FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Clark, SB Turnipseed, SB Madson, MR Hurlbut, JA Kuck, LR Sofos, JN AF Clark, SB Turnipseed, SB Madson, MR Hurlbut, JA Kuck, LR Sofos, JN TI Confirmation of sulfamethazine, sulfathiazole, and sulfadimethoxine residues in condensed milk and soft-cheese products by liquid chromatography/tandem mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MULTIPLE SULFONAMIDE RESIDUES; BOVINE-MILK; ANTIBIOTICS; HONEY; ALBENDAZOLE; EGGS AB A liquid chromatography/tandem mass spectrometry method (LC/MS/MS) is described for the simultaneous detection of 3 sulfonamide drug residues at 1.25 ppb in condensed milk and soft-cheese products. The 3 sulfonamide drugs of interest are sulfathiazole (STZ), sulfamethazine (SMZ), and sulfadimethoxine (SDM). The method includes extraction of the product with phosphate buffer, centrifugation of the diluted product, and application of a portion of the extract onto a polymeric solid-phase extraction cartridge. The cartridge is washed with water, and the sulfonamides are eluted with methanol. After evaporation, the residue is dissolved in 0.1% formic acid solution, and the solution is filtered before analysis by LC/MS/MS. The LC/MS/MS program involved a series of time-scheduled selected-reaction monitoring transitions. The transitions of MH+ to the common product ions at m/z 156,108, and 92 were monitored for each residue. In addition, SMZ and SDM had a fourth significant and unique product ion transition that could be measured. Validation was performed with control and fortified-control condensed bovine milk with 2.5, 5, and 10 ppb sulfonamides. This method was applied to imported flavored and unflavored condensed milk and cream cheese bars. The presence of STZ and SMZ residues was confirmed in 3 out of 6 products. C1 US FDA, Denver, CO 80225 USA. Western Washington Univ, Dept Chem, Bellingham, WA 98225 USA. Univ Colorado, Boulder, CO 80309 USA. Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. RP Turnipseed, SB (reprint author), US FDA, POB 25087, Denver, CO 80225 USA. EM sherri.turnipseed@fda.hhs.gov NR 24 TC 21 Z9 22 U1 1 U2 10 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2005 VL 88 IS 3 BP 736 EP 743 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 932BN UT WOS:000229529300016 PM 16001847 ER PT J AU Himata, K Warner, C Currie, D Graves, Q Diachenko, G AF Himata, K Warner, C Currie, D Graves, Q Diachenko, G TI The use of electrodialysis to prepare aqueous bread extracts for bromate determination by chemiluminescence SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FLOW REACTOR DETECTION; POTASSIUM BROMATE; LIQUID-CHROMATOGRAPHY; F344 RATS AB A cleanup procedure based on electrodialysis is described for the preparation of aqueous bread extracts for bromate determination by chemiluminescence. The technique utilizes electrophoresis with 3 chambers separated by semipermeable membranes. The relative merits of reverse osmosis (RO), ultrafiltration, and nanofiltration membranes with various molecular weight cutoffs were evaluated. The best results were obtained with an RO membrane manufactured from thin-film (composite) polysulfone as support for polyamide. A 0.14M sodium sulfate solution in the center or collection chamber provides optimum conductivity. Aqueous hydroxylamine sulfate (30mM) was selected for the anode compartment as a reductant for the anode oxidation products. The constant current mode at 150 mA with a potential of ca 100 volts was used. After electrophoretic separation, the bromate concentration in the collection chamber was typically 2 to 3 times greater than the concentration in the bread extract. The chemiluminescent reaction of bromate with sulfite with hydrocortisone as the enhancer was selected for detection of bromate. The emission, with a wavelength maximum at 575 nm, was found to "glow" rather than "flash" after the reagents were mixed; therefore, it was possible to optimize the light collection period. The method was validated with a variety of commercial bread products. White bread, hot dog buns, hamburger rolls, and a multigrain bread from 7 different manufacturers were studied. C1 US FDA, Off Food Addit Safety, College Pk, MD 20740 USA. Yamazaki Baking Co, Cent Lab, Tokyo 1300025, Japan. Univ Maryland, College Pk, MD 20742 USA. RP Warner, C (reprint author), US FDA, Off Food Addit Safety, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM charles.warner@cfsan.fda.gov NR 14 TC 5 Z9 5 U1 0 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2005 VL 88 IS 3 BP 794 EP 799 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 932BN UT WOS:000229529300023 PM 16001854 ER PT J AU Iyengar, P Espina, V Williams, TW Lin, Y Berry, D Jelicks, LA Lee, H Temple, K Graves, R Pollard, J Chopra, N Russell, RG Sasisekharan, R Trock, BJ Lippman, M Calvert, VS Petricoin, EF Liotta, L Dadachova, E Pestell, RG Lisanti, MP Bonaldo, P Scherer, PE AF Iyengar, P Espina, V Williams, TW Lin, Y Berry, D Jelicks, LA Lee, H Temple, K Graves, R Pollard, J Chopra, N Russell, RG Sasisekharan, R Trock, BJ Lippman, M Calvert, VS Petricoin, EF Liotta, L Dadachova, E Pestell, RG Lisanti, MP Bonaldo, P Scherer, PE TI Adipocyte-derived collagen VI affects early mammary tumor progression in vivo, demonstrating a critical interaction in the tumor/stroma microenvironment SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article ID OLIGODENDROCYTE PRECURSOR CELLS; BETHLEM MYOPATHY; BREAST-CANCER; EXTRACELLULAR-MATRIX; BRAIN-TUMORS; AXON GROWTH; PROTEOGLYCAN; INDUCTION; MODEL; NG2 AB The interactions of transformed cells with the surrounding stromal cells are of importance for tumor progression and metastasis. The relevance of adipocyte-derived factors to breast cancer cell survival and growth is wen established. However, it remains unknown which specific adipocyte-derived factors are most critical in this process. Collagen VI is abundantly expressed in adipocytes. Collagen(-/-) mice in the background of the mouse mammary tumor virus/polyoma virus middle T oncogene (MMTV-PyMT) mammary cancer model demonstrate dramatically reduced rates of early hyperplasia and primary tumor growth. Collagen VI promotes its growth-stimulatory and pro-survival effects in part by signaling through the NG2/chondroitin sulfate proteoglycan receptor expressed on the surface of malignant ductal epithelial cells to sequentially activate Akt and β-catenin and stabilize cyclin D1. Levels of the carboxyterminal domain of collagen VIα 3, a proteolytic product of the full-length molecule, are dramatically upregulated in murine and human breast cancer lesions. The same fragment exerts potent growth-stimulatory effects on MCF-7 cells in vitro. Therefore, adipocytes play a vital role in defining the ECM environment for normal and tumor-derived ductal epithelial cells and contribute significantly to tumor growth at early stages through secretion and processing of collagen VI. C1 Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Cell Biol, Bronx, NY 10461 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Med, Bronx, NY 10461 USA. NCI, Pathol Lab, Bethesda, MD 20892 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Mol Pharmacol, New York, NY USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Harvard Univ, MIT, Div Hlth Sci & Technol, Cambridge, MA 02138 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Physiol & Biophys, New York, NY USA. Univ Chicago, Comm Human Nutr & Nutrit Biol, Chicago, IL 60637 USA. SUNY Buffalo, Sch Med & Biomed Sci, Dept Biochem & Mol Biol, Buffalo, NY 14260 USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Dev & Mol Biol, New York, NY USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Pathol, New York, NY USA. Georgetown Univ, Sch Med, Lombardi Comprehens Canc Ctr, Washington, DC USA. MIT, Ctr Biol Engn, Cambridge, MA USA. Johns Hopkins Univ, Dept Urol, Baltimore, MD USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. FDA, Natl Canc Inst, Clin Proteom Program, Off Cellular & Gene Therapy,Ctr Biol Evaluat & Re, Bethesda, MD USA. Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Nucl Med, New York, NY USA. Univ Padua, Dept Histol Microbiol & Med Biotechnol, I-35100 Padua, Italy. RP Scherer, PE (reprint author), Albert Einstein Coll Med, Albert Einstein Canc Ctr, Dept Cell Biol, Jack & Pearl Resnick Campus,1300 Morris Pk Ave,Ch, Bronx, NY 10461 USA. EM scherer@aecom.yu.edu RI Lisanti, Michael/C-6866-2013; Williams, Terence/I-9614-2014; OI Espina, Virginia/0000-0001-5080-5972 FU NCI NIH HHS [CA100324, CA94173, P01 CA100324, R01 CA094173]; NIGMS NIH HHS [T32 GM007288, T32 GM07288]; Telethon [1201] NR 44 TC 151 Z9 155 U1 1 U2 8 PU AMER SOC CLINICAL INVESTIGATION INC PI ANN ARBOR PA 35 RESEARCH DR, STE 300, ANN ARBOR, MI 48103 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD MAY PY 2005 VL 115 IS 5 BP 1163 EP 1176 DI 10.1172/JCI200523424 PG 14 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 923KH UT WOS:000228908300017 PM 15841211 ER PT J AU Brown, SL Bright, RA Dwyer, DE Foxman, B AF Brown, SL Bright, RA Dwyer, DE Foxman, B TI Breast pump adverse events: Reports to the Food and Drug Administration SO JOURNAL OF HUMAN LACTATION LA English DT Article DE breast pump; adverse events; surveillance; breastfeeding ID CONTAMINATION; MILK AB Breast pumps are medical devices used to express milk and maintain the milk supply. The put-pose of this study was to characterize adverse events reported to the United States Food and Drug Administration (FDA) on breast pumps. Thirty-seven adverse event reports on breast pumps were identified from the Manufacturer and User Facility Device Experience database between 1992 and 2003. Four additional reports were found in the Device Experience Network database front 1992 to 1996. The most commonly reported adverse events for electric breast pumps were pain, soreness, or discomfort; the need for medical intervention; and breast tissue damage. Most frequently reported problems for manual breast pumps were breast tissue damage and infection. Contamination of breast inilk during pumping was also reported. Breast pump adverse events are likely underreported to the FDA. Reporting adverse events is important for improving the design and manufacture of breast pumps and subsequently decreasing adverse events. C1 US FDA, Ctr Devices & Radiol Hlth, Div Postmarket Surveillance, Epidemiol Branch,Off Surveillance & Biomet, Rockville, MD 20850 USA. Univ Michigan, Ctr Mol & Clin Epidemiol Infect Dis, Ann Arbor, MI 48109 USA. RP Brown, SL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Postmarket Surveillance, Epidemiol Branch,Off Surveillance & Biomet, 1350 Piccard Dr,HFZ 541, Rockville, MD 20850 USA. RI Foxman, Betsy/E-1836-2015; Bright, Roselie/D-2240-2016; OI Foxman, Betsy/0000-0001-6682-238X NR 22 TC 22 Z9 22 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0890-3344 J9 J HUM LACT JI J. Hum. Lact. PD MAY PY 2005 VL 21 IS 2 BP 169 EP 174 DI 10.1177/0890334405275445 PG 6 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 920GF UT WOS:000228676700011 PM 15886342 ER PT J AU Kawakami, K Kioi, M Liu, Q Kawakami, M Puri, RK AF Kawakami, K Kioi, M Liu, Q Kawakami, M Puri, RK TI Evidence that IL-13R alpha-2 chain in human glioma cells is responsible for the antitumor activity mediated by receptor-directed cytotoxin therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Article DE glioblastoma; interleukin-13 receptor; immunotoxin; gene therapy; antisense oligonucleotide ID INTERLEUKIN-13 RECEPTOR; IL-13 RECEPTOR; ALPHA-2 CHAIN; SIGNAL-TRANSDUCTION; PSEUDOMONAS EXOTOXIN; TARGETED CYTOTOXIN; NECK-CANCER; IN-VIVO; TUMOR IMMUNOSURVEILLANCE; PANCREATIC TUMORS AB The interleukin-13 receptor alpha 2 (IL-13R alpha 2) chain is a primary IL-13 binding and internalization component of the IL-13R system. Previous studies have shown that human brain tumors, including glioblastoma multiforme (GBM), overexpress IL-13R alpha 2 chain, while normal brain cells do not express this protein or express very low levels of it. To target IL-13R on brain tumor cells, the authors have developed an IL-13R-directed cytotoxin termed IL13-PE38QQR to induce specific cancer cell killing. To investigate the role of IL-13R alpha 2 chain in GBM, cells were treated with antisense oligonucleotide or siRNA to IL-13R alpha 2 chain, and cellular IL-13 binding and sensitivity to IL-13 cytotoxin were assessed. IL-13R alpha 2 gene interference in GBM cells showed decreased ligand binding, and consequently IL-13 cytotoxin exhibited less cytotoxicity to these cells. The authors next evaluated the antitumor activity of IL-13 cytotoxin in native IL-13R-expressing tumors and after gene transfer of IL-13R alpha 2 by injecting plasmid in U87MG tumors subcutaneously implanted in nude mice. These mice were then treated with IL-13 cytotoxin. Mean tumor size in mice receiving intraperitoneal or intratumoral IL-13 cytotoxin was significantly smaller in control tumors; however, tumor sizes were much smaller in IL-13R alpha 2-transfected tumors. Furthermore, convection-enhanced delivery of IL-13Ra2 cDNA in intracranially established U87MG glioma followed by IL-13 cytotoxin administration by the same route mediated tumor regression and prolonged survival of animals by 164% compared with control. These results indicate that IL-13R alpha 2 chain in GBM cells is essential for IL-13 cytotoxin-induced cytotoxicity and that IL-13R alpha 2 chain plays a critical biologic role in IL-13 cytotoxin-mediated therapy for GBM. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg,29B,Room 2NN10,HFM-735, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 49 TC 26 Z9 30 U1 0 U2 2 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 MAY-JUN PY 2005 VL 28 IS 3 BP 193 EP 202 DI 10.1097/01.cji.0000161393.04207.e1 PG 10 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 921RN UT WOS:000228782500004 PM 15838375 ER PT J AU Malaspina, A Moir, S Orsega, SM Vasquez, J Miller, NJ Donoghue, ET Kottilil, S Gezmu, M Follmann, D Vodeiko, GM Levandowski, RA Mican, JM Fauci, AS AF Malaspina, A Moir, S Orsega, SM Vasquez, J Miller, NJ Donoghue, ET Kottilil, S Gezmu, M Follmann, D Vodeiko, GM Levandowski, RA Mican, JM Fauci, AS TI Compromised B cell responses to influenza vaccination in HIV-infected individuals SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HUMORAL IMMUNE-RESPONSE; IMMUNODEFICIENCY-VIRUS TYPE-1; ACTIVE ANTIRETROVIRAL THERAPY; TERM ANTIBODY-PRODUCTION; ACUTE VIRAL-INFECTION; MF59-ADJUVANTED INFLUENZA; SUBUNIT VACCINE; H5N1 INFLUENZA; PLASMA VIREMIA; BONE-MARROW AB Background. Yearly influenza vaccination, although recommended for human immunodeficiency virus (HIV) infected individuals, has not received thorough evaluation in the era of antiretroviral therapy. We assessed the impact of HIV disease on B cell responses to influenza vaccination. Methods. Sixty-four HIV-infected and 17 HIV-negative individuals received the 2003-2004 trivalent inactivated influenza vaccine. Frequencies of influenza-specific antibody-secreting cells (ASCs) were measured by enzyme-linked immunospot (ELISPOT) assay, and antibody responses were measured by hemagglutination-inhibition (HI) assay. Memory responses to influenza were measured by ELISPOT assay after polyclonal activation of B cells in vitro. Results. Prevaccination HI titers were significantly higher in HIV-negative than in HIV-infected individuals. Peak HI titers and influenza-specific ASC frequencies were directly correlated with CD4(+) T cell counts in HIV-infected individuals. Influenza-specific memory B cell responses were significantly lower in HIV-infected than in HIV-negative individuals and were directly correlated with CD4(+) T cell counts. Conclusions. HIV infection is associated with a weak antibody response to influenza vaccination that is compounded by a poor memory B cell response. CD4(+) T cell count is a critical determinant of responsiveness to influenza vaccination, and the contribution of plasma HIV RNA level is suggestive and warrants further investigation. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Off Clin Res, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Nursing & Patient Care Serv, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Moir, S (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10,Rm 6A02,10 Ctr Dr, Bethesda, MD 20892 USA. EM smoir@niaid.nih.gov NR 44 TC 99 Z9 100 U1 0 U2 3 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY 1 PY 2005 VL 191 IS 9 BP 1442 EP 1450 DI 10.1086/429298 PG 9 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 913CS UT WOS:000228128800010 PM 15809902 ER PT J AU Selvapandiyan, A Stabler, K Ansari, NA Kerby, S Riemenschneider, J Salotra, P Duncan, R Nakhasi, HL AF Selvapandiyan, A Stabler, K Ansari, NA Kerby, S Riemenschneider, J Salotra, P Duncan, R Nakhasi, HL TI A novel semiquantitative fluorescence-based multiplex polymerase chain reaction assay for rapid simultaneous detection of bacterial and parasitic pathogens from blood SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article ID KALA-AZAR PATIENTS; TIME PCR ASSAY; VISCERAL LEISHMANIASIS; BACILLUS-ANTHRACIS; SENSITIVE DETECTION; PROTECTIVE ANTIGEN; CLINICAL-SAMPLES; YERSINIA-PESTIS; PATIENT BLOOD; DIAGNOSIS AB A multiplex polymerase chain reaction assay was developed for the rapid simultaneous detection of category A select bacterial agents (Bacillus anthracis and Yersinia pestis) and parasitic pathogens (Leishmania species) in blood using the Cepheid Smart Cycler platform. B. anthracis (Sterne) and Yersinia. pseudotuberculosis were used in the assay for optimization for B. anthracis and Y pestis, respectively. The specificity of the target amplicrons [protective antigen gene of B. anthracis and rRNA genes of other pathogens or human (internal control)] was evaluated by staining the amplicons with SYBR Green I and determining their individual melting temperatures (T-m). As a novel approach for pathogen semiquantitation, the Tin peak height of the amplicon was correlated with a known standard curve of pathogen-spiked samples. This assay was able to detect DNA in blood spiked with less than 50 target cells/ml for all of the pathogens. The sensitivity of this assay in blood was 100% for the detection of Leishmania donovani from leishmaniasis patients and B. anthracis (Sterne) from symptomatic mice. The time necessary for performing this assay including sample preparation was less than 1.5 hours, making this a potentially useful method for rapidly diagnosing and monitoring the efficacy of drugs or vaccines in infected individuals. C1 DETTD OBRR CBER FDA, Bethesda, MD 20892 USA. Safdarjang Hosp, Inst Pathol, Indian Council Med Res, New Delhi, India. RP Selvapandiyan, A (reprint author), DETTD OBRR CBER FDA, Bldg 29,Rm 425,8800 Rockville Pike, Bethesda, MD 20892 USA. EM selvapandiyan@cber.fda.gov RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 49 TC 23 Z9 23 U1 0 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD MAY PY 2005 VL 7 IS 2 BP 268 EP 275 DI 10.1016/S1525-1578(10)60554-5 PG 8 WC Pathology SC Pathology GA 921AP UT WOS:000228736900015 PM 15858151 ER PT J AU Takao, M Pedro, P Farlow, MR Murrell, JR Unverzagt, FW Yamaguchi, K Glazier, BS Epperson, F Bigio, E DeCarli, C Ghetti, B AF Takao, M Pedro, P Farlow, MR Murrell, JR Unverzagt, FW Yamaguchi, K Glazier, BS Epperson, F Bigio, E DeCarli, C Ghetti, B TI Gerstmann-Straussler-Scheinker disease associated with the PRNP A117V-129V mutation: Neuropathology of an asymptomatic gene carrier and five clinically affected individuals from a family. SO JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY LA English DT Meeting Abstract CT 81st Annual Meeting of the American-Association-of-Neuropathologists CY JUN 09-12, 2005 CL Arlington, VA SP Amer Assoc Neuropathol C1 Indiana Univ, Sch Med, Indiana Alzheimer Dis Ctr, Dept Pathol & Lab Med,Dept Neurol,Dept Psychiat, Indianapolis, IN USA. Mihara Mem Hosp, Gunma, Japan. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Northwestern Univ, Feinberg Sch Med, Dept Pathol, Cognit Neurol & Alzheimers Dis Ctr, Evanston, IL 60208 USA. Univ Calif Davis, Dept Neurol, Alzheimers Dis Ctr, Sacramento, CA 95817 USA. RI DeCarli, Charles/B-5541-2009 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 0022-3069 J9 J NEUROPATH EXP NEUR JI J. Neuropathol. Exp. Neurol. PD MAY PY 2005 VL 64 IS 5 MA 9 BP 433 EP 433 PG 1 WC Clinical Neurology; Neurosciences; Pathology SC Neurosciences & Neurology; Pathology GA 923YP UT WOS:000228945800019 ER PT J AU Sealey, WM Stratton, SL Mock, DM Hansen, DK AF Sealey, WM Stratton, SL Mock, DM Hansen, DK TI Marginal maternal biotin deficiency in CD-1 mice reduces fetal mass of biotin-dependent carboxylases SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Experimental Biology 2004 Annual Meeting CY APR 17-21, 2004 CL Washington, DC DE biotin; biotin-dependent carboxylases; CD-1 mice; mRNA ID PROPIONYL-COA CARBOXYLASE; HOLOCARBOXYLASE SYNTHETASE; 3-HYDROXYISOVALERIC ACID; URINARY-EXCRETION; HUMAN-CELLS; SUPPLEMENTATION; BIOTINYLATION; INDICATORS; ETHANOL; RATS AB Marginal maternal biotin deficiency reduces hepatic activity of biotin-dependent carboxylases and causes high rates of fetal birth defects in mice. We tested the hypothesis that the decreased carboxylase activity observed in deficient dams and their offspring is mediated by decreased abundance of biotinylated carboxylases, decreased expression of their mRNAs, or both. During gestation, CD-1 mice were fed a diet that induced biotin deficiency or a biotin-sufficient diet. On gestational d 17, gravid uteri were removed, and each live fetus was examined grossly for defects. The expected high incidence of cleft palate (83%) in offspring was observed. In maternal and fetal liver, acetyl-CoA carboxylase, pyruvate carboxylase, propionyl-CoA carboxylase, and β-methylcrotonyl-CoA carboxylase abundances were determined by Western blotting; the content of mRNAs for most of these enzymes and holocarboxylase synthetase was determined by real-time RT-PCR. Biotin deficiency significantly reduced the abundance of the carboxylases in maternal and fetal liver; neither the content of mRNAs for the carboxylases nor holocarboxylase synthetase changed. This study provides evidence that the decrease in carboxylase activities is attributable to a decrease in the abundance of biotinylated carboxylases; further, this effect is more severe in fetuses than dams. C1 Univ Arkansas Med Sci, Dept Biochem, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Mol Biol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Mock, DM (reprint author), Univ Arkansas Med Sci, Dept Biochem, Little Rock, AR 72205 USA. EM mockdonaldm@uams.edu FU NIDDK NIH HHS [R01 DK036823, R37 DK036823, DK-36823] NR 31 TC 20 Z9 23 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAY PY 2005 VL 135 IS 5 BP 973 EP 977 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 924BM UT WOS:000228953600002 PM 15867267 ER PT J AU Mahmood, I AF Mahmood, I TI The correction factors do help in improving the prediction of human clearance from animal data SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Editorial Material ID PHARMACOKINETIC PARAMETERS; LABORATORY-ANIMALS; RHESUS-MONKEYS; HEALTHY-VOLUNTEERS; IN-VIVO; METABOLISM; RAT; DISPOSITION; DOG; DRUG C1 US FDA, Clin Pharmacol & Toxicol Branch, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Clin Pharmacol & Toxicol Branch, Woodmont Off Ctr 2, Rockville, MD 20852 USA. EM mahmoodi@cber.fda.gov NR 46 TC 6 Z9 6 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD MAY PY 2005 VL 94 IS 5 BP 940 EP 945 DI 10.1002/jps.20299 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 921VA UT WOS:000228792200002 PM 15770644 ER PT J AU Singh, SP Chen, T Chen, L Mei, N McLain, E Samokyszyn, V Thaden, JJ Moore, MM Zimniak, P AF Singh, SP Chen, T Chen, L Mei, N McLain, E Samokyszyn, V Thaden, JJ Moore, MM Zimniak, P TI Mutagenic effects of 4-hydroxynonenal triacetate, a chemically protected form of the lipid peroxidation product 4-hydroxynonenal, as assayed in L5178Y/Tk(+/-) mouse lymphoma cells SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID THYMIDINE KINASE GENE; RESISTANT TFT MUTANTS; ETHYL-N-NITROSOUREA; INTERNATIONAL WORKSHOP; MUTATION ASSAY; HETEROZYGOSITY; TRANSFORMATION AB The lipid peroxidation product 4-hydroxynon-2-enal (4-HNE) is cytotoxic and genotoxic at superphysiological concentrations. To characterize the mechanism of action of 4-HNE, we assessed genotoxic damage by 4-HNE and by 4-HNE triacetate [4-HNE(Ac)(3)] using the mouse lymphoma assay that measures the mutant frequency in the Tk gene. As a strong electrophile, 4-HNE reacts readily with nucleophilic centers on cellular components. When added extracellularly, it may react preferentially with proteins in culture medium or on the cell surface and not reach deeper cellular targets such as nuclear DNA. Therefore, 4-HNE(Ac)(3), a protected form of 4-HNE that is metabolically converted to 4-HNE in cells (Neely MD, Amarnath V, Weitlauf C, and Montine TJ, Chem Res Toxicol 15:40-47, 2002), was assayed in addition to 4-HNE. When added in serum-containing medium, 4-HNE was not mutagenic in the mouse lymphoma assay up to 38 mu M (cytotoxicity = 13%). In contrast, exposure to 4-HNE(Ac)(3), which mimics intracellular formation of 4-HNE, resulted in dose-dependent induction of mutations. At 17 mu M 4-HNE(Ac)(3) (cytotoxicity = 33%), the mutant frequency was 719 x 10(-6) (>7-fold higher than the spontaneous mutant frequency). Loss of heterozygosity analysis in the Tk mutants revealed that the majority of mutations induced by 4-HNE(Ac)(3) resulted from clastogenic events affecting a large segment of the chromosome. The results indicate that, in the presence of serum that approximates physiological conditions, 4-HNE generated intracellularly but not extracellularly is a strong mutagen via a clastogenic action at concentrations that may occur during oxidative stress. C1 Univ Arkansas Med Sci Hosp, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. Cent Arkansas Vet Healthcare Syst, Little Rock, AR USA. US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR USA. Shanghai Jiao Tong Univ, Coll Life Sci & Technol, Shanghai 200030, Peoples R China. RP Zimniak, P (reprint author), Univ Arkansas Med Sci Hosp, Dept Pharmacol & Toxicol, 4301 W Markham St, Little Rock, AR 72205 USA. EM zimniakpiotr@uams.edu RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 FU NIA NIH HHS [P01 AG20641]; NIEHS NIH HHS [R01 ES07804] NR 36 TC 19 Z9 21 U1 0 U2 0 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD MAY PY 2005 VL 313 IS 2 BP 855 EP 861 DI 10.1124/jpet.104.080754 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 916BJ UT WOS:000228357900043 PM 15701709 ER PT J AU Anderson, DL Cunningham, WC AF Anderson, DL Cunningham, WC TI Analysis of total diet study foods for gamma-ray emitting radionuclides SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article AB Foods collected for radionuclide analysis under the Food and Drug Administration's (FDA's) Total Diet Study (TDS) Program were analyzed by the Center for Food Safety and Applied Nutrition (CFSAN) as quality assurance (QA) for analyses performed at FDA's Winchester Engineering and Analytical Center (WEAC). 200-ml QA portions were analyzed for gamma-ray emitting fission products and naturally occurring radionuclides. Efficiency, pileup correction, absorption effects, and accuracy were determined by analyzing a variety of certified reference materials and KNO3 and KCl solutions. K-40 results agreed well with those from WEAC and with total K results from other techniques. Count times as low as 2 minutes were sufficient to confirm that radioactivity concentrations were below regulatory limits. C1 US FDA, Elemental Res Branch, College Pk, MD 20740 USA. RP Anderson, DL (reprint author), US FDA, Elemental Res Branch, HFS-338,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM david.anderson@cfsan.fda.gov NR 9 TC 4 Z9 5 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD MAY PY 2005 VL 264 IS 2 BP 371 EP 376 DI 10.1007/s10967-005-0723-8 PG 6 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 918CO UT WOS:000228516700017 ER PT J AU Myers, MR AF Myers, MR TI Effect of pulse characteristics on temperature rise due to ultrasound absorption at a bone/soft-tissue interface SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ACOUSTIC RADIATION FORCE AB The transient temperature rise at a bone/soft-tissue interface is an important quantity in the safety evaluation of procedures involving trains of high-intensity ultrasound pulses. Mathematical models based upon the time-averaged intensity of the pulse train can provide rapid estimates of the temperature rise, but are known to underestimate the temperature rise during the on-time of the pulse. This paper extends a previous analytical model to account for pulse shape, and provides error estimates for simulations employing time-averaged intensities. A simple analytic expression for the interface temperature that accounts for both bone and soft-tissue properties is provided. The analytic expression agrees well with temperature rise predictions based upon the finite-element method, when the insonation time is large compared to the pulse repetition period. In this case of large relative insonation time, the pulse shape is found to be inconsequential. © 2005 Acoustical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. EM matthew.myers@fda.hhs.gov RI CHEN, Jiangang/A-1549-2011 NR 11 TC 2 Z9 2 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 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2005 VL 117 IS 5 BP 3281 EP 3287 DI 10.1121/1.1879232 PG 7 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 925QV UT WOS:000229068700059 PM 15957794 ER PT J AU Wear, KA Laib, A Stuber, AP Reynolds, JC AF Wear, KA Laib, A Stuber, AP Reynolds, JC TI Comparison of measurements of phase velocity in human calcaneus to Biot theory SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ULTRASONIC WAVE-PROPAGATION; BOVINE CANCELLOUS BONE; TRABECULAR BONE; ACOUSTIC PROPAGATION; STRATIFIED MODEL; FREQUENCY RANGE; ELASTIC WAVES; CORTICAL BONE; DISPERSION; DEFORMATION AB Biot's theory for elastic propagation in porous media has previously been shown to be useful for modeling the dependence of phase velocity on porosity in bovine cancellous bone in vitro. In the present study, Biot's theory is applied to measurements of porosity-dependent phase velocity in 53 human calcanea in vitro. Porosity was measured using microcomputed tomography for some samples (n = 23) and estimated based on bone mineral densitometry for the remaining samples (n = 30). The phase velocity at 500 kHz was measured in a water tank using a through-transmission technique. Biot's theory performed well for the prediction of the dependence of sound speed on porosity. The trend was quasilinear, but both the theory and experiment show similar slight curvature. The root mean square error (RMSE) of predicted versus measured sound speed was 15.8 m/s. © 2005 Acoustical Society of America. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. SCANCO Med AG, CH-8303 Bassersdorf, Switzerland. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-140,12720 Twinbrook Pky, Rockville, MD 20852 USA. EM Kaw@cdrh.fda.gov NR 40 TC 46 Z9 47 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 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAY PY 2005 VL 117 IS 5 BP 3319 EP 3324 DI 10.1121/1.1886388 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 925QV UT WOS:000229068700063 PM 15957798 ER PT J AU Lim, HW Gilchrest, BA Cooper, KD Bischoff-Ferrari, HA Rigel, DS Cyr, WH Miller, S DeLeo, VA Lee, TK Demko, CA Weinstock, MA Young, A Edwards, LS Johnson, TM Stone, SP AF Lim, HW Gilchrest, BA Cooper, KD Bischoff-Ferrari, HA Rigel, DS Cyr, WH Miller, S DeLeo, VA Lee, TK Demko, CA Weinstock, MA Young, A Edwards, LS Johnson, TM Stone, SP TI Sunlight, tanning booths, and vitamin D SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID DNA-REPAIR CAPACITY; D INSUFFICIENCY; HUMAN-SKIN; ULTRAVIOLET-RADIATION; INDUCED SUPPRESSION; D SUPPLEMENTATION; OXIDATIVE STRESS; BREAST-CANCER; ELDERLY-WOMEN; SERUM-LEVELS C1 Henry Ford Hosp, Dept Dermatol, Detroit, MI 48202 USA. Boston Univ, Sch Med, Boston, MA 02215 USA. Case Western Reserve Univ, Sch Med, Cleveland, OH 44106 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Cambridge, MA 02138 USA. NYU, Sch Med, Dept Dermatol, New York, NY USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. St Lukes Roosevelt Hosp, Dept Dermatol, New York, NY USA. British Columbia Canc Agcy, Canc Control Res Program, Vancouver, BC V5Z 4E6, Canada. Case Western Reserve Univ, Sch Dent Med, Cleveland, OH 44106 USA. Brown Univ, Sch Med, Dept Dermatol, Providence, RI 02912 USA. Univ London Kings Coll, St Johns Inst Dermatol, London WC2R 2LS, England. Amer Acad Dermatol Assoc, Washington, DC USA. Univ Michigan, Dept Dermatol, Ann Arbor, MI 48109 USA. So Illinois Univ, Sch Med, Div Dermatol, Springfield, IL USA. RP Lim, HW (reprint author), Amer Acad Dermatol Inc, POB 4014, Schaumburg, IL 60168 USA. EM hlim1@hfhs.org OI Young, Antony/0000-0002-4163-6772; Cooper, Kevin/0000-0002-1986-3602 NR 85 TC 52 Z9 52 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0190-9622 J9 J AM ACAD DERMATOL JI J. Am. Acad. Dermatol. PD MAY PY 2005 VL 52 IS 5 BP 868 EP 876 DI 10.1016/j.jaad.2005.03.015 PG 9 WC Dermatology SC Dermatology GA 926JT UT WOS:000229120200016 PM 15858480 ER PT J AU Momosaki, S Nakashima, Y Kojiro, M Tabor, E AF Momosaki, S Nakashima, Y Kojiro, M Tabor, E TI HBsAg-negative hepatitis B virus infections in hepatitis C virus-associated hepatocellular carcinoma SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE hepatitis B surface antigen; hepatitis B virus; hepatitis C virus; hepatocellular carcinoma ID SURFACE-ANTIGEN; CORE PROMOTER; LIVER-DISEASE; HIGH PREVALENCE; HBV INFECTION; DNA; GENE; MUTATIONS; EXPRESSION; REPLICATION AB This study was conducted to evaluate reports that hepatitis B virus (HBV) DNA sequences can be found in the serum and/ or tumour tissue from some hepatocellular carcinoma (HCC) patients who have no detectable hepatitis B surface antigen ( HBsAg) in their sera. Such HBV infections would be highly atypical, because prospective studies have shown a clear succession of specific serologic markers during and after most HBV infections. As most HBsAg- negative HCC patients in Japan have hepatitis C virus (HCV) infections, the present study was conducted to determine whether some of these patients actually have unrecognized HBV infections. Thirty newly diagnosed HCC patients from Kurume, Japan, with antibody to the hepatitis C virus (anti-HCV) were studied. None of the 30 had HBsAg detectable in their serum. Of 22 for whom test results for antibodies to the hepatitis B core antigen (anti-HBc) and antibodies to HBsAg (anti-HBs) were available, 14 (64%) had anti- HBc and antiHBs, four (18%) had anti- HBc alone, and four ( 18%) had no HBV markers. Nested polymerase chain reaction was used to detect the HBV surface ( S), core ( C), polymerase ( P) and core promoter gene sequences in the HCC tissues and in the adjacent nontumorous liver tissues. HBV DNA was detected in HCC and/ or adjacent nontumorous liver in 22 of 30 (73%) patients [ detected in both HCC and nontumorous liver in 19/30 patients (63%)]. Among the 22 patients with detectable HBV DNA, more than one HBV gene was detected in 10 (46%). Among the four patients whose sera were negative for all HBV markers, three had HBV DNA in either HCC and nontumorous liver ( two cases) or only in the nontumorous liver ( one case); HBV DNA could not be detected in tissues from the fourth patient. In 18 of 21 (86%) patients with detectable HBV core promoter sequences, mutations at both nucleotides 1762 ( A - GT) and 1764 ( G - A) in the core promoter region were found. No deletions were detected in the core promoter gene region of the type reported to be associated with some cases of HBsAg- negative HBV infection. Thus, HBV DNA was detectable in 22 ( 73%) HBsAg- negative, anti- HCV- positive HCCs, including three (10%) who were also negative for anti- HBc and anti-HBs. HBV mutations at both nucleotides 1762 ( A - GT) and 1764 ( G - A) in the core promoter region were found in the majority of cases, mutations that have previously been reported in HBV that is integrated in HCC DNA. In serologic surveys to determine etiologic associations of HCC, patients such as those in this study would have been incorrectly designated as having 'HCV- associated HCC,' whereas the data in this study suggest that HBV could have played a role in the development of their HCCs. C1 US FDA, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. Kurume Univ, Dept Pathol, Kurume, Fukuoka 830, Japan. RP Tabor, E (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-300,1401 Rockville Pike,400N, Rockville, MD 20852 USA. EM tabor@cber.fda.gov NR 26 TC 14 Z9 14 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD MAY PY 2005 VL 12 IS 3 BP 325 EP 329 DI 10.1111/j.1365-2893.2005.00586.x PG 5 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 918PI UT WOS:000228559700014 PM 15850475 ER PT J AU Taylor, DR Puig, M Darnell, MER Mihalik, K Feinstone, SM AF Taylor, DR Puig, M Darnell, MER Mihalik, K Feinstone, SM TI New antiviral pathway that mediates hepatitis C virus replicon interferon sensitivity through ADAR1 SO JOURNAL OF VIROLOGY LA English DT Article ID PROTEIN-KINASE PKR; ADENOSINE-DEAMINASE; RNA REPLICATION; CELL-LINES; VA RNA1; INHIBITION; TRANSLATION; INITIATION; MECHANISM; FORM AB While many clinical hepatitis C virus (HCV) infections are resistant to alpha interferon (IFN-alpha) therapy, subgenomic in vitro self-replicating HCV RNAs (HCV replicons) are characterized by marked IFN-alpha sensitivity. IFN-alpha treatment of replicon-containing cells results in a rapid loss of viral RNA via translation inhibition through double-stranded RNA-activated protein kinase (PKR) and also through a new pathway involving RNA editing by an adenosine deaminase that acts on double-stranded RNA (ADAR1). More than 200 genes are induced by IFN-alpha, and yet only a few are attributed with an antiviral role. We show that inhibition of both PKR and ADAR1 by the addition of adenovirus-associated RNA stimulates replicon expression and reduces the amount of inosine recovered from RNA in replicon cells. Small inhibitory RNA, specific for ADAR1, stimulated the replicon 40-fold, indicating that ADAR1 has a role in limiting replication of the viral RNA. This is the first report of ADAR's involvement in a potent antiviral pathway and its action to specifically eliminate HCV RNA through adenosine to inosine editing. These results may explain successful HCV replicon clearance by IFN-alpha in vitro and may provide a promising new therapeutic strategy for HCV as well as other viral infections. C1 US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD 20892 USA. RP Taylor, DR (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, HFM-448,8800 Rockville Pike, Bethesda, MD 20892 USA. EM taylord@cber.fda.gov NR 26 TC 105 Z9 111 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2005 VL 79 IS 10 BP 6291 EP 6298 DI 10.1128/JVI.79.10.6291-6298.2005 PG 8 WC Virology SC Virology GA 922CV UT WOS:000228814400040 PM 15858013 ER PT J AU Archer, JC Mabry-Smith, R Shojaee, S Threet, J Eckert, JJ Litman, VE AF Archer, JC Mabry-Smith, R Shojaee, S Threet, J Eckert, JJ Litman, VE TI Dioxin and furan levels found in tampons SO JOURNAL OF WOMENS HEALTH LA English DT Article ID ENDOMETRIOSIS AB Background: Human exposure to dioxins and furans through diet and other sources has been of concern for many years. One specific concern, related to exposure in women's health, is the possible link to endometriosis. Although there are differences in opinion about this link, the concern from the public is real. Congressional interest has prompted investigations to determine the amounts of dioxins and furans present in feminine hygiene products available within the United States. Methods: Tampon samples were analyzed via Gas Chromatography/High Resolution Mass Spectrometry (GC/HRMS) using a Micromass AutoSpec Ultima high resolution mass spectrometer at 10,000 mass resolution. As data were confirmed and quantified using direct isotope dilution, only the 17 2,3,7,8-chlorine-containing dioxin and furan concentrations were calculated from these analyses. Results: A total toxic equivalence (TEQ), using the World Health Organization's toxic equivalency factor (TEF) values, was calculated for each sample. The calculated TEQs for samples were not statistically different from those of the calculated TEQs using the average limit of detection (LOD) values. Conclusions: Data show results similar to those reported by DeVito and Schecter (Environ Health Perspect 2002; 110: 23) in that most of the dioxins and furans were below the detection limit or estimated detection limits (EDLs). C1 US FDA, Pacific Reg Lab, Bothell, WA USA. Immediat Off Assistant Secretary Hlth, Off Secretary, Washington, DC USA. US FDA, Arkansas Reg Lab, Jefferson, AR USA. RP Litman, VE (reprint author), 3900 NCTR Rd,Bldg 26, Jefferson, AR 72079 USA. EM VLitman@ora.fda.gov NR 13 TC 4 Z9 4 U1 4 U2 16 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1540-9996 J9 J WOMENS HEALTH JI J. Womens Health PD MAY PY 2005 VL 14 IS 4 BP 311 EP 315 DI 10.1089/jwh.2005.14.311 PG 5 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 932ZN UT WOS:000229593400005 PM 15916504 ER PT J AU Delmonte, P Kataoka, A Corl, BA Bauman, DE Yurawecz, MP AF Delmonte, P Kataoka, A Corl, BA Bauman, DE Yurawecz, MP TI Relative retention order of all isomers of cis/trans conjugated linoleic acid FAME from the 6,8- to 13,15-positions using silver ion HPLC with two elution systems SO LIPIDS LA English DT Article AB CLA, defined as. one,or more octaclecadienoic. acids (18:2) with conjugated double bonds, has been reported to be active in a number of biological systems. GC and silver ion HPLC (Ag+-HPLC) have been the primary techniques for identifying specific CLA isomers in both foods and biological extracts. Recently, GC relative retention times were reported for all c c, c/t (c,t and t,c), and t,t CLA FAME from the 6,8- to the 13,1 5-positions in octadecadienoic acid (18:2). Presented here is the rela-, live retention order of the same CLA FAME using Ag+-HPLC with two different elution systems. The first elution system, consisting of 0.1 % acetonitrile/0.5`/` diethyl ether (DE) /hexane, has been used previously to monitor CLA composition in foods. Also presented here is the retention order of CLA FAME using 2%. acetic acid/hexane elution solvent', which has advantages of more stable retention volumes and a complementary elution order of CLA FAME isomers. The data are reported using retention volumes (RV) adjusted for toluene, an estimator for dead volume, and relative to c9,t1 1-18:2. Measurement of relative RV in the analysis of 88 samples of cow plasma, milk, and rumen fluids using Ag+-HPLC is also presented here. The % CV ranged from 1.04 to 1.62 for t, t isomers and from 0 to 0.48 for c/t isomers. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. RP Yurawecz, MP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM mpy@cfsan.fda.gov RI Corl, Benjamin/P-3150-2016 OI Corl, Benjamin/0000-0002-6495-3279 NR 6 TC 33 Z9 33 U1 0 U2 4 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 221 W BRADLEY AVE, CHAMPAIGN, IL 61821-1827 USA SN 0024-4201 J9 LIPIDS JI Lipids PD MAY PY 2005 VL 40 IS 5 BP 509 EP 514 DI 10.1007/s11745-005-1411-3 PG 6 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 941VD UT WOS:000230241400010 PM 16094861 ER PT J AU Chen, HZ Hopper, SL Cerniglia, CE AF Chen, HZ Hopper, SL Cerniglia, CE TI Biochemical and molecular characterization of an azoreductase from Staphylococcus aureus, a tetrameric NADPH-dependent flavoprotein SO MICROBIOLOGY-SGM LA English DT Article ID HUMAN SKIN; AZO DYES; AEROBIC AZOREDUCTASE; CLONING; CARCINOGENESIS; RECONSTITUTION; PURIFICATION; BACTERIA; ENZYME; FMN AB Azo dyes are a predominant class of colourants used in tattooing, cosmetics, foods and consumer products. A gene encoding NADPH-flavin azoreductase (Azol) from the skin bacterium Staphylococcus aureus ATCC 25923 was identified and overexpressed in Escherichia coli. RT-PCR results demonstrated that the azol gene was constitutively expressed at the mRNA level in S. aureus. Azol was found to be a tetramer with a native molecular mass of 85 kDa containing four non-covalently bound FMN. Azol requires NADPH, but not NADH, as an electron donor for its activity. The enzyme was resolved to dimeric apoprotein by removing the flavin prosthetic groups using hydrophobic-interaction chromatography. The dimeric apoprotein was reconstituted on-column and in free stage with FMN, resulting in the formation of a fully functional native-like tetrameric enzyme. The enzyme cleaved the model azo dye 2-[4-(dimethylamino)phenylazo]benzoic acid (Methyl Red) into N,N-dimethyl-p-phenylenediamine and 2-aminobenzoic acid. The apparent K-m values for NADPH and Methyl Red substrates were 0-074 and 0(.)057 mM, respectively. The apparent V-max was 0(.)4 mu M min(-1) (mg protein)(-1). Azol was also able to metabolize Orange 11, Amaranth, Ponceau BS and Ponceau S azo dyes. Azol represents the first azoreductase to be identified and characterized from human skin microflora. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Chen, HZ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM hchen@nctr.fda.gov NR 30 TC 112 Z9 117 U1 0 U2 12 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 MAY PY 2005 VL 151 BP 1433 EP 1441 DI 10.1099/mic.0.27805-0 PN 5 PG 9 WC Microbiology SC Microbiology GA 928LC UT WOS:000229272100012 PM 15870453 ER PT J AU Spiridonov, NA Wong, L Zerfas, PM Starost, MF Pack, SD Paweletz, CP Johnson, GR AF Spiridonov, NA Wong, L Zerfas, PM Starost, MF Pack, SD Paweletz, CP Johnson, GR TI Identification and characterization of SSTK, a serine/threonine protein kinase essential for male fertility SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID NUCLEAR PROTEINS; SPERMIOGENESIS; CHROMATIN; GENE; SPERMATOGENESIS; PHOSPHORYLATION; MEIOSIS; HSP70-2; MICE; CONDENSATION AB Here we describe and characterize a small serine/threonine kinase (SSTK) which consists solely of the Nand Globes of a protein kinase catalytic domain. SSTK protein is highly conserved among mammals, and no close homologues were found in the genomes of nonmammalian organisms. SSTK specifically interacts with HSP90-1β, HSC70, and HSP70 proteins, and this association appears to be required for SSTK kinase activity. The SSTK transcript was most abundant in human and mouse testes but was also detected in all human tissues tested. In the mouse testis, SSTK protein was localized to the heads of elongating spermatids. Targeted deletion of the SSTK gene in mice resulted in male sterility due to profound impairment in motility and morphology of spermatozoa. A defect in DNA condensation in SSTK null mutants occurred in elongating spermatids at a step in spermiogenesis coincident with chromatin displacement of histones by transition proteins. SSTK phosphorylated histones H1, H2A, H2AX, and H3 but not H2B or H4 or transition protein I in vitro. These results demonstrate that SSTK is required for proper postmeiotic chromatin remodeling and male fertility. Abnormal sperm chromatin condensation is common in sterile men, and our results may provide insight into the molecular mechanisms underlying certain human infertility disorders. C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. Natl Inst Allergy & Infect Dis, Lab Immunopathol, NIH, Bethesda, MD 20892 USA. Univ Hlth Sci, Uniformed Serv, Dept Anat Physiol & Genet, Inst Mol Med, Bethesda, MD 20814 USA. RP Spiridonov, NA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, HFD-122,Bldg 29A,Rm 3B-20, Bethesda, MD 20892 USA. EM spiridonov@cber.fda.gov; johnsong@cber.fda.gov RI Spiridonov, Nikolay/B-6287-2014; Pack, Svetlana/C-2020-2014 NR 35 TC 53 Z9 58 U1 2 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0270-7306 J9 MOL CELL BIOL JI Mol. Cell. Biol. PD MAY PY 2005 VL 25 IS 10 BP 4250 EP 4261 DI 10.1128/MCB.25.10.4250-4261.2005 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 923DB UT WOS:000228888100035 PM 15870294 ER PT J AU Slikker, W Acuff, K Boyes, WK Chelonis, J Crofton, KM Dearlove, GE Li, A Moser, VC Newland, C Rossi, J Schantz, S Sette, W Sheets, L Stanton, M Tyl, S Sobotka, TJ AF Slikker, W Acuff, K Boyes, WK Chelonis, J Crofton, KM Dearlove, GE Li, A Moser, VC Newland, C Rossi, J Schantz, S Sette, W Sheets, L Stanton, M Tyl, S Sobotka, TJ TI Behavioral test methods workshop SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article; Proceedings Paper CT 29th Annual Meeting of the Neurobehavioral-Teratology-Society/24th Annual Meeting of the Behavioral-Toxicology-Society held in Conjunction with the 45th Annual Meeting of the Teratology-Society CY JUN 25-28, 2005 CL St Pete Beach, FL SP NeurobehavTeratol Soc, Behav Toxicol Soc, Teratol Soc DE behavior; dose-response; experimental design; safety assessment; test method selection; training; validation; control of confounds; data variability; data analysis; data interpretation and risk assessment ID HEALTH-RISK ASSESSMENT; DEVELOPMENTAL NEUROTOXICITY; RECOMMENDATIONS; TOXICOLOGY; EXPOSURE; BATTERY; DESIGN AB A one and a half day workshop on behavioral testing was conducted in order to discuss experimental procedures and practices that may help enhance the utility of behavioral data as a reliable index of neurotoxicity and in the safety evaluation of chemical substances. The workshop was open to participation by all sectors of the neuroscience community including academia, government, testing laboratories, and industry. The level of confidence with which changes in behavior can reliably signal adverse effects on the nervous system depends, in part, on the scientific quality of the data generated. With an emphasis on education and problem solving, the workshop focused on the practical aspects and scientific rationale underlying valid and high quality testing. In behavioral testing, there are numerous experimental factors that may impact on the quality of data. These include such elements as experimental design, selection of test methods, the care and precision in the conduct of behavioral testing, procedures to minimize bias and potential confounds, appropriateness of statistical analyses, and data interpretation. In plenary session investigators experienced in behavioral testing discussed the significance of these various experimental factors to data quality, outlined problematic issues, and presented a synopsis of approaches for addressing each of the factors as outlined in a draft of a primer developed by the Interagency Committee on Neurotoxicology (ICON). During the remainder of the workshop, open discussions in small breakout groups were used to address the problematic issues identified by the plenary speakers and explore alternative approaches for dealing with them. Finally, all workshop participants were reconvened in plenary session for summation of breakout group discussions and final recommendations. Information from the workshop was used to form the basis of this manuscript and will be used to help finalize a behavioral test methods primer being drafted by the ICON. The overall conclusions from the workshop were that consensus can be reached on the fundamentals of behavioral assessment, and that aspects of behavioral assessment including experimental design, test method selection, training, validation, control of confounds, data variability, data analysis, and data interpretation need to be carefully considered in the planning and conduct of behavioral safety assessments. (c) 2005 Elsevier Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, US FDA, Jefferson, AR 72079 USA. Procter & Gamble Co, Cincinnati, OH 45202 USA. US EPA, Washington, DC 20460 USA. Univ Arkansas, Little Rock, AR 72204 USA. Auburn Univ, Auburn, AL 36849 USA. Univ Illinois, Chicago, IL 60680 USA. Univ Delaware, Newark, DE 19716 USA. US FDA, CFSAN, Rockville, MD 20857 USA. RP Slikker, W (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, US FDA, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM wslikker@nctr.fda.gov RI Crofton, Kevin/J-4798-2015 OI Crofton, Kevin/0000-0003-1749-9971 NR 35 TC 15 Z9 15 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAY-JUN PY 2005 VL 27 IS 3 BP 417 EP 427 DI 10.1016/j.ntt.2005.02.003 PG 11 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 942GM UT WOS:000230270900005 PM 15939202 ER PT J AU Brorson, K Sofer, G Robertson, G Lute, S Martin, J Aranha, H Haque, M Satoh, S Yoshinari, K Moroe, I Morgan, M Yamaguchi, F Carter, J Krishnan, M Stefanyk, J Etzel, M Riorden, W Korneyeva, M Sundaram, S Wilkommen, H Wojciechowski, P AF Brorson, K Sofer, G Robertson, G Lute, S Martin, J Aranha, H Haque, M Satoh, S Yoshinari, K Moroe, I Morgan, M Yamaguchi, F Carter, J Krishnan, M Stefanyk, J Etzel, M Riorden, W Korneyeva, M Sundaram, S Wilkommen, H Wojciechowski, P TI "Large pore size" virus filter test method recommended by the PDA virus filter task force SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Article ID INVERTED TERMINAL REPEATS; MEMBRANE-FILTER; DNA-REPLICATION; PERFORMANCE; PARTICLES; PROTEIN; PR772 C1 US FDA, Div Monoclonal Antibodies, CDER, Bethesda, MD 20892 USA. GE Healthcare, Piscataway, NJ 08855 USA. PDA, Bethesda, MD 20814 USA. Pall Life Sci, E Hills, NY 11548 USA. Asahi Kasai Corp, Chiyoda Ku, Tokyo 1018481, Japan. Millipore Corp, Bedford, MA 01730 USA. Univ Wisconsin, Coll Engn, Madison, WI 53706 USA. Bayer Corp, Clayton, NC 27520 USA. Schering Plough Corp, Kenilworth, NJ 07033 USA. Clearant Europe GMBH, CH-4002 Basel, Switzerland. Centocor Inc, Malvern, PA 19355 USA. RP Aranha, H (reprint author), US FDA, Div Monoclonal Antibodies, CDER, 29 Lincoln Dr, Bethesda, MD 20892 USA. NR 27 TC 8 Z9 8 U1 0 U2 0 PU PARENTERAL DRUG ASSOC INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 620, BETHESDA, MD 20814 USA SN 1079-7440 J9 PDA J PHARM SCI TECH JI PDA J. Pharm. Sci. Technol. PD MAY-JUN PY 2005 VL 59 IS 3 BP 177 EP 186 PG 10 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA 939GC UT WOS:000230059500002 PM 16048117 ER PT J AU Spiridonov, NA Konovalov, DA Arkhipov, VV AF Spiridonov, NA Konovalov, DA Arkhipov, VV TI Cytotoxicity of some Russian ethnomedicinal plants and plant compounds SO PHYTOTHERAPY RESEARCH LA English DT Article DE Russia traditional medicine; medicinal plants; cancer; cytotoxicity; lymphoblastoid Raji cells ID PROTEIN-KINASE-C; INHIBITOR; CHELERYTHRINE; ANTITUMOR; EXTRACT; GROWTH; TUMOR; MICE AB The cytotoxic action of crude ethanol extracts from 61 plant species used in Russian ethnomedicine for alleviating symptoms of diseases in cancer patients was studied on cultured human lymphoblastoid Raji cells. Extracts from Chelidonium majus, Potentilla erecta, Chamaenerium angustfolium, Filipendula ulmaria and Inula helenium possessed marked cytotoxicity, suppressing the growth of the cells at concentrations of 10 and 50 mu g/mL. The cytotoxicity of purified active compounds from selected plant species was evaluated along with pharmaceutical antineoplastic drugs methotrexate, fluorouracil, cyclophosphamide and vinblastine. Sesquiterpene lactones helenin, telekin and artemisinin, aromatic polyacetylene capillin, and alkaloid preparation sanguirythrine suppressed cell growth at concentrations of 1-2 mu g/mL, which exceeds the cytotoxicity of cyclophosphamide and fluorouracil. Copyright (c) 2005 John Wiley & Sons, Ltd. C1 Russian Acad Sci, Inst Theoret & Expt Biophys, Pushchino 142292, Moscow Region, Russia. Pyatigorsk State Pharmaceut Acad, Pyatigorsk, Russia. RP Spiridonov, NA (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM-541,Bldg 29A,Room 3B-20,29 Lincoln Dr, Bethesda, MD 20892 USA. EM spiridonov@cber.fda.gov RI Spiridonov, Nikolay/B-6287-2014; OI Konovalov, Dmitry/0000-0002-0960-6127 NR 33 TC 41 Z9 50 U1 3 U2 19 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0951-418X J9 PHYTOTHER RES JI Phytother. Res. PD MAY PY 2005 VL 19 IS 5 BP 428 EP 432 DI 10.1002/ptr.1616 PG 5 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 960FN UT WOS:000231575700010 PM 16106386 ER PT J AU Gray, JE Archer, BR Butler, PF Hobbs, BB Mettler, FA Pizzutiello, RJ Schueler, BA Strauss, KJ Suleiman, OH Yaffe, MJ AF Gray, JE Archer, BR Butler, PF Hobbs, BB Mettler, FA Pizzutiello, RJ Schueler, BA Strauss, KJ Suleiman, OH Yaffe, MJ CA Am Assoc Physicists Med Tas Grp Re TI Reference values for diagnostic radiology: Application and impact SO RADIOLOGY LA English DT Article AB Reference values (RVs) are recommended by the American Association of Physicists in Medicine for four radiographic projections, computed tomography, fluoroscopy, and dental radiography. RVs are used to compare radiation doses from individual pieces of radiographic equipment with doses from similar equipment assessed in national surveys. RVs recommended by the American Association of Physicists in Medicine have been developed from the Nationwide Evaluation of X-ray Trends survey performed by the state radiation protection agencies with the cooperation and support of the U.S. Food and Drug Administration, the Conference of Radiation Control Program Directors, and the American College of Radiology. The RVs selected by the American Association of Physicists in Medicine represent, approximately, the 80th percentile of the survey distributions. Consequently, equipment exceeding the RVs is using higher radiation doses than is 80% of the equipment in the surveys. Radiation doses for specific projections, with standard phantoms, should be measured annually, as recommended by the American College of Radiology. When the RVs are exceeded, the medical physicist should investigate the cause and determine, in cooperation with the responsible radiologist, whether these doses are justified or the imaging system should be optimized to reduce patient radiation doses. RVs are a useful tool for comparing patient radiation doses at institutions throughout the United States and for providing information about radiographic equipment performance. (C) RSNA, 2005. C1 Baylor Coll Med, Houston, TX 77030 USA. Amer Coll Radiol, Reston, VA USA. Univ Western Ontario, London, ON, Canada. Univ New Mexico, Albuquerque, NM 87131 USA. Upstate Med Phys, Victor, NY USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. Childrens Hosp, Boston, MA 02115 USA. US FDA, Rockville, MD 20857 USA. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. RP Gray, JE (reprint author), 2 Sci Rd, Glenwood, IL 60425 USA. EM jgray@landauerinc.com NR 16 TC 70 Z9 72 U1 0 U2 2 PU RADIOLOGICAL SOC NORTH AMERICA PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523 USA SN 0033-8419 J9 RADIOLOGY JI Radiology PD MAY PY 2005 VL 235 IS 2 BP 354 EP 358 DI 10.1148/radiol.2352020016 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 918TT UT WOS:000228571200002 PM 15758190 ER PT J AU Gomatam, S Karr, AF Reiter, JP Sanil, AP AF Gomatam, S Karr, AF Reiter, JP Sanil, AP TI Data dissemination and disclosure limitation in a world without microdata: A risk-utility framework for remote access analysis servers SO STATISTICAL SCIENCE LA English DT Article DE data confidentiality; data utility; disclosure risk; microdata; regression server; remote access server; statistical disclosure limitation ID TABULAR DATA RELEASES; STATISTICAL DATABASES; CONFIDENTIALITY; SYSTEMS AB Given the public's ever-increasing concerns about data confidentiality, in the near future statistical agencies may be unable or unwilling, or even may not be legally allowed, to release any genuine microdata-data on individual units, such as individuals or establishments. In such a world, an alternative dissemination strategy is remote access analysis servers, to which users submit requests for output from statistical models fit using the data, but are not allowed access to the data themselves. Analysis servers, however, are not free from the risk of disclosure, especially in the face of multiple, interacting queries. We describe these risks and propose quantifiable measures of risk and data utility that can be used to specify which queries can be answered and with what output. The risk-utility framework is illustrated for regression models. C1 US FDA, Rockville, MD 20850 USA. Natl Inst Stat Sci, Res Triangle Pk, NC 27709 USA. Duke Univ, Inst Stat & Decis Sci, Durham, NC 27708 USA. Natl Inst Stat Sci, Res Triangle Pk, NC 27709 USA. RP Gomatam, S (reprint author), US FDA, Rockville, MD 20850 USA. EM svg@cdrh.fda.gov; karr@niss.org; jerry@stat.duke.edu; ashish@niss.org NR 40 TC 43 Z9 43 U1 1 U2 2 PU INST MATHEMATICAL STATISTICS PI BEACHWOOD PA PO BOX 22718, BEACHWOOD, OH 44122 USA SN 0883-4237 J9 STAT SCI JI Stat. Sci. PD MAY PY 2005 VL 20 IS 2 BP 163 EP 177 DI 10.1214/08834230500000043 PG 15 WC Statistics & Probability SC Mathematics GA 956DO UT WOS:000231279300008 ER PT J AU Lugovtsev, VY Vodeiko, GM Levandowski, RA AF Lugovtsev, VY Vodeiko, GM Levandowski, RA TI Mutational pattern of influenza B viruses adapted to high growth replication in embryonated eggs SO VIRUS RESEARCH LA English DT Article DE influenza B virus; adaptation; growth characteristics; genotype ID A-VIRUS; RNA-POLYMERASE; AMINO-ACID; EVOLUTIONARY PATTERN; NUCLEAR-LOCALIZATION; ANTIGENIC VARIANTS; REVERSE GENETICS; PB2 SUBUNIT; CAP-BINDING; VIRAL-RNA AB Improved replication Of influenza viruses in embryonated chicken eggs (CE) permits increased vaccine production and availability. We investigated the growth properties of influenza B viruses in relation to specific mutations occurring after serial passage in CE. In serial passage experiments yielding high growth variants of B/VictoriaJ504/2000, mutations predicted to alter amino acid (AA) composition occurred only near the receptor-binding pocket of the hemagglutinins (HA) and in no other genes. Two B/Victoria/504/2000 high growth variants had the same AA substitutions in HA (Rl62M and D196Y), but the higher yield variant had a third Substitution (G 14 1 E), which also altered antigenic characteristics. In a serial passage experiment yielding a high growth variant of B/Hong Kong/330/2001, mutations predicted to alter AA composition occur-red only in PB2 and NP in domains predicted to relate to RNP formation and function. Our results indicate that adaptation of influenza B viruses to high-yield replication by serial passage in CE requires few mutations either in internal or external genes. Specific modifications of genes or a combination of genes could be used to optimize or create influenza B viruses for specific growth substrates. (c) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Lugovtsev, VY (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM lugovtsev@cber.fda.gov NR 64 TC 14 Z9 15 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD MAY PY 2005 VL 109 IS 2 BP 149 EP 157 DI 10.1016/j.virusres.2004.11.016 PG 9 WC Virology SC Virology GA 912QZ UT WOS:000228095800005 PM 15763145 ER PT J AU Thorpe, SJ Fox, B Heath, A Dolman, C Virata, ML Yu, MW Thorpe, R AF Thorpe, SJ Fox, B Heath, A Dolman, C Virata, ML Yu, MW Thorpe, R TI International collaborative study to evaluate a candidate reference preparation to define an appropriate specified limit of anti-D in intravenous immunoglobulin products SO VOX SANGUINIS LA English DT Article DE anti-D; haemagglutination; IVIG; reference method; specification ID RH-D ACTIVITY AB Background and Objectives The aim of the study was to evaluate a lyophilized intravenous immunoglobulin (IVIG) preparation containing anti-D (02/228; nominal reciprocal titre of 8) for its suitability to define the maximum limit of anti-D in IVIG products when used in a proposed reference method of direct haemagglutination of papain-treated erythrocytes, in an international collaborative study. Materials and Methods Twenty laboratories tested 02/228 along with a negative control IVIG preparation and four IVIG samples containing different levels of anti-D. Nineteen laboratories performed direct haemagglutination methodology using papain-treated erythrocytes; five of these laboratories and one additional laboratory performed their in-house haemagglutination methodology (all indirect antiglobulin tests). Results The mode titre of 02/228, obtained by using the proposed reference method, was 8 (62.5% of tests). However, there was wide variation in haemagglutination titres between laboratories for three of the four samples. Correcting the titres of the samples relative to those of the proposed reference preparation reduced the interlaboratory variability and increased the frequency of the mode titres in three out of four samples. The indirect antiglobulin tests also showed wide interlaboratory variability and were less sensitive than the direct method in four laboratories. Eleven of the 14 laboratories that expressed an opinion considered that the level of anti-D in 02/228 was appropriate to define a specified limit. Conclusions Our results demonstrate the necessity of using a reference preparation to define the maximum level of anti-D in IVIG products and ensure sufficient sensitivity in haemagglutination testing methodology. On the basis of these results, members of the European Pharmacopoeia Expert Group 6B recommended revision of the appropriate monograph to include this new specification and test. The Food and Drug Administration in the USA intends to adopt the same maximal specification defined by the reference preparation and to recommend the same test for the safety of IVIG products. Preparations 02/228 and 02/226 were also established by the World Health Organization as International Reference Reagents to standardize haemagglutination testing for anti-D in normal IVIG products. C1 Natl Inst Biol Stand & Controls, Div Haematol, Potters Bar EN6 3QG, Herts, England. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Thorpe, R (reprint author), Natl Inst Biol Stand & Controls, Div Haematol, Blanche Lane, Potters Bar EN6 3QG, Herts, England. EM sthorpe@nibsc.ac.uk RI Thorpe, Susan/E-1808-2013; Dolman, Carl/E-2485-2013; Fox, Bernard/E-2523-2013; Thorpe, Robin/E-6853-2013 OI Dolman, Carl/0000-0002-7774-6375; NR 7 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD MAY PY 2005 VL 88 IS 4 BP 278 EP 287 DI 10.1111/j.2005.1423-0410.00622.x PG 10 WC Hematology SC Hematology GA 924JK UT WOS:000228974900009 PM 15877651 ER PT J AU Coste, J Reesink, HW Engelfriet, CP Laperche, S Brown, S Busch, MP Cuijpers, HT Elgin, R Ekermo, B Epstein, JS Flesland, O Heier, HE Henn, G Hernandez, JM Hewlett, IK Hyland, C Keller, AJ Krusius, T Levicnik-Stezina, S Levy, G Lin, CK Margaritis, AR Muylle, L Neiderhauser, C Pastila, S Pillonel, J Pineau, J van der Poel, CL Politis, C Roth, WK Sauleda, S Seed, CR Sondag-Thull, D Stramer, SL Strong, M Vamvakas, EC Velati, C Vesga, MA Zanetti, A AF Coste, J Reesink, HW Engelfriet, CP Laperche, S Brown, S Busch, MP Cuijpers, HT Elgin, R Ekermo, B Epstein, JS Flesland, O Heier, HE Henn, G Hernandez, JM Hewlett, IK Hyland, C Keller, AJ Krusius, T Levicnik-Stezina, S Levy, G Lin, CK Margaritis, AR Muylle, L Neiderhauser, C Pastila, S Pillonel, J Pineau, J van der Poel, CL Politis, C Roth, WK Sauleda, S Seed, CR Sondag-Thull, D Stramer, SL Strong, M Vamvakas, EC Velati, C Vesga, MA Zanetti, A TI Implementation of donor screening for infectious agents transmitted by blood by nucleic acid technology: update to 2003 SO VOX SANGUINIS LA English DT Article ID ANTI-HBC; HBSAG; NAT C1 Sanquin Blood Bank NW, NL-1006 AC Amsterdam, Netherlands. R&D Agents TRansmissibles Transfus, EFS Pyrenees Mediterranee Lab, F-34000 Montpellier, France. Sanquin Diagnost Serv, NL-1006 AC Amsterdam, Netherlands. Sanquin Res, NL-1006 AC Amsterdam, Netherlands. Inst Natl Transfus Sanguine, Ctr Natl Reference Hepatites B & C Transfus, F-75739 Paris, France. Australian Red Cross Blood Serv, Brisbane, Qld, Australia. Blood Donat Ctr Vienna, A-1040 Vienna, Austria. Dienst Bloed Rode Kruis Vlaanderen, B-4800 Mechelen, Belgium. Red Cross, Blood Transfus Serv, B-4020 Liege, Belgium. Canadian Blood Serv, Med Sci & Res Affairs, Ottawa, ON K1G 4J5, Canada. Finnish Red Cross & Blood Transfus Serv, Blood & Blood Components Kivihaantie, F-00310 Helsinki, Finland. R&D Agents Transfus Etab Francais Sang Pyrenees M, F-34094 Montpellier, France. Inst Natl Transfus Sanguine, Ctr Natl Reference Hepatites B & C TRansfus, Dept Agents Transmissibles Sang, F-75015 Paris, France. InVS, F-94415 St Maurice, France. DRK Blutspendedienst Baden Wurttemberg Hessen, D-60528 Frankfurt, Germany. Gen Athens Hosp G Gennimatas, Reg Blood Transfus Ctr 3, G-11527 Athens, Greece. Hong Kong Red Cross Blood Transfus Serv, Kowloon, Hong Kong, Peoples R China. Sondrio Hosp, Transfus Med & Haematol Dept, I-23100 Sondrio, Italy. Univ Milan, Inst Virol, I-20133 Milan, Italy. Sanquin Diagnost Serv, NL-1066 AD Amsterdam, Netherlands. Sanquin Blood Supply Fdn, NL-1006 AN Amsterdam, Netherlands. Natl Hosp Norway, Univ Hosp, Inst Immunol, N-0027 Oslo, Norway. Univ Oslo, Ulleval Hosp, Dept Immunol & Transfus Med, N-0407 Oslo, Norway. Blood Transfus Ctr Slovenia, Ctr Testing Blood Blood Donors, SI-1000 Ljubljana, Slovenia. Ctr TRansfus I Banc Teixits, E-08035 Barcelona, Spain. Ctr Vasco Transfus & Tejidos Humanos, E-48960 Galdakao Vizcaya, Spain. Linkoping Univ Hosp, Dept Transfus Med, SE-58185 Linkoping, Sweden. Blood Transfus Serv SRC, CH-3001 Bern, Switzerland. RBTS Bern Ag, Reference Lab BTS SRC, CH-3001 Bern, Switzerland. Natl Blood Serv, London NW9 5BG, England. Blood Syst Res Inst, San Francisco, CA USA. Amer Red Cross, Gaithersburg, MD USA. Puget Sound Blood Ctr, Seattle, WA 98104 USA. US FDA, Rockville, MD 20857 USA. RP Coste, J (reprint author), Sanquin Blood Bank NW, POB 9137, NL-1006 AC Amsterdam, Netherlands. EM joliette.coste@efs.sante.fr; h.reesink@sanquin.nl; p.engelfriet@sanquin.nl; slaperche@ints.fr; mpbusch@itsa.ucsf.edu; t.cuijpers@sanquin.nl; roger.eglin@nbs.nhs.uk; bengt.ekermo@lio.se; oystein.flesland@rikshospitalet.no; hanserik.heier@ulleval.no; gabriela.henn@roteskreuz.at; jmhernandez@vhebron.net; chyland@arcbs.redcross.org.au; tom.krusius@bts.redcross.fi; snezna.levicnik@ztm.si; guy.levy@redcross.ch; cklin@ha.org.hk; ludo.muylle@rodekruis.be; j.pillonel@invs.sante.fr; c.vanderpoel@sanquin.nl; cpolitis@hol.gr; d.sondag@redcross.be; stramers@usa.redcross.org; stephen.vamvakas@bloodservices.ca; claudio.velati@katamail.com; mvesga@hgda.osakidtza.net; alessandro.zanetti@unimi.it OI Seed, Clive/0000-0002-0234-4507 NR 9 TC 87 Z9 92 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD MAY PY 2005 VL 88 IS 4 BP 289 EP 298 DI 10.1111/j.1423-0410.2005.00636_1.x PG 10 WC Hematology SC Hematology GA 924JK UT WOS:000228974900011 PM 15877653 ER PT J AU Busch, MP Stramer, SL Strong, DM Hewlett, IK Epstein, JS AF Busch, MP Stramer, SL Strong, DM Hewlett, IK Epstein, JS TI Implementation of donor screening for infectious agents transmitted by blood by nucleic acid technology: update to 2003 SO VOX SANGUINIS LA English DT Article ID ANTI-HBC; HBSAG; RISK; HCV C1 Blood Syst Res Inst, San Francisco, CA USA. Amer Red Cross, Gaithersburg, MD USA. Puget Sound Blood Ctr, Seattle, WA 98104 USA. US FDA, Rockville, MD 20857 USA. RP Busch, MP (reprint author), Blood Syst Res Inst, San Francisco, CA USA. EM mpbusch@itsa.ucsf.ed NR 8 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD MAY PY 2005 VL 88 IS 4 BP 298 EP 301 DI 10.1111/j.1423-0410.2005.00636_2.x PG 4 WC Hematology SC Hematology GA 924JK UT WOS:000228974900012 ER PT J AU Moon, H Ahn, H Kodell, RL AF Moon, H Ahn, H Kodell, RL TI An age-adjusted bootstrap-based Poly-k test SO STATISTICS IN MEDICINE LA English DT Article DE bioassay; competing risk; single sacrifice; survival-adjusted test; trend test ID ANIMAL CARCINOGENICITY; BIOASSAYS; MORTALITY AB The assumption of an asymptotic normal distribution of some test statistics may be invalid in certain dose-response trend tests. For instance, the survival-adjusted Cochran-Armitage test, known as the Poly-k test, is asymptotically standard normal under the null hypothesis. However, the asymptotic normality is not valid if there is a deviation from the tumour onset distribution that is assumed in this test or if the competing risks survival rates differ across groups. We develop an age-adjusted bootstrap-based method to assess the significance of assumed asymptotic normal tests for animal carcinogenicity data. The proposed method differs from conventional bootstrap methods in the aspect of preserving the mortality rate in each dose group under the null hypothesis of equal tumour incidence rates among the groups. We investigate an empirical distribution of the Poly-3 (P3) trend test statistic using the proposed age-adjusted bootstrap-based method and compare it with the P3 test statistic referenced to the assumed standard normal distribution. A simulation study is conducted to evaluate the robustness of these tests to various Weibull-family tumour onset distributions. The proposed method is applied to National Toxicology Program data sets to evaluate a dose-related trend of a test substance on the incidence of neoplasms. Published in 2004 by John Wiley T Sons, Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. RP Moon, H (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM hmoon@nctr.fda.gov FU NCI NIH HHS [1 R29 CA77289-06] NR 25 TC 5 Z9 5 U1 0 U2 3 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 APR 30 PY 2005 VL 24 IS 8 BP 1233 EP 1244 DI 10.1002/sim.1967 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 915BF UT WOS:000228271900007 PM 15573413 ER PT J AU Nutan, MTH Soliman, MS Taha, EI Khan, MA AF Nutan, MTH Soliman, MS Taha, EI Khan, MA TI Optimization and characterization of controlled release multi-particulate beads coated with starch acetate SO INTERNATIONAL JOURNAL OF PHARMACEUTICS LA English DT Article DE starch acetate; multi-particulate coated beads; Box-Behnken optimization design; controlled release; excipient compatibility; mathematical modeling ID DRUG-RELEASE; PELLETS; COATINGS; SURFACE; POLYMER AB The objectives of the present study were (1) to model the effects of process and formulation variables on in vitro release profile of a model drug dyphylline from multi-particulate beads coated with starch acetate (SA); (2) to validate the models using R-2 and tack of fit values: (3) to optimize the formulation by response surface methodology (RSM); (4) to characterize the optimized product by thermal. X-ray and infrared spectroscopic analyses. Dyphylline loaded inert beads were coated using organic solution of SA with high degree of substitution. A three-factor, three-level Box-Behnken design was used for the optimization procedure with coating weight gain (X-1), plasticizer concentration (X-2) and curing temperature (X-3) as the independent variables. The regression equation generated for Y-5 (cumulative percent drug released after 12 h) was Y-5 = 89.83 - 11.98X(1), + 2.82X(2), - 4.31X(1)(2) + 1.90X(1)X(2) Optimization was done by maximizing drug release in 12 In and placing constraints at dissolution time points of 0.5, 1, 4 and 8 h. The drug, release data of the optimized product were close to that predicted by the model. The models could explain 99% of variability in responses. Thermal, X-ray and infrared analyses suggested absence of any significant interaction of the drug with the excipients used in the formulation. SEM photographs showed the integrity of the coating layer. (c) 2005 Elsevier B.V. All rights reserved. C1 Texas Tech Univ, Sch Pharm, Dept Pharmaceut Sci, Ctr Hlth Sci, Amarillo, TX USA. RP Khan, MA (reprint author), DPQR, CDER, FDA, Life Sci Bldg 64, Silver Spring, MD 20993 USA. EM KhanM@cder.fda.gov NR 33 TC 17 Z9 23 U1 0 U2 7 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 APR 27 PY 2005 VL 294 IS 1-2 BP 89 EP 101 DI 10.1016/j.ijpharm.2005.01.013 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 920FU UT WOS:000228675600008 PM 15814233 ER PT J AU Bolan, R Amezola, P Kerndt, P Soreth, J Taylor, M Heffelfinger, J Weinstock, H Greenberg, M Janowski, M AF Bolan, R Amezola, P Kerndt, P Soreth, J Taylor, M Heffelfinger, J Weinstock, H Greenberg, M Janowski, M CA CDC TI Inadvertent use of Bicillin (R) C-R to treat syphilis infection - Los Angeles, California, 1999-2004 (Reprinted from MMWR, vol 54, pg 217-219, 2005) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID CLINICAL MANIFESTATIONS; HIV C1 Los Angeles Gay & Lesbian Ctr, Los Angeles, CA USA. Los Angeles Cty Dept Hlth Serv, Los Angeles, CA USA. US FDA, Rockville, MD 20857 USA. CDC, Div STD Prevent, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. RP Bolan, R (reprint author), Los Angeles Gay & Lesbian Ctr, Los Angeles, CA USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 27 PY 2005 VL 293 IS 16 BP 1967 EP 1968 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 919XS UT WOS:000228651500008 ER PT J AU Maisel, WH AF Maisel, WH TI Report from the meeting of the Circulatory System Devices Panel of the Food and Drug Administration Center for Devices and Radiologic Health - September 21, 2004 SO CIRCULATION LA English DT Article DE United States Food and Drug Administration; cardiopulmonary resuscitation; hypothermia; device approval; heart arrest C1 Brigham & Womens Hosp, Div Cardiovasc, Boston, MA 02115 USA. US FDA, Circulatory Syst Devices Panel, Washington, DC 20204 USA. RP Maisel, WH (reprint author), Brigham & Womens Hosp, Div Cardiovasc, 75 Francis St, Boston, MA 02115 USA. EM wmaisel@partners.org NR 0 TC 2 Z9 2 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 APR 26 PY 2005 VL 111 IS 16 BP 2143 EP 2145 DI 10.1161/01.CIR.0000162928.65553.0A PG 3 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 920BA UT WOS:000228660800019 PM 15851621 ER PT J AU Turesky, RJ Taylor, J Schnackenberg, L Freeman, JP Holland, RD AF Turesky, RJ Taylor, J Schnackenberg, L Freeman, JP Holland, RD TI Quantitation of carcinogenic heterocyclic aromatic amines and detection of novel heterocyclic aromatic amines in cooked meats and grill scrapings by HPLC/ESI-MS SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE heterocyclic aromatic amines; mutagens; LC/MS ID TANDEM MASS-SPECTROMETRY; LIQUID-CHROMATOGRAPHY; COLORECTAL-CANCER; FOOD-PRODUCTS; MODEL SYSTEMS; BEEF; QUANTIFICATION; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; COOKING; RISK AB A tandem solid-phase extraction method was used to isolate carcinogenic heterocyclic aromatic amines (HAAs) from cooked meats. The following 10 HAAs were identified by HPLC/ESI-MS/MS: 2-amino-9H-pyrido[2,3-b]indole (2-A alpha C), 2-amino-3-methyl-9H-pyrido[2,3-b]indole (MeA alpha C), 2-amino-3-methylimidazo[4,5-f]quinoline (IQ), 2-amino-3-methylimidazo[4,5-f]quinoxaline (IQx), 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MelQx), 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline (4,8-DiMelQx), 2-amino-3,7,8-trimethylimidazo[4,5-f]quinoxaline (7,8-DiMelQx), 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 2-amino-1,7,9-trimethylimidazo[4,5-g]quinoxaline (7,9-DiMelgQx), and 2-amino-1-methylimidazo[4,5-b]quinoline (10[4,5-b]); the latter HAA has not previously been reported in cooked meats. The concentrations of these HAAs ranged from < 0.03 to 15 ppb in cooked meats and poultry, to 75 ppb in cooked beef extract, and to 85 ppb in grill scrapings. The product ion scan mode was used to confirm the identities of these HAAs. Six other compounds were detected that appear to contain the N-methylimidazoquinoxaline skeleton on the basis of their product ion spectra, and these compounds are probable isomers of IQx, 8-MelQx, and DiMelQx. A number of known HAAs and novel HAAs of unknown genotoxic potential are formed at appreciable levels in cooked meats. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Turesky, RJ (reprint author), Wadsworth Ctr, NYS Dept Hlth, Div Environm Dis Prevent, Empire State Pl,POB 509, Albany, NY 12201 USA. EM Rturesky@wadsworth.org NR 36 TC 57 Z9 60 U1 2 U2 17 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 APR 20 PY 2005 VL 53 IS 8 BP 3248 EP 3258 DI 10.1021/jf048290g PG 11 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 916TH UT WOS:000228408600066 PM 15826085 ER PT J AU Tsai, CA Wang, SJ Chen, DT Chen, JJ AF Tsai, CA Wang, SJ Chen, DT Chen, JJ TI Sample size for gene expression microarray experiments SO BIOINFORMATICS LA English DT Article ID POWER AB Motivation: Microarray experiments often involve hundreds or thousands of genes. In a typical experiment, only a fraction of genes are expected to be differentially expressed; in addition, the measured intensities among different genes may be correlated. Depending on the experimental objectives, sample size calculations can be based on one of the three specified measures: sensitivity, true discovery and accuracy rates. The sample size problem is formulated as: the number of arrays needed in order to achieve the desired fraction of the specified measure at the desired family-wise power at the given type I error and (standardized) effect size. Results: We present a general approach for estimating sample size under independent and equally correlated models using binomial and beta-binomial models, respectively. The sample sizes needed for a two-sample z-test are computed; the computed theoretical numbers agree well with the Monte Carlo simulation results. But, under more general correlation structures, the beta-binomial model can underestimate the needed samples by about 1-5 arrays. C1 US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biometr 2, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Alabama, Biostat & Bioinformat Unit, Birmingham, AL 35294 USA. RP Chen, JJ (reprint author), US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov OI Tsai, Chen-An/0000-0002-7490-4331 NR 13 TC 35 Z9 36 U1 1 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1367-4803 J9 BIOINFORMATICS JI Bioinformatics PD APR 15 PY 2005 VL 21 IS 8 BP 1502 EP 1508 DI 10.1093/bioinformatics/bti162 PG 7 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 916QX UT WOS:000228401800033 PM 15564298 ER PT J AU Ottinger, MA Wu, JM Hazelton, JL Abdelnabi, MA Thompson, N Quinn, ML Donoghue, D Schenck, F Ruscio, M Beavers, J Jaber, M AF Ottinger, MA Wu, JM Hazelton, JL Abdelnabi, MA Thompson, N Quinn, ML Donoghue, D Schenck, F Ruscio, M Beavers, J Jaber, M TI Assessing the consequences of the pesticide methoxychlor: neuroendocrine and behavioral measures as indicators of biological impact of an estrogenic environmental chemical SO BRAIN RESEARCH BULLETIN LA English DT Article; Proceedings Paper CT 2nd International Meeting on Steroids and the Nervous System CY FEB 22-26, 2003 CL Turin, ITALY SP Serono Fdn DE neuroendocrine systems; sexual behavior; Estrogens; Japanese quail ID COTURNIX-COTURNIX-JAPONICA; MALE JAPANESE QUAIL; SEXUAL-DIFFERENTIATION; EMBRYONIC-DEVELOPMENT; STEROID-HORMONES; I RELEASE; ESTRADIOL; EXPOSURE; DIETHYLSTILBESTROL; PLASMA AB Japanese quail provide an advantageous avian model for assessing long-term biological consequences of endocrine disrupting chemicals (EDCs). These studies examined route of exposure and vulnerability to biological impact of EDCs over the life cycle in a precocial avian model, the Japanese quail. Embryonic exposure occurs with maternal deposition and methoxychlor, (MXC) accumulated with maternal exposure. Egg injections of MXC or estradiol at selected stages of development impacted hypothalamic neuroendocrine systems in hatchlings and affected sexual maturation, with evidence for long-term effects on neurotransmitters and male behavior. Two-generation dietary studies were conducted to examine transgenerational effects of EDCs. Adult quail (P 1) were exposed to dietary MXC (0,0.5 and 5 ppm), with continued exposure in their offspring (F1), and control diet for all F2 chicks. Toxicological end points, including fertility, hatching success, and 14-day viability were unaffected. F1 and F2 male offspring from MXC-treated pairs MXC had impaired mating behavior and altered plasma hormones. These studies confirm neuroendocrine and behavioral measures as reliable indices of exposure to an estrogenic EDC. Moreover, maternal deposition remains a primary route of EDC exposure, with potential deleterious consequences for field birds, especially precocial species that appear to be particularly sensitive to embryonic EDC exposure. (c) 2004 Elsevier Inc. All rights reserved. C1 Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. Univ Arkansas, Dept Poultry Sci, Fayetteville, AR 72701 USA. US FDA, SE Reg Lab, Atlanta, GA USA. Wildlife Int Ltd, Easton, MD USA. RP Ottinger, MA (reprint author), Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. EM maotting@umd.edu NR 45 TC 22 Z9 24 U1 0 U2 10 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0361-9230 J9 BRAIN RES BULL JI Brain Res. Bull. PD APR 15 PY 2005 VL 65 IS 3 BP 199 EP 209 DI 10.1016/j.brainresbull.2004.11.019 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 919KJ UT WOS:000228616600004 PM 15811582 ER PT J AU Shirota, H Gursel, I Gursel, M Klinman, DM AF Shirota, H Gursel, I Gursel, M Klinman, DM TI Suppressive oligodeoxynucleotides protect mice from lethal endotoxic shock SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INDUCED IMMUNE ACTIVATION; STIMULATORY CPG MOTIFS; INTERFERON-GAMMA; GENE-EXPRESSION; BACTERIAL-DNA; INDUCED ARTHRITIS; B-CELLS; LIPOPOLYSACCHARIDE; MURINE AB Endotoxic shock is a life-threatening condition caused by exposure to bacterial LPS. LPS triggers the release of acute phase, proinflammatory, and Th1 cytokines that facilitate the development of endotoxic shock. Synthetic oligodeoxynucleotides (ODN) expressing suppressive TTAGGG motifs effectively down-regulate the production of proinflammatory and Th1 cytokines elicited by a variety of immune stimuli. The current results demonstrate that suppressive ODN protect mice from LPS-induced endotoxic shock. Underlying this protective effect is the ability of suppressive ODN to bind to and prevent the phosphorylation of STAT1 and STAT4, thereby blocking the signaling cascade mediated by LPS-induced IFN-beta and IL-12. These findings suggest that suppressive ODN might be of use in the treatment of endotoxic shock. C1 USDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), USDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A,Room 3D 10, Bethesda, MD 20892 USA. EM klinman@cber.fda.gov RI Gursel, Mayda /H-1812-2012; OI Gursel, Ihsan/0000-0003-3761-1166 NR 42 TC 60 Z9 72 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2005 VL 174 IS 8 BP 4579 EP 4583 PG 5 WC Immunology SC Immunology GA 914NN UT WOS:000228234600019 PM 15814679 ER PT J AU Foley, JF Yu, CR Solow, R Yacobucci, M Peden, KWC Farber, JM AF Foley, JF Yu, CR Solow, R Yacobucci, M Peden, KWC Farber, JM TI Roles for CXC chemokine ligands 10 and 11 in recruiting CD4(+) T cells to HIV-1-infected monocyte-derived macrophages, dendritic cells, and lymph nodes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; IFN-GAMMA; INTERFERON-GAMMA; ALPHA-CHEMOATTRACTANT; INDUCIBLE PROTEIN-10; RECEPTOR EXPRESSION; HIV-1 INFECTION; RHESUS MACAQUES; GENE-EXPRESSION; IN-VITRO AB We investigated roles for chemoattractants; in dissemination of HIV-1 by examining the induction of T cell-active chemokines in HIV-1-infected human monocyte-derived macrophages and dendritic cells. Of the 12 chemokines analyzed, mRNAs for two, CXCL10 and CXCL11, ligands for the chemokine receptor CXCR3, were up-regulated in both cell types upon infection by HIV-1. Induction of these chemokine genes in infected cultures was dependent on both viral entry and reverse transcriptase activity, but not on the HIV-1 envelope glycoprotein. Conditioned medium from infected cells was chemotactic for freshly isolated human CD4(+) T cells, and chemotaxis was abolished by pretreatment with an Ab against CXCR3. A lymph node from an HIV-1-infected individual expressed CXCL10 and CXCL11 mRNAs in the paracortex, including venules, as detected by in situ hybridization, whereas neither mRNA was detected after highly active antiretroviral therapy. Because CCR5 on CD4(+) T cells is found predominantly on cells that also express CXCR3, these data implicate CXCL10 and CXCL11 in the recruitment of susceptible T cells to HIV-1-infected lymph nodes, macrophages, and dendritic cells. This recruitment might enhance the sequestration of T cells in infected lymphoid organs and the spread of infection between cells, contributing to the immunopathology of AIDS. C1 Natl Inst Allergy & Infect Dis, Lab Mol Immunol, Bethesda, MD 20892 USA. Ctr Biol Evaluat & Res Food & Durg Adm, Lab Retrovirus Res, Bethesda, MD 20892 USA. RP Farber, JM (reprint author), Natl Inst Allergy & Infect Dis, Lab Mol Immunol, Bldg 10,Room 11N288,MSC 1888, Bethesda, MD 20892 USA. EM peden@cber.fda.gov NR 62 TC 36 Z9 36 U1 4 U2 6 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2005 VL 174 IS 8 BP 4892 EP 4900 PG 9 WC Immunology SC Immunology GA 914NN UT WOS:000228234600056 PM 15814716 ER PT J AU Fang, H Cordoba-Rodriguez, R Lankford, CSR Frucht, DM AF Fang, H Cordoba-Rodriguez, R Lankford, CSR Frucht, DM TI Anthrax lethal toxin blocks MAPK kinase-dependent IL-2 production in CD4(+) T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID ANTIGEN RECEPTOR; FACTOR CLEAVES; TYROSINE/THREONINE PHOSPHORYLATION; CULTURED MACROPHAGES; ADAPTIVE IMMUNITY; N-TERMINUS; RELEASE; IDENTIFICATION; LYMPHOCYTES; APOPTOSIS AB Anthrax lethal toxin (LT) is a critical virulence factor that cleaves and inactivates MAPK kinases (MAPKKs) in host cells and has been proposed as a therapeutic target in the treatment of human anthrax infections. Despite the potential use of anti-toxin agents in humans, the standard activity assays for anthrax LT are currently based on cytotoxic actions of anthrax LT that are cell-, strain-, and species-specific, which have not been demonstrated to occur in human cells. We now report that T cell proliferation and IL-2 production inversely correlate with anthrax LT levels in human cell assays. The model CD4(+) T cell tumor line, Jurkat, is a susceptible target for the specific protease action of anthrax LT. Anthrax LT cleaves and inactivates MAPKKs in Jurkat cells, whereas not affecting proximal or parallel TCR signal transduction pathways. Moreover, anthrax LT specifically inhibits PMA/ ionomycin- and anti-CD3-induced IL-2 production in Jurkat cells. An inhibitor of the protease activity of anthrax LT completely restores IL-2 production by anthrax LT-treated Jurkat cells. Anthrax LT acts on primary CD4(+) T cells as well, cleaving MAPKKs and leading to a 95 % reduction in anti-CD3-induced proliferation and IL-2 production. These findings not only will be useful in the development of new human cell-based bioassays for the activity of anthrax LT, but they also suggest new mechanisms that facilitate immune evasion by Bacillus anthracis. Specifically, anthrax LT inhibits IL-2 production and proliferative responses in CD4(+) T cells, thereby blocking functions that are pivotal in the regulation of immune responses. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Frucht, DM (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Div Monoclonal Antibodies, Bldg 29B Room 3NN22, Bethesda, MD 20892 USA. EM frucht@cber.fda.gov NR 29 TC 51 Z9 54 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 15 PY 2005 VL 174 IS 8 BP 4966 EP 4971 PG 6 WC Immunology SC Immunology GA 914NN UT WOS:000228234600065 PM 15814725 ER PT J AU Cieslak, J Ausin, C Chmielewski, MK Kauffman, JS Snyder, J Del-Grosso, A Beaucage, SL AF Cieslak, J Ausin, C Chmielewski, MK Kauffman, JS Snyder, J Del-Grosso, A Beaucage, SL TI P-31 NMR study of the desulfurization of oligonucleoside phosphorothioates effected by "aged" trichloroacetic acid solutions SO JOURNAL OF ORGANIC CHEMISTRY LA English DT Article ID PHOSPHATE/THIOPHOSPHATE PROTECTING GROUP; SULFUR-TRANSFER REAGENT; SOLID-PHASE SYNTHESIS; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; OLIGODEOXYRIBONUCLEOTIDES AB When employing phosphoramidites 1a-d in the solid-phase synthesis of oligonucleoside phosphorothioates, the thermolytic 2-[N-methyl-N-(2-pyridyl)] aminoethyl thiophosphate protecting group is lost to a large extent during the course of the synthesis. The resulting phosphorothioate diesters are then substantially desulfurized upon recurring exposure to a commercial solution of deblocking reagent during chain assembly. This problem is caused by the secondary decomposition product(s) of the reagent and is alleviated by using a fresh solution of the deblocking reagent prepared from solid trichloroacetic acid. C1 US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & review, Rockville, MD 20852 USA. Lancester Labs, Lancaster, PA 17605 USA. RP Beaucage, SL (reprint author), US FDA, Div Therapeut Prot, Ctr Drug Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM beaucage@cber.fda.gov NR 14 TC 6 Z9 6 U1 1 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0022-3263 J9 J ORG CHEM JI J. Org. Chem. PD APR 15 PY 2005 VL 70 IS 8 BP 3303 EP 3306 DI 10.1021/jo050035n PG 4 WC Chemistry, Organic SC Chemistry GA 916EB UT WOS:000228367100055 PM 15823001 ER PT J AU Bala, S Weaver, J Hastings, KL AF Bala, S Weaver, J Hastings, KL TI Clinical relevance of preclinical testing for allergic side effects SO TOXICOLOGY LA English DT Article; Proceedings Paper CT Drug Hypersensitivity Meeting 2004 CY MAY 05-08, 2004 CL Bern, SWITZERLAND DE drug; hypersensitivity; allergy; immune; systemic; contact; respiratory; animal models; preclinical testing; biomarkers ID LYMPH-NODE ASSAY; FLOW-CYTOMETRY; CELL-PROLIFERATION; HYPERSENSITIVITY; EXPRESSION; IRRITANT; MICE; CHEMICALS; RESPONSES; PROFILES AB Immune-mediated hypersensitivity reactions include exaggerated Immoral or cell mediated responses to specific antigens and may culminate in adverse, potentially life threatening effects. The immune status of the host and presence of infections or other disorders can alter the kind and extent of immune mediated side effects in individuals. Such variability in the immune status may influence the type of idiosyncratic reaction(s) that patients manifest. The issues typically encountered from a drug development standpoint include the potential for contact hypersensitivity, respiratory sensitivity, systemic hypersensitivity, photoallergy, and pseudoallergy. There are no accepted in vitro or in vivo models available to measure and predict all types of hypersensitivity reactions in humans. There is a need for the development of preclinical models to predict all types of hypersensitivity reactions in humans. The FDA immunotoxicology guidance document recommends doing preclinical testing in animal models for topical and inhalational drugs before initiation of multiple dose studies in humans. Any signs of potential immune related drug hypersensitivity should be further evaluated in an attempt to further understand the potential for hypersensitivity reactions in humans. In summary, existing preclinical models have limited capability for prediction of drug allergy in humans except for topical and inhalational drugs. Additional tools are needed to evaluate drugs in early development and improve performance of existing assays. Published by Elsevier Ireland Ltd. C1 US FDA, CDER, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. US FDA, CDER, Div Appl Pharmacol Res, Off Testing & Res, Rockville, MD 20857 USA. US FDA, CDER, Off New Drugs, Rockville, MD 20857 USA. RP Bala, S (reprint author), US FDA, CDER, Div Special Pathogen & Immunol Drug Prod, 5600 Fishers Lane, Rockville, MD 20857 USA. EM balas@cder.fda.gov NR 25 TC 11 Z9 14 U1 0 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD APR 15 PY 2005 VL 209 IS 2 SI SI BP 195 EP 200 DI 10.1016/j.tox.2004.12.030 PG 6 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 917BC UT WOS:000228429800019 PM 15767036 ER PT J AU Deszo, EL Steenbergen, SM Freedberg, DI Vimr, ER AF Deszo, EL Steenbergen, SM Freedberg, DI Vimr, ER TI Escherichia coli K1 polysialic acid O-acetyltransferase gene, neuO, and the mechanism of capsule form variation involving a mobile contingency locus SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE Escherichia coli K1 form variation; polysialic acid capsule acetylation; N-acetylneuraminic acid; lysogenic bacteriophage ID SIALIC-ACID; NUCLEOTIDE-SEQUENCE; ENDO-N; EVOLUTION; POLYSACCHARIDE; ACETYLATION; ADAPTATION; PROTEINS; BACTERIA; IDENTIFICATION AB Potential O-acetylation of the sialic acid residues of Escherichia coli K1, groups W-135, Y, and C meningococci, and group B Streptococcus capsular polysaccharides modifies their immunogenicity and susceptibility to glycosidases. Despite the biological importance of O-acetylation, no sialic or polysialic acid O-acetyltransferase has been identified in any system. Here we show that the E. coli K1 O-acetyltransferase encoded by neuO is genetically linked to the endo-neuraminidase tail protein gene of a chromosomal accretion element, designated CUS-3, with homology to lambdoid bacteriophage. Molecular epidemiological analysis established concordance between O-acetyltransferase and CUS-3 in a set of E. coli K1 strains. Deleting neuO eliminated enzymatic activity, which was restored by complementation in trans, and confirmed by C-13-NMR analysis of the acetylated product. Analysis of mutants that accumulate intracellular polysialic acid because of export defects (kpsM and kpsS) or an inability to synthesize the sialic acid precursor, N-acetylmannosamine (neuC), indicated that NeuO does not require constant association with its substrate for activity. DNA sequencing and PCR analysis of neuO from strains that had undergone random capsule form variation showed that slip strand DNA mispairing or unequal recombination resulted in gain or loss of (5'-AAGACTC-3')(n) heptanucleoticle repeats (where n approximate to 14-39) located in the neuO 5' region. These repeats code for a previously undescribed structure designated the poly(Psi) motif. The unexpected discovery of the neuO contingency locus (hypervariable gene controlling expression of a surface epitope) in E. coli, and of a potential phage for redistributing variant neuO alleles, provides a robust system for investigating the functions of localized hypermutability in pathogen evolution. C1 Univ Illinois, Dept Pathobiol, Lab Sialobiol, Urbana, IL 61802 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD 20892 USA. RP Vimr, ER (reprint author), Univ Illinois, Dept Pathobiol, Lab Sialobiol, Urbana, IL 61802 USA. EM ervimr@uiuc.edu FU NIAID NIH HHS [2R01 AI 42015-06, R01 AI042015] NR 47 TC 53 Z9 54 U1 2 U2 8 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD APR 12 PY 2005 VL 102 IS 15 BP 5564 EP 5569 DI 10.1073/pnas.0407428102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 916HS UT WOS:000228376600050 PM 15809431 ER PT J AU Venable, RM Delaglio, F Norris, SE Freedberg, DI AF Venable, RM Delaglio, F Norris, SE Freedberg, DI TI The utility of residual dipolar couplings in detecting motion in carbohydrates: application to sucrose SO CARBOHYDRATE RESEARCH LA English DT Article DE sucrose; residual dipolar coupling; carbohydrate structure; carbohydrate dynamics; heteronuclear NMR ID LIQUID-CRYSTALLINE MEDIUM; C-13 NMR RELAXATION; AQUEOUS-SOLUTION; CONFORMATIONAL-ANALYSIS; FORCE-FIELD; OPTICAL-ROTATION; HYDROXYL PROTONS; PROTEINS; OLIGOSACCHARIDES; MACROMOLECULES AB The solution structure and dynamics of sucrose are examined using a combination of NMR residual dipolar coupling and molecular mechanics force fields. It is found that the alignment tensors of the individual rings are different, and that fitting 35 measured residual dipolar couplings to structures with specific phi, psi values indicates the presence of three major conformations: 0, psi = (120 degrees, 270 degrees), (45 degrees, 300 degrees) and (90 degrees, 180 degrees). Furthermore, fitting two structures simultaneously to the 35 residual dipolar couplings results in a substantial improvement in the fits. The existence of multiple conformations having similar stabilities is a strong indication of motion, due to the interconversion among these states. Results from four molecular mechanics force fields are in general agreement with the experimental results. However, there are major disagreements between force fields. Because fits of residual dipolar couplings to structures are dependent on the force field used to calculate the structures, multiple force fields were used to interpret NMR data. It is demonstrated that the pucker of the fructofuranosyl ring affects the calculated potential energy surface, and the fit to the residual dipolar couplings data. Previously published C-13 nuclear relaxation results suggesting that sucrose is rigid are not inconsistent with the present results when motional timescales are considered. (c) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. NIDDK, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. RP Freedberg, DI (reprint author), US FDA, Ctr Biol Evaluat & Res, Biophys Lab, 1401 Rockville Pike, Rockville, MD 20852 USA. EM freedberg@cber.fda.gov NR 66 TC 27 Z9 27 U1 1 U2 11 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0008-6215 J9 CARBOHYD RES JI Carbohydr. Res. PD APR 11 PY 2005 VL 340 IS 5 BP 863 EP 874 DI 10.1016/j.carres.2005.01.025 PG 12 WC Biochemistry & Molecular Biology; Chemistry, Applied; Chemistry, Organic SC Biochemistry & Molecular Biology; Chemistry GA 914ET UT WOS:000228208700008 PM 15780252 ER PT J AU Stadel, BV Colman, E Sahlroot, T AF Stadel, BV Colman, E Sahlroot, T TI Misleading use of risk ratios SO LANCET LA English DT Letter C1 US FDA, Div Metab & Endocrine Drug Prod, Off Drug Evaluat 2, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Stadel, BV (reprint author), US FDA, Div Metab & Endocrine Drug Prod, Off Drug Evaluat 2, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM stadel@cder.fda.gov NR 3 TC 2 Z9 2 U1 0 U2 0 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD APR 9 PY 2005 VL 365 IS 9467 BP 1306 EP 1307 DI 10.1016/S0140-6736(05)61024-0 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 914HY UT WOS:000228219600022 PM 15823376 ER PT J AU Hoashi, T Watabe, H Muller, J Yamaguchi, Y Vieira, WD Hearing, VJ AF Hoashi, T Watabe, H Muller, J Yamaguchi, Y Vieira, WD Hearing, VJ TI MART-1 is required for the function of the melanosomal matrix protein PMEL17/GP100 and the maturation of melanosomes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID OCULOCUTANEOUS ALBINISM TYPE-1; SUBCELLULAR-LOCALIZATION; ENDOPLASMIC-RETICULUM; MELANOGENIC COMPLEX; MOUSE MELANOMA; TYROSINASE; BIOGENESIS; GP100; DIFFERENTIATION; TRAFFICKING AB More than 125 genes that regulate pigmentation have been identified to date. Of those, MART-1 has been widely studied as a melanoma-specific antigen and as a melanosome-specific marker. Whereas the functions of other melanosomal proteins, such as tyrosinase, tyrosinase-related protein-1, dopachrome tautomerase, and Pmel17, are known, the function of MART-1 in melanogenesis, is unclear. A role for MART-1 in pigmentation is expected because its expression pattern and subcellular distribution is quite similar to the other melanosomal proteins and usually correlates with melanin content. We investigated the function of MART-1 using a multi-disciplinary approach, including the use of siRNA to inhibit MART-1 function and the use of transfection to re-express MART-1 in MART-1-negative cells. We show that MART-1 forms a complex with Pmel17 and affects its expression, stability, trafficking, and the processing which is required for melanosome structure and maturation. We conclude that MART-1 is indispensable for Pmel17 function and thus plays an important role in regulating mammalian pigmentation. C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Rockville, MD 20852 USA. RP Hearing, VJ (reprint author), NCI, Cell Biol Lab, NIH, Bldg 37,Rm 2132, Bethesda, MD 20892 USA. EM hearingv@nih.gov RI Yamaguchi, Yuji/B-9312-2008 NR 34 TC 85 Z9 91 U1 1 U2 9 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 8 PY 2005 VL 280 IS 14 BP 14006 EP 14016 DI 10.1074/jbc.M413692200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 912QW UT WOS:000228095500103 PM 15695812 ER PT J AU Roden, DM Temple, R AF Roden, DM Temple, R TI The US Food and Drug Administration Cardiorenal Advisory Panel and the drug approval process SO CIRCULATION LA English DT Article DE US Food and Drug Administration; drugs, cardiovascular; drug approval; risk factors; trials ID LEFT-VENTRICULAR DYSFUNCTION; PLACEBO-CONTROLLED TRIALS; ACTIVE-CONTROL TRIALS; HEART-FAILURE; RANDOMIZED TRIAL; DE-POINTES; MORTALITY; EPTIFIBATIDE; PROLONGATION; TERFENADINE C1 Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Dept Pharmacol, Nashville, TN 37232 USA. US FDA, Ctr Drug Evaluat & Res, Off Med Policy, Rockville, MD 20857 USA. RP Roden, DM (reprint author), Vanderbilt Univ, Sch Med, Div Clin Pharmacol, Dept Med, 532 Med Res Bldg I, Nashville, TN 37232 USA. EM dan.roden@vanderbilt.edu FU NHLBI NIH HHS [HL65962, HL46681, HL49989] NR 27 TC 11 Z9 11 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD APR 5 PY 2005 VL 111 IS 13 BP 1697 EP 1702 DI 10.1161/01.CIR.0000161370.77463.0F PG 6 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 913CZ UT WOS:000228129900019 PM 15811869 ER PT J AU Sommers, CL Lee, J Steiner, KL Gurson, JM DePersis, CL El-Khoury, D Fuller, CL Shores, EW Love, PE Samelson, LE AF Sommers, CL Lee, J Steiner, KL Gurson, JM DePersis, CL El-Khoury, D Fuller, CL Shores, EW Love, PE Samelson, LE TI Mutation of the phospholipase C-gamma 1-binding site of LAT affects both positive and negative thymocyte selection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID T-CELL DEVELOPMENT; TEC FAMILY KINASES; ANTIGEN RECEPTOR; TYROSINE RESIDUES; THYMIC EMIGRANTS; ADAPTER PROTEIN; TRANSGENIC MICE; POINT MUTATION; ACTIVATION; SIGNAL AB Linker for activation of T cells (LAT) is a scaffolding adaptor protein that is critical for T cell development and function. A mutation of LAT (Y136F) that disrupts phospholipase C-gamma 1 activation and subsequent calcium influx causes a partial block in T cell development and leads to a severe lymphoproliferative disease in homozygous knock-in mice. One possible contribution to the fatal disease of LAT Y136F knock-in mice could be from autoreactive T cells generated in these mice because of altered thymocyte selection. To examine the impact of the LAT Y136F mutation on thymocyte positive and negative selection, we bred this mutation onto the HY T cell receptor (TCR) transgenic, recombination activating gene-2 knockout background. Female mice with this genotype showed a severe defect in positive selection, whereas male mice exhibited a phenotype resembling positive selection (i.e.,development and survival of CD8(hi) HY TCR-specific T cells) instead of negative selection. These results support the hypothesis that in non-TCR transgenic, LAT Y136F knock-in mice, altered thymocyte selection leads to the survival and proliferation of autoreactive T cells that would otherwise be negatively selected in the thymus. C1 NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Samelson, LE (reprint author), NCI, Mol & Cellular Biol Lab, NIH, Bethesda, MD 20892 USA. EM samelson@helix.nih.gov FU NCI NIH HHS [Z01 BC010304-07] NR 43 TC 57 Z9 58 U1 0 U2 1 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 APR 4 PY 2005 VL 201 IS 7 BP 1125 EP 1134 DI 10.1081/jem.20011869 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 913WW UT WOS:000228187300013 PM 15795236 ER PT J AU Brinker, A Nourjah, P AF Brinker, A Nourjah, P TI Patient characteristics associated with outpatient prescriptions for nabumetone and oxaprozin versus celecoxib and rofecoxib SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIAL; RHEUMATOID-ARTHRITIS; GASTROINTESTINAL TOXICITY; DOUBLE-BLIND; CYCLOOXYGENASE; OSTEOARTHRITIS; INHIBITORS; RISK; IBUPROFEN C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP Brinker, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Div Drug Risk Evaluat, 5600 Fishers Lane, Rockville, MD 20857 USA. EM brinkera@cder.fda.gov NR 24 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD APR 1 PY 2005 VL 62 IS 7 BP 739 EP 743 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 912ON UT WOS:000228088900011 PM 15790802 ER PT J AU Lopez-Rivera, A Suarez-Isla, BA Eilers, PO Beaudry, CG Hall, S Amandi, MF Furey, A James, KJ AF Lopez-Rivera, A Suarez-Isla, BA Eilers, PO Beaudry, CG Hall, S Amandi, MF Furey, A James, KJ TI Improved high-performance liquid chromatographic method for the determination of domoic acid and analogues in shellfish: effect of pH SO ANALYTICAL AND BIOANALYTICAL CHEMISTRY LA English DT Article DE amnesic shellfish poisoning; domoic acid; ion-trap mass spectrometry ID MASS-SPECTROMETRY; CAPILLARY ELECTROPHORESIS; MARINE NEUROTOXIN; SEAFOOD; PHYTOPLANKTON; MUSSELS; CONFIRMATION; EXTRACTION AB Domoic acid (DA) is a naturally-occurring amino acid that causes a form of human intoxication called amnesic shellfish poisoning (ASP) following the consumption of shellfish. A rapid and sensitive HPLC-UV method has been developed for analysis of DA and analogues in shellfish without the need for SPE clean-up. Isocratic chromatographic separation of DA and its isomers from shellfish matrix interferences and from the prevalent amino acid, tryptophan, was achieved by careful control of the mobile phase pH. The optimised pH was found to be 2.5 when using a Luna(2) C-18 column. Sample extraction was verified with control extracts from shellfish spiked at 5.0 and 10.0 mu g/g of DA and with certified reference material. The average extraction efficiency was 98.5%. The calibration, based on mussel tissue spiked with DA standard, was linear in the range 0.05-5.0 mu g/ml (r=0.9999) and the detection limit (signal:noise 3:1) was better than 25 ng/ml. The DA assay achieved good precision; %RSD=1.63 (intra-day, n=6) and %RSD=3.7 (inter-day, n=8). This method was successfully applied to a variety of shellfish species, allowing the rapid screening of a large number of samples per day (20-30), without the need for SPE clean-up. Quantitative data were obtained for shellfish samples containing domoic acid in the concentration range 0.25-330 mu g/g. Using the same chromatographic conditions, LC-MS3 was used to determine DA and its isomers, isodomoic acid D and epi-domoic acid, in scallop tissues. C1 Univ Chile, Inst Biomed Sci, Fac Med, Lab Marine Toxins, Santiago, Chile. US FDA, CFSAN, Washington, DC 20204 USA. Cork Inst Technol, Dept Chem, Mass Spect Ctr Proteom & Biotoxin Res, PROTEOBIO, Cork, Ireland. RP Lopez-Rivera, A (reprint author), Univ Chile, Inst Biomed Sci, Fac Med, Lab Marine Toxins, Independencia 1027, Santiago, Chile. EM amlopez@med.uchile.cl OI Furey, Ambrose/0000-0003-4119-4318 NR 28 TC 20 Z9 21 U1 0 U2 17 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1618-2642 J9 ANAL BIOANAL CHEM JI Anal. Bioanal. Chem. PD APR PY 2005 VL 381 IS 8 BP 1540 EP 1545 DI 10.1007/s00216-005-3109-4 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 920XG UT WOS:000228728200009 PM 15770470 ER PT J AU Shingfield, KJ Reynolds, CK Lupoli, B Toivonen, V Yurawecz, MP Delmonte, P Griinari, JM Grandison, AS Beever, DE AF Shingfield, KJ Reynolds, CK Lupoli, B Toivonen, V Yurawecz, MP Delmonte, P Griinari, JM Grandison, AS Beever, DE TI Effect of forage type and proportion of concentrate in the diet on milk fatty acid composition in cows given sunflower oil and fish oil SO ANIMAL SCIENCE LA English DT Article DE linoleic acid; milk fat; polyenoic fatty acids; trans fatty acids ID CONJUGATED LINOLEIC-ACID; LACTATING DAIRY-COWS; TRANS OCTADECENOIC ACID; BOVINE-MILK; DUODENAL FLOW; MICROBIAL BIOHYDROGENATION; HOLSTEIN COWS; CLA ISOMERS; SHEEP RUMEN; LINSEED OIL AB Based on the potential benefits of cis-9, trans- 11 conjugated linoleic acid (CLA) for human health there is a need to develop effective strategies for enhancing milk fat CLA concentrations. In this experiment, the effect of forage type and level of concentrate in the diet on milk fatty acid composition was examined in cows given a mixture of fish oil and sunflower oil. Four late lactation Holstein-British Friesian cows were used in a 4 x 4 Latin-square experiment with a 2 x 2 factorial arrangement of treatments and 21-day experimental periods. Treatments consisted of grass (G) or maize (M) silage supplemented with low (L) or high (H) levels of concentrates (65: 35 and 35: 65; forage: concentrate ratio, on a dry matter (DM) basis, respectively) offered as a total mixed ration at a restricted level of intake (20 kg DM per day). Lipid supplements (30 g/kg DM) containing fish oil and sunflower oil (2: 3 w/w) were offered during the last 14 days of each experimental period. Treatments had no effect on total DM intake, milk yield, milk constituent output or milk fat content, but milk protein concentrations were lower (P<0.05) for G than M diets (mean 43.0 and 47.3 g/kg, respectively). Compared with grass silage, milk fat contained higher (P<0.05) amounts Of C-12: 0, C-14: 0, trans C-18:1 and long chain >= C20 (n-3) polyunsaturated fatty acids (PUFA) and lower (P<0.05) levels Of C-18:0 and trans C-18:2 when maize silage was offered. Increases in the proportion of concentrate in the diet elevated (P<0.05) C-18:2 (n-6) and long chain >= C20 (n-3) PUFA content, but reduced (P<0.05) the amount Of C-18:3 (n-3). Concentrations of trans-11 C-18:1 in milk were independent of forage type, but tended (P<0.10) to be lower for high concentrate diets (mean 7.2 and 4.0 g/100 g fatty acids, for L and H respectively). Concentrations of trans-10 C-18:1 were higher (P<0.05) in milk from maize compared with grass silage (mean 10.3 and 4.1 g/100 g fatty acids, respectively) and increased in response to high levels of concentrates in the diet (mean 4.1 and 10.3 g/100 g fatty acids, for L and H, respectively). Forage type had no effect (P>0.05) on total milk conjugated linoleic acid (CLA) (2.7 and 2.8 g/100 g fatty acids, for M and G, respectively) or cis-9, trans-11 CLA content (2.2 and 2.4 g/100 g fatty acids). Feeding high concentrate diets tended (P<0.10) to decrease total CLA (3.3 and 2.2 g/100 g fatty acids, for L and H, respectively) and cis-9, trans-11 CLA (2.9 and 1/7 g/100 g fatty acids) concentrations and increase milk trans-9, cis-11 CLA and trans-10, cis-12 CLA content. In conclusion, the basal diet is an important determinant of milk fatty acid composition when a supplement of fish oil and sunflower oil is given. C1 MTT Agrifood Res Finland, Anim Prod Res, FIN-31600 Jokioinen, Finland. Univ Reading, Dept Anim Sci, Ctr Dairy Res, Reading RG6 6AT, Berks, England. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Univ Helsinki, Dept Anim Sci, Helsinki, Finland. Univ Reading, Sch Food Biosci, Reading RG6 6AP, Berks, England. RP Shingfield, KJ (reprint author), MTT Agrifood Res Finland, Anim Prod Res, FIN-31600 Jokioinen, Finland. EM kevin.shingfield@mtt.fi NR 65 TC 117 Z9 117 U1 2 U2 18 PU BRITISH SOC ANIMAL SCIENCE PI PENICUIK PA PUBLICATIONS DEPT, PO BOX 3, PENICUIK EH26 ORZ, MIDLOTHIAN, SCOTLAND SN 1357-7298 J9 ANIM SCI JI Anim. Sci. PD APR PY 2005 VL 80 BP 225 EP 238 PN 2 PG 14 WC Agriculture, Dairy & Animal Science SC Agriculture GA 918OO UT WOS:000228555600014 ER PT J AU Rawson, NSB Nourjah, P Grosser, SC Graham, DJ AF Rawson, NSB Nourjah, P Grosser, SC Graham, DJ TI Factors associated with celecoxib and rofecoxib utilization SO ANNALS OF PHARMACOTHERAPY LA English DT Article DE celecoxib; cyclooxygenase-2 inhibitors; determinants of prescribing; disease burden; nonsteroidal antiinflammatory drugs; rofecoxib ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; RANDOMIZED CONTROLLED-TRIAL; GASTROINTESTINAL TOXICITY; RHEUMATOID-ARTHRITIS; ELDERLY PERSONS; INHIBITORS; OSTEOARTHRITIS; POPULATION; NAPROXEN; DISEASE AB BACKGROUND: The cyclooxygenase-2 (COX-2) selective nonsteroidal antiinflammatory drugs (NSAIDs) celecoxib and rofecoxib (before its removal) are marketed as having fewer gastrointestinal (GI)-related complications than nonselective NSAIDs. However, adverse reaction data suggest that the use of COX-2 selective NSAIDs is associated with clinically significant GI events. OBJECTIVE: To assess whether patients receiving celecoxib and rofecoxib have a greater underlying disease burden than patients prescribed nonselective NSAIDs. METHODS: The study population consisted of members of 11 health plans, aged > 34 years, with a pharmacy claim for celecoxib or rofecoxib or a nonselective NSAID dispensed between February 1, 1999, and July 31, 2001, who had been continuously enrolled for > 364 days before the dispensing date. Celecoxib and rofecoxib patients were randomly selected without replacement from a pool of eligible users in each of the 30 months. Nonselective NSAID users were randomly chosen without replacement within each month on a 2:1 ratio to cases; they could be chosen in more than one month. Univariate analyses comparing 9000 cases and 18 000 controls were performed, followed by a multiple logistic regression analysis conditioned on time. RESULTS: Increasing age, treatment by a rheumatologist or an orthopedic specialist, treatment with a high number of different medications in the past year, treatment with oral corticosteroids in the past year, and having had a previous GI bleed increased the likelihood of receiving celecoxib or rofecoxib, whereas treatment with a high number of nonselective NSAID prescriptions in the past year decreased it. Treatment with a high number of different medications was a predictor of increased prevalence of underlying diabetes mellitus and cardiovascular disease. CONCLUSIONS: Patients having a greater underlying disease burden were more likely to receive COX-2 selective NSAIDs than nonselective ones. Paradoxically, patients at higher risk for cardiovascular disease were channeled toward treatment with COX-2 selective NSAIDs, many of which may confer an increased risk of acute myocardial infarction and other adverse cardiovascular outcomes. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Rockville, MD 20857 USA. Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN USA. RP Graham, DJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, 5600 Fishers Ln,HFD-400, Rockville, MD 20857 USA. EM grahamd@cder.fda.gov FU FDA HHS [FD-U-0001643-03, FD-U-0002067-01-03] NR 25 TC 9 Z9 9 U1 0 U2 0 PU HARVEY WHITNEY BOOKS CO PI CINCINNATI PA PO BOX 42696, CINCINNATI, OH 45242 USA SN 1060-0280 J9 ANN PHARMACOTHER JI Ann. Pharmacother. PD APR PY 2005 VL 39 IS 4 BP 597 EP 602 DI 10.1345/aph.1E298 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 908UE UT WOS:000227814900001 PM 15755796 ER PT J AU Kim, YH Freeman, JP Moody, JD Engesser, KH Cerniglia, CE AF Kim, YH Freeman, JP Moody, JD Engesser, KH Cerniglia, CE TI Effects of pH on the degradation of phenanthrene and pyrene by Mycobacterium vanbaalenii PYR-1 SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; SP STRAIN PYR-1; IDENTIFICATION; PERMEABILITY; FLUORANTHENE; METABOLISM; ENVELOPE; SOILS AB The effects of pH on the growth of Mycobacterium vanbaalenii PYR-1 and its degradation of phenanthrene and pyrene were compared at pH 6.5 and pH 7.5. Various degradation pathways were proposed in this study, based on the identification of metabolites from mass and NMR spectral analyses. In tryptic soy broth, M. vanbaalenii PYR-1 grew more rapidly at pH 7.5 (mu' = 0.058 h(-1)) than at pH 6.5 (mu' = 0.028 h(-1)). However, resting cells suspended in phosphate buffers with the same pH values displayed a shorter lag time for the degradation of phenanthrene and pyrene at pH 6.5 ( 6 h) than at pH 7.5 ( 48 h). The one-unit pH drop increased the degradation rates fourfold. Higher levels of both compounds were detected in the cytosol fractions obtained at pH 6.5. An acidic pH seemed to render the mycobacterial cells more permeable to hydrophobic substrates. The major pathways for the metabolism of phenanthrene and pyrene were initiated by oxidation at the K-regions. Phenanthrene-9,10- and pyrene-4,5- dihydrodiols were metabolized via transient catechols to the ring fission products, 2,2'-diphenic acid and 4,5-dicarboxyphenanthrene, respectively. The metabolic pathways converged to form phthalic acid. At pH 6.5, M. vanbaalenii PYR-1 produced higher levels of the O-methylated derivatives of non-K-region phenanthrene- and pyrene-diols. Other non-K-region products, such as cis-4-(1-hydroxynaphth-2-yl)-2-oxobut-3-enoic acid, 1,2-dicarboxynaphthalene and benzocoumarin-like compounds, were also detected in the culture fluids. The non-K-region polycyclic aromatic hydrocarbon oxidation might be a significant burden to the cell due to the accumulation of toxic metabolites. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Chem, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Stuttgart, ISWA, Abt Biol Abluftreinigung, D-7000 Stuttgart, Germany. RP Cerniglia, CE (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ccerniglia@nctr.fda.gov NR 37 TC 93 Z9 104 U1 1 U2 25 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD APR PY 2005 VL 67 IS 2 BP 275 EP 285 DI 10.1007/s00253-004-1796-y PG 11 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 917ZA UT WOS:000228506700016 PM 15592827 ER PT J AU Netzeva, TI Worth, AP Aldenberg, T Benigni, R Cronin, MTD Gramatica, P Jaworska, JS Kahn, S Klopman, G Marchant, CA Myatt, G Nikolova-Jeliazkova, N Patlewicz, GY Perkins, R Roberts, DW Schultz, TW Stanton, DT van de Sandt, JJM Tong, WD Veith, G Yang, CH AF Netzeva, TI Worth, AP Aldenberg, T Benigni, R Cronin, MTD Gramatica, P Jaworska, JS Kahn, S Klopman, G Marchant, CA Myatt, G Nikolova-Jeliazkova, N Patlewicz, GY Perkins, R Roberts, DW Schultz, TW Stanton, DT van de Sandt, JJM Tong, WD Veith, G Yang, CH TI Current status of methods for defining the applicability domain of (quantitative) structure-activity relationships - The report and recommendations of ECVAM Workshop 52 SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Article ID ESTROGEN-RECEPTOR BINDING; NORMAL BOILING POINTS; COMPUTER-ASSISTED PREDICTION; NATIONAL-TOXICOLOGY-PROGRAM; MULTICASE EXPERT-SYSTEM; CHEMICAL-STRUCTURE; SKIN-SENSITIZATION; CLASSIFICATION; MUTAGENICITY; SALMONELLA C1 Commiss European Communities, Joint Res Ctr, ECVAM, Inst Hlth & Consumer Protect, I-21020 Ispra, VA, Italy. RIVM, Bilthoven, Netherlands. Ist Super Sanita, Expt & Computat Carcinogenesis Unit, Environm & Hlth Dept, I-00161 Rome, Italy. Liverpool John Moores Univ, Sch Pharm & Chem, Liverpool L3 5UX, Merseyside, England. Univ Insubria, Dept Struct & Funct Biol, QSAR, Varese, Italy. Univ Insubria, Dept Struct & Funct Biol, Environm Chem Res Unit, Varese, Italy. Procter & Gamble Co, Cent Prod Safety, Cincinnati, OH 45202 USA. Accelrys Inc, San Diego, CA USA. Multicase Inc, Beachwood, OH USA. Univ Leeds, Dept Chem, Lhasa Ltd, Leeds LS2 9JT, W Yorkshire, England. Leadscope Inc, Columbus, OH USA. Bulgarian Acad Sci, Inst Parallel Proc, Sofia, Bulgaria. Unilever, SEAC, Sharnbrook, Beds, England. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Ctr Toxicoinformat, Jefferson, AR 72079 USA. Univ Tennessee, Coll Vet Med, Biol Act Testing & Modelling Lab, Knoxville, TN USA. Procter & Gamble Co, Miami Valley Lab, Cincinnati, OH USA. TNO, Food & Chem Risk Anal Dept, Zeist, Netherlands. OECD, Environm Hlth & Safety Div, Paris, France. RP Worth, AP (reprint author), Commiss European Communities, Joint Res Ctr, ECVAM, Inst Hlth & Consumer Protect, I-21020 Ispra, VA, Italy. EM andrew.worth@jrc.it RI Jeliazkova, Nina/D-2499-2010 NR 52 TC 291 Z9 295 U1 1 U2 39 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD APR PY 2005 VL 33 IS 2 BP 155 EP 173 PG 19 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 921JP UT WOS:000228760700010 PM 16180989 ER PT J AU Fang, GC Wu, YS Fu, PPC Chang, CN Chen, MH Ho, TT Huang, SH Rau, JY AF Fang, GC Wu, YS Fu, PPC Chang, CN Chen, MH Ho, TT Huang, SH Rau, JY TI Metallic elements study of fine and coarse particulates using a versatile air pollutant system at a traffic sampling site SO ATMOSPHERIC RESEARCH LA English DT Article DE coarse particulate; fine particulate; traffic; versatile air pollutant system ID POLYCYCLIC AROMATIC-HYDROCARBONS; VOLATILE ORGANIC-COMPOUNDS; CENTRAL TAIWAN; SOURCE APPORTIONMENT; CARBONYL-COMPOUNDS; SIZE DISTRIBUTION; UNITED-STATES; HONG-KONG; IN-SOURCE; PM2.5 AB Daytime and nighttime period sampling programs were carded out by a versatile air pollutant system (VAPS) to collect the fine (PM2.5) and coarse (PM2.5-10) particulates simultaneously at a traffic sampling site in front of Hungkuang University during August to October 2003. Chemical analyses of metallic elements were accomplished by a flame atomic absorption spectrophotometer coupled with hollow cathode lamps. Statistical methods, such as correlation coefficients and principal component analysis (PCA), were used to compare chemical components and to find the possible emission sources at this traffic sampling site. The variations of metallic element concentrations in fine and coarse particulates during daytime and nighttime were also discussed in this study. (c) 2004 Elsevier B.V. All rights reserved. C1 Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. RP Fang, GC (reprint author), Hungkuang Univ, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. EM gcfang@sunrise.hk.edu.tw NR 29 TC 11 Z9 11 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0169-8095 J9 ATMOS RES JI Atmos. Res. PD APR PY 2005 VL 75 IS 1-2 BP 1 EP 14 DI 10.1016/j.atmosres.2004.10.005 PG 14 WC Meteorology & Atmospheric Sciences SC Meteorology & Atmospheric Sciences GA 915XF UT WOS:000228344000001 ER PT J AU Araujo, RP Petricoin, EF Liotta, LA AF Araujo, RP Petricoin, EF Liotta, LA TI A mathematical model of combination therapy using the EGFR signaling network SO BIOSYSTEMS LA English DT Article DE cancer treatment; combination therapy; EGFR network; signal transduction; kinase inhibitors ID GROWTH-FACTOR RECEPTOR; CELL LUNG-CANCER; PROTEIN-KINASE-A; TYROSINE KINASE; INHIBITORS; CHEMOTHERAPY; RADIATION; ZD1839 AB An increasing awareness of the significance of abnormal signal transduction in tumors and the concomitant development of target-based drugs to selectively modulate aberrantly-activated signaling pathways has given rise to a variety of promising new strategies in cancer treatment. This paper uses mathematical modeling to investigate a novel type of combination therapy in which multiple nodes in a signaling cascade are targeted simultaneously with selective inhibitors, pursuing the hypothesis that such an approach may induce the desired signal attenuation with lower doses of the necessary agents than when one node is targeted in isolation. A mathematical model is presented which builds upon previous theoretical work on EGFR signaling, simulating the effect of administering multiple kinase inhibitors in various combinations. The model demonstrates that attenuation of biochemical signals is significantly enhanced when multiple upstream processes are inhibited, in comparison with the inhibition of a single upstream process. Moreover, this enhanced attenuation is most pronounced in signals downstream of serially-connected target points. In addition, the inhibition of serially-connected processes appears to have a supra-additive (synergistic) effect on the attenuation of downstream signals, owing to the highly non-linear relationships between network parameters and signals. (c) 2004 Elsevier Ireland Ltd. All rights reserved. C1 NCI, FDA, Clin Proteom Program, Lab Pathol,Ctr Canc Res,NIH, Bethesda, MD 20892 USA. US FDA, NCI, Clin Proteom Program, Off Cell & Gene Therapies,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Araujo, RP (reprint author), NCI, FDA, Clin Proteom Program, Lab Pathol,Ctr Canc Res,NIH, 8800 Rockville Pike,Bldg 29A,HFM 710, Bethesda, MD 20892 USA. EM araujor@mail.nih.gov NR 17 TC 58 Z9 61 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0303-2647 J9 BIOSYSTEMS JI Biosystems PD APR PY 2005 VL 80 IS 1 BP 57 EP 69 DI 10.1016/j.biosystems.2004.10.002 PG 13 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 908TF UT WOS:000227812400006 PM 15740835 ER PT J AU Ferguson, SA Berry, KJ Hansen, DK Wall, KS White, G Antony, AC AF Ferguson, SA Berry, KJ Hansen, DK Wall, KS White, G Antony, AC TI Behavioral effects of prenatal folate deficiency in mice SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article DE folic acid; deficiency; behavior; anxiety; central nervous system; mice ID FOLIC-ACID; PLUS-MAZE; ANXIETY; MOUSE; GESTATION; EXPOSURE; RAT AB BACKGROUND: Folate supplementation decreases the incidence of birth defects such as neural tube defects (NTDs). We and others have shown that gestational dietary folate deficiency that does not produce overt NTDs can alter fetal neural histology. Accordingly, murine offspring were examined for the possible functional consequences of prenatal folate deficiency. METHODS: CD-1 mice were fed a diet of chow containing 400, 600, or 1200 nmol of folic acid/kg of chow for eight weeks prior to breeding and until GD18, at which time all dams were placed on folate-replete chow. Behavioral tests of male and female offspring included righting reflex, negative geotaxis, forelimb hanging, motor coordination, open field activity, and elevated plus maze activity. RESULTS: Of greatest significance, the adult offspring that were prenatally folate-deficient exhibited more anxiety-related behavior in the elevated plus maze. Offspring of the 400 nmol of folic acid/kg of chow diet group exhibited significantly shorter durations in the open arms and longer durations in the closed arms. Further, these two behaviors were dose-related. There was also a trend for the prenatally folate-deficient adult mice to exhibit more thigmotaxis (wall-hugging) behavior in the open field, entering the central area less frequently than controls. There were few other differences in tested behaviors between folate-deficient and folate-replete mice. CONCLUSIONS: Prenatal folate deficiency that is repleted at birth can manifest later with increased anxiety 9-12 weeks after birth. Birth Defects Research (Part A) 73:249-252, 2005. (c) 2005 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, FDA, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, FDA, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Charles Rivers Labs, FDA, Jefferson, AR 72079 USA. Univ Indianapolis, Dept Med, Sch Med, Indianapolis, IN 46227 USA. Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN 46202 USA. RP Ferguson, SA (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, FDA, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sferguson@nctr.fda.gov NR 25 TC 22 Z9 23 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD APR PY 2005 VL 73 IS 4 BP 249 EP 252 DI 10.1002/bdra.20111 PG 4 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 920OC UT WOS:000228699000007 PM 15744731 ER PT J AU Smith, FM Stephens, RB Petricoin, EF Liotta, LA Kennedy, MJ Reynolds, JV AF Smith, FM Stephens, RB Petricoin, EF Liotta, LA Kennedy, MJ Reynolds, JV TI Exploring the proteome as a response predictor for rectal cancer undergoing neoadjuvant radiochemotherapy SO BRITISH JOURNAL OF SURGERY LA English DT Meeting Abstract CT Annual Meeting of the Association-of-Surgeons-of-Great-Britian-and-Ireland CY APR 13-15, 2005 CL Glasgow, SCOTLAND SP Assoc Surg Great Britian & Ireland C1 St James Hosp, Dept Surg, Dublin, Ireland. St James Hosp, Acad Unit Clin & Mol Oncol, Dublin, Ireland. Trinity Coll Dublin, Dublin, Ireland. NCI, FDA NCI Clin Proteom Program, Pathol Lab, Ctr Canc Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0007-1323 J9 BRIT J SURG JI Br. J. Surg. PD APR PY 2005 VL 92 SU 1 BP 152 EP 152 PG 1 WC Surgery SC Surgery GA 922MY UT WOS:000228843200314 ER PT J AU Ricicki, EM Soglia, JR Teitel, C Kane, R Kadlubar, F Vouros, P AF Ricicki, EM Soglia, JR Teitel, C Kane, R Kadlubar, F Vouros, P TI Detection and quantification of N-(deoxyguanosin-8-yl)-4-aminobiphenyl adducts in human pancreas tissue using capillary liquid chromatography-microelectrospray mass spectrometry SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID FORMED DNA-ADDUCTS; AROMATIC-AMINES; METABOLIC-ACTIVATION; 4-AMINOBIPHENYL-DNA ADDUCTS; CIGARETTE-SMOKE; BLADDER-CANCER; CARCINOGEN 4-AMINOBIPHENYL; URINARY-BLADDER; TOBACCO-SMOKE; HUMAN-LIVER AB Cigarette smoking has been associated with various cancers including bladder and pancreas. 4-Aminobiphenyl has been isolated as a constituent of cigarette smoke and has been established as a carcinogen in various animal models and humans. In rodents and humans, 4-aminobiphenyl is N-hydroxylated and forms adducts to DNA, the predominant one being N-(deoxyguanosin-8-yl)-4-aminobiphenyl (dG-CS-ABP). In this study, we report a micro-electrospray mass spectrometric (mu ESI-MS) isotope dilution method for the detection and quantification of dG-C8-ABP in human pancreatic tissue. A reverse phase capillary column (320 mu m ID) was connected to a triple quadrupole mass spectrometer via a commercially available micro-ESI source. The system was operated in the selected reaction monitoring mode transmitting the [M + H](+) -> [M + H - 116](+) transitions for both the analyte and the isotopically labeled internal standard. Twelve human pancreas samples were analyzed, where six were current smokers (three male and three female) and six were considered nonsmokers (three female and three male). Of the samples analyzed, six showed dG-C8-ABP levels above the limit of quantification for the method, five were considered to have levels that were undetectable, and one was discarded due to inconsistent internal standard signal. The age of the human subjects ranged from 17 to 63, and, in samples where adduct was present, levels ranged anywhere from 1 to 60/10(8) nucleotides. Although no correlation between smoking preference, age, or gender was proven with this particular sample pool, this report demonstrates that capillary LC-mu ESI-MS can provide a sensitive and definitive method for DNA adduct analysis in human tissue. C1 Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. Northeastern Univ, Dept Chem & Chem Biol, Boston, MA 02115 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Thermo Elect Corp, San Jose, CA 95134 USA. RP Vouros, P (reprint author), Northeastern Univ, Barnett Inst, Boston, MA 02115 USA. EM p.vouros@neu.edu FU NCI NIH HHS [IROICA69390] NR 50 TC 32 Z9 33 U1 2 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 APR PY 2005 VL 18 IS 4 BP 692 EP 699 DI 10.1021/tx0496921 PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 919LV UT WOS:000228620400009 PM 15833029 ER PT J AU Russek-Cohen, E Martinez, MN Nevius, AB AF Russek-Cohen, E Martinez, MN Nevius, AB TI A SAS/IML program for simulating pharmacokinetic data SO COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE LA English DT Article DE Monte Carlo simulation; SAS; bioequivalence; population kinetics; veterinary pharmacokinetics ID DRUG ABSORPTION; BIOEQUIVALENCE; BIOAVAILABILITY; DISPOSITION; PLASMA; SHEEP; BREED; PERFORMANCE; PROPOFOL; NONMEM AB Data simulation can be an invaluable toot for optimizing the design of bioequivalence trials. It can be particularly useful when exploring alternative approaches for assessing product comparability especially in the context of encountering various complex experimental situations that can occur in veterinary medicine. With this in mind, we designed a novel SAS/IML program to generate pharmacokinetic datasets that reflect the various kinetic, population, and study design characteristics that complicate the bioequivalence evaluation of animal health products. Developing this simulation program within SAS provides an opportunity to utilize the statistical capabilities of this software platform. Published by Elsevier Ireland Ltd. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Univ Maryland, Dept Anim & Avian Sci, College Pk, MD 20742 USA. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. EM erussek@umd.edu; mmartin1@cvm.fda.gov; anevius@cvm.fda.gov NR 43 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0169-2607 J9 COMPUT METH PROG BIO JI Comput. Meth. Programs Biomed. PD APR PY 2005 VL 78 IS 1 BP 39 EP 60 DI 10.1016/j.cmpb.2004.10.007 PG 22 WC Computer Science, Interdisciplinary Applications; Computer Science, Theory & Methods; Engineering, Biomedical; Medical Informatics SC Computer Science; Engineering; Medical Informatics GA 916IU UT WOS:000228379400005 PM 15780889 ER PT J AU Toy, P Popovsky, MA Abraham, E Daniel, R Ambruso, DR Holness, LG Kopko, PM McFarland, JG Nathens, AB Silliman, CC Stroncek, D AF Toy, P Popovsky, MA Abraham, E Daniel, R Ambruso, DR Holness, LG Kopko, PM McFarland, JG Nathens, AB Silliman, CC Stroncek, D CA Natl Heart Lung Blood Inst TI Transfusion-related acute lung injury: Definition and review SO CRITICAL CARE MEDICINE LA English DT Article; Proceedings Paper CT TRALI Consensus Conference CY APR 01-02, 2004 CL Toronto, CANADA DE blood transfusion; red blood cell transfusion; platelet transfusion; acute lung injury; acute respiratory distress syndrome; shock lung; critical care ID RESPIRATORY-DISTRESS SYNDROME; EUROPEAN CONSENSUS CONFERENCE; CLINICAL-TRIAL COORDINATION; PLATELET-ACTIVATING-FACTOR; NEUTROPHIL NADPH OXIDASE; STORED-BLOOD COMPONENTS; PULMONARY-EDEMA; LEUKOCYTE ANTIBODIES; MASSIVE TRANSFUSION; RELEVANT OUTCOMES AB Background., Transfusion-related acute lung injury (TRALI) is now the leading cause of transfusion-associated mortality, even though it is probably still underdiagnosed and underreported. National Heart, Lung, and Blood Institute Action. The National Heart, Lung, and Blood Institute convened a working group to identify areas of research needed in TRALI. The working group identified the immediate need for a common definition and thus developed the clinical definition in this report. Major Concepts in the Definition. The major concept is that TRALI is defined as new acute lung injury occurring during or within 6 hrs after a transfusion, with a clear temporal relationship to the transfusion. Also, another important concept is that acute lung injury temporally associated with multiple transfusions can be TRALI, because each unit of blood or blood component can carry one or more of the possible causative agents: antileukocyte antibody, biologically active substances, and other yet unidentified agents. Recommendation. Using the definition in this report, clinicians can diagnose and report TRALI cases to the blood bank; importantly, researchers can use this definition to determine incidence, pathophysiology, and strategies to prevent this leading cause of transfusion-associated mortality. C1 UCSF, Sch Med, Lab Med, San Francisco, CA 94143 USA. Haemonet Corp, Braintree, MA USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. Univ Colorado, Sch Med, Hlth Sci Ctr, Dept Med, Denver, CO 80202 USA. Bonfils Blood Ctr, Denver, CO USA. US FDA, Ctr Biol Evaluat & Res, Div Blood Applicat, Off Blood Res & Review, Rockville, MD 20857 USA. Blood Source, Sacramento, CA USA. Blood Ctr SE Wisconsin Inc, Platelet & Neutrophil Immunol Lab, Milwaukee, WI 53233 USA. Univ Washington, Seattle, WA 98195 USA. Harborview Med Ctr, Harborview Injury Prevent Ctr, Acute Care Sect, Seattle, WA 98104 USA. Harborview Med Ctr, Harborview Injury Prevent Ctr, Surg Crit Care Serv, Seattle, WA 98104 USA. NIH, Warren G Magnuson Clin Ctr, Lab Serv Sect, Dept Transfus Med, Bethesda, MD 20892 USA. RP Toy, P (reprint author), UCSF, Sch Med, Lab Med, Box 0100, San Francisco, CA 94143 USA. NR 49 TC 329 Z9 353 U1 0 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0090-3493 J9 CRIT CARE MED JI Crit. Care Med. PD APR PY 2005 VL 33 IS 4 BP 721 EP 726 DI 10.1097/01.CCM.0000159849.94750.51 PG 6 WC Critical Care Medicine SC General & Internal Medicine GA 915FF UT WOS:000228282700004 PM 15818095 ER PT J AU Tong, WD Hong, HX Xie, Q Shi, LM Fang, H Perkins, R AF Tong, Weida Hong, Huixiao Xie, Qian Shi, Leming Fang, Hong Perkins, Roger TI Assessing QSAR Limitations - A Regulatory Perspective SO CURRENT COMPUTER-AIDED DRUG DESIGN LA English DT Article DE SAR/QSAR; model limitation; model uncertainty; applicability domain; model validation; chance correlation; decision forest; consensus modeling AB Wider acceptance of QSARs would result in a constellation of benefits and savings to both private and public sectors. For this to occur, particularly in regulatory applications, a model's limitations need to be identified. We define a model's limitations as encompassing assessment of overall prediction accuracy, applicability domain and chance correlation. A general guideline is presented in this review for assessing a model's limitations with emphasis on and examples of application with consensus modeling methods. More specifically, we discuss the commonalities and differences between external validation and cross-validation for assessing a model's limitations. We illustrate two common ways of assessing overall prediction accuracy, depending on whether or not the intended application domain is predefined. Since even a high quality model will have different confidence in accuracy for predicting different chemicals, we further demonstrate using the novel Decision Forest consensus modeling method a means to determine prediction confidence (i.e., certainty for an individual chemical's prediction) and domain extrapolation (i.e., the prediction accuracy for a chemical that is outside the chemistry space defined by the training chemicals). We show that prediction confidence and domain extrapolation are related measures that together determine the applicability domain of a model, and that prediction confidence is the more important measure. Lastly, the importance of assessing chance correlation is emphasized, and illustrated with several examples of models having a high degree of chance correlations despite cross-validation indicating high prediction accuracy. Generally, a dataset with a skewed distribution, small data size and/or low signal/noise ratio tends to produce a model with high chance correlation. We conclude that it is imperative to assess all three aspects (i.e., overall accuracy, applicability domain and chance correlation) of a model for the regulatory acceptance of QSARs. C1 [Tong, Weida; Shi, Leming] NCTR, Ctr Toxicoinformat, Jefferson, AR 72079 USA. [Hong, Huixiao; Xie, Qian; Fang, Hong; Perkins, Roger] Z Tech Inc, Div Bioinformat, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), NCTR, Ctr Toxicoinformat, 3900 NCTR Rd,HFT 020, Jefferson, AR 72079 USA. EM Wtong@nctr.fda.gov NR 35 TC 25 Z9 25 U1 2 U2 9 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y-2, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1573-4099 EI 1875-6697 J9 CURR COMPUT-AID DRUG JI Curr. Comput.-Aided Drug Des. PD APR PY 2005 VL 1 IS 2 BP 195 EP 205 DI 10.2174/1573409053585663 PG 11 WC Chemistry, Medicinal; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Computer Science GA V17TD UT WOS:000207958600005 ER PT J AU Kawakami, K AF Kawakami, K TI Cancer gene therapy utilizing interleukin-13 receptor alpha 2 chain SO CURRENT GENE THERAPY LA English DT Review DE cancer gene therapy; interleukin-13; cytokine receptor; immunotherapy; tumor vaccine; immunotoxin ID CONVECTION-ENHANCED DELIVERY; CIRCULARLY PERMUTED INTERLEUKIN-4; SQUAMOUS-CELL CARCINOMA; HUMAN-MALIGNANT GLIOMA; KAPOSIS-SARCOMA CELLS; IL-13 RECEPTOR; PSEUDOMONAS EXOTOXIN; NECK-CANCER; SIGNAL-TRANSDUCTION; TARGETED CYTOTOXIN AB Cancer cells are known to express cell surface molecules such as specific antigens or cytokine receptors, e.g., EGFR, Fas/CD95, gp100, HER-2/neu, IL-131R alpha 2, and MAGE. Among them, interleukin-13 receptor (IL-13R) alpha 2 chain is expressed on certain types of cancer cells including glioblastoma, AIDS Kaposi's sarcoma, and head and neck cancer. This protein is one of the receptor components for IL-13, a Th2 cell-derived pleiotropic immune regulatory cytokine. IL-13R alpha 2 chain on these cancer cells can be targeted with a receptor-directed cytotoxin termed IL13-PE to induce specific cancer cell killing, however, this molecule does not mediate cytotoxicity to cells that do not express or express low levels of IL-13R alpha 2. In order to achieve a broad therapeutic window for IL13-PE, plasm id-mediated gene transfer of IL-13Ra2 in cancer cells was employed in vitro and in vivo. Cancer cells transfected with IL-13R alpha 2 demonstrated increased binding to IL-13 and sensitivity to IL13-PE in vitro. In vivo intratumoral gene transfer of IL-13R alpha 2 profoundly enhanced the antitumor activity of IL13-PE, providing complete elimination of established tumor in some xenografts. In this review article, current findings from IL-13R alpha 2 gene transfer in a variety of human cancer models in nude mice are summarized. In addition, safety issues and possible future directions utilizing this therapeutic approach are discussed. C1 Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Bunkyo Ku, Tokyo 1138655, Japan. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD USA. Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Tokyo, Japan. RP Kawakami, K (reprint author), Univ Tokyo, Grad Sch Med, Dept Adv Clin Sci & Therapeut, Bunkyo Ku, 7-3-1 Hongo, Tokyo 1138655, Japan. EM kawakami-k@umin.ac.jp NR 123 TC 8 Z9 11 U1 0 U2 2 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 1566-5232 J9 CURR GENE THER JI Curr. Gene Ther. PD APR PY 2005 VL 5 IS 2 BP 213 EP 223 DI 10.2174/1566523053544227 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 908XZ UT WOS:000227824800006 PM 15853729 ER PT J AU Wuilloud, RG Shah, M Kannamkumarath, SS Altamirano, JC AF Wuilloud, RG Shah, M Kannamkumarath, SS Altamirano, JC TI The potential of inductively coupled plasma-mass spectrometric detection for capillary electrophoretic analysis of pesticides SO ELECTROPHORESIS LA English DT Article; Proceedings Paper CT Winter Conference on Plasma Spectrochemistry CY JAN 05-10, 2004 CL Ft Lauderdale, FL DE capillary electrophoresis; inductively coupled plasma-mass spectrometry; organophosphorus pesticides; phosphorus detection; river water ID SOLID-PHASE EXTRACTION; GAS-CHROMATOGRAPHY; LIQUID-CHROMATOGRAPHY; ORGANOPHOSPHATE TOXICITY; FLUORESCENCE DETECTION; RESIDUE ANALYSIS; HUMAN EXPOSURE; ICP-MS; GLYPHOSATE; WATER AB In this work, the potential of inductively coupled plasma-mass spectrometry (ICP-MS)coupled to capillary electrophoresis (CE) to determine organophosphorus pesticides (OPPs) is demonstrated. Element specific detection of P-31 with ICP-MS is performed for the detection of OPPs. Three common OPPs, including glyphosate, glufosinate, and aminomethylphosphonic acid (AMPA), were analyzed by CE-ICP-MS to demonstrate its applicability for the analysis of OPPs. The advantages of using ICP-MS with respect to other common detectors, such as flame photometric detection (FPD), for CE analysis of OPPs are shown. Additionally, different CE separation conditions were studied to achieve complete baseline separation of the pesticide compounds in short migration times. Two CE buffer systems were evaluated for the separation of OPPs using ICP-MS detection. A buffer solution containing 40 mmol circle L-1 ammonium acetate at pH 9.0 and an applied voltage of +20 kV were finally selected leading to a separation time of 10.0 min. Both migration time and area relative standard deviations (%RSD) were evaluated and their respective values were in the intervals of 1.1-3.3% and 2.75.3%. Detection limits obtained with the CE-ICP-MS system were in the range of 0.110.19 mg circle L-1 (as compound) yielding an enhancement of 130- to 230-fold with respect to FPD. The proposed methodology was finally applied for the determination of the OPPs mentioned above in natural river water samples.* C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45221 USA. Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. RP Wuilloud, RG (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45221 USA. EM rgwuilloud@yahoo.com.ar RI Wuilloud, Rodolfo/N-6821-2014 OI Wuilloud, Rodolfo/0000-0002-2962-7718 FU NIEHS NIH HHS [ES04908] NR 33 TC 26 Z9 30 U1 0 U2 4 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD APR PY 2005 VL 26 IS 7-8 BP 1598 EP 1605 DI 10.1002/elps.200410098 PG 8 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 921SC UT WOS:000228784000035 PM 15765486 ER PT J AU Ivanov, AP Dragunsky, EM AF Ivanov, AP Dragunsky, EM TI ELISA as a possible alternative to the neutralization test for evaluating the immune response to poliovirus vaccines SO EXPERT REVIEW OF VACCINES LA English DT Review DE binding inhibition; blocking; ELISA; neutralization test; poliovirus ID LINKED-IMMUNOSORBENT-ASSAY; VIRUS NEUTRALIZATION; BINDING-INHIBITION; HUMAN-SERA; INDIRECT IMMUNOFLUORESCENCE; DETECT ANTIBODIES; TISSUE-CULTURE; IDENTIFICATION; INFECTION; MICE AB This review describes several enzyme-linked immunosorbent assay (ELISA) techniques proposed to replace the neutralization test for detecting neutralization-relevant antibodies to polloviruses in recipients of inactivated pollovirus vaccine and oral poliovirus vaccine, and for seroepidemiologic studies. Comparisons of results from ELISA and the neutralization test suggest that ELISA variants, based on the principle of blocking or binding inhibition that emulate the neutralization test, might offer an alternative to the neutralization test. However, to replace the neutralization test with ELISA would first require extensive studies with very large numbers of serum samples, including sera having low titers of neutralizing antibodies, in order to obtain reliable and statistically sound validation. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Ivanov, AP (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM ivanov@cber.fda.gov; dragunsky@cber.fda.gov NR 32 TC 10 Z9 11 U1 0 U2 10 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1476-0584 J9 EXPERT REV VACCINES JI Expert Rev. Vaccines PD APR PY 2005 VL 4 IS 2 BP 167 EP 172 DI 10.1586/14760584.4.2.167 PG 6 WC Immunology SC Immunology GA 982YZ UT WOS:000233199600017 PM 15889990 ER PT J AU Gioia, CAC de Sousa, AB Cruz, SC Junior, FCS Andrade, AFB Sassi, RM Frasch, CE Milagres, LG AF Gioia, CAC de Sousa, AB Cruz, SC Junior, FCS Andrade, AFB Sassi, RM Frasch, CE Milagres, LG TI Effect of a booster dose of serogroup B meningococcal vaccine on antibody response to Neisseria meningitidis in mice vaccinated with different immunization schedules SO FEMS IMMUNOLOGY AND MEDICAL MICROBIOLOGY LA English DT Article DE vaccine; Neisseria meningitidis; bactericidal antibody and serological memory ID OUTER-MEMBRANE PROTEIN; SERUM BACTERICIDAL ACTIVITY; BRAZILIAN CHILDREN; AVIDITY; DISEASE; PORA; ANTIGENS; EFFICACY; TRIAL AB The generation and maintenance of memory antibody response by different primary immunization schedules with the Cuban-produced outer membrane protein based vaccine was investigated in a murine model. We analyzed the duration of the antibody response (IgG-ELISA and bactericidal titer) and the effect of a booster dose on the antibody response. The IgG avidity index was determined in an attempt to find a marker for memory development. This study also included an analysis of IgG subclasses induced by primary and booster immunization. The specificity of bactericidal antibodies was investigated using local strains of the same serotype/serosubtype (4,7:P1.19,15) as the vaccine strain and mutant strains lacking major outer membrane proteins. A significant recall response was induced by a booster dose given 7 months after a primary series of 2, 3 or 4 doses of vaccine. The primary antibody response showed a positive dose-effect. In contrast, a negative dose-effect was found on the booster bactericidal antibody response. There was a significant increase in IgG1 levels after the fourth and booster doses. Three doses of vaccine were required to induce a significant increase in IgG avidity. Two injections of vaccine induced a significant antibody response to PorA protein, while 4 injections induced a larger range of specificities. (c) 2005 Federation of European Microbiological Societies. Published by Elsevier B.V. All rights reserved. C1 Univ Estado Rio de Janeiro, Disciplina Microbiol & Imunol, BR-20551030 Rio De Janeiro, Brazil. Fundacao Univ Fed Rio Grande, Univ Hosp, Dept Patol Microbiol & Imunol, BR-96200400 Rio Grande, RS, Brazil. US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA. RP Milagres, LG (reprint author), Univ Estado Rio de Janeiro, Disciplina Microbiol & Imunol, Bl 28 Setembro,87,Fundos 3 Andar, BR-20551030 Rio De Janeiro, Brazil. EM lucimar@uerj.br RI Mendoza Sassi, Raul Andres/A-9976-2009 OI Mendoza Sassi, Raul Andres/0000-0002-4641-9056 NR 23 TC 8 Z9 8 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-8244 J9 FEMS IMMUNOL MED MIC JI FEMS Immunol. Med. Microbiol. PD APR 1 PY 2005 VL 44 IS 1 BP 35 EP 42 DI 10.1016/j.femsim.2004.11.013 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 912ZV UT WOS:000228120200004 PM 15780576 ER PT J AU Sprando, RL Collins, TFX Black, TN Olejnik, N Sapienza, P Ramos-Valle, M Ruggles, DI AF Sprando, RL Collins, TFX Black, TN Olejnik, N Sapienza, P Ramos-Valle, M Ruggles, DI TI Maternal exposure to androstenedione does not induce developmental toxicity in the rat SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE androstenedione; fetus; rats; estrous cycle ID SERUM TESTOSTERONE CONCENTRATIONS; ANDROGENIC STEROID USE; YOUNG MEN; ORAL ANDROSTENEDIONE; ANABOLIC-STEROIDS; SCHOOL-STUDENTS; SUPPLEMENTATION; ADAPTATIONS AB Thirty-day old female rats received corn oil or androstenedione (in corn oil) at one of four concentiations (5.0, 10.0, 30.0 or 60.0 mg/kg body weight) by gavage for two weeks prior to mating, during the mating period and until gestation day (GD) 19. Caesarean sections were performed on GD 20. No dose related changes were observed in serum androstenedione, estradiol, LH, FSH, testosterone or progesterone. A statistically significant decrease in estrous cycle length was observed in the 60.0 mg/kg dose group only. Feed and fluid consumption, mean body weight gain, organ weight and fetal parameters were not affected by androstenedione treatment. At the doses given, androstenedione had no specific effect on the development of individual bones or soft tissues. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sprando, RL (reprint author), US FDA, Dept Toxicol, 8301 Muirkirk Rd, Beltsville, MD 20708 USA. EM rsprando@cfsan.fda.gov NR 28 TC 4 Z9 4 U1 1 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD APR PY 2005 VL 43 IS 4 BP 505 EP 513 DI 10.1016/j.fct.2004.11.020 PG 9 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 902BZ UT WOS:000227327600002 PM 15721196 ER PT J AU Flynn, TJ Sapienza, PP Wiesenfeld, PW Ross, IA Sahu, S Kim, CS O'Donnell, MW Collins, TFX Sprando, RL AF Flynn, TJ Sapienza, PP Wiesenfeld, PW Ross, IA Sahu, S Kim, CS O'Donnell, MW Collins, TFX Sprando, RL TI Effects of oral androstenedione on steroid metabolism in liver of pregnant and non-pregnant female rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE androstenedione; steroids; liver; endocrine disruption; cytochromes P450 ID ANABOLIC-ANDROGENIC STEROIDS; SERUM TESTOSTERONE; YOUNG-WOMEN; IN-VITRO; EXPRESSION; MICROSOMES; INGESTION; ENZYMES AB It is unknown whether androstenedione, a steroidal dietary supplement taken to enhance athletic performance, can affect physiological hormone levels by altering liver enzyme activities that metabolize steroid hormones. Altered homone levels could be especially devastating during pregnancy. Mature female rats were gavaged with 0, 5, 30 or 60 mg/kg/day androstenedione beginning two weeks prior to mating and continuing through gestation day 19. Non-pregnant female rats were gavaged over the same time frame with 0 or 60 mg/kg/day androstenedione. Livers were removed from dams on gestation day 20 and from non-pregnant rats after five weeks' treatment. Liver microsomes were incubated with 200 muM testosterone, and the reaction products were isolated and analyzed by HPLC. In pregnant rats, formation of 6alpha-, 15beta-, 7alpha-, 16beta-, and 20-hydroxytestosterone was increased significantly vs. control at the highest dose level only. Formation of 6beta-hydroxytestosterone increased significantly at both the 30 and 60 mg/kg/day dose levels. In non-pregnant rats, 60 mg/kg/day androstenedione significantly increased formation of 15beta-, 6beta-, 16beta-, and 20-hydroxytestosterone. The data suggest that high oral doses of androstenedione can induce some female rat liver cytochromes P450 that metabolize steroid hormones and that the response to androstenedione does not differ between pregnant and non-pregnant female rats. Published by Elsevier Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Laurel, MD 20708 USA. RP Flynn, TJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM tflynn@cfsan.fda.gov OI Flynn, Thomas/0000-0002-7248-0643 NR 27 TC 4 Z9 4 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD APR PY 2005 VL 43 IS 4 BP 537 EP 542 DI 10.1016/j.fct.2004.12.007 PG 6 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 902BZ UT WOS:000227327600006 PM 15721200 ER PT J AU Sprando, RL Collins, TFX Black, TN Olejnik, N Rorie, JI Eppley, RM Ruggles, DI AF Sprando, RL Collins, TFX Black, TN Olejnik, N Rorie, JI Eppley, RM Ruggles, DI TI Characterization of the effect of deoxynivalenol on selected male reproductive endpoints SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE deoxnivalenol; mycotoxin; rat; testis; spermatogenesis; sperm motility ID SPRAGUE-DAWLEY RATS; FEED RESTRICTION; WINTER-WHEAT; ADULT-RATS; VOMITOXIN; MYCOTOXINS; MICE; 4-DEOXYNIVALENOL; FERTILITY; FOODS AB The effect of deoxynivalenol (DON) exposure on male reproductive function was assessed in the rat. Male rats were divided into a control group (n=15 rats) and four treatment groups (0.5 mg/kg, n = 15; 1.0 mg/kg, n = 15; 2.5 mg/kg, n =: 15; and 5.0 mg/kg DON, n = 16) and exposed to DON daily for 28 days via gastric intubation. Both body weight gain and the final body weight of animals in the 5.0 mg/kg dose group and feed consumption in animals in the 2.5 mg/kg and 5.0 mg/kg dose groups were significantly reduced compared to controls. Fluid consumption was not affected in any of the treated groups. Epididymal and seminal vesicle weights expressed per gram of body weight and brain weight were significantly reduced, compared to control weights, in animals from the 2.5 and 5.0 mg/kg dose groups while prostate weight expressed per gram of brain weight and body weight was significantly lower than controls only in the 5.0 mg/kg dose group. A statistically significant, dose-related decrease in homogenization resistant testicular spermatid counts, spermatid numbers, absolute cauda epididymal sperm numbers and cauda epididymal sperm numbers per gram of cauda epididymis was observed in the 5.0 mg/kg DON treatment group. Sperm tail abnormalities (broken tails) in the 5.0 mg/kg dose group were significantly higher than in the control group. Sperm swimming speed (VSL and VCL) was significantly increased only in the 2.5 mg/kg dose group. Serum FSH and LH concentrations were increased in a dose dependent manner across all treated groups while serum testosterone concentrations were decreased in a dose-related manner across all dose groups. An increase in germ cell degeneration, sperm retention and abnormal nuclear morphology was observed in the 2.5 mg/kg and 5.0 mg/kg dose groups. Treatment related effects included lesions in the non-glandular stomach, thymic lymphoid depletion and splenic hematopoiesis in the 5.0 mg/kg treatment group. (C) 2005 Elsevier Ltd. All rights reserved. C1 US FDA, Dev & Reprod Toxicol Branch, Div Toxicol & Nutr Prod Studies, Off Appl Res & Safety Assessment,Ctr Food Safety, Laurel, MD 20708 USA. RP Sprando, RL (reprint author), US FDA, Dev & Reprod Toxicol Branch, Div Toxicol & Nutr Prod Studies, Off Appl Res & Safety Assessment,Ctr Food Safety, 8301 Muirkirk Rd, Laurel, MD 20708 USA. EM rsprando@cfsan.fda.gov NR 40 TC 23 Z9 28 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD APR PY 2005 VL 43 IS 4 BP 623 EP 635 DI 10.1016/j.fct.2004.12.017 PG 13 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 902BZ UT WOS:000227327600017 PM 15721211 ER PT J AU Dahari, H Major, M Zhang, XN Mihalik, K Rice, CM Perelson, AS Feinstone, SM Neumann, AU AF Dahari, H Major, M Zhang, XN Mihalik, K Rice, CM Perelson, AS Feinstone, SM Neumann, AU TI Mathematical modeling of primary hepatitis C infection: Noncytolytic clearance and early blockage of virion production SO GASTROENTEROLOGY LA English DT Article ID B VIRUS-INFECTION; DYNAMICS IN-VIVO; CD8(+) T-CELLS; TERM-FOLLOW-UP; HCV-RNA LEVELS; VIRAL CLEARANCE; LIVER-TRANSPLANTATION; CHIMPANZEE SERA; PLUS RIBAVIRIN; KINETICS AB Background B Aims: Although hepatitis C virus kinetics and immune determinants during primary infection have been described, the virus-host interplay is not fully understood. We used mathematical modeling to elucidate and quantify virus-host dynamics. Methods: Ten chimpanzees were infected intrahepatically with H77-RNA (n = 3) or intravenously with infected serum. Blood samples were taken 1-3 times per week for 6 months. A new model was fitted to the observed HCV RNA and alanine aminotransferase (ALT) kinetics. Results: After infection, viral levels increased in a biphasic manner with a transient decline in between. This can be explained by a partial block (mean, 91%) of virion production, possibly due to an endogenous type I interferon response. After reaching maximum levels, a long viral plateau (mean, 6A log cp/mL) can be explained by blind homeostasis and lack of susceptible cells. Modest elevations in ALT levels (21-93 IU/L) were concurrently observed, indicating a shorter half-life of infected versus noninfected hepatocytes (mean ratio, 2.6). Following the ALT flare, viral titers rapidly declined to a lower (mean, 4.5 log cp/mL; n = 6) or undetectable level (n = 4). This decline is compatible with increased cell death (mean minimal estimate half-life, 28.7 days) and non-cytolytic clearance (mean maximal estimate half-life, 24.1 days) of infected cells. Conclusions: Our results quantify virus-host dynamics during primary HCV infection and suggest that endogenous type I interferon slows virus production in the early acute phase. Partial or effective virus control correlates with the half-life of infected cells regulated by both cytolytic and noncytolytic mechanisms. C1 Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. Santa Fe Inst, Santa Fe, NM 87501 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatitis Viruses, Bethesda, MD 20014 USA. Rockefeller Univ, Ctr Study Hepatitis C, Lab Virol & Infect Dis, New York, NY 10021 USA. Los Alamos Natl Lab, Div Theoret, Los Alamos, NM USA. RP Neumann, AU (reprint author), Bar Ilan Univ, Fac Life Sci, IL-52900 Ramat Gan, Israel. EM neumann@mail.biu.ac.il FU NCI NIH HHS [CA85833]; NCRR NIH HHS [RR06555] NR 48 TC 56 Z9 57 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR PY 2005 VL 128 IS 4 BP 1056 EP 1066 DI 10.1053/j.gastro.2005.01.049 PG 11 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 914SS UT WOS:000228248600028 PM 15825086 ER PT J AU DiGirolamo, A Thompson, N Martorell, R Fein, S Grummer-Strawn, L AF DiGirolamo, A Thompson, N Martorell, R Fein, S Grummer-Strawn, L TI Intention or experience? Predictors of continued breastfeeding SO HEALTH EDUCATION & BEHAVIOR LA English DT Article DE breastfeeding; intentions; experiences ID PLANNED BEHAVIOR; REASONED ACTION; INCOME WOMEN; INFANT; DURATION; ATTITUDES; DECISION; DETERMINANTS; BARRIERS; FATHERS AB Despite the known benefits of breastfeeding, many women do not breastfeed their infants or stop breastfeeding early. This study examines the effects of prenatal intention and initial breastfeeding experiences on breastfeeding initiation and duration among 1,665 U.S. women completing questionnaires on infant feeding practices. Outcomes included no initiation of breastfeeding at birth and termination at < 10 weeks, 10 to < 20 weeks, or 20 to < 30 weeks. Predictor variables included intended breastfeeding duration and early breastfeeding experiences with analyses controlling for demographic characteristics, previous breastfeeding experience, and prenatal intentions to work after delivery. Prenatal intentions to never initiate or to stop breastfeeding early were significant risk factors for all breastfeeding outcomes. Initial breastfeeding experiences were significant risk factors for early termination. This study supports using the intention construct from the theory of reasoned action to predict initiation of behavior but suggests the need to include initial experience when predicting maintenance of behavior. C1 Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, Atlanta, GA 30322 USA. Emory Univ, Rollins Sch Publ Hlth, Dept Behav Sci & Hlth Educ, Atlanta, GA 30322 USA. US FDA, Consumer Studies Team, College Pk, MD USA. Ctr Dis Control & Prevent, Div Nutr & Phys Activ, Atlanta, GA USA. RP DiGirolamo, A (reprint author), Emory Univ, Rollins Sch Publ Hlth, Dept Global Hlth, 1518 Clifton Rd,NE, Atlanta, GA 30322 USA. EM adigiro@sph.emory.edu RI Martorell, Reynaldo /I-2539-2012 NR 45 TC 87 Z9 92 U1 3 U2 18 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1090-1981 J9 HEALTH EDUC BEHAV JI Health Educ. Behav. PD APR PY 2005 VL 32 IS 2 BP 208 EP 226 DI 10.1177/1090198104271971 PG 19 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 907DH UT WOS:000227695000005 PM 15749967 ER PT J AU Tabor, E AF Tabor, E TI Persistence of antibody after hepatitis B vaccine and the question of boosters SO HEPATOLOGY LA English DT Letter C1 US FDA, Off Blood Res & Review, Rockville, MD 20857 USA. RP Tabor, E (reprint author), US FDA, Off Blood Res & Review, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0270-9139 J9 HEPATOLOGY JI Hepatology PD APR PY 2005 VL 41 IS 4 BP 940 EP 940 DI 10.1002/hep.20606 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 911MD UT WOS:000228006000033 PM 15791611 ER PT J AU Lima, JJ Beasley, BN Parker, RB Johnson, JA AF Lima, JJ Beasley, BN Parker, RB Johnson, JA TI A pharmacodynamic model of the effects of control led-onset extended-release verapamil on 24-hour ambulatory blood pressure SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE verapamil; circadian rhythm; pharmacokinetic/pharmacodynamic model; ambulatory blood pressure ID ESSENTIAL-HYPERTENSION; CIRCADIAN VARIATION; VARIABILITY AB Objective: To formulate and evaluate a pharmacodynamic model that characterizes the effects of S-verapamil on the circadian 24-hour ambulatory blood pressure (ABP). Methods: ABP was recorded in 19 hypertensive patients off drug, and following administration of the targeted dose of COER-V given once daily for at least 30 days. Blood samples were collected after the last dose for determination of the pharmacokinetic of S-verapamil. ABP vs. time was analyzed using a cosinor function, and the effects of S-verapamil on ABP were fitted using the pharmacodynamic model. Results: COER-V decreased average systolic and diastolic blood pressures (mesors): baseline, 142 +/- 10 and 90 +/- 7; treated, 132 +/- 8.8 and 83 +/- 6.6 mmHg, respectively (p < 0.001). COER-V had no effect on the amplitude, cycle or the time shift (acrophase). The mean +/- SD time to peak and maximal S-verapamil concentrations were 9.5 +/- 1.2 hours and 46.4 +/- 35.8 ng/ml, respectively. Model estimates of the maximal inhibited systolic (EmaxS), diastolic (EmaxD) pressures and C-50 were 101 +/- 14 mmHg, 61 +/- 9.9 mmHg and 32.9 +/- 22.8 ng/ml, respectively. The model fit of the data was satisfactory and parameter estimates were precise. Conclusions: The model may be useful to characterize the relationship between plasma concentrations of verapamil and the anti hypertensive effects of the drug and may be suitable for characterizing the effect of drugs on biological functions displaying oscillatory behavior. C1 Nemours Childrens Clin, Ctr Clin Pediat Pharmacol & Pharmacogenet, Jacksonville, FL 32207 USA. Univ Tennessee, Coll Pharm, Memphis, TN 38163 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Florida, Coll Pharm, Gainesville, FL USA. RP Lima, JJ (reprint author), Nemours Childrens Clin, Ctr Clin Pediat Pharmacol & Pharmacogenet, 807 Nira St, Jacksonville, FL 32207 USA. EM Jlima@nemours.org NR 18 TC 2 Z9 2 U1 0 U2 1 PU DUSTRI-VERLAG DR KARL FEISTLE PI DEISENHOFEN-MUENCHEN PA BAHNHOFSTRASSE 9 POSTFACH 49, D-82032 DEISENHOFEN-MUENCHEN, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD APR PY 2005 VL 43 IS 4 BP 187 EP 194 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 912QI UT WOS:000228093900004 PM 15966465 ER PT J AU Bash, MC Zhu, PX Gulati, S McKnew, D Rice, PA Lynn, F AF Bash, MC Zhu, PX Gulati, S McKnew, D Rice, PA Lynn, F TI por variable-region typing by DNA probe hybridization in broadly applicable to epidemiologic studies of Neisseria gonorrhoaea SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID OUTER-MEMBRANE PROTEIN; FIELD GEL-ELECTROPHORESIS; GONOCOCCAL INFECTIONS; GENETIC DIVERSITY; HYBRID PORINS; IB GENE; TRANSMISSION; POPULATION; STRAIN; SEROVARS AB The porin gene (porB) of Neisseria gonorrhoeae encodes the major outer membrane protein identified as PI or Por. To examine the utility of por variable-region (VR) typing, porB from 206 isolates was characterized by using oligonucleotide probes in a checkerboard hybridization assay that identifies the sequence types of five VRs of both PIA and PIB porB alleles. The strains represented temporally and geographically distinct isolates, isolates from a large cluster, epidemiologically linked partner isolates, and a collection of strains from disseminated gonococcal infections. By using rigorous epidemiologic criteria for transmission of infection between sex partners, por VR typing was more discriminatory than serovar typing in classifying isolates from both members of 43 epidemiologically linked pairs: 39 of 43 pairs were classified as coinciding by por VR typing compared to 43 of 43 by serovar determination (P = 0.058). porB sequence data confirmed the accuracy of the por VR method. Relationships between VR type and serovar typing monoclonal antibodies were observed for all six PIB and three of six PIA antibodies. por VR typing is a molecular tool that appears to have broad applicability. This method can be adapted to a wide range of technologies from simple hybridization to microarray and may allow for typing from noncultured clinical specimens. C1 Uniformed Serv Univ Hlth Sci, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Rockville, MD 20852 USA. Boston Univ, Ctr Med, Dept Med, Evans Biomed Res Ctr, Boston, MA 02215 USA. Boston Univ, Med Ctr, Sect Infect Dis, Boston, MA 02215 USA. Childrens Natl Med Ctr, Div Infect Dis, Washington, DC USA. RP Bash, MC (reprint author), Uniformed Serv Univ Hlth Sci, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, HFM-428, Rockville, MD 20852 USA. EM mbash@helix.nih.gov NR 47 TC 10 Z9 11 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 2005 VL 43 IS 4 BP 1522 EP 1530 DI 10.1128/JCM.43.4.1522-1530.2005 PG 9 WC Microbiology SC Microbiology GA 916RS UT WOS:000228404100004 PM 15814961 ER PT J AU Noah, CW Shaw, CI Ikeda, JS Kreuzer, KS Sofos, JN AF Noah, CW Shaw, CI Ikeda, JS Kreuzer, KS Sofos, JN TI Development of green fluorescent protein-expressing bacterial strains and evaluation for potential use as positive controls in sample analyses SO JOURNAL OF FOOD PROTECTION LA English DT Article ID GENE-EXPRESSION; MARKER; PSEUDOMONAS AB Strains of enterohemorrhagic Escherichia coli O157:H7 and Salmonella Typhimurium were engineered to express the gene for a modified green fluorescent protein (GFP) and were evaluated for potential use as positive controls in sample analyses. The strains fluoresced when observed as colonies with a handheld UV lamp or as individual cells under a fluorescent microscope. The strains maintained their fluorescence following growth in three series of transfer experiments including 8 to I I passages from broth to broth and twice for 15 consecutive transfers from broth onto Trypticase soy agar plates. Cultures also maintained stability in the ability to fluoresce when agar plates were refrigerated (4 degrees C) for up to 12 days. Growth characteristics of the GFP-positive strains were comparable to those of corresponding control strains. The GFP-positive strains were successfully identified using rapid diagnostic methods and were differentiated from their corresponding non-GFP strains by pulsedfield gel electrophoresis but not by repetitive extragenic palindromic PCR. The GFP-positive and the control strains were recovered successfully from individually inoculated food samples (Feta cheese, raw shrimp, cooked shrimp, and cooked crawfish). However, in one Feta cheese sample and one raw shrimp sample inoculated with combined GFP-positive and GFP-negative cultures, colonies of the GFP-positive strains were not observed under UV light; fluorescing cells in one of the inoculated samples (raw shrimp) were revealed by microscopy. In general, the isolates from the inoculated foods were GFP positive by microscopic examination; the pure isolates could also be restreaked onto Trypticase soy agar, and colonies could be visually examined under UV light. Because GFP strains are not known to occur naturally in the environment, the use of the Salmonella GFP-positive strain may offer advantages as a positive control even when distinct and rare serotypes are available. The GFP-positive E. coli O157:H7 strain may also prove beneficial for use as a positive control strain for sample analyses. C1 US FDA, Denver Dist Off, Denver, CO 80225 USA. Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. RP Noah, CW (reprint author), US FDA, Denver Dist Off, 6th Ave & Kipling St, Denver, CO 80225 USA. EM cnoah@ora.fda.gov NR 18 TC 25 Z9 25 U1 4 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 2005 VL 68 IS 4 BP 680 EP 686 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 913KV UT WOS:000228151400004 PM 15830656 ER PT J AU Blau, DM McCluskey, BJ Ladely, SR Dargatz, DA Fedorka-Cray, PJ Ferris, KE Headrick, ML AF Blau, DM McCluskey, BJ Ladely, SR Dargatz, DA Fedorka-Cray, PJ Ferris, KE Headrick, ML TI Salmonella in dairy operations in the United States: Prevalence and antimicrobial drug susceptibility SO JOURNAL OF FOOD PROTECTION LA English DT Article ID RESISTANT SALMONELLA; RISK-FACTORS; HERDS; ENTERICA; CATTLE; COWS; TRANSMISSION; OUTBREAK AB Salmonella serotypes are important foodborne pathogens of humans that can be acquired through consumption of contaminated meat and dairy products. Salmonella infection also can be a significant animal health issue. As part of a national study of U.S. dairy operations conducted between March and September 2002, fecal samples were collected from representative cows in 97 dairy herds in 21 states and were cultured to determine the prevalence of Salmonella shedding. Salmonella was recovered from the feces of at least one cow in 30.9% of the herds. Overall, 7.3% of fecal samples were culture positive for Salmonella. The three most frequently recovered serotypes were Salmonella Meleagridis (24.1%), Salmonella Montevideo (11.9%), and Salmonella Typhimurium (9.9%). The susceptibilities of Salmonella isolates recovered were determined using a panel of 16 antimicrobial drugs. Salmonella isolates recovered from dairy cows had relatively little resistance to these antimicrobial agents; 83.0% of the isolates were susceptible to all antimicrobials tested. This study provides updated information on the prevalence and susceptibility patterns of Salmonella in dairy herds and on cow and herd characteristics. These data contribute to our understanding of the ecology of Salmonella in the dairy farm environment. C1 USDA, Ctr Epidemiol, Anim & Plant Hlth Inspect Serv, Ft Collins, CO 80526 USA. USDA, Ctr Anim Hlth, Anim & Plant Hlth Inspect Serv, Ft Collins, CO 80526 USA. USDA, Antimicrobial Resistance Res Unit, Agr Res Serv, Athens, GA 30604 USA. USDA, Natl Vet Serv Labs, Anim & Plant Hlth Inspect Serv, Ames, IA 50010 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Dargatz, DA (reprint author), USDA, Ctr Epidemiol, Anim & Plant Hlth Inspect Serv, Ft Collins, CO 80526 USA. EM david.a.dargatz@aphis.usda.gov NR 26 TC 42 Z9 42 U1 1 U2 9 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD APR PY 2005 VL 68 IS 4 BP 696 EP 702 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 913KV UT WOS:000228151400006 PM 15830658 ER PT J AU Newton, KM Buist, DSM Miglioretti, DL Beverly, K Hortsfield, CL Chan, KA Andrade, SE Wei, FF Connelly, M Kessler, L AF Newton, KM Buist, DSM Miglioretti, DL Beverly, K Hortsfield, CL Chan, KA Andrade, SE Wei, FF Connelly, M Kessler, L TI The impact of comorbidities on hormone use - After the 2002 release of the Women's Health Initiative SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE hormone therapy; women; menopause; estrogen; fracture ID ESTROGEN PLUS PROGESTIN; RANDOMIZED CONTROLLED-TRIAL; POSTMENOPAUSAL WOMEN; THERAPY; DISEASE; MEMORY AB OBJECTIVE: Determine the impact of fracture, coronary disease, and diabetes on changes in rates of discontinuation and initiation of estrogen therapy with (EPT) and without (ET) progestin, before (September 1. 1999 to June 30, 2002. baseline) versus 5 months after (follow-up) release of the Women's Health Initiative EPT trial results (WHI). DESIGN, SETTING, AND PARTICIPANTS: Observational cohort; 169,586 women 40 to 80 years old from 5 U.S. HMOs. METHODS: We used pharmacy data to identify ET and EPT users. A woman was a user any month she filled >= 1 estrogen prescription and in subsequent months based upon the number of pills/patches dispensed. We used inpatient and outpatient claims to identify fracture January 1, 1999 to June 30, 2002 and pharmacy data to identify disease-based groups of medications for diabetes and cardiovascular disease. MEASURES: EPT/ET prevalence, initiation, and discontinuation rates. RESULTS: Baseline to follow-up EPT and ET prevalence declined 45% and 22%, respectively, with no difference by comorbidity. Follow-up EPT initiation was half the baseline rate irrespective of comorbidity. Compared to baseline, follow-up EPT discontinuation rates increased among women with diabetes (relative risk [RR], 6.9; 95% confidence interval [CI], 5.6 to 8.4), cardiovascular disease (RR, 5.5; 95% Cl, 4.9 to 6.2), fracture [RR, 3.8; 95% Cl, 2.4 to 5.7), and no comorbidity [RR, 4.4; 95% Cl, 3.9 to 4.9). The RRs for follow-up versus baseline EPT discontinuation were higher among women with diabetes (P<.01) and cardiovascular disease (P<.01) versus women without these comorbidities. ET discontinuation rates among these same groups were elevated 2- to 2.8-fold. CONCLUSIONS: Diabetes and cardiovascular disease were associated with higher EPT discontinuation rates post-WHI compared to women without comorbidity; comorbidity had little impact on changes in prevalence or initiation of ET/EPT after release of the WHI. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Sch Publ Hlth & Community Med, Seattle, WA 98195 USA. Kaiser Permanente, Denver, CO USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA USA. HMO Res Networks Ctr Educ & Res Therapeut, Worcester, MA USA. Meyers Primary Care Inst, Worcester, MA USA. HealthPartners Res Fdn, Minneapolis, MN USA. Harvard Pilgrim Hlth Care, Dept Ambulatory Care & Prevent, Boston, MA USA. Harvard Vanguard Med Assoc, Menopause Consultat Serv, Boston, MA USA. US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Newton, KM (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave,Suite 1600, Seattle, WA 98101 USA. EM newton.k@9hc.org OI Chan, Kinwei/0000-0001-8161-1986 FU AHRQ HHS [U18 HS011843, U18HS11843-01]; NCI NIH HHS [U19 CA079689] NR 18 TC 10 Z9 10 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0884-8734 EI 1525-1497 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD APR PY 2005 VL 20 IS 4 BP 350 EP 356 DI 10.1111/j.1525-1497.2005.04059.x PG 7 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 922KH UT WOS:000228836300007 PM 15857493 ER PT J AU Rubin, SA Afzal, MA Powell, CL Bentley, ML Auda, GR Taffs, RE Carbone, KM AF Rubin, SA Afzal, MA Powell, CL Bentley, ML Auda, GR Taffs, RE Carbone, KM TI The rat-based neurovirulence safety test for the assessment of mumps virus neurovirulence in humans: An international collaborative study SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article ID HEMAGGLUTININ-NEURAMINIDASE GENE; VACCINE STRAIN; NUCLEOTIDE-SEQUENCE; ASEPTIC-MENINGITIS; RUBELLA VACCINE; INBRED STRAINS; CHILDREN; MEASLES; NORVEGICUS; MIXTURE AB Because of the highly neurotropic and neurovirulent properties of wild-type mumps viruses, most national regulatory organizations require neurovirulence testing of virus seeds used in the production of mumps vaccines. Such testing has historically been performed in monkeys; however, some data suggest that testing in monkeys does not necessarily discriminate among the relative neurovirulent risks of mumps virus strains. To address this problem, a collaborative study was initiated by the National Institute for Biological Standards and Control in the United Kingdom and the Food and Drug Administration in the United States, to test a novel rat-based mumps virus neurovirulence safety test. Results indicate that the assay correctly assesses the neurovirulence potential of mumps viruses in humans and is robust and reproducible. C1 US FDA, DVP, OVRR, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Off Director, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Natl Inst Biol Stand & Controls, Div Virol, Potters Bar EN6 3QG, Herts, England. RP Rubin, SA (reprint author), US FDA, DVP, OVRR, Ctr Biol Evaluat & Res, Bldg 29A,Rm 1A-21,8800 Rockville Pike, Bethesda, MD 20892 USA. EM rubins@cber.fda.gov NR 24 TC 32 Z9 34 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR 1 PY 2005 VL 191 IS 7 BP 1123 EP 1128 DI 10.1086/428098 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 903IB UT WOS:000227418200015 PM 15747248 ER PT J AU Beer, JZ Yamaguchi, Y Tadokoro, T Batzer, J Coelho, SG Zmudzka, BZ Miller, SA Wolber, R Hearing, VJ AF Beer, JZ Yamaguchi, Y Tadokoro, T Batzer, J Coelho, SG Zmudzka, BZ Miller, SA Wolber, R Hearing, VJ TI UV-induced redistribution of epidermal melanin in different races - a defensive response? SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. Beiersdorf AG, Skin Res, Res & Dev, Hamburg, Germany. RI Yamaguchi, Yuji/B-9312-2008 NR 0 TC 0 Z9 0 U1 1 U2 1 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 808 BP A135 EP A135 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901350 ER PT J AU King, KE Ponnamperuma, RM Weinberg, WC AF King, KE Ponnamperuma, RM Weinberg, WC TI COOH-terminal differences between Delta Np63 isotypes mediate distinct biological effects in association with altered transcription factor binding SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 US FDA, CDER, Off Biotechnol Prod, Bethesda, MD 20014 USA. RI Weinberg, Wendy/A-8920-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 140 BP A24 EP A24 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179900141 ER PT J AU Miller, SA Zmudzka, BZ Coelho, SG Beer, JZ AF Miller, SA Zmudzka, BZ Coelho, SG Beer, JZ TI Comparison of different UV exposure regimens for cosmetic tanning SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 818 BP A137 EP A137 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901361 ER PT J AU Yamaguchi, Y Takahashi, K Zmudzka, BZ Kornhauser, A Miller, SA Tadokoro, T Berens, W Itami, S Katayama, I Beer, JZ Hearing, VJ AF Yamaguchi, Y Takahashi, K Zmudzka, BZ Kornhauser, A Miller, SA Tadokoro, T Berens, W Itami, S Katayama, I Beer, JZ Hearing, VJ TI Melanin in the upper epidermis not only protects against UV-induced DNA damage but also facilitates apoptosis in its vicinity SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract CT 66th Annual Meeting of the Society-for-Investigative-Dermatology CY MAY 04-07, 2005 CL St Louis, MO SP Soc Investigat Dermatol C1 NCI, Cell Biol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Ctr Food Safety & Nutr, College Pk, MD USA. Osaka Univ, Grad Sch Med, Suita, Osaka, Japan. RI Yamaguchi, Yuji/B-9312-2008 NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 2005 VL 124 IS 4 SU S MA 830 BP A139 EP A139 PG 1 WC Dermatology SC Dermatology GA 913UT UT WOS:000228179901373 ER PT J AU Kim Il, P Erickson, BD Cerniglia, CE AF Kim Il, P Erickson, BD Cerniglia, CE TI A membrane-array method to detect specific human intestinal bacteria in fecal samples using reverse transcriptase-PCR and chemiluminescence SO JOURNAL OF MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article DE human intestinal microflora; membrane array; RT-PCR; chemiluminescence detection ID IN-SITU HYBRIDIZATION; TARGETED OLIGONUCLEOTIDE PROBES; RIBOSOMAL-RNA; HUMAN FECES; POPULATIONS; QUANTIFICATION; IDENTIFICATION; MICROFLORA; PRIMERS; DESIGN AB A membrane-based oligonucleotide array was used to detect predominant bacterial species in human fecal samples. Digoxygenin-labeled 16S rDNA probes were generated by PCR from DNA that had been extracted from fecal samples or slurries. These probes were hybridized to an array of 120 oligonucleotides with sequences specific for 40 different bacterial species commonly found in human feces, followed by color development using an alkaline phosphatase-conjugated antibody and NBT/BCIP. Twenty of the species were detected by this method, but E coli, which was present at similar to 1 x 10(5) W CFU per gram feces, was not detected. To improve the sensitivity of this assay, reverse transcriptase-PCR was used to generate probes from RNA extracted from fecal cultures. Coupled with a chemiluminescence detection method, this approach lowered the detection limit for E. coli from similar to 1 X 10(6) to <= 1 X 10(5). These results indicate that the membrane-array method with reverse transcriptase-PCR and chemilurninescence detection can simultaneously identify bacterial species present in fecal samples at cell concentrations as low as <= 1 x 10(5) CFU per gram. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ccerniglia@nctr.fda.gov NR 38 TC 0 Z9 0 U1 1 U2 1 PU KOREAN SOC MICROBIOLOGY & BIOTECHNOLOGY PI SEOUL PA KOREA SCI TECHNOL CENTER #507, 635-4 YEOGSAM-DONG, KANGNAM-GU, SEOUL 135-703, SOUTH KOREA SN 1017-7825 J9 J MICROBIOL BIOTECHN JI J. Microbiol. Biotechnol. PD APR PY 2005 VL 15 IS 2 BP 310 EP 320 PG 11 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 922CP UT WOS:000228813800014 ER PT J AU Mahmood, I AF Mahmood, I TI Interspecies scaling of biliary excreted drugs: A comparison of everal methods SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE preclinical pharmacokinetics; allometric scaling; correction factors; clearance; monkey liver blood flow; biliary excretion; the rule of exponents; bile flow; UDP-glucuronyl transferase (UDPGT); mean absolute error ID LABORATORY-ANIMALS; PHARMACOKINETICS; HUMANS; ANTAGONIST; MONKEYS; RATS; EXTRAPOLATION; DISPOSITION; PARAMETERS; CLEARANCE AB The objective of this study was to evaluate the predictive performance of several methods of interspecies scaling for the prediction of human clearance of drugs which are excreted in the bile. Ten methods of allometric scaling were used to predict human clearance of biliary excreted drugs from animal data. The methods included the simple allometric approach; the rule of exponents; the rule of exponents with a correction factor; the ratio of human and monkey liver blood flow x monkey clearance; product of clearance and bile flow; product of clearance and UDGPT; product of clearance, bile flow, and UDGPT; and a modified version of the last three approaches in association with the rule of exponents. The results of the study indicate that among these ten approaches, the rule of exponents with the correction factor is the best approach for the prediction of human clearance for drugs which are excreted in the bile. The worst approach is the product of clearance, bile flow, and UDGPT. The simple allometry and the monkey liver blood flow (MLBF) approaches gave almost similar results. For some drugs the simple allometry predicted clearance better than the MLBF approach and vice versa. (c) 2005 Wiley-Liss, Inc. and the American Pharmacists Association. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 6, Clin Pharmacol & Toxicol Branch HFD579, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 6, Clin Pharmacol & Toxicol Branch HFD579, Woodmont Off Ctr 2, Rockville, MD 20852 USA. EM Mahmoodi@CDER.FDA.GOV NR 19 TC 35 Z9 36 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0022-3549 J9 J PHARM SCI-US JI J. Pharm. Sci. PD APR PY 2005 VL 94 IS 4 BP 883 EP 892 DI 10.1002/jps.20313 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 913KL UT WOS:000228150400018 PM 15736194 ER PT J AU Jones, P Sundlof, SF AF Jones, P Sundlof, SF TI Pharmacovigilance of veterinary medicines SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Editorial Material C1 European Med Agcy, London, England. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Jones, P (reprint author), European Med Agcy, London, England. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD APR PY 2005 VL 28 IS 2 BP 127 EP 128 DI 10.1111/j.1365-2885.2005.00653.x PG 2 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 916BY UT WOS:000228361600001 PM 15842302 ER PT J AU Desmezieres, E Gupta, N Vassell, R He, Y Peden, K Sirota, L Yang, ZN Wingfield, P Weiss, CD AF Desmezieres, E Gupta, N Vassell, R He, Y Peden, K Sirota, L Yang, ZN Wingfield, P Weiss, CD TI Human immunodeficiency virus (HIV) gp41 escape mutants: Cross-resistance to peptide inhibitors of HIV fusion and altered receptor activation of gp120 SO JOURNAL OF VIROLOGY LA English DT Article ID TYPE-1 ENVELOPE GLYCOPROTEIN; TRANSMEMBRANE PROTEIN GP41; MEMBRANE-FUSION; COILED-COIL; INTERHELICAL INTERACTIONS; FUNCTIONAL-ANALYSIS; ENFUVIRTIDE T-20; ATOMIC-STRUCTURE; 6-HELIX BUNDLE; DOMAIN AB Human immunodeficiency virus (HIV) infects cells by fusing with cellular membranes. Fusion occurs when the envelope glycoprotein (Env) undergoes conformational changes while binding to cellular receptors. Fusogenic changes involve assembly of two heptad repeats in the ectodomain of the gp41 transmembrane subunit to form a six-helix bundle (6HB), consisting of a trimeric N heptad repeat (N-HR) coiled-coil core with three antiparallel C heptad repeats (C-HRs) that pack in the coiled-coil grooves. Peptides corresponding to the N-and C-HRs (N and C peptides, respectively) interfere with formation of the 6HB in a dominant-negative manner and are emerging as a new class of antiretroviral therapeutics for treating HIV infection. We generated an escape mutant virus with resistance to an N peptide and show that early resistance involved two mutations, one each in the N- and C-HRs. The mutations conferred resistance not only to the selecting N peptide but also to C peptides, as well as other types of N-peptide inhibitors. Moreover, the N-HR mutation altered sensitivity to soluble CD4. Biophysical studies suggest that the 6HB with the resistance mutations is more stable than the wild-type 6HB and the 6HB formed by inhibitor binding to either wild-type or mutant C-HR. These findings provide new insights into potential mechanisms of resistance to HIV peptide fusion inhibitors and dominant-negative inhibitors in general. The results are discussed in the context of current models of Env-mediated membrane fusion. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Biostat, Bethesda, MD 20892 USA. Natl Inst Arthritis & Musculoskeletal Dis, Prot Express Lab, NIH, Bethesda, MD USA. RP Weiss, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, HFM-466,Bldg 29,Room 532,8800 Rockville Pike, Bethesda, MD 20892 USA. EM cdweiss@helix.nih.gov RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 43 TC 17 Z9 18 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 2005 VL 79 IS 8 BP 4774 EP 4781 DI 10.1128/JVI.79.4.4774-4781.2005 PG 8 WC Virology SC Virology GA 912JJ UT WOS:000228073700022 PM 15795263 ER PT J AU Hampshire, V Davis, JA AF Hampshire, V Davis, JA TI The role of the veterinary staff in mouse breeding colony management SO LAB ANIMAL LA English DT Article ID SYSTEM; MICE AB The rapid increase in the production and use of transgenic mice has been a boon for biomedical research and a challenge for the animal care and use programs responsible for providing housing and medical care to these animals. The authors suggest ways in which the veterinary staff can successfully organize and manage transgenic mouse breeding programs to reduce uncontrolled breeding and the problems associated with it. C1 US FDA, Ctr Vet Med, Rockville, MD 20892 USA. NINDS, NIH, Bethesda, MD 20892 USA. RP Hampshire, V (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20892 USA. EM vhampshi@cvm.fda.gov NR 9 TC 3 Z9 3 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD APR PY 2005 VL 34 IS 4 BP 45 EP 49 DI 10.1038/laban0405-45 PG 5 WC Veterinary Sciences SC Veterinary Sciences GA 914DB UT WOS:000228204000011 PM 15806090 ER PT J AU Parsons, BL Beland, FA Von Tungeln, LS Delongchamp, RR Fu, PP Heflich, RH AF Parsons, BL Beland, FA Von Tungeln, LS Delongchamp, RR Fu, PP Heflich, RH TI Levels of 4-aminobiphenyl-induced somatic H-ras mutation in mouse liver DNA correlate with potential for liver tumor development SO MOLECULAR CARCINOGENESIS LA English DT Article DE biomarker; carcinogenesis; point mutation; risk assessment; oncogene; ras ID C57BL/6J MALE-MICE; C3H-HEJ MALE-MICE; GENOTYPIC SELECTION; RODENT BIOASSAY; B6C3F1 MOUSE; COMPARATIVE CARCINOGENICITY; RISK-ASSESSMENT; NEONATAL MOUSE; HEPATOCARCINOGENESIS; TUMORIGENICITY AB The utility of liver H-ras codon 61 CAA to AAA mutant fraction as a biomarker of liver tumor development was investigated using neonatal male mice treated with 4-aminobiphenyl (4-ABP). Treatment with 0.1, 0.3, or 1.0 mu mol 4-ABP produced dose-dependent increases in liver DNA adducts in B6C3F(1) and C57BL/6N mice. Eight months after treatment with 0.3 mu mol 4-ABP or the DMSO vehicle, H-ras codon 61 CAA to AAA mutant fraction was measured in liver DNA samples (n = 12) by allele-specific competitive blocker-polymerase chain reaction (ACB-PCR). A significant increase in average mutant fraction was found in DNA of 4-ABP-treated mice, with an increase from 1.3 x 10(-5) (control) to 44.9 x 10(-5) (treated) in B6C3F(1) mice and from 1.4 x 10(-5) to 7.0 x 10(-5) in C57BL/6N mice. Compared with C57BL/6N mutant fractions, B6C3F(1) mutant fractions were more variable and included some particularly high mutant fractions, consistent with the more rapid development of liver foci expected in B6C3F(1) mouse liver. Twelve months after treatment, liver tumors developed in 79.2% of 4-ABP-treated and 22.2% of control B6C3F(1) mice; thus measurement of H-ras mutant fraction correlated with subsequent tumor development. This study demonstrates that ACB-PCR can directly measure background levels of somatic oncogene mutation and detect a carcinogen-induced increase in such mutation. Published 2005 Wiley-Liss, Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 33 TC 17 Z9 17 U1 0 U2 1 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 APR PY 2005 VL 42 IS 4 BP 193 EP 201 DI 10.1002/mc.20083 PG 9 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 913QF UT WOS:000228167200002 PM 15761837 ER PT J AU Sheehan, KM Calvert, VS Kay, EW Lu, YL Fishman, D Espina, V Aquino, J Speer, R Araujo, R Mills, GB Liotta, LA Petricoin, EF Wulfkuhle, JD AF Sheehan, KM Calvert, VS Kay, EW Lu, YL Fishman, D Espina, V Aquino, J Speer, R Araujo, R Mills, GB Liotta, LA Petricoin, EF Wulfkuhle, JD TI Use of reverse phase protein microarrays and reference standard development for molecular network analysis of metastatic ovarian carcinoma SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID CANCER-CELL-LINES; C-KIT; CLINICAL PROTEOMICS; PROSTATE-CANCER; BREAST-CANCER; TRASTUZUMAB HERCEPTIN; KINASE INHIBITORS; ANTICANCER DRUGS; ZD1839 IRESSA; MAP KINASE AB Cancer can be defined as a deregulation or hyperactivity in the ongoing network of intracellular and extracellular signaling events. Reverse phase protein microarray technology may offer a new opportunity to measure and profile these signaling pathways, providing data on posttranslational phosphorylation events not obtainable by gene microarray analysis. Treatment of ovarian epithelial carcinoma almost always takes place in a metastatic setting since unfortunately the disease is often not detected until later stages. Thus, in addition to elucidation of the molecular network within a tumor specimen, critical questions are to what extent do signaling changes occur upon metastasis and are there common pathway elements that arise in the metastatic microenvironment. For individualized combinatorial therapy, ideal therapeutic selection based on proteomic mapping of phosphorylation end points may require evaluation of the patient's metastatic tissue. Extending these findings to the bedside will require the development of optimized protocols and reference standards. We have developed a reference standard based on a mixture of phosphorylated peptides to begin to address this challenge. C1 US FDA, FDA NCI, Clin Prote Program,Off Cell Tissue & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, FDA NCI, Clin Prote Program,Lab Pathol,Ctr Canc Res, NCI,NIH, Bethesda, MD 20892 USA. Beaumont Hosp, Dept Pathol, Dublin 9, Ireland. Royal Coll Surgeons Ireland, Dublin 2, Ireland. Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Houston, TX 77054 USA. NYU, Natl Ovarian Canc Early Detect Program, New York, NY 10016 USA. RP Wulfkuhle, JD (reprint author), US FDA, FDA NCI, Clin Prote Program,Off Cell Tissue & Gene Therapy, Ctr Biol Evaluat & Res, Bldg 29A-2D12,HFM 710,8800 Rockville Pike, Bethesda, MD 20892 USA. EM wulfkuhlecber@fda.gov OI Espina, Virginia/0000-0001-5080-5972 FU NCI NIH HHS [P01 CA64602, P50CA83639A] NR 79 TC 202 Z9 213 U1 2 U2 8 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 1535-9476 J9 MOL CELL PROTEOMICS JI Mol. Cell. Proteomics PD APR PY 2005 VL 4 IS 4 BP 346 EP 355 DI 10.1074/mcp.T500003-MCP200 PG 10 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 911DB UT WOS:000227980600002 PM 15671044 ER PT J AU Williams, CL Boucher, PE Stibitz, S Cotter, PA AF Williams, CL Boucher, PE Stibitz, S Cotter, PA TI BvgA functions as both an activator and a repressor to control Bvg(i) phase expression of bipA in Bordetella pertussis SO MOLECULAR MICROBIOLOGY LA English DT Article ID RESPONSE REGULATOR BVGA; RNA-POLYMERASE; FHA PROMOTER; TRANSCRIPTIONAL ACTIVATION; DIFFERENTIAL REGULATION; RESPIRATORY-INFECTION; GENETIC-ANALYSIS; VIRULENCE GENES; TOXIN PROMOTER; DNA-BINDING AB The Bordetella bipA gene is expressed maximally when the BvgAS phosphorelay is semi-active, i.e. in the Bvg-intermediate (Bvg(i)) phase. We used a BvgA-FeBABE cleavage approach together with site-directed mutagenesis and bipA-lacZ fusion analyses to determine precisely where BvgA-phosphate (BvgAsimilar toP) binds at the bipA promoter and how that binding contributes to the complex transcription pattern displayed by bipA. BvgAsimilar toP bound with high affinity and cooperatively with RNAP to sequences at the bipA promoter immediately 5' to and overlapping those bound by RNAP to activate transcription under Bvg(i) phase conditions. bipA therefore, like fhaB, appears to be similar to classical class-II promoters with regard to the mechanism by which its transcription is activated. BvgAsimilar toP bound with relatively low affinity to sequences immediately 3' of those bound by RNAP at the bipA promoter and this binding mediated repression of bipA transcription under Bvg(+) phase conditions. BvgAsimilar toP binding to these sequences occurred simultaneously, if not cooperatively, with RNAP, indicating that BvgAsimilar toP represses bipA expression by inhibiting transcription initiation and/or elongation, rather than by competing with RNAP for binding. As bipA is the first Bvg(i) phase gene to be characterized, and the first gene shown to be repressed by BvgAsimilar toP directly, our results will provide a basis for comparison as additional Bvg-regulated genes are identified and characterized. C1 Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. RP Cotter, PA (reprint author), Univ Calif Santa Barbara, Dept Mol Cellular & Dev Biol, Santa Barbara, CA 93106 USA. EM cotter@lifesci.ucsb.edu RI Meares, Claude/A-8345-2011 FU NIAID NIH HHS [AI43986] NR 45 TC 30 Z9 30 U1 0 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD APR PY 2005 VL 56 IS 1 BP 175 EP 188 DI 10.1111/j.1365-2958.2004.04526.x PG 14 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 904LH UT WOS:000227499000015 PM 15773988 ER PT J AU Lineback, DR AF Lineback, DR TI Role of diet in blood glucose response and related health outcomes: Summary of a meeting SO NUTRITION REVIEWS LA English DT Review DE blood glucose; carbohydrates; diet; glycemic index; glycemic response ID IOWA WOMENS HEALTH; LOW-GLYCEMIC-INDEX; TYPE-2 DIABETES-MELLITUS; BREAST-CANCER; OLDER WOMEN; POSTPRANDIAL GLUCOSE; INSULIN RESPONSES; HEART-DISEASE; MIXED MEALS; RISK AB Consumption of foods that elicit a marked glycemic response have been proposed as risk factors for obesity and insulin resistance. A group of experts from around the world participated in a discussion of scientific issues about the role of diet in blood glucose response and related health outcomes. The goal was to determine how diet can best be used to prevent rather than to treat disease. This was an informed discussion rather than a formal, evidence-based review. To resolve debate on this topic, well-controlled research with healthy individuals is needed. C1 Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Lineback, DR (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, 0220 Symons Hall, College Pk, MD 20742 USA. EM lineback@umd.edu NR 51 TC 2 Z9 2 U1 2 U2 3 PU INT LIFE SCIENCES INST NORTH AMERICA PI WASHINGTON PA ONE THOMAS CIRCLE, N W, 9TH FLOOR, WASHINGTON, DC 20005 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD APR PY 2005 VL 63 IS 4 BP 126 EP 131 DI 10.1111/j.1753-4887.2005.tb00131.x PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 912ZL UT WOS:000228119100004 PM 15869127 ER PT J AU Faris, OP Shein, MJ AF Faris, OP Shein, MJ TI Government viewpoint: US food & drug administration: Pacemakers, ICDs and MRI SO PACE-PACING AND CLINICAL ELECTROPHYSIOLOGY LA English DT Editorial Material ID IN-VITRO; SAFETY; VIVO C1 US FDA, Div Cardiovasc Devices, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Shein, MJ (reprint author), US FDA, Div Cardiovasc Devices, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 6 TC 42 Z9 42 U1 1 U2 1 PU BLACKWELL FUTURA PUBLISHING, INC PI MALDEN PA 350 MAIN STREET, MALDEN, MA 01248-5018 USA SN 0147-8389 J9 PACE JI PACE-Pacing Clin. Electrophysiol. PD APR PY 2005 VL 28 IS 4 BP 268 EP 269 DI 10.1111/j.1540-8159.2005.50035.x PG 2 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical SC Cardiovascular System & Cardiology; Engineering GA 921UF UT WOS:000228789900005 PM 15826256 ER PT J AU Baylor, MS Johann-Liang, R AF Baylor, MS Johann-Liang, R TI Enfurvirtide safety in human immunodeficiency virus-infected children SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Letter C1 US FDA, Div Antiviral Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD USA. RP Baylor, MS (reprint author), US FDA, Div Antiviral Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD USA. NR 3 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 APR PY 2005 VL 24 IS 4 BP 389 EP 390 DI 10.1097/01.inf.0000157923.23777.c4 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 918RU UT WOS:000228566100024 PM 15818309 ER PT J AU Lee, JW Weiner, RS Sailstad, JM Bowsher, RR Knuth, DW O'Brien, PJ Fourcroy, JL Dixit, R Pandite, L Pietrusko, RG Soares, HD Quarmby, V Vesterqvist, OL Potter, DM Witliff, JL Fritche, HA O'Leary, T Perlee, L Kadam, S Wagner, JA AF Lee, JW Weiner, RS Sailstad, JM Bowsher, RR Knuth, DW O'Brien, PJ Fourcroy, JL Dixit, R Pandite, L Pietrusko, RG Soares, HD Quarmby, V Vesterqvist, OL Potter, DM Witliff, JL Fritche, HA O'Leary, T Perlee, L Kadam, S Wagner, JA TI Method validation and measurement of biomarkers in nonclinical and clinical samples in drug development: A conference report SO PHARMACEUTICAL RESEARCH LA English DT Article DE biomarkers; nonclinical and clinical drug development; quantitative method development and validation ID ROLLING-CIRCLE AMPLIFICATION; SURROGATE END-POINTS; DIABETES-MELLITUS; MICROARRAYS; RECOMMENDATIONS; MACROMOLECULES; IMMUNOASSAYS; OPTIMIZATION; MARKERS; ASSAYS AB Biomarkers are increasingly used in drug development to aid scientific and clinical decisions regarding the progress of candidate and marketed therapeutics. Biomarkers can improve the understanding of diseases as well as therapeutic and off-target effects of drugs. Early implementation of biomarker strategies thus promises to reduce costs and time-to-market as drugs proceed through increasingly costly and complex clinical development programs. The 2003 American Association of Pharmaceutical Sciences/Clinical Ligand Assay Society Biomarkers Workshop (Salt Lake City, UT, USA, October 24-25, 2003) addressed key issues in biomarker research, with an emphasis on the validation and implementation of biochemical biomarker assays, covering from preclinical discovery of efficacy and toxicity biomarkers through clinical and postmarketing implementation. This summary report of the workshop focuses on the major issues discussed during presentations and open forums and noted consensus achieved among the participants on topics from nomenclature to best practices. For example, it was agreed that because reliable and accurate data provide the basis for sound decision making, biomarker assays must be validated in a manner that enables the creation of such data. The nature of biomarker measurements often precludes direct application of regulatory guidelines established for clinical diagnostics or drug bioanalysis, and future guidance on biomarker assay validation should therefore be adaptable enough that validation criteria do not stifle creative biomarker solutions. C1 MDS Pharma Serv, Lincoln, NE USA. Bristol Myers Squibb Co, Princeton, NJ USA. Trimeris Inc, Durham, NC USA. LINCO Diagnost Serv, St Charles, MO USA. Jasper Clin, Kalamazoo, MI USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Walter Reed Army Med Ctr, Bethesda, MD USA. Merck & Co Inc, W Point, PA USA. GlaxoSmithKline, Res Triangle Pk, NC USA. Millenium Pharmaceut, Cambridge, MA USA. Pfizer Global Res, Groton, CT USA. Genetech Inc, San Francisco, CA USA. Univ Louisville, Louisville, KY 40292 USA. Univ Texas, MD Anderson Hosp, Austin, TX 78712 USA. US FDA, Rockville, MD 20857 USA. Mol Staging Inc, New Haven, CT USA. RP Lee, JW (reprint author), MDS Pharma Serv, Lincoln, NE USA. EM jean.lee@mdsinc.com NR 37 TC 93 Z9 97 U1 0 U2 6 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD APR PY 2005 VL 22 IS 4 BP 499 EP 511 DI 10.1007/s11095-005-2484-z PG 13 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 919TV UT WOS:000228641400021 PM 15846456 ER PT J AU Chilukuri, DM Shah, JC AF Chilukuri, DM Shah, JC TI Local delivery of vancomycin for the prophylaxis of prosthetic device-related infections SO PHARMACEUTICAL RESEARCH LA English DT Article DE local delivery; prosthetic device; biofilm infection; surgical wound infection; vancomycin; implants; antibiotic; pharmacokinetics; efficacy; glyceryl monostearate ID IMPREGNATED POLYMETHYLMETHACRYLATE BEADS; FOREIGN-BODY INFECTIONS; STAPHYLOCOCCUS-EPIDERMIDIS; ANTIBIOTIC-PROPHYLAXIS; IN-VITRO; BIOFILMS; EFFICACY; PREVENTION; TOBRAMYCIN; DIFFUSION AB Purpose. To evaluate the in vivo efficacy and pharmacokinetics of vancomycin delivered from glycerylmonostearate (GMS) implants in a prosthetic-device based biofilm infection model. Methods. A biofilm infection model was developed in male Sprague-Dawley rats by implanting a vascular graft on the dorsal side of each rat and infecting it with 1.5 x 10(8) cfu/ml Staphylococcus epidermidis. The rats were divided into 3 groups of 6 rats each: 1) the control group that received no antibiotics, 2) the IM group that received multiple IM injections of vancomycin at a dose of 25 mg/kg every 6 h for a total of 12 doses, and 3) the implant group that received GMS implants designed to deliver vancomycin at a total dose of 300 mg/kg for a period of 4 days. The pharmacokinetics of vancomycin was determined from IM and implant groups by analyzing for vancomycin in blood using HPLC. In vivo efficacy was studied by evaluation of the wound site and the prosthetic device upon excision, for evidence of infection in the form of purulent discharge at the wound site and yellowish discoloration of the prosthetic device and inflammation as sign of biofilm formation. Microbiological evaluation on the wound site and the prosthetic device was performed by culturing the swabs at the wound site and the prosthetic device in sterile tryptic soy broth for 36 - 48 h at 37 degrees C. Results. Vancomycin was successfully delivered in a sustained manner for 100 h from GMS implants and the resulting plasma profile showed that the concentrations, after an initial burst, plateaued at about of 4.77 +/- 1.43 mu g/ml with less fluctuations than the IM group in which the plasma concentrations fluctuated between 2.73 +/- 0.94 mu g/ml and 19.26 +/- 3.67 mu g/ml. Upon excision of the wound site, all the animals in the control group developed infection in the form of purulent discharge and yellowish discoloration of the prosthetic device. However, none of the rats in the implant group showed evidence of infection clearly demonstrating the efficacy of the local delivery system in preventing infection. Systemically delivered vancomycin by IM injections failed to prevent infection in four out of six rats. Microbiological evaluation of the wound site and prosthetic device resulted in isolation of biofilm-producing organisms such as Staphylococcus epidermidis, Enterococcus faecalis, and Staphylococcus aureus. These organisms were isolated in greater number of animals in the control group compared to the IM and implant groups. Conclusions. The GMS implants as a delivery system for vancomycin were successful in preventing infection in all the animals compared to the IM and control groups demonstrating the efficacy of a local delivery system in a prosthetic device related biofilm infection model. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20850 USA. Pfizer Inc, Global R&D, Pharmaceut R&D, Groton, CT 06340 USA. RP Chilukuri, DM (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20850 USA. EM chilukurid@cder.fda.gov NR 31 TC 25 Z9 25 U1 0 U2 5 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES JI Pharm. Res. PD APR PY 2005 VL 22 IS 4 BP 563 EP 572 DI 10.1007/s11095-005-2492-z PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 919TV UT WOS:000228641400006 PM 15846464 ER PT J AU Soliman, MS Khan, MA AF Soliman, MS Khan, MA TI Preparation and in vitro characterization of a semi-solid dispersion of flurbiprofen with Gelucire 44/14 and Labrasol SO PHARMAZIE LA English DT Article ID HARD GELATIN CAPSULES; WATER-SOLUBLE DRUG; SOLID DISPERSIONS; BIOAVAILABILITY; FORMULATIONS; ABSORPTION; PIROXICAM; DELIVERY; DISSOLUTION; VEHICLES AB Flurbiprofen is characterized by low solubility in water and has been implicated in causing gastro intestinal ulceration. The purpose of this study was to increase the dissolution characteristics of flurbiprofen by preparing a semi-solid dispersion with Gelucire 44/14 and Labrasol (F1) in hard gelatin capsules. The results were evaluated by comparing several in vitro parameters with powdered drug filled into hard gelatin capsules. The in vitro dissolution testing of the dosage forms was performed in different media (simulated gastric fluid, pH 1.2; citrate buffer pH 4.5; phosphate buffers pH 6.8 and 7.2, and water). Characterization of semi-solid dispersions and physical mixtures was performed using Fourier transform-infrared spectroscopy (FT-IR), Differential scanning calorimetry (DSC), particle size analysis and turbidity measurement. The results suggest that all semi-solid dispersions of flurbiprofen showed a remarkable improvement in the rate and extent of drug dissolution. The dissolution of F1 exhibited significant improvement in all dissolution media at different pH. The dissolution of flurbiprofen within 30 min in pH 1.2 was (55%), in pH 4.5 67%, pH 6.8 96%, pH 7.2 98% and in water 88%. FT-IR indicated no strong drug: excipient interactions, and DSC studies indicated a loss of crystalline nature of the drug. The particle size analysis revealed an average size diameter from 194 to 278 nm. Therefore, a semi-solid dispersion of flurbiprofen with Gelucire and Labrasol may have the potential of improved bioavailability because of the enhanced in vitro properties. C1 Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX USA. RP Khan, MA (reprint author), US FDA, CDER, DPQR, HFD-940,10903 New Hampshire Ave,Life Sci Bldg 64, Silver Spring, MD 20903 USA. EM Khanm@cder.fda.gov NR 30 TC 5 Z9 5 U1 0 U2 5 PU GOVI-VERLAG PHARMAZEUTISCHER VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCCARL MANNICH STR 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD APR PY 2005 VL 60 IS 4 BP 288 EP 293 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 918HJ UT WOS:000228532600011 PM 15881610 ER PT J AU Epstein, JS AF Epstein, JS TI Insights on donor screening for West Nile virus SO TRANSFUSION LA English DT Editorial Material C1 US FDA, Off Blood Res & Review, Rockville, MD 20852 USA. RP Epstein, JS (reprint author), US FDA, Off Blood Res & Review, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. EM epsteinj@cber.FDA.gov NR 10 TC 9 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD APR PY 2005 VL 45 IS 4 BP 460 EP 462 DI 10.1111/j.0041-1132.2005.45041.x PG 3 WC Hematology SC Hematology GA 908GV UT WOS:000227776400002 PM 15819662 ER PT J AU Kannamkumarath, SS Wrobel, K Wuilloud, RG AF Kannamkumarath, SS Wrobel, K Wuilloud, RG TI Studying the distribution pattern of selenium in nut proteins with information obtained from SEC-UV-ICP-MS and CE-ICP-MS SO TALANTA LA English DT Article DE SEC-UV-LCP-MS; Brazil nuts; CE-ICP-MS; selenomethionine; selenoeystine; selenoproteins; speciation ID SIZE-EXCLUSION CHROMATOGRAPHY; PLASMA-MASS SPECTROMETRY; PERFORMANCE LIQUID-CHROMATOGRAPHY; ATOMIC-ABSORPTION-SPECTROMETRY; MOLECULAR-WEIGHT FRACTIONS; CAPILLARY-ELECTROPHORESIS; SPECIATION ANALYSIS; ELEMENT SPECIATION; INFANT FORMULAS; BREAST-MILK AB In this work, size exclusion chromatography (SEC) with UV and inductively coupled plasma mass spectrometry (ICP-MS) detection was used to study the association of selenium to proteins present in Brazil nuts (Bertholletia excelsa) under five different extraction conditions. As expected, better solubilization of proteins was observed using 0.05 mol L-1 sodium hydroxide and 1% sodium dodecylsulfate (SDS) in Tris/HCl buffer (0.05 mol L-1, pH 8) as compared to 0.05 mol L-1 HCl, 0.05 mol L-1 Tris/HCI or hot water (60 degrees C). Due to non-destructive character of Tris-SDS treatment, this was applied for studying molecular weight (MW) distribution patterns of selenium-containing nut proteins. Three different SEC columns were used for obtaining complete MW distribution of selenium: Superdex 75, Superdex Peptide, and Superdex 200 were tested with 50 mmol L-1 Tris buffer (pH 8), 150 mmol L-1 ammonium bicarbonate buffer (pH 7.8), phosphate (pH 7.5), and CAPS (pH 10.0) mobile phases. Using Superdex 200 column, the elution of at least three MW fractions was observed with UV detection (200-10 kDa) and ICP-MS chromatogram showed the co-elution of selenium with the two earlier fractions. The apparent MWs of these selenium-containing fractions were respectively about 107 and 50 kDa, as evaluated from the column calibration. For further characterization of individual selenium species, the defatted nuts were hydrolyzed with protemase K and analyzed by capillary electrophoresis (CE) with ICP-MS detection. The suitability of CE for the separation of selenite, selenate, selenocystine and selenomethionine in the presence of the nut sample matrix is demonstrated. Complete separation of the above mentioned selenium species was obtained within a migration time of 7 min. In the analysis of nut extracts with CE-ICP-MS, selenium was found to be present mainly as selenomethionine. (c) 2004 Elsevier B.V. All rights reserved. C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. Univ Guanajuato, Inst Invest Cient, Guanajuato 36000, Mexico. US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Kannamkumarath, SS (reprint author), Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. EM kannamkumass@ornl.gov RI Wuilloud, Rodolfo/N-6821-2014 OI Wuilloud, Rodolfo/0000-0002-2962-7718 NR 33 TC 37 Z9 44 U1 1 U2 27 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0039-9140 J9 TALANTA JI Talanta PD MAR 31 PY 2005 VL 66 IS 1 BP 153 EP 159 DI 10.1016/j.talanta.2004.10.010 PG 7 WC Chemistry, Analytical SC Chemistry GA 920KA UT WOS:000228686600023 PM 18969975 ER PT J AU Stewart, RS Piccardo, P Ghetti, B Harris, DA AF Stewart, RS Piccardo, P Ghetti, B Harris, DA TI Neurodegenerative illness in transgenic mice expressing a transmembrane form of the prion protein SO JOURNAL OF NEUROSCIENCE LA English DT Article DE prion; transgenic; neurodegeneration; Golgi; transmembrane; mutation ID ENDOPLASMIC-RETICULUM; SIGNAL SEQUENCE; PRP; APOPTOSIS; SCRAPIE; INFECTION; MEMBRANE; CONTAINS; TOPOLOGY; DISEASES AB Although PrPSc is thought to be the infectious form of the prion protein, it may not be the form that is responsible for neuronal cell death in prion diseases. (PrP)-Pr-Ctm is a transmembrane version of the prion protein that has been proposed to be a neurotoxic intermediate underlying prion-induced pathogenesis. To investigate this hypothesis, we have constructed transgenic mice that express L9R-3AV PrP, a mutant prion protein that is synthesized exclusively in the (PrP)-Pr-Ctm form in transfected cells. These mice develop a fatal neurological illness characterized by ataxia and marked neuronal loss in the cerebellum and hippocampus. (PrP)-Pr-Ctm in neurons cultured from transgenic mice is localized to the Golgi apparatus, rather than to the endoplasmic reticulum as in transfected cell lines. Surprisingly, development of the neurodegenerative phenotype is strongly dependent on coexpression of endogenous, wild-type PrP. Our results provide new insights into the cell biology of (PrP)-Pr-Ctm, the mechanism by which it induces neurodegeneration, and possible cellular activities of PrPC. C1 Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Indiana Univ, Sch Dent, Div Neuropathol, Indianapolis, IN 46202 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Harris, DA (reprint author), Washington Univ, Sch Med, Dept Cell Biol & Physiol, 660 S Euclid Ave, St Louis, MO 63110 USA. EM dharris@cellbiology.wustl.edu FU NIA NIH HHS [P30 AG10133]; NINDS NIH HHS [NS40975] NR 34 TC 47 Z9 49 U1 1 U2 8 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 MAR 30 PY 2005 VL 25 IS 13 BP 3469 EP 3477 DI 10.1523/JNEUROSCI.0105-05.2005 PG 9 WC Neurosciences SC Neurosciences & Neurology GA 911WU UT WOS:000228038200024 PM 15800202 ER PT J AU Ghosh, M Sauder, C Carbone, KM Malik, TH AF Ghosh, M Sauder, C Carbone, KM Malik, TH TI Detection of anti-Borna disease virus antibodies by Western blot analysis SO PSYCHIATRY RESEARCH LA English DT Letter ID PROTEIN C1 US FDA, CBER, OVRR, DVP, Bethesda, MD 20892 USA. Univ Pittsburgh, Grad Sch Publ Hlth, Pittsburgh, PA 15261 USA. Johns Hopkins Univ, Dept Psychiat, Baltimore, MD USA. Johns Hopkins Univ, Dept Med, Baltimore, MD USA. RP Malik, TH (reprint author), US FDA, CBER, OVRR, DVP, Bldg 29A,Room SC14,8800 Rockville Pike, Bethesda, MD 20892 USA. EM malik@cber.fda.gov NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0165-1781 J9 PSYCHIAT RES JI Psychiatry Res. PD MAR 30 PY 2005 VL 134 IS 1 BP 105 EP 105 DI 10.1016/j.psychres.2004.10.002 PG 1 WC Psychiatry SC Psychiatry GA 917XK UT WOS:000228502400012 PM 15808296 ER PT J AU Norling, L Lute, S Emery, R Khuu, W Voisard, M Xu, Y Chen, Q Blank, G Brorson, K AF Norling, L Lute, S Emery, R Khuu, W Voisard, M Xu, Y Chen, Q Blank, G Brorson, K TI Impact of multiple re-use of anion-exchange chromatography media on virus removal SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 17th International Symposium on Preparative and Process Chromatography CY MAY 23-26, 2004 CL Baltimore, MD DE viral clearance; biotechnology; bioprocessing; anion-exchange media; monoclonal antibodies; chromatography media lifetime ID TIME QUANTITATIVE PCR; REVERSE-TRANSCRIPTASE ASSAY; PHARMACEUTICAL PROTEIN-PURIFICATION; BIOTECHNOLOGY PRODUCT VALIDATION; GEL-FILTRATION CHROMATOGRAPHY; MAB CELL-CULTURE; COLUMN LIFETIME; LIQUID-CHROMATOGRAPHY; MONITOR RETROVIRUS; BASIC PH AB We evaluated viral clearance in multiply-cycled anion-exchange media run in flow-through mode. We found that anion-exchange columns do not lose viral clearance capacity after extensive re-use, if they are cleaned with recommended buffers that do not chemically degrade the media. In contrast, anion-exchange (AEX) columns that are not cleaned or are cleaned with buffers that chemically degrade the media lost viral clearance capacity after extended use. In these cases, other performance attributes that changed at the same time were increased band spreading. decreased DNA clearance and accumulating backpressure that prevented re-use past 80-120 cycles. Thus, our data Suggests that flow through mode anion-exchange columns that are cleaned with recommended cleaning buffers, and periodically monitored for band spreading, DNA clearance and/or backpressure need not be re-evaluated for viral clearance at the end of the validated media lifetime. (c) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. Genentech Inc, Dept Recovery Sci, San Francisco, CA 94080 USA. Amersham Inc, Piscataway, NJ 08855 USA. RP Brorson, K (reprint author), US FDA, Off Biotechnol Prod, Ctr Drug Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM brorson@cber.fda.gov NR 43 TC 50 Z9 54 U1 2 U2 8 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD MAR 28 PY 2005 VL 1069 IS 1 BP 79 EP 89 DI 10.1016/j.chroma.2004.09.072 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 912LP UT WOS:000228080100008 PM 15844485 ER PT J AU Klauda, JB Brooks, BR MacKerell, AD Venable, RM Pastor, RW AF Klauda, JB Brooks, BR MacKerell, AD Venable, RM Pastor, RW TI An ab initio study on the torsional surface of alkanes and its effect on molecular simulations of alkanes and a DPPC bilayer SO JOURNAL OF PHYSICAL CHEMISTRY B LA English DT Article ID NUCLEAR MAGNETIC-RESONANCE; DYNAMICS SIMULATIONS; N-ALKANES; CONFORMATIONAL ENERGIES; FORCE-FIELD; HYDROCARBON CHAINS; LIPID BILAYERS; RESP MODEL; PHASE; EQUILIBRIUM AB Energies of 119 conformations of normal alkanes from butane to heptane were calculated at approximately the CCSD(T)/cc-pVQZ level. Energies of gauche (g) conformers relative to trans (t) decrease as chain length increases. In what is termed the "positive pentane effect", adjacent gauche conformers of the same sign are stabilized compared to nonadjacent conformers; e.g., for hexane the energies of tgt, tgg, and gtg are 0.600, 0.930, and 1.18 kcal/mol, respectively. Torsional terms in the CHARMM27 (C27) force field were fit to the calculated QM energies to yield a revised potential, C27r. Molecular dynamics simulations of normal alkanes (heptane, decane, tridecane, and pentadecane) with C27r yield higher populations of gauche states, increased transition rates, and improved agreement with experiment as compared to C27. In addition, C27r simulations of a hydrated DPPC lipid bilayer yield improved agreement with the experimental NMR deuterium order parameters for the aliphatic chain ends. C1 FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NIH, Biophys Chem Lab, Bethesda, MD 20892 USA. RP Pastor, RW (reprint author), FDA, Ctr Biol Evaluat & Res, Biophys Lab, 1401 Rockville Pike, Rockville, MD 20852 USA. EM pastor@cber.fda.gov RI Klauda, Jeffery/A-4345-2008; OI MacKerell, Alex/0000-0001-8287-6804 FU NIGMS NIH HHS [GM51501] NR 52 TC 218 Z9 221 U1 4 U2 50 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1520-6106 J9 J PHYS CHEM B JI J. Phys. Chem. B PD MAR 24 PY 2005 VL 109 IS 11 BP 5300 EP 5311 DI 10.1021/jp0468096 PG 12 WC Chemistry, Physical SC Chemistry GA 907RB UT WOS:000227734500067 PM 16863197 ER PT J AU Graham, DJ Staffa, JA La Grenade, L Shatin, B Schech, SD Andrade, SE Gurwitz, JH Goodman, MJ Chan, KA Platt, R AF Graham, DJ Staffa, JA La Grenade, L Shatin, B Schech, SD Andrade, SE Gurwitz, JH Goodman, MJ Chan, KA Platt, R TI Rhabdomyolysis and lipid-lowering drugs - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Off Drug Safety, Rockville, MD 20857 USA. Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN USA. Meyers Primary Care Inst, Worcester, MA USA. Hlth Partners Res Fdn, Minneapolis, MN USA. Harvard Univ, Sch Med, Boston, MA USA. RP Graham, DJ (reprint author), US FDA, Off Drug Safety, Rockville, MD 20857 USA. EM grahamd@cder.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 23 PY 2005 VL 293 IS 12 BP 1448 EP 1449 DI 10.1001/jama.293.12.1448-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 908KA UT WOS:000227784700017 ER PT J AU Kim, PW Perl, TM Keelaghan, EF Langenberg, P Perencevich, EN Harris, AD Song, XY Roghmann, MC AF Kim, PW Perl, TM Keelaghan, EF Langenberg, P Perencevich, EN Harris, AD Song, XY Roghmann, MC TI Risk of mortality with a bloodstream infection is higher in the less severely ill at admission SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE adults; bloodstream infection; cohort study; intensive care unit; mortality ID FACTORS INFLUENCING PROGNOSIS; CLASSIFICATION-SYSTEM; NOSOCOMIAL INFECTIONS; BACTEREMIA; EPIDEMIOLOGY; PREVENTION; OUTCOMES; APACHE; LENGTH; COHORT AB Rationale: Health care-associated bloodstream infections are common in critically ill patients; however, investigators have had difficulty in quantifying the clinical impact of these infections given the high expected mortality among these patients. Objective: To estimate the impact of health care-associated bloodstream infections on in-hospital mortality after adjusting for severity of illness at critical care admission. Method: A cohort of medical and surgical intensive care unit patients. Measurements: Severity of illness at admission, bloodstream infection, and in-hospital mortality. Main Results: Among the 2,783 adult patients, 269 developed unit-associated bloodstream infections. After adjusting for severity of illness, patients with a lower initial severity of illness who developed an infection had a greater than twofold higher risk for in-hospital mortality (hazard ratio [HR] = 2.42, 95% confidence interval [CI] 1.70, 3.44) when compared with patients without infection and with a similar initial severity of illness. In contrast, patients with a higher initial severity of illness who subsequently developed an infection did not have an increased risk for in-hospital mortality (HR = 0.96, 95%CI 0.76, 1.23) when compared with patients without infection but with a similar initial severity of illness. Conclusions: These results suggest that these infections in less ill patients have a higher attributable impact on subsequent mortality than in more severely ill patients. Focusing interventions to prevent bloodstream infections in less severely ill patients would be expected to have a greater benefit in terms of mortality reduction. C1 VA Maryland Hlth Care Syst, Epidemiol Sect, Baltimore, MD 21201 USA. US FDA, Div Antiinfect Drug Prod, Rockville, MD 20857 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. Johns Hopkins Univ Hosp, Dept Hosp Epidemiol & Infect Control, Baltimore, MD 21287 USA. Johns Hopkins Med Inst, Dept Med, Div Infect Dis, Baltimore, MD 21205 USA. RP Roghmann, MC (reprint author), VA Maryland Hlth Care Syst, Epidemiol Sect, 100 N Greeme St,Lower Level, Baltimore, MD 21201 USA. EM mroghman@epi.umaryland.edu FU ODCDC CDC HHS [UR8/CCU 315092-03] NR 21 TC 25 Z9 25 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 61 BROADWAY, FL 4, NEW YORK, NY 10006 USA SN 1073-449X EI 1535-4970 J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 15 PY 2005 VL 171 IS 6 BP 616 EP 620 DI 10.1164/rccm.200407.916OC PG 5 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 905HV UT WOS:000227560100012 PM 15591469 ER PT J AU Foley, DM Trimboli, SL Lamb, J Gogley, J Thompson, J Caporaso, F Calicchia, M Prakash, A AF Foley, DM Trimboli, SL Lamb, J Gogley, J Thompson, J Caporaso, F Calicchia, M Prakash, A TI Acid-adaptation does not increase the resistance of Listeria monocytogenes to irradiation in a seafood salad SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE stress hardening; stress adaptation; sensory testing; seafood salad ID ESCHERICHIA-COLI O157-H7; GAMMA-IRRADIATION; SENSORY QUALITIES; VIRULENCE; RECOVERY; SURVIVAL; PRODUCTS AB Stress adaptation of microbial cells enables the cells to survive better when they are subsequently exposed to other types of stresses. In the food industry, pathogens are commonly stressed during food processing and this is a concern where pathogens such as Listeria monocytogenes are involved. Research was conducted to determine if acid adaptation of L. monocytogenes provides resistance to ionizing irradiation. Three different strains of L. monocytogenes were acid-adapted using three different acids (acetic, citric, lactic) in Tryptic Soy Broth, at a pH 5.5 for 1 h, 4 h, or continuous acid exposure. The acid-adapted L. monocytogenes were then exposed to a low level of gamma irradiation (0.59-0.72 kGy) along with a non-acid adapted L. monocytogenes control. In a test tube study, the 1-h acetic acid-adapted L. monocytogenes strains showed the greatest difference from the control, a reduced kill of 1.1 log CFU/g but this difference was not significant by ANOVA (p=0.054). The reduction achieved after 4 h and continuous acid exposure also did not significantly differ from the control. To determine whether acid adaptation affected radiation resistance within a food product, a refrigerated storage shelf-life study was completed. Acetic acid was used to acid adapt a three-strain cocktail of L. monocytogenes for a period of I h. The organisms were then inoculated into a seafood salad (pH 5.15) and subsequently exposed to low dose gamma irradiation (0.7 to 4.5 kGy). L. monocytogenes was reduced or eliminated by irradiation regardless of acid adaptation; no increased resistance was observed. (C) 2004 Elsevier B.V All rights reserved. C1 Chapman Univ, Dept Biol Sci, Orange, CA 92866 USA. Chapman Univ, Dept Phys Sci, Orange, CA 92866 USA. US FDA, Microbiol Branch, Pacific Reg Lab SW, Los Angeles, CA 90015 USA. Food Safety Solut Inc, Los Angeles, CA USA. RP Foley, DM (reprint author), Chapman Univ, Dept Biol Sci, Orange, CA 92866 USA. EM dfoley@chapman.edu 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 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD MAR 15 PY 2005 VL 99 IS 2 BP 147 EP 156 DI 10.1016/j.ijfoodmicro.2004.07.018 PG 10 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 904ZD UT WOS:000227536200004 PM 15734563 ER PT J AU Wang, YP Yan, J Fu, PP Chou, MW AF Wang, YP Yan, J Fu, PP Chou, MW TI Human liver microsomal reduction of pyrrolizidine alkaloid N-oxides to form the corresponding carcinogenic parent alkaloid SO TOXICOLOGY LETTERS LA English DT Article DE riddelliine N-oxide; retrorsine N-oxide; monocrotaline N-oxide; riddelliine; retrorsine; monocrotaline; pyrrolizidine alkaloid; dehydroretronecine; DNA adducts; P-32-postlabeling; human liver microsomal metabolism ID DNA ADDUCT FORMATION; METABOLIC-ACTIVATION; IN-VITRO; RIDDELLIINE; RATS; INDICINE; CONVERSION; VIVO; MICE AB Retronecine-based pyrrolizidine alkaloids, such as riddelliine, retrorsine, and monocrotaline, are toxic to domestic livestock and carcinogenic to laboratory rodents. Previous in vitro metabolism studies showed that (+/-)6,7-dihydro-7-hydroxy-1-(hydroxymethyl)-5H-pyrrolizine (DHP) and pyrrolizidine alkaloid N-oxides were the major metabolites of these compounds. DHP is the reactive metabolite of pyrrolizidine alkaloids and pyrrolizidine alkaloid N-oxides are generally regarded as detoxification products. However, a previous study of rat liver microsomal metabolism of riddelliine N-oxide demonstrated that DHP and its parent compound, riddelliine, were generated as the major metabolites of riddelliine N-oxide. In this study the metabolic activation of the three retronecine-based pyrrolizidine alkaloid N-oxides by human liver microsomes is investigated under oxidative and hypoxic conditions. Results shows that both the DHP and the corresponding parent pyrrolizidine alkaloids are the major metabolites of the human liver microsomal metabolism of pyrrolizidine alkaloid N-oxides. Under oxidative conditions, reduction of the N-oxide to pyrrolizidine alkaloid is inhibited and while under hypoxic conditions, DHP formation is dramatically decreased. The oxidative and reductive products generated from the metabolism of pyrrolizidine alkaloid N-oxides are substrate-, enzyme- and time-dependent. In the presence of troleandomycin, a microsomal CYP3A inhibitor, DHP formation is inhibited by more than 70%, while the N-oxide reduction was not affected. The level of microsomal enzyme activity in human liver is comparable with rats. The rate of in vitro metabolism by either human and rat liver microsomes follows the order of riddelliine greater than or equal to retrorsine > monocrotaline, and DHP-derived DNA adducts are detected and quantified by P-32-postlabeling/HPLC analysis. Similar DHP-derived DNA adducts are found in liver DNA of F344 rats gavaged with the pyrrolizidine alkaloid N-oxides (1.0 mg/kg). The levels of in vivo DHP-DNA adduct formation is correlated with the level of in vitro DHP formation. Our results indicate that pyrrolizidine alkaloid N-oxides may be hepatocarcinogenic to rats through a genotoxic mechanism via the conversion of the N-oxides to their corresponding parent pyrrolizidine alkaloids, and these results may be relevant to humans. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM mchou@nctr.fda.gov NR 31 TC 45 Z9 45 U1 3 U2 19 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0378-4274 J9 TOXICOL LETT JI Toxicol. Lett. PD MAR 15 PY 2005 VL 155 IS 3 BP 411 EP 420 DI 10.1016/j.toxlet.2004.11.010 PG 10 WC Toxicology SC Toxicology GA 892JE UT WOS:000226645800009 PM 15649625 ER PT J AU Mei, N Guo, L Fu, PP Heflich, RH Chen, T AF Mei, N Guo, L Fu, PP Heflich, RH Chen, T TI Mutagenicity of comfrey (Symphytum Officinale) in rat liver SO BRITISH JOURNAL OF CANCER LA English DT Article DE comfrey; transgenic rat; cII gene; pyrrolizidine alkaloid; tandem base substitution ID VENO-OCCLUSIVE DISEASE; PYRROLIZIDINE ALKALOIDS; CARCINOGENIC ACTIVITY; VENOOCCLUSIVE DISEASE; HERB TEA; INGESTION; TOXICITY AB Comfrey is a rat liver toxin and carcinogen that has been used as a vegetable and herbal remedy by humans. In order to evaluate the mechanisms underlying its carcinogenicity, we examined the mutagenicity of comfrey in the transgenic Big Blue rat model. Our results indicate that comfrey is mutagenic in rat liver and the types of mutations induced by comfrey suggest that its tumorigenicity results from the genotoxicity of pyrrolizidine alkaloids in the plant. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biochem Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Hepatotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Chen, T (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, HFT-130,3900 NCTR Rd, Jefferson, AR 72079 USA. EM tchen@nctr.fda.gov RI Guo, Lei/E-9232-2011; mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 23 TC 30 Z9 31 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0007-0920 J9 BRIT J CANCER JI Br. J. Cancer PD MAR 14 PY 2005 VL 92 IS 5 BP 873 EP 875 DI 10.1038/sj.bjc.6602420 PG 3 WC Oncology SC Oncology GA 908YY UT WOS:000227827300014 PM 15726100 ER PT J AU Berthold, I Pombo, ML Wagner, L Arciniega, JL AF Berthold, I Pombo, ML Wagner, L Arciniega, JL TI Immunogenicity in mice of anthrax recombinant protective antigen in the presence of aluminum adjuvants SO VACCINE LA English DT Article DE anthrax vaccine; aluminum-containing adjuvant; immunogenicity; mice ID BACILLUS-ANTHRACIS; VACCINE; EFFICACY; SAFETY; IMMUNIZATION; MODEL AB The only US-licensed anthrax vaccine for human use, as well as several experimental vaccines containing solely purified recombinant protective antigen (rPA), are formulated using aluminum hydroxide (Al(OH)3) as an adjuvant. It has been suggested that effective adjuvanticity of aluminum salts for protein antigens depends, at least partially, on the degree of adsorption of the antigen to the adjuvant. On the other hand, the ease of antigen desorption from the adjuvant in a quantitative fashion may facilitate the assessment of vaccine characteristics in the laboratory. In this regard, aluminum phosphate (AIPO(4)), although deemed a "weaker" adjuvant than Al(OH)3, appears superior to the latter. To investigate the possibility of formulating rPA vaccines with AIM, as well as the significance of the adsorption of this antigen to the aluminum salt for adjuvanticity, we studied the effect of AlPO4 and Al(OH)(3) on the induction of anti-rPA antibodies in mice. In a first immunization experiment the adjuvanticity of AlPO4 combined with rPA was examined. Antibodies against rPA were measured using an ELISA. Results indicated that AlPO4 is able to significantly increase the antibody response to rPA, irrespective of its degree of adsorption to the adjuvant. Based on these results, in a second experiment mice were immunized twice, with different formulations of rPA containing either AlPO4 or Al(OH)3, and rPA-antibodies were measured using ELISA and an in vitro toxin neutralization assay. Comparable immune responses to rPA were obtained with both aluminum salts. Additionally, results with AlPO4 as adjuvant confirmed that, in this mouse model, binding of the protein to the adjuvant is not essential for adjuvanticity, whereas the amount of adjuvant has an influence on the antibody response induced. (c) 2004 Elsevier Ltd. All rights reserved. C1 US FDA, CBER DBPAP, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Inst Nacl Higiene Rafael Rangel, Caracas 1051, Venezuela. RP Berthold, I (reprint author), US FDA, CBER DBPAP, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. EM ingeberthold@web.de; mariluzpombo@telcel.net.ve; Arciniega@cber.fda.gov NR 29 TC 39 Z9 40 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 MAR 14 PY 2005 VL 23 IS 16 BP 1993 EP 1999 DI 10.1016/j.vaccine.2004.10.014 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 908EI UT WOS:000227769800014 PM 15734073 ER PT J AU Arvidson, KB Mayer, J Twaroski, ML Benz, RD Matthews, EJ Kruhlak, NL Cheeseman, MA Yang, CH AF Arvidson, KB Mayer, J Twaroski, ML Benz, RD Matthews, EJ Kruhlak, NL Cheeseman, MA Yang, CH TI Making FDA toxicity data available to the public: FDA ToxML database for genetic toxicity. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 US FDA, CFSAN, OFAS, College Pk, MD 20740 USA. US FDA, CDER, OPS, ICSAS, College Pk, MD 20740 USA. EM Kirk.Arvidson@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 068-CINF BP U607 EP U607 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177704067 ER PT J AU Brorson, K AF Brorson, K TI Nomenclature standards for virus filters. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. EM brorson@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 180-BIOT BP U206 EP U206 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701168 ER PT J AU Hanson, M Rajagopalan, N Lute, S Brorson, K Moreira, A AF Hanson, M Rajagopalan, N Lute, S Brorson, K Moreira, A TI Impact of sodium butyrate supplementation on global gene expression and monoclonal antibody glycosylation patterns in murine hybridoma cells. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Univ Maryland, CDER, FDA, Bethesda, MD 20892 USA. Univ Maryland, Dept Chem & Biochem Engn, Bethesda, MD 20892 USA. EM mhanson1@umbc.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 230-BIOT BP U214 EP U214 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701214 ER PT J AU Jackson, LS Al-Taher, F Jablonski, JE Fleischman, G AF Jackson, LS Al-Taher, F Jablonski, JE Fleischman, G TI Acrylamide formation in home-prepared foods SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Chicago, IL 60616 USA. EM Lauren.Jackson@cfsan.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 062-AGFD BP U37 EP U37 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177700077 ER PT J AU Jhoo, JW Ang, CYW Mei, N Dragull, K Chen, T Tang, CS AF Jhoo, JW Ang, CYW Mei, N Dragull, K Chen, T Tang, CS TI Content and mutagenicity of pipermethystine in kava dietary supplements SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Hawaii Manoa, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA. RI mei, nan/E-8915-2011 OI mei, nan/0000-0002-3501-9014 NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 057-AGFD BP U36 EP U36 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177700072 ER PT J AU Jhoo, JW Moody, JD Schnackenberg, L Heinze, TM Dragull, K Tang, CS Ang, CYW AF Jhoo, JW Moody, JD Schnackenberg, L Heinze, TM Dragull, K Tang, CS Ang, CYW TI Identification of C-glycoside flavonoids as potential mutagenic compounds in Kava. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Hawaii Manoa, Dept Mol Biosci & Bioengn, Honolulu, HI 96822 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 134-AGFD BP U50 EP U50 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177700149 ER PT J AU Khachik, F AF Khachik, F TI Distribution, metabolism, and the role of tomato carotenoids in disease prevention SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. EM khachik@umd.edu RI Khachik, Frederick/C-5055-2009 NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 013-AGFD BP U29 EP U29 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177700028 ER PT J AU Lindeman, P AF Lindeman, P TI Team biologics inspectional findings. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 US FDA, OE DCMO, Alameda, CA 94502 USA. EM philip.lindeman@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 177-BIOT BP U206 EP U206 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701165 ER PT J AU Lute, S Brorson, K Cabatingan, M Saravara, T Bolton, G LaCasse, D Carter, J Sukomar, M Combs, J Bailey, M Rubino, M AF Lute, S Brorson, K Cabatingan, M Saravara, T Bolton, G LaCasse, D Carter, J Sukomar, M Combs, J Bailey, M Rubino, M TI Enterobacteriophage Phi X174 clearance versus flow decay in NFP virus filters. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. EM lute@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 268-BIOT BP U220 EP U220 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701252 ER PT J AU MacCuspie, RI Banerjee, IA Krause, P Matsui, H AF MacCuspie, RI Banerjee, IA Krause, P Matsui, H TI Trace level pathogen identification by antibody nanotube networks. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod, Rockville, MD 20857 USA. EM rmaccuspie@gc.cuny.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 332-PMSE BP U1155 EP U1155 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066605332 ER PT J AU Mattamal, GJ AF Mattamal, GJ TI USFDA perspective on the regulations of cyanoacrylate polymer tissue adhesives in clinical applications SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 US FDA, Div Gen Restorat & Neurol Devices, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. EM george.mattamal@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 44-PMSE BP U1109 EP U1110 PN 2 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 008UQ UT WOS:000235066605044 ER PT J AU Negin, RS Freedberg, DI AF Negin, RS Freedberg, DI TI How chair-like is the structure of glucose? SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Bethesda, MD 20814 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Bethesda, MD 20814 USA. EM Russell_Negin@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 102-CARB BP U270 EP U270 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701519 ER PT J AU Shaikh, B Rummel, N Gieseker, C Reimschuessel, R AF Shaikh, B Rummel, N Gieseker, C Reimschuessel, R TI Depletion of albendazole in the muscle tissue of channel catfish. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 Ctr Vet Med, Res Off, Food & Drug Adm, Laurel, MD 20708 USA. EM bshaikh@cvm.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 160-AGFD BP U55 EP U55 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177700175 ER PT J AU Swann, PG AF Swann, PG TI Scientific considerations for the development of follow-on protein products. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 US FDA, Ctr Drug Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. EM patrick.swann@fda.hhs.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 183-BIOT BP U206 EP U206 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701171 ER PT J AU Venable, RM Freedberg, DI AF Venable, RM Freedberg, DI TI Utility of residual dipolar couplings in detecting motion in carbohydrates. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract CT 229th National Meeting of the American-Chemical-Society CY MAR 13-17, 2005 CL San Diego, CA SP Amer Chem Soc C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Bethesda, MD 20892 USA. EM daron_freedberg@nih.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD MAR 13 PY 2005 VL 229 MA 104-CARB BP U271 EP U271 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 913TZ UT WOS:000228177701521 ER PT J AU Chen, HJ Brown, A Zhang, XJ Faas, F Ercal, N Poirier, L Fitzgerald, R Breckenridge, J Eidt, J Moursi, MM AF Chen, HJ Brown, A Zhang, XJ Faas, F Ercal, N Poirier, L Fitzgerald, R Breckenridge, J Eidt, J Moursi, MM TI D-alpha and mixed-tocopherols decrease homocysteine mediated increases in intimal hyperplasia following endarterectomy SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Arkansas Med Sci, CAVHS, Little Rock, AR 72205 USA. UMR, Dept Chem, Rolla, MO 65409 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1058 EP A1058 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900399 ER PT J AU Gomes, AV Edmondson, RD Zong, CG Berhane, B Young, G Jones, RC Thyparambil, S Pantaleon, D Ping, PP AF Gomes, AV Edmondson, RD Zong, CG Berhane, B Young, G Jones, RC Thyparambil, S Pantaleon, D Ping, PP TI Characterization of the murine cardiac 26S proteasome by biochemical and proteomic methods SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 Univ Calif Los Angeles, Los Angeles, CA 90095 USA. NCTR, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 3 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1319 EP A1319 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610902277 ER PT J AU Herman, E Zhang, J Knapton, A Rifai, N Sistare, F AF Herman, E Zhang, J Knapton, A Rifai, N Sistare, F TI The utility of monitoring cardiac troponin T to detect cardiac injury induced by low doses of isoproterenol in rats SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 US FDA, Div Appl Pharmacol Res, LSB, Silver Spring, MD 20993 USA. Childrens Hosp, Boston, MA 02115 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1530 EP A1530 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903601 ER PT J AU Subramaniam, S Grundel, E White, KD Rader, JI AF Subramaniam, S Grundel, E White, KD Rader, JI TI HPTLC analysis of Blue Cohosh for alkaloids SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 FDA, CFSAN, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1033 EP A1033 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900285 ER PT J AU Sundaresan, PR Slavoff, SA Grundel, E White, KD Rader, JI AF Sundaresan, PR Slavoff, SA Grundel, E White, KD Rader, JI TI Comparison of neoclerodane diterpenoids from two sub species of Teucriurn genus by a reversed phase HPLC analytical method SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 ONPLDS, DRAT, College Pk, MD USA. OSAS, DGSS, College Pk, MD USA. US FDA, CFSAN, College Pk, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1033 EP A1033 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610900286 ER PT J AU Tuo, JS Ning, BT Bojanowski, CM Lin, ZL Kadlubar, FF Chew, E Chan, CC AF Tuo, JS Ning, BT Bojanowski, CM Lin, ZL Kadlubar, FF Chew, E Chan, CC TI Variation in regulatory region of Cockyne Syndrome B gene and disposition towards age-related macular degeneration in Caucasian Patients SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 NEI, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1510 EP A1510 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903505 ER PT J AU Zaitseva, M Romantseva, T Manischewitz, J Wang, J Goucher, D Golding, H AF Zaitseva, M Romantseva, T Manischewitz, J Wang, J Goucher, D Golding, H TI Role of CD4/CXCR4 association in the increased CXCR4-dependent HIV-1 fusion in activated T cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunologists, Amer Physiol Soc, Amer Soc Biochem & Mol Biol, Amer Soc Invest Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut, Int Union Physiol Sci C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2005 VL 19 IS 5 SU S BP A1435 EP A1435 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZS UT WOS:000227610903163 ER PT J AU Boudreau, MD Olson, GR Pogribna, M Pogribny, I Beland, FA AF Boudreau, MD Olson, GR Pogribna, M Pogribny, I Beland, FA TI Consumption of Aloe barbadensis Miller (Aloe vera) induces hyperplasia in the colon of F-344 rats and B6C3F1 mice SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Charles River Labs, Jefferson, AR 72079 USA. NR 0 TC 2 Z9 2 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A450 EP A451 PN 1 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610703155 ER PT J AU Dnyanmote, AV Sawant, SP Lock, EA Latendresse, JR Mehendale, HM AF Dnyanmote, AV Sawant, SP Lock, EA Latendresse, JR Mehendale, HM TI Role of diabetes-induced advancement of cell cycle in lower progression of DCVC-initiated renal injury and survival SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Univ Louisana, Monroe, LA 71209 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Natl Ctr Toxicol Res, Chalk River Labs, Div Pathol, Jefferson, AR 72079 USA. RI Latendresse, John/A-9215-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A112 EP A112 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610700516 ER PT J AU Donthamsetty, S Mitra, MS Philip, BK Chilakapati, J Latendresse, JR Mehendale, HM AF Donthamsetty, S Mitra, MS Philip, BK Chilakapati, J Latendresse, JR Mehendale, HM TI G(1)-S phase arrest by ethanol pretreatment: a possible mechanism for potentiation of aflatoxin B1 hepatotoxicity SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Univ Louisiana, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Latendresse, John/A-9215-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A99 EP A99 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610700458 ER PT J AU Leak, LV Calvert, VS Wulkuhle, JD Liotta, LA Petricoin, EP AF Leak, LV Calvert, VS Wulkuhle, JD Liotta, LA Petricoin, EP TI The application of reverse protein microarrays for proteomic evaluation of signal pathway profiling during lymph angiogenesis SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Howard Univ, Washington, DC 20059 USA. NCI, FDA, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, CBER, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A168 EP A168 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610701137 ER PT J AU Lee, CJ Lee, LH Frasch, CE AF Lee, CJ Lee, LH Frasch, CE TI Mucosal immunity of pneumococcal glycoconjugate SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20852 USA. Ctr Biol Evaluat & Res, Div Vaccine Related Prod & Applicat, Rockville, MD 20852 USA. Ctr Biol Evaluat & Res, Div Vaccine Related Prod & Applicat, Rockville, MD 20852 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A4 EP A4 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610700019 ER PT J AU Limaye, PB Bhave, VS Palkar, PS Latendresse, JR Yu, ST Reddy, JK Mehendale, HM AF Limaye, PB Bhave, VS Palkar, PS Latendresse, JR Yu, ST Reddy, JK Mehendale, HM TI Toxicant-induced progression of liver injury can be prevented by calpastatin overexpression in the liver SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Univ Louisiana, Dept Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. Northwestern Univ, Dept Pathol, Feinberg Sch Med, Chicago, IL 60611 USA. RI Latendresse, John/A-9215-2009 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A99 EP A99 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610700456 ER PT J AU Pogribna, M Pogribny, I Gibson, JB Melnyk, S James, SJ AF Pogribna, M Pogribny, I Gibson, JB Melnyk, S James, SJ TI Folate/methionine metabolism in children with Down syndrome: nutritional intervention with folinic acid and betaine SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. UAMS, Little Rock, AR 72202 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A51 EP A51 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610700237 ER PT J AU Poirier, L Ross, S Pogribna, M Wise, C James, SJ Dragan, Y Pogribny, I AF Poirier, L Ross, S Pogribna, M Wise, C James, SJ Dragan, Y Pogribny, I TI Irreversible global DNA hypomethylation during hepatocarcinogenesis induced by dietary methyl deficiency SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NCI, Bethesda, MD 20892 USA. UAMS, Little Rock, AR 72205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A219 EP A219 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610701375 ER PT J AU Steele, AD Warfel, JM D'Agnillo, F AF Steele, AD Warfel, JM D'Agnillo, F TI Anthrax lethal toxin inhibits chemokine release by endothelial cells SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A355 EP A355 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610702360 ER PT J AU Yarovinsky, F Andersen, JF Khurana, S King, LR Aliberti, J Golding, H Sher, A AF Yarovinsky, F Andersen, JF Khurana, S King, LR Aliberti, J Golding, H Sher, A TI Structural determinants of the interaction between Toxoplasma gondii cyclophilin and the HIV-1 co-receptor CCR5 SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 LPD, Bethesda, MD 20894 USA. NIAID, LMVR, NIH, Bethesda, MD 20894 USA. FDA, CBER, Bethesda, MD 20892 USA. RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A939 EP A939 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610706513 ER PT J AU Zong, CG Gomes, AV Qiao, X Berhane, B Edmondson, R Pantaleon, D Loo, J Ping, PP AF Zong, CG Gomes, AV Qiao, X Berhane, B Edmondson, R Pantaleon, D Loo, J Ping, PP TI Proteomic characterization of the murine 20S proteasome in normal and cardioprotected hearts SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 Univ Calif Los Angeles, Los Angeles, CA 90095 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A712 EP A712 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610705112 ER PT J AU Zubkova, I Zaitseva, M AF Zubkova, I Zaitseva, M TI Mouse model of thymic reconstitution following ionizing irradiation SO FASEB JOURNAL LA English DT Meeting Abstract CT Experimental Biology 2005 Meeting/35th International Congress of Physiological Sciences CY MAR 31-APR 06, 2005 CL San Diego, CA SP Amer Assoc Anatomists, Amer Assoc Immunol, Amer Phtsiol Soc & Int Union Physiol Sci, Amer Soc Biochem & Mole Biol, Amer Soc Investigat Pathol, Amer Soc Nutr Sci, Amer Soc Pharmacol & Exptl Therapeut C1 FDA, CBER, Lab Retroviral Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 4 PY 2005 VL 19 IS 4 SU S BP A12 EP A12 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 905ZQ UT WOS:000227610700056 ER PT J AU Gao, LF Xu, DQ Wen, LJ Zhang, XY Shao, YT Zhao, XJ AF Gao, LF Xu, DQ Wen, LJ Zhang, XY Shao, YT Zhao, XJ TI Inhibition of STAT3 expression by siRNA suppresses growth and induces apoptosis in laryngeal cancer cells SO ACTA PHARMACOLOGICA SINICA LA English DT Article DE STAT3; RNA interference; laryngeal neoplasms; apoptosis ID BREAST-CARCINOMA CELLS; DOUBLE-STRANDED-RNA; CONSTITUTIVE ACTIVATION; IN-VIVO; INTERFERENCE; MICE; PROLIFERATION; TRANSCRIPTION; VITRO AB Aim: To determine the inhibitory effect of the synthetic STAT3 siRNA on the expression of STAT3 gene in human laryngeal cancer cell lines Hep2 and to investigate the effect of STAT3 siRNA on growth and apoptosis in Hep2 cells. Methods: A pair of DNA templates coding siRNA against STAT3-mRNA was synthesized to reconstruct plasmid of pSilencer1.0-U6 siRNA-STAT3. Hep2 cells were transfected with RPMI-1640 media (untreated), plasmid (empty), and STAT3 siRNA, respectively. Northern blot and Western blot analysis of STAT3 and pTyr-STAT3 expression in Hep2 cells and Western blot analysis of Bcl-2 expression in the Hep2 cell was performed 72 h after transfection. MTT, flow cytometry, and AO/EB assay were used for determination of cells proliferation and apoptosis in Hep2 cells. Results: pTyr-STAT3 was markedly expressed in untreated Hep2 cells and the vector-treated Hep2 cells, whereas pTyr-STAT3 expression was significantly reduced in STAT3 siRNA-transfected Hep2 cells, indicating that STAT3 siRNA inhibited the activity of STAT3. Transfection of Hep2 cells with STAT3 siRNA significantly inhibited STAT3 expression at both mRNA and protein level in Hep2 cells and the inhibition was characterized by time-dependent transfection. Treatment of Hep2 cells with STAT3 siRNA resulted in dose-dependent growth inhibition of Hep2, this significantly increased apoptotic cell rate, and decreased Bcl-2 expression level in Hep2 cells. STAT3 siRNA had an effect on induction of either early or late stage apoptosis. Conclusion: This study demonstrates that STAT3 siRNA effectively inhibits STAT3 gene expression in Hep2 cells leading to growth suppression and induction of apoptosis in Hep2 cells. The use of siRNA technique may provide a novel therapeutic approach to treat laryngeal cancer and other malignant tumors expressing constitutively activated STAT3. C1 Jilin Univ, Dept Pathophysiol, Basic Sch Med, Changchun 130021, Peoples R China. Ctr Biol Evaluat & Res, Food & Drug Adm, Lab Enter & Sexually Tranmitted Dis, Bethesda, MD 20892 USA. Jilin Univ, Hosp 2, Dept ENT, Changchun 130021, Peoples R China. Jilin Univ, Hosp 2, Dept Thorac & Cardiovasc Surg, Changchun 130021, Peoples R China. RP Zhao, XJ (reprint author), Jilin Univ, Dept Pathophysiol, Basic Sch Med, Changchun 130021, Peoples R China. EM pro_2@jlu.edu.cn NR 29 TC 40 Z9 48 U1 0 U2 6 PU SHANGHAI INST MATERIA MEDICA PI SHANGHAI PA 555 ZU CHONG ZHI RD, ZHANG JIANG HI-TECH PARK, SHANGHAI, PUDONG 201203, PEOPLES R CHINA SN 1671-4083 J9 ACTA PHARMACOL SIN JI Acta Pharmacol. Sin. PD MAR PY 2005 VL 26 IS 3 BP 377 EP 383 DI 10.1111/j.1745-7254.2005.00053.x PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 906NB UT WOS:000227647800019 PM 15715937 ER PT J AU Leiderman, DB Shoptaw, S Montgomery, A Bloch, DA Elkashef, A LoCastro, J Vocci, F AF Leiderman, DB Shoptaw, S Montgomery, A Bloch, DA Elkashef, A LoCastro, J Vocci, F TI Cocaine Rapid Efficacy Screening Trial (CREST): a paradigm for the controlled evaluation of candidate medications for cocaine dependence SO ADDICTION LA English DT Article DE clinical trials; cocaine; design; medications ID INTERVIEW AB Aim Development of effective medications for the treatment of cocaine dependence remains a major priority for the National Institute on Drug Abuse (NIDA) at the National Institutes of Health. The Cocaine Rapid Efficacy Screening Trial (CREST) paradigm was developed by the Division of Treatment Research and Development (DT RAD) at NIDA with the goal of enhancing pilot clinical trial validity when systematically assessing a range of medications and drug classes for potential utility in treatment of cocaine dependence. Design CREST utilizes a randomized, controlled, parallel group, blinded methodology for comparing one or more marketed medications against a standard, pharmaceutical grade placebo. The trial design is comprised of a flexible 2-4-week screening/baseline period followed by randomization to an 8-week treatment period. Measures Standard measures of outcomes for the CREST included urinary benzoylecgonine (primary metabolite of cocaine), retention, cocaine craving, depression, clinical global impression and HIV-risk behaviors. In order to facilitate comparisons of data from the CREST studies across sites, drug classes and time, standardized procedures, measures and psychosocial counseling were used. Results A total of 19 medications were evaluated in out-patient treatment research clinics in Boston, Cincinnati, Los Angeles, New York and Philadelphia. Conclusions Findings supported decisions to move forward three medications (cabergoline, reserpine, tiagabine) using full-scale, adequately powered, randomized placebo-controlled trial designs. Lessons learned from the CREST experience continue to shape cocaine pharmacotherapy trial design and execution. C1 US FDA, Ctr Drug Evaluat & Res, Controlled Subst Staff, Rockville, MD 20852 USA. Univ Calif Los Angeles, Integrated Subst Abuse Programs, Los Angeles, CA USA. Univ Calif Los Angeles, Friends Res Inst, Los Angeles, CA USA. NIDA, Div Treatment Res & Dev, Bethesda, MD USA. Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Biostat, Stanford, CA 94305 USA. Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst Medicat Dev Res Unit, Boston, MA USA. RP Leiderman, DB (reprint author), US FDA, Ctr Drug Evaluat & Res, Controlled Subst Staff, HFD 009,5515 Secur Lane 1201, Rockville, MD 20852 USA. EM leidermand@cder.fda.gov FU NIDA NIH HHS [Y01 DA 50038-05] NR 16 TC 27 Z9 28 U1 1 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 2005 VL 100 SU 1 BP 1 EP 11 DI 10.1111/j.1360-0443.2005.00988.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 907PB UT WOS:000227729200001 PM 15773068 ER PT J AU Ciraulo, DA Sarid-Segal, O Knapp, CM Ciraulo, AM LoCastro, J Bloch, DA Montgomery, MA Leiderman, DB Elkashef, A AF Ciraulo, DA Sarid-Segal, O Knapp, CM Ciraulo, AM LoCastro, J Bloch, DA Montgomery, MA Leiderman, DB Elkashef, A TI Efficacy screening trials of paroxetine, pentoxifylline, riluzole, pramipexole and venlafaxine in cocaine dependence SO ADDICTION LA English DT Article DE antidepressant; cocaine dependence; dopamine agonist; glutamate inhibitor; phosphodiesterase inhibitor; SSRI ID D-3 DOPAMINE-RECEPTOR; SELECTIVE-INHIBITION; FLUOXETINE TREATMENT; NUCLEUS-ACCUMBENS; SEEKING BEHAVIOR; GLUTAMATE; ANTIDEPRESSANTS; ANTAGONIST; FATALITIES; RELEASE AB Aims The two studies presented here were conducted to assess the efficacy of paroxetine, pentoxifylline, riluzole, venlafaxine and pramipexole as medications for the treatment of cocaine dependence. Design A multi-arm, modified blinded, placebo-controlled design was used. Setting The studies were conducted at the Boston VA Healthcare System and the Boston University School of Medicine Medication Development Research Unit (MDRU). Participants Participants met criteria for cocaine dependence during a 2-week screening period. Intervention Following random assignment to one of the treatment groups, subjects received active medication or placebo for 8 weeks in combination with cognitive behavioral counseling. In the first study the efficacy of the antidepressant paroxetine (20 mg daily), the phosphodiesterase inhibitor pentoxifylline (1200 mg daily) and the glutamate release inhibitor riluzole (100 mg daily) was assessed. The antidepressant venlafaxine (15 0 mg daily) and the dopamine agonist pramipexole (1.5 mg daily) were evaluated in the second study. Measurements Urine benzoylecgonine (BE) concentrations, self-report of cocaine use and global impression scores served as primary outcome measures. Secondary measures included assessments of cocaine craving and psychiatric functioning. Adverse events were monitored during the treatment period. Findings None of the active medications produced greater reductions in urine BE concentrations over the treatment period than did placebo. There were trends for BE levels to become reduced in the pentoxifylline group during the first 4 weeks of treatment and for Addiction Severity Index (ASI) drug composite scores to be lower in the pentoxyfylline group at end-point compared to the placebo group. Significant within-group reductions in reported cocaine use and craving were found for all treatment groups, but none of the active medications were superior to placebo on these measures. The accuracy of self-reported cocaine use declined over the study period. Overall, the active medications were well tolerated. Conclusions This study does not support the use of paroxetine, pentoxifylline, riluzole, venlafaxine or pramipexole for the treatment of cocaine dependence. However, these results need to be interpreted with caution because of the small size and lack of homogeneity of the experimental groups. C1 Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst Medicat Dev Res Unit, Boston, MA USA. Stanford Univ, Sch Med, Dept Hlth & Res Policy, Div Biostat, Stanford, CA 94305 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NIDA, Medicat Dev Div, Bethesda, MD 20892 USA. RP Ciraulo, DA (reprint author), Boston Univ, Sch Med, Div Psychiat, Doctors Off Bldg,Suite 914,720 Harrison Ave, Boston, MA 02118 USA. EM dciraulo@bu.edu FU NIDA NIH HHS [N01 DA 28837] NR 35 TC 30 Z9 30 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 2005 VL 100 SU 1 BP 12 EP 22 DI 10.1111/j.1360-0443.2005.00985.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 907PB UT WOS:000227729200002 PM 15730346 ER PT J AU Ciraulo, DA Knapp, C Rotrosen, J Sarid-Segal, O Ciraulo, AM LoCastro, J Greenblatt, DJ Leiderman, D AF Ciraulo, DA Knapp, C Rotrosen, J Sarid-Segal, O Ciraulo, AM LoCastro, J Greenblatt, DJ Leiderman, D TI Nefazodone treatment of cocaine dependence with comorbid depressive symptoms SO ADDICTION LA English DT Article DE antidepressant; cocaine dependence; 5-HT2 antagonist; triazolopyridine ID METHADONE-MAINTENANCE; IMIPRAMINE TREATMENT; FLUOXETINE TREATMENT; 5-HT2C RECEPTORS; CONTROLLED-TRIAL; INTERVIEW GUIDE; RATING-SCALE; DOUBLE-BLIND; PHARMACOKINETICS; BENZOYLECGONINE AB Aims In the current study, nefazodone, an antidepressant with dual action on serotonin and norepinephrine reuptake as well as 5-HT2A receptor antagonist effects, was studied in subjects with cocaine dependence and depressive symptoms, to determine its efficacy in reducing cocaine use. Design An 8-week, double blind, placebo-controlled design was used. Setting The study was conducted at the Medication Development Research Unit (MDRU) at the VA Boston Healthcare System and the Manhattan Department of Veterans Affairs (DVA) Medical Center. Participants Subjects (n = 69) met Diagnostic and Statistical Manual version IV (DSM-IV) criteria for cocaine dependence and had Hamilton Depression Scores of 12 or higher. Intervention Subjects were assigned randomly to receive nefazodone 200 mg twice daily (n = 34) or matching placebo (n = 3 5). All subjects received individual counseling. Measurements Urinary measurements of benzoylecgonine (BE, three times per week) and self-reports of cocaine use were the primary outcome measures. Secondary outcome measures included assessments of psychiatric functioning, cocaine craving and social functioning. Findings Median weekly BE declined more rapidly in the nefazodone than in the placebo group. Median urine BE at baseline was, however, significantly greater in nefazodone than in the placebo group. Scores for strength of cocaine craving also decreased more rapidly in the nefazodone group compared to the placebo group. Both groups had equivalent improvement in mood, psychosocial functioning and self-reported cocaine use. Conclusions These results suggest that nefazodone administration can reduce cocaine craving after it has been administered for several weeks. Although the nefazodone group had a greater rate of decrease in BE levels than the placebo group, the interpretation of this finding is obscured by significant group differences in baseline BE levels. C1 Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst Medicat Dev Res Unit, Boston, MA USA. NYU, Sch Med, Dept Psychiat, New York, NY USA. VA New York Harbor Healthcare, New York, NY USA. Tufts Univ, Sch Med, Dept Pharmacol & Expt Therapeut, Boston, MA 02111 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Ciraulo, DA (reprint author), Boston Univ, Sch Med, Div Psychiat, Doctors Off Bldg,Suite 914,720 Harrison Ave, Boston, MA 02118 USA. EM dciraulo@bu.edu FU NIDA NIH HHS [N01 DA-28837] NR 39 TC 15 Z9 16 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 2005 VL 100 SU 1 BP 23 EP 31 DI 10.1111/j.1360-0443.2005.00984.x PG 9 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 907PB UT WOS:000227729200003 PM 15730347 ER PT J AU Elkashef, A Holmes, TH Bloch, DA Shoptaw, S Kampman, K Reid, MS Somoza, ER Ciraulo, D Rotrosen, J Leiderman, D Montgomery, A Vocci, F AF Elkashef, A Holmes, TH Bloch, DA Shoptaw, S Kampman, K Reid, MS Somoza, ER Ciraulo, D Rotrosen, J Leiderman, D Montgomery, A Vocci, F TI Retrospective analyses of pooled data from CREST I and CREST II trials for treatment of cocaine dependence SO ADDICTION LA English DT Article DE cocaine; pharmacotherapy; statistics ID INTERVIEW GUIDE; RATING-SCALE; SUCCESS; ABUSE AB Aim To analyze pooled data from the Cocaine Rapid Evaluation Screening Trial (CREST). Pooling data from these small pilot trials into four major drug classes permitted data exploration for treatment and covariate effects with increased sample size. Design Small pilot trials were conducted to screen fifteen medications as prospective treatments for cocaine dependence. Studies included a flexible 2-week to 4-week screening/baseline period followed by an 8-week randomized treatment condition. Participants were randomized equally to one of up to three active medications or placebo. Setting Five Medications Development Research Units at the five academic centers of University of Cincinnati, New York University, University of Pennsylvania, University of California Los Angeles and Boston University. Participants The pooled data set consisted of 3 5 7 total subjects. Standardized inclusion and exclusion criteria were employed in subject selection to enhance consistency of cocaine-dependent study participants across all sites (see reports on individual trials in this supplement for details). All participants provided at least two urine samples that were positive for cocaine metabolite during a two-week period prior to being randomized. Intervention All subjects in these trials, those randomized to placebo and active medications, received active treatment in the form of evidence-based cognitive behavioral therapy. Measures Quantitative urine benzoylecgonine (BE), self-report of cocaine use, and total Brief Substance Craving Scale (BSCS) scores were compared between each class of medication and its matched-placebo group. Findings Regression analysis of pooled data did not identify any statistically significant differences between treatment and matched-placebo for any of the four classes. Exploration of the effects of baseline covariates indicated that gender and African American status were associated significantly with outcome. Female gender was consistently associated with poorer outcomes for medication and placebo groups, while the direction of association between African American status and outcome differed by treatment groups. Retention was also examined: dropout rates may have been somewhat higher for placebo than treatment. groups during the early active-treatment period. Classification trees were used to identify characteristics of subjects who were abstinent for at least two weeks during the eight-week trial; only 4.0% of females while 17.9% of males achieved this criterion. Conclusions Results presented here may prove useful for planning future clinical trials for therapies targeting cocaine dependence. C1 Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Biostat, Stanford, CA 94305 USA. NIDA, Div Pharmacotherapies & Med Consequences Drug Abu, NIH, Dept Hlth & Human Serv, Bethesda, MD USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Calif Los Angeles, Integrated Substance Abuse Programs, Los Angeles, CA USA. Friends Res Inst Inc, Los Angeles, CA USA. Philadelphia Vet Affairs Med Ctr, Philadelphia, PA USA. NYU, Sch Med, New York, NY USA. VA New York Harbor Healthcare Syst, Dept Psychiat, New York, NY USA. Cincinnati VA Med Ctr, Cincinnati, OH USA. Univ Cincinnati, Coll Med, CinARC, Cincinnati, OH USA. Boston Univ, Sch Med, Div Psychiat, Boston, MA 02118 USA. VA Boston Healthcare Syst, MDRU, Boston, MA 02118 USA. RP Holmes, TH (reprint author), Stanford Univ, Sch Med, Dept Hlth Res & Policy, Div Biostat, HRP Redwood Bldg, Stanford, CA 94305 USA. EM tholmes@stanford.edu FU NIDA NIH HHS [1 Y01 DA 50038] NR 19 TC 23 Z9 23 U1 0 U2 1 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0965-2140 J9 ADDICTION JI Addiction PD MAR PY 2005 VL 100 SU 1 BP 91 EP 101 DI 10.1111/j.1360-0443.2005.00986.x PG 11 WC Substance Abuse; Psychiatry SC Substance Abuse; Psychiatry GA 907PB UT WOS:000227729200009 PM 15730353 ER PT J AU Rader, JI AF Rader, Jeanne I. TI Folic acid fortification of enriched cereal-grain products in the United States SO AGRO FOOD INDUSTRY HI-TECH LA English DT Article ID MICROBIOLOGICAL ASSAY; FOOD FORTIFICATION; PLASMA HOMOCYSTEINE; TOTAL FOLATE; EXTRACTION AB Folic acid fortification of enriched cereal-grain products became mandatory in the U.S. on January 1, 1998. The fortification was instituted to increase folate intake among women of child-bearing age to reduce their risk of neural tube birth defect (NTD)-affected pregnancies. The process used by the U.S. Food and Drug Administration (FDA) in modeling the level of fortification followed the agency's food fortification policy and illustrates the complex issues that emerge when fortification of a nation's food supply is evaluated as a means for addressing a public health concern. Decisions regarding fortification addressed the competing challenges imposed by considerations of effectiveness for the target population and safety for the much larger non-target population. Recent data show significant improvements in folate status and temporally associated declines in NTDs in the U.S. following initiation of the fortification program. Interest in effects of increased intakes on risks of NTDs or vascular or other diseases will continue to be balanced against the general lack of data about safety of continuous high intakes. Careful monitoring over time is needed to determine that the program functions as intended. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Nutrit Prod Labeling & Dietary Supplements, Div Res & Appl Technol, College Pk, MD 20740 USA. RP Rader, JI (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Nutrit Prod Labeling & Dietary Supplements, Div Res & Appl Technol, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 21 TC 0 Z9 0 U1 1 U2 2 PU TEKNOSCIENZE PUBL PI MILAN PA VIA AURELIO SAFFI 23, 20123 MILAN, ITALY SN 1722-6996 J9 AGRO FOOD IND HI TEC JI Agro Food Ind. Hi-Tech PD MAR-APR PY 2005 VL 16 IS 2 BP 28 EP 30 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 062EA UT WOS:000238926200010 ER PT J AU Muni, NI Califf, RM Foy, JR Boam, AB Zuckerman, BD Kuntz, RE AF Muni, NI Califf, RM Foy, JR Boam, AB Zuckerman, BD Kuntz, RE TI Coronary drug-eluting stent development: Issues in trial design SO AMERICAN HEART JOURNAL LA English DT Article ID DOUBLE-BLIND; RESTENOSIS; PACLITAXEL; MULTICENTER; DELIVERY; DISEASE; DEVICES; HUMANS C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Duke Univ, Med Ctr, Dept Cardiol, Durham, NC USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Med, Boston, MA USA. Harvard Univ, Sch Med, Brigham & Womens Hosp, Dept Clin Biometr, Boston, MA USA. RP Muni, NI (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-450,9200 Corp Blvd, Rockville, MD 20850 USA. EM neal.muni@fda.hhs.gov NR 23 TC 8 Z9 8 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAR PY 2005 VL 149 IS 3 BP 415 EP 433 DI 10.1016/j.ahj.2004.09.001 PG 19 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 917RV UT WOS:000228487800009 PM 15864230 ER PT J AU McGregor, JC Kim, PW Perencevich, EN Bradham, DD Furuno, JP Kaye, KS Fink, JC Langenberg, P Roghmann, MC Harris, AD AF McGregor, JC Kim, PW Perencevich, EN Bradham, DD Furuno, JP Kaye, KS Fink, JC Langenberg, P Roghmann, MC Harris, AD TI Utility of the Chronic Disease Score and Charlson Comorbidity Index as comorbidity measures for use in epidemiologic studies of antibiotic-resistant organisms SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Article DE comorbidity; drug resistance; bacterial; predictive value of tests; ROC curve; sensitivity and specificity ID STAPHYLOCOCCUS-AUREUS BACTEREMIA; ANTIMICROBIAL SURVEILLANCE PROGRAM; BLOOD-STREAM INFECTIONS; CONTROL-GROUP SELECTION; INTENSIVE-CARE UNITS; RISK-FACTORS; METHICILLIN-RESISTANT; PSEUDOMONAS-AERUGINOSA; HOSPITALIZED-PATIENTS; LOGISTIC-REGRESSION AB Comorbidity is a known risk factor for antibiotic-resistant bacterial infections. Although aggregate comorbidity measures are useful in epidemiologic research, none of the existing measures was developed for use with this outcome. This study compared the utility of two comorbidity measures, the Charlson Comorbidity Index and the Chronic Disease Score, in assessing the comorbidity-attributable risk of nosocomial infections with methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococci (VRE). Two case-control studies were conducted at the University of Maryland Medical System in Baltimore, Maryland. Cases were inpatients with a first positive clinical culture of MRSA or VRE at least 48 hours postadmission (July 1, 1998-July 1, 2001). Three inpatient controls were randomly selected per case. The MRSA study included 2,164 patients, and the VRE study included 1,948. The scores' discrimination and calibration were measured by using the c statistic and Hosmer-Lemeshow chi-square test. The Charlson Comorbidity Index (c = 0.653) and Chronic Disease Score (c = 0.608) were similar discriminators of MRSA and VRE (c = 0.670 and c = 0.647, respectively). Calibration of the scores was poor for both outcomes (p < 0.05). A revised comorbidity measure specific to resistant infections would likely provide a better assessment of the comorbidity-attributable risk of antibiotic-resistant infections. C1 Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. US FDA, Div Antiinfect Drug Prod, Off Drug Evaluat 4, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. VA MD Hlth Care Syst, Baltimore, MD USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. Univ Maryland, Med Ctr, Dept Med, Div Nephrol, Baltimore, MD 21201 USA. RP McGregor, JC (reprint author), Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, 100 N Greene St,Lower Level, Baltimore, MD 21201 USA. EM jmcgrego@epi.umaryland.edu RI McGregor, Jessina/A-7625-2008; OI Fink, Jeffrey/0000-0002-5622-5052; Roghmann, Mary-Claire/0000-0003-1063-9257 NR 74 TC 120 Z9 120 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD MAR 1 PY 2005 VL 161 IS 5 BP 483 EP 493 DI 10.1093/aje/kwi068 PG 11 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 899DX UT WOS:000227126200009 PM 15718484 ER PT J AU Levy, MM Baylor, MS Bernard, GR Fowler, R Franks, TJ Hayden, FG Helfand, R Lapinsky, SE Martin, TR Niederman, MS Rubenfeld, GD Slutsky, AS Stewart, TE Styrt, BA Thompson, BT Harabin, AL AF Levy, MM Baylor, MS Bernard, GR Fowler, R Franks, TJ Hayden, FG Helfand, R Lapinsky, SE Martin, TR Niederman, MS Rubenfeld, GD Slutsky, AS Stewart, TE Styrt, BA Thompson, BT Harabin, AL TI Clinical issues and research in respiratory failure from severe acute respiratory syndrome SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE acute lung injury; acute respiratory distress syndrome; infectious disease ID CRITICALLY-ILL PATIENTS; MECHANICALLY VENTILATED PATIENTS; INTENSIVE-CARE UNIT; SARS-ASSOCIATED CORONAVIRUS; COMMUNITY-ACQUIRED PNEUMONIA; ACUTE LUNG INJURY; DISTRESS-SYNDROME; INTERFERON-ALPHA; GASTROESOPHAGEAL-REFLUX; VENOUS THROMBOEMBOLISM AB The National Heart, Lung, and Blood Institute, along with the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases, convened a panel to develop recommendations for treatment, prevention, and research for respiratory failure from severe acute respiratory syndrome (SARS) and other newly emerging infections. The clinical and pathological features of acute lung injury (ALI) from SARS appear indistinguishable from ALI from other causes. The mainstay of treatments for ALI remains supportive. Patients with ALI from SARS who require mechanical ventilation should receive a lung protective, low tidal volume strategy. Adjuvant treatments recommended include prevention of venous thromboembolism, stress ulcer prophylaxis, and semirecumbent positioning during ventilation. Based on previous experience in Canada, infection control resources and protocols were recommended. Leadership structure, communication, training, and morale are an essential aspect of SAIRS management. A multicenter, placebo-controlled trial of corticosteroids for late SARS is justified because of widespread clinical use and uncertainties about relative risks and benefits. Studies of combined pathophysiologic endpoints were recommended, with mortality as a secondary endpoint. The group recommended preparation for studies, including protocols, ethical considerations, Web-based registries, and data entry systems. C1 NHLBI, Div Lung Dis, NIH, Bethesda, MD 20892 USA. Brown Univ, Rhode Isl Hosp, Dept Med, Providence, RI 02903 USA. US FDA, Div Antiviral Drug Prod, Rockville, MD 20857 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37212 USA. Armed Forces Inst Pathol, Dept Pulm & Mediastinal Pathol, Washington, DC 20306 USA. Univ Virginia, Dept Internal Med, Charlottesville, VA USA. Ctr Dis Control & Prevent, Resp & Enter Viruses Branch, Atlanta, GA USA. VA Puget Sound Med Ctr, Div Pulm & Crit Care Med, Seattle, WA USA. Winthrop Univ Hosp, Dept Med, Mineola, NY 11501 USA. Univ Washington, Harborview Med Ctr, Dept Pulm & Crit Care Med, Seattle, WA 98195 USA. Massachusetts Gen Hosp, Dept Med, Pulm & Crit Care Unit, Boston, MA 02114 USA. Sunnybrook & Womens Coll Hlth Sci Ctr, Interdept Div Crit Care Med, Toronto, ON, Canada. Mt Sinai Hosp, Dept Med, Toronto, ON M5G 1X5, Canada. Mt Sinai Hosp, Dept Crit Care Med, Toronto, ON M5G 1X5, Canada. Univ Hlth Network, Toronto, ON, Canada. St Michaels Hosp, Dept Med, Toronto, ON M5B 1W8, Canada. St Michaels Hosp, Dept Crit Care, Toronto, ON M5B 1W8, Canada. RP Harabin, AL (reprint author), NHLBI, Div Lung Dis, NIH, 6,701 Rockledge Dr,Room 10018, Bethesda, MD 20892 USA. EM harabin@nih.gov RI Slutsky, Arthur/A-6013-2008; Lapinsky, Stephen/C-4624-2015 OI Slutsky, Arthur/0000-0002-6063-3876; Lapinsky, Stephen/0000-0002-6930-0306 NR 84 TC 25 Z9 26 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD MAR 1 PY 2005 VL 171 IS 5 BP 518 EP 526 DI 10.1164/rccm.200405-621WS PG 9 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 900EF UT WOS:000227197500016 PM 15591472 ER PT J AU Stone, JH Rajapakse, VN Hoffman, GS Specks, U Merkel, PA Spiera, RF Davis, JC Clair, EWS McCune, J Ross, S Hitt, BA Veenstra, TD Conrads, TP Liotta, LA Petricoin, EF AF Stone, John H. Rajapakse, Vinodh N. Hoffman, Gary S. Specks, Ulrich Merkel, Peter A. Spiera, Robert F. Davis, John C. Clair, E. William St. McCune, Joseph Ross, Sally Hitt, Ben A. Veenstra, Timothy D. Conrads, Thomas P. Liotta, Lance A. Petricoin, Emanuel F., III CA Wegeners Granulomatosis Etanercept TI A Serum Proteomic Approach to Gauging the State of Remission in Wegener's Granulomatosis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID OVARIAN-CANCER; ETANERCEPT TRIAL; PROSTATE-CANCER; METHOTREXATE; PREDNISONE; PATTERNS; ANTIBODY; BLOOD; CARE AB Objective. To identify serum ion patterns that distinguish remission from active disease in patients with Wegener's granulomatosis (WG). Methods. Using sera collected in the WG Etanercept Trial, we selected samples from patients who either were undergoing a period of extended disease remission or had recent flares of active WG. Unfractionated samples were randomized into sets for training and testing, such that remission sera and active disease sera could be analyzed without batch bias. Molecular species within the sera were ionized by high-resolution, matrix-assisted laser desorption ionization time-of-flight mass spectrometry. We then used a bioinformatics pattern-recognition tool to identify optimal combinations of ions. During the training stage, the clinical data (remission versus active disease) were provided in association with the spectral data from each sample. In the testing stage, we performed blinded testing on a previously unexamined set of samples. Results. The most robust model, trained on a total of 82 samples (42 remission, 40 active disease), included 7 key ions with mass:charge ratios of 803.239, 2,171.672, 2,790.574, 3,085.237, 5,051.726, 5,833.989, and 6,630.465. The combined relative amplitudes of these 7 ions identified 5 distinct clusters of either remission or active disease samples during the training stage. In the testing stage, this model segregated 72 samples into the same 5 clusters, including I large remission cluster (n = 28) and another large active disease cluster (n = 32). Three smaller clusters of active disease or remission samples were also identified, with remission clusters populated by 2 samples in one cluster and 8 in another, and an active disease cluster populated by 2 samples. The model categorized 35 of 37 remission samples correctly (sensitivity 95%, 95% confidence interval [95% CI] 82.1-99.4) and 32 of 35 active disease samples correctly (specificity 91%, 95% CI 78.1-98.1). Conclusion. This serum proteomic profiling approach appears to be useful in distinguishing between states of stable clinical remission and active disease. Further validation and refinement of this strategy may help clinicians apply immunosuppressive therapies more judiciously among their patients, thereby avoiding morbidity and mortality from excessive treatment. Identification of the most robust and clinically useful combinations of ions will permit the rational selection of molecules for sequencing and analysis. C1 [Stone, John H.] Johns Hopkins Univ, Johns Hopkins Vasculitis Ctr, Sch Med, Baltimore, MD 21224 USA. [Rajapakse, Vinodh N.; Ross, Sally; Liotta, Lance A.; Petricoin, Emanuel F., III] NCI, FDA Clin Proteom Program, Bethesda, MD 20892 USA. [Hoffman, Gary S.] Cleveland Clin Fdn, Lerner Coll Med, Cleveland, OH 44195 USA. [Specks, Ulrich] Mayo Clin, Rochester, MN USA. [Merkel, Peter A.] Boston Univ, Sch Med, Boston, MA 02118 USA. [Spiera, Robert F.] Beth Israel Deaconess Med Ctr, New York, NY 10003 USA. [Davis, John C.] Univ Calif San Francisco, San Francisco, CA 94143 USA. [Clair, E. William St.] Duke Univ, Durham, NC USA. [McCune, Joseph] Univ Michigan, Ann Arbor, MI 48109 USA. [Hitt, Ben A.] Correlogic Inc, Bethesda, MD USA. [Veenstra, Timothy D.; Conrads, Thomas P.] NCI, Biomed Proteom Program, Mass Spectrometry Ctr, Frederick, MD 21701 USA. RP Stone, JH (reprint author), Johns Hopkins Univ, Johns Hopkins Vasculitis Ctr, Sch Med, 5501 Hopkins Bayview Circle,JHAAC 1B23, Baltimore, MD 21224 USA. EM jstone@jhmi.edu FU FDA HHS [FD-R-001652-01]; NCRR NIH HHS [M01-RR0-0042, M01-RR0-00533, M01-RR-30, M01-RR0-2719]; NIAMS NIH HHS [K24-AR-049185-01, N01-AR-9-2240] NR 35 TC 29 Z9 30 U1 0 U2 1 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 MAR PY 2005 VL 52 IS 3 BP 902 EP 910 DI 10.1002/art.20938 PG 9 WC Rheumatology SC Rheumatology GA 905LU UT WOS:000227570600029 PM 15751091 ER PT J AU Rezapkin, G Dragunsky, E Chumakov, K AF Rezapkin, G Dragunsky, E Chumakov, K TI Improved ELISA test for determination of potency of Inactivated Poliovirus Vaccine (IPV) SO BIOLOGICALS LA English DT Article ID D-ANTIGEN; CLINICAL-EVALUATION; WILD-TYPE AB An improved ELISA test for determination of potency of Inactivated Poliovirus Vaccine (IPV) is proposed. The method is based on the use of IgG purified from immune rabbit serum conjugated with biotin. Optimized and validated materials for the test can be stored for a long time in the form of ready-to-use kits. Optimization included selection of anti-poliovirus rabbit antibody batches with the best specificity to D-antigen as well as finding the most efficient parameters for all steps of ELISA protocol. The assay is based on direct ("sandwich") ELISA scheme, in which antigens are captured on ELISA plates coated with purified rabbit polyclonal D-antigen specific IgG raised against wild polioviruses of three serotypes. D-antigen specificity of the IgG was at least 10 times higher than to H-antigen (heat-inactivated virus). The presence of antigen was detected using biotin-conjugated IgG from the same source. Eight-point dose-response curves were obtained for each sample and the reference vaccine. The protocol ensured low background (less than 0.2 OD), linear response over the entire range of optical density measurements (up to 3.0 OD), and high precision of data (assay variability was about 3%). The quantitative results and the validity of the test were determined by two numerical approaches, linear regression and a new analysis procedure called the local interpolation method. For the first approach we also proposed a new method for testing of parallelism of regression lines. The ELISA protocol for all three types of poliovirus is based on standard off-the-shelf reagents, and is highly reproducible and reliable. An in-house Reference Reagent was formulated and calibrated against the International Reference for IPV. Published by Elsevier Ltd on behalf of The International Association for Biologicals. C1 Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Chumakov, K (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 470, Rockville, MD 20852 USA. EM chumakov@cber.fda.gov NR 14 TC 8 Z9 11 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 2005 VL 33 IS 1 BP 17 EP 27 DI 10.1016/j.biologicals.2004.11.003 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 904QL UT WOS:000227512700003 PM 15713553 ER PT J AU Rezapkin, G Martin, J Chumakov, K AF Rezapkin, G Martin, J Chumakov, K TI Analysis of antigenic profiles of inactivated poliovirus vaccine and vaccine-derived polioviruses by block-ELISA method SO BIOLOGICALS LA English DT Article ID MONOCLONAL-ANTIBODIES; TYPE-1 POLIOVIRUS; WILD-TYPE; ESCAPE MUTANTS; CLEAVAGE SITES; NEUTRALIZATION; STRAINS; POLIOMYELITIS; OUTBREAK; CIRCULATION AB A new block-ELISA test for quantitative evaluation of relative reactivity of antigenic sites was developed and used to reveal the detailed epitope structure of inactivated poliovirus vaccines (IPV) and live poliovirus strains. Poliovirus was captured on ELISA plates coated with rabbit anti-poliovirus IgG and blocked by monoclonal antibodies (Mabs) specific to individual epitopes before the remaining reactive antigenic sites were quantified by polyclonal anti-poliovirus IgG conjugate. The decrease of conjugate binding by the pre-treatment with a Mab reflects its contribution to the overall reactivity of poliovirus antigen. The level of block activity of Mabs for a given antigen can be expressed as a percent of reduction of antigenic reactivity as determined by ELISA test. It can be normalized by expressing this value as a ratio to the block activity of a reference sample. The data on the blocking-activity of a panel of monoclonal antibodies specific to different antigenic sites represents the epitope composition (antigenic profile) of a sample. Quantitative differences in epitope composition were determined for nine samples of inactivated poliovirus vaccine (IPV) and compared with the International Reference Reagent. This method could be used for monitoring consistency of IPV production, comparison of vaccines made by different manufacturers, and for the analysis of antigenically modified strains of attenuated poliovirus. Antigenic structures of two isolates of type I vaccine-derived poliovirus (VDPV) were compared with the structures of parental Sabin I and wild-type Mahoney strains using 17 monoclonal antibodies and revealed significant differences, suggesting that the method can be used for screening of field isolates and rapid identification of antigenically divergent VDPV strains. (C) 2004 The International Association for Biologicals. Published by Elsevier Ltd. All rights reserved. C1 Food & Drug Adm, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. RP Chumakov, K (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM 470, Rockville, MD 20852 USA. EM chumakov@cber.fda.gov NR 42 TC 19 Z9 23 U1 1 U2 4 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 2005 VL 33 IS 1 BP 29 EP 39 DI 10.1016/j.biologicals.2004.11.001 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 904QL UT WOS:000227512700004 PM 15713554 ER PT J AU Nitcheva, DK Piegorsch, WW West, RW Kodell, RL AF Nitcheva, DK Piegorsch, WW West, RW Kodell, RL TI Multiplicity-adjusted inferences in risk assessment: Benchmark analysis with quantal response data SO BIOMETRICS LA English DT Article DE benchmark dose; low-dose extrapolation; multistage model; quantal data; quantitative risk assessment; safety assessment; simultaneous inferences ID ANIMAL CARCINOGENICITY EXPERIMENTS; CONFIDENCE BANDS AB A primary objective in quantitative risk or safety assessment is characterization of the severity and likelihood of an adverse effect caused by a chemical toxin or pharmaceutical agent. In many cases data are not available at low doses or low exposures to the agent, and inferences at those doses must be based on the high-dose data. A modern method for making low-dose inferences is known as benchmark analysis, where attention centers on the dose at which a fixed benchmark level of risk is achieved. Both upper confidence limits on the risk and lower confidence limits on the "benchmark dose" are of interest. In practice, a number of possible benchmark risks may be under study; if so, corrections must be applied to adjust the limits for multiplicity. In this short note, we discuss approaches for doing so with quantal response data. C1 Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. S Carolina Canc Ctr, Columbia, SC 29203 USA. Univ S Carolina, Dept Stat, Columbia, SC 29208 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72709 USA. RP Nitcheva, DK (reprint author), Univ S Carolina, Dept Epidemiol & Biostat, Columbia, SC 29208 USA. EM nitcheva@gwm.sc.edu OI Piegorsch, Walter/0000-0003-2725-5604 FU NCI NIH HHS [R01-CA76031] NR 20 TC 12 Z9 12 U1 0 U2 1 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 2005 VL 61 IS 1 BP 277 EP 286 DI 10.1111/j.0006-341X.2005.031211.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 905NX UT WOS:000227576600033 PM 15737104 ER PT J AU Holland, RD Gehring, T Taylor, J Lake, BG Gooderham, NJ Turesky, RJ AF Holland, RD Gehring, T Taylor, J Lake, BG Gooderham, NJ Turesky, RJ TI Formation of a mutagenic heterocyclic aromatic amine from creatinine in urine of meat eaters and vegetarians SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID TANDEM MASS-SPECTROMETRY; COMMERCIAL BEEF EXTRACT; LIQUID-CHROMATOGRAPHY; COOKED FOODS; FRIED BEEF; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO(4,5-B)PYRIDINE PHIP; 2-AMINO-3-METHYLIMIDAZO<4,5-F>QUINOLINE IQ; COLORECTAL-CANCER; DNA-ADDUCTS; HUMAN LIVER AB Liquid chromatography electrospray ionization mass spectrometry (MS) with a triple quadrupole MS was used to identify known and novel heterocyclic aromatic amines (HAAs) in human urine. The identities of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (8-MeIQx) and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) were confirmed by their product ion spectra. The constant neutral loss scan mode was employed to probe for other analytes in urine that display the transition [M + H](+) -> [M + H - CH3 center dot](+center dot), which is common to HAAs containing an N-methylimidazo moiety, and led to the detection of a previously unreported isomer of 8-MeIQx [Holland, R., et al. (2004) Chem. Res. Toxicol. 17, 1121-1136]. We now report the identification of another novel HAA, 2-amino-1-methylimidazo[4,5-b]quinoline (IQ[4,5-b]), an isomer of the powerful animal carcinogen 2-amino-3-methylimidazo[4,5-f]quinoline (IQ). The amounts of IQ[4,5-b] measured in the urine of human volunteers who consumed grilled beef ranged from 15 to 135% of the ingested dose, while the amounts of 8-MeIQx and PhIP excreted in urine were on average <2% of the ingested dose. Base treatment of urine at 70 degrees C increased the concentrations of 8-MeIQx and PhIP by as much as 6-fold, indicating the presence of phase II conjugates; however, the amount of IQ[4,5-b] increased by more than 100-fold. IQ[4,5-b] was also detected in the urine of vegetarians following base hydrolysis. The formation of IQ[4,5-b], but not IQ, 8-MeIQx, or PhIP, also occurred in urine incubated at 37 degrees C. Creatinine and 2-aminobenzaldehyde are likely precursors of IQ[4,5-b]. The detection of IQ[4,5-b] in the urine of both meat eaters and vegetarians suggests that this HAA may be present in nonmeat staples or that IQ [4,5-b] formation may occur endogenously within the urinary bladder or other biological fluids. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. BIBRA Int, Carshalton SM5 4DS, Surrey, England. Univ London Imperial Coll Sci Technol & Med, Div Biomed Sci, London SW7 2AZ, England. RP Turesky, RJ (reprint author), New York State Dept Hlth, Wadsworth Ctr, Div Environm Dis Prevent, Empire State Plaza,POB 509, Albany, NY 12201 USA. EM Rturesky@wadsworth.org NR 70 TC 11 Z9 11 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD MAR PY 2005 VL 18 IS 3 BP 579 EP 590 DI 10.1021/tx049675w PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 909OH UT WOS:000227868700018 PM 15777097 ER PT J AU Cryer, DR Nicholas, SP Henry, DH Mills, DJ Stadel, BV AF Cryer, DR Nicholas, SP Henry, DH Mills, DJ Stadel, BV TI Comparative outcomes study of metformin intervention versus conventional approach - The COSMIC approach study SO DIABETES CARE LA English DT Article ID LACTIC-ACIDOSIS AB OBJECTIVE - Metformin was approved by the Food and Drug Administration in 1995 subject to the conduct of a randomized trial to evaluate the risk of lactic acidosis or other serious adverse events (SAEs) with this agent, under usual care conditions. RESEARCH DESIGN AND METHODS - The Comparative Outcomes Study of Metformin Intervention versus Conventional (COSMIC) Approach Study was a randomized, open-label, active-comparator, parallel-group, 1-year trial in type 2 diabetic, patients suboptimally controlled on diet or sulfonylurea. Patients received metformin (n = 7,227) or other usual care treatments (n 1,505). The primary end point was the incidence of SAEs, death, and hospitalization. RESULTS - SAEs occurred in 10.3% (95% CI 9.6-11.1%) of the metformin group and in 11.0% (9.5-12.7%) of the usual care group (P = 0.431). Lactic acidosis did not occur. All-cause mortality (1.1% [0.9-1.4%] vs. 1.3% [0.8-2.0%], P = 0.596) and hospitalization (9.4% [8.810.1%] vs. 10.4% [8.9-12.1%], P = 0.229) were similar between groups. CONCLUSIONS - The incidence of SAEs was similar between groups. Lactic acidosis was not observed. Metformin may be safely prescribed for type 2 diabetes if contraindications and warnings are respected. This study demonstrates the utility of large, simple trials for risk evaluation of treatments for common diseases. C1 Bristol Myers Squibb Co, Princeton, NJ USA. Food & Drug Adm, Rockville, MD USA. RP Cryer, DR (reprint author), Bristol Myers Squibb Co, 777 Scudders Mill Rd, Plainsboro, NJ 08536 USA. EM dennis.cryer@bms.com NR 20 TC 60 Z9 65 U1 1 U2 7 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1701 N BEAUREGARD ST, ALEXANDRIA, VA 22311-1717 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD MAR PY 2005 VL 28 IS 3 BP 539 EP 543 DI 10.2337/diacare.28.3.539 PG 5 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 903ME UT WOS:000227429200006 PM 15735184 ER PT J AU Paine, MF Ludington, SS Chen, ML Stewart, PW Huang, SM Watkins, PB AF Paine, MF Ludington, SS Chen, ML Stewart, PW Huang, SM Watkins, PB TI Do men and women differ in proximal small intestinal CYP3A or P-glycoprotein expression? SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID HUMAN LIVER; INTERINDIVIDUAL VARIATION; CYTOCHROME-P450 3A4; ORAL AVAILABILITY; ENTEROCYTE CYP3A4; GRAPEFRUIT JUICE; SEX; PHARMACOKINETICS; METABOLISM; HUMANS AB The higher systemic clearance of some CYP3A4 [ whether also P-glycoprotein (P-gp)] drug substrates in women versus men is attributed in part to a higher hepatic CYP3A4 content in women. This, combined with the general paucity of reported sex differences in the apparent oral clearance of CYP3A4 substrates, suggested a sex-dependent expression of CYP3A4 in the intestine, but in a pattern opposite to that in the liver. Accordingly, duodenal biopsies obtained from healthy men ( n = 46) and women ( n = 45) were analyzed, by Western blot, for relative CYP3A4, as well as for CYP3A5 and P-gp, expression levels. Among all subjects, CYP3A4 and P-gp varied 8- and 10-fold, respectively. CYP3A5, which was readily detected in 27% of these predominantly white individuals, varied 7-fold. For all three proteins, a sex difference was not detected ( p greater than or equal to 0.55). The lack of a difference remained for CYP3A4 and P-gp when the analysis was restricted to white individuals ( n = 74) or to individuals with undetectable CYP3A5. Comparing the 21 premenopausal women ( all were aged < 45 years) with the 43 men aged < 45 years, again no sex differences were detected in CYP3A4 and P-gp. Comparing the pre- with postmenopausal women, mean CYP3A4 content was 20% lower in the postmenopausal individuals ( p = 0.01). The lack of a sex-dependent difference in proximal intestinal CYP3A4 could account, in part, for the lack of reported sex differences in the oral, relative to systemic, clearance of some CYP3A4 substrates. Ramifications of lower intestinal CYP3A4 content in post-versus premenopausal women require further investigation. C1 Univ N Carolina, Gen Clin Res Ctr, Chapel Hill, NC USA. Univ N Carolina, Div Pharmacotherapy, Chapel Hill, NC USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Univ N Carolina, Dept Biostat, Chapel Hill, NC USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP UNC Hosp, Gen Clin Res Ctr, Room 3005,Bldg APCF,CB 7600, Chapel Hill, NC 27599 USA. EM mpaine@med.unc.edu FU NCRR NIH HHS [RR00046]; NIGMS NIH HHS [GM38149] NR 30 TC 64 Z9 65 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3995 USA SN 0090-9556 EI 1521-009X J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD MAR PY 2005 VL 33 IS 3 BP 426 EP 433 DI 10.1124/dmd.104.002469 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 897NE UT WOS:000227010100018 PM 15608139 ER PT J AU Moon, H Ahn, H Lee, JJ Kodell, RL AF Moon, H Ahn, H Lee, JJ Kodell, RL TI A weight-adjusted Peto's test when cause of death is not assigned SO ENVIRONMENTAL AND ECOLOGICAL STATISTICS LA English DT Article DE bioassay; bootstrap; competing risk; fatal tumor; single sacrifice; weight function ID ANIMAL CARCINOGENICITY EXPERIMENTS; TUMOR LETHALITY; TIME; ATTRIBUTION; INFORMATION; ABSENCE; ONSET AB A new statistical testing approach using a weighted logrank statistic is developed for rodent tumorigenicity assays that have a single terminal sacrifice but not cause-of-death data. Instead of using cause-of-death assignment by pathologists, the number of fatal tumors is estimated by a constrained nonparametric maximum likelihood estimation method. For data lacking cause-of-death information, the Peto test is modified with estimated numbers of fatal tumors and a Fleming-Harrington-type weight, which is based on an estimated tumor survival function. A bootstrap resampling method is used to estimate the weight function. The proposed testing method with the weight adjustment appears to improve the performance in various situations of single-sacrifice animal experiments. A Monte Carlo simulation study for the proposed test is conducted to assess size and power of the test. This testing approach is illustrated using a real data set. (c) 2005 Springer Science + Business Media, Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Stony Brook Univ, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. RP Moon, H (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM hmoon@nctr.fda.gov NR 24 TC 1 Z9 1 U1 0 U2 1 PU SPRINGER PI DORDRECHT PA VAN GODEWIJCKSTRAAT 30, 3311 GZ DORDRECHT, NETHERLANDS SN 1352-8505 J9 ENVIRON ECOL STAT JI Environ. Ecol. Stat. PD MAR PY 2005 VL 12 IS 1 BP 95 EP 113 DI 10.1007/s10651-005-6819-z PG 19 WC Environmental Sciences; Mathematics, Interdisciplinary Applications; Statistics & Probability SC Environmental Sciences & Ecology; Mathematics GA 934ZK UT WOS:000229747900005 ER PT J AU Akerman, GS Rosenzweig, BA Domon, OE Tsai, CA Bishop, ME McGarrity, LJ MacGregor, JT Sistare, FD Chen, JJ Morris, SM AF Akerman, GS Rosenzweig, BA Domon, OE Tsai, CA Bishop, ME McGarrity, LJ MacGregor, JT Sistare, FD Chen, JJ Morris, SM TI Alterations in gene expression profiles and the DNA-damage response in ionizing radiation-exposed TK6 cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE TIK6 cells; ionizing radiation; microarray; gene expression ID TRANSCRIPTIONAL REPRESSOR ATF3; STRAND BREAK REPAIR; CYCLIN-G; LYMPHOBLASTOID-CELLS; GENOTOXIC STRESS; MISMATCH REPAIR; EXCISION-REPAIR; TARGET GENE; LIGASE-III; APOPTOSIS AB Identifying genes that are differentially expressed in response to DNA damage may help elucidate markers for genetic damage and provide insight into the cellular responses to specific genotaxic agents. We utilized cDNA microarrays to develop gene expression profiles for ionizing radiation-exposed human lymphoblastoid TK6 cells. In order to relate changes in the expression profiles to biological responses, the effects of ionizing radiation on cell viability, cloning efficiency, and micronucleus formation were measured. TK6 cells were exposed to 0.5, 1, 5, 10, and 20 Gy ionizing radiation and cultured for 4 or 24 hr. A significant (P < 0.0001) decrease in cloning efficiency was observed at all doses at 4 and 24 hr after exposure. Flow cytometry revealed significant decreases in cell viability at 24 hr in cells exposed to 5 (P < 0.001), 10 (P < 0.0001), and 20 Gy (P < 0.0001). An increase in micronucleus frequency occurred at both 4 and 24 hr at 0.5 and 1 Gy; however, insufficient binucleated cells were present for analysis at the higher doses. Gene expression profiles were developed from mRNA isolated from cells exposed to 5, 10, and 20 Gy using a 350 gene human cDNA array platform. Overall, more genes were differentially expressed at 24-hr than at the 4-hr time point. The genes upregulated (> 1.5-fold) or downregulated (< 0.67-fold) at 4 hr were those primarily involved in the cessation of the cell cycle, cellular detoxification pathways, DNA repair, and apoptosis. At 24 hr, glutathione-associated genes were induced in addition to genes involved in apoptosis. Genes involved in cell cycle progression and mitosis were downregulated at 24 hr. Real-time quantitative PCR was used to confirm the microarray results and to evaluate expression levels of selected genes at the low doses (0.5 and 1.0 Gy). The expression profiles reflect the cellular and molecular responses to ionizing radiation related to the recognition of DNA damage, a halt in progression through the cell cycle, activation of DNA-repair pathways, and the promotion of apoptosis. Environ. Mol. Mutagen. 45:188-205, 2005. Published 2005 Wiley-Liss, Inc. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Appl Pharmacol Res, Ctr Drug Evaluat & Res, Silver Spring, MD USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Off Washington Operat, Rockville, MD 20857 USA. RP Morris, SM (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM smorris@nctr.fda.gov OI Tsai, Chen-An/0000-0002-7490-4331 NR 72 TC 39 Z9 42 U1 0 U2 3 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PD MAR-APR PY 2005 VL 45 IS 2-3 BP 188 EP 205 DI 10.1002/em.20091 PG 18 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 914XX UT WOS:000228262500010 PM 15657912 ER PT J AU Zhang, L Lizzio, EF Chen, T Kozlowski, S AF Zhang, L Lizzio, EF Chen, T Kozlowski, S TI Peptide immunization excludes antigen-specific T cells from splenic lymphoid compartments SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE vaccination; T lymphocytes; cell trafficking; cytokines; apoptosis ID IN-VIVO; TOLERANCE INDUCTION; ADOPTIVE TRANSFER; CLONAL EXPANSION; CLASS-II; LYMPHOCYTES; VACCINES; RECEPTOR; VISUALIZATION; ADJUVANT AB Using adoptive transfer of TCR-transgenic T cells, we examined the homing of transgenic T cells to splenic compartments in situ. After systemic immunization with peptide or protein antigen, the location of clonotypic T cells, cytokine production, cell surface markers, and apoptosis were assessed. There were distinct differences in the splenic homing of CD4(+) TCR-transgenic T cells in mice immunized with peptide as compared to mice immunized with whole-protein antigen. T cells in peptide immunized mice were found almost exclusively in the splenic red pulp, but not in the T and B cell zones (white pulp), while the majority of T cells immunized with whole protein were found in the white pulp. Many more Fas ligand-expressing and apoptotic cells were present after peptide immunization than after whole-protein immunization. Localization of IL-4-, IL-2- and IFN-gamma-producing cells to the lymphocyte-containing splenic white pulp was only observed with whole-protein immunization. The unique homing and increased apoptosis of immune cells post peptide immunization may help explain the ineffectiveness of many peptide vaccines. Linkage of the same peptide epitope to a carrier protein increased white pulp T cell localization and decreased apoptosis, suggesting a strategy to enhance peptide vaccine responses. C1 US FDA, Div Monoclonal Antibodies, Off Biotechnol Prod,Off Pharm Sci, Ctr Drug Evaluat & Res, Bethesda, MD 20014 USA. RP Kozlowski, S (reprint author), Bldg 29B,Rm 3NN08,HFM 561,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Kozlowski@cber.fda.gov NR 26 TC 3 Z9 3 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD MAR PY 2005 VL 35 IS 3 BP 776 EP 785 DI 10.1002/eji.200425479 PG 10 WC Immunology SC Immunology GA 906II UT WOS:000227633900012 PM 15714585 ER PT J AU Liljebjelke, KA Hofacre, CL Liu, TR White, DG Ayers, S Young, S Maurer, JJ AF Liljebjelke, KA Hofacre, CL Liu, TR White, DG Ayers, S Young, S Maurer, JJ TI Vertical and horizontal transmission of Salmonella within integrated broiler production system SO FOODBORNE PATHOGENS AND DISEASE LA English DT Article ID FIELD GEL-ELECTROPHORESIS; POLYMERASE-CHAIN-REACTION; ANTIMICROBIAL SUSCEPTIBILITY; ESCHERICHIA-COLI; UNITED-STATES; CONTAMINATION; SEROTYPES; POULTRY; CHICKENS; ENRICHMENT AB Salmonella remains one of the leading causes of food-borne illness in the United States, and many key questions regarding the introduction and persistence in animal production systems still remain. In order to understand the ecology of Salmonella within an integrated commercial broiler production system, 289 Salmonella enterica were recovered from two integrated poultry farms during the production and processing of seven consecutive flocks. The variety and prevalence of Salmonella serotypes differed between farms. Overall, 15 serotypes were identified, with the most common being Typhimurium (55%), Montevideo (7.9%), Kentucky (9%), and Enteritidis (9.7%). Salmonella Typhimurium and Enteritidis isolates recovered from processed carcasses from Farm One were further characterized using pulsed-field gel electrophoresis (PFGE), and were shown to be indistinguishable from isolates recovered from the poultry house environment and mice trapped on this farm. Additionally, the same broiler S. Typhimurium and S. Enteritidis strains, identified by PFGE, were also isolated from samples taken at a company breeder farm, suggesting vertical transmission of these Salmonella serotypes in this poultry production system. Results indicate that management practices at the breeder level may have a profound effect on the transmission and persistence of salmonellae within an integrated production system, as well as on the potential contamination of poultry-derived products. C1 Univ Georgia, Coll Vet Med, Dept Infect Dis, Athens, GA USA. Univ Georgia, Coll Vet Med, Dept Avian Med, Athens, GA 30602 USA. US FDA, Ctr Vet Med, Laurel, MD USA. Univ Georgia, Coll Agr & Environm Sci, Ctr Food Safety, Griffin, GA USA. RP Maurer, JJ (reprint author), 953 Coll Stn Rd, Athens, GA 30602 USA. EM jmaurer@vet.uga.edu RI Tast Lahti, Elina/R-8664-2016 NR 42 TC 57 Z9 59 U1 1 U2 11 PU MARY ANN LIEBERT INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1535-3141 J9 FOODBORNE PATHOG DIS JI Foodborne Pathog. Dis. PD SPR PY 2005 VL 2 IS 1 BP 90 EP 102 DI 10.1089/fpd.2005.2.90 PG 13 WC Food Science & Technology SC Food Science & Technology GA 050YG UT WOS:000238126200011 PM 15992303 ER PT J AU Kainz, W Casamento, JP Ruggera, PS Chan, DD Witters, DM AF Kainz, W Casamento, JP Ruggera, PS Chan, DD Witters, DM TI Implantable cardiac pacemaker electromagnetic compatibility testing in a novel security system simulator SO IEEE TRANSACTIONS ON BIOMEDICAL ENGINEERING LA English DT Article DE EMC; EMI; metal detector; pacemaker; simulator AB This paper describes a novel simulator to perform electromagnetic compatibility (EMC) tests for active implantable medical devices (AIMDs) with electromagnetic fields emitted by security systems. The security system simulator was developed in response to over 100 incident reports over 17 years related to the interference of AIMD's with security systems and the lack of a standardized test method. The simulator was evaluated regarding field homogeneity, signal distortion, and maximum magnetic field strength levels. Small three-axis probes and a three-axis scanning system were designed to determine the spatial and temporal characteristics of the fields emitted by 12 different types of walk through metal detectors (WTMDs). Tests were performed on four implanted pacemakers with a saline phantom and correlated to a newly developed test method performed "in air" (without the phantom). Comparison of the simulator thresholds with tests performed in real WTMDs showed that the simulator is able to mimic the pacemaker interference. The interference thresholds found in the simulator indicate that pulsed magnetic fields are more likely to cause interference in pacemakers than sinusoidal fields. The security system simulator will help biomedical engineers, manufacturers of medical devices, and manufacturers of security systems to identify incompatible combinations of WTMDs and AIMDs early in the development stage. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20851 USA. RP Kainz, W (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20851 USA. EM wxk@cdrh.fda.gov; jpc@cdrh.fda.gov; psr@cdrh.fda.gov; ddc@cdrh.fda.gov; dmw@cdrh.fda.gov NR 13 TC 18 Z9 18 U1 2 U2 8 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855 USA SN 0018-9294 J9 IEEE T BIO-MED ENG JI IEEE Trans. Biomed. Eng. PD MAR PY 2005 VL 52 IS 3 BP 520 EP 530 DI 10.1109/TBME.2004.843293 PG 11 WC Engineering, Biomedical SC Engineering GA 899JA UT WOS:000227139500019 PM 15759582 ER PT J AU Finn, S Han, J Farnsworth, R Yang, A Puri, R Ikonomi, P AF Finn, S. Han, J. Farnsworth, R. Yang, Amy Puri, Raj Ikonomi, P. TI High passage number of continuous cell line affects the transcriptome SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Meeting Abstract C1 Amer Type Culture Collect, Mol Authenticat Resource Ctr, Mannassas, VA 20110 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. EM pikonomi@atcc.org NR 0 TC 0 Z9 0 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SPR PY 2005 VL 41 BP 6A EP 6A PG 1 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA V44IC UT WOS:000202995400020 ER PT J AU Fink, DW AF Fink, Donald W., Jr. TI Stem cells and the FDA: Regulatory considerations for proceeding to clinical trials SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Meeting Abstract C1 US FDA, Off Cellular Tissue & Gene Therapies, Div Cell & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM finkd@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD SPR PY 2005 VL 41 BP 7A EP 7A PG 1 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA V44IC UT WOS:000202995400023 ER PT J AU Sundaresan, PR Marmillot, P Liu, QH Mitchell, GV Grundel, E Lakshman, MR AF Sundaresan, PR Marmillot, P Liu, QH Mitchell, GV Grundel, E Lakshman, MR TI Effects of dietary taurocholate, fat and protein on the storage and metabolism of dietary beta-carotene and alpha-tocopherol in ferrets SO INTERNATIONAL JOURNAL FOR VITAMIN AND NUTRITION RESEARCH LA English DT Article DE beta-carotene; retinoids; alpha-tocopherol; taurocholate; ferrets; protein; fat; HPLC; liver; plasma ID RETINOL-BINDING PROTEIN; SERUM VITAMIN-A; PREALBUMIN CONCENTRATIONS; CALORIE MALNUTRITION; RATS; ABSORPTION; SUPPLEMENTATION; BIOAVAILABILITY; CARBOHYDRATE; CONVERSION AB Dietary factors affecting tissue storage of beta-carotene (BC), alpha-tocopherol (alpha-T), and retinol (ROL) in mammals include taurocholate, protein, and fat. Few studies have examined the effects of these factors on the storage of BC, retinyl esters, and alpha-T in a mammalian system that is similar to humans. The main objective of the study was to investigate the effects of taurocholate (TC), fat, and protein on the absorption and metabolism of BC and alpha-T in ferret tissues. Three 4-week experiments were conducted using groups of 5-6 ferrets per treatment. All diets contained 0.2% BC. In Experiment 1, taurocholate was fed at concentrations of 0, 0.5, or 1%. Effects of two concentrations of dietary fat (6 and 23%) and three concentrations of protein (10, 20, and 40%) were also studied in Experiments 2 and 3, respectively. Tissues were analyzed for BC, retinoids, and alpha-T by high-pressure liquid chromatography (HPLC). Taurocholate enhanced hepatic and plasma concentrations of BC (2.3- to 3-fold), retinyl palmitate [(RP) 3.2- to 9.5-fold], retinyl stearate [(RS) 2.9- to 6- fold], and hepatic alpha-T (6- to 13-fold) at p < 0.05. High-fat diets elevated hepatic BC, RP, RS, and retinyl linoleate (RL) concentrations (2- to 3.6-fold, p < 0.05). In contrast, high-protein diets lowered hepatic RL 1.8-fold and alpha-T 8-fold (p < 0.05). Our results indicate the importance of taurocholate, fat, and protein in achieving adequate levels of vitamins A and E in mammals. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, Div Res & Appl Technol, Washington, DC 20204 USA. George Washington Univ, Vet Affairs Med Ctr, Ctr Med, Lipid Res Lab,ISIT, Washington, DC 20422 USA. RP Lakshman, MR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, Div Res & Appl Technol, Washington, DC 20204 USA. EM Raj.Lakshman@Med.VA.GOV FU NCI NIH HHS [R01 CA 82492] NR 37 TC 2 Z9 3 U1 1 U2 1 PU VERLAG HANS HUBER PI BERN 9 PA LANGGASS-STRASSE 76, CH-3000 BERN 9, SWITZERLAND SN 0300-9831 J9 INT J VITAM NUTR RES JI Int. J. Vitam. Nutr. Res. PD MAR PY 2005 VL 75 IS 2 BP 133 EP 141 DI 10.1021/0300-9831.74.2.133 PG 9 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 928EN UT WOS:000229254000006 PM 15929634 ER PT J AU Tournas, VH AF Tournas, VH TI Moulds and yeasts in fresh and minimally processed vegetables, and sprouts SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE moulds; yeasts; fresh vegetables; sprouts ID ESCHERICHIA-COLI; STRAINS; PLANTS AB A limited survey of fresh and minimally processed vegetables, and sprouts was conducted in the Washington, DC area to determine if potentially toxigenic and pathogenic fungi were present in these commodities. Thirty-nine ready-to-eat salads, 29 whole fresh vegetables and 116 sprout samples (bean, alfalfa, broccoli, crunchy, garlic, spicy, onion, clover, lentil and multi-seed sprouts) were purchased from 13 local supermarkets and tested for yeast and mould counts as well as the presence of toxigenic moulds. Yeasts were the most prevalent organisms found in these samples, at levels ranging from less than 100 to 4.0 x 10(8) cfu/g. Mould counts generally ranged from less than 100 to 4.0 x 10(4) cfu/g. Two crunchy sprout samples, however, contained unusually high numbers of Penicillium (1.1 x 10(8) and 1.3 x 10(8) cfu/g), two alfalfa sprout samples contained Geotrichum populations about 10(6) cfu/g, and two alfalfa sprout samples had Cladosporium counts higher than 2.5 x 10(5) cfu/g. The most common moulds found in fresh and minimally processed vegetables were Cladosporium, Alternaria and Penicillium; less common was Geotrichum. The most frequently isolated moulds from sprouts were Alternaria, Cladosporium, Penicillium, and Phoma. Phoma was especially common in alfalfa sprouts. Fusarium, Rhizopus, Mucor, and Geotrichum were isolated less often. Published by Elsevier B.V. C1 US FDA, Div Nat Prod, College Pk, MD 20740 USA. RP Tournas, VH (reprint author), US FDA, Div Nat Prod, 5100 Paitn Branch Pkwy, College Pk, MD 20740 USA. EM vtournas@cfsan.fda.gov NR 21 TC 50 Z9 58 U1 3 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD MAR 1 PY 2005 VL 99 IS 1 BP 71 EP 77 DI 10.1016/j.ijfoodmicro.2004.08.009 PG 7 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 902PY UT WOS:000227370200007 PM 15718030 ER PT J AU Davis, D Mackay, T Utian, W Grinspoon, S AF Davis, D Mackay, T Utian, W Grinspoon, S TI Topic VII: What is the role of hormonal menopausal therapy in HIV-infected and at-risk women? Effect of estrogen receptors (Reports from the FDA, NIH, ACOG, and NAMS) and the role of testosterone and bone density SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT Conference on Fertility Regulation and Systemic Hormones in HIV-infected and At-Risk Women CY JAN 13-15, 2003 CL McLean, VA SP NIH, Off AIDS Res, NICHD ID UP HERS-II; ESTROGEN/PROGESTIN REPLACEMENT; DISEASE OUTCOMES; HEART C1 US FDA, DHHS, Rockville, MD 20857 USA. RP Davis, D (reprint author), US FDA, DHHS, Rockville, MD 20857 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 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 MAR PY 2005 VL 38 SU 1 BP S45 EP S48 DI 10.1097/01.qai.0000167047.73428.47 PG 4 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 927YO UT WOS:000229238500027 PM 15867623 ER PT J AU Zheng, JH AF Zheng, JH TI Topic IV: Hormonal influence on treatment and the effect of treatments on contraceptive methods - Data from the United States Food and Drug Administration SO JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES LA English DT Article; Proceedings Paper CT Conference on Fertility Regulation and Systemic Hormones in HIV-infected and At-Risk Women CY JAN 13-15, 2003 CL McLean, VA SP NIH, Off AIDS Res, NICHD C1 US FDA, DHHS, Rockville, MD 20857 USA. RP Zheng, JH (reprint author), US FDA, DHHS, Rockville, MD 20857 USA. NR 16 TC 1 Z9 1 U1 0 U2 0 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 MAR PY 2005 VL 38 SU 1 BP S24 EP S26 DI 10.1097/01.qai.0000167035.48772.13 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 927YO UT WOS:000229238500018 PM 15867608 ER PT J AU Valdez, KE Cuneo, SP Gorden, PJ Turzillo, AM AF Valdez, KE Cuneo, SP Gorden, PJ Turzillo, AM TI The role of thecal androgen production in the regulation of estradiol biosynthesis by dominant bovine follicles during the first follicular wave SO JOURNAL OF ANIMAL SCIENCE LA English DT Article DE bovine; granulosa cells; ovary; steroidogenesis; theca interna ID HORMONAL-REGULATION; OVARIAN FOLLICLES; CELL-FUNCTION; EXPRESSION; AROMATASE; SELECTION; HEIFERS; ENZYMES; RNA AB The first wave of follicular development following ovulation in cattle is characterized by selection and growth of a large, estrogenic dominant follicle. After the follicle becomes morphologically dominant, concentrations of estradiol in its follicular fluid decrease abruptly. The purpose of this study was to determine whether this decrease in estrogen production is caused by an insufficient supply of androgen from theca interna or decreased aromatization of androgen precursor by granulosa cells. Dominant follicles were collected from Holstein heifers on d 4, 6, or 8 of the first follicular wave (n = 5/d). Amounts of 17 alpha-hydroxylase mRNA in theca interna were sevenfold higher (P < 0.01) on d 4 than on d 8. After 3 h in culture, secretion of androstenedione by theca interna collected on d 4 (236 +/- 44 pg/mu g of protein) tended to be lower (P = 0.055) compared with d 6 (517 +/- 162 pg/mu g protein) and was lower (P < 0.05) compared with d 8 (387 +/- 51 pg/mu g of protein). In granulosa cells, amounts of aromatase mRNA decreased (P < 0.05) on d 8 compared with d 6 but not d 4. In vitro secretion of estradiol was higher in granulosa cells collected on d 4 (3.5 +/- 0.8 ng/[10(5) cells x 3 h]) compared with d 6 (1.8 +/- 0.6 ng/[10(5) cells x 3 h]; P < 0.05) and tended to be higher on d 4 than on d 8 (2.2 +/- 0.2 ng/[10(5) cells x 3 h]; P = 0.058). We conclude that the decrease in estradiol production observed during atresia of the dominant follicle is not due to lack of androgen substrate for aromatization or downregulated expression of the aromatase gene, but may be the direct result of decreased activity of the aromatase enzyme within granulosa cells. C1 Univ Arizona, Dept Vet Sci & Microbiol, Tucson, AZ 85724 USA. Univ Arizona, Dept Physiol, Tucson, AZ 85724 USA. Univ Arizona, Dept Anim Sci, Tucson, AZ 85724 USA. Dairy Vet Serv, Chandler, AZ 85225 USA. RP Valdez, KE (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. EM adele.turzillo@fda.hhs.gov NR 19 TC 13 Z9 13 U1 1 U2 3 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PD MAR PY 2005 VL 83 IS 3 BP 597 EP 603 PG 7 WC Agriculture, Dairy & Animal Science SC Agriculture GA 019OL UT WOS:000235846500013 PM 15705756 ER PT J AU Altamirano, JC Gratz, SR Wolnik, KA AF Altamirano, JC Gratz, SR Wolnik, KA TI Investigation of pyrrolizidine alkaloids and their N-oxides in commercial comfrey-containing products and botanical materials by liquid chromatography electrospray ionization mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID OFFICINALE L; HERBAL TEAS; PLANTS; TOXICITY; DISEASE; LIVER AB Pyrrolizidine alkaloids (PAs) and their N-oxides are found in several plant families throughout the world. PAs are potentially toxic to the liver and/or lungs in humans and may cause acute liver failure, cirrhosis, pneumonitis, or pulmonary hypertension. PAs are also carcinogenic to animals, and they have been linked to the development of hepatocellular and skin squamous cell carcinomas as well as liver angiosarcomas. According to experimental studies, the quantity of PAs in some herbal teas and dietary supplements is sufficient to be carcinogenic in exposed individuals. A method for the extraction and identification of PAs and their N-oxides in botanical materials and commercial comfrey-containing products has been developed using liquid chromatography electrospray ionization mass spectrometry. Following optimization of the extraction procedure and the chromatographic conditions, the method was applied to the analysis of 10 herbal remedies. All of the products that were labeled to contain comfrey were found to contain measurable quantities of PAs. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Gratz, SR (reprint author), US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. EM sgratz@ora.fda.gov NR 29 TC 12 Z9 12 U1 4 U2 13 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 MAR-APR PY 2005 VL 88 IS 2 BP 406 EP 412 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 911KH UT WOS:000228000600005 PM 15859063 ER PT J AU Rupp, HS Anderson, CR AF Rupp, HS Anderson, CR TI Determination of oxytetracycline in salmon by liquid chromatography with metal-chelate fluorescence detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TETRACYCLINE ANTIBIOTICS; CHLORTETRACYCLINE; EXTRACTION; RESIDUES; TISSUES; MUSCLE; MILK AB A liquid chromatography (LC) method is described for the determination of oxytetracycline (OTC) in farmed Atlantic salmon muscle tissue. The method involves homogenization of salmon tissue, extraction of OTC into Mcllvaine-EDTA buffer, acid precipitation of proteins, cleanup through tandem solid-phase extraction cartridges (Strata-X and aminopropyl), elution with mobile phase containing slightly alkaline buffer and Mg2+, and LC separation with metal-chelate induced fluorescence detection. Salmon tissue was fortified with 0.10, 0.25, 0.50, 0.75, and 1.0 mu g/g (ppm) oxytetracycline. Average absolute recoveries were 84, 76, 70, 76, and 85%, respectively, with relative standard deviation (RSD) values all less than 9%. The interassay average recovery was 78%, with a 4.2% RSD. Determination was based on a standard graph using peak areas with standard solutions equivalent to 0.0625, 0.125, 0.25, 0.50, and 1.0 ppm in tissue. A set of 5 matrix controls (unfortified salmon tissue) were also analyzed, in which no OTC was detected. The lowest standard was used as the limit of quantitation. C1 US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, Bothell, WA 98021 USA. RP Rupp, HS (reprint author), US FDA, Seafood Prod Res Ctr, Pacific Reg Lab NW, 23rd Dr SE, Bothell, WA 98021 USA. EM heidi.rupp@fda.gov NR 20 TC 12 Z9 12 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 MAR-APR PY 2005 VL 88 IS 2 BP 505 EP 510 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 911KH UT WOS:000228000600020 PM 15859078 ER PT J AU Chou, HJ AF Chou, HJ TI Determination of diethanolamine in shampoo products containing fatty acid diethanolamides by liquid chromatography with a thermal energy analyzer SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID N-NITROSODIETHANOLAMINE; ALKANOLAMINES; COSMETICS AB A liquid chromatography (LC) method using a thermal energy analyzer (TEA) is described for the determination of diethanolamine (DEA) in shampoo products containing fatty acid diethanolamides. DEA was converted to N-nitrosodiethanolamine (NDELA) by dissolving a portion of the product in 6M acetic acid and mixing with sodium nitrite for 1 h at room temperature. The reaction mixture was dried, dissolved in acetone, and analyzed for NDELA by LC-TEA. The recovery of DEA from 2 shampoo products at fortification levels of 25, 250, and 1000 ppm ranged from 70 to 105%. Twenty shampoo products were analyzed by this method, and 19 were found to contain DEA at levels ranging from 140 to 15 200 ppm. C1 US FDA, College Pk, MD 20740 USA. RP Chou, HJ (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM hchou@cfsan.fda.gov NR 14 TC 3 Z9 3 U1 1 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2005 VL 88 IS 2 BP 592 EP 594 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 911KH UT WOS:000228000600030 PM 15859088 ER PT J AU Croinin, T Grippe, VK Merkel, TJ AF Croinin, T Grippe, VK Merkel, TJ TI Activation of the vrg6 promoter of Bordetella pertussis by RisA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID VIR-REPRESSED GENES; VIRULENCE FACTORS; RNA-POLYMERASE; FHA PROMOTER; BINDING; BVGA; IDENTIFICATION; SEQUENCES; TOXIN; LOCUS AB The BvgAS two-component system positively regulates the expression of the virulence genes of Bordetella pertussis and negatively regulates a second set of genes whose function is unknown. The BvgAS-mediated regulation of the bvg-repressed genes is accomplished through the activation of expression of the negative regulator, BvgR. A second two-component regulatory system, RisAS, is required for expression of the bvg-repressed surface antigens VraA and VraB. We examined the roles of BvgR and RisA in the regulation of four bvg-repressed genes in B. pertussis. Our analyses demonstrated that all four genes are repressed by the product of the bvgR locus and are activated by the product of the risA locus. Deletion analysis of the vrg6 promoter identified the upstream and downstream boundaries of the promoter and, in contrast to previously published results, demonstrated that sequences downstream of the start of transcription are not required for the regulation of expression of vrg6. Gel mobility-shift experiments demonstrated sequence-specific binding of RisA to the vrg6 and vrg18 promoters, and led to the identification of two putative RisA binding sites. Finally, transcriptional analysis and Western blot analysis demonstrated that BvgR regulates neither the expression nor the stability of RisA. C1 US FDA, CBER, DBPAP, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), US FDA, CBER, DBPAP, Lab Resp & Special Pathogens, Bldg 29,Rm 418,8800 Rockeville Pike, Bethesda, MD 20892 USA. EM merkel@cber.fda.gov RI O Croinin, Tadhg/B-8503-2008 NR 40 TC 7 Z9 7 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2005 VL 187 IS 5 BP 1648 EP 1658 DI 10.1128/JB.187.5.1648-1658.2005 PG 11 WC Microbiology SC Microbiology GA 900BY UT WOS:000227191600012 PM 15716435 ER PT J AU Schnackenberg, LK Beger, RD AF Schnackenberg, LK Beger, RD TI Whole-molecule calculation of Log P based on molar volume, hydrogen bonds, and simulated C-13 NMR spectra SO JOURNAL OF CHEMICAL INFORMATION AND MODELING LA English DT Article ID WATER PARTITION-COEFFICIENTS; RELATIONSHIP QSDAR MODELS; PARAMETER; CHROMATOGRAPHY; SOLUBILITY; SOLVATION; CONSTANTS; BINDING; P(OCT) AB The prediction of Log P is usually accomplished using either substructure or whole-molecule approaches. However, these methods are complicated, and previous whole-molecule approaches have not been successful for the prediction of Log P in very complex molecules. The observed chemical shifts in nuclear magnetic resonance (NMR) spectroscopy are related to the electrostatics at the nucleus, which are influenced by solute-solvent interactions. The different solvation effects on a molecule by either water or methanol have a strong effect on the NMR chemical shift value. Therefore, the chemical shift values observed in an aqueous and organic solvent should correlate to Log P. This paper develops a rapid, objective model of Log P based on molar volume, hydrogen bonds, and differences in calculated C-13 NMR chemical shifts for a diverse set of compounds. A partial least squares (PLS) model of Log P built on the sum of carbon chemical shift differences in water and methanol, molar volume, number of hydrogen bond donors and acceptors in 162 diverse compounds gave an r(2) value of 0.88. The average r(2) for 10 training models of Log P made from 90% of the data was 0.87 +/- 0.01. The average q(2) for 10 leave-10%-out cross-validation test sets was 0.87 +/- 0.05. C1 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. EM rbeger@nctr.fda.gov NR 28 TC 10 Z9 12 U1 2 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1549-9596 J9 J CHEM INF MODEL JI J. Chem Inf. Model. PD MAR-APR PY 2005 VL 45 IS 2 BP 360 EP 365 DI 10.1021/ci049643e PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Computer Science, Information Systems; Computer Science, Interdisciplinary Applications SC Pharmacology & Pharmacy; Chemistry; Computer Science GA 911PZ UT WOS:000228018000020 PM 15807500 ER PT J AU Bishop, SC McCord, BR Gratz, SR Loeliger, JR Witkowski, MR AF Bishop, SC McCord, BR Gratz, SR Loeliger, JR Witkowski, MR TI Simultaneous separation of different types of amphetamine and piperazine designer drugs by capillary electrophoresis with a chiral selector SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; capillary electrophoresis; benzylpiperazines; amphetamines; chiral separation ID MCPP; METHAMPHETAMINE; URINE; BLOOD; MDMA; SPECTROMETRY; CYCLODEXTRIN; METABOLITE; TRAZODONE; PLASMA AB The recent emergence of a new class of piperazine-type compounds has brought about the need for laboratory screening methods for both seized drugs and toxicological samples. These piperazine compounds, which include 1-benzylpiperazine (BZP) and 1-(3-trifluoromethylphenyl)piperazine (TFMPP), exhibit comparable physiological effects and can be substituted for the classic amphetamine-type drugs. We have optimized a chiral capillary electrophoresis (CE) separation that detects a set of 6 piperazine and 4 chiral amphetamine compounds in under 23 min using a 200 mM phosphate buffer at a pH = 2.8 with 20 mM hydroxypropyl-beta-cyclodextrin (HPbetaCD). In addition to the above compounds, a series of "clandestine" BZP diHCl samples were also analyzed using this method to assess the ruggedness of the procedure. The novel CE separation was tailored to simultaneously detect these piperzine compounds in addition to amphetamine-type drugs. Distinct migration time and UV-spectral data were obtained for all compounds of interest. C1 Florida Int Univ, Dept Chem, Int Forens Res Inst, Miami, FL 33199 USA. Ohio Univ, Dept Chem & Biochem, Clippinger Labs 136, Athens, OH 45701 USA. US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP McCord, BR (reprint author), Florida Int Univ, Dept Chem, Int Forens Res Inst, Univ Pk, Miami, FL 33199 USA. NR 30 TC 8 Z9 9 U1 0 U2 2 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAR PY 2005 VL 50 IS 2 BP 326 EP 335 PG 10 WC Medicine, Legal SC Legal Medicine GA 904II UT WOS:000227488900009 PM 15813543 ER PT J AU Zhao, XX Xu, B Bhattacharjee, A Oldfield, CM Wientjes, FB Feldman, GM Cathcart, MK AF Zhao, XX Xu, B Bhattacharjee, A Oldfield, CM Wientjes, FB Feldman, GM Cathcart, MK TI Protein kinase C delta regulates p67phox phosphorylation in human monocytes SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE PKC delta; NADPH oxidase; superoxide anion; inflammation ID LOW-DENSITY-LIPOPROTEIN; ACTIVATED HUMAN MONOCYTES; CHRONIC GRANULOMATOUS-DISEASE; OXIDASE COMPONENT P67(PHOX); SUPEROXIDE ANION PRODUCTION; NEUTROPHIL NADPH OXIDASE; LIPID OXIDATION; GENE-EXPRESSION; P47(PHOX); TRANSLOCATION AB Phosphorylation of the reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase components p67phox and p47phox accompanies the assembly and activation of this enzyme complex. We have previously reported that activation of human monocytes with opsonized zymosan (ZOP), a potent stimulator of NADPH oxidase activity, results in the phosphorylation of p67phox and p47phox. In this study, we investigated the regulation of p67phox phosphorylation. Although protein kinase C (PKC)alpha has previously been shown to regulate NADPH oxidase activity, we found that inhibition of PKCalpha had no effect on p67phox phosphorylation. Our studies demonstrate that pretreatment of monocytes with antisense oligodeoxyribonucleotides specific for PKCdelta or rottlerin, a selective inhibitor for PKCdelta, inhibited the phosphorylation of p67phox in monocytes, and Go6976, a specific inhibitor for conventional PKCs, PKCalpha and PKCbeta, had no such inhibitory effect. Additional studies indicate that ZOP stimulation of monocytes induces PKCdelta and p67phox to form a complex. We also demonstrate that lysates from activated monocytes as well as PKCdelta immunoprecipitates from activated monocytes can phosphorylate p67phox in vitro and that pretreatment of monocytes with rottlerin blocked the phosphorylation in each case. We further show that recombinant PKCdelta can phosphorylate p67phox in vitro. Finally, we show that PKCdelta-deficient monocytes produce significantly less superoxide anion in response to ZOP stimulation, thus emphasizing the functional significance of the PKCdelta regulation of p67phox phosphorylation. Taken together, this is the first report to describe the requirement of PKCdelta in regulating the phosphorylation of p67phox and the related NADPH oxidase activity in primary human monocytes. C1 Cleveland Clin Fdn, Dept Cell Biol, Lerner Res Inst, Cleveland, OH 44195 USA. UCL, Dept Med, London, England. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Off Therapeut Res & Review, Bethesda, MD USA. RP Cathcart, MK (reprint author), Cleveland Clin Fdn, Dept Cell Biol, Lerner Res Inst, 9500 Euclid Ave, Cleveland, OH 44195 USA. EM cathcam@ccf.org FU NHLBI NIH HHS [HL 61971, HL 51068] NR 35 TC 47 Z9 49 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PD MAR PY 2005 VL 77 IS 3 BP 414 EP 420 DI 10.1189/jlb.0504284 PG 7 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 904IF UT WOS:000227488600017 PM 15591124 ER PT J AU Baggett, S Protiva, P Mazzola, EP Yang, H Ressler, ET Basile, MJ Weinstein, IB Kennelly, EJ AF Baggett, S Protiva, P Mazzola, EP Yang, H Ressler, ET Basile, MJ Weinstein, IB Kennelly, EJ TI Bioactive benzophenones from Garcinia xanthochymus fruits SO JOURNAL OF NATURAL PRODUCTS LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; INHIBITORY NATURAL-PRODUCTS; SPICATA HOOK F; POLYISOPRENYLATED BENZOPHENONES; PRENYLATED XANTHONES; C-H; BIFLAVONOIDS; DERIVATIVES; GUTTIFERAE; CONSTITUTION AB A MeOH extract of Garcinia xanthochymus fruits was subjected to activity-guided fractionation, yielding two new benzophenones, guttiferone H (1) and gambogenone (2). Compound 1 contains a seven-membered ring attached to the bicyclo[3.3.1]nonane system at positions 7 and 8 and displayed cytotoxicity in the SW-480 colon cancer cell line (IC50 = 12 mu M). Compound 2 has a novel benzophenone bicyclo [3.3.2] decane system and displayed cytotoxicity in the SW-480 colon cancer cell line (IC50 = 188,mu M). Both 1 and 2 induced apoptosis in SW-480 colon cancer cells and displayed antioxidant activity in the 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay (IC50 = 64 and 38.7 mu M, respectively). The structures of 1 and 2 were established by 1D and 2D NMR data analysis. Eleven known compounds, aristophenone A, alloathyriol, amentoflavone, 3,8"-biapigenin, cycloxanthochymol, (+/-)-fukugetin, (+/-)-fukugiside, guttiferone E, isoxanthochymol, (+/-)-volkensiflavone, and xanthochymol, were also obtained. The 11 known compounds were also tested against SW-480 colon cancer cells and in the DPPH assay. C1 CUNY, Lehman Coll, Dept Sci Biol, Bronx, NY 10468 USA. CUNY, Grad Sch, Bronx, NY 10468 USA. CUNY, Univ Ctr, Bronx, NY 10468 USA. Columbia Univ, Ctr Med, Dept Med, New York, NY 10032 USA. Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Chem & Biochem, College Pk, MD 20742 USA. Univ Miami, Sch Med, Dept Neurol, Miami, FL 33136 USA. RP Kennelly, EJ (reprint author), CUNY, Lehman Coll, Dept Sci Biol, 250 Bedford Pk Blvd W, Bronx, NY 10468 USA. EM Edward.Kennelly@lehman.cuny.edu FU NCCIH NIH HHS [F31-AT00062]; NIGMS NIH HHS [GM 27029, S06GM08225] NR 44 TC 82 Z9 86 U1 3 U2 22 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0163-3864 J9 J NAT PROD JI J. Nat. Prod. PD MAR PY 2005 VL 68 IS 3 BP 354 EP 360 DI 10.1021/np0759579 PG 7 WC Plant Sciences; Chemistry, Medicinal; Pharmacology & Pharmacy SC Plant Sciences; Pharmacology & Pharmacy GA 910JP UT WOS:000227927700009 PM 15787435 ER PT J AU Saviola, J AF Saviola, James TI The FDA's role in medical device clinical studies of human subjects SO JOURNAL OF NEURAL ENGINEERING LA English DT Article AB This paper provides an overview of the United States Food and Drug Administration's (FDA) role as a regulatory agency in medical device clinical studies involving human subjects. The FDA's regulations and responsibilities are explained and the device application process discussed. The specific medical device regulatory authorities are described as they apply to the development and clinical study of retinal visual prosthetic devices. The FDA medical device regulations regarding clinical studies of human subjects are intended to safeguard the rights and safety of subjects. The data gathered in pre-approval clinical studies provide a basis of valid scientific evidence in order to demonstrate the safety and effectiveness of a medical device. The importance of a working understanding of applicable medical device regulations from the beginning of the device development project is emphasized particularly for novel, complex products such as implantable visual prosthetic devices. C1 [Saviola, James] US FDA, Vitreoretinal & Extraocular Devices Branch, Div Ophthalm & ENT Devices, Off Device Evaluat, Rockville, MD 20857 USA. RP Saviola, J (reprint author), US FDA, Vitreoretinal & Extraocular Devices Branch, Div Ophthalm & ENT Devices, Off Device Evaluat, Rockville, MD 20857 USA. NR 0 TC 8 Z9 8 U1 0 U2 1 PU IOP PUBLISHING LTD PI BRISTOL PA TEMPLE CIRCUS, TEMPLE WAY, BRISTOL BS1 6BE, ENGLAND SN 1741-2560 EI 1741-2552 J9 J NEURAL ENG JI J. Neural Eng. PD MAR PY 2005 VL 2 IS 1 SI SI BP S1 EP S4 DI 10.1088/1741-2560/2/1/001 PG 4 WC Engineering, Biomedical; Neurosciences SC Engineering; Neurosciences & Neurology GA V43HJ UT WOS:000209672200001 PM 15876645 ER PT J AU Han, J Yang, LM Puri, RK AF Han, J Yang, LM Puri, RK TI Analysis of target genes induced by IL-13 cytotoxin in human glioblastoma cells SO JOURNAL OF NEURO-ONCOLOGY LA English DT Article DE cDNA microarray; gene expression profiles; IL-13 cytotoxin; IL-13R alpha 2 receptor ID INTERLEUKIN-13 RECEPTOR-ALPHA; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; THYMIDYLATE SYNTHASE; EXPRESSION PROFILES; SIGNAL-TRANSDUCTION; CYTOKINE RECEPTOR; MALIGNANT GLIOMAS; FUSION CYTOTOXIN; CARCINOMA-CELLS AB IL-13 cytotoxin comprised of IL-13 and a mutated form of Pseudomonas exotoxin (fusion protein termed IL-13-PE38QQR) has been shown to inhibit protein synthesis leading to necrotic and apoptotic cell death in glioblastoma cells that express high levels of interleukin-13 receptors (IL-13R). To identify target genes of cell death and other cellular genes with IL-13 receptors in glioblastoma cells, we utilized the cDNA microarrays to analyze global gene expression profiles after IL-13 cytotoxin and IL-13 treatment. IL-13 cytotoxin mediated cytotoxicity to U251 cells in a dose-dependant manner. Hierarchical cluster analysis of differentially expressed genes in U251 glioma cells at different time points after IL-13 cytotoxin treatment showed three major groups, each representing a specific expression pattern. Randomly selected differentially expressed genes from each group were confirmed by RT-PCR analysis. Most down-regulated genes belong to cell adhesion, motility, angiogenesis, DNA repair, and metabolic pathways. While up-regulated genes belong to cell cycle arrest, apoptosis, signaling and various metabolic pathways. Unexpectedly, at early time points, both IL-13 and IL-13 cytotoxin induced several genes belonging to different pathways most notably IL-8, DIO2, END1, and ALDH1A3 indicating that these genes are early response genes and their products may be associated with IL-13R. In addition, IL-13 cytotoxin induced IL-13R alpha 2 mRNA expression during the treatment in glioma cells. Our results indicate that novel cellular genes are involved with IL-13 receptors and that IL-13 cytotoxin induced cell death involves various target genes in human glioblastoma cells. On going studies will determine the role of associated genes and their products in the IL-13R functions in glioma cells. C1 NIH, CBER, FDA, Ctr Informat Technol,Bioinformat & Mol Anal Sect, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, CBER,NCI Genom Program,Div Cellular & Gene Therap, Bethesda, MD USA. RP Puri, RK (reprint author), NIH, CBER, FDA, Ctr Informat Technol,Bioinformat & Mol Anal Sect, Bldg 29B,Rm 2NN10,29 Lincoln Dr, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 60 TC 9 Z9 11 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-594X J9 J NEURO-ONCOL JI J. Neuro-Oncol. PD MAR PY 2005 VL 72 IS 1 BP 35 EP 46 DI 10.1007/s11060-004-3119-7 PG 12 WC Oncology; Clinical Neurology SC Oncology; Neurosciences & Neurology GA 914BW UT WOS:000228200600006 PM 15803373 ER PT J AU Gaigalas, AK Wang, LL Schwartz, A Marti, GE Vogt, RF AF Gaigalas, AK Wang, LL Schwartz, A Marti, GE Vogt, RF TI Quantitating fluorescence intensity from fluorophore: Assignment of MESF values SO JOURNAL OF RESEARCH OF THE NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY LA English DT Article DE cytometry; FITC; fluorescein; fluorescence yield; MESF; microspheres AB A procedure is presented to convert the comparison of measured fluorescence signals into a comparison of fluorescence yields (FY). The fluorescence yield, which is a property of a solution or a suspension, is defined as the product of the fluorophore concentration and the molecular quantum yield. The paper revises the measurement model which relates the measured fluorescence signal to the FY. The equality of FY of two solutions provides an equivalence between the concentrations of fluorophore in the two solutions. The equivalence is the basis for quantitation in terms of molecules of equivalent soluble fluorophore (MESF). The quantitation procedure starts with the measurement of fluorescence signals from a serial dilution of fluorescein solutions to obtain a calibration of a fluorometer. The fluorometer is used to measure the fluorescence signal of a suspension of microspheres with immobilized fluorescein isothiocyanate (FITC). The calibration is used to obtain the concentration of soluble fluorophores which gives the same fluorescence signal as the microsphere suspension. The number concentration of microspheres is measured and the equality of fluorescence yields is used to obtain the number of soluble fluorescein molecules equivalent to a single microsphere. C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Ctr Quantitat Cytometry, San Juan, PR 00919 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. CDC, Div Sci Lab, Atlanta, GA 30341 USA. RP Gaigalas, AK (reprint author), Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. EM adolfas.gaigalas@nist.gov NR 8 TC 17 Z9 18 U1 0 U2 8 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 1044-677X J9 J RES NATL INST STAN JI J. Res. Natl. Inst. Stand. Technol. PD MAR-APR PY 2005 VL 110 IS 2 BP 101 EP 114 DI 10.6028/jres.110.010 PG 14 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 918CY UT WOS:000228518100003 PM 27308107 ER PT J AU Brown, L Li, XF AF Brown, L Li, XF TI Confidence intervals for two sample binomial distribution SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE confidence intervals; binomial distribution; two-sample problem; Wald interval; Newcombe's interval; Jeffrey's prior ID CONTINGENCY-TABLES; PROPORTIONS; DIFFERENCE AB This paper considers confidence intervals for the difference of two binomial proportions. Some currently used approaches are discussed. A new approach is proposed. Under several generally used criteria, these approaches are thoroughly compared. The widely used Wald confidence interval] (CI) is far from satisfactory, while the Newcombe's Cl, new recentered CI and score CI have very good performance. Recommendations for which approach is applicable under different situations are given. (C) 2004 Elsevier B.V. All rights reserved. C1 Univ Penn, Wharton Sch, Dept Stat, Philadelphia, PA 19104 USA. US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20850 USA. RP Brown, L (reprint author), Univ Penn, Wharton Sch, Dept Stat, 3730 Walnut St, Philadelphia, PA 19104 USA. EM lbrown@wharton.upenn.edu NR 22 TC 34 Z9 35 U1 2 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD MAR 1 PY 2005 VL 130 IS 1-2 BP 359 EP 375 DI 10.1016/j.jspi.2003.09.039 PG 17 WC Statistics & Probability SC Mathematics GA 892IZ UT WOS:000226645200023 ER PT J AU Lugovtsev, VY Vodeiko, GM Strupczewski, CM Levandowski, RA AF Lugovtsev, VY Vodeiko, GM Strupczewski, CM Levandowski, RA TI Simple and rapid strategy for genetic characterization of influenza B virus reassortants SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE influenza; reassortment; genotyping; SSCP ID STRAND CONFORMATION POLYMORPHISM; POLYMERASE CHAIN-REACTION; GENOME COMPOSITION; A VIRUSES; PCR-SSCP; RT-PCR; RESTRICTION; MUTATIONS; STRAINS; DNA AB Genetic reassortment of influenza viruses is widely used for creating viruses with specific phenotypes. Reassortment of two influenza viruses, each with eight RNA segments potentially yields as many as 256 gene segment combinations. Therefore, confirmation that progeny viruses possess genomes corresponding to the specified phenotypes can be laborious and time-consuming. To establish a convenient method for genotyping influenza virus reassortants, we adapted single-strand conformation polymorphism analysis (SSCP) using standard laboratory equipment. By varying the concentration of polyacrylamide between 4-6% and the concentration of glycerol between 5-8% in the gel, together with adding PCR primers to the DNA sample during the denaturing step, optimal conditions can be found for SSCP with little effort. The described method has high accuracy and reliability, and provides a tool for rapid, cost-effective genetic screening and assessment of the purity and genetic stability of the reassortant viruses. This method should be useful in basic research applications and in preparing reassortant viruses for vaccine use. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Lugovtsev, VY (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM Lugovtsev@cber.fda.gov NR 32 TC 9 Z9 9 U1 0 U2 1 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 MAR PY 2005 VL 124 IS 1-2 BP 203 EP 210 DI 10.1016/j.jviromet.2004.11.024 PG 8 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 895SH UT WOS:000226883100027 PM 15664070 ER PT J AU Feigelstock, DA Thompson, P Kaplan, GG AF Feigelstock, DA Thompson, P Kaplan, GG TI Growth of hepatitis A virus in a mouse liver cell line SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSGENIC MICE; RICH REGION; IDENTIFICATION; PREVALENCE; EXPRESSION; ANTIBODIES; INFECTION; RECEPTOR; DISEASE; CULTURE AB Hepatitis A virus (HAV) has been adapted to grow efficiently in primate and some nonprimate cell lines but not in cells of murine origin. To understand the inability of the virus to grow in mouse cells, we studied the replication of HAV in immortalized and nontransformed MMH-D3 mouse liver cells, which require growth factors and collagen to maintain their phenotype. HAV grew in MMH-D3 cells transfected with virion RNA but not in those infected with viral particles, indicating a cell entry block for HAV. However, MMH-D3 cells cultured under suboptimal conditions in the absence of growth factors acquired susceptibility to HAV infection. Serial passages of the virus in MMH-D3 cells under suboptimal growth conditions resulted in the selection of HAV variants that grew efficiently in MMH-D3 cells cultured under both optimal and suboptimal conditions. Nucleotide sequence analysis of the MMH-D3 cell-adapted HAV revealed that N1237D and D2132G substitutions were present in the capsid regions of six viral clones. These two mutations are most likely located on the surface of the virion and may play a role in the entry of HAV into the mouse liver cells. Our results demonstrate that mouse hepatocyte-like cells code for all factors required for the efficient growth of HAV in cell culture. C1 US FDA, Ctr Biol Evaluat & Res, Hepatatis Lab, Bethesda, MD 20852 USA. RP Kaplan, GG (reprint author), US FDA, Ctr Biol Evaluat & Res, Hepatatis Lab, Bethesda, MD 20852 USA. EM GK@helix.nih.gov NR 38 TC 9 Z9 9 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAR PY 2005 VL 79 IS 5 BP 2950 EP 2955 DI 10.1128/JVI.79.5.2950-2955.2005 PG 6 WC Virology SC Virology GA 898TF UT WOS:000227098400031 PM 15709014 ER PT J AU Byrnes, KR Waynant, RW Ilev, IK Wu, XJ Barna, L Smith, K Heckert, R Gerst, H Anders, JJ AF Byrnes, KR Waynant, RW Ilev, IK Wu, XJ Barna, L Smith, K Heckert, R Gerst, H Anders, JJ TI Light promotes regeneration and functional recovery and alters the immune response after spinal cord injury SO LASERS IN SURGERY AND MEDICINE LA English DT Review DE astrocytes; corticospinal tract; footprint analysis; low power laser irradiation; macrophage; microglia; photobiomodulation; rat; retrograde and anterograde tract tracing ID AXOTOMIZED RUBROSPINAL NEURONS; MYELIN-ASSOCIATED INHIBITORS; OLFACTORY ENSHEATHING CELLS; NEURITE GROWTH-INHIBITORS; CHEMOKINE MESSENGER-RNA; POWER LASER IRRADIATION; RAT-LIVER MITOCHONDRIA; CENTRAL-NERVOUS-SYSTEM; ADULT-RAT; CORTICOSPINAL TRACT AB Background and Objectives: Photobiomodulation (PBM) has been proposed as a potential therapy for spinal cord injury (SCI). We aimed to demonstrate that 810 nm light can penetrate deep into the body and promote neuronal regeneration and functional recovery. Study Design/Materials and Methods: Adult rats underwent a T9 dorsal hemisection, followed by treatment with an 810 nm, 150 mW diode laser (dosage = 1,589 J/cm(2)). Axonal regeneration and functional recovery were assessed using single and double label tract tracing and various locomotor tasks. The immune response within the spinal cord was also assessed. Results: PBM, with 6% power penetration to the spinal cord depth, significantly increased axonal number and distance of regrowth (P < 0.001). PBM also returned aspects of function to baseline levels and significantly suppressed immune cell activation and cytokine/chemokine expression. Conclusion: Our results demonstrate that light, delivered transcutaneously, improves recovery after injury and suggests that light will be a useful treatment for human SCI. C1 Uniformed Serv Univ Hlth Sci, Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. US FDA, Ctr Devices & Radiol Hlth, ElectroOpt Branch, Rockville, MD 20857 USA. RP Byrnes, KR (reprint author), Georgetown Univ, Dept Neurosci, Room EP16A,3970 Reservoir Rd NW, Washington, DC 20057 USA. EM krb27@georgetown.edu OI Byrnes, Kimberly/0000-0002-7501-7734 NR 104 TC 137 Z9 144 U1 2 U2 11 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. PD MAR PY 2005 VL 36 IS 3 BP 171 EP 185 DI 10.1002/lsm.20143 PG 15 WC Dermatology; Surgery SC Dermatology; Surgery GA 911AE UT WOS:000227972600001 PM 15704098 ER PT J AU Amat, A Rigau, J Waynant, RW Ilev, IK Anders, JJ AF Amat, A Rigau, J Waynant, RW Ilev, IK Anders, JJ TI Electromagnetic interaction between laser light and ATP: A non-absorptive mechanism SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Univ Rovira & Virgili, Reus, Spain. US FDA, Rockville, MD 20857 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 26 BP 10 EP 10 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000027 ER PT J AU Byrnes, KR Wu, XJ Waynant, RW Ilev, IK Anders, JJ AF Byrnes, KR Wu, XJ Waynant, RW Ilev, IK Anders, JJ TI Low power laser irradiation alters gene expression of olfactory ensheathing cells in vitro SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 Georgetown Univ, Washington, DC USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 179 BP 54 EP 54 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000167 ER PT J AU Romanczyk, TB Eisenbeiss, R Graning, R Amat, A Longo, L Waynant, R Ilev, I Anders, JJ AF Romanczyk, TB Eisenbeiss, R Graning, R Amat, A Longo, L Waynant, R Ilev, I Anders, JJ TI Light as a re-placement for mitogenic factors on progenitor cells SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 USUHS, Neurosci Program, Bethesda, MD USA. Villa Julie Coll, Stevenson, MD USA. USUHS, Sch Med, Bethesda, MD USA. USUHS, APG, Bethesda, MD USA. Univ Siena, I-53100 Siena, Italy. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 181 BP 55 EP 55 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000169 ER PT J AU Waynant, RW Ilev, I Amat, A AF Waynant, RW Ilev, I Amat, A TI Laser therapy - Still a lot of explaining to do SO LASERS IN SURGERY AND MEDICINE LA English DT Meeting Abstract CT 25th Annual Meeting of the American-Society-for-Laser-Medicine-and-Surgery CY MAR 30-APR 03, 2005 CL Buena Vista, FL SP Amer Soc Laser Med & Surg C1 US FDA, Div Phys, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0196-8092 J9 LASER SURG MED JI Lasers Surg. Med. PD MAR PY 2005 SU 17 MA 183 BP 56 EP 56 PG 1 WC Dermatology; Surgery SC Dermatology; Surgery GA 912GQ UT WOS:000228066000171 ER PT J AU Thomas, JA Chakrabarti, K Kaczmarek, R Romanyukha, A AF Thomas, JA Chakrabarti, K Kaczmarek, R Romanyukha, A TI Contrast-detail phantom scoring methodology SO MEDICAL PHYSICS LA English DT Article DE digital mammography; contrast-detail phantom; image quality control ID DIGITAL MAMMOGRAPHY SYSTEM; SCREEN-FILM MAMMOGRAPHY; IMAGE QUALITY; OPTIMIZATION AB Published results of medical imaging studies which make use of contrast detail mammography (CDMAM) phantom images for analysis are difficult to compare since data are often not analyzed in the same way. In order to address this situation, the concept of ideal contrast detail curves is suggested. The ideal contrast detail curves are constructed based on the requirement of having the same product of the diameter and contrast (disk thickness) of the minimal correctly determined object for every row of the CDMAM phantom image. A correlation and comparison of five different quality parameters of the CDMAM phantom image determined for obtained ideal contrast detail curves is performed. The image quality parameters compared include: (1) contrast detail curve-a graph correlation between "minimal correct reading" diameter and disk thickness; (2) correct observation ratio-the ratio of the number of correctly identified objects to the actual total number of objects multiplied by 100; (3) image quality figure-the sum of the product of the diameter of the smallest scored object and its relative contrast; (4) figure-of-merit-the zero disk diameter value obtained from extrapolation of the contrast detail curve to the origin (e.g., zero disk diameter); and (5) k-factor-the product of the thickness and the diameter of the smallest correctly identified disks. The analysis carried out showed the existence of a nonlinear relationship between the above parameters, which means that use of different parameters of CDMAM image quality potentially can cause different conclusions about changes in image quality. Construction of the ideal contrast detail curves for CDMAM phantom is an attempt to determine the quantitative limits of the CDMAM phantom as employed for image quality evaluation. These limits are determined by the relationship between certain parameters of a digital mammography system and the set of the gold disks sizes in the CDMAM phantom. Recommendations are made on selections of CDMAM phantom regions which should be used for scoring at different image quality and which scoring methodology may be most appropriate. Special attention is also paid to the use of the CDMAM phantom for image quality assessment of digital mammography systems particularly in the vicinity of the Nyquist frequency. (c) 2005 American Association of Physicists in Medicine. C1 Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, Bethesda, MD 20879 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Thomas, JA (reprint author), Uniformed Serv Univ Hlth Sci, Dept Radiol & Radiol Sci, 4301 Jones Bridge Rd, Bethesda, MD 20879 USA. EM aromanyukha@usuhs.mil NR 17 TC 26 Z9 26 U1 0 U2 3 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD MAR PY 2005 VL 32 IS 3 BP 807 EP 814 DI 10.1118/1.1862097 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 910DN UT WOS:000227910600018 PM 15839353 ER PT J AU Schnackenberg, L Beger, RD Dragan, Y AF Schnackenberg, Laura Beger, Richard D. Dragan, Yvonne TI NMR-based metabonomic evaluation of livers from rats chronically treated with tamoxifen, mestranol, and phenobarbital SO METABOLOMICS LA English DT Article DE tamoxifen; mestranol; phenobarbital; metabonomics; metabolomics AB In this study, we look at the metabolic effects of long-term dosing with tamoxifen, mestranol or phenobarbital on the liver. Tamoxifen, mestranol and phenobarbital have all been reported to act as promoters of hepatic tumors. While tamoxifen and mestranol are known to have estrogenic activity, in the liver phenobarbital is a non-estrogenic compound. Aqueous and lipophilic liver extracts from control and chronically treated Fisher 344 rats were evaluated by nuclear magnetic resonance spectroscopy (NMR). In both the aqueous and lipophilic sample sets, the estrogenic action of mestranol appears to be responsible for the clustering of these samples with those animals treated with tamoxifen. Phenobarbital does not have estrogenic activity and, therefore, clusters away from the estrogenic and control groups. In the lipophilic samples, the fatty acid peak (CH2)(n) was higher in tamoxifen-treated rats than in control, phenobarbital- or mestranol-treated rats. In the aqueous samples, serine and choline levels were higher in phenobarbital-treated rats than controls, which may be an indication that the folate-homocysteine metabolic pathways were altered. C1 [Schnackenberg, Laura; Beger, Richard D.; Dragan, Yvonne] Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), Natl Ctr Toxicol Res, Div Syst Toxicol, Jefferson, AR 72079 USA. EM rbeger@NCTR.FDA.GOV NR 82 TC 14 Z9 17 U1 0 U2 4 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1573-3882 J9 METABOLOMICS JI Metabolomics PD MAR PY 2005 VL 1 IS 1 BP 87 EP 94 DI 10.1007/s11306-005-1110-8 PG 8 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA V63QM UT WOS:000204301600010 ER PT J AU Schild, LJ Phillips, DH Osborne, MR Hewer, A Beland, FA Churchwell, MI Brown, K Gaskell, M Wright, E Poirier, MC AF Schild, LJ Phillips, DH Osborne, MR Hewer, A Beland, FA Churchwell, MI Brown, K Gaskell, M Wright, E Poirier, MC TI Hepatic DNA adduct dosimetry in rats fed tamoxifen: a comparison of methods SO MUTAGENESIS LA English DT Article ID TANDEM MASS-SPECTROMETRY; BREAST-CANCER; ALPHA-HYDROXYTAMOXIFEN; HUMAN ENDOMETRIUM; IN-VITRO; N-DESMETHYLTAMOXIFEN; METABOLIC-ACTIVATION; LIVER CELLS; IDENTIFICATION; TRIALS AB Liver homogenates from rats fed tamoxifen (TAM) in the diet were shared among four different laboratories. TAM-DNA adducts were assayed by high pressure liquid chromatography-electrospray tandem mass spectrometry (HPLC-ES-MS/MS), TAM-DNA chemiluminescence immunoassay (TAM-DNA CIA), and P-32-postlabeling with either thin layer (P-32-P-TLC) or liquid chromatography (P-32-P-HPLC) separation. In the first study, rats were fed a diet containing 500 p.p.m. TAM for 2 months, and the values for measurements of the (E)-alpha-(deoxyguanosin-N-2-yl)-tamoxifen (dG-N-2-TAM) adduct in replicate rat livers varied by 3.5-fold when quantified using 'in house' TAM-DNA standards, or other approaches where appropriate. In the second study, rats were fed 0, 50, 250 or 500 p.p.m. TAM for 2 months, and TAM-DNA values were quantified using both 'in house' approaches as well as a newly synthesized [N-methyl-H-3]TAM-DNA standard that was shared among all the participating groups. In the second study, the total TAM-DNA adduct values varied by 2-fold, while values for the dG-N-2-TAM varied by 2.5-fold. Ratios of dG-N-2-TAM:(E)-alpha-(deoxyguanosin-N-2-yl)-N-desmethyltamoxifen (dG-N-2-N-desmethyl-TAM) in the second study were similar to 1:1 over the range of doses examined. The study demonstrated a remarkably good agreement for TAM-DNA adduct measurements among the diverse methods employed. C1 NCI, Carcinogen DNA Interact Sect, NIH, Bethesda, MD 20892 USA. Inst Canc Res, Sutton SM2 5NG, Surrey, England. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Leicester, Bioctr, Canc Biomarkers & Prevent Grp, Leicester LE1 7RH, Leics, England. RP Poirier, MC (reprint author), NCI, Carcinogen DNA Interact Sect, NIH, Bldg 37,Room 4032m37 Convent Dr MSC-4255, Bethesda, MD 20892 USA. EM poirierm@exchange.nih.gov OI Phillips, David/0000-0001-8509-3485 NR 44 TC 14 Z9 14 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0267-8357 J9 MUTAGENESIS JI Mutagenesis PD MAR PY 2005 VL 20 IS 2 BP 115 EP 124 DI 10.1093/mutage/gei015 PG 10 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 919SB UT WOS:000228636800006 PM 15755801 ER PT J AU Dobrovolsky, VN McGarrity, LJ VonTungeln, LS Mittelstaedt, RA Morris, SM Beland, FA Heflich, RH AF Dobrovolsky, VN McGarrity, LJ VonTungeln, LS Mittelstaedt, RA Morris, SM Beland, FA Heflich, RH TI Micronucleated erythrocyte frequency in control and azidothymidine-treated Tk(+/+), Tk(+/-)and Tk(-/-) mice SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE erythrocyte frequency; azidothymidine; micronucleus; thymidine kinase; nucleoside analog reverse-transcriptase inhibitor; DNA damage; pyrimidine metabolism ID THYMIDINE KINASE-1; FLOW-CYTOMETRY; TK GENE; 3'-AZIDO-3'-DEOXYTHYMIDINE; RETICULOCYTES; ZIDOVUDINE; CELLS; CARCINOGENICITY; HETEROZYGOSITY; ACTIVATION AB The first step in the activation of the anti-retroviral nucleoside analogue azidothymidine (AZT) involves its conversion to a 5'-monophosphate. In this study, we have evaluated the role of cytosolic thymidine kinase (Tk), the major enzyme involved in phosphorylating thymidine and its analogues, in the nuclear DNA damage produced by AZT in neonatal mice. Tk(+/+), Tk(+/-) and Tk(-/-) mice were treated intraperitoneally with 200 mg/kg/day of AZT on postnatal days 1 through 8, and micronuclei were measured in peripheral blood 24h after the last dose. AZT treatment increased the micronucleus (MN) frequencies to similar extents in both the reticulocytes (RETs) and normochromatic erythrocytes (NCEs) of Tk(+/+) and Tk(+/-) mice; AZT did not increase the frequency of micronucleated RETs (MN-RETs) or micronucleated NCEs (MN-NCEs) in Tk(-/-) mice. Unexpectedly, neonatal Tk(-/-) mice treated with the vehicle had significantly elevated MN frequencies for both RETs and NCEs relative to Tk(+/+) and Tk(+/-) mice (e.g., similar to3.4% MN-RETs and similar to4.8% MN-NCEs in Tk(-/-) mice versus similar to0.7 and similar to0.6% MN-RETs and MN-NCEs in neonatal Tk(+/+) mice). Additional assays performed on untreated Tk(-/-) mice showed that elevated spontaneous MN frequencies persisted until at least 20 weeks of age, which approaches the average lifespan of Tk(-/-) mice. These results indicate that metabolism by Tk is necessary for the genotoxicity of AZT in neonatal mice; however, the genotoxicity of AZT is not altered by reducing the Tk gene dose by half. The elevated spontaneous MN frequencies in Tk(-/-) mice suggest the presence of an endogenous genotoxic activity in these mice. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Dobrovolsky, VN (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM vdobrovolsky@nctr.fda.gov NR 27 TC 11 Z9 11 U1 0 U2 0 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 MAR 1 PY 2005 VL 570 IS 2 BP 227 EP 235 DI 10.1016/j.mrfmmm.2004.11.006 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 902TF UT WOS:000227378700008 PM 15708581 ER PT J AU Pogge, A Slikker, W AF Pogge, A Slikker, W TI Neuroimaging: New approaches for neurotoxicology (vol 25, pg 525, 2004) SO NEUROTOXICOLOGY LA English DT Correction C1 Natl Ctr Toxicol Res, Dept Neurotoxicol, Jefferson, AR 72079 USA. RP Pogge, A (reprint author), Natl Ctr Toxicol Res, Dept Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM apogge@nctr.fda.gov NR 1 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAR PY 2005 VL 26 IS 2 BP 293 EP 293 DI 10.1016/j.neuro.2004.11.003 PG 1 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 904QT UT WOS:000227513500016 ER PT J AU Kaminskas, E Farrell, AT Wang, YC Sridhara, R Pazdur, R AF Kaminskas, E Farrell, AT Wang, YC Sridhara, R Pazdur, R TI FDA drug approval summary: Azacitidine (5-azacytidine, Vidaza((TM))) for injectable suspension SO ONCOLOGIST LA English DT Article DE azacitidine; Vidaza((TM)); myelodysplastic syndromes; refractory anemia; leukemia ID MYELODYSPLASTIC SYNDROMES; LEUKEMIA; METHYLATION; INHIBITION; P15(INK4B); CELLS; DNA AB On May 19, 2004, azacitidine (5-azacytidine; Vidaza (TM); Pharmion Corporation, Boulder, CO, http://www. pharmion.com) for injectable suspension received regular approval by the U.S. Food and Drug Administration (FDA) for the treatment of all subtypes of myelodysplastic syndrome (MDS). This report summarizes the basis for this approval. Effectiveness was demonstrated in one randomized, controlled trial comparing azacitidine administered s.c. with best supportive care (observation group) and in two single-arm studies, one in which azacitidine was administered s.c. and in the other in which it was administered i.v. The dose of azacitidine, 75 mg/m(2)/day for 7 days every 28 days, was the same in all three studies. In the randomized trial, study participants were well matched with respect to age, sex, race, performance status, MDS subtype, and use of transfusion during the 3 months before study entry. Patients in the observation arm were permitted by protocol to cross over to azacitidine treatment if their disease progressed according to prespecified criteria. During the course of the study, more than half of the patients in the observation arm did cross over to the azacitidine treatment arm. The primary efficacy end point was the overall response rate. Response consisted of complete or partial normalization of blood cell counts and of bone marrow morphology. The response rate in the azacitidine arm was about 16%; there were no responses in the observation arm. The response rates in the two single-arm studies were similar (13% and 19%). The responses were sustained, with median durations of 11 months and 17 months respectively. Responding patients who were transfusion dependent at study entry lost the need for transfusions. In addition, about 19% of patients had less than partial responses (termed improvement), and two-thirds of them became transfusion independent. Common adverse events associated with azacitidine treatment were gastrointestinal (nausea, vomiting, diarrhea, constipation, and anorexia), hematologic (neutropenia, thrombocytopenia), fevers, rigors, ecchymoses, petechiae, injection site events, arthralgia, headache, and dizziness. Liver function abnormalities occurred in 16% of patients with intercurrent hepatobiliary disorders and in two patients with previously diagnosed liver cirrhosis. Renal failure occurred in patients during sepsis and hypotension. There were no deaths attributed to azacitidine. Azacitidine, the first drug approved by the U.S. FDA for MDS, has a favorable safety profile and provides a clinical benefit of eliminating transfusion dependence and complete or partial normalization of blood counts and bone marrow blast percentages in responding patients. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Kaminskas, E (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-150, Rockville, MD 20857 USA. EM kaminskase@cder.fda.gov NR 18 TC 165 Z9 177 U1 1 U2 13 PU ALPHAMED PRESS PI MIAMISBURG PA ONE PRESTIGE PLACE, STE 290, MIAMISBURG, OH 45342-3758 USA SN 1083-7159 J9 ONCOLOGIST JI Oncologist PD MAR PY 2005 VL 10 IS 3 BP 176 EP 182 DI 10.1634/theoncologist.10-3-176 PG 7 WC Oncology SC Oncology GA 911UQ UT WOS:000228031500002 PM 15793220 ER PT J AU Woolery-Antill, M Carroll, E Wallen, G Jarosinski, P Corey, B Wieland, H Dagher, R AF Woolery-Antill, M Carroll, E Wallen, G Jarosinski, P Corey, B Wieland, H Dagher, R TI Navigating the potholes along the research highway: Implementing a research study. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD MAR PY 2005 VL 32 IS 2 MA 225 BP 486 EP 486 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 907XV UT WOS:000227752400250 ER PT J AU Friedman, RL AF Friedman, RL TI Aseptic processing contamination case studies and the pharmaceutical quality system SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Editorial Material ID EQUIPMENT AB This paper summarizes parenteral drug contamination case studies presented at industry conferences and a Food and Drug Administration advisory committee meeting in the period of 2000-2004. CGMP deficiencies associated with each contamination event are discussed. The key role of a well-functioning quality system in contamination prevention is emphasized. C1 US FDA, Ctr Drug Evaluat & Res, Div Mfg & Prod Qual, Rockville, MD 20857 USA. RP Friedman, RL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Mfg & Prod Qual, Rockville, MD 20857 USA. NR 34 TC 1 Z9 1 U1 1 U2 2 PU PARENTERAL DRUG ASSOC INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 620, BETHESDA, MD 20814 USA SN 1079-7440 J9 PDA J PHARM SCI TECH JI PDA J. Pharm. Sci. Technol. PD MAR-APR PY 2005 VL 59 IS 2 BP 118 EP 126 PG 9 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA 924MT UT WOS:000228983600004 PM 15971544 ER PT J AU Hauck, WW Capen, RC Callahan, JD De Muth, JE Hsu, H Lansky, D Sajjadi, NC Seaver, SS Singer, RR Weisman, D AF Hauck, WW Capen, RC Callahan, JD De Muth, JE Hsu, H Lansky, D Sajjadi, NC Seaver, SS Singer, RR Weisman, D TI Assessing parallelism prior to determining relative potency SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Article DE bioassay; parallelism; similarity; hypothesis testing AB In the course of preparing a revision to Chapter (111) of the US Pharmacopeia, the revision committee came to a unanimous agreement that the method for assessing parallelism that is currently presented in (111) and in the European Pharmacopeia's Chapter 5.3 is flawed and should be replaced. The symptoms are that perfectly acceptable assay results may fail due to good precision and that obviously faulty assay results may pass due to poor precision. The flaw is that the wrong statistical technique has been used. We propose an alternative approach based on the equivalence testing paradigm that does not have these shortcomings. Equivalence testing requires the establishment of equivalence limits. Specific approaches for establishing equivalence limits are discussed. C1 Thomas Jefferson Univ, Biostat Sect, Philadelphia, PA 19107 USA. Merck & Co Inc, Vaccine Biometr Res, W Point, PA 19486 USA. Callahan Associates Inc, La Jolla, CA 92037 USA. Univ Wisconsin, Extens Serv Pharm, Madison, WI 53705 USA. US FDA, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Lansky Consulting, LLC, Burlington, VT 05401 USA. Sajjadi Associates Inc, Encinitas, CA 92024 USA. Seaver Associates, LLC, Concord, MA 01742 USA. Prot Design Labs Inc, Fremont, CA 94555 USA. Eli Lilly & Co, Lilly Corp Ctr, Stat & Math Sci, Indianapolis, IN 46285 USA. RP Hauck, WW (reprint author), Thomas Jefferson Univ, Biostat Sect, 211 S 9th 602, Philadelphia, PA 19107 USA. EM whauck@mail.jci.tju.edu NR 7 TC 17 Z9 18 U1 1 U2 9 PU PARENTERAL DRUG ASSOC INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 620, BETHESDA, MD 20814 USA SN 1079-7440 J9 PDA J PHARM SCI TECH JI PDA J. Pharm. Sci. Technol. PD MAR-APR PY 2005 VL 59 IS 2 BP 127 EP 137 PG 11 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA 924MT UT WOS:000228983600005 PM 15971545 ER PT J AU Shatin, D Gardner, JS Stergachis, A Blough, D Graham, D AF Shatin, D Gardner, JS Stergachis, A Blough, D Graham, D TI Impact of mailed warning to prescribers on the co-prescription of tramadol and antidepressants' SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE antidepressants; contraindicated; codispensing; 'Dear Doctor'; drugs/adverse effects; product surveillance; postmarketing; risk communication; tramadol ID DRUG; CISAPRIDE; SEIZURES; WITHDRAWAL; MARKET; RISK; CARE; PAIN AB Purpose An evaluation was made of the effectiveness in changing prescribing behavior of 'Dear Health Professional (DHP)' letters mailed by the manufacturer to physicians and other health professionals advising them of safety information on co-prescribing of tramadol and antidepressants. Methods A retrospective cohort analysis of prescription claims of all plan members from 12 UnitedHealth Group-affiliated health plans who received a first prescription for tramadol between I April 1995 and 31 December 1996. The prevalence of co-prescribing of antidepressants and tramadol relative to the date of the 'DHP' communication was determined. Results 9218 plan members received an initial prescription for tramadol within the observation period. Prior to the date of the 'DHP' communication 1061/4774 (22.2%) members received a prescription for an antidepressant within 30 days of their first prescription for tramadol. Following the date of the communication 844/4444 (19.0%) of members received an antidepressant within 30 days of their first prescription for tramadol. An overall decreasing linear trend in antidepressant coprescribing was evident over the observation period, but there was no statistically significant acceleration in the decrease following this communication. Conclusions The mailed 'DHP' advisory letter did not affect the rate of co-prescribing of tramadol with antidepressants. Copyright (c) 2004 John Wiley C Sons, Ltd. C1 UnitedHlth Grp, Ctr Hlth Care Policy & Evaluat, Minneapolis, MN 55344 USA. Univ Washington, Dept Pharm, Seattle, WA 98195 USA. Univ Washington, Dept Epidemiol, Seattle, WA 98195 USA. US FDA, Rockville, MD 20857 USA. RP Shatin, D (reprint author), UnitedHlth Grp, Ctr Hlth Care Policy & Evaluat, MN002-0260,12125 Technol Dr, Minneapolis, MN 55344 USA. EM Deborah_shatin@uhc.com NR 19 TC 24 Z9 24 U1 0 U2 2 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 MAR PY 2005 VL 14 IS 3 BP 149 EP 154 DI 10.1002/pds.961 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 904RR UT WOS:000227515900002 PM 15386714 ER PT J AU Wysowski, DK Governale, LA AF Wysowski, DK Governale, LA TI Use of menopausal hormones in the United States, 1992 through June, 2003 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE menopause; hormone replacement; conjugated estrogen; progestin; Premarin; Provera; medroxyprogesterone ID ESTROGEN PLUS PROGESTIN; HEALTHY POSTMENOPAUSAL WOMEN; RANDOMIZED CONTROLLED-TRIAL; REPLACEMENT THERAPY; BREAST-CANCER AB Purpose The Women's Health Initiative (WHI) study that documented an unfavorable benefit to risk ratio of Prempro and subsequently an increased risk of stroke with menopausal estrogen prompted us to investigate the use during 1992 through June 2003 of menopausal hormones in the United States. Methods Two pharmaceutical research databases from IMS Health, the National Prescription Audit Plus (TM) and the National Disease and Therapeutic Index (TM), were accessed and analyzed. Results The number of dispensed outpatient prescriptions for oral menopausal estrogens and oral combination estrogen-progestins increased 2.5-fold (153%) from 34.5 million dispensed in 1992 to a high of 87.3 million in 2000. For July 2002 through June 2003, the year following the publication of the results of the WHI trial, prescriptions for these products declined to 59.6 million, a 32% decrease from their peak in 2000. Prescriptions for transdermal estrogen and transdermal combination estrogen-progestin products increased from 5.2 million dispensed in 1992 to their peak of 8.3 million in 2000, and declined 10% to 7.5 million during July 2002 through June 2003. By contrast, prescriptions for oral menopausal progestins rose to 17.5 million in 1995 and then steadily declined. In the year after the WHI, prescriptions for oral progestins decreased 49% to 8.9 million from their peak in 1995. The earlier decline in oral progestin prescriptions was primarily due to the marketing in 1995 of the popular oral combination estrogen-progestin drugs. Conclusions Prescriptions dispensed for menopausal hormones increased substantially between 1992 and peaked in 2000. By June 2003, prescriptions for oral menopausal estrogens and oral combination estrogen-progestins had declined by about one-third from their peak year. Copyright (c) 2004 John Wiley C Sons, Ltd. C1 US FDA, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Div Drug Risk Evaluat, HFD-430,Parklawn Bldg,Room 15-B-08, Rockville, MD 20857 USA. EM wysowski@cder.fda.gov NR 18 TC 36 Z9 36 U1 1 U2 2 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 MAR PY 2005 VL 14 IS 3 BP 171 EP 176 DI 10.1002/pds.985 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 904RR UT WOS:000227515900005 PM 15386701 ER PT J AU Palamakula, A Soliman, M Khan, MMA AF Palamakula, A Soliman, M Khan, MMA TI Regional permeability of coenzyme Q10 in isolated rat gastrointestinal tracts SO PHARMAZIE LA English DT Article ID SMALL-INTESTINE; EXPRESSION; TRANSPORTERS; Q(10); ACID AB The objective of the study was to identify the region with the maximum permeability for low bioavailable coenzyme Q10 (CoQ) in the gastrointestinal tract. To evaluate the regional differences in permeability, male Sprague-Dawley rats, 250-300 g, were anesthetized and the gastrointestinal segments were isolated. Stomach, duodenum, jejunum, ileum and colon tissues were mounted on a Navicyte side-by-side diffusion apparatus. Radiolabeled CoQ 1 mu M in DMEM, pH 7.4, 37 degrees C was added to the donor side and the samples withdrawn from the receiver compartment at predetermined time intervals were analyzed using a scintillation counter. Membrane integrity was monitored by C-14-mannitol permeability. The apical to basal permeability coefficients (Papp x 10(-6), cm/s) were 0.32 +/- 0.13, 3.14 +/- 0.89, 1.36 +/- 1.4, 0.83 +/- 0.40, and 1.59 +/- 0.13, for CoQ through rat stomach, duodenum, jejunum, ileum, and colon tissues respectively. The basolateral to apical permeability coefficients (Papp x 10-6, cm/s) were 1.6 +/- 0.2, 2.2 +/- 1.2, 0.88 +/- 0.12, 1.6 +/- 0.42, and 1.9 +/- 0.41 respectively. Therefore the region of maximum CoQ permeability is duodenum followed by colon and ileum. Jejunum and stomach regions also have fairly high permeability. Therefore CoQ formulations should be made with an aim to target the duodenum to get maximum dosage effect. C1 Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX 79106 USA. RP Palamakula, A (reprint author), US FDA, CDER, DPQR, 10903 New Hampshire Ave, Silver Spring, MD 20903 USA. EM khanm@cder.fda.gov RI Palamakula, Anitha/E-3741-2010 NR 16 TC 5 Z9 6 U1 1 U2 1 PU GOVI-VERLAG PHARMAZEUTISCHER VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCCARL MANNICH STR 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD MAR PY 2005 VL 60 IS 3 BP 212 EP 214 PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 907VP UT WOS:000227746500011 PM 15801676 ER PT J AU Dionne, RA Bartoshuk, L Mogil, J Witter, J AF Dionne, RA Bartoshuk, L Mogil, J Witter, J TI Individual responder analyses for pain: does one pain scale fit all? SO TRENDS IN PHARMACOLOGICAL SCIENCES LA English DT Editorial Material ID RHEUMATOID-ARTHRITIS; CLINICAL PAIN; RECEPTOR GENE; INTENSITY; HUMANS; TARGET AB The outcomes of clinical trials are based on the mean responses of large numbers of subjects but fail to address inter-individual differences. The molecular mechanisms that underlie pain vary among individuals over time and among different types of pain to produce wide inter-individual variations in pain perception and response. Gender, ethnicity, temperament and genetic factors also contribute to individual variation in pain sensitivity and responses to analgesics. Pain measurement scales can be used differently across individuals based on the past pain experiences of individuals. We propose that individual responder analyses could be used in clinical trials to better detect analgesic activity across patient groups and within sub-groups, and to identify molecular-genetic mechanisms that contribute to individual variation. C1 NIDCR, NIH, Bethesda, MD 20892 USA. Yale Univ, Sch Med, New Haven, CT 06520 USA. McGill Univ, Dept Psychol, Montreal, PQ H3A 1B1, Canada. McGill Univ, Ctr Res Pain, Montreal, PQ H3A 1B1, Canada. US FDA, Rockville, MD 20850 USA. RP Dionne, RA (reprint author), NIDCR, NIH, 10 Ctr Dr,Room 1N-103, Bethesda, MD 20892 USA. EM raymond.dionne@nih.gov NR 33 TC 63 Z9 65 U1 1 U2 6 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0165-6147 J9 TRENDS PHARMACOL SCI JI Trends Pharmacol. Sci. PD MAR PY 2005 VL 26 IS 3 BP 125 EP 130 DI 10.1016/j.tips.2005.01.009 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 910LR UT WOS:000227933400004 PM 15749157 ER PT J AU Rolka, H Bracy, D Russel, C Fram, D Ball, R AF Rolka, H Bracy, D Russel, C Fram, D Ball, R TI Using simulation to assess the sensitivity and specificity of a signal detection tool for multidimensional public health surveillance data SO STATISTICS IN MEDICINE LA English DT Article; Proceedings Paper CT Symposium on Statistical Methods -Study Design and Decision-Making in Public Health CY JAN 27-29, 2003 CL Atlanta, GA SP US Ctr Dis Control & Prevent, Agcy Toxic Substances & Dis Registry DE surveillance; Monte Carlo; simulation ID INFECTIOUS-DISEASE; REPORTING SYSTEM; PHARMACOVIGILANCE; BIOTERRORISM; OUTBREAKS; EVENTS AB The objective of the work described in this paper is to develop a means for characterizing the validity of an empirical methodology for detecting signals potentially related to complicated adverse event (AE) coding terms in multidimensional public health surveillance data. The signal detection tool under evaluation is the multi-item gamma Poisson shrinkage (MGPS) estimation program. We were interested in its potential application to passive surveillance system monitoring. to screen for 'signals' of complicated adverse event coding terms (AE terms) in complex and noisy data. The research was to design and produce a flexible and user-friendly utility for probabilistically defining, complicated signals in a database. iterating large numbers of applications of the MGPS detection algorithm and establishing proportions of correct detection events. We sought to establish the specificity of the MGPS by developing a random background using a gradient that ranged from rigorous (but not very relevant) to relevant (but noisy). To establish the sensitivity, signals were defined based on recognized public health issues of interest (such as the introduction of a new vaccine into the population). Methods of representing a signal included a simple pair-wise association consisting of a new vaccine and one AE term. as well as a more realistic complex of multiple AE terms comprising a 'syndrome'. A web application has been developed to create and insert signals with user-defined probabilities in multiple iterations of simulated random background data. Three forms of simulated data based on the vaccine adverse event reporting system (VAERS) cumulative spontaneous database were defined to serve as background noise against which to contrast introduced vaccine adverse event signals: (1) completely random associations between vaccines and AE terms, (2) random associations of vaccine sets and AE term sets preserving naturally observed vaccine co-occurrences and AE term co-occurrences and (3) samples from the actual VAER data as reported. Rates of detection by the MGPS algorithm can be established for specific signal patterns at varying probabilistic intensities in a choice of random background data forms. Knowing these rates is important for determining the degree of response to an MGPS signal detection event in 'live' data. Published in 2005 by John Wiley Sons, Ltd. C1 CDC, NCPHI, Epidemiol Program Off, Div Publ Hlth Surveillance & Informat, Atlanta, GA 30333 USA. DynTel Corp, Atlanta, GA 30329 USA. Lincoln Technol Inc, Wellesley Hills, MA 02481 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Rolka, H (reprint author), CDC, NCPHI, Epidemiol Program Off, Div Publ Hlth Surveillance & Informat, Mailstop E06,Clifton Rd, Atlanta, GA 30333 USA. EM hrolka@cdc.gov NR 21 TC 18 Z9 19 U1 0 U2 4 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD FEB 28 PY 2005 VL 24 IS 4 BP 551 EP 562 DI 10.1002/sim.2035 PG 12 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 893SP UT WOS:000226739800007 PM 15678409 ER PT J AU Inoue, S Golding, B Scott, D AF Inoue, S Golding, B Scott, D TI Programming of CTL with heat-killed Brucella abortus and antigen allows soluble antigen alone to generate effective secondary CTL SO VACCINE LA English DT Article DE CTL response; antigen dose; CD4 T cells ID T-CELL RESPONSES; DENDRITIC CELLS; CROSS-PRESENTATION; IN-VIVO; ANTITUMOR IMMUNITY; CD8-T-CELL MEMORY; CD4-T-CELL HELP; V3 LOOP; MECHANISM; VACCINE AB Optimal generation of cytotoxic T cell (CTL) responses continues to be a challenge in the production of vaccines against pathogens such as HIV-1, in part because it is difficult to introduce soluble protein antigens (Ag) into the MHC class I pathway. Using heat-killed Brucella abortus (HKBA) as an adjuvant and ovalbumin (ova) protein as an Ag, we demonstrated that a high dose of Ag was required for systemic and effective CTL. In an adoptive transfer model, primary and secondary ova-specific OT-1 CD8 cell expansion by HKBA plus high dose of ova were partially CD4 T cell-dependent. Interestingly, primary stimulation with HKBA plus ova allowed effective secondary stimulation with ova alone that was equivalent to HKBA plus ova in terms of IFN-gamma production from Ag-specific CD8 cells. Thus a combination of adequate Ag dose, and selection of appropriate adjuvants can meet the threshold not only for primary effective CTL responses to soluble protein Ags but for secondary CTL responses following stimulation with protein Ag alone. (C) 2004 Elsevier Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. RP Inoue, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. EM inoue@cber.fda.gov NR 33 TC 4 Z9 4 U1 1 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD FEB 25 PY 2005 VL 23 IS 14 BP 1730 EP 1738 DI 10.1016/j.vaccine.2004.09.034 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 902AR UT WOS:000227324100014 PM 15705479 ER PT J AU Liu, F Pan, C Drumm, P Ang, CYW AF Liu, F Pan, C Drumm, P Ang, CYW TI Liquid chromatography-mass spectrometry studies of St. John's wort methanol extraction: active constituents and their transformation SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE Hypericum perforatum L.; St. John's wort; hyperforins; hypericins; LC/MS identification ID HYPERICUM-PERFORATUM L; HYPERFORIN; STABILITY; QUANTIFICATION; CELLS; FORMS; L. AB The influence of light and solution pit on the stability behavior of phloroglucinols (hyperforin and adhyperforin) and naphthodianthrones (hypericin, pseudohypericin, protohypericin and protopseudohypericin) extracted with methanol from St. John's wort powder (Hypericum perforatum L.) were studied using liquid chromatography-in mass spectrometry (LC-MS). When exposed to light, hyperforin and adhyperforin in this extract solution degraded rapidly, particularly at pH 7, where within 12 h complete transformation was observed. Contrastingly, when protected from light, the Solutions regardless of pH, underwent minimal transformation after 36 h. Under light and neutral pH conditions, phloroglucinols and naphthodianthrones had different stability behaviors, which were attributed to the different oxidation mechanisms. Four experiments performed on naphthodianthrones exhibited serious transformation at acidic pHs. One hyperforin transformation product was studied using LC-MS. The molecular structure was proposed on the basis of ion fragmentation patterns obtained from MS/MS studies. (C) 2004 Elsevier B.V. All rights reserved. C1 Novartis Pharmaceut Corp, E Hanover, NJ 07936 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Pan, C (reprint author), Novartis Pharmaceut Corp, E Hanover, NJ 07936 USA. EM charles.pan@pharma.novartis.com NR 28 TC 27 Z9 28 U1 1 U2 19 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 FEB 23 PY 2005 VL 37 IS 2 BP 303 EP 312 DI 10.1016/j.jpba.2004.10.034 PG 10 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 904FS UT WOS:000227482100013 PM 15708671 ER PT J AU Zhang, BL Zhang, YQ Shacter, E Zheng, Y AF Zhang, BL Zhang, YQ Shacter, E Zheng, Y TI Mechanism of the guanine nucleotide exchange reaction of Ras GTPase - Evidence for a GTP/GDP displacement model SO BIOCHEMISTRY LA English DT Article ID STRUCTURAL BASIS; ACTIVATING PROTEINS; KINETIC MECHANISM; CATALYTIC DOMAIN; BINDING PROTEINS; GENE-PRODUCT; GUANOSINE; SWITCH; CDC42; RAC1 AB Ras GTPases function as binary switches in the signaling pathways controlling cell growth and differentiation by cycling between the inactive GDP-bound and the active GTP-bound states. They are activated through interaction with guanine nucleotide exchange factors (GEFs) that catalyze the exchange of bound GDP with cytosolic GTP. In a conventional scheme, the biochemical roles of GEFs are postulated as stimulating the release of the bound GDP and stabilizing a nucleotide-free transition state of Ras. Herein we have examined in detail the catalyzed GDP/GTP exchange reaction mechanism by a Ras specific GEF, GRF1. In the absence of free nucleotide, GRF1 could not efficiently stimulate GDP dissociation from Ras. The release of the Ras-bound GDP was dependent upon the concentration and the structure of the incoming nucleotide, in particular, the hydrophobicity of the beta and gamma phosphate groups, suggesting that the GTP binding step is a prerequisite for GDP dissociation, is the rate-limiting step in the GEF reaction, or both. Using a pair of fluorescent guanine nucleotides (N-methylanthraniloyl GDP and 2',3'-O-(2,4,6-trinitrocyclohexadienylidene)-GTP) as donor and acceptor probes, we were able to detect fluorescence resonance energy transfer between the incoming GTP and the departing GDP on Ras under controlled kinetic conditions, providing evidence that there may exist a novel intermediate of the GEF-Ras complex that transiently binds to two nucleotides simultaneously. Furthermore, we found that Ras was capable of binding pyrophosphate (PPi) with a dissociation constant of 26 muM and that PPi and GMP, but neither alone, synergistically potentiated the GRF1-stimulated GDP dissociation from Ras. These results strongly support a GEF reaction mechanism by which nucleotide exchange occurs on Ras through a direct GTP/GDP displacement model. C1 Ctr Drug Evaluat & Res Food & Drug Adm, Off Biotechnol Prod, Div Therapeut Prot, Lab Biochem, Bethesda, MD 20892 USA. Childrens Hosp, Res Fdn, Div Exp Hematol, Cincinnati, OH 45229 USA. RP Zhang, BL (reprint author), Ctr Drug Evaluat & Res Food & Drug Adm, Off Biotechnol Prod, Div Therapeut Prot, Lab Biochem, Bethesda, MD 20892 USA. EM Baolin.zhang@fda.gov RI Zheng, Yi/J-7235-2015 OI Zheng, Yi/0000-0001-7089-6074 NR 49 TC 23 Z9 25 U1 2 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD FEB 22 PY 2005 VL 44 IS 7 BP 2566 EP 2576 DI 10.1021/bi048755w PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 898KH UT WOS:000227075200035 PM 15709769 ER PT J AU Schmued, LC Stowers, CC Scallet, AC Xu, LL AF Schmued, LC Stowers, CC Scallet, AC Xu, LL TI Fluoro-Jade C results in ultra high resolution and contrast labeling of degenerating neurons SO BRAIN RESEARCH LA English DT Article DE neumpathology; neurotoxicology; kainic acid; apoptosis; necrosis; excitotoxicity; hypoxia ID RAT FOREBRAIN; KAINIC ACID; LOCALIZATION; EXPOSURE; METHAMPHETAMINE; PROGRESSION; CORTEX; MYELIN; DAMAGE AB The causes and effects of neuronal degeneration are of major interest to a wide variety of neuroscientists. Paralleling this growing interest is an increasing number of methods applicable to the detection of neuronal degeneration. The earliest methods employing aniline dyes were methodologically simple, but difficult to interpret due to a lack of staining specificity. In an attempt to circumvent this problem, numerous suppressed silver methods have been introduced. However, these methods are labor intensive, incompatible with most other histochemical procedures and notoriously capricious. In an attempt to develop a tracer with the methodological simplicity and reliability of conventional stains but with the specificity of an ideal suppressed silver preparation, the Fluoro-Jade dyes were developed. Fluoro-Jade C, like its predecessors, Fluoro-Jade and Fluoro-Jade B, was found to stain all degenerating neurons, regardless of specific insult or mechanism of cell death. Therefore, the patterns of neuronal degeneration seen following exposure to either the glutamate agonist, kainic acid, or the inhibitor of mitochondrial respiration, 3-NPA, were the same for all of the Fluoro-Jade dyes. However, there was a qualitative difference in the staining characteristics of the three fluorochromes. Specifically, Fluoro-Jade C exhibited the greatest signal to background ratio, as well as the highest resolution. This translates to a stain of maximal contrast and affinity for degenerating neurons. This makes it ideal for localizing not only degenerating nerve cell bodies, but also distal dendrites, axons and terminals. The dye is highly resistant to fading and is compatible with virtually all histological processing and staining protocols. Triple labeling was accomplished by staining degenerating neurons with Fluoro-Jade C, cell nuclei with DAPI and activated astrocytes with GFAP immunofluoresence. Published by Elsevier B.V. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Vanderbilt Univ, Dept Chem Engn, Nashville, TN 37235 USA. ORISE, Inst Sci & Educ, Oak Ridge, TN 37813 USA. RP Schmued, LC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM lschmued@nctr.fda.gov NR 23 TC 319 Z9 329 U1 4 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 21 PY 2005 VL 1035 IS 1 BP 24 EP 31 DI 10.1016/j.brainres.2004.11.054 PG 8 WC Neurosciences SC Neurosciences & Neurology GA 905BL UT WOS:000227542400003 PM 15713273 ER PT J AU Gupta, N Arthos, J Khazanie, P Steenbeke, TD Censoplano, NM Chung, EA Cruz, CC Chaikin, MA Daucher, M Kottilil, S Mavilio, D Schuck, P Sun, PD Rabin, RL Radaev, S Van Ryk, D Cicala, C Fauci, AS AF Gupta, N Arthos, J Khazanie, P Steenbeke, TD Censoplano, NM Chung, EA Cruz, CC Chaikin, MA Daucher, M Kottilil, S Mavilio, D Schuck, P Sun, PD Rabin, RL Radaev, S Van Ryk, D Cicala, C Fauci, AS TI Targeted lysis of HIV-infected cells by natural killer cells armed and triggered by a recombinant immunoglobulin fusion protein: implications for immunotherapy SO VIROLOGY LA English DT Article DE natural killer cell; antibody dependent cellular cytotoxicity; immunotherapy; HIV; CD16; recombinant antibody ID DEPENDENT CELLULAR CYTOTOXICITY; SEROPOSITIVE INDIVIDUALS; ANTIBODY; RECEPTOR; NEUTRALIZATION; GLYCOPROTEIN; EPITOPE; INVIVO; SIGNAL; SITES AB Natural killer (NK) cells play an important role in both innate and adaptive antiviral immune responses. The adaptive response typically requires that virus-specific antibodies decorate infected cells which then direct NK cell lysis through a CD16 mediated process termed antibody-dependent cellular cytotoxicity (ADCC). In this report, we employ a highly polymerized chimeric IgG1/IgA immunoglobulin (Ig) fusion protein that, by virtue of its capacity to extensively crosslink CD16, activates NK cells while directing the lysis of infected target cells. We employ HIV as a model system, and demonstrate that freshly isolated NK cells preloaded with an HIV gp120-specific chimeric IgG1/IgA fusion protein efficiently lyse HIV-infected target cells at picomolar concentrations. NK cells pre-armed in this manner retain the capacity to kill targets over an extended period of time. This strategy may have application to other disease states including various viral infections and cancers. Published by Elsevier Inc. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIH, Prot Biophys Resource, DPBS, ORS, Bethesda, MD 20892 USA. NIAID, Immunogenet Lab, NIH, Bethesda, MD 20892 USA. US FDA, Div Bacterial Parasit & Allergen Prod, CBER, Bethesda, MD 20892 USA. RP Arthos, J (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 10 6A08,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jarthos@niaid.nih.gov OI Schuck, Peter/0000-0002-8859-6966; Mavilio, Domenico/0000-0001-6147-0952 NR 26 TC 21 Z9 24 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 0042-6822 J9 VIROLOGY JI Virology PD FEB 20 PY 2005 VL 332 IS 2 BP 491 EP 497 DI 10.1016/j.virol.2004.12.018 PG 7 WC Virology SC Virology GA 896EU UT WOS:000226918200003 PM 15680414 ER PT J AU Liotta, LA Lowenthal, M Mehta, A Conrads, TP Veenstra, TD Fishman, DA Petricoin, EF AF Liotta, LA Lowenthal, M Mehta, A Conrads, TP Veenstra, TD Fishman, DA Petricoin, EF TI Importance of communication between producers and consumers of publicly available experimental data SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Editorial Material ID FLIGHT MASS-SPECTROMETRY; PROSTATE-CANCER; OVARIAN-CANCER; LASER DESORPTION/IONIZATION; RAPID IDENTIFICATION; PROTEOMIC PATTERNS; SERUM; BIOMARKERS; RESOLUTION AB The application of mass spectrometry to discover new cancer biomarkers is in its infancy. Many of these new markers are low-abundance proteins that exist as fragments associated with carrier proteins. Although reproducibility is key to the use of mass spectrometry for ion fingerprint analysis, the scientific community has yet to establish a common platform or standardized operating procedures that are necessary for intra- and inter-laboratory comparison. In an effort to assist others who are perfecting mass spectrometry platforms for profiling, ongoing experimental data were posted for public consumption. An unintended consequence of unrestricted access to experimental data is the risk of inappropriate conclusions drawn and publicly disseminated that could have been avoided by communication between the producers and consumers of the data. Such disputes, however, should not divert us from the validation of this promising new approach. C1 NCI, US FDA, Clin Proteom Program, Off Cell Therapy & Gene Therapy,CBER, Bethesda, MD 20892 USA. NCI, US FDA, Clin Proteom Program, Lab Pathol,CCR, Bethesda, MD 20892 USA. NCI, Inst Biomed Proteom Program, Lab Proteom & Analyt Technol, SAIC Frederick Inc, Frederick, MD 21701 USA. NYU, Natl Ovarian Canc Early Detect Program, New York, NY USA. RP Petricoin, EF (reprint author), NCI, US FDA, Clin Proteom Program, Off Cell Therapy & Gene Therapy,CBER, Bethesda, MD 20892 USA. EM petricoin@cber.fda.gov NR 24 TC 58 Z9 62 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD FEB 16 PY 2005 VL 97 IS 4 BP 310 EP 314 DI 10.1093/jnci/dji053 PG 5 WC Oncology SC Oncology GA 898WW UT WOS:000227107900015 PM 15713967 ER PT J AU Baladron, V Ruiz-Hidalgo, MJ Nueda, ML Diaz-Guerra, MJM Garcia-Ramirez, JJ Bonvini, E Gubina, E Laborda, J AF Baladron, V Ruiz-Hidalgo, MJ Nueda, ML Diaz-Guerra, MJM Garcia-Ramirez, JJ Bonvini, E Gubina, E Laborda, J TI dlk acts as a negative regulator of Notch1 activation through interactions with specific EGF-like repeats SO EXPERIMENTAL CELL RESEARCH LA English DT Review DE 3T3-L1; Balb/c 14; dlk; Notch1; CSL/RBP-Jk/CBF-1; luciferase; yeast two-hybrid system ID HOMEOTIC PROTEIN DLK; INHIBITS ADIPOCYTE DIFFERENTIATION; DELTA-LIKE PROTEIN; T-CELL DEVELOPMENT; FACTOR-I PREF-1; GAMMA-SECRETASE; NEURONAL DIFFERENTIATION; NUCLEAR-LOCALIZATION; SIGNALING PATHWAY; HUMAN HOMOLOG AB The protein dlk, encoded by the Dlk1 gene, belongs to the Notch epidermal growth factor (EGF)-like family of receptors and ligands, which participate in cell fate decisions during development. The molecular mechanisms by which dlk regulates cell differentiation remain unknown. By using the yeast two-hybrid system, we found that dlk interacts with Notch1 in a specific manner. Moreover, by using luciferase as a reporter gene under the control of a CSL/RBP-Jk/CBF-1-dependent promoter in the dlk-negative, Notch1-positive Balb/c cell line. we found that addition of synthetic dlk EGF-like peptides to the culture medium or forced expression of dlk decreases endogenous Notch activity. Furthermore, the expression of the gene Hes-1, a target for Notch 1 activation, diminishes in confluent Balb/c14 cells transected with an expression construct encoding for the extracellular EGF-like region of dlk. The expression of Dlk1 and Notch1 increases in 3T3-L1 cells maintained in a confluent state for several days, which is associated with a concomitant decrease in Hes-1 expression. On the other hand. the decrease of Dlk1 expression in 3T3-L1 cells by antisense cDNA transfection is associated with an increase in Hes-1 expression. The-se results suggest that dlk functionally interacts in vivo with Notch1, which may lead to the regulation of differentiation processes modulated by Notch1 activation and signaling, including adipogenesis. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Castilla La Mancha, Biochem & Mol Biol Branch, Dept Inorgan Chem Organ Chem & Biochem, Med Sch,RCBR, Albabeie 02006, Spain. US FDA, Immunobiol Lab, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Laborda, J (reprint author), Univ Castilla La Mancha, Biochem & Mol Biol Branch, Dept Inorgan Chem Organ Chem & Biochem, Med Sch,RCBR, Cambus Albaceie,Avda Almansa S-N, Albabeie 02006, Spain. EM Jorge.Laborda@uclm.es RI Garcia-Ramirez, Jose/L-2153-2014; Nueda, Maria-Luisa/L-3044-2014; Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014; Baladron, Victoriano/L-1758-2014; Martinez Diaz-Guerra, Maria/M-2855-2014; OI Garcia-Ramirez, Jose/0000-0002-8348-3727; Laborda, Jorge/0000-0002-9210-838X; Baladron, Victoriano/0000-0003-4574-8760; Martinez Diaz-Guerra, Maria Jose/0000-0003-3843-3912 NR 109 TC 106 Z9 111 U1 0 U2 8 PU ELSEVIER INC PI SAN DIEGO PA 525 B STREET, STE 1900, SAN DIEGO, CA 92101-4495, UNITED STATES SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD FEB 15 PY 2005 VL 303 IS 2 BP 343 EP 359 DI 10.1016/j.yexcr.2004.10.001 PG 17 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 891HL UT WOS:000226571800013 PM 15652348 ER PT J AU Sugiyama, T Gursel, M Takeshita, F Cohan, C Conover, J Kaisho, T Akira, S Klinman, DM Ishii, KJ AF Sugiyama, T Gursel, M Takeshita, F Cohan, C Conover, J Kaisho, T Akira, S Klinman, DM Ishii, KJ TI CpG RNA: Identification of novel single-stranded RNA that stimulates human CD14(+)CD11c(+) monocytes SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TOLL-LIKE RECEPTORS; DENDRITIC CELLS; BACTERIAL-DNA; RIBOSOMAL-RNA; CUTTING EDGE; ACTIVATION; OLIGODEOXYNUCLEOTIDES; RECOGNITION; TLR9; INNATE AB Synthetic immunostimulatory nucleic acids such as CpG DNA are being harnessed therapeutically as vaccine adjuvants, anticancer or antiallergic agents. Efforts to identify nucleic acid-based agents capable of more specifically modulating the immune system are being developed. The current study identifies a novel class of single-stranded oligoribonucleotides (ORN) containing umnethylated CpG motifs and a poly(G) run at the 3' end (CpG ORN) that directly stimulate human CD14(+)CD11c(+) monocytes but not dendritic cells or B cells. CpG ORN activate NF-kappaB and p38 MAPK, resulting in IL-6 and IL-12 production and costimulatory molecule up-regulation but not IFNalpha. Methylation of cytosine at the 5' portion in core CpG motif abrogates such activation. TLR3, 7, 8, or 9 alone did not confer response to CpG ORN, in contrast to previously reported respective nucleic acid ligands. These data suggest that CpG ORN represent a novel class of synthetic immunostimulatory nucleic acids with distinct target cells, receptors, and functions from that of previously known immunomodulatory nucleic acids. C1 Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Suita, Osaka 5650871, Japan. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RIKEN, Res Ctr Allergy & Immunol, Lab Host Def, Yokohama, Kanagawa, Japan. Yokohama City Univ, Sch Med, Dept Mol Biodef Res, Yokohama, Kanagawa 232, Japan. Osaka Univ, Japan Sci & Technol Agcy, Osaka, Japan. RP Ishii, KJ (reprint author), Osaka Univ, Microbial Dis Res Inst, Dept Host Def, 3-1 Yamadaoka, Suita, Osaka 5650871, Japan. EM kenishii@biken.osaka-u.ac.jp RI Akira, Shizuo/C-3134-2009; Kaisho, Tsuneyasu/B-4130-2012; Gursel, Mayda /H-1812-2012; Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 34 TC 50 Z9 54 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2005 VL 174 IS 4 BP 2273 EP 2279 PG 7 WC Immunology SC Immunology GA 897EL UT WOS:000226986700061 PM 15699162 ER PT J AU Molefe, DF Chen, JJ Howard, PC Miller, BJ Sambuco, CP Forbes, PD Kodell, RL AF Molefe, DF Chen, JJ Howard, PC Miller, BJ Sambuco, CP Forbes, PD Kodell, RL TI Tests for effects on tumor frequency and latency in multiple dosing photococarcinogenicity experiments SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article; Proceedings Paper CT International Conference of the International-Indian-Statistical-Association CY JUN 14-16, 2002 CL NO Illinois Univ, Dekalb, IL SP Int Indian Statist Assoc HO NO Illinois Univ DE single induction; multiple induction; likelihood ratio; chemoprevention; Weibull; Poisson; negative binomial; logrank; multiple tumor ID CANCER CHEMOPREVENTION EXPERIMENTS; STATISTICAL-ANALYSIS; TG.AC MOUSE; PHOTOCARCINOGENESIS; INHIBITION; MODELS; MICE AB A multiple induction test procedure that extends a single induction test procedure proposed by Kodell and Chen (Biometrical J. 43(4) (2001) 447) based on the work of Kokoska et al. (Anticancer Res. 13 (1993) 1357) is introduced. The new procedure can detect overall differences between two groups as well as isolate differences in the distribution of the number of induced tumors and the distribution of their times to observation. This "frequency-latency" procedure is illustrated with an analysis of data from a multiple dosing experiment, using a likelihood ratio method of testing. The results of the frequency-latency test are compared to those of the logrank test, the negative binomial test, and the test proposed by Dunson et al. (Toxicol. Sci. 55 (2000) 293). A Monte Carlo simulation study is performed to evaluate the accuracy of the parameter estimates of the frequency-latency procedure as well as to study the Type I error rates of the frequency-latency test, the logrank test, and the negative binomial test. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Natl Toxicol Program Ctr Phototox, Jefferson, AR 72079 USA. Charles River Co, Argus Res Lab, Horsham, PA USA. RP Kodell, RL (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. EM rkodell@nctr.fda.gov NR 23 TC 1 Z9 1 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD FEB 15 PY 2005 VL 129 IS 1-2 BP 39 EP 58 DI 10.1016/j.jspi.2004.06.038 PG 20 WC Statistics & Probability SC Mathematics GA 886JE UT WOS:000226222300004 ER PT J AU Kerns, W Schwartz, L Blanchard, K Burchiel, S Essayan, D Fung, E Johnson, R Lawton, M Louden, C MacGregor, J Miller, F Nagarkatti, P Robertson, D Sistare, F Snyder, P Thomas, H Wagner, B Ward, A Zhang, J AF Kerns, W Schwartz, L Blanchard, K Burchiel, S Essayan, D Fung, E Johnson, R Lawton, M Louden, C MacGregor, J Miller, F Nagarkatti, P Robertson, D Sistare, F Snyder, P Thomas, H Wagner, B Ward, A Zhang, J CA Expert Working Grp Drug-Induced Vasc TI Drug-induced vascular injury - a quest for biomarkers SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review ID CIRCULATING ENDOTHELIAL-CELLS; C-REACTIVE PROTEIN; CORONARY ARTERIAL LESIONS; ACUTE CARDIOVASCULAR TOXICITY; SOLUBLE ADHESION MOLECULES; VON-WILLEBRAND-FACTOR; ACUTE-PHASE PROTEINS; IN-VIVO; RECEPTOR ANTAGONIST; ADENOSINE AGONIST C1 Univ New Mexico, Albuquerque, NM 87131 USA. CBER, FDA, Rockville, MD 20857 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Virginia Commonwealth Univ, Richmond, VA 23284 USA. Purdue Univ, W Lafayette, IN 47907 USA. NYU, Med Ctr, New York, NY 10016 USA. OI Miller, Frederick/0000-0003-2831-9593 NR 153 TC 49 Z9 50 U1 0 U2 3 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB 15 PY 2005 VL 203 IS 1 BP 62 EP 87 DI 10.1016/j.taap.2004.08.001 PG 26 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 903ED UT WOS:000227407400008 PM 15694465 ER PT J AU Wysowski, DK Chang, JT AF Wysowski, DK Chang, JT TI Alendronate and risedronate: Reports of severe bone, joint, and muscle pain SO ARCHIVES OF INTERNAL MEDICINE LA English DT Letter C1 US FDA, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Div Drug Risk Evaluat, HFD-430,Parklawn Bldg,Room 15B-08, Rockville, MD 20857 USA. EM diane.wysowski@fda.hhs.gov NR 0 TC 56 Z9 60 U1 0 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9926 J9 ARCH INTERN MED JI Arch. Intern. Med. PD FEB 14 PY 2005 VL 165 IS 3 BP 346 EP 347 DI 10.1001/archinte.165.3.346-b PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 896RY UT WOS:000226952400018 PM 15710802 ER PT J AU White, KL Germolec, DR Booker, CD Hernendez, DM McCay, JA Delclos, KB Newbold, RR Weis, C Guo, TL AF White, KL Germolec, DR Booker, CD Hernendez, DM McCay, JA Delclos, KB Newbold, RR Weis, C Guo, TL TI Dietary methoxychlor exposure modulates splenic natural killer cell activity, antibody-forming cell response and phenotypic marker expression in F-0 and F-1 generations of Sprague Dawley rats SO TOXICOLOGY LA English DT Article DE methoxychlor; developmental exposure; immunomodulation; rat; endocrine disrupter ID ESTROGEN-RECEPTOR; INUTERO EXPOSURE; MICE; DIETHYLSTILBESTROL; IMMUNE; BETA; METABOLITES; ACTIVATION; TOXICOLOGY; CHEMICALS AB Methoxychlor, a chlorinated hydrocarbon pesticide, is a persistent environmental contaminant that has been identified in human reproductive tissues. Methoxychlor has been shown to be estrogenic in both in vivo and in vitro studies. As an endocrine disrupter, it may have the potential to adversely affect endocrine, reproductive, and immune systems in animals. The present study evaluated methoxychlor's immunotoxic potential in F-0 (dams) and F-1 generations of Sprague Dawley rats exposed to an isoflavone-free diet containing methoxychlor at concentrations of 10, 100, and 1000 ppm. In dams, exposure to methoxychlor from gestation day 7 to postpartum day 51 (65 days total exposure) produced a significant increase in the NK activity (1000 ppm) and the percentages of T cells (1000 ppm), helper T cells (1000 ppm) and macrophages (100 and 1000 ppm). In contrast, a decrease in the numbers of splenocytes and B cells was observed at the 100 and 1000 ppm concentrations. In F-1 males, exposure to methoxychlor gestationally, lactationally and through feed from postnatal day 22-64 (78 days total exposure) produced an increase in the spleen IgM antibody-forming cell response to sheep red blood cells (100 and 1000 ppm) and the activity of NK cells (1000 ppm). However, there was a decrease in the terminal body weight (1000ppm), spleen weight (1000 ppm), thymus weight (100 and 1000ppm), and the numbers of splenocytes (1000ppm), B cells (100 and 1000ppm), cytotoxic T cells (1000ppm) and NK cells (100 and 1000ppm). In F-1 females, exposure to methoxychlor produced a decrease in the terminal body weight (1000 ppm) and the percentages of cytotoxic T cells (10, 100 and 1000 ppm). These results demonstrate that developmental and adult dietary exposure to methoxychlor modulates immune responses in Sprague Dawley rats. Immunological changes were more pronounced in the F-1 generation male rats that were exposed during gestation and postpartum, when compared to the F-0 and F-1 generation females. Increases in antibody-forming cell response and NK cell activity, and altered spleen cell subpopulation numbers were observed in the F-1 generation male rats, without similar changes to the F-1 generation females. (C) 2004 Elsevier Ireland Ltd. All rights reserved. C1 Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. NIEHS, Mol Toxicol Lab, Res Triangle Pk, NC 27709 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Guo, TL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, Richmond, VA 23298 USA. EM tlguo@hsc.vcu.edu FU NIEHS NIH HHS [ES 55094]; PHS HHS [224-93-0001] NR 42 TC 19 Z9 21 U1 1 U2 1 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD FEB 14 PY 2005 VL 207 IS 2 BP 271 EP 281 DI 10.1016/j.tox.2004.09.011 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 892JB UT WOS:000226645500010 PM 15596257 ER PT J AU Parry, J Su, L Luther, M Zhou, KQ Yurawecz, MP Whittaker, P Yu, LL AF Parry, J Su, L Luther, M Zhou, KQ Yurawecz, MP Whittaker, P Yu, LL TI Fatty acid composition and antioxidant properties of cold-pressed marionberry, boysenberry, red raspberry, and blueberry seed oils SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE alpha-linolenic acid; fatty acid composition; antioxidant; phenolic; tocopherol; carotenoid; radical scavenging activity; OSI; berry seed oil ID HEART-DISEASE; LINOLEIC-ACID; FREE-RADICALS; WHEAT-GRAIN; RISK; HEALTH; CANCER; ASSAY; RATS; BRAN AB Cold-pressed marionberry, boysenberry, red raspberry, and blueberry seed oils were evaluated for their fatty acid composition, carotenoid content, tocopherol profile, total phenolic content (TPC), oxidative stability index (OSI), peroxide value, and antioxidant properties. All tested seed oils contained significant levels of alpha-linolenic acid ranging from 19.6 to 32.4 g per 100 g of oil, along with a low ratio of n-6/n-3 fatty acids (1.64-3.99). The total carotenoid content ranged from 12.5 to 30.0 mumoles per kg oil. Zeaxanthin was the major carotenoid compound in all tested berry seed oils, along with beta-carotene, lutein, and cryptoxanthin. Total tocopherol was 260.6-2276.9 mumoles per kg oil, including alpha-, gamma-, and delta-tocopherols. OSI values were 20.07, 20.30, and 44.76 h for the marionberry, red raspberry, and boysenberry seed oils, respectively. The highest TPC of 2.0 mg gallic acid equivalents per gram of oil was observed in the red raspberry seed oil, while the strongest oxygen radical absorbance capacity was in boysenberry seed oil extract (77.9 mumol trolox equivalents per g oil). All tested berry seed oils directly reacted with and quenched DPPH radicals in a dose- and time-dependent manner. These data suggest that the cold-pressed berry seed oils may serve as potential dietary sources of tocopherols, carotenoids, and natural antioxidants. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Yu, LL (reprint author), Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. EM LY46@umail.umd.edu NR 33 TC 105 Z9 113 U1 4 U2 35 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD FEB 9 PY 2005 VL 53 IS 3 BP 566 EP 573 DI 10.1021/jf048615t PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 894HX UT WOS:000226782900012 PM 15686403 ER PT J AU Yang, YS Faustino, PJ Pine, PS Davis, H Grunberg, N Phillips, J Lyon, RC Yu, LX Ciavarella, AB Del Grosso, AV Hanig, JP AF Yang, YS Faustino, PJ Pine, PS Davis, H Grunberg, N Phillips, J Lyon, RC Yu, LX Ciavarella, AB Del Grosso, AV Hanig, JP TI Determination of plasma and brain levels of isotretinoin in mice following single oral dose by high-performance liquid chromatography SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE accutane; isotretinoin; HPLC; pharmacokinetics; mice ID TRANS-RETINOIC ACID; 13-CIS-RETINOIC ACID; ALL-TRANS; 4-OXO-13-CIS-RETINOIC ACID; CYNOMOLGUS MONKEY; MAJOR METABOLITE; HUMAN-BLOOD; PHARMACOKINETICS; IDENTIFICATION; VOLUNTEERS AB An isocratic reversed-phase high-performance liquid chromatographic method was established and validated according to FDA's Guidance for Industry, "Bioanalytical Method Validation", for the determination of isotretinoin in plasma and brain tissue from mice following single and multiple oral doses of Accutane(R). Plasma sample preparation included deproteination with acetonitrile-perchloric acid followed by centrifugation. Brain tissue was homogenized and extracted with acetonitrile-perchlorie acid followed by centrifugation. The supernatants were analyzed by high-performance liquid chromatography (HPLC). Benz[alpha]anthrancene-7,12-dione was used as the internal standard. Chromatographic separation was achieved on a C-18 column using an acetonitrile-aqueous 0.5% acetic acid (85:15, v/v) elution. The average 9 extraction efficiency was >95% for plasma and >82% for brain. The lower limit of quantification was 30 ng/mL for plasma and was 30 ng/0.1 g for brain tissue, respectively. The linear range for plasma was 30-600 ng/mL, and 15-300 ng/0.1 g for brain. Maximum concentrations of isotretinoin in both plasma and brain were observed at I h after single oral dosing (25 mg/kg). The maximum concentrations in plasma and brain were 2.36 mug/mL and 0.34 mug/g, respectively. The mean area under curve (AUC) in plasma was 6.13 mug h/mL. The mean eliminate half-life in plasma was estimated as 46 min. (C) 2004 Published by Elsevier B.V. C1 US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Silver Spring, MD 20993 USA. US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol, Silver Spring, MD 20993 USA. Uniformed Serv Univ Hlth Sci, Dept Med & Clin Psychol, Bethesda, MD 20814 USA. US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Rockville, MD 20855 USA. US FDA, Ctr Biol Evaluat & Res, Analyt Chem Lab, Rockville, MD 20852 USA. RP Faustino, PJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM faustinop@cder.fda.gov NR 28 TC 3 Z9 5 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD FEB 7 PY 2005 VL 37 IS 1 BP 157 EP 163 DI 10.1016/j.jpba.2004.10.002 PG 7 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 897OJ UT WOS:000227014200019 PM 15664756 ER PT J AU Maniere, I Godard, T Doerge, DR Churchwell, MI Guffroy, M Laurentie, M Poul, JM AF Maniere, I Godard, T Doerge, DR Churchwell, MI Guffroy, M Laurentie, M Poul, JM TI DNA damage and DNA adduct formation in rat tissues following oral administration of acrylamide SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE acrylamide; DNA damage; comet assay; DNA adducts; in vivo; rat ID COMET ASSAY; IN-VIVO; N-METHYLOLACRYLAMIDE; HEMOGLOBIN ADDUCTS; HEATED FOODSTUFFS; ALKYLATION DAMAGE; MAILLARD REACTION; MAMMALIAN-CELLS; PROPYLENE-OXIDE; FRIED POTATOES AB Acrylamide is present as a contaminant in the human diet in heated food products. It has been found to be carcinogenic in laboratory rats and has been classified as probably carcinogenic in humans. In order to clarify the possible involvement of a primary genotoxic mechanism in acrylamide-induced carcinogenicity, both the presence of DNA damage, measured by the comet assay, and the formation of N7-(2-carbamoyl-2-hydroxyethyl)guanine (N7-GA-Gua) and N3-(2-carbamoyl-2-hydroxyethyl)adenine (M-GA-Ade), derived from reaction of the active metabolite glycidamide (GA) with the DNA, analyzed by LUMS/MS, were assessed in selected rat tissues. Rats were administered with single oral doses of acrylamide (18, 36 or 54 mg/kg body weight (b.w.) and the organs (blood leukocytes, brain, bone marrow, liver, testes and adrenals) were sampled at different times after treatment. Results from GA-induced DNA adduct measurements indicated a relatively even organ distribution of the adducts in brain, testes and liver. Organ-specificity in acrylamide carcinogenesis can therefore not be explained by a selective accumulation of GA-DNA adducts in the target organs, at least not after a single dose exposure. The DNA adduct profiles and half-lives were similar in the different organs; except that the N3-GA-Ade adduct was more rapidly removed from tissues than the N7-GA-Gua adduct. Increased extent of DNA migration, as measured by the in vivo rat comet assay, was found in brain and testes, and these specific results seem to be in accordance with the known organ-specificity in acrylamide carcinogenesis in rat. Only weak and transient DNA damage was recorded in the liver, bone marrow and adrenals. The DNA-damaging effect of the compound observed in the blood leukocytes could be a simple biomarker of acrylamide exposure and genotoxicity. (C) 2004 Elsevier B.V. All rights reserved. C1 Agence Francaise Secur Sanitaire Aliments, Lab Etud Rech Medicaments Vet & Desinfectants, F-35302 Fougeres, France. Agence Francaise Secur Sanitaire Aliments, Agence Natl Medicament Vet, F-35302 Fougeres, France. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Paris 13, Ctr Rech, Aventis Pharma, Vitry Sur Seine, France. RP Maniere, I (reprint author), Agence Francaise Secur Sanitaire Aliments, Lab Etud Rech Medicaments Vet & Desinfectants, BP 90203, F-35302 Fougeres, France. EM i.maniere@fougeres.afssa.fr NR 51 TC 55 Z9 71 U1 0 U2 18 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD FEB 7 PY 2005 VL 580 IS 1-2 BP 119 EP 129 DI 10.1016/j.mrgentox.2004.10.012 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 898DI UT WOS:000227055900013 PM 15668114 ER PT J AU Doerge, DR da Costa, GG McDaniel, LP Churchwell, MI Twaddle, NC Beland, FA AF Doerge, DR da Costa, GG McDaniel, LP Churchwell, MI Twaddle, NC Beland, FA TI DNA adducts derived from administration of acrylamide and glycidamide to mice and rats SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE acrylamide; glycidamide; mass spectrometry; DNA adducts ID HEMOGLOBIN ADDUCTS; N-METHYLOLACRYLAMIDE; DRINKING-WATER; MOUSE; ACRYLONITRILE; ONCOGENICITY; MUTAGENICITY; GENOTOXICITY; METABOLITE; TOXICITY AB Acrylamide (AA) is an important industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in chronic rodent bioassays. Recent findings of AA in many common starchy foods have sparked renewed interest in determining toxic mechanisms and in understanding the cancer, neurotoxicity, and reproductive risks from typical human exposures. Dosing mice and rats with AA (50 mg/kg) led to presence of glycidamide (GA) in serum and tissues. Furthermore, GA-derived DNA adducts of adenine and guanine were formed in all tissues examined, including both target tissues identified in rodent carcinogenicity bioassays and in non-target tissues. Dosing rats and mice with an equimolar amount of GA typically produced higher levels of DNA adducts than observed with AA. Kinetics of DNA adduct formation and accumulation were measured following oral administration of a single dose of AA (50 mg/kg) or from repeat dosing (1 mg/kg/day), respectively. The formation of these DNA adducts is consistent with previously reported multagenicity of AA and GA in vitro, which involved reaction of GA with adenine and guanine bases. These results provide strong support for a genotoxic mechanism of AA carcinogenicity in rodents. The kinetic/biomarker approaches described here may represent a meaningful way to extrapolate cancer risks to actual human exposures from food, which are much lower. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov NR 34 TC 106 Z9 108 U1 2 U2 16 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD FEB 7 PY 2005 VL 580 IS 1-2 BP 131 EP 141 DI 10.1016/j.mrgentox.2004.10.013 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 898DI UT WOS:000227055900014 PM 15668115 ER PT J AU Graham, DJ Campen, D Hui, R Spence, M Cheetham, C Levy, G Shoor, S Graham, D AF Graham, DJ Campen, D Hui, R Spence, M Cheetham, C Levy, G Shoor, S Graham, D TI Risk of acute myocardial infarction and sudden cardiac death in patients treated with cyclo-oxygenase 2 selective and non-selective non-steroidal anti-inflammatory drugs: nested case-control study SO LANCET LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CORONARY HEART-DISEASE; CARDIOVASCULAR EVENTS; RHEUMATOID-ARTHRITIS; GASTROINTESTINAL TOXICITY; ENDOTHELIAL FUNCTION; COX-2 INHIBITION; ELDERLY PERSONS; CLINICAL-TRIALS; NAPROXEN AB Background Controversy has surrounded the question about whether high-dose rofecoxib increases or naproxen decreases the risk of serious coronary heart disease. We sought to establish if risk was enhanced with rofecoxib at either high or standard doses compared with remote non-steroidal anti-inflammatory drug (NSAID) use or celecoxib use, because celecoxib was the most common alternative to rofecoxib. Methods We used data from Kaiser Permanente in California to assemble a cohort of all patients age 18-84 years treated with a NSAID between Jan 1, 1999, and Dec 31, 2001, within which we did a nested case-control study. Cases of serious coronary heart disease (acute myocardial infarction and sudden cardiac death) were risk-set matched with four controls for age, sex, and health plan region. Current exposure to cyclo-oxygenase 2 selective and non-selective NSAIDs was compared with remote exposure to any NSAID, and rofecoxib was compared with celecoxib. Findings During 2 302 029 person-years of follow-up, 8143 cases of serious coronary heart disease occurred, of which 2210 (27.1%) were fatal. Multivariate adjusted odds ratios versus celecoxib were: for rofecoxib (all doses), 1.59 (95% CI 1.10-2.32, p=0.015); for rofecoxib 25 mg/day or less, 1.47 (0.99-2.17, p=0.054); and for rofecoxib greater than 25 mg/day, 3.58 (1.27-10.11, p=0.016). For naproxen versus remote NSAID use the adjusted odds ratio was 1.14 (1.00-1.30, p=0.05). Interpretation Rofecoxib use increases the risk of serious coronary heart disease compared with celecoxib use. Naproxen use does not protect against serious coronary heart disease. C1 US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Kaiser Permanente, Permanente Med Grp, Oakland, CA USA. Kaiser Permanente, Pharm Outcomes Res Grp, Oakland, CA USA. Kaiser Permanente, So Calif Permanente Med Grp, Oakland, CA USA. Vanderbilt Univ, Sch Med, Dept Prevent Med, Nashville, TN 37212 USA. Vanderbilt Univ, Sch Med, Ctr Educ & Res Therapeut, Nashville, TN 37212 USA. Nashville Vet Adm Med Ctr, Ctr Geriatr Res Educ & Clin, Nashville, TN USA. RP Graham, DJ (reprint author), US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. EM GRAHAMD@cder.fda.gov FU AHRQ HHS [HS1-0384]; FDA HHS [FD-U-001641] NR 41 TC 545 Z9 575 U1 3 U2 31 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD FEB 5 PY 2005 VL 365 IS 9458 BP 475 EP 481 DI 10.1016/S0140-6736(05)17864-7 PG 7 WC Medicine, General & Internal SC General & Internal Medicine GA 894SS UT WOS:000226812500024 PM 15705456 ER PT J AU Braun, MM Wise, RP Wood, JJ AF Braun, MM Wise, RP Wood, JJ TI Epoetin and pure red-cell aplasia SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. RP Braun, MM (reprint author), US FDA, Rockville, MD 20852 USA. EM braunm@cber.fda.gov NR 2 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 3 PY 2005 VL 352 IS 5 BP 511 EP 512 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 893NE UT WOS:000226725400022 PM 15689594 ER PT J AU Budnitz, DS Pollock, DA Mendelsohn, AB Weidenbach, KN McDonald, AK Annest, JL AF Budnitz, DS Pollock, DA Mendelsohn, AB Weidenbach, KN McDonald, AK Annest, JL TI Emergency department visits for outpatient adverse drug events: Demonstration for a national surveillance system SO ANNALS OF EMERGENCY MEDICINE LA English DT Article ID HOSPITALIZED-PATIENTS; PREVENTABILITY; INJURIES AB Study objective: This project demonstrates the operational feasibility and epidemiologic usefulness of modifying a national injury surveillance system for active surveillance of outpatient adverse drug events treated in hospital emergency departments (EDs). Methods: Coders were trained to identify and report physician-documented adverse drug event's in 9 of 64 National Electronic Injury Surveillance System-All Injury Program hospital EDs (occurring July 17, 2002, to September 30, 2002). Feasibility was measured by timeliness and completeness of adverse drug event reporting. Outcomes (ED discharge disposition and injury type) and associated variables (age, sex, drug category, and adverse drug event mechanism) were measured. Results: There were 598 patients with physician-documented adverse drug events (7 per 1,000 visits). Nearly 70% of adverse drug event cases were reported within 7 days of the ED visit; key data elements (drug name, disposition from ED, and event description) were completed for more than 98% of cases. Nine percent of patients with adverse drug events were hospitalized, and unintentional overdoses was the most common mechanism of adverse drug events (39%). Patients with unintentional overdoses were more likely to be hospitalized than those with adverse drug reactions (adjusted odds ratio [OR] 5.9, 95% confidence interval [Cl] 2.2 to 16; adverse-effects referent; allergic reactions, adjusted OR 0.7, 95% Cl 0.2 to 2.4). Warfarin and insulins were associated with 16% of adverse drug events overall and 33% of-adverse drug events in patients aged 50 years or older. Conclusion: Active surveillance for outpatient adverse drug events using the National Electronic Injury Surveillance System-All Injury Program is feasible. Ongoing, population-based ED surveillance can help characterize the burden of outpatient adverse drug events, prioritize areas for further research and intervention, and monitor progress on adverse drug event prevention. C1 CDCP, Div Appl Publ Hlth Training, Epidem Intelligence Serv, Program Epidemiol, Atlanta, GA 30341 USA. CDCP, Natl Ctr Injury Prevent & Control, Div Injury & Disabil Outcomes & Programs, Atlanta, GA 30341 USA. Off Drug Safety Food & Drug Adm, Div Surveillance Res & Commun Support, Rockville, MD USA. Consumer Prod Safety Commiss, Div Hazard & Injury Data Syst, Directorate Epidemiol, Washington, DC USA. Natl Ctr Injury Prevent & Control, Off Stat & Programming, Ctr Dis Control & Prevent, Atlanta, GA USA. RP Budnitz, DS (reprint author), CDC, NCIPC, DIDOP, 4770 Buford Hwy,MS-F41, Atlanta, GA 30341 USA. EM dbudnitz@cdc.gov NR 36 TC 42 Z9 43 U1 4 U2 5 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0196-0644 J9 ANN EMERG MED JI Ann. Emerg. Med. PD FEB PY 2005 VL 45 IS 2 BP 197 EP 206 DI 10.1016/j.annemergmed.2004.09.020 PG 10 WC Emergency Medicine SC Emergency Medicine GA 893GP UT WOS:000226707600013 PM 15671977 ER PT J AU Belluco, C Calvert, V Mammano, E Espina, VE Wulfkuhle, JD Nitti, D Lise, M Liotta, LA Petricoin, EF AF Belluco, C Calvert, V Mammano, E Espina, VE Wulfkuhle, JD Nitti, D Lise, M Liotta, LA Petricoin, EF TI Kinase substrate protein microarray analysis reveals a specific signaling pathway profile in colorectal cancer liver metastasis SO ANNALS OF SURGICAL ONCOLOGY LA English DT Meeting Abstract CT 58th Annual Cancer Symposium CY MAR 03-06, 2005 CL Atlanta, GA SP Soc Surg Oncol C1 Univ Padua, Dept Oncol & Surg Sci, Padua, Italy. US FDA, CBER, Bethesda, MD 20014 USA. NCI, CCR, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1068-9265 J9 ANN SURG ONCOL JI Ann. Surg. Oncol. PD FEB PY 2005 VL 12 IS 2 SU S BP S78 EP S78 PG 1 WC Oncology; Surgery SC Oncology; Surgery GA 895FU UT WOS:000226847100226 ER PT J AU Rafii, F Park, M Novak, JS AF Rafii, F Park, M Novak, JS TI Alterations in DNA gyrase and topoisomerase IV in resistant mutants of Clostridium perfringens found after in vitro treatment with fluoroquinolones SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID ESCHERICHIA-COLI; QUINOLONE RESISTANCE; STREPTOCOCCUS-PNEUMONIAE; BACTEROIDES-FRAGILIS; ANAEROBIC-BACTERIA; DETERMINING REGION; POINT MUTATION; GATIFLOXACIN; MOXIFLOXACIN; MECHANISM AB To compare mutations in the DNA gyrase (gyrA and gyrB) and topoisomerase IV (parC and parE) genes of Clostridium perfringens, which are associated with in vitro exposure to fluoroquinolones, resistant mutants were selected from eight strains by serial passage in the presence of increasing concentrations of norfloxacin, ciprofloxacin, gatifloxacin, or trovafloxacin. The nucleotide sequences of the entire gyrA, gyrB, parC, and parE genes of 42 mutants were determined. DNA gyrase was the primary target for each fluoroquinolone, and topoisomerase IV was the secondary target. Most mutations appeared in the quinolone resistance-determining regions of gyrA (resulting in changes of Asp-87 to Tyr or Gly-81 to Cys) and parC (resulting in changes of Asp-93 or Asp-88 to Tyr or Ser-89 to Ile); only two mutations were found in gyrB, and only two mutations were found in parE. More mutants with multiple gyrA and parC mutations were produced with gatifloxacin than with the other fluoroquinolones tested. Allelic diversity was observed among the resistant mutants, for which the drug MICs increased 2- to 256-fold. Both the structures of the drugs and their concentrations influenced the selection of mutants. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. USDA ARS, ERRC, Microbial Food Safety Res Unit, Wyndmoor, PA 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 37 TC 18 Z9 19 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD FEB PY 2005 VL 49 IS 2 BP 488 EP 492 DI 10.1128/AAC.49.2.488-492.2005 PG 5 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 893HM UT WOS:000226709900002 PM 15673722 ER PT J AU Dong, L Ito, SC Ishii, KJ Klinman, DM AF Dong, L Ito, SC Ishii, KJ Klinman, DM TI Suppressive oligodeoxynucleotides delay the onset of glomerulonephritis and prolong survival in lupus-prone NZB x NZW mice SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INDUCED IMMUNE ACTIVATION; ANTI-DNA ANTIBODIES; INTERFERON-GAMMA; BACTERIAL-DNA; MURINE LUPUS; IFN-GAMMA; T-CELL; INDUCED ARTHRITIS; CPG MOTIFS; ERYTHEMATOSUS AB Objective. Synthetic oligodeoxynucleotides (ODN) expressing TTAGGG motifs suppress the production of proinflammatory cytokines and have been proven effective at blocking the development of certain organ-specific autoimmune diseases. We undertook this study to determine whether suppressive ODN alter the development of systemic antoimmunity, by evaluating their effect on the progression of lupus-like disease in NZB X NZW (NZB/NZW) mice. Methods. We repeatedly treated mice with suppressive ODN before or after the onset of proteinuria. We monitored the effect of treatment on the onset, severity, and immunologic correlates of disease. Results. Treatment with suppressive ODN significantly prolonged lifespan while delaying the onset and progression of glomerulonephritis in NZB/NZW mice. Clinical improvement was accompanied by a significant reduction in anti-double-stranded DNA autoantibody production and by significantly reduced secretion of interferon-gamma and interleukin-12 in vivo. Conclusion. Suppressive ODN may be of benefit in the treatment of chronic systemic autoimmune diseases such as systemic lupus erythematosus. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, 29 Lincoln Dr,Bldg 29A,Room 3D10, Bethesda, MD 20892 USA. EM Klinman@CBER.FDA.GOV RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 49 TC 104 Z9 113 U1 0 U2 2 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 FEB PY 2005 VL 52 IS 2 BP 651 EP 658 DI 10.1002/art.20810 PG 8 WC Rheumatology SC Rheumatology GA 896BR UT WOS:000226910100035 PM 15692999 ER PT J AU O'Neill, RT AF O'Neill, RT TI A tribute to Joachim Rohmel upon his retirement from the Federal Institute of Drugs SO BIOMETRICAL JOURNAL LA English DT Biographical-Item C1 US FDA, Ctr Drug Evaluat & Res, Off Biostat, Rockville, MD 20857 USA. RP O'Neill, RT (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat, 5600 Fishers Lane,HFD 240, Rockville, MD 20857 USA. EM ONeill@cder.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD FEB PY 2005 VL 47 IS 1 BP 10 EP 11 DI 10.1002/bimj.200410091 PG 2 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 904QY UT WOS:000227514000004 ER PT J AU Hung, HMJ Wang, SJ O'Neill, R AF Hung, HMJ Wang, SJ O'Neill, R TI A regulatory perspective on choice of margin and statistical inference issue in non-inferiority trials SO BIOMETRICAL JOURNAL LA English DT Article; Proceedings Paper CT Conference on Therapeutic Equivalence - Clinical Issues and Statistical Methodology in Noninferiority Trials CY DEC 12-13, 2003 CL Dusseldorf, RUSSIA DE efficacy; non-inferiority margin; preservation of active control effect; historical trial ID ACTIVE-CONTROLLED-TRIALS; PLACEBO-CONTROLLED TRIALS; CLINICAL-TRIALS; NONINFERIORITY TRIALS; PRACTICAL ISSUES; EQUIVALENCE; DESIGN; DELTA AB Without a placebo arm, any non-inferiority inference involving assessment of the placebo effect under the active control trial setting is, difficult. The statistical risk for falsely concluding non-inferiority cannot be evaluated unless the constancy assumption approximately holds that the effect of the active control under the historical trial setting where the control effect can be assessed carries to the noninferiority trial setting. The constancy assumption cannot be checked because of missing the placebo arm in the non-inferiority trial. Depending on how serious the violation of the assumption is thought to be, one may need to seek an alternative design strategy that includes a cushion for a very conservative non-inferiority analysis or shows superiority of the experimental treatment over the control. Determination of the non-inferiority margin depends on what objective the non-inferiority analysis is intended to achieve. The margin can be a fixed margin or a margin functionally defined. Between-trial differences always exist and need to be properly considered. C1 US FDA, CDER, OPaSS, Div Biometr 1, Rockville, MD 20852 USA. US FDA, CDER, OPaSS, Div Biometr 2, Rockville, MD 20857 USA. US FDA, CDER, OPaSS, Off Biostat, Rockville, MD 20857 USA. RP Hung, HMJ (reprint author), US FDA, CDER, OPaSS, Div Biometr 1, HFD-710,Room 5062,WOC2,1451 Rockville Pike, Rockville, MD 20852 USA. EM hung@cder.fda.gov NR 32 TC 63 Z9 71 U1 1 U2 8 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD FEB PY 2005 VL 47 IS 1 BP 28 EP 36 DI 10.1002/bimj.200410084 PG 9 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 904QY UT WOS:000227514000006 PM 16395994 ER PT J AU Tsong, Y Zhang, J AF Tsong, Y Zhang, J TI Testing superiority and non-inferiority hypotheses in active controlled clinical trials SO BIOMETRICAL JOURNAL LA English DT Article; Proceedings Paper CT Conference on Therapeutic Equivalence - Clinical Issues and Statistical Methodology in Noninferiority Trials CY DEC 12-13, 2003 CL Dusseldorf, RUSSIA DE superiority test; non-inferiority test; switching; simultaneous test ID STATISTICAL-METHODS; PLACEBO; EQUIVALENCE AB Switching between testing for superiority and non-inferiority has been an important statistical issue in the design and analysis of active controlled clinical trial. In practice, it is often conducted with a two-stage testing procedure. It has been assumed that there is no type I error rate adjustment required when either switching to test for non-inferiority once the data fail to support the superiority claim or switching to test for superiority once the null hypothesis of non-inferiority is rejected with a pre-specified non-inferiority margin in a generalized historical control approach. However, when using a cross-trial comparison approach for non-inferiority testing, controlling the type I error rate sometimes becomes an issue with the conventional two-stage procedure. We propose to adopt a single-stage simultaneous testing concept as proposed by Ng (2003) to test both non-inferiority and superiority hypotheses simultaneously. The proposed procedure is based on Fieller's confidence interval procedure as proposed by Hauschke et al. (1999). C1 US FDA, CDER, OPaSS, Off Biostat, Rockville, MD 20857 USA. RP Tsong, Y (reprint author), US FDA, CDER, OPaSS, Off Biostat, Rockville, MD 20857 USA. EM Tsong@cder.fda.gov NR 19 TC 15 Z9 15 U1 0 U2 3 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PD FEB PY 2005 VL 47 IS 1 BP 62 EP 74 DI 10.1002/bimj.200410089 PG 13 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 904QY UT WOS:000227514000009 PM 16395997 ER PT J AU Calvo, KR Liotta, LA Petricoin, EF AF Calvo, KR Liotta, LA Petricoin, EF TI Clinical proteomics: From biomarker discovery and cell signaling profiles to individualized personal therapy SO BIOSCIENCE REPORTS LA English DT Article DE Clinical Proteomics; mass spectroscopy; protein microarrays; combinatory theraphy; oncology; pathology; microdissection ID LASER CAPTURE MICRODISSECTION; HUMAN BREAST-CANCER; PHASE PROTEIN MICROARRAYS; PROSTATE-CANCER; GENE-EXPRESSION; TISSUE PROTEOMICS; OVARIAN-CANCER; POTENTIAL BIOMARKERS; PATTERN DIAGNOSTICS; MASS-SPECTROMETRY AB The discovery of new highly sensitive and specific biomarkers for early disease detection and risk stratification coupled with the development of personalized "designer" therapies holds the key to future treatment of complex diseases such as cancer. Mounting evidence confirms that the low molecular weight (LMW) range of the circulatory proteome contains a rich source of information that may be able to detect early stage disease and stratify risk. Current mass spectrometry (MS) platforms can generate a rapid and high resolution portrait of the LMW proteome. Emerging novel nanotechnology strategies to amplify and harvest these LMW biomarkers in vivo or ex vivo will greatly enhance our ability to discover and characterize molecules for early disease detection, subclassification and prognostic capability of current proteomics modalities. Ultimately genetic mutations giving rise to disease are played out and manifested on a protein level, involving derangements in protein function and information flow within diseased cells and the interconnected tissue microenvironment. Newly developed highly sensitive, specific and linearly dynamic reverse phase protein microarray systems are now able to generate circuit maps of information flow through phosphoprotein networks of pure populations of microdissected tumor cells obtained from patient biopsies. We postulate that this type of enabling technology will provide the foundation for the development of individualized combinatorial therapies of molecular inhibitors to target tumor-specific deranged pathways regulating key biologic processes including proliferation, differentiation, apoptosis, immunity and metastasis. Hence future therapies will be tailored to the specific deranged molecular circuitry of an individual patient's disease. The successful transition of these groundbreaking proteomic technologies from research tools to integrated clinical diagnostic platforms will require ongoing continued development, and optimization with rigorous standardization development and quality control procedures. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Off Cell Therapies & Gene Therapies, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Calvo, KR (reprint author), NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. EM calvok@mail.nih.gov RI Calvo, Katherine/A-8109-2009; OI Calvo, Katherine/0000-0002-0771-4191 NR 76 TC 91 Z9 96 U1 2 U2 14 PU PORTLAND PRESS LTD PI LONDON PA THIRD FLOOR, EAGLE HOUSE, 16 PROCTER STREET, LONDON WC1V 6 NX, ENGLAND SN 0144-8463 J9 BIOSCIENCE REP JI Biosci. Rep. PD FEB PY 2005 VL 25 IS 1-2 BP 107 EP 125 DI 10.1007/s10540-005-2851-3 PG 19 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 973ZH UT WOS:000232560600009 PM 16222423 ER PT J AU Lozier, JN Tayebi, N Zhang, P AF Lozier, JN Tayebi, N Zhang, P TI Mapping of genes that control the antibody response to human factor IX in mice SO BLOOD LA English DT Article ID COAGULATION-FACTOR-IX; SEVERE HEMOPHILIA-A; INHIBITOR DEVELOPMENT; FACTOR-VIII; TRANSGENE EXPRESSION; NEPHROTIC SYNDROME; IMMUNE TOLERANCE; MOUSE; SPECIFICITY; GENETICS AB We tested the hypothesis that the antibody response to human factor IX in mice is controlled by genetic factors, especially histocompatibility antigens. Seven inbred mouse strains were immunized against human factor IX by adenoviral gene transfer or serial injections of human factor IX protein. A/J mice had the highest antibody response and 2 C57 mouse strains had the lowest response. We used the adenovirus vector to immunize 26 recombinant inbred mouse strains (AXB and BXA) derived from AM and C57BL/6J mice and observed highly significant linkage (logarithmic odds [LOD] scores similar to4.8) for the polymorphic D17Mit62 marker that is 1 centimorgan (similar to300 000 base pair [bpl]) from the mouse major histocompatibility complex (MHC) locus (H-2). Experiments in mice with chimeric MHC genes indicated that class laK or class II H-2 (or both) genes were critical, but other genes contributed to the antibody response. Polymorphic markersfrom chromosomes 1 and 10 that are near important immunoregulatory genes such as interleukin 10 and the interferon-gamma gene show suggestive linkage (LOD scores of similar to2.3-2.6) to the factor IX antibody response. This study confirms the hypothesis that H-2 (and other) genes control factor IX antibody development in mice and suggests their potential importance for factor IX antibody development in humans with hemophilia B. (C) 2005 by The American Society of Hematology. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Lozier, JN (reprint author), 1401 Rockville Pike HFM 340, Rockville, MD 20852 USA. EM lozier@cber.fda.gov NR 33 TC 24 Z9 24 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 FEB 1 PY 2005 VL 105 IS 3 BP 1029 EP 1035 DI 10.1182/blood-2004-03-1126 PG 7 WC Hematology SC Hematology GA 891QX UT WOS:000226596700028 PM 15383460 ER PT J AU Ambrosone, CB Ahn, J Singh, KK Rezaishiraz, H Furberg, H Sweeney, C Coles, B Trovato, A AF Ambrosone, CB Ahn, J Singh, KK Rezaishiraz, H Furberg, H Sweeney, C Coles, B Trovato, A TI Polymorphisms in genes related to oxidative stress (MPO, MnSOD, CAT) and survival after treatment for breast cancer SO CANCER RESEARCH LA English DT Article ID MANGANESE SUPEROXIDE-DISMUTASE; MYELOPEROXIDASE (-463)G->A POLYMORPHISM; PROMOTER REGION; ALLELIC ASSOCIATION; HYDROGEN-PEROXIDE; GASTRIC-CANCER; CELL-LINES; RISK; CATALASE; CHEMOTHERAPY AB The proximate cause of cancer cell death by radiation therapy and a number of therapeutic agents is through generation of reactive oxygen species, resulting in DNA damage as well as mitochondrial membrane disruption, triggering the apoptotic cascade. Because mitochondrial manganese superoxide dismutase catalyzes conversion of superoxide radicals to H2O2, with catalase neutralizing H2O2 and myeloperoxidase converting H2O2 to highly reactive hypochlorous acid, we hypothesized that gene variants could impact the efficacy of treatment for breast cancer and improve survival. Women who were treated with radiation and/or chemotherapy for incident breast cancer at the Arkansas Cancer Research Center from 1985 to 1996 were identified. DNA was extracted from paraffin-embedded normal tissue (n = 279), and MnSOD, CAT, and MPO genotypes were determined using mass spectrometry. Cox proportional hazards models were adjusted for age, race, stage with node status, and estrogen receptor and progesterone receptor status. Women who were homozygous for MPO I G alleles, associated with increased transcription, had better survival (hazard ratio, 0.60; 95% confidence interval, 0.38-0.95; P = 0.03) than those with common alleles. Both CAT TT and MnSOD CC genotypes were associated with nonsignificant reduced hazard of death. When we combined genotypes associated with higher levels of reactive oxygen species for MnSOD and MPO, women with MnSOD CC and MPO GG genotypes had a Mold decrease in hazard of death (hazard ratio, 0.33; 95% confidence interval, 0.13-0.80; P = 0.01). These data indicate that gene variants that impact oxidative stress modify prognosis after treatment for breast cancer. C1 New York State Dept Hlth, Roswell Pk Canc Inst, Dept Epidemiol, Buffalo, NY 14263 USA. New York State Dept Hlth, Roswell Pk Canc Inst, Dept Canc Genet, Buffalo, NY 14263 USA. New York State Dept Hlth, Roswell Pk Canc Inst, Dept Hlth Behav, Buffalo, NY 14263 USA. Cornell Univ, Div Nutr Sci, Ithaca, NY USA. Univ N Carolina, Dept Genet, Chapel Hill, NC USA. Hlth Res Ctr, Dept Family & Prevent Med, Salt Lake City, UT USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR USA. Mt Sinai Sch Med, Dept Oncol Sci, New York, NY USA. RP Ambrosone, CB (reprint author), New York State Dept Hlth, Roswell Pk Canc Inst, Dept Epidemiol, Elm & Carlton St, Buffalo, NY 14263 USA. EM christine.ambrosone@roswellpark.org OI Sweeney, Carol/0000-0003-1113-7160 NR 45 TC 91 Z9 94 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 FEB 1 PY 2005 VL 65 IS 3 BP 1105 EP 1111 PG 7 WC Oncology SC Oncology GA 893SN UT WOS:000226739600056 PM 15705913 ER PT J AU Cherng, SH Xia, QS Blankenship, LR Freeman, JP Wamer, WG Howard, PC Fu, PP AF Cherng, SH Xia, QS Blankenship, LR Freeman, JP Wamer, WG Howard, PC Fu, PP TI Photodecomposition of retinyl palmitate in ethanol by UVA light-formation of photodecomposition products, reactive oxygen species, and lipid peroxides SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SINGLET OXYGEN; DNA-ADDUCTS; CHLORAL HYDRATE; VITAMIN-A; ACID; SKIN; PHOTOMUTAGENICITY; DAMAGE; ANHYDRORETINOL; IDENTIFICATION AB Photodecomposition of retinyl palmitate (RP), an ester and the storage form of vitamin A (retinol), in ethanol under UVA light irradiation was studied. The resulting photodecomposition products were separated by reversed-phase HPLC and identified by spectral analysis and comparison with the chromatographic and spectral properties of synthetically prepared standards. The identified products include 5,6-epoxy-RP, 4-keto-RP, 11-ethoxy-12-hydroxy-RP, 13-ethoxy-14-hydroxy-RP, anhydroretinol (AR), palmitic acid, ethyl palmitate, and four tentatively assigned cis and trans isomeric 15-ethoxy-ARs. AR was formed as a mixture of all-trans-AR, 6Z-cis-AR, 8Z-cis-AR, and 12Z-cis-AR with all-trans-AR predominating. 5,6-Epoxy-RP, 4-keto-RP, 11-ethoxy-12-hydroxy-RP, and 13-ethoxy-14-hydroxy-RP were also formed from reaction of RP with alkylperoxy radicals generated by thermal decomposition of 2,2'-azobis(2,4-dimethylvaleronitrile). Formation of these photodecomposition products was inhibited in the presence of sodium azide (NaN3) a free radical inhibitor. These results suggest that formation of 5,6-epoxy-RP, 4-keto-RP, 11-ethoxy-12-hydroxy-RP, and 13-ethoxy-14-hydroxy-RP from photoirradiation of RP is mediated by a light-initiated free radical chain reaction. AR and the isomeric 11-ethoxy-ARs were not formed from reaction of RP with alkylperoxy radicals generated from 2,2'-azobis(2,4-dimethylvaleronitrile), and their formation was not inhibited when NaN3 was present during the photoirradiation of RP. We propose that these products were formed through an ionic photodissociation mechanism, which is similar to the reported formation of AR through ionic photodissociation of retinyl acetate. RP and all its identified photodecomposition products described above (i) were not mutagenic in Salmonella typhimurium tester strains TA98, TA100, TA102, and TA104 in the presence and absence of S9 activation enzymes, (ii) were not photomutagenic in Salmonella typhimurium TA102 upon UVA irradiation, and (iii) did not bind with calf thymus DNA in the presence of microsomal metabolizing enzymes. These results suggest that RP and its decomposition products are not genotoxic; however, photoirradiation of RP, 5,6-epoxy-RP, and AR with UVA light in the presence of methyl linoleate resulted in lipid peroxide (methyl linoleate hydroperoxides) formation. The lipid peroxide formation was inhibited by dithiothreitol (DTT) (free radical scavenger), NaN3 (singlet oxygen and free radical scavenger), and superoxide dismutase (SOD) (superoxide scavenger) but was enhanced by the presence of deuterium oxide (D2O) (enhancement of singlet oxygen lifetime). These results suggest that photoirradiation of RP, 5,6-epoxy-RP, and AR by UVA light generated reactive oxygen species resulting in lipid (methyl linoleate) peroxidation. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Fu, PP (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM pfu@nctr.fda.gov NR 54 TC 41 Z9 42 U1 1 U2 9 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 FEB PY 2005 VL 18 IS 2 BP 129 EP 138 DI 10.1021/tx049807l PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 899TM UT WOS:000227168000005 PM 15720116 ER PT J AU Hazarika, M White, RM Booth, BP Wang, YC Ham, DYL Liang, CY Rahman, A Gobburu, JVS Li, N Sridhara, R Morse, DE Lostritto, R Garvey, P Johnson, JR Pazdur, R AF Hazarika, M White, RM Booth, BP Wang, YC Ham, DYL Liang, CY Rahman, A Gobburu, JVS Li, N Sridhara, R Morse, DE Lostritto, R Garvey, P Johnson, JR Pazdur, R TI Pemetrexed in malignant pleural mesothelioma SO CLINICAL CANCER RESEARCH LA English DT Article ID LEUKEMIA GROUP-B; PHASE-II TRIAL; CISPLATIN; THERAPY; GEMCITABINE; CANCER AB Purpose: This report describes the data and analysis leading to the approval of pemetrexed (LY 231514, MTA, Alimta, Eli Lilly and Co., Indianapolis, IN) by the U.S. Food and Drug Administration (FDA) of a New Drug Application for the treatment of malignant pleural mesothelioma (MPM). Experimental Design: The FDA review of the efficacy and safety of pemetrexed assessed in a randomized clinical trial of 448 patients with unresectable MPM comparing pemetrexed plus cisplatin with cisplatin alone, as well as preclinical pharmacology and chemistry data, are described. The basis for marketing approval is discussed. Results: In one randomized, single-blind, multicenter international trial, 226 patients were randomized to the pemetrexed and cisplatin arm and 222 patients were randomized to cisplatin alone. Median survival times were 12.1 months for pemetrexed and cisplatin and 9.3 months for cisplatin (P = 0.021; hazard ratio, 0.766; 95% confidence interval, 0.61-0.96). Myelosuppression, predominantly neutropenia, was the most common toxicity of pemetrexed plus cisplatin. Other common adverse events were fatigue, leucopenia, nausea, dyspnea, vomiting, chest pain, anemia, thrombocytopenia, and anorexia. Conclusions: Pemetrexed in combination with cisplatin was approved by the FDA on February 4, 2004 for the treatment of patients with MPM whose disease is either unresectable or who are otherwise not candidates for curative surgery. The recommended dose of pemetrexed is 500 mg/m(2) intra venous infusion over 10 minutes on day 1 of each 21-day cycle in combination with 75 mg/m(2) cisplatin infused over 2 hours beginning 30 minutes after the pemetrexed infusion. Patients must receive oral folic acid and vitamin B-12 injections before the start and during therapy to reduce severe toxicities. Patients should also receive corticosteroids with the chemotherapy to decrease the incidence of skin rash. Approval was based on a demonstration of survival improvement in a single randomized trial. Response rates and time to tumor progression were not included in product labeling because of inconsistencies in assessments among the investigators, independent radiologic reviewers, and the FDA, reflecting the difficulty of radiographic assessments in malignant mesothelioma. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hazarika, M (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-150,Room 2080,5600 Fishers Lane, Rockville, MD 20857 USA. EM HazarikaM@cder.fda.gov NR 21 TC 74 Z9 76 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD FEB 1 PY 2005 VL 11 IS 3 BP 982 EP 992 PG 11 WC Oncology SC Oncology GA 893SV UT WOS:000226740400005 PM 15709163 ER PT J AU Gorski, JC Renbarger, JL Vuppalanchi, R Miller, M Galinsky, E Hall, SD AF Gorski, JC Renbarger, JL Vuppalanchi, R Miller, M Galinsky, E Hall, SD TI Effect of MDR1 genotype (G2677T) on the disposition of ciprofloxacin in adults. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 Indiana Univ, Sch Med, US FDA,Sch Pharm, Off Womens Hlth,Purdue Univ, Indianapolis, IN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P31 EP P31 DI 10.1016/j.clpt.2004.12.010 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500115 ER PT J AU Kenna, L Sun, H Ahwah, C Li, M Lee, S Choi, J Stockbridge, N Parekh, A Malinowski, H AF Kenna, L Sun, H Ahwah, C Li, M Lee, S Choi, J Stockbridge, N Parekh, A Malinowski, H TI Development of a QT database with analytic tools: Preliminary results. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P13 EP P13 DI 10.1016/j.clpt.2004.11.053 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500048 ER PT J AU Kim, M Castillo, E Jarugula, VR Parekh, A Furlong, LA Hunt, JP Malinowski, HJ AF Kim, M Castillo, E Jarugula, VR Parekh, A Furlong, LA Hunt, JP Malinowski, HJ TI Labeling of drugs that interact with oral contraceptives. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 US FDA, CDER, Off New Drugs, Rockville, MD 20857 USA. US FDA, CDER, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P13 EP P13 DI 10.1016/j.clpt.2004.11.051 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500046 ER PT J AU Lucksiri, A Vuppalanchi, R Hilligoss, JK Hamman, MA Li, L Chien, JY Huang, S Hall, SD AF Lucksiri, A Vuppalanchi, R Hilligoss, JK Hamman, MA Li, L Chien, JY Huang, S Hall, SD TI Dose dependent inhibition of midazolam elimination by ketoconazole: Effect of CYP3A5 genotype. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 Purdue Univ, Sch Pharm, Indiana Univ, Eli Lilly & Co,US FDA, W Lafayette, IN 47907 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P35 EP P35 DI 10.1016/j.clpt.2004.12.025 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500130 ER PT J AU Men, Y Wesnes, K Venitz, J AF Men, Y Wesnes, K Venitz, J TI PK/PD modeling of the interaction between IV scopolamine (SCP) and physostigmine (PHY) in healthy elderly volunteers. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 US FDA, Cognit Drug Res Ltd, VCU, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P2 EP P2 DI 10.1016/j.clpt.2004.11.009 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500004 ER PT J AU Paine, MF Ludington, SS Chen, ML Stewart, PW Huang, SM Watkins, PB AF Paine, MF Ludington, SS Chen, ML Stewart, PW Huang, SM Watkins, PB TI Does sex influence proximal small intestinal CYP3A or P-GP expression? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract CT 106th Annual Meeting of the American-Society-for-Clinical-Pharmacology-and-Therapeutics CY MAR 02-06, 2005 CL Orlando, FL SP Amer Soc Clin Pharmacol & Therapeut C1 Univ N Carolina, Food & Drug Adm, Chapel Hill, NC USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2005 VL 77 IS 2 SU S BP P2 EP P2 DI 10.1016/j.clpt.2004.11.011 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 895GI UT WOS:000226848500006 ER PT J AU Hastings, KL AF Hastings, KL TI Commentary on Hormetic Dose-Response Relationships in Immunology: Occurrence, quantitative features of the dose response, mechanistic foundations, and clinical implications SO CRITICAL REVIEWS IN TOXICOLOGY LA English DT Editorial Material ID CYCLOSPORINE-A C1 US FDA, Off New Frugs, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hastings, KL (reprint author), US FDA, Off New Frugs, Ctr Drug Evaluat & Res, HFD-530,5600 Fishers Lane, Rockville, MD 20857 USA. EM hastingsk@cder.fda.gov NR 5 TC 1 Z9 1 U1 1 U2 1 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-8444 J9 CRIT REV TOXICOL JI Crit. Rev. Toxicol. PD FEB-MAR PY 2005 VL 35 IS 2-3 BP 297 EP 298 DI 10.1080/10408440590917053 PG 2 WC Toxicology SC Toxicology GA 906JP UT WOS:000227637300002 PM 15839379 ER PT J AU Frasch, CE AF Frasch, CE TI Recent developments in Neisseria meningitidis group A conjugate vaccines SO EXPERT OPINION ON BIOLOGICAL THERAPY LA English DT Review DE bacterial vaccine; conjugate vaccine; meningitis; meningococcus; Neisseria meningitidis; polysaccharide ID SUB-SAHARAN AFRICA; INFLUENZAE TYPE-B; CAPSULAR POLYSACCHARIDE VACCINE; GROUP-C CONJUGATE; TOXOID CONJUGATE; MENINGOCOCCAL MENINGITIS; IMMUNOLOGICAL MEMORY; UNITED-KINGDOM; OLIGOSACCHARIDE-PROTEIN; IMMUNE-RESPONSES AB Meningococcal disease, both endemic and epidemic, remains a major cause of meningitis in many countries. Protective immunity is mediated primarily, by bacteriocidal antibodies against the capsular polysaccharides for serogroups other than B, and against non-capsular surface components for group B. This article focuses on the development of conjugate vaccines for serogroup, A, with special emphasis on the needs of Africa. The first licensed (1999) meningococcal conjugate was against group C in the UK and was > 90% effective in infants, children and young adults. The problem now is to develop a highly immunogenic group A meningococcal conjugate vaccine for use in developing countries as an alternative to the presently licensed group AC polysaccharide vaccine. Immunogenicity studies on the group A polysaccharide show the polysaccharide itself to be uniquely immunogenic in young children compared with other polysaccharides, making comparative studies with a highly immunogenic conjugate of considerable importance. C1 US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, Rockville, MD 20852 USA. RP Frasch, CE (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Polysaccharides, Div Bacterial Parasit & Allergen Prod, 1401 Rockville Pike, Rockville, MD 20852 USA. EM Frasch@cber.fda.gov NR 42 TC 18 Z9 18 U1 0 U2 2 PU ASHLEY PUBLICATIONS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEY CENTRAL, LONDON N3 1QB, ENGLAND SN 1471-2598 J9 EXPERT OPIN BIOL TH JI Expert Opin. Biol. Ther. PD FEB PY 2005 VL 5 IS 2 BP 273 EP 280 DI 10.1517/14712598.5.2.273 PG 8 WC Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Research & Experimental Medicine GA 908FH UT WOS:000227772300013 PM 15757388 ER PT J AU Romeo, MJ Espina, V Lowenthal, M Espina, BH Petricoin, EF Liotta, LA AF Romeo, MJ Espina, V Lowenthal, M Espina, BH Petricoin, EF Liotta, LA TI CSF proteome: a protein repository for potential biomarker identification SO EXPERT REVIEW OF PROTEOMICS LA English DT Review DE 2D gel electrophoresis; biomarkers; central nervous system; cerebrospinal fluid; ELISA; immunoblotting; isoelectric focusing; MALDI; mass spectrometry; neurodegenerative; protein; proteomics ID HUMAN CEREBROSPINAL-FLUID; NEURON-SPECIFIC ENOLASE; TRAUMATIC BRAIN-INJURY; STANFORD MICROARRAY DATABASE; CREUTZFELDT-JAKOB-DISEASE; FLIGHT-MASS SPECTROMETRY; ALZHEIMERS-DISEASE; 2-DIMENSIONAL ELECTROPHORESIS; PARKINSONS-DISEASE; TAU-PROTEIN AB Proteomic analysis is not limited to the analysis of serum or tissues. Synovial, peritoneal, pericardial and cerebrospinal fluid represent unique proteomes for disease diagnosis and prognosis. In particular, cerebrospinal fluid serves as a rich source of putative biomarkers that are not solely limited to neurologic disorders. Peptides, proteolytic fragments and antibodies are capable of crossing the blood-brain barrier, thus providing a repository of pathologic information. Proteomic technologies such as immunoblotting, Isoelectric focusing, 2D gel electrophoresis and mass spectrometry have proven useful for deciphering this unique proteome. Cerebrospinal fluid proteins are generally less abundant than their corresponding serum counterparts, necessitating the development and use of sensitive analytical techniques. This review highlights some of the promising areas of cerebrospinal fluid proteomic research and their clinical applications. C1 NCI, Pathol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Our Lady Good Counsel High Sch, Wheaton, MD USA. US FDA, Ctr Biol Evaluat & Res, Off Cellular & Genet Therapy, Bethesda, MD 20892 USA. RP Romeo, MJ (reprint author), NCI, Pathol Lab, Ctr Canc Res, NIH, 9000 RockvillePike,Bldg 10,Room 2A33, Bethesda, MD 20892 USA. EM romeoma@mail.nih.gov; espinav@mail.nih.gov; lowenthm@mail.nih.gov; beespina@yahoo.com; petricoin@cber.fda.gov; lance@helix.nih.gov OI Espina, Virginia/0000-0001-5080-5972 NR 105 TC 82 Z9 88 U1 1 U2 11 PU FUTURE DRUGS LTD PI LONDON PA UNITEC HOUSE, 3RD FL, 2 ALBERT PLACE, FINCHLEYY CENTRAL, LONDON N3 1QB, ENGLAND SN 1478-9450 J9 EXPERT REV PROTEOMIC JI Expert Rev. Proteomics PD FEB PY 2005 VL 2 IS 1 BP 57 EP 70 DI 10.1586/14789450.2.1.57 PG 14 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 939ZZ UT WOS:000230114700006 PM 15966853 ER PT J AU Bischoff, KM White, DG Hume, ME Poole, TL Nisbet, DJ AF Bischoff, KM White, DG Hume, ME Poole, TL Nisbet, DJ TI The chloramphenicol resistance gene cmlA is disseminated on transferable plasmids that confer multiple-drug resistance in swine Escherichia coli SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE antibiotic resistance; conjugation; integrons ID SULFONAMIDE RESISTANCE; FLORFENICOL RESISTANCE; ANTIMICROBIAL RESISTANCE; FOOD ANIMALS; ENTEROCOCCI; VANCOMYCIN; INTEGRONS; PERSISTENCE; PREVALENCE; AVOPARCIN AB A recent study of P-hemolytic Escherichia coli isolated from diarrheic swine found that 53% were resistant to chloramphenicol, a drug that has been prohibited from use in food animals in the US since the mid-1980s. To identify the factors governing the persistence of chloramphenicol resistance in the absence of specific selection pressure, the location of the chloramphenicol resistance gene cmlA and its linkage to other resistance determinants were investigated. Southern blot analysis of plasmid DNA from 46 swine E coli isolates indicated that cmlA was present on large plasmids greater than 100 kbp. Fifty-two percent of the isolates were able to transfer chloramphenicol resistance to an E. coli recipient at conjugation frequencies ranging from 10(-3) to 10(-8) per recipient. Antimicrobial susceptibility tests on transconjugant strains demonstrated that resistance to sulfamethoxazole, tetracycline, and kanamycin frequently transferred along with chloramphenicol resistance. The transconjugant strains possessed at least two distinct class I integrons that linked cmlA to both aminoglycoside resistance genes aadA1 and aadA2 and either to sul1 or to sul3 sulphonamide resistance genes. These results suggest that in the absence of specific chloramphenicol selection pressure, the cmlA a gene is maintained by virtue of gene linkage to genes encoding resistance to antimicrobials that are currently approved for use in food animals. Published by Elsevier B.V. on behalf of the Federation of European Microbiological Societies. C1 USDA ARS, Natl Ctr Agr Utilizat Res, So Plains Agr Res Ctr, Peoria, IL 61604 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Bischoff, KM (reprint author), USDA ARS, Natl Ctr Agr Utilizat Res, So Plains Agr Res Ctr, 1815 N Univ St, Peoria, IL 61604 USA. EM bischoffk@ncaur.usda.gov NR 33 TC 69 Z9 76 U1 2 U2 14 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1097 J9 FEMS MICROBIOL LETT JI FEMS Microbiol. Lett. PD FEB 1 PY 2005 VL 243 IS 1 BP 285 EP 291 DI 10.1016/j.femsle.2004.12.017 PG 7 WC Microbiology SC Microbiology GA 895PI UT WOS:000226875000039 PM 15668031 ER PT J AU Sahu, SC Sapienza, PP Sprando, RL Collins, TF Ross, IA Flynn, TJ Wiesenfeld, PL O'Donnell, MW Kim, CS AF Sahu, SC Sapienza, PP Sprando, RL Collins, TF Ross, IA Flynn, TJ Wiesenfeld, PL O'Donnell, MW Kim, CS TI Hepatotoxicity of androstenedione in pregnant rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE androstenedione; hepatotoxicity; liver toxicity ID HEPATIC DRUG-METABOLISM; LIPID-PEROXIDATION; DNA-DAMAGE; LIVER; ACID; DEHYDROGENASE AB Androstenedione, a naturally occurring steroid hormone, is a dietary supplement used to enhance athletic performance. Little is known, however, about the safety of its use by young adults including women of child bearing age. To test the possible hepatotoxic effects of androstenedione use, this study was undertaken using a rat model. Pregnant rats (six rats/dose) were exposed to androstenedione in corn oil by gastric intubation at 0, 5, 30 or 60 mg/kg body weight/day beginning 2 weeks before mating and continuing through gestation day 19. On gestation day 20, blood and livers were collected from the pregnant rats for analysis of hepatotoxicity endpoints: serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), lactate dehydrogenase (LDH), glutathione (GSH) and glutathione S-transferase (GST), total microsomal P450, nuclear DNA damage and lipid peroxidation. Under these experimental conditions, no significant differences were observed in any of these biomarkers over the concentration range examined. Published by Elsevier Ltd. C1 US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sahu, SC (reprint author), US FDA, Div Toxicol, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, MOD-1 Labs,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM ssahu@cfsan.fda.gov OI Flynn, Thomas/0000-0002-7248-0643 NR 25 TC 8 Z9 9 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD FEB PY 2005 VL 43 IS 2 BP 341 EP 344 DI 10.1016/j.fct.2004.11.005 PG 4 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 889WJ UT WOS:000226473200018 PM 15621347 ER PT J AU Lineback, DR AF Lineback, DR TI The best coverage of the annual meeting SO FOOD TECHNOLOGY LA English DT Letter C1 Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Lineback, DR (reprint author), Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA 525 WEST VAN BUREN, STE 1000, CHICAGO, IL 60607-3814 USA SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD FEB PY 2005 VL 59 IS 2 BP 70 EP 70 PG 1 WC Food Science & Technology SC Food Science & Technology GA 897FS UT WOS:000226990000015 ER PT J AU Xie, H Gursel, I Ivins, BE Singh, M O'Hagan, DT Ulmer, JB Klinman, DM AF Xie, H Gursel, I Ivins, BE Singh, M O'Hagan, DT Ulmer, JB Klinman, DM TI CpG oligodeoxynucleotides adsorbed onto polylactide-co-glycolide microparticles improve the immunogenicity and protective activity of the licensed anthrax vaccine SO INFECTION AND IMMUNITY LA English DT Article ID NECROSIS-FACTOR-ALPHA; HEPATITIS-B-VACCINE; CATIONIC MICROPARTICLES; BACILLUS-ANTHRACIS; BACTERIAL-DNA; INTERFERON-GAMMA; SURFACE-ANTIGEN; RHESUS MACAQUES; MOTIFS; SAFETY AB To reduce the biothreat posed by anthrax, efforts are under way to improve the protection afforded by vaccination. This work examines the ability of inummostimulatory CpG oligodeoxynucleotides (ODN) adsorbed onto cationic polylactide-co-glycolide (PLG) microparticles (CpG ODN-PLG) to accelerate and boost the protective immunity elicited by Anthrax Vaccine Adsorbed (AVA, the licensed human anthrax vaccine). The results indicate that coadministering CpG ODN-PLG with AVA induces a stronger and faster immunoglobulin G response against the protective antigen of anthrax than AVA alone. Immunized mice were protected from lethal anthrax challenge within 1 week of vaccination with CpG ODN-PLG plus AVA, with the level of protection correlating with serum immunoglobulin G anti-protective antigen titers. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Ft Detrick, MD 21702 USA. Maryland & Chiron Vaccines, Emeryville, CA USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A,Rm 3D10, Bethesda, MD 20892 USA. EM Klinman@cber.fda.gov OI Gursel, Ihsan/0000-0003-3761-1166 NR 42 TC 76 Z9 80 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD FEB PY 2005 VL 73 IS 2 BP 828 EP 833 DI 10.1128/IAI.73.2.828-833.2005 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 893PM UT WOS:000226731700019 PM 15664922 ER PT J AU Sambandamurthy, VK Derrick, SC Jalapathy, KV Chen, B Russell, RG Morris, SL Jacobs, WR AF Sambandamurthy, VK Derrick, SC Jalapathy, KV Chen, B Russell, RG Morris, SL Jacobs, WR TI Long-term protection against tuberculosis following vaccination with a severely attenuated double lysine and pantothenate auxotroph of Mycobacterium tuberculosis SO INFECTION AND IMMUNITY LA English DT Article ID CALMETTE-GUERIN INFECTION; CD8(+) T-CELLS; BOVIS BCG; INTERFERON-GAMMA; IMMUNE-RESPONSE; MICE DEFICIENT; CD4; DIFFERENTIATION; POPULATIONS; RESISTANCE AB We report the safety and immunogenicity of a double lysine and pantothenate auxotroph of Mycobacterium tuberculosis in mice. The DeltalysDelta DeltapanCD mutant is completely attenuated in immunocompromised SCID and gamma interferon knockout mice yet induces short-term and long-term protection in immunocompetent and CD4-deficient mice following single-dose subcutaneous vaccination. C1 Albert Einstein Coll Med, Howard Hughes Med Inst, Bronx, NY 10461 USA. Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. Georgetown Univ, Dept Pathol, Lombardi Canc Ctr, Washington, DC USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Jacobs, WR (reprint author), Albert Einstein Coll Med, Howard Hughes Med Inst, 1300 Morris Pk Ave, Bronx, NY 10461 USA. EM jacobsw@hhmi.org FU NIAID NIH HHS [AI 26170, R01 AI026170, R37 AI026170] NR 43 TC 74 Z9 77 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 FEB PY 2005 VL 73 IS 2 BP 1196 EP 1203 DI 10.1128/IAI.73.2.1196-1203.2005 PG 8 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 893PM UT WOS:000226731700061 PM 15664964 ER PT J AU Kussebi, F Karamloo, F Rhyner, C Schmid-Grendelmeier, P Salagianni, M Mannhart, C Akdis, M Soldatova, L Markovic-Housley, Z von Beust, BR Kundig, T Kemeny, DM Blaser, K Crameri, R Akdis, CA AF Kussebi, F Karamloo, F Rhyner, C Schmid-Grendelmeier, P Salagianni, M Mannhart, C Akdis, M Soldatova, L Markovic-Housley, Z von Beust, BR Kundig, T Kemeny, DM Blaser, K Crameri, R Akdis, CA TI A major allergen gene-fusion protein for potential usage in allergen-specific immunotherapy SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE specific immunnotherapy; allergy; bee venom; T cells; IgE ID BIRCH POLLEN ALLERGEN; T-CELL EPITOPES; BEE VENOM; BLOCKING ANTIBODIES; PHOSPHOLIPASE A(2); IGE; INDUCTION; FRAGMENTS; RESPONSES; BINDING AB Background: Specific immunotherapy is a common treatment of allergic diseases and could potentially be applied to other immunologic disorders. Despite its use in clinical practice, more defined and safer allergy vaccine preparations are required. Differences between epitopes of IgE that recognize the 3-dimensional structure of allergens and T cells that recognize linear amino acid sequences provide a suitable tool for novel vaccine development for specific immunotherapy. Objective: The aim of the study was to delete B-cell epitopes and prevent IgE crosslinking, but to preserve T-cell epitopes by fusion of 2 major allergens of bee venom because of a change in the conformation. Methods: By genetic engineering, we produced a fusion protein composed of the 2 major bee venom allergens: phospholipase A(2) (Api m 1) and hyaluronidase (Api m 2). Results: The Api m [1/2] fusion protein induced T-cell proliferation and both T(H)1-type and T(H)2-type cytokine responses. In contrast, IgE reactivity was abolished, and profoundly reduced basophil degranulation and type 1 skin test reactivity was observed. Pretreatment of mice with Api m [1/2] fusion protein significantly suppressed the development of specific IgE as well as other antibody isotypes after immunization with the native allergen. Conclusion: The novel fusion protein of 2 major allergens bypasses IgE binding and mast cell/basophil IgE FcepsilonRI crosslinking and protects from IgE development. C1 Swiss Inst Allergy & Asthma Res, CH-7270 Davos, Switzerland. Dept Dermatol, Allergy Unit, Zurich, Switzerland. Rayne Inst, Sch Med, Dept Immunol, London, England. US FDA, Ctr Biol Evaluat & Res, Div Allergen Prod & Parasitol, Lab Immunobiochem, Bethesda, MD 20014 USA. Univ Basel, Biozentrum, Div Struct Biol, Basel, Switzerland. RP Kussebi, F (reprint author), Charite Univ, Childrens Hosp, Dept Pneumol & Immunol, Augustenburger Pl 1, D-13353 Berlin, Germany. EM fatimah.kussebi@charite.de NR 30 TC 68 Z9 76 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2005 VL 115 IS 2 BP 323 EP 329 DI 10.1016/j.jaci.2004.011.041 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 897YU UT WOS:000227043600017 PM 15696088 ER PT J AU Evans, RL Rushing, LG Billedeau, SA Holder, CL Siitonen, PH AF Evans, RL Rushing, LG Billedeau, SA Holder, CL Siitonen, PH TI Trace analysis of ethinyl estradiol in casein diet using gas chromatography with electron capture detection SO JOURNAL OF CHROMATOGRAPHIC SCIENCE LA English DT Article ID LIQUID-CHROMATOGRAPHY; MASS-SPECTROMETRY; ANIMAL CHOW; ETHINYLESTRADIOL; RESIDUES; CATTLE; ASSAY C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Siitonen, PH (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM psiitonen@nctr.fda.gov NR 27 TC 4 Z9 5 U1 0 U2 0 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0021-9665 J9 J CHROMATOGR SCI JI J. Chromatogr. Sci. PD FEB PY 2005 VL 43 IS 2 BP 76 EP 80 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 902RG UT WOS:000227373600005 PM 15826365 ER PT J AU Andrade, SE Graham, DJ Staffa, JA Schech, SD Shatin, D La Grenade, L Goodman, MJ Platt, R Gurwitz, JH Chan, KA AF Andrade, SE Graham, DJ Staffa, JA Schech, SD Shatin, D La Grenade, L Goodman, MJ Platt, R Gurwitz, JH Chan, KA TI Health plan administrative databases can efficiently identify serious myopathy and rhabdomyolysis SO JOURNAL OF CLINICAL EPIDEMIOLOGY LA English DT Article DE positive predictive value; myopathy; rhabdomyolysis; automated databases; statins; fibrates ID RISK AB Objective: We evaluated the positive predictive values (PPVs) of specific criteria based upon International Classification of Diseases, 9th revision (ICD-9-CM) codes documented in health plan administrative databases for identification of cases of serious myopathy and rhabdomyolysis. Study Design and Setting: We conducted a retrospective study among patients enrolled in I I geographically dispersed managed care organizations. Cohorts of new users of specific statins and fibrates were identified by selecting patients with an initial dispensing of the drug during the period 1 January 1998 to 30 June 2001. Potential cases of serious myopathy or rhabdomyolysis were identified using specific criteria based upon ICD-9-CM codes suggesting a muscle disorder or acute renal failure. Results: A total of 194 hospitalizations meeting the criteria for chart review selection were identified among 206,732 new users of statins and 15,485 new users of fibrates. Overall, 31 cases of serious, clinically important myopathy or rhabdomyolysis (18%) were confirmed through chart review. Of these, 26 (84%) had a claim including codes for myoglobinuria (ICD-9-CM 791.3) or other disorders of muscle, ligament, and fascia (ICD-9-CM 728.89). A PPV of 74% (26 of 35 patients meeting criteria) was found for a composite definition that included (1) a primary or secondary discharge code for myoglobinuria, (2) a primary code for "other disorders of muscle," or (3) a secondary code for "other disorders of muscle" accompanied by a claim for a CK test within 7 days of hospitalization or a discharge code for acute renal failure. Conclusion: For rare adverse events such as serious myopathy or rhabdomyolysis, large population-based databases that include diagnosis and laboratory test claims data can facilitate epidemiologic research. (C) 2005 Elsevier Inc. All rights reserved. C1 Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Fallon Fdn, Worcester, MA 01605 USA. Ctr Drug Evaluat & Res, Off Drug Safety, Rockville, MD 20857 USA. Ctr Hlth Care Policy & Evaluat, Eden Prairie, MN 55344 USA. HealthPartners Res Fdn, Minneapolis, MN 55425 USA. Brigham & Womens Hosp, Channing Lab, Boston, MA 02115 USA. Harvard Univ, Sch Med, Dept Ambulatory Care & Prevent, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. RP Andrade, SE (reprint author), Univ Massachusetts, Sch Med, Meyers Primary Care Inst, Fallon Fdn, 630 Plantat St, Worcester, MA 01605 USA. EM sandrade@meyersprimary.org OI Chan, Kinwei/0000-0001-8161-1986 NR 7 TC 30 Z9 30 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0895-4356 J9 J CLIN EPIDEMIOL JI J. Clin. Epidemiol. PD FEB PY 2005 VL 58 IS 2 BP 171 EP 174 DI 10.1016/j.jclinepi.2004.10.004 PG 4 WC Health Care Sciences & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 898NN UT WOS:000227083600012 PM 15680751 ER PT J AU Benton, K AF Benton, K TI Regulatory expectations for cellular therapy products: Manufacturing and product testing SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Meeting Abstract CT 18th International Congress on Endovascular Interventions CY FEB 13-17, 2005 CL Scottsdale, AZ SP Int Soc Endovasc Specialists C1 US FDA, Off Cellular Tissue & Gene Therapies, Ctr Biol Res & Review, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD FEB PY 2005 VL 12 SU 1 BP 3 EP 4 PG 2 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 898EP UT WOS:000227059300007 ER PT J AU Cavanaugh, KJ AF Cavanaugh, KJ TI Role of CDRH in the review of cell and gene product submissions SO JOURNAL OF ENDOVASCULAR THERAPY LA English DT Meeting Abstract CT 18th International Congress on Endovascular Interventions CY FEB 13-17, 2005 CL Scottsdale, AZ SP Int Soc Endovasc Specialists C1 US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ALLIANCE COMMUNICATIONS GROUP DIVISION ALLEN PRESS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 1526-6028 J9 J ENDOVASC THER JI J. Endovascular Ther. PD FEB PY 2005 VL 12 SU 1 BP 9 EP 9 PG 1 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 898EP UT WOS:000227059300016 ER PT J AU Edghill-Smith, Y Bray, M Whitehouse, CA Miller, D Mucker, E Manischewitz, J King, LR Robert-Guroff, M Hryniewicz, A Venzon, D Meseda, C Weir, J Nalca, A Livingston, V Wells, J Lewis, MG Huggins, J Zwiers, SH Golding, H Franchini, G AF Edghill-Smith, Y Bray, M Whitehouse, CA Miller, D Mucker, E Manischewitz, J King, LR Robert-Guroff, M Hryniewicz, A Venzon, D Meseda, C Weir, J Nalca, A Livingston, V Wells, J Lewis, MG Huggins, J Zwiers, SH Golding, H Franchini, G TI Smallpox vaccine does not protect Macaques with AIDS from a lethal Monkeypox virus challenge SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Trans-Natl Institutes of Health/United States Food and Drug Administration Intramural Biodefense Symposium CY APR 22-23, 2004 CL Bethesda, MD ID EXPRESSION; MVA AB It is unknown whether smallpox vaccination would protect human immunodeficiency virus type 1 (HIV-1) infected individuals, because helper CD4(+) cells, the targets of HIV-1 infection, are necessary for the induction of both adaptive CD8(+) cell and B cell responses. We have addressed this question in macaques and have demonstrated that, although smallpox vaccination is safe in immunodeficient macaques when it is preceded by immunization with highly attenuated vaccinia strains, the macaques were not protected against lethal monkeypox virus challenge if their CD4(+) cell count was <300 cells/mm(3). The lack of protection appeared to be associated with a defect in vaccinia-specific immunoglobulin (Ig) switching from IgM to IgG. Thus, vaccination strategies that bypass CD4(+) cell help are needed to elicit IgG antibodies with high affinity and adequate tissue distribution and to restore protection against smallpox in severely immunocompromised individuals. C1 NCI, Anim Models & Retroviral Vaccines Sect, Bethesda, MD 20892 USA. NCI, Immune Biol Retroviral Infect Sect, Bethesda, MD 20892 USA. NCI, Biostat & Data Management Sect, Bethesda, MD 20892 USA. NIAID, Biodef Clin Res Branch, Off Clin Res, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. USA, Med Res Inst Infect Dis, Div Virol, Ft Detrick, MD 21702 USA. So Res Inst, Frederick, MD USA. RP Franchini, G (reprint author), NCI, Anim Models & Retroviral Vaccines Sect, 41-D804, Bethesda, MD 20892 USA. EM franchig@mail.nih.gov RI Venzon, David/B-3078-2008 FU NIAID NIH HHS [N01-AI-15451] NR 18 TC 47 Z9 49 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD FEB 1 PY 2005 VL 191 IS 3 BP 372 EP 381 DI 10.1086/427265 PG 10 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 885BH UT WOS:000226130500008 PM 15633096 ER PT J AU Mansfield, E O'Leary, TJ Gutman, SI AF Mansfield, E O'Leary, TJ Gutman, SI TI Food and drug administration regulation of in vitro diagnostic devices SO JOURNAL OF MOLECULAR DIAGNOSTICS LA English DT Article AB The Food and Drug Administration regulates the sale and distribution of laboratory devices under a statutory and regulatory framework that is unfamiliar to most clinical laboratory scientists. In this article we briefly describe the criteria that are used to classify and review in vitro diagnostic devices. We discuss the similarities and differences between devices that are not subject to premarket review, and those that are required to undergo either a premarket application or premarket notification [510(k)] pathway. we then discuss the methods that the Food and Drug Administration uses to assess the performance of in vitro diagnostic devices in the marketplace as a component of the total life cycle approach to medical device regulation. C1 Dept Vet Affairs, Biomed Lab, R&D Serv, Washington, DC 20420 USA. US FDA, Off In Vitro Diagnost Device Evaluat & Safety, Rockville, MD 20857 USA. RP O'Leary, TJ (reprint author), Dept Vet Affairs, Biomed Lab, R&D Serv, 810 Vermont Ave, Washington, DC 20420 USA. EM timothy.oleary@verizon.net NR 0 TC 29 Z9 30 U1 1 U2 2 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 1525-1578 J9 J MOL DIAGN JI J. Mol. Diagn. PD FEB PY 2005 VL 7 IS 1 BP 2 EP 7 DI 10.1016/S1525-1578(10)60002-5 PG 6 WC Pathology SC Pathology GA 908XQ UT WOS:000227823900001 PM 15681468 ER PT J AU Parney, IF Kunwar, S McDermott, M Berger, M Prados, M Cha, S Croteau, D Puri, RK Chang, SM AF Parney, IF Kunwar, S McDermott, M Berger, M Prados, M Cha, S Croteau, D Puri, RK Chang, SM TI Neuroradiographic changes following convection-enhanced delivery of the recombinant cytotoxin interleukin 13-PE38QQR for recurrent malignant glioma SO JOURNAL OF NEUROSURGERY LA English DT Article; Proceedings Paper CT 8th Annual Meeting of the Society-for-Neuro-Oncology CY NOV 13-16, 2003 CL Keystone, CO SP Soc Neuro Oncol DE glioma; convection-enhanced delivery; interleukin-13; Pseudomonas exotoxin; magnetic resonance imaging ID GENE-THERAPY; INTRALESIONAL IMMUNOTHERAPY; INTRACEREBRAL CLYSIS; MR; GLIOBLASTOMA; RECEPTOR; BRAIN; MACROMOLECULES; TOMOGRAPHY; MODEL AB Object. Convection-enhanced delivery (CED) is a novel method for delivering therapeutic agents to infiltrative brain tumor cells. For agents administered by CED, changes on magnetic resonance (MR) imaging directly resulting from catheter placement, infusion, and the therapeutic compound may confound any interpretation of tumor progression. As part of an ongoing multiinstitutional Phase I study, 14 patients with recurrent malignant glioma underwent CED of interleukin (IL) 13-PE38QQR, a recombinant cytotoxin consisting of human IL-13 conjugated with a truncated Pseudomonas exotoxin. Serial neuroradiographic changes were assessed in this cohort of patients. Methods. Patients were treated in two groups: Group 1 patients received IL13-PE38QQR before and after tumor resection; Group 2 patients received infusion only after tumor resection. Preoperative and postinfusion MR images were obtained prospectively at specified regular intervals. Changes were noted along catheter tracks on postresection MR images obtained in all patients. A simple grading system was developed to describe these changes. When MR imaging changes appeared to be related to IL13-PE38QQR, patients were followed up without instituting new antitumor therapy. Conclusions. As CED of therapeutic agents becomes more common, clinicians and investigators must become aware of associated neuroimaging changes that should be incorporated into toxicity assessment. We have developed a simple grading system to facilitate communication about these changes among investigators. Biological imaging modalities that could possibly distinguish these changes from recurrent tumor should be evaluated. In this study the authors demonstrate the challenges in determining efficacy when surrogate end points such as time to tumor progression as defined by new or progressive contrast enhancement on MR imaging are used with this treatment modality. C1 Univ Calif San Francisco, Brai Tumor Res Ctr, Dept Neurol Surg, Neurooncol Serv, San Francisco, CA 94143 USA. Univ Calif San Francisco, Brai Tumor Res Ctr, Dept Radiol, San Francisco, CA 94143 USA. NeoPharm Inc, Lake Forest, IL USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Chang, SM (reprint author), Univ Calif San Francisco, Brai Tumor Res Ctr, Dept Neurol Surg, Neurooncol Serv, 400 Parnassus Ave,A808, San Francisco, CA 94143 USA. EM changs@neurosurg.ucsf.edu FU NCI NIH HHS [P01 CA13525] NR 24 TC 65 Z9 65 U1 0 U2 3 PU AMER ASSOC NEUROLOGICAL SURGEONS PI ROLLING MEADOWS PA 5550 MEADOWBROOK DRIVE, ROLLING MEADOWS, IL 60008 USA SN 0022-3085 J9 J NEUROSURG JI J. Neurosurg. PD FEB PY 2005 VL 102 IS 2 BP 267 EP 275 DI 10.3171/jns.2005.102.2.0267 PG 9 WC Clinical Neurology; Surgery SC Neurosciences & Neurology; Surgery GA 897YQ UT WOS:000227043200012 PM 15739554 ER PT J AU Sun, HH Mangner, TJ Collins, JM Muzik, O Douglas, K Shields, AF AF Sun, HH Mangner, TJ Collins, JM Muzik, O Douglas, K Shields, AF TI Imaging DNA synthesis in vivo with F-18-FMAU and PET SO JOURNAL OF NUCLEAR MEDICINE LA English DT Article DE FMAU; PET; proliferation ID POSITRON-EMISSION-TOMOGRAPHY; 1-(2'-DEOXY-2'-FLUORO-1-BETA-D-ARABINOFURANOSYL)-5-METHYLURACIL FMAU; THYMIDINE; ANALOG; FLUORINE-18-FLUORODEOXYGLUCOSE; PROLIFERATION; CHEMOTHERAPY; LYMPHOMA; DEFECTS; TUMORS AB We imaged DNA synthesis in vivo with PET and F-18-1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine (FMAU), which is phosphorylated by thymidine kinases and incorporated into DNA. Methods: We produced F-18-FMAU and injected the tracer into 5 normal dogs and studied them by imaging or biodistribution for up to 2.5 h. The pharmacokinetics of FMAU in blood and urine were determined using high-performance liquid chromatography analysis. At the end of each study, selected tissues were removed to measure the total activity retained in these tissues. In addition, the selected tissues were extracted by acid precipitation, by which the macromolecules can be precipitated to determine the radioactivity of F-18-FMAU incorporated into DNA. Results: Imaging and tissue analysis showed increased activity in the lymph nodes, stomach, small intestine, and bone marrow, with mean standardized uptake values of 1.4, 1.6, 2.3, and 3.9, respectively, because of varying degrees of increased cell proliferation. In contrast, F-18-FMAU was distributed with tissue-to-muscle ratios of approximately 1.0 in nonproliferative organs such as lung, liver, and kidneys. Analysis of the tissue extracts using acid precipitation demonstrated that 88% of activity in marrow and 65% of activity in small intestine was acid precipitated. However, more than 90% of activity in the non-proliferating tissues such as heart and lungs was in the supernatant. Increased activity was seen in the heart because of a high level of thymidine kinase 2 and in the gallbladder because of excretion. Analysis of blood and urine demonstrated that more than 95% of activity was present as intact F-18-FMAU at the end of the studies. Conclusion: The results showed that F-18-FMAU was selectively retained in DNA of the proliferating tissues and was resistant to degradation. These features indicate that F-18-FMAU might be an alternative to C-11-thymidine for imaging DNA synthesis in normal tissues and tumors. C1 Wayne State Univ, Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Dept Med, Detroit, MI 48201 USA. Wayne State Univ, Dept Radiol, Detroit, MI 48201 USA. US FDA, Rockville, MD 20857 USA. Wayne State Univ, Dept Pediat, Detroit, MI 48201 USA. RP Shields, AF (reprint author), Wayne State Univ, Karmanos Canc Inst, 4HWCRC,4100 John R St, Detroit, MI 48201 USA. EM shieldsA@karmanos.org FU NCI NIH HHS [CA 82645, CA 83131] NR 21 TC 54 Z9 55 U1 0 U2 3 PU SOC NUCLEAR MEDICINE INC PI RESTON PA 1850 SAMUEL MORSE DR, RESTON, VA 20190-5316 USA SN 0161-5505 J9 J NUCL MED JI J. Nucl. Med. PD FEB PY 2005 VL 46 IS 2 BP 292 EP 296 PG 5 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 896JD UT WOS:000226929500034 PM 15695789 ER PT J AU Whiting, SJ Calvo, MS AF Whiting, SJ Calvo, MS TI Dietary recommendations for vitamin D: A critical need for functional end points to establish an estimated average requirement SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Vitamin D Insufficiency held at the 2004 Experimental Biology Meeting CY APR 18, 2004 CL Washington, DC SP Amer Soc Nutr Sci DE vitamin D; requirement; dietary reference intakes; functional indicators; calciotropic; noncalciotropic ID SUPPLEMENT USE; UNITED-STATES; BONE TURNOVER; CALCIUM; 25-HYDROXYVITAMIN-D; OSTEOPOROSIS; EFFICACY; DISEASE; WINTER; LEVEL AB From its inaugural value in 1941, the Recommended Dietary Allowance (RDA) for adults for vitamin D has remained close to 400 IU (10 mug) level. This original recommended intake was based on the observation that the amount of vitamin D activity in a teaspoon of cod liver oil was sufficient to prevent rickets in infants. Since that time until 1997, determination of vitamin D requirements and status was more conjecture than science. In 1997, when the recommended intake level of vitamin D was set as an adequate intake value rather than an RDA, much has been learned about metabolism of vitamin D. The circulating metabolite 25-hydroxyvitamin D is the major static indicator of vitamin D status. Using its response to diet in the absence of sun exposure, a dose-response study suggests a mean requirement of at least 500 IU (12.5 mug) from which an RDA could be set. Other factors may need adjustment, such as sun exposure and body fat. However, functional indicators of status are needed. The role of vitamin D in calcium metabolism (i.e., calciotropic functions) is better understood; bone turnover and parathyroid hormone are potential indicators. Vitamin D has noncalciotropic functions arising from extrarenal synthesis of the active metabolite 1,25 dihydroxyvitamin D involving cell proliferation and immunity, from which function indicators of status may be derived. Despite gaps in our knowledge, there are data from which new dietary reference intake values for vitamin D may be set. C1 Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK, Canada. Food & Drug Adm, Off Appl Res & Safety Assessment, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Whiting, SJ (reprint author), Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK, Canada. EM susan.whiting@usask.ca NR 39 TC 60 Z9 62 U1 0 U2 7 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2005 VL 135 IS 2 BP 304 EP 309 PG 6 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 894GU UT WOS:000226779700028 PM 15671232 ER PT J AU Trumbo, PR AF Trumbo, PR TI The level of evidence for permitting a qualified health claim: FDA's review of the evidence for selenium and cancer and vitamin E and heart disease SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Symposium on Nutrient Disease Relationships held at the 2004 Experimental Biology Meeting CY JAN 19, 2004 CL Washington, DC DE qualified health claims; vitamin E; selenium ID RANDOMIZED CONTROLLED TRIAL; BETA-CAROTENE SUPPLEMENTS; ALPHA-TOCOPHEROL; MYOCARDIAL-INFARCTION; INTERMITTENT CLAUDICATION; ANTIOXIDANT VITAMINS; INTERVENTION TRIALS; CORONARY-DISEASE; ANGINA-PECTORIS; E CONSUMPTION AB Health claims are authorized for the labeling of foods when there is significant scientific agreement among qualified experts on the evidence for a relationship between a food or food component (substance) and a disease. Qualified health claims are permitted when there is less scientific evidence for a substance-disease relationship, therefore requiring qualifying language. The evidence for a relationship between vitamin E and heart disease and selenium and cancer was reviewed by the U.S. FDA. It was determined that there was insufficient evidence to permit a qualified health claim for vitamin E and cancer, whereas there was some evidence for permitting a qualified health claim for selenium and cancer. The rationale for these conclusions is discussed below. C1 Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Trumbo, PR (reprint author), Food & Drug Adm, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. EM PaulaTrumbo@fda.gov NR 25 TC 16 Z9 17 U1 0 U2 1 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD FEB PY 2005 VL 135 IS 2 BP 354 EP 356 PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 894GU UT WOS:000226779700038 PM 15671242 ER PT J AU Tavris, DR Dey, S Weintraub, WS Shaw, RE Gallauresi, BA Brindi, RG Mitchell, K AF Tavris, DR Dey, S Weintraub, WS Shaw, RE Gallauresi, BA Brindi, RG Mitchell, K CA ACC-NCDR Am Coll Cardiology TI Risk of local adverse events following cardiac catheterization by hemostasis device and gender SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 Amer Coll Cardiol, Bethesda, MD USA. US FDA, Rockville, MD 20857 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 40A EP 40A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808200171 ER PT J AU Tovar, OH AF Tovar, OH TI Adverse event reports on automatic external defibrillators from 1996-2003 SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Meeting Abstract CT 54th Annual Scientific Session of the American-College-of-Cardiology CY MAR 06, 2005 CL Orlando, FL SP Amer Coll Cardiol C1 US FDA, Rockville, MD 20857 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 0735-1097 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB 1 PY 2005 VL 45 IS 3 SU A BP 205A EP 205A PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 894RB UT WOS:000226808200896 ER PT J AU Slikker, W Scallet, A Hanig, J Schmued, L Wang, C AF Slikker, W Scallet, A Hanig, J Schmued, L Wang, C TI Anesthetic blockade of N-methyl-D-aspartate receptors produces loss of monkey frontal cortical neurons in culture. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, OPS OTR DAPR, Washington, DC 20204 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 478 BP 237A EP 238A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101017 ER PT J AU Sheehan, KM Fishman, DA Liotta, LA Petricoin, EF Wulfkuhle, JD AF Sheehan, KM Fishman, DA Liotta, LA Petricoin, EF Wulfkuhle, JD TI Mapping the molecular network of metastatic ovarian carcinoma: Theranostics using proteomics. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NCI, FDA, Clin Prote Program, Pathol Lab, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 628 BP 285A EP 285A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101167 ER PT J AU Srinivasan, S Petricoin, EF Liotta, LA Fishman, DA AF Srinivasan, S Petricoin, EF Liotta, LA Fishman, DA TI Effects of autotaxin (atx) mediated invasion of ovarian epithelial cells on protein signaling cascades. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NIH, Dept Therapeut Prot, CBER, FDA,Clin Prote Program, Bethesda, MD 20892 USA. NCI, Pathol Lab, Bethesda, MD 20892 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 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 630 BP 285A EP 286A PG 2 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101169 ER PT J AU Aquino, JA Fishman, DA Coukos, G Liotta, LA Petricoin, EF Wulfkuhle, JD AF Aquino, JA Fishman, DA Coukos, G Liotta, LA Petricoin, EF Wulfkuhle, JD TI Multiplexed kinase substrate and signal transduction profiling of human ovarian cancer: Towards patient tailored therapeutics. SO JOURNAL OF THE SOCIETY FOR GYNECOLOGIC INVESTIGATION LA English DT Meeting Abstract CT 52nd Annual Meeting of the Society-for-Gynecologic-Investigation CY MAR 23-26, 2005 CL Los Angeles, CA SP Soc Gynecolog Invest C1 NCI, FDA Clin Proteom Program, Bethesda, MD 20892 USA. NYU, Sch Med, New York, NY USA. Univ Penn, Philadelphia, PA 19104 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1071-5576 J9 J SOC GYNECOL INVEST JI J. Soc. Gynecol. Invest. PD FEB PY 2005 VL 12 IS 2 SU S MA 902 BP 370A EP 370A PG 1 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 902CN UT WOS:000227329101440 ER PT J AU Cerniglia, CE Kotarski, S AF Cerniglia, CE Kotarski, S TI Approaches in the safety evaluations of veterinary antimicrobial agents in food to determine the effects on the human intestinal microflora SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID WITHDRAWAL TIME-ESTIMATION; DRUG RESIDUES; FLORA; RESISTANCE; ECOLOGY; MODELS AB The administration of antimicrobial agents to livestock creates potential for antibiotic residues to enter the food supply and be consumed by humans. Therefore, as a process of food animal drug registration, national regulatory agencies and international committees evaluate data regarding the chemical, microbiologic, pharmacokinetic, pharmacodynamic, pharmacologic, toxicologic, and antimicrobial properties of veterinary drugs to assess the safety of ingested antimicrobial residues to consumers. Currently, European, Australian and United States guidelines for veterinary drug registration require a safety assessment of microbiologic hazards from consumption of antimicrobial residues taking into account the potentially adverse effects on human intestinal microflora. The main concerns addressed are selection of resistant bacteria in the gastrointestinal tract and disruption of the colonization barrier of the resident intestinal microflora. Current requirements differ among national agencies. Efforts are ongoing internationally to review and harmonize approaches and test methods and protocols for application to these microbiologic safety evaluations of antimicrobial drug residues in food. This review describes the background to current regulatory approaches used in applying in vitro and in vivo methods to set a microbiologic acceptable daily intake for residues in food derived from animals treated with an antimicrobial agent. This paper also examines the current research needs to support these evaluations. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Pfizer Anim Hlth, Kalamazoo, MI USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM ccerniglia@nctr.fda.gov NR 55 TC 35 Z9 40 U1 1 U2 7 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD FEB PY 2005 VL 28 IS 1 BP 3 EP 20 DI 10.1111/j.1365-2885.2004.00595.x PG 18 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 899GM UT WOS:000227132900002 PM 15720510 ER PT J AU Liu, T Ye, ZP AF Liu, T Ye, ZP TI Attenuating mutations of the matrix gene of influenza A/WSN/33 virus SO JOURNAL OF VIROLOGY LA English DT Article ID TEMPERATURE-SENSITIVE PHENOTYPE; A VIRUS; M1 PROTEIN; NUCLEAR EXPORT; VIRAL RIBONUCLEOPROTEINS; NS2 PROTEIN; ASSOCIATION; RNA; DOMAIN; A/ANN-ARBOR/6/60 AB The matrix protein (MI) of influenza virus plays an essential role in viral replication. Our previous studies have shown that basic amino acids 101RKLKR105 of M1 are involved in RNP binding and nuclear localization. For the present work, the functions of 101RKLKR105 were studied by introducing mutations into the M gene of influenza virus A/WSN/33 by reverse genetic methods. Individual substitution, R101S or R105S, had a minimal effect on viral replication. In contrast, the double mutation R101S-R105S was synergistic and resulted in temperature sensitivity reflected by reduced viral replication at a restrictive temperature. To investigate the in vivo effect on infection, BALB/c mice were infected with either A/WSN/33 wild-type (Wt) or mutant viruses and assessed for signs of illness, viral replication in the lungs, and survival rates. The results from mouse studies indicated that the R101S-R105S double mutant virus was strongly attenuated, while single mutant viruses R101S and R105S were minimally attenuated compared to AiWSN33 Wt under the same conditions. In challenge studies, mice immunized by infection with R101S-R105S were fully protected from lethal challenge with A/WSN/33. The replication and attenuating properties of R101S-R105S suggest its potential in development of live influenza virus vaccines. C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Viral Prod,Lab Pediat & Resp Viral Dis, Bethesda, MD USA. RP Ye, ZP (reprint author), Bldg 29A,Rm 2B17,8800 Rockville Pike, Bethesda, MD 20982 USA. EM yez@cber.fda.gov NR 40 TC 13 Z9 15 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2005 VL 79 IS 3 BP 1918 EP 1923 DI 10.1128/JVI.79.3.1918-1923.2005 PG 6 WC Virology SC Virology GA 892FB UT WOS:000226634300057 PM 15650216 ER PT J AU Yu, L Markoff, L AF Yu, L Markoff, L TI The topology of bulges in the long stem of the flavivirus 3 ' stem-loop is a major determinant of RNA replication competence SO JOURNAL OF VIROLOGY LA English DT Article ID WEST-NILE VIRUS; YELLOW-FEVER VIRUS; JAPANESE ENCEPHALITIS-VIRUS; SECONDARY STRUCTURE; GENOMIC RNA; 3'-UNTRANSLATED REGION; NONCODING REGION; ACTING ELEMENTS; VIRAL-RNA; PROTEIN AB All flavivirus genomes contain a 3'terminal stem-loop secondary structure (3'SL) formed by the most downstream similar to100 nucleotides (nt) of the viral RNA. The 3'SL is required for virus replication and has been shown to bind both virus-coded and cellular proteins. Results of the present study using an infectious DNA for WN virus strain 956 initially demonstrated that the dengue virus serotype 2 (DEN2) 3'SL nucleotide sequence could not substitute for that of the WN 3'SL to support WN genome replication. To determine what WN virus-specific 3'SL nucleotide sequences were required for WN virus replication, WN virus 3'SL nucleotide sequences were selectively deleted and replaced by analogous segments of the DEN2 3'SL nucleotide sequence such that the overall 3'SL secondary structure was not disrupted. Top and bottom portions of the WN virus 3'SL were defined according to previous studies Q. L. Blackwell and M. A. Brinton, J. Virol. 71:6433-6444, 1997; L. Zeng, L., B. Falgout, and L. Markoff, J. Virol. 72:7510-7522, 1998). A bulge in the top portion of the long stem of the WN 3'SL was essential for replication of mutant WN RNAs, and replication-defective RNAs failed to produce negative strands in transfected cells. Introduction of a second bulge into the bottom portion of the long stem of the wild-type WN 3'SL markedly enhanced the replication competence of WN virus in mosquito cells but had no effect on replication in mammalian cells. This second bulge was identified as a host cell-specific enhancer of flavivirus replication. Results suggested that bulges and their topological location within the long stem of the 3'SL are primary determinants of replication competence for flavivirus genomes. C1 US FDA, CBER, Lab Vector Borne Virus Dis, Div Viral Prod,Off Vaccines Res & Review, Bethesda, MD 20892 USA. RP Markoff, L (reprint author), US FDA, CBER, Lab Vector Borne Virus Dis, Div Viral Prod,Off Vaccines Res & Review, Bldg 29A,Room 1B17,8800 Rockville Pike, Bethesda, MD 20892 USA. EM markoff@cber.fda.gov NR 44 TC 58 Z9 62 U1 1 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD FEB PY 2005 VL 79 IS 4 BP 2309 EP 2324 DI 10.1128/JVI.79.4.2309-2324.2005 PG 16 WC Virology SC Virology GA 894DZ UT WOS:000226772100033 PM 15681432 ER PT J AU Khan, SA Nawaz, MS Khan, AA Hopper, SL Jones, RA Cerniglia, CE AF Khan, SA Nawaz, MS Khan, AA Hopper, SL Jones, RA Cerniglia, CE TI Molecular characterization of multidrug-resistant Enterococcus spp. from poultry and dairy farms: detection of virulence and vancomycin resistance gene markers by PCR SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE multiplex-PCR; vancomycin; vanA; vanB; vanC; virulence; pathogenicity island ID GLYCOPEPTIDE RESISTANCE; ANTIMICROBIAL RESISTANCE; LEVEL RESISTANCE; SURFACE PROTEIN; FAECALIS; FAECIUM; ANIMALS; GALLINARUM; INFECTION; COMMUNITY AB Thirty multidrug-resistant Enterococcus spp. strains, including two from the milk of cows with mastitis, nine from chicken litter and 19 from turkey litter, were isolated. Twenty-five were identified by biochemical methods as E. gallinarum and five as E.faecalis. Most of the isolates were resistant to vancomycin, gentamicin, streptomycin, tetracycline, erythromycin, bacitracin, kanamycin and nalidixic acid but sensitive to ciprofloxacin, sulfamethoxazole, chloramphenicol, ampicillin and ofloxacin. Attempts were made by partial amplification of the gene sequences to detect the vancomycin resistance markers vanA (734-bp), vanB (420-bp), vanCl (531-bp), and vanC2-C3 (673-bp); virulence markers cylA (427-bp) and cylB (225-bp) for enterococcal cytolysin and a biofilm-forming surface protein (Esp). Individual and multiplex-PCR assays for vancomycin resistance markers revealed the vanCl gene in 22 E. gallinarum strains. None of the remaining isolates including five E. faecalis strains (MIC=2 mug ml(-1)) and three E. gallinarum strains (MIC = 8 mug ml(-1)) had any of the van genes tested. Analysis by pulsed-field gel electrophoresis (PFGE) and a comparison of sinal banding profiles showed I I different patterns. Probing with a DIG-labeled vanCl PCR product indicated a common 38.0 kb Smal DNA fragment in all the E. gallinarum strains harboring the vanCl gene. The genes cylA and cylB were detected only in one clinical E. gallinarum isolate and two quality control clinical strains of E. faecalis (ATCC 5 1299 and 29212). None of the virulence factors were found in milk or poultry isolates. Intermediate level resistance to vancomycin in enterococci from the US animal farms was predominantly due to the presence of vanCl gene. Published by Elsevier Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Ctr Vet Med, Div Microbiol Studies, Rockville, MD 20855 USA. RP Khan, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM skhan@nctr.fda.gov NR 35 TC 21 Z9 29 U1 2 U2 10 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD FEB PY 2005 VL 19 IS 1 BP 27 EP 34 DI 10.1016/j.mcp.2004.09.001 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 894OU UT WOS:000226802300004 PM 15652217 ER PT J AU Veal-Carr, WL Stibitz, S AF Veal-Carr, WL Stibitz, S TI Demonstration of differential virulence gene promoter activation in vivo in Bordetella pertussis using RIVET SO MOLECULAR MICROBIOLOGY LA English DT Article ID SIGNAL-TRANSDUCTION; RESPIRATORY-TRACT; RNA-POLYMERASE; FILAMENTOUS HEMAGGLUTININ; TRANSCRIPTIONAL ACTIVATOR; ADENYLATE-CYCLASE; MAMMALIAN-CELLS; FHA PROMOTER; TOXIN; BVGA AB Bordetella pertussis, the etiologic agent of whooping cough, causes disease by employing an array of virulence factors controlled by the BvgA-BvgS two-component signal transduction system. Regulation by this system has been extensively characterized in vitro, where bvg-activated genes are repressed in a process known as phenotypic modulation. Differential regulation of these genes by the response regulator BvgA results in promoters that are activated early, middle, or late after being released from modulation. However, the in vivo environmental signal and regulation pattern has not been described. In order to investigate BvgAS-mediated regulation of B. pertussis virulence factors in vivo using the mouse aerosol challenge model, we have adapted the recombinase-based in vivo technology (RIVET) system for use in B. pertussis. We have demonstrated that these strains show resolution during in vitro growth under non-modulating conditions. In addition, we have demonstrated that modulating strains by growth on media containing MgSO4 does not affect virulence in the mouse aerosol challenge model. We have therefore used the RIVET system to reveal the time-course of gene expression in vivo for selected B. pertussis virulence factors (cya, fha, prn and ptx). Our data indicate that this method can be effectively used to monitor and compare in vivo and in vitro gene expression in B. pertussis, and that temporal regulation patterns previously observed in vitro are mirrored in vivo. C1 US FDA, Div Bacterial Prasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Veal-Carr, WL (reprint author), US FDA, Div Bacterial Prasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. EM carrw@cber.fda.gov NR 50 TC 36 Z9 38 U1 1 U2 3 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD FEB PY 2005 VL 55 IS 3 BP 788 EP 798 DI 10.1111/j.1365-2958.2004.04418.x PG 11 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 889QP UT WOS:000226457800012 PM 15661004 ER PT J AU Turesky, RJ AF Turesky, RJ TI Interspecies metabolism of heterocyclic aromatic amines and the uncertainties in extrapolation of animal toxicity data for human risk assessment SO MOLECULAR NUTRITION & FOOD RESEARCH LA English DT Review DE cancer risk; heterocyclic aromatic amines; interspecies metabolism; polymorphisms; review ID GLUTATHIONE S-TRANSFERASES; DNA ADDUCT FORMATION; FEMALE F344 RATS; FOOD MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; N-ACETYLTRANSFERASE EXPRESSION; ACCELERATOR MASS-SPECTROMETRY; DOSE-RESPONSE RELATIONSHIPS; CIGARETTE-SMOKE CONDENSATE; HUMAN CYTOCHROME-P450 1A2; MAMMARY EPITHELIAL-CELLS AB Heterocyclic aromatic amines (HAAs) are potent bacterial mutagens that are formed in cooked meats, tobacco smoke condensate, and diesel exhaust. Many HAAs are carcinogenic in experimental animal models. Because of their wide-spread occurrence in the diet and environment, HAAs may contribute to some common types of human cancers. The extrapolation of animal toxicity data on HAAs to assess human health risk has many uncertainties, which can lead to tenuous risk assessment estimates. Perhaps the most critical and variable parameters in interspecies extrapolation are the effects of dose, species differences in catalytic activities of xenobiotic metabolism enzymes (XMEs), human XME polymorphisms that lead to interindividual differences in carcinogen metabolism, and dietary constituents that may either augment or diminish the carcinogenic potency of these genotoxins. The impact of these parameters on the metabolism and toxicological properties of HAAs and uncertainties in extrapolation of animal toxicity data for human risk assessment are presented in this article. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR USA. RP Turesky, RJ (reprint author), New York State Dept Hlth, Wadsworth Ctr, Div Environm Dis & Prevent, POB 509, Albany, NY 12201 USA. EM Rxt07@health.state.ny.us NR 188 TC 38 Z9 38 U1 2 U2 11 PU WILEY-V C H VERLAG GMBH PI WEINHEIM PA PO BOX 10 11 61, D-69451 WEINHEIM, GERMANY SN 1613-4125 J9 MOL NUTR FOOD RES JI Mol. Nutr. Food Res. PD FEB PY 2005 VL 49 IS 2 BP 101 EP 117 DI 10.1002/mnfr.200400076 PG 17 WC Food Science & Technology SC Food Science & Technology GA 900VK UT WOS:000227242200002 PM 15617087 ER PT J AU Nowell, S Green, B Tang, YM Wiese, R Kadlubar, FF AF Nowell, S Green, B Tang, YM Wiese, R Kadlubar, FF TI Examination of human tissue cytosols for expression of sulfotransferase isoform 1A2 (SULT1A2) using a SULT1A2-specific antibody SO MOLECULAR PHARMACOLOGY LA English DT Article ID SALMONELLA-TYPHIMURIUM; HYDROXY ARYLAMINES; ACTIVATION; ACETYLTRANSFERASES; CELLS AB Sulfotransferase isoform 1A2 (SULT1A2) is a member of the cytosolic sulfotransferase family of phase II detoxification enzymes. Studies with recombinant enzymes have shown that SULT1A2 can catalyze the bioactivation of several procarcinogens, indicating a potential role in chemical carcinogenesis. However, previous studies have suggested that the SULT1A2 transcript has a splicing defect that might prevent it from becoming translated into protein; therefore, we sought to determine the expression of SULT1A2 in tissues. An antibody directed against a region of human SULT1A2 that differs from other known sulfotransferase isoforms was developed and used to screen a large number of cytosolic fractions from various tissues. Although the SULT1A2 antibody recognized recombinant SULT1A2 and did not cross-react with other SULT isoforms, the expression of SULT1A2 was not detected in any tissue examined. These studies suggest that if SULT1A2 is expressed as protein, the levels are very low and that SULT1A2 probably does not play a physiological role in chemical carcinogenesis. C1 Roswell Pk Canc Inst, Buffalo, NY 14263 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Cedars Sinai Med Ctr, Inst Med Genet, Los Angeles, CA 90048 USA. Pierce Biotechnol, Rockford, IL USA. RP Nowell, S (reprint author), Roswell Pk Canc Inst, BSB S704,Elm & Carlton St, Buffalo, NY 14263 USA. EM susan.nowell@roswellpark.org NR 14 TC 11 Z9 11 U1 0 U2 2 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 FEB PY 2005 VL 67 IS 2 BP 394 EP 399 DI 10.1124/mol.104.006171 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 888ZK UT WOS:000226412900006 PM 15528404 ER PT J AU McMahon, AW Iskander, J Haber, P Chang, SJ Woo, EJ Braun, MM Ball, R AF McMahon, AW Iskander, J Haber, P Chang, SJ Woo, EJ Braun, MM Ball, R TI Adverse events after inactivated influenza vaccination among children less than 2 years of age: Analysis of reports from the Vaccine Adverse Event Reporting System, 1990-2003 SO PEDIATRICS LA English DT Article DE influenza vaccine; adverse events; infants ID TETANUS-PERTUSSIS VACCINE; YOUNG-CHILDREN; ROTAVIRUS VACCINE; VIRUS-VACCINE; UNITED-STATES; SAFETY; ADULTS; IMMUNIZATION; SEIZURES; RISK AB Background. In April 2002, the Advisory Committee on Immunization Practices ( ACIP) encouraged providers to vaccinate healthy 6- to 23-month-old infants and children with trivalent influenza vaccine (TIV). Objectives. To describe adverse events (AEs) reported to the Vaccine Adverse Event Reporting System (VAERS) after TIV vaccination among children <2 years of age and to compare reports before the ACIP guideline (January 1990 to June 2002) and after the ACIP guideline (July 2002 to June 2003). Methods. VAERS is a passive vaccine safety surveillance system begun by the Food and Drug Administration and the Centers for Disease Control and Prevention in 1990. We reviewed reports to VAERS for children <2 years of age who received TIV, alone or in combination with other vaccines. Influenza seasons were defined as the period from July 1 of one year to June 30 of the following year. Results. Between 1990 and 2003, VAERS received 166 TIV reports for children <2 years of age. There were 62 reports (37%) after administration of TIV alone and 104 reports (63%) after administration of TIV and &GE;1 other vaccine. Approximately one third of reports (N=61) were in the post-ACIP guideline period. The 4 most frequent AE coding terms were fever (N=59, 35%), unspecified or urticarial rash ( 42, 25%), seizure (28, 17%), and injection site reaction (28, 17%). The median number of days from vaccination to symptom onset, the percentage of reports that represented serious AEs, and the gender distribution were similar in the pre-ACIP guideline and post-ACIP guideline periods. The percentage of reports describing an underlying medical condition for the subject decreased from 58% before the ACIP guideline to 37% after the ACIP guideline. Nineteen of 28 seizure reports (68%) described fever with the seizure within 2 days after vaccination. Seizure was the most frequent coding term (N=10, 7 with fever) among 23 serious reports. The annual number of TIV-related VAERS reports for children <2 years of age increased in the post-ACIP guideline period, probably at least in part because of an increase in the number of vaccinees after the ACIP announcement. The safety profiles in the pre-ACIP guideline and post-ACIP guideline periods were similar. Conclusions. In October 2003, the ACIP recommended that all healthy children 6 to 23 months of age be vaccinated with TIV, starting in the 2004-2005 influenza season. This study provides generally reassuring, although limited, data regarding the safety of TIV among children in this age range. Continued surveillance for seizures and other clinically significant AEs is warranted and will continue. C1 US FDA, Ctr Biol Evaluat & Res, Div Epidemiol, Off Biostat & Epidemiol, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Immunizat Safety Branch, Epidemiol & Surveillance Div, Natl Immunizat Program, Atlanta, GA USA. RP McMahon, AW (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Epidemiol, Off Biostat & Epidemiol, 1401 Rockville Pike, Rockville, MD 20852 USA. EM mcmahon@cber.fda.gov NR 41 TC 46 Z9 49 U1 1 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD FEB PY 2005 VL 115 IS 2 BP 453 EP 460 DI 10.1542/peds.2004-1519 PG 8 WC Pediatrics SC Pediatrics GA 893NB UT WOS:000226725000045 PM 15687455 ER PT J AU Godar, DE Lucas, AD AF Godar, DE Lucas, AD TI Ultraviolet-A1 (340-400 nm)-mediated receptor and cytokine changes of transformed lymphocytes SO PHOTODERMATOLOGY PHOTOIMMUNOLOGY & PHOTOMEDICINE LA English DT Article DE apoptosis; cytokines; receptors; ultraviolet ID MESSENGER-RNA EXPRESSION; PROGRAMMED CELL-DEATH; UV-INDUCED IMMEDIATE; HIGH-DOSE UVA1; LUPUS-ERYTHEMATOSUS; DELAYED APOPTOSIS; ATOPIC-DERMATITIS; INTERFERON-GAMMA; RADIATION; PHOTOTHERAPY AB Background: Ultraviolet-A1 (340-400 nm) (UVA1) radiation causes singlet-oxygen damage that depolarizes mitochondrial membranes triggering immediate apoptosis (Tless than or equal to4 h), while it also causes oxidative damage to DNA inducing delayed apoptosis (Tgreater than or equal to24 h). In this study, we examined some potential therapeutic endpoints associated with UVA1-mediated immediate and delayed apoptosis, such as receptor and cytokine changes. Methods: We quantified the number of membrane-bound CD3 receptors on transformed T lymphocytes (Jurkat) and the number of membrane-bound CD19 receptors on transformed B lymphocytes (Daudi) using flow cytometry. We also quantified the release of the cytokines interferon gamma (IFN-gamma) and interleukin-2 (IL-2) using enzyme-linked immunosorbent assays. Results: Out of the entire population of cells, only the apoptotic Daudi cells immediately decreased CD19 expression via capping, while only the apoptotic Jurkat cells increased CD3 receptor expression 24 h post-exposure. Both receptor changes occurred in a UVA1 dose-dependent manner. We also examined other T-cell receptors, such as CD4, CD25, and CD69, but they did not change for up to 24 h following exposure. During UVA1-triggered immediate apoptosis of Jurkat T cells, IFN-gamma levels increased in a dose-dependent manner at 4 h, but returned to baseline levels at 24 h post-exposure, whereas, there was no significant change in IL-2 at 4 or 24 h. Conclusion: Thus, UVA1-triggered immediate apoptosis causes a rapid decrease in the number of CD19 receptors on Daudi B cells and release of IFN-gamma from Jurkat T cells at 4 h, and UVA1-mediated delayed apoptosis causes an increase in the number of CD3 receptors on Jurkat T cells. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd HFZ-120, Rockville, MD 20850 USA. EM DEG@CDRH.FDA.GOV OI GODAR, DIANNE/0000-0002-7690-5223 NR 34 TC 4 Z9 4 U1 0 U2 1 PU BLACKWELL MUNKSGAARD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0905-4383 J9 PHOTODERMATOL PHOTO JI Photodermatol. Photoimmunol. Photomed. PD FEB PY 2005 VL 21 IS 1 BP 23 EP 31 DI 10.1111/j.1600-0781.2005.00133.x PG 9 WC Dermatology SC Dermatology GA 882OS UT WOS:000225948800004 PM 15634220 ER PT J AU Joshi, BH Puri, RK AF Joshi, BH Puri, RK TI Optimization of expression and purification of two biologically active chimeric fusion proteins that consist of human interleukin-13 and Pseudomonas exotoxin in Escherichia coli SO PROTEIN EXPRESSION AND PURIFICATION LA English DT Article DE IL-13 receptors; Pseudomonas exotoxin; inclusion bodies; cytotoxicity; immunotoxin ID SINGLE-CHAIN IMMUNOTOXINS; RECEPTOR-ALPHA CHAIN; INCLUSION-BODIES; ANTITUMOR-ACTIVITY; TRANSFERRIN RECEPTOR; DIPHTHERIA-TOXIN; ANTHRAX TOXIN; ANTI-TAC; CELLS; CYTOTOXICITY AB We have previously reported that a variety of solid human tumor cell lines express a large number of receptors for interleukin- 13 (IL-13). These receptors could be targeted with a chimeric fusion protein consisting of human IL-13 and a truncated form of Pseudomonas exotoxin (PE). We describe here optimization of critical steps involved in high yield expression of two recombinant chimeric fusion proteins for obtaining highly purified and biologically active cytotoxins in Escherichia coli. The chimeric constructs of human IL-13 and two 38 kDa truncated PEs: (i) PE38 and (ii) PE38QQR. (three lysine residues in PE38 at 590, 606. and 613 substituted with two glutamine and one arginine) were used for protein expression in pET prokaryotic expression vector system with kanamycin as a selection antibiotic. Our results suggest that fresh transformation of E coli and induction by isopropyl-beta-D-thiogalactopyranosid,(IPTG) for 6 h resulted in maximum protein expression. To further improve the yield. we used a genetically modified E. coli strain. BL21 (DE3)pLysS. which carries a plasmid for lysozyme with a weak promoter that inhibits T7 RNA polymerase and minimizes protein production in the absence of IPTG. Use of this strain eliminated the need for lysozyme digestion of the induced bacteria to release inclusion bodies, which resulted in expression of purer protein as compared to the conventional BL21(DE3) strain. Additional protocol optimizations included 16 h solubilization of inclusion bodies, constitution of refolding buffer. and timing of dialysis. These proteins were finally purified by Q-Sepharose, mono-Q, and gel filtration chromatography. Between 14-22 and 21-28mg highly purified and biologically active protein was obtained from 1 L of BL21 (DE3) and BL21 (DE3) pLysS bacteria culture, respectively. As IL-13R targeting for brain tumor therapy offers an exciting treatment option. optimization of production of IL-13PE will enhance production of clinical grade material for Phase III clinical trials. Published by Elsevier Inc. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eval, Bethesda, MD USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Off Cellular Tissue & Gene Therapies,Ctr Biol Eval, Bethesda, MD USA. EM Puri@cber.fda.gov NR 40 TC 25 Z9 28 U1 1 U2 12 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-5928 J9 PROTEIN EXPRES PURIF JI Protein Expr. Purif. PD FEB PY 2005 VL 39 IS 2 BP 189 EP 198 DI 10.1016/j.pep.2004.10.012 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 889IP UT WOS:000226437000009 PM 15642470 ER PT J AU Ensign, JS AF Ensign, JS TI A patient's perspective on psychologist prescribing SO PSYCHIATRIC SERVICES LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU AMER PSYCHIATRIC PUBLISHING, INC PI ARLINGTON PA 1000 WILSON BOULEVARD, STE 1825, ARLINGTON, VA 22209-3901 USA SN 1075-2730 J9 PSYCHIAT SERV JI Psychiatr. Serv. PD FEB PY 2005 VL 56 IS 2 BP 219 EP 219 DI 10.1176/appi.ps.56.2.219 PG 1 WC Health Policy & Services; Public, Environmental & Occupational Health; Psychiatry SC Health Care Sciences & Services; Public, Environmental & Occupational Health; Psychiatry GA 902RL UT WOS:000227374100020 PM 15703355 ER PT J AU Bartholomew, MJ Vose, DJ Tollefson, LR Travis, CC AF Bartholomew, MJ Vose, DJ Tollefson, LR Travis, CC TI A linear model for managing the risk of antimicrobial resistance originating in food animals SO RISK ANALYSIS LA English DT Article DE Campylobacter; fluoroquinolones; linear risk model; risk analysis ID CAMPYLOBACTER-JEJUNI; UNITED-STATES; INFECTIONS; ENTERITIS; GASTROENTERITIS; CHICKENS; POULTRY; ILLNESS; HEALTH; TRAVEL AB A linear population risk model used by the U. S. Food and Drug Administration (FDA) Center for Veterinary Medicine (CVM) estimates the risk of human cases of campylobacteriosis caused by fluoroquinolone-resistant Campylobacter. Among the cases of campylobacteriosis attributed to domestically produced chicken, the fluoroquinolone resistance is assumed to result from the use of fluoroquinolones in poultry in the United States. Properties of the linear population risk model are contrasted with those of a farm-to-fork model commonly used for microbial risk assessments. The utility of the linear population model for the purpose for which it was used by CVM is discussed. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Risk Media Ltd, F-24400 Les Leches, France. SAIC, Knoxville, TN 37909 USA. RP Bartholomew, MJ (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. EM mbarthol@cvm.fda.gov NR 49 TC 20 Z9 21 U1 2 U2 3 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0272-4332 J9 RISK ANAL JI Risk Anal. PD FEB PY 2005 VL 25 IS 1 BP 99 EP 108 DI 10.1111/j.0272-4332.2005.00570.x PG 10 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 908GI UT WOS:000227775100010 PM 15787760 ER PT J AU Felten, RP Ogden, NRP Pena, C Provost, MC Schlosser, MJ Witten, CM AF Felten, RP Ogden, NRP Pena, C Provost, MC Schlosser, MJ Witten, CM TI The Food and Drug Administration medical device review process - Clearance of a clot retriever for use in ischemic stroke SO STROKE LA English DT Article DE acute care; stroke, ischemic C1 US FDA, Div Gen Restorat & Neurol Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20815 USA. RP Witten, CM (reprint author), US FDA, Div Gen Restorat & Neurol Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-410, Rockville, MD 20815 USA. EM cmw@cdrh.fda.gov NR 0 TC 25 Z9 25 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 404 EP 406 DI 10.1161/01.STR.0000153063.54972.91 PG 3 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 890JN UT WOS:000226507600061 PM 15625290 ER PT J AU Simak, J Gelderman, MP Yu, H Wright, V Alberts-Grill, N Stranix, JT Baird, AE AF Simak, J Gelderman, MP Yu, H Wright, V Alberts-Grill, N Stranix, JT Baird, AE TI Circulating endothelial microparticles in acute stroke: Relation to clinical severity, lesion volume, and outcome SO STROKE LA English DT Meeting Abstract CT 30th International Stroke Conference CY FEB 02-04, 2005 CL New Orleans, LA SP Amer Stroke Assoc C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NINDS, NIH, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 0 TC 0 Z9 0 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0039-2499 J9 STROKE JI Stroke PD FEB PY 2005 VL 36 IS 2 BP 475 EP 475 PG 1 WC Clinical Neurology; Peripheral Vascular Disease SC Neurosciences & Neurology; Cardiovascular System & Cardiology GA 904UR UT WOS:000227523800290 ER PT J AU Hinderling, PH Hartmann, D AF Hinderling, PH Hartmann, D TI The pH dependency of the binding of drugs to plasma proteins in man SO THERAPEUTIC DRUG MONITORING LA English DT Review DE plasma proteins; binding; pH dependency; humans ID HUMAN-SERUM-ALBUMIN; HUMAN ALPHA-1-ACID GLYCOPROTEIN; ADRENOCEPTOR BLOCKING-DRUGS; BETA-RECEPTOR-ANTAGONISTS; OBSTRUCTIVE LUNG-DISEASE; N-B TRANSITION; EQUILIBRIUM DIALYSIS; PROPRANOLOL BINDING; ALPHA(1)-ACID GLYCOPROTEIN; COUMARIN ANTICOAGULANTS AB An analysis of pH-induced changes of drug binding may contribute to the understanding of the mechanisms involved and the clinical relevance. A literature search was performed, and acceptance criteria set up, to select reported data for quantitative evaluation. The relationship between percentage of unbound drug, fu, and pH was analyzed, and the relevance of physicochemical characteristics of the ligand drugs and the importance of hydrogen ion-induced changes in plasma proteins for the pH sensitivity of the binding were evaluated. With all basic and the majority of acidic drugs, fu depended linearly on pH. Basic drugs showed a consistent behavior with fu decreasing with increasing pH. Acidic compounds behaved differently: With some, fu increased, and with others fu decreased, with pH, and with a third group of acids fu was pH independent. Large differences in the pH sensitivity of the plasma protein binding among individual compounds were found. The fu in plasma for some bases and acids increased up to 136% and 95%, respectively, at pH values seen in severe acidemia or alkemia. These changes in fin could be clinically relevant with narrow-therapeutic-range drugs. Physicochemical properties and other characteristics of the ligands affect the pH sensitivity of the interaction with plasma proteins, but there was clear evidence indicating that pH-induced changes in the plasma proteins are also involved in the observed pH-dependent interaction with ligands. It is generally accepted that the unbound, free fraction in whole blood or plasma is an important determinant of the pharmacokinctics and phar-macodynamics of drugs.(1) pH-dependent protein binding and consequent changes in the free fraction have been reported for many drugs.(2) From a basic science point of view, the systematic study of pH-induced perturbations of the drug-protein interaction may provide insight into the mechanism and forces involved in the binding of drugs to plasma proteins. From a clinical viewpoint it may be of interest to know the extent of pH-induced changes in the unbound fraction of drugs under extreme acidemic or alkalemic conditions. Arterial blood pH values compatible with life reportedly range between 6.7 and 8.0.(3-5) pH values as low as 6.3 have been measured in survivors of drowning accidents.(6) To the best knowledge of the authors, a review and interpretation of pH-associated changes in the protein binding of drugs has not been attempted to date. The goals of this investigation were to (1) review published results of studies that determined the impact of pH changes on the protein binding of drugs in man, (2) select representative data using predetermined criteria, (3) determine relevant factors impacting the pH sensitivity of the drug-protein interaction, and (4) attempt to interpret the results and their clinical relevance. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20852 USA. RP Hinderling, PH (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, HFD 860,DPEI,Room 5022 WOCII,1451 Rockville Pike, Rockville, MD 20852 USA. EM hinderlingp@cder.fda.gov NR 129 TC 26 Z9 28 U1 1 U2 14 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD FEB PY 2005 VL 27 IS 1 BP 71 EP 85 DI 10.1097/00007691-200502000-00014 PG 15 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA 894BI UT WOS:000226764400014 PM 15665750 ER PT J AU Whitton, C Sands, D Lee, T Chang, A Longstaff, C AF Whitton, C Sands, D Lee, T Chang, A Longstaff, C TI A reunification of the US ("NIH") and International Unit into a single standard for Thrombin SO THROMBOSIS AND HAEMOSTASIS LA English DT Article DE Thrombin standardization; clotting assays ID ALPHA-THROMBIN AB The existence of two different units for Thrombin in widespread international use has caused confusion for many years. The holders of the WHO International Standard (IS) for Alpha Thrombin and the US Standard (also known as the "NIH Standard") now report on a collaboration to reunite the International Unit (IU) and the US unit ("NIH unit"). A study was organised involving 25 laboratories in 15 countries to investigate the possibility of preparing a common Standard with a common unit and to investigate aspects of methodology that cause divergence of results using the IS and US Standard. Laboratories were asked to measure the potency of two candidate replacement standards (C, 01/578 and D, 01/580), and potencies were calculated relative to both the existing US Standard (lot J) and the IS (89/588). Data analysis of a total of 128 assays indicated that sample D would make an ideal replacement joint Standard with a potency of 110 IU/ampoule (equivalent to 110 US units per ampoule) based on data from clotting assays. No significant differences in results were observed using fibrinogen of human or bovine origin, or using human plasma. Comparisons of chromogenic and clotting assays indicated that sample D had a similar high proportion of alpha thrombin to the current IS for Alpha Thrombin (89/588). Sample D was adopted as the IS for Thronnbin (01/580) and the US Standard (lot K) with a potency of 110 IU/ampoule. C1 Natl Inst Biol Stand & Controls, Div Haematol, Potters Bar EN6 3QG, Herts, England. Natl Inst Biol Stand & Controls, Informat Div, Potters Bar EN6 3QG, Herts, England. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Longstaff, C (reprint author), Natl Inst Biol Stand & Controls, Div Haematol, Blanche Lane S Mimms, Potters Bar EN6 3QG, Herts, England. EM clongstaff@nibsc.ac.uk RI Longstaff, Colin/D-2413-2013 OI Longstaff, Colin/0000-0001-7608-208X NR 11 TC 9 Z9 9 U1 3 U2 5 PU SCHATTAUER GMBH-VERLAG MEDIZIN NATURWISSENSCHAFTEN PI STUTTGART PA HOLDERLINSTRASSE 3, D-70174 STUTTGART, GERMANY SN 0340-6245 J9 THROMB HAEMOSTASIS JI Thromb. Haemost. PD FEB PY 2005 VL 93 IS 2 BP 261 EP 266 DI 10.1160/TH04-10-0677 PG 6 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 897AC UT WOS:000226975300013 PM 15711741 ER PT J AU Doerge, DR Young, JF McDaniel, LP Twaddle, NC Churchwell, MI AF Doerge, DR Young, JF McDaniel, LP Twaddle, NC Churchwell, MI TI Toxicokinetics of acrylamide and glycidamide in B6C3F(1) mice SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE acrylamide; glycidamide; B6C3F(1) mice ID HEMOGLOBIN ADDUCTS; N-METHYLOLACRYLAMIDE; MAILLARD REACTION; RATS; METABOLITE; MOUSE; DNA; ACRYLONITRILE; ONCOGENICITY; TOXICITY AB Acrylamide (AA) is a widely studied industrial chemical that is neurotoxic, mutagenic to somatic and germ cells, and carcinogenic in rodents. The recent discovery of AA at ppm levels in a wide variety of commonly consumed foods has energized research efforts worldwide to define toxic mechanisms, particularly toxicokinetics and bioavailability. This study compares the toxicokinetics of AA and its epoxide metabolite glycidamide (GA) in serum and tissues of male and female B6C3F1 mice following acute dosing by intravenous, gavage, and dietary routes at 0.1 mg/kg AA or intravenous and gavage dosing with an equimolar amount of GA. AA was rapidly absorbed from oral dosing, was widely distributed to tissues, was efficiently converted to GA, and increased levels of GA-DNA adducts were observed in liver after complete elimination from serum. GA dosing also resulted in rapid absorption, wide distribution to tissues, and produced liver DNA adduct levels that were approximately 40% higher than those from an equimolar dose of AA. While oral administration was found to attenuate AA bioavailability to 23% from the diet and to 32-52% from aqueous gavage, a first-pass effect or other kinetic change resulted in higher relative internal exposure to GA when compared to the intravenous route. A similar effect on relative GA exposure was also evident as the administered dose was reduced, which suggests that as dosing rate decreases, the conversion of AA to GA is more efficient. These findings are critical to the assessment of genotoxicity of AA at low doses in the food supply, which appears to depend on total exposure to GA. Published by Elsevier Inc. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT 110, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov NR 35 TC 57 Z9 60 U1 1 U2 7 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD FEB 1 PY 2005 VL 202 IS 3 BP 258 EP 267 DI 10.1016/j.taap.2004.07.001 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 894GI UT WOS:000226778500005 PM 15667831 ER PT J AU Ravina, B Eidelberg, D Ahlskog, JE Albin, RL Brooks, DJ Carbon, M Dhawan, V Feigin, A Fahn, S Guttman, M Gwinn-Hardy, K McFarland, H Innis, R Katz, RG Kieburtz, K Kish, SJ Lange, N Langston, JW Marek, K Morin, L Moy, C Murphy, D Oertel, WH Oliver, G Palesch, Y Powers, W Seibyl, J Sethi, KD Shults, CW Sheehy, P Stoessl, AJ Holloway, R AF Ravina, B Eidelberg, D Ahlskog, JE Albin, RL Brooks, DJ Carbon, M Dhawan, V Feigin, A Fahn, S Guttman, M Gwinn-Hardy, K McFarland, H Innis, R Katz, RG Kieburtz, K Kish, SJ Lange, N Langston, JW Marek, K Morin, L Moy, C Murphy, D Oertel, WH Oliver, G Palesch, Y Powers, W Seibyl, J Sethi, KD Shults, CW Sheehy, P Stoessl, AJ Holloway, R TI The role of radiotracer imaging in Parkinson disease SO NEUROLOGY LA English DT Review ID POSITRON-EMISSION-TOMOGRAPHY; STRIATAL DOPAMINE TRANSPORTER; RANDOMIZED CONTROLLED-TRIAL; SURROGATE END-POINTS; QUALITY-OF-LIFE; DIFFERENTIAL-DIAGNOSIS; F-18 FLUORODEOXYGLUCOSE; INITIAL TREATMENT; SUBSTANTIA-NIGRA; LEVODOPA AB Radiotracer imaging (RTI) of the nigrostriatal dopaminergic system is a widely used but controversial biomarker in Parkinson disease (PD). Here the authors review the concepts of biomarker development and the evidence to support the use of four radiotracers as biomarkers in PD: [F-18] fluorodopa PET, (+)-[C-11] dihydrotetrabenazine PET, [I-123] beta-CIT SPECT, and [F-18] fluorodeoxyglucose PET. Biomarkers used to study disease biology and facilitate drug discovery and early human trials rely on evidence that they are measuring relevant biologic processes. The four tracers fulfill this criterion, although they do not measure the number or density of dopaminergic neurons. Biomarkers used as diagnostic tests, prognostic tools, or surrogate endpoints must not only have biologic relevance but also a strong linkage to the clinical outcome of interest. No radiotracers fulfill these criteria, and current evidence does not support the use of imaging as a diagnostic tool in clinical practice or as a surrogate endpoint in clinical trials. Mechanistic information added by RTI to clinical trials may be difficult to interpret because of uncertainty about the interaction between the interventions and the tracer. C1 NINDS, Ctr Neurosci, NIH, Bethesda, MD 20892 USA. N Shore Long Isl Jewish Hlth Syst, Inst Med Res, Ctr Neurosci, Manhasset, NY USA. Mayo Clin, Dept Neurol, Rochester, MN USA. Univ Michigan, Dept Neurol, Ann Arbor, MI USA. Ann Arbor VAMC GRECC, Ann Arbor, MI USA. Univ London Imperial Coll Sci Technol & Med, Fac Med, London, England. Columbia Univ Coll Phys & Surg, Dept Neurol, New York, NY 10032 USA. Ctr Addict & Mental Hlth, Human Neurochem Pathol Lab, Toronto, ON, Canada. NIMH, NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. Univ Rochester, Dept Neurol, Rochester, NY 14627 USA. Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Biostat, Boston, MA 02115 USA. Parkinsons Inst, Sunnyvale, CA USA. Inst Neurodegenerat Disorders, New Haven, CT USA. Univ Marburg, Dept Neurol, Marburg, Germany. Med Univ S Carolina, Dept Biometry, Charleston, SC 29425 USA. Med Univ S Carolina, Dept Epidemiol, Charleston, SC 29425 USA. Washington Univ, Sch Med, Dept Neurol, St Louis, MO 63110 USA. Med Coll Georgia, Dept Neurol, Augusta, GA 30912 USA. Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA. Univ British Columbia, Pacific Parkinsons Res Ctr, Vancouver, BC V5Z 1M9, Canada. RP Ravina, B (reprint author), NINDS, Ctr Neurosci, NIH, Room 2225,6001 Execut Blvd, Bethesda, MD 20892 USA. EM ravinab@ninds.nih.gov RI Gwinn, Katrina/C-2508-2009; Eidelberg, David/F-5214-2011; OI Brooks, David/0000-0003-2602-2518 NR 60 TC 201 Z9 206 U1 1 U2 9 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD JAN 25 PY 2005 VL 64 IS 2 BP 208 EP 215 PG 8 WC Clinical Neurology SC Neurosciences & Neurology GA 890JJ UT WOS:000226507200007 PM 15668415 ER PT J AU Andersen, WC Roybal, JE Gonzales, SA Turnipseed, SB Pfenning, AP Kuck, LR AF Andersen, WC Roybal, JE Gonzales, SA Turnipseed, SB Pfenning, AP Kuck, LR TI Determination of tetracycline residues in shrimp and whole milk using liquid chromatography with ultraviolet detection and residue confirmation by mass spectrometry SO ANALYTICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT 5th EURORESIDUE Conference CY MAY 10-12, 2004 CL Noordwijkerhout, NETHERLANDS DE tetracyclines; shrimp; milk ID ANTIBIOTICS; OXYTETRACYCLINE; TISSUES; MUSCLE; CHLORTETRACYCLINE; VALIDATION; KIDNEY; FOODS; PHASE AB Two methods have been developed for the simultaneous determination of tetracycline, oxytetracycline, and chlortetracycline in shrimp and in whole milk. These methods were designed to simplify sample extraction and clean-up steps and to be fast and convenient for routine testing in a regulatory environment. Both methods rely on a simple extraction of the shrimp or milk matrix with succinic acid followed by isolation on a copolymeric solid phase extraction column. Chromatographic separation was achieved using a polar end-capped C8 column with an isocratic mobile phase consisting of organic acid, acetonitrile, and methanol, where 0.1% formic acid or 0.01 M oxalic acid was used as the acid. Formic acid allowed direct confirmation of the three residues by liquid chromatography-tandem mass spectrometry (LC-MS-MS). LC with ultraviolet absorbance at 370 nm resulted in the quantitation of all three tetracycline residues from shrimp and milk samples fortified at 50, 100, 200, 300, and 400 ng g(-1). Average recoveries were greater than 75% with R.S.D. values less than 10%. All three tetracycline residues were confirmed in shrimp (25-400 ng g(-1)) and milk (50-300 ng g(-1)) samples by LC-MS-MS. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. RP Andersen, WC (reprint author), US FDA, Anim Drugs Res Ctr, POB 25087, Denver, CO 80225 USA. EM wendy.andersen@fda.hhs.gov NR 18 TC 63 Z9 72 U1 3 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD JAN 24 PY 2005 VL 529 IS 1-2 BP 145 EP 150 DI 10.1016/j.aca.2004.08.012 PG 6 WC Chemistry, Analytical SC Chemistry GA 896DP UT WOS:000226915100023 ER PT J AU Turnipseed, SB Roybal, JE Andersen, WC Kuck, LR AF Turnipseed, SB Roybal, JE Andersen, WC Kuck, LR TI Analysis of avermectin and moxidectin residues in milk by liquid chromatography-tandem mass spectrometry using an atmospheric pressure chemical ionization/atmospheric pressure photoionization source SO ANALYTICA CHIMICA ACTA LA English DT Article; Proceedings Paper CT 5th EURORESIDUE Conference CY MAY 10-12, 2004 CL Noordwijkerhout, NETHERLANDS DE avermectins; moxidectin; no-discharge atmospheric pressure chemical ionization; atmospheric pressure photoionization; milk ID ELECTROSPRAY-IONIZATION; FLUORESCENCE DETECTION; CONFIRMATION; IVERMECTIN; DORAMECTIN; ABAMECTIN; LIVER AB The avermectins-ivermectin (IVR), doramectin (DOR), eprinomectin (EPR)-and also the milbemycin moxidectin (MOX) are anthelmintic compounds that may be administered to cattle. Different ionization techniques, including atmospheric pressure photoionization (APPI), were evaluated for the detection of these residues in milk. The ionization response of these compounds using APPI was compared with that obtained by atmospheric pressure chemical ionization (APCI), a combination of APPI and APCI, and electrospray. It was found that the relative response of these drugs with different ionization protocols varied depending on the compound and the mobile phase. When monitoring negative ions, the use of the UV lamp increased the MS response. However, the best response for these compounds was obtained by operating the APCI/APPI source in the positive ion mode without any discharge current applied to the corona needle, whether the UV lamp was on or not. Using this mode of ionization, an MS-MS method was established to monitor the product ion scans of the sodiated molecular ions with an ion trap instrument. Milk fortified with these compounds (0.5-20 ng g(-1)) and milk samples from dosed animals were analyzed after isolating the residues with a simple solid phase extraction method. EPR, DOR and IVR were confirmed in all of the extracts analyzed. MOX was confirmed in all samples fortified at 5 ng g(-1) or higher. Acceptable recoveries (greater than or equal to60%) and relative standard deviations (R.S.D. values less than or equal to20%) were observed for the residues at the following levels: EPR and IVR (1-20 ng g(-1)); DOR and MOX (5-20 ng g(-1)). (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, POB 25087, Denver, CO 80225 USA. EM sherri.turnipseed@fda.hhs.gov NR 21 TC 56 Z9 57 U1 1 U2 19 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0003-2670 J9 ANAL CHIM ACTA JI Anal. Chim. Acta PD JAN 24 PY 2005 VL 529 IS 1-2 BP 159 EP 165 DI 10.1016/j.aca.2004.07.061 PG 7 WC Chemistry, Analytical SC Chemistry GA 896DP UT WOS:000226915100025 ER PT J AU McMahon, AW Bryant-Genevier, MC Woo, EJ Braun, MM Ball, R AF McMahon, AW Bryant-Genevier, MC Woo, EJ Braun, MM Ball, R TI Photophobia following smallpox vaccination SO VACCINE LA English DT Letter ID UNITED-STATES; COMPLICATIONS; RISKS C1 US FDA, Off Biostat & Epidemiol, Rockville, MD 20852 USA. RP McMahon, AW (reprint author), US FDA, Off Biostat & Epidemiol, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 5 TC 5 Z9 5 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 JAN 19 PY 2005 VL 23 IS 9 BP 1097 EP 1098 DI 10.1016/j.vaccine.2004.08.035 PG 2 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 889VA UT WOS:000226469600003 PM 15629350 ER PT J AU Miller, DL Ross, JJ AF Miller, DL Ross, JJ TI Vaccine INDs: review of clinical holds SO VACCINE LA English DT Article; Proceedings Paper CT 7th Annual Conference on Vaccine Research CY MAY 24-26, 2004 CL Arlington, VI SP Natl Inst Biol Standards & Control DE vaccine IND; clinical hold; pre-IND AB A sponsor developing a vaccine or related product for clinical study in the U.S. must submit an Investigational New Drug Application (IND) to the Food and Drug Administration (FDA). Evaluation of information submitted to the IND may prompt a clinical hold., for reasons described in 21 CFR 312.42. Our review of clinical hold letters issued to sponsors during a 2-year period identified the most often cited reason for a clinical hold, insufficient information (21 CFR 312.42 (b) (1) (iv)), and indicated that the majority of INDs were specifically deficient in clinical information. In addition. sponsors who sought formal pre-IND advice decreased the likelihood of their resulting IND being placed on clinical hold. (C) 2004 Elsevier Ltd. All rights reserved. C1 US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Miller, DL (reprint author), US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-475, Rockville, MD 20852 USA. EM daryll.miller@fds.hhs.gov; jennifer.ross@fda.hhs.gov NR 1 TC 5 Z9 5 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 JAN 19 PY 2005 VL 23 IS 9 BP 1099 EP 1101 DI 10.1016/j.vaccine.2004.08.038 PG 3 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 889VA UT WOS:000226469600004 PM 15629351 ER PT J AU Moore, DF Li, H Jeffries, N Wright, V Cooper, RA Elkahloun, A Gelderman, MP Zudaire, E Blevins, G Yu, H Goldin, E Baird, AE AF Moore, DF Li, H Jeffries, N Wright, V Cooper, RA Elkahloun, A Gelderman, MP Zudaire, E Blevins, G Yu, H Goldin, E Baird, AE TI Using peripheral blood mononuclear cells to determine a gene expression profile of acute ischemic stroke - A pilot investigation SO CIRCULATION LA English DT Article DE cerebral infarction; genes; ischemia; stroke ID CEREBRAL-ISCHEMIA; MULTIPLE-SCLEROSIS; NEURONAL APOPTOSIS; GENOMIC RESPONSES; HYPOXIA; DISEASE; PROTEIN; HYPOGLYCEMIA; PATHOGENESIS; MICROARRAY AB Background - Direct brain biopsy is rarely indicated during acute stroke. This study uses peripheral blood mononuclear cells (PBMCs) to determine whether a systemic gene expression profile could be demonstrated in patients with acute ischemic stroke. Methods and Results - Using oligonucleotide microarrays, we compared the gene expression profile of an index cohort of 20 patients with confirmed ischemic stroke on neuroimaging studies with that of 20 referent subjects. Validation studies used quantitative real-time polymerase chain reaction to measure the levels of 9 upregulated genes in the index cohort, and an independent cohort of 9 patients and 10 referent subjects was prospectively studied to determine the accuracy of the Prediction Analysis for Microarrays list to classify stroke. After correction for multiple comparisons with the Bonferroni technique, 190 genes were significantly different between the stroke and referent groups. Broad classes of genes included white blood cell activation and differentiation (approximate to60%), genes associated with hypoxia and vascular repair, and genes potentially associated with an altered cerebral microenvironment. Real-time polymerase chain reaction confirmed increased mRNA expression in 9 of 9 upregulated stroke-associated genes in the index cohort. A panel of 22 genes derived from the Prediction Analysis for Microarrays algorithm in the index cohort classified stroke in the validation cohort with a sensitivity of 78% and a specificity of 80%. Control for the Framingham stroke risk score revealed only a partial dependence of the stroke gene expression profile in PBMCs on vascular risk. Conclusions - This study demonstrated an altered gene expression profile in PBMCs during acute ischemic stroke. Some genes with altered expression were consistent with an adaptive response to central nervous system ischemia. C1 NINDS, Stroke Neurosci Unit, NIH, Bethesda, MD 20892 USA. NINDS, Biostat Branch, NIH, Bethesda, MD 20892 USA. NINDS, Micro Array Core Facil, NIH, Bethesda, MD 20892 USA. NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. NINDS, Dev & Metab Neurol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Lab Cellular Hematol, CBER, Rockville, MD 20857 USA. NCI, Cell & Canc Biol Branch, NIH, Bethesda, MD 20892 USA. RP Moore, DF (reprint author), NINDS, Stroke Neurosci Unit, NIH, 10 Ctr Dr,MSC1294,Room 3N258, Bethesda, MD 20892 USA. EM bairda@ninds.nih.gov NR 37 TC 119 Z9 124 U1 0 U2 6 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0009-7322 J9 CIRCULATION JI Circulation PD JAN 18 PY 2005 VL 111 IS 2 BP 212 EP 221 DI 10.1161/01.CIR.0000152105.79665.C6 PG 10 WC Cardiac & Cardiovascular Systems; Peripheral Vascular Disease SC Cardiovascular System & Cardiology GA 888HW UT WOS:000226365800016 PM 15630028 ER PT J AU Saulez, MN Cebra, CK Heidel, JR Walker, RD Singh, R Bird, KE AF Saulez, MN Cebra, CK Heidel, JR Walker, RD Singh, R Bird, KE TI Encrusted cystitis secondary to Corynebacterium matruchotii infection in a horse SO JAVMA-JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID PHOSPHOLIPID-PHOSPHATE COMPLEXES; HEMATURIA; IDENTIFICATION; CALCIFICATION; PROTEOLIPIDS; ENDOCARDITIS; BACTERIA; SEQUENCE; D2 AB A 17-year-old gelding was evaluated because of dysuria, inappetence, and weight loss. Cystoscopy revealed severe mucosal ecchymoses with luminal hemorrhage and accumulations of crystalloid sludge. Analysis of a urine sample revealed isosthenuria, an alkaline pH, pyuria, hematuria, bacteriuria, and numerous calcium carbonate crystals. Histologic examination of bladder mucosa biopsy specimens revealed severe neutrophilic infiltration with mineralization. A diagnosis of encrusted cystitis exacerbated by sabulous urolithiasis was made. A Corynebacterium sp susceptible to penicillin, sulfonamide, and enrofloxacin was cultured from the urine and the bladder mucosa biopsy specimens. The horse was treated with penicillin G potassium, IV, for 5 days, followed by trimethoprim-sulfamethoxazole for 4 weeks. Bladder lavage was performed daily for the first 3 days with a balanced electrolyte solution and dimethyl sulfoxide in an attempt to aid expulsion of necrotic debris and crystalline sludge from the bladder. Molecular phylogenetic analysis based on the 16S rDNA gene sequence was used to identify the isolate and determine its phylogenetic position. Results indicated that the isolate was closely related to Corynebacterium matruchotii. To our knowledge, encrusted cystitis secondary to C matruchotii has not been previously identified in a horse. C1 McGee Med Ctr, Hagyard Equine Med Inst, Lexington, KY 40511 USA. Oregon State Univ, Coll Vet Med, Dept Clin Sci, Corvallis, OR 97331 USA. Oregon State Univ, Vet Diagnost Lab, Corvallis, OR 97331 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Saulez, MN (reprint author), Coll Vet Sci, Equine Res Ctr, Private Bag X04, ZA-0110 Onderstepoort, South Africa. NR 30 TC 4 Z9 4 U1 1 U2 3 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 JAVMA-J AM VET MED A JI JAVMA-J. Am. Vet. Med. Assoc. PD JAN 15 PY 2005 VL 226 IS 2 BP 246 EP + DI 10.2460/javma.2005.226.246 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 888SZ UT WOS:000226395800022 PM 15706976 ER PT J AU Brown, SA Merritt, K Woods, TO Busick, DN AF Brown, SA Merritt, K Woods, TO Busick, DN TI Effects on instruments of the World Health Organization - Recommended protocols for decontamination after possible exposure to transmissible spongiform encephalopathy-contaminated tissue SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH PART B-APPLIED BIOMATERIALS LA English DT Article DE Creutzfeldt-Jakob disease; mad cow disease; decontamination; surgical instruments; corrosion ID CREUTZFELDT-JAKOB-DISEASE; SCRAPIE AB It has been recommended by the World Health Organization (WHO) and Centers for Disease Control and Prevention (CDC) that rigorous decontamination protocols be used on surgical instruments that have been exposed to tissue possibly contaminated with Creutzfeldt-Jakob disease (CJD). This study was designed to examine the effects of these protocols on various types of surgical instruments. The most important conclusions are: (1) autoclaving in IN NaOH will cause darkening of some instruments; (2) soaking in IN NaOH at room temperature damages carbon steel but not stainless steel or titanium; (3) soaking in chlorine bleach will badly corrode gold-plated instruments and will damage some, but not all, stainless-steel instruments, especially welded and soldered Joints. Damage became apparent after the first exposure and therefore long tests are not necessary to establish which instruments will be damaged. (C) 2004 Wiley Periodicals, Inc. C1 US FDA, CDRH, Off Sci & Technol, Rockville, MD 20850 USA. RP Brown, SA (reprint author), US FDA, CDRH, Off Sci & Technol, HFZ-150,9200 Corp Blvd, Rockville, MD 20850 USA. EM sab@cdrh.fda.gov NR 16 TC 25 Z9 26 U1 2 U2 2 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 15 PY 2005 VL 72B IS 1 BP 186 EP 190 DI 10.1002/jbm.b.30125 PG 5 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 883KU UT WOS:000226011300024 PM 15449256 ER PT J AU Ito, S Ishii, KI Gursel, M Shirotra, H Ihata, A Klinman, DM AF Ito, S Ishii, KI Gursel, M Shirotra, H Ihata, A Klinman, DM TI CpG oligodeoxynucleotides enhance neonatal resistance to Listeria infection SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; INTERFERON-GAMMA PRODUCTION; BACTERIAL-DNA; MONOCYTOGENES INFECTION; MACROPHAGE ACTIVATION; IMMUNOSTIMULATORY DNA; DEPENDENT PROTECTION; CYTOKINE PRODUCTION; MONONUCLEAR-CELLS; FACTOR-ALPHA AB Infection by Listeria monocytogenes causes serious morbidity and mortality during the neonatal period. Previous studies established that immuhostimulatory CpG oligodeoxynucleotides (ODN) can increased the resistance of adult mice to many infectious pathogens, including Listeria. This work examines the capacity of CpG ODN to stimulate a protective immune response to newborns. Results indicate that dendritic cells, macrophages, and B cells from 3-day-old mice respond to CpG stimulation by secreting IFN-gamma, IL-12, and/or TNF-alpha. Spleen cells from CpG-treated neonates produce large amounts of cytokine and NO when exposed to bacteria in vitro. Newborns treated with CpG ODN are protected from lethal Listeria challenge and generate Ag-specific CD4 and CD8 T cells that afford long-term protection against subsequent infection. These results demonstrate that cellular elements of the neonatal immune system respond to stimulation by CpG ODN, thereby reducing host susceptibillity to infectious pathogens. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. Osaka Univ, Microbial Dis Res Inst, Dept Host Def, Osaka, Japan. RP Klinman, DM (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bldg 29A,Room 3D10,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Kliaman@CBER.FDA.GOV RI Gursel, Mayda /H-1812-2012; OI Ishii, Ken/0000-0002-6728-3872 NR 45 TC 44 Z9 45 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JAN 15 PY 2005 VL 174 IS 2 BP 777 EP 782 PG 6 WC Immunology SC Immunology GA 888FV UT WOS:000226360500026 PM 15634898 ER PT J AU Brittain, E Lin, D AF Brittain, E Lin, D TI A comparison of intent-to-treat and per-protocol results in antibiotic non-inferiority trials SO STATISTICS IN MEDICINE LA English DT Article DE non-inferiority trial; design; intent-to-treat; antibiotics ID EQUIVALENCE; ISSUES AB While the intent-to-treat (ITT) analysis is widely accepted for superiority trials, there remains debate about its role in non-inferiority trials. It is often said that the ITT tends to be anti-conservative in the demonstration of non-inferiority. This concern has led to some reliance on per-protocol (PP) analyses that exclude patients on the basis of post-baseline events, despite the inherent bias of such analyses. We compare ITT and PP results from antibiotic trials presented to the public at the FDA's Anti-infective Drug Advisory Committee from 1999 to 2003. While the number of available trials is too small to produce clear conclusions, these data did not support the assumption that the ITT would lead to smaller treatment difference than the PP, in the setting of antibiotic trials. Possible explanations are discussed. Published in 2004 by John Wiley Sons, Ltd. C1 US FDA, Div Biometr 3, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. RP Lin, D (reprint author), US FDA, Div Biometr 3, Off Biostat, Ctr Drug Evaluat & Res, HFD-725,9201 Corp Blvd, Rockville, MD 20850 USA. EM lind@cder.fda.gov NR 8 TC 42 Z9 42 U1 1 U2 3 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 2005 VL 24 IS 1 BP 1 EP 10 DI 10.1002/sim.1934 PG 10 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 884RG UT WOS:000226103000001 PM 15532089 ER PT J AU Chiesa, R Piccardo, P Dossena, S Nowoslawski, L Roth, KA Ghetti, B Harris, DA AF Chiesa, R Piccardo, P Dossena, S Nowoslawski, L Roth, KA Ghetti, B Harris, DA TI Bax deletion prevents neuronal loss but not neurological symptoms in a transgenic model of inherited prion disease SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article DE synapse; apoptosis; neurodegeneration; cerebellum ID CEREBELLAR GRANULE CELLS; CREUTZFELDT-JAKOB-DISEASE; DEFICIENT MICE; INSERTIONAL MUTATION; ALZHEIMERS-DISEASE; MURINE SCRAPIE; NERVOUS-SYSTEM; SYNAPSE LOSS; DEATH; APOPTOSIS AB Transgenic Tg(PG14) mice express a mutant prion protein containing 14 octapeptide repeats, whose human homologue is associated with an inherited prion dementia. These mice develop a progressive neurological disorder characterized by ataxia and cerebellar atrophy, with massive apoptotic degeneration of granule neurons. Bax, a proapoptotic gene of the Bcl-2 family, plays a key role in regulating cell death in the nervous system. To analyze the role of Bax in the Tg(PG14) phenotype, we crossed Tg(PG14) mice with Bax(-/-) mice to obtain Tg(PG14)/Bax(-/-) offspring. Bax deletion effectively rescued cerebellar granule neurons from apoptosis, implying that these cells die via a Bax-dependent process. Surprisingly, however, the age at which symptoms began and the duration of the clinical phase of the illness were not altered in Tg(PG14)/Bax(-/-) mice. In addition, Bax deletion failed to prevent shrinkage of the molecular layer of the cerebellum and loss of synaptophysin-positive synaptic endings. Our analysis indicates that synaptic loss makes a critical contribution to the Tg(PG14) phenotype. These results provide insights into the pathogenesis of prion diseases and have important implications for the treatment of these disorders. C1 Ist Ric Farmacol Mario Negri, Dulbecco Telethon Inst, I-20157 Milan, Italy. Ist Ric Farmacol Mario Negri, Dept Neurosci, I-20157 Milan, Italy. Washington Univ, Sch Med, Dept Cell Biol & Physiol, St Louis, MO 63110 USA. Indiana Univ, Sch Med, Div Neuropathol, Indianapolis, IN 46202 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP Chiesa, R (reprint author), Ist Ric Farmacol Mario Negri, Dulbecco Telethon Inst, I-20157 Milan, Italy. EM chiesa@marionegri.it; dharris@cellbiology.wustl.edu OI Roth, Kevin/0000-0002-0643-995X FU NIA NIH HHS [P30 AG010133, P30 AG 10133]; NIGMS NIH HHS [GM 0831]; NINDS NIH HHS [NS 35107, NS 40975, R01 NS035107, R01 NS040975]; Telethon [TCP00083] NR 38 TC 67 Z9 68 U1 1 U2 1 PU NATL ACAD SCIENCES PI WASHINGTON PA 2101 CONSTITUTION AVE NW, WASHINGTON, DC 20418 USA SN 0027-8424 J9 P NATL ACAD SCI USA JI Proc. Natl. Acad. Sci. U. S. A. PD JAN 4 PY 2005 VL 102 IS 1 BP 238 EP 243 DI 10.1073/pnas.0406173102 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 886HB UT WOS:000226216400043 PM 15618403 ER PT B AU Agrawal, A Huang, S Pfefer, J Lee, MH Drezek, R AF Agrawal, A Huang, S Pfefer, J Lee, MH Drezek, R GP IEEE TI Quantitative evaluation of nanoshells as a contrast agent for optical coherence tomography SO 2005 Conference on Lasers & Electro-Optics (CLEO), Vols 1-3 LA English DT Proceedings Paper CT Conference on Lasers and Electro-Optics (CLEO) CY MAY 22-27, 2005 CL Baltimore, MD ID THERAPY AB We have quantitatively assessed the effectiveness of nanoshells to enhance the quality of optical coherence tomography images. Depending on the scattering characteristics of the sample, nanoshells can increase image signal intensities by 2-5 decibels. (c) 2005 Optical Society of America C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Agrawal, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 8 TC 0 Z9 0 U1 0 U2 1 PU OPTICAL SOC AMERICA PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA BN 1-55752-795-4 PY 2005 BP 2049 EP 2051 PG 3 WC Optics SC Optics GA BDP70 UT WOS:000234819902168 ER PT B AU Wang, SJ AF Wang, SJ GP IEEE TI Utility of high dimensional genomic composite biomarkers in therapeutic and/or diagnostic development SO 2005 Emerging Information Technology Conference (EITC) LA English DT Proceedings Paper CT Emerging Information Technology Conference (EITC) CY AUG 15-16, 2005 CL Taipei, TAIWAN ID MICROARRAY DATA; CANCER; CLASSIFICATION; PREDICTION; DISCOVERY; MEDICINE AB The recent advances of the high throughput biotechnology have made the genome-wide scanning, single nucleotide polymorphisms (SNP) profiling and proteomic pattern profiling possible, in addition to the more traditional candidate genes approach. In this paper, we will collectively use the term genomics to refer to the various technologies. As a result, a massive exciting biological data generated from the genomic technology has increased the complexity of the research questions we seek to answer. The added characteristics of using genomics in therapeutic drug development and in the codevelopment of genomic biomarker diagnostic test have been publicly discussed and have received much attention. Pharmacogenomics (PG) is the science of determining how the clinical benefits and related adverse effects of a drug vary among a population of patients targeted based on genomic features of the patient's disease tissue, blood sample or biological specimen. The genoinic features obtained from microarrays, SNP-arrays, proteomic arrays are to be selected to determine the genomic composite biomarker (GCB) classifier. The bioinformatics involved has helped brought down the high dimensional genoinics to a much reduced dimension in selecting the GCB classifier. The dimension reduction has contributed to the designing of an adaptive and flexible pharmacogenomic clinical trial contrasting the more conventional well-controlled double-blind randomized clinical trials. C1 US FDA, Off Biostat, Off Pharmacoepidemiol & Stat Sci, Ctr Drg Evaluat & Res, Rockville, MD 20857 USA. RP Wang, SJ (reprint author), US FDA, Off Biostat, Off Pharmacoepidemiol & Stat Sci, Ctr Drg Evaluat & Res, Rockville, MD 20857 USA. NR 32 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-9328-7 PY 2005 BP 13 EP 16 PG 4 WC Computer Science, Information Systems; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Engineering, Electrical & Electronic SC Computer Science; Engineering GA BDZ91 UT WOS:000236376100004 ER PT S AU Ilev, IK Waynant, RW AF Ilev, IK Waynant, RW GP IEEE TI Confocal fiber-optic nanobiosensing SO 2005 IEEE LEOS Annual Meeting Conference Proceedings (LEOS) SE IEEE Lasers and Electro-Optics Society (LEOS) Annual Meeting LA English DT Proceedings Paper CT 18th Annual Meeting of the IEEE-Lasers-and-Electro-Optical-Society CY OCT 22-28, 2005 CL Sydney, AUSTRALIA SP IEEE Lasers & Elect Opt Soc DE confocal microscopy; fiber optic biosensors; noninvasive optical sensing AB A novel concept for noninvasive high-resolution confocal biosensing based on simple apertureless fiber-optic confocal designs including either dual-confocal or single-fiber sensor systems is developed. The method can be employed for precise micron/submicron sensing the optical properties of various tissue layers and bulk samples. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Engn Labs, Div Phys, HFZ-130,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. 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 1092-8081 BN 0-7803-9217-5 J9 IEEE LEOS ANN MTG PY 2005 BP 163 EP 164 DI 10.1109/LEOS.2005.1547929 PG 2 WC Engineering, Electrical & Electronic; Optics SC Engineering; Optics GA BDR62 UT WOS:000235109700084 ER PT B AU Weininger, S Pfefer, J Chang, I AF Weininger, S Pfefer, J Chang, I GP IEEE TI Factors to consider in a risk analysis for safe surface temperature SO 2005 IEEE Symposium on Product Safety Engineering (PSES) LA English DT Proceedings Paper CT IEEE Symposium on Product Safety Engineering (PSES) CY OCT 03-04, 2005 CL Schaumburg, IL SP IEEE ID THERMAL-DAMAGE; OPTICAL-PROPERTIES; TISSUE; PHOTOCOAGULATION; BIREFRINGENCE; HEMOLYSIS; COLLAGEN; ALBUMIN; MODEL; SKIN AB The determination that a product is "safe" from a surface temperature perspective when contacting human tissue is a complex problem. Current voluntary and regulatory requirements point to the need to identify the hazards and mitigate these where necessary. This paper starts the discussion of what to consider in this hazard analysis activity by identifying important clinical (human) and device aspects that may need to be considered. C1 US FDA, CDRH, Off Sci & Engn Labs, Rockville, MD 20857 USA. RP Weininger, S (reprint author), US FDA, CDRH, Off Sci & Engn Labs, Rockville, MD 20857 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-9350-3 PY 2005 BP 83 EP 91 PG 9 WC Engineering, Multidisciplinary SC Engineering GA BDY68 UT WOS:000236206700013 ER PT S AU Witters, DM Buzduga, V Seidman, S Kainz, W Casamento, J Ruggera, P AF Witters, DM Buzduga, V Seidman, S Kainz, W Casamento, J Ruggera, P BE Sanson, LD TI Hand-held metal detectors and medical devices: Measurements and testing for electromagnetic compatibility SO 39TH ANNUAL 2005 INTERNATIONAL CARNAHAN CONFERENCE ON SECURITY TECHNOLOGY, PROCEEDINGS SE CARNAHAN CONFERENCE ON SECURITY TECHNOLOGY LA English DT Proceedings Paper CT 39th Annual International Carnahan Conference on Security Technology CY OCT 11-14, 2005 CL Las Palmas, SPAIN SP IEEE Lexington Sect, IEEE Aerosp & Elect Syst Soc, Chung Shan Inst Sci, Natl Cent Univ AB This work examines the electromagnetic compatibility (EMC) of several priority medical devices, such as implanted cardiac pacemakers and implanted nerve stimulators, with the emissions from 28 different hand-held metal detectors (HHMDs). The HHMD emissions were measured and mapped to assess the waveforms, magnitude, and distribution of emission field strengths. Testing with the sample medical devices was performed using a saline filled torso simulator for the implantable type devices. Emissions from the HHMDs were observed to disrupt the function of some of the sample medical devices. One HHMD exhibited significantly higher emissions than the other metal detectors, and caused significant disruptions on several of the sample medical device. The findings and data from this work are being used to help develop standards for characterizing the performance of medical devices. C1 Ctr Devices & Radiol Hlth, Food & Drug Adm HFZ 130, Rockville, MD 20852 USA. RP Witters, DM (reprint author), Ctr Devices & Radiol Hlth, Food & Drug Adm HFZ 130, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. EM dmw@cdrh.fda.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 SN 0737-1160 BN 0-7803-9245-0 J9 CAR C SECUR PY 2005 BP 312 EP 314 DI 10.1109/CCST.2005.1594830 PG 3 WC Computer Science, Artificial Intelligence; Computer Science, Information Systems; Computer Science, Theory & Methods; Imaging Science & Photographic Technology SC Computer Science; Imaging Science & Photographic Technology GA BDZ97 UT WOS:000236384200070 ER PT J AU Bhattaram, VA Booth, BP Ramchandani, RP Beasley, BN Wang, YN Tandon, V Duan, JZ Baweja, RK Marroum, PJ Uppoor, RS Rahman, NA Sahajwalla, CG Powell, JR Mehta, MU Gobburu, JVS AF Bhattaram, VA Booth, BP Ramchandani, RP Beasley, BN Wang, YN Tandon, V Duan, JZ Baweja, RK Marroum, PJ Uppoor, RS Rahman, NA Sahajwalla, CG Powell, JR Mehta, MU Gobburu, JVS TI Impact of pharmacometrics on drug approval and labeling decisions: A survey of 42 new drug applications SO AAPS JOURNAL LA English DT Review DE regulatory decisions; modeling; simulation; FDA; dose-response ID CONGESTIVE-HEART-FAILURE; MARROW TRANSPLANTATION; INTRAVENOUS NESIRITIDE; BUSULFAN; PHARMACOKINETICS; EXPERIENCE C1 US FDA, Rockville, MD 20852 USA. RP Gobburu, JVS (reprint author), 1451 Rockville Pike,Rm 2039,HFD 860, Rockville, MD 20852 USA. EM jogarao.gobburu@fda.hhs.gov NR 20 TC 68 Z9 78 U1 0 U2 3 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1550-7416 J9 AAPS J PY 2005 VL 7 IS 3 BP E503 EP E512 DI 10.1208/aapsj070351 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 007SY UT WOS:000234991200001 PM 16353928 ER PT J AU Jadhav, PR Gobburu, JVS AF Jadhav, PR Gobburu, JVS TI A new equivalence based metric for predictive check to qualify mixed-effects models SO AAPS JOURNAL LA English DT Review DE model validation; model qualification; posterior predictive check; test statistic; discrepancy variable ID HEALTHY-VOLUNTEERS; SIMULATION-MODEL; IVABRADINE C1 Ctr Drug Evaluat & Res, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20852 USA. Virginia Commonwealth Univ, Med Coll Virginia, Dept Pharmaceut, Richmond, VA 23298 USA. RP Gobburu, JVS (reprint author), 1451 Rockville Pike,Rm 2039,HFD-860, Rockville, MD 20852 USA. EM jogarao.gobburu@fda.hhs.gov NR 16 TC 22 Z9 22 U1 0 U2 0 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1550-7416 J9 AAPS J PY 2005 VL 7 IS 3 BP E523 EP E531 DI 10.1208/aapsj070353 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 007SY UT WOS:000234991200003 PM 16353930 ER PT J AU Kenna, LA Labbe, L Barrett, JS Pfister, M AF Kenna, LA Labbe, L Barrett, JS Pfister, M TI Modeling and simulation of adherence: Approaches and applications in therapeutics SO AAPS JOURNAL LA English DT Review DE adherence; modeling; simulation; PK/PD; NONMEM ID ADVERSE DRUG-REACTIONS; AIDS CLINICAL-TRIAL; PATIENT COMPLIANCE; ANTIRETROVIRAL THERAPY; HORMONAL CONSEQUENCES; DISCONTINUATION RATES; MEDICATION COMPLIANCE; HOSPITALIZED-PATIENTS; PROTEASE INHIBITORS; CYCLOSPORINE ERA C1 US FDA, CDER, OCPB, PKLN, Rockville, MD 20857 USA. Univ Montreal, Fac Pharm, Montreal, PQ H3T 1J4, Canada. Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA. Bristol Myers Squibb Co, Strateg Modeling & Simulat, Princeton, NJ 08543 USA. RP Kenna, LA (reprint author), US FDA, CDER, OCPB, PKLN, 13B17,HFD 870,5600 Fishers Lane, Rockville, MD 20857 USA. EM kennal@cder.fda.gov NR 104 TC 1 Z9 2 U1 1 U2 2 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1550-7416 J9 AAPS J PY 2005 VL 7 IS 2 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 007SX UT WOS:000234991100015 ER PT J AU Martinez, M Soback, S AF Martinez, M Soback, S TI Challenges and Issues in Veterinary Pharmacology and Animal Health 2004 - Preface SO AAPS JOURNAL LA English DT Editorial Material C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Kimron Vet Inst, Minist Agr, IL-50250 Bet Dagan, Israel. RP Martinez, M (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA. EM marilyn.martinez@fda.hhs.gov NR 10 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1550-7416 J9 AAPS J PY 2005 VL 7 IS 2 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 007SX UT WOS:000234991100001 ER PT J AU Reimschuessel, R Stewart, L Squibb, E Hirokawa, K Brady, T Brooks, D Shaikh, B Hodsdon, C AF Reimschuessel, R Stewart, L Squibb, E Hirokawa, K Brady, T Brooks, D Shaikh, B Hodsdon, C TI Fish drug analysis - Phish-Pharm: A searchable database of pharmacokinetics data in fish SO AAPS JOURNAL LA English DT Software Review DE aquatic; fish; drug; pharmacokinetics; residues; database; Web ID RAINBOW-TROUT; AQUACULTURE INDUSTRY; TEMPERATURE; VETERINARY; PERSPECTIVE; GENTAMICIN AB Information about drug residues and pharmacokinetic parameters in aquatic species is relatively sparse. In addition, it is difficult to rapidly compare data between studies due to differences in experimental conditions, such as water temperatures and salinity. To facilitate the study of aquatic species drug metabolism, we constructed a Fish Drug/Chemical Analysis Phish-Pharm (FDA-PP) database. This database consists of more than 400 articles that include data from 90 species (64 genera) of fish. Data fields include genus, species, water temperatures, the average animal weight, sample types analyzed, drug (or chemical) name, dosage, route of administration, metabolites identified, method of analysis, protein binding, clearance, volume of distribution in a central compartment (Vc) or volume of distribution at steady-state (Vd), and drug half-lives (t(1/2)). Additional fields list the citation, authors, title, and Internet links. The document will be periodically updated, and users are invited to submit additional data. Updates will be announced in future issues of The AAPS Journal. This database will be a valuable resource to investigators of drug metabolism in aquatic species as well as government and private organizations involved in the drug approval process for aquatic species. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Northwestern Univ, Evanston, IL 60201 USA. Univ Maryland, College Pk, MD 20770 USA. St Georges Univ, St Georges, Grenada. US FDA, Coll Vet Med, Rockville, MD 20855 USA. Independent Comp, Drumore, PA 17518 USA. RP Reimschuessel, R (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM renate.reimschuessel@fda.hhs.gov NR 36 TC 2 Z9 2 U1 1 U2 1 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1550-7416 J9 AAPS J PY 2005 VL 7 IS 2 PG 40 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 007SX UT WOS:000234991100005 ER PT J AU Roth, WL AF Roth, WL TI Use of anatomical and kinetic models in the evaluation of human food additive safety SO AAPS JOURNAL LA English DT Review DE species extrapolation; growth models; toxicokinetics; food additive safety C1 US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Roth, WL (reprint author), US FDA, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM wroth@cfsan.fda.gov NR 13 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1550-7416 J9 AAPS J PY 2005 VL 7 IS 2 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 007SX UT WOS:000234991100006 ER PT J AU Storey, S AF Storey, S TI Challenges with the development and approval of pharmaceuticals for fish SO AAPS JOURNAL LA English DT Review DE aquaculture; fish; drug approval; FDA ID SALMO-SALAR L.; RAINBOW-TROUT; ATLANTIC SALMON; 17-ALPHA-METHYLTESTOSTERONE; AQUACULTURE C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Storey, S (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl,HFV-131, Rockville, MD 20855 USA. EM sstorey@cvm.fda.gov NR 35 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1550-7416 J9 AAPS J PY 2005 VL 7 IS 2 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 007SX UT WOS:000234991100007 ER PT J AU Cogdill, RP Anderson, CA Delgado, M Chisholm, R Bolton, R Herkert, T Afnan, AM Drennen, JK AF Cogdill, RP Anderson, CA Delgado, M Chisholm, R Bolton, R Herkert, T Afnan, AM Drennen, JK TI Process analytical technology case study: Part II. Development and validation of quantitative near-infrared calibrations in support of a process analytical technology application for real-time release SO AAPS PHARMSCITECH LA English DT Article DE PAT; process analytical technology; near-infrared spectroscopy; chemometrics; pharmaceutical analysis ID TABLET HARDNESS; SPECTROSCOPY; REFLECTANCE; SIZE C1 Duquesne Univ, Ctr Pharmaceut Technol, Pittsburgh, PA 16066 USA. AstraZeneca, Macclesfield SK10 4TF, Cheshire, England. AstraZeneca GmbH, D-68723 Plankstadt, Germany. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20852 USA. RP Drennen, JK (reprint author), Duquesne Univ, Sch Pharm, Pittsburgh, PA 15282 USA. EM drennen@duq.edu NR 25 TC 0 Z9 0 U1 1 U2 7 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PY 2005 VL 6 IS 2 AR UNSP 38 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993CY UT WOS:000233931500018 ER PT J AU Cogdill, RP Anderson, CA Delgado-Lopez, M Molseed, D Chisholm, R Bolton, R Herkert, T Afnan, AM Drennen, JK AF Cogdill, RP Anderson, CA Delgado-Lopez, M Molseed, D Chisholm, R Bolton, R Herkert, T Afnan, AM Drennen, JK TI Process analytical technology case study part I: Feasibility studies for quantitative near-infrared method development SO AAPS PHARMSCITECH LA English DT Article DE process analytical technology; near-infrared spectroscopy; chemometrics; tablet analysis; multivariate analysis; pharmaceutical analysis ID SPECTROSCOPY; REFLECTANCE; TABLETS; SPECTRA C1 Duquesne Univ, Ctr Pharmaceut Technol, Pittsburgh, PA 16066 USA. AstraZeneca, Macclesfield SK10 4TF, Cheshire, England. AstraZeneca GmbH, D-68723 Plankstadt, Germany. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20852 USA. RP Drennen, JK (reprint author), Duquesne Univ, Ctr Pharmaceut Technol, Pittsburgh, PA 16066 USA. EM drennen@duq.edu NR 30 TC 4 Z9 4 U1 0 U2 5 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PY 2005 VL 6 IS 2 AR UNSP 37 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993CY UT WOS:000233931500017 ER PT J AU Parikh, DK Ghosh, TK AF Parikh, DK Ghosh, TK TI Feasibility of Transdermal delivery of fluoxetine SO AAPS PHARMSCITECH LA English DT Review DE transdermal; fluoxetine; microemulsion; enhancer; ethanol ID O/W MICROEMULSIONS; STRATUM-CORNEUM; SKIN PERMEATION; ETHANOL C1 Massachusetts Coll Pharm & Hlth Sci, Boston, MA USA. Pfizer Inc, Ann Arbor, MI 48105 USA. US FDA, Off Clin Pharmacol & Biopharmaceut, CDER, Rockville, MD 20857 USA. RP Parikh, DK (reprint author), 2800 Plymouth Rd, Ann Arbor, MI 48105 USA. EM darshan.parikh@cpfizer.com NR 33 TC 3 Z9 3 U1 0 U2 1 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PY 2005 VL 6 IS 2 AR UNSP 22 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 993CY UT WOS:000233931500002 ER PT J AU Tatavarti, AS Fahmy, R Wu, HQ Hussain, AS Marnane, W Bensley, D Hollenbeck, G Hoag, SW AF Tatavarti, AS Fahmy, R Wu, HQ Hussain, AS Marnane, W Bensley, D Hollenbeck, G Hoag, SW TI Assessment of NIR spectroscopy for nondestructive analysis of physical and chemical attributes of sulfamethazine bolus dosage forms SO AAPS PHARMSCITECH LA English DT Article DE sulfamethazine; near infrared (NIR); corn starch paste granulation; partial least squares (PLS); principal component analysis (PCA) ID NEAR-INFRARED SPECTROSCOPY; PARTICLE-SIZE; WATER; IDENTIFICATION; GRANULATION; TABLETS C1 Univ Maryland, Sch Pharm, Baltimore, MD 21201 USA. US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20855 USA. US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Hoag, SW (reprint author), Univ Maryland, Sch Pharm, 20 N Pine St, Baltimore, MD 21201 USA. EM shoag@rx.umaryland.edu NR 22 TC 6 Z9 6 U1 0 U2 0 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1530-9932 J9 AAPS PHARMSCITECH JI AAPS PharmSciTech PY 2005 VL 6 IS 1 AR 15 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 974ER UT WOS:000232574600010 ER PT J AU Anum, D Sedegah, M Dodoo, D Koram, K Kumar, S Rogers, W Akanmori, B AF Anum, D. Sedegah, M. Dodoo, D. Koram, K. Kumar, S. Rogers, W. Akanmori, B. TI An interferon gamma elispot assay for quantitation of T-cell responses against pre-erythrocytic malaria vaccine candidate antigens [MIM-DA-143360] SO ACTA TROPICA LA English DT Meeting Abstract C1 Noguchi Mem Inst Med Res, Legon, Ghana. USN, Med Res Ctr, Silver Spring, MD USA. US FDA, Ctr Biol Review & Res, Rockville, MD 20857 USA. Naval Med Res Unit 3, Cairo, Egypt. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0001-706X J9 ACTA TROP JI Acta Trop. PY 2005 VL 95 BP S308 EP S308 PG 1 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA V80CY UT WOS:000205415600495 ER PT J AU Breman, J Rosen, J Manclark, C Meade, B Collins, W Lobel, H Saliou, P Robert, J Campaore, P Miller, M AF Breman, J. Rosen, J. Manclark, C. Meade, B. Collins, W. Lobel, H. Saliou, P. Robert, J. Campaore, P. Miller, M. TI Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines [MIM-JB-140947] SO ACTA TROPICA LA English DT Meeting Abstract C1 NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NIH, Howard Hughes Med Inst, Res Program, Bethesda, MD 20892 USA. US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA USA. Aventis Pasteur, Paris, France. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0001-706X J9 ACTA TROP JI Acta Trop. PY 2005 VL 95 BP S233 EP S234 PG 2 WC Parasitology; Tropical Medicine SC Parasitology; Tropical Medicine GA V80CY UT WOS:000205415600371 ER PT S AU Williams, AE AF Williams, AE BE Vyas, GN Williams, AE TI How do industry and government approach product standardization? SO ADVANCES IN TRANSFUSION SAFETY SE DEVELOPMENTS IN BIOLOGICALS LA English DT Proceedings Paper CT 3rd Symposium on Advances in Transfusion Safety CY JUN 04-06, 2003 CL Natl Inst Hlth, Bethesda, MD SP US FDA, Amer Assoc Blood Banks, Natl Heart, Lung & Blood Inst, US Dept Defense, Int Assoc Biol HO Natl Inst Hlth C1 FDA, CBER, OBRR, Rockville, MD 20852 USA. RP Williams, AE (reprint author), FDA, CBER, OBRR, HFM-300,1401 Rockville Pike, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1424-6074 BN 3-8055-7935-7 J9 DEV BIOLOGICALS JI Dev. Biols PY 2005 VL 120 BP 167 EP 169 PG 3 WC Biotechnology & Applied Microbiology; Hematology; Public, Environmental & Occupational Health SC Biotechnology & Applied Microbiology; Hematology; Public, Environmental & Occupational Health GA BDW89 UT WOS:000235894600022 PM 16050170 ER PT J AU Oda, N Canelos, PB Essayan, DM Plunkett, BA Myers, AC Huang, SK AF Oda, N Canelos, PB Essayan, DM Plunkett, BA Myers, AC Huang, SK TI Interleukin-17F induces pulmonary neutrophilia and amplifies antigen-induced allergic response SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article DE cytokine; interleukin-17F; pulmonary inflammation ID CUTTING EDGE; CYTOKINE; IL-17; LUNG; INFLAMMATION; EXPRESSION; MICE; FAMILY; ML-1; RECRUITMENT AB Interleukin (IL)-17F is a recently described human cytokine belonging to the IL-17 gene family, but its in vivo function remains to be determined. To this end, a full-length mouse IL-17F cDNA sequence with a 483-bp coding region sequence was first identified. Pulmonary gene transfer of an IL-17F expression construct (pcDNAmIL-17F) in mice was used to investigate its regulatory role. The results showed first that a significant increase in the number of neutrophils was seen in the bronchoalveolar lavage fluids of IL-17F-transduced mice, concomitant with increased expression of genes encoding C-X-C chemokines and inflammatory cytokines when compared with mock and phosphate-buffered saline control animals. Mucosal transfer of the IL-17F gene in ovalbumin (OVA)-sensitized mice before antigen (Ag) challenge enhanced the levels of Ag-induced pulmonary neutrophilia, but not eosinophilia, goblet cell hyperplasia, and mucin gene expression. However, no significant change in the levels of Th2 cytokine expression was noted. A significant enhancement of ventilatory timing in response to inhaled methacholine was also seen in IL-17F-transduced, Ag-sensitized mice, whereas a small but significant increase was found in IL-17F-transduced, naive mice. These results suggest a role for IL-17F in the induction of neutrophilia in the lungs and in the exacerbation of Ag-induced pulmonary inflammation. C1 Johns Hopkins Asthma & Allergy Ctr, Baltimore, MD 21224 USA. US FDA, Rockville, MD 20857 USA. RP Huang, SK (reprint author), Johns Hopkins Asthma & Allergy Ctr, 5501 Hopkins Bayview Circle, Baltimore, MD 21224 USA. EM skhuang@jhmi.edu RI Huang, Shau-Ku/F-5509-2010 FU NIAID NIH HHS [AI-052468, AI-40274] NR 26 TC 91 Z9 106 U1 0 U2 0 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN 1 PY 2005 VL 171 IS 1 BP 12 EP 18 DI 10.1164/rccm.200406-778OC PG 7 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 883BJ UT WOS:000225984800004 PM 15477493 ER PT J AU Posadas, EM Simpkins, F Liotta, LA MacDonald, C Kohn, EC AF Posadas, EM Simpkins, F Liotta, LA MacDonald, C Kohn, EC TI Proteomic analysis for the early detection and rational treatment of cancer - realistic hope? SO ANNALS OF ONCOLOGY LA English DT Review DE cancer; early detection; laser capture microdissection; proteomics; surface-enhanced laser desorption ionization; tissue lysate arrays ID LASER CAPTURE MICRODISSECTION; PROTEIN BIOCHIP TECHNOLOGY; PROSTATE-SPECIFIC ANTIGEN; IMMOBILIZED PH GRADIENTS; OVARIAN-CANCER; MASS-SPECTROMETRY; 2-DIMENSIONAL ELECTROPHORESIS; BREAST-CANCER; IDENTIFICATION; SERUM AB Proteomics is an emerging field in medical science focused on the library of proteins specific to a given biosystem, the proteome, and understanding relationships therein. This field incorporates technologies that can be applied to serum and tissue in order to extract important biological information to aid clinicians and scientists in understanding the dynamic biology of their system of interest, such as a patient with cancer. These tools include laser capture microdissection, tissue lysate arrays and mass spectrometry approaches. These new technologies are more potent coupled with advanced bioinformatics analysis. They are used to characterize the content of, and changes in, the proteome induced by physiological changes, benign and pathologic. The application of these tools has assisted in the discovery of new biomarkers and may lead to new diagnostic tests and improvements in therapeutics. These tools additionally can provide a molecular characterization of cancers, which may allow for individualized molecular therapy. Understanding the basic concepts and tools used will illustrate how best to apply these technologies for patient benefit for the early detection of cancer and improved patient care. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. NCI, FDA, Clin Proteom Program, Bethesda, MD USA. RP Posadas, EM (reprint author), Bldg 10,Room 12N226,10 Ctr Dr MSC 1906, Bethesda, MD 20892 USA. EM posadase@mail.nih.gov NR 41 TC 72 Z9 88 U1 1 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD JAN PY 2005 VL 16 IS 1 BP 16 EP 22 DI 10.1093/annonc/mdi004 PG 7 WC Oncology SC Oncology GA 885JR UT WOS:000226153400005 PM 15598930 ER PT J AU Struble, K Naeger, LK AF Struble, K Naeger, LK TI FDA analysis of the effect of baseline protease genotype on virological response to ATV/RTV vs LPV/RTV in the treatment-experienced subjects in study AI424045 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 14th International HIV Drug Resistance Workshop CY JUN 07-11, 2005 CL Quebec City, CANADA C1 US FDA, Ctr New Drug Evaluat, Div Antiviral Drug Prod, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2005 VL 10 SU 1 BP S31 EP S31 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 972RL UT WOS:000232470800032 ER PT J AU Struble, K Naeger, LK AF Struble, K Naeger, LK TI FDA analysis of the effect of baseline protease genotype on virological response to ATV/RTV vs LPV/RTV in the treatment - experienced subjects in study AI424045 SO ANTIVIRAL THERAPY LA English DT Meeting Abstract CT 14th International HIV Drug Resistance Workshop CY JUN 07-11, 2005 CL Quebec City, CANADA C1 US FDA, Ctr New Drug Evaluat, Div Antiviral Drug Prod, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU INT MEDICAL PRESS LTD PI LONDON PA 2-4 IDOL LANE, LONDON EC3R 5DD, ENGLAND SN 1359-6535 J9 ANTIVIR THER JI Antivir. Ther. PY 2005 VL 10 IS 4 MA 029 BP S31 EP S31 PG 1 WC Infectious Diseases; Pharmacology & Pharmacy; Virology SC Infectious Diseases; Pharmacology & Pharmacy; Virology GA 965PQ UT WOS:000231963100045 ER PT J AU Calci, KR Meade, GK Tezloff, RC Kingsley, DH AF Calci, KR Meade, GK Tezloff, RC Kingsley, DH TI High-pressure inactivation of hepatitis A virus within oysters SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID HUMAN ENTERIC VIRUSES; HIGH HYDROSTATIC-PRESSURE; MERCENARIA-MERCENARIA; SHELF-LIFE; SHELLFISH; MUSSELS; CLAMS; ACCUMULATION; DEPURATION; OUTBREAK AB Previous results demonstrated that hepatitis A virus (HAV) could be inactivated by high hydrostatic pressure (HHP) (D. H. Kingsley, D. Hoover, E. Papafragkou, and G. P. Richards, J. Food Prot. 65:1605-1609, 2002); however, direct evaluation of HAV inactivation within contaminated oysters was not performed. In this study, we report confirmation that HAV within contaminated shellfish is inactivated by HHP. Shellfish were initially contaminated with HAV by using a flowthrough system. PFU reductions of > 1, > 2, and > 3 log(10) were observed for 1-min treatments at 350, 375, and 400 megapascals, respectively, within a temperature range of 8.7 to 10.3degreesC. Bioconcentration of nearly 6 log(10) PFU of HAV per oyster was achieved under simulated natural conditions. These results suggest that HHP treatment of raw shellfish will be a viable strategy for the reduction of infectious HAV. C1 Delaware State Univ, USDA ARS, WW Baker Ctr, Microbial Food Safety Res Unit, Dover, DE 19901 USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Kingsley, DH (reprint author), Delaware State Univ, USDA ARS, WW Baker Ctr, Microbial Food Safety Res Unit, Dover, DE 19901 USA. EM dkingsle@desu.edu NR 38 TC 82 Z9 88 U1 2 U2 19 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JAN PY 2005 VL 71 IS 1 BP 339 EP 343 DI 10.1128/AEM.71.1.339-343.2005 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 889QZ UT WOS:000226458800043 PM 15640207 ER PT J AU Cerutti, S Martinez, LD Wuilloud, RG AF Cerutti, S Martinez, LD Wuilloud, RG TI Knotted reactors and their role in flow-injection on-line preconcentration systems coupled to atomic spectrometry-based detectors SO APPLIED SPECTROSCOPY REVIEWS LA English DT Review DE knotted reactors; preconcentration; flow-injection; atomic spectrometry techniques ID ULTRA-TRACE AMOUNTS; PLASMA-MASS SPECTROMETRY; RARE-EARTH-ELEMENTS; ABSORPTION-SPECTROMETRY; SORPTION PRECONCENTRATION; BIOLOGICAL SAMPLES; NATURAL-WATERS; COPRECIPITATION-PRECONCENTRATION; SPECTROPHOTOMETRIC DETERMINATION; ENVIRONMENTAL-SAMPLES AB The progress in flow-injection (FI) on-line separation and preconcentration employing knotted reactors (KRs) as a sorption medium for organometallic complexes associated to atomic spectrometry techniques is reviewed in this article, focusing the attention on the more frequently complexing agents used. In the last years, the KR has demonstrated to be an excellent alternative in the FI on-line preconcentration procedures; the on-line preconcentration and separation of different metallic species on the inner walls of the KR have been developed utilizing diverse organic and inorganic reagents. The choice of complexing reagents, the coupling of the FI preconcentration system to atomic spectrometry techniques, and the application of the methodologies developed to different samples are discussed. C1 Natl Univ San Luis, Fac Chem, Dept Analyt Chem, RA-5700 San Luis, Argentina. Consejo Nacl Invest Cient & Tecn, Buenos Aires, DF, Argentina. US FDA, Forens Chem Ctr, Cincinnati, OH USA. RP Martinez, LD (reprint author), Natl Univ San Luis, Fac Chem, Dept Analyt Chem, POB 375, RA-5700 San Luis, Argentina. EM ldm@unsl.edu.ar OI Wuilloud, Rodolfo/0000-0002-2962-7718 NR 64 TC 40 Z9 40 U1 0 U2 5 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0570-4928 J9 APPL SPECTROSC REV JI Appl. Spectrosc. Rev. PD JAN-MAR PY 2005 VL 40 IS 1 BP 71 EP 101 DI 10.1081/LAPS38313 PG 31 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 891SN UT WOS:000226601400003 ER PT S AU Baggett, S Mazzola, EP Kennelly, EJ AF Baggett, Scott Mazzola, Eugene P. Kennelly, Edward J. BE UrRahman, A TI THE BENZOPHENONES: ISOLATION, STRUCTURAL ELUCIDATION AND BIOLOGICAL ACTIVITIES SO BIOACTIVE NATURAL PRODUCTS (PT L) SE Studies in Natural Products Chemistry LA English DT Article; Book Chapter ID INHIBITORY NATURAL-PRODUCTS; 2 POLYISOPRENYLATED BENZOPHENONES; INDICA FRUIT RIND; PRENYLATED BENZOPHENONE; HYPERICUM-SAMPSONII; FLORAL RESINS; GARCINIA-XANTHOCHYMUS; CLUSIA-ROSEA; RAIN-FOREST; POLYPRENYLATED BENZOPHENONES AB The benzophenones are a group of ca. 146 compounds comprising a 13-carbon core that can be prenylated and/or further cyclized producing numerous structurally unique compounds. Benzophenones have a limited natural distribution and are concentrated in the Clusiaceae and a few other plant families such as the Moraceae. Benzophenones display many biological activities including antioxidant, antimicrobial, antifungal, cytotoxic, and anti-HIV activities. This chapter reviews the biosynthesis, sources, isolation, structural determination, and biological activities of benzophenones. Our experiences with the activity-guided isolation and structural elucidation of xanthochymol by 1D and 2D NMR from Garcinia xanthochymus fruits are discussed in detail. C1 [Baggett, Scott; Kennelly, Edward J.] CUNY, Dept Biol Sci, Lehman Coll, Bronx, NY 10468 USA. [Baggett, Scott; Kennelly, Edward J.] CUNY, Grad Ctr, Bronx, NY 10468 USA. [Mazzola, Eugene P.] Univ Maryland, Dept Chem & Biochem, FDA Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Baggett, S (reprint author), CUNY, Dept Biol Sci, Lehman Coll, 250 Bedford Pk Blvd W, Bronx, NY 10468 USA. NR 124 TC 27 Z9 27 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1572-5995 BN 978-0-08-045847-2 J9 STUD NAT PROD CHEM JI Stud. Nat. Prod. Chem. PY 2005 VL 32 BP 721 EP 771 PG 51 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BCV84 UT WOS:000311627900017 ER PT S AU Vanderveen, JE AF Vanderveen, JE BE Caldwell, JA Wesensten, NJ TI The need for monitoring metabolic status SO Biomonitoring for Physiological and Cognitive Performance during Military Operations SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Biomonitoring for Physiological and Cognitive Performance during Military Operations CY MAR 31-APR 01, 2005 CL Orlando, FL SP SPIE, Ball Aerosp & Technol Corp, Univ Cent Florida, Coll Opt & Photon, Florida Space Inst, FOI, Swedish Defense Res Agcy, Univ Central Florida DE metabolic monitoring; biomarkers; human performance ID BONE-MINERAL DENSITY; BIOCHEMICAL MARKERS; FRACTURES; PREDICTION; SITES; WOMEN AB Modem military operations utilize complex technologies that require high levels of readiness and sustained cognitive and physical performance of combat military combat personnel. These military operations often depend on weapon systems that use advanced computer technology coupled with an array of sensors that provide continuous information on the battlefield environment and on equipment function. However there is a lack of real-time information on status of the personnel who control these systems and who are vital to mission success. Failure of the human element renders the weapon system useless so it is important to know if an individual is physically and cognitively fit to perform his or her task. Based on the premise that status of metabolic processes provide an early indication of a change in an individuals physiological status, monitoring of selective biomarkers of metabolism and organ function can provide insight on the individual's ability to perform mission tasks. During combat individuals may not be aware that they have reached a compromised physiological condition due to dehydration, physical exertion, stress, fatigue, sleep deprivation, exposure to toxins or other condition that may affect physical and cognitive performance and health. Systems that can provide the individual or his or her commander with information about significant changes in one or more metabolic functions could permit timely intervention to correct the condition. In the event that serious injury has already occurred to an individual, metabolic monitoring can provide valuable intelligence needed for decisions on achieving mission objectives. C1 US FDA, College Pk, MD 20740 USA. RP Vanderveen, JE (reprint author), US FDA, 5100 Paint Branch Pkwy,HFS-300, College Pk, MD 20740 USA. NR 21 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5782-5 J9 P SOC PHOTO-OPT INS PY 2005 VL 5797 BP 1 EP 7 DI 10.1117/12.603362 PG 7 WC Behavioral Sciences; Instruments & Instrumentation; Physiology SC Behavioral Sciences; Instruments & Instrumentation; Physiology GA BCR90 UT WOS:000230979900001 ER PT J AU Rosenberg, AS Worobec, AS AF Rosenberg, AS Worobec, AS TI A risk-based approach to immunogenicity concerns fo therapeutic protein products SO BIOPHARM INTERNATIONAL LA English DT Article ID ANTIBODIES; TOLERANCE; DOGS; MICE AB Manufacturing changes - such as changes in formulation or source material can impact a product's immunogenicity. C1 US FDA, CDER, Div Therapeut Prot, Rockville, MD 20857 USA. US FDA, CDER, Div Therapeut Biol Oncol Prod, Rockville, MD 20852 USA. RP Rosenberg, AS (reprint author), US FDA, CDER, Div Therapeut Prot, Bldg 29A,Room 2D-16,5600 Fishers Lane, Rockville, MD 20857 USA. EM amy.rosenberg@fda.gov; alexandra.worobec@fda.gov NR 6 TC 35 Z9 37 U1 0 U2 3 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1542-166X J9 BIOPHARM INT JI Biopharm. Int. PD JAN PY 2005 VL 18 IS 1 BP 32 EP + PG 3 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 888HD UT WOS:000226363900007 ER PT J AU Klauda, JB Brooks, BR MacKerell, AD Venable, RM Pastor, RW AF Klauda, JB Brooks, BR MacKerell, AD Venable, RM Pastor, RW TI Lipid bilayers: Structural and dynamical properties with an improved force field fit to ab initio quantum mechanics SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract CT 49th Annual Meeting of the Biopysical-Society CY FEB 12-16, 2005 CL Long Beach, CA SP Biopys Soc C1 NHLBI, NIH, Bethesda, MD 20892 USA. Univ Maryland, Baltimore, MD 21201 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RI Klauda, Jeffery/A-4345-2008 NR 0 TC 1 Z9 1 U1 0 U2 1 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD JAN PY 2005 VL 88 IS 1 SU S BP 148A EP 149A PN 2 PG 2 WC Biophysics SC Biophysics GA 888MM UT WOS:000226378500718 ER PT J AU Xiao, SH Hansen, DK Horsley, ETM Tang, YS Khan, RA Stabler, SP Jayaram, HN Antony, AC AF Xiao, SH Hansen, DK Horsley, ETM Tang, YS Khan, RA Stabler, SP Jayaram, HN Antony, AC TI Maternal folate deficiency results in selective upregulation of folate receptors and heterogeneous nuclear ribonucleoprotein-E1 associated with multiple subtle aberrations in fetal tissues SO BIRTH DEFECTS RESEARCH PART A-CLINICAL AND MOLECULAR TERATOLOGY LA English DT Article ID NEURAL-TUBE DEFECTS; NORMAL PLASMA VITAMIN-B-12; MESSENGER-RNA STABILITY; BINDING-PROTEIN; KB-CELLS; EMBRYONIC-DEVELOPMENT; TRANS-FACTOR; RISK FACTOR; HALF-LIFE; ACID AB BACKGROUND: Homocysteine, which increases in folate deficiency, can upregulate folate receptors (FR) at the translational level by increasing the interaction between a short cis-element in the 5'-untranslated region of FR-alpha mRNA and heterogeneous nuclear ribonucleoprotein-E1 (hnRNP-E1). Perturbation of this RNA-protein interaction on GD8.5 induces neural tube defects and neurocristopathies in mice. FR upregulation can also reduce cell proliferation independently of folate deficiency in some human cells. Accordingly, we tested the hypothesis that sustained murine maternal folate deficiency would negatively impact pregnancy outcomes, upregulate FR, and selectively reduce fetal cell proliferation. METHODS: Dams were fed chow with various levels of folic add added for eight weeks before and throughout pregnancy. Following sacrifice on GD17, dams were compared for folate and homocysteine status as well as pregnancy outcomes. Fetuses from some groups were evaluated by specific biochemical, molecular, and immunohistochemical studies for FR, hnRNP-E1, and apoptosis. RESULTS: When compared to dams fed a folate-replete diet, those dams on a folate-depleted diet developed reduced red cell folates and hyperhomocysteinemia and an inverse dose-dependent upregulation of FR and hnRNP-E1 on GD17 without alterations in cell number in the majority of tissues. However, FR overexpression was accompanied by a significant reduction in the net number of cells in the midgut, lung, pons, tongue, and olfactory epithelium, and with premature differentiation in dorsal root ganglion cells and dysplasia of taste buds. By contrast, in the brain, spinal cord, diaphragm, and primordium of follicles of vibrissae, there was less FR expression, which accompanied a net reduction in number of cells and architectural anomalies. Subtle "immunohistochemical footprints" of apoptosis on GD17 fetuses corresponded with net cell loss in the lung and olfactory epithelium. Upregulation of FR could be explained by a homocysteine-induced RNA-protein interaction in folate-depleted fetuses that led to a proportionate increase in murine FR biosynthesis. CONCLUSIONS: Maternal folate deficiency results in selective upregulation of FR and hnRNP-E1 associated with multiple aberrations in fetal tissues that include increased cell loss, architectural anomalies, and premature differentiation. The potential significance of these findings to explain the wide spectrum of folate-responsive birth defects in humans is discussed. (C) 2005 Wiley-Liss, Inc. C1 Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. Indiana Univ, Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA. Richard L Roudebush Vet Affairs Med Ctr, Indianapolis, IN USA. US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Colorado, Hlth Sci Ctr, Denver, CO USA. RP Antony, AC (reprint author), Indiana Univ, Sch Med, Dept Med, 1044 W Walnut St,R4-266, Indianapolis, IN 46202 USA. EM aantony@iupui.edu FU NCI NIH HHS [R01CA58919]; NIA NIH HHS [R01AG09384]; NICHD NIH HHS [R01HD39295] NR 61 TC 28 Z9 35 U1 0 U2 4 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1542-0752 J9 BIRTH DEFECTS RES A JI Birth Defects Res. Part A-Clin. Mol. Teratol. PD JAN PY 2005 VL 73 IS 1 BP 6 EP 28 DI 10.1002/dbra.20105 PG 23 WC Developmental Biology; Toxicology SC Developmental Biology; Toxicology GA 892RO UT WOS:000226667900002 PM 15641086 ER PT J AU Buxton, MB Bondi, SM Au, A Crothers, J Carey, LA DeMichele, A Dorsey, KC Dressler, L Harden, AT Gray, JW Haqq, CM Madhavan, S Perou, C Petricoin, EF AF Buxton, MB Bondi, SM Au, A Crothers, J Carey, LA DeMichele, A Dorsey, KC Dressler, L Harden, AT Gray, JW Haqq, CM Madhavan, S Perou, C Petricoin, EF CA I-SPY Clin Investigators TI Methods to optimize tissue collection and assay performance from 16-gauge core biopsies in the I-SPY Trial. SO BREAST CANCER RESEARCH AND TREATMENT LA English DT Meeting Abstract CT 28th Annual San Antonio Breast Cancer Symposium CY DEC 08-11, 2005 CL San Antonio, TX SP San Antonio Canc Inst, Baylor Coll Med, an NCI-Designated Clin Canc Ctr, Canc Therapy & Res Ctr, Univ Texas San Antonio, Hlth Sci Ctr C1 Univ Calif San Francisco, San Francisco, CA 94143 USA. Univ N Carolina, Chapel Hill, NC USA. Univ Penn, Philadelphia, PA 19104 USA. NCI, Rockville, MD USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 0167-6806 J9 BREAST CANCER RES TR JI Breast Cancer Res. Treat. PY 2005 VL 94 SU 1 BP S54 EP S55 PG 2 WC Oncology SC Oncology GA 985VP UT WOS:000233407100147 ER PT J AU Malejka-Giganti, D Bennett, KK Culp, SJ Beland, FA Shinozuka, H Bliss, RL AF Malejka-Giganti, D Bennett, KK Culp, SJ Beland, FA Shinozuka, H Bliss, RL TI Suppression of 7,12-dimethylbenz[a]anthracene-induced mammary carcinogenesis by pre-initiation treatment of rats with beta-naphthoflavone coincides with decreased levels of the carcinogen-derived DNA adducts in the mammary gland SO CANCER DETECTION AND PREVENTION LA English DT Article DE mammary gland carcinogenesis; suppression; 7,12-dimethylbenz[a]anthracene; beta-naphthoflavone; phase I/phase II enzymes; mammary DNA adducts in vivo; enzyme activity determination; nifedipine oxidation (NIFOX) ID BIG BLUE(R) RATS; SPRAGUE-DAWLEY; HA-RAS; AROMATIC-HYDROCARBONS; DIETARY SELENITE; EPITHELIAL-CELLS; METABOLISM; LIVER; 7,12-DIMETHYLBENZANTHRACENE; EXPRESSION AB Background: Mechanisms underlying prevention by beta-naphthoflavone (beta-NF) of mammary carcinogenesis initiated with 7,12-dimethyl-benz[alpha]anthracene (DMBA) in the rat were elucidated. Methods and results: Treatment of female Sprague-Dawley rats with beta-NF at 40 mg/kg b.wt. for 4 days by oral gavage in corn oil before a single oral dose of DMBA (112 mg/kg b.wt.) suppressed mammary gland carcinogenesis as shown by an increase in the median latent period from 10 to 24 weeks and a 60% decrease in the multiplicity of mammary adenocarcinomas. In contrast, a 20-day treatment with beta-NF starting 3 weeks after DMBA had no significant effects on mammary tumorigenesis. The activities of phase I and phase II enzymes were examined in the liver and mammary gland 24 h after treatment of rats with beta-NF, DMBA, or beta-NF followed by DMBA as in the first bioassay. Treatment with either beta-NF or DMBA increased the hepatic activities of cytochrome P450 (CYP)1A1, 1A2, and 2B1/2, and glutathione S-transferase, and the mammary activity of CYP1A1 The activity of mammary CYP2B1/2 induced by DMBA was decreased by beta-NF. In the liver, the increase of UDP-glucuronosyl transferase (GT) activity in rats treated with beta-NF and DMBA was 2.3-fold greater than in rats treated with DMBA alone. Thus, treatment with beta-NF likely increased the rate of glucuronidation of DMBA dihydrodiols leading to carcinogen detoxification. The levels of the DMBA adducts determined by P-32-postlabeling of the mammary gland DNA were decreased in the beta-NF-pretreated rats. Conclusion: The beta-NF-induced increase in the hepatic UDP-GT activity and decrease in the mammary DNA-DMBA adducts occurred under the same treatment regimen that led to suppression of DMBA-induced mammary carcinogenesis. (c) 2005 International Society for Preventive Oncology. Published by Elsevier Ltd. All rights reserved. C1 Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA. Univ Minnesota, Ctr Comprehens Canc, Minneapolis, MN 55455 USA. RP Malejka-Giganti, D (reprint author), Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. EM malej001@umn.edu FU NCI NIH HHS [CA-28000] NR 45 TC 6 Z9 6 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0361-090X J9 CANCER DETECT PREV JI Cancer Detect. Prev. PY 2005 VL 29 IS 4 BP 338 EP 347 DI 10.1016/j.cdp.2005.01.005 PG 10 WC Oncology SC Oncology GA 972MV UT WOS:000232458800005 PM 16054776 ER PT J AU Espina, V Geho, D Mehta, AI Petricoin, EF Liotta, LA Rosenblatt, KP AF Espina, V Geho, D Mehta, AI Petricoin, EF Liotta, LA Rosenblatt, KP TI Pathology of the future: Molecular profiling for targeted therapy SO CANCER INVESTIGATION LA English DT Review DE laser capture microdissection; microarray; pathology; protein; proteomics; tissue; translational research ID GENE-EXPRESSION PROFILES; CATALYZED REPORTER DEPOSITION; B-CELL LYMPHOMA; LASER CAPTURE MICRODISSECTION; ACUTE LYMPHOBLASTIC-LEUKEMIA; HUMAN BREAST-CANCER; PROSTATE-CANCER; SIGNAL AMPLIFICATION; PROTEIN MICROARRAYS; OVARIAN-CANCER AB Recent evidence suggests that each patient's cancer has a unique subset of molecular pathogenetic derangements. These derangements may both genetic and proteomic alterations. Genomic and proteomic research tools enable genome-wide assessment of gene expression as well as kinase driven cell signaling events. These tools are illuminating the molecular derangements of individual tumors, even if these tumors have similar morphological characteristics. A combination of laser capture microdissection with multiplexed phosphoproteomic analysis using reverse phase protein microarray technology is being used to identify protein molecular signatures of individual tumors. The in vivo state of multiple kinase driven signal pathways may be evaluated by reverse phase protein microarray with a panel of specific antibodies developed based upon our knowledge of biological processes. Molecular profiling of individual patient's tumors is currently being evaluated in clinical trials at the National Institutes of Health, National Cancer Institute for monitoring Epidermal Growth Factor (EGF) cell signaling events for patients with breast and ovarian cancer. C1 NCI, Pathol Lab, Bethesda, MD 20892 USA. Howard Hughes Med Inst, NIH, Bethesda, MD 20817 USA. US FDA, Ctr Biol Evaluat & Res, Off Cellular & Gene Therapy, Bethesda, MD 20014 USA. SW Texas State Univ, Pathol Lab, Dallas, TX USA. RP Espina, V (reprint author), 9000 Rockville Pike,Bldg 10,Room BIB53, Bethesda, MD 20982 USA. OI Espina, Virginia/0000-0001-5080-5972 NR 81 TC 45 Z9 49 U1 1 U2 4 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0735-7907 J9 CANCER INVEST JI Cancer Invest. PY 2005 VL 23 IS 1 BP 36 EP 46 DI 10.1081/CNV-200046434 PG 11 WC Oncology SC Oncology GA 906JE UT WOS:000227636200008 PM 15779867 ER PT S AU Jackson, LS Al-Taher, F AF Jackson, LS Al-Taher, F BE Friedman, M Mottram, D TI Effects of consumer food preparation on acrylamide formation SO CHEMISTRY AND SAFETY OF ACRYLAMIDE IN FOOD SE ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY LA English DT Article; Proceedings Paper CT 1st International Symposium on Chemistry and Safety of Acrylamide in Food CY MAR 29-31, 2004 CL Anaheim, CA DE acrylamide; consumers; cooking; frying; toasting; bread; potato; browning ID FRENCH FRIES; HEATED FOODSTUFFS; MAILLARD REACTION; LC-MS/MS; POTATOES; ONCOGENICITY; ASPARAGINE; EXPOSURE; WORKERS; BAKING AB Acrylamide is formed in high-carbohydrate foods during high temperature processes such as frying, baking, roasting and extrusion. Although acrylamide is known to form during industrial processing of food, high levels of the chemical have been found in home-cooked foods, mainly potato- and grain-based products. This chapter will focus on the effects of cooking conditions (e.g. time/temperature) on acrylamide formation in consumer-prepared foods, the use of surface color (browning) as an indicator of acrylamide levels in some foods, and methods for reducing acrylamide levels in home-prepared foods. As with commercially processed foods, acrylamide levels in home-prepared foods tend to increase with cooking time and temperature. In experiments conducted at the NCFST, we found that acrylamide levels in cooked food depended greatly on the cooking conditions and the degree of "doneness", as measured by the level of surface browning. For example, French fries fried at 150-190 degrees C for up to 10 min had acrylamide levels of 55 to 2130 mu g/kg (wet weight), with the highest levels in the most processed (highest frying times/temperatures) and the most highly browned fries. Similarly, more acrylamide was formed in "dark" toasted bread slices (43.7-610.7 mu g/kg wet weight), than "light" (8.27-217.5 mu g/kg) or "medium" (10.9-213.7 mu g/kg) toasted slices. Analysis of the surface color by colorimetry indicated that some components of surface color ("a" and "L" values) correlated highly with acrylamide levels. This indicates that the degree of surface browning could be used as an indicator of acrylamide formation during cooking. Soaking raw potato slices in water before frying was effective at reducing acrylamide levels in French fries. Additional studies are needed to develop practical methods for reducing acrylamide formation in home-prepared foods without changing the acceptability of these foods. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. IIT, NCFST, Summit Argo, IL 60501 USA. RP Jackson, LS (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM Lauren.Jackson@cfsan.fda.gov NR 43 TC 12 Z9 12 U1 0 U2 12 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013, UNITED STATES SN 0065-2598 BN 0-387-23920-0 J9 ADV EXP MED BIOL JI Adv.Exp.Med.Biol. PY 2005 VL 561 BP 447 EP 465 PG 19 WC Food Science & Technology; Medicine, Research & Experimental; Toxicology SC Food Science & Technology; Research & Experimental Medicine; Toxicology GA BDB40 UT WOS:000232360300034 PM 16438318 ER PT S AU Tong, WD Hong, HX Fang, H Xie, Q Perkins, R Walker, JA AF Tong, WD Hong, HX Fang, H Xie, Q Perkins, R Walker, JA BE Lavine, BK TI From Decision Tree to Heterogeneous Decision Forest: A novel chemometrics approach for structure-activity relationship modeling SO CHEMOMETRICS AND CHEMOINFORMATICS SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Chemometrics and Chemoinformatics held at the 224th American-Chemical-Society National Meeting CY AUG 21-22, 2004 CL Boston, MA SP Amer Chem Soc ID ESTROGEN-RECEPTOR BINDING; FORECASTS AB The techniques of combining the predictions of multiple classification models to produce a single model have been investigated for many years. In earlier applications, the multiple models to be combined have been developed by altering the training set. The use of these so-called resampling techniques, however, enhance the risk of reducing predictivity of the models to be combined and/or over fitting the noise in the data, which might result in poorer prediction of the composite model than the individual models. In this paper, we suggest a novel approach, named Heterogenious Decision Forest (HDF), that combines multiple Decision Tree models. Each Decision Tree model is developed using a unique set of descriptors. When models of similar predictive quality are combined using the HDF method, quality compared to the individual models is consistently and significantly improved in both training and testing steps. An example will be presented for prediction of binding affinity of 232 chemicals to the estrogen receptor. C1 Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US EPA, TSCA, ITC, Washington, DC 20460 USA. Northrop Grumman Informat Technol, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Biometry & Risk Assessment, 3900 NCTR Rd,HFT 20, Jefferson, AR 72079 USA. EM wtong@nctr.fda.gov NR 18 TC 1 Z9 1 U1 1 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3858-8 J9 ACS SYM SER PY 2005 VL 894 BP 173 EP 185 PG 13 WC Chemistry, Multidisciplinary; Chemistry, Analytical SC Chemistry GA BDP27 UT WOS:000234713600012 ER PT J AU Rafii, F Park, M Wynne, R AF Rafii, F Park, M Wynne, R TI Evidence for active drug efflux in fluoroquinolone resistance in Clostridium hathewayi SO CHEMOTHERAPY LA English DT Article DE anaerobic bacteria; Clostridium hathewayi; efflux pump; fluoroquinolone resistance; multidrug transporter ID VITRO ANTIBACTERIAL ACTIVITIES; ENTERICA SEROVAR TYPHIMURIUM; STREPTOCOCCUS-PNEUMONIAE; STAPHYLOCOCCUS-AUREUS; BACTEROIDES-FRAGILIS; CIPROFLOXACIN; NORFLOXACIN; STRAINS; PERFRINGENS; PUMPS AB Background: Most fluoroquinolones have shown limited effectiveness against anaerobic bacteria. Evidence for a multidrug efflux pump, like those involved in fluoroquinolone resistance in some other bacteria, was investigated in Clostridium hathewayi. Methods: A parent strain of C. hathewayi was isolated from human intestinal microflora on a medium with a low concentration of norfloxacin and a mutant strain was selected from it on a medium with a high concentration of norfloxacin. Fluoroquinolone sensitivity, drug accumulation, and the effects of different concentrations of fluoroquinolones on the kinetics of growth in the presence and absence of efflux pump inhibitors were measured. Results: Both strains were resistant to several fluoroquinolones and dyes. The pump inhibitor reserpine increased the sensitivity of both strains to some drugs; it affected the growth kinetics and the efflux of norfloxacin and ethidium bromide. Conclusion:The efflux of fluoroquinolone appears to be one reason for fluoroquinolone resistance in C. hathewayi. Copyright (C) 2005 S. Karger AG, Basel. C1 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 frafii@nctr.fda.gov NR 35 TC 12 Z9 14 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 0009-3157 J9 CHEMOTHERAPY JI Chemotherapy PY 2005 VL 51 IS 5 BP 256 EP 262 DI 10.1159/000087253 PG 7 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 961NX UT WOS:000231670200006 PM 16088123 ER PT J AU Cohen, MH Johnson, JR Pazdur, R AF Cohen, MH Johnson, JR Pazdur, R TI US food and drug administration drug approval summary: Conversion of imatinib mesylate (ST1571; Gleevec) tablets from accelerated approval to full approval SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOGENOUS LEUKEMIA; CHRONIC MYELOID-LEUKEMIA; CYTOGENETIC RESPONSES; PHASE AB Imatinib mesylate (Gleevec, Novartis Pharmaceuticals East Manruer, NJ) received accelerated approval on May 10, 2001 for the treatment of patients with chronic myeloid leukemia (CML) in (a) chronic phase after failure of IFN-alpha therapy, (b) accelerated phase, and (e) blast crisis. The accelerated approval was accompanied by a postmarketing commitment by Novartis Pharmaceuticals to continue patient follow-up to determine duration of treatment response and survival. The present review, based on a safety and efficacy report submitted on December 20, 2002, summarizes data applicable to the conversion of these three CML indications to full approval status. Results: Chronic phase CML: Five hundred thirty-two chronic phase CML patients who had not benefited from prior IFN therapy were treated at a starting imatinib mesylate dose of 400 mg p.o. qd; dose escalation to 800 mg p.o. qd was allowed. Patients had received a median of 14 months of IFN therapy at doses greater than or equal to25 million IU/wk and were all in late chronic phase, with a median time from diagnosis of 32 months. Median duration of imatinib mesylate treatment was 29 months, with 81% of patients treated for greater than or equal to24 months (maximum 31.5 months). Initial favorable treatment responses were sustained. An estimated 87.8% of patients who had a major cytogenetic response maintained their response 2 years after their initial response. After 2 years of treatment, an estimated 85.4% of patients were free of progression to accelerated phase or blast crisis, and the estimated overall survival was 90.8% (95% confidence interval, 88.3-93.2). Accelerated phase CML: Patients enrolled totaled 293: 235 with CML accelerated phase, 48 with relapsed/refractory acute lymphocytic leukemia, 2 with relapsed/refractory acute myclocytic leukemia, and 8 with relapsed/refractory CML in lymphoid blast crisis. Patients received imatinib mesylate 400 or 600 mg p.o. qd. Dose escalation was permitted, to a maximum of 800 mg/d, taken as 400 mg bid. Efficacy results were improved in patients receiving imatinib mesylate 600 mg qd versus patients receiving 400 mg qd. The median duration of hematologic response was 29 versus 17 months and the estimated 24-month maintained hematologic response rate was 61% versus 42%. The median survival of patients treated with imatinib mesylate 600 mg qd was not reached versus 20.9 months for patients receiving 400 mg qd. Estimated 24-month survival rate was 66% versus 46%. The median survival in the advanced leukemia population (acute lymphocytic leukemia, acute myclocytic leukemia, and lymphoid blast crisis) was only 5 months, and only two patients are still on treatment. Blast crisis CML: A total of 260 patients were recruited. The imatinib mesylate dose was initially 400 mg qd (37 patients) but was subsequently increased to 600 mg qd (223 patients). Patients receiving imatinib mesylate 600 mg qd had a higher hematologic response rate than did patients receiving 400 mg (33% versus 16%). Major cytogenetic responses occurred in 15% of the 260 study patients. The overall median survival was 6.9 months: 7.1 months for patients treated with imatinib mesylate 600 mg and 4.7 months for patients receiving imatinib mesylate 400 mg. Estimated 12-month survival rate for all study patients was 32.1% and estimated 24-month survival rate was 18.3%. Safety: Imatinib mesylate was generally well tolerated, but relatively frequent reports of common toxicity criteria grade 3/4 neutropenia and thrombocytopenia were encountered. The most frequently reported adverse events included gastrointestinal disturbances, edema, rash, and musculoskeletal complaints. These rarely led to discontinuation of therapy. Conclusions: The results confirm those of the interim analysis and suggest that imatinib mesylate represents an effective therapeutic agent for the treatment of patients with CML in chronic phase after failure of IFN-alpha therapy, in blast crisis, and in accelerated phase. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Cohen, MH (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. EM cohenma@cder.fda.gov NR 9 TC 76 Z9 78 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN 1 PY 2005 VL 11 IS 1 BP 12 EP 19 PG 8 WC Oncology SC Oncology GA 884TW UT WOS:000226110300004 PM 15671523 ER PT J AU Ko, HS AF Ko, HS TI Approaches to immunogenicity of human protein products. SO CLINICAL IMMUNOLOGY LA English DT Meeting Abstract CT 5th Annual Meeting of the Federation-of-Clinical-Immunology-Society CY MAY 12-16, 2005 CL Boston, MA SP Fed Clin Immunol Soc C1 US FDA, Div Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1521-6616 J9 CLIN IMMUNOL JI Clin. Immunol. PY 2005 VL 115 SU 1 BP S56 EP S56 PG 1 WC Immunology SC Immunology GA 926DY UT WOS:000229104400155 ER PT J AU Mahmood, I Green, MD AF Mahmood, I Green, MD TI Pharmacokinetic and pharmacodynamic considerations in the development of therapeutic proteins SO CLINICAL PHARMACOKINETICS LA English DT Review ID RECOMBINANT-HUMAN-ERYTHROPOIETIN; FOLLICLE-STIMULATING-HORMONE; MOLECULAR-WEIGHT PROTEINS; LIVER BLOOD-FLOW; GROWTH-HORMONE; PLASMINOGEN-ACTIVATOR; CLINICAL-PHARMACOLOGY; INTERFERON ALPHA-2A; CONTINUOUS INFUSION; HEALTHY-SUBJECTS AB With an increasing number of therapeutic proteins moving into preclinical and clinical development, pharmacokinetic factors play an important role in the development of these macromolecules. It is also important that the pharmacokinetic evaluation of these compounds be done as accurately as possible. For macromolecules, evaluation of pharmacokinetic parameters is often complicated by a number of factors. Bioanalytical methods are essential for any pharmacokinetic study, but for many therapeutic proteins the immunoassay and bioassay methodologies are often nonspecific and sometimes the estimation of pharmacokinetic parameters becomes assay dependent. In vivo binding proteins, metabolites and antibody formation may also interfere with bioanalytical methodologies and thus may have significant impact on the pharmacokinetics of therapeutic proteins. There are also difficulties in identifying and quantifying metabolites as well as the binding of therapeutic proteins to endogenous proteins. Some macromolecules exhibit species specificity that complicates the preclinical pharmacological and toxicological evaluation of these compounds. Antibody formation is a particular problem in the preclinical evaluation of therapeutic proteins. Changes in structure or sequence of protein molecules (glycosylation or pegylation) may cause changes in the pharmacokinetics of these compounds. The size of therapeutic proteins may become a hindrance for absorption. Low absorption of intact molecules across biological membranes frequently occurs. Other factors that may affect the pharmacokinetics of a therapeutic protein are immunogenicity, presence of endogenous protein, time of drug administration, and rate and site of drug delivery. The relationship between pharmacokinetics and pharmacodynamics of therapeutic proteins is complex and in most cases is unclear. In many cases the mechanism and site of action are unknown for these compounds. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 6, Clin Pharmacol & Toxicol Branch, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Evaluat 6, Clin Pharmacol & Toxicol Branch, Woodmont Off Ctr 2,1451 Rockville Pike, Rockville, MD 20852 USA. EM Mahmoodi@CDER.FDA.Gov NR 87 TC 77 Z9 78 U1 0 U2 12 PU ADIS INT LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2005 VL 44 IS 4 BP 331 EP 347 DI 10.2165/00003088-200544040-00001 PG 17 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 925TI UT WOS:000229075800001 PM 15828849 ER PT J AU Watson, JT Jones, RC Siston, AM Diaz, PS Gerber, SI Crowe, JB Satzger, RD AF Watson, JT Jones, RC Siston, AM Diaz, PS Gerber, SI Crowe, JB Satzger, RD TI Outbreak of food-borne illness associated with plant material containing raphides SO CLINICAL TOXICOLOGY LA English DT Article DE disease outbreaks; calcium oxalate; Araceae; toxic plants; food poisoning ID DIEFFENBACHIA; PHILODENDRON AB Background. Many botanicals, particularly ornamental houseplants, contain crystals of calcium oxalate called raphides. Raphides have known toxic effects when chewed, including painful edema, vesicle formation, and dysphagia. We report a food-borne illness outbreak associated with ingestion of raphides. Methods. On February 24, 2003, the Chicago Department of Public Health was notified of multiple cases of oral burning and facial edema associated with lunch in an office cafeteria on February 21. The investigation included a case-control study, interviews with kitchen staff, an environmental inspection, and laboratory analysis of leftover foods. Results. Ten cases were identified, including one admitted to the Intensive Care Unit for potential airway obstruction secondary to severe edema, and another seen by Emergency Department staff for oral edema and pain. Ten of 10 case-patients reported oral stinging and burning, and 8 of 10 reported dysphagia. Four of 10 case-patients continued to have symptoms 2 weeks later. Food from the cafeteria's international buffet was consumed by 10 of 10 case-patients and by I of 22 control subjects (odds ratio=undefined); each of the 10 case-patients reported consumption of a Chinese vegetable entree from the international buffet and had no other foods in common. Plant material from the Chinese vegetable entree contained raphides. Conclusion. This outbreak was associated with consumption of raphides resembling those from common botanicals. Clinicians and public health practitioners should be aware of raphide-containing plants as a potential cause of food-borne illness. C1 Chicago Dept Publ Hlth, Epidem Intelligence Serv, Chicago, IL 60612 USA. Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA USA. US FDA, Forens Chem Ctr, Cincinnati, OH USA. RP Watson, JT (reprint author), Chicago Dept Publ Hlth, Epidem Intelligence Serv, 2160 W Ogden Ave, Chicago, IL 60612 USA. EM watson_john@cdph.org NR 8 TC 4 Z9 4 U1 1 U2 4 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0731-3810 J9 CLIN TOXICOL JI Clin. Toxicol. PY 2005 VL 43 IS 1 BP 17 EP 21 DI 10.1081/CLT-200044721 PG 5 WC Toxicology SC Toxicology GA 917PZ UT WOS:000228476400004 PM 15732442 ER PT J AU Alderson, NE AF Alderson, NE TI Untitled SO CLINICAL TRIALS LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Alderson, NE (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 4 BP 271 EP 272 DI 10.1191/1740774505cn108ed PG 2 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975GD UT WOS:000232648100001 ER PT J AU Woodcock, J AF Woodcock, J TI FDA introductory comments: clinical studies design and evaluation issues SO CLINICAL TRIALS LA English DT Article C1 US FDA, Rockville, MD 20857 USA. RP Woodcock, J (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 2 TC 12 Z9 12 U1 0 U2 1 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 4 BP 273 EP 275 DI 10.1191/1740774505cn096oa PG 3 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975GD UT WOS:000232648100002 PM 16281424 ER PT J AU Temple, R AF Temple, R TI How FDA currently makes decisions on clinical studies SO CLINICAL TRIALS LA English DT Article ID RANDOMIZED TRIAL; HEART-FAILURE; CARVEDILOL; SURVIVAL C1 US FDA, Ctr Drug Evaluat & Res, Off Med Policy, Rockville, MD 20857 USA. RP Temple, R (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Med Policy, 5600 Fishers Lane, Rockville, MD 20857 USA. EM Temple@cder.fda.gov NR 6 TC 12 Z9 12 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 4 BP 276 EP 281 DI 10.1191/1740774505cn097oa PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975GD UT WOS:000232648100003 PM 16281425 ER PT J AU Berry, D Goodman, SN Louis, TA Temple, R AF Berry, D Goodman, SN Louis, TA Temple, R TI Floor discussion SO CLINICAL TRIALS LA English DT Editorial Material C1 Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. John Hopkins Sch Med & Publ Hlth, Dept Oncol, Baltimore, MD 21218 USA. John Hopkins Sch Med & Publ Hlth, Dept Pediat, Baltimore, MD 21218 USA. John Hopkins Sch Med & Publ Hlth, Dept Epidemiol & Biostat, Baltimore, MD 21218 USA. John Hopkins Sch Med & Publ Hlth, Dept Biostat, Baltimore, MD 21218 USA. US FDA, Ctr Drug Evaluat & Res, Off Med Policy, Rockville, MD USA. RP Berry, D (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Biostat & Appl Math, Houston, TX 77030 USA. NR 0 TC 19 Z9 20 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 4 BP 301 EP 304 DI 10.1191/1740774505cn101oa PG 4 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975GD UT WOS:000232648100007 ER PT J AU Kessler, L Greenhouse, JB Lachenbruch, PA Gould, L Cornblath, D Katz, R AF Kessler, L Greenhouse, JB Lachenbruch, PA Gould, L Cornblath, D Katz, R TI Panel discussion of case study 1 SO CLINICAL TRIALS LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. Carnegie Mellon Univ, Dept Stat, Pittsburgh, PA 15213 USA. US FDA, Div Biostat, Ctr Biol Evaluat & Res, Rockville, MD USA. Johns Hopkins Sch Med, Dept Neurol, Baltimore, MD 21218 USA. RP Kessler, L (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 4 BP 319 EP 324 DI 10.1191/1740774505cn103oa PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975GD UT WOS:000232648100010 ER PT J AU Campbell, G Witten, C Wittes, J Irony, T Gatsonis, C AF Campbell, G Witten, C Wittes, J Irony, T Gatsonis, C TI Panel discussion of case study 2 SO CLINICAL TRIALS LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Div Gen & Restorat Neurol Dis, Rockville, MD USA. Stat Collaborat, Washington, DC USA. US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Gen Surg Devices Branch, Rockville, MD USA. Brown Univ, Ctr Stat Sci, Providence, RI USA. Brown Univ, Community Hlth Grad Program, Providence, RI USA. RP Campbell, G (reprint author), US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 4 BP 334 EP 339 DI 10.1191/1740774505cn105oa PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975GD UT WOS:000232648100012 ER PT J AU Walton, M Simon, R Rockhold, F DuMouchel, W Koch, G O'Neill, R AF Walton, M Simon, R Rockhold, F DuMouchel, W Koch, G O'Neill, R TI Panel discussion of case study 3 SO CLINICAL TRIALS LA English DT Editorial Material C1 US FDA, Div Therapeut Biol Internal Med, Rockville, MD 20857 USA. NCI, Biometr Res Branch, Bethesda, MD USA. Univ N Carolina, Sch Publ Hlth, Biometr Consulting Lab, Dept Biostat, Chapel Hill, NC USA. US FDA, Off Biostat, Ctr Devices & Radiol Hlth, Rockville, MD USA. RP Walton, M (reprint author), US FDA, Div Therapeut Biol Internal Med, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 4 BP 352 EP 358 DI 10.1191/1740774505cn106oa PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975GD UT WOS:000232648100014 ER PT J AU Campbell, G AF Campbell, G TI The experience in the FDA's center for devices and radiological health with Bayesian strategies SO CLINICAL TRIALS LA English DT Article C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Campbell, G (reprint author), 1350 Piccard Dr,HFZ-550, Rockville, MD 20850 USA. EM gxc@cdrh.fda.gov NR 16 TC 11 Z9 11 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 4 BP 359 EP 363 DI 10.1191/1740774505cn093oa PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975GD UT WOS:000232648100015 PM 16281433 ER PT J AU Alderson, NE Campbell, G D'Agostino, R Ellenberg, S Lindborg, S O'Neill, R Rubin, D Siegel, J AF Alderson, NE Campbell, G D'Agostino, R Ellenberg, S Lindborg, S O'Neill, R Rubin, D Siegel, J TI Statistical issues: a roundtable discussion SO CLINICAL TRIALS LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Biostat, Rockville, MD 20857 USA. Boston Univ, Dept Math & Stat, Boston, MA USA. US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD USA. US FDA, Off Biostat, Ctr Devices & Radiol Hlth, Rockville, MD USA. Harvard Univ, Dept Stat, Cambridge, MA 02138 USA. RP Alderson, NE (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Biostat, Rockville, MD 20857 USA. NR 0 TC 8 Z9 8 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 4 BP 364 EP 372 DI 10.1191/1740774505cn107oa PG 9 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975GD UT WOS:000232648100016 ER PT J AU Woodcock, J Temple, R Midthun, K Schultz, D Sundlof, S AF Woodcock, J Temple, R Midthun, K Schultz, D Sundlof, S TI FDA senior management perspectives SO CLINICAL TRIALS LA English DT Editorial Material C1 US FDA, Off Med Policy, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Woodcock, J (reprint author), US FDA, Off Med Policy, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU HODDER ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 1740-7745 J9 CLIN TRIALS JI Clin. Trials PY 2005 VL 2 IS 4 BP 373 EP 378 DI 10.1191/1740774505cn109oa PG 6 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 975GD UT WOS:000232648100017 ER PT S AU Gomes, AV Zong, CG Edmondson, RD Berhane, BT Wang, GW Le, S Young, G Zhang, J Vondriska, TM Whitelegge, JP Jones, RC Joshua, IG Thyparambil, S Pantaleon, D Qiao, J Loo, J Ping, PP AF Gomes, AV Zong, CG Edmondson, RD Berhane, BT Wang, GW Le, S Young, G Zhang, J Vondriska, TM Whitelegge, JP Jones, RC Joshua, IG Thyparambil, S Pantaleon, D Qiao, J Loo, J Ping, PP BE Sideman, S Beyar, R Landesberg, A TI The murine cardiac 26S proteasome - An organelle awaiting exploration SO COMMUNICATIVE CARDIAC CELL SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 3rd Larry and Horti Fairberg Cardiac Workshop on Communicative Cardiac Cell CY JAN 15-19, 2005 CL Sintra, PORTUGAL SP Israel Inst Technol, Technion, Portugal Minist Sci & Technol DE protein degradation; proteomics; 26S proteasome; ubiquitination ID ISCHEMIA-REPERFUSION INJURY; REGULATORY COMPLEX; YEAST PROTEASOME; 20S PROTEASOME; S PROTEASOME; RAT-LIVER; UBIQUITIN; PATHWAY; PROTEOLYSIS; INHIBITOR AB Multiprotein complexes have been increasingly recognized as essential functional units for a variety of cellular processes, including the protein degradation system. Selective degradation of proteins in eukaryotes is primarily conducted by the ubiquitin proteasome system. The current knowledge base, pertaining to the proteasome complexes in mammalian cells, relies largely upon information gained in the yeast system, where the 265 proteasome is hypothesized to contain a 20S multiprotein core complex and one or two 19S regulatory complexes. To date, the molecular structure of the proteasome system, the proteomic composition of the entire 265 multiprotein complexes, and the specific designated function of individual components within this essential protein degradation system in the heart remain virtually unknown. A functional proteomic approach, employing multidimensional chromatography purification combined with liquid chromatography tandem mass spectrometry and protein chemistry, was utilized to explore the murine cardiac 265 proteasome system. This article presents an overview on the subject of protein degradation in mammalian cells. In addition, this review shares the limited information that has been garnered thus far pertaining to the molecular composition, function, and regulation of this important organelle in the cardiac cells. C1 Univ Calif Los Angeles, Dept Physiol & Med, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Cardiac Proteom & Signaling Lab, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Sch Med, Cardiovasc Res Lab, Los Angeles, CA 90095 USA. Univ Calif Los Angeles, Dept Chem, Los Angeles, CA 90095 USA. Natl Ctr Toxicol Res, Food & Drug Adm, Jefferson, AR 72079 USA. Univ Louisville, Dept Physiol & Biophys, Louisville, KY 40202 USA. Univ Calif Los Angeles, Pasarow Mass Spectrometry Lab, Dept Psychiat & Behavior Sci, Los Angeles, CA 90095 USA. RP Ping, PP (reprint author), Univ Calif Los Angeles, Dept Physiol & Med, 675 CE Young Dr,MRL Bldg,Suite 1609, Los Angeles, CA 90095 USA. EM peipeiping@earthlink.net OI Ping, Peipei/0000-0003-3583-3881; Berhane, Beniam/0000-0002-1963-376X; Gomes, Aldrin/0000-0002-9819-3036 NR 42 TC 21 Z9 24 U1 0 U2 5 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-547-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1047 BP 197 EP 207 DI 10.1196/annals.1341.018 PG 11 WC Cell Biology; Multidisciplinary Sciences SC Cell Biology; Science & Technology - Other Topics GA BCY65 UT WOS:000231874400018 PM 16093497 ER PT J AU Shukla, HD Sharma, SK AF Shukla, HD Sharma, SK TI Clostridium botulinum: A bug with beauty and weapon SO CRITICAL REVIEWS IN MICROBIOLOGY LA English DT Review DE C. botulinum; genome; bioweapon; botulism; neurotransmitter ID TETANUS NEUROTOXINS; UNITED-STATES; TOXIN; VACCINATION; COMPONENT; SEQUENCE; IMMUNE; MICE; FOOD AB Clostridium botulinum, a Gram-positive, anaerobic spore-forming bacteria, is distinguished by its significant clinical applications as well as its potential to be used as bioterror agent. Growing cells secrete botulinum neurotoxin (BoNT), the most poisonous of all known poisons. While BoNT is the causative agent of deadly neuroparalytic botulism, it also serves as a remarkably effective treatment for involuntary muscle disorders such as blepharospasm, strabismus, hemifacial spasm, certain types of spasticity in children, and other ailments. BoNT is also used in cosmetology for the treatment of glabellar lines, and is well-known as the active component of the anti-aging medications Botox(R) and Dysport(R). In addition, recent reports show that botulinum neurotoxin can be used as a tool for pharmaceutical drug delivery. However, BoNT remains the deadliest of all toxins, and is viewed by biodefense researchers as a possible agent of bioterrorism (BT). Among seven serotypes, C. botulinum type A is responsible for the highest mortality rate in botulism, and thus has the greatest potential to act as biological weapon. Genome sequencing of C. botulinum type A Hall strain (ATCC 3502) is now complete, and has shown the genome size to be 3.89 Mb with a G+C content of approximately 28.2%. The bacterium harbors a 16.3 kb plasmid with a 26.8% G+C content-slightly lower than that of the chromosome. Most of the virulence factors in C. botulinum are chromosomally encoded; bioinformatic analysis of the genome sequence has shown that the plasmid does not harbor toxin genes or genes for related virulence factors. Interestingly, the plasmid does harbor genes essential to replication, including dnaE, which encodes the alpha subunit of DNA polymerase III which has close similarity with its counterpart in C. perfringens strain 13. The plasmid also contains similar genes to those that encode the ABC-type multidrug transport ATPase, and permease. The presence of ABC-type multidrug transport ATPase, and permease suggests putative involvement of efflux pumps in bacteriocin production, modification, and export in C. botulinum. The C. botulinum plasmid additionally harbors genes for LambdaBa04 prophage and site-specific recombinase that are similar to those found in the Ames strain of Bacillus anthracis; these genes and their products may play a role in genomic rearrangement. Completion of genome sequencing for C. botulinum will provide an opportunity to design genomic and proteomic-based systems for detecting different serotypes of C. botulinum strains in the environment. The completed sequence may also facilitate identification of potential virulence factors and drug targets, as well as help characterize neurotoxin-complexing proteins, their polycistronic expression, and phylogenetic relationships between different serotypes. C1 Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, Baltimore, MD 21202 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Shukla, HD (reprint author), Univ Maryland, Ctr Marine Biotechnol, Inst Biotechnol, 600 E Lombard St, Baltimore, MD 21202 USA. EM shukla@umbi.umd.edu NR 55 TC 45 Z9 49 U1 7 U2 51 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-841X J9 CRIT REV MICROBIOL JI Crit. Rev. Microbiol. PY 2005 VL 31 IS 1 BP 11 EP 18 DI 10.1080/10408410590912952 PG 8 WC Microbiology SC Microbiology GA 908SF UT WOS:000227809800002 PM 15839401 ER PT J AU Tournas, VH AF Tournas, VH TI Spoilage of vegetable crops by bacteria and fungi and related health hazards SO CRITICAL REVIEWS IN MICROBIOLOGY LA English DT Review DE fungi; bacteria; fresh vegetables; spoilage; health hazards ID LISTERIA-MONOCYTOGENES; ALFALFA SPROUTS; FUSARIUM-SAMBUCINUM; TOXIN PRODUCTION; SHIGELLA-SONNEI; OUTBREAK; SALMONELLA; LETTUCE; INFECTIONS; PRODUCE AB After harvest, vegetables are often spoiled by a wide variety of microorganisms including many bacterial and fungal species. The most common bacterial agents are Erwinia carotovora, Pseudomonas spp., Corynebacterium, Xanthomonas campestris, and lactic acid bacteria with E. carotovora being the most common, attacking virtually every vegetable type. Fungi commonly causing spoilage of fresh vegetables are Botrytis cinerea, various species of the genera Alternaria, Aspergillus, Cladosporium, Colletotrichum, Phomopsis, Fusarium, Penicillium, Phoma, Phytophthora, Pythium and Rhizopus spp., Botrytis cinerea, Ceratocystis fimbriata, Rhizoctonia solani, Sclerotinia sclerotiorum, and some mildews. A few of these organisms show a substrate preference whereas others such as Botrytis cinerea, Colletotrichum, Alternaria, Cladosporium, Phytophthora, and Rhizopus spp., affect a wide variety of vegetables causing devastating losses. Many of these agents enter the plant tissue through mechanical or chilling injuries, or after the skin barrier has been broken down by other organisms. Besides causing huge economic losses, some fungal species could produce toxic metabolites in the affected sites, constituting a potential health hazard for humans. Additionally, vegetables have often served as vehicles for pathogenic bacteria, viruses, and parasites and were implicated in many food borne illness outbreaks. In order to slow down vegetable spoilage and minimize the associated adverse health effects, great caution should be taken to follow strict hygiene, good agricultural practices (GAPs) and good manufacturing practices (GMPs) during cultivation, harvest, storage, transport, and marketing. C1 US FDA, Div Nat Prod, College Pk, MD 20740 USA. RP Tournas, VH (reprint author), US FDA, Div Nat Prod, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM vtournas@cfsan.fda.gov NR 70 TC 61 Z9 67 U1 8 U2 40 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-841X J9 CRIT REV MICROBIOL JI Crit. Rev. Microbiol. PY 2005 VL 31 IS 1 BP 33 EP 44 DI 10.1080/10408410590886024 PG 12 WC Microbiology SC Microbiology GA 908SF UT WOS:000227809800004 PM 15839403 ER PT J AU Lee, CJ Lee, LH Gu, XX AF Lee, CJ Lee, LH Gu, XX TI Mucosal immunity induced by pneumococcal glycoconjugate SO CRITICAL REVIEWS IN MICROBIOLOGY LA English DT Review DE mucosal immunity; pneumococcal glycoconjugate; CpG adjuvant ID IMMUNODEFICIENCY-VIRUS TYPE-1; HEAT-LABILE ENTEROTOXIN; CPG DNA; INTRANASAL IMMUNIZATION; INTRAMUSCULAR IMMUNIZATION; VACCINE DEVELOPMENT; SYSTEMIC IMMUNITY; BACTERIAL TOXINS; SURFACE-ANTIGEN; IGA ANTIBODIES AB Host defenses against Streptococcus pneumoniae involve opsonophagocytosis mediated by antibodies and complement. Because the pneumococcus is a respiratory pathogen, mucosal immunity may play an important role in the defense against infection. The mechanism for protection in mucosal immunity consists of induction of immunity by the activation of lymphocytes within the mucosal-associated lymphoid tissues, transport of antigen-specific B and T cells from inductive sites through bloodstream and distribute to distant mucosal effector sites. Secretory IgA is primarily involved in protection of mucosal surfaces. Mucosal immunization is an effective way of inducing immune responses at mucosal surfaces. Several mucosal vaccines are in various stages of development. A number of mucosal adjuvants have been proposed. CpG oligodeoxynucleotide (ODN) has been shown to be an effective mucosal adjuvant for various antigens. Mucosal immunity induced by intranasal immunization was studied with a pneumococcal glycoconjugate, using CpG ODN as adjuvant. Mice immunized with type 9V polysaccharide (PS) conjugated to inactivated pneumolysin (Ply) plus CpG produced high levels of 9V PS IgG and IgA antibodies compared to the group that received the conjugate alone. High levels of subclasses of IgG1, IgG2 and IgG3 antibodies were also observed in sera of mice immunized with 9V PS-Ply plus CpG. In addition, high IgG and IgA antibody responses were observed in sera of young mice immunized with 9V PS-Ply plus CpG or the conjugate plus non-CpG compared with the group received the conjugate alone. These results reveal that mucosal immunization with pneumococcal glycoconjugate using CpG as adjuvant can confer protective immunity against pneumococcal infection. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Natl Inst Deafness & Other Commun Disorders, NIH, Rockville, MD USA. RP Lee, CJ (reprint author), US FDA, Ctr Biol & Res, Rockville, MD 20852 USA. EM lee_chi@cber.fda.gov NR 65 TC 14 Z9 15 U1 0 U2 3 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1040-841X J9 CRIT REV MICROBIOL JI Crit. Rev. Microbiol. PY 2005 VL 31 IS 3 BP 137 EP 144 DI 10.1080/10408410591005093 PG 8 WC Microbiology SC Microbiology GA 956JY UT WOS:000231297200001 PM 16170904 ER PT J AU Kraeling, MEK Bronaugh, RL AF Kraeling, MEK Bronaugh, RL TI In vitro percutaneous absorption of acrylamide and styrene from cosmetic vehicles through fuzzy rat and human skin SO CUTANEOUS AND OCULAR TOXICOLOGY LA English DT Article DE percutaneous absorption; acrylamide; styrene; fuzzy rat skin; human skin ID DERMAL ABSORPTION; METABOLISM; INTRAPERITONEAL AB Acrylamide (ACR) and styrene (STY) are residual monomers that remain as impurities in polymers used in hair, nail, and skin care products. These residual monomers may be substantially absorbed through skin. Acrylamide is known to be a neurotoxin in humans and a carcinogen in animals, while styrene has been reported to cause neurotoxic effects in humans and animals and carcinogenic effects in rodents. Therefore, studies were conducted to measure the extent of ACR and STY absorption in fuzzy rat and human skin relevant to exposures from personal care products using in vitro diffusion cell techniques. [C-14]-ACR was applied to skin in flow through diffusion cells for 24 h using an oil-in-water (O/W) emulsion at doses of 2.2 and 13.3 mu g/cm(2) (fuzzy rat skin) and 0.2, 2.2, and 13.3 mu g/cm(2) (human skin). [C-14]-ACR was also applied to human skin using a 2% polyacrylamide gel cream at a dose of 0.3 mu g/cm(2). [C-14]-STY was applied to fuzzy rat and human skin using the O/W emulsion at a dose of 4.1 mu g/cm(2). The total amount of ACR or STY that penetrated into skin layers and receptor fluid at the end of the 24 h experiment was measured and expressed as the percent of applied dose penetrated. Absorption was defined as the amount of ACR or STY absorbed into the receptor fluid. At the both the 2.2 and 13.3 mu g/cm(2) dose levels using the O/W emulsion, ACR was rapidly absorbed through both fuzzy rat and human skin, with peak absorption occurring at 6 h. For fuzzy rat skin, total ACR penetrated was 52.9 +/- 1.3% at the lower dose level and 49.7 +/- 2.4% at the higher dose level. For human skin, total ACR penetrated was very similar with and 48.9 +/- 1.4% (0.2 mu g/cm(2) dose level), 49.5 +/- 4.4% (2.2 mu g/cm(2) dose level), and 60.6 +/- 12.1% (13.3 mu g=cm(2) dose level). The total ACR penetrated was reduced to 38.7 +/- 11.9% when ACR was applied using the 2% polyacrylamide gel cream (0.3 mu g/cm(2) dose level). The amounts of total STY that penetrated into fuzzy rat and human skin using the O/W emulsion vehicle were identical at 1.3% ( 4.1 mu g/cm(2) dose level). Although absorption of STY was relatively low, it was nevertheless rapid with peak absorption occurring at 6 h. Approximately 84 - 92% of the total ACR or STY penetrated was absorbed into the receptor fluid while only 8 - 16% of the total ACR or STY penetrated remained in the skin at 24 h. For these monomers, rodent skin satisfactorily simulated the barrier properties of human skin; there was no significant difference in ACR and STY absorption between fuzzy rat and human skin. C1 US FDA, Off Cosmet & Colors, BRF, Laurel, MD 20708 USA. RP Kraeling, MEK (reprint author), US FDA, Off Cosmet & Colors, BRF, HFS-128,8301 Muirkirk Rd, Laurel, MD 20708 USA. EM margaret.kraeling@fda.hhs.gov NR 34 TC 6 Z9 6 U1 1 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0731-3829 J9 CUTAN OCUL TOXICOL JI Cutan. Ocul. Toxicol. PY 2005 VL 24 IS 1 BP 65 EP 79 DI 10.1081/CUS-200051384 PG 15 WC Ophthalmology; Toxicology SC Ophthalmology; Toxicology GA 949CQ UT WOS:000230762900006 ER PT J AU Etheridge, SM Roesler, CS AF Etheridge, SM Roesler, CS TI Effects of temperature, irradiance, and salinity on photosynthesis, growth rates, total toxicity, and toxin composition for Alexandrium fundyense isolates from the Gulf of Maine and Bay of Fundy SO DEEP-SEA RESEARCH PART II-TOPICAL STUDIES IN OCEANOGRAPHY LA English DT Article DE Alexandrium; environmental factors; growth; paralytic shellfish poisoning; photosynthesis; toxicity ID RED-TIDE DINOFLAGELLATE; PROTOGONYAULAX-TAMARENSIS; GYMNODINIUM-CATENATUM; GONYAULAX-TAMARENSIS; SHELLFISH; DYNAMICS; PHYTOPLANKTON; LIGHT; CATENELLA; CANADA AB The objective of this study was to determine the effects of temperature, irradiance, and salinity on photosynthesis, growth rate, total toxicity, and toxin composition for two Alexandrium fundyense isolates in the laboratory. The A. fundyense cultures studied were isolated from coastal waters off Monhegan Island (MI) in the GoM and the Bay of Fundy (BoF). Laboratory experiments demonstrated that temperature exerted the greatest impact on chlorophyll -specific maximal photosynthetic rates with negligible effects by light or salinity. Temperature and irradiance exerted the greatest influence on species-specific growth rates, with the MI isolate exhibiting greater maximal growth rates. The BoF isolate was generally more toxic, with temperature inducing the greatest change in cellular toxicity, followed by irradiance and salinity. Variations in toxicity were due to changes in toxin concentration, the relative toxin composition, or both depending on the isolate and experimental condition. The lack of a clear relationship between photosynthesis or growth and toxicity suggests that toxicity is, at least in part, driven directly by environmental conditions. Isolate-specific A. fundyense responses to the environment incorporated into modeling efforts may ultimately enhance predictive and monitoring capabilities for PSP outbreaks. (c) 2005 Elsevier Ltd. All rights reserved. C1 Univ Connecticut, Dept Marine Sci, Groton, CT 06340 USA. Bigelow Lab Ocean Sci, Boothbay Harbor, ME 04575 USA. RP Etheridge, SM (reprint author), US FDA, HFS-426,8301 Muirkirk Rd,Room G-205, Laurel, MD 20708 USA. EM stacey.etheridge@cfsan.fda.gov OI DeGrasse, Stacey/0000-0001-7808-4193 NR 29 TC 53 Z9 54 U1 9 U2 27 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0967-0645 J9 DEEP-SEA RES PT II JI Deep-Sea Res. Part II-Top. Stud. Oceanogr. PY 2005 VL 52 IS 19-21 BP 2491 EP 2500 DI 10.1016/j.dsr2.2005.06.026 PG 10 WC Oceanography SC Oceanography GA 997RT UT WOS:000234265800008 ER PT J AU Beger, RD Buzatu, DA Wilkes, JG AF Beger, Richard D. Buzatu, Dan A. Wilkes, Jon G. BE Gad, SC TI COMBINING NMR SPECTRAL INFORMATION WITH ASSOCIATED STRUCTURAL FEATURES TO FORM COMPUTATIONALLY NONINTENSIVE, RUGGED, AND OBJECTIVE MODELS OF BIOLOGICAL ACTIVITY SO DRUG DISCOVERY HANDBOOK SE Pharmaceutical Development Series LA English DT Article; Book Chapter ID NUCLEAR-MAGNETIC-RESONANCE; CORTICOSTEROID-BINDING GLOBULIN; AUTOMATED STRUCTURE EVALUATION; ARYL-HYDROCARBON RECEPTOR; RELATIONSHIP QSDAR MODELS; ANALYSIS COSCOSA MODELS; C-13 NMR; CHEMICAL-SHIFTS; ESTROGEN-RECEPTOR; POLYCHLORINATED DIBENZODIOXINS C1 [Beger, Richard D.; Buzatu, Dan A.; Wilkes, Jon G.] US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Div Syst Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 67 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47172-878-8 J9 PHARM DEV PY 2005 BP 227 EP 286 DI 10.1002/0471728780.ch6 D2 10.1002/0471728780 PG 60 WC Chemistry, Medicinal; Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BYH31 UT WOS:000298786800008 ER PT J AU Johann-Liang, R James, AN Behr, VL Struble, K Birnkrant, DB AF Johann-Liang, R James, AN Behr, VL Struble, K Birnkrant, DB TI Reporting of deaths during pre-approval clinical trials for advanced HIV-infected populations SO DRUG SAFETY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS AB The Division of Antiviral Drug Products of the US FDA has regulatory authority over the investigational new drugs under development by various sponsors to treat HIV-infected populations. The FDA and the sponsors of investigational new drugs use the Code of Federal Regulations to guide the entire drug development process, in order to ensure that safe and efficacious drugs are brought to market. To achieve this goal, diligent monitoring for safety during the pre-approval phase of new drug development is particularly crucial. When deciding what adverse experiences on clinical trials should be expeditiously reported, the Division recommends a conservative interpretation of the Code of Federal Regulations, where an adverse experience in a clinical trial of advanced HIV-infected patients is considered to be 'associated with the use of the drug' when the relationship cannot be ruled out with objective evidence. Fatal adverse experiences for subjects on clinical trials should be especially scrutinised. Safety reporting should be expedited when death occurs during clinical trials of advanced HIV-infected populations. The three components of an expedited reportable death occurrence, namely 'serious', 'unexpected' and 'associated with the drug use' as they relate to advanced HIV-infected populations, are discussed in this article. An occurrence of death is by definition serious. Unexpected experiences are unlisted adverse experiences, but need to be put into the context of specificity and severity. 'Associated with the drug use' has been clarified as 'relationship to the drug cannot be ruled out'. Because death in the advanced HIV-infected/AIDS population is usually a complex event, the possible contribution of the study drug is difficult to rule out. Thus, if the three components of the reporting requirement are met or insufficient information is available to make a firm determination of causality by the seventh day of the reporting period, the Division of Antiviral Drug Products expects expedited death reports on subjects participating in investigational new drug clinical studies. C1 US FDA, Div Antiviral Drug Prod HFD 530, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. RP Johann-Liang, R (reprint author), US FDA, Div Antiviral Drug Prod HFD 530, Ctr Drug Evaluat & Res, 9201 Corp Blvd, Rockville, MD 20850 USA. EM johannliangr@cder.fda.gov NR 8 TC 1 Z9 1 U1 0 U2 0 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2005 VL 28 IS 7 BP 559 EP 564 DI 10.2165/00002018-200528070-00001 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 945RI UT WOS:000230519400001 PM 15963004 ER PT J AU La Grenade, L Lee, L Weaver, J Bonnel, R Karwoski, C Governale, L Brinker, A AF La Grenade, L Lee, L Weaver, J Bonnel, R Karwoski, C Governale, L Brinker, A TI Comparison of reporting of Stevens-Johnson syndrome and toxic epidermal necrolysis in association with selective COX-2 inhibitors SO DRUG SAFETY LA English DT Article ID ANTIINFLAMMATORY DRUGS; RISK AB Background: Stevens-Johnson syndrome and toxic epidermal necrolysis are closely related severe acute life-threatening, drug-induced skin disorders. The US FDA Adverse Events Reporting System (AERS) has received reports of Stevens-Johnson syndrome and toxic epidermal necrolysis associated with the use of the recently introduced selective cyclo-oxygenase (COX)-2 inhibitor NSAIDs, two of which are also sulfonamides. Objective: The objective of this study is to review cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the FDA associated with the use of the selective COX-2 inhibitor NSAIDs celecoxib, rofecoxib and valdecoxib, and to compare reporting rates of the two conditions associated with these drugs to each other, meloxicam (an oxicam NSAID that came on the US market at a similar time) and the background incidence rate. Methods: We reviewed all US cases of Stevens-Johnson syndrome and toxic epidermal necrolysis reported to the FDA AERS database associated with the use of celecoxib, rofecoxib, valdecoxib and meloxicam since these agents were first marketed. We utilised AERS and drug use data to calculate reporting rates for each drug after the first 2 years of marketing. We obtained the background rate from the medical literature. Results: Up to the end of March 2004, there were 63 cases of Stevens-Johnson syndrome/toxic epidermal necrolysis reported with valdecoxib use, 43 with celecoxib, 17 with rofecoxib (the non-sulfonamide coxib) and none for meloxicam. In the first 2 years of marketing the reporting rate for Stevens-Johnson syndrome/toxic epidermal necrolysis with valdecoxib was 49 cases per million person-years of use, 6 cases per million person-years for celecoxib and 3 cases per million person-years for rofecoxib. The reporting rates for the sulfonamide coxibs were substantially higher than the background rate of 1.9 cases per million population per year, with the valdecoxib rate being 8-9 times that of celecoxib and approximately 25 times that of the background rate. Conclusion: There is a strong association between Stevens-Johnson syndrome/toxic epidermal necrolysis and the use of the sulfonamide COX-2 inhibitors, particularly valdecoxib. Physicians should be aware of the possibility of this serious life-threatening event when prescribing these drugs and advise patients to discontinue use at the earliest possible sign or symptom. C1 US FDA, Rockville, MD 20857 USA. RP La Grenade, L (reprint author), Ctr Drug Evaluat & Res, Off Druf Safety, HFD-430,15B-08,5600 Fishers Lane, Rockville, MD 20857 USA. EM lagrenadel@cder.fda.gov NR 26 TC 39 Z9 39 U1 0 U2 4 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2005 VL 28 IS 10 BP 917 EP 924 DI 10.2165/00002018-200528100-00008 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 976MF UT WOS:000232736900008 PM 16180941 ER PT J AU Almenoff, J Tonning, JM Gould, AL Szarfman, A Hauben, M Ouellet-Hellstrom, R Ball, R Hornbuckle, K Walsh, L Yee, C Sacks, ST Yuen, N Patadia, V Blum, M Johnston, M Gerrits, C Seifert, H LaCroix, K AF Almenoff, J Tonning, JM Gould, AL Szarfman, A Hauben, M Ouellet-Hellstrom, R Ball, R Hornbuckle, K Walsh, L Yee, C Sacks, ST Yuen, N Patadia, V Blum, M Johnston, M Gerrits, C Seifert, H LaCroix, K TI Perspectives on the use of data mining in pharmacovigilance SO DRUG SAFETY LA English DT Article ID EVENT REPORTING SYSTEM; ADVERSE DRUG-REACTIONS; SIGNAL GENERATION; SAFETY SURVEILLANCE; CLINICAL JUDGMENT; COMMON-SENSE; ODDS RATIO; DISPROPORTIONALITY; BETA(2)-AGONISTS; PANCREATITIS AB In the last 5 years, regulatory agencies and drug monitoring centres have been developing computerised data-mining methods to better identify reporting relationships in spontaneous reporting databases that could signal possible adverse drug reactions. At present, there are no guidelines or standards for the use of these methods in routine pharmacovigilance. In 2003, a group of statisticians, pharmacoepidemiologists and pharmacovigilance professionals from the pharmaceutical industry and the US FDA formed the Pharmaceutical Research and Manufacturers of America-FDA Collaborative Working Group on Safety Evaluation Tools to review best practices for the use of these methods. In this paper, we provide an overview of: (i) the statistical and operational attributes of several currently used methods and their strengths and limitations; (ii) information about the characteristics of various postmarketing safety databases with which these tools can be deployed; (iii) analytical considerations for using safety data-mining methods and interpreting the results; and (iv) points to consider in integration of safety data mining with traditional pharmacovigilance methods. Perspectives from both the FDA and the industry are provided. Data mining is a potentially useful adjunct to traditional pharmacovigilance methods. The results of data mining should be viewed as hypothesis generating and should be evaluated in the context of other relevant data. The availability of a publicly accessible global safety database, which is updated on a frequent basis, would further enhance detection and communication about safety issues. C1 GlaxoSmithKline Inc, Global Clin Safety & Pharmacovigilance, Res Triangle Pk, NC 27709 USA. US FDA, Rockville, MD 20857 USA. Merck Res Labs, West Point, PA USA. Pfizer Inc, New York, NY USA. NYU, Sch Med, Dept Med, New York, NY USA. New York Med Coll, Dept Pharmacol, Valhalla, NY 10595 USA. New York Med Coll, Dept Community & Prevent Med, Valhalla, NY 10595 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. AstraZeneca LP, Wilmington, DE USA. Johnson & Johnson Pharmaceut Res & Dev LLC, Titusville, NJ USA. Hoffmann La Roche Inc, Nutley, NJ 07110 USA. Allergan Pharmaceut Inc, Irvine, CA 92715 USA. Wyeth Res, Collegeville, PA USA. Schering Plough Res Inst, Springfield, NJ USA. RP Almenoff, J (reprint author), GlaxoSmithKline Inc, Global Clin Safety & Pharmacovigilance, 5 Moore Dr,Mail Stop 5-4214-4C,POB 13398, Res Triangle Pk, NC 27709 USA. EM june.s.almenoff@gsk.com NR 75 TC 102 Z9 104 U1 1 U2 10 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 1311, NEW ZEALAND SN 0114-5916 J9 DRUG SAFETY JI Drug Saf. PY 2005 VL 28 IS 11 BP 981 EP 1007 DI 10.2165/00002018-200528110-00002 PG 27 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 986AQ UT WOS:000233421300002 PM 16231953 ER PT J AU Gurley, BJ Gardner, SF Hubbard, MA Williams, DK Gentry, WB Cui, YY Ang, CYW AF Gurley, BJ Gardner, SF Hubbard, MA Williams, DK Gentry, WB Cui, YY Ang, CYW TI Clinical assessment of effects of botanical supplementation on cytochrome P450 phenotypes in the elderly - St John's wort, garlic oil, Panax ginseng and Ginkgo biloba SO DRUGS & AGING LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; DRUG-METABOLIZING-ENZYMES; ALTERNATIVE MEDICINE USE; SOLID-PHASE EXTRACTION; HERBAL MEDICINES; IN-VIVO; DIALLYL SULFIDE; HYPERICUM-PERFORATUM; ECHINACEA-PURPUREA; UNITED-STATES AB Objectives: Elderly patients are more likely to ingest prescription medications concurrently with botanical supplements, and may therefore be vulnerable to herb-drug interactions. Phytochemical-mediated modulation of cytochrome P450 (CYP) activity may underlie many herb-drug interactions. Some evidence suggests that CYP activity may decrease in the elderly. If so, herb-mediated changes in CYP activity may take on greater clinical relevance in this population. In this study, single timepoint, phenotypic metabolic ratios were used to determine whether long-term supplementation of St John's wort, garlic oil, Panax ginseng, and Ginkgo biloba affected CYP1A2, CYP2D6, CYP2E1 or CYP3A4 activity in elderly subjects. Methods: Twelve healthy volunteers between the ages of 60 and 76 years (mean age 67 years) were randomly assigned to receive each botanical supplement for 28 days followed by a 30-day washout period. Probe drug cocktails of midazolam, caffeine, chlorzoxazone and debrisoquine were administered before and at the end of supplementation. Pre- and post-supplementation phenotypic ratios were determined for CYP3A4, CYP1A2, CYP2E1 and CYP2D6 using 1-hydroxymidazolam/midazolam serum ratios (1-hour), paraxanthine/caffeine serum ratios (6-hour), 6-hydroxychlorzoxazone/chlorzoxazone serum ratios (2-hour) and debrisoquine urinary recovery ratios (8-hour), respectively. The content of purported 'active' phytochemicals was determined for each supplement. Results: Comparisons of pre- and post-St John's wort phenotypic ratios revealed significant induction of CYP3A4 (approximate to 140%) and CYP2E1 activity (approximate to 28%). Garlic oil inhibited CYP2E1 activity by approximately 22%. P. ginseng inhibition of CYP2D6 was statistically significant, but the magnitude of the effect (approximate to 7%) did not appear to be clinically relevant. None of the supplements tested in this study appeared to affect CYP1A2 activity. Conclusions: Elderly subjects, like their younger counterparts, are susceptible to herb-mediated changes in CYP activity, especially those involving St John's wort. Pharmacokinetic herb-drug interactions stemming from alterations in CYP activity may adversely affect drug efficacy and/or toxicity. When compared with earlier studies that employed young subjects, the data suggest that some age-related changes in CYP responsivity to botanical supplementation may exist. Concomitant ingestion of botanical supplements with prescription medications, therefore, should be strongly discouraged in the elderly. C1 Univ Arkansas Med Sci, Coll Pharm, Dept Pharmaceut Sci, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Pharm, Dept Pharm Practice, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Biometry, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Coll Med, Dept Anesthesiol, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Gurley, BJ (reprint author), Univ Arkansas Med Sci, Coll Pharm, Dept Pharmaceut Sci, 4301 W Markham St,Slot 522, Little Rock, AR 72205 USA. EM gurleybillyj@uams.edu FU NCRR NIH HHS [M01 RR014288, M01RR14288]; NIA NIH HHS [R03 AG017733-01, R03AG17733-01] NR 60 TC 126 Z9 140 U1 8 U2 24 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 1170-229X J9 DRUG AGING JI Drugs Aging PY 2005 VL 22 IS 6 BP 525 EP 539 DI 10.2165/00002512-200522060-00006 PG 15 WC Geriatrics & Gerontology; Pharmacology & Pharmacy SC Geriatrics & Gerontology; Pharmacology & Pharmacy GA 947YO UT WOS:000230683400006 PM 15974642 ER PT J AU Manianatha, MG Shelton, SD Rhodes, BS Bishop, ME Lyn-Cook, LE Aidoo, A AF Manianatha, MG Shelton, SD Rhodes, BS Bishop, ME Lyn-Cook, LE Aidoo, A TI 17 beta-estradiol and not genistein modulates lacl mutant frequency and types of mutation induced in the heart of ovariectomized big blue rats treated with 7,12-dimethylbenz[a]anthracene SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE DMBA; lacl; GE; E-2; MF; OVX; BB rats ID MOLECULAR ANALYSIS; IN-VITRO; CANCER; DNA; REPLACEMENT; ESTRADIOL; OXIDATION; PRODUCTS; SEQUENCE; TISSUE AB In industrialized countries, heart disease rates are higher among women after menopause. Recent studies indicate that consumption of phytoestorogens, e.g., isoflavones such as genistein (GE), may have potential cardiovascular health benefits; however, no studies have evaluated the effect of these agents on toxicant-induced damage in the heart. Since estrogen receptors are found in the heart, and GE mimics estrogenic effects, we have examined whether or not dietary GE or 17 beta-estradiol (E2) modulates the loci mutant frequency (MF) in the heart of ovariectomized (OVX) Big Blue rats exposed to the model carcinogen 7,12-dimethylbenz[a]anthracene (DMBA). Groups of female rats were administered 80 mg/kg DMBA or vehicle by gavage and were chronically fed with diets containing 0, 250, or 1,000 mug/g GE or 5 mug/g E2. Sixteen weeks after carcinogen treatment, the animals were sacrificed and the hearts were removed and processed for determining the frequency and types of mutations in the heart tissue. GE and E2 supplementation alone resulted in nonsignificant increases in MF. The DMBA-induced lacl MF in the heart was sevenfold higher than the control (119.8 +/- 18.7 x 10(-6) vs. 17.4 +/- 3.2 x 10(-6); P < 0.001). GE in the diet had no significant effect on DMBA mutagenicity, while feeding E2 to DMBA-treated rats caused a significant reduction in the MF (119.8 18.7 x 10-6 vs. 61.4 +/- 13.5 x 10(-6); P < 0.017). DNA sequence analysis revealed that the majority of DMBA-induced mutations in rats fed control diet were A:T-T:A (42%) and G:C-->T:A (19%) transversions, followed by G:C-->A:T (13%) and A:T-->G:C (8%) transitions. Feeding E2 altered the DMBA-induced mutational spectra by decreasing A:T-->T:A (23%) and G:C-->T:A (13%) transversions and increasing G:C-->A:T (24%) and A:T-->G:C (21%) transitions. Taken together, the results suggest that DMBA can induce gene mutations in heart tissue of OVX rats, and while dietary GE had little or no effect on DMBA-induced mutation, dietary E2 reduced the mutagenicity of DMBA. Published 2004 Wiley-Liss, Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Cent Arkansas, Dept Biol Sci, Conway, AR USA. RP Manianatha, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM mmanjanatha@nctr.fda.gov NR 38 TC 0 Z9 0 U1 0 U2 1 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2005 VL 45 IS 1 BP 70 EP 79 DI 10.1002/em.20080 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 893QV UT WOS:000226735200008 ER PT J AU Sun, HH Sloan, A Mangner, TJ Vaishampayan, U Muzik, O Collins, JM Douglas, K Shields, AF AF Sun, HH Sloan, A Mangner, TJ Vaishampayan, U Muzik, O Collins, JM Douglas, K Shields, AF TI Imaging DNA synthesis with [F-18]FMAU and positron emission tomography in patients with cancer SO EUROPEAN JOURNAL OF NUCLEAR MEDICINE AND MOLECULAR IMAGING LA English DT Article DE FMAU; PET; proliferation ID PHASE-I TRIAL; 1-(2'-DEOXY-2'-FLUORO-1-BETA-D-ARABINOFURANOSYL)-5-METHYLURACIL FMAU; CELLULAR PROLIFERATION; PROSTATE-CANCER; PET; VIVO; NUCLEOSIDES; ANALOGS; AGENTS; TUMORS AB Purpose: FMAU (1-(2'-deoxy-2'-fluoro-beta-D-arabinofuranosyl)thymine) is a thymidine analog that can be phosphorylated by thymidine kinase and incorporated into DNA. This first-in-human study of [F-18]FMAU was conducted as a pilot in patients to determine its biodistribution and suitability for imaging DNA synthesis in tumors using positron emission tomography (PET). Methods: Fourteen patients with diverse cancers (brain, prostate, colorectal, lung, and breast) were imaged with [F-18]FMAU. We obtained dynamic PET images for 60 min and a whole-body image. Blood and urine samples were analyzed by high-performance liquid chromatography to measure metabolites and clearance. Results: Active tumors in the breast, brain, lung and prostate were clearly visualized with standardized uptake values (SUVs) of 2.19, 1.28, 2.21, and 2.27-4.42, respectively. Unlike with other tracers of proliferation, low uptake of [F-18]FMAU was seen in the normal bone marrow (SUVmean 0.7), allowing visualization of metastatic prostate cancer (SUV 3.07). Low background was also observed in the brain, pelvis, and thorax, aside from heart uptake (SUV 3.36-8.78). In the abdomen, increased physiological uptake was seen in the liver (SUV 10.07-20.88) and kidneys (SUV 7.18-15.66) due to metabolism and/or excretion, but the urinary bladder was barely visible (SUVmean 2.03). On average, 95% of the activity in the blood was cleared within 10 min post injection and an average of 70% of the activity in the urine was intact FMAU at 60 min post injection. Conclusion: Tumors in the brain, prostate, thorax, and bone can be clearly visualized with FMAU. In the upper abdomen, visualization is limited by the physiological uptake by the liver and kidneys. C1 Wayne State Univ, Dept Med, Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Dept Radiol, Karmanos Canc Inst, Detroit, MI 48201 USA. Wayne State Univ, Dept Pediat, Karmanos Canc Inst, Detroit, MI 48201 USA. US FDA, Rockville, MD 20857 USA. RP Shields, AF (reprint author), Wayne State Univ, Dept Med, Karmanos Canc Inst, 4100 John R St,4 HWCRC, Detroit, MI 48201 USA. EM shieldsA@karmanos.org FU NCI NIH HHS [CA 82645, CA 83131] NR 21 TC 82 Z9 83 U1 0 U2 2 PU SPRINGER PI NEW YORK PA 233 SPRING STREET, NEW YORK, NY 10013 USA SN 1619-7070 J9 EUR J NUCL MED MOL I JI Eur. J. Nucl. Med. Mol. Imaging PD JAN PY 2005 VL 32 IS 1 BP 15 EP 22 DI 10.1007/s00259-004-1713-8 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 890MX UT WOS:000226516600003 PM 15586282 ER PT J AU Begley, T Castle, L Feigenbaum, A Franz, R Hinrichs, K Lickly, T Mercea, P Milana, M O'Brien, A Rebre, S Rijk, R Piringer, O AF Begley, T Castle, L Feigenbaum, A Franz, R Hinrichs, K Lickly, T Mercea, P Milana, M O'Brien, A Rebre, S Rijk, R Piringer, O TI Evaluation of migration models that might be used in support of regulations for food-contact plastics SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE food-contact plastics; migration; modelling; diffusion; polyolefin; polystyrene; polyester; polyamide ID POLYMER ADDITIVE MIGRATION; WORST-CASE MIGRATION; MATHEMATICAL-MODELS; PREDICTION AB Materials and articles intended to come into contact with food must be shown to be safe because they might interact with food during processing, storage and the transportation of foodstuffs. Framework Directive 89/109/EEC and its related specific Directives provide this safety basis for the protection of the consumer against inadmissible chemical contamination from food-contact materials. Recently, the European Commission charged an international group of experts to demonstrate that migration modelling can be regarded as a valid and reliable tool to calculate 'reasonable worst-case' migration rates from the most important food-contact plastics into the European Union official food simulants. The paper summarizes the main steps followed to build up and validate a migration estimation model that can be used, for a series of plastic food-contact materials and migrants, for regulatory purposes. Analytical solutions of the diffusion equation in conjunction with an 'upper limit' equation for the migrant diffusion coefficient, D-P, and the use of 'worst case' partitioning coefficients K-P,K-F were used in the migration model. The results obtained were then validated, at a confidence level of 95%, by comparison with the available experimental evidence. The successful accomplishment of the goals of this project is reflected by the fact that in Directive 2002/72/EC, the European Commission included the mathematical modelling as an alternative tool to determine migration rates for compliance purposes. C1 US FDA, College Pk, MD 20740 USA. Cent Sci Lab, York Y041 1LZ, N Yorkshire, England. INRA, CPCB, F-51697 Reims, France. Fraunhofer Inst IVV, D-85354 Freising Weihenstephan, Germany. Cognis GmbH, D-40551 Dusseldorf, Germany. DOW, Midland, MI 48674 USA. Fabes GmbH, D-80992 Munich, Germany. Ist Super Sanita, I-0161 Rome, Italy. PIRA Int, Leatherhead KT22 7RU, Surrey, England. Atofina, F-92300 Levallois Perret, France. TNO, NL-3700 AJ Zeist, Netherlands. RP Begley, T (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM fabes@t-online.de RI MILANA, Maria Rosaria/L-6411-2014 NR 14 TC 112 Z9 122 U1 5 U2 56 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD JAN PY 2005 VL 22 IS 1 BP 73 EP 90 DI 10.1080/02652030400028035 PG 18 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 903NL UT WOS:000227432700010 PM 15895614 ER PT J AU Beland, FA Benson, RW Mellick, PW Kovatch, RM Roberts, DW Fang, JL Doerge, DR AF Beland, FA Benson, RW Mellick, PW Kovatch, RM Roberts, DW Fang, JL Doerge, DR TI Effect of ethanol on the tumorigenicity of urethane (ethyl carbamate) in B6C3F(1) mice SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE urethane; ethanol; DNA adducts; proliferating cell nuclear antigen; cytochrome p450 2E1; carcinogenesis ID CHROMATOGRAPHY MASS-SPECTROMETRY; RAT-LIVER MICROSOMES; VINYL CARBAMATE; N-NITROSODIMETHYLAMINE; TUMOR-INCIDENCE; RISK-ASSESSMENT; DNA-ADDUCTS; LUNG-TUMORS; ALCOHOLIC BEVERAGES; K-RAS AB Urethane is a carcinogen to which there is widespread exposure through the consumption of fermented foods and alcoholic beverages. In this study, we have assessed the carcinogenicity of urethane in combination with ethanol. Male and female B6C3F(1) mice (48 mice per sex per group) were exposed to 0, 10, 30, or 90ppm urethane in the presence of 0%, 2.5%, or 5% ethanol in drinking water ad libitum for two years, at which time the extent of tumorigenesis was assessed. Additional mice (four per sex per group) received the same doses for four weeks to assess serum levels of urethane and ethanol, DNA adduct formation, and the induction of microsomal cytochromes P450, cell proliferation, and apoptosis. Urethane decreased cell replication in the livers of female, but not male, mice, decreased cell replication in the lungs of both sexes, and induced cytochrome P450 2E1 in the livers of female mice. Hepatic levels of the DNA adduct 1, N-6- ethenodeoxyadenosine were increased by exposure to urethane and decreased by treatment with ethanol. Animal weights and survival were not affected by ethanol; in contrast, urethane administration decreased body weights and survival. Urethane caused dose-dependent increases in liver, lung, and harderian gland adenoma or carcinoma and hemangiosarcoma of the liver and heart in both sexes, mammary gland and ovarian tumors in females, and squamous cell papilloma or carcinoma of the skin and forestomach in males. The increase in hepatocellular tumors occurred in a relatively linear manner and was attributed to the formation of 1, N-6-ethenodeoxyadenosine in hepatic DNA coupled with an increase in cell replication. Hemangiosarcomas were observed only at the 90ppm urethane dose and were probably a result of bigh-dose urethane-induced toxicity. Lung alveolar/bronchiolar and harderian gland adenoma or carcinoma increased in a relatively linear manner, suggestive of a genotoxic mechanism for tumor induction. Ethanol induced a dose-dependent trend in hepatocellular adenoma or carcinoma in male mice, with the incidence being marginally increased at the highest dose. In female mice administered 10ppm and 90ppm urethane, ethanol caused dose-related increases in alveolar/bronchiolar adenoma or carcinoma and hemangiosarcoma of the heart, respectively. This may be due to ethanol decreasing the first-pass clearance of urethane, thus, increasing systemic distribution. In male mice a different relationship was observed: ethanol caused a dose-related decrease in alveolar/bronchiolar and harderian gland adenoma or carcinoma in mice administered 30ppm urethane. (C) 2004 Elsevier Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110, Jefferson, AR 72079 USA. EM fbeland@nctr.fda.gov NR 97 TC 63 Z9 73 U1 0 U2 13 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0278-6915 J9 FOOD CHEM TOXICOL JI Food Chem. Toxicol. PD JAN PY 2005 VL 43 IS 1 BP 1 EP 19 DI 10.1016/j.fct.2004.07.018 PG 19 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 889ME UT WOS:000226446300001 PM 15582191 ER PT J AU Crawford, LM AF Crawford, LM TI Remarks of The Acting FDA Commissioner: FDLI's 48th Annual Conference SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, Rockville, MD 20857 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2005 VL 60 IS 2 BP 99 EP 102 PG 4 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 952VC UT WOS:000231032600001 PM 16097087 ER PT J AU Masoudi, GF AF Masoudi, GF TI Developments in Food and Drug Law SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Rockville, MD 20857 USA. RP Masoudi, GF (reprint author), US FDA, Rockville, MD 20857 USA. NR 12 TC 0 Z9 0 U1 0 U2 3 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 2005 VL 60 IS 2 BP 107 EP 116 PG 10 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 952VC UT WOS:000231032600003 PM 16097088 ER PT J AU Niedelman, SM AF Niedelman, SM TI Remarks at the Food and Drug Law Institute's 48th Annual Conference SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Rockville, MD 20857 USA. RP Niedelman, SM (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2005 VL 60 IS 2 BP 117 EP 126 PG 10 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 952VC UT WOS:000231032600004 PM 16097089 ER PT J AU Muni, NI Gross, TP Boam, AB Wang, S Zuckerman, BD AF Muni, NI Gross, TP Boam, AB Wang, S Zuckerman, BD TI Challenges in regulating breakthrough medical devices SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Muni, NI (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 7 TC 2 Z9 2 U1 0 U2 4 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 2005 VL 60 IS 2 BP 137 EP 142 PG 6 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 952VC UT WOS:000231032600006 PM 16097092 ER PT J AU Kelly, DP Bachorik, LL AF Kelly, DP Bachorik, LL TI Promoting public health and protecting consumers in a global economy: An overview of HHS/FDA's international activities SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, HHS, Rockville, MD 20857 USA. RP Kelly, DP (reprint author), US FDA, HHS, Rockville, MD 20857 USA. NR 0 TC 4 Z9 4 U1 0 U2 2 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2005 VL 60 IS 3 BP 339 EP 346 PG 8 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 975DW UT WOS:000232642200002 PM 16304741 ER PT J AU Molzon, JA AF Molzon, JA TI The International Conference on Harmonization Common Technical Document - Global submission format? SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, CDER, Int Programs, Rockville, MD 20857 USA. RP Molzon, JA (reprint author), US FDA, CDER, Int Programs, Rockville, MD 20857 USA. NR 0 TC 7 Z9 7 U1 2 U2 3 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 2005 VL 60 IS 3 BP 447 EP 451 PG 5 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 975DW UT WOS:000232642200010 PM 16304749 ER PT S AU Coles, BF Kadlubar, FF AF Coles, BF Kadlubar, FF BE Sies, H Packer, L TI Human alpha class glutathione S-transferases: Genetic polymorphism, expression, and susceptibility to disease SO GLUTHIONE TRANSFERASES AND GAMMA-GLUTAMYL TRANSPEPTIDASES SE Methods in Enzymology LA English DT Review; Book Chapter ID CORONARY-ARTERY-DISEASE; ANTICANCER DRUG-RESISTANCE; HUMAN TISSUES; HUMAN LIVER; INTERINDIVIDUAL VARIATION; FUNCTIONAL POLYMORPHISM; ALDEHYDE DEHYDROGENASE; GENOMIC ORGANIZATION; LIPID-PEROXIDATION; ALLERGIC RESPONSES AB The human alpha class glutathione S-transferases (GSTs) consist of 5 genes, hGSTA1-hGSTA5, and 7 pseudogenes on chromosome 6p12.1-6p12.2. hGSTA1-hGSTA4 have been well characterized as proteins, but hGSTA5 has not been detected as a gene product. hGSTA1-1 (and to a lesser extent hGSTA2-2) catalyzes the GSH-dependent detoxification of carcinogenic metabolites of environmental pollutants and tobacco smoke (e.g., polycyclic aromatic hydrocarbon diolepoxides) and several alkylating chemotherapeutic agents and has peroxidase activity toward fatty acid hydroperoxides (FA-OOH) and phosphatidyl FA-OOH. hGSTA3-3 has high activity for the GSH-dependent Delta(5)-Delta(4) isomerization of steroids, and hGSTA4-4 has high activity for the GSH conjugation of 4-hydroxynonenal. hGSTA4 is expressed in many tissues; hGSTA1-1. and hGSTA2-2 are expressed at high levels in liver, intestine, kidney, adrenal gland, and testis; and hGSTA3 is expressed in steroidogenic tissues. Functional, allelic, single nucleotide polymorphisms occur in an SP1-binding element of hGSTA1 and in the coding regions of hGSTA2 and hGSTA3. The main effects of these polymorphisms are the low hepatic expression of hGSTA1 in individuals homozygous for hGSTA1*B and the low specific activity of the hGSTA2E-2E variant toward FA-OOH. These properties suggest that alpha class GSTs will be involved in susceptibility to diseases with an environmental component (such as cancer, asthma, and cardiovascular disease) and in response to chemotherapy. Although hGSTM1, hGSTT1, and hGSTP1 have been associated with such diseases (on the basis of genetic polymorphisms as indicators of expression), alpha class GSTs have been little studied in this respect. Nevertheless, hGSTA1*B has been associated with increased susceptibility to colorectal cancer and with increased efficacy of chemotherapy for breast cancer. Methods for identification and quantitation of human alpha class GST protein, mRNA, and genotype are reviewed, and the potential for GST-alpha in plasma to be used as a marker for hepatic expression and induction is discussed. C1 Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. RP Coles, BF (reprint author), Natl Ctr Toxicol Res, Div Pharmacogenom & Mol Epidemiol, Jefferson, AR 72079 USA. NR 88 TC 85 Z9 90 U1 2 U2 9 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182806-9 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2005 VL 401 BP 9 EP 42 DI 10.1016/S0076-6879(05)01002-5 PG 34 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BDP51 UT WOS:000234746200002 PM 16399377 ER PT J AU Song, YS Hepp, MA AF Song, Yoon S. Hepp, Mark A. BE Han, JH TI US Food and Drug Administration approach to regulating intelligent and active packaging components SO INNOVATIONS IN FOOD PACKAGING LA English DT Article; Book Chapter C1 [Song, Yoon S.] US FDA, Div Food Proc & Packaging, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. [Hepp, Mark A.] US FDA, Off Food Addit Safety, College Pk, MD 20740 USA. RP Song, YS (reprint author), US FDA, Div Food Proc & Packaging, Natl Ctr Food Safety & Technol, HFH-450,6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA BN 978-0-08-045517-4 PY 2005 BP 475 EP 481 DI 10.1016/B978-012311632-1/50058-9 PG 7 WC Food Science & Technology SC Food Science & Technology GA BCR32 UT WOS:000311093000027 ER PT J AU Shah, M Wuilloud, RG Kannamkumaratha, SS Caruso, JA AF Shah, M Wuilloud, RG Kannamkumaratha, SS Caruso, JA TI Iodine speciation studies in commercially available seaweed by coupling different chromatographic techniques with UV and ICP-MS detection SO JOURNAL OF ANALYTICAL ATOMIC SPECTROMETRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; SIZE-EXCLUSION CHROMATOGRAPHY; MASS-SPECTROMETRIC DETECTION; BIOLOGICAL SAMPLES; SELENIUM; PROTEINS; IDENTIFICATION; MILK AB Speciation of iodine in commercially available commonly consumed seaweed samples was performed using a multidimensional chromatographic approach coupled with inductively coupled plasma mass spectrometry (ICP-MS) for element specific detection. Analysis of alkaline extract (0.1 mol l(-1) NaOH) by size-exclusion chromatography coupled to ICP-MS ( 0.03 mol l(-1) Tris- HCl, pH 8.0) indicated the association of iodine with both high as well as low molecular weight fractions in Wakame, while in case of Kombu, only low molecular weight iodine species were found. Likely association of iodine with protein as well as polyphenolic species was indicated in the case of Wakame. Anion-exchange chromatography coupled to ICP-MS (0.005 mol l(-1) NaOH) confirmed that the most predominant inorganic iodine species present in both type of seaweeds is iodide. Protein bound iodinated species were hydrolyzed by enzymatic digestion using Proteinase K. Analysis of the hydrolysate using reversed-phase HPLC-ICP- MS (0.01 mol l(-1) Tris-HCl pH 7.3 : 0.01 mol l(-1) Tris- HCl pH 7.3 and 50% MeOH) revealed the presence of monoiodotyrosine and di-iodotyrosine in Wakame, which was later identified by matching the chromatographic retention time with the retention time of commercially available standards. C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Caruso, JA (reprint author), Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. EM joseph.caruso@uc.edu NR 31 TC 50 Z9 52 U1 2 U2 20 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0267-9477 J9 J ANAL ATOM SPECTROM JI J. Anal. At. Spectrom. PY 2005 VL 20 IS 3 BP 176 EP 182 DI 10.1039/b415756g PG 7 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 907HL UT WOS:000227707000002 ER PT J AU Wray-Cahen, D Pritchard, W Ashby, A Russek-Cohen, E Vossoughi, J Karanian, J AF Wray-Cahen, D. Pritchard, W. Ashby, A. Russek-Cohen, E. Vossoughi, J. Karanian, J. TI Gender, age, and hormonal status affect recovery time from general anesthesia in pigs SO JOURNAL OF ANIMAL SCIENCE LA English DT Meeting Abstract DE gender; anesthesia; age C1 [Wray-Cahen, D.; Pritchard, W.; Ashby, A.; Russek-Cohen, E.; Karanian, J.] US FDA, Laurel, MD USA. [Vossoughi, J.] Biomed Res Fdn, Olney, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PY 2005 VL 83 SU 1 BP 260 EP 260 PG 1 WC Agriculture, Dairy & Animal Science SC Agriculture GA V44GD UT WOS:000202990301080 ER PT J AU Hayes, JR Wagner, DD English, LL Carr, LE Joseph, SW AF Hayes, JR Wagner, DD English, LL Carr, LE Joseph, SW TI Distribution of streptogramin resistance determinants among Enterococcus faecium from a poultry production environment of the USA SO JOURNAL OF ANTIMICROBIAL CHEMOTHERAPY LA English DT Article DE enterococci; antibiotic resistance; quinupristin/dalfopristin; MLS ID QUINUPRISTIN-DALFOPRISTIN; MEAT AB Objectives: The impact of agricultural use of antimicrobials on the present and future efficacy of therapeutic drugs in human medicine is a growing public concern. Quinupristin/dalfopristin has been approved to treat human disease caused by vancomycin-resistant Enterococcus faecium and is related to virginiamycin, a streptogramin complex that has long been used in USA agriculture poultry production. Methods: Streptogramin-resistant isolates of E. faecium from poultry production environments on the eastern seaboard were recovered without selection for streptogramin resistance and examined using ribotyping to evaluate clonal bias. Colony PCR screening for the previously described streptogramin resistance determinants erm(A), erm(B), msr(C), vgb(A), vat(D) and vat(E) was performed to determine the prevalence of streptogramin resistance mechanisms from these environments. Results: The collection of E. faecium isolates was unevenly distributed among 28 ribogroups and did not cluster geographically. The most prevalent ribogroups was composed of isolates that possessed diverse antimicrobial resistance profiles. Of the 127 isolates examined, 63% were resistant to quinupristin/dalfopristin. The resistance determinants erm(A) and erm(B) were observed among 6% and 10%, respectively, of streptogramin-resistant isolates. msr(C) was detected in a single isolate that was resistant to macrolide and lincosamide antimicrobials. The streptogramin B hydrolase vgb(A) and the streptogramin A acetyltransferases genes vat(D) and vat(E) were not detected in any of the E. faecium isolates. Conclusions: These results indicate that there is widespread resistance to streptogramin antimicrobials among E. faecium throughout the poultry production region in this study and that the mechanisms of resistance to streptogramin antimicrobials within this population remain largely uncharacterized. C1 Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Univ Maryland, Dept Biol Resources Engn, College Pk, MD 20742 USA. RP Joseph, SW (reprint author), Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. EM sj13@umail.umd.edu NR 11 TC 22 Z9 23 U1 0 U2 0 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 2005 VL 55 IS 1 BP 123 EP 126 DI 10.1093/jac/dkh491 PG 4 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 887MB UT WOS:000226309100021 PM 15574480 ER PT J AU Cieri, UG AF Cieri, UG TI Identification and estimation of the levo isomer in raw materials and finished products containing atropine and/or hyoscyamine SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The belladonna alkaloids atropine sulfate and hyoscyamine sulfate, occasionally used as anticholinergic and antimuscarinic agents, have identical molecular formulas but different stereo configurations. Hyoscyamine sulfate contains almost 100% of the levo isomer, whereas atropine sulfate is composed of equal parts of dextro and levo isomers. It is believed that the therapeutic properties of these alkaloids are due exclusively or primarily to the levo isomer. Currently available methods determine only the total amount of atropine (hyoscyamine) sulfate. A method has been developed and is reported for the identification and estimation of the levo and dextro isomers of atropine and hyoscyamine. Reference solutions are prepared in methanol at the following weights per 100 mL: 8.0 mg atropine sulfate; 4.0 mg hyoscyamine sulfate; 7.0 mg scopolamine hydrobromide; and 10.0 mg homatropine methylbromide. Samples of raw materials are similarly prepared in methanol, commercial products are also extracted or diluted with methanol, and solutions are filtered. Liquid chromatography is used for separations on a 25 cm Chirobiotic T2 column. The mobile phase is prepared by mixing 3.0 mL acetic acid and 2.0 mL triethylamine with 1000 mL methanol. The injection volume is 100 or 200 muL; the flow rate is about 0.35 mL/min. Fluorescence detection is at 255 nm excitation and 285 nm emission. Scopolamine hydrobromide and hyoscyamine eluted after 20 and 60 min, respectively. Atropine sulfate generated 2 peaks after 60 and 65 min. Homatropine methylbromide also produced 2 peaks after 70 and 85 min. Samples tested in this study included raw materials and commercial tablets or injections containing belladonna alkaloids. In all cases, the percentage calculated was that of the levo isomer relative to the total amount of atropine (hyoscyamine) present. C1 US FDA, Philadelphia, PA 19106 USA. RP Cieri, UG (reprint author), US FDA, 2nd & Chestnut Sts, Philadelphia, PA 19106 USA. EM ucieri@ora.fda.gov NR 5 TC 3 Z9 3 U1 0 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2005 VL 88 IS 1 BP 1 EP 4 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 893HN UT WOS:000226710000002 PM 15759719 ER PT J AU DeVries, JW Rader, JI Keagy, PM Hudson, CA AF DeVries, JW Rader, JI Keagy, PM Hudson, CA TI Microbiological assay-trienzyme procedure for total folates in cereals and cereal foods: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID TRI-ENZYME EXTRACTION; FOLIC-ACID; FORTIFICATION; PRODUCTS AB In 1996, U.S. Food and Drug Administration regulations mandated the fortification of enriched cereal-grain products with folic acid, thereby emphasizing the need for validated methods for total folates in foods, particularly cereal products. The AOAC Official Methods (944.12,960.46) currently used for the analysis of folate in foods for compliance purposes are microbiological methods. When the fortification regulations were finalized, no Official AOAC or Approved AACC methods for folate in cereal-grain products were in place. The AOAC Official Method (992.05) for folic acid in infant formula does not incorporate important improvements in the extraction procedure and was not considered suitable for the analysis of folates in foods in general. A microbiological assay protocol using a trienzyme extraction procedure was prepared and submitted for comments to 40 laboratories with recognized experience in folate analysis. On the basis of comments, the method was revised to have the conjugase (gamma-glutamyl-carboxy-peptidase) treatment follow a protease treatment, to include the use of cryoprotected inoculum, and to include the spectroscopic standardization of the standard and optional use of microtiter plates. Thirteen laboratories participated in a collaborative study of 10 required and 10 optional cereal.-grain products, including flour, bread, cookies, baking mixes, and ready-to-eat breakfast cereals. The majority of the participating laboratories performed the assay by the standard test tube method; others used the microtiter plate modification for endpoint quantitation with equal success. For the required products, the relative standard deviation between laboratories (RSDR) ranged from 7.4 to 21.6% for 8 fortified (or enriched) products compared with expected (Horwitz equation-based) values of 11-20%. RSDR values were higher (22.7-52.9%) for 2 unfortified cereal-grain products. For the optional products, the RSDR ranged from 1.8 to 11.2% for 8 fortified products. RSDR values were higher (27.9-28.7%) for 2 unfortified cereal-grain products. Based on the results of the collaborative study, the microbiological assay with trienzyme extraction is recommended for adoption as Official First Action. C1 Gen Mills Inc, Medall Labs, Minneapolis, MN 55427 USA. US FDA, Ctr Food Safety & Nutr, College Pk, MD 20740 USA. USDA, Western Reg Res Ctr, Albany, CA 94710 USA. RP DeVries, JW (reprint author), Gen Mills Inc, Medall Labs, 9000 Plymouth Ave N, Minneapolis, MN 55427 USA. EM jon.devries@genmills.com NR 19 TC 23 Z9 23 U1 0 U2 14 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2005 VL 88 IS 1 BP 5 EP 15 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 893HN UT WOS:000226710000003 PM 15759720 ER PT J AU Hu, LH Jhoo, JW Ang, CYW Dinovi, M Mattia, A AF Hu, LH Jhoo, JW Ang, CYW Dinovi, M Mattia, A TI Determination of six kavalactones in dietary supplements and selected functional foods containing Piper methysticum by isocratic liquid chromatography with internal standard SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MASS-SPECTROMETRY; KAVA LACTONES; EXTRACT AB Kava (Piper methysticum) dietary products have been sold worldwide for treatment of nervous anxiety, tension, and restlessness. Recent reports showed potential association of kava usage and liver injuries. This study was conducted to develop simple and reliable methodologies for the extraction and determination of 6 major kavalactones: (+)-methysticin, (+)-dihydromethysticin, (+)-kavain, (+)-dihydrokavain, yangonin, and desmethoxy-yangonin. Ultrasonic extraction techniques and isocratic reversed-phase liquid chromatography (LC) were optimized for different types of samples, including capsules containing kava root extract or root powder, raw root material, tea bags, and snack bar. A suitable internal standard, 5,7-dihydroxyflavone, was used for LC calibration. Kavalactones were completely separated in 30 min using a Luna C18-2 column at 60degreesC with an isocratic mobile phase consisting of 2-propanol-acetonitrile-water-acetic acid (16 + 16 + 68 + 0.1, v/v/v/v). Within-laboratory, intraday, and interday method variation (% relative standard deviation) for most samples extracted by methanol or methanol-water mixture were < 5%. Lower levels of kavalactone contents and higher variations were observed for tea bags from water extraction or infusion as compared to methanol extraction. Labeling information of tea bags based on methanol extraction could be misleading to consumers. Analytical recoveries of snack bar fortified at 10 and 20 mug/g were > 84% with RSD values < 8%. Methods developed in this study offer a simple and reproducible means for analysis of kavalactones in various matrixes of dietary products. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, Div Biotechnol & GRAS Review, College Pk, MD 20740 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, HFT-230,3900 NCTR Rd, Jefferson, AR 72079 USA. EM cang@nctr.fda.gov NR 21 TC 7 Z9 7 U1 1 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2005 VL 88 IS 1 BP 16 EP 25 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 893HN UT WOS:000226710000004 PM 15759721 ER PT J AU Mann, DL Ware, GM Bonnin, E Eitenmiller, RR AF Mann, DL Ware, GM Bonnin, E Eitenmiller, RR TI Liquid chromatographic analysis of vitamin B-6 in reconstituted infant formula: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A liquid chromatographic (LC) method was validated for the determination of total vitamin B-6 in infant formula. Total vitamin B-6 was quantified by converting the phosphorylated and free vitamers into pyridoxine. Pyridoxine was determined by ion pair reversed-phase LC with fluorescence detection. The method was subjected to an AOAC collaborative study involving a factory-manufactured, milk- and soy-based infant formula. Each was spiked at 3 concentrations in the range of 0-1 mug/g and sent as blind duplicate to participant laboratories. Nine laboratories returned valid data which were statistically analyzed for outliers and precision parameters. The repeatability relative standard deviation (RSDr) ranges were 2.0-4.0 and 3.5-5.9% for fortified milk- and soy-based formulas, respectively. The reproducibility relative standard deviation (RSDR) ranges were 8.2-8.4 and 6.7-11.2% for fortified milk- and soy-based formulas, respectively. HORRAT values ranged from 0.42 to 0.53, indicating that the precision of the method is acceptable. The mean RSDr:RSDR values were 0.60 and 0.55 for milk- and soy-based formulas, respectively. As expected, RSDs for the unfortified samples were higher, but their HORRAT values (0.81 and 2.06) helped define a realistic limit of quantitation as 0.05 mug/g. Recovery data were quantitative and varied between 81.4 and 98.0% (mean = 89.8%) for each of 6 spiked materials. C1 US FDA, SE Reg Lab, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Bonnin, E (reprint author), US FDA, SE Reg Lab, 60 8th St NE, Atlanta, GA 30309 USA. EM ebonnin@ora.fda.gov NR 9 TC 5 Z9 5 U1 1 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2005 VL 88 IS 1 BP 30 EP 37 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 893HN UT WOS:000226710000006 PM 15759723 ER PT J AU Park, DL Coates, S Brewer, VA Garber, EAE Abouzied, M Johnson, K Ritter, B McKenzie, D AF Park, DL Coates, S Brewer, VA Garber, EAE Abouzied, M Johnson, K Ritter, B McKenzie, D TI Performance tested method(SM) multiple laboratory validation study of ELISA-based assays for the detection of peanuts in food SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Performance Tested Method(SM) multiple laboratory validations for the detection of peanut protein in 4 different food matrixes were conducted under the auspices of the AOAC Research Institute. In this blind study, 3 commercially available ELISA test kits were validated: Neogen Veratox((R)) for Peanut, R-Biopharm RIDASCREEN((R)) FAST Peanut, and Tepnel BioKits for Peanut Assay. The food matrixes used were breakfast cereal, cookies, ice cream, and milk chocolate spiked at 0 and 5 ppm peanut. Analyses of the samples were conducted by laboratories representing industry and international and U.S governmental agencies. All 3 commercial test kits successfully identified spiked and peanut-free samples. The validation study required 60 analyses on test samples at the target level 5 mug peanut/g food and 60 analyses at a peanut-free level, which was designed to ensure that the lower 95% confidence limit for the sensitivity and specificity would not be <90%. The probability that a test sample contains an allergen given a prevalence rate of 5% and a positive test result using a single test kit analysis with 95% sensitivity and 95% specificity, which was demonstrated for these test kits, would be 50%. When 2 test kits are run simultaneously on all samples, the probability becomes 95%. It is therefore recommended that all field samples be analyzed with at least 2 of the validated kits. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, College Pk, MD 20740 USA. AOAC, Res Inst, Gaithersburg, MD 20877 USA. Neogen Corp, Lansing, MI 48912 USA. R Biopharm Inc, Marshall, MI 49068 USA. ELISA Technol Inc, Gainesville, FL 32609 USA. RP Park, DL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM dpark@cfsan.fda.gov NR 14 TC 24 Z9 27 U1 0 U2 6 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2005 VL 88 IS 1 BP 156 EP 160 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 893HN UT WOS:000226710000020 PM 15759737 ER PT J AU Whitaker, TB Williams, KM Trucksess, MW Slate, AB AF Whitaker, TB Williams, KM Trucksess, MW Slate, AB TI Immunochemical analytical methods for the determination of peanut proteins in foods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ALLERGY; AFLATOXIN AB Peanut proteins can cause allergenic reactions that can result in respiratory and circulatory effects in the body sometimes leading to shock and death. The determination of peanut proteins in foods by analytical methods can reduce the risk of serious reactions in the highly sensitized individual by allowing for the detection of these proteins in a food at various stages of the manufacturing process. The method performance of 4 commercially available enzyme-linked immunosorbent assay (ELISA) kits was evaluated for the detection of peanut proteins in milk chocolate, ice cream, cookies, and breakfast cereals: ELISA-TEK Peanut Protein Assay, now known as "Bio-Kit" for peanut proteins, from ELISA Technologies Inc.; Veratox for Peanut Allergens from Neogen Corp.; RIDASCREEN Peanut Kit from R-Biopharm GmbH; and ProLisa from Canadian Food Technology Ltd. The 4 test kits were evaluated for accuracy (recovery) and precision using known concentrations of peanut or peanut proteins in the 4 food matrixes. Two different techniques, incurred and spiked, were used to prepare samples with 4 known concentrations of peanut protein. Defatted peanut flour was added in the incurred samples, and water-soluble peanut proteins were added in the spiked samples. The incurred levels were 0.0, 10, 20, and 100 mug whole peanut per g food; the spiked levels were 0.0, 5, 10, and 20 mug peanut protein per g food. Performance varied by test kit, protein concentration, and food matrix. The Veratox kit had the best accuracy or lowest percent difference between measured and incurred levels of 15.7% when averaged across all incurred levels and food matrixes. Recoveries associated with the Veratox kit varied from 93 to 115% for all food matrixes except cookies. Recoveries for all kits were about 50% for cookies. The analytical precision, as measured by the variance, increased with an increase in protein concentration. However, the coefficient of variation (CV) was stable across the 4 incurred protein levels and was 7.0% when averaged across the 4 food matrixes and analytical kits. The R-Biopharm test kit had the best precision or a CV of 4.2% when averaged across all incurred levels and food matrixes. Because measured protein values varied by test kit and food matrix, a method was developed to normalize or transform measured protein concentrations to an adjusted protein value that was equal to the known protein concentration. The normalization method adjusts measured protein values to equal the true protein value regardless of the type test kit or type food matrix. C1 N Carolina State Univ, USDA ARS, Raleigh, NC 27695 USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Whitaker, TB (reprint author), N Carolina State Univ, USDA ARS, Box 7625, Raleigh, NC 27695 USA. EM tom_whitaker@ncsu.edu NR 11 TC 27 Z9 29 U1 1 U2 5 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2005 VL 88 IS 1 BP 161 EP 174 PG 14 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 893HN UT WOS:000226710000021 PM 15759738 ER PT J AU Slayne, MA Lineback, DR AF Slayne, MA Lineback, DR TI Acrylamide: Considerations for risk management SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The presence of acrylamide in many carbohydrate-rich foods is due to its formation during conventional heating and preparation methods. Although acrylamide is established to be a toxic substance, the implications to public health from the amounts found in food are not clear. A better scientific understanding is required to help determine whether, and to what extent, formal risk management action might be necessary. Since acrylamide in food was highlighted in 2002, numerous investigations and initiatives have been developed, including international collaborations across governments, industry, research organizations, and consumer representations. The newly generated information is being used to help the overall understanding of this issue. In particular, new information on health aspects will be important to update the scientific risk assessment. The basis for decisions on possible risk management measures would then be clearer. If future risk assessment concludes that the amounts of acrylamide in food can pose a health threat, then options for risk management will need to be considered, such as limits, guide levels, codes of practice, guidance information, and advice to the food and catering industries and to consumers. In the meantime, it is possible to benefit from progress already made on how acrylamide is formed in food and on ways to lower the amounts present. Raising awareness to the approaches that can reduce the presence of acrylamide in food should be encouraged. Where feasible, such approaches can be assessed for practical use in production, processing, and preparation of the relevant food products. C1 Commiss European Communities, Directorate Gen Hlth & Consumer Protect, B-1049 Brussels, Belgium. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Slayne, MA (reprint author), Commiss European Communities, Directorate Gen Hlth & Consumer Protect, Rue Loi 200, B-1049 Brussels, Belgium. EM martin.slayne@cec.eu.int NR 25 TC 9 Z9 9 U1 0 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2005 VL 88 IS 1 BP 227 EP 233 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 893HN UT WOS:000226710000029 PM 15759745 ER PT J AU Lineback, D Wenzl, T Ostermann, OP de la Calle, B Anklam, E Taeymans, D AF Lineback, D Wenzl, T Ostermann, OP de la Calle, B Anklam, E Taeymans, D TI Overview of acrylamide monitoring databases SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Since high acrylamide levels in carbohydrate-rich food were reported in 2002, many research activities were started in order to gain knowledge on occurrence, formation, and prevention of this compound in food products. Among them, monitoring programs were conducted in many countries worldwide by official bodies as well as by the food industry. National and international bodies set up monitoring databases. In 2003, both the European Commission and the World Health Organization posted calls for data and placed their spreadsheets for the submission of data on the Web. The goal of the databases is to collect data for a reliable estimation of the exposure of consumers to acrylamide via the food chain. This paper describes the assessment of the data quality and outlines the composition of the data in the 2 databases, to date. C1 Commiss European Communities, Joint Res Ctr, Inst Reference Mat & Measurements, B-2440 Geel, Belgium. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Confederat Food & Drink Ind European Un, B-1040 Brussels, Belgium. RP Ostermann, OP (reprint author), Commiss European Communities, Joint Res Ctr, Inst Reference Mat & Measurements, Retieseweg 111, B-2440 Geel, Belgium. EM ole-peter.ostermann@cec.eu.int RI Wenzl, Thomas/B-9578-2015 OI Wenzl, Thomas/0000-0003-2017-3788 NR 3 TC 19 Z9 20 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2005 VL 88 IS 1 BP 246 EP 252 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 893HN UT WOS:000226710000032 PM 15759748 ER PT J AU Hungerford, JM AF Hungerford, JM TI Committee on natural toxins and food allergens - Marine and freshwater toxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Review ID SHELLFISH POISONING TOXINS; TANDEM MASS-SPECTROMETRY; LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY; PROPOSED AZASPIRACID-1 STRUCTURE; FLUOROMETRIC MICROPLATE ASSAY; LINKED-IMMUNOSORBENT-ASSAY; SODIUM-CHANNEL ACTIVATORS; JACK CARANX-LATUS; ABC RING-SYSTEM; DOMOIC ACID C1 US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. RP Hungerford, JM (reprint author), US FDA, Seafood Prod Res Ctr, 22201 23rd Dr SE, Bothell, WA 98021 USA. EM James.Hungerford@fda.gov NR 175 TC 12 Z9 14 U1 0 U2 10 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2005 VL 88 IS 1 BP 299 EP 313 PG 15 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 893HN UT WOS:000226710000039 PM 15759755 ER PT J AU Trucksess, MW AF Trucksess, MW TI Mycotoxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Review ID PERFORMANCE LIQUID-CHROMATOGRAPHY; IMMUNOAFFINITY COLUMN CLEANUP; TANDEM MASS-SPECTROMETRY; SOLID-PHASE EXTRACTION; OCHRATOXIN-A; AFLATOXIN M-1; PENICILLIUM-EXPANSUM; FUMONISIN B-1; GAS-CHROMATOGRAPHY; GREEN COFFEE C1 US FDA, College Pk, MD 20740 USA. RP Trucksess, MW (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM mtruckse@cfsan.fda.gov NR 116 TC 6 Z9 6 U1 1 U2 3 PU AOAC INT PI GAITHERSBURG PA 481 N FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 EI 1944-7922 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2005 VL 88 IS 1 BP 314 EP 324 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 893HN UT WOS:000226710000040 PM 15759756 ER PT J AU Andrews, WH Hammack, TS AF Andrews, WH Hammack, TS TI Food microbiology, non-dairy SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article C1 US FDA, College Pk, MD 20740 USA. RP Andrews, WH (reprint author), US FDA, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM wallace.andrews@fda.hhs.gov; thomas.hammack@fda.hhs.gov NR 5 TC 1 Z9 1 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 2005 VL 88 IS 1 BP 346 EP 355 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 893HN UT WOS:000226710000045 PM 15759760 ER PT J AU Kunkle, CA Schmitt, MP AF Kunkle, CA Schmitt, MP TI Analysis of a DtxR-regulated iron transport and siderophore biosynthesis gene cluster in Corynebacterium diphtheriae SO JOURNAL OF BACTERIOLOGY LA English DT Article ID TOXIN REPRESSOR DTXR; LEGIONELLA-PNEUMOPHILA; ESCHERICHIA-COLI; BACTERIA; IDENTIFICATION; SYSTEM; STRAINS; MUTANT; HEME; TRANSCRIPTION AB This report describes a genetic locus associated with siderophore biosynthesis and transport in Corynebacterium diphtheriae. A BLAST search of the C. diphtheriae genome identified a seven-gene cluster that included four genes, designated ciuA, ciuB, ciuC, and ciuD, whose predicted products are related to ABC-type iron transporters. Downstream from ciuD is the ciuE gene, whose predicted product is similar to the aerobactin biosynthetic enzymes IucA and IucC. The CiuE protein, which has a predicted mass of 121,582 Da and is approximately twice the size of either lucC or IucA, is homologous to each of these proteins in both its N- and C-terminal regions. C diphtheriae ciuE deletion mutants exhibited a defect in siderophore production, iron uptake, and growth in low-iron medium. Mutations in the ciuA gene, whose predicted product is a lipoprotein component of an iron transport system, resulted in a severe defect in iron uptake and reduced ability to use the C. diphtheriae siderophore as an iron source. Site-directed mutations in irp6A, a gene previously reported to be associated with siderophore transport, had no effect on iron uptake or the utilization of the C diphtheriae siderophore as an iron source. Transcriptional analysis demonstrated that expression of ciuA and ciuE is DtxR and iron regulated, and DNase I protection experiments confirmed the presence of DtxR binding sites upstream from each of these genes. Thus, this iron- and DtxR-regulated gene cluster is involved in the synthesis and transport of the C diphtheriae siderophore. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Lab Bacterial Toxins, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Lab Bacterial Toxins, 8800 Rockville Pike,Bldg 29,Room 108, Bethesda, MD 20892 USA. EM schmitt@cber.fda.gov NR 45 TC 26 Z9 27 U1 2 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD JAN PY 2005 VL 187 IS 2 BP 422 EP 433 DI 10.1128/JB.187.2.422-433.2005 PG 12 WC Microbiology SC Microbiology GA 889CY UT WOS:000226422300003 PM 15629913 ER PT J AU Choudhuri, S Valerio, LG AF Choudhuri, S Valerio, LG TI Usefulness of studies on the molecular mechanism of action of herbals/botanicals: The case of St. John's Wort SO JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY LA English DT Article DE St. John's Wort; hyperforin; hypericin; herbal/botanical; PXR; CYP3A4; MDR1; P-glycoprotein; (P-gp); safety; molecular mechanism ID PREGNANE-X-RECEPTOR; CONSTITUTIVE ANDROSTANE RECEPTOR; HYPERICUM-PERFORATUM EXTRACTS; RANDOMIZED CONTROLLED TRIAL; NUCLEAR RECEPTOR; XENOBIOTIC RECEPTOR; DRUG-INTERACTIONS; CHEMICAL-CONSTITUENTS; SIGNALING PATHWAY; CLINICAL-TRIALS AB The use of herbals/botanicals has been gaining wide popularity in recent years in the United States as well as in other parts of the world. The mechanism of action of most of these herbals/botanicals has not been subjected to thorough scientific investigations. St. John's wort (Hypericum perforatum) represents a useful case study in this sense. Traditionally, it is used as a natural treatment for depression; however, in recent years its molecular mechanism of action has been elucidated by a number of laboratories across the world. Such studies have helped understand potential interactions of St. John's wort with drugs and other xenobiotics. St. John's wort activates a nuclear receptor called pregnane X receptor (PXR). PXR is a ligand-activated transcription factor that induces a number of xenobiotic-metabolizing enzymes and transporters including cytochrome P4503A4 (CYP3A4) in humans. Because CYP3A4 alone metabolizes about 60% of all clinically relevant drugs, induction of CYP3A4 may result in the rapid elimination of these drugs and a consequent reduction in drug efficacy. Ironically, such enzyme-inducing effects may not produce any immediate adverse symptomatology in the person taking St. John's wort. Therefore, the case of St. John's wort should serve as a good example of the usefulness and importance of studies on the mechanism of action of the herbals/botanicals, particularly those with widespread use. Scientists, physicians, and other health professionals can make use of the knowledge from such studies as an additional risk management tool. (C) 2005 Wiley Periodicals, Inc. C1 US FDA, Div Biotechnol, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, College Pk, MD 20740 USA. US FDA, GRAS Notice Review, Off Food Addit Safety, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Choudhuri, S (reprint author), US FDA, Div Biotechnol, Ctr Food Safety & Appl Nutr, Off Food Addit Safety, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Supratim.Choudhuri@cfsan.fda.gov; Luis.Valerio@cfsan.gda.gov NR 78 TC 12 Z9 13 U1 0 U2 2 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 1095-6670 J9 J BIOCHEM MOL TOXIC JI J. Biochem. Mol. Toxicol. PY 2005 VL 19 IS 1 BP 1 EP 11 DI 10.1002/jbt.20057 PG 11 WC Biochemistry & Molecular Biology; Toxicology SC Biochemistry & Molecular Biology; Toxicology GA 901WI UT WOS:000227312500001 PM 15736155 ER PT J AU Rothmann, M AF Rothmann, M TI Type I error probabilities based on design-stage strategies with applications to noninferiority trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE noninferiority trials; active controlled trials ID ACTIVE-CONTROL TRIALS; PLACEBO-CONTROLLED TRIALS; ISSUES AB When testing the equality of means from two different populations, a t-test or large sample normal test tend to be performed. For these tests, when the sample size or design for the second sample is dependent on the results of the first sample, the type I error probability is altered for each specific possibility in the null hypothesis. We will examine the impact on the type I error probabilities for two confidence interval procedures and procedures using test statistics when the design for the second sample or experiment is dependent on the results from the first sample or experiment (or series of experiments). Ways for controlling a desired maximum type I error probability or a desired type I error rate will be discussed. Results are applied to the setting of noninferiority comparisons in active controlled trials where the use of a placebo is unethical. C1 FDA, WOCII, Ctr Drug Evaluat & Res, Div Biometr 1, Rockville, MD 20857 USA. RP Rothmann, M (reprint author), FDA, WOCII, Ctr Drug Evaluat & Res, Div Biometr 1, 5600 Fishers lane, Rockville, MD 20857 USA. EM Rothmannm@cder.fda.gov NR 10 TC 8 Z9 8 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 2005 VL 15 IS 1 BP 109 EP 127 DI 10.1081/BIP-200040847 PG 19 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 024PG UT WOS:000236207800009 PM 15702608 ER PT J AU Lachenbruch, PA Foulkes, MA Williams, AE Epstein, JS AF Lachenbruch, PA Foulkes, MA Williams, AE Epstein, JS TI Potential use of the scan statistic for quality control in blood product manufacturing SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE blood collection; quality control; rare events; scan statistics AB There are minimal standards for the processing of whole blood components, and to apply those standards requires a system of quality assurances. Excessive indications of failures in compliance trigger inspections and other remedial actions, but the demarcation of what is excessive is a critical issue. Issues of low volume in some production facilities, low expected frequency of nonconformance, multiple nonindependent statistical tests, and controlling both the false-positive and false-negative rates all complicate quality assurance procedures. The scan statistic is a statistic that computes the number of events in a moving window throughout the period of risk. Monitoring plans based on scan statistics are developed to estimate the probability that a process that is under control. C1 OBE, CBER, FDA, Div Biostat, Rockville, MD 20852 USA. RP Lachenbruch, PA (reprint author), OBE, CBER, FDA, Div Biostat, 1401 Rockville Pike,HFM-215, Rockville, MD 20852 USA. EM lachenbruch@cber.fda.gov NR 5 TC 4 Z9 4 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 2005 VL 15 IS 2 BP 353 EP 366 DI 10.1081/BIP-200048790 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 024YK UT WOS:000236232300013 PM 15796300 ER PT J AU Zhang, JJ Yi, T Zhao, LP AF Zhang, JJ Yi, T Zhao, LP TI Evaluation of nine strategies for analyzing a cDNA toxicology microarray data set SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE cDNA microarray; false discovery rate ( FDR); one- and two-group comparison; panel data analysis; replicates; t-tests ID DIFFERENTIALLY EXPRESSED GENES; MODELS AB Microarray technology with two-color-based cDNA is commonly used for drug development, as well as for a much broader range of biomedical research. Among all the applications, two-group design is probably most commonly used for comparing, e. g., normal and abnormal tissue samples, tissues treated and untreated, or individuals responded and not responded to a drug. Despite the apparent simplicity, there are numerous methods for analyzing such data in a statistically rigorous manner. Here, we discuss nine different analytical strategies, each of which is derived under a set of "reasonable" assumptions. Some of them resemble methods developed for different contexts. In the absence of the truth, investigators should consider underlying assumptions before taking one or more of these strategies for analyzing data from a particular experiment. The issue here is what are the similarities and differences between these analytical strategies. We present these strategies in the context of an actual microarray experiment performed at the U. S. Food and Drug Administration. C1 US FDA, Off Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Fred Hutchinson Canc Res Ctr, Program Biostat, Seattle, WA USA. RP Zhang, JJ (reprint author), US FDA, Off Biostat, Ctr Drug Evaluat & Res, HFD-705,12720 Twinbrook Pkwy, Rockville, MD 20857 USA. EM zhangjua@cder.fda.gov; lzhao@fhcrc.org FU NCI NIH HHS [R01CA106320] NR 15 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 1054-3406 J9 J BIOPHARM STAT JI J. Biopharm. Stat. PY 2005 VL 15 IS 3 BP 403 EP 418 DI 10.1081/BIP-200056518 PG 16 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 024YM UT WOS:000236232500002 PM 15920888 ER PT J AU Wang, SJ Hung, HMJ AF Wang, SJ Hung, HMJ TI Adaptive covariate adjustment in clinical trials SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE adaptive strategy; blinded; covariate adjustment; efficiency; randomized clinical trial AB In analysis of covariance (ANCOVA), as a result of covariate adjustment, the estimated mean difference between the two comparative treatment groups may have a better precision than the unadjusted estimate. The extent of improvement of precision depends on the correlation between the outcome variable and the covariate selected for adjustment. Therefore, for this purpose, it is desirable to apply a proper transformation to this covariate so that the transformed covariate has a stronger correlation with the outcome variable. The best predictor from the covariate for the outcome variable is the conditional expectation of the outcome variable given the covariate. Thus, a viable strategy is using regression modeling approach to search for a statistical model to well approximate the conditional expectation based on external and/or current trial data. We propose an adaptive strategy to achieve this goal if the current data are needed to help the search. C1 US FDA, CDER, Div Biometr 2, OB OPaSS, Rockville, MD 20857 USA. US FDA, CDER, Div Biometr 1, OB OPaSS, Rockville, MD 20857 USA. RP Wang, SJ (reprint author), US FDA, CDER, Div Biometr 2, OB OPaSS, 9B07,5600 Fishers Lane,HFD-715, Rockville, MD 20857 USA. EM wangs@cder.fda.gov NR 4 TC 6 Z9 6 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 2005 VL 15 IS 4 BP 605 EP 611 DI 10.1081/BIP-200062280 PG 7 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 024YO UT WOS:000236232700006 PM 16022166 ER PT J AU Hung, HMJ Cui, L Wang, SJ Lawrence, J AF Hung, HMJ Cui, L Wang, SJ Lawrence, J TI Adaptive statistical analysis following sample size modification based on interim review of effect size SO JOURNAL OF BIOPHARMACEUTICAL STATISTICS LA English DT Article DE adaptive test; confidence interval; estimation; group sequential trial; non-sequential trial; power; type I error ID DESIGNING CLINICAL-TRIALS; CONDITIONAL POWER; 2-STAGE DESIGNS; REESTIMATION; INFERENCE; ERROR AB In designing a comparative clinical trial, the required sample size is a function of the effect size, the value of which is unknown and at best may be estimated from historical data. Insufficiency in sample size as a result of overestimating the effect size can be destructive to the success of the clinical trial. Sample size re-estimation may need to be properly considered as a part of clinical trial planning. This paper is intended to give the motivations for the sample size re-estimation based partly on the effect size observed at an interim analysis and for a resulting simple adaptive test strategy. The performance of this adaptive design strategy is assessed by comparing it with a fixed maximum sample size design that is properly adjusted in anticipation of the possible sample size adjustment. C1 US FDA, CDER, Div Biometr 1, OB OPaSS, Rockville, MD 20852 USA. Sanofi Aventis Pharmaceut Inc, Dept Biostat, Bridgewater, NJ USA. US FDA, CDER, Div Biometr 2, OB OPaSS, Rockville, MD 20852 USA. RP Hung, HMJ (reprint author), US FDA, CDER, Div Biometr 1, OB OPaSS, HFD-710,Room 5062,WOC2,1452 Rockville Pike, Rockville, MD 20852 USA. EM hung@cder.fda.gov NR 37 TC 14 Z9 15 U1 1 U2 7 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 2005 VL 15 IS 4 BP 693 EP 706 DI 10.1081/BIP-200062855 PG 14 WC Pharmacology & Pharmacy; Statistics & Probability SC Pharmacology & Pharmacy; Mathematics GA 024YO UT WOS:000236232700013 PM 16022173 ER PT J AU Scallet, AC Muskhelishvili, L Slikker, W Kadlubar, FF AF Scallet, AC Muskhelishvili, L Slikker, W Kadlubar, FF TI Sex differences in cytochrome P4501B1, an estrogen-metabolizing enzyme, in the rhesus monkey telencephalon SO JOURNAL OF CHEMICAL NEUROANATOMY LA English DT Article DE in situ hybridization; immunohistochemistry; sex differences; catecholestrogen; estrogen; dopamine ID CATECHOL-O-METHYLTRANSFERASE; PITUITARY-GLAND; MESSENGER-RNA; HUMAN CYP1B1; MCF-7 CELLS; FEMALE RATS; BRAIN; CATECHOLESTROGENS; HYPOTHALAMUS; ESTRADIOL AB The metabolic enzyme CYPIBI is a recently cloned member of the cytochrorne P450 superfamily, expressed widely throughout primate tissue, including the CNS. Although CYPIBI protein is known to metabolize estradiol to catecholestrogens in the uterus. its localization and function in brain have not yet been described. To better understand CYPIBI distribution, we have combined in situ hybridization (ISH) for its mRNA with immunohistochemistry (IHC) for the CYPIBI protein in selected brain regions of male and female adult rhesus monkey mulatta). Blocks of formalin-fixed tissue obtained from the frontal cortex, hippocampus. thalamus, and amygdala were processed and embedded in paraffin. The), were then sectioned and stained as described for human tissue [Muskhelishvili, L., Thompson. P.A., Kusewitt, D.F., Wang, C., Kadlubar. F.F. 2001. In situ hybridization and immunohistochemical analysis of cytochrome P450 I B I expression in human normal tissues. J. Histochem. Cytochern. 49, 229-236]. Results indicated widespread distribution of CYPIBI mRNA in both male and female monkey frontal cortex, hippocampus. thalamus, and amygdala. In contrast, although CYPIBI protein was co-localized with its mRNA in the female brains, it was primarily restricted to hippocampal pyramidal neurons in the male brains. These results suggest that CYPIBI may subserve widespread metabolic functions in the female primate brain but have more restricted actions within the hippocampal pyramidal neurons of the male. Published by Elsevier B.V. C1 NCTR FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, FDA, Charles River Labs, Jefferson, AR 72079 USA. NCTR FDA, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Scallet, AC (reprint author), NCTR FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM ascallet@nctr.fda.gov NR 54 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0891-0618 J9 J CHEM NEUROANAT JI J. Chem. Neuroanat. PD JAN PY 2005 VL 29 IS 1 BP 71 EP 80 DI 10.1016/j.jchemneu.2004.09.003 PG 10 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 889FL UT WOS:000226428800006 PM 15589702 ER PT J AU Yu, JG Lin, JS Benjamin, WH Waites, KB Lee, CH Nahm, MH AF Yu, JG Lin, JS Benjamin, WH Waites, KB Lee, CH Nahm, MH TI Rapid multiplex assay for serotyping pneumococci with monoclonal and polyclonal antibodies SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; CONJUGATE VACCINE; LATEX; 6B; IMMUNOASSAY; PCR AB We have developed and characterized a rapid semiautomated pneumococcal serotyping system incorporating a pneumococcal lysate preparation protocol and a multiplex serotyping assay. The lysate preparation incorporates a bile solubility test to confirm pneumococcal identification that also enhances assay specificity. The multiplex serotyping assay consists of 24 assays specific for 36 serotypes: serotypes 1, 2, 3, 4, 5, 6A, 6B, 7A/7F, 8, 9L/9N, 9V, 10A/10B/39/(33C), 11A/11D/11F, 12A/12B/12F, 14, 15B/(15C), 17F, 18C, 19A, 19F, 20, 22A/22F, 23F, and 33A/33F. The multiplex assay requires a How cytometer, two sets of latex particles coated with pneumococcal polysaccharides, and serotype-specific antibodies. Fourteen newly developed monoclonal antibodies specific for common serotypes and a pool of polyclonal rabbit sera for some of the less-common serotypes are used. The two monoclonal antibodies specific for serotypes 18C and 23F recognize serotype-specific epitopes that have not been previously described. These monoclonal antibodies make the identification of the 14 common serotypes invariant. The specificity of the serotyping assay is fully characterized with pneumococci of all known (i.e., 90) serotypes. The assay is sensitive enough to use bacterial lysates diluted 20 fold. Our serotyping system can identify not only all the serotypes in pneumococcal vaccines but also most (>90%) of clinical isolates. This system should be very useful in serotyping clinical isolates for evaluating pneumococcal vaccine efficacy. C1 Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. US FDA, Bethesda, MD 20014 USA. RP Nahm, MH (reprint author), 845 19th St S,BBRB 614, Birmingham, AL 35249 USA. EM Nahm@uab.edu OI Nahm, Moon/0000-0002-6922-1042 FU NIAID NIH HHS [N01AI30021] NR 26 TC 31 Z9 32 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2005 VL 43 IS 1 BP 156 EP 162 DI 10.1128/JCM.43.1.156-162.2005 PG 7 WC Microbiology SC Microbiology GA 888NB UT WOS:000226380400021 PM 15634965 ER PT J AU Lynn, F Hobbs, MM Zenilman, JM Behets, FMTF Van Damme, K Rasamindrakotroka, A Bash, MC AF Lynn, F Hobbs, MM Zenilman, JM Behets, FMTF Van Damme, K Rasamindrakotroka, A Bash, MC TI Genetic typing of the porin protein of Neisseria gonorrhoeae from clinical noncultured samples for strain characterization and identification of mixed gonococcal infections SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID SEXUALLY-TRANSMITTED INFECTIONS; OUTER-MEMBRANE PROTEIN; CHLAMYDIA-TRACHOMATIS; TRICHOMONAS-VAGINALIS; VARIABLE REGIONS; DIVERSITY; SPECIMENS; AMPLICOR; WOMEN; RECOMBINATION AB Molecular methods that characterize the Neisseria gonorrhoeae porin protein Por are needed to study gonococcal pathogenesis in the natural host and to classify strains from direct clinical samples used with nucleic acid amplification-based tests. We have defined the capabilities of por variable region (VR) typing and determined suitable conditions to apply the method to direct clinical specimens. Nested PCR from spiked urine samples detected 1 to 10 copies of template DNA; freezing spiked whole urine greatly reduced the ability to amplify porB. In a laboratory model of mixed gonococcal infections, the por type of one strain could be determined in the presence of a 100-fold excess of another. por VR typing was used to examine clinical samples from women enrolled in studies conducted in Baltimore, Md., and Madagascar. por type was determined from 100% of paired cervical swab and wick samples from 20 culture-positive women from Baltimore; results for eight individuals (40%) suggested infection with more than one strain. In frozen urine samples from Madagascar, porB was amplified and typed from 60 of 126 samples from ligase chain reaction (LCR)-positive women and 3 samples from LCR-negative women. The por VR types of 13 samples (21%) suggested the presence of more than one gonococcal strain. Five por types, identified in >45% of women with typed samples, were common to both geographic areas. Molecular typing is an important adjunct to nucleic acid amplification-based diagnostics. Methods that utilize direct clinical samples and can identify mixed infections may contribute significantly to studies of host immunity, gonococcal epidemiology, and pathogenesis. C1 Ctr Biol Evaluat & Res, Div Bacterial Allergen & Parasit Prod, Off Vaccines Res & Review, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. Johns Hopkins Univ, Sch Med, Div Allergies & Infect Dis, Baltimore, MD USA. Univ N Carolina, Dept Med, Chapel Hill, NC USA. Minist Hlth, Antananarivo, Madagascar. RP Bash, MC (reprint author), Ctr Biol Evaluat & Res, Div Bacterial Allergen & Parasit Prod, Off Vaccines Res & Review, 1401 Rockville Pike,HFM-428, Rockville, MD 20852 USA. EM bash@cber.fda.gov FU NIAID NIH HHS [K24 AI001633, K24AI01633, U19 AI031496, U19AI31496] NR 35 TC 24 Z9 25 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JAN PY 2005 VL 43 IS 1 BP 368 EP 375 DI 10.1128/JCM.43.1.368-375.2005 PG 8 WC Microbiology SC Microbiology GA 888NB UT WOS:000226380400052 PM 15634996 ER PT J AU Wray-Cahen, D Pritchard, W Ashby, A Russek-Cohen, E Vossoughi, J Karanian, J AF Wray-Cahen, D. Pritchard, W. Ashby, A. Russek-Cohen, E. Vossoughi, J. Karanian, J. TI Gender, age, and hormonal status affect recovery time from general anesthesia in pigs SO JOURNAL OF DAIRY SCIENCE LA English DT Meeting Abstract DE gender; anesthesia; age C1 [Wray-Cahen, D.; Pritchard, W.; Ashby, A.; Russek-Cohen, E.; Karanian, J.] US FDA, Laurel, MD USA. [Russek-Cohen, E.] Biomed Res Fdn, Olney, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 2 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. PY 2005 VL 88 SU 1 BP 260 EP 260 PG 1 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA V44GC UT WOS:000202990201210 ER PT J AU Tolleson, WH AF Tolleson, WH TI Human melanocyte biology, toxicology, and pathology SO JOURNAL OF ENVIRONMENTAL SCIENCE AND HEALTH PART C-ENVIRONMENTAL CARCINOGENESIS & ECOTOXICOLOGY REVIEWS LA English DT Review DE melanocytes; melanin; melanoma; ocular toxicity; ototoxicity; oxidative stress ID CATECHOL-O-METHYLTRANSFERASE; SYSTEMIC IMMUNE SUPPRESSION; ULTRAVIOLET-LIGHT EXPOSURE; RETINAL-PIGMENT EPITHELIUM; PLATELET-ACTIVATING-FACTOR; TYROSINASE-RELATED PROTEIN; CULTURED HUMAN MELANOCYTES; FLIGHT MASS-SPECTROMETRY; CREST-DERIVED MELANOCYTE; KOYANAGI-HARADA-DISEASE AB The human melanocytes of the skin, hair, eyes, inner ears, and covering of the brain provide physiologic functions important in organ development and maintenance. Melanocytes develop from embryonic neural crest progenitors and share certain traits with other neural crest derivatives found in the adrenal medulla and peripheral nervous system. The distinctive metabolic feature of melanocytes is the synthesis of melanin pigments from tyrosine and cysteine precursors involving over 100 gene products. These complex biochemical mechanisms create inherent liabilities for melanocytic cells if intracellular systems necessary for compartmentalization, detoxification, or repair are compromised. Melanocyte disorders may involve pigmentation, sensory functions, autoimmunity, or malignancy. Environmental factors such as ultraviolet radiation and chemical exposures, combined with heritable traits, represent the principal hazards associated with melanocyte disorders. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM wtolleson@nctr.fda.gov NR 271 TC 52 Z9 55 U1 3 U2 12 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 2005 VL 23 IS 2 BP 105 EP 161 DI 10.1080/10590500500234970 PG 57 WC Oncology; Environmental Sciences; Toxicology SC Oncology; Environmental Sciences & Ecology; Toxicology GA 978DY UT WOS:000232855000001 PM 16291526 ER PT J AU Seo, KH Brackett, RE AF Seo, KH Brackett, RE TI Rapid, specific detection of Enterobacter sakazakii in infant formula using a real-time PCR assay SO JOURNAL OF FOOD PROTECTION LA English DT Article ID OPERON; OUTBREAK AB Enterobacter sakazakii is a rare cause of invasive infection with high mortality rates in neonates. Powdered milk-based infant formulas have been associated with the E. sakazakii-related outbreaks in premature or other immunocompromised infants. In this study, an assay was developed for the specific detection of E. sakazakii in infant formula using an application of the fluorogenic 5' nuclease assay (TaqMan). A set of primers and probe was designed using the E. sakazaki, partial macromolecular synthesis operon: the rpsU gene 3' end and the primase (dnaG) gene 5' end. The specificity of the. assay was evaluated using 68 Enterobacter and 55 non-Enterobacter strains. The newly developed assay enables us to detect 100 CFU/ml in pure culture and in reconstituted infant formula in 50 cycles of PCR without enrichment. The assay was specific enough to discriminate E. sakazakii from all other Enterobacter and non-Enterobacter strains tested. The developed real-time PCR assay could save up to 5 days and eliminate the need for plating samples on selective or diagnostic agars and for biochemical confirmation steps. The real-time PCR assay could be used to rapidly screen infant formula samples for L sakazakii and would be a boon to food industries and regulatory agencies. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods & Beverages, College Pk, MD 20740 USA. RP Seo, KH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Plant & Dairy Foods & Beverages, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM kseo@cfsan.fda.gov NR 11 TC 111 Z9 119 U1 0 U2 14 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 2005 VL 68 IS 1 BP 59 EP 63 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 886ZU UT WOS:000226272600008 PM 15690804 ER PT J AU Edelson-Mammel, SG Whiting, RC Joseph, SW Buchanan, RL AF Edelson-Mammel, SG Whiting, RC Joseph, SW Buchanan, RL TI Effect of prior growth conditions on the thermal inactivation of 13 strains of Listeria monocytogenes in two heating menstrua SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; PHASE ACID RESISTANCE; STATIONARY-PHASE; SHOCK; MILK AB The thermal tolerance of 13 Listeria monocytogenes Strains was tested using a submerged heating coil apparatus. The strains were grown individually for 18 It at 37degreesC in acidogenic tryptic soy broth (without dextrose) supplemented with 1% glucose and 1% glutamine (TSB+G) or nonacidogenic tryptic soy broth supplemented with 1% glutamine but containing no glucose (dextrose) (TSB-G). The former medium results in cells induced for pH-dependent, stationary-phase acid resistance, whereas the latter medium allows L. monocytogenes to grow to high numbers in the absence of glucose, yielding cells that are not induced for pH-dependent, stationary-phase acid resistance. The average final pH values of the 18-h TSB+G and the TSB-G cultures were 4.7 and 6.7, respectively. The cells grown in the acid resistance-inducing and non-acid resistance-inducing media were then tested in two heating menstrua that consisted of brain heart infusion broth adjusted to pH 3.0 and water activity (a(w)) of 0.987 or pH 7.0 and a(w) 0.970. In 14 of the 26 menstruum-strain combinations tested, the acid resistance-induced strains were more heat resistant then the equivalent noninduced cultures. No difference in the pattern of thermal resistance in response to induction of acid resistance was apparent among the different serovars tested. The results suggest that the ability of prior induction of acid resistance to enhance thermal resistance can vary substantially among L. monocytogenes strains. C1 Ctr Food Safety & Appl Nutr, Dept Hlth & Human Serv, US FDA, College Pk, MD 20740 USA. Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Buchanan, RL (reprint author), Ctr Food Safety & Appl Nutr, Dept Hlth & Human Serv, US FDA, College Pk, MD 20740 USA. EM Robert.Buchanan@cfsan.fda.gov NR 17 TC 16 Z9 17 U1 1 U2 5 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JAN PY 2005 VL 68 IS 1 BP 168 EP 172 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 886ZU UT WOS:000226272600026 PM 15690821 ER PT J AU Isaacs, S Aramini, J Ciebin, B Farrar, JA Ahmed, R Middleton, D Chandran, AU Harris, LJ Howes, M Chan, E Pichette, AS Campbell, K Gupta, A Lior, LY Pearce, M Clark, C Rodgers, F Jamieson, F Brophy, I Ellis, A AF Isaacs, S Aramini, J Ciebin, B Farrar, JA Ahmed, R Middleton, D Chandran, AU Harris, LJ Howes, M Chan, E Pichette, AS Campbell, K Gupta, A Lior, LY Pearce, M Clark, C Rodgers, F Jamieson, F Brophy, I Ellis, A CA Salmonella Enteritidis PT30 Outbre TI An international outbreak of salmonellosis associated with raw almonds contaminated with a rare phage type of Salmonella enteritidis SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ENTERICA SEROTYPE ENTERITIDIS; FIELD GEL-ELECTROPHORESIS; ESCHERICHIA-COLI; MICROBIAL FLORA; ENVIRONMENTS; CANADA; MEATS AB During the winter of 2000 to 2001, an outbreak due to Salmonella Enteritidis (SE) phage type 30 (PT30), a rare strain. was detected in Canada. The ensuing investigation involved Canadian and American public health and food regulatory agencies and an academic research laboratory. Enhanced laboratory surveillance. including phage typing and pulsed-field eel electrophoresis, was used to identify cases. Case questionnaires were administered to collect information about food and environmental exposures. A case-control study with 16 matched case-control pairs was conducted to test the hypothesis of an association between raw whole almond consumption and infection. Almond samples were collected from case homes. retail outlets. and the implicated processor, and environmental samples were collected from processing equipment and associated farms for microbiological testing. One hundred sixty-eight laboratory-confirmed cases of SE PT30 infection (157 in Canada. I I in the United States) were identified between October 2000 and July 2001. The case-control study identified raw whole almonds as the source of infection (odds ration, 21.1; 95% confidence interval, 3.6 to infinity). SE PT30 was detected in raw whole natural almonds collected from home, retail, distribution, and warehouse sources and from environmental swabs of processing equipment and associated farmers' orchards. The frequent and prolonged recovery of this specific organism from a large agricultural area was an unexpected finding and may indicate significant diffuse contamination on these farms. Identification of almonds as the source of a foodborne outbreak is a previously undocumented finding. leading to a North American recall of this product and a review of current industry practices. C1 Ctr Infect Dis Prevent & Control, Foodborne Waterborne & Zoonot Infect Div, Hlth Canada, Guelph, ON N1G 5B2, Canada. Minist Hlth & Long Term Care, Cent Publ Hlth Lab, Lab Branch, Etobicoke, ON M9P 3T1, Canada. Calif Dept Hlth Serv, Food & Drug Branch, Sacramento, CA 94234 USA. Hlth Canada, Natl Microbiol Lab, Natl Lab Enter Pathogens, Winnipeg, MB R3E 3R2, Canada. Minist Hlth & Long Term Care, Dis Control Serv, Pub Hlth Branch, Toronto, ON M2M 4K5, Canada. Hlth Canada, Populat & Publ Hlth Branch, Canadian Field Epidemiol Program, Ottawa, ON K1A 0K9, Canada. Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA. Canadian Food Inspect Agcy, Burnaby, BC V5G 4P2, Canada. US FDA, Rockville, MD 20857 USA. CDC, Epidem Intelligent Serv, Div Appl Publ Hlth Training, Epidemiol Program Off, Atlanta, GA 30333 USA. Natl Ctr Infect Dis, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. Vancouver Isl Hlth Author, Victoria, BC V8T 4E2, Canada. Dept Hlth & Wellness, Provincial Epidemiol Serv, Fredericton, NB E3A 3N6, Canada. RP Isaacs, S (reprint author), Ctr Infect Dis Prevent & Control, Foodborne Waterborne & Zoonot Infect Div, Hlth Canada, 160 Res Lane,Unit 206, Guelph, ON N1G 5B2, Canada. EM sandy_isaacs@hc-sc.gc.ca RI Harris, Linda/B-5030-2011; Jamieson, Frances/B-2040-2013 OI Harris, Linda/0000-0002-1911-752X; NR 36 TC 116 Z9 120 U1 2 U2 25 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 2005 VL 68 IS 1 BP 191 EP 198 PG 8 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 886ZU UT WOS:000226272600031 PM 15690826 ER PT J AU Hughes, MA Green, CS Lowchyj, L Lee, GM Grippe, VK Smith, MF Huang, LY Harvill, E Merkel, TJ AF Hughes, MA Green, CS Lowchyj, L Lee, GM Grippe, VK Smith, MF Huang, LY Harvill, E Merkel, TJ TI MyD88-dependent signaling confers protection to Bacillus anthracis spore challenge in mice: Implications for Toll-like receptor signaling SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract CT 38th Annual Meeting of the Society-for-Leukocyte-Biology CY SEP 21-24, 2005 CL Sir William Dunn Sch Pathol, Oxford, ENGLAND SP Soc Leukocyte Biol HO Sir William Dunn Sch Pathol C1 Univ Virginia, Dept Internal Med, Div Infect Dis, Charlottesville, VA 22903 USA. US FDA, Ctr Biol Evaluat & Res, Lab Resp & Special Pathogens, Bethesda, MD USA. Univ Virginia, Dept Internal Med, Div Gastroenterol, Charlottesville, VA 22903 USA. US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Bethesda, MD USA. Penn State Univ, Immunol Res Labs, Dept Vet Sci, University Pk, PA 16802 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 2005 SU S MA 132 BP 58 EP 59 PG 2 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 962PB UT WOS:000231743600132 ER PT J AU Sheng, L Klutch, M Lewis, AM Peden, K AF Sheng, Li Klutch, Michael Lewis, Andrew M. Peden, Keith TI Detection of neutralization antibodies to primate polyomaviruses using a single-cycle reporter virus assay SO JOURNAL OF NEUROVIROLOGY LA English DT Meeting Abstract C1 [Sheng, Li; Klutch, Michael; Lewis, Andrew M.; Peden, Keith] US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PY 2005 VL 14 SU 2 BP 71 EP 71 PG 1 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA V80CU UT WOS:000205415200054 ER PT J AU Piegorsch, WW Webster West, R Pan, W Kodell, RL AF Piegorsch, WW Webster West, R Pan, W Kodell, RL TI Low dose risk estimation via simultaneous statistical inferences SO JOURNAL OF THE ROYAL STATISTICAL SOCIETY SERIES C-APPLIED STATISTICS LA English DT Article DE bench-mark dose; environmental risk assessment; non-quantal dose-response; simultaneous confidence bands; simultaneous inference ID UPPER CONFIDENCE-LIMITS; QUANTITATIVE RESPONSES; LINEAR-REGRESSION; MODEL; BANDS; CARCINOGENS; INTERVALS AB The paper develops and studies simultaneous confidence bounds that are useful for making low dose inferences in quantitative risk analysis. Application is intended for risk assessment studies where human, animal or ecological data are used to set safe low dose levels of a toxic agent, but where study information is limited to high dose levels of the agent. Methods are derived for estimating simultaneous, one-sided, upper confidence limits on risk for end points measured on a continuous scale. From the simultaneous confidence bounds, lower confidence limits on the dose that is associated with a particular risk (often referred to as a bench-mark dose) are calculated. An important feature of the simultaneous construction is that any inferences that are based on inverting the simultaneous confidence bounds apply automatically to inverse bounds on the bench-mark dose. C1 Univ S Carolina, Dept Stat, LeConte Coll 216, Columbia, SC 29208 USA. Natl Ocean Serv, Charleston, SC USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Piegorsch, WW (reprint author), Univ S Carolina, Dept Stat, LeConte Coll 216, Columbia, SC 29208 USA. EM piegorsc@stat.sc.edu OI Piegorsch, Walter/0000-0003-2725-5604 NR 42 TC 22 Z9 22 U1 1 U2 2 PU BLACKWELL PUBL LTD PI OXFORD PA 108 COWLEY RD, OXFORD OX4 1JF, OXON, ENGLAND SN 0035-9254 J9 J ROY STAT SOC C-APP JI J. R. Stat. Soc. Ser. C-Appl. Stat. PD JAN PY 2005 VL 54 BP 245 EP 258 DI 10.1111/j.1467-9876.2005.00481.x PN 1 PG 14 WC Statistics & Probability SC Mathematics GA 864PL UT WOS:000224645300016 ER PT J AU Gao, G Stuver, SO Okayama, A Tsubouchi, H Mueller, NE Tabor, E AF Gao, G Stuver, SO Okayama, A Tsubouchi, H Mueller, NE Tabor, E TI The minimum number of clones necessary to sequence in order to obtain the maximum information about hepatitis C virus quasispecies: a comparison of subjects with and without liver cancer SO JOURNAL OF VIRAL HEPATITIS LA English DT Article DE hepatitis C virus; hepatocellular carcinoma; quasispecies ID HYPERVARIABLE REGION-1; INFECTION; DIVERSITY AB Most studies of hepatitis C virus (HCV) quasispecies have reported the results of sequencing only three to five clones per sample. The possibility that sequencing so few clones might not provide a representative picture of the quasispecies present in a sample has never been evaluated. The present study was conducted to evaluate whether sequencing greater numbers of clones results in better information about the HCV quasispecies number and distribution, and to compare the HCV quasispecies in liver cancer cases and controls. RNA was extracted from serial serum samples from six subjects with HCV-associated liver cancer and 11 age- and sex-matched HCV-infected controls without liver cancer. The hypervariable region 1 (HVR1) of the HCV genome was amplified, cloned, and sequenced. For further studies of 12 serum samples from two liver cancer cases and two matched controls, successive groups of 10 additional clones were sequenced up to a total of 50 clones per serum sample. When only 10 clones were sequenced from each specimen, no consistent differences were seen between the number of HCV quasispecies in the six liver cancer cases and the 11 controls. However, sequencing 40 clones from each of 12 samples from two liver cancer cases and two controls revealed a greater number of quasispecies in liver cancer cases than in controls. Testing an additional 10 clones (50 clones per sample) did not significantly increase the number of quasispecies detected. C1 US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Rockville, MD 20852 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Boston Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA USA. Miyazaki Med Coll, Dept Internal Med 2, Miyazaki 88916, Japan. RP Tabor, E (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, 1401 Rockville Pike,HFM-300, Rockville, MD 20852 USA. EM tabor@cber.fda.gov OI Stuver, Sherri/0000-0002-4027-2663 NR 11 TC 4 Z9 4 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 1352-0504 J9 J VIRAL HEPATITIS JI J. Viral Hepatitis PD JAN PY 2005 VL 12 IS 1 BP 46 EP 50 DI 10.1111/j.1365-2893.2005.00546.x PG 5 WC Gastroenterology & Hepatology; Infectious Diseases; Virology SC Gastroenterology & Hepatology; Infectious Diseases; Virology GA 889QR UT WOS:000226458000007 PM 15655047 ER PT J AU Cherkasova, EA Yakovenko, ML Rezapkin, GV Korotkova, EA Ivanova, OE Eremeeva, TP Krasnoproshina, LI Romanenkova, NI Rozaeva, NR Sirota, L Agol, VI Chumakov, KM AF Cherkasova, EA Yakovenko, ML Rezapkin, GV Korotkova, EA Ivanova, OE Eremeeva, TP Krasnoproshina, LI Romanenkova, NI Rozaeva, NR Sirota, L Agol, VI Chumakov, KM TI Spread of vaccine-derived poliovirus from a paralytic case in an immunodeficient child: an insight into the natural evolution of oral polio vaccine SO JOURNAL OF VIROLOGY LA English DT Article ID TYPE-2 POLIOVIRUS; POLIOMYELITIS; PATIENT; ERADICATION; STRAINS; RECOMBINANT; CIRCULATION; SEWAGE; REPLICATION; PERSISTENCE AB Sabin strains used in the manufacture of oral polio vaccine (OPV) replicate in the human organism and can give rise to vaccine-derived polioviruses. The increased neurovirulence of vaccine derivatives has been known since the beginning of OPV use, but their ability to establish circulation in communities has been recognized only recently during the latest stages of the polio eradication campaign. This important observation called for studies of their emergence and evolution as well as extensive surveillance to determine the scope of this phenomenon. Here, we present the results of a study of vaccine-derived isolates from an immunocompromised poliomyelitis patient, the contacts, and the local sewage. All isolates were identified as closely related and slightly evolved vaccine derivatives with a recombinant type 2/type I genome. The strains also shared several amino acid substitutions including a mutation in the VP1 protein that was previously shown to be associated with the loss of attenuation. Another mutation in the VP3 protein resulted in altered immunological properties of the isolates, possibly facilitating virus spread in immunized populations. The patterns and rates of the accumulation of synonymous mutations in isolates collected from the patient over the extended period of excretion suggest either a substantially nonuniform rate of mutagenesis throughout the genome, or, more likely, the strains may have been intratypic recombinants between coevolving derivatives with different degrees of divergence from the vaccine parent. This study provides insight into the early stages of the establishment of circulation by runaway vaccine strains. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Moscow MV Lomonosov State Univ, AN Belozersky Inst Phys Chem Biol, Moscow, Russia. II Mechnikov Vaccine & Serum Inst, Moscow, Russia. Russian Acad Med Sci, MP Chumakov Inst Poliomyeltitis & Viral Encephali, Moscow, Moscow Region, Russia. St Petersburg Pasteur Inst, St Petersburg, Russia. RP Chumakov, KM (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-470, Rockville, MD 20852 USA. EM chumakov@cber.fda.gov RI Agol, Vadim/E-1941-2013; OI Ivanova, O.E./0000-0003-1784-4827 NR 44 TC 32 Z9 50 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 JAN PY 2005 VL 79 IS 2 BP 1062 EP 1070 DI 10.1128/JVI.79.2.1062.1070.2005 PG 9 WC Virology SC Virology GA 885IG UT WOS:000226149700042 PM 15613335 ER PT J AU Zaragoza, C Li, RM Fahle, GA Fischer, SH Raffeld, M Lewis, AM Kopp, JB AF Zaragoza, C Li, RM Fahle, GA Fischer, SH Raffeld, M Lewis, AM Kopp, JB TI Squirrel monkeys support replication of BK virus more efficiently than simian virus 40: an animal model for human BK virus infection SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSPLANT RECIPIENTS; HUMAN PAPOVAVIRUS; RHESUS-MONKEYS; BRAIN TUMORS; JC-VIRUS; SV40; URINE; NEPHROPATHY; HAMSTERS; KIDNEYS AB We performed experiments to test the suitability of squirrel monkeys (Saimiri sciureus) as an experimental model for BK virus (BKV) and simian virus 40 (SV40) infection. Four squirrel monkeys received intravenous inoculation with BKV Gardner strain, and six squirrel monkeys received intravenous inoculation with SV40 777 strain. Eight of 10 monkeys received immunosuppression therapy, namely, cyclophosphamide subcutaneously either before or both before and after viral inoculation. The presence of viral infection was assessed by quantitative real-time PCR amplification of viral DNA from blood, urine, and 10 tissues. We found that squirrel monkeys were susceptible to infection with BKV, with high viral copy number detected in blood and viral genome detected in all tissues examined. BKV genome was detected in urine from only one monkey, while three monkeys manifested focal interstitial nephritis. BKV T antigen was expressed in renal peritubular capillary endothelial cells. By contrast, SV40 was detected at very low copy numbers in only a few tissues and was not detected in blood. We conclude that the squirrel monkey is a suitable animal for studies of experimental BKV infection and may facilitate studies of viral entry, pathogenesis, and therapy. C1 NIDDKD, Kidney Dis Sect, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Dept Lab Med, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Dept Hlth & Human Serv, Bethesda, MD USA. RP Kopp, JB (reprint author), NIDDKD, Kidney Dis Sect, NIH, 10-3N116, Bethesda, MD 20892 USA. EM jbkopp@nih.gov OI Kopp, Jeffrey/0000-0001-9052-186X NR 22 TC 8 Z9 8 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 2005 VL 79 IS 2 BP 1320 EP 1326 DI 10.1128/JVI.79.2.1320-1326.2005 PG 7 WC Virology SC Virology GA 885IG UT WOS:000226149700066 PM 15613359 ER PT J AU Saebo, A Perfield, JW Delmonte, P Yurawecz, MP Lawrence, P Brenna, JT Bauman, DE AF Saebo, A Perfield, JW Delmonte, P Yurawecz, MP Lawrence, P Brenna, JT Bauman, DE TI Milk fat synthesis is unaffected by abomasal infusion of the conjugated diene 18 : 3 isomers cis-6, trans-10, cis-12 and cis-6,trans-8,cis-12 SO LIPIDS LA English DT Article ID LINOLEIC-ACID CLA; DAIRY-COWS; DIETARY SUPPLEMENTATION; BODY-COMPOSITION; METHYL-ESTERS; ISOMERS; TISSUES; IDENTIFICATION; INHIBITION; METABOLISM AB It has been previously established that trans-10,cis-12 CLA is a potent inhibitor of milk fat synthesis. Although the mechanism of this action is not completely understood, it has been speculated that eicosanoid-like metabolites of this isomer formed by the activity of tissue desaturases may be responsible for its activity. The objective of this study was to investigate the effects of an enrichment containing an 18:3 conjugated diene, produced in the metabolism of trans-10,cis-12 CLA, on milk fat synthesis. Three rumen-fistulated Holstein cows (210 +/- 8 d in milk) were randomly assigned in a 3 x 3 Latin square experiment. Treatments were W control, (ii) trans-10,cis-12 CLA supplement (2.1 g/d; positive control), (iii) enrichment providing two conjugated diene 18:3 isomers (2.6 g/d of cis-6,trans-10,cis-12 and 4.0 g/d of cis-6,trans-8,cis-12) and trans-10;cis-12 CLA (2.1 g/d). Treatments were abomasally infused for 5 d at 4-h intervals, and there was a 7-d interval between periods. Milk yield, dry matter intake, and milk protein yield were unaffected by treatments. In contrast, the trans-10,cis-12 CLA supplement reduced milk fat yield by 27%, Whereas the supplement enriched with conjugated diene 18:3 isomers (treatment iii) had no effect on milk fat yield beyond that attributable to its trans-10,cis-12 CLA content. The transfer efficiency of trans-10,cis-12 CLA into milk fat was 25 and 24% for treatments ii and iii, respectively., At the same time, the abomasally infused conjugated diene 18:3 isomers were transferred to milk fat with an efficiency of 33 and 41% for cis-6,trans-10,cis-12 and;cis-6,trans-8,cis-12 18:3, respectively. Overall, short-term abomasal infusion of the conjugated diene 18:3 isomers had no effect on milk fat synthesis, thereby offering no support for an involvement of metabolites of trans-10,cis-12 CLA in the regulation of milk fat synthesis. C1 Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. Nat ASA, N-6160 Hovdebygda, Norway. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Cornell Univ, Div Nutrit Sci, Ithaca, NY 14853 USA. RP Bauman, DE (reprint author), Cornell Univ, Dept Anim Sci, 262 Morrison Hall, Ithaca, NY 14853 USA. EM deb6@cornell.edu RI Brenna, James/A-4167-2008 FU NIGMS NIH HHS [GM071534] NR 35 TC 11 Z9 11 U1 0 U2 3 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 221 W BRADLEY AVE, CHAMPAIGN, IL 61821-1827 USA SN 0024-4201 J9 LIPIDS JI Lipids PD JAN PY 2005 VL 40 IS 1 BP 89 EP 95 PG 7 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 906UN UT WOS:000227669400010 PM 15825834 ER PT J AU Tsai, CA Lee, TC Ho, IC Yang, UC Chen, CH Chen, JJ AF Tsai, CA Lee, TC Ho, IC Yang, UC Chen, CH Chen, JJ TI Multi-class clustering and prediction in the analysis of microarray data SO MATHEMATICAL BIOSCIENCES LA English DT Article DE bagged clustering; bagging fuzzy clustering; gene selection; k-nn classification; rand statistic; shaded similarity matrix plot ID GENE-EXPRESSION DATA; PATTERNS; CLASSIFICATION; TUMOR; ARSENITE AB DNA microarray technology provides tools for studying the expression profiles of a large number of distinct genes simultaneously. This technology has been applied to sample clustering and sample prediction. Because of a large number of genes measured, many of the genes in the original data set are irrelevant to the analysis. Selection of discriminatory genes is critical to the accuracy of clustering and prediction. This paper considers statistical significance testing approach to selecting discriminatory gene sets for multi-class clustering and prediction of experimental samples. A toxicogenomic data set with nine treatments (a control and eight metals, As, Cd, Ni, Cr, Sb, Pb, Cu, and AsV with a total of 55 samples) is used to illustrate a general framework of the approach. Among four selected gene sets, a gene set Omega(1) formed by the intersection of the F-test and the set of the union of one-versus-all t-tests performs the best in terms of clustering as well as prediction. Hierarchical and two modified partition (k-means) methods all show that the set Omega(1) is able to group the 55 samples into seven clusters reasonably well, in which the As and AsV samples are considered as one cluster (the same group) as are the Cd and Cu samples. With respect to prediction, the overall accuracy for the gene set Omega(1) using the nearest neighbors algorithm to predict 55 samples into one of the nine treatments is 85%. (C) 2004 Elsevier Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT 20, Jefferson, AR 72079 USA. Natl Yang Ming Univ, Inst Biopharmaceut Sci, Taipei 112, Taiwan. Acad Sinica, Inst Biomed Sci, Taipei 115, Taiwan. Natl Yang Ming Univ, Inst Biochem, Taipei 112, Taiwan. Acad Sinica, Inst Stat Sci, Taipei 115, Taiwan. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT 20, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov RI Lee, TC/B-3245-2011; OI Tsai, Chen-An/0000-0002-7490-4331 NR 24 TC 17 Z9 19 U1 0 U2 3 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD JAN PY 2005 VL 193 IS 1 BP 79 EP 100 DI 10.1016/j.mbs.2004.07.002 PG 22 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 899JT UT WOS:000227141400003 PM 15681277 ER PT B AU Mattamal, GJ AF Mattamal, George J. BE Helmus, M Medlin, D TI USFDA perspective on the regulations of cyanoacrylate polymer tissue adhesives in clinical applications SO Medical Device Materials II: Proceedings from the Materials & Processes for Medical Devices Conference 2004 LA English DT Proceedings Paper CT Materials and Processes for Medical Devices (MPMD) CY AUG 25-27, 2004 CL St Paul, MN SP ASM Int ID DEGRADATION AB A brief description of the uses and clinical applications of synthetic cyanoacrylate polymer adhesive/glues devices that have been cleared and/or approved by FDA over the last 15 years. This includes cyanoacrylate Class I devices (Exempt and not Exempt devices), Class II cyanoacrylate devices such as Dental Cements and Orthodontic Bracket Adhesives, and Class III (PMA) devices such as Dermabond (TM), Indermil (TM) Tissue Adhesive, and Trufill (R) n-Butyl Cyanoacrylate Embolic Agent. By citing an example of recently FDA approved Class III(PMA) devices in the Cyanoacrylate technology, the author provides a brief discussion of the FDA approval process of medical devices. It includes the FDA issues regarding the published guidance document for "Cyanoacrylate Topical Tissue Adhesives" that will provide guidance to regulatory personnel and manufacturers in the preparation of IDE applications and in the development of valid scientific evidence to support PMA applications for cyanocrylate tissue adhesives intended for topical approximation of skin and others. Also, the author provides a short regulatory description of US FDA; under what laws its operates, how FDA evaluates new devices for marketing, and how the device regulatory system works, for example, Class I, Class II, and Class III cyanoacrylate medical devices. C1 US FDA, Div Gen Restorat & Neurol Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Mattamal, GJ (reprint author), US FDA, Div Gen Restorat & Neurol Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 13 TC 0 Z9 0 U1 0 U2 3 PU ASM INTERNATIONAL PI MATERIALS PARK PA 9503 KINSMAN RD, MATERIALS PARK, OH 44073 USA BN 978-0-87170-824-3 PY 2005 BP 315 EP 321 PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA BFY36 UT WOS:000245431900056 ER PT S AU Samuelson, FW Wagner, RF AF Samuelson, FW Wagner, RF BE Eckstein, MP Jiang, Y TI Bootstrapped MRMC confidence intervals SO Medical Imaging 2005: Image Perception, Observer Performance, and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE receiver operating characteristic (ROC); MRMC; bootstrap; components of variance models ID OPERATING CHARACTERISTIC ANALYSIS; OF-VARIANCE MODELS; ROC ANALYSIS; MULTIREADER; COMPONENTS; VALIDATION; READERS AB The multiple-reader, multiple-case (MRMC) paradigm of Swets and Pickett (1982) for ROC analysis was expressed as a components of variance model by Dorfman, Berbaum, and Metz (1992) and validated by Roe and Metz (1997) for Type I error rates. Our group proposed an analysis of the MRMC components of variance model using bootstrap (Beiden, Wagner. and Cam bell, 2000) experiments instead of jackknife pseudo-values. These approaches have been challenged by some contemporary authors (e.g. Zhou, Obuchowski, and McClish, 2002). The purpose of the present paper is to formally compare the models and to carry out validation tests of their performance. We investigate different approaches to statistical inference, including several types of nonparametric bootstrap confidence intervals and report on validation and simulation experiments of Type I errors. C1 US FDA, CDRH, HRZ 140, Rockville, MD 20857 USA. RP Samuelson, FW (reprint author), US FDA, CDRH, HRZ 140, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 12 TC 2 Z9 2 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 0-8194-5723-X J9 P SOC PHOTO-OPT INS PY 2005 VL 5749 BP 15 EP 20 DI 10.1117/12.597660 PG 6 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BCF61 UT WOS:000229068500003 ER PT S AU Petrick, N Gallas, BD Samuelson, FW Wagner, RF Myers, KJ AF Petrick, N Gallas, BD Samuelson, FW Wagner, RF Myers, KJ BE Eckstein, MP Jiang, Y TI Influence of panel size and expert skill on truth panel performance when combining expert ratings SO Medical Imaging 2005: Image Perception, Observer Performance, and Technology Assessment SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE panel truth; expert panel; observer study; Monte Carlo simulations; ideal observer; computer-aided diagnosis; receiver-operating characteristic curve AB The focus of this manuscript is to investigate the statistical properties of expert panels used as a substitute for clinical truth through a simplistic Monte Carlo simulation model. We use Gaussian models to simulate both normal and abnormal distributions of ideal-observer test statistics. These distributions are designed to produce an ideal observer area under the ROC curve (AUC) of 0.85. Expert observers are modeled as an ideal observer test statistic degraded by a zero-mean Gaussian random variable. Different expert skill levels are achieved by changing the added variance. The experts' skill ranges between 0.6 and 0.8 in AUC. We combine decisions from 2-10 experts into a panel score by taking the median of all expert ratings as the panel test statistic. In experiment 1, truth panels made up of 2, 4, 8 and 10 experts who had the same skill level (AUC = 0.8) achieved mean AUCs of 0.82, 0.83, 0.84, and 0.84, respectively. For experiment 2, the experts' skill level was varied uniformly between 0.6 and 0.8 in AUC. Panel performance decreased in experiment 2 compared to the fixed skill level panels in experiment 1. However, panels composed of 8 and 10 experts still achieved an AUC greater than 0.80, the maximum of any individual expert. These simulation experiments, while idealized and simplistic, are a starting point for understanding the implications of using a panel of experts as surrogate truth in ROC studies when a gold standard is not available. C1 US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, Rockville, MD 20852 USA. RP Petrick, N (reprint author), US FDA, NIBIB, CDRH, Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 5 TC 2 Z9 2 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 0-8194-5723-X J9 P SOC PHOTO-OPT INS PY 2005 VL 5749 BP 49 EP 57 DI 10.1117/12.596286 PG 9 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BCF61 UT WOS:000229068500007 ER PT S AU Kyprianou, IS Ganguly, A Rudin, S Bednarek, DR Gallas, BD Myers, KJ AF Kyprianou, IS Ganguly, A Rudin, S Bednarek, DR Gallas, BD Myers, KJ BE Eckstein, MP Jiang, Y TI Efficiency of the human observer compared to an ideal observer based on a generalized NEQ which incorporates scatter and geometric unsharpness: Evaluation with a 2AFC experiment SO MEDICAL IMAGING 2005: IMAGE PERCEPTION, OBSERVER PERFORMANCE, AND TECHNOLOGY ASSESSMENT SE Proceedings of SPIE LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE MTF; NPS; NEQ; DQE; SNR; system; generalized; detectability; observer; angiography; microrangiography ID BASIC IMAGING PROPERTIES; MODULATION TRANSFER-FUNCTION; DIGITAL RADIOGRAPHY; MICRO-ANGIOGRAPHY; MAMMOGRAPHY; QUALITY; INFORMATION; PERFORMANCE; REDUCTION; CONTRAST AB Under certain assumptions the detectability of the ideal observer can be defined as the integral of the system Noise Equivalent Quanta multiplied by the squared object spatial frequency distribution. Using the detector Noise-EquivalentQuanta (NEQ(D)) for the calculation of detectability inadequately describes the performance of an x-ray imaging system because it does not take into account the effects of patient scatter and geometric unsharpness. As a result, the ideal detectability index is overestimated, and hence the efficiency of the human observer in detecting objects is underestimated. We define a Generalized-NEQ (GNEQ) for an x-ray system referenced at the object plane that incorporates the scatter fraction, the spatial distributions of scatter and focal spot, the detector MTFD, and the detector Normalized-Noise-Power-Spectrum (NNPSD). This GNEQ was used in the definition of the ideal detectability for the evaluation of the human observer efficiency during a two Alternative Forced Choice (2-AFC) experiment, and was compared with the case where only the NEQ(D) was used in the detectability calculations. The 2-AFC experiment involved the detection of images of polyethylene tubes (diameters between 100-300 mu m) filled with iodine contrast (concentrations between 0-120 Mg/cm(3)) placed onto a uniform head equivalent phantom placed near the surface of a microangiographic detector (43 mu m pixel size). The resulting efficiency of the human observer without regarding the effects of scatter and geometric unsharpness was 30%. When these effects were considered the efficiency was increased to 70%. The ideal observer with the GNEQ can be a simple optimization method of a complete imaging system. C1 US FDA, CDER, NIBIB, Lab Assessment Med Imaging Syst, Rockville, MD 20852 USA. RP US FDA, CDER, NIBIB, Lab Assessment Med Imaging Syst, 12720 Twinbrook Pkwy HFZ 140, Rockville, MD 20852 USA. EM iacovos.kyprianou@fda.hhs.gov FU NIBIB NIH HHS [R01 EB002873-03, R01 EB002873-01, R01 EB002873-02, R01 EB002873-04, R01 EB002873]; NINDS NIH HHS [R01 NS038746, R01 NS038746-02, R01 NS038746-01, R01 NS038746-03] NR 47 TC 6 Z9 6 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 0-8194-5723-X J9 PROC SPIE PY 2005 VL 5749 BP 251 EP 262 DI 10.1117/12.595870 PG 12 WC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging SC Imaging Science & Photographic Technology; Radiology, Nuclear Medicine & Medical Imaging GA BCF61 UT WOS:000229068500028 PM 21311735 ER PT S AU Badano, A Sempau, J Jennings, RJ AF Badano, A Sempau, J Jennings, RJ BE Flynn, MJ TI Statistics of the scintillation output using a combined x-ray/electron/optical Monte Carlo method SO Medical Imaging 2005: Physics of Medical Imaging, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE columnar phosphor; pulse-height distribution; swank factor; detective quantum efficiency; Monte Carlo simulation; cesium iodide AB Simulations of digital imaging systems based on scintillator screens usually employ a Poisson model for the phosphor conversion gain. However, the statistics of the scintillation output are determined by complex phenomena that involve many sources of variability including inhomogeneities in the crystalline and screen structure, variations in the deposited energy for each primary quantum available for excitation, variations in the relationship between radiate and non-radiative decay processes, energy dependencies in the conversion gain variance, and spread of secondary quanta. We use a combined x-ray/electron/optical Monte Carlo code to study the statistics of the scintillation output in columnar phosphors. The simulation code is the result of merging the x-ray transport code PENELOPE and the optical transport code DETECT-II. Using an improved geometric model for the columnar structure, we present results concerning pulse-height spectra of the scintillation output (and corresponding Swank factors) as a function of x-ray energy. This study improves our understanding of the underlying causes of conversion gain variations and should facilitate more accurate simulation efforts for the investigation and optimization of image acquisition systems based on scintillator screens. C1 US FDA, Ctr Devices & Radiol Hlth, NIBIB,Div Imaging & Appl Math, Lab Assessment Med Imaging Syst,Off Sci & Engn La, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, NIBIB,Div Imaging & Appl Math, Lab Assessment Med Imaging Syst,Off Sci & Engn La, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 NR 3 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5719-1 J9 P SOC PHOTO-OPT INS PY 2005 VL 5745 BP 361 EP 365 DI 10.1117/12.596724 PN 1-2 PG 5 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BCL61 UT WOS:000229929500039 ER PT S AU Badano, A Sempau, J Boswell, JS AF Badano, A Sempau, J Boswell, JS BE Flynn, MJ TI Combined x-ray/electron/optical Monte Carlo code based on PENELOPE and DETECT-II SO Medical Imaging 2005: Physics of Medical Imaging, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE phosphor blur; columnar phosphor; pulse-height distribution; Swank factor; Monte Carlo simulation; Cesium Iodide ID INTRAVASCULAR BRACHYTHERAPY; DOSIMETRY CHARACTERIZATION; COLUMNAR PHOSPHORS; SIMULATION; LEKSELL-GAMMA-KNIFE(R); EFFICIENCY; DEVICES; MODEL AB We describe MANTIS (Monte carlo x-rAy electroN opTical Imaging Simulation), a tool for simulating imaging systems that tracks x rays, electrons, and optical photons in the same geometric model. The x-ray and electron transport and involved physics models are from the PENELOPE package and include elastic and inelastic scattering, and bremsstrahlung from 100 eV to 1 GeV. The optical transport and corresponding physics models are from DETECT-II and include Fresnel refraction and reflection at material boundaries, bulk absorption and scattering. X rays are generated using the flexible source description from PENELOPE. When x rays or electrons interact and deposit energy in the scintillator, the code generates a number of optical quanta at that location, according to a model for the conversion process. The optical photons are then tracked until they reach an absorption event that in some cases contributes to the electronic signal. We demonstrate the capabilities of the new tool with respect to x-ray source, object to be imaged, and detector models. Of particular importance is the improved geometric description of structured phosphors that can handle tilted columns in needle-like phosphor screens. Examples of the simulation output with respect to signal blur and pulse-height distributions of the scintillation light are discussed and compared with previously published experimental results. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RI Sempau, Josep/J-7834-2013; OI Sempau, Josep/0000-0002-2754-7685; badano, aldo/0000-0003-3712-6670 NR 19 TC 0 Z9 0 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5719-1 J9 P SOC PHOTO-OPT INS PY 2005 VL 5745 BP 870 EP 876 DI 10.1117/12.596726 PN 1-2 PG 7 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BCL61 UT WOS:000229929500091 ER PT S AU Badano, A Gallas, BD Fifadara, DH AF Badano, A Gallas, BD Fifadara, DH BE Galloway, RL Cleary, KR TI Visual detection with non-Lambertian displays: model and human observer results SO Medical Imaging 2005: Visualization, Image-Guided Procedures, and Display, Pts 1 and 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 2005 Conference CY FEB 15-17, 2005 CL San Diego, CA SP SPIE DE viewing angle; liquid-crystal display; model observer; grayscale display function ID LIQUID-CRYSTAL DISPLAYS; CONTRAST AB Many investigators have now recognized that deviations from the on-axis grayscale presentation function in non-Lambertian displays affect the way images are presented to the human observer. However, the quantification of that effect in terms of detection performance has not yet been reported. In the past, we have described physical measurements of the off-axis changes in display luminance and contrast, and on the incorporation of such measurements into a simple mathematical transformation acting on image data that mimics the effect of off-axis viewing. In this paper, we report on the performance of model and human observers with respect to on- and off-axis viewing. The model observers used are the ideal linear observer with off-axis template knowledge and a human-like observer that incorporates quantization due to limited bit-depth and contrast sensitivity of the human visual system. Our results for diagonal viewing at 30 and 45 degrees from the display normal in a 5-million-pixel, monochrome, in-plane-switching, dual-domain AMLCD suggest severe degradation in detection performance. A human-like model which considers the contrast sensitivity of the visual system - not the ideal linear observer - can be used to approximately map off-axis grayscale changes into detectability maps for non-Lambertian displays. This investigation contributes to the setting of viewing angle requirements for medical imaging monitors based on robust observer performance data. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 5 TC 3 Z9 3 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 0-8194-5718-3 J9 P SOC PHOTO-OPT INS PY 2005 VL 5744 BP 271 EP 278 DI 10.1117/12.596721 PN 1-2 PG 8 WC Engineering, Biomedical; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BCH33 UT WOS:000229312400030 ER PT B AU Yin, JJ Yu, L Yurawecz, MP Roach, J Kramer, JKG AF Yin, JJ Yu, L Yurawecz, MP Roach, J Kramer, JKG BE Zhao, B Liu, G Packer, L TI Dual antioxidation and prooxidation characteristics of conjugated linoleic acids SO Natural Antioxidants and Micronutrients LA English DT Proceedings Paper CT 3rd International Symposium on Natural Antioxidants/2nd Meeting of the Society-for-Free-Radical-Research Asia (SFRR Asia) CY JUN 24-29, 2005 CL Shanghai, PEOPLES R CHINA SP Soc Free Rad Res ID RADICAL SCAVENGING PROPERTIES; LIPID-PEROXIDATION; MEMBRANES; OXYGEN AB CLA are natural food components and may have health beneficial effects. This study evaluated c9,t11-CLA, tl0,c12-CLA, and linoleic acid (LA) for their potential influence on the physicochemical properties of the phosphatidylcholine (PC) in liposome systems or ethanol solutions using four PC samples including soy PC, egg yolk PC (egg PC), rat heart PC and brain PC. The results showed that PC containing individual CLA isomers and LA differed in their capacities to react with and quench DPPH radicals in ethanol solution and in liposome, suggesting that both fatty acid composition and testing lipid system may alter the estimation of DPPH radical-lipid interactions. This study also demonstrated the effects of fatty acid composition on phase transition temperature of phospholipids bilayer systems. In addition, incorporation of LA and CLA isomers in the phospholipids exhibited significant influence on lipid peroxidation. Finally, the test lipid system, ethanol solution or liposome of PC, may alter the influence of fatty acid composition on lipid peroxidation in phospholipids. These results provide relevant information for better understanding of the physicochemical mechanism(s) involved in the biological actions of CLA, LA and other fatty acid. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD USA. NR 12 TC 0 Z9 0 U1 0 U2 1 PU MEDIMOND PUBLISHING CO PI BOLOGNA PA VIA RUBBIANI 6/2, 40124 BOLOGNA, ITALY BN 88-7587-184-1 PY 2005 BP 91 EP 99 PG 9 WC Biochemistry & Molecular Biology; Nutrition & Dietetics; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Nutrition & Dietetics; Pharmacology & Pharmacy GA BDJ49 UT WOS:000233810300014 ER PT S AU Ali, SF Imam, SZ Itzhak, Y AF Ali, SF Imam, SZ Itzhak, Y BE Slikker, W Andrews, RJ Trembly, B TI Role of peroxynitrite in methamphetamine-induced dopaminergic neurodegeneration and neuroprotection by antioxidants and selective NOS inhibitors SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE peroxynitrite; reactive oxygen species (ROS); reactive nitrogen species (RNS); methamphetamine (METH); 3-nitrotyrosine (3-NT); neuronal nitric oxide synthase (nNOS) C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33152 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. EM sali@nctr.fda.gov NR 0 TC 8 Z9 8 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 97 EP 98 DI 10.1196/annals.1344.053 PG 2 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800012 PM 16179512 ER PT S AU Przybyla-Zawislak, BD Thorn, BT Alia, SF Dennis, RA Amato, A Virmani, A Binienda, ZK AF Przybyla-Zawislak, BD Thorn, BT Alia, SF Dennis, RA Amato, A Virmani, A Binienda, ZK BE Slikker, W Andrews, RJ Trembly, B TI Identification of rat hippocampal mRNAs altered by the mitochondrial toxicant, 3-NPA SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE microarrays; RT-PCR; hippocampus; gene expression; Slco1c1; Slc17a7; glutamate vesicular transporter; 3-nitropropionic acid (3-NPA); rat ID CDNA MICROARRAY EXPERIMENTS; BLOOD-BRAIN-BARRIER; LONG-TERM-MEMORY; 3-NITROPROPIONIC ACID; ENERGY-METABOLISM; GLUTAMATE; EXPRESSION; TRANSPORTER; VULNERABILITY; NEUROGENESIS AB 3-Nitropropionic acid (3-NPA) is a model mitochondrial inhibitor that causes selective neurodegeneration in brain. 3-NPA-induced neurodegeneration occurs via a secondary neurotoxicity, caused initially by ATP depletion and redox changes in the cell. It is known that the hippocampal degeneration caused by mitochondrial dysfunction affects learning and memory, cognitive functions commonly disturbed in neurodegenerative diseases. The 3-NPA-treated animal model can be used to study molecular mechanisms underlying selective degeneration in the brain. In this study, a microarray approach was utilized to define changes in the expression of 530 genes in the rat hippocampus after acute exposure to 3-NPA at 30 mg/kg, sc. The microarray data were collected at 30 min, 2 h, and 4 h post-3-NPA. Statistical modeling using an ANOVA mixed model applied to Van der Waerden scores of rank-transformed intensity data was used to assign statistical significance to 44 transcripts. These transcripts represent genes associated with energy metabolism, calcium homeostasis, the cytoskeleton, neurotransmitter metabolism, and other cellular functions. Changes in the transcripts of genes encoding 2 transporters [blood-brain specific anion transporter (Slco1c1) and sodium-dependent inorganic phosphate cotransporter (Slc17a7)] were confirmed by real-time RT-PCR. In conclusion, this study identified 2 new potential targets for enhancement of neuroprotection or inhibition of neurodegeneration associated with ATP depletion in the hippocampus. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Geriatr, Little Rock, AR 72205 USA. Z Tech Inc, Jefferson, AR USA. Sigma Tau Res Inc, Gaithersburg, MD USA. Sigma Tau Hlth Sci SpA, Rome, Italy. RP Przybyla-Zawislak, BD (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. EM bzawislak@nctr.fda.gov NR 31 TC 8 Z9 8 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 162 EP 173 DI 10.1196/annals.1344.014 PG 12 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800019 PM 16179520 ER PT S AU Binienda, Z Przybyla-Zawislak, B Virmani, A Schmued, L AF Binienda, Z Przybyla-Zawislak, B Virmani, A Schmued, L BE Slikker, W Andrews, RJ Trembly, B TI L-carnitine and neuroprotection in the animal model of mitochrondrial dysfunction SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE 3-nitropropionic acid; carnitine; mitochondria; striatum; neuroprotection ID INHIBITOR 3-NITROPROPIONIC ACID; ACETYL-L-CARNITINE; SUCCINATE-DEHYDROGENASE; RAT-BRAIN; PERMEABILITY TRANSITION; FATTY-ACIDS; NEUROTOXICITY; VULNERABILITY; MITOCHONDRIA; DISEASES AB We have shown previously that pretreatment with L-carnitine (LC) prior to 3-nitropropionic acid (3-NPA) exposure, while not significantly attenuating succinate dehydrogenase (SDH) inhibition, prevented hypothermia and oxidative stress. The plant and fungal toxin, 3-NPA, acts as an inhibitor of mitochondrial function via irreversible inactivation of the mitochondrial inner membrane enzyme, SDH. Inhibition of SDH disturbs electron transport, leading to cellular energy deficits and oxidative stress-related neuronal injury. In the study presented here, a neurohistological method was applied to examine the mitochondriotropic effect of LC pretreatment against 3-NPA-induced neurotoxicity. Twenty adult male Sprague-Dawley rats randomly divided into two groups (n = 10/group) were injected twice with 3-NPA at 30 mg/kg sc, at 2 days apart, or received LC pretreatment at 100 mg/kg, at 30-40 min before 3-NPA 4 administration. Rats in both groups were perfused 7 days later and their brains harvested. Degenerating neurons were identified and localized via the fluorescent marker Fluoro-Jade B. Data analysis showed that LC was protective against 3-NPA-induced toxicity, as reflected by both reduced mortality and significantly reduced neuronal degeneration. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Sigma Tau Hlth Sci, Res & Dev, I-00040 Pomezia, Italy. RP Binienda, Z (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132, Jefferson, AR 72079 USA. EM zbinienda@nctr.fda.gov NR 29 TC 22 Z9 24 U1 0 U2 4 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 174 EP 182 DI 10.1196/annals.1344.015 PG 9 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800020 PM 16179521 ER PT S AU Virmani, A Gaetani, F Binienda, Z AF Virmani, A Gaetani, F Binienda, Z BE Slikker, W Andrews, RJ Trembly, B TI Effects of metabolic modifiers such as carnitines, coenzyme Q10, and PUFAs against different forms of neurotoxic insults: Metabolic inhibitors, MPTP, and methamphetamine SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA ID ACETYL-L-CARNITINE; PARKINSONS-DISEASE; MITOCHONDRIAL DYSFUNCTION; OXIDATIVE DAMAGE; BRAIN; Q(10); CELLS; MPP+; 1-METHYL-4-PHENYLPYRIDINIUM; DEGENERATION AB A number of strategies using the nutritional approach are emerging for the protection of the brain from damage caused by metabolic toxins, age, or disease. Neural dysfunction and metabolic imbalances underlie many diseases, and the inclusion of metabolic modifiers may provide an alternative and early intervention approach that may prevent further damage. Various models have been developed to study the impact of metabolism on brain function. These have also proven useful in expanding our understanding of neurodegeneration processes. For example, the metabolic compromise induced by inhibitors such as 3-nitropropionic acid (3-NPA), rotenone, and 1-methyl-4-phenylpyridinium (MPP+) can cause neurodegeneration in animal models and these models are thought to simulate the processes that may lead to diseases such as Huntington's and Parkinson's diseases. These inhibitors of metabolism are thought to selectively kill neurons by inhibiting various mitochondrial enzymes. However, the eventual cell death is attributed to oxidative stress damage of selectively vulnerable cells, especially highly differentiated neurons. Various studies indicate that the neurotoxicity resulting from these types of metabolic compromise is related to mitochondrial dysfunction and may be ameliorated by metabolic modifiers such as L-carnitine (L-C), creatine, and coenzyme Q10, as well as by antioxidants such as lipoic acid, vitamin E, and resveratrol. Mitochondrial function and cellular metabolism are also affected by the dietary intake of essential polyunsaturated fatty acids (PUFAs), which may regulate membrane composition and influence cellular processes, especially the inflammatory pathways. Cellular metabolic function may also be ameliorated by caloric restriction diets. L-C is a naturally occurring quaternary ammonium compound that is a vital cofactor for the mitochondrial entry and oxidation of fatty acids. Any factors affecting L-C levels may also affect ATP levels. This endogenous compound, L-C, together with its acetyl ester, acetyl-L-carnitine (ALC), also participates in the control of the mitochondrial acyl-CoA/CoA ratio, peroxisomal oxidation of fatty acids, and production of ketone bodies. A deficiency of carnitine is known to have major deleterious effects on the CNS. We have examined L-C and its acetylated derivative, ALC, as potential neuroprotective compounds using various known metabolic inhibitors, as well as against drugs of abuse such as methamphetamine. C1 Sigma Tau Hlth Sci, Res & Dev, I-00040 Pomezia, Italy. US FDA, Natl Ctr Toxicol Res, Neurophysiol Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Virmani, A (reprint author), Sigma Tau Hlth Sci, Res & Dev, Via Treviso 4, I-00040 Pomezia, Italy. EM ashraf.virmani@st-hs.it NR 41 TC 40 Z9 42 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 183 EP 191 DI 10.1196/annals.1344.016 PG 9 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800021 PM 16179522 ER PT S AU Slikker, W Xu, ZJ Wang, C AF Slikker, W Xu, ZJ Wang, C BE Slikker, W Andrews, RJ Trembly, B TI Systems biology/systems toxicology - Application to developmental neurotoxicology/neuroprotection SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE systems biology; systems toxicology; ketamine; phencyclidine; NMDA antagonists; neurotoxicity C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM wslikker@nctr.fda.gov; wslikker@nctr.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 309 EP 310 DI 10.1196/annals.1344.056 PG 2 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800032 PM 16179536 ER PT S AU Imam, SZ Duhart, HM Skinner, JT Ali, SF AF Imam, SZ Duhart, HM Skinner, JT Ali, SF BE Slikker, W Andrews, RJ Trembly, B TI Cocaine induces a differential dose-dependent alteration in the expression profile of immediate early genes, transcription factors, and caspases in PC12 cells: A possible mechanism of neurotoxic damage in cocaine addiction SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE cocaine; psychostimulants; dopamine; immediate early genes; apoptosis; transcription ID DOPAMINE NEURONS; BRAIN; TRANSPORTERS; METABOLISM; EXPOSURE; ABUSERS; USERS AB Cocaine is a widely used drug of abuse and psychostimulant that acts on the central nervous system by blocking the dopamine reuptake sites. PC12 cells, a rat pheochromocytoma clonal line, in the presence of nerve growth factor (NGF), multiply and differentiate into competent neurons that can synthesize, store, and secrete the neurotransmitter dopamine (DA). In the present study, we evaluated the effect of increasing doses of cocaine on the expression of immediate early genes (IEGs), c-fos and c-jun, and closely related transcription factors, SP-1 and NF-k beta, at 24 h after the exposure to cocaine (50, 100, 200, 500, 1000, 2500 mu M) in NGF-differentiated PC12 cells. Cocaine (50-500 mu M) resulted in significant induction of the expression of c-jos, c-jun, SP-1, and NF-k beta. However, higher concentrations of cocaine (1000 and 2500 mu M) resulted in the downregulation of these expressions after 24 h. To further understand the role of dose-dependent changes in the mechanisms of cell death, we evaluated the protein expression of apoptotic markers. A concentration-dependent increase in the expression of caspase-9 and -3 was observed up to 500 mu M cocaine. However, the higher dose did not show any expression. We also evaluated the effect of increasing doses of cocaine on DA concentration and the expression of dopamine transporter (DAT). A significant dose-dependent decrease in the concentration of DA as well as the expression of DAT was observed 24 h after the exposure of PC12 cells to cocaine. Therefore, in the present study, we reported that cocaine has both upstream and downstream regulatory actions on some IEGs and transcription factors that can regulate the mechanism of cell death, and these effects on gene expression are independent of its action on the dopaminergic system. C1 S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78229 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Imam, SZ (reprint author), S Texas Vet Hlth Care Syst, San Antonio, TX 78229 USA. EM simam@satx.rr.com; sali@nctr.fda.gov NR 23 TC 19 Z9 19 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 482 EP 490 DI 10.1196/annals.1344.042 PG 9 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800049 PM 16179556 ER PT S AU Slikker, W Young, JF Corley, RA Dorman, DC Conolly, RB Knudsen, TB Erstad, BL Luecke, RH Faustman, EM Timchalk, C Mattison, DR AF Slikker, W Young, JF Corley, RA Dorman, DC Conolly, RB Knudsen, TB Erstad, BL Luecke, RH Faustman, EM Timchalk, C Mattison, DR BE Slikker, W Andrews, RJ Trembly, B TI Improving predictive modeling in pediatric drug development: Pharmacokinetics, pharmacodynamics, and mechanistic modeling SO NEUROPROTECTIVE AGENTS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th International Conference on Neuroprotective Agents CY NOV 14-19, 2004 CL Pacific Grove, CA SP Cent Arkansas Chapter SIGMA XI, Natl Ctr Toxicol Res, FDA, US EPA DE PBPK; pharmacokinetics; pharmacodynamics; pediatrics; children; modeling ID EXPOSURE-DISEASE CONTINUUM; PROTOTYPE OCULAR TERATOGEN; HEALTH RISK ASSESSMENT; METABOLIZING-ENZYMES; MANGANESE DEPOSITION; HAZARDOUS SUBSTANCES; COMPUTATIONAL MODEL; BASAL GANGLIA; RAT; CHILDREN AB A workshop was conducted on November 18-19, 2004, to address the issue of improving predictive models for drug delivery to developing humans. Although considerable progress has been made for adult humans, large gaps remain for predicting pharmacokinetic/pharmacodynamic (PK/PD) outcome in children because most adult models have not been tested during development. The goals of the meeting included a description of when, during development, infants/children become adultlike in handling drugs. The issue of incorporating the most recent advances into the predictive models was also addressed: both the use of imaging approaches and genomic information were considered. Disease state, as exemplified by obesity, was addressed as a modifier of drug pharmacokinetics and pharmacodynamics during development. Issues addressed in this workshop should be considered in the development of new predictive and mechanistic models of drug kinetics and dynamics in the developing human. C1 US FDA, Natl Ctr Toxicol Res, Res Off, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Pacific NW Natl Lab, Ctr Biol Monitoring & Modeling, Richman, WA USA. CIIT, Ctr Hlth Res, Res Triangle Pk, NC USA. Univ Louisville, Birth Defects Ctr, Syst Anal Lab, Louisville, KY USA. Univ Arizona, Coll Pharm, Dept Pharm Practice & Sci, Tucson, AZ 85721 USA. Univ Missouri, Dept Chem Engn, Columbia, MO USA. Univ Washington, Inst Risk Analysis & Risk Commun, Seattle, WA 98195 USA. NICHHD, NIH, Bethesda, MD 20892 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Res Off, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM wslikker@nctr.fda.gov; wslikker@nctr.fda.gov RI Mattison, Donald/C-2015-2009; Mattison, Donald/L-4661-2013; OI Mattison, Donald/0000-0001-5623-0874; Faustman, Elaine/0000-0002-3085-6403 NR 58 TC 6 Z9 7 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-578-8 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1053 BP 505 EP 518 DI 10.1196/annals.1344.044 PG 14 WC Multidisciplinary Sciences; Clinical Neurology; Neurosciences; Pharmacology & Pharmacy SC Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BDR63 UT WOS:000235109800051 PM 16179559 ER PT J AU Perez-de la Cruz, V Gonzalez-Cortes, C Galvan-Arzate, S Medina-Campos, ON Perez-Severiano, F Ali, SF Pedraza-Chaverri, J Santamaria, A AF Perez-de la Cruz, V Gonzalez-Cortes, C Galvan-Arzate, S Medina-Campos, ON Perez-Severiano, F Ali, SF Pedraza-Chaverri, J Santamaria, A TI 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) SO NEUROSCIENCE LA English DT Article DE excitotoxic damage; peroxynitrite; oxidative/nitrosative stress; NMDA receptor; iron porphyrinate; neuroprotection ID ACID-INDUCED NEUROTOXICITY; INDUCED LIPID-PEROXIDATION; QUINOLINIC ACID; NITRIC-OXIDE; CORPUS STRIATUM; DOPAMINERGIC NEUROTOXICITY; DECOMPOSITION CATALYSTS; SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; IN-VIVO AB Oxidative/nitrosative stress is involved in NMDA receptor-mediated excitotoxic brain damage produced by the glutamate analog quinolinic acid. The purpose of this work was to study a possible role of peroxynitrite, a reactive oxygen/nitrogen species, in the course of excitotoxic events evoked by quinolinic acid in the brain. The effects of Fe(TPPS) (5,10,15,20-tetrakis (4-sulfonatophenyl)porphyrinate iron (III)), an iron porphyrinate and putative peroxynitrite decomposition catalyst, were tested on lipid peroxidation and mitochondrial function in brain synaptic vesicles exposed to quinolinic acid, as well as on peroxynitrite formation, nitric oxide synthase and superoxide dismutase activities, lipid peroxidation, caspase-3-like activation, DNA fragmentation, and GABA levels in striatal tissue from rats lesioned by quinolinic acid. Circling behavior was also evaluated. Increasing concentrations of Fe(TPPS) reduced lipid peroxidation and mitochondrial dysfunction induced by quinollnic acid (100 mu M) in synaptic vesicles in a concentration-dependent manner (10800 mu M). In addition, Fe(TPPS) (10 mg/kg, i.p.) administered 2 h before the striatal lesions, prevented the formation of peroxynitrite, the increased nitric oxide synthase activity, the decreased superoxide dismutase activity and the increased lipid peroxidation induced by quinolinic acid (240 nmol/mu l) 120 min after the toxin infusion. Enhanced caspase-3-like activity and DNA fragmentation were also reduced by the porphyrinate 24 h after the injection of the excitotoxin. Circling behavior from quinolinic acid-treated rats was abolished by Fe(TPPS) six days after quinolinic acid injection, while the striatal levels of GABA, measured one day later, were partially recovered. The protective effects that Fe(TPPS) exerted on quinolinic acid-induced lipid peroxidation and mitochondrial dysfunction in synaptic vesicles suggest a primary action of the porphyrinate as an antioxidant molecule. In vivo findings suggest that the early production of peroxynitrite, altogether with the enhanced risk of superoxide anion (O-2 (.) (-)) and nitric oxide formation (its precursors) induced by quinolinic acid in the striatum, are attenuated by Fe(TPPS) through a recovery in the basal activities of nitric oxide synthase and superoxide dismutase. The porphyrinate-mediated reduction in DNA fragmentation simultaneous to the decrease in caspase-3-like activation from quinolinic acid-lesioned rats suggests a prevention in the risk of peroxynitrite-mediated apoptotic events during the course of excitotoxic damage in the striatum. In summary, the protective effects that Fe(TPPS) exhibited both under in vitro and in vivo conditions support an active role of peroxynitrite and its precursors in the pattern of brain damage elicited by excitotoxic events in the experimental model of Huntington's disease. The neuroprotective mechanisms of Fe(TPPS) ate discussed. (c) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 Inst Nacl Neurol & Neurocirurg Manuel Velasco Sua, Lab Aminoacidos Excitadores, Mexico City 14269, DF, Mexico. Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City 04510, DF, Mexico. Inst Nacl Neurol & Neurocirurg Manuel Velasco Sua, Dept Neuroquim, Mexico City 14269, DF, Mexico. US FDA, Neurochem Lab, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Santamaria, A (reprint author), Insurgentes Sur 3877, Mexico City 14269, DF, Mexico. EM absada@yahoo.com NR 50 TC 49 Z9 50 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 135 IS 2 BP 463 EP 474 DI 10.1016/j.neuroscience.2005.06.027 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 970OM UT WOS:000232319500015 PM 16111817 ER PT J AU Shin, EJ Suh, SK Lim, YK Jhoo, WK Hjelle, OP Ottersen, OP Shin, CY Ko, KH Kim, WK Kim, DS Chun, W Ali, S Kim, HC AF Shin, EJ Suh, SK Lim, YK Jhoo, WK Hjelle, OP Ottersen, OP Shin, CY Ko, KH Kim, WK Kim, DS Chun, W Ali, S Kim, HC TI Ascorbate attenuates trimethyltin-induced oxidative burden and neuronal degeneration in the rat hippocampus by maintaining glutathione homeostasis SO NEUROSCIENCE LA English DT Article DE trimethyltin; ascorbate; oxidative burdens; glutathione homeostasis; hippocampus; neuronal degeneration ID KAINATE-INDUCED NEUROTOXICITY; SUPEROXIDE-DISMUTASE; LIPID-PEROXIDATION; RADICAL PRODUCTION; KAINIC ACID; BRAIN; DAMAGE; CELLS; NMDA; DEXTROMETHORPHAN AB The specific role of endogenous glutathione in response to neuronal degeneration induced by trimethyltin (TMT) in the hippocampus was examined in rats. A single injection of TMT (8 mg/kg, i.p.) produced a rapid increase in the formation of hydroxyl radical and in the levels of malondialdehyde (MDA) and protein carbonyl. TMT-induced seizure activity significantly increased after this initial oxidative stress, and remained elevated for up to 2 weeks post-TMT. Although a significant loss of hippocampal Cornus Ammonis CA1, CA3 and CA4 neurons was observed at 3 weeks post-TMT, the elevation in the level of hydroxyl radicals, MDA, and protein carbonyl had returned to near-control levels at that time. In contrast, the ratio of reduced to oxidized glutathione remained significantly decreased at 3 weeks post-TMT, and the glutathione-like immunoreactivity of the pyramidal neurons was decreased. However glutathione-positive glia-like cells proliferated mainly in the CA1, CA3, and CA4 sectors and were intensely immunoreactive. Double labeling demonstrated the co-localization of glutathione-immunoreactive glia-like cells and reactive astrocytes, as indicated by immunostaining for glial fibrillary acidic protein. This suggests that astroglial cells were mobilized to synthesize glutathione in response to the TMT insult. The TMT-induced changes in glutathione-like immunoreactivity appear to be concurrent with changes in the expression levels of glutathione peroxidase and glutathione reductase. Ascorbate treatment significantly attenuated TMT-induced seizures, as well as the initial oxidative stress, impaired glutathione homeostasis, and neuronal degeneration in a dose-dependent manner. These results suggest that ascorbate is an effective neuroprotectant against TMT. The initial oxidative burden induced by TMT may be a causal factor in the generation of seizures, prolonged disturbance of endogenous glutathione homeostasis, and consequent neuronal degeneration. (c) 2005 Published by Elsevier Ltd on behalf of IBRO. C1 Kangweon Natl Univ, Coll Pharm, Neurotoxicol Program, Chunchon 200701, South Korea. Korea Food & Drug Adm, Seoul 122074, South Korea. Univ Oslo, Inst Basic Med Sci, Dept Anat, Ctr Mol Biol & Neurosci, N-0317 Oslo, Norway. Seoul Natl Univ, Coll Pharm, Seoul 151742, South Korea. Ewha Womans Univ, Sch Med, Ewha Inst Neurosci, Seoul 110783, South Korea. Kangweon Natl Univ, Coll Pharm, Dept Pharmacol, Chunchon 200701, South Korea. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Kim, HC (reprint author), Kangweon Natl Univ, Coll Pharm, Neurotoxicol Program, Chunchon 200701, South Korea. EM kimhc@kangwon.ac.kr NR 59 TC 57 Z9 61 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 133 IS 3 BP 715 EP 727 DI 10.1016/j.neuroscience.2005.02.030 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 939HZ UT WOS:000230064600010 PM 15908128 ER PT J AU Wang, C Sadovova, N Fu, X Schmued, L Scallet, A Hanig, J Slikker, W AF Wang, C Sadovova, N Fu, X Schmued, L Scallet, A Hanig, J Slikker, W TI The role of the N-methyl-D-aspartate receptor in ketamine-induced apoptosis in rat forebrain culture SO NEUROSCIENCE LA English DT Article DE NMDA receptor; ketamine; antagonist; antisense oligonucleotide; neurodegeneration; apoptosis ID CORTICAL-NEURONS; UP-REGULATION; CHRONIC PHENCYCLIDINE; ADULT BRAIN; CELL-DEATH; NMDA; ETHANOL; GLUTAMATE; NEUROTOXICITY; NECROSIS AB Recent data suggest that anesthetic drugs may cause widespread and dose-dependent apoptotic neurodegeneration during development. The window of vulnerability to this neurotoxic effect, particularly with N-methyl-D-aspartate (NMDA) antagonists such as ketamine, is restricted to the period of synaptogenesis. The purposes of this study are to determine whether treatment of forebrain cultures with ketamine results in a dose-related increase in neurotoxicity and whether upregulation of NMDA receptor subunit NR1 promotes ketamine-induced apoptosis. Forebrain cultures were treated for 12 h with 0.1, 1, 10 and 20 μ M ketamine or co-incubated with NR1 antisense oligonucleotide (2 μ M). After washout of the ketamine, cultures were kept in serum-containing medium (in presence of glutamate) for 24 h. Application of ketamine (10 and 20 μ M) resulted in a substantial increase in DNA fragmentation as measured by cell death enzyme-linked immunosorbent assay, increased number of terminal dUTP nick-end labeling positive cells, and a reduction in mitochondrial metabolism of the dye 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide. No significant effect was seen in the release of lactate dehydrogenase, indicating that cell death presumably occurred via an apoptotic mechanism. Co-incubation of ketamine with NRII antisense significantly reduced ketamine-induced apoptosis. Western analysis showed that neurotoxic concentrations of ketamine increased Bax and NR1 protein levels. NR1 antisense prevented this increase caused by ketamine, suggesting that ketamine-induced cell death is associated with a compensatory upregulation of the NMDA receptor. These data suggest that NR1 antisense offers neuroprotection from apoptosis in vitro, and that upregulation of the NR1 following ketamine administration is, at least, partially responsible for the observed apoptosis. Published by Elsevier Ltd on behalf of IBRO. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Food & Drug Adm, Jefferson, AR 72079 USA. Chalk River Labs, Jefferson, AR USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Wang, C (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Food & Drug Adm, HFT-132, Jefferson, AR 72079 USA. EM cwang@nctr.fda.gov; wslikker@nctr.fda.gov NR 38 TC 97 Z9 107 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4522 J9 NEUROSCIENCE JI Neuroscience PY 2005 VL 132 IS 4 BP 967 EP 977 DI 10.1016/j.neuroscience.2005.01.053 PG 11 WC Neurosciences SC Neurosciences & Neurology GA 924NV UT WOS:000228986400009 PM 15857702 ER PT J AU James, SJ Slikker, W Melnyk, S New, E Pogribna, M Jernigan, S AF James, SJ Slikker, W Melnyk, S New, E Pogribna, M Jernigan, S TI Thimerosal neurotoxicity is associated with glutathione depletion: Protection with glutathione precursors SO NEUROTOXICOLOGY LA English DT Article DE thimerosal; neurotoxicity; glutathione; N-acetylcysteine ID NEURONAL GLUTATHIONE; RAT-BRAIN; ASTROCYTES; METABOLISM; APOPTOSIS; CYSTEINE; CELLS; METHYLMERCURY; CYSTINE AB Thimerosol is an antiseptic containing 49.5% ethyl mercury that has been used for years as a preservative in many infant vaccines and in flu vaccines. Environmental methyl mercury has been shown to be highly neurotoxic, especially to the developing brain. Because mercury has a high affinity for thiol (sulfhydryl (-SH)) groups, the thiol-containing antioxidant, glutathione (GSH), provides the major intracellular defense against mercury-induced neurotoxicity. Cultured neuroblastoma cells were found to have lower levels of GSH and increased sensitivity to thimerosol toxicity compared to glioblastoma cells that have higher basal levels of intracellular GSH. Thimerosal-induced cytotoxicity was associated with depletion of intracellular GSH in both cell lines. Pretreatment with 100 muM glutathione ethyl esteror Nacetylcysteine (NAC), but not methionine, resulted in a significant increase in intracellular GSH in both cell types. Further pretreatment of the cells with glutathione ethyl ester or NAC prevented cytotoxicity with exposure to 15 muM Thimerosal. Although Thimerosal has been recently removed from most children's vaccines, it is still present in flu vaccines given to pregnant women, the elderly, and to children in developing countries. The potential protective effect of GSH or NAC against mercury toxicity warrants further research as possible adjunct therapy to individuals still receiving Thimerosal-containing vaccinations. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72202 USA. Arkansas Childrens Hosp, Inst Res, Little Rock, AR 72202 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP James, SJ (reprint author), Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72202 USA. EM jamesjill@uams.edu NR 27 TC 103 Z9 108 U1 1 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD JAN PY 2005 VL 26 IS 1 BP 1 EP 8 DI 10.1016/j.neuro.2004.07.012 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 872ZU UT WOS:000225249000001 PM 15527868 ER PT J AU Tan, YX Shi, LM Tong, WD Wang, C AF Tan, YX Shi, LM Tong, WD Wang, C TI Multi-class cancer classification by total principal component regression (TPCR) using microarray gene expression data SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PARTIAL-LEAST-SQUARES; SUPPORT VECTOR MACHINES; TUMOR CLASSIFICATION; LINEAR-REGRESSION; CROSS-VALIDATION; CELL LINES; ERROR RATE; PREDICTION; DISCOVERY; PROFILES AB DNA microarray technology provides a promising approach to the diagnosis and prognosis of tumors on a genome-wide scale by monitoring the expression levels of thousands of genes simultaneously. One problem arising from the use of microarray data is the difficulty to analyze the high-dimensional gene expression data, typically with thousands of variables (genes) and much fewer observations (samples), in which severe collinearity is often observed. This makes it difficult to apply directly the classical statistical methods to investigate microarray data. In this paper, total principal component regression (TPCR) was proposed to classify human tumors by extracting the latent variable structure underlying microarray data from the augmented subspace of both independent variables and dependent variables. One of the salient features of our method is that it takes into account not only the latent variable structure but also the errors in the microarray gene expression profiles (independent variables). The prediction performance of TPCR was evaluated by both leave-one-out and leave-half-out cross-validation using four well-known microarray datasets. The stabilities and reliabilities of the classification models were further assessed by re-randomization and permutation studies. A fast kernel algorithm was applied to decrease the computation time dramatically. (MATLAB source code is available upon request.) C1 Univ Calif Los Angeles, Cedars Sinai Med Ctr, Dept Med, David Geffen Sch Med, Los Angeles, CA 90048 USA. US FDA, Natl Ctr Toxicol Res, Ctr Toxicoinformat, Div Syst Toxicol, Jefferson, AR 72079 USA. RP Wang, C (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctr, Dept Med, David Geffen Sch Med, Los Angeles, CA 90048 USA. EM charles.wang@cshs.org FU NCRR NIH HHS [M01 RR000425, M01-RR00425] NR 60 TC 40 Z9 42 U1 2 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 1 BP 56 EP 65 DI 10.1093/nar/gki144 PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 889XU UT WOS:000226477000005 PM 15640445 ER PT J AU Grajkowski, A Pedras-Vasconcelos, J Wang, VV Ausin, C Hess, S Verthelyi, D Beaucage, SL AF Grajkowski, A Pedras-Vasconcelos, J Wang, VV Ausin, C Hess, S Verthelyi, D Beaucage, SL TI Thermolytic CpG-containing DNA oligonucleotides as potential immunotherapeutic prodrugs SO NUCLEIC ACIDS RESEARCH LA English DT Article ID PHOSPHATE/THIOPHOSPHATE PROTECTING GROUP; PHASE OLIGODEOXYRIBONUCLEOTIDE SYNTHESIS; SULFUR-TRANSFER REAGENT; BACTERIAL-DNA; 3H-1,2-BENZODITHIOL-3-ONE 1,1-DIOXIDE; PROOLIGONUCLEOTIDE APPROACH; PHOSPHATE PROTECTION; TACARIBE VIRUS; PHOSPHOROTHIOATES; OLIGODEOXYNUCLEOTIDES AB A CpG-containing DNA oligonucleotide functionalized with the 2-(N-formyl-N-methyl)aminoethyl thiophosphate protecting group (CpG ODN fma1555) was prepared from phosphoramidites 1a-d using solid-phase techniques. The oligonucleotide behaved as a prodrug by virtue of its conversion to the well-studied immunomodulatory CpG ODN 1555 through thermolytic cleavage of the 2-(N-formyl-N-methyl)aminoethyl thiophosphate protecting group. Such a conversion occurred at 37 degrees C with a half-time of 73 h. The immunostimulatory properties of CpG ODN fma1555 were evaluated in two in vivo assays, one of which consisted of mice challenged in the ear with live Leishmania major metacyclic promastigotes. Local intradermal administration of CpG ODN fma1555 was as effective as that of CpG ODN 1555 in reducing the size of Leishmania lesions over time. In a different infectious model, CpG ODN 1555 prevented the death of Tacaribe-infected mice (43% survival) when administered between day 0 and 3 post infection. Administration of CpG ODN fma1555 three days before infection resulted in improved immunoprotection (60-70% survival). Moreover, co-administration of CpG ODN fma1555 and CpG ODN 1555 in this model increased the window for therapeutic treatment against Tacaribe virus infection, and thus supports the use of thermolytic oligonucleotides as prodrugs in the effective treatment of infectious diseases. C1 US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Immunol Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, Bethesda, MD 20892 USA. NIDDKD, Bioorgan Chem Lab, NIH, Bethesda, MD 20892 USA. RP Beaucage, SL (reprint author), US FDA, Chem Lab, Div Therapeut Prot, Ctr Drug Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM beaucage@cber.fda.gov NR 45 TC 22 Z9 23 U1 2 U2 8 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 11 BP 3550 EP 3560 DI 10.1093/nar/gki657 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 943ID UT WOS:000230345800017 PM 15972797 ER PT J AU Thompson, KL Rosenzweig, BA Pine, PS Retief, J Turpaz, Y Afshari, CA Hamadeh, HK Damore, MA Boedigheimer, M Blomme, E Ciurlionis, R Waring, JF Fuscoe, JC Paules, R Tucker, CJ Fare, T Coffey, EM He, Y Collins, PJ Jarnagin, K Fujimoto, S Ganter, B Kiser, G Kaysser-Kranich, T Sina, J Sistare, FD AF Thompson, KL Rosenzweig, BA Pine, PS Retief, J Turpaz, Y Afshari, CA Hamadeh, HK Damore, MA Boedigheimer, M Blomme, E Ciurlionis, R Waring, JF Fuscoe, JC Paules, R Tucker, CJ Fare, T Coffey, EM He, Y Collins, PJ Jarnagin, K Fujimoto, S Ganter, B Kiser, G Kaysser-Kranich, T Sina, J Sistare, FD TI Use of a mixed tissue RNA design for performance assessments on multiple microarray formats SO NUCLEIC ACIDS RESEARCH LA English DT Article ID GENE-EXPRESSION MEASUREMENTS; OLIGONUCLEOTIDE MICROARRAYS; ARRAYS; PLATFORMS; ACCURACY; DATABASE; NOISE AB The comparability and reliability of data generated using microarray technology would be enhanced by use of a common set of standards that allow accuracy, reproducibility and dynamic range assessments on multiple formats. We designed and tested a complex biological reagent for performance measurements on three commercial oligonucleotide array formats that differ in probe design and signal measurement methodology. The reagent is a set of two mixtures with different proportions of RNA for each of four rat tissues (brain, liver, kidney and testes). The design provides four known ratio measurements of > 200 reference probes, which were chosen for their tissue-selectivity, dynamic range coverage and alignment to the same exemplar transcript sequence across all three platforms. The data generated from testing three biological replicates of the reagent at eight laboratories on three array formats provides a benchmark set for both laboratory and data processing performance assessments. Close agreement with target ratios adjusted for sample complexity was achieved on all platforms and low variance was observed among platforms, replicates and sites. The mixed tissue design produces a reagent with known gene expression changes within a complex sample and can serve as a paradigm for performance standards for microarrays that target other species. C1 US FDA, Ctr Drug Evaluat & Res, Silver Spring, MD 20993 USA. Affymetrix Inc, Santa Clara, CA 95051 USA. Amgen Inc, Thousand Oaks, CA 91320 USA. Abbott Labs, Abbott Pk, IL 60064 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Inst Environm Hlth Sci, Natl Ctr Toxicogenom, Res Triangle Pk, NC 27709 USA. Rosetta Inpharmat LLC, Seattle, WA 98109 USA. Agilent Technol, Palo Alto, CA 94304 USA. Iconix Pharmaceut Inc, Mountain View, CA 94043 USA. GE Healthcare, Chandler, AZ 85248 USA. Merck & Co Inc, West Point, PA 19486 USA. RP Thompson, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, White Oak Life Sci Bldg 64,10903 New Hampshire Av, Silver Spring, MD 20993 USA. EM karol.thompson@fda.hhs.gov RI Kiser, Gretchen/A-3228-2013 NR 27 TC 20 Z9 22 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PY 2005 VL 33 IS 22 AR e187 DI 10.1093/nar/gni186 PG 12 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 000BP UT WOS:000234436200002 PM 16377776 ER PT J AU Aidoo, A Bishop, ME Shelton, SD Lyn-Cook, LE Chen, T Manjanatha, MG AF Aidoo, A Bishop, ME Shelton, SD Lyn-Cook, LE Chen, T Manjanatha, MG TI Effects of daidzein, genistein, and 17 beta-estradiol on 7,12-dimethylbenz[alpha]anthracene-induced mutagenicity and uterine dysplasia in ovariectomized rats SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID HORMONE REPLACEMENT THERAPY; BIG BLUE(R) RATS; ENDOGENOUS HPRT GENE; SPRAGUE-DAWLEY RATS; BREAST-CANCER RISK; POSTMENOPAUSAL WOMEN; ESTROGEN; SOY; PHYTOESTROGENS; CARCINOGENESIS AB Phytoestrogens, primarily isoflavones daidzein (DZ) and genistein (GE), are increasingly used by postmenopausal women as an alternative to hormone replacement therapy due to reports that estrogen therapy increases the risk of breast and endometrial cancers. These compounds, as estrogen receptor agonists, may influence chemical carcinogenesis in estrogen-responsive tissues such as the uterus. We utilized ovariectomized (OVX) rats to model menopause and assessed the effects of dietary DZ GE, or 17 beta-estradiol (E2) on carcinogen-induced mutagenesis and carcinogenesis in the rat uterus. Big Blue (R) transgenic rats (derived from Fischer 344 strain) were exposed to 7,12-dimethylbenz[a]anthracene (DMBA) in the presence or absence of the supplements. At 16- or 20-wk sacrifice, the uteri were removed and processed to determine mutant frequencies (MFs) and immunohistochemical or histopathological parameters, respectively. In rats treated with DMBA alone, a significant increase in lacI MFs (P < 0.01) in both OVX and intact (INT) rats was observed. The DMBA-induced MFs were not significantly altered by dietary DZ, GE, or E2 in both OVX and INT rats. Although dysplasia was not induced in the uterus of OVX and INT rats treated with DMBA alone, it was detected in 55% of OVX rats fed E2 alone and in 100% of OVX rats fed E2 along with DMBA exposure. Cell proliferation also was significantly higher in OVX rats fed E2 and treated with DMBA. In rats fed the isoflavones and treated with DMBA, the incidence of dysplasia was either reduced or virtually absent in both OVX and INT groups. These results indicate that a high incidence of dysplasia was associated with E2 feeding with or without DMBA treatment in the OVX rats, whereas the incidence was low in rats fed DZ or GE and treated with DMBA, suggesting a weak estrogen receptor agonist of DZ or GE in the rat uterus. The absence of dysplasia in OVX rats exposed to DMBA alone also suggests, in part, a promotional mechanism via estrogen- or isoflavone-driven cell proliferation. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Aidoo, A (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM aaidoo@nctr.fda.gov NR 47 TC 5 Z9 6 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 2005 VL 53 IS 1 BP 82 EP 90 DI 10.1207/s15327914nc5301_10 PG 9 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 001PG UT WOS:000234548200010 PM 16351510 ER PT J AU Woolery-Antill, M Carroll, E Wallen, G Jarosinski, P Corey, B Wieland, H Dagher, R AF Woolery-Antill, M Carroll, E Wallen, G Jarosinski, P Corey, B Wieland, H Dagher, R TI Assessing constipation in the pediatric oncology population: A pilot study. SO ONCOLOGY NURSING FORUM LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU ONCOLOGY NURSING SOCIETY PI PITTSBURGH PA 125 ENTERPRISE DR, PITTSBURGH, PA 15275 USA SN 0190-535X J9 ONCOL NURS FORUM JI Oncol. Nurs. Forum PD JAN PY 2005 VL 32 IS 1 BP 204 EP 204 PG 1 WC Oncology; Nursing SC Oncology; Nursing GA 889OW UT WOS:000226453300211 ER PT S AU Pfefer, TJ Sharma, D Agrawal, A Matchette, LS AF Pfefer, TJ Sharma, D Agrawal, A Matchette, LS BE Gannot, I TI Evaluation of a fiberoptic-based system for optical property measurement in highly attenuating turbid media SO Optical Fibers and Sensors for Medical Applications V SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Conference on Optical Fibers and Sensors for Medical Applications V CY JAN 22-23, 2005 CL San Jose, CA SP SPIE DE light-tissue interaction; optical properties; reflectance spectroscopy ID DIFFUSE-REFLECTANCE MEASUREMENTS; FLUORESCENCE SPECTROSCOPY; NONINVASIVE DETERMINATION; ABSORPTION-COEFFICIENTS; TISSUE; SCATTERING; PROBE; PHANTOMS; DESIGN; MODEL AB Fluorescence- and reflectance-based imaging techniques have a strong potential to improve clinical detection of pathologies such as cervical neoplasia. However, quantitative understanding of data collected by these approaches necessitates information on tissue optical properties in vivo. At present, there is minimal in vivo data on the optical properties of many tissues in the wavelength range that is most relevant - the ultraviolet A to visible. We report here on the development and evaluation of a second-generation diffuse reflectance system for measurement of tissue optical properties using a linear-array fiber optic probe with maximum separation distance of 2.5 mm. Improvements over the prior system include the implementation of an imaging spectrograph, a high sensitivity CCD camera and in-line neutral density filters to maximize dynamic range and signal to noise ratio. Absolute measurements of tissue reflectance were enabled through calibration of the reflectance system. Multivariate calibration models for optical property prediction were generated using a neural network algorithm and reflectance distributions calculated by a Monte Carlo model. Spatially-resolved reflectance data sets were measured in well-characterized tissue phantoms at 405 nm for absorption coefficients (mu(a)) from 1 to 25 cm(-1) and reduced scattering coefficients (mu(s)') from 5 to 25 cm(-1). These models were used to estimate the optical properties of tissue phantoms from reflectance measurements. By comparing predicted and known optical properties, the average percent error for mu(a) and mu(s)' was found to be +/- 3.2% and +/- 5.6%, respectively. These results indicate a level of accuracy that is more than twice that of our prior approach. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Pfefer, TJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 25 TC 3 Z9 3 U1 0 U2 2 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-5665-9 J9 P SOC PHOTO-OPT INS PY 2005 VL 5691 BP 163 EP 171 DI 10.1117/12.591101 PG 9 WC Engineering, Biomedical; Instruments & Instrumentation; Optics SC Engineering; Instruments & Instrumentation; Optics GA BCF23 UT WOS:000229016900019 ER PT J AU Dworkin, RH Turk, DC Farrar, JT Haythornthwaite, JA Jensen, MP Katz, NP Kerns, RD Stucki, G Allen, RR Bellamy, N Carr, DB Chandler, J Cowan, P Dionne, R Galer, BS Hertz, S Jadad, AR Kramer, LD Manning, DC Martin, S McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robbins, W Robinson, JP Rothman, M Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Wernicke, J Witter, J AF Dworkin, RH Turk, DC Farrar, JT Haythornthwaite, JA Jensen, MP Katz, NP Kerns, RD Stucki, G Allen, RR Bellamy, N Carr, DB Chandler, J Cowan, P Dionne, R Galer, BS Hertz, S Jadad, AR Kramer, LD Manning, DC Martin, S McCormick, CG McDermott, MP McGrath, P Quessy, S Rappaport, BA Robbins, W Robinson, JP Rothman, M Royal, MA Simon, L Stauffer, JW Stein, W Tollett, J Wernicke, J Witter, J TI Core outcome measures for chronic pain clinical trials: IMMPACT recommendations SO PAIN LA English DT Review ID QUALITY-OF-LIFE; LOW-BACK-PAIN; RANDOMIZED CONTROLLED-TRIAL; PLACEBO-CONTROLLED TRIAL; CONSORT STATEMENT; HEALTH-STATUS; POSTHERPETIC NEURALGIA; NEUROPATHIC PAIN; INSTRUMENTS; SCORES C1 Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. Univ Washington, Seattle, WA 98195 USA. Univ Penn, Philadelphia, PA 19104 USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. Harvard Univ, Boston, MA 02115 USA. Yale Univ, New Haven, CT USA. Univ Munich, D-80539 Munich, Germany. AstraZeneca, Wilmington, DE USA. Univ Queensland, Brisbane, Qld, Australia. Tufts Univ, Boston, MA 02111 USA. Merck & Co Inc, Blue Bell, PA USA. Amer Chron Pain Assoc, Rocklin, CA USA. Natl Inst Dent & Craniofacial Res, Bethesda, MD USA. Endo Pharmaceut Inc, Chadds Ford, PA USA. US FDA, Rockville, MD 20857 USA. Univ Toronto, Hlth Network, Toronto, ON, Canada. Purdue Pharma, Stamford, CT USA. Novartis Pharmaceut, E Hanover, NJ USA. Pfizer Global Res & Dev, Ann Arbor, MI USA. NINDS, Bethesda, MD 20892 USA. Univ Rochester, Rochester, NY 14627 USA. Dalhousie Univ, Halifax, NS B3H 3J5, Canada. GlaxoSmithKline Inc, Res Triangle Pk, NC USA. NeurogesX, San Carlos, CA USA. Johnson & Johnson Consumer Prod Inc, Raritan, NJ USA. Elan Pharmaceut, San Diego, CA USA. Abbott Labs, Lake Forest, IL USA. Univ Calif San Diego, San Diego, CA 92103 USA. US Dept Vet Affairs, Washington, DC USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. RP Dworkin, RH (reprint author), Univ Rochester, Sch Med & Dent, Dept Anesthesiol, Rochester, NY 14642 USA. EM robert_dworkin@urmc.rochester.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 NR 85 TC 1117 Z9 1134 U1 16 U2 80 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-3959 J9 PAIN JI Pain PD JAN PY 2005 VL 113 IS 1-2 BP 9 EP 19 DI 10.1016/j.pain.2004.09.012 PG 11 WC Anesthesiology; Clinical Neurology; Neurosciences SC Anesthesiology; Neurosciences & Neurology GA 891PG UT WOS:000226592400005 PM 15621359 ER PT J AU Taha, EI Samy, AM Kassem, AA Khan, MA AF Taha, EI Samy, AM Kassem, AA Khan, MA TI Response surface methodology for the development of self-nanoemulsified drug delivery system (SNEDDS) of all-trans-retinol acetate SO PHARMACEUTICAL DEVELOPMENT AND TECHNOLOGY LA English DT Article ID VITAMIN-A; BETA-CAROTENE; HUMAN PLASMA; EMULSIFICATION; FORMULATION; SIZE AB The purpose was to prepare, characterize, and optimize a self-nanoemulsified drug delivery system (SNEDDS) of a model lipophilic compound, all-trans-retinol acetate. As part of the optimization process, the main effects, interaction effects, and quadratic effects of the formulation ingredients were investigated. Method. A three-factor, three-level Box-Behnken design was used to explore the quadratic response surfaces and construct a second-order polynomial model in the form: Y = A+ A(1)X(1)+ A(2)X(2)+ A(3)X(3)+ A(4)X(1)X(2)+ A(5)X(2)X(3)+ A(6)X(1)X(3)+ A(7)X(1)(2)+ A(8)X(2)(2)+ A(9)X(3)(2)+ E. Amount of added oil (X1), surfactant (X2), and cosurfactant (X3) were selected as the factors. Particle size (Y1), turbidity (Y2), and cumulative amount of the active ingredient emulsified after 10 (Y3) and 30 (Y4) min were the observed variables. Response surface plots were used to demonstrate the effect of factors ( X1), ( X2), and ( X3) on the response ( Y4). Amount of added soybean oil ( X1), Cremophor EL (X2), and Capmul MCM-C8 (X3) showed a significant effect on the emulsification rates, as well as on the physical properties of the resultant emulsion ( particle size and turbidity). Observed and predicted values of Y4 obtained from the constructed equations were in close agreement. Response surface methodology was then used to predict the levels of factors X1, X2, and X3 under the constrained variables for an optimum response. Applied constraints were 0< Y1< 0.5, 1< Y2< 20, 60< Y3< 80, and 90< Y4< 100. The predicted values were 0.0704 mu m for particle size ( Y1), 18.95 NTU for turbidity ( Y2), 88.88% for drug release after 10 min (Y3), and 110.7% drug release after 30 min (Y4). Two new formulations were prepared according to the predicted levels. The observed and predicted values were in close agreement. C1 Texas Tech Univ, Hlth Sci Ctr, Sch Pharm, Dept Pharmaceut Sci, Amarillo, TX USA. Al Azhar Univ, Fac Pharm, Dept Pharmaceut Sci, Cairo, Egypt. RP Khan, MA (reprint author), US FDA, CDER, DPQR, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM Khanm@cder.fda.gov NR 15 TC 21 Z9 22 U1 2 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1083-7450 J9 PHARM DEV TECHNOL JI Pharm. Dev. Technol. PY 2005 VL 10 IS 3 BP 363 EP 370 DI 10.1081/PDT-200065675 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 965UY UT WOS:000231977100003 PM 16176016 ER PT J AU Arlett, P Moseley, J Seligman, PJ AF Arlett, Peter Moseley, Jane Seligman, Paul J. BE Strom, BL TI A View from Regulatory Agencies SO PHARMACOEPIDEMIOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID ADVERSE DRUG-REACTIONS; LOW-MAGNITUDE ASSOCIATIONS; PRACTICE RESEARCH DATABASE; GENERAL-PRACTICE; SIGNAL GENERATION; UNITED-KINGDOM; EPIDEMIOLOGIC RESEARCH; REPLACEMENT THERAPY; HEALTH SURVEILLANCE; ACTIVE SUBSTANCES C1 [Arlett, Peter] European Commiss, DG Enterprise & Ind, Pharmaceut Unit, Brussels, Belgium. [Moseley, Jane] Med & Healthcare Prod Regulatory Agcy, London, England. [Seligman, Paul J.] US FDA, Off Pharmacoepidemiol & Stat Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Arlett, P (reprint author), European Commiss, DG Enterprise & Ind, Pharmaceut Unit, Brussels, Belgium. EM peter.arlett@cec.eu.int; jane.moseley@mhra.gsi.gov.uk; seligmanp@cder.fda.gov NR 111 TC 1 Z9 1 U1 0 U2 1 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-05987-6 PY 2005 BP 103 EP 130 PG 28 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BYG80 UT WOS:000298629600009 ER PT J AU Bright, RA AF Bright, Roselie A. BE Strom, BL TI Pharmacoepidemiologic Studies of Devices SO PHARMACOEPIDEMIOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID PERMANENT CARDIAC-PACEMAKERS; SOFT CONTACT-LENSES; UNITED-STATES; ULCERATIVE KERATITIS; HOSPITAL PERSONNEL; PATIENTS RECORDS; BREAST IMPLANTS; ADVERSE EVENTS; MEDICAL DEVICE; LATEX ALLERGY C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Bright, RA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. EM rxb@cdrh.fda.gov NR 76 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-05987-6 PY 2005 BP 487 EP 500 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BYG80 UT WOS:000298629600032 ER PT J AU Graham, DJ Mosholder, AD Gelperin, K Avigan, MI AF Graham, David J. Mosholder, Andrew D. Gelperin, Kate Avigan, Mark I. BE Strom, BL TI Pharmacoepidemiology and Risk Management SO PHARMACOEPIDEMIOLOGY, 4TH EDITION LA English DT Article; Book Chapter ID CONTRAINDICATED DRUGS; UNITED-STATES; CISAPRIDE; CLOZAPINE; MORTALITY; PRODUCT; TRIAL; TROGLITAZONE; OMAPATRILAT; MEDICATIONS C1 [Graham, David J.; Mosholder, Andrew D.; Gelperin, Kate; Avigan, Mark I.] US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Silver Spring, MD 20993 USA. RP Graham, DJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, 10903 New Hampshire Ave, Silver Spring, MD 20993 USA. EM grahamd@cder.fda.gov; mosholdera@cder.fda.gov; GelperinK@cder.fda.gov; aviganm@cder.fda.gov NR 66 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-05987-6 PY 2005 BP 515 EP 530 PG 16 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA BYG80 UT WOS:000298629600034 ER PT J AU Cluxton, RJ Li, ZL Heaton, PC Weiss, SR Zuckerman, IH Moomaw, CJ Hsu, VD Rodriguez, EM AF Cluxton, RJ Li, ZL Heaton, PC Weiss, SR Zuckerman, IH Moomaw, CJ Hsu, VD Rodriguez, EM TI Impact of regulatory labeling for troglitazone and rosiglitazone on hepatic enzyme monitoring compliance: findings from the state of Ohio medicaid program SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE troglitazone; rosiglitazone; hepatotoxicity; regulatory actions; monitoring compliance ID CISAPRIDE; DRUGS AB Purpose Troglitazone, the first drug of the thiazolidinediones class for type II diabetes, was first marketed in March 1997 and was removed from the U.S. market 36 months later after 90 cases of liver failure were reported despite multiple warnings containing liver enzyme monitoring recommendations. Rosiglitazone has been available since June 1999 and is still on the market. The purpose of this study was to evaluate the impact of labeled hepatic enzyme monitoring for troglitazone and rosiglitazone. Methods Drug cohorts were assembled, using population-based fee-for-service Medicaid claims, for patients between 18 and 65 years of age who had received at least one troglitazone (n = 7226) or rosiglitazone (n = 1480) prescription between 1 April, 1997, and 21 March, 2000. The outcome of interest was the percentage of patients, based on their first treatment episode, who had baseline and post-baseline liver enzyme testing. Results Overall baseline testing was under 9% before regulatory actions, increased to 14% after the first two 'Dear Doctor' letters issued by the FDA in October and December 1997, and peaked to about 26% afterwards. Coincident with the marketing of rosiglitazone and the fourth 'Dear Doctor' letter issued in June 1999, baseline testing dropped to 18%. Baseline testing increased 2.5-fold (race-sex-age adjusted) after regulatory action. Achieving 50% post-baseline testing took approximately 6 months for both drugs. Conclusion Regulatory actions had only modest effects on the incidence of liver monitoring. More effective and timely communication strategies, health provider prescribing interventions and modification of health provider behaviors to enhance compliance with recommended risk management measures need to be identified, evaluated and implemented. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Univ Cincinnati, Coll Pharm, Cincinnati, OH 45267 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Maryland, Sch Pharm, Ctr Drugs & Publ Policy, Baltimore, MD 21201 USA. Univ Cincinnati, Med Ctr, Inst Hlth Policy & Hlth Serv Res, Cincinnati, OH 45267 USA. RP Heaton, PC (reprint author), Univ Cincinnati, Coll Pharm, 3225 Eden Ave, Cincinnati, OH 45267 USA. EM Pam.Heaton@uc.edu NR 16 TC 18 Z9 18 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 JAN PY 2005 VL 14 IS 1 BP 1 EP 9 DI 10.1002/pds.1048 PG 9 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 883SM UT WOS:000226036000001 PM 15546159 ER PT J AU Frueh, FW Goodsaid, F Rudman, A Huang, SM Lesko, LJ AF Frueh, FW Goodsaid, F Rudman, A Huang, SM Lesko, LJ TI The need for education in pharmacogenomics: a regulatory perspective SO PHARMACOGENOMICS JOURNAL LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20852 USA. RP Frueh, FW (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, 1451 Rockville Pike,HFD-860,Room 2040, Rockville, MD 20852 USA. NR 3 TC 21 Z9 26 U1 0 U2 2 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1470-269X J9 PHARMACOGENOMICS J JI Pharmacogenomics J. PY 2005 VL 5 IS 4 BP 218 EP 220 DI 10.1038/sj.tpj.6500316 PG 3 WC Genetics & Heredity; Pharmacology & Pharmacy SC Genetics & Heredity; Pharmacology & Pharmacy GA 958IY UT WOS:000231439100001 PM 16041391 ER PT J AU Fu, PKL Abuzakhm, S Turro, C AF Fu, PKL Abuzakhm, S Turro, C TI Photoinduced DNA cleavage and cellular damage in human dermal fibroblasts by 2,3-diaminophenazine SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID ORTHO-PHENYLENEDIAMINE; HYDROGEN-PEROXIDE; O-PHENYLENEDIAMINE; ETHIDIUM-BROMIDE; BINDING; INTERCALATION; DERIVATIVES; COMPLEXES; OXIDATION; PHENAZINE AB Aromatic amines, such as o-phenyleinediamine (OPD), have been used extensively in commercial hair dyes and in the synthesis of agricultural pesticides. Air oxidation of OPD results in the formation of 2,3-diaminophenazine (DAP). Although the mutagenic toxicity of DAP has been shown in both prokaryotic and eukaryotic systems, its phototoxicity remains largely unexplored. This study focuses on the pH-dependent photophysical properties of DAP and demonstrates its ability to photoinduce DNA damage to pUC19 plasmid in vitro. The photocytotoxicity of DAP toward human skin fibroblasts was also measured. DAP exhibits weak intercalative binding to double-stranded DNA with a binding constant K-b = 3.5 x 10(3) M-1. Furthermore, upon irradiation with visible light, DAP is able to nick plasmid DNA in the presence of oxygen. The concentration of DAP that resulted in 50% cell death was 172 +/- 9 muM in the dark and 13 +/- 1 muM after irradiation of the DAP-treated cell cultures with visible light (400-700 nm, 30 min, 5 J/cm(2)). The 13-fold increase in toxicity upon exposure to visible light shows the need for further study of the photocytotoxicity of contaminants such as DAP. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. RP Fu, PKL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM patty.fu@FDA.GOV; turro@chemistry.ohio-state.edu RI Turro, Claudia/H-5335-2015 OI Turro, Claudia/0000-0003-3202-5870 FU NIGMS NIH HHS [R01 GM64040-01] NR 60 TC 9 Z9 9 U1 2 U2 6 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JAN-FEB PY 2005 VL 81 IS 1 BP 89 EP 95 DI 10.1562/2004-07-20-RA-237.1 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 898WL UT WOS:000227106800013 PM 15493959 ER PT S AU Chen, FH Small, DA McDermott, MK Bentley, WE Payne, GF AF Chen, FH Small, DA McDermott, MK Bentley, WE Payne, GF BE Cheng, HN Gross, RA TI Biomimetic approach to biomaterials: Amino acid-residue-specific enzymes for protein grafting and cross-linking SO POLYMER BIOCATALYSIS AND BIOMATERIALS SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on Polymer Biocatalysis and Biomaterials held at the 2003 ACS National Meeting CY SEP, 2003 CL New York, NY SP Amer Chem Soc ID GEL-FORMATION; TRANSGLUTAMINASE; GELATIN; PROTEOGLYCANS; POLYMERS; CHITOSAN; TISSUES; NMR AB Nature creates a range of functional materials using proteins and polysaccharides as starting materials, and enzymes as assembly catalysts. Inspired by nature, we are examining how proteins and polysaccharides can be enzymatically assembled into conjugates and crosslinked networks. Specifically, we used tyrosinase to conjugate proteins to the polysaccharide chitosan, and a microbial transglutaminase to catalyze protein crosslinking. We review results from our studies and suggest how the unique properties of the resulting biomaterials can be exploited in medical applications. C1 Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, College Pk, MD 20742 USA. Univ Maryland, Dept Chem & Biochem Engn, Baltimore, MD 21250 USA. Univ Maryland, Dept Chem Engn, College Pk, MD 20742 USA. US FDA, Div Mech & Mat Sci, Off Sci & Technol, Rockville, MD 20850 USA. RP Payne, GF (reprint author), Univ Maryland, Inst Biotechnol, Ctr Biosyst Res, 5115 Plant Sci Bldg, College Pk, MD 20742 USA. EM payne@umbi.umd.edu NR 36 TC 1 Z9 1 U1 2 U2 9 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3917-7 J9 ACS SYM SER PY 2005 VL 900 BP 107 EP 118 PG 12 WC Chemistry, Multidisciplinary; Materials Science, Biomaterials; Polymer Science SC Chemistry; Materials Science; Polymer Science GA BCK35 UT WOS:000229731100008 ER PT J AU Khan, AA Nawaz, MS West, CS Khan, SA Lin, J AF Khan, AA Nawaz, MS West, CS Khan, SA Lin, J TI Isolation and molecular characterization of fluoroquinolone-resistant Escherichia coli from poultry litter SO POULTRY SCIENCE LA English DT Article DE fluoroquinolone resistance; multiple antibiotic resistance; gyr A gene; poultry litter; ribotyping ID URINARY-TRACT-INFECTIONS; QUINOLONE RESISTANCE; MUTATIONS; SUSCEPTIBILITY; CAMPYLOBACTER; CIPROFLOXACIN; MECHANISMS; CHICKENS; CANCER; HUMANS AB Nineteen fluoroquinolone-resistant Escherichia coli strains were isolated from poultry litter. Sixteen of the 19 strains were serotyped to groups 6, 8, 53, 56, 153, and 174. Three strains were not serotyped to any known group. All isolates were resistant to multiple antibiotics. Most strains were resistant to gentamicin, kanamycin, chloramphenicol, and streptomycin. Ribotyping of the multidrug-resistant isolates with restriction enzyme Pvull showed 5 different ribogroups, suggesting independent development of resistance instead of clonal spread. Quinolone resistance was associated with mutations of the quinolone resistance-determining region (QRDR) of the gyr A gene in all cases. To determine the incidence of gyr A mutations in fluoroquinolone-resistant E. coli isolates, a rapid PCR--based assay was used by amplifying a 164-bp region of the gyr A gene containing the mutation sites followed by digestion of the PCR product with restriction enzyme HinfI A higher level of resistance to ciprofloxacin [minimum inhibitory concentration (MIC) > 4 mu g] was associated with double mutations, but the mutants with a low level of resistance (MIC < 2 mu g) had only a single mutation. Those strains that were ciprofloxacin-resistant (MIC < 2 mu g) had a single mutation of a C-to-T transition at position 248 (Ser 83 -> Leu) or a G-to-A transition at position 259 (Asp 87 -> Asn). The ciprofloxacin-resistant (MIC > 4 mu g) isolates had mutations at both positions. Fluoroquinolone resistance was present among different serotypes and ribotypes, and drug resistance profiles suggest that the incidence of resistance does not indicate a clonal population in avian E. coli. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, PRL SW, Los Angeles, CA 90015 USA. RP Khan, AA (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM Ashraf@nctr.fda.gov NR 22 TC 12 Z9 12 U1 0 U2 0 PU POULTRY SCIENCE ASSOC INC PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874-9604 USA SN 0032-5791 J9 POULTRY SCI JI Poult. Sci. PD JAN PY 2005 VL 84 IS 1 BP 61 EP 66 PG 6 WC Agriculture, Dairy & Animal Science SC Agriculture GA 908UA UT WOS:000227814500009 PM 15685943 ER PT B AU Katzper, M AF Katzper, M BE Kuhl, ME Steiger, NM Armstrong, FB Joines, JA TI Clinical trial factors in a pain transition state model SO Proceedings of the 2005 Winter Simulation Conference, Vols 1-4 LA English DT Proceedings Paper CT 2005 Winter Simulation Conference (WSC 05) CY DEC 04-07, 2005 CL Orlando, FL SP Amer Stat Assoc, ACM SIGSIM, IEEE Comp Soc, IEEE SMC, Inst Ind Engineers, INFORMS SIM, NIST, Soc Modeling & Simulat Int ID ANALGESICS AB This paper presents a pain state transition model which accounts for constraints used in clinical trials. The pain transition state model is an approach for summarizing, presenting and modeling pain state transitions in a population. Data used are from the ibuprofen arm of a number of clinical trials measuring dental extraction pain. The data determine the state transition coefficients of the model. The pain process in the presence of an analgesic is thus fully characterized. C1 US FDA, CDER, Rockville, MD 20857 USA. RP Katzper, M (reprint author), US FDA, CDER, Rockville, MD 20857 USA. 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 BN 0-7803-9519-0 PY 2005 BP 2232 EP 2235 DI 10.1109/WSC.2005.1574511 PG 4 WC Computer Science, Interdisciplinary Applications; Computer Science, Software Engineering; Operations Research & Management Science SC Computer Science; Operations Research & Management Science GA BDY77 UT WOS:000236253403024 ER PT B AU Tollefson, L AF Tollefson, Linda BE Smith, RA TI Impact of antimicrobial use in animals and regulatory response SO Proceedings of the Thirty-Eighth Annual Conference of the American Association of Bovine Practitioners LA English DT Proceedings Paper CT 38th Annual Conference of the American-Association-of-Bovine-Practitioners CY SEP, 2003 CL Salt Lake City, UT SP Amer Assoc Bovine Practitioners ID DRUG-RESISTANT SALMONELLA; CAMPYLOBACTER-JEJUNI; UNITED-STATES; ANTIBIOTIC-RESISTANCE; MULTIDRUG-RESISTANT; FOOD ANIMALS; INFECTIONS; QUINOLONE; HUMANS; MECHANISMS AB There is accumulating evidence that the use of antimicrobials in food-producing animals has adverse human-health consequences. The use of these drugs in food animals selects for resistant pathogens and resistance genes that may be transferred to humans through the consumption or handling of foods of animal origin. Recent studies have demonstrated that antimicrobial resistance among foodborne bacteria may cause excess cases of illness, prolonged duration of illness, and increased rates of bacteremia, hospitalization and death. The US Food and Drug Administration (FDA) is committed to resolving the public health impact arising from the use of antimicrobial drugs in food-producing animals. The FDAs goal is to ensure that significant human antimicrobial therapies are not compromised or lost while providing for the safe use of antimicrobials in food animals. The FDA published a guidance document titled "Evaluating the Safety of Antimicrobial New Animal Drugs with Regard to their Microbiological Effects on Bacteria of Human Health Concern" that outlines a pathway drug sponsors can use to address concerns about antimicrobial resistance prior to approval of their drug.(30) The process uses a qualitative risk assessment approach to assess the potential of the intended use of a product to develop resistance in bacteria that may harm humans. The level of risk determines the level of risk management that is required for the drug to be approved. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Tollefson, L (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA. NR 36 TC 0 Z9 0 U1 0 U2 2 PU BOVINE PRACTITIONER PI STILLWATER PA 3404 LIVE OAK LANE, STILLWATER, OK 74075 USA PY 2005 BP 52 EP 56 PG 5 WC Agriculture, Dairy & Animal Science; Veterinary Sciences SC Agriculture; Veterinary Sciences GA BGJ67 UT WOS:000247655100012 ER PT J AU Wagner, RF AF Wagner, RF TI Lessons from my dinners with the giants of modern image science SO RADIATION PROTECTION DOSIMETRY LA English DT Article; Proceedings Paper CT 2nd Malmo Conference on Medical X-Ray Imaging CY APR 23-25, 2004 CL Malmo Univ Hosp, Malmo, SWEDEN SP European Commiss, Radiat Protect Res Programme HO Malmo Univ Hosp ID COMPUTER-ASSIST SYSTEMS; QUALITY; NOISE; MAMMOGRAMS; SNR AB The author traces some critical moments in the history of Image Science in the lost half century from first-hand or once-removed experience. The Image Science used in the field of medical imaging today had its origins in the analysis of photon detection developed for modern television, conventional photography, and the human visual system. Almost all "model observers" used in image assessment today converge to the model originally used by Albert Rose in his analysis of those classic photo-detectors. A more general statistical analysis of the various "deftets" of conventional and unconventional photon-imaging technologies was provided by Shaw. A number of investigators in medical imaging elaborated the work of these pioneers into a synthesis with the general theory of signal detectability and extended this work to the various forms of CT, energy-spectral-dependent imaging, and the further complication of anatomical-background-noise limited imaging. The author calls for further extensions of this work to the problem of under-sampled and thus artefact-limited imaging that will be important issues for high-speed CT and MRI. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Wagner, RF (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ 142, Rockville, MD 20850 USA. EM rfw@cdrh.fda.gov NR 38 TC 2 Z9 2 U1 0 U2 0 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. PY 2005 VL 114 IS 1-3 SI SI BP 4 EP 10 DI 10.1093/rpd/nch503 PG 7 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 937ME UT WOS:000229927400002 PM 15933075 ER PT S AU Chen, JJ Kodell, RL Chen, YJ AF Chen, James J. Kodell, Ralph L. Chen, Yi-Ju BE Edler, L Kitsos, CP TI Designs and Models for Mixtures: Assessing Cumulative Risk SO RECENT ADVANCES IN QUANTITATIVE METHODS IN CANCER AND HUMAN HEALTH RISK ASSESSMENT SE Wiley Series in Probability and Statistics LA English DT Article; Book Chapter C1 [Chen, James J.; Kodell, Ralph L.; Chen, Yi-Ju] US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. [Chen, Yi-Ju] Penn State Univ, University Pk, PA 16802 USA. RP Chen, JJ (reprint author), US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jchen@nctr.fda.gov; rkodell@nctr.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND SN 1940-6517 BN 978-0-47085-770-0 J9 WILEY SER PROBAB ST PY 2005 BP 299 EP 316 D2 10.1002/0470857706 PG 18 WC Oncology; Mathematical & Computational Biology; Public, Environmental & Occupational Health SC Oncology; Mathematical & Computational Biology; Public, Environmental & Occupational Health GA BZH99 UT WOS:000301664500025 ER PT B AU McNamara, SH AF McNamara, Stephen H. BE Hasler, CM TI Food and Drug Administration Regulation of Dietary Supplements SO REGULATION OF FUNCTIONAL FOODS AND NUTRACEUTICALS: A GLOBAL PERSPECTIVE LA English DT Article; Book Chapter C1 [McNamara, Stephen H.] US FDA, Rockville, MD 20857 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47027-767-6 PY 2005 BP 89 EP 100 DI 10.1002/9780470277676.ch6 D2 10.1002/9780470277676 PG 12 WC Food Science & Technology SC Food Science & Technology GA BAD23 UT WOS:000303838200007 ER PT J AU Walsh, EM Lietzan, EK Hutt, PB AF Walsh, Elizabeth Martell Lietzan, Erika King Hutt, Peter Barton BE Hasler, CM TI The Importance of the Court Decision in Pearson v. Shalala to the Marketing of Conventional Food and Dietary Supplements in the United States SO REGULATION OF FUNCTIONAL FOODS AND NUTRACEUTICALS: A GLOBAL PERSPECTIVE LA English DT Article; Book Chapter C1 [Lietzan, Erika King] Pharmaceut Res & Manufacturers Amer PhRMA, Washington, DC USA. [Hutt, Peter Barton] US FDA, Rockville, MD 20857 USA. [Hutt, Peter Barton] Harvard Univ, Sch Law, Cambridge, MA 02138 USA. [Hutt, Peter Barton] Stanford Law Sch, Stanford, CA USA. NR 49 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47027-767-6 PY 2005 BP 109 EP 135 DI 10.1002/9780470277676.ch8 D2 10.1002/9780470277676 PG 27 WC Food Science & Technology SC Food Science & Technology GA BAD23 UT WOS:000303838200009 ER PT J AU Kracov, DA Rubin, PD Dwyer, LM AF Kracov, Daniel A. Rubin, Paul D. Dwyer, Lisa M. BE Hasler, CM TI Dietary Supplements and Drug Constituents: The Pharmanex v. Shalala Case and Implications for the Pharmaceutical and Dietary Supplement Industries SO REGULATION OF FUNCTIONAL FOODS AND NUTRACEUTICALS: A GLOBAL PERSPECTIVE LA English DT Article; Book Chapter C1 [Dwyer, Lisa M.] Patton Boggs LLP, Food & Drug Law Practice Grp, Washington, DC USA. [Dwyer, Lisa M.] US FDA, Rockville, MD 20857 USA. NR 2 TC 3 Z9 3 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47027-767-6 PY 2005 BP 137 EP 148 DI 10.1002/9780470277676.ch9 D2 10.1002/9780470277676 PG 12 WC Food Science & Technology SC Food Science & Technology GA BAD23 UT WOS:000303838200010 ER PT B AU Mansour, M AF Mansour, Mark BE Hasler, CM TI Codex and Its Competitors: The Future of the Global Regulatory and Trading Regime for Food and Agricultural Products SO REGULATION OF FUNCTIONAL FOODS AND NUTRACEUTICALS: A GLOBAL PERSPECTIVE LA English DT Article; Book Chapter C1 US FDA, Rockville, MD 20857 USA. RP Mansour, M (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-47027-767-6 PY 2005 BP 377 EP 388 DI 10.1002/9780470277676.ch22 D2 10.1002/9780470277676 PG 12 WC Food Science & Technology SC Food Science & Technology GA BAD23 UT WOS:000303838200023 ER PT J AU Slikker, W Xu, ZJ Wang, C AF Slikker, W Xu, ZJ Wang, C TI Application of a systems biology approach to developmental neurotoxicology SO REPRODUCTIVE TOXICOLOGY LA English DT Review DE system biology; neurotoxicology; development; ketamine; NMDA receptor antagonist; apoptosis ID CELL-ADHESION MOLECULE; NF-KAPPA-B; APOPTOSIS-INDUCING FACTOR; D-ASPARTATE RECEPTORS; LONG-TERM POTENTIATION; DEVELOPING RAT-BRAIN; NMDA RECEPTOR; CORTICAL-NEURONS; NERVOUS-SYSTEM; VISUAL-CORTEX AB Systems biology can be applied to enhance the understanding of complex biological processes such as apoptosis in the developing brain. Systems biology, as applied to toxicology, provides a structure to arrange information in the form of a biological model. The approach allows for the subsequent and iterative perturbation of the initial model with the use of toxicants, and the comparison of the resulting data against the proposed biological model. It is postulated that the exposure of the developing rat to NMDA antagonists, e.g., ketamine or phencyclidine (PCP), causes a compensatory up-regulation of NMDA receptors, thereby making cells bearing these receptors more vulnerable to excitotoxic effects of endogenous glutamate. Although comprehensive gene expression/proteomic studies and mathematical modeling remain to be accomplished, a biological model has been established and perturbed in an iterative manner to allow confirmation of the biological pathway for NMDA antagonist-induced brain cell death in the developing rat. (C) 2004 Elsevier Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM wslikker@nctr.fda.gov NR 136 TC 24 Z9 29 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD JAN-FEB PY 2005 VL 19 IS 3 BP 305 EP 319 DI 10.1016/j.reprotox.2004.10.003 PG 15 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 900QS UT WOS:000227230000005 PM 15686866 ER PT J AU Belyakov, IM Kuznetsov, VA Kelsall, B Klinman, D Moniuszko, M Lemon, M Markham, PD Pal, R Clements, JD Lewis, MG Strober, W Franchini, G Berzofsky, JA AF Belyakov, Igor M. Kuznetsov, Vladimir A. Kelsall, Brian Klinman, Dennis Moniuszko, Marcin Lemon, Michael Markham, Phillip D. Pal, Ranajit Clements, John D. Lewis, Mark G. Strober, Warren Franchini, Genoveffa Berzofsky, Jay A. TI Can vaccine-induced mucosal high avidity CD8+CTL delay AIDS-viral dissemination from mucosa? SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Belyakov, Igor M.; Moniuszko, Marcin; Lemon, Michael; Franchini, Genoveffa; Berzofsky, Jay A.] NCI, Vaccine Branch, Bethesda, MD 20892 USA. [Kuznetsov, Vladimir A.] Genome Inst Singapore, Div Informat & Math Sci, Singapore 138672, Singapore. [Strober, Warren] NIAID, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. [Klinman, Dennis] US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. [Markham, Phillip D.; Pal, Ranajit] Adv BioSci Labs Inc, Kensington, MD 20895 USA. [Clements, John D.] Tulane Univ, Sch Med, Dept Microbiol & Immunol, New Orleans, LA 70112 USA. [Lewis, Mark G.] So Res Inst, Frederick, MD USA. EM berzofsk@helix.nih.gov NR 0 TC 0 Z9 0 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 PY 2005 VL 2 SU 1 AR S100 DI 10.1186/1742-4690-2-S1-S100 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600179 ER PT J AU Golding, H Needham, J Khurana, S AF Golding, Hana Needham, James Khurana, Surender TI HIV-1 infections during vaccine trials: Identifying new epitopes for differential diagnosis of HIV-1 infections in the face of vaccine-induced antibodies SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Golding, Hana; Needham, James; Khurana, Surender] US FDA, Ctr Biol Evaluat & Res, Div Viral Product, Bethesda, MD 20892 USA. EM goldingh@cber.FDA.gov NR 0 TC 0 Z9 0 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 PY 2005 VL 2 SU 1 AR S68 DI 10.1186/1742-4690-2-S1-S68 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600157 ER PT J AU Gupta, N Desmezieres, E Vassell, R He, Y Wingfield, P Weiss, CD AF Gupta, Nidhi Desmezieres, Emmanuel Vassell, Russell He, Yong Wingfield, Paul Weiss, Carol D. TI HIV escape from peptide fusion inhibitors SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Gupta, Nidhi; Desmezieres, Emmanuel; Vassell, Russell; He, Yong; Weiss, Carol D.] US FDA, CBER, Bethesda, MD 20892 USA. [Wingfield, Paul] NIAMS, NIH, Bethesda, MD 20892 USA. EM gupta@ncber.fda.gov NR 0 TC 0 Z9 0 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 PY 2005 VL 2 SU 1 AR P34 DI 10.1186/1742-4690-2-S1-P34 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600027 ER PT J AU Khurana, S Needham, J Golding, H AF Khurana, Surender Needham, James Golding, Hana TI HIV-1 infections during vaccine trials: Identifying new peptides for differential diagnosis of HIV-1 infections in the face of vaccine-generated antibodies SO RETROVIROLOGY LA English DT Meeting Abstract C1 [Khurana, Surender; Needham, James; Golding, Hana] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. EM khuranas@cber.FDA.gov NR 0 TC 0 Z9 0 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 PY 2005 VL 2 SU 1 AR P48 DI 10.1186/1742-4690-2-S1-P48 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600036 ER PT J AU Zaitseva, M Romantseva, T Manischewitz, J Wang, J Golding, H AF Zaitseva, Marina Romantseva, Tatiana Manischewitz, Jody Wang, Jiun Golding, Hana TI Increased CXCR4-dependent HIV-1 fusion in activated T cells: Role of CD4/CXCR4 association SO RETROVIROLOGY LA English DT Meeting Abstract C1 CBER, Div Viral Prod, Bethesda, MD 20892 USA. US FDA, CDER, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. EM zaitseva@cber.fda.gov NR 0 TC 0 Z9 0 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 PY 2005 VL 2 SU 1 AR P143 DI 10.1186/1742-4690-2-S1-P143 PG 1 WC Virology SC Virology GA V52KE UT WOS:000203541600100 ER PT J AU Valappil, T Kelaghan, J Macaluso, M Artz, L Austin, H Fleenor, ME Robey, L Hook, EW AF Valappil, T Kelaghan, J Macaluso, M Artz, L Austin, H Fleenor, ME Robey, L Hook, EW TI Female condom and male condom failure among women at high risk of sexually transmitted diseases SO SEXUALLY TRANSMITTED DISEASES LA English DT Article ID RANDOMIZED CONTROLLED-TRIAL; CONTROLLED CLINICAL-TRIAL; LATEX CONDOM; CONTRACEPTIVE EFFICACY; POLYURETHANE CONDOM; VAGINAL INTERCOURSE; HIV TRANSMISSION; HOMOSEXUAL MEN; UNITED-STATES; SEX WORKERS AB Objective: The objective of this study was to study the frequency and determinants of breakage and slippage during female and male condom use. Goal: The goal of this study was to determine condom breakage and slippage rate. Study: We conducted a 6-month prospective follow-up study of women attending 2 sexually transmitted disease clinics. Breakage and slippage rates were computed. Logistic regression was used to evaluate baseline characteristics and time-dependent behaviors. Results: A total of 869 women used condoms in 20,148 acts of intercourse. Breakage was less common for female condoms (0.1%; 95% confidence interval [CI], 0.05-0.21) than for male condoms (3.1%; 95% CI, 2.80-3.42). Slippage was more common for female condoms (5.6%; 95% CI, 5.10-6.13) than for male condoms (1.1%; 95% CI, 0.90-1.28). Rates significantly decreased with use and increased with number of previous failures. From first use to >15 uses, combined failure rate fell from 20% to 1.2% for female condoms (P <0.0001) and 9% to 2.3% for male condoms (P <0.01). Conclusions: Both condoms may provide good protection against sexually transmitted diseases. Experience determines success with either condom. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. Univ Alabama, Sch Publ Hlth, Dept Epidemiol, Birmingham, AL USA. NICHHD, Rockville, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Emory Univ, Atlanta, GA 30322 USA. Jefferson Cty Dept Hlth, Birmingham, AL USA. Madison Cty Hlth Dept, Huntsville, AL USA. RP Valappil, T (reprint author), US FDA, Ctr Drug Evaluat & Res, HFD-725,9201 Corp Blvd, Rockville, MD 20850 USA. EM valappilt@cder.fda.gov RI Macaluso, Maurizio/J-2076-2015 OI Macaluso, Maurizio/0000-0002-2977-9690 FU NICHD NIH HHS [N01-HD-1-3,135] NR 51 TC 39 Z9 39 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0148-5717 J9 SEX TRANSM DIS JI Sex. Transm. Dis. PD JAN PY 2005 VL 32 IS 1 BP 35 EP 43 DI 10.1097/01.olq.0000148295.60514.0b PG 9 WC Infectious Diseases SC Infectious Diseases GA 885XZ UT WOS:000226192000006 PM 15614119 ER PT J AU Lachenbruch, T AF Lachenbruch, T TI Memories of Stata SO STATA JOURNAL LA English DT Article C1 US FDA, Div Biostat, Rockville, MD 20857 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Univ Iowa, Iowa City, IA 52242 USA. Univ Calif Los Angeles, Los Angeles, CA 90024 USA. RP Lachenbruch, T (reprint author), US FDA, Div Biostat, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU STATA PRESS PI COLLEGE STATION PA 4905 LAKEWAY PARKWAY, COLLEGE STATION, TX 77845 USA SN 1536-867X J9 STATA J JI Stata J. PY 2005 VL 5 IS 1 BP 38 EP 38 PG 1 WC Social Sciences, Mathematical Methods; Statistics & Probability SC Mathematical Methods In Social Sciences; Mathematics GA 960RA UT WOS:000231609700006 ER PT S AU Freedberg, DI AF Freedberg, DI BE MireSluis, AR TI Using nuclear magnetic resonance spectroscopy to characterize biologicals SO State of the Art Analytical Methods for the Characterization of Biological Products and Assessment of Comparability SE DEVELOPMENTS IN BIOLOGICALS LA English DT Proceedings Paper CT Meeting on State of the Art Analytical Methods for the Characterization of Biological Products and Assessment of Comparability CY JUN 10-13, 2003 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth C1 Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Freedberg, DI (reprint author), Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 5 TC 7 Z9 7 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1424-6074 BN 3-8055-7998-5 J9 DEV BIOLOGICALS JI Dev. Biols PY 2005 VL 122 BP 77 EP 83 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Medicinal; Chemistry, Analytical; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy; Chemistry GA BDT78 UT WOS:000235276900005 PM 16375252 ER PT S AU Simek, SL AF Simek, SL BE MireSluis, AR TI Characterization of gene therapy products and the impact of manufacturing changes on product comparability SO State of the Art Analytical Methods for the Characterization of Biological Products and Assessment of Comparability SE DEVELOPMENTS IN BIOLOGICALS LA English DT Proceedings Paper CT Meeting on State of the Art Analytical Methods for the Characterization of Biological Products and Assessment of Comparability CY JUN 10-13, 2003 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth AB Gene therapy products represent a novel and complex class of products. Ensuring product safety, identity, purity and potency following a manufacturing change extends not only to assessing the final formulated product but also all the components used during product manufacturing. CBER has implemented a stepwise approach to product characterization and compliance with cGMPs, which increases as the study moves from phase 1 toward phase 3 and licensing. It is important that product characterization be performed early in product development because without full product characterization it will be difficult to determine the impact of the manufacturing process on the product as well as the impact any manufacturing change will have on the product. To demonstrate product comparability a thorough understanding of the manufacturing process, including product characterization, is necessary; so that the impact of a manufacturing change can be accurately assessed. C1 CBER FDA, Off Cellular Tissues & Gene Therapies, Div Cellular & Gene Therapies, Rockville, MD USA. RP Simek, SL (reprint author), CBER FDA, Off Cellular Tissues & Gene Therapies, Div Cellular & Gene Therapies, Rockville, MD USA. NR 3 TC 6 Z9 6 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1424-6074 BN 3-8055-7998-5 J9 DEV BIOLOGICALS JI Dev. Biols PY 2005 VL 122 BP 139 EP 144 PG 6 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Medicinal; Chemistry, Analytical; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy; Chemistry GA BDT78 UT WOS:000235276900011 PM 16375258 ER PT S AU Slater, JE AF Slater, JE BE MireSluis, AR TI Characterization of allergen extracts SO State of the Art Analytical Methods for the Characterization of Biological Products and Assessment of Comparability SE DEVELOPMENTS IN BIOLOGICALS LA English DT Proceedings Paper CT Meeting on State of the Art Analytical Methods for the Characterization of Biological Products and Assessment of Comparability CY JUN 10-13, 2003 CL Natl Inst Hlth, Bethesda, MD HO Natl Inst Hlth ID STANDARDIZATION; POTENCY AB Allergen vaccines are complex extracts of natural products, and are used for the diagnosis and treatment of allergic diseases. In the U.S., 19 allergen extracts have been standardized. For these vaccines, the potency is estimated by the skin test responses of highly allergic individuals, and surrogate in vitro tests are established for lot release and quality control. The surrogate tests differ for different extracts. National reference standards to which manufactured lots are compared are maintained at FDA/CBER. Allergen standardization has facilitated the establishment of data-driven release limits. C1 US FDA, CBER, Off Vaccines Regulat & Res, Div Bacterial Parasit & Allergen,Lab Immunobioche, Bethesda, MD 20014 USA. RP Slater, JE (reprint author), US FDA, CBER, Off Vaccines Regulat & Res, Div Bacterial Parasit & Allergen,Lab Immunobioche, Bethesda, MD 20014 USA. NR 18 TC 5 Z9 6 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 1424-6074 BN 3-8055-7998-5 J9 DEV BIOLOGICALS JI Dev. Biols PY 2005 VL 122 BP 145 EP 152 PG 8 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Chemistry, Medicinal; Chemistry, Analytical; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy; Chemistry GA BDT78 UT WOS:000235276900012 PM 16375259 ER PT J AU Anello, C O'Neill, RT Dubey, S AF Anello, C O'Neill, RT Dubey, S TI Multicentre trials: a US regulatory perspective SO STATISTICAL METHODS IN MEDICAL RESEARCH LA English DT Review AB Multicentre trials are very common in the field of drug development. In recent years, multicentre trials have taken on a multinational and multiregional aspect. We provide a conceptual framework for the use of multicentre trials in the context of drug development, from the perspective of drug regulation in the United States. In this paper, we review some regulatory history, milestones and standards as they relate to multicentre trials. Special attention is given to the similarities and differences in the approaches to multicentre trials in the following documents; Guideline for the Format and Content of the Clinical and Statistical Sections of New Drug Applications, International Conference on Harmonization, Draft Guideline on Statistical Principles for clinical trials and the Guidance for Industry Providing Clinical Evidence of Effectiveness for Human Drug and Biologic Products. The paper includes a consideration of some of the issues in the analysis of data from multicentre trials. C1 US FDA, Ctr Drug Evaluat & Res, Off Biostat, Off Pharmacoepidemiol & Stat Sci, Rockville, MD 20857 USA. RP Anello, C (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat, Off Pharmacoepidemiol & Stat Sci, Rockville, MD 20857 USA. EM charles.anello@fda.hhs.gov NR 25 TC 22 Z9 24 U1 0 U2 3 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0962-2802 J9 STAT METHODS MED RES JI Stat. Methods Med. Res. PY 2005 VL 14 IS 3 BP 303 EP 318 DI 10.1191/0962280205sm398oa PG 16 WC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Statistics & Probability SC Health Care Sciences & Services; Mathematical & Computational Biology; Medical Informatics; Mathematics GA 934XN UT WOS:000229743000006 PM 15969305 ER PT J AU Xu, Z Cawthon, D McCastlain, KA Slikker, W Ali, SF AF Xu, Z Cawthon, D McCastlain, KA Slikker, W Ali, SF TI Selective alterations of gene expression in mice induced by MPTP SO SYNAPSE LA English DT Article DE gene expression; MPTP; Parkinson's disease; dopamine ID VESICULAR MONOAMINE TRANSPORTER; ALPHA-SYNUCLEIN AGGREGATION; TYROSINE-HYDROXYLASE GENE; PARKINSONS-DISEASE; DOPAMINERGIC-NEURONS; DIFFERENTIAL EXPRESSION; SUBSTANTIA-NIGRA; KNOCKOUT MICE; NEUROTOXICITY; MODEL AB 1-methyl-4-phenyl-1,2,4,6,-tetrahydropyridine (MPTP) is a selective neurotoxin that produces striatal dopamine depletion resulting in parkinsonism like symptoms in humans and is, therefore, used to generate animal models for Parkinson's disease (PD). In this study, C57BL/6N mice were treated with MPTP acutely (3 x 20 mg/kg, 2-hour interval, one day injection). Mice were then sacrificed 24 hours after the last injection and brain tissue was collected for analysis. Significant decrease of striatal dopamine (DA) and the metabolites (DOPAC, HVA) was observed after MPTP treatment. MPTP also reduced protein expression of tyrosine hydroxylase (TH) in the striatum. Real time RT-PCR was used to examine selective genes of the dopaminergic system in the substantia nigra. Our data demonstrated that MPTP significantly decreased gene expression of TH, dopamine transporter (DAT), and vesicle monoamine transporter (VMAT), coinciding with the pattern of dopamine concentration changes and protein expression after MPTP treatment. Although a significant decrease of DA metabolites was observed in striatum, there was no change in the expression of monoamine oxidases (MAO-A, MAO-B) or catechol O-methyltransferase (COMT), indicating that these changes might be simply a consequence of reduced monoamine levels. In addition, gene expression of alpha-synuclein was also decreased with MPTP treatment, but there was no change in beta-synuclein and parkin. This is the first study using real-time PCR to indicate that MPTP selectively alters gene expression and provides information for clinical studies in PD. Future studies will focus on gene expression of other pathways that may be affected by MPTP treatment and investigation of gene expression in specific cell types in vivo using LCM technology. (C) 2004 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res Food & Drug Adm, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Ali, SF (reprint author), Natl Ctr Toxicol Res Food & Drug Adm, Neurochem Lab, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. EM Sali@nctr.fda.gov NR 42 TC 37 Z9 43 U1 0 U2 0 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD JAN PY 2005 VL 55 IS 1 BP 45 EP 51 DI 10.1002/syn.20089 PG 7 WC Neurosciences SC Neurosciences & Neurology GA 874IE UT WOS:000225343300005 PM 15499605 ER PT S AU Grajkowski, A Pedras-Vasconcelos, J Ausin, C Verthelyi, D Beaucage, SL AF Grajkowski, A Pedras-Vasconcelos, J Ausin, C Verthelyi, D Beaucage, SL BE ChoChung, YS Gerwirtz, AM Stein, CA TI Design and development of thermolytic DNA oligonucleotide prodrugs SO THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th NIH Symposium on Therapeutic Oligonucleotides CY DEC 13-14, 2004 CL NIH, Bethesda, MD HO NIH DE oligonucleotide prodrugs; thermolytic phosphate/thiophosphate deprotection; thermolabile thiophosphate protecting groups; CpG-oligonucleotides; 2-(N-formyl-N-methyl)aminoethyl group; Leishmania major infection; Tacaribe virus ID PHOSPHATE/THIOPHOSPHATE PROTECTING GROUP; PHASE OLIGODEOXYRIBONUCLEOTIDE SYNTHESIS; PROOLIGONUCLEOTIDE APPROACH; BACTERIAL-DNA; PHOSPHOROTHIOATES; CONGENERS; STABILITY; ANTISENSE AB Deoxyribonucleoside phosphoramidites functionalized with the thermolytic 2-(N-formyl-N-methyl)aminoethyl group for phosphorus protection (1a-d) have been prepared and employed in the solid-phase synthesis of CpG ODN fma1555. Given that this modified oligonucleotide can be converted to the immunomodulatory CpG ODN 1555 under neutral conditions at 37 degrees C, its biologic activity was demonstrated in vivo by studies showing that intraperitoneal administration of CpG ODN fma1555 in mice resulted in the activation of cytokine-secreting splenocytes. Furthermore, administration of CpG ODN fma1555 to mice that were challenged intradermally in the ear with live L. major metacyclic promastigotes, reduced the severity of Leishmania skin lesions over time to an extent similar to that obtained with CpG ODN 1555. In another infectious model experiment, CpG ODN fma1555 protected newborn mice from death (65% survival) when administered 3 days before infection with the aggressive Tacaribe (TCRV) virus. A comparable immunoprotection was obtained by treatment of TCRV-infected mice with CpG ODN 1555 administered on the same day of infection (45% survival). However, when TCRV-infected mice were treated with CpG ODN fma1555 on the day of infection, they died as a consequence of the relatively slow conversion of the oligonucleotide prodrug to the bioactive CpG ODN 1555. Co-administration of both CpG ODN 1555 and CpG ODN fma1555 to mice 3 days prior to TCRV infection or on the day of infection provided protection from death (45-65% survival) and thus widened the immunoprotection window against TCRV-infection. C1 US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Chem Lab, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Immunol Lab, Bethesda, MD 20892 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Therapeut Prot, Chem Lab, 8800 Rockville Pike, Bethesda, MD 20892 USA. EM beaucage@cder.fda.gov NR 30 TC 2 Z9 2 U1 2 U2 9 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-608-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1058 BP 26 EP 38 DI 10.1196/annals.1359.005 PG 13 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BEA63 UT WOS:000236466000003 PM 16394123 ER PT S AU Klinman, DM Gursel, I Klaschik, S Dong, L Currie, D Shirota, H AF Klinman, DM Gursel, I Klaschik, S Dong, L Currie, D Shirota, H BE ChoChung, YS Gerwirtz, AM Stein, CA TI Therapeutic potential of oligonucleotides expressing immunosuppressive TTAGGG motifs SO THERAPEUTIC OLIGONUCLEOTIDES: TRANSCRIPTIONAL AND TRANSLATIONAL STRATEGIES FOR SILENCING GENE EXPRESSION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT 7th NIH Symposium on Therapeutic Oligonucleotides CY DEC 13-14, 2004 CL NIH, Bethesda, MD HO NIH DE suppressive oligodeoxynucleotide; therapy; cytokine; inhibition; lupus; arthritis; toxic shock ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; 4TH INTERNATIONAL WORKSHOP; COLLAGEN-INDUCED ARTHRITIS; INDUCED IMMUNE ACTIVATION; BACTERIAL-DNA; SUPPRESSIVE OLIGODEOXYNUCLEOTIDES; REACTIVE ARTHRITIS; CUTTING EDGE; CPG MOTIFS; IN-VIVO AB Synthetic oligodeoxynucleotides (ODNs) expressing immunosuppressive TTAGGG motifs downregulate the production of proinflammatory and Th1 cytokines. The ability of these "suppressive ODNs" to slow or prevent the development of diseases characterized by over-exuberant immune stimulation was examined. Suppressive ODNs significantly reduced disease severity in murine models of arthritis, lupus, and LPS-induced toxic shock. These beneficial effects were accompanied by a significant reduction in serum autoantibody and cytokine levels. Underlying these protective effects was the ability of suppressive ODNs to bind to and prevent the phosphorylation of STAT1 and STAT4, thereby blocking the signaling cascade central to the initiation and/or perpetuation of these disease states. These findings suggest that suppressive ODNs might find use in the treatment of acute and chronic diseases characterized by excessive immune stimulation. C1 US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Res, Bldg 29A Rm 3D 10, Bethesda, MD 20892 USA. EM klinman@cber.fda.gov OI Gursel, Ihsan/0000-0003-3761-1166 NR 41 TC 20 Z9 23 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-608-3 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2005 VL 1058 BP 87 EP 95 DI 10.1196/annals.1359.015 PG 9 WC Biochemistry & Molecular Biology; Multidisciplinary Sciences SC Biochemistry & Molecular Biology; Science & Technology - Other Topics GA BEA63 UT WOS:000236466000008 PM 16394128 ER PT J AU Woo, JJY AF Woo, JJY TI FDA perspectives on supplement use by patients on antithrombotic therapy: Dietary supplement regulatory overview SO THROMBOSIS RESEARCH LA English DT Article; Proceedings Paper CT Conference on Dietary Supplements, Coagulation and Antithrombotic Therapies CY JAN 13-14, 2005 CL NIH, Bethesda, MD HO NIH C1 US FDA, Clin Evaluat Team Leader, Div Dietary Supplement Programs, Off Nutr Prod Labeling & Dietary Supplements, College Pk, MD 20740 USA. RP Woo, JJY (reprint author), US FDA, Clin Evaluat Team Leader, Div Dietary Supplement Programs, Off Nutr Prod Labeling & Dietary Supplements, Room 4D032,CPK1, College Pk, MD 20740 USA. EM jason.woo@cfsan.fda.gov NR 0 TC 1 Z9 1 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2005 VL 117 IS 1-2 SI SI BP 193 EP 196 DI 10.1016/j.thromres.2005.06.019 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 987AM UT WOS:000233490800028 PM 16253311 ER PT J AU Kim, MJ AF Kim, MJ TI FDA perspectives on supplement use by patients on antithrombotic therapy SO THROMBOSIS RESEARCH LA English DT Article; Proceedings Paper CT Conference on Dietary Supplements, Coagulation and Antithrombotic Therapies CY JAN 13-14, 2005 CL NIH, Bethesda, MD HO NIH C1 US FDA, CDER, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Kim, MJ (reprint author), US FDA, CDER, Off Clin Pharmacol & Biopharmaceut, 5600 Fishers Lane,HFD-870, Rockville, MD 20857 USA. EM KIMMYO@cder.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2005 VL 117 IS 1-2 SI SI BP 197 EP 200 DI 10.1016/j.thromres.2005.06.023 PG 4 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 987AM UT WOS:000233490800029 PM 16188297 ER PT J AU Wang, WL Merchlinsky, M Inman, J Golding, B AF Wang, WL Merchlinsky, M Inman, J Golding, B TI Identification of a novel immunodominant cytotoxic T lymphocyte epitope derived from human factor VIII in a murine model of hemophilia A SO THROMBOSIS RESEARCH LA English DT Article DE factor VIII; CTL epitope; hemophilia A; gene therapy; animal model ID COAGULATION-FACTOR-VIII; GENE-TRANSFER; IN-VIVO; IMMUNE-RESPONSES; FLOW-CYTOMETRY; CELL EPITOPE; EFFECTOR; VECTOR; MICE; RECOGNITION AB Gene therapy of hemophilia A could be complicated by the development of immune responses against the vector as well as the Factor VIII (FVIII) transgene. Previous efforts have been focused on identifying FVIII inhibitor antibody epitopes, whereas the cytotoxic T lymphocyte (CTL) epitopes have not been characterized. CTL would kill cells expressing such epitopes and thus limit the efficacy of gene therapy. To investigate CTL responses against human FVIII in a mouse model of hemophilia A, a computer algorithm program (BIMAS) was employed to predict CTL epitopes of human FVIII. The potential binding of these predicted peptides to MHC class I K-b was evaluated in a TAP-deficient cell line. When recombinant vaccinia virus expressing B domain-deleted human FVIII (vv-FVIII) was used to immunize E16 hemophilia A mice, a specific CTL response against FVIII152-159 was generated. In contrast, a CTL response to four other FVIII peptides was not detected. Therefore, FVIII152-159 represents a dominant CTL epitope. Identification of this epitope raises the possibility that CTL response to FVIII gene-transduced cells can be diminished by deliberatively mutating the dominant CTL epitope white retaining the biologic function of FVIII for hemophilia A gene therapy. Published by Elsevier Ltd. C1 US FDA, Lab Plasma Derivat, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Off Vaccine Res & Review, Ctr Biol Evaluat & Review, Bethesda, MD 20892 USA. NIAID, Bethesda, MD 20892 USA. RP Wang, WL (reprint author), US FDA, Lab Plasma Derivat, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. EM wangw@cber.fda.gov NR 41 TC 4 Z9 4 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0049-3848 J9 THROMB RES JI Thromb. Res. PY 2005 VL 116 IS 4 BP 335 EP 344 DI 10.1016/j.thromres.2004.12.011 PG 10 WC Hematology; Peripheral Vascular Disease SC Hematology; Cardiovascular System & Cardiology GA 955DQ UT WOS:000231205900010 PM 16038719 ER PT J AU Peters, TS AF Peters, TS TI Do preclinical testing strategies help predict human hepatotoxic potentials? SO TOXICOLOGIC PATHOLOGY LA English DT Article DE hepatotoxicity; drug development; preclinical testing ID IDIOSYNCRATIC DRUG TOXICITY; INDUCED LIVER DISORDERS; CLARITHROMYCIN; TUBERCULOSIS; FIALURIDINE; TOXICOLOGY; HEPATITIS; INFECTION; ANIMALS; FAILURE AB Overt hepatotoxicity due to drug administration is a real and present issue in drug development and regulatory circles. Preclinical drug development is intended to identify potential risks and target tissues prior to introduction of new molecular entities into the human population. The standard regimen is testing at various multiples of the intended human therapeutic dose in at least 2 species of animals, one rodent (rats of mice), one non-rodent (dogs, nonhuman primates, minipigs, and rabbits, as examples) for at least two weeks of repeated dosing. Experience has shown that this regimen "works" most of the tune. However, preclinical models are not infallible and are not always predictive. Whether the lack of predictivity is due to individual human genetic sensitivities, immunologically mediated phenomena, disease mediation or idiosyncratic reactions, the annual models are limited in detecting these characteristics and other low incidence phenomena. While it is uncommon for drug developers to continue development with products that elicit overt hepatic toxicity early in the annual testing, some products have made it through the approval process and then shown significant adverse effects. Some of the drugs (acetaminophen, isoniazid, trovafloxacin, troglitazone, bromfenac, clarithromycin, telithromycin) that have shown this propensity will be discussed in detail front early preclinical development to marketing and, in some instances, to limitations to usage or removal from the U.S. marketplace. C1 US FDA, CDER, Rockville, MD 20857 USA. RP Peters, TS (reprint author), US FDA, CDER, 9201 Corp Blvd, Rockville, MD 20850 USA. EM peterst@cder.fda.gov NR 42 TC 51 Z9 51 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 1 BP 146 EP 154 DI 10.1080/01926230590522121 PG 9 WC Pathology; Toxicology SC Pathology; Toxicology GA 897NQ UT WOS:000227012300018 PM 15805066 ER PT J AU Lee, WM Senior, JR AF Lee, WM Senior, JR TI Recognizing drug-induced liver injury: Current problems, possible solutions SO TOXICOLOGIC PATHOLOGY LA English DT Article DE causality attribution; diagnosis of exclusion; information required; true incidence; risk factors; prospective safety study; hepatotoxicity mechanisms ID CAUSALITY ASSESSMENT; UNITED-STATES; CONSENSUS MEETINGS; ADVERSE REACTIONS; FAILURE; HEPATOTOXICITY; EVENTS; SAFETY; RISK; SURVEILLANCE AB Currently there are three major problems in understanding drug-induced liver injury (DILI): (1) reliably establishing whether the liver disease was caused by the drug, or by another process: (2) determining the true incidence of and clinical risk factors for drug-induced hepatotoxicity; and (3) elaborating the mechanisms by which injury occurs to hepatocytes and other liver cells. We have focused here on the first two problems, as issues that may be amenable to actions in the near future, but the third may take substantially longer to work out. The first problem requires sufficient information for medical differential diagnosis. There are no pathognomonic indicators of DILI; even liver biopsy is not diagnostic. Making the correct attribution of causality requires analyzing the temporal relationship of drug exposure to illness and excluding all other possible causes. The second problem, determining incidence, cannot be done entirely adequately using Currently available methods, whether by clinical trials, by spontaneous adverse event reports, or by retrospective epidemiologic studies. There is need for prospective safety studies to establish the true incidence of DILI caused by a drug, to identify risk factors for it, and to collect biologic materials for analytic studies toward better understanding mechanisms of DILI. C1 US FDA, Off Pharmacoepidemiol & Stat Sci, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Texas, SW Med Ctr, Dept Internal Med, Dallas, TX 75390 USA. RP Senior, JR (reprint author), US FDA, Off Pharmacoepidemiol & Stat Sci, Ctr Drug Evaluat & Res, HFD-030,5600 Fishers Lane,Parklawn Bldg 15B-33B, Rockville, MD 20857 USA. EM semorj@cder.fda.gov NR 50 TC 99 Z9 109 U1 0 U2 5 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 1 BP 155 EP 164 DI 10.1080/01926230590522356 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 897NQ UT WOS:000227012300019 PM 15805067 ER PT J AU Muskhelishvili, L Wingard, SK Latendresse, JR AF Muskhelishvili, L Wingard, SK Latendresse, JR TI Proliferating cell nuclear antigen - A marker for ovarian follicle counts SO TOXICOLOGIC PATHOLOGY LA English DT Article DE PCNA; immunohistochemistry; ovarian follicles; counts ID DNA-REPAIR; INITIATION; EXPRESSION; TOXICITY; PROTEIN; GROWTH; CYCLE; KI-67; BRDU; PCNA AB Enumerating ovarian follicles is an effective way to estimate the extent of ovarian toxicity in female rodents exposed to xenobiotics. Differential follicle Counts are useful in safety assessment bioassays and in interspecies extrapolation of ovarian toxicity. Counting the follicles in H&E-stained sections is labor intensive. tedious, and costly. In the Present Study we demonstrated that in rat formalin-fixed, paraffin-embedded ovary sections follicles of all degrees of maturity can be visualized by the use of antibody directed against proliferating cell nuclear antigen (PCNA). Follicles are easily distinguished from ovarian background with the ability to detect and identify primordial follicles being enhanced. This translates into a significant decrease in variability of follicle counts, labor, and cost. Specifically, variability dropped from 11% to 0.2%, the counting time was reduced by 46%. and the cost by 48%. C1 Natl Ctr Toxicol Res, Toxicol Pathol Associates, Jefferson, AR 72079 USA. RP Muskhelishvili, L (reprint author), Natl Ctr Toxicol Res, Toxicol Pathol Associates, 3900 NCTR Rd,MC 923, Jefferson, AR 72079 USA. EM lmuskhelishvili@nctr.fda.gov RI Latendresse, John/A-9215-2009 NR 20 TC 39 Z9 41 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 3 BP 365 EP 368 DI 10.1080/01926230590930164 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 922KE UT WOS:000228836000008 PM 15805074 ER PT J AU Regan, KS Cline, JM Creasy, D Davis, B Foley, GL Lanning, L Latendresse, JR Makris, S Morton, D Rehm, S Stebbins, K AF Regan, KS Cline, JM Creasy, D Davis, B Foley, GL Lanning, L Latendresse, JR Makris, S Morton, D Rehm, S Stebbins, K CA STP Ovary Evaluation Working Grp TI STP position paper: Ovarian follicular counting in the assessment of rodent reproductive toxicity SO TOXICOLOGIC PATHOLOGY LA English DT Article ID OOCYTE DESTRUCTION; FOLLICLES; RATS; TUMORIGENESIS; MICE C1 Wake Forest Univ, Sch Med, Winston Salem, NC 27109 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. Otsuka Maryland Res Inst, Rockville, MD USA. NCTR, Jefferson, AR USA. US EPA, OPPTS, Washington, DC 20460 USA. Dow Chem Co USA, Midland, MI 48674 USA. RP Regan, KS (reprint author), Care of Klaunig J, Toxicol Pathol Editorial Off, 199 Grassmur Turn, Pine Hill, NJ 08021 USA. RI Latendresse, John/A-9215-2009 NR 30 TC 24 Z9 25 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0192-6233 J9 TOXICOL PATHOL JI Toxicol. Pathol. PY 2005 VL 33 IS 3 BP 409 EP 412 DI 10.1080/01926230490515355 PG 4 WC Pathology; Toxicology SC Pathology; Toxicology GA 922KE UT WOS:000228836000016 PM 15805082 ER PT J AU Holsapple, MP Burns-Naas, LA Hastings, KL Ladics, GS Lavin, AL Makris, SL Yang, Y Luster, MI AF Holsapple, MP Burns-Naas, LA Hastings, KL Ladics, GS Lavin, AL Makris, SL Yang, Y Luster, MI TI A proposed testing framework for developmental immunotoxicology (DIT) SO TOXICOLOGICAL SCIENCES LA English DT Editorial Material DE developmental immunotoxicology; DIT; immune system; developmental and reproductive toxicology; risk assessment; roundtable; study design; testing methods ID SPRAGUE-DAWLEY RATS; CRITICAL WINDOWS; RISK-ASSESSMENT; IMMUNE-SYSTEM; EXPOSURE; LEAD; WORKSHOP; SRBC AB A group of thirty immunotoxicology experts from the U.S. and E.U. representing government, industry, and academia met in May 2003, in Washington, D.C., to reach consensus regarding the most appropriate methods to assess developmental immunotoxicology (DIT) for hazard identification, including under what conditions such testing might be required. The following points represent the major conclusions from this roundtable discussion: (1) the rat is the preferred model; (2) any DIT protocol should be based on immune assays already validated; (3) DIT methods should be incorporated into standard developmental and reproductive toxicity protocols to the extent possible rather than a "stand-alone" protocol; (4) the approach to address DIT potential should be similar for chemicals and drugs, but the experimental design should be flexible and should reflect the specific questions to be answered; (5) it is possible to utilize a study design that assesses all critical windows in one protocol, with the results leading to further study of specific effects, as warranted; (6) animals should be exposed throughout the treatment protocol; (7) the triggers for DIT may include structure-activity-relationships, results from other toxicity studies, the intended use of a drug/chemical and/or its anticipated exposure of neonates and/or juveniles. C1 ILSI HESI, Washington, DC 20005 USA. Pfizer Global Res & Dev, San Diego, CA 92121 USA. US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Rockville, MD 20857 USA. DuPont Co Inc, Haskell Lab Toxicol & Ind Med, Newark, DE 19714 USA. ILSI Hlth Sci & Environm Sci Inst, Washington, DC 20005 USA. US EPA, Washington, DC 20460 USA. NIOSH, Ctr Dis Control, Morgantown, WV 26505 USA. RP Holsapple, MP (reprint author), ILSI HESI, 1 Thomas Circle,9th Floor, Washington, DC 20005 USA. EM mholsapple@ilsi.org NR 35 TC 45 Z9 46 U1 0 U2 3 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 2005 VL 83 IS 1 BP 18 EP 24 DI 10.1093/toxsci/kfh299 PG 7 WC Toxicology SC Toxicology GA 878WJ UT WOS:000225677700003 PM 15456913 ER PT J AU Choudhuri, S AF Choudhuri, S TI Gene regulation and molecular toxicology SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Review DE epigenetic mechanisms; expression; gene; post-transcriptional regulation; post-translational regulation; regulation; transcription; translation ID MESSENGER-RNA STABILITY; ORGANIC ANION TRANSPORTER; BULGED-OUT NUCLEOTIDES; ANTISENSE RNA; ESCHERICHIA-COLI; RAT-LIVER; TRANSCRIPTION FACTOR; TRYPANOSOMA-BRUCEI; IN-VITRO; ADENOSINE-TRIPHOSPHATASE AB The study of gene expression has become a cornerstone of molecular toxicology and toxicogenomics. Front a toxicological standpoint, constitutive expression levels of a gene could be just as important in determining the outcome of toxicity as the inducible expression. There are six distinct steps at which gene expression can be controlled; these are transcription, RNA processing, RNA transport, translation, mRNA degradation, and control of protein activity. While this overall paradigm of gene regulation is still valid, the complexity of genetic regulation begins mostly at the level of transcription and certain post-transcriptional events. A thorough understanding of the complexity and fluidity of gene and genome structure and their regulation is an integral part in the theory and practice of molecular toxicology and toxicogenomics. The present article is an attempt to briefly summarize our understanding of gene regulation beginning from the cistron concept. Relevance of molecular toxicology to gene regulatory mechanisms has been emphasized with examples wherever appropriate. C1 US FDA, DBGNR, Ctr Food Safety & Appl Nutr, OFAS, College Pk, MD 20740 USA. RP Choudhuri, S (reprint author), US FDA, DBGNR, Ctr Food Safety & Appl Nutr, OFAS, HFS-255,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. EM Supratim.Choudhuri@cfsan.fda.gov NR 164 TC 7 Z9 7 U1 2 U2 10 PU INFORMA HEALTHCARE PI LONDON PA TELEPHONE HOUSE, 69-77 PAUL STREET, LONDON EC2A 4LQ, ENGLAND SN 1537-6516 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD JAN-FEB PY 2005 VL 15 IS 1 BP 1 EP 23 DI 10.1080/15376520590890686 PG 23 WC Toxicology SC Toxicology GA 886TU UT WOS:000226256400001 ER PT J AU Brennan, MJ AF Brennan, MJ TI The tuberculosis vaccine challenge SO TUBERCULOSIS LA English DT Article DE mycobacterium tuberculosis; tuberculosis vaccines; BCG vaccine; vaccine trials ID BACILLE CALMETTE-GUERIN; MYCOBACTERIUM-TUBERCULOSIS; PROTECTIVE IMMUNITY; BCG VACCINATION; MICE; PROTEIN; IMMUNIZATION; AUXOTROPH; EFFICACY; DISEASE AB Although antibiotic treatments for tuberculosis are available, because of re-infection, drug resistance, AIDS, and economic reasons, it is unlikely that we will be able to control the global spread of tuberculosis without an effective vaccine. A number of new candidate vaccines for tuberculosis are under development and some are being evaluated for safety in normal human subjects in clinical trials. Additional vaccine candidates have been shown to be safe and effective when administered prior to infection in animal models. However, in areas of the world where tuberculosis is endemic, up to two thirds of the population are already infected with Mycobocterium tuberculosis, and it is unlikely that a new pre-exposure vaccine would have a substantial impact on disease for decades. In contrast, a vaccine that could be delivered to individuals already infected could reduce the disease burden. At this time, it is unclear whether the new TB vaccines can be safety and effectively used in populations already infected with M. tuberculosis, immunized with BCG vaccine or infected with HIV. This presents a major challenge to pre-clinical testing and clinical evaluation as well as eventual uptake of the new TB vaccines into areas of the world that are most at risk for tuberculosis. Published by Elsevier Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. RP Brennan, MJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bldg 29 Rm 503 HFM-431,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 38 TC 29 Z9 35 U1 2 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 1472-9792 J9 TUBERCULOSIS JI Tuberculosis PD JAN-MAR PY 2005 VL 85 IS 1-2 BP 7 EP 12 DI 10.1016/j.tube.2004.09.001 PG 6 WC Immunology; Microbiology; Respiratory System SC Immunology; Microbiology; Respiratory System GA 902AG UT WOS:000227322900002 PM 15687021 ER PT J AU Tabor, E AF Tabor, Edward BE Thomas, H Lemon, S Zuckerman, A TI The natural history of hepatitis C and hepatocellular carcinoma SO VIRAL HEPATITIS, 3RD EDITION LA English DT Article; Book Chapter ID B-VIRUS INFECTION; PRIMARY LIVER-CANCER; INTERFERON THERAPY; UNITED-STATES; ALCOHOLIC CIRRHOSIS; HCV INFECTION; VIRAL GENOMES; BLOOD-DONORS; JAPAN; PREVALENCE C1 US FDA, Off Blood Res & Review, Rockville, MD 20852 USA. RP Tabor, E (reprint author), US FDA, Off Blood Res & Review, 1401 Rockville Pike,HFM 300, Rockville, MD 20852 USA. NR 60 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE PUBL PI OXFORD PA OSNEY MEAD, OXFORD OX2 0EL, ENGLAND BN 978-0-470-98713-1 PY 2005 BP 520 EP 525 DI 10.1002/9780470987131.ch32 D2 10.1002/9780470987131 PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA BZS84 UT WOS:000302866100033 ER PT J AU Stark, CJ Atreya, CD AF Stark, Caren J. Atreya, C. D. TI Molecular advances in the cell biology of SARS-CoV and current disease prevention strategies SO VIROLOGY JOURNAL LA English DT Review AB In the aftermath of the SARS epidemic, there has been significant progress in understanding the molecular and cell biology of SARS-CoV. Some of the milestones are the availability of viral genome sequence, identification of the viral receptor, development of an infectious cDNA clone, and the identification of viral antigens that elicit neutralizing antibodies. However, there is still a large gap in our understanding of how SARS-CoV interacts with the host cell and the rapidly changing viral genome adds another variable to this equation. Now the SARS-CoV story has entered a new phase, a search for preventive strategies and a cure for the disease. This review highlights the progress made in identifying molecular aspects of SARS-CoV biology that is relevant in developing disease prevention strategies. Authors conclude that development of successful SARS-CoV vaccines and antivirals depends on the progress we make in these areas in the immediate future. C1 [Stark, Caren J.; Atreya, C. D.] US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. EM starkc@cber.fda.gov; atreya@cber.fda.gov FU National Vaccines Program Office (NVPO); Oak Ridge Institute for Science and Education (ORISE) FX We thank Stephen Feinstone and Ron Lundquist of CBER, FDA for their critiques and the National Vaccines Program Office (NVPO) for a grant to CDA. CJS is supported by a postdoctoral fellowship administered by the Oak Ridge Institute for Science and Education (ORISE). NR 68 TC 1 Z9 1 U1 0 U2 6 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. PY 2005 VL 2 AR 35 DI 10.1186/1743-422X-2-35 PG 8 WC Virology SC Virology GA V26AR UT WOS:000208519000035 PM 15833113 ER PT S AU Calam, D Wood, DJ Bristow, A Das, REG Padilla, A Unger, G Shin, J Heath, A Van Aken, WG Aralkawa, Y Barrowcliffe, T Bektimirov, T Leal, EC Ciesiolka, T Decker, R Egan, W Gairola, S Grossberg, SE Hancox, T Jivapaisampong, T Lelie, N Lower, J Madej, RM Marcovina, S Miede, P Min, H Phillips, P Schild, G Solkhey, J Spieser, JM Wielgosz, R Zhou, T Zoon, K AF Calam, D. Wood, D. J. Bristow, A. Das, R. E. Gaines Padilla, A. Unger, G. Shin, J. Heath, A. Van Aken, W. G. Aralkawa, Y. Barrowcliffe, T. Bektimirov, T. Leal, E. Chaves Ciesiolka, T. Decker, R. Egan, W. Gairola, S. Grossberg, S. E. Hancox, T. Jivapaisampong, T. Lelie, N. Lower, J. Madej, R. M. Marcovina, S. Miede, P. Min, H. Phillips, P. Schild, G. Solkhey, J. Spieser, J-M. Wielgosz, R. Zhou, Tiequn Zoon, K. CA WHO GP WHO TI WHO Expert Committe on Biological Standardization - Fifty-fifth report - Introduction SO WHO EXPERT COMMITTEE ON BIOLOGICAL STANDARDIZATION SE WHO Technical Report Series LA English DT Article ID ACCELERATED DEGRADATION TESTS; LIVE FLAVIVIRUS VACCINES; STABILITY; DESIGN C1 MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow, Russia. Mahidol Univ, Bangkok 10700, Thailand. Walter Reed Army Med Ctr, Walter Reed Army Inst Res, Washington, DC 20307 USA. OraVax Inc, Cambridge, MA 02139 USA. Pasteur Merieux Connaught, Lyon, France. Univ Texas, Med Branch, Galveston, TX 77550 USA. Ctr Dis Control & Prevent, Ft Collins, CO USA. Franklin Quest Co, Salt Lake City, UT USA. Minist Publ Hlth, Nonthaburi, Thailand. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. WHO, CH-1211 Geneva, Switzerland. RP Calam, D (reprint author), MP Chumakov Inst Poliomyelitis & Viral Encephalit, Moscow, Russia. NR 51 TC 0 Z9 0 U1 3 U2 6 PU WORLD HEALTH ORGANIZATION PI GENEVA PA DISTRIBUTION & SALES SERVICE, 1211 27 GENEVA, SWITZERLAND SN 0512-3054 BN 978-92-4-120932-8 J9 WHO TECH REP SER JI WHO Tech. Rep. Ser. PY 2005 VL 932 BP 1 EP 137 PG 137 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BFR39 UT WOS:000243994400001 ER PT J AU Bowyer, JF Delongchamp, RR Jakab, RL AF Bowyer, JF Delongchamp, RR Jakab, RL TI Glutamate N-methyl-D-aspartate and dopamine receptors have contrasting effects on the limbic versus the somatosensory cortex with respect to amphetamine-induced neurodegeneration SO BRAIN RESEARCH LA English DT Article DE amphetamine; neurotoxicity; somatosensory cortex; piriform cortex; limbic cortex; cortical amygdaloid nucleus; NMDA receptor; dopamine receptor ID CORTICOTROPIN-RELEASING-FACTOR; QUANTITATIVE AUTORADIOGRAPHIC LOCALIZATION; EXCITATORY AMINO-ACIDS; NEURONAL DEGENERATION; METHAMPHETAMINE NEUROTOXICITY; BODY-TEMPERATURE; RAT-BRAIN; DRUG-ADDICTION; HYPERTHERMIA; ANTAGONIST AB The roles that glutamate N-methyl-D-aspartate (NMDA) and dopamine D1-like and D2-like receptors play in the cortical neurotoxicity occurring in rats exposed to multiple doses of amphetamine (AMPH) for 2 days was evaluated. Neurodegeneration in rats that did not become hyperthermic during AMPH exposure was quantified by counting isolectin B4-labeled phagocytic microglia and Fluoro-Jade (F-J)labeled neurons in the somatosensory parietal cortex, piriform cortex and posterolateral cortical amygdaloid nucleus (PLCo). The NMDA receptor antagonist, dizocilpine (0.63 mg/kg day) blocked AMPH-incluced neurodegeneration in the somatosensory cortex. However, it did not affect degeneration in the piriform cortex and PLCo indicating that limbic degeneration was not NMDA-mediated. The dopamine antagonists, eticlopride (D2/3, 0.25 mg/kg day) and SCH-23390 (D1, 0.25 mg/kg day), blocked the stereotypic behavior and neurodegeneration in the somatosensory cortex. However, eticlopride had a lesser protective effect in the limbic regions. As well, the dopamine D2/D3 agonist quinpirole (1.5 mg/kg day) protected against cortical neurodegeneration when it was given during AMPH exposure and continued until sacrifice. The dopamine D1 agonist (SKF-38393, 12.5 mg/kg day) had no significant effect on neurodegeneration. These data indicate that there are significant differences in NMDA and dopamine D2 modulation of AMPH-induced neurodegeneration in the somatosensory cortex compared to the limbic cortices, and limbic cortical degeneration is not necessarily dependent on excessive stimulation of NMDA receptors as it is in the somatosensory cortex. Although excessive dopamine receptor stimulation during amphetamine exposure may trigger the neurodegenerative processes, continued D2 stimulation after AMPH exposure is neuroprotective in the cortex. Published by Elsevier B.V. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. EM jbowyer@nctr.fda.gov NR 66 TC 11 Z9 12 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD DEC 31 PY 2004 VL 1030 IS 2 BP 234 EP 246 DI 10.1016/j.brainres.2004.10.013 PG 13 WC Neurosciences SC Neurosciences & Neurology GA 880FW UT WOS:000225775400007 PM 15571672 ER PT J AU Villalba, L Witter, J AF Villalba, L Witter, J TI Rofecoxib, Merck, and the FDA SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20850 USA. RP Villalba, L (reprint author), US FDA, Rockville, MD 20850 USA. NR 1 TC 0 Z9 0 U1 1 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD DEC 30 PY 2004 VL 351 IS 27 BP 2876 EP 2877 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 883IH UT WOS:000226004300019 ER PT J AU Ratnasinghe, LD Abnet, C Qiao, YL Modali, R Stolzenberg-Solomon, R Dong, ZW Dawsey, SM Mark, SD Taylor, PR AF Ratnasinghe, LD Abnet, C Qiao, YL Modali, R Stolzenberg-Solomon, R Dong, ZW Dawsey, SM Mark, SD Taylor, PR TI Polymorphisms of XRCC1 and risk of esophageal and gastric cardia cancer SO CANCER LETTERS LA English DT Article DE esophageal cancer; gastric cardia cancer; polymorphism; XRCC1 ID NUTRITION INTERVENTION TRIALS; DISEASE-SPECIFIC MORTALITY; SQUAMOUS-CELL CARCINOMA; DNA-REPAIR PROFICIENCY; BREAST-CANCER; CASE-COHORT; GENE XRCC1; MINERAL SUPPLEMENTATION; CHINESE POPULATION; VITAMIN AB Background: Linxian, a rural county in North Central China, has among the highest rates of esophageal squamous cell carcinoma and gastric cardia adenocarcinoma in the world. In a nested case-cohort study that originated from two cancer prevention trials in Linxian, we examined the relationship between these cancers and two polymorphisms in the DNA repair gene XRCC1. Methods: We conducted a case-cohort study among individuals in the cohort who were alive and cancer free in 199 1, and had blood samples for DNA extraction. Real time Taqman analyses were conducted to genotype incident cancer cases (n = 221, 131 esophageal and 90 gastric cardia cancer cases) that developed through May 1996, and on an age- and sex-matched reference cohort (n = 454). We used Cox proportional hazard models to estimate relative risks (RR) and 95% confidence intervals (95% CI). Results: We observed no association between the variant genotype in XRCC1 Arg194Trp (codon 194 arganine to tryptophan substitution) and esophageal or gastric cardia cancer. However, carrying at least one copy of the variant allele in XRCC1 Arg399Gln (codon 399 arganine to glutamine substitution) was associated with reduced risk of gastric cardia cancer (RR: 0.60, 95% CI: 0.37-0.97) and the combined category esophageal/gastric cancer (RR: 0.67, 95% CI: 0.48-0.95). In combined polymorphisms analyses, we observed a significant reduction in risk of combined esophageal/gastric cancer among individuals that had both the XRCC1 Arg194Trp and Arg399Gln variant genotyopes (RR: 0.47, 95% CI: 0.26-0.84). Conclusions: Our results suggest that the XRCC1 Arg399Gln variant genotype is associated with reduced risk of upper GI cancer and that individuals with both XRCC1 variant genotypes are also at significantly reduced risk of upper GI cancer in this high-risk Chinese population. (C) 2004 Published by Elsevier Ireland Ltd. C1 US FDA, Natl Ctr Toxicol Res, Ctr Struct Genomics, Jefferson, AR 72079 USA. NCI, Canc Prevent Studies Branch, Clin Res Ctr, Rockville, MD USA. Chinese Acad Med Sci, Beijing 100037, Peoples R China. BioServe Biotechnol Ltd, Laurel, MD USA. NCI, Nutr Epidemiol Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. NCI, Biostat Branch, Div Canc Epidemiol & Genet, Rockville, MD USA. RP Ratnasinghe, LD (reprint author), US FDA, Natl Ctr Toxicol Res, Ctr Struct Genomics, 3900 NCTR Dr, Jefferson, AR 72079 USA. EM lratnasinghe@nctr.fda.gov RI Qiao, You-Lin/B-4139-2012; Abnet, Christian/C-4111-2015 OI Qiao, You-Lin/0000-0001-6380-0871; Abnet, Christian/0000-0002-3008-7843 NR 29 TC 48 Z9 55 U1 0 U2 5 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD DEC 28 PY 2004 VL 216 IS 2 BP 157 EP 164 DI 10.1016/j.canlet.2004.03.012 PG 8 WC Oncology SC Oncology GA 875IY UT WOS:000225414900003 PM 15533591 ER PT J AU Angeles-Boza, AM Bradley, PM Fu, PKL Wicke, SE Bacsa, J Dunbar, KR Turro, C AF Angeles-Boza, AM Bradley, PM Fu, PKL Wicke, SE Bacsa, J Dunbar, KR Turro, C TI DNA binding and photocleavage in vitro by new dirhodium(II) dppz complexes: Correlation to cytotoxicity and photocytotoxicity SO INORGANIC CHEMISTRY LA English DT Review ID DRUG-RESISTANCE; EXCITED-STATE; DIPYRIDOPHENAZINE COMPLEXES; ELECTRON-TRANSFER; LIGHT-SWITCH; PHOTOPHYSICAL PROPERTIES; PHOTODYNAMIC THERAPY; HETEROCYCLIC BASES; ANTITUMOR-ACTIVITY; CRYSTAL-STRUCTURE AB Two new dirhodium(II) complexes possessing the intercalating dppz ligand (dppz = dipyrido[3,2-a:2',3'-c]phenazine), cis-[Rh-2(mu-O2CCH3)(2)(dppz)(eta(1)-O2CCH3)(CH3OH)](+) (1) and cis-[Rh-2(mu-O2CCH3)(2)(dPPZ)(2)](2+) (2), were synthesized and characterized as potential agents for photochemotherapy. Various techniques show that 1 binds to DNA through intercalation, although some aggregation of the complex on the DNA surface is also present. In contrast, 2 does not intercalate between the DNA bases; however, strong hypochromic behaviour is observed in the presence of DNA, which can be attributed to intermolecular pi-stacking of 2 enhanced by the polyanion. The apparent DNA binding constants determined using optical titrations are compared to those from dialysis experiments. Both complexes photocleave pUC18 plasmid in vitro under irradiation with visible light (lambda(irr) greater than or equal to 395 nm, 15 min), resulting in the nicked, circular form. Greater photocleavage is observed for 1 relative to 2, which may be due to the ability of 1 to intercalate between the DNA bases. The cytotoxicity toward human skin cells (Hs-27) measured as the concentration at which 50% cell death is recorded, LC50, was found to be 135 +/- 8 muM for 2 in the dark (30 min), which is significantly lower than those of 1 (LC50 = 27 +/- 2 muM) and Rh-2(O2CCH3)(4) (LC50 = 15 +/- 2 muM). Irradiation of cell cultures containing 1 and Rh-2(O2CCH3)(4) with visible light (400-700 nm, 30 min) has little effect on their cytotoxicity, with LC50 values of 21 +/- 3 and 13 +/- 2 muM, respectively. Interestingly, a 3.4-fold increase in the toxicity of 2 is observed when the cell cultures are irradiated (400-700 nm, 30 min), resulting in LC50 = 39 +/- 1 muM. The greater toxicity of 1 compared to 2 in the dark may be related to the ability of the former compound to intercalate between the DNA bases. The lower cytotoxicity of 2, together with its significantly greater photocytotoxicity, makes this complex a potential agent for photodynamic therapy (PDT). These results suggest that intercalation or strong DNA binding may not be a desirable property of a potential PDT agent. C1 Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. US FDA, College Pk, MD 20740 USA. RP Turro, C (reprint author), Texas A&M Univ, Dept Chem, College Stn, TX 77843 USA. EM dunbar@mail.chem.tamu.edu; turro@chemistry.ohio-state.edu RI Angeles-Boza, Alfredo/C-6563-2008; Dunbar, Kim/B-6488-2015; Turro, Claudia/H-5335-2015; BACSA, JOHN/L-8501-2016 OI Angeles-Boza, Alfredo/0000-0002-5560-4405; Dunbar, Kim/0000-0001-5728-7805; Turro, Claudia/0000-0003-3202-5870; FU NIGMS NIH HHS [R01 GM64040-01] NR 111 TC 121 Z9 122 U1 4 U2 31 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0020-1669 J9 INORG CHEM JI Inorg. Chem. PD DEC 27 PY 2004 VL 43 IS 26 BP 8510 EP 8519 DI 10.1021/ic049091h PG 10 WC Chemistry, Inorganic & Nuclear SC Chemistry GA 881YY UT WOS:000225906700046 PM 15606200 ER PT J AU Williams, LD Churchwell, MI Doerge, DR AF Williams, LD Churchwell, MI Doerge, DR TI Multiresidue confirmation of beta-agonists in bovine retina and liver using LC-ES/MS/MS SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE beta-agonists; mass spectrometry; retina; clenbuterol; ractopamine ID CLENBUTEROL; RESIDUES; CATTLE AB Misuse of numerous beta-agonist drugs for their growth promoting effects in livestock production requires significant regulatory enforcement activities worldwide. The proof of illegal drug use needed for regulatory action usually requires the high degree of specificity derived from mass spectrometric analysis of suspect tissues and body fluids. In this paper, we describe a multiresidue screening method for confirmation of nine beta-agonist compounds in bovine liver and retina. A wide range of analyte structures was selected in order to demonstrate applicability to other chemically related beta-agonists for which standards are not currently available. The class-specific method, which is based on mixed mode cation exchange/reverse phase solid phase extraction, reverse phase gradient LC separation using a cyanopropyl-silica phase, and tandem mass spectrometry (MS/MS) in the multiple reaction monitoring (MRM) mode, yields high analyte recoveries at the target level of 1 ppb (ng/g). In addition, acquisition of multiple MRM transitions for each analyte permits simultaneous confirmation of beta-agonists at the level of I ppb in liver and retina by using intensity ratios between fragment ions and protonated molecules. Estimated values for the limit of quantification (LOQ) for individual beta-agonists were 0.08-0.3 ppb in liver and 0.02-0.5 in retina; the estimated limits of confirmation, using accepted criteria from international regulatory agencies, were 0.25-0.8 ppb in liver and 0.1-1 ppb in retina. This method should be useful in supporting regulatory enforcement programs that monitor P-agonist misuse. (C) 2004 Elsevier B.V. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM ddoerge@nctr.fda.gov NR 8 TC 50 Z9 58 U1 0 U2 10 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 DEC 25 PY 2004 VL 813 IS 1-2 BP 35 EP 45 DI 10.1016/j.jchromb.2004.09.005 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 875IH UT WOS:000225413200003 PM 15556513 ER PT J AU Srisodsai, A Kurotani, R Chiba, Y Sheikh, F Young, HA Donnelly, RP Kimura, S AF Srisodsai, A Kurotani, R Chiba, Y Sheikh, F Young, HA Donnelly, RP Kimura, S TI Interleukin-10 induces uteroglobin-related protein (UGRP) 1 gene expression in lung epithelial cells through homeodomain transcription factor T/EBP/NKX2.1 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ENHANCER-BINDING PROTEIN; FACTOR-I; CYTOKINE PRODUCTION; HOMEOBOX GENE; DNA-BINDING; B GENE; A GENE; IL-10; PROMOTER; RECEPTOR AB UGRP1 is a downstream target gene for homeodomain transcription factor T/EBP/NKX2.1, which is predominantly expressed in lung epithelial cells, and may play an anti-inflammatory role in lung inflammation. To understand the role of UGRP1 in inflammation, its expression was investigated in relation to cytokine signaling. In vivo experiments using mouse embryonic lung organ culture and intranasal administration of interleukin (IL) 10 revealed that constitutive expression of Ugrp1 mRNA is enhanced by IL-10. Increase of protein levels was also demonstrated by immunohistochemistry using embryonic lungs. This IL-10 induction of Ugrp1 gene expression occurs at the transcriptional level when examined using mouse embryonic lung primary cultures. In human lung NCI-H441 cells that in contrast to mouse lung cells, do not exhibit constitutive expression of the gene, expression of the UGRP1 gene was induced in a rapid and stable fashion. Two T/EBP, but not STAT3, binding sites located in the human UGRP1 gene promoter are responsible for IL-10 induction of the UGRP1 gene as judged by transfection, gel shift, and chromatin immunoprecipitation analyses. The IL-10 receptor chains, IL-10R1 and IL-10R2, are expressed in H441 cells, however, STAT3 was only weakly activated upon IL-10 treatment. In contrast, STAT3 was strongly activated when the cells were treated with other cytokines such as IL-22 and interferon-beta but UGRP1 expression was not increased. Together these results demonstrate that IL-10 induces UGRP1 gene expression in lung epithelial cells through a T/EBP/NKX2.1-dependent pathway. The results further suggest that UGRP1 might be a target for IL-10 anti-inflammatory activities in the lung. C1 NCI, Lab Metab, NIH, Bethesda, MD 20892 USA. US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Expt Immunol Lab, Frederick, MD 21701 USA. RP Kimura, S (reprint author), NCI, Lab Metab, NIH, Bldg 37,Rm 3112B,9000 Rockville Pike, Bethesda, MD 20892 USA. EM shioko@helix.nih.gov RI Young, Howard/A-6350-2008 OI Young, Howard/0000-0002-3118-5111 NR 46 TC 15 Z9 20 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 24 PY 2004 VL 279 IS 52 BP 54358 EP 54368 DI 10.1074/jbc.M405331200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 880MJ UT WOS:000225793600058 PM 15485815 ER PT J AU Derrick, SC Yang, AL Morris, SL AF Derrick, SC Yang, AL Morris, SL TI A polyvalent DNA vaccine expressing an ESAT6-Ag85B fusion protein protects mice against a primary infection with Mycobacterium tuberculosis and boosts BCG-induced protective immunity SO VACCINE LA English DT Article DE tuberculosis; BCG; vaccine ID CALMETTE-GUERIN; EFFICACY; ESAT-6; PREVENTION; IMMUNOGENICITY; CHALLENGE; SINGLE; MOUSE; MODEL; TRIAL AB In this study, we evaluated the protective efficacy of a DNA vaccine (pE6/85) expressing an ESAT6-Ag85B fusion protein against a primary Mycobacterium tuberculosis infection in mice. In short-term studies, vaccination with pE6/85 protected as well as Mycobacterium bovis BCG immunization with similar lung pathology and bacterial burdens detected 28 days after a low dose aerogenic challenge (>1.0 log(10) reduction relative to naives). In a survival experiment, the protection induced by pE6/85 immunization was also not significantly different than that elicited by BCG vaccination with the mean-times-to-death (+/- standard error of the mean) being 102 +/- 20, 271 +/- 32 and 299 +/- 14 days for naive, pE6/85 and BCG-vaccinated mice, respectively. Furthermore, boosting with pE6/85 but not BCG or a DNA vaccine cocktail at 1 year after an initial BCG immunization (when BCG-induced protection was declining), augmented protection in the lung at 15 and 18 months to levels detected at 3 months post-BCG vaccination. (C) 2004 Elsevier Ltd. All rights reserved. C1 US FDA, CBER, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. RP Morris, SL (reprint author), US FDA, CBER, Lab Mycobacterial Dis & Cellular Immunol, Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. EM morris@cber.fda.gov FU NIAID NIH HHS [N01 AI-75320] NR 30 TC 72 Z9 80 U1 0 U2 1 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 DEC 21 PY 2004 VL 23 IS 6 BP 780 EP 788 DI 10.1016/j.vaccine.2004.07.036 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 882KC UT WOS:000225936800008 PM 15542202 ER PT J AU Finlayson, JS AF Finlayson, JS TI John Ferry - the most important man I never knew SO BIOPHYSICAL CHEMISTRY LA English DT Editorial Material C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20892 USA. RP Finlayson, JS (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, 1401 Rockville Pike, Rockville, MD 20892 USA. EM scottd@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-4622 J9 BIOPHYS CHEM JI Biophys. Chem. PD DEC 20 PY 2004 VL 112 IS 2-3 BP 153 EP 154 DI 10.1016/j.bpc.2004.07.014 PG 2 WC Biochemistry & Molecular Biology; Biophysics; Chemistry, Physical SC Biochemistry & Molecular Biology; Biophysics; Chemistry GA 885YS UT WOS:000226193900009 PM 15688528 ER PT J AU Yarovinsky, F Andersen, JF King, LR Caspar, P Aliberti, J Golding, H Sher, A AF Yarovinsky, F Andersen, JF King, LR Caspar, P Aliberti, J Golding, H Sher, A TI Structural determinants of the anti-HIV activity of a CCR5 antagonist derived from Toxoplasma gondii SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; CYCLOPHILIN-A; CRYSTAL-STRUCTURE; CYCLOSPORINE-A; CELL LINE; INFECTION; RECEPTOR; BINDING; ENTRY; INHIBITION AB The protozoan parasite Toxoplasma gondii possesses a protein, cyclophilin-18 (C-18), which binds to the chemokine receptor CCR5, induces interleukin-12 production from murine dendritic cells, and inhibits fusion and infectivity of human immunodeficiency virus 1 (HIV-1) R5 viruses by co-receptor antagonism. Site-directed mutagenesis was employed to identify the domains in C-18 responsible for its CCR5 binding and antiviral functions. To do so we focused on amino acid differences with Plasmodium falciparum cyclophilin, which, although 53% identical with C-18, has minimal binding activity for CCR5, and we generated 22 mutants with substitutions in the regions of non-homology located on the putative surface of the molecule. Two mutations situated on the face of C-18, predicted to be involved in its interaction with the ligand cyclosporin A, were shown to be critical for CCR5-binding and the inhibition of HIV-1 fusion and infectivity. In contrast, four mutations in C-18 specifically designed to abolish the peptidylprolyl cis-trans-isomerase activity of the protein failed to inactivate its CCR5 binding and HIV inhibitory activities. Interleukin-12 induction by C-18, on the other hand, was abrogated by mutations effecting either the CCR5 binding or enzymatic function of the molecule. These findings shed light on the structural basis of the molecular mimicry of the chemokine function by a pathogen-derived protein and provide a basis for further modification of C-18 into an antiviral agent. C1 NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Lab Malaria & Vector Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Sher, A (reprint author), NIAID, Parasit Dis Lab, Immunobiol Sect, NIH, Bethesda, MD 20892 USA. EM asher@mail.nih.gov RI Aliberti, Julio/G-4565-2012; Aliberti, Julio/I-7354-2013 OI Aliberti, Julio/0000-0003-3420-8478 NR 36 TC 17 Z9 18 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD DEC 17 PY 2004 VL 279 IS 51 BP 53635 EP 53642 DI 10.1074/jbc.M410550200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 878XL UT WOS:000225680600100 PM 15469936 ER PT J AU Russell, M Pool, V Kelso, JA Tomazic-Jezic, VJ AF Russell, M Pool, V Kelso, JA Tomazic-Jezic, VJ TI Vaccination of persons allergic to latex: a review of safety data in the Vaccine Adverse Event Reporting System (VAERS) SO VACCINE LA English DT Article DE natural dry rubber latex; allergy or hypersensitivity; vaccination ID VIAL CLOSURES; ANAPHYLAXIS; SYRINGES; RISK AB Vaccine products currently licensed in the US and other countries are marketed in vials and syringes that may contain natural latex allergens. Little scientific information exists regarding the safety of vaccination of latex-allergic individuals. A review of data within the Vaccine Adverse Event Reporting System (VAERS), a large registry of reported possible vaccine adverse reactions was conducted. A search of the database, which contains >160,000 vaccine adverse event reports. revealed only 28 cases of possible immediate-type hypersensitivity reactions in vaccine recipients with a history of allergy to latex. Given the large number Of immunizations administered every year in the US. the reported risk of allergic reactions possibly due to latex contamination of vaccines appears to be very small. Published by Elsevier Ltd. C1 CDC, NIP, Immunizat Safety Branch, Atlanta, GA 30333 USA. USN, Med Ctr, San Diego, CA 92134 USA. US FDA, CDRH, DLS, Off Sci & Technol, Rockville, MD 20852 USA. RP Russell, M (reprint author), Ctr Dis Control, Natl Ctr Infect Dis, Div Global Migrat & Quarantine, Mail Stop E03, Atlanta, GA 30333 USA. EM yzr8@cdc.gov NR 21 TC 16 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 DEC 16 PY 2004 VL 23 IS 5 BP 664 EP 667 DI 10.1016/j.vaccine.2004.06.042 PG 4 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 882KB UT WOS:000225936700013 PM 15542187 ER PT J AU Munitic, I Williams, JA Yang, YL Bei, D Lucas, PJ El Kassar, N Gress, RE Ashwell, JD AF Munitic, I Williams, JA Yang, YL Bei, D Lucas, PJ El Kassar, N Gress, RE Ashwell, JD TI Dynamic regulation of IL-7 receptor expression is required for normal thymopoiesis SO BLOOD LA English DT Article ID T-CELL DEVELOPMENT; INTERLEUKIN-7 RECEPTOR; DEFICIENT MICE; TRANSGENIC MICE; THYMOCYTE DIFFERENTIATION; NEGATIVE SELECTION; UP-REGULATION; CUTTING EDGE; MEMORY CELLS; GAMMA-CHAIN AB Interleukin-7 receptor (IL-7R) levels are tightly controlled during ontogeny: high on double-negative (DN) cells, absent on double-positive (DP) cells, and high once again on thymocytes undergoing positive selection. To determine if loss of IL-7-mediated survival signals in DP cells is necessary for normal antigen-specific selection, we created T-lineage-specific lL-7R alpha chain (IL-7Ralpha) transgenic (Tg) mice in which IL-7R is expressed throughout ontogeny. There was no effect of the IL-7Ralpha Tg on negative selection. Surprisingly, however, although the thymi of IL-7Ralpha Tg mice were comparable at birth, there was a decrease in thymocyte number as the mice aged. This was found to be due to competition between DN and IL-7R-expressing DP cells for endogenous IL-7, which resulted in decreased levels of Bcl-2 in DIN cells, increased DIN apoptosis, and decreased DN cell number. Therefore, the down-regulation of IL-7R on DP cells is an "altruistic" act required for maintaining an adequate supply of local IL-7 for DN cells. (C) 2004 by The American Society of Hematology. C1 NCI, Lab Immune Cell Biol, Natl Inst Hlth, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Rockville, MD 20857 USA. NCI, Expt Immunol Branch, Bethesda, MD 20892 USA. RP Ashwell, JD (reprint author), NCI, Lab Immune Cell Biol, Natl Inst Hlth, Bldg 37,Rm 3002,9000 Rockville Pike, Bethesda, MD 20892 USA. EM jda@pop.nci.nih.gov NR 57 TC 69 Z9 70 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 DEC 15 PY 2004 VL 104 IS 13 BP 4165 EP 4172 DI 10.1182/blood-2004-06-2484 PG 8 WC Hematology SC Hematology GA 877VC UT WOS:000225601000053 PM 15328149 ER PT J AU Dagher, R Ning, L Abraham, S Rahman, A Sridhara, R Pazdur, R AF Dagher, R Ning, L Abraham, S Rahman, A Sridhara, R Pazdur, R TI Approval summary: Docetaxel in combination with prednisone for the treatment of androgen-independent hormone-refractory prostate cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID PHASE-II TRIAL; TAXOTERE; CHEMOTHERAPY; MITOXANTRONE AB Purpose: Docetaxel, a taxane previously approved for the treatment of breast cancer and non-small cell lung cancer, was approved by the United States Food and Drug Administration on May 19, 2004 for use in combination with prednisone for the treatment of metastatic androgen-independent (hormone-refractory) prostate cancer. The purpose of this summary is to review the database supporting this approval. Experimental Design: In a randomized, global study enrolling 1,006 patients, two schedules of docetaxel were compared with mitoxantrone + prednisone as follows: MTZ q 3w, mitoxantrone 12 mg/m2 every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; TXT q 3w, docetaxel 75 mg/m(2) every 21 days + prednisone 5 mg twice a day for a total of 10 cycles; and TXT qw, docetaxel 30 mg/m(2) days 1, 8, 15, 22, and 29 every 6 weeks + prednisone 5 mg twice a day for a total of 5 cycles. Results: There was a statistically significant overall survival advantage shown for the TXT q 3w arm over MTZ q 3w (median survival 18.9 months versus 16.5 months, P = 0.0094). No overall survival advantage was shown for TXT qw compared with MTZ q 3w. The most commonly occurring adverse events included anemia, neutropenia, infection, nausea, sensory neuropathy, fluid retention, alopecia, nail changes, diarrhea, and fatigue. Conclusions: This report describes the Food and Drug Administration review supporting this first approval of a combination therapy for hormone-refractory prostate cancer based on demonstration of a survival benefit. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Dagher, R (reprint author), US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. EM dagherr@cder.fda.gov NR 18 TC 47 Z9 48 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD DEC 15 PY 2004 VL 10 IS 24 BP 8147 EP 8151 DI 10.1158/1078-0432.CCR-04-1402 PG 5 WC Oncology SC Oncology GA 882SE UT WOS:000225957800005 PM 15623588 ER PT J AU Kenna, LA Sheiner, LB AF Kenna, LA Sheiner, LB TI Estimating treatment effect in the presence of non-compliance measured with error: precision and robustness of data analysis methods SO STATISTICS IN MEDICINE LA English DT Article DE compliance; adherence; missing data; measurement error; calibration ID LOGISTIC-REGRESSION; PROTEASE INHIBITORS; SELECTING VALUES; INPUT VARIABLES; CLINICAL-TRIALS; COMPUTER CODE; ADHERENCE; MEDICATION; UNCERTAINTY; THERAPY AB Non-compliance with the nominal prescribed dosage causes unintended variability in actual drug exposure during clinical trials. In the ideal case that compliance is not a confounder, and it is known-hence actual dosage is known-true dose-response can be validly estimated. Measuring compliance presents a challenge, however. A simulation study of the case that dosage history questionnaires (C-Q-usually over-optimistic estimates of actual compliance) are available in all subjects enrolled in a clinical trial, but accurate compliance measurements (C-e.g. from electronic medication event monitors), are only available in a (random) fraction of subjects is reported. It reveals that a 'Maximum Penalized Marginal Likelihood' (MPML) method which uses all compliance data, effectively calibrating C-Q to C, is superior to other methods which use only one compliance measure, or both, or neither (neither = ITT, intention to treat, which assumes actual dosage equals nominal dosage), but do not calibrate. MPML yields the most precise estimates of dose-response over widely varying clinical trial designs, extremes in quality and quantity of compliance information, and a range of drug effect sizes. It is most beneficial when compliance data are sparse and maintains good performance even when its key assumptions are somewhat violated. Copyright (C) 2004 John Wiley Sons, Ltd. C1 Univ Calif San Francisco, Dept Lab Med & Biopharmaceut Sci, San Francisco, CA 94143 USA. RP Kenna, LA (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, HFD 870 Room 13B 17, Rockville, MD 20857 USA. EM kennal@cder.fda.gov FU NIAID NIH HHS [AI38858]; NIGMS NIH HHS [GM26676] NR 35 TC 8 Z9 8 U1 1 U2 2 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 15 PY 2004 VL 23 IS 23 BP 3561 EP 3580 DI 10.1002/sim.1830 PG 20 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 874HM UT WOS:000225341500001 PM 15534899 ER PT J AU Chen, L Tsong, Y AF Chen, L Tsong, Y TI Comment on: estimate of standard deviation for a log-transformed variable using arithmetic means and standard deviations SO STATISTICS IN MEDICINE LA English DT Letter ID SKEWED DISTRIBUTIONS C1 US FDA, Ctr Drug Evaluat & Res, Off Biostat,Off Pharmacoepidemiol & Stat Sci, Rockville, MD 20857 USA. RP Chen, L (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat,Off Pharmacoepidemiol & Stat Sci, 12720 Twonbrook Pkwy, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 U1 2 U2 5 PU JOHN WILEY & SONS LTD PI CHICHESTER PA THE ATRIUM, SOUTHERN GATE, CHICHESTER PO19 8SQ, W SUSSEX, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD DEC 15 PY 2004 VL 23 IS 23 BP 3713 EP 3716 DI 10.1002/sim.1900 PG 4 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 874HM UT WOS:000225341500011 PM 15534898 ER PT J AU Santiago-Lopez, D Vazquez-Roman, B Perez-De La Cruz, V Barrera, D Rembao, D Salinas-Lara, C Pedraza-Chaverri, J Galvan-Arzate, S Ali, SF Santamaria, A AF Santiago-Lopez, D Vazquez-Roman, B Perez-De La Cruz, V Barrera, D Rembao, D Salinas-Lara, C Pedraza-Chaverri, J Galvan-Arzate, S Ali, SF Santamaria, A TI Peroxynitrite decomposition catalyst, iron metalloporphyrin, reduces quinolinate-induced neurotoxicity in rats SO SYNAPSE LA English DT Article DE iron porphyrinates; oxidative/nitrergic stress; excitotoxicity; antioxidant defense; neurotoxicity ID ACID-INDUCED NEUROTOXICITY; NITRIC-OXIDE; DOPAMINERGIC NEUROTOXICITY; HUNTINGTONS-DISEASE; OXIDATIVE STRESS; CORPUS STRIATUM; IN-VIVO; DAMAGE; MODEL; ANTIOXIDANT C1 Inst Nacl Neurol & Neurociruga, Lab Aminoacidos Excitadores, Dept Neuroquim, Mexico City 14269, DF, Mexico. Univ Nacl Autonoma Mexico, Fac Med, Dept Farmacol, Mexico City 04510, DF, Mexico. Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Dept Neuropatol, Mexico City 14269, DF, Mexico. Univ Nacl Autonoma Mexico, Fac Quim, Dept Biol, Mexico City 04510, DF, Mexico. Inst Nacl Neurol & Neurocirugia Manuel Velasco Su, Dept Neuroquim, Mexico City 14269, DF, Mexico. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Santamaria, A (reprint author), Inst Nacl Neurol & Neurociruga, Lab Aminoacidos Excitadores, Dept Neuroquim, Insurgentes Sur 3877, Mexico City 14269, DF, Mexico. EM absada@yahoo.com NR 27 TC 14 Z9 14 U1 1 U2 2 PU WILEY-LISS PI HOBOKEN PA DIV JOHN WILEY & SONS INC, 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0887-4476 J9 SYNAPSE JI Synapse PD DEC 15 PY 2004 VL 54 IS 4 BP 233 EP 238 DI 10.1002/syn.20084 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 868GS UT WOS:000224902700006 PM 15484207 ER PT J AU Slikker, W Andersen, ME Bogdanffy, MS Bus, JS Cohen, SD Conolly, RB David, RM Doerrer, NG Dorman, DC Gaylor, DW Hattis, D Rogers, JM Setzer, RW Swenberg, JA Wallace, K AF Slikker, W Andersen, ME Bogdanffy, MS Bus, JS Cohen, SD Conolly, RB David, RM Doerrer, NG Dorman, DC Gaylor, DW Hattis, D Rogers, JM Setzer, RW Swenberg, JA Wallace, K TI Dose-dependent transitions in mechanisms of toxicity SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review DE dose-dependent transitions; mechanisms of toxicity; dose-response ID HUMAN CYTOCHROME-P450 ENZYMES; INDUCED HEPATIC NECROSIS; SPRAGUE-DAWLEY RATS; STRAND-BREAK REPAIR; INTACT MALE RATS; RISK-ASSESSMENT; ETHYLENE-GLYCOL; PHARMACOKINETIC MODEL; INHALATION EXPOSURE; CARCINOGENIC RISK AB Scientists and decision makers from all sectors agree that risk assessments should be based on the best available science. Several years ago, the Health and Environmental Sciences Institute (HESI), a global branch of the International Life Sciences Institute (ILSI), identified the need for better scientific understanding of dose-dependent transitions in mechanisms of toxicity as one avenue by which the best and latest science can be integrated into the decision making process. In July 2001, the HESI Project Committee on Dose-Dependent Transitions in Mechanisms of Toxicity established a group of academic, government, and industry scientists to engage in active technical discourse on the issue of dose-dependent transitions in mechanisms of toxicity. Over the next 18 months, case studies were examined. These case studies included acetaminophen, butadiene, ethylene glycol, formaldehyde, manganese, methylene chloride, the peroxisome proliferator-activated receptor, progesterone/hydroxyflutamide, propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc (Slikker, W., Jr., Andersen, M.E., Bogdanffy, M.S., Bus, J.S., Cohen, S.D., Conolly, R.B., David, R.M., Doerrer, N.G., Dorman, D.C., Gaylor, D.W., Hattis, D., Rogers, J.M., Selzer, R.W., Swenberg, J.A., Wallace, K., 2004. Dose-dependent transitions in mechanisms of toxicity: case studies. Toxicol. Appl. Pharmacol., 201(3), 226-294 (this issue)). The HESI Project Committee sponsored two technical workshops in 2003. The first of these workshops took place on February 12-13, 2003, and was co-sponsored by the Agency for Toxic Substances and Disease Registry.. the American Chemistry Council, the National Institute of Environmental Health Sciences, the Society of Toxicology, and the U.S. Environmental Protection Agency. Additional support was provided by Health Canada. Invited experts from government, academia, and industry provided scientific perspectives and recommendations at the workshop. The purpose of the workshop was to examine approaches to dose-response analysis, learn from the case study examples, and gather feedback from invited participants on the impact of dose-dependent transitions on the risk assessment process. The second forum consisted of a workshop in March 2003 at the Society of Toxicology Annual Meeting in Salt Lake City, UT. This paper addresses the issues discussed at both workshops, and presents the consensus conclusions drawn by expert participants. Published by Elsevier Inc. C1 ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. CIIT Ctr Hlth Res, Res Triangle Pk, NC 27709 USA. DuPont Co Inc, Haskell Lab Hlth & Environm Sci, Newark, DE 19714 USA. Dow Chem Co USA, Midland, MI 48674 USA. Massachusetts Coll Pharm & Allied Hlth Sci, Worcester, MA 01610 USA. Eastman Kodak Co, Rochester, NY 14652 USA. Gaylor & Assoc LLC, Eureka Springs, AR 72631 USA. Clark Univ, Worcester, MA 01610 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. Univ Minnesota, Duluth, MN 55812 USA. RP Doerrer, NG (reprint author), ILSI Hlth & Environm Sci Inst, 1 Thomas Circle NW,9th Floor, Washington, DC 20005 USA. EM ndoerrer@ilsi.org OI Andersen, Melvin/0000-0002-3894-4811; Setzer, Rhyne/0000-0002-6709-9186 NR 116 TC 86 Z9 88 U1 0 U2 11 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 15 PY 2004 VL 201 IS 3 BP 203 EP 225 DI 10.1016/j.taap.2004.06.019 PG 23 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 882JI UT WOS:000225934800001 PM 15582645 ER PT J AU Slikker, W Andersen, ME Bogdanffy, MS Bus, JS Cohen, SD Conolly, RB David, RM Doerrer, NG Dorman, DC Gaylor, DW Hattis, D Rogers, JM Setzer, RW Swenberg, JA Wallace, K AF Slikker, W Andersen, ME Bogdanffy, MS Bus, JS Cohen, SD Conolly, RB David, RM Doerrer, NG Dorman, DC Gaylor, DW Hattis, D Rogers, JM Setzer, RW Swenberg, JA Wallace, K TI Dose-dependent transitions in mechanisms of toxicity: case studies SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Review DE dose-dependent transitions; mechanisms of toxicity; dose response; acetaminophen; butadiene; ethylene glycol; formaldehyde; manganese; methylene chloride; peroxisome proliferator-activated receptor; progesterone/hydroxyflutamide; propylene oxide; vinyl acetate; vinyl chloride; vinylidene chloride; zinc ID GLUTATHIONE-S-TRANSFERASE; INDUCED HEPATIC-NECROSIS; ACTIVATED RECEPTOR-GAMMA; ACETAMINOPHEN-INDUCED HEPATOTOXICITY; SPRAGUE-DAWLEY RATS; PROTEIN CROSS-LINKS; SISTER-CHROMATID EXCHANGES; CHRONIC INHALATION TOXICITY; MANGANESE OXIDE AEROSOL; PARA-BENZOQUINONE IMINE AB Experience with dose response and mechanisms of toxicity has shown that multiple mechanisms may exist for a single agent along the continuum of the full dose-response curve. It is highly likely that critical, limiting steps in any given mechanistic pathway may become overwhelmed with increasing exposures, signaling the emergence of new modalities of toxic tissue injury at these higher doses. Therefore, dose-dependent transitions in principal mechanisms of toxicity may occur, and could have significant impact on the interpretation of reference data sets for risk assessment. To illustrate the existence of dose-dependent transitions in mechanisms of toxicity, a group of academic, government, and industry scientists, formed under the leadership of the ILSI Health and Environmental Sciences Institute (HESI), developed a series of case studies. These case studies included acetaminophen, butadiene, ethylene glycol, formaldehyde, manganese, methylene chloride, peroxisome proliferator-activated receptor (PPAR), progesterone/hydroxyflutamide, propylene oxide, vinyl acetate, vinyl chloride, vinylidene chloride, and zinc. The case studies formed the basis for technical discourse at two scientific workshops in 2003. Published by Elsevier Inc. C1 ILSI Hlth & Environm Sci Inst, Washington, DC 20005 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. CIIT Ctr Hlth Res, Res Triangle Pk, NC 27709 USA. DuPont Co Inc, Haskell Lab Hlth & Environm Sci, Wilmington, DE 19898 USA. Dow Chem Co USA, Midland, MI 48674 USA. Massachusetts Coll Pharm & Allied Hlth Sci, Worcester, MA 01610 USA. Eastman Kodak Co, Rochester, NY 14652 USA. Gaylor & Assoc LLC, Eureka Springs, AR 72631 USA. Clark Univ, Worcester, MA 01610 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27709 USA. Univ N Carolina, Chapel Hill, NC 27599 USA. Univ Minnesota, Duluth, MN 55812 USA. RP Doerrer, NG (reprint author), ILSI Hlth & Environm Sci Inst, 1 Thomas Circle NW,9th Floor, Washington, DC 20005 USA. EM ndoerrer@ilsi.org OI Andersen, Melvin/0000-0002-3894-4811; Setzer, Rhyne/0000-0002-6709-9186 NR 576 TC 92 Z9 93 U1 1 U2 20 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD DEC 15 PY 2004 VL 201 IS 3 BP 226 EP 294 DI 10.1016/j.tapp.2004.06.027 PG 69 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 882JI UT WOS:000225934800002 PM 15582646 ER PT J AU Watson, WD Srivastava, M Leighton, X Glasman, M Faraday, M Fossam, LH Pollard, HB Verma, A AF Watson, WD Srivastava, M Leighton, X Glasman, M Faraday, M Fossam, LH Pollard, HB Verma, A TI Annexin 7 mobilizes calcium from endoplasmic reticulum stores in brain SO BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR CELL RESEARCH LA English DT Article; Proceedings Paper CT 8th European Symposium on Calcium-Binding Proteins in Normal and Transformed Cells CY JUL 28-31, 2004 CL Hinxton Hall, Campus, Cambridge, ENGLAND SP European Calcium Soc, VisiTech Int, European Union, High Level Sci Conf, British Soc Cell Biol, Raytek, Leica Microsyst, Zeiss, Univ Imaging, Med Solut & Imp HO Hinxton Hall, Campus DE annexin 7; knockout mouse; endoplasmic reticulum; calcium; IP3 receptor; signaling; brain ID INOSITOL 1,4,5-TRISPHOSPHATE; VII SYNEXIN; EXPRESSION; RECEPTORS; MOUSE; GENE; ANX7 AB Mobilization of intracellular calcium from inositol-1,4,5 -triphosphate (IP3)-sensitive endoplasmic reticulum (ER) stores plays a prominent role in brain function. Mice heterozygous for the annexin A7 (Anx7) gene have a profound reduction in IP3 receptor function in pancreatic islets along with defective insulin secretion. We examined IP3-sensitive calcium pools in the brains of Anx7 (+/-) mice by utilizing ATP/Mg2+-dependent Ca-45(2+) uptake into brain membrane preparations and tissue sections. Although the Anx7 (+/-) mouse brain displayed similar levels of IP3 binding sites and thapsigargin-sensitive Ca-45(2+) uptake as that seen in wild-type mouse brain, the Anx7 (+/-) mouse brain Ca2+ pools showed markedly reduced sensitivity to IP3. A potent and saturable Ca2+-releasing effect of recombinant ANX7 protein was demonstrated in mouse and rat brain membrane preparations, which was additive with that of IP3. We propose that ANX7 mobilizes Ca2+ from an endoplasmic reticulum-like pool, which can be recruited to enhance IP3-mediated Ca2+ release. (C) 2004 Elsevier B.V.All rights reserved. C1 Dept Anat Physiol & Genet, Bethesda, MD 20814 USA. USN, Natl Med Ctr, Dept Neurol, Bethesda, MD 20814 USA. Dept Psychol Med, Bethesda, MD 20814 USA. FDA, CDER, Div Neuropharmacol Drug Prod, Rockville, MD 20852 USA. Uniformed Serv Univ Hlth Sci, Dept Neurol, Bethesda, MD 20814 USA. RP Pollard, HB (reprint author), Dept Anat Physiol & Genet, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. EM hpollard@usuhs.mil NR 22 TC 13 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-4889 J9 BBA-MOL CELL RES JI Biochim. Biophys. Acta-Mol. Cell Res. PD DEC 6 PY 2004 VL 1742 IS 1-3 SI SI BP 151 EP 160 DI 10.1016/j.bbamcr.2004.10.008 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 893XK UT WOS:000226754200016 PM 15590065 ER PT J AU Raiche, J Rodriguez-Juarez, R Pogribny, I Kovalchuk, O AF Raiche, J Rodriguez-Juarez, R Pogribny, I Kovalchuk, O TI Sex- and tissue-specific expression of maintenance and de novo DNA methyltransferases upon low dose X-irradiation in mice SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE radiation; DNA methylation; DNA methyltransferases; sex hormones ID INDUCED GENOMIC INSTABILITY; IONIZING-RADIATION; METHYLATION PATTERNS; RAY-IRRADIATION; CANCER-CELLS; IN-VITRO; 5-METHYLCYTOSINE; DIFFERENTIATION; CARCINOGENESIS; DNMT3B AB DNA methylation is crucial for normal development, proliferation, and proper maintenance of genome stability for a given organism. A variety of DNA damaging agents that are known to affect genome stability were also shown to alter DNA methylation patterns. We have recently pioneered the studies in the area of the radiation effects on DNA methylation, and found that radiation exposure led to substantial dose-dependent and tissue-specific DNA hypomethylation, which was much more pronounced in spleen and liver of female animals. The exact mechanisms of radiation-induced DNA hypomethylation are still to be uncovered. We have previously shown that one of those mechanisms may potentially be DNA repair related. Another possible mechanism may be linked to changes in the expression of DNA methyltransferases (DNMTs). In the current study, we examined the radiation-induced changes in expression of maintenance DNMT1, and de novo methyltransferases DNMT3a and DNMT3b in spleen and liver of irradiated animals. This was paralleled by the studies of acute and chronic IR-induced methylation changes in spleen and liver of intact animals, as well as in animals with altered sex hormone status. Here we report that radiation-induced DNA methylation changes correlated with radiation-induced alterations in expression of DNA methyltransferases. We present the data on tissue-specificity in radiation-induced expression of DNA methyltransferases, and prove that changes in the expression of de novo methyltransferases DNMT3a and DNMT3b are the most important in radiation-induced DNA methylation alterations. We also discuss the role of sex hormones, especially estrogen, in the generation of the sex-specific radiation-induced methylation changes. (C) 2004 Elsevier Inc. All rights reserved. C1 Univ Lethbridge, Dept Biol Sci, Lethbridge, AB T1K 3M4, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Kovalchuk, O (reprint author), Univ Lethbridge, Dept Biol Sci, 4401 Univ Dr, Lethbridge, AB T1K 3M4, Canada. EM olga.kovalchuk@uleth.ca NR 38 TC 58 Z9 68 U1 0 U2 6 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD DEC 3 PY 2004 VL 325 IS 1 BP 39 EP 47 DI 10.1016/j.bbrc.2004.10.002 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 871YU UT WOS:000225173400007 PM 15522198 ER PT J AU Duffy, PH Lewis, SM Mayhugh, MA Trotter, RW Latendresse, JR Thorn, BT Feuers, RJ AF Duffy, PH Lewis, SM Mayhugh, MA Trotter, RW Latendresse, JR Thorn, BT Feuers, RJ TI The effects of different levels of dietary restriction on neoplastic pathology in the male Sprague-Dawley rat SO AGING CLINICAL AND EXPERIMENTAL RESEARCH LA English DT Article DE dietary; neoplastic; pathology; restriction ID CHRONIC CALORIC RESTRICTION; AIN-93M PURIFIED DIET; INCREASED CARCINOGENICITY; FISCHER-344 RATS; DOSE LEVELS; LIFE-SPAN; SURVIVAL; GROWTH; VARIABLES AB Background and aims: The primary purpose of this study was to evaluate the effects of varied levels of dietary restriction (DR) on neoplastic pathologies in rodents at 58 and 110 weeks of age. Methods: Male Sprague-Dawley (SD) rats were divided into four nutritional groups; an ad libitum (AL) control group, and three dietary restricted (DR) groups that were fed the NIH-31 diet reduced in amount by 10, 25, and 40%. Results: At 110 weeks of age, compared to AL rats, the incidence of benign tumors was significantly lower in all DR groups while primary tumors were significantly lower in the 10 and 40% DR groups; no malignant tumors were detected in the 10% DR group. Most defined mortalities were caused by neoplastic lesions. All levels of DR reduced the percentage of tumor-bearing animals, the incidence of skin tumors (combined), and the total number of tumors. Pituitary, skin, and pancreatic tumors were the most prolific lesions; pituitary and skin tumors were the most fatal. Compared to AL rats, the time to onset of skin and pancreatic tumors was longer in all of the DR groups. Conclusion: In many cases, the incidences of neoplastic lesions were similar among the DR groups, clearly indicating that the DR effect is not linear and that even a very low level of DR (10%) can have a significant effect on many important neoplastic lesions and tumor burden. The main effect of DR was to decrease the incidence of some neoplastic lesions and to increase the time to onset and/or decrease the progression of tumors, thereby increasing the 110-week survival rate of DR rats. ((C))2004, Editrice Kurtis. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, US FDA, Jefferson, AR 72079 USA. US FDA, Bionet Corp, Jefferson, AR USA. US FDA, Charles River Lab, Jefferson, AR USA. US FDA, ROW Sci Inc, Jefferson, AR USA. US FDA, Div Chem, Natl Ctr Toxicol Res, Jefferson, AR USA. RP Duffy, PH (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, US FDA, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM pduffy@nctr.fda.gov RI Latendresse, John/A-9215-2009 NR 23 TC 8 Z9 8 U1 0 U2 1 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 2004 VL 16 IS 6 BP 448 EP 456 PG 9 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA 890EK UT WOS:000226494300006 PM 15739595 ER PT J AU Calvo, MS Whiting, SJ Barton, CN AF Calvo, MS Whiting, SJ Barton, CN TI Vitamin D fortification in the United States and Canada: current status and data needs SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article; Proceedings Paper CT Conference on Vitamin D and Health in the 21st Century CY OCT 09-10, 2003 CL Bethesda, MD SP NCI, NIH, DHHS, US Ctr Dis Control & Prevent, USDA Agr Res Serv, NIAMS, DNRC, NIDDK, ORWH, Coca Cola N Amer, Natl Dairy Council DE usual vitamin D intake; food fortification; dietary supplements; vitamin D insufficiency; dietary requirements; nutrition labeling ID D INSUFFICIENCY; BREAST-CANCER; SERUM 25-HYDROXYVITAMIN-D; HYPOVITAMINOSIS-D; D SUPPLEMENTATION; FORTIFIED MILK; CALCIUM INTAKE; HIP-FRACTURES; FLUID MILK; WOMEN AB Most circulating 25-hydroxyvitamin D originates from exposure to sunlight; nevertheless, many factors can impair this process, necessitating periodic reliance on dietary sources to maintain adequate serum concentrations. The US and Canadian populations are largely dependent on fortified foods and dietary supplements to meet these needs, because foods naturally rich in vitamin D are limited. Fluid milk and breakfast cereals are the predominant vehicles for vitamin D in the United States, whereas Canada fortifies fluid milk and margarine. Reports of a high prevalence of hypovitaminosis D and its association with increased risks of chronic diseases have raised concerns regarding the adequacy of current intake levels and the safest and most effective way to increase vitamin D intake in the general population and in vulnerable groups. The usual daily intakes of vitamin D from food alone and from food and supplements combined, as estimated from the US third National Health and Nutrition Examination Survey, 1988-1994, show median values above the adequate intake of 5 mug/d for children 6-11 y of age; however, median intakes are generally below the adequate intake for female subjects > 12 y of age and men > 50 y. In Canada, there are no national survey data for estimation of intake. Cross-sectional studies suggest that current US/Canadian fortification practices are not effective in preventing hypovitaminosis D, particularly among vulnerable populations during the winter, whereas supplement use shows more promise. Recent prospective intervention studies with higher vitamin D concentrations provided evidence of safety and efficacy for fortification of specific foods and use of supplements. C1 CFSAN, MOD 1, Off Appl Res & Saftey Assessment MSC, US FDA, Laurel, MD 20910 USA. CFSAN, Off Math Assessment & Serv CNB, US FDA, Laurel, MD 20910 USA. Univ Saskatchewan, Coll Pharm & Nutr, Saskatoon, SK S7N 0W0, Canada. RP Calvo, MS (reprint author), CFSAN, MOD 1, Off Appl Res & Saftey Assessment MSC, US FDA, Bldg 8301,Muirkirk Rd, Laurel, MD 20910 USA. EM mona.calvo@cfsan.fda.gov NR 59 TC 140 Z9 146 U1 1 U2 23 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 DEC PY 2004 VL 80 IS 6 SU S BP 1710S EP 1716S PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 879ID UT WOS:000225708700006 PM 15585792 ER PT J AU Davis, JA Brown, AT Alshafie, T Poirier, LA Cruz, CP Wang, YF Eidt, JF Moursi, MM AF Davis, JA Brown, AT Alshafie, T Poirier, LA Cruz, CP Wang, YF Eidt, JF Moursi, MM TI Saratin (an inhibitor of platelet-collagen interaction) decreases platelet aggregation and homocysteine-mediated postcarotid endarterectomy intimal hyperplasia in a dose-dependent manner SO AMERICAN JOURNAL OF SURGERY LA English DT Article; Proceedings Paper CT 56th Annual Meeting of the Southwestern Surgical Congress CY APR 18-21, 2004 CL Monterey, CA DE carotid endarterectomy; saratin; intimal hyperplasia; homocysteine; platelet ID CAROTID-ENDARTERECTOMY; PLASMA HOMOCYSTEINE; ARTERY STENOSIS; ADHESION; MODEL; ANGIOPLASTY; INCREASES; ENZYMES; DIET AB Background: This study investigated Saratin's (Merck KGaA, Darmstadt, Germany) prevention of platelet adhesion and intimal hyperplasia at different doses and in the hyperhomocystinemia rat carotid endarterectomy (CEA) model. Methods: Rats were divided into two groups: (1) platelet adhesion or (2) luminal stenosis because of intimal hyperplasia. At CEA, rats received 0, 0.5, 5.0, 10.0, or 20.0 mug Saratin on the artery. Post-CEA platelet aggregation was evaluated by standard error of the mean. Intimal hyperplasia group received either (1) control or (2) 4.5 g/kg DL-homocystine diets for two weeks followed by CEA and treated with diluent or 5.0 mug Saratin. Endpoints included platelet adhesion, intimal hyperplasia, plasma homocysteine (HCys), and its metabolic enzymes cystathionine beta-synthase (CBS) and methylenetetrahydrofolate reductase (MTHFR). Results: Platelet adhesion: post-CEA, platelet adhesion was reduced by 63%, 67%, and 67% in Saratin doses greater than or equal to5.0 mug. Intimal hyperplasia: 5.0 mug Saratin in the HCys group decreased intimal hyperplasia by 45% compared with the non-Saratin-treated HCys group. Plasma HCys levels were not altered with Saratin treatment in the HCys groups nor were CBS or MTHFR. Conclusions: Saratin significantly inhibited platelet adhesion at greater than or equal to5.0 mug, and Saratin at 5.0 Ag attenuated luminal stenosis in a hyperhomocysteinemic rat CEA model. (C) 2004 Excerpta Medica Inc. All rights reserved. C1 Univ Arkansas Med Sci, Cent Arkansas Vet HealthCare Syst, Vasc Serv, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Moursi, MM (reprint author), Univ Arkansas Med Sci, Cent Arkansas Vet HealthCare Syst, Vasc Serv, 112-PV, Little Rock, AR 72205 USA. EM moursimohammedm@exchange.uams.edu NR 30 TC 8 Z9 9 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9610 J9 AM J SURG JI Am. J. Surg. PD DEC PY 2004 VL 188 IS 6 BP 778 EP 785 DI 10.1016/j.amjsurg.2004.08.061 PG 8 WC Surgery SC Surgery GA 885UW UT WOS:000226183600047 PM 15619499 ER PT J AU Richardson, DD Kannamkumarath, SS Wuilloud, RG Caruso, JA AF Richardson, DD Kannamkumarath, SS Wuilloud, RG Caruso, JA TI Hydride generation interface for speciation analysis coupling capillary electrophoresis to inductively coupled plasma mass spectrometry SO ANALYTICAL CHEMISTRY LA English DT Article ID ATOMIC FLUORESCENCE SPECTROMETRY; MODIFIED ELECTROOSMOTIC FLOW; LIQUID-CHROMATOGRAPHY; ARSENIC COMPOUNDS; ELEMENTAL SPECIATION; ELECTROTHERMAL VAPORIZATION; WATER SAMPLES; SEPARATOR; SELENIUM; URINE AB A novel hydride generation (HG) interface for coupling capillary electrophoresis (CE) with inductively coupled plasma mass spectrometry (ICPMS) is presented in this work. The CE-HG-ICPMS interface was applied to the separation and quantitation of common arsenic species. Lack of a commercially available HG interface for CE-ICPMS led to a three concentric tube design allowing alleviation of back pressure commonly observed in CE-HG-ICPMS. Due to the high sensitivity and element-specific detection of ICPMS, quantitative analysis of As(III), As(V), monomethylarsonic acid, and dimethylarsinic acid was achieved. Optimization of CE separation conditions resulted in the use of 20 mmol L-1 sodium borate with 2% osmotic flow modifier (pH 9.0) and -20 kV applied potential for baseline resolution of each arsenic species in the shortest time. Hydride generation conditions were optimized through multiple electrophoretic separation analyses with 5% HCl and 3% NaBH4 (in 0.2% NaOH) determined to be the optimum conditions. After completion of system optimization, detection limits obtained for the arsenic species were less than 40 ng L-1 with electromigration time precision less than 1% within a total analysis time of 9.0 min. Finally, the interface was used for speciation analysis of arsenic in river and tap water samples. C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. US FDA, Cincinnati, OH 45237 USA. RP Caruso, JA (reprint author), Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. EM joseph.caruso@uc.edu RI Wuilloud, Rodolfo/N-6821-2014 OI Wuilloud, Rodolfo/0000-0002-2962-7718 FU NIEHS NIH HHS [ES04908] NR 27 TC 21 Z9 21 U1 1 U2 14 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD DEC 1 PY 2004 VL 76 IS 23 BP 7137 EP 7142 DI 10.1021/ac049066t PG 6 WC Chemistry, Analytical SC Chemistry GA 876YR UT WOS:000225535300047 PM 15571371 ER PT J AU Alayash, AI AF Alayash, AI TI Redox biology of blood SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Editorial Material ID NITRIC-OXIDE; S-NITROSOHEMOGLOBIN; OXYHEMOGLOBIN; HEMOGLOBIN; HEME C1 US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Bethesda, MD 20014 USA. RP US FDA, Ctr Biol Evaluat & Res, Lab Biochem & Vasc Biol, Bethesda, MD 20014 USA. EM Alayash@cber.fda.gov NR 22 TC 8 Z9 8 U1 0 U2 1 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD DEC PY 2004 VL 6 IS 6 BP 941 EP 943 DI 10.1089/1523086042259887 PG 3 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 869XZ UT WOS:000225019300001 PM 15548891 ER PT J AU Yeh, LH Alayash, AI AF Yeh, LH Alayash, AI TI Effects of cell-free hemoglobin on hypoxia-inducible factor (HIF-1 alpha) and heme oxygenase (HO-1) expressions in endothelial cells subjected to hypoxia SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Article ID CROSS-LINKED HEMOGLOBIN; NITRIC-OXIDE SYNTHASE; REDOX SIDE REACTIONS; BLOOD SUBSTITUTES; FACTOR-I; SIGNAL-TRANSDUCTION; GENE; MECHANISMS; ACTIVATION; INDUCTION AB We have investigated the impact of diaspirin cross-linked hemoglobin (DBBF-Hb), a blood substitute, on cell signaling pathways that are modulated in part by biological peroxides (i.e., hydrogen peroxide, lipid peroxide, and peroxynitrite). Bovine aortic endothelial cells (BAECs) subjected to hypoxia expressed hypoxia-inducible factor (HIF-1alpha) in a time course that paralleled the expressions of heme oxygenase (HO-1). Co-incubation of the oxy form (HbFe(2+)) with hypoxic BAECs resulted in an increase in the expression of HIF-1alpha in a manner that corresponded linearly with the decay of HbFe(2+) and accumulation of the ferric form (HbFe(3+)). Inclusion of HbFe(3+) with hypoxic BAECs produced twice as much expression in the HIF-1alpha and HO-1 proteins as opposed to HbFe(2+) alone, or HbFe(2+) plus hypoxia. In addition, higher and more persistent levels of the ferryl form (HbFe(4+)), due to the consumption of endogenous peroxides, were found in the hypoxic media containing hemoglobin. Nitric oxide (NO) released from an NO donor reduced the levels of HIF-lalpha in the hypoxic cells treated with either HbFe(2+) or HbFe(3+), but had little or no effect on the levels of HO-1. DBBF-Hb modulates key cell-signaling pathways by competing with peroxides required for the deactivation of HIF-1alpha, which may modulate important physiological mediators. C1 US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, Bethesda, MD 20892 USA. RP US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, 8800 Rockville Pike,Bldg 29,Room 112, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 52 TC 21 Z9 21 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD DEC PY 2004 VL 6 IS 6 BP 944 EP 953 DI 10.1089/1523086042259850 PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 869XZ UT WOS:000225019300002 PM 15548892 ER PT J AU Buehler, PW Alayash, AI AF Buehler, PW Alayash, AI TI Oxygen sensing in the circulation: "Cross talk" between red blood cells and the vasculature SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID HYPOXIA-INDUCIBLE FACTOR-1; ENDOTHELIAL GROWTH-FACTOR; ADVENTITIAL VASA VASORUM; FACTOR GENE-EXPRESSION; NITRIC-OXIDE; FACTOR-I; SIGNAL-TRANSDUCTION; S-NITROSOHEMOGLOBIN; ERYTHROPOIETIN GENE; CYTOCHROME-OXIDASE AB Oxygen (O-2) sensing in blood and regulation of microvascular tone appear to involve hemoglobin (Hb) conformational changes resulting from O-2 desaturation. This observation has prompted the thought that Hb functions as both an O-2 sensor and regulator of microvasular blood flow to meet local tissue oxygen demand. The mechanism(s) by which this is accomplished has recently been the subject of increasing debate. Three primary hypotheses are described within the literature and include release of adenosine 5'-triphosphate by red blood cells (RBCs), release of S-nitrosylated molecules from RBCs originally bound to beta93 cysteine residues of oxyHb, and nitrite conversion and storage of nitric oxide by Hb at the site of ferric (Fe3+) and ferrous (Fe2+) Hb. Within extravascular cells, the global regulator of oxygen homeostasis is hypoxia-inducible factor-1 (HIF-1). This transcriptional factor is tightly regulated by O-2 and cellular redox-sensitive mechanisms. HIF-1 activation is responsible for the up-regulation of proteins, which increase O-2 supply. We believe that there are important and yet unexplored mechanisms by which RBCs can directly or indirectly communicate via redox intermediates with extravascular sites as part of the global O-2 sensing mechanism. C1 US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, Bethesda, MD 20892 USA. RP US FDA, CBER, NIH, Lab Biochem & Vasc Biol,Div Hematol, Bldg 29,Room 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM alayash@cber.fda.gov NR 86 TC 21 Z9 21 U1 1 U2 3 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD DEC PY 2004 VL 6 IS 6 BP 1000 EP 1010 DI 10.1089/1523086042259814 PG 11 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 869XZ UT WOS:000225019300007 PM 15548897 ER PT J AU Elkins, CA Mullis, LB AF Elkins, CA Mullis, LB TI Bile-mediated aminoglycoside sensitivity in Lactobacillus species likely results from increased membrane permeability attributable to cholic acid SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ANTIBIOTIC SUSCEPTIBILITY; JOHNSONII 100-100; SUBSTRATE-SPECIFICITY; ESCHERICHIA-COLI; SALT HYDROLASE; RESISTANCE; BACTERIA; PROBIOTICS; SAFETY; GENES AB Few studies have been conducted on antimicrobial resistance in lactobacilli, presumably because of their nonpathogenic nature as anaerobic commensals. We assessed resistance in 43 type strains and isolates representing 14 species by using agar disk diffusion and MIC analysis in MRS medium. Most noteworthy were two general phenotypes displayed by nearly every strain tested: (i) they were more susceptible (up to 256-fold in some cases) to the deconjugated bile acid cholic acid than to the conjugate taurocholic or taurodeoxycholic acid, and (ii) they became susceptible to aminoglycosides when assayed on agar medium containing 0.5% fractionated bovine bile (ox gall). Two-dimensional MIC analyses of one representative strain, Lactobacillus plantarum WCFS1, at increasing concentrations of ox gall (0 to 30.3 mg/ml) displayed corresponding decreases in resistance to all of the aminoglycosides tested and ethidium bromide. This effect was clinically relevant, with the gentamicin MIC decreasing from > 1,000 to 4 mug/ml in just 3.8 mg of ox gall per ml. In uptake studies at pH 6.5, [G-H-3]gentamicin accumulation increased over control levels when cells of this strain were exposed to bile acids or reserpine but not when they were exposed to carbonyl cyanide m-chlorophenylhydrazone. The effect was dramatic, particularly with cholic acid, increasing up to 18-fold, whereas only modest increases, 3-and 5-fold, could be achieved with taurocholic acid and ox gall, respectively. Since L. plantarum, particularly strain WCFS1, is known to encode bile salt hydrolase (deconjugation) activity, our data indicate that mainly cholic acid, but not taurocholic acid, effectively permeabilizes the membrane to aminoglycosides. However, at pHs approaching neutral conditions in the intestinal lumen, aminoglycoside resistance due to membrane impermeability may be complemented by a potential efflux mechanism. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. 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 NR 49 TC 38 Z9 39 U1 1 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD DEC PY 2004 VL 70 IS 12 BP 7200 EP 7209 DI 10.1128/AEM.70.12.7200-7209.2004 PG 10 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 879LM UT WOS:000225719300033 PM 15574918 ER EF