-deficient mice, confirming a T cell-intrinsic defect. CD4(+) T cells isolated from Tpl2(-/-) mice showed poor induction of T-bet and failure to up-regulate Stat4 protein, which is associated with impaired TCR-dependent extracellular signal-regulated kinase activation. These data underscore the role of Tpl2 as a regulator of T helper cell lineage decisions and demonstrate that Tpl2 has an important functional role in the regulation of Th1 responses. C1 [Watford, Wendy T.; Hissong, Bruce D.; Durant, Lydia R.; Muul, Linda M.; Kanno, Yuka; Tato, Cristina M.; Ramos, Haydee L.; Berger, Alan E.; Mielke, Lisa; Pesu, Marko; Solomon, Benjamin; O'Shea, John J.] NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. [Yamane, Hidehiro; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Sher, Alan; Jankovic, Dragana] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. [Frucht, David M.] US FDA, Cell Biol Lab, Div Monoclonal Antibodies, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. [Tsichlis, Philip N.] Tufts Med Ctr, Mol Oncol Res Inst, Boston, MA 02111 USA. RP Watford, WT (reprint author), NIAMSD, Lymphocyte Cell Biol Sect, Mol Immunol & Inflammat Branch, NIH, Bethesda, MD 20892 USA. EM watfordw@mail.nih.gov RI Kanno, Yuka/B-5802-2013; Pesu, marko/L-6344-2013; OI Kanno, Yuka/0000-0001-5668-9319 FU National Institute of Arthritis; National Institutes of Health [1 K22 AR53953-01, R01 CA095431] FX This research was supported, in part, by the Intramural Research Program of the National Institute of Arthritis and Musculoskeletal and Skin Diseases of the National Institutes of Health. W. T. Watford is supported by National Institutes of Health grant # 1 K22 AR53953-01. P. Tsichlis is supported by National Institutes of Health grant # R01 CA095431. NR 44 TC 48 Z9 51 U1 0 U2 2 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD NOV 24 PY 2008 VL 205 IS 12 BP 2803 EP 2812 DI 10.1084/jem.20081461 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 378BE UT WOS:000261295300014 PM 19001140 ER PT J AU Ng, TH AF Ng, Tie-Hua TI Noninferiority hypotheses and choice of noninferiority margin SO STATISTICS IN MEDICINE LA English DT Article DE active control; noninferiority margin; binary; odds ratio; mean ratio; hazard ratio ID NON-INFERIORITY TRIALS; EQUIVALENCE; DESIGN AB Ng (Drug Inf. J. 1993: 27:705-719: Durg Inf. J. 2001; 35:1517-1527) proposed that the noninferiority (NI) margin should be a small fraction of the therapeutic effect of the active control as compared with placebo in the setting of testing the NI hypothesis of the mean difference with a continuous outcome. For testing the NI hypothesis of the mean ratio with a continuus outcome, a similar NI margin on a log scale is proposed. This approach may also be applied in the setting of testing, the NI hypothesis for survival data based on hazard ratios. Some pitfalls of testing the NI hypotheses with binary endpoints based on the difference or the ratio of proportions will be discussed. Testing the NI hypothesis with binary endpoints based oil the odds ratio is proposed. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 US FDA, Rockville, MD 20852 USA. RP Ng, TH (reprint author), US FDA, 1401 Rockville Pike,200S HFM-219, Rockville, MD 20852 USA. EM tiehua.ng@fda.hhs.gov NR 22 TC 11 Z9 13 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD NOV 20 PY 2008 VL 27 IS 26 BP 5392 EP 5406 DI 10.1002/sim.3367 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 371AI UT WOS:000260803800006 PM 18680173 ER PT J AU Herishanu, Y Vire, B Liu, DL Gibellini, F Marti, GE White, T Njuguna, N Raghavachari, N Liu, PC Pittaluga, S Munson, PJ Wilson, WH Wiestner, A AF Herishanu, Yair Vire, Berengere Liu, Delong Gibellini, Federica Marti, Gerald E. White, Therese Njuguna, Ndegwa Raghavachari, Nalini Liu, Poching Pittaluga, Stefania Munson, Peter J. Wilson, Wyndham H. Wiestner, Adrian TI The Role of the Microenvironment for CLL Proliferation and Survival: Gene Expression Profiling of Leukemic Cells Derived from Blood, Bone Marrow and Lymph Nodes Reveals the B-Cell Receptor and NF-kappa B as Dominant Signaling Pathways SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Herishanu, Yair; Vire, Berengere; Gibellini, Federica; Njuguna, Ndegwa; Wiestner, Adrian] NHLBI, Hematol Branch, NIH, Bethesda, MD 20892 USA. [Liu, Delong; Munson, Peter J.] NIH, Stat Comp Lab, DCB, CIT, Bethesda, MD 20892 USA. [Marti, Gerald E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Raghavachari, Nalini; Liu, Poching] NHLBI, Genom Core Facil, NIH, Bethesda, MD 20892 USA. [Pittaluga, Stefania] NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 139 EP 139 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700357 ER PT J AU Hsi, ED Said, J Johnson, JL Jung, SH Lai, R Jones, D Chadburn, A Cheson, BD Wilson, WH AF Hsi, Eric D. Said, Jonathan Johnson, Jeffrey L. Jung, Sinho Lai, Raymond Jones, Dan Chadburn, Amy Cheson, Bruce D. Wilson, Wyndham H. TI Biologic Prognostic Markers in Diffuse Large B-Cell Lymphoma Patients Treated with Dose Adjusted EPOCH-R: a CALGB 50103 Correlative Science Study SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Hsi, Eric D.] Cleveland Clin, Cleveland, OH 44106 USA. [Said, Jonathan] Univ Calif Los Angeles, Med Ctr, Los Angeles, CA 90024 USA. [Johnson, Jeffrey L.; Jung, Sinho] Duke Univ, Med Ctr, CALGB Stat Off, Durham, NC USA. [Lai, Raymond] Cross Canc Ctr, Edmonton, AB, Canada. [Jones, Dan] Univ Texas MD Anderson Canc Ctr, Dept Hematopathol, Houston, TX 77030 USA. [Chadburn, Amy] New York Presbyterian Hosp, New York, NY USA. [Cheson, Bruce D.] Georgetown Univ Hosp, Lombardi Canc Ctr, Washington, DC 20007 USA. [Wilson, Wyndham H.] FDA, CBER, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 181 EP 181 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104700477 ER PT J AU Zhang, XY To, L Reiser, J Hemenway, CS Sadelain, MW La Russa, VF AF Zhang, Xian-Yang To, Lisa Reiser, Jakob Hemenway, Charles S. Sadelain, Michel W. La Russa, Vincent F. TI Strategies for Therapeutic Peptide Delivery by Mesenchymal Stem Cells SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [To, Lisa] Louisiana State Univ, Sch Med, New Orleans, LA USA. [Reiser, Jakob] US FDA, Bethesda, MD 20014 USA. [Hemenway, Charles S.] Loyola Univ, Med Ctr, Maywood, IL 60153 USA. [La Russa, Vincent F.] Mem Sloan Kettering Canc Ctr, Cytotherapy Lab, New York, NY 10021 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 319 EP 319 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701087 ER PT J AU Gelderman-Fuhrmann, M Vostal, JG AF Gelderman-Fuhrmann, Monique Vostal, Jaroslav G. TI Rejuvenation of Aged Human Red Cells Improves Their in Vivo Recovery in a Mouse Model. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Gelderman-Fuhrmann, Monique] US FDA, Lab Cellular Hematol, Rockville, MD 20857 USA. [Vostal, Jaroslav G.] Lab Cellular Hem, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 365 EP 365 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104701215 ER PT J AU Semberova, J Holada, K Simakova, O Gelderman-Fuhrmann, MP Simak, J AF Semberova, Jana Holada, Karel Simakova, Olga Gelderman-Fuhrmann, Monique P. Simak, Jan TI Carbon Nanotubes Activate Platelets by Facilitating Extracellular Ca2+ Influx. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology/ASH/ASCO Joint Symposium CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol, Sanofi Aventis U.S. C1 [Semberova, Jana; Gelderman-Fuhrmann, Monique P.; Simak, Jan] CBER FDA, Lab Cellular Hematol, Rockville, MD USA. [Holada, Karel] Charles Univ Prague, Inst Microbiol & Immunol, Prague, Czech Republic. [Simakova, Olga] USUHS, Bethesda, MD USA. RI Simak, Jan/C-1153-2011 NR 0 TC 2 Z9 2 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 365 EP 366 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701216 ER PT J AU Robinson, BW Cao, K Hilden, JM Dinndorf, PA Heerema, NA Sather, HN McGlennen, R Hunger, SP Reaman, GH Wang, LS Felix, CA AF Robinson, Blaine W. Cao, Kajia Hilden, Joanne M. Dinndorf, Patricia A. Heerema, Nyla A. Sather, Harland N. McGlennen, Ron Hunger, Stephen P. Reaman, Gregory H. Wang, Li-San Felix, Carolyn A. TI Age Is the Strongest Determinant of Leukemia Blast Cell Gene Expression in MLL-Rearranged Infant ALL and MLL-AF4 Directs a Distinct Gene Expression Profile Related to CNS Disease SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Felix, Carolyn A.] Childrens Hosp Philadelphia, Div Oncol, Dept Pediat, Philadelphia, PA 19104 USA. [Cao, Kajia; Wang, Li-San] Univ Penn, Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. [Hilden, Joanne M.] Peyton Manning Children Hosp St Pincent, Indianapolis, IN USA. [Dinndorf, Patricia A.] US FDA, Silver Spring, MD USA. [Heerema, Nyla A.] Ohio State Univ, Dept Pathol, Columbus, OH 43210 USA. [Sather, Harland N.] Univ So Calif, Arcadia, CA USA. [McGlennen, Ron] Univ Minnesota, Med Ctr, Minneapolis, MN 55455 USA. [Hunger, Stephen P.] Univ Colorado Denver, Sch Med, Aurora, CO USA. [Hunger, Stephen P.] Childrens Hosp, Aurora, CO USA. [Reaman, Gregory H.] Childrens Natl Med Ctr, Washington, DC 20010 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 437 EP 438 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104701422 ER PT J AU Roa, SS Mohan, KVK Atreya, CD AF Roa, Shilpakala Sarnath Mohan, Ketha V. K. Atreya, Chintamani D. TI High Sensitivity Detection of Bacillus Cereus in Plasma Samples SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Roa, Shilpakala Sarnath; Mohan, Ketha V. K.; Atreya, Chintamani D.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 694 EP 695 PG 2 WC Hematology SC Hematology GA 389OP UT WOS:000262104702323 ER PT J AU Kannan, M Mohan, KVK Kulkarni, S Atreya, CD AF Kannan, Mecanathan Mohan, Ketha V. K. Kulkarni, Sandhya Atreya, Chintamani D. TI Potential Use of miRNAs as Platelet Biomarkers of Storage SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Kannan, Mecanathan; Mohan, Ketha V. K.; Kulkarni, Sandhya; Atreya, Chintamani D.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 695 EP 695 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104702324 ER PT J AU Podar, K Zhang, J Tonon, G Grabher, C Lababidi, S Raab, MS Vallet, S Zhou, YM Cartron, MA Sattler, M Chauhan, D Anderson, KC AF Podar, Klaus Zhang, Jing Tonon, Giovanni Grabher, Clemens Lababidi, Samir Raab, Marc S. Vallet, Sonia Zhou, Yiming Cartron, Marie-Astrid Sattler, Martin Chauhan, Dharminder Anderson, Kenneth C. TI C-Myc- Dependent Stabilization of Hif-1alpha in MM: Therapeutic Implications. SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Podar, Klaus] Harvard Univ, Sch Med, Dana Farber Canc Inst, Boston, MA 02115 USA. [Lababidi, Samir] US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Vallet, Sonia] Massachusetts Gen Hosp, Ctr Multiple Myeloma, Boston, MA 02114 USA. [Zhou, Yiming; Cartron, Marie-Astrid] Univ Arkansas Med Sci, Myeloma Inst Res & Therapy, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 949 EP 949 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703189 ER PT J AU Mohan, KVK Rao, SS Atreya, CD AF Mohan, Ketha V. K. Rao, Shilpakala Sainath Atreya, Chintamani D. TI Novel Antimicrobial Peptide-Based Blood Safety Strategies for Bacterial Reduction SO BLOOD LA English DT Meeting Abstract CT 50th Annual Meeting of the American-Society-of-Hematology CY DEC 06-09, 2008 CL San Francisco, CA SP Amer Soc Hematol C1 [Mohan, Ketha V. K.; Rao, Shilpakala Sainath; Atreya, Chintamani D.] US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD NOV 16 PY 2008 VL 112 IS 11 BP 1047 EP 1047 PG 1 WC Hematology SC Hematology GA 389OP UT WOS:000262104703481 ER PT J AU Yang, MH Kostov, Y Bruck, HA Rasooly, A AF Yang, Minghui Kostov, Yordan Bruck, Hugh A. Rasooly, Avraharn TI Carbon Nanotubes with Enhanced Chemiluminescence Immunoassay for CCD-Based Detection of Staphylococcal Enterotoxin B in Food SO ANALYTICAL CHEMISTRY LA English DT Article ID LINKED-IMMUNOSORBENT-ASSAY; FIELD-EFFECT TRANSISTORS; SIZED CANTILEVER SENSORS; REAL-TIME; ELECTROCHEMICAL IMMUNOSENSOR; KIT TECRA; ENZYME; BIOSENSOR; AUREUS; AGENTS AB Enhanced chemiluminescence (ECL) detection can significantly enhance the sensitivity of immunoassays but often requires expensive and complex detectors. The need for these detectors limits broader use of ECL in immunoassay applications. To make ECL more practical for immunoassays, we utilize a simple cooled charge-coupled device (CCD) detector combined with carbon nanotubes (CNTs) for primary antibody immobilization to develop a simple and portable point-of-care immunosensor. This combination of ECL, CNT, and CCD detector technologies is used to improve the detection of Staphylococcal enterotoxin B (SEB) in food. Anti-SEB primary antibodies were immobilized onto the CNT surface, and the antibody-nanotube mixture was immobilized onto a polycarbonate surface. SEB was then detected by an ELISA assay on the CNT-polycarbonate surface with an ECL assay. SEB in buffer, soy milk, apple juice, and meat baby food was assayed with a LOD of 0.01 ng/mL using our CCD detector, a level similar to the detection limit obtained with a fluorometric detector when using the CNTs. This level is far more sensitive than the conventional ELISA, which has a LOD of similar to 1 ng/mL. Our simple, versatile, and inexpensive point-of-care immunosensor combined with the CNT-ECL immunoassay method described in this work can also be used to simplify and increase sensitivity for many other types of diagnostics and detection assays. C1 [Yang, Minghui; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Rasooly, Avraharn] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Bruck, Hugh A.] UMCP, College Pk, MD 20742 USA. [Rasooly, Avraharn] NCI, Bethesda, MD 20892 USA. RP Rasooly, A (reprint author), NCI, NIH, 6130 Execut Blvd EPN,Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov FU Intramural NIH HHS [Z99 CA999999] NR 60 TC 57 Z9 63 U1 6 U2 43 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD NOV 15 PY 2008 VL 80 IS 22 BP 8532 EP 8537 DI 10.1021/ac801418n PG 6 WC Chemistry, Analytical SC Chemistry GA 372OM UT WOS:000260910900023 PM 18855418 ER PT J AU Joshi, BH Leland, P Calvo, A Green, JE Puri, RK AF Joshi, Bharat H. Leland, Pamela Calvo, Alfonso Green, Jeffrey E. Puri, Raj K. TI Human Adrenomedullin Up-regulates Interleukin-13 Receptor alpha 2 Chain in Prostate Cancer In vitro and In vivo: A Novel Approach to Sensitize Prostate Cancer to Anticancer Therapy SO CANCER RESEARCH LA English DT Article ID CHIMERIC FUSION PROTEINS; CELL CARCINOMA-CELLS; HUMAN GLIOMA-CELLS; PSEUDOMONAS EXOTOXIN; IL-13 RECEPTOR; SIGNAL-TRANSDUCTION; PANCREATIC TUMORS; GENE-TRANSFER; MUTATED FORM; EXPRESSION AB Interleukin-13 (IL-13) receptor alpha 2 (IL-13R alpha 2), a high-affinity IL-13 binding subunit and a tumor antigen, is amplified in a variety of human tumor cell lines and tumors in vivo. By cDNA microarray, we have shown that gene transfer of human and rat adrenomedullin (AM) up-regulates IL-13R alpha 2 in a human prostate tumor cell line. Here, we show that IL-13R alpha 2 mRNA and protein are also up-regulated in PC-3 prostate tumor cells by recombinant AM (rAM) and human synthetic AM peptide in a dose-dependent manner in vitro and in vivo in mouse prostate tumor model. The 8- to 10-fold up-regulation of IL-13R alpha 2 by rAM or AM peptide in prostate tumor cells in vitro and in vivo increased their sensitivity to IL-13PE cytotoxin consisting of IL-13 and a truncated form of Pseudomonas exotoxin. Immunodeficient mice with established prostate tumors transfected with AM or treated with AM peptide showed reduction in tumor size by intra-tumoral administration of IL-13PE in a dose-dependent manner. At the highest dose (three 100 mu g/kg/d every alternate day), >70% reduction of tumor size was observed compared with controls (P <= 0.01). These results indicate that two completely unrelated hormones (AM and IL-13) are closely related to each other and that we have identified a novel role of AM in sensitizing certain types of prostate tumors to IL-13R-directed therapeutic agent. [Cancer Res 2008;68(22):9311-7] C1 [Joshi, Bharat H.; Leland, Pamela; Puri, Raj K.] US FDA, Tumor Vaccines & Biotechno Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Green, Jeffrey E.] NCI, Cell Biol & Genet Lab, NIH, Bethesda, MD 20892 USA. [Calvo, Alfonso] Univ Navarra, Dept Histol & Pathol, E-31080 Pamplona, Spain. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechno Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov FU Intramural Program of the NIH; Center for Cancer Research; National Cancer Institute and FDA; Center for Biologies Evaluation and Research FX Grant support: Intramural Program of the NIH, Center for Cancer Research, National Cancer Institute and FDA, Center for Biologies Evaluation and Research. NR 37 TC 9 Z9 9 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD NOV 15 PY 2008 VL 68 IS 22 BP 9311 EP 9317 DI 10.1158/0008-5472.CAN-08-2810 PG 7 WC Oncology SC Oncology GA 375TQ UT WOS:000261136600027 PM 19010904 ER PT J AU Sheth, AN Wiersma, P Atrubin, D Dubey, V Zink, D Skinner, G Doerr, F Juliao, P Gonzalez, G Burnett, C Drenzek, C Shuler, C Austin, J Ellis, A Maslanka, S Sobel, J AF Sheth, Anandi N. Wiersma, Petra Atrubin, David Dubey, Vinita Zink, Donald Skinner, Guy Doerr, Fran Juliao, Patricia Gonzalez, German Burnett, Cindy Drenzek, Cherie Shuler, Carrie Austin, John Ellis, Andrea Maslanka, Susan Sobel, Jeremy TI International Outbreak of Severe Botulism with Prolonged Toxemia Caused by Commercial Carrot Juice SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID CLOSTRIDIUM-BOTULINUM; FOODBORNE BOTULISM; TOXIN PRODUCTION; UNITED-STATES; OUTGROWTH AB Background. On 8 September 2006, 3 Georgia residents presented with symptoms of food-borne botulism, a potentially fatal illness caused by Clostridium botulinum neurotoxins. Methods. Investigators reviewed medical records and interviewed patients and family members. Foods from patients' homes and samples of the implicated commercial beverage were tested for botulinum toxin and C. botulinum by standard methods. Results. The patients presented with cranial neuropathies and flaccid paralysis; all patients required mechanical ventilation. The 3 Georgia patients had consumed carrot juice from the same bottle before illness onset. An additional case in Florida and 2 in Ontario, Canada, were subsequently identified in patients who had consumed carrot juice. Serum samples obtained from 5 patients tested positive for botulinum toxin type A-in one patient, 12 days after illness onset, and in another patient, 25 days after illness onset. Carrot juice produced by 1 manufacturer, recovered from patients' homes in Georgia, Florida, and Ontario, yielded type A toxin. The juice contained no added sugar, salt, or preservative; inappropriate refrigeration likely resulted in botulinum toxin production. Conclusion. This outbreak was caused by commercially produced, internationally distributed carrot juice that was contaminated with botulinum toxin. When toxemia persists, treatment for botulism should be considered even if diagnosed weeks after illness onset. The implicated pasteurized carrot juice had no barriers to growth of C. botulinum other than refrigeration; additional protective measures for carrot juice are needed to prevent future outbreaks. The US Food and Drug Administration has since issued industry guidance to reduce the risk of C. botulinum intoxication from low-acid refrigerated juices. C1 [Sheth, Anandi N.; Wiersma, Petra; Juliao, Patricia] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA 30333 USA. [Sheth, Anandi N.; Juliao, Patricia; Sobel, Jeremy] Enter Dis Epidemiol Branch, Atlanta, GA USA. [Maslanka, Susan] Enter Dis Lab Branch, Outbreak Invest Unit, Atlanta, GA USA. [Wiersma, Petra; Gonzalez, German; Burnett, Cindy; Drenzek, Cherie; Shuler, Carrie] Georgia Div Publ Hlth, Atlanta, GA USA. [Atrubin, David] Hillsborough Cty Hlth Dept, Tampa, FL USA. [Zink, Donald] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Skinner, Guy] US FDA, Natl Ctr Food Safety & Technol, Summit, NJ USA. [Doerr, Fran] IIT, Chicago, IL 60616 USA. [Dubey, Vinita] Toronto Publ Hlth, Toronto, ON, Canada. [Austin, John] Hlth Canada, Ottawa, ON K1A 0L2, Canada. [Ellis, Andrea] Publ Hlth Agcy Canada, Guelph, ON, Canada. RP Sheth, AN (reprint author), Ctr Dis Control & Prevent, Epidem Intelligence Serv, 1600 Clifton Rd NE,Mailstop D-63, Atlanta, GA 30333 USA. EM asheth@cdc.gov OI Austin, John/0000-0001-8824-0495 FU CDC; FDA; Health Canada; Public Health Agency of Canada; Georgia Division of Public Health; Hillsborough County Health Department FX Financial support. CDC, FDA, Health Canada, Public Health Agency of Canada, Georgia Division of Public Health, and Hillsborough County Health Department. NR 15 TC 39 Z9 42 U1 2 U2 13 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD NOV 15 PY 2008 VL 47 IS 10 BP 1245 EP 1251 DI 10.1086/592574 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 360ST UT WOS:000260078800001 PM 18834318 ER PT J AU Hu, XM Zhang, D Pang, H Caudle, WM Li, YC Gao, HM Liu, YX Qian, L Wilson, B Di Monte, DA Ali, SF Zhang, J Block, ML Hong, JS AF Hu, Xiaoming Zhang, Dan Pang, Hao Caudle, W. Michael Li, Yachen Gao, Huiming Liu, Yuxin Qian, Li Wilson, Belinda Di Monte, Donato A. Ali, Syed F. Zhang, Jing Block, Michelle L. Hong, Jau-Shyong TI Macrophage Antigen Complex-1 Mediates Reactive Microgliosis and Progressive Dopaminergic Neurodegeneration in the MPTP Model of Parkinson's Disease SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BETA-2 INTEGRIN CD11B/CD18; NADPH OXIDASE ACTIVATION; SUBSTANTIA-NIGRA; OXIDATIVE STRESS; NITRIC-OXIDE; CELL-DEATH; IN-VITRO; HLA-DR; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; NEUROTOXICITY AB Neuronal death is known to trigger reactive microgliosis. However, little is known regarding the manner by which microglia are activated by injured neurons and how microgliosis participates in neurodegeneration. In this study we delineate the critical role of macrophage Ag complex-1 (MAC1), a member of the beta(2) integrin family, in mediating reactive microgliosis and promoting dopaminergic (DAergic) neurodegeneration in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of Parkinson's disease. MAC1 deficiency greatly attenuated the DAergic neurodegeneration induced by MPTP or 1-methyl-4-phenyl-pyridium iodide (MPP+) exposure both in vivo and in vitro, respectively. Reconstituted experiments created by adding microglia from MAC1(-/-) or MAC1(+/+) mice back to MAC1(+/+) neuron-enriched cultures showed that microglia with functional MAC1 expression was mandatory for microglia-enhanced neurotoxicity. Both in vivo and in vitro morphological and Western blot studies demonstrated that MPTP/MPP+ produced less microglia activation in MAC1(-/-) mice than MAC1(+/+) mice. Further mechanistic studies revealed that a MPP+-mediated increase in superoxide production was reduced in MAC1(-/-) neuron-glia cultures compared with MAC1(+/+) cultures. The stunted production of superoxide in MAC1(-/-) microglia is likely linked to the lack of translocation of the cytosolic NADPH oxidase (PHOX) subunit (p47(phox)) to the membrane. In addition, the production of PGE(2) markedly decreased in neuron plus MAC1(-/-) microglia cocultures vs neuron plus MAC1(+/+) microglia cocultures. Taken together, these results demonstrate that MAC1 plays a critical role in MPTP/MPP+-induced reactive microgliosis and further support the hypothesis that reactive microgliosis is an essential step in the self-perpetuating cycle leading to progressive DAergic neurodegeneration observed in Parkinson's disease. The Journal of Immunology, 2008, 181: 7194-7204. C1 [Hu, Xiaoming; Zhang, Dan; Pang, Hao; Li, Yachen; Gao, Huiming; Liu, Yuxin; Qian, Li; Wilson, Belinda; Block, Michelle L.; Hong, Jau-Shyong] NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Res Triangle Pk, NC 27709 USA. [Caudle, W. Michael; Zhang, Jing] Univ Washington, Dept Pathol, Seattle, WA 98104 USA. [Di Monte, Donato A.] Parkinsons Inst, Sunnyvale, CA USA. [Ali, Syed F.] US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Jefferson, AR 72079 USA. [Block, Michelle L.] Virginia Commonwealth Univ, Dept Anat & Neurobiol, Richmond, VA 23298 USA. RP Hong, JS (reprint author), NIEHS, Neuropharmacol Sect, Lab Pharmacol & Chem, Mail Drop F1-01,POB 12233, Res Triangle Pk, NC 27709 USA. EM hong3@niehs.nih.gov RI gao, huiming/C-8454-2012 FU Intramural Research Program of the National Instrunes of Health; National Institutes of Health Pathway to Independence Award [NIEHS IK99ES01549-01] FX This work was supported by the Intramural Research Program of the National Instrunes of Health. National Institute of Environmental Health Sciences. M.L.B. was supported by the National Institutes of Health Pathway to Independence Award (NIEHS IK99ES01549-01). NR 60 TC 57 Z9 59 U1 1 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD NOV 15 PY 2008 VL 181 IS 10 BP 7194 EP 7204 PG 11 WC Immunology SC Immunology GA 372PQ UT WOS:000260913900060 PM 18981141 ER PT J AU Arvidson, KB AF Arvidson, Kirk B. TI FDA toxicity databases and real-time data entry SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE Food safety; QSAR; SAR; Controlled vocabulary; Genetic toxicity databases; Quantitative structure-activity relationship modeling; Safety review; Safety assessment; Subchronic; Chronic teratogeniciry; Structure-searchable databases; Food additives; Food contact substances AB Structure-searchable electronic databases are valuable new tools that are assisting the FDA in its mission to promptly and efficiently review incoming submissions for regulatory approval of new food additives and food contact substances. The Center for Food Safety and Applied Nutrition's Office of Food Additive Safety (CFSAN/OFAS), in collaboration with Leadscope, Inc., is consolidating genetic toxicity data submitted in food additive petitions from the 1960s to the present day. The Center for Drug Evaluation and Research Office of, Pharmaceutical Science's Informatics and Computational Safety Analysis Staff (CDER/OPS/ICSAS) is separately gathering similar information from their submissions. Presently, these data are distributed in various locations such as paper files, microfiche, and non-standardized toxicology memoranda. The organization of the data into a consistent, searchable format will reduce paperwork, expedite the toxicology review process, and provide valuable information to industry that is currently available only to the FDA. Furthermore, by combining chemical structures with genetic toxicity information, biologically active moieties can be identified and used to develop quantitative structure-activity relationship (QSAR) modeling and testing guidelines. Additionally, chemicals devoid of toxicity data can be compared to known structures, allowing for improved safety review through the identification and analysis of structural analogs. Four database frameworks have been created: bacterial mutagenesis, in vitro chromosome aberration, in vitro mammalian mutagenesis, and in vivo micronucleus. Controlled vocabularies for these databases have been established. The four separate genetic toxicity databases are compiled into a single, structurally-searchable database for easy accessibility of the toxicity information. Beyond the genetic toxicity databases described here, additional databases for subchronic, chronic, and teratogenicity studies have been prepared. Published by Elsevier Inc. C1 US FDA, Div Food Contact Notificat, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Arvidson, KB (reprint author), US FDA, Div Food Contact Notificat, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-275, College Pk, MD 20740 USA. EM kirk.arvidson@fda.hhs.gov NR 0 TC 9 Z9 9 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 15 PY 2008 VL 233 IS 1 BP 17 EP 19 DI 10.1016/j.taap.2007.12.033 PG 3 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 380PO UT WOS:000261477800006 PM 18656494 ER PT J AU Mahajan, B Selvapandiyan, A Gerald, NJ Majam, V Zheng, H Wickramarachchi, T Tiwari, J Fujioka, H Moch, JK Kumar, N Aravind, L Nakhasi, HL Kumar, S AF Mahajan, Babita Selvapandiyan, Angamuthu Gerald, Noel J. Majam, Victoria Zheng, Hong Wickramarachchi, Thilan Tiwari, Jawahar Fujioka, Hisashi Moch, J. Kathleen Kumar, Nirbhay Aravind, L. Nakhasi, Hira L. Kumar, Sanjai TI Centrins, Cell Cycle Regulation Proteins in Human Malaria Parasite Plasmodium falciparum SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SPINDLE POLE BODY; CHLAMYDOMONAS-REINHARDTII; CALCIUM-BINDING; SACCHAROMYCES-CEREVISIAE; LEISHMANIA-DONOVANI; MAXIMUM-LIKELIHOOD; TRYPANOSOMA-BRUCEI; MURINE CENTRIN; GENE; DUPLICATION AB Molecules and cellular mechanisms that regulate the process of cell division in malaria parasites remain poorly understood. In this study we isolate and characterize the four Plasmodium falciparum centrins (PfCENs) and, by growth complementation studies, provide evidence for their involvement in cell division. Centrins are cytoskeleton proteins with key roles in cell division, including centrosome duplication, and possess four Ca2+-binding EF hand domains. By means of phylogenetic analysis, we were able to decipher the evolutionary history of centrins in eukaryotes with particular emphasis on the situation in apicomplexans and other alveolates. Plasmodium possesses orthologs of four distinct centrin paralogs traceable to the ancestral alveolate, including two that are unique to alveolates. By real time PCR and/or immunofluorescence, we determined the expression of PfCEN mRNA or protein in sporozoites, asexual blood forms, gametocytes, and in the oocysts developing inside mosquito mid-gut. Immunoelectron microscopy studies showed that centrin is expressed in close proximity with the nucleus of sporozoites and asexual schizonts. Furthermore, confocal and widefield microscopy using the double staining with alpha-tubulin and centrin antibodies strongly suggested that centrin is associated with the parasite centrosome. Following the episomal expression of the four PfCENs in a centrin knock-out Leishmania donovani parasite line that exhibited a severe growth defect, one of the PfCENs was able to partially restore Leishmania growth rate and overcome the defect in cytokinesis in such mutant cell line. To our knowledge, this study is the first characterization of a Plasmodium molecule that is involved in the process of cell division. These results provide the opportunity to further explore the role of centrins in cell division in malaria parasites and suggest novel targets to construct genetically modified, live attenuated malaria vaccines. C1 [Kumar, Sanjai] US FDA, CBER, DETTD, OBRR, Rockville, MD 20852 USA. [Tiwari, Jawahar] US FDA, Ctr Biol Evaluat & Res, Div Biostat, Rockville, MD 20852 USA. [Fujioka, Hisashi] Case Western Reserve Univ, Dept Pharmacol, Cleveland, OH 44106 USA. [Moch, J. Kathleen] Walter Reed Army Inst Res, Dept Immunol, Silver Spring, MD 20910 USA. [Kumar, Nirbhay] Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. [Aravind, L.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), US FDA, CBER, DETTD, OBRR, 1401 Rockville Pike HFM-313, Rockville, MD 20852 USA. EM sanjai.kumar@fda.hhs.gov NR 64 TC 20 Z9 21 U1 0 U2 3 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD NOV 14 PY 2008 VL 283 IS 46 BP 31871 EP 31883 DI 10.1074/jbc.M800028200 PG 13 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 370KJ UT WOS:000260760800070 PM 18693242 ER PT J AU Ovanesov, MV Ayhan, Y Wolbert, C Moldovan, K Sauder, C Pletnikov, MV AF Ovanesov, Mikhail V. Ayhan, Yavuz Wolbert, Candie Moldovan, Krisztina Sauder, Christian Pletnikov, Mikhail V. TI Astrocytes play a key role in activation of microglia by persistent Borna disease virus infection SO JOURNAL OF NEUROINFLAMMATION LA English DT Article ID SV40 LARGE T; GENE-EXPRESSION; INNATE IMMUNITY; BRAIN-INJURY; CELL-LINE; RAT; NEURONS; CHEMOKINE; MODEL; CNS AB Neonatal Borna disease virus (BDV) infection of the rat brain is associated with microglial activation and damage to certain neuronal populations. Since persistent BDV infection of neurons is nonlytic in vitro, activated microglia have been suggested to be responsible for neuronal cell death in vivo. However, the mechanisms of activation of microglia in neonatally BDV-infected rat brains remain unclear. Our previous studies have shown that activation of microglia by BDV in culture requires the presence of astrocytes as neither the virus nor BDV-infected neurons alone activate microglia. Here, we evaluated the mechanisms whereby astrocytes can contribute to activation of microglia in neuron-glia-microglia mixed cultures. We found that persistent infection of neuronal cells leads to activation of uninfected astrocytes as measured by elevated expression of RANTES. Activation of astrocytes then produces activation of microglia as evidenced by increased formation of round-shaped, MHCI-, MHCII- and IL-6-positive microglia cells. Our analysis of possible molecular mechanisms of activation of astrocytes and/or microglia in culture indicates that the mediators of activation may be soluble heat-resistant, low molecular weight factors. The findings indicate that astrocytes may mediate activation of microglia by BDV-infected neurons. The data are consistent with the hypothesis that microglia activation in the absence of neuronal damage may represent initial steps in the gradual neurodegeneration observed in brains of neonatally BDV-infected rats. C1 [Ovanesov, Mikhail V.; Ayhan, Yavuz; Wolbert, Candie; Moldovan, Krisztina; Pletnikov, Mikhail V.] Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. [Sauder, Christian] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. EM ovanesov@gmail.com; yayhan1@jhmi.edu; cwolbert03@sprintpcs.com; kmoldov1@jhu.edu; christian.sauder@fda.hhs.gov; mpletnik@jhmi.edu FU [R01MH048948] FX The study was supported by R01MH048948 (MVP). The authors also want to express their gratitude to Drs Ellen Silbergeld and Jeniffer Nyland (JH Bloomberg School of Public Health) for their generous help with multiplex assays. John Hiscott, PhD, McGill University, Montreal, Canada, Dr Peter Collins and Dr Ulla Buchholz, NIH, Bethesda, MD, USA for their generous permission to work with and donation of VSV-GFP virus. The authors would like to thank Dr Friedemann Weber (University of Freiburg, Freiburg, Germany) for his insightful discussion of the study. NR 49 TC 27 Z9 28 U1 1 U2 3 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-2094 J9 J NEUROINFLAMM JI J. Neuroinflamm. PD NOV 11 PY 2008 VL 5 AR 50 DI 10.1186/1742-2094-5-50 PG 14 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA 380AE UT WOS:000261437100001 PM 19014432 ER PT J AU Lindsey, NP Schroeder, BA Miller, ER Braun, MM Hinckley, AF Marano, N Slade, BA Barnett, ED Brunette, GW Horan, K Staples, JE Kozarsky, PE Hayes, EB AF Lindsey, Nicole P. Schroeder, Betsy A. Miller, Elaine R. Braun, M. Miles Hinckley, Alison F. Marano, Nina Slade, Barbara A. Barnett, Elizabeth D. Brunette, Gary W. Horan, Katherine Staples, J. Erin Kozarsky, Phyllis E. Hayes, Edward B. TI Adverse event reports following yellow fever vaccination SO VACCINE LA English DT Article DE Yellow fever; Vaccine; Adverse event; VAERS ID INACTIVATED INFLUENZA VACCINE; VISCEROTROPIC DISEASE; SUBCUTANEOUS INJECTION; ELDERLY ADULTS; CLINICAL-TRIAL; ADVANCED AGE; RISK-FACTOR; SAFETY; IMMUNOGENICITY; BRAZIL AB Yellow fever (YF) vaccine has been used for prevention of YF since 1937 with over 500 million doses administered. However, rare reports of severe adverse events following vaccination have raised concerns about the vaccine's safety. We reviewed reports of adverse events following YF vaccination reported to the U.S. Vaccine Adverse Event Reporting System (VAERS) from 2000 to 2006. We used estimates of age and sex distribution of administered closes obtained from a 2006 survey of authorized vaccine providers to calculate age- and sex-specific reporting rates of all serious adverse events (SAE), anaphylaxis, YF vaccine-associated neurotropic disease, and YF vaccine-associated viscerotropic disease. Reporting rates of SAEs were substantially higher in males and in persons aged :60 years. These findings reinforce the generally acceptable safety profile of YF vaccine, but highlight: the importance of physician and traveler education regarding the risks and benefits of YF vaccination, particularly for travelers >= 60 years of age. Vaccination should be limited to persons traveling to areas where the risk of YF is expected to exceed the risk of serious adverse events after vaccination, or if not medically contraindicated, where national regulations require proof of vaccination to prevent introduction of YF. Published by Elsevier Ltd. C1 [Lindsey, Nicole P.; Hinckley, Alison F.; Staples, J. Erin; Hayes, Edward B.] Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Natl Ctr Zoonot Vector Borne & Enter Dis, Ft Collins, CO 80521 USA. [Schroeder, Betsy A.; Marano, Nina; Brunette, Gary W.; Horan, Katherine; Kozarsky, Phyllis E.] Ctr Dis Control & Prevent, Natl Ctr Preparedness Detect & Control Infect Dis, Div Global Migrat & Quarantine, Atlanta, GA USA. [Miller, Elaine R.; Slade, Barbara A.] Ctr Dis Control & Prevent, Immunizat Safety Off, Off Chief Sci Officer, Atlanta, GA USA. [Braun, M. Miles] US FDA, Ctr Biol Evaluat & Res, Div Epidemiol, Rockville, MD 20857 USA. [Barnett, Elizabeth D.] Boston City Hosp, Maxwell Finland Lab Infect Dis, Clin Immunizat Safety Assessment Ctr, Boston, MA 02118 USA. [Kozarsky, Phyllis E.] Emory Univ, Sch Med, Div Infect Dis, Dept Med, Atlanta, GA USA. RP Lindsey, NP (reprint author), Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Natl Ctr Zoonot Vector Borne & Enter Dis, 3150 Rampart Rd, Ft Collins, CO 80521 USA. EM nplindsey@cdc.gov OI Barnett, Elizabeth/0000-0003-4822-5949 NR 42 TC 123 Z9 126 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 NOV 11 PY 2008 VL 26 IS 48 BP 6077 EP 6082 DI 10.1016/j.vaccine.2008.09.009 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 381LS UT WOS:000261538200007 PM 18809449 ER PT J AU Derrick, SC Perera, LP Dheenadhayalan, V Yang, A Kolibab, K Morris, SL AF Derrick, Steven C. Perera, L. P. Dheenadhayalan, Veerabadran Yang, Amy Kolibab, Kristopher Morris, Sheldon L. TI The safety of post-exposure vaccination of mice infected with Mycobacterium tuberculosis SO VACCINE LA English DT Article DE Tuberculosis; Vaccine; Safety ID DNA VACCINATION; PROTECTIVE IMMUNITY; FUSION PROTEIN; MOUSE MODEL; GUINEA-PIGS; VACCINES; BCG; EFFICACY; DISEASE AB New post-exposure tuberculosis vaccination strategies are being developed to prevent disease in individuals latently infected with Mycobacterium tuberculosis. However, concerns about the potential induction of deleterious Koch-like reactions after immunization of persons with latent tuberculosis has limited progress in assessing the effectiveness of post-exposure vaccination. To evaluate the safety of immunization after M. tuberculosis infection, two mouse models were established, a drug treatment low bacterial burden model and an active disease model. Twelve different M. tuberculosis antigen preparations and vaccines (including DNA, subunit, viral vectored, and live, attenuated vaccines) were evaluated using these mouse models. In the low bacterial burden model, post-exposure vaccination did not induce significant reactivational disease and only injection of BCG evoked increases in]Ling inflammatory responses at I month after the immunizations. Additionally, although significant increases in lung inflammation were seen for animals injected with the hps65 DNA vaccine or a M. tuberculosis culture supernatant preparation, no differences in the survival periods were detected between vaccinated and non-vaccinated mice at 10 months post-immunization using the low bacterial burden model. For the active disease model, significantly more lung inflammation was observed at I month after administration of the hsp65 DNA vaccine but none of the antigen preparations tested increased the lung bacterial burdens at this early time point. Furthermore, vaccination of diseased mice with BCG or TB DNA vaccines did not significantly affect mortality rates compared to non-vaccinated controls at 10 months post-immunization. Overall, these data suggest that while the potential risk of inducing Koch-like reactions is low after immunization of persons with latent tuberculosis, extreme caution is still needed as post-exposure vaccines progress from pre-clinical experiments into the initial phases of clinical testing. Published by Elsevier Ltd. C1 [Derrick, Steven C.; Yang, Amy; Kolibab, Kristopher; Morris, Sheldon L.] US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. [Perera, L. P.] NCI, Metab Branch, Ctr Canc Res, Bethesda, MD 20892 USA. [Dheenadhayalan, Veerabadran] Aeras Global TB Vaccine Fdn, Rockville, MD 20850 USA. RP Derrick, SC (reprint author), Bldg 29,Room 509,29 Lincoln Dr, Bethesda, MD 20892 USA. EM steven.derrick@fda.hhs.gov NR 29 TC 14 Z9 17 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 NOV 11 PY 2008 VL 26 IS 48 BP 6092 EP 6098 DI 10.1016/j.vaccine.2008.09.011 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 381LS UT WOS:000261538200009 PM 18809446 ER PT J AU Murata, H Teferedegne, B Sheng, L Lewis, AM Peden, K AF Murata, Haruhiko Teferedegne, Belete Sheng, Li Lewis, Andrew M., Jr. Peden, Keith TI Identification of a neutralization epitope in the VP1 capsid protein of SV40 SO VIROLOGY LA English DT Article DE SV40; VP1; Neutralization; Epitope; Monoclonal antibody ID HUMAN POLYOMAVIRUS; SIMIAN VIRUS-40; HUMAN CANCER; JC VIRUS; BK VIRUS; SIMIAN-VIRUS-40; VECTORS; ANTIBODIES; RESOLUTION; THERAPY AB Three SV40 escape Mutants were identified by selection in the presence of monoclonal antibodies with neutralizing activity. The VP1 amino acid alterations in these Mutants were: (1) K73 -> E (in loop BC); (2) D77 -> E (in loop BC): (3) K171 -> R (in loop EF): and (4) Q175 -> H (in loop EF). These residues are clustered in close proximity to each other oil the surface of the native capsid protein, strongly suggesting that they form a conformational epitope directly recognized by the neutralizing antibody. To Our knowledge, the present Study represents the first experimental mapping of a neutralization epitope of a polyomavirus family member. Structural information regarding the neutralization epitope should be useful for clarifying, the extent of cross-reactivity exhibited by the humoral immune response towards related primate polyomaviruses (e.g., SV40, BKV, and JCV). Published by Elsevier Inc. C1 [Teferedegne, Belete; Sheng, Li; Peden, Keith] FDA, CBER, Div Viral Prod, Lab Retrovirus Res, Bethesda, MD 20892 USA. [Murata, Haruhiko; Teferedegne, Belete; Lewis, Andrew M., Jr.] FDA, CBER, Div Viral Prod, Lab DNA Viruses, Bethesda, MD 20892 USA. RP Peden, K (reprint author), FDA, CBER, Div Viral Prod, Lab Retrovirus Res, Bldg 29A,Room 3D08,29 Lincoln Dr, Bethesda, MD 20892 USA. EM keith.peden@fda.hhs.gov FU NCI/FDA Interagency Oncology Task Force FX We thank Walter Scott for providing the SV40 monoclonal antibodies; Michael Klutch for advice and technical assistance; and Ron Lundquist, Ira Berkower, and Steve Feinstone for comments oil the manuscript. HM was supported by the NCI/FDA Interagency Oncology Task Force Fellowship Training Program 4 (for Cancer Prevention Fellows). NR 27 TC 15 Z9 15 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD NOV 10 PY 2008 VL 381 IS 1 BP 116 EP 122 DI 10.1016/j.virol.2008.07.032 PG 7 WC Virology SC Virology GA 368BB UT WOS:000260595200016 PM 18789470 ER PT J AU Lau, P Verrier, JD Nielsen, JA Johnson, KR Notterpek, L Hudson, LD AF Lau, Pierre Verrier, Jonathan D. Nielsen, Joseph A. Johnson, Kory R. Notterpek, Lucia Hudson, Lynn D. TI Identification of Dynamically Regulated MicroRNA and mRNA Networks in Developing Oligodendrocytes SO JOURNAL OF NEUROSCIENCE LA English DT Article DE microRNA; posttranscriptional regulation; oligodendrocyte; PMP22; myelin; glia ID PERIPHERAL MYELIN PROTEIN-22; MAMMALIAN MICRORNAS; ANIMAL MICRORNAS; GENOMIC ANALYSIS; GENE-EXPRESSION; BRAIN; DISEASE; DIFFERENTIATION; SPECIFICATION; DROSOPHILA AB MicroRNAs (miRNAs) play important roles in modulating gene expression at the posttranscriptional level. In postnatal oligodendrocyte lineage cells, the miRNA expression profile (" microRNAome") contains 43 miRNAs whose expression dynamically changes during the transition from A2B5(+) oligodendrocyte progenitor cells to premyelinating GalC(+) cells. The combination of microRNAome profiling with analyses of the oligodendrocyte transcriptome reveals a target bias for a class of miRNAs which includes miR-9. We show that miR-9 is downregulated during oligodendrocyte differentiation. In addition, miR-9 expression level inversely correlates with the expression of its predicted targets, among which is the peripheral myelin protein PMP22. We found that PMP22 mRNA but not protein is detectable in oligodendrocytes, whereas Schwann cells producing PMP22 protein lack miR-9. We demonstrate that miR-9 interacts with the 3' untranslated region of PMP22 and downregulates its expression. Our results support models in which miRNAs can act as guardians of the transcriptome. C1 [Lau, Pierre; Nielsen, Joseph A.; Hudson, Lynn D.] NINDS, Sect Dev Genet, Natl Inst Hlth, Bethesda, MD 20892 USA. [Johnson, Kory R.] NINDS, Bioinformat Neurosci Grp, Informat Technol Program, Div Intramural Res,NIH, Bethesda, MD 20892 USA. [Verrier, Jonathan D.; Notterpek, Lucia] Univ Florida, McKnight Brain Inst, Dept Neurosci, Gainesville, FL 32610 USA. RP Hudson, LD (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM hudsonl1@od.nih.gov FU National Institute of Neurological Disorders and Stroke; Muscular Dystrophy Association; McKnight Brain Institute; Joshua Benjamin Weitzel Fund for Developmental Neurobiology FX This work was supported by intramural funds from National Institute of Neurological Disorders and Stroke (NINDS) (L. D. H.), the Muscular Dystrophy Association (L. N.), the McKnight Brain Institute (L. N.), and the Joshua Benjamin Weitzel Fund for Developmental Neurobiology (L. N.). We thank Naser Muja (Johns Hopkins University, Baltimore, MD) for preliminary experiments and Jo Ann Berndt (NINDS) and Elena Romm (NINDS) for expert technical assistance. We are indebted to Dragan Maric (NINDS) for purification of oligodendrocytes and Abdel Elkahloun (National Human Genome Research Institute) for Affymetrix microarray processing. We are grateful to Jim Nagle (NINDS) and Deborah Kauffman (NINDS) for their support in DNA sequencing. We thank Christopher Brown (Applied Biosystems) and David Armistead (Applied Biosystems) for their expertise in real-time PCR. We thank Monique Dubois- Dalcq (NINDS) for critical reading of this manuscript. The miRNA microarray data reported in this study is deposited in the European Molecular Biology Laboratory/European Bioinformatics Institute ArrayExpress database (accession E-MEXP-1589) and the DNA microarray data in the Gene Expression Omnibus database (accession GSE11218). NR 43 TC 132 Z9 142 U1 1 U2 11 PU SOC NEUROSCIENCE PI WASHINGTON PA 11 DUPONT CIRCLE, NW, STE 500, WASHINGTON, DC 20036 USA SN 0270-6474 J9 J NEUROSCI JI J. Neurosci. PD NOV 5 PY 2008 VL 28 IS 45 BP 11720 EP 11730 DI 10.1523/JNEUROSCI.1932-08.2008 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 369AV UT WOS:000260665900030 PM 18987208 ER PT J AU Yu, L Putnak, JR Pletnev, AG Markoff, L AF Yu, Li Putnak, J. Robert Pletnev, Alexander G. Markoff, Lewis TI Attenuated West Nile viruses bearing 3 ' SL and envelope gene substitution mutations SO VACCINE LA English DT Article DE Live West Nile vaccine; Flavivirus 3 ' SL mutation; Attenuation of neurovirulence ID JAPANESE ENCEPHALITIS-VIRUS; CD8(+) T-CELLS; LETHAL CHALLENGE; MOLECULAR-BASIS; UNITED-STATES; NY99 STRAIN; GENOMIC RNA; VACCINE; FLAVIVIRUS; NEUROVIRULENCE AB Four viable West Nile (WN) 3'SL-mutant Viruses were evaluated for neuroinvasiveness and neurovirulence in mice. All mutants were highly attenuated for neuroinvasiveness. However, only one of these four (WNmutE virus) was significantly attenuated for neurovirulence. To attenuate WNmutE virus further, we introduced five substitution mutations into the envelope (env) gene segment in wild-type (wt) WN and WNmutE genomes, based on differences in the env gene Sequence between the live Japanese encephalitis vaccine (SA14-14-2) and its virulent parent. The env gene mutations had an attenuating effect in the context of the wt WNV genome but only a Marginal enhancing effect on the attenuation of WNmutE virus. Published by Elsevier Ltd. C1 [Yu, Li; Markoff, Lewis] US FDA, Div Viral Prod, Lab Vector Borne Virus Dis, Bethesda, MD 20892 USA. [Putnak, J. Robert] Walter Reed Army Inst Res, Div Communicable Dis & Immunol, Silver Spring, MD 20910 USA. [Pletnev, Alexander G.] NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Yu, L (reprint author), Bg 29A,Room 1B18,NIH Campus,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Li.Yu@fda.hhs.gov FU National Vaccine Program FX The authors thank Dr. V. Yamshchikov for the gift of the West Nile Virus strain B956 infectious DNA. This work was partially supported by a grant from the National Vaccine Program. NR 36 TC 19 Z9 20 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD NOV 5 PY 2008 VL 26 IS 47 BP 5981 EP 5988 DI 10.1016/j.vaccine.2008.08.064 PG 8 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 384MZ UT WOS:000261750200014 PM 18805457 ER PT J AU Karbiwnyk, CM Faul, KC Turnipseed, SB Andersen, WC Miller, KE AF Karbiwnyk, Christine M. Faul, Kent C. Turnipseed, Sherri B. Andersen, Wendy C. Miller, Keith E. TI Determination of oxytocin in a dilute IV solution by LC-MSn SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Oxytocin; IV solution; Liquid chromatography; Ion-trap mass spectrometry ID PERFORMANCE LIQUID-CHROMATOGRAPHY; HYPOTHALAMIC PARAVENTRICULAR NUCLEUS; CAPILLARY-ZONE-ELECTROPHORESIS; MASS-SPECTROMETRY; BIOLOGICAL SAMPLES; REVERSED-PHASE; NEUROHYPOPHYSEAL PEPTIDES; ELECTROSPRAY-IONIZATION; ARGININE-VASOPRESSIN; HPLC METHOD AB The most common drug prescribed to induce labor in the United States is oxytocin, a peptide hormone composed of nine amino acids. Oxytocin is often reconstituted in intravenous (IV) saline solutions at less than 0.05 units ml(-1) (125 ng ml(-1)) to be delivered at 1-4 drops per minute. Existing LC-UV methods for oxytocin do not have sufficient detection limits to quantitate and/or confirm oxytocin in IV solutions without sample concentration. A determinative and confirmatory method for oxytocin was developed using an LC-MSn ion trap instrument with an electrospray ionization (ESI) interface in positive ion mode. Separation was achieved on a C-18 column using an isocratic elution of water with 50% acetonitrile (v/v) and water with 0.05% formic acid (v/v) at a flow rate of 250 mu l min(-1). Data was acquired from the selected ion monitoring (SIM) of the precursor ion (m/z 1007.3) and MS2 scans from the collision induced dissociation of m/z 1007.3 at 30% collision energy. In this method, MS2 full scans were utilized to obtain three structurally significant ions for the unambiguous identification of oxytocin. Calibration standards, prepared in de-ionized water from 0.006 to 0.046 units ml(-1), were linear with an R-2 value of 0.9983. The methods LOD and LOQ were 0.00084 and 0.0029 units ml(-1) (2 and 7 ng ml(-1)), respectively. This LC-MSn method was used to determine the amount of oxytocin in a 0.04 units ml(-1) clinical sample that was prepared in 0.9% sodium chloride IV solution. Published by Elsevier B.V. C1 [Karbiwnyk, Christine M.; Turnipseed, Sherri B.; Andersen, Wendy C.] US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. [Faul, Kent C.] US FDA, Denver Dist Lab, Denver, CO 80225 USA. [Miller, Keith E.] Univ Denver, Denver, CO USA. RP Karbiwnyk, CM (reprint author), US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. EM christine.karbiwnyk@fda.hhs.gov NR 35 TC 9 Z9 10 U1 2 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD NOV 4 PY 2008 VL 48 IS 3 BP 672 EP 677 DI 10.1016/j.jpba.2008.06.016 PG 6 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 362KL UT WOS:000260196500023 PM 18678458 ER PT J AU Van Wagoner, RM Deeds, JR Satake, M Ribeiro, AA Place, AR Wright, JLC AF Van Wagoner, Ryan M. Deeds, Jonathan R. Satake, Masayuki Ribeiro, Anthony A. Place, Allen R. Wright, Jeffrey L. C. TI Isolation and characterization of karlotoxin 1, a new amphipathic toxin from Karlodinium veneficum SO TETRAHEDRON LETTERS LA English DT Article DE Karlotoxin; Hemolytic toxin; Dinoflagellate; Amphidinol ID DINOFLAGELLATE AMPHIDINIUM-SP; MEMBRANE-PERMEABILIZING ACTIVITIES; SPIN-COUPLING CONSTANTS; MARINE DINOFLAGELLATE; CONFIGURATION ANALYSIS; POLYHYDROXYL COMPOUND; LSU RDNA; ANTIFUNGAL; KLEBSII; MICRUM AB The karlotoxins (KmTxs) are a family of compounds produced by the dinoflagellate Karlodinium veneficum which cause membrane permeabilization. The structure of KmTx 1, determined using extensive 2D NMR spectroscopy, is very similar to that of the amphidinols and related compounds, though KmTx I features unique structural modifications of the conserved core region. The structure of KmTx I differs from that reported for KmTx 2, the only other reported karlotoxin to date, in lacking chlorination at its terminal alkene and possessing a hydrophobic arm that is two carbons longer. (C) 2008 Elsevier Ltd. All rights reserved. C1 [Van Wagoner, Ryan M.; Satake, Masayuki; Wright, Jeffrey L. C.] Univ N Carolina, Ctr Marine Sci, Wilmington, NC 28409 USA. [Deeds, Jonathan R.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Ribeiro, Anthony A.] Univ Durham, Med Ctr, Duke NMR Ctr, Durham, NC 27710 USA. [Ribeiro, Anthony A.] Univ Durham, Med Ctr, Dept Radiol, Durham, NC 27710 USA. [Ribeiro, Anthony A.] Univ Durham, Med Ctr, Dept Biochem, Durham, NC 27710 USA. [Place, Allen R.] Univ Maryland, Inst Biotechnol, Ctr Marine Biotechnol, Baltimore, MD 21202 USA. RP Wright, JLC (reprint author), Univ N Carolina, Ctr Marine Sci, 5600 Marvin K Moss Lane, Wilmington, NC 28409 USA. EM wrightj@uncw.edu RI Place, Allen/F-9267-2013 FU NIH [5P41GM076300-01, R01 A1057588]; North Carolina Dept. of Health and Human Services [01505-04]; NOAA-ECOHAB [MML-106390A]; NCI [P30-CA-14236]; NOAA [NA04NOS4780276]; CDC [U50/CCU 323376]; Maryland Department of Health and Mental Hygiene; Center of Marine Biotechnology [08-192]; ECOHAB [289]; NSF; NC Biotechnology Center; Duke University; NSF, Division of Biological Infrastructure [DBI-0100085] FX We express gratitude to C. Tomas and A.C. Tatters (UNCW-CMS) for performing hemolytic assays on purified KmTx 1. Funding supporting this research was provided by the NIH (5P41GM076300-01, JLCW; R01 A1057588, AAR), the North Carolina Dept. of Health and Human Services (01505-04, JLCW), NOAA-ECOHAB (MML-106390A, JLCW), NCI (P30-CA-14236, AAR), NOAA Coastal Ocean Program (NA04NOS4780276, University of Maryland Biotechnology Institute), the CDC (U50/CCU 323376, ARP), and the Maryland Department of Health and Mental Hygiene (ARP). This is contribution #08-192 from the Center of Marine Biotechnology and contribution #289 from the ECOHAB program. NMR instrumentation in the Duke NMR Center was funded by the NSF, the NIH, the NC Biotechnology Center and Duke University. We thank Mr. F. Sun (University of Illinois at Urbana-Champaign) for collecting high-resolution MS data. The Q-Tof Ultima mass spectrometer (UIUC) was purchased in part with a grant from the NSF, Division of Biological Infrastructure (DBI-0100085). NR 38 TC 41 Z9 41 U1 0 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0040-4039 J9 TETRAHEDRON LETT JI Tetrahedron Lett. PD NOV 3 PY 2008 VL 49 IS 45 BP 6457 EP 6461 DI 10.1016/j.tetlet.2008.08.103 PG 5 WC Chemistry, Organic SC Chemistry GA 365HW UT WOS:000260397500021 PM 20798789 ER PT J AU Li, H Giger, ML Yuan, YD Chen, WJ Horsch, K Lan, L Jamieson, AR Sennett, CA Jansen, SA AF Li, Hui Giger, Maryellen L. Yuan, Yading Chen, Weijie Horsch, Karla Lan, Li Jamieson, Andrew R. Sennett, Charlene A. Jansen, Sanaz A. TI Evaluation of Computer-aided Diagnosis on a Large Clinical Full-field Digital Mammographic Dataset SO ACADEMIC RADIOLOGY LA English DT Article DE Computer-aided diagnosis; full-field digital mammography; breast mass classification ID MAXIMUM-LIKELIHOOD-ESTIMATION; SCREEN-FILM MAMMOGRAPHY; BREAST-CANCER; DIGITIZED MAMMOGRAMS; DETECTION CAD; ROC CURVES; CLASSIFICATION; MASSES; BENIGN; LESIONS AB Rationale and Objectives. To convert and optimize our previously developed computerized analysis methods for use with images from full-field digital mammography (FFDM) for breast mass classification to aid in the diagnosis of breast cancer. Materials and Methods. An institutional review board approved protocol was obtained, with waiver of consent for retrospective use of mammograms and pathology data. Seven hundred thirty-nine FFDM images, which contained 287 biopsy-proven breast mass lesions, of which 148 lesions were malignant and 139 lesions were benign, were retrospectively collected. Lesion margins were delineated by an expert breast radiologist and were used as the truth for lesion-segmentation evaluation. Our computerized image analysis method consisted of several steps: 1) identified lesions were automatically extracted from the parenchymal background using computerized segmentation methods: 2) a set of image characteristics (mathematic descriptors) were automatically extracted from image data of the lesions and surrounding tissues; and 3) selected features were merged into an estimate of the probability of malignancy using a Bayesian artificial neural network classifier. Performance of the analyses was evaluated at various stages of the conversion using receiver-operating characteristic analysis. Results. An area under the curve value of 0.81 was obtained in the task of distinguished between malignant and benign mass lesions in a round-robin by case evaluation on the entire FFDM dataset. We failed to show a statistically significant difference (P = .83) compared to results from our previous study in which the computerized classification was performed on digitized screen-film mammograms. Conclusions. Our computerized analysis methods developed on digitized screen-film mammography can be converted for use with FFDM. Results show that the computerized analysis methods for the diagnosis of breast mass lesions on FFDM are promising, and can potentially be used to aid clinicians in the diagnostic interpretation of FFDM. C1 [Li, Hui; Giger, Maryellen L.; Yuan, Yading; Horsch, Karla; Lan, Li; Jamieson, Andrew R.; Sennett, Charlene A.; Jansen, Sanaz A.] Univ Chicago, Dept Radiol, Chicago, IL 60637 USA. [Chen, Weijie] US FDA, Lab Assessment Med Imaging Syst, Div Imaging & Appl Math, Off Sci & Engn Labs,CDRH, Silver Spring, MD USA. RP Li, H (reprint author), Univ Chicago, Dept Radiol, 5841 S Maryland Ave, Chicago, IL 60637 USA. EM huili@uchicago.edu RI Yuan, Yading/C-5435-2011; Chen, Weijie/A-3712-2012; OI Giger, Maryellen/0000-0001-5482-9728 FU NCI NIH HHS [P50 CA125183-010001, P50 CA125183, P50 CA125183-020001, P50 CA125183-030001, P50-CA125183, R01 CA089452, R01 CA089452-01, R01 CA089452-02, R01 CA089452-03, R01 CA089452-04, R01 CA089452-05, R01-CA89452, R21 CA113800, R21 CA113800-01A1, R21 CA113800-02, R21-CA113800] NR 42 TC 18 Z9 18 U1 2 U2 4 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 NOV PY 2008 VL 15 IS 11 BP 1437 EP 1445 DI 10.1016/j.acra.2008.05.004 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 369PY UT WOS:000260707600010 PM 18995194 ER PT J AU Chan-Tack, KM Struble, KA Birnkrant, DB AF Chan-Tack, Kirk M. Struble, Kimberly A. Birnkrant, Debra B. TI Intracranial Hemorrhage and Liver-Associated Deaths Associated with Tipranavir/Ritonavir: Review of Cases from the FDA's Adverse Event Reporting System SO AIDS PATIENT CARE AND STDS LA English DT Article ID RITONAVIR; AIDS AB Tipranavir (TPV), a protease inhibitor, has box warnings for intracranial hemorrhage (ICH) and hepatotoxicity (including hepatic failure and death). A box warning is a labeling statement about serious adverse events leading to significant injury and/or death. A box warning is the most serious warning placed in the labeling of a prescription medication. As a result of the respective morbidity and mortality associated with ICH and hepatic failure, the Food and Drug Administration's (FDA's) Adverse Event Reporting System (AERS) was searched for reports of these adverse events in HIV-infected patients receiving a tipranavir/ritonavir (TPV/r)-based regimen. This search comprised part of the FDA's safety analysis for traditional approval. From July 2006 to March 2007, 10 cases of ICH were identified in AERS. From June 2005 to March 2007, 12 cases of liver-associated deaths were identified. One patient experienced liver failure and fatal ICH. Most patients with these events had additional risk factors. Among patients with liver-associated deaths, 3 had HIV-RNA less than 400 copies per milliliter at the time of hepatic failure. Among 10 patients who discontinued TPV/r when hepatic failure developed, median number of days post-TPV/r to death was 23 (range, 2-69 days). Review of AERS did not identify new safety concerns regarding ICH. Among most patients with liver-associated deaths, death appears to occur soon after hepatic failure develops. If considering TPV/r, careful assessment of risk/benefit is suggested for patients at risk for ICH and hepatic failure. C1 [Chan-Tack, Kirk M.] US FDA, CDER, OND, DAVP, Silver Spring, MD 20993 USA. RP Chan-Tack, KM (reprint author), US FDA, CDER, OND, DAVP, 10903 New Hampshire Ave,Bldg 22,Room 6337, Silver Spring, MD 20993 USA. EM kirk.chan-tack@fda.hhs.gov NR 13 TC 15 Z9 15 U1 0 U2 0 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1087-2914 J9 AIDS PATIENT CARE ST JI Aids Patient Care STDS PD NOV PY 2008 VL 22 IS 11 BP 843 EP 850 DI 10.1089/apc.2008.0043 PG 8 WC Public, Environmental & Occupational Health; Infectious Diseases SC Public, Environmental & Occupational Health; Infectious Diseases GA 378SM UT WOS:000261344200002 PM 19025478 ER PT J AU Elkins, CA Munoz, ME Mullis, LB Stingley, RL Hart, ME AF Elkins, Christopher A. Enriqueta Munoz, Maria Mullis, Lisa B. Stingley, Robin L. Hart, Mark E. TI Lactobacillus-mediated inhibition of clinical toxic shock syndrome Staphylococcus aureus strains and its relation to acid and peroxide production SO ANAEROBE LA English DT Article DE Lactobacillus; Staphylococcus; Toxic shock syndrome; Vaginal microbiota; Lactic acid; Peroxide; Probiotic ID DELBRUECKII SUBSP LACTIS; HYDROGEN-PEROXIDE; VAGINAL LACTOBACILLI; BACTERIA; PROBIOTICS; TRACT; WOMEN; IDENTIFICATION; 5-DEGREES-C; INFECTIONS AB The inhibitory activities of 39 strains representing 20 different species of Lactobacillus toward a menstrual toxic shock syndrome (TSS) Staphylococcus aureus archetype strain MN8 were investigated. Nearly every strain (38 of 39) produced an inhibitory effect under both aerobic and anaerobic conditions when assayed on agar medium. In addition, the MN8 inhibition was conserved against at least 10 other clinical TSS S. aureus isolates and, interestingly, required actively growing cultures of Lactobacillus (verified with a two-well co-culture system in broth medium). This general uniform inhibition could be ameliorated by organic buffer (PIPES) supplied in the growth medium and, with only one exception, MRS medium adjusted with non-organic acid (HCl) failed to support growth of TSS strains at or below pH 5.5. By comparison, the vast majority of lactobacilli in this Study decreased culture pH to a range of 4-5. Hydrogen peroxide production by the lactobacilli was also assessed and verified by two different methodologies revealing a broad spectrum of phenotypes that, contrary to reports touting its effectiveness, did not seem to correspond with our inhibition studies. Furthermore, resistances to peroxide by MN8, other TSS strains, and a subset of lactobacilli used in this study were nearly identical whereas the S. aureus collection was slightly more sensitive to racemic lactic acid than the lactobacilli. Collectively, these data suggest that the underlying inhibition toward Staphylococcus is generally conserved in Lactobacillus sp. and is related to a common factor in this genus involving promotion of acidic conditions. Published by Elsevier Ltd. C1 [Elkins, Christopher A.; Mullis, Lisa B.; Stingley, Robin L.; Hart, Mark E.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Enriqueta Munoz, Maria] Univ Autonoma Baja California, Fac Ciencias Quim & Ingn, Tijuana, Mexico. RP Elkins, CA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM chris.elkins@fda.hhs.gov RI Hart, Mark/B-8976-2013 FU United States Food and Drug Administration [E0725501]; U.S. Department of Energy; U.S. Food and Drug Administration FX The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 33 TC 6 Z9 6 U1 1 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 1075-9964 J9 ANAEROBE JI Anaerobe PD NOV PY 2008 VL 14 IS 5 BP 261 EP 267 DI 10.1016/j.anaerobe.2008.08.003 PG 7 WC Microbiology SC Microbiology GA 386ZS UT WOS:000261922100003 PM 18926917 ER PT J AU Stewart, SFC Robinson, RA Nelson, RA Malinauskas, RA AF Stewart, Sandy F. C. Robinson, Ronald A. Nelson, Robert A. Malinauskas, Richard A. TI Effects of thrombosed vena cava filters on blood flow: Flow visualization and numerical modeling SO ANNALS OF BIOMEDICAL ENGINEERING LA English DT Article DE Vena cava filter; Thrombosis; Blood flow; Flow visualization; Computational fluid mechanics; Wall shear stress ID DEEP-VEIN THROMBOSIS; PULMONARY-EMBOLISM; IN-VIVO; FOLLOW-UP; TRAPEASE; SYSTEM; HEMODYNAMICS; PERMANENT; OCCLUSION; GRAFT AB Inferior vena cava (IVC) filters are used to prevent pulmonary embolism (PE) in patients with deep vein thrombosis for whom anticoagulation is contraindicated. IVC filters have been shown to be effective in trapping embolized clots and preventing PE; however, among the commercially available designs, the optimal balance of clot capture efficiency, clot dissolution, and prevention of to vena cava occlusion is unknown. Clot capture efficiency has been quantified in numerous in vitro studies, in which model clots are released into a mock circulation system, with the relative capture efficiency of various IVC filters analyzed statistically. In general, two-stage filters have been found to be more efficient than one-stage filters. However, other factors may play a role in the ultimate dissolution of clots and in the overall effect of the resulting blood flow on caval vasculature. Clot dissolution has been shown to increase with increasing wall shear stress, while low and oscillating wall shear stresses are known to have a deleterious effect on vessel walls, causing intimal hyperplasia. This paper describes the effect of IVC filters on blood flow, velocity patterns, and wall shear stress by flow visualization and computational fluid dynamics. C1 [Stewart, Sandy F. C.; Robinson, Ronald A.; Nelson, Robert A.; Malinauskas, Richard A.] US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Stewart, SFC (reprint author), US FDA, Off Sci & Engn Labs, Ctr Devices & Radiol Hlth, White Oak Bldg 62,Rm 2210,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM sandy.stewart@fda.hhs.gov NR 40 TC 15 Z9 15 U1 1 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0090-6964 J9 ANN BIOMED ENG JI Ann. Biomed. Eng. PD NOV PY 2008 VL 36 IS 11 BP 1764 EP 1781 DI 10.1007/s10439-008-9560-6 PG 18 WC Engineering, Biomedical SC Engineering GA 363IF UT WOS:000260260300002 PM 18787955 ER PT J AU Zhao, S White, DG Friedman, SL Glenn, A Blickenstaff, K Ayers, SL Abbott, JW Hall-Robinson, E McDermott, PF AF Zhao, S. White, D. G. Friedman, S. L. Glenn, A. Blickenstaff, K. Ayers, S. L. Abbott, J. W. Hall-Robinson, E. McDermott, P. F. TI Antimicrobial Resistance in Salmonella enterica Serovar Heidelberg Isolates from Retail Meats, Including Poultry, from 2002 to 2006 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ESCHERICHIA-COLI; UNITED-STATES; NURSING-HOME; OUTBREAK; INFECTIONS; BLA(CMY-2); DISEASE AB Salmonella enterica serovar Heidelberg frequently causes food-borne illness in humans. There are few data on the prevalence, antimicrobial susceptibility, and genetic diversity of Salmonella serovar Heidelberg isolates in retail meats. We compared the prevalences of Salmonella serovar Heidelberg in a sampling of 20,295 meats, including chicken breast (n = 5,075), ground turkey (n = 5,044), ground beef (n = 5,100), and pork chops (n = 5,076), collected during 2002 to 2006. Isolates were analyzed for antimicrobial susceptibility and compared genetically using pulsed-field gel electrophoresis (PFGE) and PCR for the bla CMY gene. A total of 298 Salmonella serovar Heidelberg isolates were recovered, representing 21.6% of all Salmonella serovars from retail meats. One hundred seventy-eight (59.7%) were from ground turkey, 110 (36.9%) were from chicken breast, and 10 (3.4%) were from pork chops; none was found in ground beef. One hundred ninety-eight isolates (66.4%) were resistant to at least one compound, and 49 (16.4%) were resistant to at least five compounds. Six isolates (2.0%), all from ground turkey, were resistant to at least nine antimicrobials. The highest resistance in poultry isolates was to tetracycline (39.9%), followed by streptomycin (37.8%), sulfamethoxazole (27.7%), gentamicin (25.7%), kanamycin (21.5%), ampicillin (19.8%), amoxicillin-clavulanic acid (10.4%), and ceftiofur (9.0%). All isolates were susceptible to ceftriaxone and ciprofloxacin. All ceftiofur-resistant strains carried bla CMY. PFGE using XbaI and BlnI showed that certain clones were widely dispersed in different types of meats and meat brands from different store chains in all five sampling years. These data indicate that Salmonella serovar Heidelberg is a common serovar in retail poultry meats and includes widespread clones of multidrug-resistant strains. C1 [Zhao, S.; White, D. G.; Friedman, S. L.; Glenn, A.; Blickenstaff, K.; Ayers, S. L.; Abbott, J. W.; Hall-Robinson, E.; McDermott, P. F.] US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. RP McDermott, PF (reprint author), US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM patrick.mcdermott@fda.hhs.gov NR 33 TC 53 Z9 59 U1 1 U2 11 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD NOV PY 2008 VL 74 IS 21 BP 6656 EP 6662 DI 10.1128/AEM.01249-08 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 365TB UT WOS:000260429600021 PM 18757574 ER PT J AU Kozora, E Hanly, JG Lapteva, L Filley, CM AF Kozora, Elizabeth Hanly, John G. Lapteva, Larissa Filley, Christopher M. TI Cognitive Dysfunction in Systemic Lupus Erythematosus Past, Present, and Future SO ARTHRITIS AND RHEUMATISM LA English DT Review ID CENTRAL-NERVOUS-SYSTEM; MAGNETIC-RESONANCE-SPECTROSCOPY; CEREBRAL-BLOOD-FLOW; GLUTAMATE-RECEPTOR ANTIBODIES; POSITRON-EMISSION-TOMOGRAPHY; CORTICOTROPIN-RELEASING-FACTOR; FAMILY-BASED ASSOCIATION; P-PROTEIN ANTIBODIES; KINASE M-ZETA; NEUROPSYCHIATRIC LUPUS C1 [Kozora, Elizabeth] Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. [Kozora, Elizabeth; Filley, Christopher M.] Univ Colorado, Denver Sch Med, Boulder, CO 80309 USA. [Kozora, Elizabeth] Hosp Special Surg, New York, NY 10021 USA. [Hanly, John G.] Queen Elizabeth 2 Hlth Sci Ctr, Halifax, NS, Canada. [Hanly, John G.] Dalhousie Univ, Halifax, NS, Canada. [Lapteva, Larissa] US FDA, Bethesda, MD 20014 USA. [Filley, Christopher M.] Denver Vet Affairs Med Ctr, Denver, CO USA. RP Kozora, E (reprint author), Natl Jewish Med & Res Ctr, 1400 Jackson St,B106, Denver, CO 80206 USA. EM kozorae@njc.org NR 186 TC 40 Z9 41 U1 3 U2 5 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD NOV PY 2008 VL 58 IS 11 BP 3286 EP 3298 DI 10.1002/art.23991 PG 13 WC Rheumatology SC Rheumatology GA 374JO UT WOS:000261039800003 PM 18975345 ER PT J AU Xu, F Karnaukhova, E Vostal, JG AF Xu, Fei Karnaukhova, Elena Vostal, Jaroslav G. TI Human cellular prion protein interacts directly with clusterin protein SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE LA English DT Article DE Prion; Clusterin; Protein interaction; Two-hybrid system; Chaperone ID BOVINE SPONGIFORM ENCEPHALOPATHY; PRPC DIRECTLY INTERACTS; ALZHEIMERS-DISEASE; APOLIPOPROTEIN-J; COMPLEX; CELLS; MICE; AGGREGATION; EXPRESSION; MUTATIONS AB Prion protein is a glycosyl-phosphatidyl-inositol anchored glycoprotein localized on the surface and within a variety of cells. Its conformation change is thought to be essential for the proliferation of prion neurodegenerative diseases. Using the yeast two-hybrid assay we identified an interaction between prion protein and clusterin, a chaperone glycoprotein. This interaction was confirmed in a mammalian system by in vivo co-immunoprecipitation and in vitro by circular dichroism analysis. Through deletion mapping analysis we demonstrated that the a subunit, but not the beta subunit, of clusterin binds to prion and that the C-terminal 62 amino acid segment of the putative alpha helix region of clusterin is essential for the binding interaction. The full prion protein as well as the N-terminal section (aa 23-95) and C-terminal (aa 96-231) were shown to interact with clusterin. These findings provide new insights into the molecular mechanisms of interaction between prion and clusterin protein and contribute to the understanding of prion protein's physiological function. Published by Elsevier B.V. C1 [Xu, Fei; Karnaukhova, Elena; Vostal, Jaroslav G.] US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Vostal, JG (reprint author), US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM jaroslav.vostal@fda.hhs.gov NR 42 TC 10 Z9 10 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0925-4439 J9 BBA-MOL BASIS DIS JI Biochim. Biophys. Acta-Mol. Basis Dis. PD NOV PY 2008 VL 1782 IS 11 BP 615 EP 620 DI 10.1016/j.bbadis.2008.08.004 PG 6 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 377PP UT WOS:000261263400001 PM 18786636 ER PT J AU Kim, SJ Kweon, O Jones, RC Edmondson, RD Cerniglia, CE AF Kim, Seong-Jae Kweon, Ohgew Jones, Richard C. Edmondson, Ricky D. Cerniglia, Carl E. TI Genomic analysis of polycyclic aromatic hydrocarbon degradation in Mycobacterium vanbaalenii PYR-1 SO BIODEGRADATION LA English DT Article DE degradation; genomic analysis; Mycobacterium vanbaalenii PYR-1; polycyclic aromatic hydrocarbons; proteome analysis ID SP STRAIN PYR-1; PSEUDOMONAS-PUTIDA KT2440; STREPTOMYCES-COELICOLOR A3(2); BETA-KETOADIPATE PATHWAY; MOLECULAR CHARACTERIZATION; DEGRADING MYCOBACTERIUM; PHENANTHRENE DEGRADATION; NAPHTHALENE DIOXYGENASE; PYRENE DEGRADATION; CATABOLIC PATHWAYS AB Mycobacterium vanbaalenii PYR-1 is well known for its ability to degrade a wide range of high-molecular-weight (HMW) polycyclic aromatic hydrocarbons (PAHs). The genome of this bacterium has recently been sequenced, allowing us to gain insights into the molecular basis for the degradation of PAHs. The 6.5 Mb genome of PYR-1 contains 194 chromosomally encoded genes likely associated with degradation of aromatic compounds. The most distinctive feature of the genome is the presence of a 150 kb major catabolic region at positions 494 similar to 643 kb (region A), with an additional 31 kb region at positions 4,711 similar to 4,741 kb (region B), which is predicted to encode most enzymes for the degradation of PAHs. Region A has an atypical mosaic structure made of several gene clusters in which the genes for PAH degradation are complexly arranged and scattered around the clusters. Significant differences in the gene structure and organization as compared to other well-known aromatic hydrocarbon degraders including Pseudomonas and Burkholderia were revealed. Many identified genes were enriched with multiple paralogs showing a remarkable range of diversity, which could contribute to the wide variety of PAHs degraded by M. vanbaalenii PYR-1. The PYR-1 genome also revealed the presence of 28 genes involved in the TCA cycle. Based on the results, we proposed a pathway in which HMW PAHs are degraded into the beta-ketoadipate pathway through protocatechuate and then mineralized to CO(2) via TCA cycle. We also identified 67 and 23 genes involved in PAH degradation and TCA cycle pathways, respectively, to be expressed as proteins. C1 [Kim, Seong-Jae; Kweon, Ohgew; Cerniglia, Carl E.] US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Jones, Richard C.; Edmondson, Ricky D.] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM carl.cerniglia@hhs.fda.gov FU Oak Ridge Institute for Science and Education FX We thank Robin L. Stingley and Ashraf A. Khan for critical review of the manuscript and Thomas D. Yun for graphical assistance. The authors acknowledge Charles D. Miller and Ronald C. Sims at the Utah State University and the staff of the Joint Genome Institute for their efforts with the genome sequencing of M. vanbaalenii PYR-1. This work was supported by an appointment to the Postgraduate Research Program at the National Center for Toxicological Research administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration. NR 79 TC 57 Z9 60 U1 5 U2 48 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0923-9820 J9 BIODEGRADATION JI Biodegradation PD NOV PY 2008 VL 19 IS 6 BP 859 EP 881 DI 10.1007/s10532-008-9189-z PG 23 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 351GG UT WOS:000259412100009 PM 18421421 ER PT J AU Cordoba-Rodriguez, RV AF Cordoba-Rodriguez, Ruth V. TI Aggregates in MAbs and Recombinant Therapeutic Proteins: A Regulatory Perspective SO BIOPHARM INTERNATIONAL LA English DT Article ID NATIVE-STATE; ANTIBODY; MICE AB The dynamics of a protein aggregate mixture are complex and require multiple analytical methods for detection, evaluation, and monitoring. A successful assessment of aggregates in protein-based pharmaceuticals rests on a science-driven, risk-based program that evaluates the protein stability profile and determines the impact that a given aggregate mixture will have on the safety and efficacy of the drug product during its lifecycle. This article provides a regulatory perspective on aggregates in protein-based pharmaceuticals, including their characterization, detection methods, and various control strategies that have been implemented by manufacturers. C1 US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Rockville, MD 20857 USA. RP Cordoba-Rodriguez, RV (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Rockville, MD 20857 USA. EM Ruth.Cordoba-Rodriguez@fda.hhs.gov NR 27 TC 23 Z9 23 U1 0 U2 6 PU ADVANSTAR COMMUNICATIONS INC PI WOODLAND HILLS PA 6200 CANOGA AVE, 2ND FLR, WOODLAND HILLS, CA 91367 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD NOV PY 2008 VL 21 IS 11 BP 44 EP + PG 8 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 375PT UT WOS:000261126500007 ER PT J AU Liang, XJ Yin, JJ Taylor, B Winkovitch, SM Garfield, SH Shen, DW Gottesman, MM Aszalos, A AF Liang, Xing-Jie Yin, Jun-Jie Taylor, Barbara Winkovitch, Stephen M. Garfield, Susan H. Shen, Ding-Wu Gottesman, Michael M. Aszalos, Adorjan TI Disruption of microfilaments by cytochalasin B decreases accumulation of cisplatin in human epidermal carcinoma and liver carcinoma cell lines SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE cisplatin; electron spin resonance; cytochalasin B; carcinoma cell lines; microfilaments ID RESISTANT CELLS; PLEIOTROPIC DEFECT; CROSS-RESISTANCE; PLASMA-MEMBRANES; CANCER-CELLS; ACTIN; PROTEINS; MICROTUBULES; ENDOCYTOSIS; METALS AB Background Although cisplatin is a frequently used cancer chemotherapeutic drug, its effectiveness is hindered by the development of resistance in cancer cells. In order to understand the reason(s) for this resistance, the mechanism of uptake of cisplatin into cells must be characterized. While several previous studies showed structural differences between cisplatin-sensitive and resistant cells, the influence of microfilaments, known to affect transport of molecules into cells, and the influence of certain biophysical characteristics of the plasma membrane needed clarification. Results We show that resistant human epidermal carcinoma (KB-CP20) and liver carcinoma (BEL-7404-CP20) cells become relatively more resistant if their already weak microfilaments are degraded by cytochalasin B treatment (.5-2 mu M). The sensitive counterparts of these cells with intact microfilaments are not significantly affected by this treatment. We also show that the "fluidity" of the plasma membrane and the membrane potential of the sensitive and resistant cells studied do not appear to influence the uptake of cisplatin into the cells. Conclusion Our results suggest that the status of the microfilament system influences the mechanism of uptake of cisplatin into cells. C1 [Liang, Xing-Jie; Shen, Ding-Wu; Gottesman, Michael M.; Aszalos, Adorjan] Natl Canc Inst, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Yin, Jun-Jie] US FDA, Instrumentat & Biophys Branch, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Taylor, Barbara] NIH, Lab Canc Biol & Genet, Bethesda, MD 20892 USA. [Winkovitch, Stephen M.; Garfield, Susan H.] NIH, Expt Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Aszalos, A (reprint author), Natl Canc Inst, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. EM aszalosa@nih.gov RI Yin, Jun Jie /E-5619-2014 FU Intramural Research Program of the NIH; Center for Cancer Research, National Cancer Institute FX We would like to thank George Leiman for his assistance with the text and figures. This research was funded by the Intramural Research Program of the NIH, Center for Cancer Research, National Cancer Institute. NR 25 TC 6 Z9 6 U1 2 U2 10 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD NOV PY 2008 VL 62 IS 6 BP 977 EP 984 DI 10.1007/s00280-008-0687-9 PG 8 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 348CR UT WOS:000259189100006 PM 18274748 ER PT J AU Ju, YH Doerge, DR Woodling, KA Hartman, JA Kwak, J Helferich, WG AF Ju, Young H. Doerge, Daniel R. Woodling, Kellie A. Hartman, James A. Kwak, Jieun Helferich, William G. TI Dietary genistein negates the inhibitory effect of letrozole on the growth of aromatase-expressing estrogen-dependent human breast cancer cells (MCF-7Ca) in vivo SO CARCINOGENESIS LA English DT Article ID ATHYMIC NUDE-MICE; POSTMENOPAUSAL WOMEN; PHYSIOLOGICAL CONCENTRATIONS; HORMONE-THERAPY; MESSENGER-RNA; UNITED-STATES; TAMOXIFEN; ISOFLAVONES; TUMORS; GENE AB Genistein (GEN), a soy isoflavone, stimulates growth of estrogen-dependent human tumor cells (MCF-7) in a preclinical mouse model for postmenopausal breast cancer. Antiestrogens and aromatase inhibitors are frontline therapies for estrogen-dependent breast cancer. We have demonstrated that dietary GEN can negate the inhibitory effect of tamoxifen. In this study, we evaluated the interaction of dietary GEN (at 250-1000 p.p.m. in the American Institute of Nutrition 93 growth diet) and an aromatase inhibitor, letrozole (LET), on the growth of tumors in an aromatase-expressing breast cancer xenograft model (MCF-7Ca) in the presence and absence of the substrate androstenedione (AD). Dietary GEN (250 and 500 p.p.m.) or implanted AD stimulated MCF-7Ca tumor growth. Implanted LET inhibited AD-stimulated MCF-7Ca tumor growth. In the presence of AD and LET, dietary GEN (250, 500 and 1000 p.p.m.) reversed the inhibitory effect of LET in a dose-dependent manner. Uterine wet weight, plasma estradiol (E-2) levels (enzyme-linked immunosorbent assay) and total plasma GEN and LET levels (liquid chromatography-electrospray/tandem mass spectrometry) were measured. Ki-67 (cellular proliferation), aromatase and pS2 protein expression in tumors were evaluated using immunohistochemical (IHC) analysis. In conclusion, dietary GEN increased the growth of MCF-7Ca tumors implanted in ovariectomized mice and could also negate the inhibitory effect of LET on MCF-7Ca tumor growth. These findings are significant because tumors, which express aromatase and synthesize estrogen, are good candidates for aromatase therapy dietary and GEN can reverse the inhibitory effect of LET on tumor growth and adversely impact breast cancer therapy. Caution is warranted for consumption of dietary GEN by postmenopausal women with estrogen-dependent breast cancer taking LET treatment. C1 [Ju, Young H.; Hartman, James A.; Helferich, William G.] Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 61801 USA. [Doerge, Daniel R.; Woodling, Kellie A.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Helferich, WG (reprint author), Univ Illinois, Dept Food Sci & Human Nutr, 905 S Goodwin Ave,Room 580 Bevier Hall, Urbana, IL 61801 USA. EM yhju@vt.edu; helferic@uiuc.edu FU National Cancer Institute [CA77355]; National Institute on Aging [AG024387]; National Institute for Complementary and Alternative Medicine [AG024387]; Office of Dietary Supplements; Women's Health Initiative [AG024387] FX National Cancer Institute (CA77355) to W. G. H.; National Institute on Aging (P01 AG024387) to W. G. H., D. D. and Y. H. J.; National Institute for Complementary and Alternative Medicine ( P01 AG024387); Office of Dietary Supplements; Women's Health Initiative ( P01 AG024387). NR 59 TC 53 Z9 54 U1 1 U2 7 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 EI 1460-2180 J9 CARCINOGENESIS JI Carcinogenesis PD NOV PY 2008 VL 29 IS 11 BP 2162 EP 2168 DI 10.1093/carcin/bgn161 PG 7 WC Oncology SC Oncology GA 373NE UT WOS:000260977900016 PM 18632754 ER PT J AU Wilson, CA AF Wilson, C. A. TI Porcine endogenous retroviruses and xenotransplantation SO CELLULAR AND MOLECULAR LIFE SCIENCES LA English DT Review DE Porcine; retrovirus; endogenous; xenotransplantation ID CROSS-SPECIES TRANSMISSION; PIG ISLET XENOTRANSPLANTATION; BLOOD MONONUCLEAR-CELLS; MURINE LEUKEMIA-VIRUS; MINIATURE SWINE; REPLICATION-COMPETENT; HUMAN SERUM; NO EVIDENCE; PRODUCTIVE INFECTION; BIOARTIFICIAL LIVER AB Xenotransplantation is defined by the PHS as any procedure that involves the transplantation, implantation or infusion into a human recipient of either (a) live cells, tissues or organs from a nonhuman animal source, or (b) human body fluids, cells, tissues or organs that have had ex vivo contact with live nonhuman animal cells, tissues or organs (Public Health Service Guideline on Infectious Disease Issues in Xenotransplantation). Use of pigs for human xenotransplantation raises concerns about the risks of transfer of infectious agents from the pig cells to xenotransplantation recipients. The observation that the porcine germline harbors genetic loci encoding porcine endogenous retroviruses (PERVs) that are in some cases infectious for human cells has resulted in renewed scientific interest in PERVs. However, in spite of the past 10 years of investigation, the actual risk for PERV infection, replication, and pathogenic outcome in human recipients of xenotransplantation products is still undefined. (Part of a Multi-author Review). C1 US FDA, Gene Transfer & Immunogen Branch, Div Cellular & Gene Therapies, Off Cellular Tissues & Gene Therapies,Ctr Biol Ev, Bethesda, MD 20892 USA. RP Wilson, CA (reprint author), US FDA, Gene Transfer & Immunogen Branch, Div Cellular & Gene Therapies, Off Cellular Tissues & Gene Therapies,Ctr Biol Ev, 8800 Rockville Pike,Bldg 29B,Rm 5NN20, Bethesda, MD 20892 USA. EM Carolyn.wilson@fda.hhs.gov FU FDA/Center for Biologics Evaluation and Research; Scripps Research Laboratory FX While every effort was made to make this a comprehensive review, space limitations dictated that some relevant publications were omitted. PERV-related research performed in my laboratory has been supported by the FDA/Center for Biologics Evaluation and Research or by a Collaborative Research and Development Agreement with the Scripps Research Laboratory. I thank Andrew Byrnes and Takele Argaw for critical reading of the manuscript. NR 121 TC 55 Z9 62 U1 1 U2 10 PU SPRINGER BASEL AG PI BASEL PA PICASSOPLATZ 4, BASEL, 4052, SWITZERLAND SN 1420-682X J9 CELL MOL LIFE SCI JI Cell. Mol. Life Sci. PD NOV PY 2008 VL 65 IS 21 BP 3399 EP 3412 DI 10.1007/s00018-008-8498-z PG 14 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 369HC UT WOS:000260684200006 PM 18818871 ER PT J AU Verma, A Wagner, L Stibitz, S Nguyen, N Guerengomba, F Burns, DL AF Verma, Anita Wagner, Leslie Stibitz, Scott Nguyen, Nga Guerengomba, Flor Burns, Drusilla L. TI Role of the N-Terminal Amino Acid of Bacillus anthracis Lethal Factor in Lethal Toxin Cytotoxicity and Its Effect on the Lethal Toxin Neutralization Assay SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID PROTECTIVE ANTIGEN; VACCINE; IMMUNOGENICITY; TRANSLOCATION; PURIFICATION; CORRELATE AB The cytotoxic activity of lethal factor (LF), a critical reagent used in the cell-based lethal toxin neutralization assay to assess anthrax vaccines, was shown to depend on the identity of its N-terminal amino acid, which plays a role in the targeting of LF to the proteasome for degradation. These results demonstrate that care must be taken to ensure that LF preparations used in standardized cell-based assays are not altered at their N-terminal ends. C1 [Verma, Anita; Wagner, Leslie; Stibitz, Scott; Nguyen, Nga; Guerengomba, Flor; Burns, Drusilla L.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Burns, DL (reprint author), US FDA, Ctr Biol Evaluat & Res, FDA HFM 434,Bldg 29,Room 130,8800 Rockville Pike, Bethesda, MD 20892 USA. EM drusilla.burns@fda.hhs.gov FU National Institute of Allergy and Infectious Diseases; NIH; Food and Drug Administration; NIH Biodefense and Emerging Infections Research Resources Repository; NIAID [NR-142, NR-724]; Bacillus anthracis [NR-140, J774A.1]; Working Cell Bank [NR-28] FX This work was supported in part by an interagency agreement between the National Institute of Allergy and Infectious Diseases, NIH, and the Food and Drug Administration.; The following reagents were obtained from the NIH Biodefense and Emerging Infections Research Resources Repository, NIAID, NIH: anthrax LF, recombinant from Bacillus anthracis, NR-142 and NR-724; anthrax PA, recombinant from Bacillus anthracis, NR-140; and J774A.1 monocyte/macrophage (mouse), Working Cell Bank, NR-28. NR 18 TC 5 Z9 5 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD NOV PY 2008 VL 15 IS 11 BP 1737 EP 1741 DI 10.1128/CVI.00081-08 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 369DJ UT WOS:000260674200017 PM 18815235 ER PT J AU Struble, KA Chan-Tack, KM Soon, GX AF Struble, Kimberly A. Chan-Tack, Kirk M. Soon, Guoxing (Greg) TI Regulatory issues in developing new HIV protease inhibitors: risks and benefits SO CURRENT OPINION IN HIV AND AIDS LA English DT Article DE antiretroviral drug development; noninferiority; protease inhibitor; regulatory perspective AB Purpose of review To provide a regulatory perspective on developing new HIV protease inhibitors. The present review highlights the risks and benefits of certain design aspects for studies in treatment-naive and treatment-experienced patients, including timing of studies, study design options, choice of control arms, and duration of treatment. Recent findings The present review highlights published studies to illustrate the need for new therapies and highlights potential historical data to help design future HIV clinical trials better. Summary New antiretroviral agents for patients with multidrug resistance, including safer, more convenient therapies without significant drug-drug interactions, are still needed for all patients. The goals of therapy have evolved and the expectation for treatment regimens is that the majority of patients, including treatment-experienced patients, will achieve undetectable HIV RNA. New study designs, particularly for treatment-experienced patients, are needed to help identify potential risks and benefits of new treatments. C1 [Struble, Kimberly A.; Chan-Tack, Kirk M.] US FDA, Off New Drugs, Off Antimicrobial Prod, Div Antiviral Prod, Silver Spring, MD USA. [Soon, Guoxing (Greg)] US FDA, Off Biostat, Div Biometr 4, Silver Spring, MD USA. RP Struble, KA (reprint author), 10903 New Hampshire Ave,Bldg 22,Room 6347, Silver Spring, MD 20993 USA. EM Kimberly.struble@fda.hhs.gov NR 23 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1746-630X J9 CURR OPIN HIV AIDS JI Curr. Opin. HIV AIDS PD NOV PY 2008 VL 3 IS 6 BP 676 EP 680 DI 10.1097/COH.0b013e3283136cb1 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA V24OC UT WOS:000208418700012 PM 19373041 ER PT J AU Bolger, PM Carrington, CD AF Bolger, P. M. Carrington, C. D. TI Exposure Assessment of Methylmercury from the Consumption of Commercial Fish and Shellfish SO EPIDEMIOLOGY LA English DT Meeting Abstract CT 20th Annual Conference of the International-Society-for-Environmental-Epidemiology CY OCT 12-16, 2008 CL Pasadena, CA SP Int Soc Environm Epidemiol C1 [Bolger, P. M.; Carrington, C. D.] US FDA, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD NOV PY 2008 VL 19 IS 6 BP S19 EP S19 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 362IR UT WOS:000260191900030 ER PT J AU Yamaguchi, Y Coelho, SG Zmudzka, BZ Takahashi, K Beer, JZ Hearing, VJ Miller, SA AF Yamaguchi, Yuji Coelho, Sergio G. Zmudzka, Barbara Z. Takahashi, Kaoruko Beer, Janusz Z. Hearing, Vincent J. Miller, Sharon A. TI Cyclobutane pyrimidine dimer formation and p53 production in human skin after repeated UV irradiation SO EXPERIMENTAL DERMATOLOGY LA English DT Article DE apoptosis; p53; pigmentation; skin cancer; UV ID DNA-DAMAGE; ULTRAVIOLET-RADIATION; TANNING DEVICES; MELANIN CONTENT; HUMAN EPIDERMIS; BASAL-CELL; IN-VIVO; EXPOSURE; RISK; RESPONSES AB Substantial differences in DNA damage caused by a single UV irradiation were found in our previous study on skin with different levels of constitutive pigmentation. In this study, we assessed whether facultative pigmentation induced by repeated UV irradiation is photoprotective. Three sites on the backs of 21 healthy subjects with type II-III skin were irradiated at 100-600 J/m(2) every 2-7 days over a 4- to 5-week period. The three sites received different cumulative doses of UV (1900, 2900 or 4200 J/m(2)) and were biopsied 1 day after the last irradiation. Biomarkers examined included pigment content assessed by Fontana-Masson staining, melanocyte function by expression of melanocyte-specific markers, DNA damage as cyclobutane pyrimidine dimers (CPD), nuclear accumulation of p53, apoptosis determined by TUNEL assay, and levels of p21 and Ser46-phosphorylated p53. Increases in melanocyte function and density, and in levels of apoptosis were similar among the 3 study sites irradiated with different cumulative UV doses. Levels of CPD decreased while the number of p53-positive cells increased as the cumulative dose of UV increased. These results suggest that pigmentation induced in skin by repeated UV irradiation protects against subsequent UV-induced DNA damage but not as effectively as constitutive pigmentation. C1 [Yamaguchi, Yuji; Coelho, Sergio G.; Takahashi, Kaoruko; Hearing, Vincent J.] NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. [Coelho, Sergio G.; Zmudzka, Barbara Z.; Beer, Janusz Z.; Miller, Sharon A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,room 2132,MSC 4256, Bethesda, MD 20892 USA. EM hearingv@nih.gov FU Office of Science and the Center for Devices and Radiological Health; Food and Drug Administration (FDA); NIH; Ministry of Education, Culture, Sports, and Technology of Japan; FDA Office of Women's Health FX This research was supported by the Office of Science and the Center for Devices and Radiological Health, Food and Drug Administration (FDA), by the Intramural Research Program of the National Cancer Institute at NIH, by a grant-in-aid from the Ministry of Education, Culture, Sports, and Technology of Japan, and by the FDA Office of Women's Health. The opinions and conclusions stated in this paper are those of the authors and do not represent the official position of the U. S. Department of Health and Human Services. The mention of commercial products, their sources, or their use in connection with material reported herein is not to be construed as either an actual or implied endorsement of such products by the U. S. Department of Health and Human Services. NR 41 TC 23 Z9 23 U1 0 U2 6 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0906-6705 J9 EXP DERMATOL JI Exp. Dermatol. PD NOV PY 2008 VL 17 IS 11 BP 916 EP 924 DI 10.1111/j.1600-0625.2008.00722.x PG 9 WC Dermatology SC Dermatology GA 358RV UT WOS:000259936100003 PM 18363705 ER PT J AU Saviola, JF AF Saviola, James F. TI New Directions in Contact Lens Care Testing SO EYE & CONTACT LENS-SCIENCE AND CLINICAL PRACTICE LA English DT Editorial Material C1 Ctr Devices & Radiol Hlth, Off Ctr Director, Rockville, MD 20855 USA. RP Saviola, JF (reprint author), Ctr Devices & Radiol Hlth, Off Ctr Director, 7520 Standish Pl,Rm 1412 HF2-4, Rockville, MD 20855 USA. EM james.saviola@fda.hhs.gov NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1542-2321 J9 EYE CONTACT LENS JI Eye Contact Lens-Sci. Clin. Pra. PD NOV PY 2008 VL 34 IS 6 BP 300 EP 301 DI 10.1097/ICL.0b013e31818d6fff PG 2 WC Ophthalmology SC Ophthalmology GA 379ML UT WOS:000261400300002 PM 18997536 ER PT J AU Tsai, CM Jankowska-Stephens, E Freedberg, D Rahman, M Cipollo, JF AF Tsai, Chao Ming Jankowska-Stephens, Ewa Freedberg, Daron Rahman, Mizanur Cipollo, John F. TI The Fine Structure of Neisseria meningitidis Lipid Oligosaccharide from the M986 Strain and Three of its Variants SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Tsai, Chao Ming; Jankowska-Stephens, Ewa; Freedberg, Daron; Rahman, Mizanur; Cipollo, John F.] FDA Ctr Biol Evaluat & Res, Bethesda, MD 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 92 BP 962 EP 963 PG 2 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400101 ER PT J AU Ishihara, M Sonon, R Chill, L Trinh, L Shiloach, J Azadi, P AF Ishihara, Mayumi Sonon, Roberto Chill, Liat Trinh, Loc Shiloach, Joseph Azadi, Parastoo TI Characterization of Glycan Structure and the Sites of Glycosylation on the Recombinant Human alpha 1-Proteinase Inhibitor, alpha-1PI By Mass Spectrometry SO GLYCOBIOLOGY LA English DT Meeting Abstract CT Annual Meeting of the Society-for-Glycobiology CY NOV 12-15, 2008 CL Ft Worth, TX SP Soc Glycobiol C1 [Ishihara, Mayumi; Sonon, Roberto; Azadi, Parastoo] Univ Georgia, Complex Carbohydrate Res Ctr, Athens, GA 30602 USA. [Chill, Liat; Trinh, Loc; Shiloach, Joseph] NIH, Biotechnol Core Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 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 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD NOV PY 2008 VL 18 IS 11 MA 95 BP 963 EP 963 PG 1 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 361QE UT WOS:000260141400104 ER PT J AU Woodcock, J AF Woodcock, Janet TI PERSPECTIVE The Human Genome And Translational Research: How Much Evidence Is Enough? SO HEALTH AFFAIRS LA English DT Article AB Multiple new genomic diagnostic tests are currently under development. Given the lack of an efficient translational infrastructure, it is not clear how, or whether, robust evidence for their clinical value will be generated. [Health Affairs 27, no. 6 (2008): 1616-1618; 10.1377/hlthaff.27.6.1616] C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Woodcock, J (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM Janet.woodcock@fda.hhs.gov NR 4 TC 8 Z9 8 U1 2 U2 2 PU PROJECT HOPE PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 600, BETHESDA, MD 20814-6133 USA SN 0278-2715 J9 HEALTH AFFAIR JI Health Aff. PD NOV-DEC PY 2008 VL 27 IS 6 BP 1616 EP 1618 DI 10.1377/hlthaff.27.6.1616 PG 3 WC Health Care Sciences & Services; Health Policy & Services SC Health Care Sciences & Services GA 370NQ UT WOS:000260769300020 PM 18997219 ER PT J AU Mettler, FA Thorriadsen, BR Bhargavan, M Gilley, DB Gray, JE Lipoti, JA McCrohan, J Yoshizurrli, TT Mahesh, M AF Mettler, Fred A., Jr. Thorriadsen, Bruce R. Bhargavan, Mythreyi Gilley, Debbie B. Gray, Joel E. Lipoti, Jill A. McCrohan, John Yoshizurrli, Terry T. Mahesh, Mahadevappa TI MEDICAL RADIATION EXPOSURE IN THE US IN 2006: PRELIMINARY RESULTS SO HEALTH PHYSICS LA English DT Article; Proceedings Paper CT 43rd Annual Meeting of the National-Council-on-Radiation-Protection-and-Measurements CY APR 16-17, 2007 CL Washington, DC DE National Council on Radiation Protection and Measurements; dose; population; effective dose; medical radiation AB Medical radiation exposure of the U.S. population has not been systematically evaluated for almost 25 y. In 1982, the per capita dose was estimated to be 0.54 mSv and the collective dose 124,000 person-Sv. The preliminary estimates of the NCRP Scientific Committee 6-2 medical subgroup are that, in 2006, the per capita dose from medical exposure (not including dental or radiotherapy) had increased almost 600% to about 3.0 mSv and the collective dose had increased over 700% to about 900,000 person-Sv. The largest contributions and increases have come primarily from CT scanning and nuclear medicine. The 62 million CT procedures accounted for 15% of the total number procedures (excluding dental) and over half of the collective dose. Nuclear medicine accounted for about 4% of all procedures but 26% of the total collective dose. Medical radiation exposure is now approximately equal to natural background radiation. C1 [Mettler, Fred A., Jr.] NMVAHCS, Radiol & Nucl Med Serv, Albuquerque, NM 87108 USA. [Thorriadsen, Bruce R.] Univ Wisconsin, Dept Med Phys, Madison, WI 53706 USA. [Bhargavan, Mythreyi] Amer Coll Radiol, Reston, VA 20191 USA. [Gray, Joel E.] DIQUAD LLC, Steger, IL 60475 USA. [Lipoti, Jill A.] Radiat Protect Programs, New Jersey Dept Environm Protect, Trenton, NJ 08625 USA. [Lipoti, Jill A.] US FDA, CDRH, Rockville, MD 20850 USA. [McCrohan, John] Duke Univ, Sch Med, Durham, NC 27710 USA. [Mahesh, Mahadevappa] Johns Hopkins Univ Hosp, Dept Radiol, Baltimore, MD 21287 USA. RP Mettler, FA (reprint author), NMVAHCS, Radiol & Nucl Med Serv, 1501 San Pedro Blvd SE, Albuquerque, NM 87108 USA. EM fmettler@salud.unm.edu NR 12 TC 265 Z9 276 U1 4 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 NOV PY 2008 VL 95 IS 5 BP 502 EP 507 DI 10.1097/01.HP.0000326333.42287.a2 PG 6 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 361WH UT WOS:000260157700006 PM 18849682 ER PT J AU Watkins, PB Seligman, PJ Pears, JS Avigan, MI Senior, JR AF Watkins, Paul B. Seligman, Paul J. Pears, John S. Avigan, Mark I. Senior, John R. TI Using Controlled Clinical Trials to Learn More About Acute Drug-Induced Liver Injury SO HEPATOLOGY LA English DT Article ID ALANINE AMINOTRANSFERASE LEVELS; ISONIAZID PREVENTIVE THERAPY; HEPATITIS-C COINFECTION; UNITED-STATES; INDUCED HEPATOTOXICITY; MEDICAL PROGRESS; VIRUS-INFECTION; DISEASE; ACETAMINOPHEN; TROGLITAZONE AB Drug-induced liver injury (DILI) is of major interest to hepatologists and clinicians in general, patients, government regulators, and the pharmaceutical industry. Understanding why this form of injury occurs only in certain individuals has major implications for the development and availability of drug therapies and in the prevention of these events. A single controlled clinical trial may be unlikely to show cases of such rare events, but in the aggregate, clinical trials offer a unique resource for learning more about individual susceptibility and developing truly predictive new biomarkers for DILI. We pose the question as to whether clinical trials could be modified or improved to provide data that would better answer some of the outstanding issues. At a recent (March 2008) public meeting, experts from academia, industry, and regulatory bodies discussed several major issues regarding liver safety in clinical trials including: what signals of liver injury should justify stopping administration of study drug or allowing it to continue; if deliberate rechallenge should be done and under what circumstances; whether patients with liver disease should be included in clinical trials; and what kinds of new biomarkers will be needed to answer these questions more dearly. Past clinical trials have not provided data to settle those issues, and reliance has defaulted to consensus of expert opinions. Modified and better clinical trials with standardized collection of data and biospecimens are probably the best source of new and potentially valuable information to supplant current rules based on consensus of expert opinions and to understand by what mechanisms and how to distinguish those individuals who are susceptible to severe DILI. (HEPATOLOGY 2008;48:1680-1689.) C1 [Senior, John R.] US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Watkins, Paul B.] Univ N Carolina, Hamner Ctr Drug Safety Sci, Chapel Hill, NC USA. [Pears, John S.] AstraZeneca, Alderley Pk, Cheshire, England. RP Senior, JR (reprint author), US FDA, Off Surveillance & Epidemiol, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM john.senior@fda.hhs.gov NR 71 TC 56 Z9 61 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 NOV PY 2008 VL 48 IS 5 BP 1680 EP 1689 DI 10.1002/hep.22633 PG 10 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 368BP UT WOS:000260596600037 PM 18853438 ER PT J AU Wear, KA AF Wear, Keith A. TI Mechanisms for Attenuation in Cancellous-Bone-Mimicking Phantoms SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Review ID HUMAN TRABECULAR BONE; QUANTITATIVE ULTRASOUND MEASUREMENTS; FREQUENCY-DEPENDENT ATTENUATION; HUMAN FEMUR SPECIMENS; IN-VITRO; MINERAL DENSITY; HUMAN CALCANEUS; HIP FRACTURE; NUMERICAL-SIMULATION; PHASE-VELOCITY AB Broadband ultrasound attenuation (BUA) in cancellous bone is useful for prediction of osteoporotic fracture risk, but its causes are riot well understood. To investigate attenuation mechanisms, 9 cancellous-bone-mimicking phantoms containing nylon filaments (simulating bone trabeculae) embedded within soft-tissue-mimicking fluid (simulating marrow) were interrogated. The measurements of frequency-dependent attenuation coefficient had 3 separable components: 1) a linear (with frequency) component attributable to absorption in the soft-tissue-mimicking fluid 2) a quasilinear (with frequency) component, which may include absorption in and longitudinal-shear mode conversion by the nylon filaments, and 3) a nonlinear (with frequency) component, which may be attributable to longitudinal-longitudinal scattering by the nylon filaments. Tire slope of total linear (with frequency) attenuation coefficient (sum of components #1 and #2) versus frequency was found to increase linearly with volume fraction, consistent with reported measurements on cancellous bone. Backscatter coefficient measurements in the 9 phantoms supported the claim that the nonlinear (with frequency) component of attenuation coefficient (component #3) was closely associated with longitudinal-longitudinal scattering. This work represents the first experimental separation of these 3 components of attenuation in cancellous bone-mimicking phantoms.. C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. EM kaw@cdrh.fda.gov NR 103 TC 12 Z9 12 U1 0 U2 3 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 NOV PY 2008 VL 55 IS 11 BP 2418 EP 2425 DI 10.1109/TUFFC.949 PG 8 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 372AN UT WOS:000260873900009 PM 19049921 ER PT J AU Jeon, BY Derrick, SC Lim, J Kolibab, K Dheenadhayalan, V Yang, AL Kreiswirth, B Morris, SL AF Jeon, Bo Young Derrick, Steven C. Lim, JaeHyun Kolibab, Kristopher Dheenadhayalan, Veerabadran Yang, Amy Li Kreiswirth, Barry Morris, Sheldon L. TI Mycobacterium bovis BCG Immunization Induces Protective Immunity against Nine Different Mycobacterium tuberculosis Strains in Mice SO INFECTION AND IMMUNITY LA English DT Article ID BACILLE CALMETTE-GUERIN; MOUSE MODEL; GLOBAL DISSEMINATION; TANDEM REPEATS; LUNG PATHOLOGY; RABBIT MODEL; VIRULENCE; DISEASE; VACCINE; FAMILY AB Recent preclinical and epidemiologic studies have suggested that certain Mycobacterium tuberculosis genotypes (in particular, Beijing lineage strains) may be resistant to Mycobacterium bovis BCG vaccine-induced antituberculosis protective immunity. To investigate the strain specificity of BCG-induced protective responses in a murine model of pulmonary tuberculosis, C57BL/6 mice were vaccinated with BCG vaccine and then challenged 2 months later with one of nine M. tuberculosis isolates. Four of these strains were from the W-Beijing lineage (HN878, N4, NHN5, and ChS) while four were non-Beijing-type isolates (C913, CDC1551, NY669, and NY920). As a control, the WHO standard M. tuberculosis Erdman strain was evaluated in these vaccination/challenge experiments. To assess the protective responses evoked by BCG immunization, organ bacterial burdens and lung pathology were assessed in vaccinated and naive mice at 4, 12, and 20 weeks postchallenge as well as during the day of infection. At 4 weeks after the aerosol challenge with each of these strains, significantly reduced bacterial growth in the lungs and spleens and significantly improved lung pathology were seen in all vaccinated animals compared to naive controls. After 12 weeks, reduced organ bacterial burdens were detected in vaccinated animals infected with six of nine challenge strains. Although lung CFU values were lower in vaccinated mice for only three of nine groups at 20 weeks postchallenge, significantly decreased lung inflammation was seen in all immunized animals relative to controls at 20 weeks postchallenge. Taken together, these data demonstrate that BCG vaccination protects against infection with diverse M. tuberculosis strains in the mouse model of pulmonary tuberculosis and suggest that strain-specific resistance to BCG-induced protective immunity may be uncommon. C1 [Jeon, Bo Young; Derrick, Steven C.; Lim, JaeHyun; Kolibab, Kristopher; Dheenadhayalan, Veerabadran; Yang, Amy Li; Morris, Sheldon L.] US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Kreiswirth, Barry] Int Ctr Publ Hlth, TB Ctr, Publ Hlth Res Inst, Newark, NJ USA. RP Morris, SL (reprint author), US FDA, Lab Mycobacterial Dis & Cellular Immunol, Ctr Biol Evaluat & Res, Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. EM sheldon.morris@fda.hhs.gov NR 42 TC 40 Z9 40 U1 1 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 NOV PY 2008 VL 76 IS 11 BP 5173 EP 5180 DI 10.1128/IAI.00019-08 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 361YW UT WOS:000260165500042 PM 18710860 ER PT J AU Hu, L Tall, BD Curtis, SK Kopecko, DJ AF Hu, Lan Tall, Ben D. Curtis, Sherill K. Kopecko, Dennis J. TI Enhanced Microscopic Definition of Campylobacter jejuni 81-176 Adherence to, Invasion of, Translocation across, and Exocytosis from Polarized Human Intestinal Caco-2 Cells SO INFECTION AND IMMUNITY LA English DT Article ID EPITHELIAL-CELLS; INT-407 CELLS; LINE CACO-2; SIGNAL-TRANSDUCTION; EUKARYOTIC CELLS; TIGHT JUNCTIONS; SALMONELLA; TRANSPORT; VIRULENCE; SURFACE AB Campylobacter jejuni-mediated pathogenesis involves gut adherence and translocation across intestinal cells. The current study was undertaken to examine the C. jejuni interaction with and translocation across differentiated Caco-2 cells to better understand Campylobacter's pathogenesis. The efficiency of C. jejuni 81-176 invasion of Caco-2 cells was two- to threefold less than the efficiency of invasion of INT407 cells. Adherence-invasion analyses indicated that C. jejuni 81-176 adhered to most INT407 cells but invaded only about two- thirds of the host cells over 2 h (two bacteria/cell). In contrast, only 11 to 17% of differentiated Caco-2 cells were observed to bind and internalize either C. jejuni strain 81-176 or NCTC 11168, and a small percentage of infected Caco-2 cells contained 5 to 20 internalized bacteria per cell after 2 h. Electron microscopy revealed that individual C. jejuni cells adhered to the tips of host cell microvilli via intimate flagellar contacts and by lateral bacterial binding to the sides of microvilli. Next, bacteria were observed to bind at the apical host membrane surface via presumed interactions at one pole of the bacterium and with host membrane protrusions located near intercellular junctions. The latter contacts apparently resulted in coordinated, localized plasma membrane invagination, causing simultaneous internalization of bacteria into an endosome. Passage of this Campylobacter endosome intracellularly from the apical surface to the basolateral surface occurred over time, and bacterial release apparently resulted from endosome-basolateral membrane fusion (i.e., exocytosis). Bacteria were found intercellularly below tight junctions at 60 min postinfection, but not at earlier times. This study revealed unique host cell adherence contacts, early endocytosis-specific structures, and a presumptive exocytosis component of the transcellular transcytosis route. C1 [Hu, Lan; Kopecko, Dennis J.] US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Tall, Ben D.; Curtis, Sherill K.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Kopecko, DJ (reprint author), US FDA, Lab Enter & Sexually Transmitted Dis, Ctr Biol Evaluat & Res, 29 Lincoln Dr,NIH Campus,Bldg 29-420, Bethesda, MD 20892 USA. EM dennis.kopecko@fda.hhs.gov OI Tall, Ben/0000-0003-0399-3629 NR 53 TC 26 Z9 26 U1 0 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 NOV PY 2008 VL 76 IS 11 BP 5294 EP 5304 DI 10.1128/IAI.01408-07 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 361YW UT WOS:000260165500055 PM 18765731 ER PT J AU Arudchandran, A Bernstein, RM Max, EE AF Arudchandran, Arulvathani Bernstein, Ralph M. Max, Edward E. TI Single-strand DNA breaks in Ig class switch recombination that depend on UNG but not AID SO INTERNATIONAL IMMUNOLOGY LA English DT Article ID CYTIDINE DEAMINASE AID; NF-KAPPA-B; SOMATIC HYPERMUTATION; POLYMERASE-BETA; URACIL-DNA; S-MU; MICE DEFICIENT; IN-VIVO; APOBEC3G; REGION AB B lymphocytes switch from secreting IgM to secreting IgG, IgA or IgE through a DNA recombination, class switch recombination (CSR), whose mechanism is incompletely understood. CSR is thought to be triggered by activation-induced deaminase (AID), which is believed to deaminate cytosines to uracil in single-strand regions of switch region DNA. Subsequent excision of uracils by uracil DNA glycosylase (UNG) (product of the UNG gene) generates abasic sites, which are targeted for DNA cleavage, producing DNA breaks that are critical intermediates in CSR. Consistent with this model, CSR-related double-strand breaks (DSBs)-detected by ligation-mediated PCR (LMPCR)-have been reported to be dramatically reduced in B cells from either AID(-/-) or UNG(-/-) mice. Here we examine single-strand breaks (SSBs) using LMPCR and report, surprisingly, that CSR-related anti-sense strand breaks in S gamma regions are dependent only on UNG, and not AID, suggesting participation of a cytosine deaminase other than AID. This conclusion is supported by the sequences at these DNA breaks, which show a bias for a consensus sequence different from that reported for AID. The SSBs appear to be part of the normal CSR pathway since in B cells in which CSR is blocked by deletion of S mu, the content of S gamma SSBs is elevated as though the breaks resolve inefficiently owing to the lack of a recombination partner for completing mu-to-gamma CSR. These results suggest a narrower role for AID in CSR than previously recognized and prompt a search for a putative alternative cytosine deaminase participating in CSR. C1 [Arudchandran, Arulvathani; Bernstein, Ralph M.; Max, Edward E.] US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Max, EE (reprint author), US FDA, Div Therapeut Prot, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. EM edward.max@fda.hhs.gov NR 48 TC 1 Z9 2 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2008 VL 20 IS 11 BP 1381 EP 1393 DI 10.1093/intimm/dxn097 PG 13 WC Immunology SC Immunology GA 365BW UT WOS:000260381900003 PM 18794203 ER PT J AU Jin, ZX Huang, CR Dong, LL Goda, S Kawanami, T Sawaki, T Sakai, T Tong, XP Masaki, Y Fukushima, T Tanaka, M Mimori, T Tojo, H Bloom, ET Okazaki, T Umehara, H AF Jin, Zhe-Xiong Huang, Cheng-Ri Dong, Lingli Goda, Seiji Kawanami, Takafumi Sawaki, Toshioki Sakai, Tomoyuki Tong, Xiao-Peng Masaki, Yasufumi Fukushima, Toshihiro Tanaka, Masao Mimori, Tsuneyo Tojo, Hiromasa Bloom, Eda T. Okazaki, Toshiro Umehara, Hisanori TI Impaired TCR signaling through dysfunction of lipid rafts in sphingomyelin synthase 1 (SMS1)-knockdown T cells SO INTERNATIONAL IMMUNOLOGY LA English DT Article ID TYROSINE KINASE P72(SYK); RICH MEMBRANE DOMAINS; IMMUNOLOGICAL SYNAPSE; ADAPTER PROTEINS; ANTIGEN-RECEPTOR; PKC-THETA; PHOSPHATIDYLINOSITOL 3-KINASE; PLASMA-MEMBRANE; ACTIVATION; TRANSDUCTION AB During T cell activation, TCRs cluster at the center of the T cell-antigen-presenting cell interface forming the central supramolecular activation cluster. Although it has been suggested that sphingolipid- and cholesterol-rich microdomains, termed lipid rafts, form platforms for the regulation and transduction of TCR signals, an actual role for membrane sphingomyelin (SM), a key component of lipid rafts, has not been reported. After cloning a gene responsible for SM synthesis, sphingomyelin synthase (SMS) 1, we established a SM-knockdown cell line (Jurkat-SMS1/kd) by transfection of SMS1-short-interfering RNA into Jurkat T cells, which is deficient in membrane expression of SM. Upon CD3 stimulation, expression of CD69 (the earliest leukocyte activation antigen), activation-induced cell adhesion and proliferation as well as TCR clustering was severely impaired in Jurkat-SMS1/kd cells. CD3-induced tyrosine phosphorylation and association of linker for activation of T cell with ZAP-70 and Grb2 and phosphorylation of protein kinase C (PKC) theta were also severely impaired in Jurkat-SMS1/kd cells. Finally, translocation of TCR, ZAP-70 and PKC theta into lipid rafts was markedly decreased in Jurkat-SMS1/kd cells. These findings indicate that membrane SM is crucial for TCR signal transduction, leading to full T cell activation through lipid raft function. C1 [Jin, Zhe-Xiong; Huang, Cheng-Ri; Dong, Lingli; Kawanami, Takafumi; Sawaki, Toshioki; Sakai, Tomoyuki; Tong, Xiao-Peng; Masaki, Yasufumi; Fukushima, Toshihiro; Tanaka, Masao; Umehara, Hisanori] Kanazawa Med Univ, Dept Hematol & Immunol, Uchinada, Ishikawa 9200293, Japan. [Dong, Lingli] Huazhong Univ Sci & Technol, Tongji Hosp, Dept Hematol & Immunol, Wuhan 430030, Hubei, Peoples R China. [Goda, Seiji] Osaka Dent Univ, Dept Biochem, Osaka, Japan. [Mimori, Tsuneyo] Kyoto Univ, Grad Sch Med, Dept Rheumatol & Clin Immunol, Sakyo Ku, Kyoto 6068507, Japan. [Tojo, Hiromasa] Osaka Univ, Grad Sch Med, Dept Biochem & Mol Biol, Osaka 5650871, Japan. [Bloom, Eda T.] US FDA, Div Cellular & Gene Therapies HFM 725, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Okazaki, Toshiro] Tottori Univ, Fac Med, Dept Clin Lab Med Hematol, Tottori 6838504, Japan. RP Umehara, H (reprint author), Kanazawa Med Univ, Dept Hematol & Immunol, 1-1 Daigaku, Uchinada, Ishikawa 9200293, Japan. EM umehara@kanazawa-med.ac.jp FU Japanese Ministry of Education and Science and Culture; Uehara Memorial Foundation; Kanazawa Medical University Research Foundation [13557160, 15024236, 15390313, 13877075]; JSPS FX Japanese Ministry of Education and Science and Culture, Uehara Memorial Foundation and Kanazawa Medical University Research Foundation (13557160, 15024236, 15390313, 13877075, 15024236, 15390313); JSPS Grant-in-Aid research funds and Uehara Memorial Foundation to Z.-X.J. NR 57 TC 32 Z9 35 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD NOV PY 2008 VL 20 IS 11 BP 1427 EP 1437 DI 10.1093/intimm/dxn100 PG 11 WC Immunology SC Immunology GA 365BW UT WOS:000260381900007 PM 18820264 ER PT J AU De Alwis, GKH Needham, LL Barr, DB AF De Alwis, G. K. Hemakanthi Needham, Larry L. Barr, Dana B. TI Determination of Dialkyl Phosphate Metabolites of Organophosphorus Pesticides in Human Urine by Automated Solid-Phase Extraction, Derivatization, and Gas Chromatography-Mass Spectrometry SO JOURNAL OF ANALYTICAL TOXICOLOGY LA English DT Article ID ALKYL PHOSPHATES; DIALKYLPHOSPHATE METABOLITES; GENERAL-POPULATION; HUMAN EXPOSURE; INSECTICIDES; LIQUID; EXCRETION; ALKYLPHOSPHATES; CLEANUP; SAMPLES C1 [De Alwis, G. K. Hemakanthi; Needham, Larry L.; Barr, Dana B.] Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Div Sci Lab, Atlanta, GA 30341 USA. RP De Alwis, GKH (reprint author), US FDA, FDA Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM hemakanthi.dealwis@ida.hhs.gov RI Needham, Larry/E-4930-2011; Barr, Dana/E-6369-2011; Barr, Dana/E-2276-2013 FU Centers for Disease Control and Prevention (CDC); National Center for Environmental Health; Division of Laboratory Sciences FX This work was supported in part by an appointment to the Research Participation Program at the Centers for Disease Control and Prevention (CDC), National Center for Environmental Health, Division of Laboratory Sciences, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U.S. Department of Energy and CDC. NR 36 TC 12 Z9 12 U1 0 U2 6 PU PRESTON PUBL INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0146-4760 J9 J ANAL TOXICOL JI J. Anal. Toxicol. PD NOV-DEC PY 2008 VL 32 IS 9 BP 721 EP 727 PG 7 WC Chemistry, Analytical; Toxicology SC Chemistry; Toxicology GA 377TK UT WOS:000261273300001 ER PT J AU Verma, A Cheung, AM Burns, DL AF Verma, Anita Cheung, Anissa M. Burns, Drusilla L. TI Stabilization of the Pertussis Toxin Secretion Apparatus by the C Terminus of PtlD SO JOURNAL OF BACTERIOLOGY LA English DT Article ID PROTEIN SECONDARY STRUCTURE; BORDETELLA-PERTUSSIS; AGROBACTERIUM-TUMEFACIENS; IV SECRETION; SUBCELLULAR-LOCALIZATION; VIRB6; SYSTEM; OPERON; GENES; SEQUENCE AB Pertussis toxin (PT) is secreted from Bordetella pertussis by a type IV secretion system, known as the Ptl transporter, that comprises nine different proteins, PtlA to PtlI. In this study, we found that PtlD is required for the stability of three Ptl proteins, PtlE, PtlF, and PtlH. A region limited to the C-terminal 72 amino acids of PtlD (amino acids 392 to 463) was sufficient for maintaining the stability of PtlE, PtlF, and PtlH, although this region was not sufficient to support secretion of the toxin. Further analysis demonstrated that a stretch of 10 amino acids at the C-terminal end of PtlD (amino acids 425 to 434) contributes to transporter stability. C1 [Burns, Drusilla L.] US FDA, CBER, HFM 434, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP Burns, DL (reprint author), US FDA, CBER, HFM 434, Lab Resp & Special Pathogens, Bldg 29,Room 130,8800 Rockville Pike, Bethesda, MD 20892 USA. EM drusilla.burns@fda.hhs.gov NR 25 TC 4 Z9 5 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 EI 1098-5530 J9 J BACTERIOL JI J. Bacteriol. PD NOV PY 2008 VL 190 IS 21 BP 7285 EP 7290 DI 10.1128/JB.01106-08 PG 6 WC Microbiology SC Microbiology GA 361ZF UT WOS:000260166900039 PM 18723610 ER PT J AU Boehmer, JL Bannerman, DD Shefcheck, K Ward, JL AF Boehmer, J. L. Bannerman, D. D. Shefcheck, K. Ward, J. L. TI Proteomic Analysis of Differentially Expressed Proteins in Bovine Milk During Experimentally Induced Escherichia coli Mastitis SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE proteomic analysis; coliform mastitis; milk protein ID ENDOTOXIN-INDUCED MASTITIS; INNATE IMMUNE-RESPONSES; DAIRY-COWS; CLINICAL MASTITIS; MAMMARY-GLAND; ALPHA-1-ACID GLYCOPROTEIN; STAPHYLOCOCCUS-AUREUS; EPITHELIAL-CELLS; SERUM-ALBUMIN; LIPOPOLYSACCHARIDE AB The objectives of the current study were to profile changes in protein composition using 2-dimensional gel electrophoresis on whey samples from a group of 8 cows before and 18 h after infection with Escherichia coli and to identify differentially expressed milk proteins by peptide sequencing using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry post source decay. Only proteins present in whey fractions of all 8 cows were sequenced to avoid reporting a protein response unique to only a subset of infected cows. Despite the overwhelming presence of casein and B-lactoglobulin, the low abundance proteins transthyretin, lactadherin, beta-2-microglobulin precursor, alpha-1-acid glycoprotein, and complement C3 precursor could be identified in whey samples from healthy cows. Whey samples at 18 h postinfection were characterized by an abundance of serum albumin, in spots of varying mass and isoelectric point, as well as increased transthyretin and complement C3 precursor levels. Also detected at 18 h postinoculation were the antimicrobial peptides cathelicidin, indolicidin, and bactenecin 5 and 7, and the proteins beta-fibrinogen, alpha-2-HS-glycoprotein, S100-A12, and alpha-1-antiproteinase. Most notable was the detection of the acute phase protein alpha-1-acid glycoprotein in mastitic whey samples, a result not previously reported. In contrast to methods used in previous proteomic analyses of bovine milk, the methods used in the current study enabled the rapid identification of milk proteins with minimal sample preparation. Use of a larger sample size than previous analyses also allowed for more robust protein identification. Results indicate that examination of the protein profile of whey samples from cows after inoculation with E. coli could provide a rapid survey of milk protein modulation during coliform mastitis and aid in the identification of biomarkers of this disease. C1 [Boehmer, J. L.; Ward, J. L.] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Boehmer, J. L.] Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. [Shefcheck, K.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20742 USA. [Bannerman, D. D.] ARS, USDA, Bovine Funct Genom Lab, Beltsville, MD 20705 USA. RP Boehmer, JL (reprint author), US FDA, Ctr Vet Med, Laurel, MD 20708 USA. EM jamie.boehmer@fda.hhs.gov NR 35 TC 60 Z9 67 U1 3 U2 14 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 NOV PY 2008 VL 91 IS 11 BP 4206 EP 4218 DI 10.3168/jds.2008-1297 PG 13 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 363OS UT WOS:000260277200013 PM 18946125 ER PT J AU Murray, CW Egan, SK Kim, H Beru, N Bolger, PM AF Murray, Clarence William Egan, Sara Kathleen Kim, Henry Beru, Nega Bolger, Philip Michael TI US Food and Drug Administration's Total Diet Study: Dietary intake of perchlorate and iodine SO JOURNAL OF EXPOSURE SCIENCE AND ENVIRONMENTAL EPIDEMIOLOGY LA English DT Article DE Total Diet Study; dietary intakes; nutritional element; iodine; perchlorate; monitoring ID UNITED-STATES; ACCUMULATION; EXPOSURE; HISTORY; MILK AB The US Food and Drug Administration (FDA) has conducted the Total Diet Study (TDS) since 1961, which designed to monitor the US food supply for chemical contaminants, nutritional elements, and toxic elements. Recently, perchlorate was analyzed in TDS samples. Perchlorate is used as an oxidizing agent in rocket propellant, is found in other items (e. g., explosives, road flares, fireworks, and car airbags), occurs naturally in some fertilizers, and may be generated under certain climatic conditions. It has been detected in surface and groundwater and in food. Perchlorate at high (e.g., pharmacological) doses can interfere with iodide uptake into the thyroid gland, disrupting its function. The National Academy of Sciences (NAS) has identified that "the fetuses of pregnant women who might have hypothyroidism or iodide deficiency as the most sensitive population." This study reports on intake estimates of perchlorate and iodine, a precursor to iodide, using the analytical results from the TDS. Estimated average perchlorate and iodine daily intakes as well as the contribution of specific food groups to total intakes were estimated for 14 age/sex subgroups of the US population. The estimated smallest lower bound to the largest upper bound average perchlorate intakes by the 14 age/sex groups range from 0.08 to 0.39 micrograms per kilogram body weight per day (mu g/kgbw/day), compared with the US Environmental Protection Agency (EPA) reference dose (RfD) of 0.7 mu g/kgbw/day. Infants and children demonstrated the highest estimated intakes of perchlorate on a body weight basis. The estimated average iodine intakes by the 14 age/sex groups reveal a lower bound (ND=0) and upper bound (ND=LOD) range of average intakes from 138 to 353 mu g/person/day. Estimated iodine intakes by infants 6-11 months exceed their adequate intake (AI), and intakes by children and adult age/sex groups exceed their relevant estimated average requirement (EAR). C1 [Murray, Clarence William; Egan, Sara Kathleen; Kim, Henry; Beru, Nega; Bolger, Philip Michael] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Murray, CW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS-301, College Pk, MD 20740 USA. EM Clarence.Murray@fda.hhs.gov FU Center for Food Safety and Applied Nutrition (CFSAN); FDA's FX The Total Diet Study is a collaborative effort of FDA's Center for Food Safety and Applied Nutrition (CFSAN) and FDA's district offices and laboratories. Finally, the authors of this work do not have any involvement, financial, or otherwise, that might potentially bias their work. NR 19 TC 100 Z9 105 U1 3 U2 25 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 NOV PY 2008 VL 18 IS 6 BP 571 EP 580 DI 10.1038/sj.jes.7500648 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 364CJ UT WOS:000260313500009 PM 18167505 ER PT J AU Day, JB Trujillo, S Hao, YYD Whiting, RC AF Day, J. B. Trujillo, S. Hao, Y. -Y. D. Whiting, R. C. TI Thermal Resistance of Francisella tularensis in Infant Formula and Fruit Juices SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; LISTERIA-MONOCYTOGENES; HEAT-RESISTANCE; TULAREMIA OUTBREAK; INACTIVATION; DESTRUCTION; SALMONELLA; VIRULENCE; TURKEY; FAT AB Francisella tularensis is a gram-negative bacterium that can cause gastrointestinal or oropharyngeal tularemia from ingestion of contaminated food or water. Despite the potential for accidental or intentional contamination of foods with F. tularensis, little information exists on the thermal stability of this organism in food matrices. In the present study, the thermal resistance of the live vaccine strain of F. tularensis in four food products (liquid infant formula, apple juice, mango juice, and orange juice) was investigated. D-values ranged from 12 s (57.5 degrees C) to 580 s (50 degrees C) in infant formula with a z-value of 4.37 degrees C. D-values in apple juice ranged from 8 s (57.5 degrees C) to 59 s (50 degrees C) with a z-value of 9.17 degrees C. The live vaccine strain did not Survive at temperatures above 55 degrees C in mango juice and orange juice (>6-log inactivation). D-values at 55 to 47.5 degrees C were 15 results indicate to 59 s in mango juice and 16 to 105 s in orange juice with z-values of 9.28 and 12.30 degrees C, respectively. These that current pasteurization parameters used for destroying common foodborne bacterial pathogens are adequate for eliminating F. tularensis in the four foods tested. This study is the first to determine thermal inactivation of F. tularensis in specific foods and will permit comparisons with the thermal inactivation data of other more traditional foodborne pathogens. C1 [Day, J. B.; Trujillo, S.; Hao, Y. -Y. D.; Whiting, R. C.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Day, JB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 712 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM james.day@fda.hhs.gov NR 31 TC 1 Z9 1 U1 3 U2 10 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD NOV PY 2008 VL 71 IS 11 BP 2208 EP 2212 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 371SB UT WOS:000260850500007 PM 19044262 ER PT J AU Kuroda, H Kutner, RH Bazan, NG Reiser, J AF Kuroda, Hitoshi Kutner, Robert H. Bazan, Nicolas G. Reiser, Jakob TI A comparative analysis of constitutive and cell-specific promoters in the adult mouse hippocampus using lentivirus vector-mediated gene transfer SO JOURNAL OF GENE MEDICINE LA English DT Article DE beta-galactosidase; cell-specific promoters; lentiviral vectors; mouse hippocampus; X-gal staining ID MESENCHYMAL STEM-CELLS; CENTRAL-NERVOUS-SYSTEM; TRANSGENE EXPRESSION; REPORTER GENE; TRANSDUCTION; EFFICIENT; NEURONS; BRAIN; TRANSPORT; VERSATILE AB Background Viral vectors provide powerful tools for transgene delivery to the mammalian brain to assess the effects of therapeutic proteins, antisense RNAs or small interfering RNAs. A key advantage of such approaches is that specific brain regions implicated in a particular disease can be independently targeted. Methods To optimize transgene expression in sub-regions of the mouse hippocampus and with a view towards devising gene therapy strategies for Alzheimer's disease, we designed lentivirus-based reporter vectors bearing various promoters, including constitutive and cell-specific promoters. Furthermore, we devised methods allowing a side-by-side comparison of transgene expression levels in neural cells both in vitro and in vivo. Results Following stereotaxic injection into the adult mouse hippocampus, titer-adjusted lentiviral vectors bearing constitutive promoters resulted in robust and sub-region-specific transgene expression. Our results show that the human CMV-IE promoter resulted in efficient transgene expression in the entire hippocampus whereas transgene expression mediated by the hybrid hEF1 alpha/HTLV promoter was limited mainly in the dentate gyrus and the CA2/3 region. Finally, the neuron-specific human synapsin I promoter was particularly effective in the dentate gyrus. Conclusions These findings indicate that subregion-specific transgene expression in the hippocampus can be achieved following lentivirus vector-mediated gene transfer. Copyright (C) 2008 John Wiley & Sons, Ltd. C1 [Kuroda, Hitoshi; Kutner, Robert H.; Reiser, Jakob] Louisiana State Univ, Hlth Sci Ctr, Gene Therapy Program, New Orleans, LA USA. [Kuroda, Hitoshi; Bazan, Nicolas G.] Louisiana State Univ, Hlth Sci Ctr, Neurosci Ctr Excellence, New Orleans, LA USA. RP Reiser, J (reprint author), US FDA, CBER, Div Cellular & Gene Therapies, 1401 Rockville Pike,HFM-725, Rockville, MD 20852 USA. EM Reiser@fda.hhs.gov FU NIH [R01 NS 044832] FX We thank Drs Colin P. J. Glover (University of Bristol), Stefan Brene (Karolinska Institutet), Eric R. Kandel (Columbia University), Maral Mouradian (National Institutes of Health) and Paul B. Fisher (Columbia University) for providing us with the hSynl, mGluR2, m alpha CaMKII, hGFAP and hEAAT2 promoters, respectively. We also thank Dr Mark A. DeCoster and Dr Alberto Musto (LSUHSC) for technical advice on primary cultures and stereotaxic injection and Luis Marrero (LSUHSC) for advice regarding histology. This work was supported by NIH grant R01 NS 044832. NR 40 TC 22 Z9 23 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1099-498X J9 J GENE MED JI J. Gene. Med. PD NOV PY 2008 VL 10 IS 11 BP 1163 EP 1175 DI 10.1002/jgm.1249 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 375KN UT WOS:000261112800001 PM 18773500 ER PT J AU Dogra, RS Joshi, BH Lloyd, R Kasperbauer, JL Puri, RK AF Dogra, Ritika S. Joshi, Bharat H. Lloyd, Ricardo Kasperbauer, Jan L. Puri, Raj K. TI Evaluation of Interleukin-13 Receptor (IL-13R) Overexpression in Human Thyroid Cancers SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Dogra, Ritika S.; Joshi, Bharat H.; Puri, Raj K.] US FDA, Tumor Vaccine & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Lloyd, Ricardo] Mayo Clin, Dept Lab Med & Pathol, Rochester, MN USA. [Kasperbauer, Jan L.] Mayo Clin, Dept Otolaryngol Head & Neck Surg, Rochester, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 940 EP 941 PG 2 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800077 ER PT J AU Fujisawa, T Shimamura, T Husain, SR Joshi, BH Nakajima, A Puri, RK AF Fujisawa, Toshio Shimamura, Takeshi Husain, Syed R. Joshi, Bharat H. Nakajima, Atsushi Puri, Raj K. TI Interleukin 13 (IL-13) Mediates Signaling Through IL-13R alpha 2: Targeting of the Receptors by IL-13 Pseudomonas Exotoxin (IL-13PE) for Pancreatic Cancer Therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Meeting Abstract CT 23rd Annual Scientific Meeting of the International-Society-for-Biological-Therapy-of-Cancer CY OCT 31-NOV 02, 2008 CL San Diego, CA SP Int Soc Biol Therapy Canc C1 [Fujisawa, Toshio; Shimamura, Takeshi; Husain, Syed R.; Joshi, Bharat H.; Puri, Raj K.] US FDA, Ctr Biol Evaluat & Res, Off Cellular Tissue & Gene Therapy, Div Cellular Gene Therapy, Bethesda, MD USA. [Nakajima, Atsushi] Yokohama City Univ, Sch Med, Div Gastroenterol, Yokohama, Kanagawa 232, Japan. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1524-9557 J9 J IMMUNOTHER JI J. Immunother. PD NOV-DEC PY 2008 VL 31 IS 9 BP 941 EP 941 PG 1 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 364TS UT WOS:000260358800079 ER PT J AU Rios, M Daniel, S Dayton, AI Wood, O Hewlett, IK Epstein, JS Caglioti, S Stramer, SL AF Rios, M. Daniel, S. Dayton, A. I. Wood, O. Hewlett, I. K. Epstein, J. S. Caglioti, S. Stramer, S. L. TI In vitro evaluation of the protective role of human antibodies to West Nile virus (WNV) produced during natural WNV infection SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID UNITED-STATES; IMMUNOGLOBULIN-M; BLOOD-TRANSFUSION; CEREBROSPINAL-FLUID; TRANSMISSION; RNA AB Background. West Nile virus (WNV) is endemic in the United States and transmissible by transfusion. Since 2003, the US blood supply has been screened by nucleic-acid tests (NAT) for WNV in minipools (MP-NAT) of 6 or 16 specimens. WNV infection begins with low-level viremia detectable only by individual testing (ID-NAT) and no detectable WNV antibodies. Viremia then increases to levels detectable by MP-NAT, and antibodies become detectable; later, viremia decays to levels detectable only by ID-NAT before becoming undetectable. All but 1 documented WNV transmission by transfusion involved blood components negative for WNV antibodies, raising the question whether WNV antibody-positive blood components with low levels of WNV RNA are infectious. Methods. Specimens from 102 viremic donors with and without WNV antibodies were used to investigate infectivity in cultures of Vero cells and human monocyte-derived macrophages (MDMs). Results. In Vero cell culture, 54 (74%) of 73 WNV antibody-negative specimens and 10 (36%) of 28 WNV antibody-positive specimens were infectious. In a random subset of 20 specimens tested in MDM culture, 7 (88%) of 8 WNV antibody-positive specimens and 12 (100%) of 12 WNV antibody-negative specimens were infectious. Conclusion. WNV antibodies do not always protect susceptible cells from WNV infection in vitro. RNA positivity in the presence of antibody cannot be ignored as a theoretical risk for blood recipients and needs further investigation. C1 [Rios, M.; Daniel, S.; Dayton, A. I.; Wood, O.; Hewlett, I. K.; Epstein, J. S.] US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab,Off Blood Res & Review, Div Emerging Transfus Transmitted Dis, Bethesda, MD USA. [Stramer, S. L.] Amer Red Cross, Gaithersburg, MD USA. [Caglioti, S.] Blood Syst Labs, Tempe, AZ USA. RP Rios, M (reprint author), 8800 Rockville Pike,Bldg 29,Rm 131,HFM-310, Bethesda, MD USA. EM Maria.Rios@fda.hhs.gov FU Center for Biologics Evaluation and Research, Food and Drug Administration FX Financial support: Center for Biologics Evaluation and Research, Food and Drug Administration. NR 25 TC 8 Z9 8 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1537-6613 J9 J INFECT DIS JI J. Infect. Dis. PD NOV 1 PY 2008 VL 198 IS 9 BP 1300 EP 1308 DI 10.1086/592277 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 360AU UT WOS:000260030200008 PM 18771407 ER PT J AU Wear, KA Harris, GR AF Wear, Keith A. Harris, Gerald R. TI Frequency dependence of backscatter from thin, oblique, finite-length cylinders measured with a focused transducer-with applications in cancellous bone SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID TRABECULAR BONE; ULTRASONIC BACKSCATTER; SOUND-SCATTERING; MIMICKING PHANTOMS; FLUID CYLINDERS; HUMAN CALCANEUS; MODEL; ZOOPLANKTON; COEFFICIENT; ATTENUATION AB A model is presented for the echo from a thin, oblique, finite-length cylinder. The echo is calculated from the line integral of the transducer directivity pattern along the cylinder axis. The model was validated with broadband pulse-echo measurements from (1) a perpendicular (to the ultrasound beam) nylon wire as a function of lateral displacement from the beam center, (2) a tilted nylon wire as a function of the angle of inclination relative to the ultrasound beam, and (3) a quasi-parallel-nylon-wire phantom, which mimicked the scattering properties of cancellous bone. The transducer directivity pattern (as a function of position and frequency) was measured with a membrane hydrophone. The model predicts an approximately cubic frequency dependence of backscatter coefficient from the phantom, as has been observed experimentally in cancellous bone. The model also predicts the relationship between the cylinder length and the exponent of a power law fit to backscatter coefficient versus frequency, which is 4 for very short (compared to a wavelength) cylinders and asymptotically approaches 3 for very long cylinders. (C) 2008 Acoustical Society of America. [DOI: 10.1121/1.2980524] C1 [Wear, Keith A.; Harris, Gerald R.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM kaw@fda.hhs.gov FU U. S. Food and Drug Administration Office of Women's Health FX The author is grateful to Andres Laib, Scanco, Inc., for providing the micro-CT scan in Fig. 1, and to the U. S. Food and Drug Administration Office of Women's Health for providing funding. NR 28 TC 7 Z9 8 U1 0 U2 2 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD NOV PY 2008 VL 124 IS 5 BP 3309 EP 3314 DI 10.1121/1.2980524 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 371MZ UT WOS:000260836700061 PM 19045813 ER PT J AU Wang, W Butler, EN Veguilla, V Vassell, R Thomas, JT Moos, M Ye, ZP Hancock, K Weiss, CD AF Wang, Wei Butler, Ebonee N. Veguilla, Vic Vassell, Russell Thomas, J. Terrig Moos, Malcolm, Jr. Ye, Zhiping Hancock, Kathy Weiss, Carol D. TI Establishment of retroviral pseudotypes with influenza hemagglutinins from H1, H3, and H5 subtypes for sensitive and specific detection of neutralizing antibodies SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE Hemagglutinin; Influenza; Neutralization; Protease; Hemagglutinin inhibition; Pseudotype ID HEPATITIS-C VIRUS; PROCESSING ENDOPROTEASES; LENTIVIRAL VECTORS; RECEPTOR-BINDING; GENE DELIVERY; IN-VIVO; CELLS; TRANSDUCTION; PARTICLES; ENVELOPE AB Pseudotype reporter viruses provide a safe, quantitative, and high-throughput tool for assessing antibody neutralization for many viruses, including high pathogenicity H5 and H7 influenza A strains. However, adapting this system to other influenza subtypes has been hampered by variations in the protease cleavage site of hemagglutinin (HA) that make it less susceptible to the cleavage required for infectivity. In this report several proteases, reporter vectors, and cell substrates were evaluated while optimizing pseudovirus production, and robust methods were established for sensitive and specific neutralization of pseudotypes carrying influenza H1, H3, and H5 subtype HA that correlates well with titers obtained in microneutralization assays involving replicating influenza virus These findings should facilitate broad use of HA-pseudotypes that remove the need for infectious virus in a range of applications, including neutralization assays for serological surveys of viral infection and evaluations of vaccine sera. Published by Elsevier B.V. C1 [Wang, Wei; Vassell, Russell; Ye, Zhiping; Weiss, Carol D.] US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Butler, Ebonee N.; Veguilla, Vic; Hancock, Kathy] Ctr Dis Control & Prevent, Influenza Div, Natl Ctr Immunizat & Resp Dis, Atlanta, GA 30333 USA. RP Weiss, CD (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM carol.weiss@fda.hhs.gov RI Weiss, Carol/F-6438-2011; Moos, Malcolm/F-3673-2011 OI Weiss, Carol/0000-0002-9965-1289; Moos, Malcolm/0000-0002-9575-9938 FU FDA; CDC FX We thank the following persons for generously supplying key reagents for these studies: Drs. Mikhail Matrosovich, Wolfgang Garten and Hans-Dieter Klenk (University of Marburg, Germany) for pCAGGS-TMPRSS2 and pCAGGS-HAT-FLAG; Dr. Gary Nabel (NIH, Bethesda, MD) for HIV-Luc pseudotype system, HA expression vector CMV/R 8 kappa B and Hybridoma for anti-TL HA; and Drs. Maribeth Eiden (NIH, Bethesda, MD) and Carolyn Wilson (FDA, Bethesda, MD) for MLV-beta-gal pseudotype system. We gratefully acknowledge Dr. Alexander Klimov (CDC, Atlanta, GA) for ferret H5 antisera, Galina Vodieko and Christine Anderson (FDA, Bethesda. MD) for H1, H3 and H5 reference sheep HA antisera, and Dr. John Wood (NIBSC, UK) for the sheep A/Turkey/1/2005 HA anti-serum.; We also thank Drs. Jerry Weir, Maryna Eichelberger (FDA, Bethesda, MD) and Jacqueline M. Katz (CDC, Atlanta, GA) for critical reading of this manuscript. This work was support by institutional research funds from the FDA and the CDC.; Financial support: Food and Drug Administration and Centers for Disease Control and Prevention; The findings and conclusions in this report are those of the authors and do not necessarily represent the views of the Centers for Disease Control and Prevention or the Center for Biologics Evaluation and Research. NR 37 TC 46 Z9 51 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD NOV PY 2008 VL 153 IS 2 BP 111 EP 119 DI 10.1016/j.jviromet.2008.07.015 PG 9 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 367PV UT WOS:000260565200006 PM 18722473 ER PT J AU Franco, L Gomez, F Badano, A AF Franco, L. Gomez, F. Badano, A. TI Characterization and simulation of linear scintillator arrays for low-energy x-ray detection SO MEASUREMENT SCIENCE AND TECHNOLOGY LA English DT Article DE scintillators; CsI; Gadox; CdWO4; MANTIS; low-energy x-rays ID IMAGING PERFORMANCE AB Current x-ray imaging in many industrial and medical applications uses different scintillator materials coupled to photodiode arrays. Knowledge of the light distribution and photoelectron signal allows for the improvement of the imaging properties of such devices. We have measured and simulated the pixel scintillation light distribution collected by the photodiode arrays for four commercial scintillator arrays made of cesium iodide, cadmium tungstate and gadolinium oxysulfide with pitches of 0.8 mm and 1.6 mm. We used a collimated low-energy x-ray beam to study the collected signal in each array element and the effective fill factors determined from the photodiode geometry, backing material and radiation transport in the scintillator. A proper description of the optical parameters of these detectors provides excellent agreement of the experimental results with Monte Carlo simulations performed with MANTIS. C1 [Franco, L.; Gomez, F.] Univ Santiago, Fac Fis, Dpto Fis Particulas, Santiago De Compostela 15782, Spain. [Badano, A.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Franco, L (reprint author), Univ Santiago, Fac Fis, Dpto Fis Particulas, Campus S-N, Santiago De Compostela 15782, Spain. EM luciaff@usc.es RI Gomez, Faustino/L-7288-2014; OI Gomez, Faustino/0000-0002-6147-8425; badano, aldo/0000-0003-3712-6670 NR 9 TC 1 Z9 1 U1 1 U2 4 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 0957-0233 EI 1361-6501 J9 MEAS SCI TECHNOL JI Meas. Sci. Technol. PD NOV PY 2008 VL 19 IS 11 AR 115504 DI 10.1088/0957-0233/19/11/115504 PG 7 WC Engineering, Multidisciplinary; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA 357DJ UT WOS:000259826200024 ER PT J AU Singh, PP Parra, M Cadieux, N Brennan, MJ AF Singh, Prachi P. Parra, Marcela Cadieux, Nathalie Brennan, Michael J. TI A comparative study of host response to three Mycobacterium tuberculosis PE_PGRS proteins SO MICROBIOLOGY-SGM LA English DT Article ID CELL-WALL; EXPRESSION; FAMILY; GENES; NECROSIS; MACROPHAGES; PE-PGRS33; MECHANISM; APOPTOSIS; VIRULENCE AB Three Mycobacterium tuberculosis proteins, PE_PGRS 16 (Rv0977), PE-PGRS 26 (Rv1441c) and PE-PGRS 33 (Rv1818c), were expressed in Mycobacterium smegmatis and used to investigate the host response to members of this unique protein family. Following infection of macrophages with the recombinant M. smegmatis (Ms) strains, Ms-PE_PGRS 33 and MsPE_PGRS 26 were significantly more persistent (4.4 and 4.2 log c.f.u.) compared with MsPE_PGRS 16 (3.4 log c.f.u.) at day 6. Similarly, after infection of mice, Ms-PE_PGRS 33 and MsPE_PGRS 26 persisted at significantly higher levels in the spleen (3.5 and 3.2 log c.f.u.) and liver (3 and 2.6 log c.f.u.) compared with Ms-PE_PGRS 16 in the spleen (2 log c.f.u.) and in the liver (11 log c.f.u.) at day 10. Increased persistence of Ms-PE_PGRS 33 and Ms-PE_PGRS 26 was associated with cell death and increased release of lactate dehydrogenase in macrophage cultures as well as increased levels of IL-10 and, in contrast, lower levels of IL-12 and NO both in vitro and in mouse splenocytes. Conversely, poor survival of Ms-PE_PGRS 16 was associated both in macrophage cultures and in vivo with higher levels of NO and IL-12. All three PE_PGRS proteins were found to be cell-surface antigens, but immunization of mice with these PE_PGRS antigens as DNA vaccines showed no protection in a TB aerosol challenge model. In general, the results suggest that variable expression of different PE_PGRS proteins within host cells can affect either the fate of the mycobacterial pathogen or that of the host during infection and point to the importance of studying the expression and function of individual members of the PE-PGRS gene family of M. tuberculosis. C1 [Singh, Prachi P.; Parra, Marcela; Cadieux, Nathalie; Brennan, Michael J.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20910 USA. RP Brennan, MJ (reprint author), Aeras Global TB Vaccine Fdn, 1405 Res Blvd, Rockville, MD 20850 USA. EM mbrennan@aeras.org FU National Vaccine Program Office of the US Department of Health and Human Services FX We would like to thank Veerabadran Dheenadhayalan and Amy L. Yang for their useful discussions, Giovanni Delogu and Michael Niederweis for advice oil methods for identifying cell Surface proteins, and Sheldon Morris and Steven Derrick for critical reading of the manuscript. This work was Supported by a grant from the National Vaccine Program Office of the US Department of Health and Human Services to M. J. B. NR 25 TC 40 Z9 41 U1 0 U2 3 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 NOV PY 2008 VL 154 BP 3469 EP 3479 DI 10.1099/mic.0.2008/019968-0 PN 11 PG 11 WC Microbiology SC Microbiology GA 379UB UT WOS:000261420600023 PM 18957600 ER PT J AU Kotewicz, ML Mammel, MK LeClerc, JE Cebula, TA AF Kotewicz, Michael L. Mammel, Mark K. LeClerc, J. Eugene Cebula, Thomas A. TI Optical mapping and 454 sequencing of Escherichia coli O157:H7 isolates linked to the US 2006 spinach-associated outbreak SO MICROBIOLOGY-SGM LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; SINGLE-NUCLEOTIDE POLYMORPHISMS; TOXIN-ENCODING BACTERIOPHAGES; FIELD GEL-ELECTROPHORESIS; SHIGA TOXIN; GENOMIC DIVERSITY; IN-VITRO; O157-H7; STRAINS; GENE AB Optical maps for five representative clinical, food-borne and bovine-derived isolates from the 2006 Escherichia coli O157 : H7 outbreak linked to fresh spinach in the United States showed a common set of 14 distinct chromosomal markers that define the outbreak strain. Partial 454 DNA sequencing was used to characterize the optically mapped chromosomal markers. The markers included insertions, deletions, substitutions and a simple single nucleoticle polymorphism creating a BamHl site. The Shiga toxin gene profile of the spinach-associated outbreak isolates (stx(1-) stx(2+) stx2c(+)) correlated with prophage insertions different from those in the prototypical EDL933 and Sakai reference strains (stx1(+) stx2(+) stx2c(-)). The prophage occupying the yehV chromosomal position in the spinach-associated outbreak isolates was similar to the stx1(+) EDL933 cryptic prophage V, but it lacked the stxl gene. In EDL933, the stx2 genes are within prophage BP933-W at the wrbA chromosomal locus; this locus was unoccupied in the spinach outbreak isolates. Instead, the stx2 genes were found within a chimeric BP933-W-like prophage with a different integrase, inserted at the argW locus in the outbreak isolates. An extra set of Shiga toxin genes, stx2c, was found in the outbreak isolates within a prophage integrated at the sbcB locus. The optical maps of two additional clinical isolates from the outbreak showed a single, different prophage variation in each, suggesting that changes occurred in the source strain during the course of this widespread, multi-state outbreak. C1 [Kotewicz, Michael L.; Mammel, Mark K.; LeClerc, J. Eugene; Cebula, Thomas A.] US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Cebula, TA (reprint author), US FDA, Div Mol Biol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. EM thomas.cebula@FDA.HHS.gov NR 39 TC 49 Z9 49 U1 0 U2 5 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 NOV PY 2008 VL 154 BP 3518 EP 3528 DI 10.1099/mic.0.2008/019026-0 PG 11 WC Microbiology SC Microbiology GA 379UB UT WOS:000261420600027 PM 18957604 ER PT J AU Verkler, TL Delongchamp, RR Couch, LH Miller, BJ Warbritton, A Mellick, PW Howard, PC Parsons, BL AF Verkler, Tracie L. Delongchamp, Robert R. Couch, Letha H. Miller, Barbara J. Warbritton, Alan Mellick, Paul W. Howard, Paul C. Parsons, Barbara L. TI Populations of p53 Codon 270 CGT to TGT Mutant Cells in SKH-1 Mouse Skin Tumors Induced by Simulated Solar Light SO MOLECULAR CARCINOGENESIS LA English DT Article DE ACB-PCR; mutation; allele-specific amplification; skin neoplasm ID COMPETITIVE BLOCKER PCR; EPIDERMAL-CELLS; MUTATIONS; CARCINOMAS; MICE; PHOTOCARCINOGENESIS; CARCINOGENESIS; IRRADIATION; SUNLIGHT; CANCER AB The p53 codon 270 CGT to TGT mutation was investigated as a biomarker of sunlight-induced mutagenesis and carcinogenesis. The relationship between tumor development and abundance of this hotspot mutation was analyzed in mouse skin tumors induced by chronic exposure to simulated solar light (SSL). The 24 tumors analyzed had similar growth kinetics, with an average doubling time of similar to 16.4 d. Levels of the p53 codon 270 mutation were quantified in the 24 mouse skin tumors using allele-specific competitive blocker-polymerase chain reaction (ACB-PCR). All tumors contained measurable amounts of the mutation. The p53 codon 270 CGT to TGT mutant fraction (MF) ranged from 2.29 x 10(-3) to 9.42 X 10(-2), with 3.26 x 10(-2) as the median. These p53 MF measurements are lower than expected for an initiating mutation involved in the development of tumors of monoclonal origin. There was no evidence of a correlation between p53 codon 270 MF and either tumor area or an estimate of tumor cell number. Thus, the data do not support the idea that p53 mutation accumulates linearly during tumor development. To investigate how p53 mutation was distributed within tumors, 19 needle biopsies from seven different tumors were analyzed by ACB-PCR. This analysis demonstrated that p53 codon 270 mutation is heterogeneously distributed within tumors. The long-term goal of this research is to combine morphological and p53 MF measurements from tissues corresponding to the various stages of tumor development, in order to derive mathematical models relating the p53 codon 270 mutation to the development of SSL-induced skin tumors. Published 2008 Wiley-Liss, Inc. C1 [Verkler, Tracie L.; Parsons, Barbara L.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Delongchamp, Robert R.] Univ Arkansas Med Sci, Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. [Couch, Letha H.; Miller, Barbara J.; Howard, Paul C.] US FDA, Natl Ctr Toxicol Res, Natl Toxicol Program, Ctr Phototoxicol,Div Biochem Toxicol, Jefferson, AR 72079 USA. [Warbritton, Alan; Mellick, Paul W.] Toxicol Pathol Associates, Pathol Serv, Jefferson, AR USA. RP Parsons, BL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. FU NTP Center for Phototoxicology; U.S. Food & Drug Administration; NIEHS [IAG 224-93-0001] FX The authors thank Dr. Page McKinzie for her assistance with the ACB-PCR studies and Dr. Xiaoiu Zou for her assistance with imaging. The NTP Center for Phototoxicology is supported by an Interagency Agreement between the U.S. Food & Drug Administration and NIEHS (IAG 224-93-0001). The contents of this manuscript do not necessarily reflect the views or policies of the U.S. Food & Drug Administration, nor does the mention of trade names or commercial products constitute endorsement or recommendation for use. NR 29 TC 8 Z9 8 U1 0 U2 3 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 NOV PY 2008 VL 47 IS 11 BP 822 EP 834 DI 10.1002/mc.20439 PG 13 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 371BZ UT WOS:000260808100002 PM 18381587 ER PT J AU Banoo, S Bell, D Bossuyt, P Herring, A Mabey, D Poole, F Smith, PG Sriram, N Wongsrichanalai, C Linke, R O'Brien, R Perkins, M Cunningham, J Matsoso, P Nathanson, CM Olliaro, P Peeling, RW Ramsay, A AF Banoo, Shabir Bell, David Bossuyt, Patrick Herring, Alan Mabey, David Poole, Freddie Smith, Peter G. Sriram, N. Wongsrichanalai, Chansuda Linke, Ralf O'Brien, Rick Perkins, Mark Cunningham, Jane Matsoso, Precious Nathanson, Carl Michael Olliaro, Piero Peeling, Rosanna W. Ramsay, Andy TI Evaluation of diagnostic tests for infectious diseases: general principles SO NATURE REVIEWS MICROBIOLOGY LA English DT Review ID ACCURACY; MEDICINE C1 [Banoo, Shabir] Med Control Council S Africa, Pretoria, South Africa. [Bell, David] WHO, Reg Off Western Pacific, Manila, Philippines. [Bossuyt, Patrick] Univ Amsterdam, Acad Med Ctr, Dept Clin Epidemiol & Biostat, NL-1105 AZ Amsterdam, Netherlands. [Herring, Alan] Univ Bristol, Sch Vet, Bristol, Avon, England. [Mabey, David] London Sch Hyg & Trop Med, Clin Res Unit, London WC1, England. [Poole, Freddie] US FDA, Ctr Biol Evaluat & Res, Div Microbiol Devices, Rockville, MD 20857 USA. [Smith, Peter G.] London Sch Hyg & Trop Med, Infect Dis Epidemiol Unit, London WC1, England. [Sriram, N.] Tulip Grp Co, Goa, India. [Wongsrichanalai, Chansuda] US Naval Med Res Unit 2, Jakarta, Indonesia. [Linke, Ralf; O'Brien, Rick; Perkins, Mark] Fdn Innovat Diagnost FIND, Geneva, Switzerland. [Cunningham, Jane; Matsoso, Precious; Nathanson, Carl Michael; Olliaro, Piero; Peeling, Rosanna W.; Ramsay, Andy] WHO, UNICEF, UNDP, World Bank,Special Programme Res & Training Trop, CH-1211 Geneva, Switzerland. RP Banoo, S (reprint author), Med Control Council S Africa, Pretoria, South Africa. EM peelingr@who.int RI Bossuyt, Patrick/B-4557-2016 OI Bossuyt, Patrick/0000-0003-4427-0128 NR 16 TC 14 Z9 14 U1 1 U2 4 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1740-1526 J9 NAT REV MICROBIOL JI Nat. Rev. Microbiol. PD NOV PY 2008 VL 6 IS 11 SU S BP S16 EP S28 DI 10.1038/nrmicro1523 PG 13 WC Microbiology SC Microbiology GA 372EE UT WOS:000260883800004 ER PT J AU Gonzalez-Cortes, C Salinas-Lara, C Gomez-Lopez, MA Tena-Suck, ML Perez-De La Cruz, V Rembao-Bojorquez, D Pedraza-Chaverri, J Gomez-Ruiz, C Galvan-Arzate, S Ali, SF Santamaria, A AF Gonzalez-Cortes, Carolina Salinas-Lara, Citlaltepetl Artemio Gomez-Lopez, Marcos Lilia Tena-Suck, Martha Perez-De La Cruz, Veronica Rembao-Bojorquez, Daniel Pedraza-Chaverri, Jose Gomez-Ruiz, Celedonio Galvan-Arzate, Sonia Ali, Syed F. Santamaria, Abel TI Iron porphyrinate Fe(TPPS) reduces brain cell damage in rats intrastriatally lesioned by quinolinate SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE Peroxynitrite; Excitotoxicity; Oxidative/nitrergic stress; Inflammatory events ID PEROXYNITRITE DECOMPOSITION CATALYSTS; NITRIC-OXIDE; DOPAMINERGIC NEUROTOXICITY; SUPEROXIDE-DISMUTASE; HUNTINGTONS-DISEASE; CORPUS STRIATUM; ACID; NEURODEGENERATION; INFLAMMATION; EXPRESSION AB It has been recently demonstrated that the reactive nitrogen species (RNS) peroxynitrite (ONOO-) is involved in the neurotoxic pattern produced by quinolinic acid in the rat brain IV. Perez-De La Cruz, C. Gonzalez-Cortes, S. Galvan-Arzate, O.N. Medina-Campos, F. Perez-Severiano, S.F. Ali, J. Pedraza-Chaverrif, A. Santamaria, Excitotoxic brain damage involves early peroxynitrite formation in a model of Huntington's disease in rats: protective role of iron porphyrinate 5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III), Neuroscience 135 (2005) 463-474.1. The aim of this work was to investigate whether ONOO- can also be responsible for morphological alterations and inflammatory events in the same paradigm. For this purpose, we evaluated the effect of a pre-treatment with the iron porphyrinate Fe(TPPS), a well-known ONOO- decomposition catalyst (10 mg/kg, i.p., 120 min before lesion), on the quinolinate-induced striatal cell damage and immunoreactivities to glial-fibrilar acidic protein (GFAP), interleukin 6 (IL-6) and inducible nitric oxide synthase (iNOS), one and seven days after the intrastriatal infusion of quinolinate (240 nmol/mu l) to rats. The striatal tissue from animals lesioned by quinolinate showed a significant degree of damage and enhanced immunoreactivities to GFAP IL-6 and iNOS, both at 1 and 7 days post-lesion. Pre-treatment of rats with Fe(TPPS) significantly attenuated or prevented all these markers at both post-lesion times tested, except for GFAP immunoreactivity at 7 days post-lesion and iNOS immunoreactivity at 1 day post-lesion. Altogether, our results suggest that ONOO- is actively participating in triggering inflammatory events and morphological alterations in the toxic model produced by quinolinate, since the use of agents affecting its formation, such as Fe(TPPS), are effective experimental tools to reduce the brain lesions associated to excitotoxic and oxidative damage. (C) 2008 Elsevier Inc. All rights reserved. C1 [Gonzalez-Cortes, Carolina; Perez-De La Cruz, Veronica; Santamaria, Abel] Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Aminoacidos Excitadores, SSA, Insurgentes 3877, Mexico City 14269, DF, Mexico. [Salinas-Lara, Citlaltepetl; Artemio Gomez-Lopez, Marcos; Lilia Tena-Suck, Martha; Rembao-Bojorquez, Daniel] Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Dept Neuropatol, Mexico City 14269, DF, Mexico. [Pedraza-Chaverri, Jose] Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City 04510, DF, Mexico. [Galvan-Arzate, Sonia] Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Dept Neuroquim, SSA, Mexico City 14269, DF, Mexico. [Ali, Syed F.; Santamaria, Abel] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Santamaria, A (reprint author), Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Lab Aminoacidos Excitadores, SSA, Insurgentes 3877, Mexico City 14269, DF, Mexico. EM absada@yahoo.com FU CONACyT-Mexico [48370-Q]; DGAPA PAPIIT [IN 207007] FX This work was supported by CONACyT-Mexico Grant 48370-Q (A.S.) and DGAPA PAPIIT (IN 207007 (JP). NR 25 TC 6 Z9 6 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 EI 1872-9738 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD NOV-DEC PY 2008 VL 30 IS 6 BP 510 EP 519 DI 10.1016/j.ntt.2008.05.004 PG 10 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 368TX UT WOS:000260646500008 PM 18579343 ER PT J AU Alexander, JJ Colangelo, PM Cooper, CK Roberts, R Rodriguez, WJ Murphy, MD AF Alexander, John J. Colangelo, Philip M. Cooper, Charles K. Roberts, Rosemary Rodriguez, William J. Murphy, Mary D. TI Arnoxicillin for Postexposure Inhalational Anthrax in Pediatrics Rationale For Dosing Recommendations SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE anthrax; amoxicillin; postexposure prophylaxis ID ACUTE OTITIS-MEDIA; MIDDLE-EAR EFFUSION; COMPARATIVE PHARMACOKINETICS; ANTIMICROBIAL PROPHYLAXIS; HUMAN VOLUNTEERS; AMOXICILLIN; CHILDREN; PREVENTION; AMPICILLIN; AZITHROMYCIN AB We reviewed information about the safety and plasma pharmacokinetic data for arnoxicillin, specifically related to its potential use for postexposure inhalational anthrax. Amoxicillin (45 mg/kg/d) given orally in 3 divided doses to pediatric patients < 40 kg should yield an adequate time above the MIC for Susceptible Bacillus anthracis (<= 0.5 mu g/mL) over most of the dosing interval (75-100%). Doses < 45 mg/kg/d and dosing intervals longer than 8 hours should not be used for postexposure inhalational anthrax. C1 [Rodriguez, William J.; Murphy, Mary D.] US FDA, Off Pediat Therapeut, Off Commissioner, Rockville, MD 20857 USA. [Alexander, John J.; Colangelo, Philip M.; Cooper, Charles K.; Roberts, Rosemary] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Rodriguez, WJ (reprint author), US FDA, Off Pediat Therapeut, Off Commissioner, 5600 Fishers Lane,Parklawn Bldg,Rm 13B45, Rockville, MD 20857 USA. EM william.rodriguez@fda.hhs.gov NR 27 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD NOV PY 2008 VL 27 IS 11 BP 955 EP 957 DI 10.1097/INF.0b013e31817bf9a9 PG 3 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 368UO UT WOS:000260648400001 PM 18833025 ER PT J AU Colman, E Szarfman, A PharmD, JW Mosholder, A Jillapalli, D Levine, J Avigan, M AF Colman, Eric Szarfman, Ana PharmD, Jo Wyeth Mosholder, Andrew Jillapalli, Devanand Levine, Jonathan Avigan, Mark TI An evaluation of a data mining signal for amyotrophic lateral sclerosis and statins detected in FDA's spontaneous adverse event reporting system SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE data mining; statins; amyotrophic lateral sclerosis; AERS ID OF-THE-LITERATURE; BLOOD-BRAIN-BARRIER; REDUCTASE INHIBITORS; MEMORY LOSS; SAFETY; SIMVASTATIN; DISEASE; PHARMACOVIGILANCE; MICROGLIA; COUNTY AB Background We detected disproportionate reporting of amyotrophic lateral sclerosis (ALS) with HMG-CoA-reductase inhibitors (statins) in the Food and Drug Administration's (FDA) spontaneous adverse event (AE) reporting system (AERS). Purpose To describe the original ALS signal and to provide additional context for interpreting the signal by conducting retrospective analyses of data from long-term, placebo-controlled clinical trials of statins. Methods The ALS signal was detected using the multi-item gamma Poisson shrinker(MGPS) algorithm. All AERS cases of ALS reported in association with use of a statin were individually reviewed by two FDA neurologists. Manufacturers of lovastatin, pravastatin, simvastatin, fluvastatin, atorvastatin, cerivastatin, and rosuvastatin were requested to provide the number of cases of ALS diagnosed during all of their placebo-controlled statin trials that were at least 6 months in duration. Results There were 91 US and foreign reports of ALS with statins in AERS. The data mining signal scores for ALS and statins ranged from 8.5 to 1.6. Data were obtained from 41 statin clinical trials ranging in duration from 6 months to 5 years and representing approximately 200000 patient-years of exposure to statin and approximately 200000 patient-years of exposure to placebo. Nine cases of ALS were reported in statin-treated patients and 10 cases in placebo-treated patients. Conclusions Although we observed a data mining signal for ALS with statins in FDA's AERS, retrospective analyses of 41 statin clinical trials did not reveal an increased incidence of ALS in subjects treated with a statin compared with placebo. Copyright (c) 2008 John Wiley & Sons, Ltd. C1 [Colman, Eric] US FDA, Div Metab & Endocrinol Prod, Off Drug Evaluat 2, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Szarfman, Ana] US FDA, Div Cardiovasc & Renal Prod, Silver Spring, MD 20993 USA. [Jillapalli, Devanand] US FDA, Div Neurol Prod, Silver Spring, MD 20993 USA. [PharmD, Jo Wyeth; Mosholder, Andrew; Avigan, Mark] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD 20993 USA. [Szarfman, Ana] US FDA, Off Translat Sci, Off Biosta, Div Biometr 6, Silver Spring, MD 20993 USA. [Levine, Jonathan] US FDA, Off Crit Path Programs, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Levine, Jonathan] US FDA, Off Commissioner, Silver Spring, MD 20993 USA. RP Colman, E (reprint author), US FDA, Div Metab & Endocrinol Prod, Off Drug Evaluat 2, Ctr Drug Evaluat & Res, White Oak Off Bldg 22,Room 3360,10903 New Hampshi, Silver Spring, MD 20993 USA. EM eric.colman@fda.hhs.gov NR 38 TC 24 Z9 24 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD NOV PY 2008 VL 17 IS 11 BP 1068 EP 1076 DI 10.1002/pds.1643 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 373ZI UT WOS:000261011600004 PM 18821724 ER PT J AU Pine, PS Boedigheimer, M Rosenzweig, BA Turpaz, Y He, YD Delenstarr, G Ganter, B Jarnagin, K Jones, WD Reid, LH Thompson, KL AF Pine, P. S. Boedigheimer, M. Rosenzweig, B. A. Turpaz, Y. He, Y. D. Delenstarr, G. Ganter, B. Jarnagin, K. Jones, W. D. Reid, L. H. Thompson, K. L. TI Use of diagnostic accuracy as a metric for evaluating laboratory proficiency with microarray assays using mixed-tissue RNA reference samples SO PHARMACOGENOMICS LA English DT Article DE microarrays; performance; proficiency testing; quality control; standards ID PROBE LEVEL DATA; AFFYMETRIX; REPRODUCIBILITY; NORMALIZATION; PERFORMANCE; SUMMARIES; QUALITY; DESIGN AB Effective use of microarray technology in clinical and regulatory settings is contingent on the adoption of standard methods for assessing performance. The MicroArray Quality Control project evaluated the repeatability and comparability of microarray data on the major commercial platforms and laid the groundwork for the application of microarray technology to regulatory assessments. However, methods for assessing performance that are commonly applied to diagnostic assays used in laboratory medicine remain to be developed for microarray assays. A reference system for microarray performance evaluation and process improvement was developed that includes reference samples, metrics and reference datasets. The reference material is composed of two mixes of four different rat tissue RNAs that allow defined target ratios to be assayed using a set of tissue-selective analytes that are distributed along the dynamic range of measurement. The diagnostic accuracy of detected changes in expression ratios, measured as the area under the curve from receiver operating characteristic plots, provides a single commutable value for comparing assay specificity and sensitivity. The utility of this system for assessing overall performance was evaluated for relevant applications like multi-laboratory proficiency testing programs and single-laboratory process drift monitoring. The diagnostic accuracy of detection of a 1.5-fold change in signal level was found to be a sensitive metric for comparing overall performance. This test approaches the technical limit for reliable discrimination of differences between two samples using this technology. We describe a reference system that provides a mechanism for internal and external assessment of laboratory proficiency with microarray technology and is translatable to performance assessments on other whole-genome expression arrays used for basic and clinical research. C1 [Pine, P. S.; Rosenzweig, B. A.; Thompson, K. L.] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. [Boedigheimer, M.] Amgen Inc, Thousand Oaks, CA 91320 USA. RP Thompson, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. EM karol.thompson@fda.hhs NR 28 TC 6 Z9 6 U1 0 U2 1 PU FUTURE MEDICINE LTD PI LONDON PA UNITEC HOUSE, 3RD FLOOR, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON, N3 1QB, ENGLAND SN 1462-2416 J9 PHARMACOGENOMICS JI Pharmacogenomics PD NOV PY 2008 VL 9 IS 11 BP 1753 EP 1763 DI 10.2217/14622416.9.11.1753 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 381PR UT WOS:000261548900021 PM 19018728 ER PT J AU Mason, BJ AF Mason, Barbara J. TI Challenges in Comorbidity SO PSYCHIATRIC ANNALS LA English DT Editorial Material C1 NIH, Bethesda, MD 20892 USA. [Mason, Barbara J.] Scripps Res Inst, Comm Neurobiol, Lab Clin Psychopharmacol, La Jolla, CA USA. [Mason, Barbara J.] Univ Miami, Sch Med, Coral Gables, FL 33124 USA. NIDA, Translat Ctr Clin Neurobiol, Bethesda, MD 20892 USA. [Mason, Barbara J.] NIAAA, Sci Advisory Council, Rockville, MD 20852 USA. [Mason, Barbara J.] US FDA, Rockville, MD 20857 USA. RP Mason, BJ (reprint author), NIH, Bethesda, MD 20892 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 0048-5713 J9 PSYCHIAT ANN JI Psychiatr. Ann. PD NOV PY 2008 VL 38 IS 11 BP 703 EP 705 PG 7 WC Psychiatry SC Psychiatry GA 374LX UT WOS:000261046000002 ER PT J AU Mammen, EF Miyakawa, T Phillips, TF Assarian, GS Brown, JM Murano, G AF Mammen, Eberhard F. Miyakawa, Teruo Phillips, Thomas F. Assarian, Gary S. Brown, Janet M. Murano, Genesio TI Human Antithrombin Concentrates and Experimental Disseminated Intravascular Coagulation (Reprinted from Semin Thromb Hemost, vol 11, pg 373-383, 1985) SO SEMINARS IN THROMBOSIS AND HEMOSTASIS LA English DT Reprint ID HUMAN-PLASMA KALLIKREIN; TOTAL HIP-REPLACEMENT; III DEFICIENCY; AT-III; HEPARIN COFACTOR; HEPATIC-FAILURE; GABEXATE MESILATE; LIVER-DISEASE; FACTOR-XII; INHIBITION C1 [Mammen, Eberhard F.; Miyakawa, Teruo; Assarian, Gary S.; Brown, Janet M.] Wayne State Univ, Sch Med, Dept Surg, Robert S Marx Surg Labs, Detroit, MI 48201 USA. [Mammen, Eberhard F.; Miyakawa, Teruo; Assarian, Gary S.; Brown, Janet M.] Wayne State Univ, Sch Med, Dept Pathol, Detroit, MI 48201 USA. [Mammen, Eberhard F.; Miyakawa, Teruo; Assarian, Gary S.; Brown, Janet M.] Wayne State Univ, Sch Med, Dept Physiol, Detroit, MI 48201 USA. [Phillips, Thomas F.] Downstate Med Sch, Dept Surg, Brooklyn, NY USA. [Murano, Genesio] US FDA, Div Blood & Blood Prod, Bethesda, MD 20014 USA. RP Mammen, EF (reprint author), Wayne State Univ, Sch Med, Dept Surg, Robert S Marx Surg Labs, Detroit, MI 48201 USA. NR 92 TC 0 Z9 0 U1 0 U2 1 PU THIEME MEDICAL PUBL INC PI NEW YORK PA 333 SEVENTH AVE, NEW YORK, NY 10001 USA SN 0094-6176 J9 SEMIN THROMB HEMOST JI Semin. Thromb. Hemost. PD NOV PY 2008 VL 34 IS 8 BP A34 EP A44 DI 10.1055/s-2007-1004397 PG 11 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 403HA UT WOS:000263072500019 ER PT J AU Boctor, SY Wang, C Ferguson, SA AF Boctor, Sherin Y. Wang, Cheng Ferguson, Sherry A. TI Neonatal PCP is more potent than ketamine at modifying preweaning behaviors of Sprague-Dawley rats SO TOXICOLOGICAL SCIENCES LA English DT Article DE ketamine; phencyclidine; neurodegeneration; forelimb hang; negative geotaxis; pup behavior ID L-CARNITINE; NEURONAL APOPTOSIS; PERINATAL PHENCYCLIDINE; DEVELOPING CEREBELLUM; INFANT INTERACTIONS; JUVENILE RATS; YOUNG-RATS; RECEPTORS; BLOCKADE; ADULT AB Treatment with N-methyl-D-aspartate (NMDA) receptor antagonists, such as ketamine (KET) or phencyclidine (PCP), can trigger apoptotic neurodegeneration in neonatal rodents; however, little is known about the behavioral alterations resulting from such treatment. Here, rats were sc treated with saline; 10 mg/kg PCP on postnatal days (PNDs) 7, 9, and 11; 20 mg/kg KET (six injections every 2 h on PND 7); or a regimen of ketamine and 250 mg/kg L-carnitine (KLC) both administered on PND 7 with additional 250 mg/kg doses of L-carnitine given on PNDs 8-11. Postinjection, the home cage behavior of each pup was categorized on PNDs 7-11. Slant board and forelimb hang behaviors were examined on PNDs 8-11 and 12-16, respectively. The initial KET or KLC injections on PND 7 elevated abnormal home cage activity (i.e., paresis and paddling); however, KLC pup behavior returned to normal by the fourth injection, indicating the protective effects of L-carnitine against NMDA antagonist toxicity. PCP treatment caused substantial abnormal home cage activity on each injection day (PNDs 7, 9, and 11). Latencies to turn on the slant board were significantly longer on PND 8 for KET- and PCP-treated pups and PND 10 for PCP-treated pups. On PND 12, the forelimb hang time of PCP-treated pups was significantly shorter. Body weight was decreased on PNDs 8-18 in PCP-treated pups and PNDs 8-10 in KET-treated pups. These data indicate that developmental NMDA antagonist treatment causes short-term behavioral alterations which appear related to motor coordination and may be cerebellar in nature. Furthermore, single PCP injections appear more potent at altering behavior than multiple injections of KET. C1 [Ferguson, Sherry A.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Interdisciplinary Biomed Sci, Little Rock, AR 72205 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM sherry.ferguson@fda.hhs.gov FU National Center for Toxicological Research (NCTR)/Food and Drug Administration (FDA) [224-93-0001]; National Institute for Environmental Health Sciences (NIEHS)/National Toxicology Program (NTP) FX Interagency Agreement #224-93-0001 between the National Center for Toxicological Research (NCTR)/Food and Drug Administration (FDA) and the National Institute for Environmental Health Sciences (NIEHS)/National Toxicology Program (NTP). NR 39 TC 11 Z9 11 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2008 VL 106 IS 1 BP 172 EP 179 DI 10.1093/toxsci/kfn152 PG 8 WC Toxicology SC Toxicology GA 359GU UT WOS:000259975200017 PM 18667523 ER PT J AU Dobson, RLM Motlagh, S Quijano, M Cambron, RT Baker, TR Pullen, AM Regg, BT Bigalow-Kern, AS Vennard, T Fix, A Reimschuessel, R Overmann, G Shan, Y Daston, GP AF Dobson, Roy L. M. Motlagh, Safa Quijano, Mike Cambron, R. Thomas Baker, Timothy R. Pullen, Aletha M. Regg, Brian T. Bigalow-Kern, Adrienne S. Vennard, Thomas Fix, Andrew Reimschuessel, Renate Overmann, Gary Shan, Yuching Daston, George P. TI Identification and characterization of toxicity of contaminants in pet food leading to an outbreak of renal toxicity in cats and dogs SO TOXICOLOGICAL SCIENCES LA English DT Article DE melamine; cyanuric acid; triazines; food safety ID CYANURIC ACID; DEGRADATIVE PATHWAY; RING-CLEAVAGE; HEXAMETHYLMELAMINE; MELAMINE; DERIVATIVES AB This paper describes research relating to the major recall of pet food that occurred in Spring 2007 in North America. Clinical observations of acute renal failure in cats and dogs were associated with consumption of wet pet food produced by a contract manufacturer producing for a large number of companies. The affected lots of food had been formulated with wheat gluten originating from China. Pet food and gluten were analyzed for contaminants using several configurations of high-performance liquid chromatography (HPLC) and mass spectrometry (MS), which revealed a number of simple triazine compounds, principally melamine and cyanuric acid, with lower concentrations of ammeline, ammelide, ureidomelamine, and N-methylmelamine. Melamine and cyanuric acid, have been tested and do not produce acute renal toxicity. Some of the triazines have poor solubility, as does the compound melamine cyanurate. Pathological evaluation of cats and dogs that had died from the acute renal failure indicated the presence of crystals in kidney tubules. We hypothesized that these crystals were composed of the poorly soluble triazines, a melamine-cyanuric acid complex, or a combination. Sprague dawley rats were given up to 100 mg/kg ammeline or ammelide alone, a mixture of melamine and cyanuric acid (400/400 mg/kg/day), or a mixture of all four compounds (400 mg/kg/day melamine, 40 mg/kg/day of the others). Neither ammeline nor ammelide alone produced any renal effects, but the mixtures produced significant renal damage and crystals in nephrons. HPLC-MS/MS confirmed the presence of melamine and cyanuric acid in the kidney. Infrared microspectroscopy on individual crystals from rat or cat (donated material from a veterinary clinic) kidneys confirmed that they were melamine-cyanuric acid cocrystals. Crystals from contaminated gluten produced comparable spectra. These results establish the causal link between the contaminated gluten and the adverse effects and provide a mechanistic explanation for how two apparently innocuous compounds could have adverse effects in combination, that is, by forming an insoluble precipitate in renal tubules leading to progressive tubular blockage and degeneration. C1 [Daston, George P.] Procter & Gamble Co, Miami Valley Innovat Ctr, Cincinnati, OH 45253 USA. [Reimschuessel, Renate] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Daston, GP (reprint author), Procter & Gamble Co, Miami Valley Innovat Ctr, POB 538707, Cincinnati, OH 45253 USA. EM Daston.gp@pg.com NR 16 TC 278 Z9 337 U1 4 U2 56 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD NOV PY 2008 VL 106 IS 1 BP 251 EP 262 DI 10.1093/toxsci/kfn160 PG 12 WC Toxicology SC Toxicology GA 359GU UT WOS:000259975200026 PM 18689873 ER PT J AU Bowyer, JF Latendresse, JR Delongchamp, RR Muskhelishvili, L Warbritton, AR Thomas, M Tareke, E McDaniel, LP Doerge, DR AF Bowyer, J. F. Latendresse, J. R. Delongchamp, R. R. Muskhelishvili, L. Warbritton, A. R. Thomas, M. Tareke, E. McDaniel, L. P. Doerge, D. R. TI The effects of subchronic acrylamide exposure on gene expression, neurochemistry, hormones, and histopathology in the hypothalamus-pituitary-thyroid axis of male Fischer 344 rats (vol 230, pg 208, 2008) SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Correction C1 [Doerge, D. R.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Bowyer, J. F.; Thomas, M.] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Latendresse, J. R.; Muskhelishvili, L.; Warbritton, A. R.] US FDA, Natl Ctr Toxicol Res, Div Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Delongchamp, R. R.] Univ Arkansas Med Sci, Coll Publ Hlth, Dept Epidemiol, Little Rock, AR 72205 USA. [Tareke, E.] US FDA, Natl Ctr Toxicol Res, Div Personalized Nutr & Med, Jefferson, AR 72079 USA. [McDaniel, L. P.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM daniel.doerge@fda.hhs.gov RI Latendresse, John/A-9215-2009 NR 1 TC 3 Z9 3 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD NOV 1 PY 2008 VL 232 IS 3 BP 498 EP 498 DI 10.1016/j.taap.2008.07.021 PG 1 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 366IX UT WOS:000260475500016 ER PT J AU Turk, DC Dworkin, RH McDermott, MP Bellamy, N Burke, LB Chandler, JM Cleeland, CS Cowan, P Dimitrova, R Farrar, JT Hertz, S Heyse, JF Iyengar, S Jadad, AR Jay, GW Jermano, JA Katz, NP Manning, DC Martin, S Max, MB McGrath, P McQuay, HJ Quessy, S Rappaport, BA Revicki, DA Rothman, M Stauffer, JW Svensson, O White, RE Witter, J AF Turk, Dennis C. Dworkin, Robert H. McDermott, Michael P. Bellamy, Nicholas Burke, Laurie B. Chandler, Julie M. Cleeland, Charles S. Cowan, Penney Dimitrova, Rozalina Farrar, John T. Hertz, Sharon Heyse, Joseph F. Iyengar, Smriti. Jadad, Alejandro R. Jay, Gary W. Jermano, John A. Katz, Nathaniel P. Manning, Donald C. Martin, Susan Max, Mitchell B. McGrath, Patrick McQuay, Henry J. Quessy, Steve Rappaport, Bob A. Revicki, Dennis A. Rothman, Margaret Stauffer, Joseph W. Svensson, Ola White, Richard E. Witter, James TI Analyzing multiple endpoints in clinical trials of pain treatments: IMMPACT recommendations SO PAIN LA English DT Review DE Multiple endpoints; Multiplicity; Clinical trials; Treatment outcomes; Chronic pain; Acute pain; Sampling error; Type I error ID CLEAR STATISTICAL SIGNIFICANCE; FALSE DISCOVERY RATE; OUTCOME MEASURES; RHEUMATOID-ARTHRITIS; ADJUSTMENT METHODS; TESTING PROCEDURES; RANDOMIZED-TRIALS; BINARY OUTCOMES; GLOBAL TESTS; CORE SET AB The increasing complexity of randomized clinical trials and the practice of obtaining a wide variety of measurements from Study participants have made the consideration Of Multiple endpoints a critically important issue in the design, analysis, and interpretation of clinical trials. Failure to consider important outcomes call limit the validity and utility of clinical trials; specifying multiple endpoints for the evaluation of treatment efficacy, however, call increase the rate of false positive conclusions about the efficacy of a treatment. We describe the use of multiple endpoints in the design, analysis, and interpretation of pain clinical trials, and review available strategies and methods for addressing multiplicity. To decrease the probability of a Type I error (i.e., the likelihood of obtaining statistically significant results by chance) in pain clinical trials.. the use of gatekeeping procedures and other methods that correct for multiple analyses is recommended when a single primary endpoint does not adequately reflect the overall benefits of treatment. We emphasize the importance of specifying in advance the Outcomes and clinical decision rule that will serve as the basis for determining that a treatment is efficacious and the methods that will be used to control the overall Type I error rate. (C) 2008 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved. C1 [Turk, Dennis C.] Univ Washington, Dept Anesthesiol, Seattle, WA 98195 USA. [Dworkin, Robert H.; McDermott, Michael P.] Univ Rochester, Dept Anesthesiol, Rochester, NY USA. [Bellamy, Nicholas; Chandler, Julie M.] Univ Queensland, Mayne Med Sch, Brisbane, Qld, Australia. [Burke, Laurie B.; Hertz, Sharon; Rappaport, Bob A.] US FDA, Silver Spring, MD USA. [Chandler, Julie M.; Heyse, Joseph F.] Merck & Co Inc, Epidemiol, Blue Bell, PA USA. [Cleeland, Charles S.] MD Anderson Canc Ctr, Dept Symptom Relief, Houston, TX USA. [Cowan, Penney; McQuay, Henry J.] Amer Chron Pain Assoc, Rocklin, CA USA. [Dimitrova, Rozalina] Allergan Pharmaceut Inc, Clin Res, Irvine, CA 92715 USA. [Farrar, John T.] Univ Penn, Ctr Clin Epidemiol & Biostat, Philadelphia, PA 19104 USA. [Iyengar, Smriti.] Eli Lilly & Co, Lilly Corp Ctr, Indianapolis, IN 46285 USA. [Jadad, Alejandro R.] Univ Toronto, Ctr Global Hlth, Toronto, ON, Canada. [Jay, Gary W.] Schwarz Biosci, Res Triangle Pk, NC USA. [Jermano, John A.] NeurogesX Inc, San Carlos, CA USA. [Katz, Nathaniel P.] Analges Res, Needham, MA USA. [Manning, Donald C.] Celgene Corp, Summit, NJ USA. [Martin, Susan] Pfizer Inc, Ann Arbor, MI USA. [Max, Mitchell B.] Univ Pittsburgh, Dept Anesthesiol, Pittsburgh, PA USA. [McGrath, Patrick] Dalhousie Univ, Dept Psychol, Halifax, NS B3H 3J5, Canada. [McQuay, Henry J.] Univ Oxford, Oxford, England. [Quessy, Steve] GlaxoSmithKline, Res Triangle Pk, NC USA. [Revicki, Dennis A.] United Biosource Corp, Bethesda, MD USA. [Rothman, Margaret] Johnson & Johnson Consumer Prod Inc, Raritan, NJ USA. [Stauffer, Joseph W.] Alpharma, Piscataway, NJ USA. [Svensson, Ola] AstraZeneca R&D, Sodertalje, Sweden. [White, Richard E.] Endo Pharmaceut Inc, Chadds Ford, PA USA. [Witter, James] US FDA, Rockville, MD 20857 USA. RP Turk, DC (reprint author), Univ Washington, Dept Anesthesiol, POB 356540, Seattle, WA 98195 USA. EM turkdc@u.washington.edu RI Farrar, John/A-1037-2007; Bellamy, Nicholas/G-3631-2010; OI Farrar, John/0000-0001-8656-5157; McGrath, Patrick/0000-0002-9568-2571 FU US Department of Veterans Affairs; US Food and Drug Administration; US National Institutes of Health FX The views expressed in this article are those of the authors, none of whom have financial conflicts of interest related to the material presented in this manuscript. No official endorsement by the US Department of Veterans Affairs, US Food and Drug Administration, US National Institutes of Health, or the pharmaceutical companies that provided unrestricted grants to the University of Rochester Office of Professional Education should be inferred.; The authors thank Paul J. Lambiase and Mary Gleichauf for their invaluable assistance in the organization of the IMMPACT meeting. Unrestricted grants were provided to the University of Rochester Office of Professional Education to support the consensus meeting on which this article is based by Allergan, Alpharma, AstraZeneca, Celgene, Cephalon, Ell Lilly, Endo, Glaxo SmithKline, Johnson & Johnson, Merck, NeurogesX, Pfizer, and Schwarz Pharma. NR 61 TC 93 Z9 93 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 EI 1872-6623 J9 PAIN JI Pain PD OCT 31 PY 2008 VL 139 IS 3 BP 485 EP 493 DI 10.1016/j.pain.2008.06.025 PG 9 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 372IG UT WOS:000260894700003 PM 18706763 ER PT J AU Ogurtsov, AY Marino-Ramirez, L Johnson, GR Landsman, D Shabalina, SA Spiridonov, NA AF Ogurtsov, Aleksey Y. Marino-Ramirez, Leonardo Johnson, Gibbes R. Landsman, David Shabalina, Svetlana A. Spiridonov, Nikolay A. TI Expression Patterns of Protein Kinases Correlate with Gene Architecture and Evolutionary Rates SO PLOS ONE LA English DT Article AB Background: Protein kinase (PK) genes comprise the third largest superfamily that occupy similar to 2% of the human genome. They encode regulatory enzymes that control a vast variety of cellular processes through phosphorylation of their protein substrates. Expression of PK genes is subject to complex transcriptional regulation which is not fully understood. Principal Findings: Our comparative analysis demonstrates that genomic organization of regulatory PK genes differs from organization of other protein coding genes. PK genes occupy larger genomic loci, have longer introns, spacer regions, and encode larger proteins. The primary transcript length of PK genes, similar to other protein coding genes, inversely correlates with gene expression level and expression breadth, which is likely due to the necessity to reduce metabolic costs of transcription for abundant messages. On average, PK genes evolve slower than other protein coding genes. Breadth of PK expression negatively correlates with rate of non-synonymous substitutions in protein coding regions. This rate is lower for high expression and ubiquitous PKs, relative to low expression PKs, and correlates with divergence in untranslated regions. Conversely, rate of silent mutations is uniform in different PK groups, indicating that differing rates of non-synonymous substitutions reflect variations in selective pressure. Brain and testis employ a considerable number of tissue-specific PKs, indicating high complexity of phosphorylation-dependent regulatory network in these organs. There are considerable differences in genomic organization between PKs up-regulated in the testis and brain. PK genes up-regulated in the highly proliferative testicular tissue are fast evolving and small, with short introns and transcribed regions. In contrast, genes up-regulated in the minimally proliferative nervous tissue carry long introns, extended transcribed regions, and evolve slowly. Conclusions/Significance: PK genomic architecture, the size of gene functional domains and evolutionary rates correlate with the pattern of gene expression. Structure and evolutionary divergence of tissue-specific PK genes is related to the proliferative activity of the tissue where these genes are predominantly expressed. Our data provide evidence that physiological requirements for transcription intensity, ubiquitous expression, and tissue-specific regulation shape gene structure and affect rates of evolution. C1 [Ogurtsov, Aleksey Y.; Marino-Ramirez, Leonardo; Landsman, David; Shabalina, Svetlana A.] Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. [Johnson, Gibbes R.; Spiridonov, Nikolay A.] US FDA, Ctr Drug Evaluat & Res, Div Therapeut Proteins, Bethesda, MD USA. RP Ogurtsov, AY (reprint author), Natl Lib Med, Natl Ctr Biotechnol Informat, NIH, Bethesda, MD 20894 USA. EM shabalin@ncbi.nlm.nih.gov; nikolay.spiridonov@fda.hhs.gov RI Marino-Ramirez, Leonardo/I-5759-2013; Shabalina, Svetlana/N-8939-2013; Spiridonov, Nikolay/B-6287-2014; OI Marino-Ramirez, Leonardo/0000-0002-5716-8512; Shabalina, Svetlana/0000-0003-2272-7473; Landsman, David/0000-0002-9819-6675 FU Intramural Research Program of the National Institutes of Health, National Library of Medicine FX This research was supported in part by the Intramural Research Program of the National Institutes of Health, National Library of Medicine. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. NR 71 TC 9 Z9 9 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 31 PY 2008 VL 3 IS 10 AR e3599 DI 10.1371/journal.pone.0003599 PG 17 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432KK UT WOS:000265131700020 PM 18974838 ER PT J AU Schwartz, RS Burke, A Farb, A Kaye, D Lesser, JA Henry, R Virmani, R AF Schwartz, Robert S. Burke, Allen Farb, Andrew Kaye, David Lesser, John A. Henry, Rimothy Virmani, Renu TI Myocardial Microvascular Obstruction in Sudden Death from Acute Myocardial Infarction Occurs more often in Coronary Plaque Erosion than in Plaque Rupture SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Schwartz, Robert S.] Minneapolis Heart Inst Fdn, Inver Grove Heights, MN USA. [Burke, Allen; Virmani, Renu] CV Path Inst, Gaithersburg, MD USA. [Farb, Andrew] US FDA, Rockville, MD 20857 USA. [Kaye, David] Baker Heart Res Inst, Melbourne, Vic, Australia. [Lesser, John A.; Henry, Rimothy] Minneapolis Heart Inst Fdn, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S475 EP S475 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104501108 ER PT J AU Takao, CM Takahashi, M Pravica, V Barton, C Burckhart, G AF Takao, Cheryl M. Takahashi, Masato Pravica, Vera Barton, Cheryl Burckhart, Gilbert TI Vitamin K Epoxide Reductase Genotype Alters Warfarin Dose Requirements in Pediatric Patients SO CIRCULATION LA English DT Meeting Abstract CT 81st Annual Scientific Session of the American-Heart-Association CY NOV 08-12, 2008 CL New Orleans, LA SP Amer Heart Assoc C1 [Takao, Cheryl M.; Takahashi, Masato; Barton, Cheryl] Childrens Hosp Los Angeles, Los Angeles, CA 90027 USA. [Pravica, Vera] Univ So Calif, Los Angeles, CA USA. [Burckhart, Gilbert] US FDA, Silver Spring, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD OCT 28 PY 2008 VL 118 IS 18 BP S1056 EP S1056 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 389ON UT WOS:000262104504194 ER PT J AU Pogribny, IP Karpf, AR James, SR Melnyk, S Han, T Tryndyak, VP AF Pogribny, Igor P. Karpf, Adam R. James, Smitha R. Melnyk, Stepan Han, Tao Tryndyak, Volodymyr P. TI Epigenetic alterations in the brains of Fisher 344 rats induced by long-term administration of folate/methyl-deficient diet SO BRAIN RESEARCH LA English DT Article DE Rat; Brain; Folate/methyl-deficient diet; Epigenetics; DNA methylation; Gene expression ID DNA-BINDING PROTEIN; GENOMIC DNA; S-ADENOSYLMETHIONINE; METHYL DEFICIENCY; GENE-EXPRESSION; HYPERMETHYLATION; MECP2; HEPATOCARCINOGENESIS; HOMOCYSTEINE; DISORDERS AB The maintenance of the cellular epigenomic landscape, which depends on the status of the one-carbon metabolic pathway, is essential for normal central nervous system development and function. In the present study, we examined the epigenetic alterations in the brains of Fisher 344 rats induced by the long-term administration of a diet lacking of essential one-carbon nutrients, methionine, choline, and folic acid. The results demonstrated that feeding a folate/methyl-deficient diet causes global DNA hypermethylation as indicated by an increase of genomic 5-methyl-2'-deoxycytidine (5mdC) content and more importantly, by an increase of methylation within unmethylated CpG-rich DNA domains. Interestingly, these epigenetic changes were opposite to those observed in the livers of the same folate/methyl-deficient rats. The hypermethylation changes were associated with an increased protein expression of de novo DNA methyltransferase DNMT3a and methyl-CpG-binding protein 2. Additionally, the gene expression profiling identified 33 significantly up- or down-regulated genes (fold change > 1.5 and p <= 0.05) in the brains of rats fed a folate/methyldeficient diet for 36 weeks. Interestingly, we detected an up-regulation of regulatory factor X, 3 (Rfx3) gene, a sequence-specific DNA-binding protein, that mediates the transcriptional activation of silenced by methylation genes, which may be an adaptive protective brain response to hypermethylation. Together, these data suggest that the proper maintenance of the epigenomic landscape in normal brain depends on the adequate supply of essential nutrients involved in the metabolism of methyl groups. (c) Published by Elsevier B.V. C1 [Pogribny, Igor P.; Tryndyak, Volodymyr P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Karpf, Adam R.; James, Smitha R.] Roswell Pk Canc Inst, Dept Pharmacol & Therapeut, Buffalo, NY 14263 USA. [Melnyk, Stepan] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Han, Tao] Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov FU NCI NIH HHS [R01 CA116674, R01 CA116674-03] NR 42 TC 52 Z9 53 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 27 PY 2008 VL 1237 SI SI BP 25 EP 34 DI 10.1016/j.brainres.2008.07.077 PG 10 WC Neurosciences SC Neurosciences & Neurology GA 371EW UT WOS:000260815600004 PM 18694733 ER PT J AU Bagnyukova, TV Powell, CL Pavliv, O Tryndyak, VP Pogribny, IP AF Bagnyukova, Tetyana V. Powell, Christine L. Pavliv, Oleksandra Tryndyak, Volodymyr P. Pogribny, Igor P. TI Induction of oxidative stress and DNA damage in rat brain by a folate/methyl-deficient diet SO BRAIN RESEARCH LA English DT Article DE Rat; Brain; Folate/methyl-deficient diet; Oxidative stress; Apoptosis ID COULOMETRIC ELECTROCHEMICAL DETECTION; ALZHEIMERS-DISEASE; FOLIC-ACID; NEURODEGENERATIVE DISORDERS; S-ADENOSYLMETHIONINE; NERVOUS-SYSTEM; HOMOCYSTEINE; APOPTOSIS; CHOLINE; REPAIR AB The age-associated decline in cellular antioxidant defenses and resultant accumulation of DNA damage in central nervous system has been mechanistically implicated in the etiology and pathogenesis of neurodegenerative diseases. Neurons possess a high metabolic activity and are especially vulnerable to the long-term effects of continuous exposure to endogenous reactive oxygen species. It is well recognized that adequate availability of essential nutrients involved in cellular one-carbon metabolism is essential for normal brain development and function. Additionally, the synthesis of the primary low-molecular cellular antioxidant glutathione is inter-dependently linked to one-carbon metabolic pathway. Thus, any aberrant disruptions in one-carbon metabolism can result in potentially deleterious effects including cell death as a result of an imbalance in the cellular redox state. Hence, in the present study, we examined the long-term effects of a folate/methyl-deficient (FMD) diet on cellular antioxidant defenses and DNA damage in the rat brain. Feeding male Fisher 344 rats a FMD diet resulted in perturbations in the levels of one-carbon metabolites along with induction of oxidative stress and oxidative DNA damage in the brain. This was evidenced by a decrease in the reduced oxidized/glutathione ratio, imbalance of cellular antioxidant defense system; specifically, altered activity and expression of antioxidant enzymes Mn-containing superoxide dismutase (Mn-SOD), catalase, and glutathione peroxidase (GPX), increased accumulation of oxidative DNA lesions, 8-hydroxydeoxyguanosine (8-OH-dG) and DNA single-strand breaks, even in the presence of increased expression of critical DNA repair genes apurinic/apyrimidinic endonuclease 1 (Apex1) and DNA polymerase beta (Pol beta), and apoptosis in the brains of folate/methyl-deficient rats. These results indicate that chronic methyl group deficiency leads to an imbalance in cellular antioxidant defense systems, increased oxidative stress, and apoptosis. Any of these events may compromise normal central nervous system function and contribute to the development of various neurological, behavioral, and neurocognitive dysfunctions. (c) 2008 Elsevier B.V. All rights reserved. C1 [Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Powell, Christine L.] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA. [Pavliv, Oleksandra] Univ Arkansas Med Sci Hosp, Dept Pediat, Little Rock, AR 72205 USA. RP Bagnyukova, TV (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM tetyana.bagnyukova@fda.hhs.gov; igor.pogribny@fda.hhs.gov NR 38 TC 33 Z9 36 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD OCT 27 PY 2008 VL 1237 SI SI BP 44 EP 51 DI 10.1016/j.brainres.2008.07.073 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 371EW UT WOS:000260815600006 PM 18694737 ER PT J AU Junttila, IS Mizukami, K Dickensheets, H Meier-Schellersheim, M Yamane, H Donnelly, RP Paul, WE AF Junttila, Ilkka S. Mizukami, Kiyoshi Dickensheets, Harold Meier-Schellersheim, Martin Yamane, Hidehiro Donnelly, Raymond P. Paul, William E. TI Tuning sensitivity to IL-4 and IL-13: differential expression of IL-4R alpha, IL-13R alpha 1, and gamma c regulates relative cytokine sensitivity SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID SIGNAL-TRANSDUCTION; MICE LACKING; RECEPTOR COMPLEX; GENE-EXPRESSION; CUTTING EDGE; INTERLEUKIN-13; ACTIVATION; CELLS; CHAIN; STAT6 AB Interleukin (IL)-4 and -13 are related cytokines sharing functional receptors. IL-4 signals through the type I (IL-4R alpha/common gamma-chain [gamma c]) and the type II (IL-4R alpha/-13R alpha 1) IL-4 receptors, whereas IL-13 utilizes only the type II receptor. In this study, we show that mouse bone marrow-derived macrophages and human and mouse monocytes showed a much greater sensitivity to IL-4 than to IL-13. Lack of functional gamma c made these cells poorly responsive to IL-4, while retaining full responsiveness to IL-13. In mouse peritoneal macrophages, IL-4 potency exceeds that of IL-13, but lack of gamma c had only a modest effect on IL-4 signaling. In contrast, IL-13 stimulated greater responses than IL-4 in fibroblasts. Using levels of receptor chain expression and known binding affinities, we modeled the assemblage of functional type I and II receptor complexes. The differential expression of IL-4R alpha, IL-13R alpha 1, and gamma c accounted for the distinct IL-4-IL-13 sensitivities of the various cell types. These findings provide an explanation for IL-13's principal function as an "effector" cytokine and IL-4's principal role as an "immunoregulatory" cytokine. C1 [Junttila, Ilkka S.; Mizukami, Kiyoshi; Meier-Schellersheim, Martin; Yamane, Hidehiro; Paul, William E.] NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. [Dickensheets, Harold; Donnelly, Raymond P.] US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Junttila, IS (reprint author), NIAID, Immunol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM junttilai@niaid.nih.gov FU National Institute for Allergy and Infectious Diseases Intramural Program; Finnish Cultural Foundation; Finnish Medical Foundation; Emil Aaltonen Foundation FX This work was supported by National Institute for Allergy and Infectious Diseases Intramural Program, the Finnish Cultural Foundation, the Finnish Medical Foundation, and the Emil Aaltonen Foundation. NR 52 TC 79 Z9 81 U1 2 U2 4 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD OCT 27 PY 2008 VL 205 IS 11 BP 2595 EP 2608 DI 10.1084/jem.20080452 PG 14 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 368ED UT WOS:000260603200016 PM 18852293 ER PT J AU Wang, X Tryndyak, V Apostolov, EO Yin, X Shah, SV Pogribny, IP Basnakian, AG AF Wang, Xiaoying Tryndyak, Volodymyr Apostolov, Eugene O. Yin, Xiaoyan Shah, Sudhir V. Pogribny, Igor P. Basnakian, Alexei G. TI Sensitivity of human prostate cancer cells to chemotherapeutic drugs depends on EndoG expression regulated by promoter methylation SO CANCER LETTERS LA English DT Article DE endonuclease g; DNA methylation; prostate cancer; cell death; cisplatin ID ENDONUCLEASE-G; EPIGENETIC THERAPY; DNA METHYLATION; DEOXYRIBONUCLEASE-II; APOPTOSIS PROTEINS; IN-VIVO; DEATH; ACTIVATION; CISPLATIN; GENES AB Analysis of promoter sequences of all known human cytotoxic endonucleases showed that endonuclease G (EndoG) is the only endonuclease that contains a CpG island, a segment of DNA with high G+C content and a site for methylation, in the promoter region. A comparison of three human prostate cancer cell lines showed that EndoG is highly expressed in 22Rv1 and LNCaP cells. In PC3 cells, EndoG was not expressed and the EndoG CpG island was hypermethylated. The expression of EndoG correlated positively with sensitivity to cisplatin and etoposide, and the silencing of EndoG by siRNA decreased the sensitivity of the cells to the chemotherapeutic agents in the two EndoG-expressing cell lines. 5-aza-2 '-deoxycytidine caused hypomethylation of the EndoG promoter in PO cells, induced EndoG mRNA and protein expression, and made the cells sensitive to both cisplatin and etoposide. The acetylation of histories by trichostatin A, the histone deacetylase inhibitor, induced EndoG expression in 22Rv1 cells, while it had no such effect in PO cells. These data are the first indication that EndoG may be regulated by methylation of its gene promoter, and partially by histone acetylation, and that EndoG is essential for prostate cancer cell death in the used models. (c) 2008 Elsevier Ireland Ltd. All rights reserved. C1 [Wang, Xiaoying; Apostolov, Eugene O.; Basnakian, Alexei G.] Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. [Tryndyak, Volodymyr; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Wang, Xiaoying; Apostolov, Eugene O.; Yin, Xiaoyan; Shah, Sudhir V.; Basnakian, Alexei G.] Univ Arkansas Med Sci, Dept Internal Med, Div Nephrol, Little Rock, AR 72205 USA. [Shah, Sudhir V.; Basnakian, Alexei G.] Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. RP Basnakian, AG (reprint author), Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, 4301 W Markham 638, Little Rock, AR 72205 USA. EM basnakianalexeig@uams.edu FU NCI NIH HHS [R03 CA114729]; NIDDK NIH HHS [R01 DK078908] NR 71 TC 16 Z9 18 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 EI 1872-7980 J9 CANCER LETT JI Cancer Lett. PD OCT 18 PY 2008 VL 270 IS 1 BP 132 EP 143 DI 10.1016/j.canlet.2008.04.053 PG 12 WC Oncology SC Oncology GA 357LL UT WOS:000259847200013 PM 18565644 ER PT J AU Brorson, K Shen, H Lute, S Perez, JS Frey, DD AF Brorson, Kurt Shen, Hong Lute, Scott Perez, Jessica Soto Frey, Douglas D. TI Characterization and purification of bacteriophages using chromatofocusing SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE Chromatofocusing; Virus purification; Virus characterization; Bacteriophage; pH gradient elution ID ELECTROSTATIC INTERACTION CHROMATOGRAPHY; ANION-EXCHANGE CHROMATOGRAPHY; VIRUS-RETENTIVE FILTERS; GENE-THERAPY VECTORS; GEL-ELECTROPHORESIS; CHARGE REGULATION; MEMBRANE-FILTER; ELECTROKINETIC PROPERTIES; PSEUDOMONAS-AERUGINOSA; RECOMBINANT ADENOVIRUS AB The technique of chromatofocusing was applied to the characterization and purification of three bacteriophages that are routinely used for testing virus filters: phi X174, PR772, and PP7. Chemically well-defined eluent buffers were used, instead of the more commonly used chromatofocusing polyampholyte buffers. Chromatographic column packings were selected to minimize band broadening by confining bacteriophage adsorption solely to the exterior particle surface. Under the conditions used it was determined that bacteriophages could be made to focus into narrow bands in a retained pH gradient with recoveries of live phage that ranged from 15 to nearly 100% as determined by a plaque-forming assay. Retention times and apparent isoelectric point data were obtained for samples consisting either of purified bacteriophage, or samples consisting of crude preparations of bacteriophages containing host cell impurities. Isoelectric point estimates were obtained using modified, previously described models. The results obtained suggest that chromatofocusing is a simple and rapid method for obtaining approximate isoelectric points for bacteriophages and probably other types of viruses. It is also likely a useful method for purifying these materials. (C) 2008 Elsevier B.V. All rights reserved. C1 [Shen, Hong; Perez, Jessica Soto; Frey, Douglas D.] Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. [Brorson, Kurt; Lute, Scott] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Frey, DD (reprint author), Univ Maryland Baltimore Cty, Dept Chem & Biochem Engn, 1000 Hilltop Circle, Baltimore, MD 21250 USA. EM dfrey1@umbc.edu FU National Science Foundation [CTS-0442072] FX We thank Dr. Liming Zhao of Drexel University for performing the Atomic Force Microscopy experiments described in Section 3.5, and Dr. Chris Pohl, Dr. Osama El-Badry, and Dr. Ken Larkey of Dionex for helpful advice concerning the Dionex column packings used in this study. We also thank Dr. Lixin Xu, Dr. Ebenezer B. Asafu Adjaye, and Dr. Anthony Ciavarella of CDER/FDA for careful review of this manuscript. Finally, several of the authors (H.S., D.F.) thank the National Science Foundation for partial support of this work through grant CTS-0442072. NR 89 TC 25 Z9 26 U1 3 U2 24 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD OCT 17 PY 2008 VL 1207 IS 1-2 BP 110 EP 121 DI 10.1016/j.chroma.2008.08.037 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 365HX UT WOS:000260397600012 PM 18778829 ER PT J AU Nanda, S Havert, MB Calderon, GM Thomson, M Jacobson, C Kastner, D Liang, TJ AF Nanda, Santosh Havert, Michael B. Calderon, Gloria M. Thomson, Michael Jacobson, Christian Kastner, Daniel Liang, T. Jake TI Hepatic Transcriptome Analysis of Hepatitis C Virus Infection in Chimpanzees Defines Unique Gene Expression Patterns Associated with Viral Clearance SO PLOS ONE LA English DT Article AB Hepatitis C virus infection leads to a high rate of chronicity. Mechanisms of viral clearance and persistence are still poorly understood. In this study, hepatic gene expression analysis was performed to identify any molecular signature associated with the outcome of hepatitis C virus (HCV) infection in chimpanzees. Acutely HCV-infected chimpanzees with self-limited infection or progression to chronicity were studied. Interferon stimulated genes were induced irrespective of the outcome of infection. Early induction of a set of genes associated with cell proliferation and immune activation was associated with subsequent viral clearance. Specifically, two of the genes: interleukin binding factor 3 (ILF3) and cytotoxic granule-associated RNA binding protein (TIA1), associated with robust T-cell response, were highly induced early in chimpanzees with self-limited infection. Up-regulation of genes associated with CD8+ T cell response was evident only during the clearance phase of the acute self-limited infection. The induction of these genes may represent an initial response of cellular injury and proliferation that successfully translates to a "danger signal'' leading to induction of adaptive immunity to control viral infection. This primary difference in hepatic gene expression between self-limited and chronic infections supports the concept that successful activation of HCV-specific T-cell response is critical in clearance of acute HCV infection. C1 [Nanda, Santosh; Havert, Michael B.; Calderon, Gloria M.; Thomson, Michael; Liang, T. Jake] NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. [Jacobson, Christian; Kastner, Daniel] NIAMS, Genet & Genom Branch, NIH, Bethesda, MD USA. [Nanda, Santosh; Havert, Michael B.] FDA, CBER, Bethesda, MD USA. [Thomson, Michael] GlaxoSmithKline Inc, Virol Dept, Res Triangle Pk, NC USA. [Jacobson, Christian] Univ Waterloo, Dept Biol & Mech & Mechatron Engn, Waterloo, ON N2L 3G1, Canada. RP Nanda, S (reprint author), NIDDK, Liver Dis Branch, NIH, Bethesda, MD 20892 USA. EM JakeL@intra.niddk.nih.gov FU Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH FX This work was supported in part by the Intramural Research Program of the National Institute of Diabetes and Digestive and Kidney Diseases, NIH. NR 38 TC 15 Z9 15 U1 0 U2 2 PU PUBLIC LIBRARY SCIENCE PI SAN FRANCISCO PA 185 BERRY ST, STE 1300, SAN FRANCISCO, CA 94107 USA SN 1932-6203 J9 PLOS ONE JI PLoS One PD OCT 17 PY 2008 VL 3 IS 10 AR e3442 DI 10.1371/journal.pone.0003442 PG 11 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 432GV UT WOS:000265122400012 PM 18927617 ER PT J AU Aletaha, D Landewe, R Karonitsch, T Bathon, J Boers, M Bombardier, C Bombardieri, S Choi, H Combe, B Dougados, M Emery, P Gomez-Reino, J Keystone, E Koch, G Kvien, TK Martin-Mola, E Matucci-Cerinic, M Michaud, K O'Dell, J Paulus, H Pincus, T Richards, P Simon, L Siegel, J Smolen, JS Sokka, T Strand, V Tugwell, P van der Heijde, D van Riel, P Vlad, S van Vollenhoven, R Ward, M Weinblatt, M Wells, G White, B Wolfe, F Zhang, B Zink, A Felson, D AF Aletaha, D. Landewe, R. Karonitsch, T. Bathon, J. Boers, M. Bombardier, C. Bombardieri, S. Choi, H. Combe, B. Dougados, M. Emery, P. Gomez-Reino, J. Keystone, E. Koch, G. Kvien, T. K. Martin-Mola, E. Matucci-Cerinic, M. Michaud, K. O'Dell, J. Paulus, H. Pincus, T. Richards, P. Simon, L. Siegel, J. Smolen, J. S. Sokka, T. Strand, V. Tugwell, P. van der Heijde, D. van Riel, P. Vlad, S. van Vollenhoven, R. Ward, M. Weinblatt, M. Wells, G. White, B. Wolfe, F. Zhang, B. Zink, A. Felson, D. TI Reporting Disease Activity in Clinical Trials of Patients With Rheumatoid Arthritis: EULAR/ACR Collaborative Recommendations SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article ID ACTIVITY SCORE; FUNCTIONAL-CAPACITY; IMPROVEMENT AB Objective. To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods. The project followed the EULAR standardized operating procedures, which use a three-step approach: 1) expert-based definition of relevant research questions (November 2006); 2) systematic literature search (November 2006 to May 2007); and 3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). Results. Eleven relevant questions were identified for the literature search. Based on the evidence from the literature, the expert panel recommended that each trial should report the following items: 1) disease activity response and disease activity states; 2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; 3) baseline disease activity levels (in general); 4) the percentage of patients achieving a low disease activity state and remission; 5) time to onset of the primary outcome; 6) sustainability of the primary outcome; 7) fatigue. Conclusion. These recommendations endorsed by EULAR and ACR will help harmonize the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses. C1 [Aletaha, D.] Med Univ Vienna, Div Rheumatol, A-1090 Vienna, Austria. [Landewe, R.] Univ Hosp Maastricht, Maastricht, Netherlands. [Bathon, J.] Johns Hopkins Univ, Baltimore, MD USA. [Boers, M.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Bombardier, C.] Inst Work & Hlth, Toronto, ON, Canada. [Bombardieri, S.] Univ Pisa, Pisa, Italy. [Choi, H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Combe, B.] CHU Montpellier, Montpellier, France. [Dougados, M.] Paris Descartes Univ, Paris, France. [Emery, P.] Univ Leeds, Leeds, W Yorkshire, England. [Gomez-Reino, J.] Univ Santiago de Compostela, Sch Med, Santiago, Spain. [Keystone, E.] Univ Toronto, Toronto, ON, Canada. [Koch, G.] Univ N Carolina, Chapel Hill, NC USA. [Kvien, T. K.] Diakonhjemmet Hosp, Oslo, Norway. [Martin-Mola, E.] Hosp Univ La Paz, Madrid, Spain. [Matucci-Cerinic, M.] Univ Florence, Florence, Italy. [Michaud, K.; O'Dell, J.] Univ Nebraska, Omaha, NE 68182 USA. [Paulus, H.] Univ Calif Los Angeles, Los Angeles, CA USA. [Pincus, T.] NYU, Hosp Joint Dis, New York, NY USA. [Richards, P.] Univ Bristol, Bristol, Avon, England. [Simon, L.] Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. [Siegel, J.] US FDA, Rockville, MD 20857 USA. [Smolen, J. S.] Med Univ Vienna, Vienna, Austria. [Smolen, J. S.] Hietzing Hosp, Vienna, Austria. [Sokka, T.] Jyvaskyla Cent Hosp, Jyvaskyla, Finland. [Strand, V.] Stanford Univ, Portola Valley, CA USA. [Tugwell, P.] Inst Populat Hlth, Ottawa, ON, Canada. [van der Heijde, D.] Leiden Univ, Med Ctr, Leiden, Netherlands. [van Riel, P.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Vlad, S.; Zhang, B.; Felson, D.] Boston Univ, Sch Med, Boston, MA 02118 USA. [van Vollenhoven, R.] Karolinska Univ Hosp, Stockholm, Sweden. [Ward, M.] NIH, Bethesda, MD 20892 USA. [Weinblatt, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wells, G.] Univ Ottawa, Ottawa, ON, Canada. [White, B.] Medimmune Inc, Gaithersburg, MD 20878 USA. [Wolfe, F.] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Zink, A.] Charite Univ Med Berlin, Berlin, Germany. RP Aletaha, D (reprint author), Med Univ Vienna, Div Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM daniel.aletaha@meduniwien.ac.at RI Riel, P.L.C.M./H-8082-2014; OI Felson, David/0000-0002-2668-2447; Tugwell, Peter/0000-0001-5062-0556 FU Arthritis Research UK [18475] NR 19 TC 90 Z9 95 U1 0 U2 6 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD OCT 15 PY 2008 VL 59 IS 10 BP 1371 EP 1377 DI 10.1002/art.24123 PG 7 WC Rheumatology SC Rheumatology GA 362RN UT WOS:000260214900002 PM 18821648 ER PT J AU Bagnyukova, TV Tryndyak, VP Muskhelishvili, L Ross, SA Beland, FA Pogribny, IP AF Bagnyukova, Tetyana V. Tryndyak, Volodymyr P. Muskhelishvili, Levan Ross, Sharon A. Beland, Frederick A. Pogribny, Igor P. TI Epigenetic downregulation of the suppressor of cytokine signaling 1 (Socs1) gene is associated with the STAT3 activation and development of hepatocellular carcinoma induced by methyl-deficiency in rats SO CELL CYCLE LA English DT Article DE hepatocellular carcinoma; STAT3; Socs1; DNA methylation; histone lysine methylation ID HEPATIC STELLATE CELLS; GROWTH-FACTOR-BETA; LIVER FIBROSIS; PDGF-D; MOLECULAR PATHOGENESIS; DNA METHYLATION; RECEPTOR-ALPHA; CANCER; EXPRESSION; HEPATOCARCINOGENESIS AB The members of the platelet-derived growth factor (PDGF) and the transforming growth factor-beta (TGF beta) pathways are important in the induction of liver fibrosis and cirrhosis; however, their role in the subsequent progression to hepatocellular carcinoma (HCC) remains elusive. Our study provides new insights into mechanisms of dysregulation of PDGFs, TGF beta and signal transducer and activator of transcription (STAT) pathways in the pathogenesis of methyl-deficient rodent liver carcinogenesis, a remarkably relevant model to the development of HCC in humans. We demonstrated a progressive increase in the Pdgfs and TGF beta expression in preneoplastic tissue and liver tumors indicating their promotional role in carcinogenesis, particularly in progression of liver fibrosis and cirrhosis. However, activation of the STAT3 occurred only in fully developed HCC and was associated with downregulation of the Socs1 gene. The inhibition of the Socs1 expression in HCC was associated with an increase in histone H3 lysine 9, H3 lysine 27, and H4 lysine 20 trimethylation at the Socs1 promoter, but not with promoter methylation. The results of our study suggest the following model of events in hepatocarcinogenesis: during early stages, overexpression of the Socs1 effectively inhibits TGF beta- and PDGF-induced STAT3 activation, whereas, during the advanced stages of hepatocarcinogenesis, the Socs1 downregulation resulted in loss of its ability to attenuate the signal from the upregulated TGF beta and PDGFs leading to oncogenic STAT3 activation and malignant cell transformation. This model illustrates that the Socs1 acts as classic tumor suppressor by preventing activation of the STAT3 and downregulation of Socs1 and consequent activation of STAT3 may be a crucial events leading to formation of HCC. C1 [Bagnyukova, Tetyana V.; Tryndyak, Volodymyr P.; Beland, Frederick A.; Pogribny, Igor P.] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Muskhelishvili, Levan] Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. [Ross, Sharon A.] NCI, Canc Prevent Div, Bethesda, MD 20892 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov FU Oak Ridge Institute for Science and Education FX This work is supported in part (VT, TB) by the Postgraduate Research Program administered by the Oak Ridge Institute for Science and Education. NR 53 TC 20 Z9 23 U1 0 U2 3 PU LANDES BIOSCIENCE PI AUSTIN PA 1806 RIO GRANDE ST, AUSTIN, TX 78702 USA SN 1538-4101 J9 CELL CYCLE JI Cell Cycle PD OCT 15 PY 2008 VL 7 IS 20 BP 3202 EP 3210 DI 10.4161/cc.7.20.6816 PG 9 WC Cell Biology SC Cell Biology GA 363JI UT WOS:000260263200016 PM 18843197 ER PT J AU Vallelian, F Pimenova, T Pereira, CP Abraham, B Mikolajczyk, MG Schoedon, G Zenobi, R Alayash, AI Buehler, PW Schaer, DJ AF Vallelian, Florence Pimenova, Tatiana Pereira, Claudia P. Abraham, Bindu Mikolajczyk, Malgorzata G. Schoedon, Gabriele Zenobi, Renato Alayash, Abdu I. Buehler, Paul W. Schaer, Dominik J. TI The reaction of hydrogen peroxide with hemoglobin induces extensive alpha-globin crosslinking and impairs the interaction of hemoglobin with endogenous scavenger pathways SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE Hemoglobin; Haptoglobin; CD163; Hydrogen peroxide; Oxidative stress ID HEME UPTAKE; INTRAPLAQUE HEMORRHAGE; CARDIOVASCULAR-DISEASE; MACROPHAGES; HAPTOGLOBIN; MYOGLOBIN; RECEPTOR; CD163; DETERMINES; ACTIVATION AB Cell-free hemoglobin (Hb) enhances the oxidation-related toxicity associated with inflammation, ischemia, and hemolytic disorders. Hb is highly vulnerable to oxidative damage, and irreversible structural changes involving iron/heme oxidation, heme-adduct products, and amino acid oxidation have been reported. Specific structural features of Hb, such as unconstrained a-chains and molecular size, determine the efficiency of interactions between the endogenous Hb scavengers haptoglobin (Hp) and CD163. Using HPLC, mass spectrometry, and Western blotting, we show that H2O2-mediated Hb oxidation results in the formation of covalently stabilized globin multimers, with prominent intramolecular crosslinking between a-globin chains. These structural alterations are associated with reduced Hp binding, reduced CD163 interaction, and severely impaired endocytosis of oxidized Hb by the Hp-CD163 pathway. As a result, when exposed to oxidized Hb, CD163-positive HEK293 cells and human macrophages do not increase hemeoxygenase-1 (HO-1) expression, the physiological anti-oxidative macrophage response to Hb exposure. Failed Hb clearance, inadequate HO-1 expression, and the subsequent accumulation of oxidatively damaged Hb species might thus contribute to pathologies related to oxidative stress. (C) 2008 Elsevier Inc. All rights reserved. C1 [Abraham, Bindu; Mikolajczyk, Malgorzata G.; Alayash, Abdu I.; Buehler, Paul W.; Schaer, Dominik J.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. [Vallelian, Florence; Pereira, Claudia P.; Schoedon, Gabriele; Schaer, Dominik J.] Univ Zurich, Internal Med Res Unit, Zurich, Switzerland. [Pimenova, Tatiana; Zenobi, Renato] Swiss Fed Inst Technol, Dept Chem & Appl Biosci, Zurich, Switzerland. RP Buehler, PW (reprint author), NIH, LBUB, CBER, FDA, Bldg 29,8800 Rockville Pike, Bethesda, MD 20892 USA. EM paul.buehler@fda.hhs.gov; dominik.schaer@usz.ch RI Zenobi, Renato/F-1113-2010 FU Swiss National Science Foundation [310000-120658, 200020-111831]; Hartmann Muller Foundation; Helmut-Horten Foundation FX The work described in this article was supported by the Swiss National Science Foundation (SNF grant 310000-120658 to DJ.S. and SNF grant 200020-111831 to R.Z.), the Hartmann Muller Foundation (F.V.), and the Helmut-Horten Foundation (D.J.S.). NR 38 TC 36 Z9 36 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PD OCT 15 PY 2008 VL 45 IS 8 BP 1150 EP 1158 DI 10.1016/j.freeradbiomed.2008.07.013 PG 9 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 361XO UT WOS:000260161300012 PM 18708138 ER PT J AU Hong, Y Liu, TR Lee, MD Hofacre, CL Maier, M White, DG Ayers, S Wang, LH Berghaus, R Maurer, JJ AF Hong, Yang Liu, Tongrui Lee, Margie D. Hofacre, Charles L. Maier, Marie White, David G. Ayers, Sherry Wang, Lihua Berghaus, Roy Maurer, John J. TI Rapid screening of Salmonella enterica serovars Enteritidis, Hadar, Heidelberg and Typhimurium using a serologically-correlative allelotyping PCR targeting the O and H antigen alleles SO BMC MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; GENE-CLUSTER; REFERENCE COLLECTION; MOLECULAR ANALYSES; MULTIPLEX PCR; IDENTIFICATION; RFB; POLYMORPHISM; SEQUENCE; COMPLEX AB Background: Classical Salmonella serotyping is an expensive and time consuming process that requires implementing a battery of O and H antisera to detect 2,541 different Salmonella enterica serovars. For these reasons, we developed a rapid multiplex polymerase chain reaction (PCR)based typing scheme to screen for the prevalent S. enterica serovars Enteritidis, Hadar, Heidelberg, and Typhimurium. Results: By analyzing the nucleotide sequences of the genes for O-antigen biosynthesis including wba operon and the central variable regions of the H1 and H2 flagellin genes in Salmonella, designated PCR primers for four multiplex PCR reactions were used to detect and differentiate Salmonella serogroups A/D1, B, C1, C2, or E1; H1 antigen types i, g, m, r or z(10); and H2 antigen complexes, 1: 1,2; 1,5; 1,6; 1,7 or II: e,n,x; e,n,z15. Through the detection of these antigen gene allele combinations, we were able to distinguish among S. enterica serovars Enteritidis, Hadar, Heidelberg, and Typhimurium. The assays were useful in identifying Salmonella with O and H antigen gene alleles representing 43 distinct serovars. While the H2 multiplex could discriminate between unrelated H2 antigens, the PCR could not discern differences within the antigen complexes, 1,2; 1,5; 1,6; 1,7 or e, n, x; e, n, z15, requiring a final confirmatory PCR test in the final serovar reporting of S. enterica. Conclusion: Multiplex PCR assays for detecting specific O and H antigen gene alleles can be a rapid and cost-effective alternative approach to classical serotyping for presumptive identification of S. enterica serovars Enteritidis, Hadar, Heidelberg, and Typhimurium. C1 [Hong, Yang; Liu, Tongrui; Lee, Margie D.; Hofacre, Charles L.; Maier, Marie; Berghaus, Roy; Maurer, John J.] Univ Georgia, Dept Populat Hlth, Athens, GA 30602 USA. [Hong, Yang] Univ Georgia, Dept Infect Dis, Athens, GA 30602 USA. [Wang, Lihua] Univ Georgia, Dept Stat, Athens, GA 30602 USA. [Lee, Margie D.; Hofacre, Charles L.; Maurer, John J.] Univ Georgia, Ctr Food Safety & Qual Enhancement, Griffin, GA 30223 USA. [White, David G.; Ayers, Sherry] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Liu, Tongrui; Maier, Marie] USDA ARS, Russell Res Ctr, Athens, GA 30605 USA. [Liu, Tongrui] Emory Univ, Atlanta, GA 30322 USA. RP Maurer, JJ (reprint author), Univ Georgia, Dept Populat Hlth, Athens, GA 30602 USA. EM yang.hong@primuslabs.com; jmaurer@uga.edu; mdlee@uga.edu; chofacre@uga.edu; jmaurer@uga.edu; david.white@fda.hhs.gov; sherry.ayers@fda.hhs.gov; yang.hong@primuslabs.com; berghaus@uga.edu; jmaurer@uga.edu FU USDA NRICGP [99-35212-8680]; USDA Formula Funds; State of Georgia's Veterinary Medicine Agricultural Research FX USDA NRICGP grant 99-35212-8680, USDA Formula Funds, and the State of Georgia's Veterinary Medicine Agricultural Research Grant supported this work. We thank Dr. Douglas Waltman for his helpful comments and advice. NR 43 TC 28 Z9 28 U1 0 U2 11 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1471-2180 J9 BMC MICROBIOL JI BMC Microbiol. PD OCT 9 PY 2008 VL 8 AR 178 DI 10.1186/1471-2180-8-178 PG 8 WC Microbiology SC Microbiology GA 370FH UT WOS:000260747600001 PM 18845003 ER PT J AU Ali, S Hussain, S AF Ali, Syed Hussain, Saber TI Nanoparticles and nanomaterials: Friend or foe SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 45th Congress of the European-Societies-of-Toxicology CY OCT 05-08, 2008 CL Rhodes, GREECE SP European Soc Toxicol C1 [Ali, Syed; Hussain, Saber] NCTR, Neurochem Lab, Div Neurotoxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD OCT 5 PY 2008 VL 180 SU 1 BP S21 EP S21 DI 10.1016/j.toxlet.2008.06.723 PG 1 WC Toxicology SC Toxicology GA 349AV UT WOS:000259252100070 ER PT J AU Ali, S Imam, S Itzhak, Y AF Ali, Syed Imam, Syed Itzhak, Yossef TI Role of nitric oxide and peroxynitrite in methamphetamine-induced dopaminergic neurotoxicity SO TOXICOLOGY LETTERS LA English DT Meeting Abstract CT 45th Congress of the European-Societies-of-Toxicology CY OCT 05-08, 2008 CL Rhodes, GREECE SP European Soc Toxicol C1 [Ali, Syed; Imam, Syed; Itzhak, Yossef] Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD OCT 5 PY 2008 VL 180 SU 1 BP S8 EP S8 DI 10.1016/j.toxlet.2008.06.826 PG 1 WC Toxicology SC Toxicology GA 349AV UT WOS:000259252100027 ER PT J AU Weiss, CD Vassell, RA He, Y AF Weiss, C. D. Vassell, R. A. He, Y. TI Monoclonal Antibodies Targeting Heptad-Repeat Regions of gp41 SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract CT AIDS Vaccine 2008 Conference CY OCT 13-16, 2008 CL Cape Town, SOUTH AFRICA SP NIAID, Div AIDS, NIH, Div AIDS C1 [Weiss, C. D.; Vassell, R. A.; He, Y.] US FDA, 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 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD OCT PY 2008 VL 24 BP 92 EP 93 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 367CT UT WOS:000260530800233 ER PT J AU Baker-Smith, CM Benjamin, DK Grabowski, HG Reid, ED Mangum, B Goldsmith, JV Murphy, D Edwards, R Eisenstein, EL Sun, J Califf, RM Li, JS AF Baker-Smith, Carissa M. A. Benjamin, Daniel K. A. B. Grabowski, Henry G. C. Reid, Elizabeth D. Mangum, Barry Goldsmith, John V. Murphy, Dianne Edwards, Rex Eisenstein, Eric L. Sun, Jessica Califf, Robert M. Li, Jennifer S. TI Outcomes, health policy, and managed care - The economic returns of pediatric clinical trials of anti hypertensive drugs SO AMERICAN HEART JOURNAL LA English DT Article ID CHILDREN; EXCLUSIVITY; RISK AB Background Congress has authorized the United States Food and Drug Administration (FDA) to provide industry sponsors with a 6-month extension of drug marketing rights under the Pediatric Exclusivity Provision if FDA-requested pediatric drug trials are conducted. The cost and economic return of pediatric exclusivity to industry sponsors has been shown to be highly variable. We sought to determine the cost of performing pediatric exclusivity trials within a single therapeutic area and the subsequent economic return to industry sponsors. Methods We evaluated 9 orally administered anti hypertensive drugs submitted to the FDA under the Pediatric Exclusivity Provision from 1997 to 2004 and obtained key elements of the clinical trial designs and operations. Estimates of the costs of performing the studies were generated and converted into after-tax cash outflow. Market sales were obtained and converted into after-tax inflows based on 6 months of additional patent protection. Net economic return and net return-to-cost ratios were determined for each drug. Results of the 9 anti hypertensive agents studied, an average of 2 studies per drug was performed, including at least I pharmacokinetic study and a safety and efficacy study. The median cost of completing a pharmacokinetic trial was $862,000 (range $556,000 to 1.8 million). The median cost of performing safety and efficacy trials for these agents was $4.3 million (range $2.1-12.9 million). The ratio of net economic return to cost was 17 (range 4-64.7). Conclusion We found that, within a cohort of anti hypertensive drugs, the Pediatric Exclusivity Provision has generated highly variable, yet lucrative returns to industry sponsors. C1 [Benjamin, Daniel K. A. B.; Reid, Elizabeth D.; Mangum, Barry; Edwards, Rex; Eisenstein, Eric L.; Califf, Robert M.; Li, Jennifer S.] Duke Clin Res Inst, Durham, NC 27705 USA. [Baker-Smith, Carissa M. A.; Benjamin, Daniel K. A. B.; Sun, Jessica] Duke Univ, Med Ctr, Dept Pediat, Durham, NC USA. [Grabowski, Henry G. C.] Duke Univ, Dept Econ, Durham, NC USA. [Goldsmith, John V.; Murphy, Dianne] US FDA, Rockville, MD 20857 USA. RP Li, JS (reprint author), Duke Clin Res Inst, POB 17969, Durham, NC 27705 USA. EM li000001@mc.duke.edu FU NCRR NIH HHS [UL1 RR024128, UL1 RR024128-01, 1UL1RR024128-01]; NHLBI NIH HHS [T32 HL069749, T32 HL069749-04]; NICHD NIH HHS [U10 HD045962-04, 1U10-HD45962-04, U10 HD045962] NR 20 TC 16 Z9 16 U1 0 U2 4 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 OCT PY 2008 VL 156 IS 4 BP 682 EP 688 DI 10.1016/j.ahj.2008.05.001 PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 359CH UT WOS:000259963300009 PM 18926149 ER PT J AU Schantz, MM Bedner, M Long, SE Molloy, JL Murphy, KE Porter, BJ Putzbach, K Rimmer, CA Sander, LC Sharpless, KE Thomas, JB Wise, SA Wood, LJ Yen, JH Yarita, T NguyenPho, A Sorenson, WR Betz, JM AF Schantz, Michele M. Bedner, Mary Long, Stephen E. Molloy, John L. Murphy, Karen E. Porter, Barbara J. Putzbach, Karsten Rimmer, Catherine A. Sander, Lane C. Sharpless, Katherine E. Thomas, Jeanice B. Wise, Stephen A. Wood, Laura J. Yen, James H. Yarita, Takashi NguyenPho, Agnes Sorenson, Wendy R. Betz, Joseph M. TI Development of saw palmetto (Serenoa repens) fruit and extract standard reference materials SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE saw palmetto; Serenoa repens; fatty acids; phytosterols; certified reference material; standard reference material ID SUPPLEMENTS; SUITE AB As part of a collaboration with the National Institutes of Health's Office of Dietary Supplements and the Food and Drug Administration's Center for Drug Evaluation and Research, the National Institute of Standards and Technology has developed two standard reference materials (SRMs) representing different forms of saw palmetto (Serenoa repens), SRM 3250 Serenoa repens fruit and SRM 3251 Serenoa repens extract. Both of these SRMs have been characterized for their fatty acid and phytosterol content. The fatty acid concentration values are based on results from gas chromatography with flame ionization detection (GC-FID) and mass spectrometry (GC/MS) analysis while the sterol concentration values are based on results from GC-FID and liquid chromatography with mass spectrometry analysis. In addition, SRM 3250 has been characterized for lead content, and SRM 3251 has been characterized for the content of beta-carotene and tocopherols. SRM 3250 (fruit) has certified concentration values for three phytosterols, 14 fatty acids as triglycerides, and lead along with reference concentration values for four fatty acids as triglycerides and 16 free fatty acids. SRM 3251 (extract) has certified concentration values for three phytosterols, 17 fatty acids as triglycerides, beta-carotene, and gamma-tocopherol along with reference concentration values for three fatty acids as triglycerides, 17 fatty acids as free fatty acids, beta-carotene isomers, and delta-tocopherol and information values for two phytosterols. These SRMs will complement other reference materials currently available with concentrations for similar analytes and are part of a series of SRMs being developed for dietary supplements. C1 [Schantz, Michele M.; Bedner, Mary; Long, Stephen E.; Molloy, John L.; Murphy, Karen E.; Porter, Barbara J.; Putzbach, Karsten; Rimmer, Catherine A.; Sander, Lane C.; Sharpless, Katherine E.; Thomas, Jeanice B.; Wise, Stephen A.; Wood, Laura J.; Yarita, Takashi] Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA. [Yen, James H.] Natl Inst Stand & Technol, Stat Engn Div, Gaithersburg, MD 20899 USA. [NguyenPho, Agnes] Food & Drug Adm, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Sorenson, Wendy R.] Covance Labs, Madison, WI 53704 USA. [Betz, Joseph M.] Natl Inst Hlth, Off Dietary Supplements, Bethesda, MD 20892 USA. RP Schantz, MM (reprint author), Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 20899 USA. EM michele.schantz@nist.gov OI Sharpless, Katherine/0000-0001-6569-198X NR 17 TC 14 Z9 17 U1 0 U2 9 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD OCT PY 2008 VL 392 IS 3 BP 427 EP 438 DI 10.1007/s00216-008-2297-0 PG 12 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 345NK UT WOS:000259003300012 PM 18677464 ER PT J AU Aletaha, D Landewe, R Karonitsch, T Bathon, J Boers, M Bombardier, C Bombardieri, S Choi, H Combe, B Dougados, M Emery, P Gomez-Reino, J Keystone, E Koch, G Kvien, TK Martin-Mola, E Matucci-Cerinic, M Michaud, K O'Dell, J Paulus, H Pincus, T Richards, P Simon, L Siegel, J Smolen, JS Sokka, T Strand, V Tugwell, P van der Heijde, D van Riel, P Vlad, S van Vollenhoven, R Ward, M Weinblatt, M Wells, G White, B Wolfe, F Zhang, B Zink, A Felson, D AF Aletaha, D. Landewe, R. Karonitsch, T. Bathon, J. Boers, M. Bombardier, C. Bombardieri, S. Choi, H. Combe, B. Dougados, M. Emery, P. Gomez-Reino, J. Keystone, E. Koch, G. Kvien, T. K. Martin-Mola, E. Matucci-Cerinic, M. Michaud, K. O'Dell, J. Paulus, H. Pincus, T. Richards, P. Simon, L. Siegel, J. Smolen, J. S. Sokka, T. Strand, V. Tugwell, P. van der Heijde, D. van Riel, P. Vlad, S. van Vollenhoven, R. Ward, M. Weinblatt, M. Wells, G. White, B. Wolfe, F. Zhang, B. Zink, A. Felson, D. TI Reporting disease activity in clinical trials of patients with rheumatoid arthritis: EULAR/ACR collaborative recommendations SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Article ID FUNCTIONAL-CAPACITY; ACTIVITY SCORE; IMPROVEMENT AB Objective: To make recommendations on how to report disease activity in clinical trials of rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods: The project followed the EULAR standardised operating procedures, which use a three-step approach: (1) expert-based definition of relevant research questions (November 2006); (2) systematic literature search (November 2006 to May 2007); and (3) expert consensus on recommendations based on the literature search results (May 2007). In addition, since this is the first joint EULAR/ACR publication on recommendations, an extra step included a meeting with an ACR panel to approve the recommendations elaborated by the expert group (August 2007). Results: Eleven relevant questions were identified for the literature search. Based on the evidence from the literature the expert panel recommended that each trial should report the following items: (1) disease activity response and disease activity states; (2) appropriate descriptive statistics of the baseline, the endpoints and change of the single variables included in the core set; (3) baseline disease activity levels (in general); (4) the percentage of patients achieving a low disease activity state and remission; (5) time to onset of the primary outcome; (6) sustainability of the primary outcome; (7) fatigue. Conclusions: These recommendations endorsed by EULAR and ACR will help harmonise the presentations of results from clinical trials. Adherence to these recommendations will provide the readership of clinical trials with more details of important outcomes, while the higher level of homogeneity may facilitate the comparison of outcomes across different trials and pooling of trial results, such as in meta-analyses. C1 [Aletaha, D.] Med Univ Vienna, Div Rheumatol, A-1090 Vienna, Austria. [Landewe, R.] Univ Hosp Maastricht, Maastricht, Netherlands. [Bathon, J.] Johns Hopkins Univ, Baltimore, MD USA. [Boers, M.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Bombardier, C.] Inst Work & Hlth, Toronto, ON, Canada. [Bombardieri, S.] Univ Pisa, Pisa, Italy. [Choi, H.] Univ British Columbia, Vancouver, BC V5Z 1M9, Canada. [Combe, B.] CHU Montpellier, Montpellier, France. [Dougados, M.] Paris Descartes Univ, Paris, France. [Emery, P.] Univ Leeds, Leeds, W Yorkshire, England. [Gomez-Reino, J.] Univ Santiago Compostela, Sch Med, E-15706 Santiago, Spain. [Keystone, E.] Univ Toronto, Toronto, ON M5S 1A1, Canada. [Koch, G.] Univ N Carolina, Chapel Hill, NC USA. [Kvien, T. K.] Diakonhjemmet Hosp, Oslo, Norway. [Martin-Mola, E.] Hosp Univ La Paz, Madrid, Spain. [Matucci-Cerinic, M.] Univ Florence, Florence, Italy. [Michaud, K.; O'Dell, J.] Univ Nebraska, Omaha, NE 68182 USA. [Paulus, H.] Univ Calif Los Angeles, Los Angeles, CA USA. [Pincus, T.] NYU, Hosp Joint Dis, New York, NY USA. [Richards, P.] Univ Bristol, Bristol, Avon, England. [Simon, L.] Beth Israel Deaconess Med, Boston, MA USA. [Siegel, J.] US FDA, Rockville, MD 20857 USA. [Smolen, J. S.] Hietzing Hosp, Vienna, Austria. [Sokka, T.] Jyvaskyla Cent Hosp, Jyvaskyla, Finland. [Strand, V.] Stanford Univ, Portola Valley, CA USA. [Tugwell, P.] Inst Populat Hlth, Ottawa, ON, Canada. [van der Heijde, D.] Leiden Univ, Med Ctr, Leiden, Netherlands. [van Riel, P.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Vlad, S.; Zhang, B.; Felson, D.] Boston Univ, Sch Med, Boston, MA 02118 USA. [van Vollenhoven, R.] Karolinska Univ Hosp, Stockholm, Sweden. [Ward, M.] NIH, Bethesda, MD 20892 USA. [Weinblatt, M.] Brigham & Womens Hosp, Boston, MA 02115 USA. [Wells, G.] Univ Ottawa, Ottawa, ON, Canada. [White, B.] Medimmune, Gaithersburg, MD USA. [Wolfe, F.] Natl Data Bank Rheumat Dis, Wichita, KS USA. [Zink, A.] Charite Univ Med Berlin, Berlin, Germany. RP Aletaha, D (reprint author), Med Univ Vienna, Div Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM daniel.aletaha@meduniwien.ac.at OI Felson, David/0000-0002-2668-2447; Tugwell, Peter/0000-0001-5062-0556 FU EULAR; ACR FX This project was fully funded by EULAR and the ACR. NR 19 TC 96 Z9 102 U1 1 U2 5 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 OCT PY 2008 VL 67 IS 10 BP 1360 EP 1364 DI 10.1136/ard.2008.091454 PG 5 WC Rheumatology SC Rheumatology GA 359FJ UT WOS:000259971500003 PM 18791055 ER PT J AU Karonitsch, T Aletaha, D Boers, M Bombardieri, S Combe, B Dougados, M Emery, P Felson, D Gomez-Reino, J Keystone, E Kvien, TK Martin-Mola, E Matucci-Cerinic, M Richards, P van Riel, P Siegel, J Smolen, JS Sokka, T van der Heijde, D van Vollenhoven, R Ward, M Wells, G Zink, A Landewe, R AF Karonitsch, T. Aletaha, D. Boers, M. Bombardieri, S. Combe, B. Dougados, M. Emery, P. Felson, D. Gomez-Reino, J. Keystone, E. Kvien, T. K. Martin-Mola, E. Matucci-Cerinic, M. Richards, P. van Riel, P. Siegel, J. Smolen, J. S. Sokka, T. van der Heijde, D. van Vollenhoven, R. Ward, M. Wells, G. Zink, A. Landewe, R. TI Methods of deriving EULAR/ACR recommendations on reporting disease activity in clinical trials of patients with rheumatoid arthritis SO ANNALS OF THE RHEUMATIC DISEASES LA English DT Review ID COLLEGE-OF-RHEUMATOLOGY; HEALTH-ASSESSMENT QUESTIONNAIRE; PRELIMINARY REMISSION CRITERIA; MODIFYING ANTIRHEUMATIC DRUGS; PLACEBO-CONTROLLED TRIAL; C-REACTIVE PROTEIN; ACTIVITY SCORE; RESPONSE CRITERIA; FOLLOW-UP; RADIOGRAPHIC PROGRESSION AB Objective: To use an evidence-based and consensus-based approach to elaborate recommendations on how to report disease activity in clinical trials of patients with rheumatoid arthritis (RA) endorsed by the European League Against Rheumatism (EULAR) and the American College of Rheumatology (ACR). Methods: After an initial expert meeting, during which relevant research questions were identified, a systematic literature search was performed using Medline, Embase and the Cochrane Library as sources. To ensure literature retrieved was comprehensive, we emphasised search algorithms that were sensitive rather than specific. The results of the literature search were discussed by the expert panel, modified and expanded, and were used as the basis for the elaboration of the recommendation in the consensus process. Finally, an independent ACR panel approved these items with some minor modifications. Results: The following pieces of evidence were obtained from the literature search: (1) timing and the sustaining of a response is relevant to achieve better outcomes; (2) composite disease activity indices have been used to define low disease activity and remission and these definitions have been validated as has the American Rheumatism Association (ARA) remission criteria. The "patient-reported symptom state" (PASS) is not yet well validated; (3) evidence was obtained to identify those measures, scales and patient-reported instruments, for which there is a documented association with relevant outcomes; (4) baseline disease activity is associated with disease activity levels at the end of follow-up; and (5) there was not sufficient evidence relating the added benefit of MRI or ultrasound over clinical assessments. Most data stemmed from observational studies rather than clinical trials and literature review was supplemented by input from experts. The results served as the basis for the elaboration of the seven recommendations by the experts. Conclusions: The approach based on scientific evidence from the literature as well as on expert input provided sufficient information to derive recommendations on reporting disease activity in RA clinical trials. The methodology, results and conclusions of this project were endorsed by EULAR and the ACR. C1 [Aletaha, D.] Med Univ Vienna, Div Rheumatol, A-1090 Vienna, Austria. [Boers, M.] Vrije Univ Amsterdam, Med Ctr, Amsterdam, Netherlands. [Bombardieri, S.] Univ Pisa, Pisa, Italy. [Combe, B.] CHU Montpellier, Montpellier, France. [Dougados, M.] Paris Descartes Univ, Paris, France. [Emery, P.] Univ Leeds, Leeds, W Yorkshire, England. [Felson, D.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Gomez-Reino, J.] Univ Santiago Compostela, Sch Med, E-15706 Santiago, Spain. [Keystone, E.] Univ Toronto, Toronto, ON, Canada. [Kvien, T. K.] Diakonhjemmet Hosp, Oslo, Norway. [Martin-Mola, E.] Hosp Univ La Paz, Madrid, Spain. [Matucci-Cerinic, M.] Univ Florence, Florence, Italy. [Richards, P.] Univ Bristol, Bristol, Avon, England. [van Riel, P.] Radboud Univ Nijmegen, Med Ctr, NL-6525 ED Nijmegen, Netherlands. [Siegel, J.] US FDA, Rockville, MD 20857 USA. [Smolen, J. S.] Hietzing Hosp, Vienna, Austria. [Sokka, T.] Jyvaskyla Cent Hosp, Jyvaskyla, Finland. [van der Heijde, D.] Leiden Univ, Med Ctr, Leiden, Netherlands. [van Vollenhoven, R.] Karolinska Univ Hosp, Stockholm, Sweden. [Ward, M.] NIH, Bethesda, MD 20892 USA. [Wells, G.] Univ Ottawa, Ottawa, ON, Canada. [Zink, A.] Charite Univ Med Berlin, Berlin, Germany. [Landewe, R.] Univ Hosp Maastricht, Maastricht, Netherlands. RP Aletaha, D (reprint author), Med Univ Vienna, Div Rheumatol, Waehringer Guertel 18-20, A-1090 Vienna, Austria. EM daniel.aletaha@meduniwien.ac.at RI Riel, P.L.C.M./H-8082-2014; OI Felson, David/0000-0002-2668-2447 FU EULAR; ACR FX This project was fully funded by EULAR and the ACR. NR 109 TC 12 Z9 12 U1 0 U2 2 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 OCT PY 2008 VL 67 IS 10 BP 1365 EP 1373 DI 10.1136/ard.2008.092353 PG 9 WC Rheumatology SC Rheumatology GA 359FJ UT WOS:000259971500004 PM 18791056 ER PT J AU Jung, CM Heinze, TM Deck, J Strakosha, R Sutherland, JB AF Jung, Carina M. Heinze, Thomas M. Deck, Joanna Strakosha, Ruth Sutherland, John B. TI Transformation of N-phenylpiperazine by mixed cultures from a municipal wastewater treatment plant SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID FUNGUS MUCOR-RAMANNIANUS; SOLID-PHASE EXTRACTION; FLUOROQUINOLONE ENROFLOXACIN; ANTIBACTERIAL AGENTS; MASS-SPECTROMETRY; MODIFYING ENZYME; RESISTANCE GENE; ANTIBIOTICS; METABOLITES; CIPROFLOXACIN AB Samples from a wastewater treatment plant were used as inocula for mixed cultures dosed with N-phenylpiperazine (NPP), a model compound containing the piperazine ring found in many fluoroquinolones. Chemical analyses showed that NPP (50 mg liter(-1)) disappeared in 12 days, with the appearance of a transient metabolite and two nitrosated compounds. C1 [Jung, Carina M.; Deck, Joanna; Strakosha, Ruth; Sutherland, John B.] US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. [Heinze, Thomas M.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM john.sutherland@fda.hhs.gov FU Postgraduate Research Fellowship Program; Summer Student Research Program FX This work was supported in part by appointments to the Postgraduate Research Fellowship Program (C. M. J.) and the Summer Student Research Program (R. S.) at the National Center for Toxicological Research, administered by the Oak Ridge Institute for Science and Education through an interagency agreement between the U. S. Department of Energy and the U. S. Food and Drug Administration.; The views presented in this article do not necessarily reflect those of the Food and Drug Administration. NR 29 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 OCT PY 2008 VL 74 IS 19 BP 6147 EP 6150 DI 10.1128/AEM.00516-08 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 352WS UT WOS:000259528700038 PM 18676696 ER PT J AU Mizanur, RM Pohl, NL AF Mizanur, Rahman M. Pohl, Nicola L. TI Bacterial CMP-sialic acid synthetases: production, properties, and applications SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Review DE sialic acid; CMP-sialic acid synthetases; sugar nucleotide ID N-ACETYLNEURAMINIC ACID; CYTIDINE 5'-MONOPHOSPHO-N-ACETYLNEURAMINIC ACID; CELL-ADHESION MOLECULE; ESCHERICHIA-COLI K1; NEISSERIA-MENINGITIDIS; CHEMOENZYMATIC SYNTHESIS; HAEMOPHILUS-DUCREYI; GROUP-B; CAPSULAR POLYSACCHARIDE; ENZYMATIC-SYNTHESIS AB Sialic acids are abundant nine-carbon sugars expressed terminally on glycoconjugates of eukaryotic cells and are crucial for a variety of cell biological functions such as cell-cell adhesion, intracellular signaling, and in regulation of glycoproteins stability. In bacteria, N-acetylneuraminic acid (Neu5Ac) polymers are important virulence factors. Cytidine 5'-monophosphate (CMP)-N-acetylneuraminic acid synthetase (CSS; EC 2.7.7.43), the key enzyme that synthesizes CMP-N-acetylneuraminic acid, the donor molecule for numerous sialyltransferase reactions, is present in both prokaryotes and eukaryotic systems. Herein, we emphasize the source, function, and biotechnological applications of CSS enzymes from bacterial sources. To date, only a few CSS from pathogenic bacterial species such as Neisseria meningitidis, Escherichia coli, group B streptococci, Haemophilus ducreyi, and Pasteurella hemolytica and an enzyme from nonpathogenic bacterium, Clostridium thermocellum, have been described. Overall, the enzymes from both Gram-positive and Gram-negative bacteria share common catalytic properties such as their dependency on divalent cation, temperature and pH profiles, and catalytic mechanisms. The enzymes, however, can be categorized as smaller and larger enzymes depending on their molecular weight. The larger enzymes in some cases are bifunctional; they have exhibited acetylhydrolase activity in addition to their sugar nucleotidyltransferase activity. The CSSs are important enzymes for the chemoenzymatic synthesis of various sialooligosaccharides of significance in biotechnology. C1 [Mizanur, Rahman M.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Pohl, Nicola L.] Iowa State Univ, Dept Chem, Ames, IA 50011 USA. [Pohl, Nicola L.] Iowa State Univ, Inst Plant Sci, Ames, IA 50011 USA. RP Mizanur, RM (reprint author), US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM rahman.mizanur@fda.hhs.gov FU National Science Foundation [0349139]; Herman Frasch Foundation (ACS-PRF) FX This material is based in part upon work supported by the National Science Foundation under CAREER Grant No. 0349139 and the Herman Frasch Foundation (ACS-PRF). NR 77 TC 23 Z9 23 U1 2 U2 11 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD OCT PY 2008 VL 80 IS 5 BP 757 EP 765 DI 10.1007/s00253-008-1643-7 PG 9 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 349HC UT WOS:000259270900002 PM 18716769 ER PT J AU Rafii, F Park, M AF Rafii, Fatemeh Park, Miseon TI Detection and characterization of an ABC transporter in Clostridium hathewayi SO ARCHIVES OF MICROBIOLOGY LA English DT Article DE transporter; fluoroquinolone; Clostridium hathewayi; efflux pump; resistance ID MEDIATED FLUOROQUINOLONE RESISTANCE; MULTIDRUG EFFLUX TRANSPORTER; STAPHYLOCOCCUS-AUREUS; LACTOCOCCUS-LACTIS; ESCHERICHIA-COLI; MYCOBACTERIUM-TUBERCULOSIS; STREPTOCOCCUS-PNEUMONIAE; QUINOLONE RESISTANCE; DRUG-RESISTANCE; PROTEINS AB An ABC transporter gene from Clostridium hathewayi is characterized. It has duplicated ATPase domains in addition to a transmembrane protein. Its deduced amino acid sequence has conserved functional domains with ATPase components of the multidrug efflux pump genes of several bacteria. Cloning this transporter gene into C. perfringens and E. coli resulted in decreased sensitivities of these bacteria to fluoroquinolones. It also decreased the accumulation and increased the efflux of ethidium bromide from cells containing the cloned gene. Carbonyl cyanide-m-chlorophenylhydrazone (CCCP) inhibited both accumulation and efflux of ethidium bromide from these cells. The ATPase mRNA was overexpressed in the fluoroquinolone-resistant strain when exposed to ciprofloxacin. This is the first report of an ABC transporter in C. hathewayi. C1 [Rafii, Fatemeh; Park, Miseon] US FDA, Natl Ctr Toxicol Res, Div Microbiol, 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 48 TC 6 Z9 6 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0302-8933 J9 ARCH MICROBIOL JI Arch. Microbiol. PD OCT PY 2008 VL 190 IS 4 BP 417 EP 426 DI 10.1007/s00203-008-0385-3 PG 10 WC Microbiology SC Microbiology GA 350QE UT WOS:000259367400002 PM 18504552 ER PT J AU Buehler, PW Alayash, AI AF Buehler, Paul W. Alayash, Abdu I. TI All hemoglobin-based oxygen carriers are not created equally SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article; Proceedings Paper CT Conference on Hemoglobin-Based Oxygen Carriers as Blood Substitutes CY APR, 2008 CL Bethesda, MD SP NIH, FDA DE Hemoglobin; Blood substitutes; Oxidation; Nitric oxide ID BLOOD SUBSTITUTES; SCAVENGER RECEPTOR; ANTIOXIDANT ROLE; NITRIC-OXIDE; HAPTOGLOBIN; OXIDATION; CD163; HEME AB Hemoglobin (Hb)-based oxygen carriers (HBOCs) also known as "blood substitutes" have been under active clinical development over the last two decades. Cell-free Hb outside its natural protective red blood cell environment, as is the case with all HBOCs, has been shown to be vasoactive in part due to the scavenging of vascular endothelial nitric oxide (NO) and may in some instances induce heme-mediated oxidative stress. Chemical modification intended to stabilize HBOCs in the tetrameric or polymeric forms introduces conformational constraints that result in proteins with diverse allosteric responses as well as oxidative and nitrosative redox side reactions. Intra, and inter-molecular cross-linking may in some instances also determine the interactions between HBOCs and normal oxidative inactivation and clearance mechanisms. Oxygen and oxidative reactions of normal and several cross-linked Hbs as well as their interactions with endogenous plasma protein (haptoglobin) and cellular receptor pathways (macrophage CD163) differ significantly. Therefore, safety and efficacy may be addressed by designing HBOCs with modifications that limit hypertension, minimize heme destabilization and take into account endogenous Hb removal mechanisms to optimize exposure times for a given indication. Published by Elsevier B.V. C1 [Buehler, Paul W.; Alayash, Abdu I.] US FDA, LBVB, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), NIH Campus 8800 Rockville Pike,Bldg 29,Rm 112, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov NR 17 TC 31 Z9 31 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD OCT PY 2008 VL 1784 IS 10 SI SI BP 1378 EP 1381 DI 10.1016/j.bbapap.2007.12.009 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 363MH UT WOS:000260270900003 PM 18206989 ER PT J AU Cooper, CE Silaghi-Dumitrescu, R Rukengwa, M Alayash, AI Buehler, PW AF Cooper, Chris E. Silaghi-Dumitrescu, Radu Rukengwa, Martine Alayash, Abdu I. Buehler, Paul W. TI Peroxidase activity of hemoglobin towards ascorbate and urate: A synergistic protective strategy against toxicity of Hemoglobin-Based Oxygen Carriers (HBOC) SO BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS LA English DT Article; Proceedings Paper CT Conference on Hemoglobin-Based Oxygen Carriers as Blood Substitutes CY APR, 2008 CL Bethesda, MD SP NIH, FDA DE Hemoglobin; Ascorbate; Urate; Peroxidase; Ferryl; Blood substitute ID CELL-FREE HEMOGLOBIN; IN-VITRO; HYDROGEN-PEROXIDE; NITRIC-OXIDE; HEME; MYOGLOBIN; ANTIOXIDANT; MECHANISM; ACID; VIVO AB Acellular hemoglobins developed as oxygen bridging agents with volume expanding properties ("blood substitutes") are prone to autoxidation and oxidant-mediated structural changes in circulation. In the presence of hydrogen peroxide and either ascorbate or urate we show that ferric hemoglobin functions as a true enzymatic peroxidase. The activity saturates with both substrates and is linearly dependent on protein concentration. The activity is enhanced at low pH with a pK(a) of 4.7, consistent with protonation of the ferryl species (Fe(IV)-OH) as the active intermediate. To test whether these redox reactions define its behaviour in vivo we exchanged transfused guinea pigs with 50% polymerized bovine Hb (PolyHbBv) and monitored plasma levels of endogenous ascorbate and urate. immediately after transfusion, met PolyHbBv levels increased up to 30% of total Hb and remained at this level during the first 24 h post transfusion. Plasma ascorbate decreased by 50% whereas urate levels remained unchanged after transfusion. A simple kinetic model, assuming that ascorbate was a more active ferric heme reductase and peroxidase substrate than urate, was consistent with the in vivo data. The present finding confirms the primary and secondary roles of ascorbate and urate respectively in maintaining the oxidative stability of infused Hb. (c) 2008 Elsevier B.V. All rights reserved. C1 [Cooper, Chris E.; Silaghi-Dumitrescu, Radu; Rukengwa, Martine] Univ Essex, Dept Biol Sci, Colchester CO4 3SQ, Essex, England. [Alayash, Abdu I.; Buehler, Paul W.] US FDA, Lab Biochem & Vasc Biol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Cooper, CE (reprint author), Univ Essex, Dept Biol Sci, Wivenhoe Pk, Colchester CO4 3SQ, Essex, England. EM ccooper@essex.ac.uk RI Silaghi-Dumitrescu, Radu/A-2883-2008; OI Silaghi-Dumitrescu, Radu/0000-0003-3038-7747; Cooper, Chris/0000-0003-0381-3990 NR 34 TC 36 Z9 38 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-9639 J9 BBA-PROTEINS PROTEOM JI BBA-Proteins Proteomics PD OCT PY 2008 VL 1784 IS 10 SI SI BP 1415 EP 1420 DI 10.1016/j.bbapap.2008.03.019 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 363MH UT WOS:000260270900009 PM 18457681 ER PT J AU Miller, SA Coelho, SG Zmudzka, BZ Bushar, HF Yamaguchi, Y Hearing, VJ Beer, JZ AF Miller, S. A. Coelho, S. G. Zmudzka, B. Z. Bushar, H. F. Yamaguchi, Y. Hearing, V. J. Beer, J. Z. TI Dynamics of pigmentation induction by repeated ultraviolet exposures: dose, dose interval and ultraviolet spectrum dependence SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE melanogenesis; pigmentation; repeated exposures; ultraviolet radiation ID SKIN COLOR; TIME-COURSE; RADIATION; ERYTHEMA; MELANIN AB Background The dynamics of ultraviolet (UV)-induced melanogenesis have been well characterized for single UV exposures. However, our knowledge of the effects of repeated UV exposures on the development of new pigmentation is limited. Objectives To characterize the dynamics and dose dependence of pigmentation induction by repeated UV exposures using two different UV sources. Methods A total of 40 healthy subjects participated in the study: 21 were exposed to a 5% UVB/95% UVA source and 19 were exposed to a 2% UVB/98% UVA source. Skin phototypes 2-3 were represented. Subjects were exposed one to three times per week. The minimal erythemal dose and minimal melanogenic dose of all subjects were determined, and both visual and instrumental observations of the development of pigmentation and erythema were recorded. Results Dark-brown pigmentation could be produced by a cumulative UV dose of 4200 J m(-2) given as 10 exposures over 5 weeks. However, comparable pigmentation could also be induced by a cumulative dose of 2900 J m(-2) given as eight exposures over 4 weeks. The lowest cumulative dose of 1900 J m(-2) given over 4 weeks produced moderate pigmentation. The 2% UVB source led to earlier and darker pigmentation than the 5% UVB source did for equally erythemogenic doses. Conclusions These observations show that the dynamics of melanogenesis induced by repeated exposures depends on UV dose, dose interval and emission spectrum. They also indicate that increasing the UV dose above a certain level of cumulative exposure does not significantly increase the level of UV-induced pigmentation. C1 [Miller, S. A.; Zmudzka, B. Z.; Bushar, H. F.; Beer, J. Z.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. [Coelho, S. G.; Yamaguchi, Y.; Hearing, V. J.] NIH, NCI, Cell Biol Lab, Bethesda, MD 20852 USA. RP Miller, SA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. EM sharona.miller@fda.hhs.gov FU U. S. FDA Office of Women's Health; National Cancer Institute; National Institutes of Health FX This research was supported by the U. S. FDA Office of Women's Health, and in part by the Intramural Research Program of the National Cancer Institute, National Institutes of Health. The authors wish to express their sincere appreciation to Dr Katalin S. Korossey for her dermatological support and numerous valuable suggestions, and to Judith Kniskern, RN for her excellent handling of the human subjects and records. NR 26 TC 18 Z9 18 U1 0 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD OCT PY 2008 VL 159 IS 4 BP 921 EP 930 DI 10.1111/j.1365-2133.2008.08708.x PG 10 WC Dermatology SC Dermatology GA 349UB UT WOS:000259307700020 PM 18616777 ER PT J AU Petrick, N Brown, DG Suleiman, O Myers, KJ AF Petrick, N. Brown, D. G. Suleiman, O. Myers, K. J. TI Imaging as a tumor biomarker in oncology drug trials for lung cancer: The FDA perspective SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID CRITICAL PATH; DISCOVERY AB The US Food and Drug Administration (FDA) is committed to working with the oncology community to expedite the drug evaluation process in view of the many promising new oncology drugs under laboratory development and the time and expense required for such new drugs to reach the patient population. One significant advance would be to enable quantitative imaging as a tumor biomarker. The FDA is working with the pharmaceutical industry, academia, and sister stakeholders in the government, primarily through collaborative educational and research efforts, to identify how imaging can serve this function. C1 [Petrick, N.; Brown, D. G.; Myers, K. J.] US FDA, Natl Inst Biomed Imaging & Bioengn, Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst, Silver Spring, MD USA. [Suleiman, O.] US FDA, Off Oncol Drug Prod, Off New Drugs, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Petrick, N (reprint author), US FDA, Natl Inst Biomed Imaging & Bioengn, Ctr Devices & Radiol Hlth, Lab Assessment Med Imaging Syst, Silver Spring, MD USA. EM nicholas.petrick@fda.hhs.gov FU National Institute of Biomedical Imaging and Bioengineering; National Institute of Biomedical Imaging and Bioengineering/Center for Devices and Radiological Health Laboratory; National Cancer Institute [224-07-6030] FX The intramural research program of the National Institute of Biomedical Imaging and Bioengineering provides partial support for research conducted in the National Institute of Biomedical Imaging and Bioengineering/Center for Devices and Radiological Health Laboratory for the Assessment of Medical Imaging Systems. This work was supported in part by the National Cancer Institute through IAG no. 224-07-6030. NR 9 TC 10 Z9 10 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD OCT PY 2008 VL 84 IS 4 BP 523 EP 525 DI 10.1038/clpt.2008.155 PG 3 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 351CS UT WOS:000259402700020 PM 18716616 ER PT J AU Katz, R AF Katz, Russell TI FOOD AND DRUG ADMINISTRATION REGULATION SO CNS SPECTRUMS LA English DT Article C1 US FDA, Rockville, MD 20857 USA. RP Katz, R (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU M B L COMMUNICATIONS, INC PI NEW YORK PA 333 HUDSON ST, 7TH FLOOR, NEW YORK, NY 10013 USA SN 1092-8529 J9 CNS SPECTRUMS JI CNS Spectr. PD OCT PY 2008 VL 13 IS 10 SU 16 BP 45 EP 46 PG 2 WC Clinical Neurology; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 364ZF UT WOS:000260373900014 PM 18955964 ER PT J AU Girnita, DM Burckart, G Zeevi, A AF Girnita, Diana M. Burckart, Gilbert Zeevi, Adriana TI Effect of cytokine and pharmacogenomic genetic polymorphisms in transplantation SO CURRENT OPINION IN IMMUNOLOGY LA English DT Review ID ENDOTHELIAL GROWTH-FACTOR; STEM-CELL TRANSPLANTATION; VERSUS-HOST-DISEASE; BRONCHIOLITIS OBLITERANS SYNDROME; PEDIATRIC HEART-TRANSPLANTATION; SINGLE-NUCLEOTIDE POLYMORPHISMS; CARDIAC ALLOGRAFT VASCULOPATHY; FACTOR-ALPHA PROMOTER; RENAL-TRANSPLANTATION; ACUTE REJECTION AB Consolidating the information that we have on pharmacogenetics and on cytokine genetics to produce patient-oriented individualized drug regimens is an important challenge in transplantation medicine. Using a multi-variant approach based on genetic profile and other relevant clinical factors a score system may be developed to predict the severity of rejection, infection, or other complications associated with transplantation. The ultimate goal of these studies is to improve patient outcome through individualized drug regimens. C1 [Girnita, Diana M.; Zeevi, Adriana] Univ Pittsburgh, Thomas E Starzl Transplant Inst, Dept Pathol, Pittsburgh, PA 15213 USA. [Burckart, Gilbert] US FDA, Off Clin Pharmacol, Off Translat Sci, Silver Spring, MD 20993 USA. RP Zeevi, A (reprint author), Univ Pittsburgh, Thomas E Starzl Transplant Inst, Dept Pathol, Pittsburgh, PA 15213 USA. EM zeevi@pitt.edu FU National Heart Lung and Blood Institute, National Institutes of Health [5P50 HL 074 732-03] FX This work was supported by 5P50 HL 074 732-03 from the National Heart Lung and Blood Institute, National Institutes of Health. NR 80 TC 16 Z9 17 U1 0 U2 3 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0952-7915 J9 CURR OPIN IMMUNOL JI Curr. Opin. Immunol. PD OCT PY 2008 VL 20 IS 5 BP 614 EP 625 DI 10.1016/j.coi.2008.08.002 PG 12 WC Immunology SC Immunology GA 350UM UT WOS:000259378600018 PM 18706500 ER PT J AU Yan, SS Schreckenberger, PC Zheng, XT Nelson, NA Harrington, SM Tjhio, J Fedorko, DP AF Yan, S. Steve Schreckenberger, Paul C. Zheng, Xiaotian Nelson, Nancy A. Harrington, Susan M. Tjhio, Joyce Fedorko, Daniel P. TI An intrinsic pattern of reduced susceptibility to fluoroquinolones in pediatric isolates of Streptococcus pyogenes SO DIAGNOSTIC MICROBIOLOGY AND INFECTIOUS DISEASE LA English DT Article DE Sireptococcus pyogenes; pediatric isolates; M/emm type; fluoroquinolones; resistance; point mutation ID CLONAL SPREAD; EMM TYPES; RESISTANCE; CIPROFLOXACIN; PNEUMONIAE; PARC; MUTATIONS; SPAIN; GYRA AB A total of H 6 clinical isolates collected in 2003 from a tertiary pediatric hospital and a primary pediatric department in Chicago, IL, were screened for reduced susceptibility to selected fluoroquinolones by disc diffusion. Correlation between reduced susceptibility and point Mutations In the quinolone resistance-determining region of parC and gyr4 genes was evaluated, and point mutations were compared with other reports of isolates derived from adult or mixed patient populations. Nine percent of isolates had reduced susceptibility to I or more of these fluoroquinolones by Etest: ciprofloxacin, levofloxacin, and moxifloxacin. A single point mutation (Ser-79) in parC seemed responsible for the reduced susceptibility. Resistant Streptococcus pyogenes isolates were compared using M/emm type, repetitive sequence-based PCR (rep-PCR). and pulsed-field gel electrophoresis (PFGE). Rep-PCR provided no more separation of strains than M/emm typing, and PFGE results with SgrAl were more discriminatory than with Smal. The majority of these isolates were M/emm type 6. PFGE analysis using SgrAl demonstrated 2 different resistant strains among the M/emm type 6 isolates. The findings suggest that a population of S. pyogenes with an intrinsic reduced Susceptibility to fluoroquinolones exists in pediatric clinical isolates. Monitoring of amino acid changes in both parC and gyrA will assist in the prediction of emergence of high-level fluoroquinolone resistance. Published by Elsevier Inc. C1 [Fedorko, Daniel P.] NIH, Ctr Clin, Dept Lab Med, DHHS, Bethesda, MD 20892 USA. [Yan, S. Steve] US FDA, DHHS, Rockville, MD 20855 USA. [Schreckenberger, Paul C.; Tjhio, Joyce] Univ Illinois, Med Ctr, Chicago, IL 60612 USA. [Zheng, Xiaotian] Childrens Mem Hosp, Chicago, IL 60614 USA. RP Fedorko, DP (reprint author), NIH, Ctr Clin, Dept Lab Med, DHHS, Bldg 10, Bethesda, MD 20892 USA. EM dfedorko@mail.cc.nih.gov FU Intramural NIH HHS [Z99 CL999999] NR 15 TC 11 Z9 12 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0732-8893 J9 DIAGN MICR INFEC DIS JI Diagn. Microbiol. Infect. Dis. PD OCT PY 2008 VL 62 IS 2 BP 205 EP 209 DI 10.1016/j.diagmicrobio.2008.04.018 PG 5 WC Infectious Diseases; Microbiology SC Infectious Diseases; Microbiology GA 356SG UT WOS:000259797300014 PM 18554840 ER PT J AU Rao, VA Klein, S Agama, K Pommier, Y Shacter, E AF Rao, V. A. Klein, S. Agama, K. Pommier, Y. Shacter, E. TI The iron chelator di-2-pyridylketone-4,4,-dimethyl-3-thiosemicarbazone causes DNA damage in breast cancer cells SO EJC SUPPLEMENTS LA English DT Meeting Abstract CT 20th EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics CY OCT 21-24, 2008 CL Geneva, SWITZERLAND SP EORTC, NCI, AACR C1 [Rao, V. A.; Klein, S.; Shacter, E.] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. [Agama, K.; Pommier, Y.] NCI, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1359-6349 J9 EJC SUPPL JI EJC Suppl. PD OCT PY 2008 VL 6 IS 12 BP 187 EP 187 DI 10.1016/S1359-6349(08)72533-3 PG 1 WC Oncology SC Oncology GA 376ZJ UT WOS:000261221200596 ER PT J AU Manjanatha, MG Shelton, SD Dobrovolsky, VN Shaddock, JG McGarrity, LG Doerge, DR Twaddle, NW Lin, CJ Chen, JJ Mattison, DR Morrisi, SM AF Manjanatha, Mugimane G. Shelton, Sharon D. Dobrovolsky, Vasily N. Shaddock, Joseph G. McGarrity, Lynda G. Doerge, Daniel R. Twaddle, Nathan W. Lin, Chien-Ju Chen, James J. Mattison, Donald R. Morrisi, Suzanne M. TI Pharmacokinetics, Dose-Range, and Mutagenicity Studies of Methylphenidate Hydrochloride in B6C3F1 Mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE methylphenidate hydrochloride; ritalinic acid; Hprt mutation; micronucleus assay ID MICRONUCLEUS TEST; ENANTIOMERS; DISORDER; MONKEY; RAT AB Methylphenidate hydrochloride (MPH) is one of the most frequently prescribed pediatric drugs for the treatment of attention deficit hyperactivity disorder. In a recent study, increased hepatic adenomas were observed in B6C3F1 mice treated with MPH in their diet. To evaluate the reactive metabolite, ritalinic acid (RA) of MPH and its mode of action in mice, we conducted extensive investigations on the pharmacokinetics (PK) and genotoxicity of the drug in B6C3F1 mice. For the PK study, male B6C3F1 mice were gavaged once with 3 mg/kg body weight (BW) of MPH and groups of mice were sacrificed at various time points (0.25-24 hr) for serum analysis of MPH and RA concentrations. Groups of male B6C3F1 mice were fed diets containing 0, 250, 500, 1,000, 2,000, or 4,000 ppm of MPH for 28 days to determine the appropriate doses for 24-week transgenic mutation studies. Also, the micronucleus frequencies (MN-RETs and MN-NCEs), and the lymphocyte Hart mutants were determined in peripheral blood and splenic lymphocytes, respectively. Mice fed 4,000 ppm of MPH lost significant BW compared to control mice (P < 0.01). There was a significant increase in the average liver weights whereas kidneys, seminal vesicle, testes, thymus, and urinary bladder weights of mice fed higher doses of MPH were significantly lower than the control group (P < 0.05). There was no significant increase in either the Hprt mutant frequency or the micronucleus frequency in the treated animals. These results indicated that although MPH induced liver hypertrophy in mice, no genotoxicity was observed. Environ. Mol. Mutagen. 49:585-593, 2008. Published 2008 Wiley-Liss, Inc. C1 [Manjanatha, Mugimane G.; Shelton, Sharon D.; Dobrovolsky, Vasily N.; Shaddock, Joseph G.; McGarrity, Lynda G.; Morrisi, Suzanne M.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Doerge, Daniel R.; Twaddle, Nathan W.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Lin, Chien-Ju; Chen, James J.] US FDA, Natl Ctr Toxicol Res, Div Personalized Med & Nutr, Jefferson, AR 72079 USA. [Mattison, Donald R.] NICHD, NIH, Ctr Res Mothers & Children, Bethesda, MD USA. RP Manjanatha, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM mugimane.manjanatha@fda.hhs.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013 OI Mattison, Donald/0000-0001-5623-0874 NR 24 TC 19 Z9 19 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD OCT PY 2008 VL 49 IS 8 BP 585 EP 593 DI 10.1002/em.20407 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 363OO UT WOS:000260276800001 PM 18618596 ER PT J AU Miura, D Dorovolsky, VN Kasahara, Y Katsuura, Y Heflich, RH AF Miura, Daishiro Dorovolsky, Vasily N. Kasahara, Yoshinori Katsuura, Yasuhiro Heflich, Robert H. TI Development of an In Vivo Gene Mutation Assay Using the Endogenous Pig-A Gene: I. Flow Cytometric Detection of CD59-Negative Peripheral Red Blood Cells and CD48-Negative Spleen T-Cells From the Rat SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE glycosylphosphatidylinositol; N-ethyl-N-nitrosourea; Alexa-488-labeled modified proaerolysin; F344 rats ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; MEMBRANE-PROTEINS; HEMATOPOIETIC-CELLS; BONE-MARROW; GENOTOXICITY; ANCHOR; LOCUS; GLYCOSYLPHOSPHATIDYLINOSITOL; BIOSYNTHESIS; LYMPHOCYTES AB The product of the phosphatidylinositol glycan complementation group A gene (Pig-A) is involved in the synthesis of glycosylphosphatidylinositol (GPI) anchors that link various protein markers to the surface of several types of mammalian cells, including hematopoietic cells. Previous observations indicate that Pig-A mutation results in the lack of GPI synthesis and the absence of GPI-anchored proteins on the cell surface. As a first step in designing a rapid assay for measuring Pig-A mutation in the rat, we developed flow cytometry (FCM) strategies for detecting GPI-negative cells in rat peripheral blood and spleen. Anti-CD59 was used to detect GPI-anchored proteins on red blood cells (RBCs), and anti-CD48 was used to detect GPI-anchored proteins on spleen T-cells. The spontaneous frequency of CD59-negative RBCs in five male F344 rats ranged from 1 X 10(-6) to 27 x 10(-6). In contrast, treatment of five rats with three doses of 40 mg/kg N-ethyl-N-nitrosourea (ENU) increased the frequency of CD59-negative RBCs to 183 x 10(-6) to 249 x 10-6 at 2 weeks and to 329 x 10(-6) to 413 x 10(-6) at 4 weeks after dosing. In the same 4-week posttreatment rats, the frequency of CD48-negative T-cells was 11 X 10(-6) to 16 x 10(-6) in control rats and 194 x 10(-6) to 473 x 10(-6) in ENU-treated rats. The frequencies of GPI-deficient cells were similar for RBCs and spleen T-cells. These results indicate that FCM detection of GPI-linked markers may form the basis for a rapid in vivo mutation assay. Although RBCs may be useful for a minimally invasive assay, T-cells are a promising tissue for both detecting GPI-deficient cells and confirming that Pig-A gene mutation is the cause of the phenotype. Environ. Mal. Mutagen. 49:614-621, 2008. Published 2008 Wiley-Liss, Inc. C1 [Miura, Daishiro; Dorovolsky, Vasily N.; Heflich, Robert H.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Miura, Daishiro; Kasahara, Yoshinori; Katsuura, Yasuhiro] TEIJIN Pharma Ltd, Tokyo, Japan. RP Heflich, RH (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM robert.heflich@fda.hhs.gov NR 36 TC 76 Z9 80 U1 0 U2 5 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 OCT PY 2008 VL 49 IS 8 BP 614 EP 621 DI 10.1002/em.20414 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 363OO UT WOS:000260276800004 PM 18626999 ER PT J AU Miura, D Dobrovolsky, VN Mittelstaedt, RA Kasahara, Y Katsuura, Y Heflich, RH AF Miura, Daishiro Dobrovolsky, Vasily N. Mittelstaedt, Roberto A. Kasahara, Yoshinori Katsuura, Yasuhiro Heflich, Robert H. TI Development of an In Vivo Gene Mutation Assay Using the Endogenous Pig-A Gene: II. Selection of Pig-A Mutant Rat Spleen T-Cells With Proaerolysin and Sequencing Pig-A cDNA From the Mutants SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE glycosylphosphatidylinositol; N-ethyl-N-nitrosourea; flow cytometry; CD48; F344 rats; aerolysin ID PAROXYSMAL-NOCTURNAL HEMOGLOBINURIA; CHANNEL-FORMING TOXIN; GPI-ANCHOR BIOSYNTHESIS; ETHYL-N-NITROSOUREA; SOMATIC MUTATIONS; FLOW-CYTOMETRY; MONOCLONAL-ANTIBODIES; BONE-MARROW; HPRT GENE; LYMPHOCYTES AB We previously reported that rat spleen T-cells and peripheral red blood cells that are deficient in glycosylphosphatidylinositol (GPI) synthesis [presumed mutants for the phosphatidylinositol glycon complementation group A gene (Pig-A)] could be detected by flow cytometry (FCM) as cells negative for GPI-linked markers (CD48 and CD59, respectively). To establish this procedure as a rapid in vivo gene mutation assay, we have examined the Pig-A gene of GPI-deficient rat spleen T-cells for DNA sequence alterations. Splenocytes were isolated from male F344 rats, primed with ionomycin and phorbol-12-myristate-13-acetate, and seeded at limiting-dilution into 96-well plates. To select for GPI-deficient T-cells, the cells were cultured for 10 days in a medium containing rat T-STIII and 2 nM proaerolysin (ProAER). The frequency of ProAER-resistant (ProAER(r)) spleen T-cells from control rats ranged from 1.3 X 10(-6) to 4.8 X 10-6, While administration of three doses of 40 mg/kg N-ethyl-N-nitrosourea increased the frequency of ProAER(r) T-cells 100-fold at 4 weeks after dosing. FCM analysis of the cells in PrOAER(r) clones revealed that they were CD48-negative, and thus presumably GPI-deficient. Sequencing of Pig-A cDNA from six ProAERr clones indicated that they all contained alterations in the Pig-A protein coding sequence; five had base pair substitutions and one had multiple exons deleted. These results indicate that GPI-deficient spleen T-cells are Pig-A gene mutants and support the use of FCM analysis of GPI-deficient cells as a rapid assay for measuring in vivo gene mutation. Environ. Mal. Mutagen. 19:622-630, 2008. Published 2008 Wiley-Liss, Inc. C1 [Miura, Daishiro; Dobrovolsky, Vasily N.; Mittelstaedt, Roberto A.; Heflich, Robert H.] US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. [Miura, Daishiro; Kasahara, Yoshinori; Katsuura, Yasuhiro] TEIJIN Pharma Ltd, Tokyo, Japan. RP Heflich, RH (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM robert.heflich@fda.hhs.gov NR 29 TC 56 Z9 61 U1 0 U2 8 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 OCT PY 2008 VL 49 IS 8 BP 622 EP 630 DI 10.1002/em.20413 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 363OO UT WOS:000260276800005 PM 18626996 ER PT J AU Reynisson, J Stiborova, M Martinek, V do Costa, GG Phillips, DH Arlt, VM AF Reynisson, Johannes Stiborova, Marie Martinek, Vaclav do Costa, Goncalo Gamboa Phillips, David H. Arlt, Volker M. TI Mutagenic Potential of Nitrenium Ions of Nitrobenzanthrones: Correlation Between Theory and Experiment SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE 3-nitrobenzanthrone; Salmonella; mutagenicity; nitrenium ion; density functional theory ID DNA ADDUCT FORMATION; AIR-POLLUTANT 3-NITROBENZANTHRONE; ENVIRONMENTAL CONTAMINANT 3-NITROBENZANTHRONE; CYTOCHROMES P450 1A1; SALMONELLA-TYPHIMURIUM; DIESEL EXHAUST; OXIDATION DICATIONS; HUMAN CARCINOGEN; THEORETICAL DFT; HUMAN CANCER AB The mutagenic activity of nine substituted nitrobenzanthrone (NBA) derivatives was recently established in the Ames assay and ranged from near inactivity to extremely high mutagenic activity (Takamura-Enya et al. [2006]: Mutagenesis 21:399-404). Using thermochemical and molecular modeling techniques, the activation pathway of these NBA derivatives, namely 1-nitro-, 2-nitro-, 3-nitro-, 9-nitro-, 11-nitro-, 1,9-dinitro-, 3,9-dinitro-, 3,11-dinitro-, and 3,9,11-trinitrobenzanthrone, and the formation of the corresponding aryl-nitrenium ions, were investigated using density functional theory calculations. The calculated properties of the NBA derivatives were systematically compared with their bacterial mutagenic potency. Accommodation of the ligand substrates into the binding pocket of the bacterial nitroreductoses was not sterically inhibited for the NBAs. Moreover, electron affinities, water elimination energies, esterification, and solvolysis energies did not reveal any possible links with the observed mutagenic potency of the NBAs. However, a strong negative linear correlation was found when the relative energies of the nitrenium ions of the mono and disubstituted NBAs were plotted against the logarithm of the mutagenic potency of the NBAs found in the different Salmonella typhimurium strains. Therefore, our data clearly indicate that the stability of the nitirenium ions is one critical determinant of the mutagenic potency of NBAs in Salmonella tester strains. Environ. Mal. Mutagen. 49:659-667, 2008. (c) 2008 Wiley-Liss, Inc. C1 [Reynisson, Johannes] Nottingham Trent Univ, Sch Sci & Technol, Nottingham NG11 8NS, England. [Stiborova, Marie; Martinek, Vaclav] Charles Univ Prague, Fac Sci, Dept Biochem, Prague, Czech Republic. [do Costa, Goncalo Gamboa] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Phillips, David H.; Arlt, Volker M.] Inst Canc Res, Sect Mol Carcinogenesis, Sutton, Surrey, England. RP Reynisson, J (reprint author), Nottingham Trent Univ, Sch Sci & Technol, Clifton Campus, Nottingham NG11 8NS, England. EM johannes.reynisson@ntu.ac.uk RI Martinek, Vaclav/E-6710-2011; Stiborova, Marie/A-5982-2015; OI Martinek, Vaclav/0000-0003-3321-4526; Stiborova, Marie/0000-0001-5430-4403; Phillips, David/0000-0001-8509-3485 FU METACentrum [MSM6383917201] FX The access to the METACentrum computing facilities provided under the research intent MSM6383917201 is acknowledged. NR 63 TC 16 Z9 16 U1 0 U2 5 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 OCT PY 2008 VL 49 IS 8 BP 659 EP 667 DI 10.1002/em.20411 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 363OO UT WOS:000260276800008 PM 18618595 ER PT J AU Levin, R Brown, MJ Kashtock, ME Jacobs, DE Whelan, EA Rodman, J Schock, MR Padilla, A Sinks, T AF Levin, Ronnie Brown, Mary Jean Kashtock, Michael E. Jacobs, David E. Whelan, Elizabeth A. Rodman, Joanne Schock, Michael R. Padilla, Alma Sinks, Thomas TI Lead exposures in US children, 2008: Implications for prevention SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE children's health; environmental health; lead poisoning; primary prevention ID NUTRITION EXAMINATION SURVEY; 3RD NATIONAL-HEALTH; UNITED-STATES; REFUGEE CHILDREN; URBAN CHILDREN; DRINKING-WATER; RISK-FACTORS; BREAST-MILK; HOUSE-DUST; NEW-YORK AB OBJECTIVE: We reviewed the sources of lead in the environments of U.S. children, contributions to children's blood lead levels, source elimination and control efforts, and existing federal authorities. Our context is the U.S. public health goal to eliminate pediatric elevated blood lead levels (EBLs) by 2010. DATA SOURCES: National, state, and local exposure assessments over the past half century have identified risk factors for EBLs among U.S. children, including age, race, income, age and location of housing, parental occupation, and season. DATA EXTRACTION AND SYNTHESIS: Recent national policies have greatly reduced lead exposure among U.S. children, but even very low exposure levels compromise children's later intellectual development and lifetime achievement. No threshold for these effects has been demonstrated. Although lead paint and dust may still account for up to 70% of EBLs in U.S. children, the U.S. Centers for Disease Control and Prevention estimates that >= 30% of current EBLs do not have an immediate lead paint source, and numerous studies indicate that lead exposures result from multiple sources. EBLs and even deaths have been associated with inadequately controlled sources including ethnic remedies and goods, consumer products, and food-related items such as ceramics. Lead in public drinking water and in older urban centers remain exposure sources in many areas. CONCLUSIONS: Achieving the 2010 goal requires maintaining current efforts, especially programs addressing lead paint, while developing interventions that prevent exposure before children are poisoned. It also requires active collaboration across all levels of government to identify and control all potential sources of lead exposure, as well as primary prevention. C1 [Levin, Ronnie; Padilla, Alma] US EPA SEP, Boston, MA 02114 USA. [Brown, Mary Jean; Sinks, Thomas] Ctr Dis Control & Prevent, Atlanta, GA USA. [Kashtock, Michael E.] US FDA, Washington, DC 20204 USA. [Jacobs, David E.] Dept Housing & Urban Dev, Washington, DC USA. [Whelan, Elizabeth A.] NIOSH, Cincinnati, OH 45226 USA. [Rodman, Joanne] US EPA, Washington, DC 20460 USA. [Schock, Michael R.] US EPA, Cincinnati, OH 45268 USA. RP Levin, R (reprint author), US EPA SEP, 1 Congress St, Boston, MA 02114 USA. EM levin.ronnie@epa.gov NR 170 TC 138 Z9 145 U1 4 U2 39 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 2008 VL 116 IS 10 BP 1285 EP 1293 DI 10.1289/ehp.11241 PG 9 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 355TA UT WOS:000259730100018 PM 18941567 ER PT J AU Bliss, D Whitebird, R Lowry, A Savik, K Wang, Q Jung, H AF Bliss, D. Whitebird, R. Lowry, A. Savik, K. Wang, Q. Jung, H. TI SEVERITY OF FECAL INCONTINENCE AND ITS RELATIONSHIP TO QUALITY OF LIFE AND ADVERSE SYMPTOMS IN COMMUNITY-LIVING PERSONS SO GERONTOLOGIST LA English DT Meeting Abstract C1 [Bliss, D.; Savik, K.] Univ Minnesota, Sch Nursing, Minneapolis, MN 55455 USA. [Whitebird, R.] HealthPartners Res Fdn, Minneapolis, MN USA. [Lowry, A.] Colon & Rectal Surg Assocaites Ltd, Minneapolis, MN USA. [Jung, H.] US FDA, Agr Res Serv, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0016-9013 EI 1758-5341 J9 GERONTOLOGIST JI Gerontologist PD OCT PY 2008 VL 48 SI 3 BP 757 EP 757 PG 1 WC Gerontology SC Geriatrics & Gerontology GA 399PA UT WOS:000262810602886 ER PT J AU Senior, JR Avigan, M AF Senior, John R. Avigan, Mark TI CLASSIFICATION SYSTEM FOR LIKELIHOOD AND SEVERITY OF DRUG-INDUCED LIVER INJURY TO SCORE CLINICAL IMPORTANCE OF THE CASE SO HEPATOLOGY LA English DT Meeting Abstract CT 59th Annual Meeting of the American-Association-for-the-Study-of-Liver-Diseases CY OCT 31-NOV 04, 2008 CL San Francisco, CA SP Amer Assoc Study Liver Dis, Moscone West Convent Ctr C1 [Senior, John R.; Avigan, Mark] US FDA, Off Surveillance & Epidemiol, Silver Spring, MD USA. NR 0 TC 2 Z9 2 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 2008 VL 48 IS 4 SU S MA 445 BP 506A EP 507A PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 356CX UT WOS:000259757400437 ER PT J AU Valerio, LG AF Valerio, L. G., Jr. TI Tools for evidence-based toxicology: computational-based strategies as a viable modality for decision support in chemical safety evaluation and risk assessment SO HUMAN & EXPERIMENTAL TOXICOLOGY LA English DT Editorial Material DE causation; chemical risk assessment; computational toxicology; evidence-based toxicology; in silico toxicology; safety evaluation ID GENETIC TOXICITY; MDL-QSAR; DISCOVERY; SOFTWARE; RODENTS C1 US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Valerio, LG (reprint author), US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,White Oak 51,Room 4218, Silver Spring, MD 20993 USA. EM Luis.Valerio@fda.hhs.gov NR 19 TC 6 Z9 7 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0960-3271 J9 HUM EXP TOXICOL JI Hum. Exp. Toxicol. PD OCT PY 2008 VL 27 IS 10 BP 757 EP 760 DI 10.1177/0960327108097689 PG 4 WC Toxicology SC Toxicology GA 394EH UT WOS:000262428000006 PM 19042961 ER PT J AU Zheng, J Meng, JH Zhao, SH Singh, R Song, WX AF Zheng, Jie Meng, Jianghong Zhao, Shaohua Singh, Ruby Song, Wenxia TI Campylobacter-induced interleukin-8 secretion in polarized human intestinal epithelial cells requires Campylobacter-secreted cytolethal distending toxin- and toll-like receptor-mediated activation of NF-kappa B SO INFECTION AND IMMUNITY LA English DT Article ID INNATE IMMUNE-RESPONSE; SALMONELLA-TYPHIMURIUM; INFLAMMATORY CYTOKINES; ESCHERICHIA-COLI; EUKARYOTIC CELLS; IL-8 SECRETION; CPG-DNA; JEJUNI; BACTERIAL; EXPRESSION AB Campylobacter jejuni and Campylobacter coli colonize and infect the intestinal epithelium and cause acute inflammatory diarrhea. The intestinal epithelium serves as a physical barrier to, and a sensor of, bacterial infection by secreting proinflammatory cytokines. This study examined the mechanisms for Campylobacter-induced secretion of the proinflammatory chemokine interleukin-8 (IL-8) by using polarized T84 human colonic epithelial cells as a model. C. jejuni increased the secretion of both IL-8 and tumor necrosis factor alpha (TNF-alpha) in polarized epithelial cells. However, the increase in IL-8 secretion was independent of Campylobacter-stimulated TNF-alpha secretion. Polarized T84 cells secreted IL-8 predominantly to the basolateral medium independently of the inoculation direction. While there was a significant correlation between the levels of IL-8 secretion and Campylobacter invasion, all 11 strains tested increased IL-8 secretion by polarized T84 cells despite their differences in adherence, invasion, and transcytosis efficiencies. Cell-free supernatants of Campylobacter-T84-cell culture increased IL-8 secretion to levels similar to those induced by live bacterial inoculation. The ability of the supernatant to induce IL-8 secretion was reduced by flagellum and cytolethal distending toxin (CDT) gene mutants, treatment of the supernatant with protease K or heat, or treatment of T84 cells with the Toll-like receptor (TLR) inhibitor MyD88 inhibitory peptide or chloroquine. NF-kappa B inhibitors or cdtB mutation plus MyD88 inhibitor, but not flaA cdtB double mutations, abolished the ability of the supernatant to induce IL-8 secretion. Taken together, our results demonstrate that Campylobacter-induced IL-8 secretion requires functional flagella and CDT and depends on the activation of NF-kappa B through TLR signaling and CDT in human intestinal epithelial cells. C1 [Song, Wenxia] Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. [Zheng, Jie; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Zhao, Shaohua; Singh, Ruby] US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Song, WX (reprint author), Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. EM wenxsong@umd.edu FU Joint Institute of Food Safety and Applied Nutrition, University of Maryland; Food and Drug Administration FX This work was supported by a research grant from the Joint Institute of Food Safety and Applied Nutrition, University of Maryland and Food and Drug Administration.; We thank Patricia Guerry-Kopecko and James Fox for providing mutant strains and Karen Swanson and Margaret Seeley for critical reading of the manuscript. NR 61 TC 58 Z9 58 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD OCT PY 2008 VL 76 IS 10 BP 4498 EP 4508 DI 10.1128/IAI.01317-07 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 349PM UT WOS:000259293100016 PM 18644884 ER PT J AU Oakley, MS McCutchan, TF Anantharaman, V Ward, JM Faucette, L Erexson, C Mahajan, B Zheng, H Majam, V Aravind, L Kumar, S AF Oakley, Miranda S. McCutchan, Thomas F. Anantharaman, Vivek Ward, Jerrold M. Faucette, Laurence Erexson, Cindy Mahajan, Babita Zheng, Hong Majam, Victoria Aravind, L. Kumar, Sanjai TI Host biomarkers and biological pathways that are associated with the expression of experimental cerebral malaria in mice SO INFECTION AND IMMUNITY LA English DT Article ID EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; SEVERE FALCIPARUM-MALARIA; UNCOUPLING PROTEIN-2; METALLOTHIONEIN EXPRESSION; MICROARRAY ANALYSIS; MEDIATED APOPTOSIS; SUSCEPTIBLE MICE; AFRICAN CHILDREN; MURINE MALARIA; RESISTANT MICE AB Cerebral malaria (CM) is a primary cause of malaria-associated deaths among young African children. Yet no diagnostic tools are available that could be used to predict which of the children infected with Plasmodium falciparum malaria will progress to CM. We used the Plasmodium berghei ANKA murine model of experimental cerebral malaria (ECM) and high-density oligonucleotide microarray analyses to identify host molecules that are strongly associated with the clinical symptoms of ECM. Comparative expression analyses were performed with C57BL/6 mice, which have an ECM-susceptible phenotype, and with mice that have ECM-resistant phenotypes: CD8 knockout and perforin knockout mice on the C57BL/6 background and BALB/c mice. These analyses allowed the identification of more than 200 host molecules (a majority of which had not been identified previously) with altered expression patterns in the brain that are strongly associated with the manifestation of ECM. Among these host molecules, brain samples from mice with ECM expressed significantly higher levels of p21, metallothionein, and hemoglobin alpha 1 proteins by Western blot analysis than mice unaffected by ECM, suggesting the possible utility of these molecules as prognostic biomarkers of CM in humans. We suggest that the higher expression of hemoglobin alpha 1 in the brain may be associated with ECM and could be a source of excess heme, a molecule that is considered to trigger the pathogenesis of CM. Our studies greatly enhance the repertoire of host molecules for use as diagnostics and novel therapeutics in CM. C1 [Kumar, Sanjai] US FDA, Malaria Res Program, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Mahajan, Babita; Zheng, Hong; Majam, Victoria; Kumar, Sanjai] NIAID, NIH, Rockville, MD USA. [Oakley, Miranda S.; McCutchan, Thomas F.] Lab Malaria & Vector Res, Rockville, MD USA. [Ward, Jerrold M.; Faucette, Laurence; Erexson, Cindy] Div Intramural Res, Infect Dis Pathogenesis Sect, Comparat Med Branch, Rockville, MD USA. [Oakley, Miranda S.] Uniformed Serv Univ Hlth Sci, Emerging Infect Dis Program, Bethesda, MD 20814 USA. [Anantharaman, Vivek; Aravind, L.] Natl Inst Hlth, Natl Ctr Biotechnol Informat, Natl Lib Med, Bethesda, MD USA. RP Kumar, S (reprint author), US FDA, Malaria Res Program, Div Emerging & Transfus Transmitted Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM Sanjai.kumar@fda.hhs.gov OI Anantharaman, Vivek/0000-0001-8395-0009 NR 70 TC 15 Z9 15 U1 3 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 OCT PY 2008 VL 76 IS 10 BP 4518 EP 4529 DI 10.1128/IAI.00525-08 PG 12 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 349PM UT WOS:000259293100018 PM 18644885 ER PT J AU Ritschel, WA Ye, W Buhse, L Reepmeyer, JC AF Ritschel, Wolfgang A. Ye, Wei Buhse, Lucinda Reepmeyer, John C. TI Stability of the nitrogen mustard mechlorethamine in novel formulations for dermatological use SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE Mechlorethamine; Nitrogen mustard; Stability; Dermal delivery; Aquaphor (R); Transcutol (R) ID PERFORMANCE LIQUID-CHROMATOGRAPHY; OINTMENT-BASED MECHLORETHAMINE; MYCOSIS-FUNGOIDES; INTRACUTANEOUS DEPOT; DELIVERY; INVITRO; SKIN; RAT; GRISEOFULVIN; ACCUMULATION AB Long term stability measurements were made for the nitrogen mustard mechlorethamine HCl at a concentration of 0.02% in six topical formulations: Aquaphor(R) ointment, Transcutol(R), Labrasol(R), 10% Transcutol(R) in Aquaphor(R). 10% Transcutol(R) in Labrasol(R), and Aquaphilic(R) ointment. The drug decomposed gradually in Aquaphor(R) ointment at room temperature, dropping to 95% in 4 weeks, 85% in 12 weeks, and 78% in 39 weeks. On the other hand, the drug decomposed rapidly in Aquaphilic(R) ointment, giving all assay of less than 20% of its initial concentration after 24 h at room temperature. Generally, mechlorethamine HCl was more stable in Aquaphor(R) ointment than in formulations containing Transcutol(R) or Labrasol(R). However, the addition of the free radical inhibitor, BHT, significantly enhanced the stability of mechlorethamine in Transcutol(R), and Labrasol(R) formulations. Four BHT-stabilizecl Transcutol and Labrasol(R) formulations gave assays in ranges of 792-99% at the end of 4 weeks, 77-98% at the end of 12 weeks, and 38-93% at the end of 41 weeks. Published by Elsevier B.V. C1 [Ye, Wei; Buhse, Lucinda; Reepmeyer, John C.] US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Pharmaceut Anal,FDA, St Louis, MO 63101 USA. [Ritschel, Wolfgang A.] Univ Cincinnati, Med Ctr, James L Winkle Coll Pharm, Cincinnati, OH 45267 USA. [Ritschel, Wolfgang A.] Univ Cincinnati, Coll Med, Dept Pharmacol & Cell Biophys, Cincinnati, OH 45267 USA. RP Reepmeyer, JC (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Pharmaceut Anal,FDA, 1114 Market St,Room 1002, St Louis, MO 63101 USA. EM john.reepmeyer@fda.hhs.gov NR 27 TC 5 Z9 5 U1 0 U2 1 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 2008 VL 362 IS 1-2 BP 67 EP 73 DI 10.1016/j.ijpharm.2008.06.016 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 403KE UT WOS:000263080700011 PM 18634862 ER PT J AU Miller, TJ Knapton, A Adeyemo, O Noory, L Weaver, J Hanig, JP AF Miller, T. J. Knapton, A. Adeyemo, O. Noory, L. Weaver, J. Hanig, J. P. TI Cytochrome c: a non-invasive biomarker of drug-induced liver injury SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE cytochrome c; liver; biomarker; hepatotoxicity; mitochondria; apoptosis; urinary biomarker ID MITOCHONDRIAL PERMEABILITY TRANSITION; XENOBIOTIC-INDUCED HEPATOTOXICITY; FULMINANT HEPATIC-FAILURE; CEREBROSPINAL-FLUID; ACETAMINOPHEN NEPHROTOXICITY; D-GALACTOSAMINE; CELL-DEATH; APOPTOSIS; MARKER; RAT AB Limitations of existing biomarkers to detect liver injury in experimental animals highlight the need for additional tools to predict human toxicity. The utility of cytochrome c (cyt c) as a biomarker in serum and urine was evaluated in two rodent liver injury models. Adult Sprague-Dawley rats treated with acetaminophen or D-galactosamine (GaIN) showed dose- and time-dependent histomorphological changes and TUNEL staining in liver consistent with hepatocellular necrosis, apoptosis and inflammation up to 72 h. Matching changes in serum alanine transaminase (ALT), aspartate transaminase (AST) and cyt c peaked at 24 h for either drug at the highest dose, cyt c falling rapidly at 48 hours with ALT and AST remained high. Intracellular transit of cyt c from mitochondria to the cytoplasm in damaged hepatocytes, and then to peripheral circulation, was observed by immunohistochemistry. Correlation coefficients between cyt c and serum diagnostic tests indicate the liver to be the primary source of cyt c. Urinary analysis for cyt c revealed time-dependent increase at 6 h, peaking at 24 h in GaIN-treated rats in contrast with irregular patterns of urinary ALT and AST activity. Histological changes detected at 6 h preceded altered ALT, AST and cyt c at 12 and 18 h, respectively, in GaIN-treated rats. These studies demonstrate cyt c to be a useful indicator of hepatic injury in rodents and support its utility as a non-invasive predictor of drug-induced hepatotoxicity, when utilized as a potential urinary biomarker. Published in 2008 by John Wiley & Sons, Ltd. C1 [Miller, T. J.; Knapton, A.; Adeyemo, O.; Noory, L.; Weaver, J.; Hanig, J. P.] US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Miller, TJ (reprint author), US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, White Oak Life Sci Bldg 64,Room 2066,10903 New Ha, Silver Spring, MD 20993 USA. EM terry.miller@fda.hhs.gov NR 54 TC 23 Z9 28 U1 1 U2 11 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 OCT PY 2008 VL 28 IS 7 BP 815 EP 828 DI 10.1002/jat.1347 PG 14 WC Toxicology SC Toxicology GA 360QR UT WOS:000260072900001 PM 18418843 ER PT J AU Wokovich, AM Brown, SA McMaster, FJ Doub, WH Cai, B Sadrieh, N Chen, ML Machado, S Shen, MY Buhse, LF AF Wokovich, Anna M. Brown, Stanley A. McMaster, Fraser J. Doub, William H. Cai, Bing Sadrieh, Nakissa Chen, Mei Ling Machado, Stella Shen, Meiyu Buhse, Lucinda F. TI Evaluation of substrates for 90 degrees peel adhesion - A collaborative study. I. Medical tapes SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE adhesion; peel; stainless steel; high density polyethylene; skin; tape ID SKIN; CONTACT AB As part of a method development for peel testing, an interlaboratory comparison among Food and Drug Administration-Center for Drug Evaluation and Research, Food and Drug Administration-Center for Devices and Radiological Health and Southwest Research Institute was conducted using medical tapes. The aim was to determine which readily available substrate [stainless steel (SS), high density polyethylene (HDPE) or Vitro-Skin (R)] would best distinguish among various medical tapes. Five medical tapes (3M 1523, 3M 1525L, 3M 1776, Mepiform (R) and Mediderm (R) 3505) were evaluated on four different substrates (SS, HDPE, Vitro-Skin, and human cadaver skin) using the following peel parameters: similar to 3 min dwell time, 90 degrees peel angle, and 300 mm/min peel rate. No substrate mimics cadaver skin for all five tapes. SS had the best ability to distinguish among the medical tapes. Overall, for quality control purposes (yielding good discrimination and precision), SS would be the optimal substrate. (c) 2008 Wiley Periodicals, Inc. C1 [Wokovich, Anna M.; Doub, William H.; Buhse, Lucinda F.] US FDA, Ctr Drug Evaluat & Res, St Louis, MO USA. [Brown, Stanley A.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [McMaster, Fraser J.] SW Res Inst, Dept Mat Engn, San Antonio, TX USA. [Cai, Bing] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Sadrieh, Nakissa; Chen, Mei Ling; Machado, Stella; Shen, Meiyu] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Wokovich, AM (reprint author), US FDA, Ctr Drug Evaluat & Res, St Louis, MO USA. EM anna.wokovich@fda.hhs.gov NR 14 TC 6 Z9 7 U1 2 U2 9 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1552-4973 J9 J BIOMED MATER RES B JI J. Biomed. Mater. Res. Part B PD OCT PY 2008 VL 87B IS 1 BP 105 EP 113 DI 10.1002/jbm.b.31075 PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 350CA UT WOS:000259328900015 PM 18386842 ER PT J AU Knudsen, JF Sokol, GH Flowers, CM AF Knudsen, J. F. Sokol, G. H. Flowers, C. M. TI Adjunctive topiramate enhances the risk of hypothermia associated with valproic acid therapy SO JOURNAL OF CLINICAL PHARMACY AND THERAPEUTICS LA English DT Article DE ammonia; bicarbonate; GABA(A) receptor; hypothermia; topiramate; valproic acid ID GABA(A) RECEPTORS; PYRAMIDAL NEURONS; CONDUCTANCE; MODULATION AB Background: Topiramate was approved for the treatment of epilepsy in 1999 and has since been approved for the prevention of migraine headache. It is structurally different from the majority of antiepileptic medications and is pharmacodynamically unique in its ability to inhibit the enzyme carbonic anhydrase. Postmarketing reports of topiramate-associated hypothermia have occurred but this adverse event has not been well characterized. Data mining of an adverse event database was used to assist in the identification of hypothermia. Objective: We sought to explore a possible association between the concomitant use of topiramate and valproic acid and the induction of hypothermia. Methods: This was a pharmacovigilance case series survey of spontaneous hypothermia, a reported adverse event in patients treated with topiramate and valproic acid, alone and in combination. The U.S. Food and Drug Administration's Adverse Events Reporting System (AERS) database was searched for reports of hypothermia in association with the use of topiramate. A data mining algorithm was used on the AERS to identify scores for hypothermia associated with antiepileptic drugs. Results: We identified 22 unduplicated reports of hypothermia in patients exposed to topiramate. Three of the 22 were confounded by patient overdoses with multiple drugs and not considered. Use of more than one antiepileptic drug was reported in most of the remaining 19 reports. Of these 19 reports, valproic acid was mentioned in 7. Two of the 19 reports mentioned topiramate only. Eleven of the 19 patients were men. The median age of the 19 patients was 40 years (range, 31/2- 82 years). Body temperatures ranged from 29.5 degrees C (moderate hypothermia) to 35 degrees C (mild hypothermia) with a median of 34 degrees C. Eleven of 18 reports of hypothermia occurred during the cooler months (one report did not indicate the time of year in which hyopthermia occurred). Comorbid conditions included hypothyroidism in six reports, five in patients who received valproic acid concomitantly with topiramate and five reports of hyperammonemia in similarly treated patients. Data mining scores (empirical Bayes geometric mean) for antiepileptic drugs ranged from a high of 5.845 for phenobarbital to 2.956 for gabapentin. Hypothermia was reported 4.7 times more frequently when topiramate was used than was statistically expected. We have found hypothermia, defined as an unintentional drop in body core temperature to < 35 degrees C, to be associated with concomitant administration of topiramate (a carbonic anhydrase inhibitor) and valproic acid in patients who have tolerated either drug alone. Data mining analysis for topiramate showed a signal of hypothermia. Topiramate was reported 4.72 times more frequently in the database than would be statistically expected when considering all other drugs. Topiramate may act pharmacodynamically to potentiate the effects of valproic acid as a result of its ability to decrease blood HCO(3)(-) and increase blood ammonia levels. C1 [Knudsen, J. F.] New Hope Canc Ctr, Hudson, FL USA. [Sokol, G. H.] Univ S Florida, H Lee Moffitt Canc Ctr, Coll Med, Tampa, FL 33682 USA. [Knudsen, J. F.] US FDA, Off Drug Evaluat l, Div Neurol & Psychiat Drug Prod, Silver Spring, MD 20993 USA. [Sokol, G. H.] US FDA, Div Oncol Drug Prod, Silver Spring, MD 20993 USA. [Flowers, C. M.] US FDA, Off Drug Surveillance, Silver Spring, MD 20993 USA. RP Knudsen, JF (reprint author), US FDA, Off Drug Evaluat l, Div Neurol & Psychiat Drug Prod, 10903 New Hampshire Ave,Bldg 22 Room 4336, Silver Spring, MD 20993 USA. EM james.knudsen@fda.hhs.gov NR 19 TC 16 Z9 17 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0269-4727 J9 J CLIN PHARM THER JI J. Clin. Pharm. Ther. PD OCT PY 2008 VL 33 IS 5 BP 513 EP 519 DI 10.1111/j.1365-2710.2008.00943.x PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 349UY UT WOS:000259310000008 PM 18834366 ER PT J AU Taylor, K Paparella, S AF Taylor, Kellie Paparella, Susan TI FATAL ERRORS WITH CEREBYX SO JOURNAL OF EMERGENCY NURSING LA English DT Editorial Material C1 [Paparella, Susan] ISMP, Huntingdon Valley, PA USA. [Taylor, Kellie] US FDA, Div Medicat Error Prevent, Silver Spring, MD USA. RP Paparella, S (reprint author), ISMP, Huntingdon Valley, PA USA. EM spaparella@ismp.org NR 4 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 0099-1767 J9 J EMERG NURS JI J. Emerg. Nurs. PD OCT PY 2008 VL 34 IS 5 BP 460 EP 461 DI 10.1016/j.jen.2008.06.014 PG 2 WC Emergency Medicine; Nursing SC Emergency Medicine; Nursing GA 363MJ UT WOS:000260271100017 PM 18804724 ER PT J AU Xi, ML Zheng, B Zhao, SH Brown, EW Meng, JH AF Xi, Meili Zheng, Be Zhao, Shaohua Brown, Eric W. Meng, Jianghong TI An Enhanced Discriminatory Pulsed-Field Gel Electrophoresis Scheme for Subtyping Salmonella Serotypes Heidelberg, Kentucky, SaintPaul, and Hadar SO JOURNAL OF FOOD PROTECTION LA English DT Article ID GENETIC RELATEDNESS; UNITED-STATES; EPIDEMIOLOGY; INFECTIONS; DIVERSITY; OUTBREAK AB Conventional pulsed-field gel electrophoresis (PFGE) protocols, used extensively as a successful approach for subtyping many salmonellae, may be inadequate for discriminating strains sharing levels of homogeneity within the same serotype. Four additional restriction enzymes (SpeI, PacI, SfiI, and NotI), :in addition to XbaI and BlnI were used in PFGE typing of 33 Salmonella Heidelberg, 27 Salmonella Kentucky, 27 Salmonella SaintPaul, and 27 Salmonella Hadar isolates that were recovered from poultry and porcine retail meats from different states of the United States. A dendrogram derived from the combined analysis of six enzymes was highly discriminatory with a Simpson index of diversity value of over 0.950. The ratio of nodes to isolates was more than 0.75 with an average of fewer than three isolates in each polytomy for all four serotypes. Two three-enzyme combinations, SpeI/NotI/SfiI for Salmonella Heidelberg and Salmonella Hadar, and SpeI/BlnI/SfiI for Salmonella Kentucky and Salmonella SaintPaul, were found to have comparable discriminatory abilities of differentiating isolates of these Salmonella serotypes with the six-enzyme combination. The enhanced discriminatory PFGE-based subtyping scheme can be used effectively for the differentiation of strains of the four Salmonella serotypes. The findings also highlight PFGE analysis as a continued essential and informative subtyping method for source tracking and outbreak investigations of these and other Salmonella pathogens. C1 [Zheng, Be; Meng, Jianghong] Northwest A&F Univ, Coll Food Sci Engn, Shaanxi, 20742, Peoples R China. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20708 USA. [Zhao, Shaohua] US FDA, Div Anim & Food Microbiol, Res Off, Ctr Vet Med, Laurel, MD 20740 USA. [Brown, Eric W.] US FDA, Div Microbiol, Ctr Food Safety & Appl Nutr, College Pk, MD USA. EM jmeng@umd.edu FU University of Maryland; U.S. Food and Drug Administration FX The authors thank Jason Abbott for assistance in data analysis. This study was supported in part by the Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland and the U.S. Food and Drug Administration. NR 18 TC 17 Z9 18 U1 3 U2 7 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD OCT PY 2008 VL 71 IS 10 BP 2067 EP 2072 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 357HR UT WOS:000259837400017 PM 18939754 ER PT J AU Jablonski, JE Jackson, LS AF Jablonski, J. E. Jackson, L. S. TI Stability of Picrotoxin during Yogurt Manufacture and Storage SO JOURNAL OF FOOD SCIENCE LA English DT Article DE liquid chromatography-mass spectrometry (LC-MS); manufacture; picrotoxin; stability; yogurt ID DERIVATIVES; RECEPTORS AB Picrotoxin is a neurotoxin found in the berries of Anamirta cocculus, a plant native to Southeast Asia. Picrotoxin has potential for being used as a biological weapon since the toxin is relatively easy to isolate and purify. Limited information exists on the stability and detection of picrotoxin added to foods before or after processing. The objective of this study was to determine the stability of picrotoxin during yogurt manufacture and storage. Direct, cup-set yogurt was produced by using methods that mimic the conditions used in full-scale production of yogurt. Milk ( full-fat or low-fat) was pasteurized at 85 degrees C for 30 min, and then cooled to 43 degrees C. Yogurt starter culture ( thermophilic culture or thermophilic + probiotic culture) and picrotoxin ( 200 mu g/mL milk) were added. Samples of yogurt during fermentation ( 5 to 6 h, 43 degrees C) and during 30 d refrigerated (4 to 6 degrees C) storage were analyzed for pH, titratable acidity, and picrototoxin levels. Regardless of starter culture used or fat content of milk, there were no significant differences in the pH and titratable acidities of the picrotoxin-spiked yogurt and the control yogurt (no added picrotoxin) during fermentation and up to 4 wk of refrigerated storage. The color or texture of the yogurt was not affected by addition of picrotoxin. Levels of picrotoxinin and picrotin ( components of picrotoxin) in yogurt, as measured by LC/MS (APCI(+)/SIR) did not change significantly during fermentation and storage. A separate experiment determined that addition of picrotoxin to milk before pasteurization (85 degrees C, 30 min) did not affect picrotoxin stability. These results indicate that picrotoxin is stable in yogurt during manufacture and storage. C1 [Jablonski, J. E.; Jackson, L. S.] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Jablonski, JE (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM joseph.jablonski@fda.hhs.gov NR 13 TC 3 Z9 3 U1 2 U2 13 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD OCT PY 2008 VL 73 IS 8 BP T121 EP T128 DI 10.1111/j.1750-3841.2008.00911.x PG 8 WC Food Science & Technology SC Food Science & Technology GA 357UU UT WOS:000259873100037 PM 19019133 ER PT J AU DeFelice, A Willard, J Lawrence, J Hung, J Gordon, MA Karkowsky, A Targum, S Throckmorton, DC Girton, J Stertz, B Glasser, SP Lipicky, RJ AF DeFelice, A. Willard, J. Lawrence, J. Hung, J. Gordon, M. A. Karkowsky, A. Targum, S. Throckmorton, D. C. Girton, J. Stertz, B. Glasser, S. P. Lipicky, R. J. TI The risks associated with short-term placebo-controlled antihypertensive clinical trials: a descriptive meta-analysis SO JOURNAL OF HUMAN HYPERTENSION LA English DT Article DE placebo; hypertension trials; risk of placebo ID ISOLATED SYSTOLIC HYPERTENSION; CORONARY HEART-DISEASE; BLOOD-PRESSURE; DRUG-TREATMENT; RANDOMIZED-TRIALS; OUTCOME TRIALS; OLDER PERSONS; ELDERLY TRIAL; DOUBLE-BLIND; STROKE AB Short-term (4-8 weeks) placebo-controlled trials are used to evaluate new antihypertensive drug treatment. To evaluate the consequences of such practice, a descriptive meta-analysis was conducted, consisting of blinded review of original case report forms for all patients who died or left a study before its completion for all short-term, placebo-controlled hypertension trials submitted to the Food and Drug Administration from 1973 through 2001. There were 93 marketing applications or supplements involving 590 individual trials that involved 86 137 randomized patients (64 438 randomized to experimental drug and 21 699 randomized to placebo) with 12 658 patient years of observation. There were 9636 dropouts (mean time to dropout was 28 days) and relative risk (RR (placebo/drug)) 1.33 (95% confidence limits, 1.28, 1.39; P<10(-16)). As expected, lack of blood pressure (BP) control was far more common in patients randomized to placebo; therapeutic failure, RR 2.53 (2.35, 2.73; P<10(-15)) and hypertensive emergency, RR 2.75 (2.19, 3.57; P<10(-15)). When administrative dropouts and dropouts resulting from inadequate BP control were excluded, the remaining 38% of dropouts were disproportionately more from drug (2810 drug, 816 placebo), RR 0.80 (0.74, 0.86; P<10(-8)). There were 43 deaths, RR 0.72 (0.33, 1.45; P = 0.37); 40 strokes, RR 1.43 (0.68, 2.81; P = 0.33) and 77 myocardial infarctions, RR 1.06 (0.62, 1.75; P = 0.82). Irreversible harm (a combination of death, stroke and myocardial infarction, 160 total events) was equally distributed between the drug and placebo groups, RR 1.03 (0.71, 1.47; P = 0.86). C1 [DeFelice, A.; Willard, J.; Gordon, M. A.; Karkowsky, A.; Targum, S.; Throckmorton, D. C.] FDA CDER, Div Cardiorenal Drug Prod, White Oak, MD USA. [Lawrence, J.; Hung, J.] FDA CDER, Div Biometr, White Oak, MD USA. [Girton, J.; Stertz, B.] Ischemia Res & Educ Fdn, San Francisco, CA USA. [Glasser, S. P.] Univ Alabama, Dept Med, Div Prevent Med, Birmingham, AL 35294 USA. [Lipicky, R. J.] Lipicky LLC, N Potomac, MD USA. RP Lipicky, RJ (reprint author), 15201 Apricot Lane, N Potomac, MD 20878 USA. EM ray@lipicky.com OI Glasser, Stephen/0000-0001-9620-6406 FU Ischemia Research Foundation (IREF) FX This study was enabled by, and could not have been completed without, support (by two primary reviewers and data entry personnel) from The Ischemia Research Foundation (IREF), Dennis Mangano, MD, Director who was also a co-principal investigator. We appreciate the permission (by signed letter) from each pharmaceutical company (too numerous to list) for us to use the data they had submitted to NDAs. The original idea for the study came from Stephen P Glasser MD, who had generated a previous publication related to antiangina trials. 35 The entire staff and document control support of the Division of Cardio-Renal Drug Products (DCRDP), FDA worked long hours to make the study possible. Albert DeFelice, PhD and Jim Willard, PhD (DCRDP) undertook major supervisory tasks in addition to their regular regulatory workload. James Hung, PhD and John Lawrence, PhD (Division of Biostatistics, FDA) provided the initial statistical analysis plan and performed the maximum likelihood and Mantel Haenszel analyses. Douglas C Throckmorton, MD, prepared the original protocol and negotiated the IREF support. The paper was originally drafted by Raymond J Lipicky and Robert Fenichel, MD, PhD and Stephen Glasser, MD made major revisions and final suggestions were made by Robert Temple, MD (Director of the Office of Medical Policy-CDER FDA). The results were initially reported in abstract form36 shortly after the original analysis. NR 36 TC 8 Z9 9 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9240 J9 J HUM HYPERTENS JI J. Hum. Hypertens. PD OCT PY 2008 VL 22 IS 10 BP 659 EP 668 DI 10.1038/jhh.2008.51 PG 10 WC Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 349NA UT WOS:000259286300003 PM 18528409 ER PT J AU Shimamura, T Fujisawa, T Husain, SR Kioi, M Nakajima, A Puri, RK AF Shimamura, Takeshi Fujisawa, Toshio Husain, Syed R. Kioi, Mitomu Nakajima, Atsushi Puri, Rai K. TI Novel role of IL-13 in fibrosis induced by nonalcoholic steatohepatitis and its amelioration by IL-13R-directed cytotoxin in a rat model SO JOURNAL OF IMMUNOLOGY LA English DT Article ID RECEPTOR ALPHA-2 CHAIN; INTERLEUKIN-13 FUSION CYTOTOXIN; FATTY LIVER-DISEASE; SIGNAL-TRANSDUCTION; HEPATIC-FIBROSIS; MALIGNANT GLIOMA; TISSUE FIBROSIS; UNITED-STATES; CANCER-CELLS; EXPRESSION AB Nonalcoholic steatohepatitis (NASH), the most common cause of chronic liver fibrosis, progresses to cirrhosis in up to 20% of patients. We report that hepatic stellate cells (HSC) in sinusoidal lesions of liver of patients with NASH express high levels of high-affinity IL-13R (IL-13R alpha 2), which is colocalized with smooth muscle actin, whereas fatty liver and normal liver specimens do not express IL-13R alpha 2. HSCs engineered to overexpress IL-13R alpha 2 respond to IL-13 and induce TGFBI promoter activity and TGF-beta 1 production. We also developed NASH in rats by feeding a choline-deficient L-amino acid diet. These rats developed liver fibrosis as assessed by H&E staining, Masson's trichrome and Sirius red staining, and hydroxyproline assays. Treatment of these rats with IL-13R-directed cytotoxin caused a substantial decline in fibrosis and liver enzymes without organ toxicity. These studies demonstrate that functional IL-13R alpha 2 are overexpressed in activated HSCs involved in NASH and that IL-13 cytotoxin ameliorates pathological features of NASH in rat liver, indicating a novel role of this cytotoxin in potential therapy. C1 [Shimamura, Takeshi; Fujisawa, Toshio; Husain, Syed R.; Kioi, Mitomu; Puri, Rai K.] US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. [Nakajima, Atsushi] Yokohama City Univ, Grad Sch Med, Div Gastroenterol, Yokohama, Kanagawa 232, Japan. RP Puri, RK (reprint author), US FDA, Tumor Vaccines & Biotechnol Branch, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bldg 29B,Room 2NN20 HFM-735,29 Lincoln Dr, Bethesda, MD 20892 USA. EM raj.puri@fda.hhs.gov OI Kioi, Mitomu/0000-0002-7981-3340 NR 49 TC 32 Z9 34 U1 0 U2 2 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 2008 VL 181 IS 7 BP 4656 EP 4665 PG 10 WC Immunology SC Immunology GA 356CG UT WOS:000259755700028 PM 18802068 ER PT J AU Calcagnini, G Triventi, M Censi, F Mattei, E Bartolini, P Kainz, W Bassen, HI AF Calcagnini, Giovanni Triventi, Michele Censi, Federica Mattei, Eugenio Bartolini, Pietro Kainz, Wolfgang Bassen, Howard I. TI In vitro investigation of pacemaker lead heating induced by magnetic resonance imaging: Role of implant geometry SO JOURNAL OF MAGNETIC RESONANCE IMAGING LA English DT Article DE pacemaker; lead heating; fluoroptic measurements; implant geometry; radiofrequency ID CARDIAC-PACEMAKERS; MRI; SYSTEMS; VIVO; 1.5-TESLA; SCANNER; SAFETY; ICDS AB Purpose: To evaluate the effect of the geometry of implantable pacemakers (PMs) on lead heating induced by magnetic resonance imaging (MRI). Materials and Methods: In vitro experiments were conducted with two different setups, using fluoroptic probes to measure the temperature increase. The first experiment consisted of a rectangular box filled with a gelled saline and a pacemaker with its leads. This box was exposed in an MRI birdcage coil to a sinusoidal 64-MHz field with a calibrated whole-body specific absorption rate (WB-SAR) of 1 W/kg. The highest SAR and temperature increase (3000 W/kg. 12 degrees C) occurred for the implant configuration having the largest area. The second experimental setup consisted of a human-shaped torso filled with gelled saline. In this setup the PM and its lead were exposed to a real MRI scanner, using clinical sequences with WB-SAR up to 2 W/kg. Results: We found that higher heating occurs for configurations with longer exposed lead lengths and that right chest PMs showed the highest temperature and local SAR (11.9 degrees C, 2345 W/kg), whereas the left chest PMs were less heated (6.3 degrees C, 1362 W/kg). Implant geometry, exposed lead length, and lead area must be considered in the wide variation of temperature increases induced by MRI. Conclusions: The amount of MRI-induced lead tip heating depends strongly on implant geometry, particularly the lead area, exposed lead length, and position of the implant in the phantom. Critical lead tip heating was found for the longer leads. Therefore, to minimize MRI-induced lead tip heating, the PM lead should be as short as possible. C1 [Calcagnini, Giovanni; Triventi, Michele; Censi, Federica; Mattei, Eugenio; Bartolini, Pietro] Italian Natl Inst Hlth, Dept Technol & Hlth, Rome, Italy. [Mattei, Eugenio] Univ Rome, Dept Informat & Syst Sci, Rome, Italy. [Kainz, Wolfgang; Bassen, Howard I.] US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD USA. RP Calcagnini, G (reprint author), Ist Super Sanita, Dept Technol & Hlth, Viale Regina Elena 299, I-00161 Rome, Italy. EM giovanni.calcagnini@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 23 TC 23 Z9 23 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 OCT PY 2008 VL 28 IS 4 BP 879 EP 886 DI 10.1002/jmri.21536 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 356PY UT WOS:000259791300009 PM 18821629 ER PT J AU Babu, US Gaines, DM Wu, Y Westphal, CD Pereira, M Raybourne, RB AF Babu, Uma S. Gaines, Dennis M. Wu, Yang Westphal, Carmen D. Pereira, Marion Raybourne, Richard B. TI Use of flow cytometry in an apoptosis assay to determine pH and temperature stability of shiga-like toxin 1 SO JOURNAL OF MICROBIOLOGICAL METHODS LA English DT Article DE Shiga-like toxins; Apoptosis; Flow cytometry; THP-1 monocytes ID HEMOLYTIC-UREMIC-SYNDROME; ESCHERICHIA-COLI INFECTION; NUCLEOTIDE-SEQUENCE; IN-VITRO; ACTIVATION; O157-H7; GENES; SITE; RNA AB Shiga toxins and Shiga-like toxins (Stx) are a relatively large group of cytotoxins produced by certain serotypes of Shigella and E coli (STEC). These toxins are responsible for diarrhea, hemorrhagic colitis and may induce hemolytic uremic syndrome (HUS) with serious consequences in young children. The toxins are proteins made up of 5 small B subunits responsible for binding to an outer membrane ligand on host cells and surround the larger, biologically active A subunit. For Shiga-like toxin 1 (Stx1), the cellular receptor is the carbohydrate globotriose. Stx1 was purified from STEC. We utilized induction of apoptosis in the human monocyte cell line THP-1, as a biological endpoint to test the stability of Stx1 activity added to fruit punch at different pH (2-9) and temperatures (4 and 20 degrees C). A flow cytometric method was used to test for early and late apoptotic events based on binding of R-phycoerytherin-labeled annexin V to exposed membrane phosphatidyl serine. Membrane permeability to 7-Amino-actinomycin corresponds with late apoptosis or necrosis. The combination of acid pH and higher storage temperature resulted in greatest degree of toxin inactivation. This approach provides a rapid and high throughput method to determine the functional activity of Stx1, and related toxins in a food matrix. Published by Elsevier B.V. C1 [Babu, Uma S.; Gaines, Dennis M.; Wu, Yang; Westphal, Carmen D.; Pereira, Marion; Raybourne, Richard B.] US FDA, Immunol Branch, Div Virulence Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Raybourne, RB (reprint author), US FDA, Immunol Branch, Div Virulence Assessment, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM Richard.raybourne@fda.hhs.gov NR 25 TC 7 Z9 7 U1 3 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-7012 J9 J MICROBIOL METH JI J. Microbiol. Methods PD OCT PY 2008 VL 75 IS 2 BP 167 EP 171 DI 10.1016/j.mimet.2008.05.014 PG 5 WC Biochemical Research Methods; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 358UH UT WOS:000259942500002 PM 18710788 ER PT J AU Xie, L Wu, HQ Shen, MY Augsburger, LL Lyon, RC Khan, MA Hussain, AS Hoag, SW AF Xie, Lin Wu, Huiquan Shen, Meiyu Augsburger, Larry L. Lyon, Robbe C. Khan, Mansoor A. Hussain, Ajaz S. Hoag, Stephen W. TI Quality-by-design (QbD): Effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powder measured by the ASTM D 6940-04 segregation tester SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE quality-by-design; segregation; powder; segregation tendency; formulation; microcrystalline cellulose; design of experiments; multivariate data analysis; ANOVA; powder physical characterization ID PROCESS ANALYTICAL TECHNOLOGY; SPONTANEOUS STRATIFICATION; SIZE SEGREGATION; GRANULAR SOLIDS; BINARY-MIXTURES; INCLINED CHUTE; PARTICLE-SIZE; FLOW; MECHANISMS; MIXES AB The objective of this study was to examine the effects of testing parameters and formulation variables on the segregation tendency of pharmaceutical powders measured by the ASTM D 6940-04 segregation tester using design of experiments (DOE) approaches. The test blends consisted of 4% aspirin (ASP) and 96% microcrystalline cellulose (MCC) with and without magnesium stearate (MgS). The segregation tendency of a blend was determined by measuring the last/first (L/F) ratio, the ratio of aspirin concentrations between the first and last samples discharged from the tester. A 2 2 factorial design was used to determine the effects of measurement parameters [amount of material loaded (W), number of segregation cycles] with number of replicates 6. ANOVA showed that W was a critical parameter for segregation testing. The L/F value deviated further from 1 (greater segregation tendency) with increasing W. A 2 3 full factorial design was used to assess the effects of formulation variables: grade of ASP (unmilled, milled), grade of MCC, and amount of lubricant, MgS. MLR and ANOVA showed that the grade of ASP was the main effect contributing to segregation tendency. Principal Component Regression Analysis established a correlation between L/F and the physical properties of the blend related to ASP and MCC, the ASP/MCC particle size ratio (PSR) and powder cohesion. The physical properties of the blend related to density and flow were not influenced by the grade of ASP and were not related to the segregation tendency of the blend. The direct relationship between L/F and PSR was determined by univariate analysis. Segregation tendency increased as the ASP to MCC particle size increased. This study highlighted critical test parameters for segregation testing and identified critical physical properties of the blends that influence segregation tendency. (C) 2008 Wiley-Liss, Inc. C1 [Wu, Huiquan; Lyon, Robbe C.; Khan, Mansoor A.] FDA, CDER, Off Pharmaceut Sci, Off Testing & Res,DPQR,HFD 940, Silver Spring, MD 20993 USA. [Xie, Lin; Augsburger, Larry L.; Hoag, Stephen W.] Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. [Shen, Meiyu] FDA, CDER, Off Translat Sci, Off Biostat,Div Biometr 6, Silver Spring, MD 20993 USA. RP Wu, HQ (reprint author), FDA, CDER, Off Pharmaceut Sci, Off Testing & Res,DPQR,HFD 940, White Oak Campus Life Sci Bldg 64 Room 1080,10903, Silver Spring, MD 20993 USA. EM huiquan.wu@fda.hhs.gov FU FDA Center for Drug Evaluation and Research (CDER) Regulatory Science and Review (RSR) [RSR 04-16]; Consortium for Industrial Pharmaceutical Education and Training (CIPET) FX This work was financially supported by the FDA Center for Drug Evaluation and Research (CDER) Regulatory Science and Review (RSR) Grant RSR 04-16 and the Consortium for Industrial Pharmaceutical Education and Training (CIPET). The authors would like to thank Mr. Edward Strickland for helping to design and construct the segregation tester, Dr. Stella G Machado and Dr. Yi Tsong at DBVI/OB/OTS/CDER/FDA for statistical guidance and support, Mr. Christopher D. Ellison at DPQR/OTR/OPS/CDER/FDA and Dr. James Prescott at Jenike & Johanson for helpful discussions. NR 37 TC 23 Z9 23 U1 1 U2 18 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD OCT PY 2008 VL 97 IS 10 BP 4485 EP 4497 DI 10.1002/jps.21320 PG 13 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 353HJ UT WOS:000259556600030 PM 18271036 ER PT J AU Garcia, RJ Kane, AS Petullo, D Reimschuessel, R AF Garcia, Roberta J. Kane, Andrew S. Petullo, David Reimschuessel, Renate TI LOCALIZATION OFOXYTETRACYCLINE INCHLAMYDOMONAS REINHARDTII (CHLOROPHYCEAE) SO JOURNAL OF PHYCOLOGY LA English DT Article DE Chlamydomonas reinhardtii; oxytetracycline; vacuoles ID ION-TETRACYCLINE INTERACTIONS; BRYOPHYTE FONTINALIS-ANTIPYRETICA; MARINE SALMON FARM; CHLAMYDOMONAS-REINHARDTII; BIOLOGICAL-FLUIDS; OXOLINIC ACID; BLOOD-PLASMA; OXYTETRACYCLINE; COMPLEXES; SEDIMENTS AB Oxytetracycline (OTC) is an important antimicrobial used in aquaculture. However, residues of OTC have been isolated from nontarget aquatic organisms, sediments, and water located near aquaculture facilities. Identifying OTC in plant material is particularly difficult due to interference from pigments and polyphenol substances but is important especially for algae since they are a primary food source for fish in early life stages. In this study, we describe the effect of OTC (0.1, 1, 10, 25, 50, 100 mu g.mL(-1)) on cell growth, and the localization of OTC (0, 1, 25, 100 mu g.mL(-1)) in vacuoles of Chlamydomonas reinhardtii P. A. Dang. (wildtype, ATCC 18798). We also present a method for semiquantifying OTC in living cells using fluorescent microscopy and Adobe Photoshop. We exposed algal cells to OTC and sampled after 2 or 7 d exposure. On day 7, OTC significantly inhibited algal growth at 1, 10, 25, 50, and 100 mu g.mL(-1). When viewed with fluorescent microscopy, cells exposed to the 25 and 100 mu g.mL(-1) contained yellow fluorescent areas, <= 1 mu m in diameter that were easily discernable against the red fluorescence of the intracellular chl. The fluorescent areas corresponded to small spherical vacuoles (i.e., polyphosphate bodies that contain calcium and magnesium complexed with polyphosphate) seen in the cells by LM. Since OTC has a high affinity for divalent cations, we suggest that OTC is localized in these vacuoles. C1 [Reimschuessel, Renate] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Petullo, David] US FDA, Ctr Vet Med, Rockville, MD 20855 USA. [Kane, Andrew S.] Univ Florida, Emerging Pathogens Inst, Gainesville, FL 32610 USA. [Garcia, Roberta J.] Univ Maryland, Marine Estuarine Environm Sci Program, Baltimore, MD 21201 USA. [Garcia, Roberta J.] VA MD Reg Coll Vet Med, Aquat Pathobiol Ctr, College Pk, MD 20742 USA. RP Reimschuessel, R (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM renate.reimschuessel@fda.hhs.gov FU University of Maryland Baltimore; SeaSpace Inc.; International Women's Fishing Association FX The authors are grateful for the support provided by the Office of Research, Center for Veterinary Medicine, U.S. FDA between the years of 2000 and 2006. We would also like to acknowledge the support for Dr. Garcia by the Program Enrichment Fellowship funded by the University of Maryland Baltimore and the financial contributions from SeaSpace Inc. and the International Women's Fishing Association. NR 47 TC 1 Z9 1 U1 1 U2 2 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0022-3646 J9 J PHYCOL JI J. Phycol. PD OCT PY 2008 VL 44 IS 5 BP 1282 EP 1289 DI 10.1111/j.1529-8817.2008.00574.x PG 8 WC Plant Sciences; Marine & Freshwater Biology SC Plant Sciences; Marine & Freshwater Biology GA 357SN UT WOS:000259866800019 PM 27041724 ER PT J AU Godar, DE AF Godar, Dianne E. TI Can dietary furocoumarins really be responsible for the increase in melanoma? SO MEDICAL HYPOTHESES LA English DT Letter C1 US FDA, Ctr Devices & Radiol Hlth, Silver Spring, MD 20993 USA. RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Dianne.Godar@fda.hhs.gov OI GODAR, DIANNE/0000-0002-7690-5223 NR 3 TC 1 Z9 1 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD OCT PY 2008 VL 71 IS 4 BP 613 EP 614 DI 10.1016/j.mehy.2008.05.008 PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 361RW UT WOS:000260145800036 PM 18585866 ER PT J AU Kyprianou, IS Badano, A Gallas, BD Myers, KJ AF Kyprianou, Iacovos S. Badano, Aldo Gallas, Brandon D. Myers, Kyle J. TI Singular value description of a digital radiographic detector: Theory and measurements SO MEDICAL PHYSICS LA English DT Article DE H matrix; MTF; system response; line spread function; edge method ID MODULATION TRANSFER-FUNCTION; IMAGING PERFORMANCE; MTF; SYSTEMS; MODEL AB The H operator represents the deterministic performance of any imaging system. For a linear, digital imaging system, this system operator can be written in terms of a matrix, H, that describes the deterministic response of the system to a set of point objects. A singular value decomposition of this matrix results in a set of orthogonal functions (singular vectors) that form the system basis. A linear combination of these vectors completely describes the transfer of objects through the linear system, where the respective singular values associated with each singular vector describe the magnitude with which that contribution to the object is transferred through the system. This paper is focused on the measurement, analysis, and interpretation of the H matrix for digital x-ray detectors. A key ingredient in the measurement of the H matrix is the detector response to a single x ray (or infinitestimal x-ray beam). The authors have developed a method to estimate the 2D detector shift-variant, asymmetric ray response function (RRF) from multiple measured line response functions (LRFs) using a modified edge technique. The RRF measurements cover a range of x-ray incident angles from 0 degrees (equivalent location at the detector center) to 30 degrees (equivalent location at the detector edge) for a standard radiographic or cone-beam CT geometric setup. To demonstrate the method, three beam qualities were tested using the inherent, Lu/Er, and Yb beam filtration. The authors show that measures using the LRF, derived from an edge measurement, underestimate the system's performance when compared with the H matrix derived using the RRF. Furthermore, the authors show that edge measurements must be performed at multiple directions in order to capture rotational asymmetries of the RRF. The authors interpret the results of the H matrix SVD and provide correlations with the familiar MTF methodology. Discussion is made about the benefits of the H matrix technique with regards to signal detection theory, and the characterization of shift-variant imaging systems. C1 [Kyprianou, Iacovos S.; Badano, Aldo; Gallas, Brandon D.; Myers, Kyle J.] US FDA, NIBIB CDRH, Lab Assessment Med Imaging Syst, Silver Spring, MD 20993 USA. RP Kyprianou, IS (reprint author), US FDA, NIBIB CDRH, Lab Assessment Med Imaging Syst, New Hampshire Ave, Silver Spring, MD 20993 USA. EM iacovos.kyprianou@fda.hhs.gov OI Gallas, Brandon/0000-0001-7332-1620; badano, aldo/0000-0003-3712-6670 NR 25 TC 10 Z9 10 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 OCT PY 2008 VL 35 IS 10 BP 4744 EP 4756 DI 10.1118/1.2975222 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 353TT UT WOS:000259591800048 PM 18975719 ER PT J AU Yin, JJ Lao, F Meng, J Fu, PP Zhao, YL Xing, GM Gao, XY Sun, BY Wang, PC Chen, CY Liang, XJ AF Yin, Jun-Jie Lao, Fang Meng, Jie Fu, Peter P. Zhao, Yuliang Xing, Gengmei Gao, Xueyun Sun, Baoyun Wang, Paul C. Chen, Chunying Liang, Xing-Jie TI Inhibition of tumor growth by endohedral metallofullerenol nanoparticles optimized as reactive oxygen species scavenger SO MOLECULAR PHARMACOLOGY LA English DT Article ID ELECTRONIC-PROPERTIES; FULLERENE; BIODISTRIBUTION; DAMAGE; CELLS; MICE; DNA AB Intraperitoneal injection of [Gd@C(82)(OH)(22)](n) nanoparticles decreased activities of enzymes associated with the metabolism of reactive oxygen species (ROS) in the tumor-bearing mice. Several physiologically relevant ROS were directly scavenged by nanoparticles, and lipid peroxidation was inhibited in this study. [Gd@C(82)(OH)(22)](n) nanoparticles significantly reduced the electron spin resonance (ESR) signal of the stable 2,2-diphenyl-1-picryhydrazyl radical measured by ESR spectroscopy. Likewise, studies using ESR with spin-trapping demonstrated efficient scavenging of superoxide radical anion, hydroxyl radical, and singlet oxygen ((1)O(2)) by [Gd@C(82)(OH)(22)](n) nanoparticles. In vitro studies using liposomes prepared from bovine liver phosphatidylcholine revealed that nanoparticles also had a strong inhibitory effect on lipid peroxidation. Consistent with their ability to scavenge ROS and inhibit lipid peroxidation, we determined that [Gd@C(82)(OH)(22)](n) nanoparticles also protected cells subjected in vitro to oxidative stress. Studies using human lung adenocarcinoma cells or rat brain capillary endothelial cells demonstrated that [Gd@C(82)(OH)(22)](n) nanoparticles reduced H(2)O(2)-induced ROS formation and mitochondrial damage. [Gd@C(82)(OH)(22)](n) nanoparticles efficiently inhibited the growth of malignant tumors in vivo. In summary, the results obtained in this study reveal antitumor activities of [Gd@C(82)(OH)(22)](n) nanoparticles in vitro and in vivo. Because ROS are known to be implicated in the etiology of a wide range of human diseases, including cancer, the present findings demonstrate that the potent inhibition of [Gd@C(82)(OH)(22)](n) nanoparticles on tumor growth likely relates with typical capacity of scavenging reactive oxygen species. C1 [Liang, Xing-Jie] Natl Ctr Nanosci & Technol China, Lab Nanobiomed & Nanosafety, Div Nanomed & Nanobiol, Beijing 100190, Peoples R China. [Meng, Jie; Zhao, Yuliang; Xing, Gengmei; Gao, Xueyun; Sun, Baoyun; Chen, Chunying] Chinese Acad Sci, Inst High Energy Phys, Lab Bioenvironm Effects Nanomat & Nanosafety, Beijing, Peoples R China. [Yin, Jun-Jie] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Fu, Peter P.] US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Wang, Paul C.] Howard Univ, Dept Radiol, Lab Mol Imaging, Washington, DC 20059 USA. RP Liang, XJ (reprint author), Natl Ctr Nanosci & Technol China, Lab Nanobiomed & Nanosafety, Div Nanomed & Nanobiol, 11 1st N Rd, Beijing 100190, Peoples R China. EM liangxj@nanoctr.cn RI Yin, Jun Jie /E-5619-2014 FU Chinese Academy of Sciences (CAS) [07165111ZX]; 973 Programs [2006CB705600]; Natural Science Foundation of China [10525524, 20751001]; National Institutes of Health/National Center for Research Resources/Research Centers in Minority Institutions [2G12RR003048]; National Institutes of Health [5U 54CA091431]; U. S. Army Medical Research and Materiel Command [W81XWH-05-1-0291] FX This study was supported by the Chinese Academy of Sciences (CAS) "Hundred Talents Program" grant 07165111ZX, 973 Programs grant 2006CB705600, Natural Science Foundation of China grants 10525524 and 20751001, and the CAS Knowledge Innovation Program. This work was also supported in part by National Institutes of Health/National Center for Research Resources/Research Centers in Minority Institutions Grant 2G12RR003048, National Institutes of Health grant 5U 54CA091431, and U. S. Army Medical Research and Materiel Command grant W81XWH-05-1-0291. NR 31 TC 85 Z9 86 U1 2 U2 45 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0026-895X J9 MOL PHARMACOL JI Mol. Pharmacol. PD OCT PY 2008 VL 74 IS 4 BP 1132 EP 1140 DI 10.1124/mol.108.048348 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 349XV UT WOS:000259317500021 PM 18635669 ER PT J AU Chen, ST Dou, JH Temple, R Agarwal, R Wu, KM Walker, S AF Chen, Shaw T. Dou, Jinhui Temple, Robert Agarwal, Rajiv Wu, Kuei-Meng Walker, Susan TI New therapies from old medicines SO NATURE BIOTECHNOLOGY LA English DT Editorial Material ID ST-JOHNS-WORT; RANDOMIZED CONTROLLED TRIAL; MAJOR DEPRESSION; DOUBLE-BLIND; TEA; EFFICACY; PLACEBO; EXTRACT C1 [Agarwal, Rajiv; Wu, Kuei-Meng; Walker, Susan] US FDA, Ctr Drug Evaluat & Res, Div Dermatol & Dent Prod, Silver Spring, MD 20993 USA. EM shaw.chen@fda.hhs.gov NR 14 TC 47 Z9 49 U1 0 U2 4 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK STREET, 9TH FLOOR, NEW YORK, NY 10013-1917 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD OCT PY 2008 VL 26 IS 10 BP 1077 EP 1083 DI 10.1038/nbt1008-1077 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 358NY UT WOS:000259926000014 PM 18846070 ER PT J AU Hardy, BJ Seguin, B Goodsaid, F Jimenez-Sanchez, G Singer, PA Daar, AS AF Hardy, Billie-Jo Seguin, Beatrice Goodsaid, Federico Jimenez-Sanchez, Gerardo Singer, Peter A. Daar, Abdallah S. TI Science and society - The next steps for genomic medicine: challenges and opportunities for the developing world SO NATURE REVIEWS GENETICS LA English DT Article ID DEVELOPING-COUNTRIES; HEALTH BIOTECH; PUBLIC-HEALTH; DIVERSITY; DATABASE; PROJECT; BIOBANK; AFRICA; INDIA; BANK AB This is a historical moment on the path to genomic medicine-the point at which theory is about to be translated into practice. We have previously described human genome variation studies taking place in Mexico, India, Thailand, and south Africa. such investments into science and technology will enable these countries to embark on the path to the medical and health applications of genomics, and to benefit economically. Here we provide a perspective on the challenges and opportunities facing these and other countries in the developing world as they begin to harness genomics for the benefit of their populations. C1 [Hardy, Billie-Jo; Seguin, Beatrice; Singer, Peter A.; Daar, Abdallah S.] Univ Hlth Network, Program Life Sci Eth & Policy, McLaughlin Rotman Ctr Global Hlth, Toronto, ON M5G 1L7, Canada. [Hardy, Billie-Jo; Seguin, Beatrice; Singer, Peter A.; Daar, Abdallah S.] Univ Toronto, MaRS Ctr, Toronto, ON M5G 1L7, Canada. [Goodsaid, Federico] US FDA, Genom Grp, Off Clin Pharmacol, Off Translat Sci,Ctr Drug Evaluat & Res, Silver Spring, MD 20903 USA. [Jimenez-Sanchez, Gerardo] Natl Inst Genom Med, Mexico City 01900, DF, Mexico. [Seguin, Beatrice] Univ Toronto, Leslie Dan Fac Pharm, Toronto, ON M5S 3M2, Canada. [Singer, Peter A.; Daar, Abdallah S.] Toronto Med Discovery Tower, MaRS Ctr, McLaughlin Ctr Mol Med, Toronto, ON M5G 1L7, Canada. RP Daar, AS (reprint author), Univ Hlth Network, Program Life Sci Eth & Policy, McLaughlin Rotman Ctr Global Hlth, South Tower,Suite 406,101 Coll St, Toronto, ON M5G 1L7, Canada. EM a.daar@utoronto.ca NR 38 TC 18 Z9 20 U1 1 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1471-0056 J9 NAT REV GENET JI Nat. Rev. Genet. PD OCT PY 2008 VL 9 SU S BP S23 EP S27 DI 10.1038/nrg2444 PG 6 WC Genetics & Heredity SC Genetics & Heredity GA 357JC UT WOS:000259841100006 PM 18802418 ER PT J AU Dee, DL Sharma, AJ Cogswell, ME Grummer-Strawn, LM Fein, SB Scanlon, KS AF Dee, Deborah L. Sharma, Andrea J. Cogswell, Mary E. Grummer-Strawn, Laurence M. Fein, Sara B. Scanlon, Kelley S. TI Sources of supplemental iron among breastfed infants during the first year of life SO PEDIATRICS LA English DT Article DE breastfeeding; complementary feeding; dietary iron; infant feeding ID HUMAN-MILK; DEFICIENCY; FOOD AB OBJECTIVES. Primary prevention of iron deficiency requires adequate iron intake. Although recommendations exist to promote adequate intake of iron among infants through iron-rich foods and iron supplements, few studies have examined adherence to these recommendations. Our objectives were to describe the consumption of iron-rich foods, oral iron supplements, and iron-fortified formula among US infants and to assess adherence to iron-intake recommendations. METHODS. We analyzed data from the Infant Feeding Practices Study II, a longitudinal study of mothers and infants followed from late pregnancy through the first year of their infant's life. Mothers completed near-monthly questionnaires that assessed how frequently they fed their infants breast milk, formula, infant cereals, and meats in the previous 7 days and whether their infants were given an oral iron supplement >= 3 times per week during the previous 2 weeks. We examined use of iron-fortified formula among infants who consumed formula; intake of cereal, meat, oral iron supplements, and formula among infants consuming any breast milk; and whether 6-month-old breastfed and mixed-fed ( breast milk and formula) infants consumed sources of supplemental iron with recommended frequency. RESULTS. At 6 months of age, 18% of the term breastfed and mixed-fed infants had not received infant cereal or meat in the previous 7 days, and 15% had not received infant cereal, meat, regular iron supplements, or formula; among solely breastfed infants, 23% had not received infant cereal, meat, or regular iron supplements. Fifty-eight percent of the mixed-fed infants and 70% of the solely breastfed infants received <2 daily servings of infant cereal, meat, or formula combined and did not receive oral iron supplements >= 3 times per week. Among preterm breastfed and mixed-fed infants, none received oral iron supplements >= 3 times per week before 3 months of age, 2% received them at 3 months, and 13% received them at 10.5 months. CONCLUSIONS. Our findings indicate that recommendations regarding iron intake among breastfed infants are not being followed by a substantial proportion of mothers. C1 [Dee, Deborah L.] Ctr Dis Control & Prevent, Epidem Intelligence Serv, Off Career & Workforce Dev, Atlanta, GA 30341 USA. [Dee, Deborah L.; Sharma, Andrea J.; Grummer-Strawn, Laurence M.; Scanlon, Kelley S.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. [Cogswell, Mary E.] Ctr Dis Control & Prevent, Natl Ctr Birth Defects & Dev Disabil, Atlanta, GA 30341 USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Dee, DL (reprint author), Ctr Dis Control & Prevent, Epidem Intelligence Serv, Off Career & Workforce Dev, 4770 Buford Hwy NE,Mail Stop K 25, Atlanta, GA 30341 USA. EM ddee@cdc.gov OI Sharma, Andrea/0000-0003-0385-0011 FU Food and Drug Administration; Centers for Disease Control and Prevention; Office of Women's Health; National Institutes of Health; Maternal and Child Health Bureau in the US Department of Health and Human Services FX This study was funded by the Food and Drug Administration, Centers for Disease Control and Prevention, Office of Women's Health, National Institutes of Health, and Maternal and Child Health Bureau in the US Department of Health and Human Services. NR 16 TC 10 Z9 10 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S98 EP S104 DI 10.1542/peds.2008-1315m PG 7 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800012 PM 18829838 ER PT J AU DiGirolamo, AM Grummer-Strawn, LM Fein, SB AF DiGirolamo, Ann M. Grummer-Strawn, Laurence M. Fein, Sara B. TI Effect of maternity-care practices on breastfeeding SO PEDIATRICS LA English DT Article DE breast feeding; maternity; hospital ID ANALGESIA; HOSPITALS; SUCCESS AB OBJECTIVE. Our goal was to assess the impact of "Baby-Friendly"hospital practices and other maternity-care practices experienced by mothers on breastfeeding duration. METHODS. This analysis of the Infant Feeding Practices Study II focused on mothers who initiated breastfeeding and intended prenatally to breastfeed for >2 months, with complete data on all variables (n = 1907). Predictor variables included indicators of 6 "Baby-Friendly" practices (breastfeeding initiation within 1 hour of birth, giving only breast milk, rooming in, breastfeeding on demand, no pacifiers, fostering breastfeeding support groups) along with several other maternity-care practices. The main outcome measure was breastfeeding termination before 6 weeks. RESULTS. Only 8.1% of the mothers experienced all 6 "Baby-Friendly" practices. The practices most consistently associated with breastfeeding beyond 6 weeks were initiation within 1 hour of birth, giving only breast milk, and not using pacifiers. Bringing the infant to the room for feeding at night if not rooming in and not giving pain medications to the mother during delivery were also protective against early breastfeeding termination. Compared with the mothers who experienced all 6 "Baby-Friendly"practices, mothers who experienced none were similar to 13 times more likely to stop breastfeeding early. Additional practices decreased the risk for early termination. CONCLUSIONS. Increased "Baby-Friendly"hospital practices, along with several other maternity-care practices, improve the chances of breastfeeding beyond 6 weeks. The need to work with hospitals to implement these practices continues to exist, as illustrated by the small proportion of mothers who reported experiencing all 6 of the "Baby-Friendly"hospital practices measured in this study. C1 [DiGirolamo, Ann M.] Emory Univ, Hubert Dept Global Hlth, Atlanta, GA 30307 USA. [Grummer-Strawn, Laurence M.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, US Dept HHS, College Pk, MD USA. RP DiGirolamo, AM (reprint author), Emory Univ, Hubert Dept Global Hlth, 1518 Clifton Rd NE, Atlanta, GA 30307 USA. EM adigiro@sph.emory.edu NR 19 TC 145 Z9 149 U1 1 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S43 EP S49 DI 10.1542/peds.2008-1315e PG 7 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800004 PM 18829830 ER PT J AU Fein, SB Mandal, B Roe, BE AF Fein, Sara B. Mandal, Bidisha Roe, Brian E. TI Success of strategies for combining employment and breastfeeding SO PEDIATRICS LA English DT Article DE breastfeeding; infant care; mothers ID MATERNAL EMPLOYMENT; UNITED-STATES; HUMAN-MILK; WORK; DURATION; WOMEN; INITIATION; WORKPLACE; BARRIERS; MOTHERS AB OBJECTIVE. Return to work is associated with diminished breastfeeding intensity and duration. Although more mothers breastfeed after returning to work now than earlier, research has not documented the strategies that mothers use for combining paid work and breastfeeding or their effect on breastfeeding outcomes. This study examined which strategies are associated with smaller decrements in breastfeeding intensity and longer durations. PARTICIPANTS AND METHODS. We analyzed 810 mothers from the Infant Feeding Practices Study II who worked and breastfed. We used regression and censored regression models to analyze 4 strategies that mothers used to combine these 2 activities: ( 1) feed directly from the breast only; ( 2) both pump and feed directly; ( 3) pump only; and ( 4) neither pump nor breastfeed during the work day. Outcomes were the difference in percentage of milk feeds that were breast milk between the month before and after return to work and duration of breastfeeding after return to work. RESULTS. Forty-three percent of mothers pumped milk at work only; 32% fed the infant directly from the breast only. These 2 strategies, along with pumping and feeding directly, were statistically similar and superior to neither pumping nor breastfeeding during the work day for the outcome of change in breastfeeding intensity. For the outcome of breastfeeding duration, the 2 strategies that included directly feeding from the breast were associated with longer duration than pumping only, whereas the strategy of neither pumping nor breastfeeding during the work day was associated with the shortest duration. CONCLUSIONS. Feeding the infant from the breast during the work day is the most effective strategy for combining breastfeeding and work. Ways to enable direct feeding include on-site child care, telecommuting, keeping the infant at work, allowing the mother to leave work to go to the infant, and having the infant brought to the work site. Establishing ways for mothers to feed from the breast after return to work is important to meet US breastfeeding goals. C1 [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. [Mandal, Bidisha] Washington State Univ, Sch Econ Sci, Pullman, WA 99164 USA. [Roe, Brian E.] Ohio State Univ, Dept Agr Environm & Dev Econ, Columbus, OH 43210 USA. RP Fein, SB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 020, College Pk, MD USA. EM sara.fein@fda.hhs.gov RI Roe, Brian/A-7386-2009 OI Roe, Brian/0000-0003-4228-2889 FU Food and Drug Administration; Centers for Disease Control and Prevention; Office of Women's Health; National Institutes of Health; Maternal and Child Health Bureau FX This study was funded by the Food and Drug Administration, Centers for Disease Control and Prevention, Office of Women's Health, National Institutes of Health, and Maternal and Child Health Bureau in the US Department of Health and Human Services. NR 38 TC 49 Z9 50 U1 0 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S56 EP S62 DI 10.1542/peds.2008-1315g PG 7 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800006 PM 18829832 ER PT J AU Fein, SB Labiner-Wolfe, J Scanlon, KS Grummer-Strawn, LM AF Fein, Sara B. Labiner-Wolfe, Judith Scanlon, Kelley S. Grummer-Strawn, Laurence M. TI Selected complementary feeding practices and their association with maternal education SO PEDIATRICS LA English DT Article DE infant nutrition; complementary feeding; weaning; nutritional requirements; diet ID FOOD PATTERNS; TODDLERS; INFANTS; NUTRIENT; TRACKING; CHILDREN; GUIDELINES; CHILDHOOD; HEALTH AB OBJECTIVE. As infants transition from a milk-based diet to one that includes most food groups, the timing of the transition, how infants are fed, and the quality of their diet can have important health implications. Our objective is to describe these factors for US infants. METHODS. We analyzed data from the Infant Feeding Practices Study II. Sample sizes varied for relevant questions from similar to 1600 to similar to 2400. We analyzed the prevalence of 14 feeding practices and their association with the mothers' education and also examined participants' use of commercial baby foods. RESULTS. Approximately 21% of the mothers introduced solid foods before 4 months; 7% introduced solids after 6 months. Twenty-nine percent of the mothers introduced >3 new foods per week to infants aged 5 to 10 months. Approximately 20% of the mothers fed juice before 6 months, fed cow's milk before 12 months, and fed infants <5 times per day after 5 months. Fourteen percent of the mothers chewed food for their infant. Approximately 15% of the mothers fed <1 serving daily of either a fruit or vegetable to infants aged >= 9 months, half added salt to their infant's food, and more than one third who added salt used noniodized salt. Approximately 20% fed reduced-fat cow's milk at 1 year. Almost half of the 10-month-old infants had eaten restaurant food in a restaurant in the previous week, 22% had eaten carry-out food, and 28% had eaten either type of restaurant food >= 2 times. The prevalence of 8 of the 14 unhealthful infant feeding practices we examined was inversely associated with maternal education. CONCLUSIONS. Nutrition and feeding guidance should be especially targeted to mothers with a high school education or less. C1 [Fein, Sara B.; Labiner-Wolfe, Judith] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Scanlon, Kelley S.; Grummer-Strawn, Laurence M.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr Phys Act & Obes, Atlanta, GA USA. RP Fein, SB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 020, College Pk, MD 20740 USA. EM sara.fein@fda.hhs.gov NR 26 TC 36 Z9 40 U1 2 U2 10 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S91 EP S97 DI 10.1542/peds.2008-1315l PG 7 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800011 PM 18829837 ER PT J AU Fein, SB Labiner-Wolfe, J Shealy, KR Li, RW Chen, J Grummer-Strawn, LM AF Fein, Sara B. Labiner-Wolfe, Judith Shealy, Katherine R. Li, Rouwei Chen, Jian Grummer-Strawn, Laurence M. TI Infant Feeding Practices Study II: Study methods SO PEDIATRICS LA English DT Article DE breastfeeding; bottle feeding; infant; nutrition; physiology; infant care ID FOOD FREQUENCY QUESTIONNAIRE; UNITED-STATES; VALIDATION; WORK AB OBJECTIVE. Our goal is to describe the methods used in the Infant Feeding Practices Study II (IFPS II), a study of infant feeding and care practices throughout the first year of life. Survey topics included breastfeeding, formula and complementary feeding, infant health, breast-pump use, food allergies, sleeping arrangements, mother's employment, and child care arrangements. In addition, mothers' dietary intake was measured prenatally and postnatally. PARTICIPANTS AND METHODS. The IFPS II sample was drawn from a nationally distributed consumer opinion panel of 500 000 households. All questionnaires were administered by mail, 1 prenatally and 10 postpartum. Qualifying criteria were used to achieve the sample goals of mothers of healthy term and late preterm singleton infants. In addition to the questionnaires about the infants, women were sent a diet-assessment questionnaire prenatally and at similar to 4 months after delivery; this questionnaire was also sent to members of a comparison group who were neither pregnant nor postpartum. RESULTS. A sample of 4902 pregnant women began the study, and similar to 2000 continued through their infant's first year. Response rates ranged from 63% to 87% for the different questionnaires. Compared with adult mothers of singletons from the nationally representative sample of the National Survey of Family Growth, IFPS II participants had a higher mean education level; were older; were more likely to be middle income, white, and employed; were less likely to smoke; and had fewer other children. Compared with women who participated in the National Immunization Survey who gave birth in 2004, IFPS II mothers were more likely to breastfeed and to breastfeed longer. CONCLUSIONS. The IFPS II provides a valuable database because of its large sample size, the frequency of its questionnaires, and its wide coverage of issues salient to infant feeding. C1 [Fein, Sara B.; Labiner-Wolfe, Judith] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Shealy, Katherine R.; Li, Rouwei; Chen, Jian; Grummer-Strawn, Laurence M.] Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Atlanta, GA USA. RP Fein, SB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 020, College Pk, MD 20740 USA. EM sara.fein@fda.hhs.gov NR 26 TC 130 Z9 130 U1 0 U2 13 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S28 EP S35 DI 10.1542/peds.2008-1315c PG 8 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800002 PM 18829828 ER PT J AU Fein, SB Grummer-Strawn, LM Raju, TNK AF Fein, Sara B. Grummer-Strawn, Laurence M. Raju, Tonse N. K. TI Infant feeding and care practices in the United States: Results from the Infant Feeding Practices Study II SO PEDIATRICS LA English DT Editorial Material C1 [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Grummer-Strawn, Laurence M.] Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. [Raju, Tonse N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, Bethesda, MD USA. RP Fein, SB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 020, College Pk, MD 20740 USA. EM sara.fein@fda.hhs.gov NR 13 TC 26 Z9 26 U1 0 U2 9 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S25 EP S27 DI 10.1542/peds.2008-1315b PG 3 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800001 PM 18829827 ER PT J AU Grummer-Strawn, LM Scanlon, KS Fein, SB AF Grummer-Strawn, Laurence M. Scanlon, Kelley S. Fein, Sara B. TI Infant feeding and feeding transitions during the first year of life SO PEDIATRICS LA English DT Article DE infant feeding; breast milk; solid food introduction ID AGED CHILDREN; TODDLERS; FOOD; GUIDELINES AB OBJECTIVE. Infancy is a time of rapid transition from a diet of virtually nothing but milk (either breast milk or infant formula) to a varied diet from nearly all food groups being consumed on a daily basis by most infants. Despite various recommendations about infant feeding, little is known about actual patterns of feeding among US infants. This article documents transitions in infant feeding patterns across the first year of life and determinants of key aspects of infant feeding. METHODS. Using data from the Infant Feeding Practices Study II, we analyzed responses to a 7-day food-recall chart that was administered every month. The sample size declined from 2907 at birth to 1782 at 12 months of age. RESULTS. Although 83% of survey respondents initiated breastfeeding, the percentage who breastfed declined rapidly to 50% at 6 months and to 24% at 12 months. Many of the women who breastfed also fed their infants formula; 52% reported that their infants received formula while in the hospital. At 4 months, 40% of the infants had consumed infant cereal, 17% had consumed fruit or vegetable products, and <1% had consumed meat. Compared with infants who were not fed solid foods at 4 months, those who were fed solid foods were more likely to have discontinued breastfeeding at 6 months (70% vs 34%) and to have been fed fatty or sugary foods at 12 months (75% vs 62%). CONCLUSIONS. Supplementing breast milk with infant formula while infants were still in the hospital was very common. Despite recommendations that complementary foods not be introduced to infants aged 4 months or younger, almost half of the infants in this study had consumed solid foods by the age of 4 months. This early introduction of complementary foods was associated with unhealthful subsequent feeding behavior. C1 [Grummer-Strawn, Laurence M.; Scanlon, Kelley S.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr Phys Act & Obes, Atlanta, GA 30341 USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Grummer-Strawn, LM (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr Phys Act & Obes, 4770 Buford Hwy,MS K25, Atlanta, GA 30341 USA. EM lxg8@cdc.gov RI Vollrath, Margarete/G-1297-2011 NR 18 TC 132 Z9 133 U1 1 U2 24 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S36 EP S42 DI 10.1542/peds.2008-1315d PG 7 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800003 PM 18829829 ER PT J AU Hauck, FR Signore, C Fein, SB Raju, TNK AF Hauck, Fern R. Signore, Caroline Fein, Sara B. Raju, Tonse N. K. TI Infant sleeping arrangements and practices during the first year of life SO PEDIATRICS LA English DT Article DE sleep; sudden infant death syndrome; SIDS; suffocation; infant mortality; risk reduction; health campaigns; breastfeeding ID DEATH-SYNDROME; UNITED-STATES; POSITION; RISK; ENVIRONMENT AB OBJECTIVES. Our goal was to examine the sleeping arrangements for infants from birth to 1 year of age and to assess the association between such arrangements and maternal characteristics. METHODS. Responses to the 3-, 6-, 9-, and 12-month questionnaires from the Infant Feeding Practices Study II were analyzed to assess sleep arrangements, including bed sharing, the latter defined as mother ever ( in a given time frame) slept with the infant on the same sleeping surface for nighttime sleep. Women were also asked about the reasons for bed sharing or not bed sharing. RESULT Approximately 2300 women responded at 3 months, and 1800 at 12 months. At 3 months, 85% of the infants slept in the same room as their mother, and at 12 months that rate was 29%. At 3 months, 26% of the mothers did not use the recommended supine position for their infant's nighttime sleep. The rate of noncompliance increased to 29% by 6 months and 36% by 12 months. The bed-sharing rates were 42% at 2 weeks, 34% at 3 months, and 27% at 12 months. Approximately two thirds of those who bed shared with their infant also shared the bed with their husband or partner, and 5% to 15% shared it with other children. The major reasons for bed sharing were to calm a fussy infant, facilitate breastfeeding, and help the infant and/ or mother sleep better. The major reasons for not lying down with the infant were safety concerns. Non-Hispanic black mothers were more likely than non-Hispanic white mothers to use nonsupine infant sleep positions and to bed share. CONCLUSIONS. More than one third of the women in this cohort were noncompliant with safe-sleeping guidelines when their infant was 3 months old. Health care providers need to advise parents of current recommendations and discuss the risks and benefits of their choices for infant sleeping practices. C1 [Hauck, Fern R.] Univ Virginia, Dept Family Med, Sch Med, Charlottesville, VA 22908 USA. [Hauck, Fern R.] Univ Virginia, Dept Publ Hlth Sci, Sch Med, Charlottesville, VA 22908 USA. [Signore, Caroline; Raju, Tonse N. K.] Eunice Kennedy Shriver Natl Inst Child Hlth & Hum, Pregnancy & Perinatol Branch, NIH, US Dept HHS, Bethesda, MD USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, US Dept HHS, College Pk, MD USA. RP Hauck, FR (reprint author), Univ Virginia, Dept Family Med, Sch Med, POB 800729, Charlottesville, VA 22908 USA. EM frh8e@virginia.edu FU Food and Drug Administration; Centers for Disease Control and Prevention; Office of Women's Health; National Institutes of Health; Maternal and Child Health Bureau in the US Department of Health and Human Services FX This study was funded by the Food and Drug Administration, Centers for Disease Control and Prevention, Office of Women's Health, National Institutes of Health, and Maternal and Child Health Bureau in the US Department of Health and Human Services. NR 25 TC 39 Z9 40 U1 3 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S113 EP S120 DI 10.1542/peds.2008-1315o PG 8 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800014 PM 18829826 ER PT J AU Labiner-Wolfe, J Fein, SB Shealy, KR AF Labiner-Wolfe, Judith Fein, Sara B. Shealy, Katherine R. TI Infant formula-handling education and safety SO PEDIATRICS LA English DT Article DE infant formula; food handling; food labeling AB OBJECTIVES. Our goal was to assess the extent to which mothers learn about proper handling of infant formula from health professionals and package labels; mothers' beliefs about the likelihood of germs being in infant formula and the importance of following safe-use directions; whether they take measures while handling infant formula to prevent foodborne illnesses and injury to their infants; and maternal characteristics associated with unsafe infant formula-handling practices. PARTICIPANTS AND METHODS. The study cohort consisted of mothers participating in the 2005-2007 Infant Feeding Practices Study II who fed their infant formula. We conducted frequency and multiple logistic regression analyses. Sample sizes for the analyses ranged from 860 to 1533. RESULTS. The majority of formula-feeding mothers did not receive instruction on formula preparation (77%) or storage (73%) from a health professional. Thirty percent did not read some of the safe-use directions on the formula package label; an approximately equal percentage (38%) thought that both powdered (which is not sterile) and ready-to-feed (which is sterile) formula were unlikely to contain germs; and 85% believed that following safe-storage directions was very important. Among the mothers of the youngest infants analyzed, 55% did not always wash their hands with soap before preparing infant formula, 32% did not adequately wash bottle nipples between uses, 35% heated formula bottles in a microwave oven, and 6% did not always discard formula left standing for >2 hours. The prevalence of these unsafe practices was similar among mothers of older infants. No consistent pattern of maternal characteristics was associated with unsafe practices. CONCLUSIONS. Many mothers do not follow safe practices when preparing infant formula. Additional research is needed to understand why more mothers do not follow safe formula-handling recommendations. C1 [Labiner-Wolfe, Judith; Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Shealy, Katherine R.] Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Atlanta, GA USA. RP Labiner-Wolfe, J (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 020, College Pk, MD 20740 USA. EM judy.labiner@fda.hhs.gov NR 12 TC 10 Z9 11 U1 2 U2 10 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S85 EP S90 DI 10.1542/peds.2008-1315k PG 6 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800010 PM 18829836 ER PT J AU Labiner-Wolfe, J Fein, SB Shealy, KR Wang, CL AF Labiner-Wolfe, Judith Fein, Sara B. Shealy, Katherine R. Wang, Cunlin TI Prevalence of breast milk expression and associated factors SO PEDIATRICS LA English DT Article DE breastfeeding; breast milk; medical device ID WORK AB OBJECTIVES. Our goal was to describe the prevalence of any, occasional, and regular breast milk expression, mothers' reasons for expressing their milk, and sociodemographic factors associated with breast milk expression. PARTICIPANTS AND METHODS. Breastfeeding mothers participating in the 2005-2007 Infant Feeding Practices Study II formed the cohort for these analyses, which were conducted among those with infants in 3 age groups: 1.5 to 4.5 months (n = 1564); > 4.5 to 6.5 months (n = 1128); and > 6.5 to 9.5 months (n = 914). For the analyses we used frequency and stepwise multiple logistic regression procedures. RESULTS. Eighty-five percent of breastfeeding mothers of infants in the youngest age group had successfully expressed milk at some time since their infant was born. When asked only about the previous 2-week period, 68% of the breastfeeding mothers of infants in this youngest age group had expressed milk, with 43% having done so occasionally and 25% on a regular schedule. Approximately one quarter of breastfeeding mothers of infants in the 2 older infant age groups also expressed milk on a regular schedule. The percentage of mothers expressing milk decreased with increasing infant age. Mothers expressed milk for various reasons. The most frequently cited reason was to get breast milk for someone else to feed their infant. In all 3 age groups, reporting any breast milk expression, compared with none, was positively associated with maternal employment, higher income, lack of previous breastfeeding experience, and living in the Midwest versus the West. In all 3 age groups, expressing milk on a regular schedule, compared with occasionally, was positively associated with maternal employment and the use of an electric versus manual breast pump. CONCLUSIONS. Breast milk expression is a very common practice. It is associated most strongly with maternal employment, a recognized barrier to breastfeeding. C1 [Labiner-Wolfe, Judith; Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. [Shealy, Katherine R.] Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Atlanta, GA USA. [Wang, Cunlin] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Labiner-Wolfe, J (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 020, College Pk, MD 20740 USA. EM judy.labiner@fda.hhs.gov NR 16 TC 68 Z9 68 U1 0 U2 8 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S63 EP S68 DI 10.1542/peds.2008-1315h PG 6 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800007 PM 18829833 ER PT J AU Li, RW Fein, SB Grummer-Strawn, LM AF Li, Ruowei Fein, Sara B. Grummer-Strawn, Laurence M. TI Association of breastfeeding intensity and bottle-emptying behaviors at early infancy with infants' risk for excess weight at late infancy SO PEDIATRICS LA English DT Article DE breastfeeding; bottle feeding; obesity; etiology; infant ID HUMAN-MILK; CARDIOVASCULAR-DISEASE; CHILDHOOD OBESITY; BODY-WEIGHT; LATER LIFE; OVERWEIGHT; ADOLESCENTS; CHILDREN; GROWTH; CONSEQUENCES AB OBJECTIVE. Our goal was to test the hypothesis that infants who were breastfed more intensively during early infancy (<= 6 months) will be less likely to have excess weight during late infancy (<= 6 months) and to examine the independent impact of infant-initiated bottle emptying and mothers' encouragement of bottle emptying on infants' risk for excess weight. METHOD. The sample consisted of 1896 mothers who participated in postpartum surveys of the Infant Feeding Practice Study II and who provided at least 1 weight measurement of their infants during the second half of infancy. We used multiple logistic regression models to assess the association between infants' risks for excess weight during the second half of infancy and 3 self-reported feeding practices during the first half of infancy after adjusting for a series of sociodemographic characteristics. The early feeding practices examined included the percentage of all milk feedings in which infants consumed breast milk (breastfeeding intensity), the frequency of bottle feedings in which infants initiated bottle emptying, and the frequency of bottle feedings in which mothers encouraged bottle emptying. RESULTS. Infants fed with low (<20% of milk feeds being breast milk) and medium (20%-80%) breastfeeding intensity in the first half of infancy were at least 2 times more likely to have excess weight during the second half of infancy than those breastfed at high intensity (>80%). Infants who often emptied bottles in early infancy were 69% more likely than those who rarely emptied bottles to have excess weight during late infancy. However, mothers' encouragement of bottle emptying was negatively associated with their infants' risk for excess weight during the second half of infancy. CONCLUSIONS. Infants' risk for excess weight during late infancy was negatively associated with breastfeeding intensity but positively associated with infant-initiated bottle emptying during early infancy. These findings not only provide evidence for the potential risk of not breastfeeding or breastfeeding at a low intensity in development of childhood obesity, but they also suggest that infant-initiated bottle emptying may be an independent risk factor as well. C1 [Li, Ruowei; Grummer-Strawn, Laurence M.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr Phys Act & Obes, Atlanta, GA 30341 USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Li, RW (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr Phys Act & Obes, 4770 Buford Hwy,Mail Stop K25, Atlanta, GA 30341 USA. EM ril6@cdc.gov FU Food and Drug Administration; Centers for Disease Control and Prevention; Office of Women's Health; National Institutes of Health; Maternal and Child Health Bureau FX This study was funded by the Food and Drug Administration, Centers for Disease Control and Prevention, Office of Women's Health, National Institutes of Health, and Maternal and Child Health Bureau in the US Department of Health and Human Services. NR 39 TC 51 Z9 56 U1 3 U2 10 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S77 EP S84 DI 10.1542/peds.2008-1315j PG 8 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800009 PM 18829835 ER PT J AU Li, RW Fein, SB Chen, J Grummer-Strawn, LM AF Li, Ruowei Fein, Sara B. Chen, Jian Grummer-Strawn, Laurence M. TI Why mothers stop breastfeeding: Mothers' self-reported reasons for stopping during the first year SO PEDIATRICS LA English DT Article DE breastfeeding; lactation; weaning; infant ID HUMAN-MILK; BIRTH COHORT; OTITIS-MEDIA; FED INFANTS; GROWTH; RISK; OVERWEIGHT; CHILDREN; DURATION; LIFE AB OBJECTIVES. Our goal was to determine why women stop breastfeeding at various times during their infant's first year. METHODS. We analyzed self-reported data from 1323 mothers who participated in the Infant Feeding Practice Study II. Mail questionnaires were sent to mothers similar to 2, 3, 4, 5, 6, 7, 9, 10 1/2, and 12 months after their child's birth, in which they were asked to rate the importance of 32 reasons for their decision to stop breastfeeding. We applied exploratory factorial analysis to extract meaningful constructs of mothers' responses to the 32 reasons. We then compared the percentages of mothers who indicated that each reason was important in their decision to stop breastfeeding among various weaning ages and used multiple logistic regression models to examine sociodemographic differences in the most frequently cited reasons for stopping breastfeeding. RESULTS. The perception that their infant was not satisfied by breast milk alone was cited consistently as 1 of the top 3 reasons in the mothers' decision to stop breastfeeding regardless of weaning age (43.5%-55.6%) and was even more frequent among Hispanic mothers and mothers with annual household incomes of <350% of the federal poverty level. Mothers' concerns about lactation and nutrition issues were the most frequently cited reasons for stopping breastfeeding during the first 2 months. Starting from the third month, self-weaning reasons were increasingly cited as important, with the statements "My baby began to bite" (31.7%), " My baby lost interest in nursing or began to wean himself or herself" (47.3%), and " Breast milk alone did not satisfy my baby" (43.5%) cited as the top 3 reasons at >= 9 months of age. CONCLUSIONS. Our findings about the major reasons why mothers stop breastfeeding at various times during their child's first year should be useful to health professionals when attempting to help mothers overcome breastfeeding barriers and to health officials attempting to devise targeted breastfeeding interventions on those issues prominent for each infant age. C1 [Li, Ruowei; Chen, Jian; Grummer-Strawn, Laurence M.] Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr Phys Act & Obes, Atlanta, GA 30341 USA. [Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Li, RW (reprint author), Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Div Nutr Phys Act & Obes, 4770 Buford Hwy,Mail Stop K25, Atlanta, GA 30341 USA. EM ril6@cdc.gov FU Food and Drug Administration; Centers for Disease Control and Prevention; Office of Women's Health; National Institutes of Health; Maternal and Child Health Bureau FX This study was funded by the Food and Drug Administration, Centers for Disease Control and Prevention, Office of Women's Health, National Institutes of Health, and Maternal and Child Health Bureau in the US Department of Health and Human Services. NR 41 TC 112 Z9 116 U1 2 U2 31 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S69 EP S76 DI 10.1542/peds.2008-1315i PG 8 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800008 PM 18829834 ER PT J AU Luccioli, S Ross, M Labiner-Wolfe, J Fein, SB AF Luccioli, Stefano Ross, Marianne Labiner-Wolfe, Judith Fein, Sara B. TI Maternally reported food allergies and other food-related health problems in infants: characteristics and associated factors SO PEDIATRICS LA English DT Article DE food allergy; food hypersensitivity; food; intolerance; diet; infants ID ADVERSE-REACTIONS; YOUNG-CHILDREN; COWS MILK; 1ST YEAR; PREVALENCE; LIFE; CHILDHOOD; HYPERSENSITIVITY; ANAPHYLAXIS; PREVENTION AB OBJECTIVE. Our goal was to identify the frequency, demographics, and diagnostic characteristics associated with maternally reported food allergies and other food-related health problems among infants aged <= 1 year. METHODS. We analyzed data from the 2005-2007 Infant Feeding Practices Study II, a longitudinal survey of 2441 US mothers of healthy singletons from pregnancy through their infant's first year. Doctor diagnosis and symptoms-based criteria were used to identify a probable-food-allergic group from maternal reports of infant health problems with food. RESULTS. More than one fifth of the 2441 mothers reported that their infant had a food-related problem; 6% (n = 143) had a probable food allergy, and 15% (n = 359) had other food-related problems. Forty percent of the infants with a food-related health problem were evaluated by a doctor. Gastrointestinal symptoms were more commonly reported in early infancy compared with skin-related symptoms, which were reported in later infancy, and 27% received medical treatment for the symptoms. Characteristics associated with increased incidence of probable food allergy included family histories of food allergy and type 1 diabetes, gestational diabetes, living in rural or urban areas, being black, and being male. Among all infants with a food-related health problem, the majority experienced their first problem by 6 months of age. Foods recognized to be major allergens were most commonly reported as the source of an allergy. CONCLUSIONS. Food-related problems occurred at a high frequency in the first year of life. A better understanding of the demographics, family history, disease manifestations, and diagnoses may provide insight into public health efforts to minimize or prevent food allergies in infancy and to help differentiate food-allergic problems from nonallergic food problems in this age group. C1 [Luccioli, Stefano; Ross, Marianne; Labiner-Wolfe, Judith; Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Luccioli, S (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy,HFS 200, College Pk, MD 20740 USA. EM stefano.luccioli@fda.hhs.gov FU Food and Drug Administration; Centers for Disease Control and Prevention; Office of Women's Health; National Institutes of Health; Maternal and Child Health Bureau in the US Department of Health and Human Services FX This study was funded by the Food and Drug Administration, Centers for Disease Control and Prevention, Office of Women's Health, National Institutes of Health, and Maternal and Child Health Bureau in the US Department of Health and Human Services. NR 40 TC 25 Z9 25 U1 0 U2 4 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S105 EP S112 DI 10.1542/peds.2008-1315n PG 8 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800013 PM 18829825 ER PT J AU Shealy, KR Scanion, KS Labiner-Wolfe, J Fein, SB Grummer-Strawn, LM AF Shealy, Katherine R. Scanion, Kelley S. Labiner-Wolfe, Judith Fein, Sara B. Grummer-Strawn, Laurence M. TI Characteristics of breastfeeding practices among US mothers SO PEDIATRICS LA English DT Article DE breastfeeding; breast milk; feeding behavior; human milk; lactation; medical; education; mothers; patient education; supplementary feeding ID HUMAN-MILK; SELF-EFFICACY; WOMEN; RECOMMENDATIONS; INFORMATION; ATTITUDES; DURATION; REMOVAL; COHORT; FAT AB OBJECTIVES. Although much has been published about breastfeeding rates, little is known about how breastfeeding is practiced in the United States. We describe the distributions and characteristics of practices related to common advice about breastfeeding during the infant's first year of life. PARTICIPANTS AND METHODS. Participants in the 2005-2007 Infant Feeding Practices Study II received monthly questionnaires during their infants' first year of life. Among breastfeeding respondents, we investigated patterns and trends in types of breastfeeding (supplementing with formula or not, and at the breast or not) and maternal report of infant feeding behaviors corresponding to common breastfeeding advice on frequency, duration, and intervals of feedings. RESULTS. More than half of the breastfeeding mothers fed their infants nothing other than breast milk until 4 months of age. Formula supplementation declined from 42% at 1 month to 15% at 1 year; adding other foods/liquids increasingly surpassed supplementing with formula beginning at 5 months of age. Six percent of the mothers reported that the only breast milk the infant was fed was expressed, rather than at the breast. Frequency of breast milk feedings per day declined from 8 at 1 month to 3.5 at 1 year. Reported feeding durations of <20 minutes increased from 46% at 1 month to 88% at 1 year. Feeding from both breasts per feeding decreased 15% over the infant's first year (from 69% to 59%). Longest interfeeding intervals more than doubled over the year. CONCLUSIONS. Exclusive breastfeeding was common up to 4 but not to 6 months of age. Breastfeeding with only expressed milk was rare. Considerable variation existed in maternal report of practices that correspond to common breastfeeding advice. More research is needed to better understand how these variations relate to breastfeeding outcomes and the role of common breastfeeding advice in infant feeding decisions. C1 [Shealy, Katherine R.; Scanion, Kelley S.; Grummer-Strawn, Laurence M.] Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, Atlanta, GA 30341 USA. [Labiner-Wolfe, Judith; Fein, Sara B.] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Shealy, KR (reprint author), Ctr Dis Control & Prevent, Div Nutr Phys Act & Obes, 4770 Buford Hwy NE,Mail Stop K25, Atlanta, GA 30341 USA. EM kshealy@cdc.gov FU Food and Drug Administration; Centers for Disease Control and Prevention; Office of Women's Health; US Department of Health and Human Services FX This study was funded by the Food and Drug Administration, Centers for Disease Control and Prevention, Office of Women's Health, National Institutes of Health, and Maternal and Child Health Bureau in the US Department of Health and Human Services. NR 32 TC 23 Z9 23 U1 0 U2 7 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD OCT PY 2008 VL 122 SU S BP S50 EP S55 DI 10.1542/peds.2008-1315f PG 6 WC Pediatrics SC Pediatrics GA 357CB UT WOS:000259822800005 PM 18829831 ER PT J AU Yu, LX AF Yu, Lawrence X. TI Pharmaceutical quality by design: Product and process development, understanding, and control (vol 25, pg 10, 2008) SO PHARMACEUTICAL RESEARCH LA English DT Correction C1 US FDA, Off Gener Drugs, Rockville, MD 20855 USA. RP Yu, LX (reprint author), US FDA, Off Gener Drugs, 7519 Standish Pl, Rockville, MD 20855 USA. EM Lawrence.Yu@fda.hhs.gov RI Yu, Lawrence/L-6280-2016 NR 1 TC 8 Z9 8 U1 1 U2 20 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD OCT PY 2008 VL 25 IS 10 BP 2463 EP 2463 DI 10.1007/s11095-008-9667-3 PG 1 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 348CE UT WOS:000259187800029 ER PT J AU Potvin, D DiLiberti, CE Hauck, WW Parr, AF Schuirman, DJ Smith, RA AF Potvin, Diane DiLiberti, Charles E. Hauck, Walter W. Parr, Alan F. Schuirman, Donald J. Smith, Robert A. TI Sequential design approaches for bioequivalence studies with crossover designs SO PHARMACEUTICAL STATISTICS LA English DT Article DE sequential design; sample size reestirnation; adaptive design; bioequivalence ID I ERROR RATE; INTERNAL PILOT; SAMPLE-SIZE; CLINICAL-TRIALS; TESTING PROCEDURE; T-TEST; POWER; MODEL AB The planning of bioequivalence (BE) studies, as for any clinical trial, requires a priori specification of an effect size for the determination of power and an assumption about the variance. The specified effect size may be overly optimistic, leading to an underpowered study. The assumed variance can be either too small or too large, leading, respectively, to studies that are underpowered or overly large. There has been much work in the clinical trials field on various types of sequential designs that include sample size reestimation after the trial is started, but these have seen only little use in BE studies. The purpose of this work was to validate at least one such method for crossover design BE studies. Specifically, we considered sample size reestimation for a two-stage trial based on the variance estimated from the first stage. We identified two methods based on Pocock's method for group sequential trials that met our requirement for at most negligible increase in type I error rate. Copyright (C) 2007 John Wiley & Sons, Ltd. C1 [Hauck, Walter W.] US Pharmacopeia, Rockville, MD 20852 USA. [Potvin, Diane] Theratechnologies Inc, Montreal, PQ, Canada. [DiLiberti, Charles E.] Barr Labs Inc, Woodclif Lake, NJ USA. [Parr, Alan F.] GlaxoSmithKline Inc, Res Triangle Pk, NC USA. [Schuirman, Donald J.] US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. [Smith, Robert A.] Bristol Myers Squibb Co, Pharmaceut Res Inst, Princeton, NJ 08543 USA. RP Hauck, WW (reprint author), US Pharmacopeia, 12601 Twinbrook Pkwy, Rockville, MD 20852 USA. EM wh@usp.org NR 27 TC 22 Z9 24 U1 1 U2 9 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 OCT-DEC PY 2008 VL 7 IS 4 BP 245 EP 262 DI 10.1002/pst.294 PG 18 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 386VO UT WOS:000261910900003 PM 17710740 ER PT J AU Carrington, CD Bolger, M AF Carrington, Clark D. Bolger, Michael TI Letter to the editor SO RISK ANALYSIS LA English DT Letter ID METHYLMERCURY; CONSUMPTION; EXPOSURE; MERCURY; SEAFOOD; WOMEN; FISH; AGE C1 [Carrington, Clark D.; Bolger, Michael] US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Carrington, CD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 7 TC 1 Z9 1 U1 1 U2 3 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD OCT PY 2008 VL 28 IS 5 BP 1137 EP 1139 DI 10.1111/j.1539-6924.2008.01056.x PG 3 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 350OT UT WOS:000259363300001 PM 18844860 ER PT J AU Chakravarty, A Sridhara, R AF Chakravarty, Aloka Sridhara, Rajeshwari TI Use of progression-free survival as a surrogate marker in oncology trials: some regulatory issues SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Article; Proceedings Paper CT 8th International Conference on Computational Processing of the Portuguese Language CY SEP 08-10, 2008 CL Aveiro, PORTUGAL SP Univ Aveiro, Inst Elect Telemat Engn Aveiro, Assoc Computat Linguist, Int Speech Commun Assoc, ISCA SIG-IL, Fund Cien Tecnol, Microsoft Intel, Springer, UZ Technol, DESIGNEED, Grande Hotel Curia ID APPROVAL AB There has been interest in using progression-free survival as a surrogate endpoint for overall survival in oncology clinical trials. In order to objectively define this endpoint, clear understanding of what progression means, how it is measured and what its implications are need to be discussed. This article discusses some regulatory aspects of using progression-free survival as an endpoint. C1 [Chakravarty, Aloka; Sridhara, Rajeshwari] US FDA, Off Biostat, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. RP Chakravarty, A (reprint author), US FDA, Off Biostat, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave,Bldg 22,Room 1214,Mail St, Silver Spring, MD 20993 USA. EM aloka.chakravarty@fda.hhs.gov NR 5 TC 21 Z9 21 U1 0 U2 0 PU SAGE PUBLICATIONS LTD PI LONDON PA 1 OLIVERS YARD, 55 CITY ROAD, LONDON EC1Y 1SP, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PD OCT PY 2008 VL 17 IS 5 BP 515 EP 518 DI 10.1177/0962280207081862 PG 4 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 362SF UT WOS:000260216700007 PM 18285437 ER PT J AU Zhang, J Snyder, RD Herman, EH Knapton, A Honchel, R Miller, T Espandiari, P Goodsaid, FM Rosenblum, IY Hanig, JP Sistare, FD Weaver, JL AF Zhang, Jun Snyder, Ronald D. Herman, Eugene H. Knapton, Alan Honchel, Ronald Miller, Terry Espandiari, Parvaneh Goodsaid, Federico M. Rosenblum, Irwin Y. Hanig, Joseph P. Sistare, Frank D. Weaver, James L. TI Histopathology of Vascular Injury in Sprague-Dawley Rats Treated with Phosphodiesterase IV Inhibitor SCH 351591 or SCH 534385 SO TOXICOLOGIC PATHOLOGY LA English DT Article DE activation and degranulation of mast cell; activation of endothelial cell and macrophage; apoptosis of endothelial and smooth muscle cells; arterial hemorrhage and necrosis; nitrotyrosine; peroxynitrite ID CYCLIC-AMP-PHOSPHODIESTERASE; FIBROBLAST-GROWTH-FACTOR; ENDOTHELIAL-CELL ACTIVATION; MAST-CELLS; TISSUE INHIBITOR; PDE4 INHIBITOR; PHASE RESPONSE; UP-REGULATION; NITRIC-OXIDE; PEROXYNITRITE AB Histopathological and immunohistochemical studies were conducted to characterize vascular injuries in rats treated with phosphodiesterase (PDE) IV inhibitors SCH 351591 or SCH 534385. Sprague-Dawley rats were administered PDE IV inhibitors by gavage at a range of doses and times. The two PDE IV inhibitors induced comparable levels of vascular injury, primarily in the mesentery and to a lesser extent in the pancreas, kidney, liver, small intestine, and stomach. Mesenteric vascular changes occurred as early as one hour, progressively developed over twenty-four to forty-eight hours, peaked at seventy-two hours, and gradually subsided from seven to nine days. The typical morphology of the vascular toxicity consisted of hemorrhage and necrosis of arterioles and arteries, microvascular injury, fibrin deposition, and perivascular inflammation of a variety of blood vessels. The incidence and severity of mesenteric vascular injury increased in a time-and dose-dependent manner in SCH 351591- or SCH 534385-treated rats. Mesenteric vascular injury was frequently associated with activation of mast cells (MC), endothelial cells (EC), and macrophages (MO). Immunohistochemical studies showed increases in CD63 immunoreactivity of mesenteric MC and in nitrotyrosine immunoreactivity of mesenteric EC and MO. The present study also provides a morphological and cellular basis for evaluating candidate biomarkers of drug-induced vascular injury. C1 [Zhang, Jun; Herman, Eugene H.; Knapton, Alan; Honchel, Ronald; Miller, Terry; Espandiari, Parvaneh; Hanig, Joseph P.; Weaver, James L.] US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD 910, Silver Spring, MD USA. [Snyder, Ronald D.] Schering Plough Res Inst, Summit, NJ USA. [Goodsaid, Federico M.] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD USA. [Rosenblum, Irwin Y.] Kyowa Pharmaceut Inc, Princeton, NJ USA. [Sistare, Frank D.] Merck Res Labs, West Point, PA USA. RP Zhang, J (reprint author), Food & Drug Adm HFD 910, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM jun.zhang@fda.hhs.gov NR 46 TC 23 Z9 23 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD OCT PY 2008 VL 36 IS 6 BP 827 EP 839 DI 10.1177/0192623308322308 PG 13 WC Pathology; Toxicology SC Pathology; Toxicology GA 463VJ UT WOS:000267460300007 PM 18776163 ER PT J AU Weaver, JL Snyder, R Knapton, A Herman, EH Honchel, R Miller, T Espandiari, P Smith, R Gu, YZ Goodsaid, FM Rosenblum, IY Sistare, FD Zhang, J Hanig, J AF Weaver, James L. Snyder, Ronald Knapton, Alan Herman, Eugene H. Honchel, Ronald Miller, Terry Espandiari, Parvaneh Smith, Roger Gu, Yi-Zhong Goodsaid, Federico M. Rosenblum, Irwin Y. Sistare, Frank D. Zhang, Jun Hanig, Joseph TI Biomarkers in Peripheral Blood Associated with Vascular Injury in Sprague-Dawley Rats Treated with the Phosphodiesterase IV Inhibitors SCH 351591 or SCH 534385 SO TOXICOLOGIC PATHOLOGY LA English DT Article DE microvascular injury; biomarkers; phosphodiesterase inhibitors ID EXPRESSION; INTERLEUKIN-6; LESIONS; STRESS; CELLS AB Drug-associated vascular injury can be caused by phosphodiesterase (PDE) IV inhibitors and drugs from several other classes. The pathogenesis is poorly understood, but it appears to include vascular and innate immunological components. This research was undertaken to identify changes in peripheral blood associated with vascular injury caused by PDE IV inhibitors. We evaluated twelve proteins, serum nitrite, and leukocyte populations in peripheral blood of rats treated with experimental PDE IV inhibitors. We found that these compounds produced histological microvascular injury in a dose-and time-dependent manner. Measurement of these serum proteins showed changes in eight of the twelve examined. Changes were seen in the levels of: tissue inhibitor of metalloproteinase-1, alpha 1-acid glycoprotein, GRO/CINC-1, vascular endothelial growth factor, C-reactive protein, haptoglobin, thrombomodulin, and interleukin-6. No changes were seen in levels of tumor necrosis factor-alpha, hepatocyte growth factor, nerve growth factor, and granulocyte-monocyte colony stimulating factor. Serum levels of nitrite were also increased. Circulating granulocyte numbers were increased, and lymphocyte numbers were decreased. The changes in these parameters showed both a dose-and time-dependent association with histopathologic changes. These biomarkers could provide an additional tool for the nonclinical and clinical evaluation of investigational compounds. C1 [Weaver, James L.; Knapton, Alan; Herman, Eugene H.; Honchel, Ronald; Miller, Terry; Espandiari, Parvaneh; Zhang, Jun; Hanig, Joseph] US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Silver Spring, MD 20993 USA. [Snyder, Ronald; Smith, Roger; Gu, Yi-Zhong] Schering Plough Res Inst, Summit, NJ USA. [Goodsaid, Federico M.] US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol, Silver Spring, MD 20993 USA. [Rosenblum, Irwin Y.] Kyowa Pharmaceut Inc, Princeton, NJ USA. [Sistare, Frank D.] Merck Res Labs, West Point, PA USA. RP Weaver, JL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Life Sci Bldg 64,HFD 910,10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM james.weaver@fda.hhs.gov NR 20 TC 16 Z9 16 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PD OCT PY 2008 VL 36 IS 6 BP 840 EP 849 DI 10.1177/0192623308322310 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 463VJ UT WOS:000267460300008 PM 18776166 ER PT J AU Fuller, CC Jawahir, SL Leano, FT Bidol, SA Signs, K Davis, C Holmes, Y Morgan, J Teltow, G Jones, B Sexton, RB Davis, GL Braden, CR Patel, NJ Deasy, MP Smith, KE AF Fuller, C. C. Jawahir, S. L. Leano, F. T. Bidol, S. A. Signs, K. Davis, C. Holmes, Y. Morgan, J. Teltow, G. Jones, B. Sexton, R. B. Davis, G. L. Braden, C. R. Patel, N. J. Deasy, M. P., III Smith, K. E. TI A multi-state Salmonella typhimurium outbreak associated with frozen vacuum-packed rodents used to feed snakes SO ZOONOSES AND PUBLIC HEALTH LA English DT Article DE Salmonella Typhimurium; frozen rodents; reptiles; pulsed-field gel electrophoresis ID REPTILE-ASSOCIATED SALMONELLOSIS; ENTERICA SEROTYPE TYPHIMURIUM; UNITED-STATES; PET RODENTS; CHILDREN; INFECTIONS; IGUANAS; ILLNESS; MMWR AB From December 2005 through January 2006, the Minnesota Department of Health (MDH) identified four human clinical isolates of Salmonella Typhimurium that were indistinguishable by pulsed-field gel electrophoresis (PFGE). During routine interviews, three of the cases reported attending the same junior high school and two handled snakes in the science classroom. MDH collected environmental samples from the school's science classroom for Salmonella culturing; these included environmental samples and frozen vacuum-packed mice purchased over the internet to feed the classroom snakes. Through PulseNet, a national molecular subtyping surveillance network for enteric bacteria, 21 human S. Typhimurium isolates with indistinguishable PFGE patterns were identified in the United States since December 2005. Each state determined whether these human cases had recent exposure to snakes fed vacuum-packed rodents. Texas state officials conducted tracebacks of the vacuum-packed mice and collected samples at the breeding facility. Nineteen of 21 cases were interviewed, and seven reported contact with frozen vacuum-packed rodents from the same internet-based supplier in Texas. In Minnesota, the outbreak PFGE subtype of S. Typhimurium was isolated from the snakes, frozen feed rodents, and the classroom environment. Three human cases were identified in Michigan, Pennsylvania, and Wyoming. The outbreak PFGE subtype of S. Typhimurium was isolated from the Pennsylvania case's frozen rodents and the Michigan case's pet snake. The outbreak PFGE subtype of S. Typhimurium was also isolated from the supplier's rodent facility. This was a S. Typhimurium outbreak associated with frozen rodents. Human transmission likely occurred through direct contact with snakes and contaminated environmental surfaces. This report represents the second recent multi-state salmonellosis outbreak associated with commercially distributed rodents. Stronger oversight of the commercial rodent industry is warranted. C1 [Fuller, C. C.; Smith, K. E.] Minnesota Dept Hlth, Acute Dis Invest & Control Sect, St Paul, MN 55164 USA. [Jawahir, S. L.; Leano, F. T.] Minnesota Dept Hlth, Publ Hlth Lab, St Paul, MN USA. [Bidol, S. A.; Signs, K.] Michigan Dept Community Hlth, Bur Epidemiol, Lansing, MI USA. [Davis, C.; Holmes, Y.; Morgan, J.; Teltow, G.] Texas Dept State Hlth Serv, Temple, TX USA. [Jones, B.; Sexton, R. B.] Texas Feed & Fertilizer Control Serv, Off Texas State Chem, College Stn, TX USA. [Davis, G. L.] US FDA, Ft Worth, TX USA. [Braden, C. R.; Patel, N. J.] Ctr Dis Control & Prevent, Atlanta, GA USA. [Deasy, M. P., III] Penn Dept Hlth, Div Infect Dis Epidemiol, Harrisburg, PA 17108 USA. RP Fuller, CC (reprint author), Minnesota Dept Hlth, Acute Dis Invest & Control Sect, 625 Robert St N, St Paul, MN 55164 USA. EM Candace.Fuller@health.state.mn.us NR 30 TC 23 Z9 29 U1 0 U2 1 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 1863-1959 J9 ZOONOSES PUBLIC HLTH JI Zoonoses Public Health PD OCT PY 2008 VL 55 IS 8-10 BP 481 EP 487 DI 10.1111/j.1863-2378.2008.01118.x PG 7 WC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences SC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences GA 347OA UT WOS:000259149700016 PM 18833597 ER PT J AU Yang, M Kostov, Y Rasooly, A AF Yang, Minghui Kostov, Yordan Rasooly, Avraham TI Carbon nanotubes based optical immunodetection of Staphylococcal Enterotoxin B (SEB) in food SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE staphylococcal enterotoxins; ELISA; carbon nanotubes; food safety ID FIELD-EFFECT TRANSISTORS; ASSAY KIT TECRA; ATOPIC-DERMATITIS; ELECTROCHEMICAL IMMUNOSENSOR; CAPILLARY-ELECTROPHORESIS; RHEUMATOID-ARTHRITIS; SUPERANTIGENS; AUREUS; TOXIN; IDENTIFICATION AB Staphylococcal enterotoxins (SEs) are a major cause of food-borne diseases. traditionally SEs assayed immunologically with ELISA. Carbon nanotubes' (CNT) unique mechanical and electronic properties combined with a large specific surface area make them attractive for biosensing. To investigate whether CNT could improve the sensitivity of ELISA assays, we developed an optical CNT immunosensor for the detection of Staphylococcal Enterotoxin B (SEB) in food. Anti-SEB antibodies were immobilized onto a CNT surface through electrostatic adsorption and then the antibody-nanotube mixture was bound onto a polycarbonate film. SEB was then detected by a "sandwich-type" ELISA assay on the polycarbonate film. The use of CNT increased the sensitivity of the immunosensor by at least 6-fold, lowering the detection limit of SEB. The CNT immunosensor was also able to detect SEB various foods. suggesting the utility of CNT for this and other optical-based immunological detection methods. Published by Elsevier B.V. C1 [Yang, Minghui; Kostov, Yordan] Univ Maryland Baltimore Cty, Ctr Adv Sensor Technol, Baltimore, MD 21250 USA. [Rasooly, Avraham] US FDA, Div Biol, Off Sci & Engn, Silver Spring, MD 20993 USA. [Rasooly, Avraham] NCI, Bethesda, MD 20892 USA. RP Rasooly, A (reprint author), NCI, NIH, 6130 Execut Blvd EPN,Room 6035A, Rockville, MD 20852 USA. EM rasoolya@mail.nih.gov NR 59 TC 28 Z9 28 U1 0 U2 11 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 SEP 30 PY 2008 VL 127 IS 1-2 BP 78 EP 83 DI 10.1016/j.ijfoodmicro.2008.06.012 PG 6 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 356IG UT WOS:000259771300013 PM 18632175 ER PT J AU Miyagi, E Schwartzkopff, F Plishka, R Buckler-White, A Clouse, KA Strebel, K AF Miyagi, Eri Schwartzkopff, Franziska Plishka, Ronald Buckler-White, Alicia Clouse, Kathleen A. Strebel, Klaus TI APOBEC3G-independent reduction in virion infectivity during long-term HIV-1 replication in terminally differentiated macrophages SO VIROLOGY LA English DT Article DE APOBEC3G; macrophages; HIV-1; Vif ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIVIRAL ACTIVITY; VIF PROTEIN; TYPE-1 VIF; HUMAN APOBEC3G; VIRAL-RNA; ANTI-HIV-1 ACTIVITY; DEAMINASE ACTIVITY; ENZYME APOBEC3G; T-LYMPHOCYTES AB APCBEC3G (APO3G) is a cellular cytidine deaminase with potent antiviral activity. In the case of HIV, the antiviral activity of APO3G is counteracted by the viral Vif protein. Monocyte-derived macrophages (MDM) are terminally differentiated, non-dividing cells Susceptible to HIV infection. Human MDM are known to express APO3G and HIV replication in these cells is dependent oil Vif. Here we analyzed the Correlation between HIV-1 replication and APO3G expression in MDM. Replication of wild type HIV-1 induced a gradual 4-5-fold reduction in APO3G expression. The efficiency of APO3G downregulation correlated with the efficiency of virus replication. Interestingly, despite downregulation of APO3G, the relative infectivity of viruses rapidly declined during the Course of infection and was already reduced similar to 90% prior to peak virus production. Cell-free virus preparations showed increased levels of a 41 kDa MA-CA processing intermediate. Sequence analysis around the MA-CA cleavage site and the protease and LTR regions did not reveal deaminase-induced hypermutation of the viral genome, suggesting that APO3G activity is not responsible for the incomplete Gag processing. Thus, the loss of infectivity of HIV-1 viruses produced from long-term infected primary macrophages is due to an APO3G-independent mechanism. Published by Elsevier Inc. C1 [Miyagi, Eri; Strebel, Klaus] NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, Bethesda, MD 20892 USA. [Schwartzkopff, Franziska; Clouse, Kathleen A.] US FDA, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. RP Strebel, K (reprint author), NIAID, Mol Microbiol Lab, Viral Biochem Sect, NIH, 4-312,4 Ctr Dr,MSC 0460, Bethesda, MD 20892 USA. EM kstrebel@nih.gov FU NIH Intramural AIDS Targeted Antiviral Program; Intramural Research Program of the NIH, NIAID FX We acknowledge Ritu Goila-Gaur, Sandra Kao, Mohammad Khan, Sandrine Opi, and Hiroaki Takeuchi for helpful discussions throughout this study and Karen Fields, Linda Tiffany, Carla Lankford, and Mark Paciga for help with macrophage Culture. We are grateful to Robert Gorelick and Michael Malim for providing valuable antibodies and we thank John Kappes for the TZM-bl indicator cell line. The latter reagent was obtained through the NIH AIDS Research and Reference Reagent Program. This work was supported by a Grant from the NIH Intramural AIDS Targeted Antiviral Program to K.S. and by the Intramural Research Program of the NIH, NIAID. NR 47 TC 8 Z9 8 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD SEP 30 PY 2008 VL 379 IS 2 BP 266 EP 274 DI 10.1016/j.virol.2008.06.033 PG 9 WC Virology SC Virology GA 353ES UT WOS:000259549500011 PM 18675436 ER PT J AU Lute, S Norling, L Hanson, M Ernery, R Stinson, D Padua, K Blank, G Chen, Q Brorson, K AF Lute, Scott Norling, Lenore Hanson, Michael Ernery, Rachel Stinson, Denise Padua, Kevin Blank, Greg Chen, Qi Brorson, Kurt TI Robustness of virus removal by protein A chromatography is independent of media lifetime SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article DE monoclonal antibodies; viral removal; protein A chromatography; media lifetime ID TIME QUANTITATIVE PCR; REVERSE-TRANSCRIPTASE ASSAY; CATION-EXCHANGE RESINS; SENSING ZONE PRINCIPLE; MAB CELL-CULTURE; MONOCLONAL-ANTIBODIES; AFFINITY SORBENTS; MONITOR RETROVIRUS; VIRAL CLEARANCE; SIZING PROCESS AB The robustness of virus clearance with respect to protein A media reuse was demonstrated using media with four matrix chemistries: Protein A immobilized ProSep A, Poros A50, Protein A ceramic Hyper DF and MabSelect SuRe, an alkali resistant protein A ligand. Endogenous retrovirus clearance, step yield, impurity clearance and other performance parameters were evaluated periodically in media cycled up to 300 times. Media lifetime was generally limited by either declining step yield or media fouling. However, clearance of endogenous retrovirus remained in an acceptable range, either increasing or remaining constant. Multiply cycled media were tested for clearance of three viruses (SV40, X-MuLV, and MMV); clearance was comparable to naive media. Overall, virus clearance by protein A chromatography appears to be extremely robust with respect to media age. Published by Elsevier B.V. C1 [Lute, Scott; Hanson, Michael; Brorson, Kurt] US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Norling, Lenore; Ernery, Rachel; Stinson, Denise; Padua, Kevin; Blank, Greg; Chen, Qi] Genentech Inc, Late Stage Purificat, Proc Dev, San Francisco, CA 94080 USA. [Hanson, Michael] Univ Maryland Baltimore Cty, Dept Chem Engn, Baltimore, MD 21250 USA. RP Brorson, K (reprint author), US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM kurt.brorson@fda.hhs.gov NR 48 TC 24 Z9 26 U1 2 U2 13 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD SEP 26 PY 2008 VL 1205 IS 1-2 BP 17 EP 25 DI 10.1016/j.chroma.2008.07.094 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 357ZB UT WOS:000259884700003 PM 18722622 ER PT J AU Pogribny, IP Tryndyak, VP Boureiko, A Melnyk, S Bagnyukova, TV Montgomery, B Rusyn, I AF Pogribny, Igor P. Tryndyak, Volodymyr P. Boureiko, Anna Melnyk, Stepan Bagnyukova, Tetyana V. Montgomery, Beverly Rusyn, Ivan TI Mechanisms of peroxisome proliferator-induced DNA hypomethylation in rat liver SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE DNA hypomethylation; DNA damage; cell proliferation; peroxisome proliferators ID MOUSE-LIVER; PPAR-ALPHA; GLOBAL DNA; HEPATOCELLULAR-CARCINOMA; METHYLATION PATTERNS; GENE-EXPRESSION; CPG ISLANDS; GC-RICH; C-MYC; CANCER AB Genomic hypomethylation is a consistent finding in both human and animal tumors and mounting experimental evidence suggests a key role for epigenetic events in tumorigenesis. Furthermore, it has been suggested that early changes in DNA methylation and histone modifications may serve as sensitive predictive markers in animal testing for carcinogenic potency of environmental agents. Alterations in metabolism of methyl donors, disturbances in activity and/or expression of DNA methyltransferases, and presence of DNA single-strand breaks could contribute to the loss of cytosine methylation during carcinogenesis; however, the precise mechanisms of genomic hypomethylation induced by chemical carcinogens remain largely unknown. This study examined the mechanism of DNA hypomethylation during hepatocarcinogenesis induced by peroxisome proliferators WY-14,643 (4-chloro-6-(2,3-xylidino)-pyrimidynylthioacetic acid) and DEHP (di-(2 -ethylhexyl)phthalate), agents acting through non-genotoxic mode of action. In the liver of male Fisher 344 rats exposed to WY-14,643 (0.1% (w/w), 5 months), the level of genomic hypomethylation increased by similar to 2-fold, as compared to age-matched controls, while in the DEHP group (1.2% (w/w), 5 months) DNA methylation did not change. Global DNA hypomethylation in livers from WY-14,643 group was accompanied by the accumulation of DNA single-strand breaks, increased cell proliferation, and diminished expression of DNA methyltransferase 1, while the metabolism of methyl donors was not affected. In contrast, none of these parameters changed significantly in rats fed DEHR Since WY14,643 is much more potent carcinogen than DEHP, we conclude that the extent of loss of DNA methylation may be related to the carcinogenic potential of the chemical agent, and that accumulation of DNA single-strand breaks coupled to the increase in cell proliferation and altered DNA methyltransferase expression may explain genomic hypomethylation during peroxisome proliferator-induced carcinogenesis. Published by Elsevier B.V. C1 [Pogribny, Igor P.; Tryndyak, Volodymyr P.; Boureiko, Anna; Bagnyukova, Tetyana V.; Montgomery, Beverly] Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. [Melnyk, Stepan] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. [Rusyn, Ivan] Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. RP Pogribny, IP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM igor.pogribny@fda.hhs.gov; ivan_rusyn@unc.edu RI Rusyn, Ivan/S-2426-2016 FU Postgraduate Research Program administered by the Oak Ridge Institute for Science and Education; National Institutes of Health [ES12686, ES11391, ES11660] FX This work was supported in part by the Postgraduate Research Program administered by the Oak Ridge Institute for Science and Education (V.T. and T.B.) and by the National Institutes of Health grants ES12686, ES11391, and ES11660. NR 51 TC 30 Z9 40 U1 1 U2 7 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 SEP 26 PY 2008 VL 644 IS 1-2 BP 17 EP 23 DI 10.1016/j.mrfmmm.2008.06.009 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 351KD UT WOS:000259422300003 PM 18639561 ER PT J AU Eichelberger, MC Hassantoufighi, A Wu, M Li, M AF Eichelberger, Maryna C. Hassantoufighi, Arash Wu, Meng Li, Min TI Neuraminidase activity provides a practical read-out for a high throughput influenza antiviral screening assay SO VIROLOGY JOURNAL LA English DT Article ID VIRUSES ISOLATED WORLDWIDE; RESISTANCE; OSELTAMIVIR; INHIBITORS; SUBSTRATE; HEMAGGLUTININ; SURVEILLANCE; REPLICATION; ADAMANTANES; ACTIVATION AB Background: The emergence of influenza strains that are resistant to commonly used antivirals has highlighted the need to develop new compounds that target viral gene products or host mechanisms that are essential for effective virus replication. Existing assays to identify potential antiviral compounds often use high throughput screening assays that target specific viral replication steps. To broaden the search for antivirals, cell-based replication assays can be performed, but these are often labor intensive and have limited throughput. Results: We have adapted a traditional virus neutralization assay to develop a practical, cell-based, high throughput screening assay. This assay uses viral neuraminidase (NA) as a read-out to quantify influenza replication, thereby offering an assay that is both rapid and sensitive. In addition to identification of inhibitors that target either viral or host factors, the assay allows simultaneous evaluation of drug toxicity. Antiviral activity was demonstrated for a number of known influenza inhibitors including amantadine that targets the M2 ion channel, zanamivir that targets NA, ribavirin that targets IMP dehydrogenase, and bis-indolyl maleimide that targets protein kinase A/C. Amantadine-resistant strains were identified by comparing IC(50) with that of the wild-type virus. Conclusion: Antivirals with specificity for a broad range of targets are easily identified in an accelerated viral inhibition assay that uses NA as a read-out of replication. This assay is suitable for high throughput screening to identify potential antivirals or can be used to identify drug-resistant influenza strains. C1 [Eichelberger, Maryna C.; Hassantoufighi, Arash] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Wu, Meng; Li, Min] Johns Hopkins Sch Med, High Throughput Biol Ctr, Baltimore, MD USA. [Wu, Meng; Li, Min] Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD USA. [Eichelberger, Maryna C.] US FDA, Ctr Biol Evaluat & Res, OVRR, Div Viral Prod, Bethesda, MD 20892 USA. RP Eichelberger, MC (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. EM Maryna.Eichelberger@fda.hhs.gov; Arash.Hassantoufighi@fda.hhs.gov; meng@jhmi.edu; minli@jhmi.edu RI Wu, Meng/F-3958-2010 FU NIH [AI071340] FX We thank Drs Daniel Perez ( University of Maryland) for providing A/Memphis/14/98; and Dr Galina Vodeiko (CBER, FDA) for providing A/Wisconsin/67/2005.A/New Caledonia and B/Malaysia were obtained from CDC. Drs Carol Weiss and Miriam Ngundi made helpful comments in preparation of the manuscript for which we are thankful. This project was funded by NIH grant AI071340. NR 32 TC 18 Z9 20 U1 1 U2 4 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1743-422X J9 VIROL J JI Virol. J. PD SEP 26 PY 2008 VL 5 AR 109 DI 10.1186/1743-422X-5-109 PG 8 WC Virology SC Virology GA 360BH UT WOS:000260031500001 PM 18822145 ER PT J AU Zhang, MJ Huang, QS Huang, Y Wood, O Yuan, WS Chancey, C Daniel, S Rios, M Hewlett, I Clouse, KA Dayton, AI AF Zhang, Mingjie Huang, Qingsheng Huang, Yong Wood, Owen Yuan, Weishi Chancey, Caren Daniel, Sylvester Rios, Maria Hewlett, Indira Clouse, Kathleen A. Dayton, Andrew I. TI beta-estradiol attenuates the anti-HIV-1 efficacy of Stavudine (D4T) in primary PBL SO RETROVIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; ANTIRETROVIRAL THERAPY; CELLULAR PHARMACOLOGY; GENDER-DIFFERENCES; REPLICATION; INHIBITORS; HIV AB Background: Female hormones are known to play an important role in predisposition for many infectious diseases. Recent work suggests there are gender effects in HIV/AIDS progression. Here we ask whether the sex steroid hormone beta-estradiol affects the replication of HIV-1 or the efficacy of a common anti-retroviral drug, Stavudine (D4T). Results: Human PBL were infected with HIV-1 in the presence or absence of combinations of sex steroid hormones and the anti-retroviral drug, D4T. After seven days in culture, viral supernatants were assayed for HIV-1 p24 protein. beta-estradiol resulted in a modest inhibition of HIV-1 replication of similar to 26%. However, 2 nM beta-estradiol increased the amount of HIV-1 replication in the presence of 50 nM D4T from a baseline of 33% (+/- SE = 5.4) to 74% (+/- SE = 5.4) of control virus levels in the absence of drug. Both results were statistically highly significant (p < 0.001). beta-estradiol did not increase the replication of a D4T-resistant strain of HIV in the presence of D4T. The effects were unlikely to be due to general cell inhibition or toxicity because these concentrations of drug and hormone cause no cytotoxicity in PBL as measured by trypan blue exclusion. Conclusion: beta-estradiol inhibited both HIV-1 replication in primary human PBL and the antiretroviral efficacy of D4T in PBL cultures. To optimize antiretroviral drug therapy, it may be necessary to monitor patient hormonal status. C1 [Zhang, Mingjie; Huang, Qingsheng; Huang, Yong; Wood, Owen; Yuan, Weishi; Chancey, Caren; Daniel, Sylvester; Rios, Maria; Hewlett, Indira; Dayton, Andrew I.] US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. [Clouse, Kathleen A.] US FDA, Ctr Drug Eveluat & Res, Rockville, MD 20857 USA. RP Dayton, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM ming.zhang@fda.hhs.gov; qingsheng.huang@fda.hhs.gov; yong.huang@fda.hhs.gov; owen.wood@fda.hhs.gov; vivian.yuan@fda.hhs.gov; caren.chancey@fda.hhs.gov; sylvester.daniel@fda.hhs.gov; maria.rios@fda.hhs.gov; indira.hewlett@fda.hhs.gov; kathleen.clouse@fda.hhs.gov; andrew.dayton@fda.hhs.gov RI Huang, Yong/G-9365-2011 FU Office of Women's Health, FDA FX The following reagents were obtained through the AIDS Research and Reference Reagent Program, Division of AIDS, NIAID, NIH: AZT Resistant HIV-1 (Cat.# 629), provided by Dr. Douglas Richman, HIV-1 BAL, HIV-1 IIIB and Stavudine (D4T). We would like to thank Chettemegre Venkateshan for extensive help with the virus infections and cell culture work, and the late Rolf Taffs for statistical advice. This work was supported in part by the Office of Women's Health, FDA. The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any Agency determination or policy. NR 13 TC 9 Z9 9 U1 0 U2 0 PU BIOMED CENTRAL LTD PI LONDON PA 236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND SN 1742-4690 J9 RETROVIROLOGY JI Retrovirology PD SEP 22 PY 2008 VL 5 AR 82 DI 10.1186/1742-4690-5-82 PG 8 WC Virology SC Virology GA 359TJ UT WOS:000260010700001 PM 18808673 ER PT J AU Sedrakyan, GZ Evans, FE Minasyan, SH Tavadyan, LA Wangila, GW Walker, RB Sorenson, JRJ AF Sedrakyan, Gegham Z. Evans, Frederick E. Minasyan, Seyran H. Tavadyan, Levon A. Wangila, Grant W. Walker, Richard B. Sorenson, John R. J. TI NMR and FTIR studies of coordinate-bonding and intramolecular and intermolecular hydrogen bonding in zine(II)(3,5-diisopropylsalicylate)(2) SO JOURNAL OF COORDINATION CHEMISTRY LA English DT Article DE bis-3,5-diisopropylsalicylatozinc(II); NMR; FTIR; coordinate bonding; intramolecular and intermolecular hydrogen bonding ID COPPER(II); COMPLEXES; PHENOL; ATOM; REACTIVITIES; ABSTRACTION; ANTIOXIDANT AB Carboxylate and salicylic OH coordinate bonding as well as intramolecular and intermolecular hydrogen bonding of bis-3,5-diisopropylsalicylatozinc(II), [Zn-II(3,5-DIPS)(2)], with Lewis bases were studied to determine mechanisms accounting for antioxidant reactivity of Zn-II(3,5-DIPS)(2). Apparent thermodynamic parameters: K-cq, Delta S-0, Delta H-0, and Delta G(0) were determined for these equilibria with bonding of two molecules of dimethyl sulfoxide-d(6) (DMSO) or ethyl acetate-d(8) (EA) to the Zn-II using NMR and FTIR. We conclude that addition of two equivalents of DMSO or EA to non-polar solutions of Zn-II(3,5-DIPS)(2) results in bonding of DMSO or EA to Zn-II via sulfoxide or ester carbonyl oxygen atoms with ternary complex formation, leading to weakening of carboxylate and salicylic OH coordinate bonding to Zn-II and strengthening intramolecular hydrogen bonding between protons of salicylic OH groups and carboxylate oxygens. Subsequent addition of two or three additional equivalents of DMSO or EA leads to intermolecular hydrogen bonding between protons of salicylic OH groups. C1 [Sedrakyan, Gegham Z.; Minasyan, Seyran H.; Tavadyan, Levon A.] Natl Acad Sci, Inst Chem Phys, Yerevan 0014, Armenia. [Evans, Frederick E.] Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. [Wangila, Grant W.; Walker, Richard B.; Sorenson, John R. J.] Univ Arkansas, Dept Chem & Phys, Pine Bluff, AR 71601 USA. [Sorenson, John R. J.] Univ Arkansas Med Sci, Div Med Chem, Coll Pharm, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. RP Tavadyan, LA (reprint author), Natl Acad Sci, Inst Chem Phys, 5-2 P Sevak St, Yerevan 0014, Armenia. EM tavadyan@ichph.sci.am FU NFSAT (Armenia) [LTTG 2003/06]; ANSEF (US); Armenian Ministry of Science and Education [N 1-22-1292] FX NMR studies were supported by the NFSAT (Armenia) fund (Grant LTTG 2003/06) and FTIR studies were supported by ANSEF (US) fund (grant) and the Armenian Ministry of Science and Education (Grant N 1-22-1292). We thank Essential Metalloclement Analyses Laboratory (USA), and Dr. Garik Martirosyan, Dr. Alexander Schahchatuni, and Dr Henrik Panosyan, Molecular Structure Research Center NAS of Armenia, for their practical assistance. NR 23 TC 1 Z9 1 U1 4 U2 5 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0095-8972 J9 J COORD CHEM JI J. Coord. Chem. PD SEP 20 PY 2008 VL 61 IS 18 BP 2861 EP 2875 DI 10.1080/00958970802087086 PG 15 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 348TG UT WOS:000259232400002 ER PT J AU Austen, F Woodcock, J Sasisekharan, R AF Austen, Frank Woodcock, Janet Sasisekharan, Ram TI Contaminated heparin - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 [Austen, Frank] Harvard Univ, Sch Med, Boston, MA 02115 USA. [Woodcock, Janet] US FDA, Rockville, MD 20857 USA. [Sasisekharan, Ram] MIT, Cambridge, MA 02139 USA. RP Austen, F (reprint author), Harvard Univ, Sch Med, Boston, MA 02115 USA. EM rams@mit.edu 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 EI 1533-4406 J9 NEW ENGL J MED JI N. Engl. J. Med. PD SEP 18 PY 2008 VL 359 IS 12 BP 1293 EP 1293 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 349DV UT WOS:000259259900020 ER PT J AU Rubin, J Walker, RD Blickenstaff, K Bodeis-Jones, S Zhao, S AF Rubin, J. Walker, R. D. Blickenstaff, K. Bodeis-Jones, S. Zhao, S. TI Antimicrobial resistance and genetic characterization of fluoroquinolone resistance of Pseudomonas aeruginosa isolated from canine infections SO VETERINARY MICROBIOLOGY LA English DT Article DE Pseudomonas aeruginosa; antimicrobial resistance; fluoroquinolones; canine; class 1 integron; QRDR ID II TOPOISOMERASE MUTATIONS; QUINOLONE RESISTANCE; CLASS-1 INTEGRONS; DOGS; MECHANISMS; ANIMALS; BACTERIA; STRAINS; REGION; OTITIS AB Infections with antimicrobial-resistant bacteria are a great challenge in both human and veterinary medicine. The purpose of this study was to determine antimicrobial susceptibility of 106 strains of Poseudomonas aeruginosa isolated from dogs with otitis and pyoderma from 2003 to 2006 in the United States. Three antimicrobial panels, including 6 classes and 32 antimicrobial agents, were used. A wide range of susceptibility patterns were noted with some isolates being resistant to between 8 and 28 (mean 16) of the antimicrobials tested. Among the beta-lactams, all isolates were resistant to ampicillin, cefoxitin, cefpodoxime, cephalothin and cefazolin followed by amoxicillin/clavulanic acid (99%), ceftiofur (97%), ceftriaxone (39%), cefotaxime (26%), and cefotaxime/clavulanic acid (20%), whereas less than 7% of isolates were resistant to ceftazidime/clavulanic acid, ceftazidime, piperacillin/tazobactam or cefepime. Two isolates were resistant to the carbapenems. Among the quinolones and fluoroquinolones, the most isolates were resistant to naladixic acid (96%), followed by orbifloxacin (52%), difloxacin (43%), enrofloxacin (31%), marbofloxacin (27%), gatifloxacin (23%), levofloxacin (21%), and ciprofloxacin (16%). Among the aminoglycosides, the most resistance was seen to kanamycin (90%), followed by streptomycin (69%), gentamicin (7%), and amikacin (3%). Of the remaining antimicrobials 100% of the isolates were resistant to chloramphenicol followed by tetracycline (98%), trimethoprim/sulfamethoxazole (57%), and sulfisoxazole (51%). Point mutations were present in gyrA, gyrB, parC, and/or parE genes among 34 of the 102 naladixic acid-resistant isolates. Two isolates contained class 1 integrons carrying aadA gene conferring streptomycin and spectinomycin resistance. The findings suggest that many antimicrobial agents commonly used in companion animals may not constitute appropriate therapy for canine pseudomonas infections. (C) 2008 Elsevier B.V. All fights reserved. C1 [Blickenstaff, K.; Bodeis-Jones, S.; Zhao, S.] US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. [Rubin, J.] Univ Saskatchewan, Western Coll Vet Med, Dept Vet Microbiol, Saskatoon, SK S74 5B4, Canada. [Walker, R. D.] Antiinfect Res Consultants, Glade Pk, CO 81523 USA. [Walker, R. D.] Mesa State Coll, Dept Biol Sci, Grand Junction, CO 81501 USA. RP Zhao, S (reprint author), US FDA, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM shaohua.zhao@FDA.HHS.GOV RI Rubin, Joseph/B-3374-2009 OI Rubin, Joseph/0000-0002-2636-406X NR 29 TC 32 Z9 32 U1 1 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD SEP 18 PY 2008 VL 131 IS 1-2 BP 164 EP 172 DI 10.1016/j.vetmic.2008.02.018 PG 9 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 353EN UT WOS:000259549000017 PM 18395369 ER PT J AU Duggirala, H Yang, X Van Manen, R AF Duggirala, H. Yang, X. Van Manen, R. TI Can disproportionality analysis play a role in monitoring drug-eluting stent safety? SO CIRCULATION LA English DT Meeting Abstract CT World Congress of Cardiology CY MAY 18-21, 2008 CL Buenos Aires, ARGENTINA SP World Heart Federat, Argentine Soc Cardiol, Argentine Federat Cardiol C1 [Duggirala, H.] US FDA, Rockville, MD 20857 USA. [Yang, X.; Van Manen, R.] Lincoln Technol, Phase Forward, Lincoln, NE USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD SEP 16 PY 2008 VL 118 IS 12 BP E439 EP E439 PG 1 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 348QK UT WOS:000259224801345 ER PT J AU Manalo, DJ Buehler, PW Baek, JH Butt, O D'Agnillo, F Alayash, AI AF Manalo, Dominador J. Buehler, Paul W. Baek, Jin Hyen Butt, Omer D'Agnillo, Felice Alayash, Abdu I. TI Acellular haemoglobin attenuates hypoxia-inducible factor-1 alpha (HIF-1 alpha) and its target genes in haemodiluted rats SO BIOCHEMICAL JOURNAL LA English DT Article DE erythropoiesis; haematocrit; haemodilution; haemoglobin (Hb); kidney; hypoxia-inducible factor-1 alpha (HIF-1 alpha) ID HYPOXIA-INDUCIBLE FACTOR; UBIQUITIN-PROTEASOME PATHWAY; HEME OXYGENASE-1 GENE; FACTOR 1-ALPHA; INTERMITTENT HYPOXIA; TRANSCRIPTION FACTORS; ENDOTHELIAL-CELLS; BOVINE HEMOGLOBIN; HIF HYDROXYLASES; FACTOR-I AB Hb (haemoglobin)-based blood substitutes represent a class of therapeutics designed to correct oxygen deficit under conditions of anaemia and traumatic blood loss. The influences of these agents on HIF-1 alpha (hypoxia-inducible factor-la) target genes involved in adaptation to hypoxia have so far not been studied. In the study presented here. rats underwent 80% ET (exchange transfusion) with either HS (hetastarch) or a polymerized Hb OG (Oxyglobin (R)). HS induced dramatic EPO (erythropoietin) gene transcription, reaching a maximum at 4 In post-ET. In contrast, OG suppressed EPO transcription until approx. 24 h post-ET. Large plasma EPO levels that were observed post-ET with HS were significantly blunted in animals transfused with OG. OG, unlike HS, induced a sharp increase in HO-1 (haem oxygenase-1) transcription at 4 In, which declined rapidly within 24 h, whereas modest increases in iNOS [inducible (nitric oxide synthase)] and constitutive NOS [eNOS (endothelial NOS)] were detected over the control. Our results demonstrate for the first time that severe haemodilution-induced erythropoietic responses in kidneys were attenuated by a low-oxygen-affinity cell-free Hb and suggest that tissue-specific oxygen-sensing pathways can be influenced by allosterically modified Hbs. C1 [Manalo, Dominador J.; Buehler, Paul W.; Baek, Jin Hyen; Butt, Omer; D'Agnillo, Felice; Alayash, Abdu I.] US FDA, LBVB, Div Hematol, CBER,NIH, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, LBVB, Div Hematol, CBER,NIH, Bldg 29,Room 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM abdu.alayash@fda.hhs.gov FU FDA/CBER; Defense Advanced Research Projects Agency FX This work was supported in part by FDA/CBER critical path funding and by a giant from the Defense Advanced Research Projects Agency. The findings and conclusions in this paper have not been formally disseminated by the FDA and should not be construed to represent any agency determination or policy. NR 50 TC 13 Z9 13 U1 1 U2 4 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0264-6021 J9 BIOCHEM J JI Biochem. J. PD SEP 15 PY 2008 VL 414 BP 461 EP 469 DI 10.1042/BJ2G080313 PN 3 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 352QP UT WOS:000259512500015 PM 18498252 ER PT J AU Schmued, L Bowyer, J Cozart, M Heard, D Binienda, Z Paule, M AF Schmued, Larry Bowyer, John Cozart, Matthew Heard, David Binienda, Zbigniew Paule, Merle TI Introducing Black-Gold II, a highly soluble gold phosphate complex with several unique advantages for the histochemical localization of myelin SO BRAIN RESEARCH LA English DT Article DE Black-Gold II; myelin; methamphetamine; kainic acid; acrylamide; Fluoro-Jade C; sphingomyelin ID HIGH-RESOLUTION; DEGENERATION; SECTIONS AB A novel gold phosphate complex called Black-Cold II with improved myelin staining properties has been developed. It differs from its predecessor, Black-Gold, in that it is highly water soluble at room temperature. This unique physical property confers a number of advantages for the high resolution staining of myelinated fibers. Specifically, it 1) allows for easier solution preparation, eliminating the need for extended heating or sonicating; 2) produces a more uniform and consistent tracer concentration, resulting in more consistent staining and 3) can be used at a 50% higher concentration, resulting in faster and more intense staining without the need for subsequent treatment with gold chloride intensifiers. To characterize the stain, both normal rat brains as well as those exposed to the neurotoxins kainic acid or methamphetamine were examined. The study also incorporates the first application of such stains to examine peripheral nerves of control and acrylamide-exposed rats. Published by Elsevier B.V. C1 [Schmued, Larry; Bowyer, John; Heard, David; Binienda, Zbigniew; Paule, Merle] US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. [Cozart, Matthew] Univ Arkansas, Ctr Med Sci, Fayetteville, AR 72701 USA. RP Schmued, L (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM larry.schmued@fda.hhs.gov FU FDA protocol [E-7111.01] FX The study was supported by FDA protocol # E-7111.01. NR 11 TC 27 Z9 27 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD SEP 10 PY 2008 VL 1229 BP 210 EP 217 DI 10.1016/j.brainres.2008.06.129 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 353UR UT WOS:000259594500020 PM 18657520 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 Residue depletion of nitrofuran drugs and their tissue-bound metabolites in channel catfish (Ictalurus punctatus) after oral dosing SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE nitrofurans; channel catfish; LC/MS-MS; depletion; bound residues ID TANDEM MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; FURAZOLIDONE RESIDUES; PHARMACOKINETICS AB The depletion of the nitrofuran drugs furazolidone, nitrofurazone, furaltadone, and nitrofurantoin and their tissue-bound metabolites [3-amino-2-oxazolidinone (AOZ), semicarbazide (SC), 3-amino-5-morpholinomethyl-2-oxazolidinone (AMOZ), and 1-aminohydantoin (AH), respectively] were examined in the muscle of channel catfish following oral dosing (1 mg/kg body weight). Parent drugs were measurable in muscle within 2 h. Peak levels were found at 4 h for furazolidone (30.4 ng/g) and at 12 h for nitrofurazone, furaltadone, and nitrofurantoin (104, 35.2, and 9.8 ng/g respectively). Parent drugs were rapidly eliminated from muscle, and tissue concentrations fell below the limit of detection (1 ng/g) at 96 h. Peak levels of tissue-bound AMOZ and AOZ (46.8 and 33.7 ng/g respectively) were measured at 12 h, and of SC and AH (31.1 and 9.1 ng/g, respectively) at 24 In. Tissue-bound metabolites were measurable for up to 56 days postdose. These results support the use of tissue-bound metabolites as target analytes for monitoring nitrofuran drugs in channel catfish. 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. RP Chu, PS (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM pak.chu@fda.hhs.gov NR 23 TC 21 Z9 25 U1 1 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD SEP 10 PY 2008 VL 56 IS 17 BP 8030 EP 8034 DI 10.1021/jf801398p PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 344OU UT WOS:000258938000066 PM 18698789 ER PT J AU Jin, T Albillos, SM Chen, YW Kothary, MH Fu, TJ Zhang, YZ AF Jin, Tengchuan Albillos, Silvia M. Chen, Yu-Wei Kothary, Mahendra H. Fu, Tong-Jen Zhang, Yu-Zhu TI Purification and characterization of the 7S vicilin from Korean pine (Pinus koraiensis) SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Pinus koraiensis; pine nut; 7S globulin; vicilin-like seed storage protein; food allergen ID SEED STORAGE PROTEIN; CHEMICAL-COMPOSITION; ANGSTROM RESOLUTION; CRYSTAL-STRUCTURES; ALLERGEN; NUTS; ANAPHYLAXIS; PEA; CONVICILIN; CANAVALIN AB Pine nuts are economically important as a source of human food. They are also of medical importance because numerous pine nut allergy cases have been recently reported. However, little is known about the proteins in pine nuts. The purpose of this study was to purify and characterize pine nut storage proteins. Reported here is the first detailed purification protocol of the 7S vicilin-type globulin from Korean pine (Pinus koraiensis) by gel filtration, anion exchange, and hydrophobic interaction chromatography. Reducing SDS-PAGE analysis indicated that purified vicilin consists of four major bands, reminiscent of post-translational protease cleavage of storage proteins during protein body packing in other species. The N-terminal ends of vicilin peptides were sequenced by Edman degradation. Circular dichroism (CID) and differential scanning calorimetry (DSC) analyses revealed that pine nut vicilin is stable up to 80 degrees C and its folding-unfolding equilibrium monitored by intrinsic fluorescence can be interpreted in terms of a two-state model. C1 [Jin, Tengchuan; Chen, Yu-Wei; Zhang, Yu-Zhu] IIT, Dept Biol Chem & Phys Sci, Chicago, IL 60616 USA. [Albillos, Silvia M.] IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Kothary, Mahendra H.] US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. [Fu, Tong-Jen] US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Zhang, YZ (reprint author), IIT, Dept Biol Chem & Phys Sci, Chicago, IL 60616 USA. EM zhangy@iit.edu RI Zhang, Yuzhu/A-7109-2009; Jin, Tengchuan/B-5883-2014; Albillos, Silvia/D-1276-2016 OI Zhang, Yuzhu/0000-0001-7882-5692; Jin, Tengchuan/0000-0002-1395-188X; Albillos, Silvia/0000-0002-3273-0126 NR 44 TC 9 Z9 10 U1 3 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 SEP 10 PY 2008 VL 56 IS 17 BP 8159 EP 8165 DI 10.1021/jf801138q PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 344OU UT WOS:000258938000083 PM 18690685 ER PT J AU Ellison, CD Ennis, BJ Hamad, ML Lyon, RC AF Ellison, Christopher D. Ennis, Bryan J. Hamad, Mazen L. Lyon, Robbe C. TI Measuring the distribution of density and tabletting force in pharmaceutical tablets by chemical imaging SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE compaction; compression; powder technology; magnesium stearate; density; near-infrared imaging; force transmission; wall friction; shear cell ID NEAR-INFRARED SPECTROSCOPY; MECHANICAL-BEHAVIOR; SOLID FORMS; COMPACTION; COMPRESSION; FRICTION; PHYSICS; POWDER; SIZE AB In pharmaceutical processing, the lubricant magnesium stearate (MgS) can affect compaction efficiency based on blend time and amount of MgS used. Insufficient lubrication produces intra-tablet variations in density. Consistent tablet density profiles and uniform compaction force, as managed by proper lubrication, are important for predictable performance. The current work demonstrates the utility of near-infrared (NIR) chemical imaging in measuring density variations within compacts, and relates these variations to tabletting forces as controlled by frictional properties and quantity of MgS. Lactose monohydrate was blended with 0%, 0.25%, or 1.0% MgS for 30 s or 30 min. Compacts were prepared of each blend, with compaction forces monitored by load cells. Frictional properties were measured by automated shear cell. NIR chemical images were collected for each tablet, and the density at each image pixel was calculated. Density distribution within compacts was well perceived within the NIR images. Uniformity of intratablet density was strongly dependent upon friction between powder and die walls: tablets with no MgS or 0.25% MgS were less uniform than tablets with 1.0% MgS. In addition, absorbance variations along tablet reflective of corresponding density variation, agreed with force transmission within the tablet and edges, final tablet ejection force. Chemical imaging techniques can be used to non-destructively assess density profiles of tablets, and confirm prediction of friction alleviation and improvement in force distribution during tabletting. The density profiles were both qualitative, showing differences in density profiles between tablets of different blends, and quantitative, providing actual density and tabletting force information within a single tablet. This work demonstrates that near-infrared chemical imaging can be an effective tool in monitoring not only the physical quality of pharmaceutical tablets, but the corresponding die forces controlling tabletting and final ejection. (c) Published by Elsevier B.V. C1 [Ellison, Christopher D.; Hamad, Mazen L.; Lyon, Robbe C.] US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. [Ennis, Bryan J.] E&G Associates, Nashville, TN 37215 USA. RP Ellison, CD (reprint author), US FDA, Div Prod Qual Res, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. EM christophe.ellison@fda.hhs.gov; bryan.ennis@powdernotes.com NR 30 TC 39 Z9 39 U1 1 U2 16 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD SEP 10 PY 2008 VL 48 IS 1 BP 1 EP 7 DI 10.1016/j.jpba.2008.04.020 PG 7 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 350GD UT WOS:000259339800001 PM 18539424 ER PT J AU Mancuso, JD Krauss, MR Audet, S Beeler, JA AF Mancuso, James D. Krauss, Margot R. Audet, Susette Beeler, Judy A. TI ELISA underestimates measles antibody seroprevalence in US military recruits SO VACCINE LA English DT Letter DE measles epidemiology; seroepidemiology; military personnel; immunizations ID MUMPS AB The prevalence of antibodies to measles, mumps, and rubella in US military recruits is of importance to public health leaders, We performed ELISA testing using a commercially available product on samples from 537 recruits obtained in 1998, of which 437 were positive (81%). We then performed a validation study in a subsample of the population using plaque reduction neutralization (PRN) to assess misclassification error. This resulted in a corrected estimate of the prevalence of immunity to measles of 96% (95% CI: 92-100%). The military vaccinates a percentage of recruits who are likely to be immune if more sensitive testing, Such as PRN, was used. Published by Elsevier Ltd. C1 [Mancuso, James D.] Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. [Krauss, Margot R.] WESTAT Corp, Rockville, MD 20850 USA. [Audet, Susette; Beeler, Judy A.] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Rockville, MD 20857 USA. RP Mancuso, JD (reprint author), Uniformed Serv Univ Hlth Sci, Dept Prevent Med & Biometr, Bethesda, MD 20814 USA. EM james.mancuso@us.army.mil NR 5 TC 8 Z9 8 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD SEP 8 PY 2008 VL 26 IS 38 BP 4877 EP 4878 DI 10.1016/j.vaccine.2008.06.028 PG 2 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 356BC UT WOS:000259752700001 PM 18586062 ER PT J AU Haidar, SH Makhlouf, F Schuirmann, DJ Hyslop, T Davit, B Conner, D Yu, LX AF Haidar, Sam H. Makhlouf, Fairouz Schuirmann, Donald J. Hyslop, Terry Davit, Barbara Conner, Dale Yu, Lawrence X. TI Evaluation of a Scaling Approach for the Bioequivalence of Highly Variable Drugs SO AAPS JOURNAL LA English DT Article DE bioequivalence; highly variable drugs; scaled bioequivalence; simulations ID SCALED AVERAGE BIOEQUIVALENCE; INDIVIDUAL BIOEQUIVALENCE; C-MAX; PRODUCTS; LIMITS AB Various approaches for evaluating the bioequivalence (BE) of highly variable drugs (CV <30%) have been debated for many years. More recently, the FDA conducted research to evaluate one such approach: scaled average BE. A main objective of this study was to determine the impact of scaled average BE on study power, and compare it to the method commonly applied currently (average BE). Three-sequence, three period, two treatment partially replicated cross-over BE studies were simulated in S-Plus. Average BE criteria, using 80-125% limits on the 90% confidence intervals for C (max) and AUC geometric mean ratios, as well as scaled average BE were applied to the results. The percent of studies passing BE was determined under different conditions. Variables tested included within subject variability, point estimate constraint, and different values for sigma (w0), which is a constant set by the regulatory agency. The simulation results demonstrated higher study power with scaled average BE, compared to average BE, as within subject variability increased. At 60% CV, study power was more than 90% for scaled average BE, compared with about 22% for average BE. A sigma (w0) value of 0.25 appears to work best. The results of this research project suggest that scaled average BE, using a partial replicate design, is a good approach for the evaluation of BE of highly variable drugs. C1 [Haidar, Sam H.; Hyslop, Terry; Davit, Barbara; Conner, Dale; Yu, Lawrence X.] US FDA, CDER, Off Gener Drugs, Rockville, MD 20855 USA. [Makhlouf, Fairouz] US FDA, CDER, Off Biostat, Silver Spring, MD USA. [Schuirmann, Donald J.] Thomas Jefferson Univ, Div Biostat, Philadelphia, PA 19107 USA. RP Haidar, SH (reprint author), US FDA, CDER, Off Gener Drugs, 7519 Standish Pl,HFD-600, Rockville, MD 20855 USA. EM Sam.haidar@fda.hhs.gov NR 21 TC 44 Z9 48 U1 2 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J PD SEP PY 2008 VL 10 IS 3 BP 450 EP 454 DI 10.1208/s12248-008-9053-4 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 370OC UT WOS:000260770500004 PM 18726698 ER PT J AU Haidar, SH Makhlouf, F Schuirmann, DJ Hyslop, T Davit, B Conner, D Yu, LX AF Haidar, Sam H. Makhlouf, Fairouz Schuirmann, Donald J. Hyslop, Terry Davit, Barbara Conner, Dale Yu, Lawrence X. TI Evaluation of a Scaling Approach for the Bioequivalence of Highly Variable Drugs SO AAPS JOURNAL LA English DT Correction C1 [Haidar, Sam H.; Hyslop, Terry; Davit, Barbara; Conner, Dale; Yu, Lawrence X.] US FDA, CDER, Off Gener Drugs, Rockville, MD 20855 USA. [Schuirmann, Donald J.] Thomas Jefferson Univ, Div Biostat, Philadelphia, PA 19107 USA. [Makhlouf, Fairouz] US FDA, CDER, Off Biostat, Silver Spring, MD USA. RP Haidar, SH (reprint author), US FDA, CDER, Off Gener Drugs, 7519 Standish Pl,HFD-600, Rockville, MD 20855 USA. EM Sam.haidar@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1550-7416 J9 AAPS J PD SEP PY 2008 VL 10 IS 3 BP 480 EP 480 DI 10.1208/s12248-008-9059-y PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 370OC UT WOS:000260770500007 ER PT J AU Reimschuessel, R Gieseker, CM Miller, RA Ward, J Boehmer, J Rummel, N Heller, DN Nochetto, C de Alwis, GKH Bataller, N Andersen, WC Turnipseed, SB Karbiwnyk, CM Satzger, D Crowe, JB Wilber, NR Reinhard, MK Roberts, JF Witkowski, MR AF Reimschuessel, Renate Gieseker, Charles M. Miller, Ron A. Ward, Jeffrey Boehmer, Jamie Rummel, Nathan Heller, David N. Nochetto, Cristina de Alwis, G. K. Hemakanthi Bataller, Neal Andersen, Wendy C. Turnipseed, Sherri B. Karbiwnyk, Christine M. Satzger, Duane Crowe, John B. Wilber, Nancy R. Reinhard, Mary K. Roberts, John F. Witkowski, Mark R. TI Evaluation of the renal effects of experimental feeding of melamine and cyanuric acid to fish and pigs SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID TUMOR LYSIS SYNDROME; URIC-ACID; FAILURE; NEPHROPATHY; CARCINOGENICITY; DERIVATIVES; EVOLUTION; CATS; RATS AB Objective-To determine whether renal crystals can be experimentally induced in animals fed melamine or the related triazine compound cyanuric acid, separately or in combination, and to compare experimentally induced crystals with those from a cat with triazine-related renal failure. Animals-75 fish (21 tilapia, 24 rainbow trout, 15 channel catfish, and 15 Atlantic salmon), 4 pigs, and 1 cat that was euthanatized because of renal failure. Procedures-Fish and pigs were fed a target dosage of melamine (400 mg/kg), cyanuric acid (400 mg/kg), or melamine and cyanuric acid (400 mg of each compound/kg) daily for 3 days and were euthanatized 1, 3, 6, 10, or 14 days after administration ceased. Fresh, frozen, and formalin-fixed kidneys were examined for crystals. Edible tissues were collected for residue analysis. Crystals were examined for composition via Raman spectroscopy and hydrophilic-interaction liquid chromatography-tandem mass spectrometry. Results-All animals fed the combination of melamine and cyanuric acid developed gold-brown renal crystals arranged in radial spheres (spherulites), similar to those detected in the cat. Spectral analyses of crystals from the cat, pigs, and fish were consistent with melamine-cyanurate complex crystals. Melamine and cyanuric acid residues were identified in edible tissues of fish. Conclusions and Clinical Relevance-Although melamine and cyanuric acid appeared to have low toxicity when administered separately, they induced extensive renal crystal formation when administered together. The subsequent renal failure may be similar to acute uric acid nephropathy in humans, in which crystal spherulites obstruct renal tubules. C1 [Reimschuessel, Renate; Gieseker, Charles M.; Ward, Jeffrey; Boehmer, Jamie; Rummel, Nathan; Heller, David N.; Nochetto, Cristina; de Alwis, G. K. Hemakanthi] US FDA, Ctr Vet Med, Laurel, MD 20708 USA. [Andersen, Wendy C.; Turnipseed, Sherri B.; Karbiwnyk, Christine M.] US FDA, Anim Drugs Res Ctr, Denver Fed Ctr, Denver, CO 80225 USA. [Satzger, Duane; Crowe, John B.; Witkowski, Mark R.] US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. [Wilber, Nancy R.] Acad Anim Hosp, Ft Lauderdale, FL 33308 USA. [Reinhard, Mary K.; Roberts, John F.] Univ Florida, Coll Vet Med, Dept Infect Dis & Pathol, Gainesville, FL 32611 USA. RP Reimschuessel, R (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 54 TC 121 Z9 161 U1 3 U2 25 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD SEP PY 2008 VL 69 IS 9 BP 1217 EP 1228 DI 10.2460/ajvr.69.9.1217 PG 12 WC Veterinary Sciences SC Veterinary Sciences GA 342PF UT WOS:000258795300018 PM 18764697 ER PT J AU Volokhov, DV Kong, H George, J Anderson, C Chizhikov, VE AF Volokhov, Dmitriy V. Kong, Hyesuk George, Joseph Anderson, Christine Chizhikov, Vladimir E. TI Biological enrichment of mycoplasma agents by cocultivation with permissive cell cultures SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; LIVE-VIRUS-VACCINES; MINK LUNG-CELLS; DIFFERENT STRAINS; GROWTH; HYORHINIS; PCR; CONTAMINATION; PNEUMONIAE; GENITALIUM AB In this study, we describe our results on the evaluation of the ability of different permissive mammalian cell lines to support the biological enrichment of mycoplasma species known to be bacterial contaminants of cell substrates. The study showed that this approach is able to significantly improve the efficiency of mycoplasma detection based on nucleic acid testing or biochemical technologies (e. g., MycoAlert mycoplasma detection). Of 10 different cell lines (Vero, MDBK, HEK-293, Hep-G2, CV-1, EBTr, WI-38, R9ab, MDCK, and High Five) used in the study, only MDCK cell culture was found to support the efficient growth of all the tested mycoplasmas (Mycoplasma arginini, M. bovis, M. fermentans, M. gallinaceum, M. gallisepticum, M. synoviae, M. hominis, M. hyorhinis, M. orale, M. salivarium, and Acholeplasma laidlawii) known to be most frequently associated with contamination of cell substrates and cell lines in research laboratories or manufacturing facilities. The infection of MDCK cells with serial dilutions of each mycoplasma species demonstrated that these common cell line contaminants can be detected reliably after 7-day enrichment in MDCK cell culture at contamination levels of 0.05 to 0.25 CFU/ml. The High Five insect cell line was also found to be able to support the efficient growth of most mycoplasma species tested, except for M. hyorhinis strain DBS1050. However, mycoplasma growth in insect cell culture was demonstrated to be temperature dependent, and the most efficient growth was observed when the incubation temperature was increased from 28 degrees C to between 35 and 37 degrees C. We believe that this type of mycoplasma enrichment is one of the most promising approaches for improving the purity and safety testing of cell substrates and other cell-derived biologics and pharmaceuticals. C1 [Volokhov, Dmitriy V.; Kong, Hyesuk; George, Joseph; Anderson, Christine; Chizhikov, Vladimir E.] US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Lab Methods Dev, Rockville, MD 20852 USA. RP Volokhov, DV (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Div Viral Prod,Lab Methods Dev, HFM 470,1401 Rockville Pike, Rockville, MD 20852 USA. EM dmitriy.volokhov@fda.hhs.gov NR 68 TC 12 Z9 14 U1 0 U2 4 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 2008 VL 74 IS 17 BP 5383 EP 5391 DI 10.1128/AEM.00720-08 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 343CB UT WOS:000258829100014 PM 18606798 ER PT J AU Zheng, J Cui, SH Teel, LD Zhao, SH Singh, R O'Brien, AD Meng, JH AF Zheng, Jie Cui, Shenghui Teel, Louise D. Zhao, Shaohua Singh, Ruby O'Brien, Alison D. Meng, Jianghong TI Identification and characterization of Shiga toxin type 2 variants in Escherichia coli isolates from animals, food, and humans SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; LENGTH-POLYMORPHISM ANALYSIS; B-SUBUNIT GENES; INTESTINAL MUCUS; 2 COPIES; STRAINS; OUTBREAK; O157-H7; CYTOTOXICITY; PROFILES AB There is considerable heterogeneity among the Shiga toxin type 2 (Stx2) toxins elaborated by Shiga toxin-producing Escherichia coli (STEC). One such Stx2 variant, the Stx2d mucus-activatable toxin (Stx2dact), is rendered more toxic by the action of elastase present in intestinal mucus, which cleaves the last two amino acids of the A2 portion of the toxin A subunit. We screened 153 STEC isolates from food, animals, and humans for the gene encoding Stx2dact by using a novel one-step PCR procedure. This method targeted the region of stx(2dact) that encodes the elastase recognition site. The presence of stx(2dact) was confirmed by DNA sequencing of the complete toxin genes. Seven STEC isolates from cows (four isolates), meat (two isolates), and a human (one isolate) that carried the putative stx(2dact) gene were identified; all were eae negative, and none was the O157:H7 serotype. Three of the isolates (CVM9322, CVM9557, and CVM9584) also carried stx(1), two (P1332 and P1334) carried stx(1) and stx(2c), and one (CL-15) carried stx(2c). One isolate, P1130, harbored only stx(2dact). The Vero cell cytotoxicities of supernatants from P1130 and stx(1) deletion mutants of CVM9322, CVM9557, and CVM9584 were increased 13- to 30-fold after treatment with porcine elastase. Thus, Stx2dact-producing strains, as detected by our one-step PCR method, can be isolated not only from humans, as previously documented, but also from food and animals. The latter finding has important public health implications based on a recent report from Europe of a link between disease severity and infection with STEC isolates that produce Stx2dact. C1 [Zheng, Jie; Cui, Shenghui; Meng, Jianghong] Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. [Teel, Louise D.; O'Brien, Alison D.] Uniformed Serv Univ Hlth Sci, Dept Microbiol & Immunol, Bethesda, MD 20814 USA. [Zhao, Shaohua; Singh, Ruby] Off Res Food & Drug Adm, Ctr Vet Med, Laurel, MD 20708 USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 0112 Skinner Bldg, College Pk, MD 20742 USA. EM jmeng@umd.edu OI O'Brien, Alison/0000-0002-1315-3204 FU Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland; U. S. Food and Drug Administration; National Institutes of Health National Institute for Allergy and Infectious Diseases [AI20148-25] FX This study was made possible by grants from the Joint Institute for Food Safety and Applied Nutrition (JIFSAN) of the University of Maryland and the U. S. Food and Drug Administration. We also acknowledge funding of the O'Brien laboratory at USUHS through National Institutes of Health National Institute for Allergy and Infectious Diseases grant AI20148-25. NR 32 TC 35 Z9 36 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 SEP PY 2008 VL 74 IS 18 BP 5645 EP 5652 DI 10.1128/AEM.00503-08 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 345SR UT WOS:000259017400007 PM 18658282 ER PT J AU Mongan, A Higgins, MA Pine, S Afshari, CA Hamadeh, HK AF Mongan, Ann Higgins, Marnie A. Pine, Scott Afshari, Cynthia A. Hamadeh, Hisham K. TI Assessment of repeated microarray experiments using mixed tissue RNA reference samples SO BIOTECHNIQUES LA English DT Article ID GENE-EXPRESSION; BIOLOGICAL-SYSTEMS; REPRODUCIBILITY; DESIGN; TECHNOLOGIES; PLATFORMS; MIAME; CEBS AB Genome-scale gene expression technologies are increasingly being applied for biological research as a whole and toxicological screening in particular. In order to monitor data quality and process drift, we adopted the use of two rat-tissue mixtures (brain, liver, kidney, and testis) previously introduced as RNA reference samples. These samples were processed every time a microarray experiment was hybridized, thereby verifying the comparability of the resulting expression data for cross-study comparison. This study presents the analysis of 21 technical replicates of these two mixed-tissue samples using affymetrix RAE230_2 GeneChip over a period of 12 months. The results show that detection sensitivity, measured by the number of present and absent sequences, is robust, and data correlation, indicated by scatter plots, varies little over time. Receiver operating characteristics (ROC) curves show the sensitivity and specificity of the current measurements are consistent with arrays previously classified as well performing. Overall, this paper shows that the inclusion of standard samples during microarray labeling and hybridization experiments is useful to benchmark the performance of microarray experiments over time and allows discovery of any process drift that, if it occurs, may confound the comparison of these datasets. C1 [Mongan, Ann] Amgen Inc, Dept Comparat Biol & Safety Sci, San Francisco, CA 94080 USA. [Higgins, Marnie A.; Afshari, Cynthia A.; Hamadeh, Hisham K.] Amgen Inc, Dept Comparat Biol & Safety Sci, Thousand Oaks, CA 91320 USA. [Pine, Scott] US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD USA. RP Mongan, A (reprint author), Amgen Inc, Dept Comparat Biol & Safety Sci, 1120 Vet Blvd,Mail Stop ASF1-2, San Francisco, CA 94080 USA. EM thuyv@amgen.com NR 17 TC 2 Z9 2 U1 1 U2 2 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD SEP PY 2008 VL 45 IS 3 BP 283 EP + DI 10.2144/000112914 PG 7 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 411GU UT WOS:000263638100019 ER PT J AU Kweder, SL AF Kweder, Sandra L. TI Drugs and biologics in pregnancy and breastfeeding: FDA in the 21(st) century SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Editorial Material C1 US PHS, Off New Drugs, Ctr Drug Evaluat & Res, US FDA, Rockville, MD 20852 USA. RP Kweder, SL (reprint author), US PHS, Off New Drugs, Ctr Drug Evaluat & Res, US FDA, Rockville, MD 20852 USA. NR 0 TC 12 Z9 14 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1542-0752 EI 1542-0760 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD SEP PY 2008 VL 82 IS 9 BP 605 EP 609 DI 10.1002/bdra.20500 PG 5 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 355MS UT WOS:000259713600001 PM 18704917 ER PT J AU Ananyeva, NM Makogonenko, YM Sarafanov, AG Pechik, IV Gorlatova, N Radtke, KP Shima, M Saenko, EL AF Ananyeva, Natalya M. Makogonenko, Yevgen M. Sarafanov, Andrey G. Pechik, Igor V. Gorlatova, Natalya Radtke, Klaus P. Shima, Midori Saenko, Evgueni L. TI Interaction of coagulation factor VIII with members of the low-density lipoprotein receptor family follows common mechanism and involves consensus residues within the A2 binding site 484-509 SO BLOOD COAGULATION & FIBRINOLYSIS LA English DT Article DE coagulation; factor VIII; hemophilia; low-density lipoprotein receptor; low-density lipoprotein receptor-related protein; megalin; very low-density lipoprotein receptor; von Willebrand factor ID VON-WILLEBRAND-FACTOR; LDL-RECEPTOR; ALPHA-2-MACROGLOBULIN RECEPTOR; BINDING-SITE; LIGHT-CHAIN; LIGAND-BINDING; HUMAN TISSUES; RAP COMPLEX; A2 SUBUNIT; FACTOR IXA AB Coagulation factor VIII interacts with several members of the low-density lipoprotein receptor family including low-density lipoprotein receptor-related protein, low-density lipoprotein receptor, and very low-density lipoprotein receptor. The present study was aimed to compare the mechanisms of factor VIII interaction with low-density lipoprotein receptor-related protein, megalin, low-density lipoprotein receptor, and very low-density lipoprotein receptor in order to reveal a general mode of these interactions. Binding of plasma-derived factor VIII and its fragments to recombinant soluble ligand-binding domain of low-density lipoprotein receptor (sLDLR1-7) and purified megalin was studied in solid phase and surface plasmon resonance assays. Full-length factor VIII and its light chain bound to the receptors with similar affinities (K(D) = 260 +/- 9 and 156 +/- 4 nmol/l, respectively, for megalin and KD = 210 3 and 174 13 nmol/l, respectively, for sLDLR1-7). Von Willebrand factor inhibited factor VIII binding to both receptors. In contrast to the light chain, exposure of the high-affinity receptor-binding site within the heavy chain K(D) = 22 +/- 4 nmol/l for megalin and 17 +/- 3 nmol/l for sLDLR1-7) required proteolytic cleavage by thrombin. This site was mapped to the A2 domain residues 484-509, based on the inhibitory effects of anti-A2 monoclonal antibody 413, and is shared by all four receptors. Using a panel of A2 mutants, we identified key amino acid residues - positively charged K466, R471, R489 and R490, and hydrophilic residues Y487 and S488 - which form the frame of this 'consensus' binding site. We conclude that interaction of factor VIII with the members of the low-density lipoprotein receptor family follows the general mode, requires dissociation of factor VIII from von Willebrand factor, and is activation sensitive. C1 [Ananyeva, Natalya M.; Makogonenko, Yevgen M.; Sarafanov, Andrey G.; Saenko, Evgueni L.] Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, Baltimore, MD 21201 USA. [Ananyeva, Natalya M.; Makogonenko, Yevgen M.; Sarafanov, Andrey G.; Saenko, Evgueni L.] Univ Maryland, Sch Med, Dept Biochem & Mol Biol, Baltimore, MD 21201 USA. [Sarafanov, Andrey G.] US FDA, Ctr Biol Evaluat & Res, Kensington, MD USA. [Pechik, Igor V.; Gorlatova, Natalya] Univ Maryland, Inst Biotechnol, Ctr Adv Res Biotechnol, Rockville, MD USA. [Radtke, Klaus P.] Bayer HealthCare LLC, Berkeley, CA USA. [Shima, Midori] Nara Med Univ, Dept Pediat, Nara, Japan. RP Ananyeva, NM (reprint author), Univ Maryland, Sch Med, Ctr Vasc & Inflammatory Dis, 800 W Baltimore St, Baltimore, MD 21201 USA. EM NAnanyeva@som.umaryland.edu FU National Institutes of Health [RO1 HL72929] FX This work was supported by Grant RO1 HL72929 (E.S.) awarded by National Institutes of Health. We express our gratitude to Dr Strickland (Center for Vascular & Inflammatory Diseases and Dept. Surgery & Physiology, University of Maryland School of Medicine) for consulting on preparation of and experimentation with LRP, megalin, and sVLDLR. NR 58 TC 9 Z9 9 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0957-5235 J9 BLOOD COAGUL FIBRIN JI Blood Coagul. Fibrinolysis PD SEP PY 2008 VL 19 IS 6 BP 543 EP 555 PG 13 WC Hematology SC Hematology GA 348KL UT WOS:000259209300012 PM 18685438 ER PT J AU Stamatas, GN Zmudzka, BZ Kollias, N Beer, JZ AF Stamatas, G. N. Zmudzka, B. Z. Kollias, N. Beer, J. Z. TI In vivo measurement of skin erythema and pigmentation: new means of implementation of diffuse reflectance spectroscopy with a commercial instrument SO BRITISH JOURNAL OF DERMATOLOGY LA English DT Article DE erythema; pigmentation; spectroscopy; ultraviolet ID CUTANEOUS ERYTHEMA; RADIATION; EXPOSURE; INVIVO; OPTICS AB Background Various physical, chemical and biological insults, including exposure to ultraviolet (UV) radiation, cause erythema and change in pigmentation in human skin. These reactions provide an important measure of the cutaneous response to the insult. Objectives To present a new implementation of a method for objective in vivo measurement of erythema and pigmentation. Methods The method is based on acquisition of reflectance spectra in the visible range using a commercially available spectrophotometer. The probe of this instrument incorporates an integrating sphere that captures the light remitted from the skin in a wide range of angles. We corrected the acquired reflectance spectra for the contribution of specular reflections by an amount given by the Fresnel equation and verified this correction experimentally. This correction is particularly important when measurements are performed on heavily pigmented skin. The corrected reflectance spectra are then transformed into absorbance spectra. To analyse these spectra, we developed an algorithm which can be used to calculate apparent concentrations of oxyhaemoglobin, deoxyhaemoglobin and melanin. This method was tested in clinical studies of skin reactions induced by exposure to UV radiation. These experiments involved three groups of subjects with progressively darker complexion (constitutive pigmentation). Each group consisted of 10 subjects. Erythema was measured 1 day after UV exposure, and pigmentation (melanin content) 1 week later. Results Distinct apparent absorbance spectra were obtained for dark, intermediate and fair skin. There was good agreement between reconstructed spectra and experimental data at relevant wavelengths. Difference absorption spectra were able to show the dose dependence of UV-induced responses, and erythema and pigmentation values obtained by the spectroscopic method showed good correlation with those derived by subjective visual grading. Conclusions The results demonstrate that the presented methodology provides an objective noninvasive way of measuring UV-induced reactions independently of the level of constitutive pigmentation. C1 [Stamatas, G. N.] Johnson & Johnson Consumer France SAS, Skin Care Res Inst, F-92787 Issy Les Moulineaux, France. [Zmudzka, B. Z.; Beer, J. Z.] US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. [Kollias, N.] Johnson & Johnson Consumer Co, CPPW, Methods & Models Dev, Skillman, NJ USA. RP Stamatas, GN (reprint author), Johnson & Johnson Consumer France SAS, Skin Care Res Inst, F-92787 Issy Les Moulineaux, France. EM gstamat@cpcus.jnj.com NR 25 TC 51 Z9 51 U1 0 U2 7 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0007-0963 J9 BRIT J DERMATOL JI Br. J. Dermatol. PD SEP PY 2008 VL 159 IS 3 BP 683 EP 690 DI 10.1111/j.1365-2133.2008.08642.x PG 8 WC Dermatology SC Dermatology GA 337YF UT WOS:000258470700022 PM 18510669 ER PT J AU Nie, L Chu, HT Korostyshevskiy, VR AF Nie, Lei Chu, Haitao Korostyshevskiy, Valeriy R. TI Bias reduction for nonparametric correlation coefficients under the bivariate normal copula assumption with known detection limits SO CANADIAN JOURNAL OF STATISTICS-REVUE CANADIENNE DE STATISTIQUE LA English DT Article DE Bias reduction; bivariate Gaussian copula mode; bivariate normal distribution; detection limit; Kendall's tau; left censoring; Pearson's correlation coefficient; Spearman's rho ID VIRAL LOAD; MODEL AB The authors derive the asymptotic mean and bias of Kendall's tau and Spearman's rho in the presence of left censoring in the bivariate Gaussian copula model. They show that tie corrections for left-censoring brings the value of these coefficients closer to zero. They also present a bias reduction method and illustrate it through two applications. C1 [Nie, Lei] US FDA, Div Biometr 4, CDER, OTS,Off Biometr, Spring, MD 20993 USA. [Chu, Haitao] Univ N Carolina, Lineberger Comprehens Canc Ctr, Chapel Hill, NC 27599 USA. [Chu, Haitao] Univ N Carolina, Dept Biostat, Chapel Hill, NC 27599 USA. [Korostyshevskiy, Valeriy R.] Georgetown Univ, Dept Biostat Bioinformat & Biomath, Washington, DC 20057 USA. RP Nie, L (reprint author), US FDA, Div Biometr 4, CDER, OTS,Off Biometr, Spring, MD 20993 USA. EM Lei.Nie@fda.hhs.gov; chuh@email.unc.edu; vrk@georgetown.edu RI Chu, Haitao /J-7576-2012; OI Chu, Haitao/0000-0003-0932-598X FU Lineberger Cancer Center; U. S. National Cancer Institute; Center of Innovative Clinical Trials in the University of North Carolina at Chapel Hill FX The authors thank the Editor and an Associate Editor for their constructive comments and suggestions in earlier versions of the paper. These comments and suggestions have greatly improved the quality and broadened the scope of the paper. The authors are grateful to Drs. Nancy Pedian and Kate Buchacz at the University of California, San Francisco, for providing the data from the cross-sectional study of HIV-infected men in the San Francisco Bay Area. Dr. Chu was supported in part by grants from the Lineberger Cancer Center, from the U. S. National Cancer Institute, and from the Center of Innovative Clinical Trials in the University of North Carolina at Chapel Hill. The authors thank Ellen McLaughlin, from the grant preparation unit, Lombardi Comprehensive Cancer Center, for her technical support. This work was done while Dr. Nie was working at Georgetown University. Views expressed in this paper are the authors' professional opinions and do not necessarily represent the official positions of the U.S. Food and Drug Administration. NR 24 TC 2 Z9 2 U1 0 U2 6 PU CANADIAN JOURNAL STATISTICS PI OTTAWA PA 675 DENBURY AVENUE, OTTAWA, ON K2A 2P2, CANADA SN 0319-5724 J9 CAN J STAT JI Can. J. Stat.-Rev. Can. Stat. PD SEP PY 2008 VL 36 IS 3 BP 427 EP 442 PG 16 WC Statistics & Probability SC Mathematics GA 360VT UT WOS:000260087000007 ER PT J AU Keller, JE AF Keller, James E. TI Characterization of new formalin-detoxified botulinum neurotoxin toxoids SO CLINICAL AND VACCINE IMMUNOLOGY LA English DT Article ID CLOSTRIDIUM-BOTULINUM; INTERNATIONAL STANDARDS; IMMUNOLOGICAL RESPONSE; IMMUNE GLOBULIN; SEROTYPE-A; B TOXINS; VACCINE; FORMALDEHYDE; ANTITOXINS; TOXICITY AB Antigenicities of several formalin-detoxified botulinum neurotoxin preparations were measured by inhibition and sandwich enzyme-linked immunosorbent assay (ELISA), and immunogenicity was studied in mice. The toxoids were derived primarily from the serotype A 150-kDa neurotoxin protein, while one toxoid was derived from the naturally occurring 900-kDa toxin-hemagglutinin complex. Antigenicity was severely compromised in two commercially available toxoids. A variety of new toxoids were synthesized in-house by optimizing formaldehyde reaction conditions. Three of the resulting toxoids were found to be antigenically identical to the native toxin, as measured by inhibition ELISA, in spite of showing a reduction of toxicity by more than 100,000-fold. Sandwich ELISAs indicated that the in-house toxoids were two-to threefold less antigenic than the neurotoxin compared to commercial toxoids, which were about 100-fold less antigenic. Mice were immunized twice, on day 0 and day 14. By day 28, relatively high toxin-specific immunoglobulin G (IgG) titers were detected in animals that had received any of the in-house toxoids, with greater than 99% being IgG1 and the remainder being IgG2. These immunized mice remained asymptomatic after being challenged with 50 to 1,000,000 50% lethal dose (LD50) units of the 900-kDa neurotoxin. In contrast, animals immunized with several different batches of commercially available toxoids did not develop measurable toxin-specific antibody titers. However, these mice survived neurotoxin challenges with 2 LD50 units but died when challenged with 6 LD50 units. Neutralizing titers measured from pools of sera generated with the in-house toxoid preparations ranged from 2.5 to 5 U/ml. In terms of predicting immunogenicity, inhibition ELISAs comparing each formalin toxoid to the parent toxin provided good insight for screening the new toxoids as well as for estimating their relative in vivo potencies. Inhibition ELISA data indicate that those toxoids that most closely resemble the native toxin are highly immunogenic and protective. The superior quality of these new toxoids makes them useful tools for continued use in ELISA development and for antitoxin production. C1 US FDA, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Keller, JE (reprint author), US FDA, Lab Resp & Special Pathogens, Div Bacterial Parasit & Allergen Prod, Off Vaccines Res & Review,Ctr Biol Evaluat & Res, HFM-434,Bldg 29,Room 122,29 Lincoln Dr,NIH Campus, Bethesda, MD 20892 USA. EM james.keller@fda.hhs.gov FU FDA/CBER; FDA/CBER-NIAID/NIH [Y1-AI-6153-01, 224-06-1322] FX Much of the ELISA analysis was performed by Pravina Mattoo (FDA/CBER) and Adaku Iwueze. Dan Li (FDA/CBER) assisted with determining mouse neutralization titers. Christine Anderson (FDA/CBER) provided the standard equine antitoxin, and Juan Arciniega (FDA/CBER) provided valuable discussion and advice during the writing of this paper. D. Sesardic (NIBSC, United Kingdom) and R. Jones (NIBSC, United Kingdom) provided valued assistance to confirm some of the neutralizing titer data. Michael Goodnough and Carl Malizio (Metabiologics, Inc.) provided very helpful information on the preparation of the commercial toxoid and subsequently performed confirmatory testing by immunizing mice with botulinum toxoids and challenging with botulinum toxin.; This work was supported by intramural FDA/CBER funding and by FDA/CBER-NIAID/NIH interagency agreement no. Y1-AI-6153-01/no.224-06-1322.; The findings and conclusions in this article have not been formally disseminated by the Food and Drug Administration and should not be construed to represent any agency determination or policy. NR 36 TC 17 Z9 17 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1556-6811 J9 CLIN VACCINE IMMUNOL JI Clin. Vaccine Immunol. PD SEP PY 2008 VL 15 IS 9 BP 1374 EP 1379 DI 10.1128/CVI.00117-08 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 344UF UT WOS:000258952100010 PM 18667637 ER EF