FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Kawakami, K Kawakami, M Husain, SR Puri, RK AF Kawakami, K Kawakami, M Husain, SR Puri, RK TI Targeting interleukin-4 receptors for effective pancreatic cancer therapy SO CANCER RESEARCH LA English DT Article ID PSEUDOMONAS EXOTOXIN; MONOCLONAL-ANTIBODY; COLORECTAL-CANCER; CARCINOMA-CELLS; MANAGEMENT; PROTEIN; 4-TOXIN; TOXIN AB We demonstrate that pancreatic cancer tissues express receptors for interleukin (IL)-4 in situ at high density. Using the approach of selective receptor targeting, we have tested the efficacy of a recombinant cytotoxin IL4-Pseudomonas exotoxin A, which is composed of a targeting moiety (IL-4) and a mutated form of Pseudomonas exotoxin. Our results demonstrate that this molecule exerts vigorous antitumor activity against human pancreatic tumors implanted s.c. in immunodeficient animals. Sixty percent of animals treated with intratumoral injections of IL4-Pseudomonas exotoxin A experienced complete disappearance of established tumors. Animals with pancreatic tumors implanted orthotopically exhibited prolonged survival that was significantly greater by comparison with untreated animals. Thus, IL-4 receptor-targeted cytotoxin represents a potent agent that may provide an effective therapy for pancreatic cancer. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therap, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therap, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 20 TC 32 Z9 33 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JUL 1 PY 2002 VL 62 IS 13 BP 3575 EP 3580 PG 6 WC Oncology SC Oncology GA 569BL UT WOS:000176579500001 PM 12097255 ER PT J AU Klinman, DM Zheng, M Gierynska, M Rouse, BT AF Klinman, DM Zheng, M Gierynska, M Rouse, BT TI DNA containing bioactive CpG motifs promote angiogenesis SO DRUG NEWS & PERSPECTIVES LA English DT Article ID NECROSIS-FACTOR-ALPHA; BACTERIAL-DNA; IMMUNOSTIMULATORY DNA; STROMAL KERATITIS; INTERFERON-GAMMA; DENDRITIC CELLS; B-CELL; ACTIVATION; RESPONSES; ADJUVANTS AB Unmethylated CpG motifs exist at high frequency in the genomes of many bacteria and viruses, including the herpes simplex virus (HSV). These motifs are intrinsically bioactive, stimulating cells of both the immune and central nervous systems. Researchers explored the notion that DNA containing CpG motifs could mediate additional effects in vivo, focusing on whether CpG DNA could directly or indirectly promote the formation of new blood vessels (angiogenesis). They found that both purified HSV DNA and synthetic oligodeoxynucleotides (ODN) containing CpG motifs stimulated new blood vessel formation. This effect was associated with the production of vascular endothelial growth factor (VEGF) and was prevented by the co-administration of anti-VEGF antibodies Results of the study suggest that bioactive CpG motifs induce the production of VEGF, thereby promoting angiogenesis, and raise the possibility that CpG ODN may be of benefit in clinical states that require revascularization. (C) 2002 Prous Science All rights reserved. C1 US FDA, Sect Retroviral Immunol, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA. NR 26 TC 7 Z9 7 U1 0 U2 0 PU PROUS SCIENCE, SA PI BARCELONA PA PO BOX 540, PROVENZA 388, 08025 BARCELONA, SPAIN SN 0214-0934 J9 DRUG NEWS PERSPECT JI Drug News Perspect. PD JUL-AUG PY 2002 VL 15 IS 6 BP 358 EP 363 DI 10.1358/dnp.2002.15.6.840034 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 595AG UT WOS:000178084200008 ER PT J AU Lolova, D Tabacova, S Petrov, I AF Lolova, D Tabacova, S Petrov, I TI Air pollution and children's exposure to lead and cadmium in a smelter region SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 Natl Ctr Hyg, Sofia, Bulgaria. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 540 BP S177 EP S177 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600508 ER PT J AU Mendell, MJ Naco, GM Wilcox, TG Sieber, WK AF Mendell, MJ Naco, GM Wilcox, TG Sieber, WK TI Lower respiratory symptom-based outcome definitions to assess risk factors for microbiologic contamination in office buildings SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley, CA 94720 USA. NIOSH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 271 BP S128 EP S128 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600260 ER PT J AU Tabacova, S Vukov, M AF Tabacova, S Vukov, M TI Poor birth outcomes in association with environmental factors in Bulgaria SO EPIDEMIOLOGY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. Natl Inst Hlth Informat, Sofia, Bulgaria. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD JUL PY 2002 VL 13 IS 4 MA 933 BP S248 EP S248 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 565PL UT WOS:000176378600861 ER PT J AU Dean-Ross, D Moody, J Cerniglia, CE AF Dean-Ross, D Moody, J Cerniglia, CE TI Utilization of mixtures of polycyclic aromatic hydrocarbons by bacteria isolated from contaminated sediment SO FEMS MICROBIOLOGY ECOLOGY LA English DT Article DE polycyclic aromatic hydrocarbon; biodegradation; mixture; bioremediation; anthracene; pyrene; fluoranthene; phenanthrene; sediment; cometabolism ID SP STRAIN PYR-1; MYCOBACTERIUM SP; ENVIRONMENTAL ASPECTS; DEGRADATION; BIOREMEDIATION; BIODEGRADATION; FLUORANTHENE; PHENANTHRENE; ANTHRACENE; METABOLISM AB The ability of sediment bacteria to utilize polycyclic aromatic hydrocarbons (PAHs) when present as components of mixtures was investigated. One strain, identified as Mycobacterium flavescens, could utilize fluoranthene in the presence of pyrene, although utilization of pyrene was slower in the presence of fluoranthene than in its absence. The second strain, a Rhodococcus species, could utilize fluoranthene in the presence of anthracene, although the presence of fluoranthene slowed the rate of utilization of anthracene. Cometabolism of fluoranthene in these strains was confirmed by the isolation of metabolites of fluoranthene and by kinetic analysis of the rate of utilization of the growth substrate in the presence of fluoranthene. In both strains, metabolism of fluoranthene occurred oil the fused ring of the fluoranthene molecule, producing 9-fluorenone-1-carboxylic acid. In the Rhodococcus sp., a second metabolite, a-(carboxymethylene)fluorene-1-carboxylic acid, was identified, indicating that this strain has the capacity to metabolize fluoranthene via ortho as well as meta cleavage. The presence of PAHs in a mixture produces interactive effects which can either increase or decrease the rate of utilization of individual PAHs, results which need to be taken into account when estimating rates of degradation in contaminated environments. (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 Indiana Univ Purdue Univ, Dept Biol, Ft Wayne, IN 46805 USA. US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Dean-Ross, D (reprint author), Indiana Univ Purdue Univ, Dept Biol, Ft Wayne, IN 46805 USA. NR 36 TC 102 Z9 122 U1 5 U2 29 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-6496 J9 FEMS MICROBIOL ECOL JI FEMS Microbiol. Ecol. PD JUL PY 2002 VL 41 IS 1 BP 1 EP 7 AR PII S0168-6496(02)00198-8 PG 7 WC Microbiology SC Microbiology GA 571ZR UT WOS:000176749500001 PM 19709233 ER PT J AU Trucksess, MW Dombrink-Kurtzman, MA Tournas, VH White, KD AF Trucksess, MW Dombrink-Kurtzman, MA Tournas, VH White, KD TI Occurrence of aflatoxins and fumonisins in Incaparina from Guatemala SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE mycotoxins; aflatoxins; fumonisins; Incaparina; moulds; corn; cottonseed ID CORN AB The occurrence of aflatoxins and fumonisins in Incaparina was investigated. Incaparin a is a mixture of corn and cottonseed flour with added vitamins, minerals and a preservative. It has been marketed as a high-protein food supplement, particularly for children on protein-deficient diets. According to estimates, 80% of Guatemalan children in their first year are given Incaparin a to provide an adequate diet. Eight samples of Incaparin a manufactured in Guatemala were collected. Five were from three different geographical locations in the USA and three were from Guatemala. Seven were examined for fungal contamination and analysed for aflatoxins and fumonisins. Aspergillus flavus was the predominant fungus in all samples purchased in the USA and in one sample purchased from Guatemala, whereas Fusarium verticillioides was present in only two samples (one from the USA and one from Guatemala). All samples contained aflatoxins, ranging from 3 to 214 ng g(-1) and <2 to 32 ng g(-1) for aflatoxin B-1 and aflatoxin B-2, respectively; and one sample contained aflatoxin G(1) (7 ng g(-1)). Total aflatoxins present ranged from 3 to 244 ng g(-1). All samples contained fumonisins, ranging from 0.2 to 1.7 μg g(-1), <0.1 to 0.6 mug g(-1), and <0.1 to 0.2 μg g(-1) for fumonisins B-1, fumonisin B-2, and fumonisin B-3, respectively. Total fumonisins present ranged from 0.2 to 2.2 μg g(-1). The identity of aflatoxin B-1 was confirmed using both the chemical derivatization method and liquid chromatographic (LC)/mass spectrometric (MS) analysis. Appropriate regulatory action was recommended for the import of Incaparina and has been in effect since 22 December 1998. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. USDA, Natl Ctr Agr Utilizat Res, Agr Res Serv, Peoria, IL 61604 USA. RP Trucksess, MW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 18 TC 16 Z9 24 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD JUL PY 2002 VL 19 IS 7 BP 671 EP 675 DI 10.1080/02652030210125092 PG 5 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 572BR UT WOS:000176754000006 PM 12113662 ER PT J AU Repique, CJ Li, A Collins, FM Morris, SL AF Repique, CJ Li, A Collins, FM Morris, SL TI DNA immunization in a mouse model of latent tuberculosis: Effect of DNA vaccination on reactivation of disease and on reinfection with a secondary challenge SO INFECTION AND IMMUNITY LA English DT Article ID HEAT-SHOCK PROTEINS; EXOGENOUS REINFECTION; MYCOBACTERIUM-TUBERCULOSIS; PERSISTENT TUBERCULOSIS; MURINE MODEL; T-CELLS; VACCINES; IMMUNOGENICITY; MICE; EXPRESSION AB Individuals who are latently infected with Mycobacterium tuberculosis can develop active disease via either endogenous reactivation of the latent bacilli or exogenous reinfection with a second mycobacterial strain. In this study, we investigated whether immunization with a tuberculosis DNA vaccine cocktail that induces significant protective responses in mice could prevent reactivation of disease in a murine latent-tuberculosis model. In addition, we assessed whether DNA vaccination could retard the growth of a secondary aerogenic infection with M. tuberculosis (exogenous reinfection) in latently infected mice. In the reactivation studies, administration of the DNA vaccine combination did not prevent recrudescence of the latent infection after injection of dexamethasone. Moreover, for the reinfection experiments, only a modest decrease in the growth of a secondary M. tuberculosis challenge in DNA-vaccinated animals, compared to controls, was observed 14 and 28 days after the reinfection of previously exposed mice. Interestingly, although proliferation of the secondary challenge was reduced significantly in a nonvaccinated chronic-infection group relative to the naive controls, the number of bacilli still increased by 500-fold 1 month after the secondary challenge in mice with active tuberculosis. These results indicate that novel immunotherapeutic approaches will be required to prevent reactivation of infection or reinfection of individuals with latent tuberculosis. C1 US FDA, Ctr Biol Evaluat & Res, LMDCI, OVRR, Bethesda, MD 20892 USA. RP Morris, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, LMDCI, OVRR, HFM-431,Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 29 TC 45 Z9 51 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 JUL PY 2002 VL 70 IS 7 BP 3318 EP 3323 DI 10.1128/IAI.70.7.3318-3323.2002 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 564ET UT WOS:000176302600002 PM 12065468 ER PT J AU Berry, DS Lynn, F Lee, CH Frasch, CE Bash, MC AF Berry, DS Lynn, F Lee, CH Frasch, CE Bash, MC TI Effect of O acetylation of Neisseria meningitidis serogroup A capsular polysaccharide on development of functional immune responses SO INFECTION AND IMMUNITY LA English DT Article ID C MENINGOCOCCAL POLYSACCHARIDES; PROTEIN CONJUGATE VACCINE; GROUP-A; IMMUNOLOGICAL PROPERTIES; ANTIBODY-RESPONSE; EPIDEMIC; INFANTS; STANDARDIZATION; IMMUNOGENICITY; CHILDREN AB The importance of O-acetyl groups to the immunogenicity of Neisseria meningitidis serogroup A polysaccharide (PS) was examined in studies using human sera and mouse immunization. In 17 of 18 postimmunization human sera, inhibition enzyme-linked immunosorbent assay indicated that the majority of antibodies binding to serogroup A PS were specific for epitopes involving O-acetyl groups. Studies with mice also showed an essential role for O-acetyl groups, where serum bactericidal titers following immunization with de-O-acetylated (de-O-Ac) conjugate vaccine were at least 32-fold lower than those following immunization with O-Ac PS-conjugate vaccine and 4-fold lower than those following immunization with native capsular PS. Inhibition studies using native and de-O-Ac PS confirmed the specificity of marine antibodies to native PS. The dramatic reduction in immunogenicity associated with removal of O-acetyl groups indicates that 0 acetylation is essential to the immunogenic epitopes of serogroup A PS. Since levels of bactericidal antibodies are correlated with protection against disease, O-acetyl groups appear to be important in protection. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat Infect Dis, Bethesda, MD 20814 USA. RP Bash, MC (reprint author), Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, HFM-428,1401 Rockville Pike, Rockville, MD 20852 USA. NR 31 TC 78 Z9 82 U1 0 U2 5 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2002 VL 70 IS 7 BP 3707 EP 3713 DI 10.1128/IAI.70.7.3707-3713.2002 PG 7 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 564ET UT WOS:000176302600047 PM 12065513 ER PT J AU Coban, C Ishii, KJ Sullivan, DJ Kumar, N AF Coban, C Ishii, KJ Sullivan, DJ Kumar, N TI Purified malaria pigment (hemozoin) enhances dendritic cell maturation and modulates the Isotype of antibodies induced by a DNA vaccine SO INFECTION AND IMMUNITY LA English DT Article ID FALCIPARUM-INFECTED ERYTHROCYTES; HUMAN MONOCYTES; BETA-HEMATIN; IMMUNITY; ANTIGEN; IMMUNIZATION; PHAGOCYTOSIS; INDUCTION AB Hemozoin (malaria pigment) has been implicated in the modulation of immune responses during malaria infection. This study was designed to evaluate the effect of purified hemozoin on the in vitro activation of myeloid dendritic cells. Our study also revealed that in addition to enhancing the maturation of dendritic cells, hemozoin also greatly promotes immunoglobulin G2a antibody responses when coadministered with a DNA vaccine plasmid encoding Pfs25, a Plasinodium falciparum transmission-blocking antigen. C1 Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Malaria Res Inst, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. RP Kumar, N (reprint author), Johns Hopkins Univ, Bloomberg Sch Publ Hlth, Dept Mol Microbiol & Immunol, Malaria Res Inst, Baltimore, MD 21205 USA. RI Coban, Cevayir/B-2129-2012; Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 FU NIAID NIH HHS [AI 47089, R01 AI045774, R01 AI047089] NR 27 TC 44 Z9 50 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUL PY 2002 VL 70 IS 7 BP 3939 EP 3943 DI 10.1128/IAI.70.7.3939-3943.2002 PG 5 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 564ET UT WOS:000176302600073 PM 12065539 ER PT J AU Gobburu, JVS Sekar, VJ AF Gobburu, JVS Sekar, VJ TI Application of modeling and simulation to integrate clinical pharmacology knowledge across a new drug application SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE modeling; simulation; regulatory; dosing adjustments ID PHARMACOKINETICS; PHARMACODYNAMICS AB Typical drug development includes few studies to find the right dose/dosing regimen and several other bridging studies evaluating various prognostic factors (e.g.: co-administration of other drugs, organ failure). The drug sponsors and the regulators use this information to formulate labeling instructions for safe and effective use of the drug. In the current article, modeling and simulation are proposed as tools to integrate the knowledge from the effectiveness/safety studies and the bridging studies. Simulations allow exploring the impact of various prognostic factors on the effectiveness and safety. The concept is exemplified using the new drug application of an anti-migraine drug. The exercise aids in integrating all the knowledge across the drug development to suggest rationale dosing strategies; effectively communicating the impact of the prognostic factors to the clinicians/regulators; and protect against any intellectual losses due to development team changes. C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Gobburu, JVS (reprint author), 1451 Rockville Pike,Room 5088,HFD-860, Rockville, MD 20852 USA. NR 12 TC 9 Z9 9 U1 0 U2 0 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD JUL PY 2002 VL 40 IS 7 BP 281 EP 288 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 578KU UT WOS:000177117200001 PM 12139204 ER PT J AU Wysowski, DK Swann, J AF Wysowski, DK Swann, J TI Use of inhalant medications with and without chlorofluorocarbon propellants in the United States, 1996-2000 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE chlorofluorocarbons; inhalant medications; bronchodilators; nasal steroids; corticosteroid; asthma; allergy rhinitis; chronic obstructive pulmonary disease ID ULTRAVIOLET-RADIATION; OZONE DEPLETION; HEALTH C1 US FDA, Div Drug Risk Evaluat 1, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Div Drug Risk Evaluat 1, Off Drug Safety, Ctr Drug Evaluat & Res, HFD-430,Parklawn Bldg,Room 15B-08, Rockville, MD 20857 USA. NR 12 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD JUL PY 2002 VL 110 IS 1 BP 51 EP 53 DI 10.1067/mai.2002.125001 PG 3 WC Allergy; Immunology SC Allergy; Immunology GA 574CF UT WOS:000176870300011 PM 12110819 ER PT J AU Cook, KK Grundel, E Jenkins, M Mitchell, GV AF Cook, KK Grundel, E Jenkins, M Mitchell, GV TI Measurement of cis and trans isomers of vitamin K-1 in rat tissues by liquid chromatography with a C-30 column SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PHYLLOQUINONE CONCENTRATIONS; CHEMICAL-REDUCTION; CAROTENOID ISOMERS; STATIONARY-PHASE; INFANT FORMULAS; SERUM; MILK; PLASMA AB The purpose of this study was to validate a method for measuring vitamin K isomers in rat tissues by liquid chromatography (LC) with fluorescence detection after simple solvent extraction. This method uses separation on a C-30 column, followed by zinc reduction and fluorescence measurement (243 nm, excitation; 430 nm, emission) to detect and quantitate vitamin K isomers. We were able to separate cis- and trans-vitamin K-1 in methylene chloride extracts of homogenized rat livers and in hexane extracts of rat plasma. Tissue extracts were evaporated and rediluted with tetrahydrofuran-methanol (1 + 1) or methanol before being injected under isocratic conditions onto the LC column. Liver tissue of Fischer 344 rats fed a vitamin K-1-containing diet ad libitum contained approximately 20 and 60 ng/g cis- and trans-vitamin K-1, respectively. Mean recoveries of vitamin K-1 isomers from spiked liver were 92 +/- 11 % for cis-vitamin K-1 and 106 +/- 5% for trans-vitamin K-1. We recovered 96 +/- 8% of trans-vitamin K, added at 1, 3, and 6 ng/mL to plasma (containing an endogenous level of 4 ng/g) from the same rats; we recovered 112 5% when trans-vitamin K, was added to human serum (National Institute of Standards and Technology Standard Reference Material 968C). This direct method shows significant potential for the selective measurement of vitamin K, isomers in tissues. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Laurel, MD 20708 USA. RP Cook, KK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 28 TC 1 Z9 1 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 JUL-AUG PY 2002 VL 85 IS 4 BP 832 EP 840 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 578EX UT WOS:000177105400004 PM 12180675 ER PT J AU Al-Khaldi, SF Martin, SA Rasooly, A Evans, JD AF Al-Khaldi, SF Martin, SA Rasooly, A Evans, JD TI DNA microarray technology used for studying foodborne pathogens and microbial habitats: minireview SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ESCHERICHIA-COLI O157-H7; POLYMERASE-CHAIN-REACTION; GENE-EXPRESSION; BACTERIAL PATHOGENESIS; MULTIPLEX PCR; RFB LOCUS; GENOMICS; MALATE; HYBRIDIZATION; METABOLISM AB Microarray analysis is an emerging technology that has the potential to become a leading trend in bacterial identification in food and feed improvement. The technology uses fluorescent-labeled probes amplified from bacterial samples that are then hybridized to thousands of DNA sequences immobilized on chemically modified glass slides. The whole gene or open reading frame(s) is represented by a polymerase chain reaction fragment of double-strand DNA, approximately 1000 base pair (bp) or 20-70 bp single-strand oligonucleotides. The technology can be used to identify bacteria and to study gene expression in complex microbial populations, such as those found in food and gastrointestinal tracts. Data generated by microarray analysis can be potentially used to improve the safety of our food supply as well as ensure the efficiency of animal feed conversion to human food, e.g., in meat and milk production by ruminants. This minireview addresses the use of microarray technology in bacterial identification and gene expression in different microbial systems and in habitats containing mixed populations of bacteria. C1 US FDA, CFSAN, Div Microbiol Studies, College Pk, MD 20740 USA. Univ Georgia, Dept Anim & Dairy Sci, Athens, GA 30602 USA. USDA, Richard B Russell Agr Res Ctr, Athens, GA 30604 USA. RP Al-Khaldi, SF (reprint author), US FDA, CFSAN, Div Microbiol Studies, HFS-517,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 36 TC 46 Z9 51 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 JUL-AUG PY 2002 VL 85 IS 4 BP 906 EP 910 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 578EX UT WOS:000177105400015 PM 12180686 ER PT J AU Ware, GM AF Ware, GM TI Method validation study of hypoglycin A determination in ackee fruit SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A study was conducted to validate the performance characteristics of a published method entitled "Reversed-Phase Liquid Chromatographic Detection of Hypoglycin A in Canned Ackee Fruit Sample." Hypoglycin A (HG-A) was extracted from ackee fruit with 80% ethanol-water, centrifuged, and filtered; the sample extract then was reacted with phenylisothiocyanate. HG-A was separated by reversed-phase chromatography as the phenyl-thiocarbamyl derivative and detected at the low nanogram level using a UV detector at 254 nm. A study was conducted to determine recovery of HG-A added to a control ackee fruit sample. A control sample containing a low level of HG-A was spiked with 403.2, 201.6, 96.8, and 48.4 mug HG-A/g ackee fruit, respectively. Twelve replicates were analyzed for each spike level. The mean percent recovery standard deviation for spike levels 403.2, 201.6, 96.8, and 48.4 mug HG-A/g were 94.37 +/- 1.27, 99.12 +/- 2.09, 107.95 +/- 5.42, and 129.18 +/- 15.32 %, respectively. The percent coefficient of variation (%CV) for spike levels 403.2, 201.6, 96.8, and 48.4 mug HG-A/g were 1.35, 2.11, 5.02, and 11.86%, respectively. The recovery data indicate that HG-A can be recovered from ackee fruit with excellent accuracy and precision. Precision data obtained from replicate assays of ackee fruit naturally contaminated with low, medium, and high HG-A levels is presented. C1 US FDA, Se Reg Lab, Atlanta, GA 30309 USA. RP Ware, GM (reprint author), US FDA, Se Reg Lab, 60 8th St, Atlanta, GA 30309 USA. NR 0 TC 7 Z9 7 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 JUL-AUG PY 2002 VL 85 IS 4 BP 933 EP 937 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 578EX UT WOS:000177105400019 PM 12180690 ER PT J AU Chizhikov, V Wagner, M Ivshina, A Hoshino, Y Kapikian, AZ Chumakov, K AF Chizhikov, V Wagner, M Ivshina, A Hoshino, Y Kapikian, AZ Chumakov, K TI Detection and genotyping of human group A rotaviruses by oligonucleotide microarray hybridization SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; DNA; EXPRESSION; MICROCHIPS; IDENTIFICATION; IMMOBILIZATION; SEROTYPES; SEQUENCE; ARRAYS; GEL AB A rapid and reliable method for the identification of five clinically relevant G genotypes (G1 to G4 and G9) of human rotaviruses based on oligonucleotide microarray hybridization has been developed. The genotype-specific oligonucleotides immobilized on the surface of glass slides were selected to bind to the multiple target regions within the VP7 gene that are highly conserved among individual rotavirus genotypes. Rotavirus cDNA was amplified in a PCR with primers common to all group A rotaviruses. A second round of nested PCR amplification was performed in the presence of indodicarbocyanine-dCTP and another pair of degenerate primers also broadly specific for all genotypes. The use of one primer containing 5'-biotin allowed us to prepare fluorescently labeled single-stranded hybridization probe by binding of another strand to magnetic beads. The identification of rotavirus genotype was based on hybridization with several individual genotype-specific oligonucleotides. This approach combines the high sensitivity of PCR with the selectivity of DNA-DNA hybridization. The specificity of oligonucleotide microchip hybridization was evaluated by testing 20 coded rotavirus isolates from different geographic areas for which genotypes were previously determined by conventional methods. Analysis of the coded specimens showed that this microarray-based method is capable of unambiguous identification of all rotavirus strains. Because of the presence of random mutations, each individual virus isolate produced a unique hybridization pattern capable of distinguishing different isolates of the same genotype and, therefore, subgenotype differentiation. This strain information indicates one of several advantages that microarray technology has over conventional PCR techniques. C1 US FDA, Ctr Biol Evaluat & Res, Lab Method Dev, Kensington, MD 20895 USA. NIAID, Infect Dis Lab, NIH, Bethesda, MD 20892 USA. RP Chizhikov, V (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Method Dev, HFM-470,1401 Rockville Pike, Rockville, MD 20852 USA. NR 26 TC 137 Z9 164 U1 0 U2 8 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 JUL PY 2002 VL 40 IS 7 BP 2398 EP 2407 DI 10.1128/JCM.40.7.2398-2407.2002 PG 10 WC Microbiology SC Microbiology GA 569MH UT WOS:000176605800014 PM 12089254 ER PT J AU Ajayi, FO Wilcox, DF Uhl, K Quinn, J AF Ajayi, FO Wilcox, DF Uhl, K Quinn, J TI Advanced science education in the regulatory arena: The Center for Drug Evaluation and research experience at the Food and Drug Administration SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article AB A challenge faced by the Center for Drug Evaluation and Research (CDER) in effectively carrying out its mission requires it to integrate the disciplines of science, medicine, law, and public policy. One way to do that is by ensuring a highly trained multidisciplinary staff, The CDER has been able to meet this requirement by identifying the core competencies needed to accomplish its mission. The use of a competency-based training model in the planning, development, and delivery of its advanced scientific education program allows CDER staff to maintain current knowledge as well as prepare for future scientific education needs, The CDER educational model could be readily adopted to meet the educational needs of other organizations. (C) 2002 the American College of Clinical Pharmacology. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Ajayi, FO (reprint author), Procter & Gamble Pharmaceut Inc, Clin Pharmacol & Pharmacokinet Dept, Mason, OH 45040 USA. NR 5 TC 0 Z9 0 U1 0 U2 1 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUL PY 2002 VL 42 IS 7 BP 711 EP 717 DI 10.1177/009127002401102650 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 565FE UT WOS:000176358000002 PM 12092738 ER PT J AU Lathers, CM AF Lathers, CM TI Educational issues in clinical pharmacology: Who are our audiences and what are their specialized needs? One specialized need: "Understanding the role of veterinary medicine in public health" SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID ILLNESS; FUTURE; RISK; EPIDEMIOLOGY; EXPERIENCE; RESISTANCE; MECHANISMS; INFECTION; OUTBREAK; DRUGS AB When considering educational issues and the need to update the curriculum for clinical pharmacologists for the new millennium, a number of questions must be raised. Who are our audiences? What are the specialized needs? This educational article identifies the audience, which includes those with diverse degrees such as MDs, PhDs, PharmDs, RNs, DVMs, and other non-AID prescribers working in academia, industry, clinical research organizations, and governments in multifaceted disciplines requiring a knowledge base of physiology, pharmacology, biochemistry, anatomy, microbiology, pathology, medicine, and the drug development process of preclinical and clinical studies complete with protocols, pharmacokinetics, and statistics. One specialized current educational issue for clinical pharmacologists to understand is the impact of animal therapeutic and subtherapeutic use of antimicrobials on antibiotic use in human medicine. (C) 2002 the American College of Clinical Pharmacology. C1 US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. RP Lathers, CM (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. NR 42 TC 0 Z9 0 U1 0 U2 2 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUL PY 2002 VL 42 IS 7 BP 718 EP 730 DI 10.1177/009127002401102669 PG 13 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 565FE UT WOS:000176358000003 PM 12092739 ER PT J AU Hawryluk, T Hirshfield, I AF Hawryluk, T Hirshfield, I TI A superantigen bioassay to detect staphylococcal enterotoxin A SO JOURNAL OF FOOD PROTECTION LA English DT Article ID AUREUS ENTEROTOXIN; LYMPHOCYTES-T; ASSAY; CELLS; TOXICITY AB Current detection methods for enterotoxins of Staphylococcus aureus are labor intensive and limited in sensitivity. Furthermore, these immunochemical protocols fail to adequately detect heat-treated enterotoxins. Staphylococcal enterotoxins cause severe gastrointestinal illness at relatively low concentrations and retain toxigenicity even after heat treatment. Presented here is a novel method to detect staphylococcal enterotoxin A (SEA). This method is a bioassay that exploits SEA's activity as a superantigen in that it induces in cytotoxic T lymphocytes a cytotoxic response against SEA-bound Raji cells. Target cell death is assayed colorimetrically with the CytoTox 96 cell lysis detection kit. In the experiments presented here, this bioassay was also able to detect heat-treated SEA, albeit with a slight compromise in sensitivity. This system detected SEA at picomolar concentrations. Because of the sensitivity of this assay, it is conceivable that it could be incorporated into current detection methods as a confirmatory test. C1 US FDA, NE Reg Lab, Microbiol Sci Branch, Jamaica, NY 11433 USA. St Johns Univ, Dept Biol Sci, Jamaica, NY 11439 USA. RP Hawryluk, T (reprint author), US FDA, NE Reg Lab, Microbiol Sci Branch, Jamaica, NY 11433 USA. NR 18 TC 3 Z9 3 U1 0 U2 1 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUL PY 2002 VL 65 IS 7 BP 1183 EP 1187 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 570PW UT WOS:000176667500020 PM 12117256 ER PT J AU Jedynak, JP Ali, SF Haycock, JW Hope, BT AF Jedynak, JP Ali, SF Haycock, JW Hope, BT TI Acute administration of cocaine regulates the phosphorylation of serine-19,-31 and-40 in tyrosine hydroxylase SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE amygdala; caudate; dopamine; nucleus accumbens; ventral tegmental area ID PROTEIN KINASE-II; RAT-BRAIN; CHROMAFFIN CELLS; DOPAMINE RELEASE; NERVE-TERMINALS; ACTIVATION; BIOSYNTHESIS; SEROTONIN; SERINE-31; RECEPTORS AB Acute cocaine can inhibit catecholamine biosynthesis by regulating the enzymatic activity of tyrosine hydroxylase via alterations in the phosphorylation state of the enzyme. The mechanisms underlying acute cocaine-dependent regulation of tyrosine hydroxylase phosphorylation have not been determined. In this study, 0, 15 or 30 mg/kg cocaine was administered intraperitoneally to rats and the phosphorylation state of tyrosine hydroxylase in the brain was examined using antibodies specific for the phosphorylated forms of serine-19, -31 and -40 in tyrosine hydroxylase. In the caudate and nucleus accumbens, cocaine dose-dependently decreased the levels of phosphorylated serine-19, -31 and -40. In the ventral tegmental area, the levels of phosphorylated serine-19, but not serine-31 and -40, were decreased by 15 and 30 mg/kg cocaine. In the amygdala, the levels of phosphorylated serine-19, but not serine-31 or -40, were decreased. The functional effects of these alterations in phosphorylation state were assessed by measuring tyrosine hydroxylase activity in vivo (accumulation of DOPA after administration of the decarboxylase inhibitor NSD-1015). Acute administration of 30 mg/kg cocaine significantly decreased l-DOPA production in caudate and accumbens but not in amygdala. These data suggest that the phosphorylation of serine-31 or -40, but not serine-19, is involved in the regulation of tyrosine hydroxylase activity by acute cocaine. C1 NIDA, Behav Neurosci Branch, Intramural Res Program, Baltimore, MD 21224 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Louisiana State Univ, Hlth Sci Ctr, Dept Biochem & Mol Biol, New Orleans, LA USA. RP Hope, BT (reprint author), NIDA, Behav Neurosci Branch, Intramural Res Program, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. RI Hope, Bruce/A-9223-2010 OI Hope, Bruce/0000-0001-5804-7061 NR 35 TC 19 Z9 19 U1 0 U2 2 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUL PY 2002 VL 82 IS 2 BP 382 EP 388 DI 10.1046/j.1471-4159.2002.00982.x PG 7 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 570HQ UT WOS:000176653200019 PM 12124439 ER PT J AU Wang, LL Gaigalas, AK Abbasi, F Marti, GE Vogt, RF Schwartz, A AF Wang, LL Gaigalas, AK Abbasi, F Marti, GE Vogt, RF Schwartz, A TI Quantitating fluorescence intensity from fluorophores: Practical use of MESF values SO JOURNAL OF RESEARCH OF THE NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY LA English DT Article DE emission spectrum matching; extinction coefficient; fluorescein; lymphocyte; MESF value; microbead; pH; quantitative flow cytometry ID FLOW-CYTOMETRY; T-CELLS; SCATTERING; EXPRESSION; SEPARATION AB The present work uses fluorescein as the model fluorophore and points out critical steps in the use of MESF (Molecules of Equivalent Soluble Fluorophores) values for quantitative flow cytometric measurements. It has been found that emission spectrum matching between a reference solution and an analyte and normalization by the corresponding extinction coefficient are required for quantifying fluorescence signals using flow cytometers. Because of the use of fluorescein, the pH value of the medium is also critical for accurate MESF assignments. Given that the emission spectrum shapes of microbead suspensions and stained biological cells are not significantly different, the percentage of error due to spectrum mismatch is estimated. We have also found that the emission spectrum of a microbead with a seven-methylene linker between the fluorescein and the bead surface (bead7) provides the best match with the spectra from biological cells. Therefore, bead7 is potentially a better calibration standard for flow cytometers than the existing one that is commercially available and used in the present study. C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. CDC, Div Sci Lab, Atlanta, GA 30341 USA. Ctr Quantitat Cytometry, San Juan, PR 00919 USA. RP Wang, LL (reprint author), Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. EM lili.wang@nist.gov; adolfas.gaigalas@nist.gov NR 17 TC 38 Z9 38 U1 3 U2 17 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 JUL-AUG PY 2002 VL 107 IS 4 BP 339 EP 353 DI 10.6028/jres.107.027 PG 15 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 589QB UT WOS:000177770600003 PM 27446735 ER PT J AU Kerr, LN Mailhot, SA Boivin, WS Hamilton, SL O'Malley, LG Boyd, SM Pierdominici, VJB Bushar, HF AF Kerr, LN Mailhot, SA Boivin, WS Hamilton, SL O'Malley, LG Boyd, SM Pierdominici, VJB Bushar, HF TI Use of Surfactants in condom water leak testing SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE condoms; water leak test; surfactant; defect detection; contact angle ID LATEX CONDOMS AB This paper identifies an appropriate surfactant solution to improve the defect detection rate of the ISO/FDA water leak test method for condoms. A surfactant solution and concentration are identified to optimize leakage testing of condoms, considering factors of safety, cost, reproducibility, and hole detection. Defect detection rates are compared using the ISO/FDA method with and without the surfactant solution. Micro-90(R) concentrated cleaning solution is selected as a suitable surfactant for water leak testing of condoms due to reliable formulation, low sudsing, low cost, and no disposal or toxicity problems. A concentration of 0.1% by volume optimizes the effectiveness of the solution while minimizing solution concentration. Detection rates of standardized defects are quantified for four condom types tested with and without surfactant solution. Use of surfactant solution in the ISO/FDA method increases the detection rates of all defect types and sizes in all the condom types tested. This increase is statistically significant for 10 (out of 48 possible) combinations of condom type, hole diameter, and hole location. C1 US FDA, Winchester, MA 01890 USA. Off Surveillance & Biometr, Ctr Dev & Radiol Hlth, Food & Drug Adm, Rockville, MD 20850 USA. RP Kerr, LN (reprint author), US FDA, Winchester, MA 01890 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0090-3973 J9 J TEST EVAL JI J. Test. Eval. PD JUL PY 2002 VL 30 IS 4 BP 313 EP 321 PG 9 WC Materials Science, Characterization & Testing SC Materials Science GA 577NV UT WOS:000177068800006 ER PT J AU Willy, ME Manda, B Shatin, D Drinkard, CR Graham, DJ AF Willy, ME Manda, B Shatin, D Drinkard, CR Graham, DJ TI A study of compliance with FDA recommendations for pemoline (Cylert (R)) SO JOURNAL OF THE AMERICAN ACADEMY OF CHILD AND ADOLESCENT PSYCHIATRY LA English DT Article DE attention-deficit/hyperactivity disorder; pemoline; labeling ID AUTOIMMUNE HEPATITIS; HEPATOTOXICITY; THERAPY AB Objective: To assess compliance with product labeling recommendations to use pemoline as second-line therapy for attention-deficit/hyperactivity disorder (ADHD) and to obtain baseline and biweekly liver enzyme tests. Method: Retrospective cohort study using administrative claims data to identify first-line therapies and liver enzyme tests among pemoline users between January 1, 1998, and March 31, 2000. Prescriptions for first-line therapy were searched for 90 days prior to the first pemoline claim. Liver enzyme testing (baseline and follow-up) was compared between two groups (the prerecommendation cohort October 1, 1998, to March 31, 1999, and the postrecommenclation cohort October 1, 1999, to March 31, 2000). Results: 1,308 patients received at least one pemoline prescription during the study period; 76% of patients less than or equal to20 years were male. ADHD was the claims-identified indication for 688 patients (52%). Despite the labeling recommendation for use as second-line therapy, only 237 ADHD patients (34%) received a first-line therapy prior to pemoline. Only 12% and 11% of the pre- and post-cohort patients, respectively, received baseline liver enzyme tests; 9% in the pre- and 12% in the postcohort received at least one liver enzyme follow-up test. Conclusions: Compliance with product labeling was low for both recommendations. Understanding the reasons for this finding could help improve risk management strategies. C1 US FDA, Off Drug Safety, Rockville, MD 20857 USA. UnitedHlth Grp, Ctr Hlth Care Policy & Evaluat, Minneapolis, MN USA. RP Willy, ME (reprint author), US FDA, Off Drug Safety, 5600 Fishers Lane,HFD 440,Room 15B-18, Rockville, MD 20857 USA. FU FDA HHS [FD-U-001643-01/02] NR 21 TC 25 Z9 25 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0890-8567 J9 J AM ACAD CHILD PSY JI J. Am. Acad. Child Adolesc. Psychiatr. PD JUL PY 2002 VL 41 IS 7 AR UNSP 0890-8567/02/4107-0785 DI 10.1097/00004583-200207000-00009 PG 6 WC Psychology, Developmental; Pediatrics; Psychiatry SC Psychology; Pediatrics; Psychiatry GA 566JQ UT WOS:000176424500009 PM 12108802 ER PT J AU Wilkes, JG Glover, KL Holcomb, M Rafii, F Cao, XX Sutherland, JB McCarthy, SA Letarte, S Bertrand, MJ AF Wilkes, JG Glover, KL Holcomb, M Rafii, F Cao, XX Sutherland, JB McCarthy, SA Letarte, S Bertrand, MJ TI Defining and using microbial spectral databases SO JOURNAL OF THE AMERICAN SOCIETY FOR MASS SPECTROMETRY LA English DT Article ID PYROLYSIS MASS-SPECTROMETRY; NOSOCOMIAL INFECTION; DIFFERENTIATION; MYCOBACTERIA; BACTERIA; COMPLEX AB This work shows how fingerprints of mass spectral patterns from microbial isolates are affected by variations in instrumental condition, by sample environment, and by sample handling factors. It describes a novel method by which pattern distortions can be mathematically corrected for variations in factors not amenable to experimental control. One uncontrollable variable is "between-batch" differences in culture media. Another, relevant for determination of noncultured extracts, is differences between the cells' environmental experience (e.g., starved environmental extracts versus cultured standards). The method suggests that, after a single growth cycle on a solid medium (perhaps, a selective one), pyrolysis MS spectra of microbial isolates can be algorithmically compensated and an unknown isolate identified using a spectral database defined by culture on a different (perhaps, nonselective) medium. This reduces identification time to as few as 24 h from sample collection. The concept also proposes a possible way to compensate certain noncultured, nonisolated samples (e.g., cells concentrated from urine or impacted from aerosol or semi-selectively extracted by immunoaffinity methods from heavily contaminated matrices) for identification within half an hour. Using the method, microbial mass spectra from different labs can be assembled into coherent databases similar to those routinely used to identify pure compounds. This type of data treatment is applicable for rapid detection in biowarfare and bioterror events as well as in forensic, research, and clinical laboratory contexts. C1 US FDA, Natl Ctr Toxicol Res, Mass Spectrometry Branch, Div Chem, Jefferson, AR 72079 USA. Foof & Drug Adm, Gulf Coast Seafood Lab, Dauphin Isl, AL USA. Univ Montreal, Montreal, PQ, Canada. RP Wilkes, JG (reprint author), US FDA, Natl Ctr Toxicol Res, Mass Spectrometry Branch, Div Chem, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 21 TC 12 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1044-0305 J9 J AM SOC MASS SPECTR JI J. Am. Soc. Mass Spectrom. PD JUL PY 2002 VL 13 IS 7 BP 875 EP 887 AR PII S1044-0305(02)00390-2 DI 10.1016/S1044-0305(02)00390-2 PG 13 WC Chemistry, Analytical; Chemistry, Physical; Spectroscopy SC Chemistry; Spectroscopy GA 576UQ UT WOS:000177024700012 PM 12148811 ER PT J AU Junod, SW AF Junod, SW TI Perspectives on the pill: An essay review SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Review C1 US FDA, Hist Off, Rockville, MD 20857 USA. RP Junod, SW (reprint author), US FDA, Hist Off, HFC-24,Room 13-51, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD JUL PY 2002 VL 57 IS 3 BP 333 EP 339 DI 10.1093/jhmas/57.3.333 PG 7 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 583LA UT WOS:000177408300005 ER PT J AU Major, ME Mihalik, K Puig, M Rehermann, B Nascimbeni, M Rice, CM Feinstone, SM AF Major, ME Mihalik, K Puig, M Rehermann, B Nascimbeni, M Rice, CM Feinstone, SM TI Previously infected and recovered chimpanzees exhibit rapid responses that control hepatitis C virus replication upon rechallenge SO JOURNAL OF VIROLOGY LA English DT Article ID IMMUNE-RESPONSES; NON-A; GENOME; RNA; IDENTIFICATION; REGION; 3'-TERMINUS; PREVENTION; CLEARANCE; HUMANS AB Responses in three chimpanzees were compared following challenge with a clonal hepatitis C virus (HCV) contained in plasma from an animal that had received infectious RNA transcripts. Two of the chimpanzees (Ch1552 and ChX0186) had recovered from a previous infection with HCV, while the third (Ch1605) was a naive animal. All animals were challenged by reverse titration with decreasing dilutions of plasma and became serum RNA positive following challenge. Ch1605 displayed a typical disease profile for a chimpanzee. We observed increasing levels of serum RNA from week 1 postinoculation (p.i.), reaching a peak of 10(6) copies/ml at week 9 p.i., and alanine aminotransferase (ALT) elevations and seroconversion to HCV antibodies at week 10 p.i. In contrast, both ChI552 and ChX0186 exhibited much shorter periods of viremia (4 weeks), low serum RNA levels (peak, 10(3) copies/ml), and minimal ALT elevations. A comparison of intrahepatic cytokine levels in ChI552 and Ch1605 showed greater and earlier gamma interferon (IFN-gamma) and tumor necrosis factor alpha responses in the previously infected animal, responses that were 30-fold greater than baseline responses at week 4 p.i. for IFN-gamma in Ch1552 compared to 12-fold in Ch1605 at week 10 p.i. These data indicate (i) that clonal HCV generated from an infectious RNA transcript will lead to a typical HCV infection in naive chimpanzees, (ii) that there are memory immune responses in recovered chimpanzees that control HCV infection upon rechallenge, and (iii) that these responses seem to be T-cell mediated, as none of the animals had detectable antibody against the HCV envelope glycoproteins. These observations have encouraging implications for the development of a vaccine for HCV. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. NIDDKD, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. RP Major, ME (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29A,Rm 1D10,HFM 448,8800 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA 85883, R01 CA085883] NR 31 TC 125 Z9 127 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 JUL PY 2002 VL 76 IS 13 BP 6586 EP 6595 DI 10.1128/JVI.76.13.6586-6595.2002 PG 10 WC Virology SC Virology GA 564BF UT WOS:000176293600019 PM 12050371 ER PT J AU Golding, H Zaitseva, M de Rosny, E King, LR Manischewitz, J Sidorov, I Gorny, MK Zolla-Pazner, S Dimitrov, DS Weiss, CD AF Golding, H Zaitseva, M de Rosny, E King, LR Manischewitz, J Sidorov, I Gorny, MK Zolla-Pazner, S Dimitrov, DS Weiss, CD TI Dissection of human immunodeficiency virus type 1 entry with neutralizing antibodies to gp41 fusion intermediates SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN MONOCLONAL-ANTIBODIES; ENVELOPE GLYCOPROTEIN; MEMBRANE-FUSION; HIV-1 GP41; TRANSMEMBRANE PROTEIN; ATOMIC-STRUCTURE; COILED-COIL; CELL-LINES; EPITOPE; PEPTIDE AB Human immunodeficiency virus type 1 (HIV-1) entry requires conformational changes in the transmembrane subunit (gp41) of the envelope glycoprotein (Env) involving transient fusion intermediates that contain exposed coiled-coil (prehairpin) and six-helix bundle structures. We investigated the HIV-1 entry mechanism and the potential of antibodies targeting fusion intermediates to block Env-mediated membrane fusion. Suboptimal temperature (31.5degreesC) was used to prolong fusion intermediates as monitored by confocal microscopy. After transfer to 37degreesC, these fusion intermediates progressed to syncytium formation with enhanced kinetics compared with effector-target (E/T) cell mixtures that were incubated only at 37degreesC. gp41 peptides DP-178, DP-107, and IQN17 blocked fusion more efficiently (5- to 10-fold-lower 50% inhibitory dose values) when added to E/T cells at the suboptimal temperature prior to transfer to 37degreesC. Rabbit antibodies against peptides modeling the N-heptad repeat or the six-helix bundle of gp41 blocked fusion and viral infection at 37degreesC only if preincubated with E/T cells at the suboptimal temperature. Similar fusion inhibition was observed with human six-helix bundle-specific monoclonal antibodies. Our data demonstrate that antibodies targeting gp41 fusion intermediates are able to bind to gp41 and arrest fusion. They also indicate that six-helix bundles can form prior to fusion and that the lag time before fusion occurs may include the time needed to accumulate preformed six-helix bundles at the fusion site. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. Vet Affairs Med Ctr, Res Ctr AIDS & HIV Infect, New York, NY 10010 USA. NYU, Sch Med, Dept Pathol, New York, NY 10016 USA. NCI, Canc Res Ctr, NIH, Frederick, MD 21702 USA. RP Golding, H (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29A,Rm 1A21,HFM-454,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011; OI Weiss, Carol/0000-0002-9965-1289; Sidorov, Igor/0000-0001-6519-4983 NR 32 TC 99 Z9 101 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUL PY 2002 VL 76 IS 13 BP 6780 EP 6790 DI 10.1128/JVI.76.13.6780-6790.2002 PG 11 WC Virology SC Virology GA 564BF UT WOS:000176293600039 PM 12050391 ER PT J AU Cherkasova, EA Korotkova, EA Yakovenko, ML Ivanova, OE Eremeeva, TP Chumakov, KM Agol, VI AF Cherkasova, EA Korotkova, EA Yakovenko, ML Ivanova, OE Eremeeva, TP Chumakov, KM Agol, VI TI Long-term circulation of vaccine-derived poliovirus that causes paralytic disease SO JOURNAL OF VIROLOGY LA English DT Article ID ACTING REPLICATION ELEMENT; CENTRAL-NERVOUS-SYSTEM; IMMUNODEFICIENT PATIENT; 5'-UNTRANSLATED REGION; POLIOMYELITIS ERADICATION; 3-DIMENSIONAL STRUCTURE; ATTENUATION PHENOTYPE; TYPE-1 POLIOVIRUS; CAPSID RESIDUES; SABIN VACCINE AB Successful implementation of the global poliomyelitis eradication program raises the problem of vaccination against poliomyelitis in the posteradication era. One of the options under consideration envisions completely stopping worldwide the use of the Sabin vaccine. This strategy is based on the assumption that the natural circulation of attenuated strains and their derivatives is strictly limited. Here, we report the characterization of a highly evolved derivative of the Sabin vaccine strain isolated in a case of paralytic poliomyelitis from a 7-month-old immunocompetent baby in an apparently adequately immunized population. Analysis of the genome of this isolate showed that it is a double (type 1-type 2-type 1) vaccine-derived recombinant. The number of mutations accumulated in both the type 1-derived and type 2-derived portions of the recombinant genome suggests that both had diverged from their vaccine predecessors similar to2 years before the onset of the illness. This fact, along with other recent observations, points to the possibility of long-term circulation of Sabin vaccine strain derivatives associated with an increase in their neurovirulence. Comparison of genomic sequences of this and other evolved vaccine-derived isolates reveals some general features of natural poliovirus evolution. They include a very high preponderance and nonrandom distribution of synonymous substitutions, conservation of secondary structures of important cis-acting elements of the genome, and an apparently adaptive character of most of the amino acid mutations, with only a few of them occurring in the antigenic determinants. Another interesting feature is a frequent occurrence of tripartite intertypic recombinants with either type 1 or type 3 homotypic genomic ends. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Russian Acad Med Sci, Inst Poliomyelitis & Viral Encephalitis, Moscow 142782, Russia. Moscow MV Lomonosov State Univ, AN Belozersky Inst Phys Chem Biol, Moscow 119899, Russia. RP Agol, VI (reprint author), Inst Poliomyelitis, Moscow 142782, Russia. RI Agol, Vadim/E-1941-2013; OI Ivanova, O.E./0000-0003-1784-4827 NR 78 TC 69 Z9 75 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 JUL PY 2002 VL 76 IS 13 BP 6791 EP 6799 DI 10.1128/JVI.76.13.6791-6799.2002 PG 9 WC Virology SC Virology GA 564BF UT WOS:000176293600040 PM 12050392 ER PT J AU Gresham, CS Gresham, CA Duffy, MJ Faulkner, CT Patton, S AF Gresham, CS Gresham, CA Duffy, MJ Faulkner, CT Patton, S TI Increased prevalence of Brucella suis and pseudorabies virus antibodies in adults of an isolated feral swine population in coastal South Carolina SO JOURNAL OF WILDLIFE DISEASES LA English DT Article DE Brucella suis; feral swine; pseudorabies virus; serologic survey; Sus scrofa; Toxoplasma gondii; Trichinella spiralis ID FLORIDA AB Two hundred twenty seven adult (>8 mo) feral swine (Sus scrofa) trapped from April through July 1999 at three locations on a coastal South Carolina (USA) peninsula with restricted ingress and egress were tested for Brucella suis and pseudorabies virus (PRV) antibodies. Approximately 44% of the animals tested positive for B. suis antibodies and 61% tested positive for antibodies to PRV. Previous surveys (1976 and 1992) of feral swine at the same location with similar methods indicated lower seroprevalences (28% and 18% for B. suis and 0% and 19% for PRV). We also found 39% of feral swine seropositive (n=179) for Trichinella spiralis and 49% seropositive (n=181) for Toxoplasma gondii. Results of repeated sampling demonstrated that seroprevalence to pathogens can increase with time in an isolated, unhunted population of feral swine suggesting an increased risk to local domestic livestock and potentially to human health. C1 Belle W Baruch Inst Coastal Ecol & Forest Sci, Georgetown, SC 29442 USA. Univ Georgia, Franklin Coll Arts & Sci, Dept Microbiol, Athens, GA 30602 USA. US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. Univ Tennessee, Coll Vet Med, Dept Comparat Med, Knoxville, TN 37996 USA. RP Gresham, CS (reprint author), Belle W Baruch Inst Coastal Ecol & Forest Sci, POB 596, Georgetown, SC 29442 USA. NR 18 TC 28 Z9 30 U1 1 U2 2 PU WILDLIFE DISEASE ASSN, INC PI LAWRENCE PA 810 EAST 10TH ST, LAWRENCE, KS 66044-8897 USA SN 0090-3558 J9 J WILDLIFE DIS JI J. Wildl. Dis. PD JUL PY 2002 VL 38 IS 3 BP 653 EP 656 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 593UX UT WOS:000178013100029 PM 12238392 ER PT J AU Corl, BA Baumgard, LH Griinari, JM Delmonte, P Morehouse, KM Yuraweczc, MP Bauman, DE AF Corl, BA Baumgard, LH Griinari, JM Delmonte, P Morehouse, KM Yuraweczc, MP Bauman, DE TI Trans-7,cis-9 CLA is synthesized endogenously by triangle(9)-desaturase in dairy cows SO LIPIDS LA English DT Article ID CONJUGATED LINOLEIC-ACID; DESATURASE MESSENGER-RNA; MILK-FAT SYNTHESIS; LACTATING COWS; ADIPOSE-TISSUE; ISOMERS; COA; DELTA(9)-DESATURASE; IDENTIFICATION; EXTRACTION AB Cis-9,trans-11 and traps-7,cis-9 CLA are the most prevalent CLA isomers in milkfat. The majority of cis-9,trans-11 CLA is synthesized endogenously by Delta(9)-desaturase. We tested the hypothesis that traps-7,cis-9 CLA originates from endogenous synthesis by inhibiting Delta(9)-desaturase with a source of cyclopropene FA (sterculic oil: SO) or with a trans-10,cis-12 CLA supplement. Experiment 1 (four cows; Latin square) involved four treatments: control, SO, partially hydrogenated vegetable oil (PHVO), and PHVO + SO. Milk, plasma, and rumen fluid were collected. Experiment 2 treatments (four cows) were 0 or 14.0 g/d of 10,12 CLA supplement; milk and plasma were collected. Samples were analyzed by GC and Ag+-HPLC to determine FA. In Experiment 1, SO decreased milkfat content of traps-7,cis-9 CLA by 68 to 71% and cis-9,trans-11 CLA by 61 to 65%. In Experiment 2, the 10,12 CLA supplement decreased milkfat content of traps-7,cis-9 CLA and cis-9,trans-11 by 44 and 25%, respectively. Correcting for the extent of treatment-induced inhibition of Delta(9)-desaturase based on changes in myristic and myristoleic acids, endogenous synthesis of traps-7,cis-9 CLA represented 85 and 102% in Experiments 1 and 2, respectively. Similar corrected values were 77 and 58% for endogenous synthesis of cis-9,trans-11 CLA. Thus, milkfat cis-9,trans-11 CLA was primarily from endogenous synthesis with a minor portion from rumen escape. In contrast, traps-7,cis-9 CLA was not present in rumen fluid in significant amounts. Results indicate this isomer in milkfat is derived almost exclusively from endogenous synthesis via Delta(9)-desaturase. C1 Cornell Univ, Dept Anim Sci, Ithaca, NY 14853 USA. Univ Helsinki, Dept Anim Sci, FIN-00014 Helsinki, Finland. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Bauman, DE (reprint author), Cornell Univ, Dept Anim Sci, 262 Morrison Hall, Ithaca, NY 14853 USA. RI Corl, Benjamin/P-3150-2016 OI Corl, Benjamin/0000-0002-6495-3279 NR 47 TC 84 Z9 89 U1 0 U2 6 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD JUL PY 2002 VL 37 IS 7 BP 681 EP 688 DI 10.1007/s11745-002-0949-4 PG 8 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA 585HY UT WOS:000177520400007 PM 12216839 ER PT J AU Klinman, DM Takeshita, F Gursel, I Leifer, C Ishii, KJ Verthelyi, D Gursel, M AF Klinman, DM Takeshita, F Gursel, I Leifer, C Ishii, KJ Verthelyi, D Gursel, M TI CpG DNA: recognition by and activation of monocytes SO MICROBES AND INFECTION LA English DT Article DE CpG DNA; monocytes; activation ID BACTERIAL-DNA; SYNTHETIC OLIGONUCLEOTIDES; CELL ACTIVATION; CUTTING EDGE; IN-VITRO; B-CELL; MOTIFS; OLIGODEOXYNUCLEOTIDES; MURINE; INFLAMMATION AB Unmethylated CpG motifs present in bacterial DNA rapidly trigger an innate immune response characterized by the activation of Ig- and cytokine-secreting cells. Synthetic oligonucleotides (ODNs) containing CpG motifs mimic this activity, triggering monocytes to proliferate, secrete and/or differentiate. Analysis of hundreds of novel ODNs led to the identification of two structurally distinct classes of CpG motif that differentially activate human monocytes. ODNs of the "K"-type interact with Toll-like receptor 9 and induce monocytes to proliferate and secrete IL-6. In contrast, "D"-type ODNs trigger monocytes to differentiate into mature dendritic cells. Published by Editions scientifiques et medicales Elsevier SAS. C1 US FDA, Retroviral Immunol Sect, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Retroviral Immunol Sect, Ctr Biol Evaluat & Res, Bldg 29A Rm 3 D 10, Bethesda, MD 20892 USA. RI Gursel, Mayda /H-1812-2012; Ishii, Ken/B-1685-2012; OI Ishii, Ken/0000-0002-6728-3872; Gursel, Ihsan/0000-0003-3761-1166 NR 24 TC 61 Z9 64 U1 0 U2 1 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD JUL PY 2002 VL 4 IS 9 BP 897 EP 901 AR PII S1286-4579(02)01614-3 DI 10.1016/S1286-4579(02)01614-3 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 596GQ UT WOS:000178156700003 PM 12106782 ER PT J AU Brown, EW Kotewicz, ML Cebula, TA AF Brown, EW Kotewicz, ML Cebula, TA TI Detection of recombination among Salmonella enterica strains using the incongruence length difference test SO MOLECULAR PHYLOGENETICS AND EVOLUTION LA English DT Article ID ESCHERICHIA-COLI; HORIZONTAL TRANSFER; NATURAL-POPULATIONS; MISMATCH REPAIR; INTRAGENIC RECOMBINATION; EVOLUTIONARY GENETICS; PHYLOGENETIC ANALYSIS; SEQUENCE-ANALYSIS; MOSAIC STRUCTURE; GND LOCUS AB Particular serovars of Salmonella enterica have emerged as significant foodborne pathogens in humans. At the chromosomal level, discrete regions in the Salmonella genome have been identified that are known to play important roles in the maintenance, survival, and virulence of S. enterica within the host. Interestingly, several of these loci appear to have been acquired by horizontal transfer of DNA among and between bacterial species. The profound importance of recombination in pathogen emergence is just now being realized, perhaps explaining the sudden interest in developing novel and facile ways for detecting putative horizontal transfer events in bacteria. The incongruence length difference (ILD) test offers one such means. ILD uses phylogeny to trace sequences that may have been acquired promiscuously by exchange of DNA during chromosome evolution. We show here that the ILD test readily detects recombinations that have taken place in several housekeeping genes in Salmonella as well as genes composing the type 1 pilin complex (14 min) and the inv-spa invasion gene complex (63 min). Moreover, the ILD test indicated that the mutS gene (64 min), whose product helps protect the bacterial genome from invasion by foreign DNA, appears to have undergone intragenic recombination within S. enterica subspecies I. ILD findings were supported using additional tests known to be independent of the ILD approach (e.g., split decomposition analysis and compatibility of sites). Taken together, these data affirm the application of the ILD test as one approach for identifying recombined sequences in the Salmonella chromosome. Furthermore, horizontally acquired sequences within mutS support a model whereby evolutionarily important recombinants of S. enterica are rescued from strains carrying defective mutS alleles via horizontal transfer. (C) 2002 Elsevier Science (USA). All rights reserved. C1 US FDA, Div Mol Biol, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Cebula, TA (reprint author), US FDA, Off Appl Res & Safety Assessment HFS025, Ctr Food Safety & Appl Nutr, MOD-1,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 71 TC 46 Z9 47 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 1055-7903 J9 MOL PHYLOGENET EVOL JI Mol. Phylogenet. Evol. PD JUL PY 2002 VL 24 IS 1 BP 102 EP 120 AR PII S1055-7903(02)00222-1 DI 10.1016/S1055-7903(02)00222-1 PG 19 WC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Evolutionary Biology; Genetics & Heredity GA 580KN UT WOS:000177233900010 PM 12128032 ER PT J AU Williams, PB Rice, DC Piepho, RW Lathers, CM Burckart, GJ AF Williams, PB Rice, DC Piepho, RW Lathers, CM Burckart, GJ TI Web-based sharing of cutting-edge teaching strategies SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Article DE pharmacology education; web-based teaching; problem-based learning; student-centered learning ID CLINICAL-PHARMACOLOGY; CURRICULA; DRUGS AB The need to implement improved teaching methods in clinical pharmacology is critically important for health care globally. This need is driven by the overwhelming amount of information currently available on appropriate drug usage, by a proliferation of new biotechnology-derived pharmacologic agents, and by an expanded prescribing authority that is being granted to health professionals who have not traditionally had this responsibility and training. This discussion emphasizes the points that (a) the technology is available to share the best teaching materials for clinical pharmacology over the Internet, (b) clinical pharmacology organizations are best positioned to facilitate this exchange of educational materials, and that (c) continued discourse about problem-based teaming and other curricular approaches to teaching clinical pharmacology is essential. The currently available information on the Internet includes case studies, slide sharing for lectures, educational programs and educational software. Clinical pharmacology organizations are not only starting to organize this information, but also to review the content of these programs and continuously add new material. These organizations have also developed a powerful toot through their journals in which to present educational series on rational therapeutics and to discuss educational approaches to instruction. Teaching forums, such as those presented annually at the American College of Clinical pharmacology Annual Meeting, are essential to encourage discussion about teaching clinical pharmacology in the broadest context of the therapeutics, the economics and the legal aspects of clinical drug use. C1 Eastern Virginia Med Sch, Norfolk, VA 23507 USA. Univ Missouri, Sch Pharm, Kansas City, MO 64110 USA. US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. Univ Pittsburgh, Pittsburgh, PA 15261 USA. RP Williams, PB (reprint author), Eastern Virginia Med Sch, 700 W Olney Rd, Norfolk, VA 23507 USA. NR 14 TC 3 Z9 3 U1 0 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD JUL PY 2002 VL 366 IS 1 BP 90 EP 95 DI 10.1007/s00210-002-0560-z PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 575JY UT WOS:000176944200015 PM 12107639 ER PT J AU Carmel, R James, SJ AF Carmel, R James, SJ TI Alcohol abuse: An important cause of severe hyperhomocysteinemia SO NUTRITION REVIEWS LA English DT Editorial Material DE alcohol; homocysteine metabolism; transmethylation; transsulfuration; hyperhomocysteinemia; S-adenosylhomocysteine ID COULOMETRIC ELECTROCHEMICAL DETECTION; PLASMA S-ADENOSYLHOMOCYSTEINE; METHIONINE METABOLISM; VITAMIN SUPPLEMENTATION; HOMOCYSTEINE METABOLISM; SERUM HOMOCYSTEINE; NITRIC-OXIDE; IN-VITRO; ETHANOL; FOLATE AB Alcohol has complex direct effects on homocysteine metabolism, which are incompletely understood, and indirect effects mediated by interactions with vitamin metabolism and other factors. Both transmethylation and transsulfuration pathways are affected. Alcohol abuse is a common cause of hyperhomocysteinemia that often fluctuates and is sometimes severe. The causative role of alcohol in hyperhomocysteinemia is often overlooked by clinicians when evaluating patients and by investigators when conducting surveys. A married couple with severe hyperhomocysteinemia owing to surreptitious alcohol abuse, a case study illustrating many of these issues, is presented. A steep rise in S-adenosylhomocysteine as well as homocysteine levels was demonstrated with increased alcohol ingestion, with a decreased S-adenosylmethionine:S-adenosylhomocysteine ratio. Both patients had severe neurologic symptoms as well as macrocytic red blood cells, which, along with the high homocysteine levels, were misattributed to cobalamin deficiency, in one case despite serum cobalamin levels that were normal. C1 New York Methodist Hosp, Dept Med, Brooklyn, NY 11215 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Carmel, R (reprint author), New York Methodist Hosp, Dept Med, Brooklyn, NY 11215 USA. FU NIDDK NIH HHS [DK32640] NR 40 TC 11 Z9 12 U1 0 U2 0 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD JUL PY 2002 VL 60 IS 7 BP 215 EP 221 DI 10.1301/00296640260184309 PN 1 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 575JC UT WOS:000176942300005 PM 12144201 ER PT J AU Lupu, D Biris, AR Misan, I Lupsa, N Biris, AS Buzatu, DA Kleeve, M AF Lupu, D Biris, AR Misan, I Lupsa, N Biris, AS Buzatu, DA Kleeve, M TI Growth of nanoscale carbon structures and their corresponding hydrogen uptake properties SO PARTICULATE SCIENCE AND TECHNOLOGY LA English DT Article DE carbon nanostructures; chemical vapor deposition; hydrogen absorption; SEM ID GRAPHITIC NANOFIBRES; NANOTUBES; STORAGE; NANOSTRUCTURES; ADSORPTION; BEHAVIOR; CATALYSTS AB Carbon nanostructures have been synthesized using the chemical vapor deposition technique (CVD) on different catalysts, using ethylene, acetylene, or methane as the hydrocarbons. Morphological characterizations obtained using a scanning electron microscope (SEM) showed that the reaction products are carbon nanofibers (CNF) with an outer diameter that depends on the reaction conditions and nature of the reactants. Hydrogen uptake measurements, performed volumetrically in a Sievert-type installation, showed the quantity of desorbed hydrogen (for pressure intervals ranging from 1 to 100 bars) depends oil the synthesis conditions and the treatment preceding the hydrogen absorption process. For carbon nanotubes that were prepared according to literature guidelines and obtained from ethylene on a Ni:Cu catalyst, the amounts of absorbed hydrogen were less than 1% by weight. C1 Univ Arkansas, Dept Appl Sci, Little Rock, AR 72204 USA. NIRDIMT, Special Mat Dept, Cluj Napoca, Romania. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Univ Arkansas, Dept Biol, Little Rock, AR 72204 USA. RP Biris, AS (reprint author), Univ Arkansas, Dept Appl Sci, ETAS 575,2801 S Univ Ave, Little Rock, AR 72204 USA. RI Biris, Alexandru/A-8507-2010; Lupu, Dan/C-3346-2009; Biris, Alexandru /C-4517-2011 NR 21 TC 16 Z9 16 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0272-6351 J9 PARTICUL SCI TECHNOL JI Part. Sci. Technol. PD JUL-SEP PY 2002 VL 20 IS 3 BP 225 EP 234 DI 10.1080/02726350290058056 PG 10 WC Engineering, Chemical SC Engineering GA 669EA UT WOS:000182337900005 ER PT J AU Drachtman, RA Cole, PD Golden, CB James, SJ Melnyk, S Aisner, J Kamen, BA AF Drachtman, RA Cole, PD Golden, CB James, SJ Melnyk, S Aisner, J Kamen, BA TI Dextromethorphan is effective in the treatment of subacute methotrexate neurotoxicity SO PEDIATRIC HEMATOLOGY AND ONCOLOGY LA English DT Article DE dextromethorphan; methotrexate; neurotoxicity ID HIGH-DOSE METHOTREXATE; AMINO-ACID ANTAGONISTS; CENTRAL-NERVOUS-SYSTEM; HOMOCYSTEIC ACID; LEUKOENCEPHALOPATHY; CHILDREN; LEUKEMIA; DYSFUNCTION; DISORDERS; RECEPTOR AB Methotrexate-induced neurotoxicity (MTX-Ntox) is a frequent complication of methotrexate (MTX) therapy for patients with both malignant and inflammatory diseases. MTX-Ntox can occur after intrathecal MTX or after low-, intermediate-, or high-dose systemic administration. Symptoms can present in the acute, subacute, or late setting form, and can range from affective disorders, malaise, and headaches, to somnolence, focal neurologic deficits, and seizures. While the pathogenesis of MTX-Ntox is likely multifactorial, one potential biochemical pathway leading from MTX to neurotoxicity involves the folate dependent remethylation of homocysteine (Hcy). MTX therapy is known to cause elevations of both plasma and CSF Hcy. Hcy is directly toxic to vascular endothelium and it and its metabolites are excitatory agonists of the N-methyl-D-aspartate (NMDA) receptor Competitive or noncompetitive antagonists might afford protection from or reversal of MTX-Ntox. Using high-performance liquid chromatography (HPLC) with coulometric electrochemical detection, the authors measured CSF Hcy in sequential patients with severe subacute MTX-Ntox. CSF Hcy was higher in these patients (n = 9, median = 0.93 muM) than in asymptomatic patients (n = 11, median 0. 2 muM, p < .01). Five patients with severe subacute MTX-Ntox (most with dysarthria and/or hemiplegia) were treated with 1-2 mg/kg oral dextromethorphan (DM), a noncompetitive antagonist of the N-methyl-D-aspartate (NMDA) receptor. All five had resolution of symptoms. These data provide additional clinical support for elevated CSF Hcy in the induction of MTX-Ntox through activation of the NMDA-receptor These data provide support for a placebo-controlled clinical trial to examine the ability of DM to prevent or alleviate MTX-Ntox. C1 Univ Med & Dent New Jersey, Canc Inst New Jersey, New Brunswick, NJ 08816 USA. Childrens Hosp Oakland, Oakland, CA USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Kamen, BA (reprint author), Univ Med & Dent New Jersey, Canc Inst New Jersey, 195 Little Albany St, New Brunswick, NJ 08816 USA. NR 36 TC 53 Z9 53 U1 1 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 0888-0018 J9 PEDIATR HEMAT ONCOL JI Pediatr. Hematol. Oncol. PD JUL-AUG PY 2002 VL 19 IS 5 BP 319 EP 327 DI 10.1080/08880010290057336 PG 9 WC Oncology; Hematology; Pediatrics SC Oncology; Hematology; Pediatrics GA 562GJ UT WOS:000176188800005 PM 12078863 ER PT J AU Yu, LX Amidon, GL Polli, JE Zhao, H Mehta, MU Conner, DP Shah, VP Lesko, LJ Chen, ML Lee, VHL Hussain, AS AF Yu, LX Amidon, GL Polli, JE Zhao, H Mehta, MU Conner, DP Shah, VP Lesko, LJ Chen, ML Lee, VHL Hussain, AS TI Biopharmaceutics classification system: The scientific basis for biowaiver extensions SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material DE Biopharmaceutics Classification System; solubility; permeability; dissolution; bioequivalence; immediate-release products ID DRUG ABSORPTION; INTESTINAL TRANSIT; BIOAVAILABILITY; TRANSPORTERS; PERMEABILITY; EXCIPIENTS C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. Univ Michigan, Coll Pharm, Dept Pharmaceut, Ann Arbor, MI 48109 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. Univ So Calif, Sch Pharm, Dept Pharmaceut Sci, Los Angeles, CA 90089 USA. RP Yu, LX (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, 5600 Fishers Lane, Rockville, MD 20857 USA. RI Lee, Vincent/A-9439-2008; Yu, Lawrence/L-6280-2016 OI Lee, Vincent/0000-0001-7708-6269; NR 26 TC 271 Z9 288 U1 2 U2 35 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JUL PY 2002 VL 19 IS 7 BP 921 EP 925 DI 10.1023/A:1016473601633 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 574PZ UT WOS:000176899900001 PM 12180542 ER PT J AU Koller, EA Doraiswamy, PN AF Koller, EA Doraiswamy, PN TI Olanzapine-associated diabetes mellitus SO PHARMACOTHERAPY LA English DT Article ID ADVERSE DRUG-REACTIONS; ATYPICAL ANTIPSYCHOTIC-DRUGS; SEVERE HYPERGLYCEMIA; GLUCOSE-TOLERANCE; KETOACIDOSIS; CLOZAPINE; COMA; EVENTS; GAIN AB Study Objective. To explore the clinical characteristics of hyperglycemia in patients treated with olanzapine. Design. Retrospective, epidemiologic survey of spontaneously reported adverse events related to olanzapine therapy. Setting. Government-affiliated drug evaluation center. Patients. Two hundred thirty-seven patients with olanzapine-associated diabetes or hyperglycemia. Intervention. One hundred ninety-six cases from January 1994-May 15, 2001, were identified with the United States Food and Drug Administration's MedWatch Drug Surveillance System, and 41 cases published through May 15, 2001, were identified with MEDLINE or through meeting abstracts. Measurements and Main Results. Of the 237 cases, 188 were new-onset diabetes, 44 were exacerbations of preexistent disease, and 5 could not be classified. Mean patient age for newly diagnosed cases was 40.7 +/- 12.9 years and male:female ratio was 1.8. Seventy-three percent of all cases of hyperglycemia appeared within 6 months of start of olanzapine therapy. Eighty patients had metabolic acidosis or ketosis, 41 had glucose levels of 1000 mg/dl or greater, and 15 patients died. When olanzapine was discontinued or the dosage decreased, 78% of patients had improved glycemic control. Hyperglycemia recurred in 8 of 10 cases with rechallenge. Conclusions. Number of reports, temporal relationship to start of olanzapine therapy, relatively young age, and improvement on drug withdrawal suggest that olanzapine may precipitate or unmask diabetes in susceptible patients. C1 US FDA, Ctr Drug Evaluat & Review, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. Duke Univ, Med Ctr, Dept Psychiat, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Durham, NC 27710 USA. RP Koller, EA (reprint author), 5600 Fishers Lane,Room 14B04, Rockville, MD 20857 USA. NR 62 TC 215 Z9 222 U1 0 U2 4 PU PHARMACOTHERAPY PUBLICATIONS INC PI BOSTON PA NEW ENGLAND MEDICAL CENTER, 806, 750 WASHINGTON ST, BOSTON, MA 02111 USA SN 0277-0008 J9 PHARMACOTHERAPY JI Pharmacotherapy PD JUL PY 2002 VL 22 IS 7 BP 841 EP 852 DI 10.1592/phco.22.11.841.33629 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 569RV UT WOS:000176616700006 PM 12126218 ER PT J AU Latendresse, JR Warbrittion, AR Jonassen, H Creasy, DM AF Latendresse, JR Warbrittion, AR Jonassen, H Creasy, DM TI Fixation of testes and eyes using a modified Davidson's fluid: Comparison with Bouin's fluid and conventional Davidson's fluid SO TOXICOLOGIC PATHOLOGY LA English DT Article DE immunohistochemistry; histochemistry; fixation; histomorphology; methods, spermatogonia; Sertoli cell antigenic markers; Davidson's fixative; Bouin's fixative ID ANDROGEN RECEPTOR EXPRESSION; SERTOLI CELLS; DEVELOPING LEYDIG AB Most recent revisions of regulatory guidelines for testing effects of chemicals on reproduction recommend Bouin's fluid (BF) or a "comparable fixative" instead of formalin to preserve the morphologic detail of testes for histopathological evaluation. However, picric acid in BF is a health and safety hazard, as well as a laboratory waste disposal problem. Furthermore, use of BF is labor intensive, requiring multiple alcohol rinses to remove picric acid for optimum preservation and immunohistochemical (IHC) detection of testicular antigens that may potentially be used to identify and quantify cells and functional proteins with critical roles in spermatogenesis. Recently a modified Davidson's fluid (mDF) has been reported as an alternative to BF to fix testes for routine histopathological examination. This study compared the overall histomorphologic clarity and the immuno- and histochemical staining of testicular specimens fixed in BF and mDF. Additionally, because conventional Davidson's fixative (DF) is used routinely for optimum fixation of eyes, preservation of ocular histomorphology by DF and mDF was compared. mDF resulted in noticeably less shrinkage of the seminiferous tubules and superior overall morphologic detail compared to BF. Unlike DF, the mDF also supported excellent staining of acrosomes with periodic acid- Schiff (PAS) reagent when staging of spermatogenesis was required. IHC detection of androgen receptor and PCNA (to directly and indirectly identify Sertoli cells) as well as protein gene product 9.5 (to label spermatogonia) was superior in mDF compared to BF- fixed specimens. For histopathological examination of the eye, apposition and preservation of rods and cones, and nuclear layers of the retina were slightly inferior with mDF compared to DF. This paper has demonstrated that mDF provides comparable, and in many respects superior preservation of the testes to that of BF, both for IHC staining and for detailed histopathological examination. It also provides an acceptable fixative for eyes, although the quality of cellular preservation is inferior to that of DF. C1 Pathol Associates Inc, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Huntingdon Life Sci, E Millstone, NJ 08875 USA. RP Latendresse, JR (reprint author), POB 26,3900 NCTR Rd, Jefferson, AR 72079 USA. RI Latendresse, John/A-9215-2009 NR 19 TC 145 Z9 154 U1 1 U2 14 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. PD JUL-AUG PY 2002 VL 30 IS 4 BP 524 EP 533 DI 10.1080/01926230290105721 PG 10 WC Pathology; Toxicology SC Pathology; Toxicology GA 596YG UT WOS:000178193600012 PM 12187944 ER PT J AU Haberny, KA Paule, MG Scallet, AC Sistare, FD Lester, DS Hanig, JP Slikker, W AF Haberny, KA Paule, MG Scallet, AC Sistare, FD Lester, DS Hanig, JP Slikker, W TI Ontogeny of the N-methyl-D-aspartate (NMDA) receptor system and susceptibility to neurotoxicity SO TOXICOLOGICAL SCIENCES LA English DT Article DE N-methyl-D-aspartate; NMDA receptor; brain cell differentiation; CNS development; synaptic plasticity; apoptosis ID SUBUNIT MESSENGER-RNAS; LONG-TERM POTENTIATION; EXCITATORY AMINO-ACIDS; OPERANT TEST BATTERY; DEVELOPING RAT-BRAIN; HUMAN FETAL BRAIN; APOPTOTIC NEURODEGENERATION; VISUAL-CORTEX; POSTNATAL-DEVELOPMENT; CEREBROCORTICAL NEURONS AB The NMDA receptor has been widely investigated in recent years as a target for the pharmacological management of seizures, pain and a variety of neurological disorders. Its role in normal central nervous system (CNS) activity and development, as well as in the development of CNS abnormalities and neurodegeneration has also been of interest. The NMDA receptor is one of three pharmacologically distinct subtypes of ionotropic receptor channels that are sensitive to the endogenous excitatory amino acid, L-glutamate. The ontogeny of the NMDA receptor, a multiple tetrameric and heteromeric channel complex with at least six known subunits, is controlled by three gene families and varies in developmental profile with species and regional brain area. NMDA receptors play a role in excitatory synaptic transmission, in the activity-dependent synaptic plasticity underlying learning and memory, and in pre- and postnatal CNS development, including brain cell differentiation, axonal growth and degeneration of unused neurons. The results of recent studies suggest that sustained alteration of NMDA receptor activation during critical periods of development may have deleterious effects on normal CNS development and function. Neonatal rats administered the NMDA receptor antagonists 2-amino-5-phosphonovalerate (AP5) and MK-801 during the first two weeks of life develop abnormal axonal arborization in the retinal connections to the superior colliculus, interfering with normal visual responses. Results from monkey studies suggest that chronic developmental exposure to high doses of a NMDA antagonist, remacemide, has pronounced and long-lasting effects on learning. Recent findings indicate that if NMDA receptors are blocked during a specific period in neonatal life (first two weeks postnatally in the rat), massive apoptotic neurodegeneration results, due not to excitotoxic overstimulation of neurons but to deprivation of stimulation. These observations require further laboratory evidence and support in order to establish their relevance to drug-induced human neurodevelopmental concerns. It is necessary to investigate the relevance of these findings in other animal species in addition to the rat, most notably, nonhuman primates, where neuronal cytoarchitecture and development are significantly different than the rodent but more like the human. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 92 TC 138 Z9 147 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 JUL PY 2002 VL 68 IS 1 BP 9 EP 17 DI 10.1093/toxsci/68.1.9 PG 9 WC Toxicology SC Toxicology GA 569DL UT WOS:000176585200003 PM 12075105 ER PT J AU Dobrovolsky, VN McGarrity, LJ Morris, SM Heflich, RH AF Dobrovolsky, VN McGarrity, LJ Morris, SM Heflich, RH TI Detection of mutation in transgenic CHO cells using green fluorescent protein as a reporter SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE gamma-radiation; green fluorescent protein (GFP); tetracycline (Tet) repressor; fluorescence activated cell sorting ID PLACENTAL ALKALINE-PHOSPHATASE; GENE-EXPRESSION; SHUTTLE VECTORS; MAMMALIAN-CELLS; IN-SITU; MICE; MOUSE; HETEROZYGOSITY; LYMPHOCYTES; INVIVO AB A novel approach was developed for rapidly estimating the frequency of specific mutations in genetically engineered Chinese hamster ovary (CHO) cells. We designed double-transgenic CHO cell lines that contain a transgene consisting of the sequence coding for green fluorescent protein under the control of a tetracycline (Tet) responsive promoter and a second transgene coding for the constitutively expressed Tet repressor. Cultures of these CHO cells were treated with gamma-radiation, N-methyl-N-nitrosourea or methyl methanesulfonate, and the fluorescence of individual cells from both control and treated cultures was measured by flow cytometry. The treatments increased the number of highly fluorescent cells, those with presumed mutations in the Tet-repressor gene. Mutant cells from gamma-radiation-exposed cultures were isolated by fluorescence-activated cell sorting, cultured, and individual clones expanded. A PCR-based analysis indicated that the highly fluorescent expanded cells had lost the transgene coding for the Tet repressor, suggesting that the system mainly detects large genetic alterations. A similar approach may be useful for making high-throughput in vivo models for mutation detection. Published by Elsevier Science B.V. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Dobrovolsky, VN (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT-120, Jefferson, AR 72079 USA. NR 26 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD JUN 27 PY 2002 VL 518 IS 1 BP 55 EP 64 AR PII S1383-5718(02)00072-4 DI 10.1016/S1383-5718(02)00072-4 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 569NG UT WOS:000176608000006 PM 12063067 ER PT J AU Mackey, AC Shaffer, D Prizant, R AF Mackey, AC Shaffer, D Prizant, R TI Seizure associated with the use of visicol for colonoscopy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Mackey, AC (reprint author), US FDA, Rockville, MD 20857 USA. NR 5 TC 13 Z9 14 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 27 PY 2002 VL 346 IS 26 BP 2095 EP 2095 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 566DN UT WOS:000176411900033 PM 12087153 ER PT J AU Zheng, M Klinman, DM Gierynska, M Rouse, BT AF Zheng, M Klinman, DM Gierynska, M Rouse, BT TI DNA containing CpG motifs induces angiogenesis SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID ENDOTHELIAL GROWTH-FACTOR; BACTERIAL-DNA; STROMAL KERATITIS; HUMAN-CELLS; ACTIVATION; MURINE; OLIGODEOXYNUCLEOTIDES; NEOVASCULARIZATION; MATURATION; INHIBITION AB New blood vessel formation in the cornea is an essential step in the pathogenesis of a blinding immunoinflammatory reaction caused by ocular infection with herpes simplex virus (HSV). By using a murine corneal micropocket assay, we found that HSV DNA (which contains a significant excess of potentially bioactive "CpG" motifs when compared with mammalian DNA) induces angiogenesis. Moreover, synthetic oligodeoxynucleotides containing CpG motifs attract inflammatory cells and stimulate the release of vascular endothelial growth factor (VEGF), which in turn triggers new blood vessel formation. In vitro, CpG DNA induces the J774A.1 murine macrophage cell line to produce VEGF. In vivo CpG-induced angiogenesis was blocked by the administration of anti-mVEGF Ab or the inclusion of "neutralizing" oligodeoxynucleotides that specifically oppose the stimulatory activity of CpG DNA. These findings establish that DNA containing bioactive CpG motifs induces angiogenesis, and suggest that CpG motifs in HSV DNA may contribute to the blinding lesions of stromal keratitis. C1 Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA. Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Div Viral Prod, Bethesda, MD 20892 USA. RP Rouse, BT (reprint author), Univ Tennessee, Dept Microbiol, Knoxville, TN 37996 USA. FU NEI NIH HHS [EY05093, R01 EY005093] NR 33 TC 76 Z9 80 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 JUN 25 PY 2002 VL 99 IS 13 BP 8944 EP 8949 DI 10.1073/pnas.132605599 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 567GZ UT WOS:000176478200085 PM 12060721 ER PT J AU Rhee, EG Mendez, S Shah, JA Wu, CY Kirman, JR Turon, TN Davey, DF Davis, H Klinman, DM Coler, RN Sacks, DL Seder, RA AF Rhee, EG Mendez, S Shah, JA Wu, CY Kirman, JR Turon, TN Davey, DF Davis, H Klinman, DM Coler, RN Sacks, DL Seder, RA TI Vaccination with heat-killed Leishmania antigen or recombinant leishmanial protein and CpG oligodeoxynucleotides induces long-term memory CD4(+) and CD8(+) T cell responses and protection against Leishmania major infection SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article DE CD4(+) T cells; CD8(+) T cells; DNA vaccines; parasitic infection; Th cells ID IMMUNOSTIMULATORY DNA-SEQUENCES; MURINE LEISHMANIASIS; IN-VIVO; CUTANEOUS LEISHMANIASIS; INDEPENDENT MECHANISM; INTERFERON-GAMMA; DENDRITIC CELLS; IMMUNE-RESPONSE; BACTERIAL-DNA; TH1 IMMUNITY AB CpG oligodeoxynucleotides (ODN) have potent effects on innate and adaptive cellular immune responses,. In this report, the ability, of CpG ODN to confer long-term immunity and protection when used as a vaccine adjuvant with a clinical grade of leishmanial antigen, autoclaved Leishmania major (ALM), or a recombinant leishmanial protein was studied. In two different Mouse models of L. major infection, vaccination with ALM plus CpG ODN was able to control infection and markedly reduce lesion development in susceptible BALB/c and resistant C57BL/6 (B6) mice, respectively, up to 12 wk after immunization. Moreover, 136 mice immunized with ALM plus CpG ODNs were still protected against infectious challenge even 6 mo after vaccination. In terms of immune correlates of protection, ALM plus CpG ODN-vaccinated mice displayed L. major-specific T helper cell I and CD8(+) response,;. In addition. complete protection was markedly abrogated in mice depleted of CD8(+) T cells at the time of vaccination. Similarly, mice vaccinated with a recombinant leishmanial protein plus CpG ODN also had long-term protection that was dependent on CD8(+) T cells in vivo. Together, these data demonstrate that CpG ODN, when used as a vaccine adjuvant with either a recombinant protein or heat-killed leishmanial antigen, can induce long-term protection against an intracellular infection in a CDS-dependent manner. C1 NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Coley Pharmaceut Grp, Ottawa, ON K1Y 4S1, Canada. US FDA, Ctr Biol Evaluat & Res, Lab Retrovirol & Immunol, Bethesda, MD 20892 USA. Infect Dis Res Inst, Seattle, WA 98104 USA. RP Seder, RA (reprint author), NIAID, Cellular Immunol Sect, Vaccine Res Ctr, NIH, Bldg 40,Room 3512,40 Convent Dr,MSC 3025, Bethesda, MD 20892 USA. NR 36 TC 133 Z9 140 U1 0 U2 3 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JUN 17 PY 2002 VL 195 IS 12 BP 1565 EP 1573 DI 10.1084/jem.20020147 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 565DR UT WOS:000176354100007 PM 12070284 ER PT J AU Haffer, AST Rogers, JR Montello, MJ Frank, EC Ostroff, C AF Haffer, AST Rogers, JR Montello, MJ Frank, EC Ostroff, C TI 2001 anthrax crisis in Washington, DC: Clinic for persons exposed to contaminated mail SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE ambulatory care; anthrax; biological warfare; diagnosis; disaster planning; protocols; team AB An anthrax prophylaxis clinic is described. In October 2001, four workers from the U.S. Postal Service's Brentwood facility in Washington, D.C., were hospitalized with inhalational anthrax; many others may have been exposed to anthrax spores. U.S. Public Health Service (USPHS) teams were deployed to establish an anthrax prophylaxis clinic that would provide education and medication to workers and people who visited the mail facility. The temporary clinic was set up at D.C. General Hospital and was staffed primarily by health care professionals from USPHS. The protocol at the clinic involved three major phases. Phase 1 consisted of gathering information from the patient and distributing educational materials. Phase 2 involved presentations by a physician and a pharmacist concerning anthrax, followed by a question-and-answer session. In phase 3, a pharmacist selected the most appropriate prophylactic agent, dispensed the medication, counseled the patient, and referred patients with flu-like symptoms or skin lesions to a physician. Two floor plans were used to maximize the number of patients seen per hour without jeopardizing patient care. The clinic operated 14 hours a day for 14 days. The 136-member health care team included 52 pharmacists, and medication was dispensed to more than 18,000 patients. The clinic may serve as a model for pharmacists and other professionals in designing and implementing disaster plans. A multidisciplinary team established and operated a clinic to treat persons who may have been exposed to anthrax through contaminated mail. C1 US FDA, Div Drug Mkt Advertising & Commun, Rockville, MD 20852 USA. US PHS, PHS Diaster Med Assistance Team 1, Washington, DC 20201 USA. NCI, Canc Therapy Evaluat Program, Protocol & Informat Off, Rockville, MD USA. US PHS, Commissioned Corps Readiness Force, Washington, DC 20201 USA. US FDA, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. US FDA, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. RP Haffer, AST (reprint author), US FDA, Div Drug Mkt Advertising & Commun, HFD-042,5600 Fishers Lane,Room 17B-17, Rockville, MD 20852 USA. NR 4 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUN 15 PY 2002 VL 59 IS 12 BP 1189 EP 1192 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 561ZY UT WOS:000176174000011 PM 12073860 ER PT J AU Montello, MJ Ostroff, C Frank, EC Haffer, AST Rogers, JR AF Montello, MJ Ostroff, C Frank, EC Haffer, AST Rogers, JR TI 2001 anthrax crisis in Washington, DC: Pharmacists' role in screening patients and selecting prophylaxis SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Article DE ambulatory care; anthrax; biological warfare; ciprofloxacin; diagnosis; disaster planning; doxycycline; pharmacists; protocols; quinolones; tetracyclines AB Pharmacists' development and use of a worksheet facilitating their rapid selection of patient-appropriate prophylactic antimicrobials in an anthrax clinic is described. A clinic housed at D.C. General Hospital, in Washington, D.C., treated most of the people-many of them postal workers-who may have been exposed to anthrax in that city during the 2001 anthrax crisis. A form was needed to assist pharmacists in the rapid selection of prophylactic antimicrobials and in patient education and counseling. A team of pharmacists collaborated on the development of a form tailored to the clinical and logistical needs of the operation. The questions on the form were based largely on the two antianthrax agents most likely to be used, ciprofloxacin and doxycycline, and were designed to identify the circumstances that would most frequently require a medication change or a modification of patient education. Yes-or-no check boxes allowed pertinent data to be captured most efficiently. A positive response to any question triggered a personal interview and assessment by a pharmacist. A treatment algorithm was also developed to ensure consistent pharmacist selection of agents in the face of potentially changing policies and staff. The worksheet questions sought to establish treatment objectives, document allergies and concomitant therapies, and identify patients who were pregnant or lactating. Pharmacists developed a patient-screening worksheet that helped determine their choice of treatment for people who may have been exposed to anthrax in Washington, D.C., during the 2001 anthrax crisis. C1 US PHS, Disaster Med Assistance Team 1, Rockville, MD 20852 USA. NCI, Protocol & Informat Off, Canc Therapeut Evaluat Program, Rockville, MD USA. US FDA, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. US PHS, Commissioned Corps Readiness Force, Washington, DC 20201 USA. US FDA, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. US FDA, Div Drug Mkt Advertising & Commun, Rockville, MD 20857 USA. RP Montello, MJ (reprint author), US PHS, Disaster Med Assistance Team 1, 6130 Execut Blvd,Execut Plaza N,Room 6118, Rockville, MD 20852 USA. NR 7 TC 8 Z9 8 U1 0 U2 1 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD JUN 15 PY 2002 VL 59 IS 12 BP 1193 EP 1199 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 561ZY UT WOS:000176174000012 PM 12073861 ER PT J AU Guo, TL White, KL Brown, RD Delclos, KB Newbold, RR Weis, C Germolec, DR McCay, JA AF Guo, TL White, KL Brown, RD Delclos, KB Newbold, RR Weis, C Germolec, DR McCay, JA TI Genistein 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 AND APPLIED PHARMACOLOGY LA English DT Article DE genistein; developmental immunotoxicity; NK cell activity; antibody-forming cell responses ID IN-VITRO; SOYBEAN ISOFLAVONES; PHYTO-ESTROGENS; MAMMARY-CANCER; MELANOMA-CELLS; EXPOSURE; DAIDZEIN; MICE; PHYTOESTROGENS; INHIBITION AB The potential effects of the phytoestrogen genistein (GEN) on the immune system were evaluated in both F, (dams) and F, generations of Sprague-Dawley rats exposed to a soy-free diet containing low (L: 25 ppm), middle (M: 250 ppm), and high (H: 1250 ppm) levels of GEN. In dams, exposure to GEN from Gestation Day 7 to Postpartum Day 51 (totally 65 days) produced a significant increase in NK cell activity (M and H), while a decrease in the percentage of helper T cells (H). In F, males, exposure to GEN gestationally, lactationally, and through feed from Postnatal Days 22 to 64 (total 78 days) produced an increase in the relative weights (% body) of spleen (L and H) and thymus (L). Furthermore, exposure to GEN increased the number of splenic B cells (H), T cells (L, M, and H), and T-cell subsets (L, M, and H). Although GEN decreased the percentages of splenic NK cells (L, M, and H), no effect on the activity of NK cells was observed. In F, females, exposure to GEN produced a decrease in terminal body weight (H), with an increase in the relative weight of spleen (L, M, and 11). Exposure to GEN also increased the number of splenic B cells (L), macrophages (L and M), T cells (H), helper T cells (L and H), and cytotoxic T cells (M and H). Additionally, exposure to GEN increased the percentages of T cells (M and H), helper T cells (H), and cytotoxic T cells (M and H). Moreover, the spleen IgM antibody-forming cell response to sheep red blood cells was enhanced (H), although the percentages of B cells were decreased (M and H). No effect on the activity of NK cells was observed; however, the percentages of splenic NK cells were decreased by GEN (L and H). In conclusion, these results demonstrate that exposure to GEN can modulate the immune responses in Sprague-Dawley rats. Furthermore, the sexual dimorphic effects of GEN in F-1 male and female rats suggest that there may be interactions between GEN and the responses modulated by sex hormones. (C) 2002 Elsevier Science (USA). 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 White, KL (reprint author), Virginia Commonwealth Univ, Dept Pharmacol & Toxicol, POB 980613, Richmond, VA 23298 USA. FU NIEHS NIH HHS [ES 55094] NR 40 TC 43 Z9 47 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD JUN 15 PY 2002 VL 181 IS 3 BP 219 EP 227 DI 10.1006/taap.2002.9418 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 568KD UT WOS:000176540200008 PM 12079431 ER PT J AU Sommers, CL Park, CS Lee, J Feng, CG Fuller, CL Grinberg, A Hildebrand, JA Lacana, E Menon, RK Shores, EW Samelson, LE Love, PE AF Sommers, CL Park, CS Lee, J Feng, CG Fuller, CL Grinberg, A Hildebrand, JA Lacana, E Menon, RK Shores, EW Samelson, LE Love, PE TI A LAT mutation that inhibits T cell development yet induces lymphoproliferation SO SCIENCE LA English DT Article ID TYROSINE RESIDUES; CD5 EXPRESSION; ACTIVATION; RECEPTOR; LINKER; RAS; PHOSPHORYLATION; SELECTION; APOPTOSIS AB Mice homozygous for a single tyrosine mutation in LAT (linker for activation of T cells) exhibited an early block in T cell maturation but later developed a polyclonal lymphoproliferative disorder and signs of autoimmune disease. T cell antigen receptor (TCR)-induced activation of phospholipase C-gamma 1 (PLC-gamma1) and of nuclear factor of activated T cells, calcium influx, interleukin-2 production, and cell death were reduced or abrogated in T cells from LAT mutant mice. In contrast, TCR-induced Erk activation was intact. These results identify a critical role for integrated PLC-gamma1 and Ras-Erk signaling through LAT in T cell development and homeostasis. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Love, PE (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. EM pel@helix.nih.gov NR 20 TC 197 Z9 206 U1 0 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JUN 14 PY 2002 VL 296 IS 5575 BP 2040 EP 2043 DI 10.1126/science.1069066 PG 4 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 563UD UT WOS:000176273300057 PM 12065840 ER PT J AU Crawford, LM AF Crawford, LM TI Synthetic secretin approved SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. 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 JUN 12 PY 2002 VL 287 IS 22 BP 2936 EP 2936 DI 10.1001/jama.287.22.2936 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 561EY UT WOS:000176128300006 ER PT J AU Crawford, LM AF Crawford, LM TI IND submission exemptions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. 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 JUN 12 PY 2002 VL 287 IS 22 BP 2936 EP 2936 DI 10.1001/jama.287.22.2936 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 561EY UT WOS:000176128300007 ER PT J AU Crawford, LM AF Crawford, LM TI Advisory Committee meetings SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. 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 JUN 12 PY 2002 VL 287 IS 22 BP 2936 EP 2936 DI 10.1001/jama.287.22.2936 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 561EY UT WOS:000176128300008 ER PT J AU Nagababu, E Ramasamy, S Rifkind, JM AF Nagababu, E Ramasamy, S Rifkind, JM TI Site-specific cross-linking of human and bovine hemoglobins differentially alters oxygen binding and redox side reactions producing rhombic heme and heme degradation SO BIOCHEMISTRY LA English DT Article ID HYDROGEN-PEROXIDE; BLOOD SUBSTITUTES; FERRYL INTERMEDIATE; HIGH COOPERATIVITY; LINKED HEMOGLOBIN; ENDOTHELIAL-CELLS; DISTAL POCKET; METHEMOGLOBIN; CARRIERS; AUTOXIDATION AB Chemically modified human or bovine hemoglobins (Hb) have been developed as oxygen-carrying therapeutics and are currently under clinical evaluation. Oxidative processes, which are in many cases enhanced when modifications are introduced that lower the oxygen affinity, can limit the safety of these proteins. We have carried out a systematic evaluation of two modified human Hbs (O-R-polyHbA(0) and DBBF-Hb) and one bovine Hb (polyHbBv). We have both measured the oxidative products present in the Hb preparations and followed the oxidative reactions during 37 degreesC incubations. Autoxidation, the primary oxidative reaction which initiates the oxidative cascade, is highly correlated with P-50 (R = 0.987; p < 0.002). However, when the results for the other oxidative processes are compared, two different classes of oxidative reactions are identified. The formation of oxyferrylHb, like the rate of autoxidation, increases for all modified Hbs. However, the subsequent reactions, which lead to heme damage and eventually heme degradation, are enhanced for the modified human Hbs but are actually suppressed for bovine-modified Hbs. The rhombic heme measured by electron paramagnetic resonance, which is the initial step that causes irreversible damage to the heme, is found to be a reliable measure of the stability of ferrylHb and has the tendency to produce degradation products. DBBF-Hb, a Hb-based oxygen carrier (HBOC) for which toxic side effects have been well documented, has the highest level of rhombic heme (41-fold greater than for HbA(0)), even though its rate of autoxidation is relatively low. These findings establish the importance of these secondary oxidative reactions over autoxidation in evaluating the toxicity of HBOCs. C1 NIA, Mol Dynam Sect, NIH, Baltimore, MD 21224 USA. RP Nagababu, E (reprint author), US FDA, NIH, Bldg 29,Room 112,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 40 TC 76 Z9 78 U1 1 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD JUN 11 PY 2002 VL 41 IS 23 BP 7407 EP 7415 DI 10.1021/bi0121048 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 559ZU UT WOS:000176057300027 PM 12044174 ER PT J AU Kutza, J Fields, K Grimm, TA Clouse, KA AF Kutza, J Fields, K Grimm, TA Clouse, KA TI Inhibition of HIV replication and macrophage colony-stimulating factor production in human macrophages by antiretroviral agents SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; MONOCYTE-DERIVED MACROPHAGES; INFECTION; PATHOGENESIS; EXPRESSION; TYPE-1; GROWTH; CELLS AB Macrophage colony-stimulating factor (M-CSF) enhances the susceptibility of macrophages to infection with HIV-1, in part by increasing the expression of CD4 and CCR5. Human monocyte-derived macrophages (MDMs) infected in vitro with HIV-1 endogenously produce M-CSF, with kinetics paralleling virus replication, which can lead to enhanced spreading of the infection. AZT and ritonavir both inhibit HIV replication, but their impact on M-CSF production by HIV-infected human MDMs is unknown. The dose response and kinetics of virus replication in the presence of AZT and ritonavir were determined for HIV-infected MDMs from HIV-seronegative donors. Harvested supernatants were monitored for reverse transcriptase activity, M-CSF production, and HIV proteins. Our data suggest that threshold levels of HIV replication must occur before maximum M-CSF production is induced. Addition of AZT or ritonavir before or after establishment of productive HIV infection dramatically reduces virus replication and M-CSF production by human MDMs. However, ongoing virus replication and M-CSF production are slow to return to baseline levels after addition of AZT or ritonavir, suggesting that HIV replication and virion release from infected macrophages continue long after initiation of antiretroviral therapy. Our results suggest that, in human macrophages, HIV-1 replication and M-CSF production are inextricably linked, such that inhibition of one leads to a concomitant reduction of the other. Low-level HIV replication and M-CSF release during ongoing antiretroviral therapies may facilitate the survival and maintenance of infected macrophages and suggests that additional therapies targeting M-CSF may be critical for elimination of macrophage reservoirs. C1 US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Monoclonal Antibodies, Rockville, MD 20852 USA. RP Kutza, J (reprint author), US FDA, CBER, OTRR, DMA HFM555, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 18 TC 10 Z9 11 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JUN 10 PY 2002 VL 18 IS 9 BP 619 EP 625 DI 10.1089/088922202760019310 PG 7 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 560WP UT WOS:000176104600002 PM 12079557 ER PT J AU Englert, RP Shacter, E AF Englert, RP Shacter, E TI Distinct modes of cell death induced by different reactive oxygen species - Amino acyl chloramines mediate hypochlorous acid-induced apoptosis SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID PEROXIDE-CHLORIDE SYSTEM; HUMAN NEUTROPHILS EMPLOY; HYDROGEN-PEROXIDE; OXIDATIVE STRESS; ENDOTHELIAL-CELLS; N-CHLOROTAURINE; GROWTH ARREST; MYELOPEROXIDASE; TAURINE; CHLORINATION AB Oxidants derived from inflammatory phagocytes compose a key element of the host immune defense system and can kill mammalian cells by one of several different mechanisms. In this report, we compare mechanisms of cell death induced in human B lymphoma cells by the inflammatory oxidants superoxide, H2O2, and HOCl. The results indicate that the mode of cell death induced depends on the nature of the oxidant involved and the medium in which the cells are treated. When human Burkitt's lymphoma cells are exposed to superoxide anion, generated as a flux from xanthine and xanthine oxidase, the cells die by a non-apoptotic mechanism (pyknosis/necrosis) identical to that seen when cells are treated with a bolus of reagent H2O2. Addition of superoxide dismutase has no effect, whereas catalase is completely protective, indicating that exogenously generated superoxide kills cells entirely through its dismutation into H2O2. In contrast, cells treated in culture media with reagent 1100 die largely by apoptosis. HOCl-induced apoptosis is mediated by aminoacyl chloramines generated in the culture media and can be mimicked by treatment of cells with taurine chloramine or with long lived chloramines generated from modified Lys or Arg. The results suggest that in a physiological milieu in which O-2(-) and H2O2 are the main oxidants being formed, the principal form of cell death may be necrotic, and under inflammatory conditions in which HOCl is generated, apoptotic cell death may predominate. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Immunol Lab, Bethesda, MD 20892 USA. Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20815 USA. RP Shacter, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Immunol Lab, Bldg 29A,Rm 2A-11,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 58 TC 65 Z9 67 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JUN 7 PY 2002 VL 277 IS 23 BP 20518 EP 20526 DI 10.1074/jcb.M200212200 PG 9 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 562NJ UT WOS:000176204500055 PM 11925431 ER PT J AU Wysowski, DK Honig, SF Beitz, J AF Wysowski, DK Honig, SF Beitz, J TI Uterine sarcoma associated with tamoxifen use. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 65 Z9 70 U1 0 U2 3 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 6 PY 2002 VL 346 IS 23 BP 1832 EP 1833 DI 10.1056/NEJM200206063462319 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 559EK UT WOS:000176012500030 PM 12050351 ER PT J AU Pastor, RW Venable, RM Feller, SE AF Pastor, RW Venable, RM Feller, SE TI Lipid bilayers, NMR relaxation, and computer simulations SO ACCOUNTS OF CHEMICAL RESEARCH LA English DT Review ID NUCLEAR MAGNETIC-RESONANCE; MOLECULAR-DYNAMICS SIMULATIONS; FLUORESCENCE DEPOLARIZATION; PHOSPHOLIPID BILAYER; ORDER PARAMETERS; MEMBRANES; MOTION; MACROMOLECULES; MODEL; DEPENDENCE AB Brownian and molecular dynamics simulations of a lipid bilayer are described, and the calculated frequency-dependent C-13 NMR T-1 relaxation times are compared with experiment. A consistent model emerges. Through fast internal motions, individual lipids average themselves into relatively cylindrical shapes on the 100 ps time scale and "wobble" in a cone-like potential on the nanosecond time scale. These motions take place in a highly fluid environment, much like a liquid alkane. Lateral diffusion of the lipids is on a significantly longer time scale because of restrictions at the bilayer/water interface, not because the interior of the bilayer is highly viscous. C1 USFDA, Lab Biophys, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Wabash Coll, Dept Chem, Crawfordsville, IN 47933 USA. RP Pastor, RW (reprint author), USFDA, Lab Biophys, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 38 TC 95 Z9 95 U1 0 U2 17 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0001-4842 J9 ACCOUNTS CHEM RES JI Accounts Chem. Res. PD JUN PY 2002 VL 35 IS 6 BP 438 EP 446 DI 10.1021/ar0100529 PG 9 WC Chemistry, Multidisciplinary SC Chemistry GA 565KA UT WOS:000176367900015 PM 12069629 ER PT J AU Wysowski, DK Farinas, E Swartz, L AF Wysowski, DK Farinas, E Swartz, L TI Comparison of reported and expected deaths in sildenafil (Viagra) users SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article ID MYOCARDIAL-INFARCTION; EXERTION AB The number of deaths (primarily due to myocardial infarction) reported to the Food and Drug Administration in men prescribed sildenafil (Viagra) are fewer than predicted based on vital statistics data. However, the prevalence of cardiovascular risk factors, including sexual activity in these men, and the incompleteness and limitations of reporting do not allow definitive conclusions concerning the incidence and etiology of myocardial infarction in men prescribed sildenafil. C1 US FDA, Div Drug Risk Evaluat 1, Off Drug Safety, Rockville, MD 20857 USA. US FDA, Div Drug Risk Evaluat 1, Off Drug Evaluat 3, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Div Drug Risk Evaluat 1, Off Drug Safety, HFD-430,5600 Fishers Lane,Room 15B-08, Rockville, MD 20857 USA. NR 4 TC 44 Z9 47 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD JUN 1 PY 2002 VL 89 IS 11 BP 1331 EP + DI 10.1016/S0002-9149(02)02342-1 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 558UN UT WOS:000175985300024 PM 12031744 ER PT J AU Kanal, E Borgstede, JP Barkovich, AJ Bell, C Bradley, WG Felmlee, JP Froelich, J Kaminski, EM Keeler, EK Lester, JW Scoumis, EA Zaremba, LA Zinninger, MD AF Kanal, E Borgstede, JP Barkovich, AJ Bell, C Bradley, WG Felmlee, JP Froelich, J Kaminski, EM Keeler, EK Lester, JW Scoumis, EA Zaremba, LA Zinninger, MD TI American College of Radiology white paper on MR safety SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article ID PATIENT-MANAGEMENT; IMAGING SAFETY; RECOMMENDATIONS; GUIDELINES; POLICIES C1 Amer Coll Radiol, Reston, VA 20191 USA. Univ Pittsburgh, Med Ctr, Dept Radiol, Magnet Resonance Serv, Pittsburgh, PA 15213 USA. Penrose St Francis Hlth Syst, Colorado Springs, CO 80907 USA. Univ Calif San Francisco, Dept Neuroradiol, San Francisco, CA 94143 USA. Yale Univ, Sch Med, Dept Anesthesiol, New Haven, CT 06520 USA. Univ Calif Irvine, Long Beach Mem Med Ctr, Dept Radiol, Long Beach, CA 90806 USA. Mayo Clin, Dept Radiol, Rochester, MN 55902 USA. Hennepin Cty Med Ctr, Dept Radiol, Minneapolis, MN 55415 USA. Natl Elect Manufacturers Assoc, Phillips Med Syst, Cleveland, OH 44143 USA. Durham Radiol Associates, Durham, NC 27704 USA. US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Rockville, MD 20850 USA. RP Zinninger, MD (reprint author), Amer Coll Radiol, 1891 Preston White Dr, Reston, VA 20191 USA. NR 18 TC 109 Z9 113 U1 2 U2 2 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD JUN PY 2002 VL 178 IS 6 AR UNSP 0361-803X/02/1786-1335 PG 13 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 557VT UT WOS:000175929800005 PM 12034593 ER PT J AU Yeung, PSM Hayes, MC DePaola, A Kaysner, CA Kornstein, L Boor, KJ AF Yeung, PSM Hayes, MC DePaola, A Kaysner, CA Kornstein, L Boor, KJ TI Comparative phenotypic, molecular, and virulence characterization of Vibrio parahaemolyticus O3 : K6 isolates SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; PANDEMIC STRAINS; O3-K6 STRAINS; EXPRESSION; EMERGENCE; SEQUENCE; SPREAD; CLONE; FOOD AB Historically, ribrioparahaemolyticus infections have been characterized by sporadic cases caused by multiple, diverse serotypes. However, since 1996, V. parahaemolyticus serotype O3:K6 strains have been associated with several large-scale outbreaks of illness, suggesting the emergence of a "new" group of organisms with enhanced virulence. We have applied three different molecular subtyping techniques to identify an appropriate method for differentiating O3:K6 isolates from other serotypes. Pulsed-field gel electrophoresis (PFGE) following NotI digestion differentiated seven closely related subtypes among 03:K6 and related strains, which were distinct from PFGE patterns for non-O3:K6 isolates. Ribotyping and tdh sequencing were less discriminatory than PFGE, but further confirmed close genetic relationships among recent 03:K6 isolates. In vitro adherence and cytotoxicity studies with human epithelial cells showed that O3:K6 isolates exhibited statistically higher levels of adherence and cytotoxicity to host cells than non-O3:K6 isolates. Epithelial cell cytotoxicity patterns were determined with a lactate dehydrogenase release assay. At 3 h postinfection, high relative cytotoxicities (>50% maximum lactate dehydrogenase activity) were found among a greater proportion of recently isolated O3:K6 and closely related strains (75%) than among the non-O3:K6 isolates (23%). A statistically significant relationship between adherence and cytotoxicity suggests that the pathogenic potential of some isolates may be associated with increased adherence to epithelial cells. Our findings suggest that enhanced adherence and cytotoxicity may contribute to the apparent unique pathogenic potential of V. parahaemolyticus O3:K6 strains. C1 Cornell Univ, Dept Food Sci, Ithaca, NY 14853 USA. Dept Hlth, Bur Labs, New York, NY 10016 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. RP Boor, KJ (reprint author), Cornell Univ, Dept Food Sci, 413 Stocking Hall, Ithaca, NY 14853 USA. RI Boor, Kathryn/B-3545-2009 OI Boor, Kathryn/0000-0001-6810-3434 NR 21 TC 45 Z9 52 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUN PY 2002 VL 68 IS 6 BP 2901 EP 2909 DI 10.1128/AEM.68.6.2901-2909.2002 PG 9 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 559MN UT WOS:000176030100036 PM 12039748 ER PT J AU Mossoba, MM Khambaty, FM Fry, FS AF Mossoba, MM Khambaty, FM Fry, FS TI Novel application of a disposable optical film to the analysis of bacterial strains: A chemometric classification of mid-infrared spectra SO APPLIED SPECTROSCOPY LA English DT Article DE bacteria; infrared; disposable optical film; principal component analysis; PCA; hierarchical cluster analysis; HCA; dendrogram ID SPECTROSCOPY; IDENTIFICATION AB A microporous polyethylene disposable optical film (DOF) that is mostly transparent to infrared light was used to characterize bacterial strains by Fourier transform infrared (FT-IR) spectroscopy for subsequent classification by principal components analysis (PCA) and hierarchical cluster analysis (HCA). Developing a methodology with a disposable infrared substrate is desirable for the FTIR measurement of pathogenic bacteria. The bacteria studied were Escherichia coli HB101, E. coli ATCC 43888, a wild-type E. coli, and one strain each of Pseudomonas aeruginosa, Bacillus cereus, and Listeria innocua. The cultures were harvested by centrifugation and the wet cells (5 mg) were placed onto DOF and dried under vacuum at room temperature for one hour. For each strain, four replicates were prepared and measured on each of six different days in order to investigate the possible sources of variance in the sampling procedure. PCA obtained for second derivative, mean-centered spectra for selected frequency ranges (1312-1339, 1026-1061, and 903-930 cm(-1)) explained over 98.1% of the total variability using the first three principal components. The scores plots exhibited six tight clusters of 24 points each (4 replicates x 6 days). Out of a total of 144 spectra, one outlier was found. The dendrograms resulting from HCA (centroid linkage method) correctly clustered all 143 remaining samples. The analysis provided excellent discrimination between the different species and, more significantly, between the different E. coli strains. This work demonstrates the potential of this procedure for the rapid, repeatable, and precise classification of bacteria, with minimum sample preparation, in food safety laboratories. C1 US FDA, Ctr Food Safety & Appl Nutr, OSAS, Div Gen Sci Support, College Pk, MD 20740 USA. OPDFB, Div Microbiol Studies, College Pk, MD 20740 USA. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, OSAS, Div Gen Sci Support, 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 13 TC 17 Z9 17 U1 1 U2 6 PU SOC APPLIED SPECTROSCOPY PI FREDERICK PA 201B BROADWAY ST, FREDERICK, MD 21701 USA SN 0003-7028 J9 APPL SPECTROSC JI Appl. Spectrosc. PD JUN PY 2002 VL 56 IS 6 BP 732 EP 736 DI 10.1366/000370202760077450 PG 5 WC Instruments & Instrumentation; Spectroscopy SC Instruments & Instrumentation; Spectroscopy GA 567YC UT WOS:000176513800009 ER PT J AU Shuren, JE Grafman, J AF Shuren, JE Grafman, J TI The neurology of reasoning SO ARCHIVES OF NEUROLOGY LA English DT Review ID ORBITOFRONTAL CORTEX; DECISION-MAKING; HUMAN AMYGDALA; HEMISPHERE; EMOTION; BRAIN C1 US FDA, Off Policy Planning & Legislat, Rockville, MD 20857 USA. NINCDS, Cognit Neurosci Sect, NIH, Rockville, MD USA. RP Shuren, JE (reprint author), US FDA, Off Policy Planning & Legislat, HF-11,Room 14-101,5600 Fishers Ln, Rockville, MD 20857 USA. OI Grafman, Jordan H./0000-0001-8645-4457 NR 20 TC 20 Z9 21 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0003-9942 J9 ARCH NEUROL-CHICAGO JI Arch. Neurol. PD JUN PY 2002 VL 59 IS 6 BP 916 EP 919 DI 10.1001/archneur.59.6.916 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 561TK UT WOS:000176158600002 PM 12056926 ER PT J AU Nambiar, S Schwartz, RH Sheridan, MJ AF Nambiar, S Schwartz, RH Sheridan, MJ TI Antibiotic use for upper respiratory tract infections - How well do pediatric residents do? SO ARCHIVES OF PEDIATRICS & ADOLESCENT MEDICINE LA English DT Article; Proceedings Paper CT 39th Interdisciplinary Conference on Antimicrobial Agents and Chemotherapy (ICAAC) CY SEP 26-29, 1999 CL SAN FRANCISCO, CALIFORNIA ID GROUP-A STREPTOCOCCI; ERYTHROMYCIN RESISTANCE; INTERNAL-MEDICINE; OTITIS-MEDIA; PHYSICIANS; CHILDREN; GUIDELINES; TEACHERS; BACTERIA AB Background: Antibiotics are often used inappropriately for the treatment of upper respiratory tract infections in children, and the emergence of resistant bacteria is a growing public health concern. Objective: To assess awareness and compliance with the Centers for Disease Control and Prevention (Atlanta, Ga) and American Academy of Pediatrics (Elk Grove Village, 111) principles for judicious antibiotic use for upper respiratory tract infections among residents from a sample of pediatric residency programs in the mid-Atlantic region of the United States. Participants and Methods: Residents at the participating programs were requested to complete a survey questionnaire. Results: Of the 524 pediatric residents surveyed, 74% (388 participants) completed the questionnaire. Familiarity with the principles increased with a year of training; 16%, 36%, and 50% of first-year (PL1), second-year (PL2), and third- or fourth-year (PL3/PL4) residents, respectively, had heard or read about the principles (x(trend)(2); P < .001) - In response to a direct question about the use of antibiotics for an otherwise well, afebrile 18-month-old child with purulent rhinorrhea, 29%, 25%, and 15% of PL1, PL2, and PL3/PL4 residents, respectively, would prescribe antibiotics within 10 days of onset of illness (x(trend)(2); P=.008). A significant difference was found between PL1 vs PL3/PL4 participants (difference = 20%; 95% CI = 3%-26%). if the same infant had a temperature of 38.8degreesC, then 63%, 45%, and 47% of PL1, PL2, and PL3/PL4 residents, respectively, would prescribe antibiotics (x(trend)(2); P=.008). Conclusions: Awareness among pediatric residents about the judicious use of antibiotics for upper respiratory tract infections is often lacking, and inappropriate use of antibiotics for this condition continues to be prevalent. This was especially noted among PL1 residents, with an improving trend noted with increasing years of training. C1 Inova Fairfax Hosp Children, Dept Pediat, Falls Church, VA USA. Inova Fairfax Hosp Children, Dept Med, Falls Church, VA USA. US FDA, Washington, DC 20204 USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. RP Nambiar, S (reprint author), Dept Infect Dis, 111 Michigan Ave NW, Washington, DC 20010 USA. NR 17 TC 6 Z9 6 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 1072-4710 J9 ARCH PEDIAT ADOL MED JI Arch. Pediatr. Adolesc. Med. PD JUN PY 2002 VL 156 IS 6 BP 621 EP 624 PG 4 WC Pediatrics SC Pediatrics GA 559ZE UT WOS:000176055900017 PM 12038897 ER PT J AU Lee, CJ AF Lee, CJ TI Quality control of polyvalent pneumococcal polysaccharide-protein conjugate vaccine by nephelometry SO BIOLOGICALS LA English DT Article ID B CONJUGATE AB A nephelometric method was used for quantitative analysis of individual polysaccharides (PSs) in a polyvalent pneumococcal conjugate vaccine using CRM197 as carrier protein. Using this method, the individual types 4, 613, 9V, 14, 18C, 19F and 23F PSs were found to range between 82.3 to 119% of the manufacturer's indicated values. During conjugation using reductive amination, pneumococcal PS was first oxidized to introduce aldehyde groups. Higher or lower levels of antigen-anti body reaction were observed in periodate activated and then reduced PS of some serotypes compared to non-treated PS. Use of oxidized and reduced PS may provide an early indication of change in conjugation process. Furthermore, since the final monovalent and polyvalent conjugate vaccines gradually change during the storage period, the nephelometry provides an useful analytical method for stability study of these vaccines. (C) 2002 The International Association for Biologicals. Published by Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Lee, CJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 9 TC 13 Z9 14 U1 1 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD JUN PY 2002 VL 30 IS 2 BP 97 EP 103 DI 10.1006/biol.2001.0320 PG 7 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 587DN UT WOS:000177625400004 PM 12127311 ER PT J AU Mancuso, JY Ahn, H Chen, JJ Mancuso, JP AF Mancuso, JY Ahn, H Chen, JJ Mancuso, JP TI Age-adjusted exact trend tests in the event of rare occurrences SO BIOMETRICS LA English DT Article DE dose-response; exact poly-3 test; exact randomization test; permutation; Peto cause-of-death test; survival adjustment ID TUMOR-INCIDENCE RATE; OF-DEATH TEST; CARCINOGENICITY EXPERIMENTS; MORTALITY; ANIMALS; ONSET; TIME AB Preclinical animal carcinogenicity studies are usually concerned with testing the statistical significance of a dose-response relationship. When the response consists of a rare event such as the development of a certain type. of tumor, exact statistical methods are often employed. The exact randomization trend test based on the multivariate hypergeometric distribution is less powerful in the presence of treatment-related risks other than the specified response. Particularly, the loss of power becomes more pronounced when competing risks cause progressively higher mortality rates with increasing dose, which is usual in practice. An age-adjusted form of the randomization test is proposed to adjust for this effect. Permutational distribution for Peto's cause-of-death (COD) test is also explored and compared with its asymptotic counterpart by simulation. The use of COD information has been a controversial issue due to the subjectivity in the pathologists' determinations as well as for economic reasons. The proposed a.-e-adjusted exact test does not require COD, and it is shown to compare favorably to the COD tests via an extensive Monte Carlo simulation. Applications of the. methods to two real data sets are included. C1 Pifzer Global Res & Dev, Groton, CT 06340 USA. SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Mancuso, JY (reprint author), Pifzer Global Res & Dev, Groton, CT 06340 USA. FU NCI NIH HHS [R29 CA77289-04] NR 27 TC 10 Z9 11 U1 0 U2 3 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 1441 I ST, NW, SUITE 700, WASHINGTON, DC 20005-2210 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD JUN PY 2002 VL 58 IS 2 BP 403 EP 412 DI 10.1111/j.0006-341X.2002.00403.x PG 10 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 561RT UT WOS:000176157000017 PM 12071414 ER PT J AU Parsons, BL Culp, SJ Manjanatha, MG Heflich, RH AF Parsons, BL Culp, SJ Manjanatha, MG Heflich, RH TI Occurrence of H-ras codon 61 CAA to AAA mutation during mouse liver tumor progression SO CARCINOGENESIS LA English DT Article ID COMPETITIVE BLOCKER PCR; GENOTYPIC SELECTION METHODS; POINT MUTATIONS; HUMAN CANCER; COAL-TAR; BENZOPYRENE; TUMORIGENESIS; MECHANISMS; MICE; RISK AB The initiating mutations of a tumor are present in each of the cancerous cells comprising the tumor. Identification and measurement of the subsequent mutations that occur during tumor progression, however, requires mutation detection in a smaller subset of the tumor cells. In this study, allele-specific competitive blocker PCR (ACB-PCR), a genotypic selection method with the sensitivity to detect a specific point mutation in the presence of a 10(5)-fold excess of wild-type DNA sequence, was used to measure H-ras codon 61 CAA to AAA mutation in mouse liver tumors that did not have this mutation as an initiating event. Twenty-one spontaneous or chemically induced mouse liver tumors, negative for the H-ras codon 61 CAA to AAA mutation by DNA sequencing or denaturing gradient gel electrophoresis, were analyzed for this mutation by ACB-PCR. The mutation was detected at some level in 71% of these tumors. The mutation was detected in adenomas and carcinomas more frequently (13 of 14 tumors) and at significantly higher mutant fractions than it was detected in histiocytic sarcomas (1 of 5 tumors). These data indicate that the same oncogenic point mutation that can be identified as a tumor-initiating event based on its clonal amplification in a tumor can also be present in only a small sub-population of tumor cells where the mutation must have been fixed at a later stage in tumor development. The occurrence of a mutation as a primary or secondary event probably reflects the stochastic nature of mutation and is likely to be affected by the mutation rate for each target site. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 23 TC 10 Z9 10 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JUN PY 2002 VL 23 IS 6 BP 943 EP 948 DI 10.1093/carcin/23.6.943 PG 6 WC Oncology SC Oncology GA 569NH UT WOS:000176608100005 PM 12082015 ER PT J AU Anderson, HA Englert, R Gursel, I Shacter, E AF Anderson, HA Englert, R Gursel, I Shacter, E TI Oxidative stress inhibits the phagocytosis of apoptotic cells that have externalized phosphatidylserine SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE apoptosis; phagocytosis; phosphatidylserine; oxidants ID PLASMA-MEMBRANE PHOSPHATIDYLSERINE; MACROPHAGE RECOGNITION; VITRONECTIN RECEPTOR; HYDROGEN-PEROXIDE; PROTEIN OXIDATION; DENDRITIC CELLS; GENERAL FEATURE; IN-VITRO; CLEARANCE; EXPOSURE AB The efficient phagocytosis of apoptotic cells by macrophages reduces the potential for an inflammatory response by ensuring that the dying cells are cleared before their Intracellular contents are released. Early apoptotic cells are targeted for phagocytosis through the translocation of phosphatidylserine (PS) from the inner to the outer leaflet of the plasma membrane. In this report, we show that the oxidant H2O2 inhibits phagocytosis of apoptotic cells even though the cells express functional PS on their surface. Thus, B lymphoma cells induced to undergo apoptosis by the chemotherapy drug etoposide are efficiently phagocytosed by macrophages in a process that is mediated by PS (Inhibitable by PS liposomes). Exposure of the apoptotic cells to H2O2 inhibits phagocytosis even though the cells still express functional PS on their surface. In addition, Jurkat cells and thymocytes induced to undergo apoptosis by H2O2 alone are poorly phagocytosed. Inhibition of phagocytosis by H2O2 cannot be attributed to oxidative inactivation or redistribution of PS on the cell surface. The results indicate that PS externalization is necessary but is not sufficient to target apoptotic cells for phagocytosis. Another phagocytosis recognition factor must therefore exist to facilitate uptake of apoptotic cells, and this factor is sensitive to modification by H2O2. C1 US FDA, Ctr Biol Evaluat & Res, Immunol Lab, Div Therapeut Prot, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Retroviral Res, Div Viral Prod, Bethesda, MD 20892 USA. USN, Uniformed Serv Univ Hlth Sci, Bethesda, MD 20879 USA. RP Anderson, HA (reprint author), US FDA, Ctr Biol Evaluat & Res, Immunol Lab, Div Therapeut Prot, Bld 29A,Rm 2A-07, Bethesda, MD 20892 USA. OI Gursel, Ihsan/0000-0003-3761-1166 NR 46 TC 35 Z9 38 U1 0 U2 3 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JUN PY 2002 VL 9 IS 6 BP 616 EP 625 DI 10.1038/sj/cdd/4401013 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 560ZP UT WOS:000176111500005 PM 12032670 ER PT J AU Joshi, BH Kawakami, K Leland, P Puri, RK AF Joshi, BH Kawakami, K Leland, P Puri, RK TI Heterogeneity in interleukin-13 receptor expression and subunit structure in squamous cell carcinoma of head and neck: Differential sensitivity to chimeric fusion proteins comprised of interleukin-13 and a mutated form of Pseudomonas exotoxin SO CLINICAL CANCER RESEARCH LA English DT Article ID KAPOSIS-SARCOMA CELLS; COMMON GAMMA-CHAIN; HUMAN GLIOMA-CELLS; SIGNAL-TRANSDUCTION; CANCER-CELLS; ALPHA CHAIN; (IL)-13 BINDING; IL-4 RECEPTORS; GENE-THERAPY; B-CELLS AB Squamous cell carcinoma of the head and neck (SCCHN) is characterized by a high proliferation index and marked propensity for local invasion resulting in poor prognosis for these patients. To develop tumor-targeted novel therapeutic agents, here we demonstrate that SCCHN cell lines express receptors for an immune regulatory cytokine, interleukin (IL) 13. By reverse transcription-PCR (RT-PCR), we found that 16 SCCHN cell lines express equally strong RT-PCR positive bands for mRNA of IL-13Ralpha1 and IL-4Ralpha chains. However, only three cell lines, HN12, YCUM911, and KCCT873, expressed a strong band for transcripts for IL-13Ralpha2 chain and five cell lines, YCUL891, KCCTC871, KCCL871, KCCTCM901, and RPMI 2650 expressed faint bands. Transcripts for IL-2Rgammac. chain were absent in all of the cell lines tested. Indirect immunofluorescence analysis for four different receptor chains confirmed RT-PCR results and showed pronounced expression of IL-13Ralpha2 protein in three high IL-13R expressing cell lines. All of the cell lines were equally positive for IL-13Ralpha1 and IL-4Ralpha chains. Receptor-binding studies demonstrated that IL-13Ralpha2-positive cell lines expressed a high density of IL-13 receptors. Using two chimeric proteins composed of IL-13 and mutated forms of Pseudomonas exotoxin (IL-13-PE38 or IL-13-PE38QQR), we found that these two fusion toxins were highly and equally cytotoxic to IL-13Ralpha2-positive SCCHN, whereas IL-13Ralpha2-negative cell lines showed low or no sensitivity to IL-13 toxins. To additionally substantiate the critical role of the IL-13Ralpha2 chain in IL-13R-mediated cytotoxicity, two head and neck tumor cell lines (YCUMS861 and KB), devoid of the transcripts of this chain, were transfected with IL-13Ralpha2 cDNA and then tested for cytotoxicity. Transient transfection of the IL-13Ralpha2 chain highly sensitized these cells to IL-13 toxin as compared with mock-transfected control cells. Thus, our results indicate that IL-13Ralpha2 is present in 50% SCCHN tumor cell lines; of these, 19% are high expresser for this chain and respond to IL-13 cytotoxin. Thus, IL-13 cytotoxin may be a useful agent for high IL-13R-expressing SCCHN. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Bldg 29 B,Room 2NN10,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 51 TC 65 Z9 65 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JUN PY 2002 VL 8 IS 6 BP 1948 EP 1956 PG 9 WC Oncology SC Oncology GA 561LJ UT WOS:000176141900037 PM 12060640 ER PT J AU Marti, GE AF Marti, GE TI The role of splenectomy in splenic marginal zone B-cell lymphoma SO CLINICAL LYMPHOMA LA English DT Editorial Material ID CHRONIC LYMPHOCYTIC-LEUKEMIA; VILLOUS LYMPHOCYTES C1 NIH, Ctr Biol Evaluat & Res, US FDA, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), NIH, Ctr Biol Evaluat & Res, US FDA, Bldg 10, Bethesda, MD 20892 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU CANCER INFORMATION GROUP, LP PI DALLAS PA 3535 WORTH ST, SAMMONS TOWER, STE 4802, DALLAS, TX 75246 USA SN 1526-9655 J9 CLIN LYMPHOMA JI Clin. Lymphoma PD JUN PY 2002 VL 3 IS 1 BP 48 EP 48 PG 1 WC Oncology SC Oncology GA 581CY UT WOS:000177274600006 PM 12141955 ER PT J AU Wang, ZQ Hamman, MA Huang, SM Lesko, LJ Hall, SD AF Wang, ZQ Hamman, MA Huang, SM Lesko, LJ Hall, SD TI Effect of St John's wort on the pharmacokinetics of fexofenadine SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID FIRST-PASS METABOLISM; P-GLYCOPROTEIN; RIFAMPIN; DIGOXIN; PHARMACODYNAMICS; ACCUMULATION; EXCRETION; INDUCTION; INDINAVIR; RECEPTOR AB Background. St John's wort is a popular over-the-counter dietary supplement and herbal remedy that has been implicated in drug interactions with several substrates of P-glycoprotein. The effect of St John's wort on P-glycoprotein activity in vivo was examined with use of fexofenadine as selective probe drug. Methods. A 3-period, open-label, fixed-schedule study design was used. Fexofenadine, 60 mg, was administered orally before administration of St John's wort, with a single dose of St John's wort (900 mg), and after 2 weeks of treatment with St John's wort (300 mg 3 times a day) to determine P-glycoprotein activity. Results: A single dose of St John's wort significantly (P<.05) increased the maximum plasma concentration of fexofenadine by 45% and significantly (P<.05) decreased the oral clearance by 20%, with no change in half-life or renal clearance. Long-term administration of St John's wort did not cause a significant change in fexofenadine disposition relative to the untreated phase. Compared with the single-dose treatment phase, long-term St John's wort caused a significant 35% decrease (P<.05) in maximum plasma concentration and a significant 47% increase (P<.05) in fexofenadine oral clearance. Conclusions. A single dose of St John's wort resulted in a significant inhibition of intestinal P-glycoprotein. Long-term treatment with St John's wort reversed the changes in fexofenadine disposition observed with single-dose administration. C1 Indiana Univ, Sch Med, Dept Med, Div Clin Pharmacol, Indianapolis, IN USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hall, SD (reprint author), Wishard Mem Hosp, OPW, Room 320,1001 W 10th St, Indianapolis, IN 46202 USA. FU FDA HHS [FD-T-001756-01]; NCRR NIH HHS [M01-RR00750]; NIGMS NIH HHS [T32GM08425] NR 26 TC 134 Z9 140 U1 0 U2 3 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 JUN PY 2002 VL 71 IS 6 BP 414 EP 420 DI 10.1067/mcp.2002.124080 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 571NT UT WOS:000176724000002 PM 12087344 ER PT J AU Doerge, DR Sheehan, DM AF Doerge, DR Sheehan, DM TI Goitrogenic and estrogenic activity of soy isoflavones SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT Work Session on Impact of Endocrine Disruptors on Brain Development and Behavior CY MAR 15-20, 2002 CL INT SCH ETHOL, ETTORE MAFORANA CTR SCI CULTURE, ERICE, ITALY HO INT SCH ETHOL, ETTORE MAFORANA CTR SCI CULTURE DE estrogen toxicity; estrogenicity; genistein; isoflavones; mass spectrometry; soy; thyroid peroxidase; thyroid toxicity ID CHROMATOGRAPHY-MASS-SPECTROMETRY; SPRAGUE-DAWLEY RATS; THYROID PEROXIDASE; PREMENOPAUSAL WOMEN; ANTITHYROID ACTION; IN-VITRO; GENISTEIN; MECHANISM; FORMULA; INHIBITION AB Soy is known to produce estrogenic isoflavones. Here, we briefly review the evidence for binding of isoflavones to the estrogen receptor, in vivo estrogenicity and developmental toxicity, and estrogen developmental carcinogenesis in rats. Genistein, the major soy isoflavone, also has a frank estrogenic effect in women. We then focus on evidence from animal and human studies suggesting a link between soy consumption and goiter, an activity independent of estrogenicity. Iodine deficiency greatly increases soy antithyroid effects, whereas iodine supplementation is protective. Thus, soy effects on the thyroid involve the critical relationship between iodine status and thyroid function. In rats consuming genistein-fortified diets, genistein was measured in the thyroid at levels that produced dose-dependent and significant inactivation of rat and human thyroid peroxidase (TPO) in vitro. Furthermore, rat TPO activity was dose-dependently reduced by up to 80%. Although these effects are clear and reproducible, other measures of thyroid function in vivo (serum levels of triiodothyronine, thyroxine, and thyroid-stimulating hormone; thyroid weight; and thyroid histopathology) were all normal. Additional factors appear necessary for soy to cause overt thyroid toxicity. These clearly include iodine deficiency but may also include additional soy components, other defects of hormone synthesis, or additional goitrogenic dietary factors. Although safety testing of natural products, including soy products, is not required, the possibility that widely consumed soy products may cause harm in the human population via either or both estrogenic and goitrogenic activities is of concern. Rigorous, high-quality experimental and human research into soy toxicity is the best way to address these concerns. Similar studies in wildlife populations are also appropriate. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Daniel M Sheehan & Associates, Little Rock, AR USA. RP Sheehan, DM (reprint author), 1422 Scott St, Little Rock, AR 72202 USA. NR 54 TC 129 Z9 139 U1 1 U2 11 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JUN PY 2002 VL 110 SU 3 BP 349 EP 353 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 565PC UT WOS:000176377800003 PM 12060828 ER PT J AU Dougherty, S Pluznik, D AF Dougherty, S Pluznik, D TI Expression of the hematopoietic stem cell marker CD34 is related to the cell cycle status SO EXPERIMENTAL HEMATOLOGY LA English DT Meeting Abstract C1 US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0301-472X J9 EXP HEMATOL JI Exp. Hematol. PD JUN PY 2002 VL 30 IS 6 SU 1 MA 57 BP 51 EP 51 PG 1 WC Hematology; Medicine, Research & Experimental SC Hematology; Research & Experimental Medicine GA 562FP UT WOS:000176187000056 ER PT J AU Bork, RH Troy, DE AF Bork, RH Troy, DE TI Locating the boundaries: The scope of Congress's power to regulate commerce SO HARVARD JOURNAL OF LAW AND PUBLIC POLICY LA English DT Article ID PROPER SCOPE; CLAUSE; FEDERALISM; ISSUES C1 US FDA, Rockville, MD 20857 USA. NR 59 TC 13 Z9 13 U1 0 U2 0 PU HARVARD SOC LAW PUBLIC POLICY PI CAMBRIDGE PA HARVARD LAW SCHOOL, CAMBRIDGE, MA 02138 USA SN 0193-4872 J9 HARVARD J LAW PUBL P JI Harv. J. Law Public Policy PD SUM PY 2002 VL 25 IS 3 BP 849 EP 893 PG 45 WC Law SC Government & Law GA 569JT UT WOS:000176599800007 ER PT J AU Baranova, I Vishnyakova, T Bocharov, A Chen, ZG Remaley, AT Stonik, J Eggerman, TL Patterson, AP AF Baranova, I Vishnyakova, T Bocharov, A Chen, ZG Remaley, AT Stonik, J Eggerman, TL Patterson, AP TI Lipopolysaccharide down regulates both scavenger receptor B1 and ATP binding cassette transporter A1 in RAW cells SO INFECTION AND IMMUNITY LA English DT Article ID CORONARY HEART-DISEASE; NF-KAPPA-B; HIGH-DENSITY-LIPOPROTEIN; NECROSIS-FACTOR-ALPHA; SMOOTH-MUSCLE CELLS; CHOLESTEROL EFFLUX; CHLAMYDIA-PNEUMONIAE; GENE-EXPRESSION; CELLULAR CHOLESTEROL; SIGNAL-TRANSDUCTION AB Lipopolysaccharide (LPS) has recently been shown to facilitate macrophage foam cell formation and has been suggested to be a proatherogenic factor. The mechanism of LPS induced cholesterol accumulation, however, is unclear. In this report, using the macrophage-like RAW 264.7 cell line, we provide experimental evidence that LPS's proatherogenic effects may at least in part reflect altered cholesterol metabolism. Data presented demonstrate that in a dose-dependent manner, LPS is able to down regulate the mRNA expression of the two primary high-density lipoprotein (HDL) receptors, scavenger receptor B1 (SR-B1) and ATP binding cassette A1 (ABCA1), with a 50% inhibitory concentration of less than 0.2 ng/ml, as well as to decrease SR-B1 protein expression by 80%. We also found that LPS treatment resulted in a significant decrease (to 20% of the control level) of the specific I-125-HDL binding as well as in 50% inhibition of the HDL-mediated cholesterol efflux compared to untreated cells. In addition, we compared the potencies of various modified LPS preparations and demonstrated that the phosphorylated lipid A portion of LPS, which is highly conserved among gram-negative microorganisms, including Chlamydia, is primarily responsible for the effects of LPS on SR-B1 and ABCA1 expression. Inhibitors of NF-kappaB activation were observed to efficiently block the suppressive effect of LPS on SR-B1 and ABCA1, suggesting a mechanism involving NF-kappaB. These data indicate that the LPS effects on cholesterol metabolism may contribute to the proatherogenic properties of LPS. C1 NHLBI, Bethesda, MD 20892 USA. NIDDK, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Patterson, AP (reprint author), NIH, Off Director, 6705 Rockledge Dr,Suite 750, Bethesda, MD 20892 USA. NR 60 TC 103 Z9 108 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2002 VL 70 IS 6 BP 2995 EP 3003 DI 10.1128/IAI.70.6.2995-3003.2002 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 554XA UT WOS:000175761400033 PM 12010990 ER PT J AU Feng, CG Woodside, KJ Vance, BA El-Khoury, D Canelles, M Lee, J Gress, R Fowlkes, BJ Shores, EW Love, PE AF Feng, CG Woodside, KJ Vance, BA El-Khoury, D Canelles, M Lee, J Gress, R Fowlkes, BJ Shores, EW Love, PE TI A potential role for CD69 in thymocyte emigration SO INTERNATIONAL IMMUNOLOGY LA English DT Article DE CD69 antigen; development; lymphocyte activation; transgenes ID ACTIVATION ANTIGEN CD69; T-CELL ACTIVATION; RECENT THYMIC EMIGRANTS; POSITIVE SELECTION; TRANSGENIC MICE; RECEPTOR; EXPRESSION; DIFFERENTIATION; CHEMOKINES; MAJORITY AB The early activation marker, CD69, is transiently expressed on activated mature T cells and on thymocytes that are undergoing positive or negative selection in the thymus. CD69 is a member of the NK gene complex family of C-type lectin-like signaling receptors; however, its function is unknown. In this report, we describe the characterization of mice that constitutively express high levels of surface CD69 on immature and mature T cells throughout development. Constitutive surface expression of CD69 did not affect T cell maturation, signaling through the TCR or thymocyte selection. However, phenotypically and functionally mature thymocytes accumulated in the medulla of CD69 transgenic mice and failed to be exported from the thymus. The retention of mature thymocytes correlated with transgene dose and CD69 surface levels. These results identify a potential role for CD69 in controlling thymocyte export, and suggest that the transient expression of CD69 on thymocytes and T cells may function to regulate thymocyte and T cell trafficking. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NCI, Expt Transplantat & Immunol Branch, NIH, Bethesda, MD 20892 USA. NIAID, Lab Mol & Cellular Immunol, NIH, Bethesda, MD 20892 USA. US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Love, PE (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. OI Woodside, Kenneth/0000-0002-7495-3758 NR 37 TC 89 Z9 92 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0953-8178 J9 INT IMMUNOL JI Int. Immunol. PD JUN PY 2002 VL 14 IS 6 BP 535 EP 544 DI 10.1093/intimm/dxf020 PG 10 WC Immunology SC Immunology GA 557MJ UT WOS:000175912100001 PM 12039905 ER PT J AU Arima, K Umeshita-Suyama, R Sakata, Y Akaiwa, M Mao, XQ Enomoto, T Dake, Y Shimazu, S Yamashita, T Sugawara, N Brodeur, S Geha, R Puri, RK Sayegh, MH Adra, CN Hamasaki, N Hopkin, JM Shirakawa, T Izuhara, K AF Arima, K Umeshita-Suyama, R Sakata, Y Akaiwa, M Mao, XQ Enomoto, T Dake, Y Shimazu, S Yamashita, T Sugawara, N Brodeur, S Geha, R Puri, RK Sayegh, MH Adra, CN Hamasaki, N Hopkin, JM Shirakawa, T Izuhara, K TI Upregulation of IL-13 concentration in vivo by the IL13 variant associated with bronchial asthma SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE IL-13; polymorphism; IL-13 receptor alpha 2 chain; allergy; bronchial asthma ID RECEPTOR-ALPHA-CHAIN; GENOME-WIDE SEARCH; SERUM IGE LEVELS; SIGNAL-TRANSDUCTION; INTERLEUKIN-4 RECEPTOR; GENETIC-VARIANTS; ILE50VAL VARIANT; ALLERGIC-ASTHMA; ATOPIC ASTHMA; T-CELLS AB Background: A substantial body of evidence exists to support the pivotal role of IL-13 in the pathogenesis of bronchial asthma. We recently found that a variant of the IL13 gene (Arg110Gln) is genetically associated with bronchial asthma, which is concordant with animal experiments using IL-13 in the development of asthma. Objective: To address whether the Gln110 variant of IL13 influences IL-13 function, contributing to the pathogenesis of bronchial asthma, we studied the functional properties of the variant. Methods: We generated 2 types of recombinant IL-13 proteins, the amino acids of which at 110 were arginine or glutamine, and analyzed the binding affinities with the IL-13 receptors, as well as the stability of the proteins. We further compared the relationship between the genotype and serum levels of IL-13. Results: The variant showed a lower affinity with the IL-13 receptor alpha2 chain, a decoy receptor, causing less clearance. The variant also demonstrated an enhanced stability in both human and mouse plasma. We further identified that asthmatic patients homozygous for the Gln110 variant have higher serum levels of IL-13 than those without the variant. Conclusion: These results suggested that the variant might act as a functional genetic factor of bronchial asthma with a unique mechanism to upregulate local and systemic IL-13 concentration in vivo. C1 Saga Med Sch, Dept Biochem, Saga 8498501, Japan. Kyushu Univ, Grad Sch Med Sci, Dept Clin Chem & Lab Med, Fukuoka, Japan. Kyoto Univ, Grad Sch Publ Hlth, Dept Hlth Promot & Human Behav, Kyoto, Japan. Univ Coll Swansea, Expt Med Unit, Swansea, W Glam, Wales. Japanese Red Cross Soc, Wakayama Med Ctr, Dept Otolaryngol, Wakayama, Japan. Wakayama Natl Hosp, Dept Pediat, Wakayama, Japan. Mitsubishi Kagaku BCL, Tokyo, Japan. Harvard Univ, Children Hosp, Div Immunol, Boston, MA 02115 USA. Harvard Univ, Dept Pediat, Boston, MA 02115 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD USA. Brigham & Womens Hosp, Lab Immunogenet & Transplantat, Boston, MA 02115 USA. Harvard Univ, Sch Med, Beth Israel Deaconess Med Ctr, Boston, MA USA. RIKEN, SNP Res Ctr, Tokyo, Japan. RP Izuhara, K (reprint author), Saga Med Sch, Dept Biochem, 5-1-1 Nabeshima, Saga 8498501, Japan. RI SUYAMA, Ritsuko/J-3494-2013; Arima, Kazuhiko/I-8962-2014 OI Arima, Kazuhiko/0000-0002-0607-8787 FU NIAID NIH HHS [AI43663] NR 49 TC 100 Z9 109 U1 0 U2 3 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 JUN PY 2002 VL 109 IS 6 BP 980 EP 987 DI 10.1067/mai.2002.124656 PG 8 WC Allergy; Immunology SC Allergy; Immunology GA 566RU UT WOS:000176442700014 PM 12063528 ER PT J AU Vierk, K Falci, K Wolyniak, C Klontz, KC AF Vierk, K Falci, K Wolyniak, C Klontz, KC TI Recalls of foods containing undeclared allergens reported to the US Food and Drug Administration, fiscal year 1999 SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE food allergy; egg; peanut; dairy; recalls ID ANAPHYLAXIS; PEANUT AB Background: Food recalls can play a role in preventing or reducing the number of allergic reactions that may occur after a product containing an undeclared allergen has been introduced into commerce. Objective: We sought to summarize the US Food and Drug Administration's records of recalls classified for fiscal year 1999 involving foods containing undeclared allergens. Methods: Food and Drug Administration food recall records were reviewed for fiscal year 1999 to identify recalls that occurred because of the undeclared presence of one or more of the following allergens: milk, eggs, fish, wheat, crustacean shellfish, tree nuts, peanuts, and soy. Each record was reviewed to determine the recalled product, the undeclared allergen present, the reason for recall, and reported adverse events. Results: Of 659 total food products classified for recall during fiscal year 1999, 236 (36%) products were recalled because they contained one or more undeclared allergens. Consumers were the party most often responsible for identifying that an undeclared allergen was present in a product (56% of recalled products). A total of 34 consumers reported allergic reactions after consumption of the recalled products. Three principal factors contributed to the presence of undeclared allergens in the recalled products: ingredient-statement omissions and errors (51% of all recalled products); manufacturing equipment cross-contact (40%); and errors by ingredient suppliers or manufacturing firm employees (5%). Conclusion: The presence of undeclared allergens in food products represents one of the more common reasons for food-product recall in the United States. A number of well-recognized allergens may be introduced into foods as a result of several different factors. C1 US FDA, Ctr Food Safety & Appl Nutr, Epidemiol Team, College Pk, MD 20740 USA. RP Vierk, K (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Epidemiol Team, HFS-728,5100 Paint Branch Pkwy,Room 2C-077, College Pk, MD 20740 USA. NR 9 TC 52 Z9 57 U1 0 U2 5 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 JUN PY 2002 VL 109 IS 6 BP 1022 EP 1026 DI 10.1067/mai.2002.124500 PG 5 WC Allergy; Immunology SC Allergy; Immunology GA 566RU UT WOS:000176442700021 PM 12063535 ER PT J AU Lathers, CM AF Lathers, CM TI Clinical pharmacology of antimicrobial use in humans and animals SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Review ID RESISTANT ENTEROCOCCUS-FAECIUM; LEVEL GLYCOPEPTIDE RESISTANCE; ANTIBIOTIC USE; BACTERIAL-RESISTANCE; FOOD ANIMALS; ESCHERICHIA-COLI; UNITED-STATES; PUBLIC-HEALTH; IMPACT; EPIDEMIOLOGY AB Veterinary public health is a frontier in the fight against human disease, charged to control and eradicate zoonotic diseases that are naturally transmitted between vertebrate animals and man. Currently there is a need for clinical pharmacologists and all health care givers to limit the development of bacterial resistance in humans to contain the increased health care expenditures related to morbidity and mortality associated with the use of antimicrobials. The development of resistance predates the use of antibiotics and will always be a problem to the successful treatment of patients. Ongoing discussion debates the extent to which antibiotic use in animals contributes to the development of antibiotic resistance in humans. The veterinary use of antibiotics as antimicrobial growth promoters is thought to influence the prevalence of resistance in animal bacteria and to be a risk factor for the emergence of antibiotic resistance in human pathogens. Transfer of antibiotic resistant bacteria from animals to humans may occur via contact, including occupational exposure and via the food chain. Resistance genes may transfer from bacteria of animals to human pathogens in the intestinal flora of humans. Prevention of the development of resistance in humans necessitates good animal husbandry and hygienic measures to prevent cross contamination and a decrease in the use of antibiotics. Appropriate use of antibiotics for food animals will preserve the long-term efficacy of existing antibiotics, support animal health and welfare, and limit the risk of transfer of antibiotic resistance to humans. Investigators must also develop new antimicrobial agents. Poole (J Pharmacy Pharmacol 2001:53:283) recommends targeting the three predominate mechanisms of development of resistance by antimicrobials (i.e., antibiotic inactivation, target site modification, and altered uptake via restricted entry and/or enhanced efflux) to specifically complement the development of novel agents with novel bacterial targets. Bacterial resistance and its selection may be evaluated by comparing the relationship to antibiotic pharmacokinetic (PK) values obtained from serum concentrations and organism MICs (minimum inhibitory concentrations: concentration-dependent killing) to reveal culture and sensitivity tests in patients. Pharmacodynamic (PD) models may be developed to identify factors associated with the probability that bacterial resistance will develop. Thomas et al (Antimicrobial Agents Chemotherapy 1998;42:521) used this combined approach of PK/PD and MICs to examine data retrospectively. The role of clinical pharmacology is to work with PK/PD models such as these to determine the best use of antibiotics in humans to minimize the development of resistance. The role of any regulatory body responsible for the protection of the public health and food safety for consumers is to assess risk and to then communicate and manage the risk. Scientific uncertainty must be interpreted to propose sound policy options. The conversion of sound science into an appropriate regulatory policy to protect the public health is most important. (C) 2002 the American College of Clinical Pharmacology. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Lathers, CM (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA. NR 62 TC 15 Z9 16 U1 2 U2 13 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUN PY 2002 VL 42 IS 6 BP 587 EP 600 DI 10.1177/00970002042006001 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 555CR UT WOS:000175776200001 PM 12043947 ER PT J AU Martinez, MN Amidon, GL AF Martinez, MN Amidon, GL TI A mechanistic approach to understanding the factors affecting drug absorption: A review of fundamentals SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Review ID FIRST-PASS METABOLISM; BIOPHARMACEUTICS CLASSIFICATION-SYSTEM; MULTIDRUG-RESISTANCE PHENOTYPE; MOLECULAR-SURFACE PROPERTIES; P-GLYCOPROTEIN EXPRESSION; BETA-LACTAM ANTIBIOTICS; BRUSH-BORDER MEMBRANE; INTESTINAL-CELL LINE; VILLUS-CRYPT AXIS; ORAL BIOAVAILABILITY AB This article provides an overview of the patient-specific and drug-specific variables that can affect drug absorption following oral product administration. The oral absorption of any chemical entity reflects a complex spectrum of events. Factors influencing product bioavailability include drug solubility, permeability, and the rate of in vivo dissolution. In this regard, the Biopharmaceutics Classification System has proven to be an important tool for predicting compounds likely to be associated with bioavailability problems. It also helps in identifying those factors that may alter the rate and extent of drug absorption. Product bioavailability can also be markedly influenced by patient attributes such as the integrity of the gastrointestinal tract, physiological status, site of drug absorption. membrane transporters, presystemic drug metabolism (intrinsic variables), and extrinsic variables such as the effect of food or concomitant medication. Through an awareness of a drug's physicochemical properties and the physiological processes affecting drug absorption. the skilled pharmaceutical scientist can develop formulations that will maximize product availability. By appreciating the potential impact of patient physiological status, phenotype, age, gender, and lifestyle, dosing regimens can be tailored to better meet the needs of the individual patient. (C) 2002 the American College of Clinical Pharmacology. C1 US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, HFV-130,7500 Standish Pl, Rockville, MD 20855 USA. NR 151 TC 244 Z9 255 U1 4 U2 56 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD JUN PY 2002 VL 42 IS 6 BP 620 EP 643 DI 10.1177/00970002042006005 PG 24 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 555CR UT WOS:000175776200005 PM 12043951 ER PT J AU Keller, SE Merker, RI Taylor, KT Tan, HL Melvin, CD Chirtel, SJ Miller, AJ AF Keller, SE Merker, RI Taylor, KT Tan, HL Melvin, CD Chirtel, SJ Miller, AJ TI Efficacy of sanitation and cleaning methods in a small apple cider mill SO JOURNAL OF FOOD PROTECTION LA English DT Article ID CRITICAL CONTROL POINT; ESCHERICHIA-COLI; ACID TOLERANCE AB The efficacy of cleaning and sanitation in a small apple cider processing plant was evaluated by surface swab methods as well as microbiological examination of incoming raw ingredients and of the final product. Surface swabs revealed that hard-to-clean areas such as apple mills or tubing for pomace and juice transfer may continue to harbor contaminants even after cleaning and sanitation. Use of poor quality ingredients and poor sanitation led to an increase of approximately 2 logs in aerobic plate counts of the final product. Reuse of uncleaned press cloths contributed to increased microbiological counts in the finished juice. Finally, using apples inoculated with Escherichia coli K-12 in the plant resulted in an established population within the plant that was not removed during normal cleaning and sanitation. The data presented in this study suggest that current sanitary practices within a typical small cider facility are insufficient to remove potential pathogens. C1 Natl Ctr Food Safety & Technol, US Food & Drug Adm, Summit Argo, IL 60501 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. El Dorado Cty Dept Agr, Placerville, CA 95667 USA. Univ Calif Davis, Dept Food Sci & Technol, Davis, CA 95616 USA. US FDA, Pacif Regional Lab Southwest, Off Regulatory Affairs, Los Angeles, CA 90015 USA. RP Keller, SE (reprint author), Natl Ctr Food Safety & Technol, US Food & Drug Adm, 6502 South Archer Ave, Summit Argo, IL 60501 USA. NR 17 TC 10 Z9 10 U1 1 U2 6 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2002 VL 65 IS 6 BP 911 EP 917 PG 7 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 560HW UT WOS:000176077500001 PM 12092722 ER PT J AU Gooch, JA DePaola, A Bowers, J Marshall, DL AF Gooch, JA DePaola, A Bowers, J Marshall, DL TI Growth and survival of Vibrio parahaemolyticus in postharvest American oysters SO JOURNAL OF FOOD PROTECTION LA English DT Article ID CHESAPEAKE-BAY; UNITED-STATES; COAST OYSTERS; VULNIFICUS; CONSUMPTION; TEMPERATURE; SHELLSTOCK; INFECTIONS; WASHINGTON; FLORIDA AB Oysters at the retail stage of distribution generally contain greater densities of Vibrio parahaemolyticus than do oysters at harvest. The objective of this study was to determine the effects of postharvest storage at 26 and 3degreesC on the growth and survival of naturally occurring V. parahaemolyticus in shellstock American oysters (Crassostrea virginica). Oysters were collected monthly from May 1998 through April 1999 from Mobile Bay, Alabama, and their V parahaemolyticus densities were determined after 0, 5, 10, and 24 h of postharvest storage at 26degreesC. After 24 h of storage at 26degreesC, oysters were transferred to a refrigerator at 3degreesC and analyzed 14 to 17 days later. V. parahaemolyticus numbers were determined by a direct plating method involving an alkaline-phosphatase-labeled DNA probe that targets the species-specific thermolabile hemolysin gene (tlh-AP) to identify suspect isolates. From April to December, when water temperatures at harvest were >20degreesC, the geometric mean harvest density of V. parahaemolyticus was 130 CFU/g. When water temperatures were <20degreesC, the geometric mean harvest density was 15 CFU/g. After harvest, V. parahaemolyticus multiplied rapidly in live oysters held at 26degreesC, showing a 50-fold increase (1.7 log CFU/,a) at 10 h and a 790-fold increase (2.9 log CFU/g) at 24 h (April through December). Average V parahaemolyticus numbers showed a sixfold decrease (0.8 log CFU/g) after approximately 14 days of refrigeration. These results indicate that V. parahaemolyticus can grow rapidly in unrefrigerated oysters. C1 US Dept Commerce, Natl Ocean & Atmospher Adm, Natl Ocean Serv, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC 29412 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. Mississippi State Univ, Dept Food Sci & Technol, Mississippi State, MS USA. RP Gooch, JA (reprint author), US Dept Commerce, Natl Ocean & Atmospher Adm, Natl Ocean Serv, Ctr Coastal Environm Hlth & Biomol Res, 219 Ft Johnson Rd, Charleston, SC 29412 USA. NR 33 TC 57 Z9 66 U1 1 U2 6 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD JUN PY 2002 VL 65 IS 6 BP 970 EP 974 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 560HW UT WOS:000176077500009 PM 12092730 ER PT J AU Ali, SF Itzhak, Y AF Ali, SF Itzhak, Y TI MDMA- and METH-induced neurotoxicity in mice: sensitization and desensitization to psychostimulants effects SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 US FDA, NCTR, Div Neurotoxicol, Neurochem Lab, Jefferson, AR USA. Univ Miami, Sch Med, Dept Psychiat, Miami, FL 33152 USA. 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 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD JUN PY 2002 VL 81 SU 1 BP 103 EP 103 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 573KU UT WOS:000176829500321 ER PT J AU Piperova, LS Sampugna, J Teter, BB Kalscheur, KF Yurawecz, MP Ku, Y Morehouse, KM Erdman, RA AF Piperova, LS Sampugna, J Teter, BB Kalscheur, KF Yurawecz, MP Ku, Y Morehouse, KM Erdman, RA TI Duodenal and milk trans octadecenoic acid and conjugated linoleic acid (CLA) isomers indicate that postabsorptive synthesis is the predominant source of cis-9-containing CLA in lactating dairy cows SO JOURNAL OF NUTRITION LA English DT Article DE conjugated linoleic acids; trans fatty acids; lactating dairy cows ID FATTY-ACIDS; BOVINE-MILK; RAT-LIVER; DIETARY; RUMEN; BIOHYDROGENATION; FLOW; DESATURATION; SEPARATION; MICROSOMES AB Duodenal and milk samples obtained from lactating cows in a previous study were analyzed to compare the content and isomer distribution of conjugated linoleic acids (CLA) and trans-18:1 fatty acids (tFA). Four diets containing either low [25 g/100 g dry matter (DM)] or high (60 g/100 g DM) forage were fed with or without 2% added buffer to four multiparous Holstein dairy cows in a 2 X 2 factorial, 4 x 4 Latin square design with 3-wk experimental periods. Duodenal flows of CLA were low (1.02-1.84 g/d), compared with that of tFA (57-120 g/d), regardless of diet. The greatest amounts of CLA and tFA, as well as the greatest proportions of trans-10-18:1 (P < 0.02), and cis-9, trans-11 (P < 0.01) and trans-10, cis-12 CLA (P < 0.01) were in the duodenal flow of cows fed the low forage unbuffered diet. In milk fat, tFA were increased by the low forage unbuffered diet and the trans-10-18:1 (P < 0.02) replaced trans-11-18:1 as the major 18:1 isomer. Milk CLA secretion (7.2-9.1 g/d) was greater (P < 0.001) than that in the duodenal flow with each diet. This was due to the increase in cis-9, trans-11-18:2 and trans-7, cis-9 CLA, resulting most likely from endogenous synthesis via Delta9-desaturation of ruminally derived tFA. For other CLA isomers, duodenal flow was always greater than milk secretion, suggesting that they essentially were produced in the rumen. C1 Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Erdman, RA (reprint author), Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. NR 49 TC 177 Z9 185 U1 0 U2 12 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD JUN PY 2002 VL 132 IS 6 BP 1235 EP 1241 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 559NY UT WOS:000176033300023 PM 12042439 ER PT J AU De Veau, IF Pedersoli, W Cullison, R Baker, J AF De Veau, IF Pedersoli, W Cullison, R Baker, J TI Pharmacokinetics of phenylbutazone in beef steers SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID METABOLITE FORMATION; DAIRY-COWS; PLASMA; CATTLE; PREGNANCY; GOATS; LACTATION; EXCRETION; MASTITIS; AGE AB Phenylbutazone was administered intravenously to a group of 11 beef steers at a dosage of 6 mg/kg of body weight. Whole plasma and protein-free plasma were analyzed for phenylbutazone residues. Pharmacokinetic parameters of total and free phenylbutazone in plasma were calculated using a noncompartmental method. In regards to whole plasma data, the mean volume of distribution at steady state (V-ss), was 140 mL/kg body weight, with a mean (+/-SEM) terminal elimination half-life (t (1/2) ) of 34 +/- 9 h. The mean clearance was 3.2 mL/h/kg body weight. The V-ss , as determined from the protein-free plasma fraction, was 54093 mL/kg body weight. This larger V-ss of free phenylbutazone compared with total plasma phenylbutazone was attributed to a high degree of plasma protein binding, as well as the greater penetration of free phenylbutazone into tissues. The mean t(1/2) of free phenylbutazone was 35 +/- 12 h. This similarity to the t(1/2) estimated from total plasma phenylbutazone data is attributed to an equilibrium between free and plasma phenylbutazone during the terminal elimination phase. The pharmacokinetic parameters of free and total plasma phenylbutazone in beef steers are statistically similar to those previously reported for lactating dairy cows. C1 US FDA, Ctr Vet Med, Res Off, Div Residue Chem, Laurel, MD 20708 USA. US FDA, Ctr Vet Med, Res Off, Div Anim Res, Laurel, MD 20708 USA. US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Div Therapeut Drugs Nonfood Anim, Rockville, MD 20855 USA. RP De Veau, IF (reprint author), US Pharmacopeia, 12601 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 28 TC 5 Z9 5 U1 0 U2 6 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 JUN PY 2002 VL 25 IS 3 BP 195 EP 200 DI 10.1046/j.1365-2885.2002.00406.x PG 6 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 566VX UT WOS:000176449900005 PM 12081615 ER PT J AU Martinez, M Langston, C Martin, T Conner, D AF Martinez, M Langston, C Martin, T Conner, D TI Challenges associated with the evaluation of veterinary product bioequivalence: an AAVPT perspective SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID PLASMA-PROTEIN BINDING; STAPHYLOCOCCUS-AUREUS ENDOCARDITIS; RANDOMIZED CLINICAL-TRIALS; CONCENTRATION-TIME CURVE; ABSORPTION RATES; INTERIM ANALYSES; DRUG ABSORPTION; IN-VITRO; BIOAVAILABILITY; PHARMACOKINETICS AB The Generic Animal Drug Patent Term Restoration Act (GADPTRA) enacted in 1988 provided the same benefits to animal drug products that were granted to human generic products. It has been over 13 years since the GADPTRA was enacted, and veterinary drug sponsors and regulators have gained enormous insight and experience into some of the unique challenges associated with the determination of product bioequivalence for veterinary dosage forms. Moreover, advances in information and technology have opened both new issues that must be addressed and new mechanisms for demonstrating product bioequivalence. While many aspects of the existing Center for Veterinary Medicine Bioequivalence Guidance continue to provide invaluable guidance to the animal drug industry, there are also aspects of this guidance that are being called into question. Therefore, during the 2001 annual meeting of the American Academy of Veterinary Pharmacology and Therapeutics, participants were asked to address issues and concerns associated with the evaluation of veterinary product bioequivalence. This manuscript provides a summary of the concerns and discussions that transpired. C1 Ctr Vet Med Food & Drug Adm, Rockville, MD 20855 USA. Univ Illinois, Coll Vet Med, Dept Vet Biosci, Chicago, IL 60680 USA. US FDA, Div Bioequivalence, Ctr Drug Res & Evaluat, Rockville, MD 20857 USA. RP Martinez, M (reprint author), Ctr Vet Med Food & Drug Adm, 7500 Standish Pl,HFV-130, Rockville, MD 20855 USA. EM mmartin1@cvm.fda.gov NR 61 TC 6 Z9 6 U1 0 U2 2 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 0140-7783 EI 1365-2885 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD JUN PY 2002 VL 25 IS 3 BP 201 EP 220 DI 10.1046/j.1365-2885.2002.00407.x PG 20 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 566VX UT WOS:000176449900006 PM 12081616 ER PT J AU Mizukoshi, E Nascimbeni, M Blaustein, JB Mihalik, K Rice, CM Liang, TJ Feinstone, SM Rehermann, B AF Mizukoshi, E Nascimbeni, M Blaustein, JB Mihalik, K Rice, CM Liang, TJ Feinstone, SM Rehermann, B TI Molecular and immunological significance of chimpanzee major histocompatibility complex haplotypes for hepatitis C virus immune response and vaccination studies SO JOURNAL OF VIROLOGY LA English DT Article ID MHC CLASS-I; T-LYMPHOCYTE RESPONSE; PEPTIDE-BINDING MOTIFS; HLA-A ALLELES; CELL EPITOPES; NUCLEOTIDE SUBSTITUTION; OVERDOMINANT SELECTION; HLA-A2.1 MOLECULES; INFECTION; RESPONSIVENESS AB The chimpanzee is a critical animal model for studying cellular immune responses to infectious pathogens such as hepatitis B and C viruses, human immunodeficiency virus, and malaria. Several candidate vaccines and immunotherapies for these infections aim at the induction or enhancement of cellular immune responses against viral epitopes presented by common human major his to compatibility complex (MHC) alleles. To identify and characterize chimpanzee MHC class I molecules that are functionally related to human alleles, we sequenced 18 different Pan troglodytes (Patr) alleles of 14 chimpanzees, 2 of them previously unknown and 3 with only partially reported sequences. Comparative analysis of Patr binding pockets and binding assays with biotinylated peptides demonstrated a molecular homology between the binding grooves of individual Patr alleles and the common human alleles HLA-A1, -A2, -A3, and -B7. Using cytotoxic T cells isolated from the blood of hepatitis C virus (HCV)-infected chimpanzees, we then mapped the Patr restriction of these HCV peptides and demonstrated functional homology between the Patr-HLA orthologues in cytotoxicity and gamma interferon (IFN-gamma) release assays. Based on these results, 21 HCV epitopes were selected to characterize the chimpanzees' cellular immune response to HCV. In each case, IFN-gamma-producing T cells were detectable in the blood after but not prior to HCV infection and were specifically targeted against those HCV peptides predicted by Patr-HLA homology. This study demonstrates a close functional homology between individual Patr and HLA alleles and shows that HCV infection generates HCV peptides that are recognized by both chimpanzees and humans with Patr and HLA orthologues. These results are relevant for the design and evaluation of vaccines in chimpanzees that can now be selected according to the most frequent human MHC haplotypes. C1 NIDDK, Liver Dis Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Hepatatis Res, Bethesda, MD 20892 USA. Rockefeller Univ, Ctr Study Hepatitis C, New York, NY 10021 USA. RP Rehermann, B (reprint author), NIDDK, Liver Dis Sect, NIH, 10 Ctr Dr,Room 9B16, Bethesda, MD 20892 USA. FU NCI NIH HHS [CA85883-01, R01 CA085883] NR 54 TC 25 Z9 27 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD JUN PY 2002 VL 76 IS 12 BP 6093 EP 6103 DI 10.1128/JVI.76.12.6093-6103.2002 PG 11 WC Virology SC Virology GA 557MK UT WOS:000175912200026 PM 12021342 ER PT J AU Kessler, L Ramsey, SD AF Kessler, L Ramsey, SD TI The outcomes of the Cancer Outcomes Research Symposium - A commentary SO MEDICAL CARE LA English DT Article ID DOCTOR-PATIENT COMMUNICATION; BREAST-CANCER; PREVALENCE; UTILITIES; QUALITY; STATES; TRIALS; LIFE C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20850 USA. Fred Hutchinson Canc Res Ctr, Div Publ Hlth Sci, Seattle, WA 98104 USA. RP Kessler, L (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, 1350 Piccard Dr,HFZ-500, Rockville, MD 20850 USA. NR 25 TC 2 Z9 2 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0025-7079 J9 MED CARE JI Med. Care PD JUN PY 2002 VL 40 IS 6 SU S BP 104 EP 108 PG 5 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 556YG UT WOS:000175876700016 ER PT J AU Zhang, H Boring, D Haverkos, H AF Zhang, H Boring, D Haverkos, H TI Human-bacteria nitric oxide cycles in HIV-1 infection SO MEDICAL HYPOTHESES LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; LIVER-INJURY MODEL; KAPOSIS-SARCOMA; ENTERIC BACTERIA; NEISSERIA-GONORRHOEAE; HYDROGEN-PEROXIDE; HYPOCHLOROUS ACID; TAT PROTEIN; REDUCTION; SYNTHASE AB The human intestinal tract harbors a complex microbiotic environment containing commensal bacteria and immunocompetent mucosal cells. There is considerable communication between the bacteria and host cells through dietary constituents and metabolic cycles. We propose that in the pathogenesis of acquired immunodeficiency syndrome (AIDS), the human immunodeficiency virus-1 (HIV-1) triggers a change in a coupled transorganism (human-bacteria) nitric oxide interchange cycle, that may influence the biosynthesis and recycling of nitric oxide (NO) in AIDS patients. Normally, nitric oxide (NO) is produced from arginine through nitrate NO3-, which is ultimately eliminated in the urine and feces. In HIV infection, however, the NO3- is converted into NO and nitrite NO2- and recirculated in the body, perhaps as a result of concomitant opportunistic bacterial infections and cellular hypoxia. Due to the efficient coupling of the human-bacteria nitric oxide cycles, persistently high levels of nitrite and the free radicals peroxynitrite (ONOO-) may occur in AIDS patients, contributing to the etiology of AIDS-related dementia, persistent immunosuppression and Kaposi's sarcoma. (C) 2002 Published by Elsevier Science Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Div Antiviral Drug Prod, Rockville, MD 20857 USA. RP Haverkos, H (reprint author), HFD-530,5600 Fishers Lane, Rockville, MD 20857 USA. NR 43 TC 2 Z9 3 U1 0 U2 0 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0306-9877 J9 MED HYPOTHESES JI Med. Hypotheses PD JUN PY 2002 VL 58 IS 6 BP 439 EP 443 DI 10.1054/mehy.2001.1403 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 596ZG UT WOS:000178196400002 PM 12323108 ER PT J AU Suleiman, O AF Suleiman, O TI Multislice CT vs. radiography debate SO MEDICAL PHYSICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2002 VL 29 IS 6 BP 1298 EP 1298 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 565ME UT WOS:000176373400515 ER PT J AU Balter, S Fletcher, D Kuan, H Miller, D Richter, D Seissl, H Shope, T AF Balter, S Fletcher, D Kuan, H Miller, D Richter, D Seissl, H Shope, T TI Fluoroscopic skin dose measurements SO MEDICAL PHYSICS LA English DT Meeting Abstract C1 Lenox Hill Hosp, New York, NY 10021 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. SUNY Stony Brook, Stony Brook, NY 11794 USA. Natl Naval Med Res Inst, Bethesda, MD USA. Siemens AG, Med Solut, Forcheim, Germany. Ctr Devices & Radiol Hlth, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2002 VL 29 IS 6 BP 1299 EP 1299 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 565ME UT WOS:000176373400518 ER PT J AU Zaremba, L Phillips, R AF Zaremba, L Phillips, R TI FDA guidelines for magnetic resonance equipment safety SO MEDICAL PHYSICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2002 VL 29 IS 6 BP 1302 EP 1303 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 565ME UT WOS:000176373400528 ER PT J AU Heaton, T Kaiser, S Peters, K Stuhlmuller, J AF Heaton, T Kaiser, S Peters, K Stuhlmuller, J TI Intravascular Brachytherapy devices: FDA perspective SO MEDICAL PHYSICS LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2002 VL 29 IS 6 BP 1317 EP 1318 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 565ME UT WOS:000176373400598 ER PT J AU Wagner, R AF Wagner, R TI Multiple-reader, multiple-case (MRMC) ROC analysis in diagnostic imaging, computer-aided diagnosis, and statistical pattern recognition SO MEDICAL PHYSICS LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2002 VL 29 IS 6 BP 1331 EP 1331 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 565ME UT WOS:000176373400657 ER PT J AU Chakrabarti, K AF Chakrabarti, K TI The medical physicist's role in a Full Field Digital Mammography (FFDM) facility SO MEDICAL PHYSICS LA English DT Meeting Abstract C1 US FDA, Div Mammog Qual, Rockville, MD 20857 USA. US FDA, Radiat Programs, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2002 VL 29 IS 6 BP 1355 EP 1355 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 565ME UT WOS:000176373400766 ER PT J AU Nishikawa, R Giger, M Gur, D Jong, R Maidment, A Schmidt, RA Sacks, WM AF Nishikawa, R Giger, M Gur, D Jong, R Maidment, A Schmidt, RA Sacks, WM TI From CAD to CD - Will computers replace radiologists as the primary reader SO MEDICAL PHYSICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Thomas Jefferson Univ Hosp, Philadelphia, PA 19107 USA. Sunnybrook & Womens Coll, Hlth Sci Ctr, Toronto, ON, Canada. Univ Pittsburgh, Pittsburgh, PA USA. Univ Chicago, Chicago, IL 60637 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2002 VL 29 IS 6 BP 1359 EP 1360 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 565ME UT WOS:000176373400785 ER PT J AU Suleiman, O AF Suleiman, O TI MQSA update SO MEDICAL PHYSICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2002 VL 29 IS 6 BP 1364 EP 1364 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 565ME UT WOS:000176373400799 ER PT J AU Spelic, D AF Spelic, D TI Preliminary results of the 2001 nationwide evaluation of X-ray Trends (NEXT) survey of adult chest radiography SO MEDICAL PHYSICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC PHYSICISTS MEDICINE AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0094-2405 J9 MED PHYS JI Med. Phys. PD JUN PY 2002 VL 29 IS 6 BP 1373 EP 1373 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 565ME UT WOS:000176373400841 ER PT J AU Fonseca, V Keebler, M Dicker-Brown, A DeSouza, C Poirier, LA Murthy, SN McNamara, DB AF Fonseca, V Keebler, M Dicker-Brown, A DeSouza, C Poirier, LA Murthy, SN McNamara, DB TI The effect of troglitazone on plasma homocysteine, hepatic and red blood cell S-adenosyl methionine, and S-adenosyl homocysteine and enzymes in homocysteine metabolism in Zucker rats SO METABOLISM-CLINICAL AND EXPERIMENTAL LA English DT Article ID INSULIN-RESISTANCE; HPLC DETERMINATION; DIABETES-MELLITUS; HEALTHY-SUBJECTS; HYPERHOMOCYSTEINEMIA; INCREASES; DISEASE; ADENOSYLMETHIONINE; HYPERINSULINEMIA; NEPHROPATHY AB We studied the effect of troglitazone on the plasma concentrations of homocysteine (tHcy), the erythrocyte and hepatic concentrations of S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH), and the hepatic activities of cystathionine-beta-synthase (COS) and methylenetetrahydrofolate reductase (MTHFR) in lean and fatty Zucker rats (a model of insulin resistance). Four groups of female Zucker rats were studied. Troglitazone (200 mg/kg) was administered by gavage daily for 3 weeks to lean and fatty Zucker rats. The other 2 groups served as controls. The blood parameters were determined at days 0, 10, and 21. The hepatic SAM and SAH concentrations and MTHFR and COS were measured in the 3-week liver samples. Plasma homocysteine fell significantly in all troglitazone-treated animals from a mean +/- SD of 7.6 +/- 1.5 mumol/L to 4.5 +/- 1.1,mumol /L (P <.02) but not in control animals (5.7 +/- 1.8 mumol /L to 5.9 +/- 1.8 mumol/L). The decreases induced by troglitazone in homocysteine were seen in both the lean and the fatty Zucker rats. This was accompanied by significant rises in the hepatic concentrations of SAH and SAM + SAH. In addition, a significant decline in the hepatic SAM/SAH ratio was observed. The mean +/- SD hepatic CbetaS (expressed as nmol of cystathionine formed at 37degreesC) in the troglitazone-treated rats was 1,226 +/- 47 nmol/h/mg protein, which was significantly higher than that in the control group (964 +/- 64 nmol/h/mg protein; P =.03). We conclude that troglitazone lowers plasma homocysteine in insulin-resistant animals. The homocysteine-lowering effects of troglitazone may be mediated in part by a shift in the concentrations of tHcy and its related metabolites from the blood to the liver as well as by an upregulation of hepatic CbetaS activity. These data support the hypothesis that insulin may regulate homocysteine metabolism through regulation of hepatic CbetaS activity, although activity of other hepatic enzymes not studied here may also contribute to these observations. Copyright 2002, Elsevier Science (USA), All rights reserved. C1 Tulane Univ, Sch Med, Sect Endocrinol, Dept Med, New Orleans, LA 70112 USA. Univ Arkansas Med Sci, Little Rock, AR USA. Natl Ctr Toxicol Res, Jefferson, AR USA. RP Fonseca, V (reprint author), Tulane Univ, Sch Med, Sect Endocrinol, Dept Med, 1430 Tulane Ave SL-53, New Orleans, LA 70112 USA. NR 23 TC 24 Z9 26 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 0026-0495 J9 METABOLISM JI Metab.-Clin. Exp. PD JUN PY 2002 VL 51 IS 6 BP 783 EP 786 DI 10.1053/meta.2002.32731 PG 4 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 558LJ UT WOS:000175967700019 PM 12037736 ER PT J AU White, DG Zhao, S McDermott, PF Ayers, S Gaines, S Friedman, S Wagner, DD Meng, J Needle, D Davis, M DebRoy, C AF White, DG Zhao, S McDermott, PF Ayers, S Gaines, S Friedman, S Wagner, DD Meng, J Needle, D Davis, M DebRoy, C TI Characterization of antimicrobial resistance among Escherichia coli O111 isolates of animal and human origin SO MICROBIAL DRUG RESISTANCE-MECHANISMS EPIDEMIOLOGY AND DISEASE LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; ANTIBIOTIC-RESISTANCE; HEMORRHAGIC COLITIS; O157-H7 INFECTIONS; SEROTYPE O157-H7; SHIGA; GENE; FOOD; MICE; IDENTIFICATION AB Fifty isolates of Escherichia coli serogroup 0111 recovered from humans and various animal species over a 24-year period (1976-1999) were examined for typical virulence-associated factors and susceptibilities to antimicrobials of human and veterinary significance. Nine H (flagellar) types were identified including nonmotile (n = 24), 32 (n = 12), negative (n = 5), and 56 (n = 3). Thirty-five (70%) isolates possessed at least one Shigatoxin-producing E. coli (STEC)-associated virulence determinants (eae, stx1, stx2, hlyA) via PCR analysis. Of these 35 isolates, 20 possessed eae, stx1, and hlyA genes, whereas three isolates possessed eae, stx1, stx2, and hylA genes. Multiple antibiotic resistance was observed in 70% of the 50 E. coli O111 isolates. The majority of isolates displayed resistance to streptomycin, sulfamethoxazole, tetracycline, and kanamycin. Bacterial resistance to ampicillin, gentamicin, chloramphenicol, trimethoprim and apramycin was also observed. Integrons were identified in 23 (46%) of the E. coli isolates assayed, with a 1-kb amplicon being most frequently observed. DNA sequencing of these integrons revealed the presence of the aadA gene, encoding resistance to streptomycin. Two integrons of 1.5 and 2 kb contained the aadA2 and either dfrI or dfrXII genes, encoding resistance to streptomycin and trimethoprim, respectively. Integrons were also identified from isolates dating back to 1982. Isolates were further genetically characterized via ribotyping, which identified 15 distinct ribogroups, with 62% of isolates clustering into four major ribogroups. Certain riboprint patterns from different animal species, including humans, were observed in isolates spanning the 24-year collection period, suggesting the dissemination of specialized pathogenic O111 clones. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Penn State Univ, Gastroenter Dis Ctr, University Pk, PA 16802 USA. RP White, DG (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd,HFV-530, Laurel, MD 20708 USA. NR 39 TC 20 Z9 21 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-6294 J9 MICROB DRUG RESIST JI Microb. Drug Resist.-Mechan. Epidemiol. Dis. PD SUM PY 2002 VL 8 IS 2 BP 139 EP 146 DI 10.1089/107662902760190699 PG 8 WC Infectious Diseases; Microbiology; Pharmacology & Pharmacy SC Infectious Diseases; Microbiology; Pharmacology & Pharmacy GA 569YZ UT WOS:000176632100009 PM 12118519 ER PT J AU Zhu, PX Klutch, MJ Bash, MC Tsang, RSW Ng, LK Tsai, CM AF Zhu, PX Klutch, MJ Bash, MC Tsang, RSW Ng, LK Tsai, CM TI Genetic diversity of three lgt loci for biosynthesis of lipooligosaccharide (LOS) in Neisseria species SO MICROBIOLOGY-SGM LA English DT Article DE Neisseria meningitidis; Neisseria gonorrhoeae; glycosyltransferase; oligosaccharide structure; antigenic variation ID OUTER-MEMBRANE PROTEIN; TERMINAL LIPOPOLYSACCHARIDE STRUCTURE; GONORRHOEAE LIPOOLIGOSACCHARIDE; GONOCOCCAL LIPOOLIGOSACCHARIDE; VARIABLE EXPRESSION; ANTIGENIC VARIATION; BETA-CHAIN; MENINGITIDIS; IDENTIFICATION; CONSERVATION AB Lipooligosaccharide (LOS) is a major virulence factor of the pathogenic Neisseria. Nine Igt genes at three chromosomal loci (Igt-1, 2, 3) encoding the glycosylltransferases responsible for the biosynthesis of LOS oligosaccharide chains were examined in 26 Neisseria meningitidis, 51 Neisseria gonorrhoeae and 18 commensal Neisseria strains. DNA hybridization, PCR and nucleotide sequence data were compared to previously reported Igt genes. Analysis of the genetic organization of the Igt loci revealed that in N. meningitidis, the Igt-1 and Igt-3 loci were hypervariable genomic regions, whereas the Igt-2 locus was conserved. In N. gonorrhoeae, no variability in the composition or organization of the three Igt loci was observed. Igt genes were detected only in some commensal Neisseria species. The genetic organization of the Igt-1 locus was classified into eight types and the Igt-3 locus was classified into four types. Two types of arrangement at Igt-1 (II and IV) and one type of arrangement at Igt-3 (IV) were novel genetic organizations reported in this study. Based on the three Igt loci, 10 LOS genotypes of N. meningitidis were distinguished. Phylogenetic analysis revealed a gene cluster, IgtH, which separated from the homologous genes IgtB and IgtE. The lgtH and IgtE genes were mutually exclusive and were located at the same position in Igt-1. The data demonstrated that pathogenic and commensal Neisseria share a common Igt gene pool and horizontal gene transfer appears to contribute to the genetic diversity of the Igt loci in Neisseria. C1 US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Zhu, PX (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. FU FDA HHS [369VFFD018551] NR 34 TC 33 Z9 33 U1 0 U2 1 PU SOC GENERAL MICROBIOLOGY PI READING PA MARLBOROUGH HOUSE, BASINGSTOKE RD, SPENCERS WOODS, READING RG7 1AG, BERKS, ENGLAND SN 1350-0872 J9 MICROBIOL-SGM JI Microbiology-(UK) PD JUN PY 2002 VL 148 BP 1833 EP 1844 PN 6 PG 12 WC Microbiology SC Microbiology GA 564FR UT WOS:000176304800024 PM 12055303 ER PT J AU Fernandez-Salas, E Suh, KS Speransky, VV Bowers, WL Levy, JM Adams, T Pathak, KR Edwards, LE Hayes, DD Cheng, C Steven, AC Weinberg, WC Yuspa, SH AF Fernandez-Salas, E Suh, KS Speransky, VV Bowers, WL Levy, JM Adams, T Pathak, KR Edwards, LE Hayes, DD Cheng, C Steven, AC Weinberg, WC Yuspa, SH TI mtCLIC/CLIC4, an organellular chloride channel protein, is increased by DNA damage and participates in the apoptotic response to p53 SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID PROGRAMMED CELL-DEATH; MOLECULAR-CLONING; SUBCELLULAR-DISTRIBUTION; P53-INDUCED APOPTOSIS; POTENTIAL MEDIATOR; FAMILY; GENE; EXPRESSION; MEMBER; P64 AB mtCLIC/CLIC4 (referred to here as mtCLIC) is a p53- and tumor necrosis factor alpha-regulated cytoplasmic and mitochondrial protein that belongs to the CLIC family of intracellular chloride channels. mtCLIC associates with the inner mitochondrial membrane. Dual regulation of mtCLIC by two stress response pathways suggested that this chloride channel protein might contribute to the cellular response to cytotoxic stimuli. DNA damage or overexpression of p53 upregulates mtCLIC and induces apoptosis. Overexpression of mtCLIC by transient transfection reduces mitochondrial membrane potential, releases cytochrome c into the cytoplasm, activates caspases, and induces apoptosis. mtCLIC is additive with Bax in inducing apoptosis without a physical association of the two proteins. Antisense mtCLIC prevents the increase in mtCLIC levels and reduces apoptosis induced by p53 but not apoptosis induced by Bax, suggesting that the two proapoptotic proteins function through independent pathways. Our studies indicate that mtCLIC, like Bax, Noxa, p53AIP1, and PUMA, participates in a stress-induced death pathway converging on mitochondria and should be considered a target for cancer therapy through genetic or pharmacologic approaches. C1 NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. NIAMSD, Struct Biol Res Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Immunobiol Lab, Bethesda, MD 20892 USA. RP Yuspa, SH (reprint author), NCI, Cellular Carcinogenesis & Tumor Promot Lab, NIH, Bethesda, MD 20892 USA. RI Weinberg, Wendy/A-8920-2009 NR 58 TC 103 Z9 108 U1 0 U2 4 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 JUN PY 2002 VL 22 IS 11 BP 3610 EP 3620 DI 10.1128/MCB.22.11.3610-3620.2002 PG 11 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 551JP UT WOS:000175557600005 PM 11997498 ER PT J AU Jang, IK Hu, RJ Lacana, E D'Adamio, L Gu, H AF Jang, IK Hu, RJ Lacana, E D'Adamio, L Gu, H TI Apoptosis-linked gene 2-deficient mice exhibit normal T-cell development and function SO MOLECULAR AND CELLULAR BIOLOGY LA English DT Article ID ANTI-FAS ANTIBODY; ALG-2 PROTEIN; CALPAIN; LYMPHOCYTES; MEMBER; GLUCOCORTICOIDS; RESISTANT; ADHESION; CLONING; DISEASE AB The apoptosis-linked gene product, ALG-2, is a member of the family of intracellular Cat(2+)-binding proteins and a part of the apoptotic machinery controlled by T-cell receptor (TCR), Fas, and glucocorticoid signals. To explore the physiologic function of ALG-2 in T-cell development and function, we generated mice harboring a null mutation in the alg-2 gene. The alg-2 null mutant mice were viable and fertile and showed neither gross developmental abnormality nor immune dysfunction. Analyses of apoptotic responses of ALG-2-deficient T cells demonstrated that ALG-2 deficiency failed to block apoptosis induced by TCR, Fas, or dexamethasone signals. These findings indicate that ALG-2 is physiologically dispensable for apoptotic responses induced by the above signaling pathways and suggest that other functionally redundant proteins might exist in mammalian cells. C1 NIAID, Immunol Lab, NIH, Rockville, MD 20852 USA. US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. RP Gu, H (reprint author), NIAID, Immunol Lab, NIH, 12441 Parklawn Dr, Rockville, MD 20852 USA. OI D'Adamio, Luciano/0000-0002-9820-4882 NR 29 TC 38 Z9 38 U1 0 U2 1 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 JUN PY 2002 VL 22 IS 12 BP 4094 EP 4100 DI 10.1128/MCB.22.12.4094-4100.2002 PG 7 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 556UB UT WOS:000175866400014 PM 12024023 ER PT J AU Keller, JE AF Keller, JE TI Translocation of botulinum neurotoxin in cultured neurons. SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 US FDA, Lab Bacterial Toxins, CBER, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PD JUN PY 2002 VL 365 SU 2 MA 69 BP R26 EP R26 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 569HE UT WOS:000176596100071 ER PT J AU Anderson, J Rappoport, CA Hanson, C Maupin, R Minkoff, H O'Sullivan, MJ Perryman, S Scott, G Spector, SA Tuomala, R Wade, N Whitley-Williams, P Wilfert, C Zorrilla, C McNamara, J Mofenson, L Watts, DH Fowler, MG Jamieson, DJ Barini-Garcia, M Hench, K Baylor, M Cargill, VA AF Anderson, J Rappoport, CA Hanson, C Maupin, R Minkoff, H O'Sullivan, MJ Perryman, S Scott, G Spector, SA Tuomala, R Wade, N Whitley-Williams, P Wilfert, C Zorrilla, C McNamara, J Mofenson, L Watts, DH Fowler, MG Jamieson, DJ Barini-Garcia, M Hench, K Baylor, M Cargill, VA CA Public Hlth Serv Task Force Perina TI Summary of the updated recommendations from the public health service task force to reduce perinatal human immunodeficiency virus-1 transmission in the United States SO OBSTETRICS AND GYNECOLOGY LA English DT Editorial Material ID INFECTED WOMEN; ZIDOVUDINE; TYPE-1; INFANTS; THERAPY; EXPOSURE; TOXICITY; DELIVERY; MODE AB Within the last decade, substantial advances have been made in the treatment of human immunodeficiency virus (HIV)-infected pregnant women and in the prevention of perinatal HIV-1 transmission, and recommendations for care continually change. Within this rapidly evolving field, the Public Health Service Task Force Perinatal HIV Guidelines Working Group, which is composed of pediatric and obstetric experts in HIV infection, community representatives, and federal agency representatives, currently meets by monthly conference calls to review new data related to prevention of mother-to-child HIV transmission and management of women with HIV infection. This group periodically issues updates to their guidelines, "Public Health Service Task Force Recommendations for Use of Antiretroviral Drugs in Pregnant HIV-1-Infected Women for Maternal Health and Interventions to Reduce Perinatal HIV-1 Transmission in the United States," which are available on the HIV/AIDS Treatment Information Service Web site (http://www.hivatis.org). (Obstet Gynecol 2002;99: 1117-26. (C) 2002 by the American College of Obstetricians and Gynecologists). C1 CDCP, Div HIV AIDS, Natl Ctr HIV STD & TB Prevent, Atlanta, GA 30333 USA. Johns Hopkins Univ, Sch Med, Dept Obstet & Gynecol, Baltimore, MD 21205 USA. Univ Calif San Francisco, San Francisco, CA 94143 USA. Texas Dept Publ Hlth, Bur Communicable Dis Control, Austin, TX USA. Louisiana State Univ, Hlth Sci Ctr, Dept Obstet & Gynecol, New Orleans, LA USA. Maimonides Hosp, Dept Obstet & Gynecol, Brooklyn, NY 11219 USA. Univ Miami, Sch Med, Dept Obstet & Gynecol, Miami, FL 33101 USA. New York State Dept Hlth, AIDS Inst, New York, NY USA. Univ Miami, Sch Med, Dept Pediat, Miami, FL USA. Univ Calif San Diego, Dept Pediat, Div Infect Dis, La Jolla, CA 92093 USA. Brigham & Womens Hosp, Dept Obstet & Gynecol, Boston, MA 02115 USA. Albany Med Ctr, Childrens Hosp, Dept Pediat, Albany, NY USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Pediat, New Brunswick, NJ 08903 USA. Univ Puerto Rico, Sch Med, Dept Obstet & Gynecol, Rio Piedras, PR 00931 USA. NIAID, Pediat Branch, Div AIDS, NIH, Bethesda, MD 20892 USA. NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Rockville, MD USA. HIV AIDS Bur, Div Training & Tech Assistance, Hlth Resources & Serv Adm, Rockville, MD USA. Maternal & Child Hlth Bur, Div Perinatal Syst & Womens Hlth, Hlth Resources & Serv Adm, Rockville, MD USA. US FDA, Div Antiviral Drug Prod, Rockville, MD 20857 USA. Off HIV AIDS Policy, Washington, DC USA. RP Jamieson, DJ (reprint author), CDCP, Div HIV AIDS, Natl Ctr HIV STD & TB Prevent, Mailstop E-45,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 19 TC 12 Z9 13 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0029-7844 J9 OBSTET GYNECOL JI Obstet. Gynecol. PD JUN PY 2002 VL 99 IS 6 BP 1117 EP 1126 AR PII S0029-7844(02)01985-3 PG 10 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 558QF UT WOS:000175977500029 ER PT J AU Morel, F Rauch, C Coles, B Le Ferrec, E Guillouzo, A AF Morel, F Rauch, C Coles, B Le Ferrec, E Guillouzo, A TI The human glutathione transferase alpha locus: genomic organization of the gene cluster and functional characterization of the genetic polymorphism in the hGSTA1 promoter SO PHARMACOGENETICS LA English DT Article DE glutathione transferase alpha; cluster; promoter; polymorphism ID S-TRANSFERASES; CHROMOSOMAL LOCALIZATION; SUBUNIT GENE; CDNA CLONE; IDENTIFICATION; EXPRESSION; SEQUENCES; ELEMENTS; REGION; GST AB By searching the human genome sequence database with human hGSTA1 and hGSTA4 cDNA sequences, we identified three PAC and one BAC clones covering more than 400 kilobases and containing the entire GST alpha gene cluster. The cluster consists of five genes: hGSTA1, hGSTA2, hGSTA3, hGSTA4 and hGSTA5, and seven pseudogenes that are distinguished as such by single-base and/or complete exon deletions. Using gene-specific probes we demonstrated that hGSTA1, hGSTA2 and hGSTA4 mRNAs are widely expressed in human tissues, whereas hGSTA3 mRNA appears to be a rare message subject to splicing defects. Although examination of the hGSTA5 gene sequence suggests that it is a functional gene, hGSTA5 mRNA could not be detected in human tissues we studied. hGSTA1 expression has been shown to be influenced by a genetic polymorphism, that consists of two alleles hGSTA1*A and hGSTA1*B, containing three linked base substitutions in the proximal promoter, at positions -567, -69 and -52. Constructs consisting of the luciferase gene controlled by variant hGSTA1 promoters showed differential expression when transfected into HePG2, GLC4 and Caco-2 cells: hGSTA1*A > hGSTA1*B. Directed mutagenesis for each base substitution indicated that the base change -52G>A was responsible for the differential promoter activity of hGSTA1*A and hGSTA1*B. The base at position -52 also altered binding of the ubiquitous transcription factor Sp1, as determined by gel shift analysis. Thus it may be postulated that hGSTA1 genotyping will be of importance to determine individual susceptibility to certain cancers or the efficacy of chemotherapeutics via its effect on hGSTA1 expression. C1 Univ Rennes 1, INSERM, U456, F-35043 Rennes, France. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Morel, F (reprint author), Univ Rennes 1, INSERM, U456, 2 Ave Pr Leon Bernard, F-35043 Rennes, France. NR 26 TC 88 Z9 93 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD JUN PY 2002 VL 12 IS 4 BP 277 EP 286 DI 10.1097/00008571-200206000-00003 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 561GL UT WOS:000176131800003 PM 12042665 ER PT J AU Gutman, S AF Gutman, S TI Regulatory issues in tumor marker development SO SEMINARS IN ONCOLOGY LA English DT Review C1 US FDA, Div Clin Lab Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Gutman, S (reprint author), US FDA, Div Clin Lab Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, HFZ-440 2098 Gaither Rd, Rockville, MD 20850 USA. NR 7 TC 10 Z9 11 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD JUN PY 2002 VL 29 IS 3 BP 294 EP 300 DI 10.1053/sonc.2002.33140 PG 7 WC Oncology SC Oncology GA 561RM UT WOS:000176156500011 PM 12063683 ER PT J AU Plakas, SM El Said, KR Jester, ELE Granade, HR Musser, SM Dickey, RW AF Plakas, SM El Said, KR Jester, ELE Granade, HR Musser, SM Dickey, RW TI Confirmation of brevetoxin metabolism in the Eastern oyster (Crassostrea virginica) by controlled exposures to pure toxins and to Karenia brevis cultures SO TOXICON LA English DT Article DE brevetoxin; Karenia brevis; brevetoxin metabolism; Eastern oyster; cytotoxicity; liquid chromatography/mass spectrometry ID NEW-ZEALAND; GREENSHELL MUSSELS; PERNA-CANALICULUS; RED-TIDE; SHELLFISH; ANALOG AB Previously, we analyzed Eastern oysters (Crassostrea virginica) naturally exposed to a Karenia brevis red tide and found that brevetoxins (PbTx) are rapidly accumulated and metabolized. Several metabolites were isolated and later identified, including a cysteine-PbTx conjugate (MH+: m/z 1018) and its sulfoxide product (m/z 1034). In the present study, we confirm and extend those findings by examining PbTx metabolism and elimination in oysters exposed to pure toxins (PbTx-2 and -3) under controlled conditions. Waterborne PbTx-3 was rapidly accumulated, but not metabolized, in the oyster and was largely eliminated within 2 weeks after exposure. In contrast, PbTx-2 was accumulated and rapidly metabolized. Metabolites of PbTx-2 included the reduction product PbTx-3 (m/z 897), and the cysteine conjugates (m/z 10 18 and 1034) isolated previously from the field samples. Levels of the metabolite PbTx-3 in PbTx-2-exposed oysters were highest immediately after exposure and declined at a rate similar to parent PbTx-3 in PbTx-3-exposed oysters. Cysteine-PbTx persisted for 8 weeks after exposure. The same metabolites were confirmed in oysters exposed to laboratory cultures of K. brevis. PbTx metabolites contribute to neurotoxic shellfish poisoning (NSP) and should be included in analytical protocols for monitoring shellfish toxicity after a K. brevis red tide event. Published by Elsevier Science Ltd. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Isl, AL 36528 USA. US FDA, Instrumentat & Biophys Branch, Washington, DC 20204 USA. RP Plakas, SM (reprint author), US FDA, Gulf Coast Seafood Lab, 1 Iberville Dr,POB 158, Dauphin Isl, AL 36528 USA. NR 11 TC 70 Z9 74 U1 0 U2 6 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0041-0101 J9 TOXICON JI Toxicon PD JUN PY 2002 VL 40 IS 6 BP 721 EP 729 AR PII S0041-0101(01)00267-7 DI 10.1016/S0041-0101(01)00267-7 PG 9 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 555UB UT WOS:000175810700008 PM 12175608 ER PT J AU Baylor, NW Egan, W Richman, P AF Baylor, NW Egan, W Richman, P TI Aluminum salts in vaccines - US perspective SO VACCINE LA English DT Article; Proceedings Paper CT Workshop on Aluminum Adjuvants in Vaccines CY MAY 11-12, 2000 CL SAN JUAN, PUERTO RICO DE aluminum; adjuvants; vaccines; clinical trials ID ADJUVANTS AB Aluminum in the form of aluminum hydroxide, aluminum phosphate or alum has been commonly used as an adjuvant in many vaccines Licensed by the US Food and Drug Administration. Chapter 21 of the US Code of Federal Regulations [610.15(a)] limits the amount of aluminum in biological products, including vaccines, to 0.85 mg/dose. The amount of aluminum in vaccines currently licensed in the US ranges from 0.85-0.125 mg/dose. Clinical studies have demonstrated that aluminum enhances the antigenicity of some vaccines such as diphtheria and tetanus toxoids. Moreover, aluminium-adsorbed diphtheria and tetanus toxoids are distinctly more effective than plain fluid toxoids for primary immunization of children. There is little difference between plain and adsorbed toxoids for booster immunization. Aluminum adjuvants have a demonstrated safety profile of over six decades; however, these adjuvants have been associated with severe local reactions such as erythema, subcutaneous nodules and contact hypersensitivity. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Bethesda, MD 20892 USA. RP Baylor, NW (reprint author), 1400 Rockville Pike, Rockville, MD 20852 USA. NR 19 TC 130 Z9 138 U1 0 U2 18 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD MAY 31 PY 2002 VL 20 SU 3 BP S18 EP S23 AR PII S0264-410X(02)00166-4 DI 10.1016/S0264-410X(02)00166-4 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 568JY UT WOS:000176539700005 PM 12184360 ER PT J AU Simak, J Holada, K Vostal, JG AF Simak, J Holada, K Vostal, JG TI Release of annexin V-binding membrane microparticles from cultured human umbilical vein endothelial cells after treatment with camptothecin SO BMC CELL BIOLOGY LA English DT Article ID PLASMA-MEMBRANE; SPHINGOMYELIN HYDROLYSIS; PHOSPHOLIPID ASYMMETRY; IN-VITRO; APOPTOSIS; SURFACE; GENERATION; VESICULATION; COAGULATION; INHIBITION AB Background: Elevated plasma counts of endothelial micoparticles (MP) have been demonstrated in various diseases with a vascular injury component. We used flow cytometry to study the MP-release from cultured human umbilical vein endothelial cells HUVEC) stimulated by various agonists. MP-release by a topoisomerase I inhibitor camptothecin has been studied in detail. Results: Overnight stimulation of HUVEC with either LPS or TNFalpha, or 30 min stimulation with thrombin, phorbol-myristate-acetate, tissue plasminogen activator, or angiotensin-II did not cause a significant release of annexin V-binding MP. In contrast, induction of apoptosis with 5 muM camptothecin, documented by 60-70% desquamation of HUVEC culture, annexin V-binding to the cells and DNA-fragmentation, led to a release of annexin V-binding MP similar to80,000 MP/10(3) cells). This MP-release was prevented by Z-Val-Ala-Asp-fluoromethyl-ketone ZVAD). Lowe concentration of camptothecin 500 nM) induced comparable MP-release without loss of the culture confluence and without increase in annexin V-binding to the cells or DNA-fragmentation. Analyzed MP were free of nucleic acids and 95% of MP were 0.3-1 mum in size. Double-labeling flow cytometry assay showed that all annexin V-binding MP expressed CD59 but only approximately 50% of these also expressed CD105. Conclusions: Camptothecin treated HUVEC released different populations of annexin V-binding membrane MP at early stage after proapoptotic stimulation before detection of phosphatidyl serine exposure on the cells of DNA fragmentation. The MP-release was ZVAD sensitive but was not enhanced at the executive phase of apoptosis. These observations offer a new insight into MP-release as a make of endothelial stimulation and injury. C1 US FDA, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Vostal, JG (reprint author), US FDA, Lab Cellular Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 32 TC 58 Z9 63 U1 1 U2 6 PU BIOMED CENTRAL LTD PI LONDON PA MIDDLESEX HOUSE, 34-42 CLEVELAND ST, LONDON W1T 4LB, ENGLAND SN 1471-2121 J9 BMC CELL BIOL JI BMC Cell Biol. PD MAY 28 PY 2002 VL 3 AR 11 DI 10.1186/1471-2121-3-11 PG 33 WC Cell Biology SC Cell Biology GA 556BP UT WOS:000175828600001 PM 12052248 ER PT J AU McKinzie, PB Parsons, BL AF McKinzie, PB Parsons, BL TI Detection of rare K-ras codon 12 mutations using allele-specific competitive blocker PCR SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE ACB-PCR; K-ras; mutation detection; basepair substitution; allele-specific amplification ID GENOTYPIC SELECTION METHODS; TAQ DNA-POLYMERASE; POINT MUTATIONS; PRIMERS AB Allele-specific competitive blocker PCR (ACB-PCR) is a sensitive allele-specific amplification method in which preferential amplification of the mutant allele occurs by using a primer that has more mismatches to the wild-type allele than to the mutant allele (mutant-specific primer, MSP). Additionally, a non-extendable primer with more mismatches to the mutant allele than to the wild-type allele (blocker primer, BP) competes with the MSP for binding to the wild-type allele, thereby reducing background amplification from the wild-type allele. ACB-PCR primer design is largely dependent upon the basepair substitution being measured, making it unclear if this method is broadly applicable. In an earlier study, an H-ras codon 61 CAA --> AAA mutation had been detected by ACB-PCR at a sensitivity of 10(-5). In this study, ACB-PCR was applied to two human K-ras codon 12 mutations: GGT --> GTT and GGT --> GAT. The method was optimized by systematically altering the concentrations of Perfect Match PCR Enhancer, MSP, BP, and dNTPs, For each mutation, mutant fractions as low as 10(-5) were detected, indicating that this assay can be used on a variety of base substitution mutations. In addition, the results suggest that the 3'-terminal mismatches between the MSP and wild-type allele may be used to predict the ACB-PCR conditions that will be appropriate for the detection of other base substitution mutations. The range of concentrations for each of these components is narrow, making this method relatively easy to apply to additional mutational targets. Published by Elsevier Science B.V. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP McKinzie, PB (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 15 TC 34 Z9 36 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD MAY 27 PY 2002 VL 517 IS 1-2 BP 209 EP 220 AR PII S1383-5718(02)00077-3 DI 10.1016/S1383-5718(02)00077-3 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 564FC UT WOS:000176303500020 PM 12034322 ER PT J AU Lafrenie, RM Lee, SF Hewlett, IK Yamada, KM Dhawan, S AF Lafrenie, RM Lee, SF Hewlett, IK Yamada, KM Dhawan, S TI Involvement of integrin alpha v beta 3 in the pathogenesis of human immunodeficiency virus type 1 infection in monocytes SO VIROLOGY LA English DT Article DE human immunodeficiency virus type 1; integrin; vitronectin receptor; monocyte/macrophage; pathogenesis ID CULTURED HUMAN MACROPHAGES; CELL-ADHESION; HUMAN MONOCYTES/MACROPHAGES; ENDOTHELIAL-CELLS; HIV-1 INFECTION; AIDS VIRUS; RECEPTOR; EXPRESSION; ENTRY; CD4 AB Attachment of HIV to macrophages is a critical early event in the establishment of infection. In the present study, we demonstrate the involvement of integrin alphavbeta3 (vitronectin receptor) in HIV infection of peripheral blood monocyte-derived macrophages. Culturing monocytes in the presence of M-CSF for 3 days upregulated expression of the alphav-containing integrins, alphavbeta3 and alphavbeta5. The increase in alphavbeta3 expression was accompanied by increased HIV-1 replication by monocytes, Immunoblot analysis showed that purified HIV-gp120 protein interacted with CD4 and alphavbeta3 in immunoprecipitation experiments. Neutralizing antibodies against the alphavbeta3 integrin interfered with the coprecipitation of alphavbeta3 with an anti-gp120 antibody and substantially inhibited HIV infection of monocytes. Neutralizing antibodies against alphavbeta5 or 01 integrins did not significantly affect HIV infection. These results indicate that HIV infection of primary monocytes requires differentiation of these cells and may involve alphavbeta3 interaction with the HIV-1 envelope protein gp120 for productive infection, (C) 2002 Elsevier Science (USA). C1 NE Ontario Reg Canc Ctr, Sudbury, ON P3E 5J1, Canada. US FDA, Ctr Biol Evaluat & Res, Mol Virol Lab, Immunopathogenesis Sect, Rockville, MD 20852 USA. Natl Inst Dent & Craniofacial Res, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. RP Lafrenie, RM (reprint author), NE Ontario Reg Canc Ctr, 41 Ramsey Lake Rd, Sudbury, ON P3E 5J1, Canada. NR 49 TC 17 Z9 19 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD MAY 25 PY 2002 VL 297 IS 1 BP 31 EP 38 DI 10.1006/viro.2002.1399 PG 8 WC Virology SC Virology GA 570FT UT WOS:000176648800004 PM 12083833 ER PT J AU Feng, ZH Hu, WW Rom, WN Beland, FA Tang, MS AF Feng, ZH Hu, WW Rom, WN Beland, FA Tang, MS TI N-hydroxy-4-aminobiphenyl-DNA binding in human p53 gene: Sequence preference and the effect of C5 cytosine methylation SO BIOCHEMISTRY LA English DT Article ID CANCER MUTATIONAL HOTSPOTS; NUCLEOTIDE EXCISION REPAIR; HUMAN URINARY-BLADDER; DNA ADDUCT FORMATION; ESCHERICHIA-COLI; 4-AMINOBIPHENYL-DNA ADDUCTS; HOT-SPOTS; MICE; QUANTITATION; DAMAGE AB 4-Aminobiphenyl (4-ABP) is a major etiological agent for human bladder cancer. Metabolically activated 4-ABP is able to interact with DNA to form adducts that may induce mutations and initiate carcinogenesis. Thirty to sixty percent of bladder cancer has a mutation in the tumor suppressor p53 gene, and the mutational spectrum bears unique features. To date the DNA binding spectrum of 4-ABP in the p53 gene is not known due to the lack of methodology to detect 4-ABP-DNA adducts at nucleotide sequence level. We have found that UvrABC nuclease, a nucleotide excision repair complex isolated from Escherichia coli, is able to incise specifically and quantitatively DNA fragments modified with N-hydroxy-4-aminobiphenyl (N-OH-4-ABP), an activated intermediate of 4-ABP. Using the UvrABC nuclease incision method, we mapped the binding spectrum of N-OH-4-ABP in DNA fragments containing exons 5, 7, and 8 of the human p53 gene and also determined the effect of C5 cytosine methylation on N-OH-4-ABP-DNA binding. We found that codon 285, a mutational hotspot at a non-CpG site in bladder cancer, is the preferential binding site for N-OH-4-ABP. We also found that C5 cytosine methylation greatly enhanced N-OH-4-ABP binding at CpG sites, and that two mutational hotspots at CpG sites, codons 175 and 248, became preferential binding sites for N-OH-4-ABP only after being methylated. These results suggest that both the unique DNA binding specificity of 4-ABP and cytosine methylation contribute to the mutational spectrum of the p53 gene in human bladder cancer. C1 NYU Med Ctr, Dept Environm Med, Tuxedo Pk, NY 10987 USA. NYU Med Ctr, Dept Med, Tuxedo Pk, NY 10987 USA. NYU Med Ctr, Dept Pathol, Tuxedo Pk, NY 10987 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Tang, MS (reprint author), NYU Med Ctr, Dept Environm Med, Tuxedo Pk, NY 10987 USA. FU NCI NIH HHS [CA86137]; NIEHS NIH HHS [ES08389, ES00260, ES10344, ES03124]; PHS HHS [M0100096] NR 35 TC 32 Z9 32 U1 0 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD MAY 21 PY 2002 VL 41 IS 20 BP 6414 EP 6421 DI 10.1021/bi020093s PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 552ZX UT WOS:000175651400024 PM 12009904 ER PT J AU Kuijpers, G Schneider, B Stadel, B Colman, E AF Kuijpers, G Schneider, B Stadel, B Colman, E TI Recombinant human parathyroid hormone - Preclinical data on rat osteosarcoma were not dismissed SO BRITISH MEDICAL JOURNAL LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. RP Kuijpers, G (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU BRITISH MED JOURNAL PUBL GROUP PI LONDON PA BRITISH MED ASSOC HOUSE, TAVISTOCK SQUARE, LONDON WC1H 9JR, ENGLAND SN 0959-535X J9 BRIT MED J JI Br. Med. J. PD MAY 18 PY 2002 VL 324 IS 7347 BP 1218 EP 1218 DI 10.1136/bmj.324.7347.1218 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 554XV UT WOS:000175763200042 PM 12016199 ER PT J AU Gershon, SK Luksenburg, H Cote, TR Braun, MM AF Gershon, SK Luksenburg, H Cote, TR Braun, MM TI Pure red-cell aplasia and recombinant erythropoietin SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20852 USA. RP Gershon, SK (reprint author), US FDA, Rockville, MD 20852 USA. NR 2 TC 99 Z9 103 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 16 PY 2002 VL 346 IS 20 BP 1584 EP 1585 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 551LV UT WOS:000175563900014 PM 12015400 ER PT J AU Mohan, KVK Ghebrehiwet, B Atreya, CD AF Mohan, KVK Ghebrehiwet, B Atreya, CD TI The N-terminal conserved domain of rubella virus capsid interacts with the C-terminal region of cellular p32 and overexpression of p32 enhances the viral infectivity SO VIRUS RESEARCH LA English DT Article DE immunofluorescence; infectivity; overexpression; p32; rubella virus capsid; yeast two-hybrid ID GLOBULAR HEADS; BINDING-PROTEIN; C1Q; RECEPTOR; GC1Q-R; P-32; IDENTIFICATION; MITOCHONDRIA; LOCALIZATION; EXPRESSION AB Cellular 'defense collagens' are produced to launch virus-specific responses to clear the invading viruses, Cellular p32. the C1q binding protein is one such protein. In this report. we identified the interaction of p32 derived from a human lung diploid cell line (WI-38) with rubella virus capsid (RVCP from Therien strain) N-terminal 28-amino acid domain, which is conserved among several RV strains including the vaccine strains. We further identified that the C-terminal 69 aa of the mature p32 is sufficient to interact with the CP. In addition, we observed that in three independent Vero 76-derived cell lines constitutively overexpressing p32. the RV infectivity was enhanced. Our results suggest that RV has evolved a strategy whereby one of its proteins is recruited to interact with, and exploit the cellular defense machinery to its advantage. (C) 2002 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viral Dis, Div Viral Prod,Sect viral Pathogenesis & Adverse, Bethesda, MD 20892 USA. SUNY Stony Brook, Dept Med, Stony Brook, NY 11794 USA. SUNY Stony Brook, Dept Pathol, Stony Brook, NY 11794 USA. RP Atreya, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viral Dis, Div Viral Prod,Sect viral Pathogenesis & Adverse, Bldg 29A,Room 2C-11,HFM-460,NIH Campus,8800 Rockv, Bethesda, MD 20892 USA. NR 33 TC 30 Z9 31 U1 0 U2 0 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 10 PY 2002 VL 85 IS 2 BP 151 EP 161 AR PII S0168-1702(02)00030-8 DI 10.1016/S0168-1702(02)00030-8 PG 11 WC Virology SC Virology GA 570FV UT WOS:000176649000004 PM 12034482 ER PT J AU Shvartsburg, AA Wilkes, JG AF Shvartsburg, AA Wilkes, JG TI Fragmentation chemistry of DMSO complexes of metal dications SO JOURNAL OF PHYSICAL CHEMISTRY A LA English DT Article ID ELECTROSPRAY MASS-SPECTROMETRY; CHARGED ALKALINE-EARTH; GAS-PHASE REACTIONS; M = MG; HYDRATION ENERGIES; EQUILIBRIA DETERMINATIONS; ARGENTINATED PEPTIDES; BINDING-ENERGIES; ION-TRAP; IONIZATION AB Recent developments in ion sources have enabled generation and mass-spectrometric investigation of multiply charged metal cations coordinated with various ligands. These ions exhibit rich dissociation chemistry, including electron transfer, proton transfer, and ligand cleavage. Dimethyl sulfoxide (DMSO) is the preeminent aprotic solvent. While complexes of two dipositive metal ions with DMSO were observed previously, the fragmentation of these species has remained essentially unknown. Here we present an extensive MS/MS investigation of DMSO complexes of doubly charged divalent metal cations. We determined the minimum sizes at which dications were stable against charge reduction as well as critical sizes above which no electron or proton transfer occurs. For intermediate sizes, low-energy fragmentation pathways were elucidated in detail. Both proton and electron transfers were observed, depending on the metal. We found diverse ligand cleavage channels, the most intense being the sequential scission of one or both carbon-sulfur bonds in one or several DMSO molecules with competitive eliminations of CH3 and CH4 neutrals. This behavior is completely different from that exhibited by acetone complexes of metal dications, or from that of acetonitrile complexes, in which ligand cleavage is always accompanied by charge reduction. Scission of a sulfur-oxygen bond in DMSO forming mostly ligated metal oxide cations is less intense; this is always associated with charge reduction. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Shvartsburg, AA (reprint author), Natl Ctr Toxicol Res, Div Chem, HFT-233,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 49 TC 27 Z9 27 U1 0 U2 7 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1089-5639 J9 J PHYS CHEM A JI J. Phys. Chem. A PD MAY 9 PY 2002 VL 106 IS 18 BP 4543 EP 4551 DI 10.1021/jp0202921 PG 9 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 550DM UT WOS:000175488400013 ER PT J AU Farmer, PB Bartsch, H Boobis, A Chipman, K Gescher, A Kadlubar, FF Manson, MM Phillips, DH Shuker, DEG Swenberg, JA Tannenbaum, SR Wild, CP AF Farmer, PB Bartsch, H Boobis, A Chipman, K Gescher, A Kadlubar, FF Manson, MM Phillips, DH Shuker, DEG Swenberg, JA Tannenbaum, SR Wild, CP TI Basic or applied, it's the interaction that counts - Toxicology must not be driven by politics: it's science that should drive decision-making. SO NATURE LA English DT Letter C1 Univ Leicester, Bioctr, Leicester LE1 7RH, Leics, England. German Canc Res Ctr, D-6900 Heidelberg, Germany. Univ London Imperial Coll Sci Technol & Med, London, England. Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England. Univ Leicester, Dept Oncol, Leicester LE1 7RH, Leics, England. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Inst Canc Res, London SW3 6JB, England. Open Univ, Dept Chem, Milton Keynes MK7 6AA, Bucks, England. Univ N Carolina, Chapel Hill, NC 27515 USA. MIT, Cambridge, MA 02139 USA. Univ Leeds, Leeds LS2 9JT, W Yorkshire, England. RP Farmer, PB (reprint author), Univ Leicester, Bioctr, Univ Rd, Leicester LE1 7RH, Leics, England. OI Boobis, Alan/0000-0003-3371-386X NR 1 TC 0 Z9 0 U1 0 U2 1 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0028-0836 J9 NATURE JI Nature PD MAY 9 PY 2002 VL 417 IS 6885 BP 117 EP 117 DI 10.1038/417117a PG 1 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 549RH UT WOS:000175460200016 PM 12000933 ER PT J AU Powers, JH Dixon, CA Goldberger, M AF Powers, JH Dixon, CA Goldberger, M TI Decisions about voriconazole versus liposomal amphotericin B - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20850 USA. RP Powers, JH (reprint author), US FDA, Rockville, MD 20850 USA. NR 3 TC 2 Z9 2 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAY 9 PY 2002 VL 346 IS 19 BP 1499 EP 1499 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 549FE UT WOS:000175433200022 ER PT J AU Malozowski, S Sahlroot, JT AF Malozowski, S Sahlroot, JT TI Sildenafil and physical exertion in men with coronary artery disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 NIDDKD, Div Diabet Endocrinol & Metab Dis, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Div Biometr 2, Rockville, MD 20857 USA. RP Malozowski, S (reprint author), NIDDKD, Div Diabet Endocrinol & Metab Dis, Bethesda, MD 20892 USA. NR 4 TC 1 Z9 1 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 MAY 8 PY 2002 VL 287 IS 18 BP 2359 EP 2359 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 548PF UT WOS:000175397000014 PM 12001945 ER PT J AU Stadel, BV AF Stadel, BV TI Hormone replacement therapy and risk of breast cancer SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Stadel, BV (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 2 TC 1 Z9 3 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 MAY 8 PY 2002 VL 287 IS 18 BP 2360 EP 2361 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 548PF UT WOS:000175397000017 PM 11988050 ER PT J AU Borio, L Inglesby, T Peters, CJ Schmaljohn, AL Hughes, JM Jahrling, PB Ksiazek, T Johnson, KM Meyerhoff, A O'Toole, T Ascher, MS Bartlett, J Breman, JG Eitzen, EM Hamburg, M Hauer, J Henderson, A Johnson, RT Kwik, G Layton, M Lillibridge, S Nabel, GJ Osterholm, MT Perl, TM Russell, P Tonat, K AF Borio, L Inglesby, T Peters, CJ Schmaljohn, AL Hughes, JM Jahrling, PB Ksiazek, T Johnson, KM Meyerhoff, A O'Toole, T Ascher, MS Bartlett, J Breman, JG Eitzen, EM Hamburg, M Hauer, J Henderson, A Johnson, RT Kwik, G Layton, M Lillibridge, S Nabel, GJ Osterholm, MT Perl, TM Russell, P Tonat, K CA Working Grp Civilian Biodef TI Hemorrhagic fever viruses as biological weapons - Medical and public health management SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Review ID RIFT-VALLEY FEVER; MARCH-APRIL 1972; LASSA FEVER; EBOLA-VIRUS; MARBURG-VIRUS; RHESUS-MONKEYS; WEST AFRICA; JUNIN VIRUS; EXPERIMENTAL-INFECTION; INTRAVENOUS RIBAVIRIN AB Objective To develop consensus-based recommendations for measures to be taken by medical and public health professionals if hemorrhagic fever viruses (HFVs) are used as biological weapons against a civilian population. Participants The Working Group on Civilian Biodefense included 26 representatives from academic medical centers, public health, military services, governmental agencies, and other emergency management institutions. Evidence MEDLINE was searched from January 1966 to January 2002. Retrieved references, relevant material published prior to 1966, and additional sources identified by participants were reviewed. Consensus Process Three formal drafts of the statement that synthesized information obtained in the evidence-gathering process were reviewed by the working group. Each draft incorporated comments and judgments of the members. All members approved the final draft. Conclusions Weapons disseminating a number of HFVs could cause an outbreak of an undifferentiated febrile illness 2 to 21 days later, associated with clinical manifestations that could include rash, hemorrhagic diathesis, and shock. The mode of transmission and clinical course would vary depending on the specific pathogen. Diagnosis may be delayed given clinicians' unfamiliarity with these diseases, heterogeneous clinical presentation within an infected cohort, and lack of widely available diagnostic tests. Initiation of ribavirin therapy in the early phases of illness may be useful in treatment of some of these viruses, although extensive experience is lacking. There are no licensed vaccines to treat the diseases caused by HFVs. C1 Johns Hopkins Sch Med, Johns Hopkins Ctr Civilian Biodef Strategies, Baltimore, MD 21202 USA. Johns Hopkins Sch Publ Hlth, Johns Hopkins Ctr Civilian Biodef Strategies, Baltimore, MD 21202 USA. Johns Hopkins Sch Publ Hlth, Dept Microbiol, Baltimore, MD 21202 USA. Johns Hopkins Sch Med, Dept Microbiol, Baltimore, MD 21202 USA. Johns Hopkins Sch Med, Dept Neurosci, Baltimore, MD 21202 USA. Johns Hopkins Sch Publ Hlth, Dept Neurosci, Baltimore, MD 21202 USA. Johns Hopkins Sch Med, Div Infect Dis, Baltimore, MD USA. Univ Texas, Med Branch, Ctr Biodef, Galveston, TX 77550 USA. NIH, Ctr Clin, Dept Crit Care Med, Bethesda, MD 20892 USA. NIH, Fogarty Int Ctr, Bethesda, MD 20892 USA. NIH, Vaccine Res Ctr, Bethesda, MD 20892 USA. USA, Med Res Inst Infect Dis, Frederick, MD USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. Univ New Mexico, Dept Biol, Albuquerque, NM 87131 USA. Univ New Mexico, Dept Med, Albuquerque, NM 87131 USA. US FDA, Off Commiss, Rockville, MD 20857 USA. US Dept HHS, Off Emergency Preparedness, Rockville, MD USA. US Dept HHS, Off Publ Hlth Preparedness, Washington, DC 20201 USA. Nucl Threat Initiat, Washington, DC USA. New York City Dept Hlth, Bur Communicable Dis, New York, NY 10013 USA. Univ Minnesota, Ctr Infect Dis Res & Policy, Minneapolis, MN USA. RP Borio, L (reprint author), Johns Hopkins Sch Med, Johns Hopkins Ctr Civilian Biodef Strategies, 111 Market Pl,Suite 830, Baltimore, MD 21202 USA. EM Lborio@jhsph.edu NR 140 TC 382 Z9 398 U1 38 U2 233 PU AMER MEDICAL ASSOC PI CHICAGO PA 330 N WABASH AVE, STE 39300, CHICAGO, IL 60611-5885 USA SN 0098-7484 EI 1538-3598 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAY 8 PY 2002 VL 287 IS 18 BP 2391 EP 2405 DI 10.1001/jama.287.18.2391 PG 15 WC Medicine, General & Internal SC General & Internal Medicine GA 548PF UT WOS:000175397000028 PM 11988060 ER PT J AU Cui, YY Ang, CYW AF Cui, YY Ang, CYW TI Supercritical fluid extraction and high-performance liquid chromatographic determination of phloroglucinols in St. John's wort (Hypericum perforatum L.) SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE Hypericum perforatum L.; St. John's wort; supercritical fluid extraction; hyperforin; adhyperforin ID ANTIDEPRESSANT ACTIVITY; MASS-SPECTROMETRY; ARRAY DETECTION; HYPERFORIN; CONSTITUENTS; DEPRESSION; SEROTONIN; STABILITY; HERB AB A small-scale supercritical fluid extraction (SFE) method was developed for the selective extraction of phloroglucinols from St. John's wort (SJW) leaf/flower mixtures using supercritical carbon dioxide (CO2). The extraction efficiency was investigated as influenced by pressure, temperature, time, and modifier. The optimized condition of SFE was carried out at 3.80 x 10(4) kpa (5500 psi) and 50 degreesC. Samples were held in static extraction for 10 min, followed by a dynamic extraction for 90 min at the flow rate of 1 mL/min. A simple and sensitive HPLC method was developed for the analysis of hyperforin and adhyperforin, the major phloroglucinols, in the SFE extract of SJW. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, HFT-230,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 29 TC 19 Z9 19 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAY 8 PY 2002 VL 50 IS 10 BP 2755 EP 2759 DI 10.1021/jf011304n PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 547WG UT WOS:000175355200005 PM 11982394 ER PT J AU Kim, YH Cha, CJ Cerniglia, CE AF Kim, YH Cha, CJ Cerniglia, CE TI Purification and characterization of an erythromycin esterase from an erythromycin-resistant Pseudomonas sp. SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE aquaculture; erythromycin A; erythromycin A enol ether; oleandomycin; mercuric chloride ID ESCHERICHIA-COLI; NUCLEOTIDE-SEQUENCE; EREB GENE AB An erythromycin esterase (molecular mass 51200 Da) was purified from Pseudomonas sp. GD100, which was isolated from a salmon hatchery sediment sample from Washington State. The pI of the protein was 4.5-4.8. The enzyme was inhibited by 1 mM mercuric acid, and had the substrate specificity for structurally related 14-membered macrolides, which decreased in the order of oleandomycin, erythromycin A and erythromycin A enol ether. The activity for erythromycin A varied with temperature, but the effect of pH was minimal at pH 6.0-9.0. The half-life of the enzyme was estimated to be 8.9 h at 35degreesC and 0.23 h at 55degreesC, and the activation energy of the catalytic reaction of erythromycin A was estimated at 16.2 kJ mol(-1). (C) 2002 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. 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. NR 21 TC 23 Z9 24 U1 0 U2 1 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 MAY 7 PY 2002 VL 210 IS 2 BP 239 EP 244 AR PII S0378-1097(02)00611-0 DI 10.1016/S0378-1097(02)00611-0 PG 6 WC Microbiology SC Microbiology GA 563FT UT WOS:000176246200012 PM 12044681 ER PT J AU Homola, J Dostalek, J Chen, SF Rasooly, A Jiang, SY Yee, SS AF Homola, J Dostalek, J Chen, SF Rasooly, A Jiang, SY Yee, SS TI Spectral surface plasmon resonance biosensor for detection of staphylococcal enterotoxin B in milk SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE biosensor; surface plasmon resonance; staphylococcal enterotoxin B ID RAPID DETECTION; SALMONELLA-TYPHIMURIUM; AGENTS; FOOD; IMMUNOSENSOR; IMMUNOASSAY AB This work evaluates a newly developed wavelength modulation-based SPR biosensor for the detection of staphylococcal enterotoxin B (SEB) in milk. Two modes of operation of the SPR biosensor are described: direct detection of SEB and sandwich assay. In the sandwich assay detection mode, secondary antibodies are bound to the already captured Toxin to amplify sensor response. Samples including SEB in buffer and SEB in milk were analyzed in this work. The SPR biosensor has been shown to be capable of directly detecting concentrations of SEB in buffer as low as 5 ng/ml. In sandwich detection mode, the lowest detection limit was determined to be 0.5 ng/ml for both buffer and milk samples. The reported wavelength modulation-based SPR sensor provides a generic platform which can be tailored for detection of various foodborne pathogens and agents for food analysis and testing. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Washington, Dept Elect Engn, Seattle, WA 98195 USA. Univ Washington, Dept Chem Engn, Seattle, WA 98195 USA. US FDA, Div Microbiol Studies, Washington, DC 20204 USA. RP Homola, J (reprint author), Univ Washington, Dept Elect Engn, Box 352500, Seattle, WA 98195 USA. RI Dostalek, Jakub/C-5052-2009; Chen, Shengfu/G-9640-2014; Homola, Jiri/F-3683-2014 OI Chen, Shengfu/0000-0002-8153-608X; Homola, Jiri/0000-0001-6258-015X NR 28 TC 201 Z9 222 U1 6 U2 51 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1605 J9 INT J FOOD MICROBIOL JI Int. J. Food Microbiol. PD MAY 5 PY 2002 VL 75 IS 1-2 BP 61 EP 69 AR PII S0168-1605(02)00010-7 DI 10.1016/S0168-1605(02)00010-7 PG 9 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 538LQ UT WOS:000174817800007 PM 11999118 ER PT J AU Lee, LH Lee, CJ Frasch, CE AF Lee, LH Lee, CJ Frasch, CE TI Development and evaluation of pneumococcal conjugate vaccines: Clinical trials and control tests SO CRITICAL REVIEWS IN MICROBIOLOGY LA English DT Review DE pneumococcus; vaccine; efficacy; carriage; quality control ID RESISTANT STREPTOCOCCUS-PNEUMONIAE; INFLUENZAE TYPE-B; CAPSULAR POLYSACCHARIDE VACCINE; UNITED-STATES; ANTIBODY-RESPONSE; NASOPHARYNGEAL CARRIAGE; HAEMOPHILUS-INFLUENZAE; OTITIS-MEDIA; TYPE-19F POLYSACCHARIDE; MATERNAL IMMUNIZATION AB Streptococcus pneumoniae is a major cause of pneumonia, meningitis, and otitis media and is responsible for disease in young children, the elderly, and immunocompromised individuals. Emerging high-level resistance to penicillin, multiple antibiotics, and tolerance to vancomycin emphasizes the importance of preventing pneumococcal infection by alternative methods such as immunization. The development of pneumococcal conjugate vaccines using the same carrier proteins as those used in Hemophilus influenzae type b vaccines has enhanced the immune response in infants and children compared with polysaccharide vaccines and has significantly improved the ability to prevent pneumococcal disease in this population worldwide. Here we review the clinical trials of multivalent pneumococcal conjugate vaccines under evaluation, identify potential carrier proteins considered for development of future pneumococcal conjugate vaccines, discuss issues regarding licensure of new candidate vaccines from a clinical trial and quality control perspective, and alternative vaccine strategies for the prevention of pneumococcal disease. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Lee, LH (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NR 95 TC 16 Z9 17 U1 1 U2 1 PU INFORMA HEALTHCARE PI NEW YORK PA 52 VANDERBILT AVE, NEW YORK, NY 10017 USA SN 1040-841X J9 CRIT REV MICROBIOL JI Crit. Rev. Microbiol. PD MAY 3 PY 2002 VL 28 IS 1 BP 27 EP 41 DI 10.1080/1040-840291046678 PG 15 WC Microbiology SC Microbiology GA 550HG UT WOS:000175497100002 PM 12003039 ER PT J AU de Jager, L Andrews, ARJ AF de Jager, L Andrews, ARJ TI Development of a screening method for cocaine and cocaine metabolites in saliva using hollow fiber membrane solvent microextraction SO ANALYTICA CHIMICA ACTA LA English DT Article DE cocaine; hollow fiber membrane solvent microextraction; saliva ID PERFORMANCE LIQUID-CHROMATOGRAPHY; CAPILLARY-ELECTROPHORESIS; URINE; BENZOYLECGONINE; FLUIDS AB Hollow fiber membrane solvent microextraction (HFMSME) has been applied as a simple and efficient means of sample preparation for the screening of drugs of abuse in saliva. Extraction of cocaine and its metabolites from a 2 ml saliva solution was achieved in 10 min. This was followed by fast GC separation allowing complete analysis to be achieved in 15 min. Using HFMSME, detection Limits ranged between 6 and 28 ng ml(-1) with average relative standard deviations of 9.0%. The effect of the presence of various foodstuffs was also investigated. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Ohio Univ, Dept Chem & Biochem, Athens, OH 45701 USA. RP de Jager, L (reprint author), Food & Drug Adm, Ctr Food Safety & Appl Nutr, OFAS, HFS 245 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 19 TC 29 Z9 29 U1 0 U2 9 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 MAY 2 PY 2002 VL 458 IS 2 BP 311 EP 320 AR PII S0003-2670(02)00063-6 DI 10.1016/S0003-2670(02)00063-6 PG 10 WC Chemistry, Analytical SC Chemistry GA 554TD UT WOS:000175752500007 ER PT J AU Asher, DM AF Asher, DM TI Transmissible spongiform encephalopathies - Past, present, and future SO BIOPHARM-THE APPLIED TECHNOLOGIES OF BIOPHARMACEUTICAL DEVELOPMENT LA English DT Editorial Material ID CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN; SCRAPIE; RESISTANT; VARIANT; MICE C1 US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Asher, DM (reprint author), US FDA, Lab Bacterial Parasit & Unconvent Agents, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review,Ctr Biol Evaluat & Res, HFM-313 FDA,1401 Rockville Pike, Rockville, MD 20852 USA. NR 25 TC 0 Z9 0 U1 0 U2 0 PU ADVANSTAR COMMUNICATIONS PI DULUTH PA 131 W FIRST ST, DULUTH, MN 55802 USA SN 1040-8304 J9 BIOPHARM-APPL T BIO JI Biopharm-Appl Technol. Biopharm. Dev. PD MAY PY 2002 SU S BP 8 EP + PG 35 WC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 552RK UT WOS:000175633200001 ER PT J AU Dolan, EA Venable, RM Pastor, RW Brooks, BR AF Dolan, EA Venable, RM Pastor, RW Brooks, BR TI Simulations of membranes and other interfacial systems using P2(1) and pc periodic boundary conditions SO BIOPHYSICAL JOURNAL LA English DT Article ID MOLECULAR-DYNAMICS SIMULATION; LIPID BILAYERS; PHOSPHOLIPID-BILAYER; COMPUTER-SIMULATION; SURFACE-TENSION; LIQUID/LIQUID INTERFACES; MELITTIN; PEPTIDES; ENERGY; AREA AB We demonstrate the ease and utility of simulating heterogeneous interfacial systems with P2(1) and Pc periodic boundary conditions which allow, for example, lipids in a membrane to switch leaflets. In preliminary tests, P2(1) was shown to yield equivalent results to P1 in simulations of bulk water, a water/vacuum interface, and pure DPPC bilayers with an equal number of lipids per leaflet; equivalence of Pc and P1 was also demonstrated for the former two systems. P2(1) was further tested in simulations involving the spreading of an octane film on water, and equilibration of a DPPC bilayer from an initial condition containing different numbers of lipids in the two leaflets. Lastly, a simulation in P2(1) of a DOPC/melittin membrane showed significant passage of lipids to the melittin-containing leaflet from the initial distribution, and lends insight into the condensation of lipids by melittin. C1 NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20854 USA. RP Brooks, BR (reprint author), Bldg 50,Rm 3406,50 South Dr,MSC 8014, Bethesda, MD 20892 USA. NR 33 TC 35 Z9 36 U1 2 U2 12 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD MAY PY 2002 VL 82 IS 5 BP 2317 EP 2325 PG 9 WC Biophysics SC Biophysics GA 546EQ UT WOS:000175259600004 PM 11964222 ER PT J AU Looker, AC Dawson-Hughes, B Calvo, MS Gunter, EW Sahyoun, NR AF Looker, AC Dawson-Hughes, B Calvo, MS Gunter, EW Sahyoun, NR TI Serum 25-hydroxyvitamin D status of adolescents and adults in two seasonal subpopulations from NHANES III SO BONE LA English DT Article DE serum 25-hydroxyvitamin D; vitamin D status; hypovitaminosis D; adolescents; adults ID VITAMIN-D STATUS; D DEFICIENCY; BONE MASS; PARATHYROID-HORMONE; CUTANEOUS SYNTHESIS; D SUPPLEMENTATION; D INSUFFICIENCY; YOUNG-ADULTS; WHITE WOMEN; BLACK-WOMEN AB Subclinical vitamin D deficiency may be common in certain subgroups in the U.S., but to date vitamin D data from other groups in the population have not been available. We used serum 25-hydroxyvitamin D (25-OHD) data from 18,875 individuals examined in the Third National Health and Nutrition Examination Survey (NHANES III 1988-1994) to assess the vitamin D status of selected groups of the noninstitutionalized U.S. adolescent and adult population. Serum 25-OHD levels were measured by a radioimmunoassay kit (DiaSorin, Inc., Stillwater, MN; normal range 22.5-94 nmol/L). Because physical exams are performed in mobile vans in NHANES, data could not be collected in northern latitudes during the winter; instead data were collected in northern latitudes during summer and in southern latitudes in winter. To address this season-latitude aspect of the NHANES design, we stratified the sample into two seasonal subpopulations (winter/lower latitude and summer/higher latitude) before examining vitamin D status. Less than 1% of the winter/lower latitude subpopulation had vitamin D deficiency (25-OHD <17.5 nmol/L). However, the prevalence of vitamin D insufficiency in this group ranged from 1%-5% with 25-OHD <25 nmol/L to 25%-57% with 25-OHD <62.5 nmol/L, even though the median latitude for this subsample (32degreesN) was considerably lower than the latitude at which vitamin D is not synthesized during winter months (similar to42degreesN). With the exception of elderly women, prevalence rates of vitamin D insufficiency were lower in the summer/higher latitude subpopulation (<1%-3% Nvith 25-OHD <25 nmol/L to 21 %49% with 25-OHD <62.5 nmol/L,). Mean 25-OHD levels were highest in non-Ilispanic whites, intermediate in Mexican Americans, and lowest in non-Ilispanic blacks. Our findings suggest that vitamin D deficiency is unlikely in the two seasonal subpopulations of noninstitutionalized adolescents and adults that can be validly assessed in NHANES III. However, vitamin D insufficiency is more common in these two seasonal subpopulations. Of particular interest is that insufficiency occurred fairly frequently in younger individuals, especially in the winter/lower latitude subsample. Our findings support continued monitoring of this vitamin in the U.S. population. (C) 2002 by Elsevier Science Inc. All rights reserved. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Hyattsville, MD 20782 USA. Tufts Univ, USDA, Human Res Ctr, Boston, MA 02111 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Ctr Dis Control & Prevent, Natl Ctr Environm Hlth, Atlanta, GA USA. Univ Maryland, Dept Food & Nutr, College Pk, MD 20742 USA. RP Looker, AC (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Room 900,6525 Belcrest Rd, Hyattsville, MD 20782 USA. NR 38 TC 511 Z9 527 U1 0 U2 16 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 8756-3282 J9 BONE JI Bone PD MAY PY 2002 VL 30 IS 5 BP 771 EP 777 AR PII S8756-3282(02)00692-0 DI 10.1016/S8756-3282(02)00692-0 PG 7 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 555QG UT WOS:000175804300018 PM 11996918 ER PT J AU Colman, E AF Colman, E TI Sir James Paget: The man and the eponym SO CALCIFIED TISSUE INTERNATIONAL LA English DT Biographical-Item C1 US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, Rockville, MD 20895 USA. RP Colman, E (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Metab & Endocrine Drug Prod, Rockville, MD 20895 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0171-967X J9 CALCIFIED TISSUE INT JI Calcif. Tissue Int. PD MAY PY 2002 VL 70 IS 5 BP 430 EP 431 DI 10.1007/s00223-001-0042-1 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 560ZM UT WOS:000176111300011 PM 11960206 ER PT J AU Ju, YH Doerge, DR Allred, KF Allred, CD Helferich, WG AF Ju, YH Doerge, DR Allred, KF Allred, CD Helferich, WG TI Dietary genistein negates the inhibitory effect of tamoxifen on growth of estrogen-dependent human breast cancer (MCF-7) cells implanted in athymic mice SO CANCER RESEARCH LA English DT Article ID STIMULATE GROWTH; RECEPTOR; TUMORS; PHYTOESTROGENS; METABOLITES; PLASMA; WOMEN; RATS AB The use of dietary isoflavone supplements by postmenopausal women with breast cancer is increasing. We investigated interactions between the soy isoflavone, genistein, and an antiestrogen, tamoxifen (TAM), on the growth of estrogen (E)-dependent breast cancer (MCF-7) cells implanted in ovariectomized athymic mice. We hypothesized that weakly estrogenic genistein negate/overwhelm the inhibitory effect of TAM on the growth of E-dependent breast tumors. Six treatment groups were used: control (C); 0.25 mg estradiol (E-2) implant (E); E-2 implant + 2.5 mg TAM implant (2.5 TE); E-2 implant + 2.5 mg TAM implant + 1000 ppm genistein (2.5 TEG); E-2 implant + 5 mg TAM implant (5 TE), and E-2 implant +5 mg TAM implant +1000 ppm genistein (5 TEG). Treatment with TAM (2.5 TE and 5 TE) suppressed E-2-stimulated MCF-7 tumor growth in ovariectomized athymic mice. Dietary genistein negated/overwhelmed the inhibitory, effect of TAM on MCF-7 tumor growth, lowered E-2 level in plasma, and increased expression of E-responsive genes (e.g., pS2, PR, and cyclin D1). Therefore, caution is warranted for postmenopausal women consuming dietary genistein while on TAM therapy for E-responsive breast cancer. C1 Univ Illinois, Dept Food Sci & Human Nutr, Urbana, IL 60801 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Helferich, WG (reprint author), Univ Illinois, Dept Food Sci & Human Nutr, 580 Bevier Hall,905 S Goodwin Ave, Urbana, IL 60801 USA. FU NCI NIH HHS [CA77355] NR 28 TC 157 Z9 159 U1 3 U2 9 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD MAY 1 PY 2002 VL 62 IS 9 BP 2474 EP 2477 PG 4 WC Oncology SC Oncology GA 546GG UT WOS:000175265000005 PM 11980635 ER PT J AU Patterson, ML Slater, JE AF Patterson, ML Slater, JE TI Characterization and comparison of commercially available German and American cockroach allergen extracts SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE cockroach; Bla g 1; Bla g 2; relative potency; total protein content; reference; German cockroach; American cockroach; allergen standardization; allergen extract ID IGE ANTIBODY-RESPONSES; BLA G 4; BLATTELLA-GERMANICA; STANDARDIZATION; ASTHMA; IMMUNOTHERAPY; STABILITY; CLONING; DUST AB Background In this study we examine the variability among unstandardized cockroach allergen extracts. Methods We obtained 24 aqueous and glycerinated cockroach allergen extracts from nine manufacturers. We used previously characterized cockroach extracts, E2-Cg and E2-Ca, as references. The modified ninhydrin assay was used to determine protein concentration of each extract. Relative potencies of extracts were determined by competition ELISA, using a human allergic serum pool. Bla g 1 and Bla g 2 levels of glycerinated German cockroach extracts were determined by ELISA using monoclonal antibodies. Extracts were also analysed by SDS-PAGE. Results Commercial cockroach allergen extracts had highly variable protein contents that were lower than the protein contents of the references. Electrophoretic data confirmed the presence of a variable number and intensity of protein bands in extracts among manufacturers. The relative potencies of the commercial extracts were between 10 and 782 BAU/mL for German cockroach and 10-250 BAU/mL for American cockroach. The mean Bla g 1 content of the commercial extracts was significantly lower than that of the reference (P = 0.001). The mean Bla g 2 content of the commercial extracts was higher than that of the E2-Cg reference but the Bla g 2 levels were more variable compared to Bla g 1. In glycerinated German cockroach extracts, protein concentrations, relative potencies and specific allergen levels were significantly correlated (P < 0.001). Conclusion Our tests indicate that commercially available cockroach allergen extracts are variable in protein content, electrophoretic banding patterns, relative potency and Bla g 2 levels. In glycerinated German cockroach extracts, protein concentrations, relative potencies and specific allergen levels were significantly correlated. C1 US FDA, Lab Immunobiochem, CBER, DBPAP,Off Vaccines Regulat & Res, Rockville, MD 20852 USA. RP Patterson, ML (reprint author), US FDA, Lab Immunobiochem, CBER, DBPAP,Off Vaccines Regulat & Res, 1401 Rockville Pike,HFM-422, Rockville, MD 20852 USA. EM pattersonm@cber.fda.gov NR 30 TC 40 Z9 43 U1 0 U2 3 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD MAY PY 2002 VL 32 IS 5 BP 721 EP 727 DI 10.1046/j.1365-2222.2002.01397.x PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 549GP UT WOS:000175436400012 PM 11994096 ER PT J AU Cohen, MH Williams, G Johnson, JR Duan, J Gobburu, J Rahman, A Benson, K Leighton, J Kim, SK Wood, R Rothmann, M Chen, G U, KM Staten, AM Pazdur, R AF Cohen, MH Williams, G Johnson, JR Duan, J Gobburu, J Rahman, A Benson, K Leighton, J Kim, SK Wood, R Rothmann, M Chen, G U, KM Staten, AM Pazdur, R TI Approval summary for imatinib mesylate capsules in the treatment of chronic myelogenous leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID CHRONIC MYELOID-LEUKEMIA; ABL TYROSINE KINASE; PHILADELPHIA-CHROMOSOME; INTERFERON-ALPHA; CHRONIC PHASE; C-KIT; GENE; INHIBITOR; BUSULFAN; GRANULOCYTE AB Purpose: Chronic myelogenous leukemia (CML) results from the breakpoint cluster region-Abl fusion gene product, a tyrosine kinase involved in cell division and apoptosis. Imatinib, an orally administered inhibitor of the breakpoint cluster region-Abl tyrosine kinase, is capable of blocking proliferation and inducing apoptosis in CML cell lines. In this report, we describe the preclinical profile of imatinib and the data submitted in the New Drug Application that led to its marketing approval. Experimental Design: Chemistry manufacturing and controls, animal toxicology, and biopharmaceutical data are described. Results of Phase I and Phase II clinical studies in patients with CML in blast crisis (CML-BC), in accelerated phase (CML-AP), and in chronic phase disease-resistant or intolerant to IFN-alpha (CML-CP) are summarized. The basis for marketing approval and postmarketing commitments by the pharmaceutical company are discussed. Results: Toxicology studies in the rat, dog, and monkey show the hematological, renal, and hepatobiliary toxicity of imatinib. Pharmacokinetic studies in patients with CML demonstrate 98% imatinib bioavailability. The elimination half-lives of the parent drug and the major active metabolite, CGP74588, from plasma are approximately 18 and 40 h, respectively. Approximately 81% of the drug is eliminated in 7 days, 68% in the feces and 13% in the urine. Cytochrome P-450 3A4 is the main enzyme responsible for imatinib metabolism. Phase I and II clinical studies were conducted. The Phase I study, in 83 CML patients, evaluated oral imatinib doses from 25 to 1000 mg/day. Dose-limiting toxicity was not observed. The three Phase H studies, in CML-CP, CML-AP, and CML-BC, enrolled 1027 patients. CML-CP patients received 400 mg/day imatinib, whereas CML-AP and CML-BC patients generally received 600 mg/day imatinib. Primary study endpoints were cytogenetic response rate (CML-CP) and hematological response rate (CML-AP and CML-BC). The cytogenetic response rate for CML-CP patients was 49%. The hematological response rate of CML-AP and CML-BC patients was 63 and 26%, respectively. The most common imatinib adverse events were nausea, vomiting, myalgia, edema, and diarrhea. Elevated liver enzymes and/or bilirubin were reported in 27 patients (2.6%). Conclusions: On May 10, 2001, imatinib mesylate (Gleevec, formerly known as STI-571 and Glivec), manufactured and distributed by Novartis Pharmaceuticals, East Hanover, NJ, was approved by the United States Food and Drug Administration for the treatment of CML in three clinical settings: CML-BC, CML-AP, and CML-CP. This report summarizes the Food and Drug Administration's review of the New Drug Application. C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Sci Invest, 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. NR 26 TC 240 Z9 251 U1 0 U2 17 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAY PY 2002 VL 8 IS 5 BP 935 EP 942 PG 8 WC Oncology SC Oncology GA 551EY UT WOS:000175547700001 PM 12006504 ER PT J AU Hirschfeld, S Pazdur, R AF Hirschfeld, S Pazdur, R TI Oncology drug development: United States Food and Drug Administration perspective SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE drug development; FDA; regulatory agency; drug approval AB The Food and Drug Administration (FDA) in the United States has multiple roles. The primary responsibilities for oncology drug products are the supervision of clinical research, the evaluation of marketing claims for new and previously approved drugs, the granting of exclusive marketing licenses for approved claims, and the monitoring of post-marketing activity for safety. Additional roles include providing incentives for developing products for rare diseases and children. The principles used for monitoring clinical studies are based on science, law and ethical guidelines. The principles used for evaluation of evidence to support marketing claims are based in science, law, regulation, and frequently the advice of a panel of external experts. Approved products should demonstrate patient benefit that is commensurate with the probable risks. The types of endpoints and their advantages and disadvantages for regulatory review are discussed. There are regulatory options available for conditional approval based on surrogate endpoints that are likely to predict patient benefit, a mechanism for reducing the time to review an application for indications with no known effective therapy, and procedures for providing access to patients for unapproved drugs. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20852 USA. RP Hirschfeld, S (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, 1451 Rockville Pike,HFD-150, Rockville, MD 20852 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 14 TC 18 Z9 19 U1 0 U2 6 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD MAY PY 2002 VL 42 IS 2 BP 137 EP 143 AR PII S1040-8428(02)00008-2 DI 10.1016/S1040-8428(02)00008-2 PG 7 WC Oncology; Hematology SC Oncology; Hematology GA 560LM UT WOS:000176083600002 PM 12007971 ER PT J AU Fujiwara, Y Kobayashi, K AF Fujiwara, Y Kobayashi, K TI Oncology drug clinical development and approval in Japan: the role of the pharmaceuticals and medical devices evaluation center (PMDEC) SO CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY LA English DT Review DE PMDEC; drug development; drug approval; off-label usage; ICH-E5 ID TRIALS AB In 1996 the Japanese Diet amended the Pharmaceutical Affairs Law (PAL) and its related laws based on 1996 report of the ad-hoc Committee for Drug Safety Ensuring Measures. Between 1996 and 2000, the drug approval system in Japan underwent a series of radical reforms. We describe in this paper the current system for drug approval, discuss the post-approval reexamination and reevaluation system, conditions under which development and review may be expedited, and mechanisms for approval of off-label usage. Finally, we discuss the impact of the International Conference on Harmonization (ICH) agreement on drug development and review in Japan. (C) 2002 Published by Elsevier Science Ireland Ltd. C1 Minist Hlth Labour & Welf, Natl Inst Hlth Sci, Pharmaceut & Med Devices Evaluat Ctr, Evaluat Div 2,Minato Ku, Tokyo 1058409, Japan. Mansfield Ctr Pacific Affairs, Washington, DC USA. RP Fujiwara, Y (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. NR 7 TC 18 Z9 18 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1040-8428 J9 CRIT REV ONCOL HEMAT JI Crit. Rev. Oncol./Hematol. PD MAY PY 2002 VL 42 IS 2 BP 145 EP 155 AR PII S1040-8428(02)00010-0 DI 10.1016/S1040-8428(02)00010-0 PG 11 WC Oncology; Hematology SC Oncology; Hematology GA 560LM UT WOS:000176083600003 PM 12007972 ER PT J AU Witter, J AF Witter, J TI Drug development in rheumatoid arthritis SO CURRENT OPINION IN RHEUMATOLOGY LA English DT Review AB In the United States, therapies to treat rheumatoid arthritis and juvenile rheumatoid arthritis are approved and regulated by the Food and Drug Administration. This article explores certain aspects of the current Food and Drug Administration guidance for drugs, devices, and biologic products intended to treat these diseases (in this article, the term "drug" refers to any therapy in rheumatoid arthritis). Newer therapeutics are targeting not only important molecular pathways but also new labeling claims intended to represent clinically relevant outcomes. Questions regarding whether the risks of these new therapies are balanced by their effectiveness will evolve. The process of improvement in clinical trial design and metrics, along with improved therapies, will undoubtedly present both familiar and new challenges in the future. Curr opin Rheumatol 2002, 14:276-280 (C) 2002 Lippincott Williams Wilkins, Inc. C1 US FDA, Rockville, MD 20850 USA. RP Witter, J (reprint author), US FDA, 9201 Corp Blvd,Room N-367, Rockville, MD 20850 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1040-8711 J9 CURR OPIN RHEUMATOL JI CURR. OPIN. RHEUMATOL. PD MAY PY 2002 VL 14 IS 3 BP 276 EP 280 DI 10.1097/00002281-200205000-00014 PG 5 WC Rheumatology SC Rheumatology GA 545JR UT WOS:000175214300014 PM 11981326 ER PT J AU Bright, RA AF Bright, RA TI The conference on the epidemiology of medical devices in women SO EPIDEMIOLOGY LA English DT Editorial Material ID RESIDUAL METAL SHAVINGS; SOFT CONTACT-LENSES; BREAST IMPLANTS; SCREENING MAMMOGRAPHY; ENDOMETRIAL RESECTION; ULCERATIVE KERATITIS; DAILY-WEAR; FOLLOW-UP; BIOPSY; VALIDATION C1 US FDA, Off Surveillance & Biometr, Div Postmarket Surveillance, Epidemiol Branch,Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Bright, RA (reprint author), US FDA, Off Surveillance & Biometr, Div Postmarket Surveillance, Epidemiol Branch,Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ 541, Rockville, MD 20850 USA. RI Bright, Roselie/D-2240-2016 NR 57 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2002 VL 13 IS 3 SU S BP S1 EP S9 DI 10.1097/00001648-200205001-00001 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 545ZE UT WOS:000175246800001 PM 12071475 ER PT J AU Brown, SL AF Brown, SL TI Epidemiology of silicone-gel breast implants SO EPIDEMIOLOGY LA English DT Article DE breast prostheses; silicone; implants ID CONNECTIVE-TISSUE DISEASES; AUGMENTATION MAMMAPLASTY; RETROSPECTIVE COHORT; WOMEN; RISK; CANCER; PREVALENCE; RUPTURE; COMPLICATIONS; SCLERODERMA AB Silicone breast implants have been marketed in the United States since 1963. Questions remain unanswered on the safety of these medical devices despite their popularity and availabilitv, In 1992, the Food and Drug Administration restricted the availability of silicone-gel breast implants to women requiring them for reconstruction after breast cancer or for other medical indications. Inflatable saline breast implants have remained available for either reconstruction or for cosmetic augmentation while manufacturers completed studies addressing issues of safety and effectiveness. The Food and Drug Administration (FDA) has less concern today regarding a putative association between breast implants and autoimmune disease because of epidemiologic studies that have indicated that there is not a large increase in risk for connective tissue disease in women with breast implants. These studies have not ruled out a small increase in risk of connective tissue disease to these women nor have they addressed the issue of an atypical syndrome related to silicone. The FDA has continuing concerns over local complications that are related to breast implants. The current review provides a brief discussion of the regulatory history of silicone implants and of FDA concerns over breast implants, implant prevalence, studies of systemic and local complications related to breast implants, and a brief description of the FDA study of silicone-gel breast implant rupture. C1 US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Brown, SL (reprint author), US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. NR 47 TC 15 Z9 16 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2002 VL 13 IS 3 SU S BP S34 EP S39 DI 10.1097/00001648-200205001-00008 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 545ZE UT WOS:000175246800008 PM 12071482 ER PT J AU Marinac-Dabic, D Krulewitch, CJ Moore, RM AF Marinac-Dabic, D Krulewitch, CJ Moore, RM TI The safety of prenatal ultrasound exposure in human studies SO EPIDEMIOLOGY LA English DT Article DE medical devices; diagnostic ultrasound; obstetrics; prenatal care ID RANDOMIZED CONTROLLED TRIAL; DIAGNOSTIC ULTRASOUND; BIRTH-WEIGHT; PREGNANCY; ROUTINE; HANDEDNESS AB Diagnostic ultrasound use in obstetrics has been growing rapidly to become an integral part of prenatal care today. The high proportion of exposure to prenatal ultrasound highlights the public health significance of routine ultrasound use. A majority of epidemiologic studies tends to support the safety of diagnostic ultrasound use during pregnancy. However, there have been some reports that there may be a relation between prenatal ultrasound exposure and adverse outcome. Some of the reported effects include growth restriction, delayed speech, dyslexia, and non-right-handedness associated with ultrasound exposure. Continued research is needed to evaluate the potential adverse effects of ultrasound exposure during pregnancy. These studies should measure the acoustic output, exposure time, number of exposures per subject, and the timing during the pregnancy when exposure(s) occurred, while controlling for potential confounding variables such as sociodemographic, medical, and obstetric risk factors. We recommend that a new consensus development conference be held to gather the needed data and provide guidelines for the future research needs, as well as respond to the rapid advances in this technology. C1 US FDA, Food & Drug Adm, Epidemiol Branch, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Univ Maryland, Sch Nursing, Baltimore, MD 21201 USA. Off Global Hlth Affairs, Off Secretary Hlth & Human Serv, Rockville, MD USA. RP Marinac-Dabic, D (reprint author), US FDA, Food & Drug Adm, Epidemiol Branch, Ctr Devices & Radiol Hlth, HFZ-540,1350 Piccard Dr,Room 330 C, Rockville, MD 20850 USA. NR 31 TC 10 Z9 10 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2002 VL 13 IS 3 SU S BP S19 EP S22 DI 10.1097/00001648-200205001-00004 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 545ZE UT WOS:000175246800004 PM 12071478 ER PT J AU Robinowitz, M AF Robinowitz, M TI Introduction to and update of "cost effectiveness in new technology in cervix cancer screening" SO EPIDEMIOLOGY LA English DT Editorial Material C1 US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Clin Lab Devices, Rockville, MD 20850 USA. RP Robinowitz, M (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Device Evaluat, Div Clin Lab Devices, Rockville, MD 20850 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2002 VL 13 IS 3 SU S BP S23 EP S25 DI 10.1097/00001648-200205001-00005 PG 3 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 545ZE UT WOS:000175246800005 PM 12071479 ER PT J AU Torrence, ME AF Torrence, ME TI Data sources: Use in the epidemiologic study of medical devices SO EPIDEMIOLOGY LA English DT Article DE data sources; medical devices; epidemiologic studies; surveillance; Medicare; National Center for Health Statistics ID PACEMAKER RECIPIENTS AB Medical device epidemiology is the study of the prevalence and incidence of use, effectiveness, and adverse events associated with medical devices in a population. The identification of large data sources with medical device data provides a large population for epidemiologic studies. Two challenges in medical device epidemiology are the ability to find data on the specific device and the exposure of a patient to that device. This paper identifies data sources both from the government and from the private sector that can be used for epidemiologic studies of medical devices and, to a limited degree, studies of medical devices in women. Each source provides data for different types of devices and in differing specificity. The paper also discusses briefly the strengths and weaknesses of each data source. More data sources are needed to enhance the study of medical device epidemiology. Additional efforts and focus are needed to enhance the ability to study medical devices in women. C1 US FDA, Food & Drug Adm, Off Surveillance & Biomet, Epidemiol Branch,Ctr Devices & Radiol Hlth, Rockville, MD USA. RP Torrence, ME (reprint author), USDA, Cooperat State Res Educ & Extens Serv, Natl Program Leader Food Safety, AgBox 2220,1400 Independence Ave SW, Washington, DC 20250 USA. NR 11 TC 3 Z9 3 U1 1 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1044-3983 J9 EPIDEMIOLOGY JI Epidemiology PD MAY PY 2002 VL 13 IS 3 SU S BP S10 EP S14 DI 10.1097/00001648-200205001-00002 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 545ZE UT WOS:000175246800002 PM 12071476 ER PT J AU Taylor, MR AF Taylor, MR TI Reforming food safety: A model for the future - The long-term success of the US food safety system requires unification of the existing agencies. Here's why and how this should occur SO FOOD TECHNOLOGY LA English DT Article C1 Resources Future Inc, Risk Resource & Environm Management Div, Washington, DC 20036 USA. US FDA, Rockville, MD 20857 USA. Food Safety & Inspect Serv, USDA, Washington, DC 20250 USA. RP Taylor, MR (reprint author), Resources Future Inc, Risk Resource & Environm Management Div, 1616 P St NW, Washington, DC 20036 USA. NR 11 TC 2 Z9 2 U1 1 U2 2 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 MAY PY 2002 VL 56 IS 5 BP 190 EP 194 PG 5 WC Food Science & Technology SC Food Science & Technology GA 554EU UT WOS:000175721700012 ER PT J AU Myers, MR Herman, BA AF Myers, MR Herman, BA TI A theoretical assessment of a thermal technique to measure acoustic power radiated by ultrasound transducers SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article AB The parameters affecting the temperature rise in an insonified absorber are studied computationally. Finite-element and analytical solutions are obtained for the transient energy equation in a cylindrical absorber. When the ultrasound beam radius is less than the radius of the absorber, the temperature field is seen to be considerably more complex than when the absorber cross section is uniformly heated. Circumstances in which power predictions based upon uniform heating would result in appreciable error are identified. The rise time required to achieve equilibrium is studied as a function of operational parameters, including absorber geometry and thermal properties as well as ultrasound beamwidth and frequency. The rise time is seen to increase approximately as the square of the absorber length, while optimized temperature rise increases linearly with absorber length, demonstrating a tradeoff in ultrasound power determination via equilibrium temperature measurements: longer lengths produce higher sensitivity, but also longer times before measurements can be made. A transient technique that may bypass this tradeoff is suggested. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-132, Rockville, MD 20852 USA. NR 4 TC 8 Z9 8 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017-2394 USA SN 0885-3010 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD MAY PY 2002 VL 49 IS 5 BP 565 EP 572 DI 10.1109/TUFFC.2002.1002455 PG 8 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 553EK UT WOS:000175662600004 PM 12046932 ER PT J AU Crawford, LM AF Crawford, LM TI Data bank submissions SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, Rockville, MD 20857 USA. 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 MAY 1 PY 2002 VL 287 IS 17 BP 2203 EP 2203 DI 10.1001/jama.287.17.2203 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 546EZ UT WOS:000175260600007 PM 11980508 ER PT J AU Crawford, LM AF Crawford, LM TI Patient safety news SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, Rockville, MD 20857 USA. 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 MAY 1 PY 2002 VL 287 IS 17 BP 2203 EP 2203 DI 10.1001/jama.287.17.2203 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 546EZ UT WOS:000175260600008 PM 11980508 ER PT J AU Crawford, LM AF Crawford, LM TI FDA-PPTA workshop SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, Rockville, MD 20857 USA. 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 MAY 1 PY 2002 VL 287 IS 17 BP 2203 EP 2203 DI 10.1001/jama.287.17.2203 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 546EZ UT WOS:000175260600006 PM 11980508 ER PT J AU Crawford, LM AF Crawford, LM TI Treatment for liver tumors SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, Rockville, MD 20857 USA. 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 MAY 1 PY 2002 VL 287 IS 17 BP 2203 EP 2203 DI 10.1001/jama.287.17.2203 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 546EZ UT WOS:000175260600005 PM 11980508 ER PT J AU Temple, RJ Himmel, MH AF Temple, RJ Himmel, MH TI Safety of newly approved drugs - Implications for prescribing SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Ctr Drug Evaluat & Res Policy, Rockville, MD 20857 USA. RP Temple, RJ (reprint author), US FDA, Ctr Drug Evaluat & Res Policy, 5600 Fishers Ln,HFD-101, Rockville, MD 20857 USA. NR 4 TC 103 Z9 105 U1 0 U2 3 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 MAY 1 PY 2002 VL 287 IS 17 BP 2273 EP 2275 DI 10.1001/jama.287.17.2273 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 546EZ UT WOS:000175260600028 PM 11980528 ER PT J AU LaCroix, DE Wolf, WR AF LaCroix, DE Wolf, WR TI Determination of niacin in infant formula by solid-phase extraction/liquid chromatography: Peer-verified method performance-interlaboratory validation SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID EXCHANGE LIQUID-CHROMATOGRAPHY; PRODUCTS; ERROR AB This paper reports the results of the interlaboratory peer validation study of AOAC Peer-Verified Method (PVM) 1:2000 for the determination of niacin in infant formula by solid-phase extraction/liquid chromatography. We have used a Data Quality Objectives (DQO) approach to address not only method variability and robustness but also accuracy of data through the use of an appropriate reference material in conjunction with the interlaboratory validation study. Our DQO included the following: (1) statistical agreement of analytical results and quantitative recovery between 2 collaborating laboratories; (2) the repeatability relative standard deviation (RSDr) values and the HORRAT (Horwitz ratio) obtained (1.07), which satisfied the criteria of the Horwitz "limits of acceptability" at the analyte level present; (3) validation of lack of interference; and (4) accuracy agreement within assigned values for a certified reference material. National Institute of Standards and Technology Standard Reference Material (NIST SRM) 1846 Infant Formula, with a certified value of 63.3 +/- 7.6 mug/g for niacin content, was used as a test material for collaborative study and accuracy assessment. Niacin values obtained by the originating laboratory were 59.7 +/- 4.0 mug/g (95% confidence interval [Cl] = 1.4 mug/g with a relative standard deviation [RSD] of 6.7%) and by the peer laboratory were 56.6 +/- 6.6 mug/g (95% Cl = 4.1 mug/g, with an RSD of 11.7%). Statistical evaluation using the means equivalence test showed that nicotinic acid values obtained by the peer laboratory were equivalent to those values obtained by the originating laboratory. Linear calibration curves and quantitative recovery were obtained. Integration of the PVM process with a readily available certified reference material gives the user confidence in the accuracy of the data generated by the method through traceability to the reference material used. C1 USDA, Beltsville Human Nutr Res Ctr, Food Composit Lab, Beltsville, MD 20705 USA. US FDA, Bothell, WA 98021 USA. RP Wolf, WR (reprint author), USDA, Beltsville Human Nutr Res Ctr, Food Composit Lab, Beltsville, MD 20705 USA. EM wolf@bhnrc.usda.gov NR 36 TC 14 Z9 14 U1 1 U2 4 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 MAY-JUN PY 2002 VL 85 IS 3 BP 654 EP 664 PG 11 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 560FY UT WOS:000176073100016 PM 12083258 ER PT J AU Wheeler, M Bennett, B Marks, H AF Wheeler, M Bennett, B Marks, H TI Isolation of light filth from ground oregano and ground marjoram: A modification using isopropanol as a defatting agent: In-house study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A procedural modification of the AOAC Official Method for extracting light filth from ground oregano and ground marjoram was tested in an intralaboratory study. The modified method specifies isopropanol defatting, 975.49A(a), rather than chloroform-isopropanol defatting, 975.49A(b), followed by direct flotation as directed in AOAC Official Method, 975.49B(b). The modified method provided comparable results in less time while also providing safety, health, and financial benefits. C1 USDA, Food Safety & Inspect Serv, OPPDE, Bethesda, MD 20205 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Wheeler, M (reprint author), USDA, Food Safety & Inspect Serv, OPPDE, 300 12TH St SW, Bethesda, MD 20205 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 85 IS 3 BP 676 EP 681 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 560FY UT WOS:000176073100018 PM 12083260 ER PT J AU Woollard, DC Indyk, HE Fong, BY Cook, KK AF Woollard, DC Indyk, HE Fong, BY Cook, KK TI Determination of vitamin K-1 isomers in foods by liquid chromatography with C-30 bonded-phase column SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID K-DEPENDENT PROTEINS; STATIONARY PHASES; PHYLLOQUINONE VITAMIN-K-1; CAROTENOID ISOMERS; NUTRITIONAL SOURCES; TISSUE DISTRIBUTION; CIS/TRANS ISOMERS; INFANT FORMULAS; RETINYL ESTERS; SEPARATION AB Vitamin K-1 was determined in a variety of foods by using reversed-phase liquid chromatography with a C-30 column followed by post-column reduction to the fluorescent hydroquinone derivatives. Lipids were removed by lipase digestion, followed by single extraction into hydrocarbon, and the protocol was extended to selected natural and processed foods. Biologically active trans- and inactive cis-vitamin K-1 isomers were measured individually to evaluate the true nutritional status of the products. Method performance parameters confirmed the validity of the technique. The use of the triacontyl-bonded C-30 phase for selective phylloquinone isomer measurement extends previously validated AOAC Method 999.15 for vitamin K-1 in milk and infant formula to a wider range of foods important in the human diet. The cis-vitamin K-1 isomer contributes up to about 15% of total phylloquinone in certain foods. C1 AgriQual NZ Ltd, Auckland, New Zealand. NZMP Fronterra, Waitoa, New Zealand. New Zealand Dairy Res Inst, Palmerston North, New Zealand. US FDA, Laurel, MD 20708 USA. RP Woollard, DC (reprint author), AgriQual NZ Ltd, POB 41, Auckland, New Zealand. NR 56 TC 18 Z9 18 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 MAY-JUN PY 2002 VL 85 IS 3 BP 682 EP 691 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 560FY UT WOS:000176073100019 PM 12083261 ER PT J AU Goering, PL Morgan, DL Ali, SF AF Goering, PL Morgan, DL Ali, SF TI Effects of mercury vapor inhalation on reactive oxygen species and antioxidant enzymes in rat brain and kidney are minimal SO JOURNAL OF APPLIED TOXICOLOGY LA English DT Article DE mercury vapor; reactive oxygen species; kidney; brain; neurotoxicity; nephrotoxicity ID ASTROCYTE CULTURES; DIFFERENT REGIONS; TRANSGENIC MICE; FREE-RADICALS; NULL MICE; METALLOTHIONEIN; EXPOSURE; TOXICITY; NEUROTOXICITY; MANGANESE AB Metals are known to induce the formation of reactive oxygen species (ROS) that initiate oxidative stress, an important mechanism of cell injury. The brain is particularly sensitive to oxidative attack because of its high level of unsaturated lipids and high rate of oxidative metabolism. The objective of this study was to determine if elemental mercury (Hg-0) vapor inhalation increases ROS production and affects activities or levels of antioxidant-related bioniolecules in the rat brain and kidney. Adult female Sprague-Dawley rats were exposed for 2 h per day for 11 consecutive days to Hg-0 vapor (1, 2, and 4 mg Hg-0 m(-3)). Brain regions (frontal cortex, cerebellum, brain stem) and kidney were assayed for total Hg, ROS and glutathione (GSH) levels, and for enzyme activities of glutathione peroxidase (GPx) and superoxide dismutase (SOD). Marked exposure-related increases (2500-5600-fold) in total Hg were detected in the brain regions and in kidney. A statistically significant increase in ROS production (ca. 30% above controls) was observed only in the cortex of rats exposed to 1 mg m(-3) Hg vapor, but no significant changes were apparent at other exposures. Although a trend towards increasing ROS production was observed in the kidney, these effects were not statistically significant. Mercury vapor exposure had no significant effects on GSH levels or GPx activity in the three brain regions, however, statistically significant decreases in GSH and GPx activity were detected in the kidneys of rats exposed to 2 mg m(-3). Mercury exposure did not cause significant effects on SOD activity in the brain or kidney. The data indicate that oxidative stress and changes in GSH and activities of antioxidant enzymes do not play a major role in Hg-0 vapor toxicity in brain and kidney. Published in 2002 by John Wiley Sons, Ltd. C1 US FDA, Ctr Devices & Radiol Hlth HFZ112, Rockville, MD 20852 USA. NIEHS, Res Triangle Pk, NC 27709 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Goering, PL (reprint author), US FDA, Ctr Devices & Radiol Hlth HFZ112, 12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 29 TC 26 Z9 33 U1 1 U2 4 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0260-437X J9 J APPL TOXICOL JI J. Appl. Toxicol. PD MAY-JUN PY 2002 VL 22 IS 3 BP 167 EP 172 DI 10.1002/jat.844 PG 6 WC Toxicology SC Toxicology GA 557JB UT WOS:000175904500005 PM 12015796 ER PT J AU Lathers, CM Smith, CM AF Lathers, CM Smith, CM TI Development of innovative teaching materials: Clinical pharmacology problem-solving (CPPS) units: Comparison with patient-oriented problem-solving units and problem-based learning - A 10-year review SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID CURRICULA; DRUGS AB The First Teaching Clinic in Clinical Pharmacology, sponsored by the American College of Clinical Pharmacology in September 1992, was designed for the preparation and development of new clinical pharmacology problem-solving (CPPS) units. CPPS units are case histories that illustrate pertinent principles in clinical pharmacology. Each unit consists of the following sections: introduction, learning objectives, pretest, four clinical pharmacology scenarios, posttest, answers to pre- and posttest questions, and selected references. The clinical pharmacology content of the CPPS units place greater emphasis on clinical information, drug selection, and risk/benefit analyses, and thus they complement the basic pharmacology presented in the patient-oriented problem-solving (POPS) units. In general, the CPPS units are intended for use by students more advanced in clinical pharmacology than first-and second-year medical students. The CPPS unit "Clinical Pharmacology of Antiepileptic Drug Use: Clinical Pearls about the Perils of Patty" was developed for use by third- and fourth-year medical students doing rotations in neurology or clinical pharmacology; advanced pharmacy students; residents in neurology; pediatrics, internal medicine, and family practice; fellows in clinical pharmacology; and those taking the board examination in clinical pharmacology. The CPPS unit titled "Geriatric Clinical Psychopharmacology" was written for third- and fourth-year medical students; residents in psychiatry, family practice, and internal medicine; fellows in clinical pharmacology; and those studying for boards in clinical pharmacology, The CPPS unit "Anisocoria and Glaucoma" was written for more advanced students of clinical pharmacology. The CPPS unit titled "Antiepileptic Drugs" was intended for second-year medical students. The second teaching clinic was held in November 1993 and focused on the development and editing of the CPPS units and their evaluations by faculty and students from academic centers. Evaluations by faculty and students have been overwhelmingly positive. Requests to use the CPPS units in various clinical pharmacology teaching programs were received from numerous schools within the United States and from abroad. The third teaching clinic in September 1995 included a follow-up focused on the uses of drug-information databases in case problem exercises. These examples are presented to demonstrate the variety of educational activities the American College of Clinical Pharmacology is sponsoring to fulfill its strategic initiative dedicated to offer innovative teaching programs and to develop new teaching materials in clinical pharmacology. Collectively; all of the teaching clinics, symposia, and workshop efforts, sponsored by the various academic professional societies alone or together over the past decade, are necessary if new and innovative teaching materials in the field of basic science and in the fields of pharmacology and clinical pharmacology are to be continuously developed to keep pace with the new; rapidly changing developments in medicine to provide the best treatment for patients in the 21st century. (C) 2002 the American College of Clinical Pharmacology. C1 US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20855 USA. SUNY Buffalo, Sch Med & Biomed Sci, Buffalo, NY 14260 USA. RP Lathers, CM (reprint author), US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, 7500 Standish Pl,Room 387,HFV-100, Rockville, MD 20855 USA. NR 33 TC 10 Z9 10 U1 1 U2 4 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 2002 VL 42 IS 5 BP 477 EP 491 DI 10.1177/00912700222011535 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 544ZL UT WOS:000175191700002 PM 12017342 ER PT J AU Erskine, RJ Walker, RD Bolin, CA Bartlett, PC White, DG AF Erskine, RJ Walker, RD Bolin, CA Bartlett, PC White, DG TI Trends in antibacterial susceptibility of mastitis pathogens during a seven-year period SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE mastitis; antibacterial; susceptibility ID BOVINE MASTITIS; ANTIMICROBIAL AGENTS; COLIFORM MASTITIS; ESCHERICHIA-COLI; MAMMARY-GLANDS; RESISTANCE; SENSITIVITY; INFECTIONS AB Milk samples collected from dairy cattle suspected of having mastitis were submitted to the Microbiology Laboratory of the Animal Health Diagnostic Laboratory, Michigan State University, for bacteriologic culture. A total of 2778 isolates, from the years 1994 to 2000, were isolated, identified, and subjected to in vitro antimicrobial susceptibility testing using the disk diffusion method, in accordance with National Committee on Clinical Laboratory Standards (NCCLS) standards. Isolates included in this study were Streptococcus uberis, Streptococcus dysgalactiae, Streptococcus agalactiae, Staphylococcus aureus, Escherichia coli, Klebsiella pneumoniae, Serratia marcesens, and Pseudomonas aeruginosa. The proportion of bacterial isolates determined to be susceptible did not change during the 7-yr period for the majority of bacterial-antibacterial interactions tested. However, analysis for linear trend in proportions determined that there were increases in the proportion of S. aureus isolates that were susceptible to ampicillin, penicillin, and erythromycin. For Strep. uberis, increases in the proportion of susceptible isolates occurred for oxacillin, sulfa-trimethoprim, gentamicin, and pirlimycin, and a decrease in the proportion of susceptible isolates occurred with penicillin. For Strep. dysgalactiae, increases in the proportion of susceptible isolates occurred with erythromycin, gentamicin, sulfa-trimethoprim, and tetracycline. For Strep. agalactiae, increases in the proportion of susceptible isolates occurred with sulfa-trimethoprim. Among E. coli isolates, there was an increase in the proportion that were susceptible to ampicillin and cephalothin. Among K pneumoniae isolates, there was an increase in the proportion that were susceptible to ceftiofur. Overall, there was no indication of increased resistance of mastitis isolates to antibacterials that are commonly used in dairy cattle. C1 Michigan State Univ, Dept Large Anim Clin Sci, E Lansing, MI 48824 USA. Michigan State Univ, Anim Hlth Diagnost Lab, E Lansing, MI 48824 USA. US FDA, Washington, DC 20204 USA. RP Erskine, RJ (reprint author), Michigan State Univ, Dept Large Anim Clin Sci, E Lansing, MI 48824 USA. NR 21 TC 140 Z9 148 U1 2 U2 32 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD MAY PY 2002 VL 85 IS 5 BP 1111 EP 1118 DI 10.3168/jds.S0022-0302(02)74172-6 PG 8 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA 555GY UT WOS:000175787400011 PM 12086045 ER PT J AU Bonnel, RA Villalba, ML Karwoski, CB Beitz, J AF Bonnel, RA Villalba, ML Karwoski, CB Beitz, J TI Deaths associated with inappropriate intravenous colchicine administration SO JOURNAL OF EMERGENCY MEDICINE LA English DT Article DE intravenous; colchicine; gout ID OVERDOSE; TOXICITY AB Intravenous (IV) colchicine is occasionally prescribed for the treatment of acute gouty arthritis. The Food and Drug Administration (FDA) recently received a report of death in a patient that was associated with inappropriate IV dosing of colchicine. This report prompted further investigation of other deaths associated with IV colchicine use in the FDA Adverse Event Reporting System (AERS) and the medical literature. A total of 20 deaths were identified. Eight patients were females, I I were males, and the gender was unknown in 1. In all cases, the recommended maximum cumulative dose of 2 to 4 mg during a course of therapy was exceeded. Dose reductions are recommended in patients with renal or hepatic disease and in the elderly. All reported adverse events were associated with colchicine toxicity, including thrombocytopenia, leukopenia, pancytopenia, agranulocytosis, aplastic anemia, acute renal failure, and disseminated intravascular coagulopathy. Death occurred within I to 40 days after drug administration. Therapeutic guidelines exist for use of IV colchicine and these guidelines should be followed to prevent serious toxicities and death. (C) 2002 Elsevier Science Inc. C1 US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Antiinflammatory Analges & Ophthalm Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Bonnel, RA (reprint author), US FDA, Off Drug Safety, Ctr Drug Evaluat & Res, 5600 Fishers Lane,Rm 15B-23,HFD-430, Rockville, MD 20857 USA. NR 13 TC 51 Z9 54 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0736-4679 J9 J EMERG MED JI J. Emerg. Med. PD MAY PY 2002 VL 22 IS 4 BP 385 EP 387 AR PII S0736-4679(02)00430-4 DI 10.1016/S0736-4679(02)00430-4 PG 3 WC Emergency Medicine SC Emergency Medicine GA 574WG UT WOS:000176912100011 PM 12113850 ER PT J AU Wagner, RD Holland, M Cerniglia, CE AF Wagner, RD Holland, M Cerniglia, CE TI An in vitro assay to evaluate competitive exclusion products for poultry SO JOURNAL OF FOOD PROTECTION LA English DT Article ID SALMONELLA-TYPHIMURIUM; BROILER CHICKS; PROBIOTIC PROPERTIES; IN-VITRO; COLONIZATION; CULTURE; BACTERIA; ESTABLISHMENT; RESISTANCE; INFECTION AB An in vitro assay was developed to measure the ability of competitive exclusion (CE) bacteria to protect Caco-2 and CRL-21117 epithelial cells from invasion by Salmonella Typhimurium. The proposed assay is needed to expedite the development of defined-flora CE products. The average significantly protective concentration of the commercial poultry-specific CE product Preempt was 4.05 log CFU/6.41 log human Caco-2 cells and 3.71 log CFU/6.89 log CFU chicken CRL-2117 cells. Enterococcus faecalis isolated from Preempt protected CRL-2117 cells, Escherichia coli isolates protected Caco-2 cells, Lactococcus lactis and Bacteroides distasonis isolates protected both cell lines, and three species of Lactobacillus isolates failed to protect either cell line. A defined mixture of 29 strains of bacteria similar to the constituents of Preempt protected both cell lines from Salmonella invasion at a concentration of 7.83 log CFU. The constituents of the defined CE culture were separated into mixtures of obligate (8.42 log CFU) and facultative (8.49 log CFU) anaerobes, which both protected the cell lines. suggesting that both types of bacteria were equally protective. Although not a substitute for in vivo testing, the in vitro CE assay is a rapid technique for the evaluation of bacterial mixtures for potential CE products. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res HFT250, Jefferson, AR 72079 USA. RP Wagner, RD (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res HFT250, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 30 TC 15 Z9 16 U1 1 U2 1 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAY PY 2002 VL 65 IS 5 BP 746 EP 751 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 549FU UT WOS:000175434500006 PM 12030283 ER PT J AU Ravert, HT Klecker, RW Collins, JM Mathews, WB Pomper, MG Wahl, RL Dannals, RF AF Ravert, HT Klecker, RW Collins, JM Mathews, WB Pomper, MG Wahl, RL Dannals, RF TI Radiosynthesis of [C-11]paclitaxel SO JOURNAL OF LABELLED COMPOUNDS & RADIOPHARMACEUTICALS LA English DT Article DE paclitaxel; anticancer; microtubule; carbon-11; positron emission tomography ID PACLITAXEL; RESISTANCE; TUMORS AB [C-11]paclitaxel, a potential solid tumor imaging agent, was synthesized by reacting [alpha-C-11]benzoyl chloride with the primary amine precursor of paclitaxel. The time for synthesis, purification, and formulation was 38 min from end of bombardment with an average specific radioactivity of 49.9 GBq/mumol (1349 mCi/mumol) at end of synthesis. The average decay corrected radiochemical yield was 7% with greater than 99% radiochemical purity. Copyright (C) 2002 John Wiley Sons, Ltd. C1 Johns Hopkins Med Inst, Dept Radiol, Div Nucl Med, Baltimore, MD 21287 USA. US FDA, Lab Clin Pharmacol, Rockville, MD 20850 USA. RP Ravert, HT (reprint author), Johns Hopkins Med Inst, Dept Radiol, Div Nucl Med, 600 N Wolfe St, Baltimore, MD 21287 USA. NR 9 TC 21 Z9 21 U1 0 U2 0 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0362-4803 J9 J LABELLED COMPD RAD JI J. Label. Compd. Radiopharm. PD MAY PY 2002 VL 45 IS 6 BP 471 EP 477 DI 10.1002/jlcr.571 PG 7 WC Biochemical Research Methods; Chemistry, Medicinal; Chemistry, Analytical SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Chemistry GA 554ZD UT WOS:000175766500002 ER PT J AU Gursel, M Verthelyi, D Gursel, I Ishii, KJ Klinman, DM AF Gursel, M Verthelyi, D Gursel, I Ishii, KJ Klinman, DM TI Differential and competitive activation of human immune cells by distinct classes of CpG oligodeoxynucleotide SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE CpG DNA; B cells; NK cells; monocytes ID IMMUNOSTIMULATORY DNA-SEQUENCES; HUMAN B-CELLS; BACTERIAL-DNA; DENDRITIC CELLS; CUTTING EDGE; SYNTHETIC OLIGONUCLEOTIDES; IN-VITRO; T-CELLS; MOTIFS; INDUCTION AB Synthetic oligodeoxynucleotides (ODN) expressing "CpG motifs" show promise as immune adjuvants, antiallergens, anticancer, and immuno-protective agents. Two structurally distinct classes of CpG ODN have been identified that stimulate human PBMC. This work establishes that both types of ODN bind to and are internalized by the same individual B cells, NK cells, and monocytes. However, the intracellular localization of "D" and "K" ODN differs, as does their functional activity: "K" type ODN trigger monocytes and B cells to proliferate and secrete IL-6 and IgM, whereas "D" type ODN induce NK cells to produce IFN-gamma and monocytes to differentiate into CD83(+)/CD86(+) dendritic cells. In monocytes, these two types of ODN (which differ in backbone composition and CpG motif) cross-inhibit one another's activity. Thus, different types of CpG ODN have distinct and in some cases incompatible effects on the same cells, a finding with important implications for the therapeutic use of these agents. 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 3 D 10,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Gursel, Mayda /H-1812-2012; Ishii, Ken/B-1685-2012; OI Ishii, Ken/0000-0002-6728-3872; Gursel, Ihsan/0000-0003-3761-1166 NR 40 TC 139 Z9 149 U1 1 U2 7 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 MAY PY 2002 VL 71 IS 5 BP 813 EP 820 PG 8 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 550DU UT WOS:000175489000010 PM 11994506 ER PT J AU Beger, RD Wilkes, JG AF Beger, RD Wilkes, JG TI Comparative structural connectivity spectra analysis (CoSCoSA) models of steroids binding to the aromatase enzyme SO JOURNAL OF MOLECULAR RECOGNITION LA English DT Article DE 3D-QSDAR; aromatase enzyme; steroid binding; CoSCoSA; C-13 NMR ID AUTOMATED STRUCTURE EVALUATION; RELATIONSHIP QSDAR MODELS; BREAST-CANCER; NMR; INHIBITORS; QSAR; SPECTROSCOPY; INDEX; N-15; H-1 AB A method that combines NMR spectral and structural information into a constructed three-dimensional (3D)-connectivity matrix is developed for modeling biological binding activity of small molecules. The 3D-connectivity matrix for a molecule is defined by associating the distances between all possible carbon-to-carbon connections with their assigned carbon NMR chemical shifts. In this project we selected from the total 3D-connectivity matrix a subset, the two-dimensional (2D) C-13-C-13 COSY and a theoretical long range 2D C-13-C-13 distance connectivity spectral plane. Patterns of C-13 chemical shifts observed at these two relative distances for 50 steroids were used to produce a mathematical relationship for the steroids' relative binding affinity (pK(i)) to the aromatase enzyme. We call this technique comparative structural connectivity spectra analysis (CoSCoSA) modeling. Using combinations of the 2D COSY and 2D long-range distance spectra as modeling parameters, we built four CoSCoSA models. One model was made from the 2D COSY spectra alone and another was developed using only the 2D long-range distance spectra. Then the COSY and long-distance spectra were combined in two different ways: starting with the combined principal components (PCs) from the separately calculated COSY and distance spectra or using the combined raw spectra (3D). The best CoSCoSA model was based on the combined PCs from COSY and distance spectra. This model had an r(2) of 0.96 and a leave-one-out cross-validation (q(2)) of 0.92. In general CoSCoSA modeling combines the quantum mechanical information inherent in NMR chemical shifts with internal molecular atom-to-atom distances to give a reliable and straightforward basis for predictive modeling. The technique has the flexibility and accuracy to outperform not only the cross-validated variance q(2) of previously published quantitative structure-activity relationships (QSAR) but also those obtained by related quantitative spectral data-activity relationships (QSDARs) lacking connectivity dimensions. Copyright (C) 2002 John Wiley Sons, Ltd. C1 US FDA, Div Chem, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Beger, RD (reprint author), US FDA, Div Chem, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 24 TC 9 Z9 9 U1 0 U2 2 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0952-3499 J9 J MOL RECOGNIT JI J. Mol. Recognit. PD MAY-JUN PY 2002 VL 15 IS 3 BP 154 EP 162 DI 10.1002/jmr.570 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 580UL UT WOS:000177254200005 PM 12203841 ER PT J AU Nimmagadda, S Mangner, TJ Muzik, O Sun, H Lawhorn-Crews, J Douglas, K Collins, JM Shields, AF AF Nimmagadda, S Mangner, TJ Muzik, O Sun, H Lawhorn-Crews, J Douglas, K Collins, JM Shields, AF TI Metabolic studies of F-18-FBAU in dogs: A PET tracer for DNA synthesis. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Wayne State Univ, Detroit, MI 48202 USA. Karmanos Canc Inst, Detroit, MI USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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 MAY PY 2002 VL 43 IS 5 SU S MA 94 BP 26P EP 27P AR UNSP 200807 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800095 ER PT J AU Sun, H Mangner, TJ Muzik, O Collins, JM Douglas, KA Shields, AF AF Sun, H Mangner, TJ Muzik, O Collins, JM Douglas, KA Shields, AF TI Imaging DNA synthesis in tumor patients with F-18-FMAU and PET. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Karmanos Canc Inst, Detroit, MI USA. Wayne State Univ, Detroit, MI 48202 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 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 MAY PY 2002 VL 43 IS 5 SU S MA 93 BP 26P EP 26P AR UNSP 201225 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560800094 ER PT J AU Nakamoto, Y Ravert, HT Hilton, J Traughber, BJ Tatsumi, M Scheffel, U Dannals, RF Pomper, MG Collins, JM Wahl, RL AF Nakamoto, Y Ravert, HT Hilton, J Traughber, BJ Tatsumi, M Scheffel, U Dannals, RF Pomper, MG Collins, JM Wahl, RL TI Dosimetry and stability evalation of C-11-paclitaxel. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 Johns Hopkins Univ, Baltimore, MD USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 MAY PY 2002 VL 43 IS 5 SU S MA 1455 BP 362P EP 362P AR UNSP 201518 PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 551KL UT WOS:000175560801366 ER PT J AU Pershing, LK Bakhtian, S Poncelet, CE Corlett, JL Shah, VP AF Pershing, LK Bakhtian, S Poncelet, CE Corlett, JL Shah, VP TI Comparison of skin stripping, in vitro release, and skin blanching response methods to measure dose response and similarity of triamcinolone acetonide cream strengths from two manufactured sources SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE corticosteroids; human; in vitro; skin stripping; vasoconstriction ID 0.05-PERCENT BETAMETHASONE DIPROPIONATE; ASSAY; BIOAVAILABILITY; GLUCOCORTICOIDS; HYDROCORTISONE; HUMANS AB The collective studies compare in vitro drug release, in vivo skin stripping, and skin blanching response methods for dose responsiveness and bioequivalence assessment of triamcinolone acetonide cream products, as a function of application duration, drug concentration, and manufacturer source. Commercially available triamcinolone acetonide creams (0.025%, 0.1%, and 0.5%) from two manufacturers were evaluated in vitro for rate and extent of drug release across synthetic membranes and in vivo for rate, extent, and variability of drug uptake into human stratum corneum and skin blanching response in human forearm skin. Data demonstrate that increasing triamcinolone acetonide cream concentration applied increased the rate and extent of drug released in vitro as well as the extent of drug uptake and skin blanching response in human skin in vivo. No difference (p < 0.05) between the two sources of 0.1% or 0.5% creams was measured by the skin stripping or skin blanching response methods. Dermatopharmacokinetic analysis of triamcinonide acetonide in. vivo is therefore dose responsive to drug concentration applied and application duration and agrees with in vivo skin blanching results. Data support the use of dermatopharmacokinetic methods for bioequivalence and bioavailability assessment of topical drug products. (C) 2002 Wiley-Liss, Inc. and the American Pharmaceutical Association. C1 Univ Utah, Sch Med, Dept Dermatol, Salt Lake City, UT 84132 USA. US FDA, Off Pharmaceut Sci, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. RP Pershing, LK (reprint author), Univ Utah, Sch Med, Dept Dermatol, 4B454 SOM,30 N 1900 E, Salt Lake City, UT 84132 USA. NR 19 TC 32 Z9 34 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 JI J. Pharm. Sci. PD MAY PY 2002 VL 91 IS 5 BP 1312 EP 1323 DI 10.1002/jps.10147 PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 548UC UT WOS:000175407400012 PM 11977107 ER PT J AU Weber, JKR Abadie, JG Key, TS Hiera, K Nordine, PC Waynant, RW Ilev, IK AF Weber, JKR Abadie, JG Key, TS Hiera, K Nordine, PC Waynant, RW Ilev, IK TI Synthesis and optical properties of rare-earth-aluminum oxide glasses SO JOURNAL OF THE AMERICAN CERAMIC SOCIETY LA English DT Article ID UP-CONVERSION; ABSORPTION; FIBERS; ER3+; GAIN AB Single-phase glasses containing 37.5 mol% Y2O3, 7 mol% La2O3, and 1 mol% Pr, Ho, Nd, Er, Sm, Tm, Eu, or Yb oxide substituted for part of the Y2O3 were synthesized by containerless melting. The spectral transmission and absorption cross sections of the glasses were determined at wavelengths from 360 to 3300 nm. The electronic transitions were broadened compared with results obtained in a crystalline yttrium aluminum garnet (YAG) host. The infrared transmission of the host glass extended to 6000 nm. The optical and physicochemical properties of these glasses are well suited for optical device applications. C1 Containerless Res Inc, Evanston, IL 60201 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Weber, JKR (reprint author), Containerless Res Inc, Evanston, IL 60201 USA. NR 17 TC 16 Z9 16 U1 1 U2 13 PU AMER CERAMIC SOC PI WESTERVILLE PA 735 CERAMIC PLACE, PO BOX 6136, WESTERVILLE, OH 43086-6136 USA SN 0002-7820 J9 J AM CERAM SOC JI J. Am. Ceram. Soc. PD MAY PY 2002 VL 85 IS 5 BP 1309 EP 1311 PG 3 WC Materials Science, Ceramics SC Materials Science GA 555HJ UT WOS:000175788400050 ER PT J AU Wu, XF Zhao, H Amos, CI Shete, S Makan, N Hong, WK Kadlubar, FF Spitz, MR AF Wu, XF Zhao, H Amos, CI Shete, S Makan, N Hong, WK Kadlubar, FF Spitz, MR TI p53 genotypes and haplotypes associated with lung cancer susceptibility and ethnicity SO JOURNAL OF THE NATIONAL CANCER INSTITUTE LA English DT Article ID GERM-LINE POLYMORPHISM; BREAST-CANCER; OVARIAN-CANCER; CODON-72 POLYMORPHISM; INCREASED RISK; GENE; MUTATIONS; INTRON-6; TP53; FREQUENCY AB Background: The p53 tumor suppressor protein is important in cell-cycle control, apoptosis, and DNA repair. Mutations in p53 have been associated with inherited cancer susceptibility. Because there is a difference in the risk of lung cancer among different ethnic groups, we examined associations between ethnicity and three polymorphisms in p53 (one exonic and two intronic) and haplotypes for the three loci and risk of lung cancer. We also examined the functionality of the p53 variants in apoptosis and DNA repair. Methods: In a case-control study, we frequency matched (by age, sex, and ethnicity) 635 lung cancer case patients and 635 control subjects. p53 genotypes and haplotypes at the three polymorphic sites were determined by restriction fragment length polymorphism analysis of lymphocyte DNA. Odds ratios (ORs) and 95% confidence intervals (CIs) for the association between genotype or haplotype and lung cancer risk were determined by logistic regression analysis. Apoptosis and DNA repair capacity were measured in 22 lymphoblastoid. cell lines to determine the functional effects of the polymorphisms. All statistical tests were two-sided. Results: Genotype and haplotype frequency distributions were strongly dependent on thnicity; variant allele frequencies were highest in African-Americans (29.1%) and lowest in Mexican-Americans (12.2%). Each of the three polymorphisms was associated with an increased risk of lung cancer among all ethnic groups. Moreover, for all three polymorphisms, increased variant allele copy number was associated with increased risk of lung cancer. Similarly, the variant haplotypes were also associated with an increased risk for lung cancer. Lymphoblastoid cell lines with all wild-type alleles at the three loci had statistically significantly higher apoptotic indices (13.66%, 95% CI = 8.61% to 18.71%) and DNA repair capacity (27.63%, 95% CI = 21.72% to 33.53%) than cell lines with at least one variant allele at all three loci (3.50%, 95% CI = 1.08% to 5.91%; and 17.48%, 95% CI = 7.99% to 26.96%, respectively). Conclusions: p53 polymorphisms may be associated with increased lung cancer risk and may affect p53 function. C1 Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Thorac Head & Neck Med Oncol, Houston, TX 77030 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Wu, XF (reprint author), Univ Texas, MD Anderson Canc Ctr, Dept Epidemiol, Box 189,1515 Holcombe Blvd, Houston, TX 77030 USA. FU NCI NIH HHS [CA 95008, R01 CA 55769, U01 CA86390, U19 CA68437]; PHS HHS [R01 74880] NR 57 TC 197 Z9 213 U1 2 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0027-8874 J9 J NATL CANCER I JI J. Natl. Cancer Inst. PD MAY 1 PY 2002 VL 94 IS 9 BP 681 EP 690 PG 10 WC Oncology SC Oncology GA 547QN UT WOS:000175343400010 PM 11983757 ER PT J AU Abel, DB Beebe, HG Dedashtian, MM Morton, MC Moynahan, M Smith, LJ Weinberg, SL AF Abel, DB Beebe, HG Dedashtian, MM Morton, MC Moynahan, M Smith, LJ Weinberg, SL CA Workshop Steering Comm Conf Partic TI Preclinical testing for aortic endovascular grafts: Results of a Food and Drug Administration workshop SO JOURNAL OF VASCULAR SURGERY LA English DT Article ID ANEURYSM REPAIR; STENT-GRAFTS; KINKING AB Background: Since their introduction into clinical trials in the United States, endovascular aortic grafts have shown various types of problems. Although details of design and construction vary between different endovascular grafts and failure modes have had a variety of causes and clinical effects, the inability of preclinical testing to predict these failures remains common to all endovascular grafts. The need to improve preclinical testing in an attempt to reduce clinical device failures resulted in a Food and Drug Administration-sponsored workshop on endovascular graft preclinical testing held in Rockville, Md, from July 31 to August 1, 2001. Format. The workshop was not designed as a consensus conference. Instead, it provided a forum for bringing stakeholders together to define problems and identify areas of agreement and disagreement. The workshop had 34 invited participants who represented device manufacturers, the medical community, the Food and Drug Administration, and testing facilities, and international attendance was more than 120 people. Outcome: Discussion centered on: 1, defining the physiologic, anatomic, and morphologic characteristics of abdominal aortic aneurysms before and after endovascular graft treatment; 2, identifying the types of failures that have been observed clinically; and 3, determining which characteristics should be considered during preclinical modeling to better predict clinical performance. Attendees agreed to the need to better define and address anatomic characteristics and changes in the aneurysm after endograft treatment to optimize preclinical testing. Much discussion and little agreement occurred on the importance of flow-related forces on graft performance or the need or ability to define and model physiologic compliance during durability testing. The discussion and conclusions are summarized in this paper and arc provided in detail at: http://www.fda.gov/cdrh/meetings/073101workshop.html. Conclusion: The workshop raised awareness of significant performance issues and the challenges of modeling the extremely variable and relatively undefined environment of abdominal aortic aneurysms. Through the interactive format of the workshop, participants identified areas of preclinical testing, device design, and aspects of the simulated environment that need further consideration. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Jobst Vasc Ctr, Toledo, OH USA. Edwards Lifesci Inc, Irvine, CA USA. Alcon Res Ltd, Ft Worth, TX USA. WL Gore & Assoc, Flagstaff, AZ USA. Biomed Device Consultants, Webster, TX USA. RP Abel, DB (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 15 TC 9 Z9 9 U1 0 U2 1 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0741-5214 J9 J VASC SURG JI J. Vasc. Surg. PD MAY PY 2002 VL 35 IS 5 BP 1022 EP 1028 DI 10.1067/mva.2002.123762 PG 7 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 557QK UT WOS:000175919100043 PM 12021723 ER PT J AU Holada, K Vostal, JG Theisen, PW MacAuley, C Gregori, L Rohwer, RG AF Holada, K Vostal, JG Theisen, PW MacAuley, C Gregori, L Rohwer, RG TI Scrapie infectivity in hamster blood is not associated with platelets SO JOURNAL OF VIROLOGY LA English DT Article ID TRANSMISSIBLE SPONGIFORM ENCEPHALOPATHY; CREUTZFELDT-JAKOB-DISEASE; PRION PROTEIN; COMPONENTS; EXPRESSION AB The infectivity of hamster scrapie strain 263K was measured in platelets isolated from blood pooled from six hamsters with clinical scrapie. The total number of infectious doses present in the blood pool was 220, out of which only 3.5 infectious doses were associated with platelets. A larger proportion of the total infectivity was recovered from the mononuclear leukocyte fraction. This result indicates that platelets are not the source of blood-borne infectivity in transmissible spongiform encephalopathy-infected hamsters. C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20892 USA. Dept Vet Affairs Med Ctr, Mol Neurovirol Lab, Baltimore, MD 21201 USA. RP Rohwer, RG (reprint author), Vet Affairs Med Ctr, Mol Neurovirol Lab, Med Res Serv 151, 10 N Greene St, Baltimore, MD 21201 USA. NR 10 TC 65 Z9 67 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2002 VL 76 IS 9 BP 4649 EP 4650 DI 10.1128/JVI.76.9.4649-4650.2002 PG 2 WC Virology SC Virology GA 541CB UT WOS:000174966700052 PM 11932431 ER PT J AU Norkin, LC Anderson, HA Wolfrom, SA Oppenheim, A AF Norkin, LC Anderson, HA Wolfrom, SA Oppenheim, A TI Caveolar endocytosis of Simian virus 40 is followed by brefeldin A-sensitive transport to the endoplasmic reticulum, where the virus disassembles SO JOURNAL OF VIROLOGY LA English DT Article ID MAJOR HISTOCOMPATIBILITY PROTEINS; CLASS-I MOLECULES; CHOLERA-TOXIN; BETA-COP; COATED VESICLES; MEMBRANE DOMAINS; GOLGI-COMPLEX; POLYOMA-VIRUS; SIMIAN-VIRUS-40; ENTRY AB Simian virus 40 (SV40) enters cells by atypical endocytosis mediated by caveolae that transports the virus to the endoplasmic reticulum (ER) instead of to the endosomal-lysosomal compartment, which is the usual destination for viruses and other cargo that enter by endocytosis. We show here that SV40 is transported to the ER via an intermediate compartment that contains beta-COP, which is best known as a component of the COPI coatamer complexes that are required for the retrograde retrieval pathway from the Golgi to the ER. Additionally, transport of SV40 to the ER, as well as infection, is sensitive to brefeldin A. This drug acts by specifically inhibiting the ARF1 GTPase, which is known to regulate assembly of COPI coat complexes on Golgi cisternae. Moreover, some beta-COP colocalizes with intracellular caveolin-1, which was previously shown to be present on a new organelle (termed the caveosome) that is an intermediate in the transport of SV40 to the ER (L. Pelkmans, J. Kartenbeck, and A. Helenius, Nat. Cell Biol. 3:473-483, 2001). We also show that the internal SV40 capsid proteins VP2 and VP3 become accessible to immunostaining starting at about 5 It. Most of that immunostaining overlays the ER, with some appearing outside of the ER. In contrast, immunostaining with anti-SV40 antisera remains confined to the ER. C1 Univ Massachusetts, Dept Microbiol, Morrill Sci Ctr IVN 203, Amherst, MA 01003 USA. US FDA, Ctr Biol Evaluat & Res, Immunol Lab, Div Therapeut Prot, Bethesda, MD 20892 USA. Hebrew Univ Jerusalem, Hadassah Med Sch, Dept Hematol, IL-91120 Jerusalem, Israel. RP Norkin, LC (reprint author), Univ Massachusetts, Dept Microbiol, Morrill Sci Ctr IVN 203, Amherst, MA 01003 USA. NR 69 TC 137 Z9 140 U1 1 U2 12 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 2002 VL 76 IS 10 BP 5156 EP 5166 DI 10.1128/JVI.76.10.5156-5166.2002 PG 11 WC Virology SC Virology GA 546DK UT WOS:000175256500047 PM 11967331 ER PT J AU Krauthamer, V Crosheck, T AF Krauthamer, V Crosheck, T TI Effects of high-rate electrical stimulation upon firing in modelled and real neurons SO MEDICAL & BIOLOGICAL ENGINEERING & COMPUTING LA English DT Article DE NEURON; refractory period; myelinated axon; leech; threshold ID MYELINATED NERVE; TRANSMISSION; CONDUCTION; POINTS; LEECH AB Many medical devices use high-rate, low-amplitude currents to affect neural function. This study examined the effect of stimulation rate upon action potential threshold and sustained firing rate for two model neurons, the rabbit myelinated fibre and the unmyelinated leech touch sensory cell. These model neurons were constructed with the NEURON simulator from electrophysiological data. Alternating-phase current pulses (0-1250 Hz), of fixed phase duration (0.2 ms), were used to stimulate the neurons, and propagation success or failure was measured. One effect of the high pulse rates was to cause a net depolarisation, and this was verified by the relief of action potential conduction block by 500 Hz extracellular stimulation in leech neurons. The models also predicted that the neurons would maintain maximum sustained firing at a number of different stimulation rates. For example, at twice threshold, the myelinated model followed the stimulus up to 500 Hz stimulation, half the stimulus rate up to 850 Hz stimulation, and it did not fire at 1250 Hz stimulation. By contrast, the unmyelinated neuron model had a lower maximum firing rate of 190 Hz, and this rate was obtained at a number of stimulation. rates, up to 1250 Hz. The myelinated model also predicted sustained firing with 1240 Hz stimulation at threshold current, but no firing when the current level was doubled. Most of these effects are explained by the interaction of stimulus pulses with the cell's refractory period. C1 US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Marquette Univ, Dept Biomed Engn, Milwaukee, WI 53233 USA. RP Krauthamer, V (reprint author), US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 22 TC 13 Z9 13 U1 0 U2 3 PU PETER PEREGRINUS LTD PI HERTS PA MICHAEL FARADAY HOUSE, SIX HILLS WAY, STEVANAGE, HERTS SG1 2AY, ENGLAND SN 0140-0118 J9 MED BIOL ENG COMPUT JI Med. Biol. Eng. Comput. PD MAY PY 2002 VL 40 IS 3 BP 360 EP 366 DI 10.1007/BF02344220 PG 7 WC Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology; Medical Informatics SC Computer Science; Engineering; Mathematical & Computational Biology; Medical Informatics GA 585DM UT WOS:000177507900015 PM 12195985 ER PT J AU Beezhold, DH Kostyal, DA Tomazic-Jezic, VJ AF Beezhold, DH Kostyal, DA Tomazic-Jezic, VJ TI Measurement of latex proteins and assessment of latex protein exposure SO METHODS LA English DT Article DE latex allergy; latex proteins; antigens; allergens; Lowry protein assay; enzyme-linked immunosorbent assay ID NATURAL-RUBBER LATEX; SKIN PRICK TEST; AMMONIATED LATEX; IGE; ALLERGEN; ANTIBODIES; INHIBITION; EXTRACTS; GLOVES; LOWRY AB Reduction of protein levels in manufactured natural rubber latex products is important for preventing sensitization and adverse allergic reactions to latex. Because of the complex nature of latex extracts, accurate protein measurement is a challenge. Standard total protein assays were effective in reducing protein levels from what were once extremely high levels, but these assays are plagued with false-positive reactions and limited sensitivity. An ELISA for antigenic protein has been standardized and promises, to provide more consistent measurement of the proteins with potential to cause adverse reactions. Antigenic proteins represent the total protein fraction with potential to be allergenic. Measuring antigenic protein in a consistent manner should help to further reduce the level of sensitizing protein and further reduce allergic reactions to latex-medical products. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Guthrie Res Inst, Sayre, PA 18840 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Beezhold, DH (reprint author), Guthrie Res Inst, 1,Guthrie Sq, Sayre, PA 18840 USA. NR 35 TC 11 Z9 11 U1 0 U2 4 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1046-2023 J9 METHODS JI Methods PD MAY PY 2002 VL 27 IS 1 BP 46 EP 51 AR PII S1046-2023(02)00050-6 DI 10.1016/S1046-2023(02)00050-6 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 570JD UT WOS:000176654400007 PM 12079416 ER PT J AU Farnham, JJ Tomazic-Jezic, VJ Stratmeyer, ME AF Farnham, JJ Tomazic-Jezic, VJ Stratmeyer, ME TI Regulatory initiatives for natural latex allergy: US perspectives SO METHODS LA English DT Article DE natural rubber; natural latex; allergy; medical devices; regulation ID RUBBER AB The US Food and Drug Administration (FDA) has regulatory authority over foods, human drugs, cosmetics, medical devices, radiological products, biologics, and veterinary products. Among these products, FDA believes that the use of medical devices, including medical gloves, condoms, catheters, and breathing bags, represents the greatest source of natural latex proteins to exposed individuals. A medical device is defined in the Federal Food Drug and Cosmetic Act (FFDCA) as an instrument, apparatus, implement, machine, etc., that is intended for use in the diagnosis or treatment of disease or is intended to affect the structure or any function of the body of a human or other animal, and that does not achieve any of its principal intended purposes through chemical action in the body. This article provides some brief, general background about FDA's medical device regulatory process and then addresses the issue of natural latex allergy. Finally we discuss the steps the Agency has taken to evaluate the magnitude and nature of the problem, and FDA's efforts to assist manufacturers, health professionals, and others in minimizing exposure and sensitization to natural latex proteins in medical devices. Published by Elsevier Science (USA). C1 US FDA, Ctr Devices & Radiol Hlth, Off Compliance, Rockville, MD 20850 USA. US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20850 USA. RP Farnham, JJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Compliance, 2094 Gaither Rd, Rockville, MD 20850 USA. NR 16 TC 2 Z9 2 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 1046-2023 J9 METHODS JI Methods PD MAY PY 2002 VL 27 IS 1 BP 87 EP 92 AR PII S1046-2023(02)00056-7 DI 10.1016/S1046-2023(02)00056-7 PG 6 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 570JD UT WOS:000176654400013 PM 12079422 ER PT J AU Andersen, B Nielsen, KF Jarvis, BB AF Andersen, B Nielsen, KF Jarvis, BB TI Characterization of Stachybotrys from water-damaged buildings based on morphology, growth, and metabolite production SO MYCOLOGIA LA English DT Article DE atranones; colony diameter; identification; macrocyclic trichothecenes; pigment production; Stachybotrys chartarum ID PULMONARY HEMORRHAGE; MACROCYCLIC TRICHOTHECENES; CHARTARUM STRAINS; EASTERN-EUROPE; MYCOTOXINS; CHROMATOGRAPHY; HEMOSIDEROSIS; HEMOLYSIN; CULTURES; INFANTS AB Stachybotrys was found to be associated with idiopathic pulmonary hemorrhage in infants in Cleveland, Ohio. Since that time, considerable effort has been put into finding the toxic components responsible for the disease. The name Stachybotrys chartarum has been applied to most of these isolates, but inconsistent toxicity results arid taxonomic confusion prompted the present study. In this study, 122 Stachybotrys isolates, mainly from,water-damaged buildings, were characterized arid identified by combining three different approaches: morphology. colony characteristics, arid metabolite production. Two different Stachybotrys taxa, S. chartarum and one undescribed species, were found in water-damaged buildings regardless of whether the buildings were in Denmark, Finland, or the USA. Furthermore, two chemotypes could be distinguished in S. chartarum One chemotype produced atranomes, whereas the other was a Macrocyclic trichothecene-producer. The second undescribed taxon produced atranones and could be differentiated from S. chartarum by its growth characteristics arid pigment production. Our results correlate with different inflammatory and toxicological properties reported for these same isolates and show that the three taxa/chemotypes should be treated separately. The co-occurrence of these three taxa/chemotypes in water-damaged buildings explains the inconsistent results in the literature concerning toxicity of Stachybotrys isolated from that environment. C1 Tech Univ Denmark, Bioctr, Mycol Grp, DK-2800 Lyngby, Denmark. Aalborg Univ, Danish Res Inst, Energy & Indoor Climate Div, DK-2970 Horsholm, Denmark. Univ Maryland, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. Univ Maryland, Dept Biochem & Chem, College Pk, MD 20742 USA. RP Andersen, B (reprint author), Tech Univ Denmark, Bioctr, Mycol Grp, Bldg 221, DK-2800 Lyngby, Denmark. EM birgittte.andersen@biocentrum.dtu.dk RI Nielsen, Kristian/C-7233-2011; Andersen, Birgitte/F-3922-2012 OI Nielsen, Kristian/0000-0002-5848-0911; Andersen, Birgitte/0000-0002-4544-9886 NR 51 TC 92 Z9 92 U1 0 U2 8 PU ALLEN PRESS INC PI LAWRENCE PA 810 E 10TH ST, LAWRENCE, KS 66044 USA SN 0027-5514 EI 1557-2536 J9 MYCOLOGIA JI Mycologia PD MAY-JUN PY 2002 VL 94 IS 3 BP 392 EP 403 DI 10.2307/3761773 PG 12 WC Mycology SC Mycology GA 556TZ UT WOS:000175866200004 PM 21156510 ER PT J AU Flynn, KM Newbold, RR Ferguson, SA AF Flynn, KM Newbold, RR Ferguson, SA TI Multigenerational exposure to dietary nonylphenol has no severe effects on spatial learning in female rats SO NEUROTOXICOLOGY LA English DT Article DE estrogen; endocrine disrupter; memory; water maze; age-related; nonylphenol ID WATER MAZE PERFORMANCE; RECEPTOR CONCENTRATIONS; OVARIECTOMIZED RATS; PITUITARY-GLAND; SEXUAL-BEHAVIOR; PREOPTIC AREA; AGED RATS; ESTRADIOL; ESTROGEN; MEMORY AB Nonylphenol is a common intermediate in the production of many consumer compounds and reportedly acts as an estrogen mimic. Because estrogen affects the spatial learning and memory in rats, the effects of nonylphenol exposure on the performance of female rats in the Morris water maze were investigated. Here, Sprague-Dawley rats (170) consumed soy-free diets containing 0, 25, 200 or 750 ppm nonylphenol (0, 2, 16 or 60 mg/kg per day) beginning on postnatal day (PND) 42 and continuing for two generations (171 and 172) with breeding occurring within treatments. Females to be behaviorally tested (n = 7-8 per treatment per generation) were ovariectomized at adulthood and assessed for spatial learning and memory between PND 125-150 (young adult age). Each rat was tested for four consecutive days (three trials per day) in the Morris water maze with the platform in a fixed location. One week later, each subject was primed with estrogen and progesterone and assessed on a single day (three trials). The F, rats continued on the same diets until PND 380-395 (middle aged) when they were re-tested as above (four consecutive days followed I week later with hormonal priming and a single test day). Latency to find the platform, path length and swim speed were averaged over the three trials per day and analyzed using repeated measures analyses of variance. There were no consistent effects of dietary nonylphenol exposure and no interactions of nonylphenol exposure on any measure of performance in either generation at the young age nor at the middle age in the F, generation. When tested at the young adult age, however hormone priming resulted in latencies and path lengths that were significantly shorter than in those exhibited during the unprimed test days, and there was no such effect when tested at middle age. Middle aged rats exhibited better performance than the same animals tested at a young age, likely as a result of familiarity and practice with the test paradigm. These data suggest that multigenerational dietary nonylphenol exposure does not cause gross alterations in, Morris water maze performance in young adult or middle aged ovariectomized female rats. (C) 2002 Elsevier Science Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NIEHS, Toxicol Lab, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Ferguson, SA (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU PHS HHS [224-93-0001] NR 42 TC 6 Z9 7 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0161-813X J9 NEUROTOXICOLOGY JI Neurotoxicology PD MAY PY 2002 VL 23 IS 1 BP 87 EP 94 AR PII S0161-813X(02)00007-4 DI 10.1016/S0161-813X(02)00007-4 PG 8 WC Neurosciences; Pharmacology & Pharmacy; Toxicology SC Neurosciences & Neurology; Pharmacology & Pharmacy; Toxicology GA 576XU UT WOS:000177033100009 PM 12164552 ER PT J AU Darnton-Hill, I Nalubola, R AF Darnton-Hill, I Nalubola, R TI Fortification strategies to meet micronutrient needs: successes and failures SO PROCEEDINGS OF THE NUTRITION SOCIETY LA English DT Article; Proceedings Paper CT Meeting of the Nutrition-Society CY JUL 10-12, 2001 CL UNIV SHEFFIELD, SHEFFIELD, ENGLAND SP Nutrit Soc HO UNIV SHEFFIELD DE micronutrient malnutrition; fortification; vitamin A; iron-deficiency anaemia; iodine-deficiency disorders ID FOLIC-ACID FORTIFICATION; VITAMIN-A; IRON FORTIFICATION; UNITED-STATES; NUTRITION; FOODS AB Food fortification is likely to have played an important role in the current nutritional health and well-being of populations in industrialized countries. Starting in the early part of the 20th century, fortification was used to target specific health conditions: goitre with iodized salt; rickets with vitamin D-fortified milk; beriberi, pellagra and anaemia with B-vitamins and Fe-enriched cereals; more recently, in the USA, risk of pregnancy affected by neural-tube defects with folic acid-fortified cereals. A relative lack of appropriate centrally-processed food vehicles, less-developed commercial markets and relatively low consumer awareness and demand, means it has taken about another 50 years for fortification to be seen as a viable option for the less-developed countries. The present paper reviews selected fortification initiatives in developing countries to identify different factors that contributed to their successful implementation, as well as the challenges that continually threaten the future of these programmes. Ultimately, the long-term sustainability of fortification programmes is ensured when consumers are willing and able to bear the additional cost of fortified foods. There has been an enormous increase in fortification programmes over the last couple of decades in developing countries. Considerable progress has been made in reducing vitamin A and I deficiencies, although less so with Fe, even as Zn and folic acid deficiencies are emerging as important public health problems. Food fortification based on sound principles and supported by clear policies and regulations can play an increasingly large role in this progress towards prevention and control of micronutrient malnutrition. C1 WHO, CH-1211 Geneva 27, Switzerland. US FDA, Washington, DC 20204 USA. RP Darnton-Hill, I (reprint author), 111 E 14th St,190, New York, NY 10003 USA. NR 57 TC 59 Z9 62 U1 2 U2 21 PU C A B I PUBLISHING PI WALLINGFORD PA C/O PUBLISHING DIVISION, WALLINGFORD OX10 8DE, OXON, ENGLAND SN 0029-6651 J9 P NUTR SOC JI Proc. Nutr. Soc. PD MAY PY 2002 VL 61 IS 2 BP 231 EP 241 DI 10.1079/PNS2002150 PG 11 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 573JD UT WOS:000176825300010 PM 12133205 ER PT J AU Muskhelishvili, L Freeman, LD Latendresse, JR Bucci, TJ AF Muskhelishvili, L Freeman, LD Latendresse, JR Bucci, TJ TI An immunohistochemical label to facilitate counting of ovarian follicles SO TOXICOLOGIC PATHOLOGY LA English DT Article DE CYP1B1; cytochrome P-450; immunohistochemistry; ovarian follicles; rodent ID CYTOCHROME-P450 1B1; MESSENGER-RNA; HUMAN CYP1B1; TOXICITY; EXPRESSION; LOCALIZATION; ENZYMES; TISSUE; ADULT; CELLS AB U. S. and internationally harmonized Health Effects Test Guidelines for Reproduction and Fertility Effects include enumeration of primordial and developing ovarian follicles as endpoints of safety tests, and the number of these structures is also of interest for other aspects of reproductive biology. Performing the counts microscopically on representative hematoxylin and eosin (H&E)-stained sections of ovary is tedious and error-prone. The ability to mark oocyte nuclei distinctly with an antibody significantly increases speed and accuracy of counting. We have identified a rabbit polyclonal antibody directed against a synthetic 14-amino acid sequence from human cytochrome P-450 1B1 (CYP1B1) that unequivocally marks rodent oocyte nuclei, in addition to nuclei of some ovarian granulosa and theca cells. Follicles of all degrees of maturity are easily distinguished from ovarian background; ability to detect and identify primordial follicles is particularly enhanced. High-contrast and high-resolution labeling was achieved with routine immunohistochemical procedures using an avidin-biotin-peroxidase method on rat and mouse tissues fixed in 10% neutral buffered formalin. C1 Pathol Associates Inc, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Muskhelishvili, L (reprint author), Pathol Associates Inc, Natl Ctr Toxicol Res, 3900 NCTR Rd,MC 923, Jefferson, AR 72079 USA. RI Latendresse, John/A-9215-2009 NR 23 TC 10 Z9 11 U1 0 U2 1 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. PD MAY 1 PY 2002 VL 30 IS 3 BP 400 EP 402 DI 10.1080/01926230252929981 PG 3 WC Pathology; Toxicology SC Pathology; Toxicology GA 558EQ UT WOS:000175953700014 PM 12051558 ER PT J AU Morton, D Lee, PN Fry, JS Fairweather, WR Haseman, JK Kodell, RL Chen, JJ Roth, AJ Soper, K AF Morton, D Lee, PN Fry, JS Fairweather, WR Haseman, JK Kodell, RL Chen, JJ Roth, AJ Soper, K TI Statistical methods for carcinogenicity studies SO TOXICOLOGIC PATHOLOGY LA English DT Editorial Material ID TUMORIGENICITY EXPERIMENTS; ANIMAL CARCINOGENESIS; REGRESSION-ANALYSIS; TUMOR; TESTS; ONSET; TIME; MORTALITY C1 Pharmacia Corp, STP Peto Working Grp, Skokie, IL 60077 USA. PN Lee Stat & Comp Ltd, Surrey SM2 5DA, England. Flower Valley Consulting Inc, Rockville, MD 20853 USA. NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Merck Res Labs, W Point, PA 19486 USA. RP Morton, D (reprint author), Pharmacia Corp, STP Peto Working Grp, 4901 Searle Pkwy, Skokie, IL 60077 USA. NR 28 TC 3 Z9 4 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. PD MAY 1 PY 2002 VL 30 IS 3 BP 403 EP 414 PG 12 WC Pathology; Toxicology SC Pathology; Toxicology GA 558EQ UT WOS:000175953700015 ER PT J AU Brennan, MJ Delogu, G AF Brennan, MJ Delogu, G TI The PE multigene family: a 'molecular mantra' for mycobacteria SO TRENDS IN MICROBIOLOGY LA English DT Review ID VIRUS NUCLEAR ANTIGEN-1; TUBERCULOSIS; PROTEINS; INHIBITION; DEGRADATION; SEQUENCE; GENE AB The PE multigene family of Mycobacterium tuberculosis is remarkable in that it is composed of approximately 100 highly homologous genes that are found only in mycobacteria. Early evidence suggests that proteins encoded by certain members of this gene family could be present in the mycobacterial cell wall, impact antigen-presentation pathways and the ensuing host immune responses, and also provide a mechanism for generating antigenic diversity in mycobacteria. C1 Food & Drug Adm, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bethesda, MD 20892 USA. Univ Sassari, Dept Biomed Sci, I-07100 Sassari, Italy. RP Brennan, MJ (reprint author), Food & Drug Adm, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Bldg 29 Rm 502 29 Lincoln Dr, Bethesda, MD 20892 USA. RI Delogu, Giovanni/I-3701-2012 OI Delogu, Giovanni/0000-0003-0182-8267 NR 21 TC 139 Z9 144 U1 0 U2 2 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD MAY PY 2002 VL 10 IS 5 BP 246 EP 249 AR PII S0966-842X(02)02335-1 DI 10.1016/S0966-842X(02)02335-1 PG 4 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 547ZA UT WOS:000175361900018 PM 11973159 ER PT J AU Favreau, JT Ryu, ML Braunstein, G Orshansky, G Park, SS Coody, GL Love, LA Fong, TL AF Favreau, JT Ryu, ML Braunstein, G Orshansky, G Park, SS Coody, GL Love, LA Fong, TL TI Severe hepatotoxicity associated with the dietary supplement LipoKinetix SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID UNITED-STATES; PHENYLPROPANOLAMINE; POTENTIATION; OBESITY AB Background: LipoKinetix (Syntrax, Cape Girardeau, Missouri) is a dietary supplement marketed for weight loss. Objective: To describe a possible causal association between LipoKinetix and hepatotoxicity. Design: Case series. Setting: Outpatient clinic, tertiary care hospital, and U.S. Food and Drug Administration databases. Intervention: Routine medical and supportive care. Measurements: Clinical and laboratory evaluation. Results: All patients developed acute hepatotoxicity within 3 months of starting LipoKinetix. At presentation, symptoms and results of laboratory tests were characteristic of acute hepatitis. All patients recovered spontaneously after LipoKinetix use was discontinued. Three of the seven patients, including one who developed fulminant hepatic failure complicated by cerebral edema,were taking LipoKinetix alone at the time of presentation. Of the four patients who were taking multiple supplements, two resumed taking supplements other than LipoKinetix without incident. Conclusions: The use of LipoKinetix may be associated with hepatotoxicity, Despite extensive evaluations, no other cause for hepatotoxicity could be identified in the seven patients studied. C1 Univ Calif Los Angeles, Cedars Sinai Med Ctrm,Sch Med, Dept Internal Med, Burns & Allen Res Inst, Los Angeles, CA 90048 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Favreau, JT (reprint author), Univ Calif Los Angeles, Cedars Sinai Med Ctrm,Sch Med, Dept Internal Med, Burns & Allen Res Inst, Becker Bldg 120,8700 Beverly Blvd, Los Angeles, CA 90048 USA. NR 19 TC 95 Z9 95 U1 1 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD APR 16 PY 2002 VL 136 IS 8 BP 590 EP 595 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 543WY UT WOS:000175125800004 PM 11955027 ER PT J AU Hicks, JE Drinkard, B Sunmers, RM Rider, LG AF Hicks, JE Drinkard, B Sunmers, RM Rider, LG TI Decreased aerobic capacity in children with juvenile dermatomyositis SO ARTHRITIS & RHEUMATISM-ARTHRITIS CARE & RESEARCH LA English DT Article DE juvenile dermatomyositis; inflammatory myopathies; aerobic capacity; exercise ID IDIOPATHIC INFLAMMATORY MYOPATHIES; VALIDATED DISEASE-ACTIVITY; POLYMYOSITIS/DERMATOMYOSITIS PATIENTS; DAMAGE INDEXES; GAS-EXCHANGE; EXERCISE; MUSCLE; CHILDHOOD; ABNORMALITIES; POLYMYOSITIS AB Objective. To determine whether patients with juvenile dermatomyositis (DM) have limited aerobic capacity compared with healthy controls. Methods. Fourteen juvenile DM patients with inactive to moderately active, stable disease (age range 7-17 years) and 14 age- and sex-matched controls performed a maximal exercise test using a cycle ergometer. Oxygen uptake and power were measured at peak exercise (VO2peak and W-peak, respectively) and at anaerobic threshold (AT and W-AT). Juvenile DM disease activity and damage were also assessed. Results. Patients with juvenile DM had significantly reduced VO2peak (19.6 ml O-2/kg/minute in juvenile DM versus 31.1 ml O-2/kg/minute in controls), peak heart rate (166 versus 184 beats per minute), W-peak (1.6 versus 2.7 watts/kg), AT (11.1 versus 18.0 ml O-2/kg/minute) and W-AT (0.6 versus 1.4 watts/kg), compared to controls (P less than or equal to 0.05 for each). Aerobic exercise parameters correlated with physician global disease activity and damage, T1-weighted magnetic resonance imaging, and Childhood Myositis Assessment Scale scores (r(s) = 0.58 - 0.82, P less than or equal to 0.05). Conclusion. Patients with juvenile DM with a range of disease activity have a decreased aerobic and work capacity compared to healthy children. Aerobic exercise limitation in juvenile DM correlates best with measures of disease damage (global damage assessment, T1-weighted magnetic resonance imaging, and disease duration). Aerobic exercise testing may be valuable in the assessment of physical endurance, and aerobic training may be indicated as part of the therapeutic regimen in myositis patients with inactive to moderately active, stable disease. C1 NIH, Ctr Clin, Bethesda, MD 20892 USA. NIAMS, Arthrit & Rheumatism Branch, NIH, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD USA. RP Drinkard, B (reprint author), NIH, Ctr Clin, 10 Ctr Dr,Bldg 10,Room 65235, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458 NR 37 TC 27 Z9 27 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0004-3591 J9 ARTHRIT RHEUM-ARTHR JI Arthritis Rheum-Arthritis Care Res. PD APR 15 PY 2002 VL 47 IS 2 BP 118 EP 123 DI 10.1002/art1.10237 PG 6 WC Rheumatology SC Rheumatology GA 540UN UT WOS:000174948100004 PM 11954004 ER PT J AU Greenhill, LL Fisher, P Mosholder, A Heiligenstein, J Vitiello, B AF Greenhill, LL Fisher, P Mosholder, A Heiligenstein, J Vitiello, B TI Approaches to standardizing safety data collection in pediatric psychopharmacology SO BIOLOGICAL PSYCHIATRY LA English DT Meeting Abstract C1 Columbia Univ, New York State Psychiat Inst, New York, NY USA. US FDA, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. Lilly Corp Ctr, Global Neurosci, Indianapolis, IN USA. NIMH, 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 0006-3223 J9 BIOL PSYCHIAT JI Biol. Psychiatry PD APR 15 PY 2002 VL 51 IS 8 SU S MA 432 BP 148S EP 148S PG 1 WC Neurosciences; Psychiatry SC Neurosciences & Neurology; Psychiatry GA 541JA UT WOS:000174980400415 ER PT J AU Okamoto, Y Douek, DC McFarland, RD Koup, RA AF Okamoto, Y Douek, DC McFarland, RD Koup, RA TI Effects of exogenous interleukin-7 on human thymus function SO BLOOD LA English DT Article ID BONE-MARROW TRANSPLANTATION; T-CELL DEVELOPMENT; RECEPTOR-GAMMA-CHAIN; SEVERE COMBINED IMMUNODEFICIENCY; NATURAL-KILLER-CELLS; IMMUNE RECONSTITUTION; DENDRITIC CELLS; IN-VIVO; DEFICIENT MICE; GROWTH-FACTOR AB Immune reconstitution is a critical component of recovery after treatment of human immunodeficiency virus (HIV) infection, cancer chemotherapy, and hematopoietic stem cell transplantation. The ability to enhance T-cell production would benefit such treatment. We examined the effects of exogenous interleukin-7 (IL-7) on apoptosis, proliferation, and the generation of T-cell receptor rearrangement excision circles (TRECs) in human thymus. Quantitative polymerase chain reaction demonstrated that the highest level of TRECs (14 692 copies/10 000 cells) was present in the CD1a(+)CD3(-)CD4(+)CD8(+) stage in native thymus, suggesting that TREC generation occurred following the cellular division in this subpopulation. In a thymic organ culture system, exogenous IL-7 increased the TREC frequency in fetal as well as infant thymus, indicating increased T-cell receptor (TCR) rearrangement. Although this increase could be due to the effect of IL-7 to increase thymocyte proliferation and decrease apoptosis of immature CD3(-) cells, the in vivo experiments using NOD/LtSz-scid mice given transplants of human fetal thymus and liver suggested that IL-7 can also directly enhance TREC generation. Our results provide compelling evidence that IL-7 has a direct effect on increasing TCR-alphabeta rearrangement and indicate the potential use of IL-7 for enhancing de novo naive T-cell generation in immunocompromised patients. (C) 2002 by The American Society of Hematology. C1 NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. NCI, Dept Expt Transplantat & Immunol, Med Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Koup, RA (reprint author), NIAID, Vaccine Res Ctr, NIH, Rm 3502,40 Convent Dr, Bethesda, MD 20892 USA. NR 71 TC 102 Z9 105 U1 1 U2 3 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 2002 VL 99 IS 8 BP 2851 EP 2858 DI 10.1182/blood.V99.8.2851 PG 8 WC Hematology SC Hematology GA 539JJ UT WOS:000174866500028 PM 11929775 ER PT J AU Du, X Marszal, E Shrake, A AF Du, X Marszal, E Shrake, A TI A novel mechanism for polymerization of alpha-1-proteinase inhibitor: Dimer as the smallest polymerizing unit. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Off Blood Res & Review, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2002 VL 223 MA 077-MEDI BP A101 EP A101 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 564CE UT WOS:000176296800593 ER PT J AU Ang, CYW AF Ang, CYW TI Extraction of active components from St. John's wort by supercritical carbon dioxide versus sonication. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 1 U2 3 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2002 VL 223 MA 272-IEC BP U667 EP U668 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 564CD UT WOS:000176296703685 ER PT J AU Cui, YY Chang, HC Luo, WH Heinze, TH Lin, LJ Mattia, A AF Cui, YY Chang, HC Luo, WH Heinze, TH Lin, LJ Mattia, A TI Determination of St. John's wort components in dietary supplements and functional foods. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2002 VL 223 MA 047-AGFD BP U38 EP U38 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 564CD UT WOS:000176296700142 ER PT J AU Geesaman, EL Buzatu, DA Wilkes, J Lay, J Darsey, JA AF Geesaman, EL Buzatu, DA Wilkes, J Lay, J Darsey, JA TI Prediction of toxic equivalency factors for dioxins, furans, and PCBS using artificial neural networks. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Arkansas, Dept Chem, Little Rock, AR 72204 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2002 VL 223 MA 171-ENVR BP U537 EP U537 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 564CD UT WOS:000176296703008 ER PT J AU Markey, JC Rudnik, O Nowak, R Decker, S James, SJ Stanton, D Pogribna, M Wilson, VL Swenson, DH AF Markey, JC Rudnik, O Nowak, R Decker, S James, SJ Stanton, D Pogribna, M Wilson, VL Swenson, DH TI Methylenetetrahydrofolate reductase (MTHFR) polymorphism in control, Alzheimer's disease (AD) and Down syndrome (DS) populations. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Saginaw Valley State Univ, Dept Biol, Freeland, MI 48623 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Louisiana State Univ, Inst Mutagenesis, Baton Rouge, LA 70803 USA. Saginaw Valley State Univ, Dept Chem, Freeland, MI 48623 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2002 VL 223 MA 353-CHED BP U213 EP U213 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 564CD UT WOS:000176296701094 ER PT J AU Pastor, RW Venable, RM AF Pastor, RW Venable, RM TI Interpretation of NMR relaxation of oligosaccharides: Don't leave your theoretical toolbox at home. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 7 PY 2002 VL 223 MA 252-COMP BP U502 EP U502 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 564CD UT WOS:000176296702809 ER PT J AU Crawford, LM AF Crawford, LM TI New therapy for non-Hodgkin lymphoma SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Crawford, LM (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 8 Z9 8 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 3 PY 2002 VL 287 IS 13 BP 1640 EP 1640 DI 10.1001/jama.287.13.1640-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 536YW UT WOS:000174730300005 PM 11926876 ER PT J AU Silvers, LE Varricchio, FE Ellenberg, SS Krueger, CL Wise, RP Salive, ME AF Silvers, LE Varricchio, FE Ellenberg, SS Krueger, CL Wise, RP Salive, ME TI Pediatric deaths reported after vaccination - The utility of information obtained from parents SO AMERICAN JOURNAL OF PREVENTIVE MEDICINE LA English DT Article DE child; follow-up studies; health personnel; parents; safety; sudden infant death; vaccines ID SYSTEM VAERS AB Background: The federally administered Vaccine Adverse Event Reporting System (VAERS) is a passive reporting system that receives domestic and foreign reports of adverse events that occur following immunization. This investigation explored whether routinely interviewing parents for follow-up of VAERS pediatric deaths would provide additional information important to vaccine safety. Methods: The study was designed to follow up 100 consecutive pediatric deaths reported to VAERS by interviewing a parent and a healthcare provider (HCP) for each case. Several strategies contributed to successful follow-up. A Standardized questionnaire was utilized to interview HCPs and parents. Overall and specific group frequencies (HCPS and parents) were calculated for each variable. McNemar's statistical tests of exact inference were calculated to assess whether there were statistically significant differences between HCP and parent knowledge by case for various variables. Results: The median age of the cases was 4 months. Approximately half of the deaths were attributed to sudden infant death syndrome. In many instances, the information was equivalent in quality. For certain variables, such as knowledge of the child's position when found in distress, more parents than HCPs indicated that they knew the answer. Conclusions: Conducting parental and HCP follow-up for pediatric deaths reported to VAERS was resource intensive. In some instances, parents were more likely than HCPs to provide information regarding some important variables about the nature of the death. None of the additional information obtained from parents, however, provided a signal or confirmation of a causal link between the vaccine and death. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20857 USA. RP Silvers, LE (reprint author), US FDA, Ctr Vet Med, MPN 2, HFV-250,7250 Standish Pl, Rockville, MD 20855 USA. NR 13 TC 9 Z9 9 U1 0 U2 1 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0749-3797 J9 AM J PREV MED JI Am. J. Prev. Med. PD APR PY 2002 VL 22 IS 3 BP 170 EP 176 AR PII S0749-3797(01)00430-5 DI 10.1016/S0749-3797(01)00430-5 PG 7 WC Public, Environmental & Occupational Health; Medicine, General & Internal SC Public, Environmental & Occupational Health; General & Internal Medicine GA 531JB UT WOS:000174411300006 PM 11897461 ER PT J AU Taplin, SH Rutter, CM Finder, C Mandelson, MT Houn, F White, E AF Taplin, SH Rutter, CM Finder, C Mandelson, MT Houn, F White, E TI Screening mammography: Clinical image quality and the risk of interval breast cancer SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Editorial Material ID CARCINOMA IN-SITU; DETECTED CANCERS; PROGRAM; DENSITY; IMPROVEMENT; TRIAL AB OBJECTIVE. We evaluated the association between clinical image quality and breast cancer occurrence within 24 months of a negative mammogram. MATERIALS AND METHODS. We identified women with breast cancer who were younger than 40 years old and older and screened from January 1, 1988, through December 3 1, 1993. We retrospectively assigned Breast Imaging Reporting and Data System (BI-RADS) assessments to their screening mammogram. We classified cancers (invasive or ductal in situ) as "screen-detected" when found after positive assessments (BI-RADS codes 3, 4, and 5) and "interval-detected" when found after negative assessments (BI-RADS codes I and 2). One reviewer evaluated mediolateral oblique and craniocaudal views for all cancer cases using a 3-point scale (failure, borderline, pass) for each measure of clinical image quality (positioning, breast compression, contrast, exposure, noise, sharpness, artifacts, overall quality). We used separate logistic regression models and evaluated the odds of interval invasive cancer or invasive plus in situ cancer as a function of each measure of quality using "pass" as the referent group. RESULTS. We found 492 screen-detected and 164 interval-detected cancers that met study criteria. Cancer detection (sensitivity) was highest (84%) among patients with proper breast positioning, but when images failed this measure (33.4%). sensitivity fell to 66.3%. After adjustment for age, film date, and breast density, interval-detected invasive cancers were more likely after images failing positioning (odds ratio, 2.57; 95% confidence interval, 1.28-5.52%). Failures in overall quality were also associated with interval cancers when cases of ductal carcinoma in situ (p = 0.037) were included. CONCLUSION. Invasive breast cancer detection by mammography may be improved through attention to correct positioning. C1 Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, Seattle, WA 98101 USA. Univ Washington, Dept Family Med, Seattle, WA 98195 USA. United States Food & Drug Adm, Div Mammog Qual, Rockville, MD 20850 USA. United States Food & Drug Adm, Radiat Programs, Rockville, MD 20850 USA. Fred Hutchinson Canc Res Ctr, Canc Prevent Res Program, Seattle, WA 98104 USA. United States Food & Drug Adm, Off Drug Evaluat 3, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Taplin, SH (reprint author), Grp Hlth Cooperat Puget Sound, Ctr Hlth Studies, 1730 Minor Ave Ste 1600, Seattle, WA 98101 USA. FU NCI NIH HHS [CA6371, K07CA71869] NR 36 TC 49 Z9 53 U1 1 U2 3 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD APR PY 2002 VL 178 IS 4 BP 797 EP 803 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 533YQ UT WOS:000174558200003 PM 11906848 ER PT J AU Smith, GW Constable, PD Foreman, JH Eppley, RM Waggoner, AL Tumbleson, ME Haschek, WM AF Smith, GW Constable, PD Foreman, JH Eppley, RM Waggoner, AL Tumbleson, ME Haschek, WM TI Cardiovascular changes associated with intravenous administration of fumonisin B-1 in horses SO AMERICAN JOURNAL OF VETERINARY RESEARCH LA English DT Article ID CARDIAC TROPONIN-I; FUSARIUM-MONILIFORME; CULTURE MATERIAL; PULMONARY-EDEMA; SPHINGOSINE; SWINE; CALCIUM; LEUKOENCEPHALOMALACIA; DECREASES; PRESSURE AB Objective-To determine whether cardiovascular dysfunction is evident in horses with leukoencephalomalacia experimentally induced by administration of fumonisin B-1. Animals-11 healthy horses of various breeds (body weight, 252 to 367 kg). Procedure Horses were randomly assigned to 3 groups and administered fumonisin B, daily. Horses received IV injections of 0 (control horses; n = 4), 0.01 (3), or 0.20 mg (4) of fumonisin B-1/kg for 7 to 28 days. Horses were examined daily for evidence of neurologic disease. When neurologic signs consistent with leukoencephalomalacia were evident, horses were anesthetized, and catheters were inserted for evaluation of the cardiovascular system. After recovery from anesthesia, hemodynamic measurements were obtained. Results-Fumonisin-treated horses with clinical signs of neurologic disease had evidence of cardiovascular dysfunction manifested as decreases in heart rate, cardiac output, right ventricular contractility (assessed by measuring the maximal rate of change of right ventricular pressure), coccygeal artery pulse pressure, and pH and base excess in venous blood as well as increases in systemic vascular resistance, compared with values for control horses. Fumonisin-treated horses with and without clinical signs of neurologic disease also had higher serum and right ventricular sphinganine and sphingosine concentrations than control horses. Conclusions and Clinical Relevance-An association was detected among fumonisin-induced neurologic disease, increased serum and myocardial sphinganine and sphingosine concentrations, and decreased cardiovascular function in horses. Fumonisin-induced decreases in cardiovascular function may contribute to the pathophysiologic development of leukoencephalomalacia in horses. C1 Univ Illinois, Dept Vet Clin Med, Urbana, IL 61802 USA. Univ Illinois, Dept Pathobiol, Urbana, IL 61802 USA. Univ Illinois, Dept Biosci, Urbana, IL 61802 USA. US FDA, Washington, DC 20204 USA. RP Smith, GW (reprint author), Univ Illinois, Dept Vet Clin Med, Urbana, IL 61802 USA. NR 49 TC 29 Z9 30 U1 0 U2 4 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0002-9645 J9 AM J VET RES JI Am. J. Vet. Res. PD APR PY 2002 VL 63 IS 4 BP 538 EP 545 DI 10.2460/ajvr.2002.63.538 PG 8 WC Veterinary Sciences SC Veterinary Sciences GA 535ZC UT WOS:000174675400012 PM 11939316 ER PT J AU Fang, GC Chang, CN Wu, YS Fu, PPC Yang, CJ Chen, CD Chang, SC AF Fang, GC Chang, CN Wu, YS Fu, PPC Yang, CJ Chen, CD Chang, SC TI Ambient suspended particulate matters and related chemical species study in central Taiwan, Taichung during 1998-2001 SO ATMOSPHERIC ENVIRONMENT LA English DT Article DE suspended particles; fine particles; coarse particles; chemical species concentration; diurnal variations ID ATMOSPHERIC AEROSOL; SIZE DISTRIBUTION; PM10 AEROSOLS; URBAN AREAS; PM2.5; PARTICLES; SUBURBAN; SITES; UK; VISIBILITY AB Ambient suspended particulate (PM2.5, PM2.5-10, TSP) was collected from June 1998 to February 2001 in Taichung, central Taiwan. In addition, the related water-soluble ionic species (Cl-, NO3, Na+, NH4+, K+, Mg2+, Ca2+) and metallic species (Fe, Zn, Pb, Ni) were also analyzed in this study. The results showed that the concentrations of particulate mass are higher in the traffic site (CCRT) than the other sampling sites in this study. Also, the fine particle (PM2.5) concentration is the dominant species of the total suspended particles in Taichung, central Taiwan. The dominant species for PM2.5 are sulfate and ammonium at all sampling sites during the period of 1998-2001. The results of diurnal variation at THUC sampling site are also discussed in this study. Overall, acidic and secondary aerosol (Cl-, NO3-, SO42- and NH4+) is a more serious air pollutant issue in southern and central Taiwan than at several sites around the world. Therefore, ambient suspended particulate monitoring in Taichung, central Taiwan will be continuing in our following study to provide more information for the government to formulate environmental strategy. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 Hungkuang Inst technol, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Hungkuang Inst Technol, Dept Comp Sci & Informat Engn, Taichung 433, Taiwan. RP Fang, GC (reprint author), Hungkuang Inst technol, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. NR 29 TC 77 Z9 88 U1 1 U2 11 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1352-2310 J9 ATMOS ENVIRON JI Atmos. Environ. PD APR PY 2002 VL 36 IS 12 BP 1921 EP 1928 AR PII S1352-2310(02)00187-5 DI 10.1016/S1352-2310(02)00187-5 PG 8 WC Environmental Sciences; Meteorology & Atmospheric Sciences SC Environmental Sciences & Ecology; Meteorology & Atmospheric Sciences GA 561MJ UT WOS:000176144300002 ER PT J AU Gubina, E Chen, T Zhang, L Lizzio, EF Kozlowski, S AF Gubina, E Chen, T Zhang, L Lizzio, EF Kozlowski, S TI CD43 polarization in unprimed T cells can be dissociated from raft coalescence by inhibition of HMG CoA reductase SO BLOOD LA English DT Article ID WISKOTT-ALDRICH SYNDROME; IMMUNOLOGICAL SYNAPSE; ANTIGEN RECOGNITION; CD4(+)CD8(+) THYMOCYTES; EXTRACELLULAR-MATRIX; NEGATIVE REGULATION; ANCHORED PROTEINS; LEUKOSIALIN CD43; LIPID RAFTS; ACTIVATION AB Movement of T-lymphocyte cell surface CD43 is associated with both antigen activation of T-cell clones and chemokine induction of T-lymphocyte motility. Here, we demonstrate that CD43 movement away from the site of T-cell receptor ligation occurs in unprimed CD4(+) T cells as well as T-cell clones. The T-cell receptor (TCR)-dependent movement of CD43 in unprimed T cells is associated with a polarized morphology and CD43 accumulation at the uropods of the cells, unlike that reported for primed T cells. The polarization of CD43 has a requirement for Src kinases and occurs in conjunction with lipid raft coalescence. Thymocytes and T-cell hybridomas, cells that have altered responses to TCR activation and lack lipid raft coalescence, do not polarize CD43 as readily as unprimed T cells. The movement of CD43 depends on the cholesterol biosynthetic pathway enzyme 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase. Blockade of this enzyme can specifically prevent CD43 redistribution without affecting cell shape polarization. The likely mechanism of this alteration in CD43 redistribution is through decreased protein prenylation because the cholesterol-dependent lipid rafts still coalesce on activation. These findings suggest that the polarization of cell shape, lipid raft coalescence, and CD43 redistribution on T-cell activation have signaling pathway distinctions. Dissecting out the relationships between various stages of molecular redistribution and lymphocyte activation may facilitate fine-tuning of immunologic responses. (C) 2002 by The American Society of Hematology. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Kozlowski, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, 29 Lincoln Dr,Bldg 29B-3NN08,HFM-561, Bethesda, MD 20892 USA. NR 59 TC 14 Z9 16 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 APR 1 PY 2002 VL 99 IS 7 BP 2518 EP 2525 DI 10.1182/blood.V99.7.2518 PG 8 WC Hematology SC Hematology GA 533ZC UT WOS:000174559300034 PM 11895788 ER PT J AU Nowell, S Sweeney, C Hammons, G Kadlubar, FF Lang, NP AF Nowell, S Sweeney, C Hammons, G Kadlubar, FF Lang, NP TI CYP2A6 activity determined by caffeine phenotyping: Association with colorectal cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN-LIVER-MICROSOMES; IN-VIVO; INTERINDIVIDUAL VARIABILITY; COUMARIN 7-HYDROXYLATION; METABOLIC-ACTIVATION; GENE POLYMORPHISM; ENZYME-ACTIVITY; AFLATOXIN B-1; SMOKING; CYP1A2 AB Cytochrome P450 2A6 (CYP2A6) catalyzes the metabolic activation of several procarcinogens including dietary and environmental nitrosamines, and the involvement of CYP2A6 in cancer development has been postulated. CYP2A6 phenotype was determined using caffeine as a probe drug in individuals participating in a case-control study of colorectal cancer (127 cases and 333 controls matched on age, gender, race, and geographic region. Conversion of the caffeine metabolite 1,7-dimethylxanthine (17X) to 1,7-dimethyl uric acid (17U) is catalyzed primarily by CYP2A6, and this activity can be assayed by comparison of urinary molar ratios of metabolites. Caffeine (200 mg) was administered to each participant, and a 4-5 h postadministration urine sample was collected. Urinary metabolites of caffeine were separated by high-performance liquid chromatography and quantified by comparison to authentic standards. We examined the distributions of the ratio, 17U:17X, according to subject characteristics among controls. In case-control comparisons, subjects in the medium and high tertiles of CYP2A6 activity had an increased risk of colorectal cancer compared with subjects with low activity. Odds ratios from a conditional logistic regression model for medium and high 17U:17X ratio were 2.0 (95% confidence interval, 1.1-3.7) and 2.6 (95% confidence interval, 1.5-4.5), respectively (P for trend 0.001). CYP2A6 phenotype has not been compared previously between cancer cases and controls. We found a strong relationship between CYP2A6 activity, measured by urinary caffeine metabolite ratio, and colorectal cancer risk. C1 Univ Arkansas Med Sci, Dept Surg Oncol, CAVHS, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, CAVHS, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Nowell, S (reprint author), Univ Arkansas Med Sci, Dept Surg Oncol, CAVHS, VA Res Slot 151 4300 W 7th St, Little Rock, AR 72205 USA. OI Sweeney, Carol/0000-0003-1113-7160 FU NCI NIH HHS [R01CA55751] NR 40 TC 32 Z9 34 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD APR PY 2002 VL 11 IS 4 BP 377 EP 383 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 540BJ UT WOS:000174908000007 PM 11927498 ER PT J AU Fang, JL Beland, FA Doerge, DR Wiener, D Guillemette, C Marques, MM Lazarus, P AF Fang, JL Beland, FA Doerge, DR Wiener, D Guillemette, C Marques, MM Lazarus, P TI Characterization of benzo(a)pyrene-trans-7,8-dihydrodiol glucuronidation by human tissue microsomes and overexpressed UDP-glucuronosyltransferase enzymes SO CANCER RESEARCH LA English DT Article ID STABLE EXPRESSION; DIOL EPOXIDES; HUMAN COLON; BENZOPYRENE; LIVER; GENE; METABOLITES; LOCUS; IDENTIFICATION; BENZO(A)PYRENE AB UDP-glueuronosyltransferase (UGT)-mediated glucuronidation of benzo(a)pyrene-trans-7,8-dihydrodiol (BPD), precursor to the potent mutagen benzo(a)pyrene-7,8-dihydrodiol-9,10-epoxide, may be an important pathway in the detoxification of benzo(a)pyrene. To better characterize this pathway in humans, high-pressure liquid chromatography (HPLC) was used to detect glucuronide conjugates of BPD formed in vitro. Three peaks were detected by HPLC after incubation of racemic BPD with human liver microsomes; these were identified as monoglucuronides by liquid chromatography-mass spectrometry analysis. Proton nuclear magnetic resonance spectroscopy of isolated fractions, combined with HPLC analysis of the glucuronide products from human liver microsomal incubations with purified benzo(a)pyrene-trans-7S,8S-dihydrodiol [(+)-BPD] and benzo(a)pyrene-trans-7R,8R-dihydrodiol [(-)-BPD] forms of BPD, indicated that peak 1 contained the 7-glucuronide of 7S,8S-BPD (BPD-7S-Gluc), peak 2 was a mixture of the 7-glucuronide of 7R,8R-BPD (BPD-7R-Gluc) and the 8-glucuronide of 7S,8S-BPD (BPD-8S-Gluc), and peak 3 contained the 8-glucuronide of 7R. 8R-BPD (BPD-8R-Gluc). In liver microsomes, peak 1 (BPD-7S-Gluc) was the largest peak observed, whereas in microsomes from aerodigestive tract tissues, peak 2 (both BPD-7R-Gluc and BPD-8S-Gluc) was the largest HPLC peak observed. The liver enzymes UGT1A1 and UGT2B7 formed BPD-7S-Gluc as the major diastereomer, whereas UGT1A8 and UGT1A10, extrahepatic enzymes present in the aerodigestive tract, preferentially formed both BPD-7R-Gluc and BPD-8S-Gluc. In addition, both UGT1A9 and UGT1A7 preferentially formed BPD-7R-Gluc. No detectable glucuronidating activity against BPD was observed by UGT1A3, UGT1A4, UGT1A6, UGT2B4, UGT2B15, or UGT2B17. The affinity of individual UGT enzymes as determined by K-m analysis was UGT1A10 > UGT1A9 > UGT1A1 > UGT1A7 for (-)-BPD and UGT1A10 > UGT1A9 > UGT2B7 similar to UGT1A1 > UGT1A7 for (+)-BPD. These results suggest that several UGTs may play an important role in the overall glucuronidation of BPD in humans, with UGT1A1, UGT1A7, UGT1A9, UGT1A10 and potentially UGT1A8 playing an important role in the glucuronidation of the procarcinogenic (-)-BPD enantiomer, and that the stereospecific activity exhibited by different UGTs against BPD is consistent with tissue-specific patterns of BPD glucuronide diastereomer formation and UGT expression. C1 Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Control, Interdisciplinary Oncol Program, Tampa, FL 33612 USA. Univ S Florida, H Lee Moffitt Canc Ctr, Dept Mol Oncol, Interdisciplinary Oncol Program, Tampa, FL 33612 USA. Univ S Florida, Dept Biochem, Tampa, FL 33612 USA. Univ S Florida, Dept Pharmacol, Tampa, FL 33612 USA. Univ S Florida, Dept Therapeut, Tampa, FL 33612 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. CHU Laval, Sch Pharm, CHUL Res Ctr, Onocol & Mol Endocrinol Res Ctr, Quebec City, PQ G1V 4G2, Canada. Inst Super Tecn, Ctr Quim Estrutural, Complexo 1, P-1049001 Lisbon, Portugal. RP Lazarus, P (reprint author), Univ S Florida, H Lee Moffitt Canc Ctr, Div Canc Control, Interdisciplinary Oncol Program, MRC-2E 12902 Magnolia Dr, Tampa, FL 33612 USA. RI Guillemette, Chantal/J-6463-2012; Wiener, Doris/A-8825-2013; Marques, M. Matilde/E-2535-2012; OI Marques, M. Matilde/0000-0002-7526-4962; Guillemette, Chantal/0000-0002-1113-1212 FU NIDCR NIH HHS [R01-DE13158, R01-DE12206]; PHS HHS [P01-68384] NR 48 TC 67 Z9 70 U1 0 U2 4 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD APR 1 PY 2002 VL 62 IS 7 BP 1978 EP 1986 PG 9 WC Oncology SC Oncology GA 539TT UT WOS:000174887700011 PM 11929814 ER PT J AU Ritter, CL Culp, SJ Freeman, JP Marques, MM Beland, FA Malejka-Giganti, D AF Ritter, CL Culp, SJ Freeman, JP Marques, MM Beland, FA Malejka-Giganti, D TI DNA adducts from nitroreduction of 2,7-dinitrofluorene, a mammary gland carcinogen, catalyzed by rat liver or mammary gland cytosol SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID SALMONELLA-TYPHIMURIUM; IN-VITRO; PRENEOPLASTIC LESIONS; 2-NITROFLUORENE; NITROFLUORENES; 1,6-DINITROPYRENE; MUTAGENICITY; ACTIVATION; POLLUTANT; AIR AB Nitrofluorenes are mutagenic and carcinogenic environmental pollutants arising chiefly from combustion of fossil fuels. Nitro aromatic compounds undergo nitroreduction to N-hydroxy arylamines that bind to DNA directly or after O-esterification. This study analyzes the DNA binding and adducts from the in vitro nitroreduction of 2,7-dinitrofluorene (2,7-diNF), a potent mammary carcinogen in the rat. Potential adduct(s) of 2,7-diNF was (were) generated by reduction of 2-nitroso-7-NF with ascorbate/H+ in the presence of calf thymus DNA. The major adduct was characterized by HPLC/ESI/MS and H-1 NMR spectrometry as N-(deoxyguanosin-8-yl)-2-amino-7-NF, and a minor one was determined by HPLC/ESI/MS to be a deoxyadenosine adduct of 2-amino-7-NF. Products from enzymatic nitroreduction were monitored by HPLC and DNA adduct formation by P-32-postlabeling. Xanthine oxidase/hypoxanthine-catalyzed nitroreduction of 2.7-diNF, 2-nitrofluorene (2-NF), and 1-nitropyrene (1-NP) yielded the respective amines to similar extents (30-50%). However, the level of the major adducts (similar to0.15/10(6) nucleotides) from 2-NF [N-(deoxyguanosin-8-yl)-2-aminofluorene] and 2,7-diNF [N-(deoxyguanosin-8-yl)-2-amino-7-NF] was less than or equal to2% that from 1-NP. In the presence of acetyl CoA, nitroreduction of 2-NF catalyzed by rat liver cytosol/NADH yielded the same adduct at a level of 2.2/10(6) nucleotides. Liver or mammary gland cytosol with acetyl CoA yielded mainly N-(deoxyguanosin-8-yl)-2-amino-7-NF from 2,7-diNF at >30 adducts/10(6) nucleotides, levels comparable to those from 1,6-dinitropyrene and 4- or 49-fold greater than the respective levels without acetyl CoA. Recovery of 2-nitroso-7-NF and 2-amino-7-NF from cytosol-catalyzed reduction of 2,7-diNF indicated nitroreduction and an N-hydroxy arylamine intermediate. Likewise, the presence of 2-acetylamino-7-NF indicated that reactivity with acyltransferase(s) was not prevented by the nitro group at C7. These data are consistent with activation of 2,7-diNF via nitroreduction to the N-hydroxy arylamine and acetyl CoA-dependent O-acetylation of the latter to bind to DNA. Enzymatic nitroreduction of 2,7-diNF was greatly enhanced by 9-oxidation. The nitroreduction of either 9-oxo-2,7-diNF or 9-hydroxy-2,7-diNF catalyzed by liver cytosol with acetyl CoA yielded two adducts (>2/10(6) nucleotides). Differences in the TLC migration of these adducts, compared to those from 2,7-diNF, and the lack of 2,7-diNF formation in the incubations suggested retention of the C9-oxidized groups. The relative ratios of the amine to amide from nitroreductions of 9-oxo-2,7-diNF and 2,7-diNF catalyzed by liver cytosol suggested that the 9-oxo group decreased reactivity with acyltransferase and, thus, the amount of N-acetoxy arylamine that binds to DNA. The mammary gland tumorigenicity of 2,7-diNF and the extent of its activation by the tumor target tissue shown herein suggest relevance of this environmental pollutant for breast cancer. C1 Vet Affairs Med Ctr, Minneapolis, MN 55417 USA. Univ Minnesota, Dept Lab Med & Pathol, Minneapolis, MN 55455 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Inst Super Tecn, Ctr Quim Estrutural, P-1049001 Lisbon, Portugal. RP Malejka-Giganti, D (reprint author), Vet Affairs Med Ctr, 151,1 Vet Dr, Minneapolis, MN 55417 USA. RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 FU NCI NIH HHS [CA-28000] NR 29 TC 19 Z9 21 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 2002 VL 15 IS 4 BP 536 EP 544 DI 10.1021/tx010172p PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 543DB UT WOS:000175085000010 PM 11952340 ER PT J AU Paehler, A Richoz, J Soglia, J Vouros, P Turesky, RJ AF Paehler, A Richoz, J Soglia, J Vouros, P Turesky, RJ TI Analysis and quantification of DNA adducts of 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline in liver of rats by liquid chromatography/electrospray tandem mass spectrometry SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID CARCINOGENIC HETEROCYCLIC AMINES; P-32 POSTLABELING ASSAY; METABOLIC-ACTIVATION; COOKED FOODS; ENVIRONMENTAL CARCINOGENS; HEPATOCELLULAR-CARCINOMA; MUTAGENIC COMPOUND; AROMATIC-AMINES; DOSE-RESPONSE; HUMAN TISSUES AB Liquid chromatography with electrospray ionization tandem mass spectrometry (LC/ESI-MS/MS) was used to measure DNA adducts of the carcinogen 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx) with a microbore C-18 reversed-phase column. Quantification of the isomeric adducts N-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (dG-C8-MeIQx) and 5-(deoxyguanosin-8-yl)-2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (dG-N-2-MeIQx) was achieved using synthetic, isotopically labeled internal standards. The reaction of the N-acetoxy ester of 2-(hydroxyamino)-3,8-dimethylimidazo[4,5-f]quinoxaline (HONH-MeIQx) with calf thymus DNA (ct DNA) resulted in formation of these adducts in a ratio of 5:1 (dG-C8-MeIQx:dG-N2-MeIQx). The detection limit by LC/ESI-MS/MS in the selected reaction monitoring (SRM) mode ([MH+ --> MH --> 116](+)) (loss of deoxyribose) approached 500 fg (1 fmol) of adduct standard, and 1 adduct per 10(8) DNA bases using 100mug of DNA following solid-phase extraction. The SRM analysis of rat liver DNA 24 h after an oral dose of MeIQx (10 and 0.5 mg/kg) revealed the presence of isomeric dG-MeIQx adducts at levels of 3.07 +/- 0.84 and 0.45 +/- 0.27 adducts per 10(7) bases, respectively. LC/ESI-MS/MS product ion spectra were acquired on both adducts from the elevated dose of MeIQx for unambiguous adduct identification. The contribution of dG-N-2-MeIQx to the total adducts in vivo was significantly more important than that observed in vitro. dG-C8-MeIQx was the principal adduct formed at the 10 mg/kg dose, (dG-C8-MeIQx:dG-N-2-MeIQx (3:2)); however, dG-N-2-MeIQx was the major lesion detected at the 0.5 mg/kg dose (dG-C8-MeIQx:dG-N-2-MelQx 1:10). The striking differences between the relative amounts of dG-C8-MeIQx and dG-N2-MeIQx formed in vivo as a function of dose suggest that reactive esters of HONH-MeIQx other than N-acetoxy-MeIQx may be formed in vivo and react preferentially with the N-2 atom of guanine, or that dG-C8-MeIQx is removed at a significantly more rapid rate than dG-N-2-MeIQx. The dG-N-2-MeIQx adduct, previously thought to be a minor adduct, is likely to be an important contributor to the genotoxic damage of MeIQx. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland. Northeastern Univ, Dept Chem, Boston, MA 02115 USA. RP Turesky, RJ (reprint author), Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. FU NCI NIH HHS [1R01CA69390-06] NR 52 TC 35 Z9 36 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 2002 VL 15 IS 4 BP 551 EP 561 DI 10.1021/tx010178e PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 543DB UT WOS:000175085000012 PM 11952342 ER PT J AU Sutherland, MF Drew, A Rolland, JM Slater, JE Suphioglu, C O'Hehir, RE AF Sutherland, MF Drew, A Rolland, JM Slater, JE Suphioglu, C O'Hehir, RE TI Specific monoclonal antibodies and human immunoglobulin E show that Hev b 5 is an abundant allergen in high protein powdered latex gloves SO CLINICAL AND EXPERIMENTAL ALLERGY LA English DT Article DE Hev b 5; latex allergy; latex gloves; monoclonal antibodies; recombinant proteins ID HEV-B-5; EPITOPES; SENSITIZATION; CLONING; WORKERS AB Background Hev b 5 is a major latex allergen recognized predominantly by latex-allergic health care workers (HCWs). Recombinant Hev b 5 (rHev b 5) was previously expressed as a fusion protein with maltose binding protein (MBP), itself an immunogenic molecule; therefore non-fusion rHev b 5 is desirable. Moreover, standardized immunological assays for the detection of Hev b 5 are currently lacking and may have important implications for both allergen avoidance and diagnosis in latex allergy. Objectives To generate and use Hev b 5-specific mAbs to determine the relative abundance of Hev b 5 in different latex extracts, correlating this with the IgE reactivity of latex-allergic HCWs and to produce non-fusion rHev b 5. Methods For the production of mAbs, mice were immunized with rHev b 5/MBP fusion protein and mAbs selected with rHev b 5/MBP but not MBP reactivity. The mAb reactivity was compared with polyclonal IgE from latex-allergic HCWs using direct and inhibition ELISA and immunoblot assays. Recombinant Hev b 5 was expressed and purified in the pPROEX-HTa bacterial expression system. Results Four Hev b 5-specific mAbs were produced. Immunoblotting and ELISA using the mAbs indicate abundant Hev b 5 in high protein powdered latex glove extracts as compared with crude latex sap extracts. High quality surgical gloves with no detectable protein have no detectable Hev b 5. Inhibition ELISAs using serum IgE from latex-allergic HCWs and Hev b 5-specific mAbs gave strong correlation. Non-fusion recombinant Hev b 5 was successfully expressed and purified, showing reactivity with both the Hev b 5-specific mAbs and serum IgE of latex-allergic HCWs. Conclusion Hev b 5-specific mAbs and human IgE from latex-allergic HCWs demonstrate the greater content of Hev b 5 in high protein powdered glove extracts. This may explain the observed higher frequency of sensitization to this allergen in HCWs. C1 Alfred Hosp, Dept Allergy Asthma & Clin Immunol, Prahran, Vic 3181, Australia. Alfred Hosp, Dept Pathol & Immunol, Prahran, Vic 3181, Australia. Monash Univ, Clayton, Vic 3168, Australia. Cooperat Res Ctr Asthma, Sydney, NSW, Australia. US FDA, Ctr Biol Evaluat & Res, Lab Immunobiochem, Rockville, MD 20857 USA. RP O'Hehir, RE (reprint author), Alfred Hosp, Dept Allergy Asthma & Clin Immunol, Commercial Rd, Prahran, Vic 3181, Australia. RI Rolland, Jennifer/E-7543-2011; O'Hehir, Robyn/H-3627-2011 OI O'Hehir, Robyn/0000-0002-3489-7595 NR 25 TC 24 Z9 28 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0954-7894 J9 CLIN EXP ALLERGY JI Clin. Exp. Allergy PD APR PY 2002 VL 32 IS 4 BP 583 EP 589 DI 10.1046/j.0954-7894.2002.01355.x PG 7 WC Allergy; Immunology SC Allergy; Immunology GA 546HX UT WOS:000175269600017 PM 11972606 ER PT J AU Putman, E van Loveren, H Bode, G Dean, J Hastings, K Nakamura, K Verdier, F van der Laan, JW AF Putman, E van Loveren, H Bode, G Dean, J Hastings, K Nakamura, K Verdier, F van der Laan, JW TI Assessment of the immunotoxic potential of human pharmaceuticals: A workshop report SO DRUG INFORMATION JOURNAL LA English DT Article DE immunotokicity; repeated dose toxicity testing; Europe; United States; Japan ID RISK ASSESSMENT; IMMUNE; TOXICOLOGY; TESTS; RATS AB The assessment of the immunotoxic potential of human pharmaceuticals has drawn considerable attention worldwide in the past few years. In Europe, the Committee for Proprietary Medicinal Products released its immunotoxicity guidance documents. The Food and Drug Administration Center for Drug Evaluation and Research in the United States and the Japanese Ministry of Health, Labor, and Welfare are in the process of finalizing similar guidance documents. This report summarizes the discussions on drug immunotoxicity assessment held at a November 2001 DIA workshop held in Noordwijk, The Netherlands. This workshop revealed that an important issue for company attendees was the timing of the immunotoxicity studies during the drug development process, The Committee for Proprietary Medicinal Products requires that immunotoxicity endpoints be monitored for all new compounds. Industry has interpreted this requirement, and the expectation that these endpoints be studied in a 28-day repeated dose study in rats, as obligatory immunotoxicity testing for all new compounds, regardless of the stage of development, The Committee for Proprietary, Medicinal Products requirements, however, are applicable only at the stage of the marketing application. Workshop participants agreed that immunotoxicity screening should preferably be carried out prior or parallel to Phase 2 development. This will substantially reduce the number of compounds that require enhanced testing for immunotoxicity (approximately, 80% of the compounds are dropped from development after Phase 1) and reduce the use of animals. Presentations and discussions at the workshop also demonstrated that there is a strong scientific basis for European requirements as included in the Revised Note for Guidance on Repeated Dose Toxicity Testing, For example, not evaluating the response to a T-cell-dependent antigen would have missed the immunotoxicological effects of several compounds, This is probably due to the dynamic nature of the immune system whereby immune effects are best demonstrated using an immune function assay, as opposed to reliance on an essentially static analysis such as histopathology. C1 Natl Inst Publ Hlth & Environm, Lab Med & Med Devices, Preclin Assessment Grp Med Evaluat Board, NL-3720 BA Bilthoven, Netherlands. Natl Inst Publ Hlth & Environm, Sect Immunobiol & Haematol, NL-3720 BA Bilthoven, Netherlands. BYK Gulden Lomberg GmbH, Hamburg, Germany. Sanofi Synthelabo, Malvern, PA USA. US FDA, Rockville, MD 20857 USA. Shionogi & Co Ltd, Osaka, Japan. Aventis Pasteur France, Marcy Letoile, France. RP van der Laan, JW (reprint author), Natl Inst Publ Hlth & Environm, Lab Med & Med Devices, Preclin Assessment Grp Med Evaluat Board, POB 1, NL-3720 BA Bilthoven, Netherlands. NR 12 TC 16 Z9 16 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD APR-JUN PY 2002 VL 36 IS 2 BP 417 EP 427 AR UNSP 0092-8615/2002 PG 11 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 556FB UT WOS:000175837700021 ER PT J AU Lennernas, H Knutson, L Knutson, T Hussain, A Lesko, L Salmonson, T Amidon, GL AF Lennernas, H Knutson, L Knutson, T Hussain, A Lesko, L Salmonson, T Amidon, GL TI The effect of amiloride on the in vivo effective permeability of amoxicillin in human jejunum: experience from a regional perfusion technique SO EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE intestinal drug permeability; drug absorption; bioavailability; bioequivalence; Biopharmaceutics Classification System; absorption interaction; oligopeptide carrier; amoxicillin; amiloride; in vivo transport; PepT1 ID OLIGOPEPTIDE TRANSPORTER PEPT-1; INTESTINAL-CELL LINE; IN-VIVO; DRUG ABSORPTION; PHARMACOKINETICS; DISSOLUTION; PARAMETERS AB The purpose of this human intestinal perfusion study (in vivo) was twofold. Firstly, we aimed to determine the effective in vivo jejunal permeability (P-eff) of arnoxicillin and to classify it according to the Biopharmaceutics Classification System (BCS). Secondly, we investigated the acute effect of amiloride on the jejunal P-eff of arnoxicillin. Amoxicillin, a beta-lactam antibiotic, has been reported to be absorbed across the intestinal mucosa by both passive diffusion and active transport. A regional single-pass perfusion of the jejunum was performed using a Loc-I-Gut((R)) perfusion tube in 14 healthy volunteers. Each perfusion lasted for 200 min and was divided into two periods of 100 min each. The concentration of amoxicillin entering the jejunal segment was 300 mg/l in both periods, and amiloride, an inhibitor of the Na+/H+ exchanger, was added at 25 mg/l in period 2. The concentrations of amoxicillin and amiloride in the outlet jejunal perfusate were measured with two different HPLC-methods. Antipyrine and [C-14]PEG 4000 were added as internal standards to the perfusion solution. Amiloride had no significant effect on the jejunal P-eff of amoxicillin. The human in vivo jejunal P-eff for amoxicillin was 0.34 +/- 0.11 X 10(-4) and 0.46 +/- 0.12 X 10(-4) cm/s in periods 1 and 2, respectively. The high jejunal P-eff for amiloride was 1.63 +/- 0.51 X 10(-4) cm/s which predicts an intestinal absorption of more than 90%. Following the BCS amoxicillin was classified as a low P-eff drug, and amiloride had no acute effect on the in vivo jejunal P-eff of amoxicillin. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Uppsala, Dept Pharm, BMC, S-75123 Uppsala, Sweden. Uppsala Univ, Dept Surg, Uppsala, Sweden. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Med Prod Agcy, Uppsala, Sweden. Univ Michigan, Dept Pharm, Ann Arbor, MI 48109 USA. RP Lennernas, H (reprint author), Univ Uppsala, Dept Pharm, BMC, Box 580, S-75123 Uppsala, Sweden. NR 32 TC 44 Z9 47 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0928-0987 J9 EUR J PHARM SCI JI Eur. J. Pharm. Sci. PD APR PY 2002 VL 15 IS 3 BP 271 EP 277 AR PII S0928-0987(02)00005-2 DI 10.1016/S0928-0987(02)00005-2 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 547NT UT WOS:000175339200005 PM 11923059 ER PT J AU Ruiz-Hidalgo, MJ Gubina, E Tull, L Baladron, V Laborda, J AF Ruiz-Hidalgo, MJ Gubina, E Tull, L Baladron, V Laborda, J TI dlk modulates mitogen-activated protein kinase signaling to allow or prevent differentiation SO EXPERIMENTAL CELL RESEARCH LA English DT Article DE dlk; cell differentiation; ERK/MAPK signaling; adipogenesis; cell to cell communication ID EPIDERMAL GROWTH-FACTOR; ADIPOCYTE DIFFERENTIATION; MAP KINASE; TYROSINE-PHOSPHATASE; MEDIATED PHOSPHORYLATION; ADIPOSE DIFFERENTIATION; 3T3-L1 PREADIPOCYTES; CELL-DIFFERENTIATION; RECEPTOR-GAMMA; S6 KINASE AB The EGF-like membrane protein dlk plays a crucial role in the control of cell differentiation. Overexpression of the protein prevents, whereas inhibition of its expression increases, adipocyte differentiation of 3T3-L1 cells in response to Insulin-like Growth Factor I (IGF-1) or insulin. We have investigated whether dlk modulates the signaling pathways known to control this process. We found that the levels of dlk expression modulated signaling through the IGF-1 receptor, causing changes in the activation levels and kinetics of Extracellular-Regulated Kinase/Mitogen-Activated Protein Kinase (ERK/MAPK) that correlated with differentiation outcome. These changes occurred in response to IGF-1 or insulin but not in response to Epidermal Growth Factor. However, the levels of expression of IGF-1 receptor, or the activation of Insulin Receptor Substrate-1 in response to IGF-1, were not affected by the levels of dlk expression. Therefore, dlk appears to modulate ERK/MAPK signaling in response to specific differentiation signals. C1 Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, Rockville, MD 20852 USA. RP Laborda, J (reprint author), Univ Castilla La Mancha, Fac Med, Campus Albacete,Edif Benjamin Palencia,Ave Espana, Albacete 02071, Spain. RI Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014; Baladron, Victoriano/L-1758-2014 OI Laborda, Jorge/0000-0002-9210-838X; Baladron, Victoriano/0000-0003-4574-8760 NR 58 TC 39 Z9 40 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD APR 1 PY 2002 VL 274 IS 2 BP 178 EP 188 DI 10.1006/excr.2001.5464 PG 11 WC Oncology; Cell Biology SC Oncology; Cell Biology GA 537ZJ UT WOS:000174789300002 PM 11900478 ER PT J AU Garthoff, LH Henderson, GR Sager, AO Sobotka, TJ O'Dell, R Thorpe, CW Trotter, WJ Bruce, VR Dallas, HL Poelma, PL Solomon, HM Bier, JW O'Donnell, MW Chi, RK Chirtel, SJ Barton, CN Brown, LH Frattali, VP Khan, MA AF Garthoff, LH Henderson, GR Sager, AO Sobotka, TJ O'Dell, R Thorpe, CW Trotter, WJ Bruce, VR Dallas, HL Poelma, PL Solomon, HM Bier, JW O'Donnell, MW Chi, RK Chirtel, SJ Barton, CN Brown, LH Frattali, VP Khan, MA TI The Autosow raised miniature swine as a model for assessing the effects of dietary soy trypsin inhibitor SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Review DE dietary soy trypsin inhibitor; neonatal miniature swine; automatic feeding; artificial rearing; toxicology ID MILK-COMPOSITION; RAT PANCREAS; PRIMIPAROUS SOWS; HUMAN-NUTRITION; GROWING SWINE; NEONATAL PIG; PROTEIN; FLOUR; CHOLECYSTOKININ; PERFORMANCE AB Toxicological effects of dietary soy trypsin inhibitor (TI) were assessed in male miniature swine, a model chosen for its similarities to human digestive physiology and anatomy. The TI preparation was extracted from defatted raw soy flour. From I through 5 weeks of age, piglets were automatically fed either a TI liquid diet [Autosow TI group (ASTI)] or a control liquid diet [Autosow control group (ASC)]. From 6 to 39 weeks of age, these animals received either swine chow and TI or swine chow and control article. The TI diets were formulated to contain a TI activity of approximately 500 mg TI/100 g dry matter. A sow control (SC) group suckled from birth to 6 weeks of age and then fed as the ASC group with swine chow plus control article from 6 to 39 weeks of age. The SC piglets grew faster than ASC piglets during postnatal weeks I and 2; however, the ASC piglets were significantly heavier than the SC piglets (P=0.001) at 6 weeks of age. Compared with the ASC group, TI caused a moderate decrease in feed consumption and a moderate but reversible decrease in growth from 2 to 5 weeks of age, but not thereafter. Some control and TI-fed Autosow-reared piglets had loose stools until 6 weeks of age; the effect was significantly greater in the TI-fed group. Otherwise, all swine were active and had normal appearance and behavior. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol Res & Nutr Prod Studies, Laurel, MD 20708 USA. Off Special Nutr, Div Programs & Enforcement Policy, Methods Res Branch, College Pk, MD 20740 USA. Div Pesticides & Ind Chem, College Pk, MD 20740 USA. Div Microbiol Studies, College Pk, MD 20740 USA. Div Math, College Pk, MD 20740 USA. Off Ctr Director, College Pk, MD 20740 USA. RP Garthoff, LH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol Res & Nutr Prod Studies, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 104 TC 11 Z9 15 U1 2 U2 11 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 2002 VL 40 IS 4 BP 487 EP 500 AR PII S0278-6915(01)00120-X DI 10.1016/S0278-6915(01)00120-X PG 14 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 544HN UT WOS:000175152300006 PM 11893408 ER PT J AU Garthoff, LH Henderson, GR Sager, AO Sobotka, TJ Gaines, DW O'Donnell, MW Chi, R Chirtel, SJ Barton, CN Brown, LH Hines, FA Solomon, T Turkleson, J Berry, D Dick, H Wilson, F Khan, MA AF Garthoff, LH Henderson, GR Sager, AO Sobotka, TJ Gaines, DW O'Donnell, MW Chi, R Chirtel, SJ Barton, CN Brown, LH Hines, FA Solomon, T Turkleson, J Berry, D Dick, H Wilson, F Khan, MA TI Pathological evaluation, clinical chemistry and plasma cholecystokinin in neonatal and young miniature swine fed soy trypsin inhibitor from 1 to 39 weeks of age SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Review DE soy; trypsin inhibitor; miniature swine; pancreas; autosow ID PANCREATIC EXOCRINE SECRETION; NEGATIVE-FEEDBACK-REGULATION; RAT PANCREAS; ENZYME SECRETION; ORNITHINE DECARBOXYLASE; SHORT-TERM; CHYMOTRYPSIN ACTIVITIES; RECEPTOR ANTAGONIST; PROTEASE INHIBITOR; GROWING SWINE AB The potential toxicity of dietary soy trypsin inhibitor (TI) was evaluated in neonatal miniature swine. From I to 6 weeks of age, two groups of male piglets were artificially reared in an Autosow and automatically fed either TI or control liquid diet. From 6 to 39 weeks of age, these two groups were fed either TI or control chow diet. A third group, sow control (SC), suckled from birth to 6 weeks of age, were also weaned to control chow from 6 to 39 weeks of age. Clinical chemistry and plasma cholecystokinin (CCK) determined at 6, 18, 30 and 39 weeks of age, and serum amylase activity with gross and histopathological analyses of major organs at 6 and 39 weeks of age are reported. TI had no effect on plasma CCK, serum amylase activity, or numerous clinical chemistry values. TI-fed piglets had a larger relative liver weight at 6 weeks of age. Relative pancreas weight decreased with age but was not affected by TI. Gross and histopathological analyses of major organs, except the spleen, were within normal limits. Increased incidence of extramedullary hematopoiesis was noted in the spleen of the TI group at 6 but not at 39 weeks of age. There was no consistent pattern in immunohistochemical foci for secretin, gastrin releasing polypeptide or CCK, and no change in DNA, RNA, mitotic index or nuclear density of pancreatic cells. At 6 weeks of age, TI increased pancreatic protein and amylase activity but not trypsin or chymotrypsin activity. None of the effects suggested that this dose of TI was toxic to either the neonatal or sexually mature miniature male swine. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol Res & Nutr Prod Studies,Muirkirk Res, Laurel, MD 20708 USA. Div Math, College Pk, MD 20740 USA. Off Sci Anal & Support, College Pk, MD 20740 USA. Vet Adm, Kansas City, MO 64108 USA. USDA, Western Reg Res Ctr, Albany, CA 94710 USA. RP Garthoff, LH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Appl Res & Safety Assessment, Div Toxicol Res & Nutr Prod Studies,Muirkirk Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 123 TC 5 Z9 6 U1 2 U2 3 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 2002 VL 40 IS 4 BP 501 EP 516 AR PII S0278-6915(01)00121-1 DI 10.1016/S0278-6915(01)00121-1 PG 16 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 544HN UT WOS:000175152300007 PM 11893409 ER PT J AU Palmai, M Buchanan, RL AF Palmai, M Buchanan, RL TI Growth of Listeria monocytogenes during germination of alfalfa sprouts SO FOOD MICROBIOLOGY LA English DT Article ID BEAN-SPROUTS; VEGETABLE SPROUTS; SALMONELLA; OUTBREAK; BACTERIA; INFECTIONS; PRODUCE; SEEDS AB A large number of micro-organisms are able to proliferate on sprouts. The microflora may occasionally contain pathogenic bacteria that can be a source of outbreaks. Listeria monocytogenes has been detected from various vegetables and has been the source of foodborne outbreaks originating from vegetables. This study investigated the capacity of L. monocytogenes to grow on germinating alfalfa sprouts in a mini-sprouter. It also assessed the inhibitory activity of Lactococcus lactis against L. monocytogenes inoculated onto sprouts (approximately 2 x 10(2) cfu g(-1)). L. monocytogenes was able to proliferate during the germination of alfalfa sprouts, reaching levels of around. 10(6) cfu g(-1) within 48 h. The level of L. monocytogenes remained constant when the sprouts were subsequently stored at 4degreesC for 7 days, When Lact. lactis was co-inoculated onto the seeds at the beginning of the sprouting process, the maximum levels of L. monocytogenes were approximately 1 log lower than those observed with the control cultures. LAB counts increased rapidly, reaching almost 10(8) cfu g(-1) in 24 h, but by the end of the first 24h the total aerobic counts exceeded the LAB counts. The extent of the inhibitory effect of Lact, lactis was substantially less on alfalfa than that observed in a model system. Published by Elsevier Science Ltd. C1 Campden & Chorleywood Food Ind Dev Inst, H-1097 Budapest, Hungary. US FDA, Ctr Food Safety & Nutr, Washington, DC 20204 USA. RP Palmai, M (reprint author), Campden & Chorleywood Food Ind Dev Inst, Ken U 5 C Bldg, H-1097 Budapest, Hungary. NR 23 TC 22 Z9 22 U1 1 U2 9 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD APR-JUN PY 2002 VL 19 IS 2-3 BP 195 EP 200 DI 10.1006/fmic.2001.0470 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 564VH UT WOS:000176333900009 ER PT J AU Orlandi, PA Chu, DMT Bier, JW Jackson, GJ AF Orlandi, PA Chu, DMT Bier, JW Jackson, GJ TI Parasites and the food supply SO FOOD TECHNOLOGY LA English DT Article ID CRYPTOSPORIDIUM-PARVUM OOCYSTS; MOLECULAR CHARACTERIZATION; CYCLOSPORA-CAYETANENSIS; AMPLIFICATION PRODUCTS; TEMPLATE PREPARATION; GASTRIC ANISAKIASIS; FOODBORNE OUTBREAK; UNITED-STATES; VIABILITY; PROTOZOA C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Orlandi, PA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. NR 65 TC 32 Z9 40 U1 2 U2 7 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 APR PY 2002 VL 56 IS 4 BP 72 EP 81 PG 10 WC Food Science & Technology SC Food Science & Technology GA 541EC UT WOS:000174971400012 ER PT J AU Americo, J Whiteley, M Brown, JL Fujioka, M Jaynes, JB Kassis, JA AF Americo, J Whiteley, M Brown, JL Fujioka, M Jaynes, JB Kassis, JA TI A complex array of DNA-binding proteins required for pairing-sensitive silencing by a polycomb group response element from the drosophila engrailed gene SO GENETICS LA English DT Article ID TRITHORAX GROUP PROTEINS; HOMEOTIC GENE; BITHORAX COMPLEX; TRANSCRIPTION FACTOR; CHROMATIN INSULATOR; REGULATORY REGION; TARGET GENES; GAGA FACTOR; TRANS; TRANSVECTION AB Regulatory DNA from the Drosophila gene engrailed causes silencing of a linked reporter gene (mini-white) in transgenic Drosophila. This silencing is strengthened in flies homozygous for the transgene and has been called "pairing-sensitive silencing." The pairing-sensitive silencing activities of a large fragment (2.6 kb) and a small subfragment (181 bp) were explored. Since pairing-sensitive silencing is often associated with Polycomb group response elements (PREs), we tested the activities of each of these engrailed fragments fit a construct designed to detect PRE activity in embryos. Both fragments were found to behave as PREs in a bxd-Ubx-lacZ reporter construct, while the larger fragment showed additional silencing capabilities. Using the mini-white reporter gene, a 139-bp minimal pairing-sensitive element (PSE) was defined. DNA mobility-shift assays using Drosophila nuclear extracts suggested that there are eight protein-binding sites within this 139-bp element. Mutational analysis showed that at least five of these sites are important for pairing-sensitive silencing. One of the required sites is for the Polycomb group protein Pleiohomeotic and another is GAGAG, a sequence bound h the protein,, GAGA factor and Pipsqueak. The identity of the other proteins is unknown. These data suggest a surprising degree of complexity in the DNA-binding proteins required for PSE function. C1 NICHHD, LMG, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapeut, Bethesda, MD 20892 USA. Thomas Jefferson Univ, Kimmel Canc Inst, Dept Microbiol & Immunol, Philadelphia, PA 19107 USA. RP Kassis, JA (reprint author), NICHHD, LMG, NIH, 6 Ctr Dr,MSC 2785, Bethesda, MD 20892 USA. OI Kassis, Judith/0000-0001-9268-3213 FU NIGMS NIH HHS [R01 GM050231, R01 GM050231-05A2, GM50231] NR 54 TC 50 Z9 50 U1 1 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD APR PY 2002 VL 160 IS 4 BP 1561 EP 1571 PG 11 WC Genetics & Heredity SC Genetics & Heredity GA 545VA UT WOS:000175237200026 PM 11973310 ER PT J AU Fitzsimmons, SP Clark, KJ Shapiro, MA AF Fitzsimmons, SP Clark, KJ Shapiro, MA TI Evolutionary relationships and polymorphisms among V kappa 10 genes from inbred and wild-derived inbred mice SO IMMUNOGENETICS LA English DT Article DE V kappa 10 genes; evolution; inbred mice; wild mice ID IMMUNOGLOBULIN-KAPPA LOCUS; CROSS-REACTIVE IDIOTYPES; MUS-MUSCULUS-CASTANEUS; VK FAMILY; ARS-A; MOUSE; ANTIBODIES; SEGMENTS; PART; DNA AB The Vkappa10 family in BALB/c mice is composed of three members, two of which are utilized in a variety of immune responses. We previously demonstrated that the product of the third gene, Vkappa10C, has never been detected as part of a functional antibody and productive rearrangements are selectively lost during B-cell development. Here we analyzed germline Vkappa10 genes from inbred and wild-derived mice by RFLP and sequencing in order to determine the origin of the Vkappa10C gene, as well as to examine the evolutionary relationships of Vkappa10 genes. Our results demonstrated that the Vkappa10 family is highly conserved across Mus species and subspecies, but that Vkappa10C is rare, being found in only inbred mice of Vkappa10 allelic group b and two of six M. in. domesticus isolates. It was not found in other M. musculus subspecies or M. spretus. Vkappa10A and Vkappa10B were found in all strains, with the exception of one M. in. domesticus isolate, which had only Vkappa10B genes. Overall, Vkappa10A sequences were more highly conserved than Vkappa10B, indicating that different selective pressures may be operating on these genes. The two Vkappa10C sequences from M. in. domesticus were 100% identical to that found in inbred mice. Vkappa10C is more closely related to Vkappa10B than to Vkappa10A and our data suggest that it is a recent duplication of the Vkappa10B gene. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Rockville, MD 20852 USA. RP Shapiro, MA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, 1401 Rockville Pike HFM-561, Rockville, MD 20852 USA. NR 24 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0093-7711 J9 IMMUNOGENETICS JI Immunogenetics PD APR PY 2002 VL 54 IS 1 BP 9 EP 19 DI 10.1007/s00251-002-0438-8 PG 11 WC Genetics & Heredity; Immunology SC Genetics & Heredity; Immunology GA 552JV UT WOS:000175617900002 PM 11976787 ER PT J AU Kumar, S Villinger, F Oakley, M Aguiar, JC Jones, TR Hedstrom, RC Gowda, K Chute, J Stowers, A Kaslow, DC Thomas, EK Tine, J Klinman, D Hoffman, SL Weiss, WW AF Kumar, S Villinger, F Oakley, M Aguiar, JC Jones, TR Hedstrom, RC Gowda, K Chute, J Stowers, A Kaslow, DC Thomas, EK Tine, J Klinman, D Hoffman, SL Weiss, WW TI A DNA vaccine encoding the 42 kDa C-terminus of merozoite surface protein 1 of Plasmodium falciparum induces antibody, interferon-gamma and cytotoxic T cell responses in rhesus monkeys: immuno-stimulatory effects of granulocyte macrophage-colony stimulating factor SO IMMUNOLOGY LETTERS LA English DT Article DE Plasmodium falciparum; rhesus monkey; merozoite surface protein 1 (MSP1); cytotoxic T cells (CTL); interferon-gamma (IFN-gamma); DNA vaccine ID AOTUS MONKEYS; PROTECTIVE IMMUNITY; PLASMID DNA; MALARIA; EXPRESSION; IMMUNOGENICITY; FRAGMENT; ANTIGEN; YOELII; MICE AB We have constructed a DNA plasmid vaccine encoding the C-terminal 42-kDa region of the merozoite surface protein1 (pMSP1(42)) from the 3D7 strain of Plasmodium falciparum (Pf3D7). This plasmid expressed recombinant MSP1(42) after in vitro transfection in mouse VM92 cells. Rhesus monkeys immunized with pMSP1(42) produced antibodies reactive with Pf3D7 infected erythrocytes by IFAT, and by ELISA against yeast produced MSP1(19) (yMSP1(19)). Immunization also induced antigen specific T cell responses Lis measured by interferon-gamma production. and by classical CTL chromium release assays, In addition. immunization with pMSP1(42) primed animals for an enhanced antibody response to a subsequent boost with the recombinant yMSP1(19). We also evaluated Granulocyte-Macrophage Colony-Stimulating Factor (GM-CSF) as an adjuvant for pMSP1(42). We tested both rhesus GM-CSF expressed from a DNA plasmid and E. coli produced recombinant human GM-CSF, Plasmids encoding rhesus GM-CSF (prhGM-CSF) and human GM-CSF (phuGM-CSF) were constructed, these plasmids expressed bio-active recombinant GMCSF. Co-immunization with a mixture of prhGM-CSF and pMSP1(42) induced higher specific antibody responses after the first dose of plasmid. but after three doses of DNA monkeys immunized with or without prhGM-CSF had the same final antibody titers and T cell responses. In comparison, rhuGM-CSF protein did not lead to accelerated antibody production after the first DNA dose. However, antibody titers ere maintained at it slightly higher level in monkeys receiving GM-CSF protein, and they had a higher response to boosting with recombinant MSP1(19). The GM-CSF plasmid or protein appears to be less potent as an adjutant in rhesus monkeys than each is in mice, and more work is needed to determine if GM-CSF can be a useful adjuvant in DNA vaccination of primates. (C) 2002 Published by Elsevier Science B.V. C1 USN, Med Res Ctr, Malaria Program, Silver Spring, MD 20910 USA. Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD 21205 USA. Emory Univ, Sch Med, Winship Canc Ctr, Dept Pathol & Lab Med, Atlanta, GA 30333 USA. NIDDK, Stem Cell Biol Sect, USN, Transplantat & Autoimmun Branch, Bethesda, MD 20889 USA. NIAID, Parasit Dis Lab, Bethesda, MD 20892 USA. Immunex Corp, Seattle, WA 98101 USA. Virogenet Corp, Troy, NY 12180 USA. US FDA, Ctr Biol Evaluat & Res, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Kumar, S (reprint author), SUNY Albany, Merck Pharmaceut, W Point, PA 19486 USA. NR 37 TC 39 Z9 42 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2478 J9 IMMUNOL LETT JI Immunol. Lett. PD APR 1 PY 2002 VL 81 IS 1 BP 13 EP 24 AR PII S0165-2478(01)00316-9 DI 10.1016/S0165-2478(01)00316-9 PG 12 WC Immunology SC Immunology GA 529UR UT WOS:000174318800002 PM 11841841 ER PT J AU Elkins, KL Cooper, A Colombini, SM Cowley, SC Kieffer, TL AF Elkins, KL Cooper, A Colombini, SM Cowley, SC Kieffer, TL TI In vivo clearance of an intracellular bacterium, Francisella tularensis LVS, is dependent on the p40 subunit of interleukin-12 (IL-12) but not on IL-12 p70 SO INFECTION AND IMMUNITY LA English DT Article ID INTERFERON-GAMMA PRODUCTION; TYPE-1 CYTOKINE RESPONSES; NECROSIS-FACTOR-ALPHA; LIVE VACCINE STRAIN; IFN-GAMMA; PROTECTIVE IMMUNITY; T-CELLS; LISTERIA-MONOCYTOGENES; IL-12-DEFICIENT MICE; ADAPTIVE IMMUNITY AB To determine the role of interleukin-12 (IL-12) in primary and secondary immunity to a model intracellular bacterium, we have comprehensively evaluated infection with Francisella tularensis LVS in three murine models of IL-12 deficiency. Mice lacking the p40 protein of IL-12 (p40 knockout [KO] mice) and mice treated in vivo with neutralizing anti-IL-12 antibodies survived large doses of primary and secondary LVS infection but never cleared bacteria and exhibited a chronic infection. In dramatic contrast, mice lacking the p35 protein (p35 KO mice) of heterodimeric IL-12 readily survived large doses of primary sublethal LVS infection as well as maximal secondary lethal challenge, with only a slight delay in clearance of bacteria. LVS-immune wild-type (WT) lymphocytes produced large amounts of gamma interferon (IFN-gamma), but p35 KO and p40 KO lymphocytes produced much less; nonetheless, similar amounts of NO were found in all cultures containing immune lymphocytes, and all immune lymphocytes were equally capable of controlling intracellular growth of LVS in vitro. Purified CD4(+) and CD8(+) T cells from both WT and p40 KO mice controlled intracellular growth, even though T cells from WT mice produced much more IFN-gamma than those from p40 KO mice, and p40 KO T cells did not adopt a Th2 phenotype. Thus, while IL-12 p70 stimulation of IFN-gamma production may be important for bacteriostasis, IL-12 p70 is not necessary for appropriate development of LVS-immune T cells that are capable of controlling intracellular bacterial growth and for clearance of primary or secondary LVS infection. Instead, an additional mechanism dependent on the IL-12 p40 protein, either alone or in another complex such as the newly discovered heterodimer IL-23, appears to be responsible for actual clearance of this intracellular bacterium. C1 US FDA, Lab Mycobacteria, Div Bacterial Parasit & Allergen Prod, CBER, Rockville, MD 20852 USA. RP Elkins, KL (reprint author), US FDA, Lab Mycobacteria, Div Bacterial Parasit & Allergen Prod, CBER, 1401 Rockville Pike,HFM 431, Rockville, MD 20852 USA. NR 51 TC 97 Z9 99 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2002 VL 70 IS 4 BP 1936 EP 1948 DI 10.1128/IAI.70.4.1936-1948.2002 PG 13 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 534FE UT WOS:000174573200030 PM 11895957 ER PT J AU Szymanski, CM Burr, DH Guerry, P AF Szymanski, CM Burr, DH Guerry, P TI Campylobacter protein glycosylation affects host cell interactions SO INFECTION AND IMMUNITY LA English DT Article ID OUTER-MEMBRANE; POSTTRANSLATIONAL MODIFICATION; MYCOBACTERIUM-TUBERCULOSIS; ESCHERICHIA-COLI; IN-VIVO; JEJUNI; FLAGELLIN; PILIN; IDENTIFICATION; GENES AB Campylobacter jejuni 81-176 pgl mutants impaired in general protein glycosylation showed reduced ability to adhere to and invade INT407 cells and to colonize intestinal tracts of mice. C1 USN, Enter Dis Program, Med Res Ctr, Silver Spring, MD 20910 USA. US FDA, Beltsville, MD USA. RP Guerry, P (reprint author), USN, Enter Dis Program, Med Res Ctr, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. RI Guerry, Patricia/A-8024-2011 NR 49 TC 155 Z9 157 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 2002 VL 70 IS 4 BP 2242 EP 2244 DI 10.1128/IAI.70.4.2242-2244.2002 PG 3 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 534FE UT WOS:000174573200069 PM 11895996 ER PT J AU Lee, CJ Lee, LH Koizumi, K AF Lee, CJ Lee, LH Koizumi, K TI Polysaccharide vaccines for prevention of encapsulated bacterial infections: Part 2 SO INFECTIONS IN MEDICINE LA English DT Article DE vaccines, conjugated; Haemophilus influenzae type b; Salmonella typhi; Group B Streptococcus; Escherichia coli; Klebsiella pneumoniae; Pseudomonas aeruginosa ID INFLUENZAE TYPE-B; VI CAPSULAR POLYSACCHARIDE; PROTEIN CONJUGATE VACCINE; TETANUS-PERTUSSIS VACCINE; HEMOLYTIC UREMIC SYNDROME; ESCHERICHIA-COLI O157-H7; SALMONELLA-TYPHI; ACELLULAR PERTUSSIS; IMMUNE-RESPONSE; HIB VACCINE AB Variability in the effect of Haemophilus influenzae type b (Hib) polysaccharide vaccines led to the development of Hib conjugate vaccines. Combination vaccines with an Hib conjugate offer continued protection to infants and young children and reduce the number of injections needed. The success of Hib conjugate vaccines has led to conjugate vaccines against other encapsulated pathogens. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Lee, CJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 43 TC 3 Z9 3 U1 0 U2 2 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD APR PY 2002 VL 19 IS 4 BP 179 EP 182 PG 4 WC Infectious Diseases SC Infectious Diseases GA 543PL UT WOS:000175110300005 ER PT J AU Chowdhury, BA Meyer, RJ AF Chowdhury, BA Meyer, RJ TI Intramuscular versus subcutaneous injection of epinephrine in the treatment of anaphylaxis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. RP Chowdhury, BA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. NR 4 TC 6 Z9 6 U1 0 U2 1 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 APR PY 2002 VL 109 IS 4 BP 720 EP 720 DI 10.1067/mai.2002.123252 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 543YZ UT WOS:000175132600027 PM 11941328 ER PT J AU Kiessling, CR Cutting, JH Loftis, M Kiessling, WM Datta, AR Sofos, JN AF Kiessling, CR Cutting, JH Loftis, M Kiessling, WM Datta, AR Sofos, JN TI Antimicrobial resistance of food-related Salmonella isolates, 1999-2000 SO JOURNAL OF FOOD PROTECTION LA English DT Article ID TYPHIMURIUM DT104 INFECTIONS; UNITED-STATES; HUMANS AB Salmonellosis is a major foodborne infection in the United States, and strains of Salmonella that are resistant to a variety of antimicrobial agents have become a major public health concern. To estimate the incidence of antimicrobial-resistant Salmonella in our food supply, the U.S. Food and Drug Administration (FDA) has initiated screening of foodborne isolates for sensitivity to antimicrobial agents, including several antibiotics. Salmonella cultures (n = 502) isolated by FDA laboratories during fiscal year 2000 (1 October 1999 through 30 September 2000) from domestic and imported food products and related samples were tested for susceptibility to each of 12 antimicrobial agents using a disc diffusion assay. Because all isolates were resistant to rifampin (5 or 25 mug), only results with the remaining 11 antimicrobial agents are discussed in this paper. Of the 502 isolates, 247 (49.2%) were resistant to one or more antimicrobial agents, and of these 247 isolates, 170 (68.8%) were resistant to one antimicrobial agent, 33 (13.4%) to two antimicrobial agents, 25 (10.1%) to three antimicrobial agents, 7 (2.8%) to four antimicrobial agents, 8 (3.2%) to five antimicrobial agents, and 2 (0.8%) each to six and seven antimicrobial agents. No isolates were resistant to norfloxacin, whereas only seven were resistant to sulfamethoxazole/trimethoprim, six to trimethoprim, three to gentamicin, and one to ciprofloxacin. These results, for the first time, provide a baseline of data on the incidence of antimicrobial-resistant Salmonella in the U.S. food supply, which should be useful in determining the evolution of antimicrobial resistance in the future. C1 US FDA, Denver Fed Ctr, Denver Dist Lab, Lakewood, CO 80225 USA. US FDA, Div Field Sci, Rockville, MD 20857 USA. Colorado State Univ, Dept Anim Sci, Ft Collins, CO 80523 USA. RP Kiessling, CR (reprint author), US FDA, Denver Fed Ctr, Denver Dist Lab, PO Box 25087, Lakewood, CO 80225 USA. NR 24 TC 38 Z9 39 U1 0 U2 0 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 2002 VL 65 IS 4 BP 603 EP 608 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 541TH UT WOS:000175000200004 PM 11952207 ER PT J AU Thunberg, RL Tran, TT Bennett, RW Matthews, RN Belay, N AF Thunberg, RL Tran, TT Bennett, RW Matthews, RN Belay, N TI Microbial evaluation of selected fresh produce obtained at retail markets SO JOURNAL OF FOOD PROTECTION LA English DT Article ID BACILLUS-CEREUS; LISTERIA-MONOCYTOGENES; VEGETABLE SPROUTS; OUTBREAK; CONTAMINATION; GROWTH; FOODS; SEEDS; ENTEROTOXIN; PERSPECTIVE AB The microbial quality of five types of fresh produce obtained at the retail level was determined by standard quantitative techniques. These techniques included aerobic plate count (APC), total coliform counts, Escherichia coli counts, and yeast and mold counts. Three different methods were used to determine total coliform counts, which consisted of MacConkey agar plate counts, Colicomplete most probable number counts, and Petrifilm E. coli (EC) plate counts. The mean APCs for sprouts, lettuce, celery, cauliflower, and broccoli were 8.7, 8.6, 7.5, 7.4, and 6.3 log(10) CFU/g, respectively. MacConkey agar counts indicated that 89 to 96% of the APCs consisted of gram-negative bacteria. Yeast and mold counts were in a range expected of fresh produce. Fresh produce was also analyzed for human pathogens. Samples were analyzed for Staphylococcus spp., Bacillus spp., Salmonella spp., Listeria spp., and Campylobacter spp. One isolate of Staphylococcus was found to be enterotoxigenic, and one species of Bacillus was also toxigenic. Neither Salmonella spp. nor Campylobacter spp. were detected in any of the produce samples. A variety of Listeria spp., including Listeria monocytogenes, were found in fresh produce. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Thunberg, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 37 TC 89 Z9 94 U1 2 U2 18 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 2002 VL 65 IS 4 BP 677 EP 682 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 541TH UT WOS:000175000200016 PM 11952219 ER PT J AU Schmeisser, H Hu, RQ Kontsek, P Bekisz, J Zoon, K AF Schmeisser, H Hu, RQ Kontsek, P Bekisz, J Zoon, K TI Amino acid substitutions in loop BC and helix c affect antigenic properties of helix D in hybrid IFN-alpha 21 alpha/alpha 2c molecules SO JOURNAL OF INTERFERON AND CYTOKINE RESEARCH LA English DT Article ID HUMAN-LEUKOCYTE INTERFERON; IMMUNODOMINANT STRUCTURES; MONOCLONAL-ANTIBODIES; ANTIVIRAL ACTIVITIES; I INTERFERONS; HUMAN-CELLS; IFN-ALPHA; RESIDUES; DOMAINS; BINDING AB We compared the antigenic properties of human interferon-alpha2c (IFN-alpha2c), IFN-alpha21a, hybrids IFN-alpha21a/alpha2c, and their mutants, using a panel of 27 anti-IFN-alpha1, anti-IFN-alpha2, and anti-IFN-alpha8/1/8 monoclonal antibodies (mAb). After immunoanalysis by ELISA, we found parental IFN-alpha2c and IFN-alpha21a to be antigenically distinct. Lack of reactivity of anti-IFN-alpha1 mAb with IFN-alpha21a indicated an antigenic distinction between subtypes alpha1 and alpha21a. The antigenic properties of hybrid IFNs consisting of the N-terminal portion (1-75) of IFN-alpha21a and the C-terminal portion (76-166) of IFN-alpha2c were analyzed with mAb recognizing defined regions of IFN-alpha2c, IFN-alpha1, and IFN-alpha8/1/8. We found that extending the sequence of IFN-alpha21a up to position 95 in hybrid molecule decreased the immunoreactivity of mAb specific for the antigenic structure formed by residues similar to112-132similar to (helix D) of IFN-alpha2c. Inserting the sequence 76-81 (loop BC) of IFN-alpha2c into the sequence of 1-95 of IFN-alpha21a restored the reactivity of anti-IFN-alpha2c mAb. Some amino acid substitutions at positions 86 and 90 (helix C) of hybrid IFN-alpha21a/alpha2c also affected the immunoreactivity of C-terminal-specific mAb, which recognize helix D, but did not influence the structure of C-terminus of IFN (aa 151-165). Changes in the structure of constructs affected not only their antiproliferative activity but also their antiviral activity on human cells. C1 Slovak Acad Sci, Inst Neuroimmunol, Bratislava, Slovakia. RP Schmeisser, H (reprint author), US FDA, Div Therapeut Prot, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 36 TC 2 Z9 2 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1079-9907 J9 J INTERF CYTOK RES JI J. Interferon Cytokine Res. PD APR PY 2002 VL 22 IS 4 BP 463 EP 472 DI 10.1089/10799900252952253 PG 10 WC Biochemistry & Molecular Biology; Cell Biology; Immunology SC Biochemistry & Molecular Biology; Cell Biology; Immunology GA 551DL UT WOS:000175544200009 PM 12034029 ER PT J AU Branham, WS Dial, SL Moland, CL Hass, BS Blair, RM Fang, H Shi, LM Tong, WD Perkins, RG Sheehan, DM AF Branham, WS Dial, SL Moland, CL Hass, BS Blair, RM Fang, H Shi, LM Tong, WD Perkins, RG Sheehan, DM TI Phytoestrogens and mycoestrogens bind to the rat uterine estrogen receptor SO JOURNAL OF NUTRITION LA English DT Article DE uterus; estrogen receptor; phytoestrogen; mycoestrogen; structure-activity relationship; rats ID BREAST-CANCER CELLS; REPRODUCTIVE-TRACT; COUMESTROL; TAMOXIFEN; PROTEINS; UTERUS; DIETHYLSTILBESTROL; ZEARALENONE; ANTAGONISM; CHEMICALS AB Consumption of phytoestrogens and mycoestrogens in food products or as dietary supplements is of interest because of both the potential beneficial and adverse effects of these compounds in estrogen-responsive target tissues. Although the hazards of exposure to potent estrogens such as diethylstilbestrol in developing male and female reproductive tracts are well characterized, less is known about the effects of weaker estrogens including phytoestrogens. With some exceptions, ligand binding to the estrogen receptor (ER) predicts uterotrophic activity. Using a well-established and rigorously validated ER-ligand binding assay, we assessed the relative binding affinity (RBA) for 46 chemicals from several chemical structure classes of potential phytoestrogens and mycoestrogens. Although none of the test compounds bound to ER with the affinity of the standard, 17beta-estradiol (E-2), ER binding was found among all classes of chemical structures (flavones, isoflavones, flavanones, coumarins, chalcones and mycoestrogens). Estrogen receptor relative binding affinities were distributed across a wide range (from similar to43 to 0.00008; E-2 = 100). These data can be utilized before animal testing to rank order estimates of the potential for in vivo estrogenic activity of a wide range of untested plant chemicals (as well as other chemicals) based on ER binding. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Jefferson Labs, ROW Sci Inc, Jefferson, AR 72079 USA. RP Branham, WS (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 56 TC 103 Z9 110 U1 1 U2 14 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD APR PY 2002 VL 132 IS 4 BP 658 EP 664 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 538ZG UT WOS:000174844500006 PM 11925457 ER PT J AU Post, LO Cope, CV Farrell, DE Baker, JD Myers, MJ AF Post, LO Cope, CV Farrell, DE Baker, JD Myers, MJ TI Influence of porcine Actinobacillus pleuropneumoniae infection and dexamethasone on the pharmacokinetic parameters of enrofloxacin SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID LIQUID-CHROMATOGRAPHY; GYRASE INHIBITORS; PRESSURE; ASSAY AB The impact of Actinobacillus pleuropneumoniae (APP) infection in swine on the pharmacokinetic parameters of enrofloxacin were determined. Twenty-four animals were used in a 2 x 2 factorial of treatment groups (six animals per group) to determine the impact of APP-induced inflammation and the antiinflammatory drug dexamethasone on enrofloxacin pharmacokinetic parameters. All animals received enrofloxacin as a single intravenous dose (5 mg/kg). Administration of dexamethasone was associated with an increase in clearance of enrofloxacin Clearance of enrofloxacin was not affected by APP. Volume of distribution at steady state was significantly increased in the dexamethasone-treated pigs. Volume of distribution at steady state was decreased by APP infection. Dexamethasone significantly increased the terminal elimination half-life of enrofloxacin. APP infection decreased the terminal elimination half-life of enrofloxacin in the infected pigs. Infection and dexamethasone significantly decreased the urine enrofloxacin/creatinine and ciprofloxacin/creatinine ratios. This study shows that APP infection does affect plasma pharmacokinetic parameters. Dexamethasone and APP infection may reduce renal clearance of enrofloxacin with a compensatory increase in intestinal clearance. Neither infection nor dexamethasone altered the metabolism of enrofloxacin to ciprofloxacin, the principal metabolite of enrofloxacin. C1 US FDA, Ctr Vet Med, Res Off, Div Anim Res, Laurel, MD 20708 USA. Off Surveillance & Compliance, Div Surveillance, Rockville, MD USA. RP Myers, MJ (reprint author), US FDA, Ctr Vet Med, Res Off, Div Anim Res, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 17 TC 14 Z9 14 U1 0 U2 1 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0022-3565 J9 J PHARMACOL EXP THER JI J. Pharmacol. Exp. Ther. PD APR PY 2002 VL 301 IS 1 BP 217 EP 222 AR UNSP 4647/974300 DI 10.1124/jpet.301.1.217 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 536YV UT WOS:000174730200027 PM 11907176 ER PT J AU Wysowski, DK Swann, J Vega, A AF Wysowski, DK Swann, J Vega, A TI Use of isotretinoin (Accutane) in the United States: Rapid increase from 1992 through 2000 SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID ACNE-VULGARIS; DEPRESSION; PREGNANCY AB Background. Isotretinoin, a drug approved to treat severe recalcitrant nodular acne, has been marketed in the United States since 1982. The drug is an effective treatment for acne that is refractory to other therapies, but it is a teratogen and can cause serious side effects. Objective: Our purpose was to describe trends in the use of isotretinoin in the United States from marketing through year 2000 and summarize characteristics of patients and prescribers. Methods: Data from 2 pharmaceutical marketing research databases, the National Prescription Audit Plus and the National Disease and Therapeutic Index, and from 2 health plan networks were obtained and analyzed. Results: Retail pharmacies dispensed 19.8 million outpatient prescriptions for isotretinoin from marketing in 1982 through 2000. From 1983 through 1993, the median annual number of prescriptions was just over 800,000; between 1992 and 2000, the number of prescriptions increased 2.5-fold (250%) to nearly 2 million in year 2000. The increases registered in the health plans were somewhat larger: about 275% increases from 1995 through 1999. There is no ICD-9 code for nodulocystic acne; consequently, the type of acne treated with isotretinoin is not determinable from these data. However, between 1993 and 2000, the proportion of isotretinoin treatment for severe acne declined from 63% to 46%, whereas the proportion of treatment for mild and moderate acne increased from 31% to 49%. Data also indicated that the sex distribution of patients was nearly even, and that 63% of male patients prescribed isotretinoin were 15 to 19 years old, whereas 51% of female patients were 15 to 24 years old. Conclusion: In the last 8 years, there has been a 2.5-fold (250%) increase in the number of dispensed prescriptions for isotretinoin in the United States. Data also reveal an increasing proportion of isotretinoin use for mild and moderate acne. C1 US FDA, Off Post Mkt Drug Risk Assessment, 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. NR 15 TC 56 Z9 58 U1 0 U2 3 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 APR PY 2002 VL 46 IS 4 BP 505 EP 509 DI 10.1067/mjd.2002.120529 PG 5 WC Dermatology SC Dermatology GA 581VB UT WOS:000177313600003 PM 11907498 ER PT J AU Wilkin, J Dahl, M Detmar, M Drake, L Feinstein, A Odom, R Powell, F AF Wilkin, J Dahl, M Detmar, M Drake, L Feinstein, A Odom, R Powell, F TI Standard classification of rosacea: Report of the National Rosacea Society Expert Committee on the Classification and Staging of Rosacea SO JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY LA English DT Article ID OCULAR ROSACEA C1 US FDA, Div Dermatol & Dent Drug Prod, Rockville, MD 20857 USA. Mayo Clin Scottsdale, Dept Dermatol, Scottsdale, AZ USA. Harvard Univ, Sch Med, Dept Dermatol, Boston, MA 02115 USA. Yale Univ, Dept Med, New Haven, CT 06520 USA. Yale Univ, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. Univ Calif San Francisco, Dept Dermatol, San Francisco, CA 94143 USA. Mater Misericordiae Hosp, Reg Ctr Dermatol, Dublin 7, Ireland. RP Wilkin, J (reprint author), Natl Rosacea Soc, 800 S NW Highway,Suite 200, Barrington, IL 60010 USA. NR 9 TC 320 Z9 352 U1 6 U2 26 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 APR PY 2002 VL 46 IS 4 BP 584 EP 587 DI 10.1067/mjd.2002.120625 PG 4 WC Dermatology SC Dermatology GA 581VB UT WOS:000177313600017 PM 11907512 ER PT J AU Junod, SW Marks, L AF Junod, SW Marks, L TI Women's trials: The approval of the first oral contraceptive pill in the United States and Great Britain SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Review ID THROMBOEMBOLISM; AMERICA; DISEASE; POLICY; DRUGS C1 US FDA, Hist Off, Rockville, MD 20857 USA. Univ Cambridge, Cambridge Grp Hist Populat & Social Struct, London N19 5EU, England. RP Junod, SW (reprint author), US FDA, Hist Off, HFC-24,Room 13-51, Rockville, MD 20857 USA. NR 136 TC 32 Z9 33 U1 0 U2 2 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD APR PY 2002 VL 57 IS 2 BP 117 EP 160 DI 10.1093/jhmas/57.2.117 PG 44 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 542NT UT WOS:000175051000001 PM 11995593 ER PT J AU Markoff, L Pang, X Houng, HS Falgout, B Olsen, R Jones, E Polo, S AF Markoff, L Pang, X Houng, HS Falgout, B Olsen, R Jones, E Polo, S TI Derivation and characterization of a dengue type 1 host range-restricted mutant virus that is attenuated and highly immunogenic in monkeys SO JOURNAL OF VIROLOGY LA English DT Article ID YELLOW-FEVER VIRUS; GENOMIC RNA; NS5 PROTEIN; NUCLEOTIDE-SEQUENCE; IDENTIFICATION; REPLICATION; VACCINE; STRAIN; FLAVIVIRUSES; EXPRESSION AB We recently described the derivation of a dengue serotype 2 virus (DEN2mutF) that exhibited a host range-restricted phenotype; it was severely impaired for replication in cultured mosquito cells (C6/36 cells). DEN2mutF virus had selected mutations in genomic, sequences predicted to form a 3' stem-loop structure (3'-SL) that is conserved among all flavivirus species. The 3'-SL constitutes the downstream terminal similar to95 nucleotides of the 3' noncoding region in flavivirus RNA. Here we report the introduction of these same mutational changes into the analogous region of an infectious DNA derived from the genome of a human-virulent dengue serotype 1 virus (DEN1), strain Western Pacific (DEN1WP). The resulting DEN1 mutant (DEN1mutF) exhibited a host range-restricted phenotype similar to that of DEN2mutF virus. DEN1mutF virus was attenuated in a monkey model for dengue infection in which viremia is taken as a correlate of human virulence. In spite of the markedly reduced levels of viremia that it induced in monkeys compared to DEN1WP, DEN1mutF was highly immunogenic. In addition, DEN1mutF-immunized monkeys retained high levels of neutralizing antibodies in serum and were protected from challenge with high doses of the DEN1WP parent for as long as 17 months after the single immunizing dose. Phenotypic revertants of DEN1mutF and DEN2mutF were each detected after a total of 24 days in C6/36 cell cultures. Complete nucleotide sequence analysis of DEN1mutF RNA and that of a revertant virus, DEN1mutFRev, revealed that (i) the DEN1mutF genome contained no additional mutations upstream from the 3'-SL compared to the DEN1WP parent genome and (ii) the DEN1mutFRev genome contained de novo mutations, consistent with our previous hypothesis that the defect in DEN2mutF replication in C6/36 cells was at the level of RNA replication. A strategy for the development of a tetravalent dengue vaccine is discussed. C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Lab Vector Borne Virus Dis, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Vet Sci, Bethesda, MD 20892 USA. Walter Reed Army Inst Res, Dept Virus Dis, Silver Spring, MD 20910 USA. RP Markoff, L (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Lab Vector Borne Virus Dis, Bldg 29A,Room 1B17, Bethesda, MD 20892 USA. NR 42 TC 50 Z9 54 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 APR PY 2002 VL 76 IS 7 BP 3318 EP 3328 DI 10.1128/JVI.76.7.3318-3328.2002 PG 11 WC Virology SC Virology GA 529ZE UT WOS:000174330500025 PM 11884557 ER PT J AU Brown, SL Pennello, G AF Brown, SL Pennello, G TI Replacement surgery and silicone gel breast implant rupture: self-report by women after mammoplasty SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Article ID COMPLICATIONS; AUGMENTATION; MAMMOGRAPHY; PREVALENCE AB Background: This study examined the prevalence of revision surgery in which silicone gel breast implants were either removed (explanted) or replaced in a cohort of women from Birmingham, Alabama. The main reason leading up to the surgery and the prevalence of ruptured implants reported after explantation are described. Methods: Data were collected from telephone interviews with 907 women previously identified in a larger cohort study of women with breast implants. Women who reported breast surgeries subsequent to their index mammoplasty were asked to consent to retrieval of the surgical records describing the surgery. Results: Surgery in which a silicone gel breast implant was removed or replaced was reported by 33% of the 907 women in this cohort. The most common reason for surgery was problems with the implant that affected the breast (103 of 303 surgeries). Of the 303 women reporting surgery, 145 (48%) reported knowing after a surgery that an implant was ruptured when it was removed, and 171 (56%) reported knowing that an implant was ruptured or leaking. Overall, 16% of the 907 women reported knowing that either of their implants was ruptured after any surgery. At least one surgical record was retrieved for 165 (54%) of the 303 women reporting surgery. Among these women, the rupture rate was 69 of 165 (42%) according to the surgical record and 85 of 165 (51.5%) according to self-reports, a statistically significant difference (p = 0.008 from McNemar's test). The mean time from implantation to surgery was 11.5 years among women reporting surgery and estimated at 21.4 years for all women. Conclusions: A third of the women in this cohort underwent additional surgery after the initial mammoplasty, and nearly half who underwent surgery reported that their implants were found to be ruptured when removed. Women considering silicone gel breast implants should be informed of the risk of additional surgeries and of the potential risk of breast implant rupture. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Epidemiol Branch,Div Postmarket Surveillance, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Biostat, Rockville, MD 20857 USA. RP Brown, SL (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Epidemiol Branch,Div Postmarket Surveillance, 1350 Piccard Dr,HFZ-541, Rockville, MD 20857 USA. NR 30 TC 12 Z9 12 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD APR PY 2002 VL 11 IS 3 BP 255 EP 264 DI 10.1089/152460902753668457 PG 10 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 546YB UT WOS:000175303000008 PM 11988135 ER PT J AU Wood, SF AF Wood, SF TI Sea differences in drug metabolism - What's in the label? SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Meeting Abstract C1 US FDA, Off Womens Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD APR PY 2002 VL 11 IS 3 MA S14 BP 312 EP 312 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 546YB UT WOS:000175303000028 ER PT J AU Patterson, NK Wood, SF AF Patterson, NK Wood, SF TI Fda monitors participation by women in clinical studies SO JOURNAL OF WOMENS HEALTH & GENDER-BASED MEDICINE LA English DT Meeting Abstract C1 US FDA, Off Womens Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1524-6094 J9 J WOMEN HEALTH GEN-B JI J. WOMENS HEALTH GENDER-BASED MED. PD APR PY 2002 VL 11 IS 3 MA P17 BP 321 EP 321 PG 1 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Obstetrics & Gynecology; Women's Studies SC Public, Environmental & Occupational Health; General & Internal Medicine; Obstetrics & Gynecology; Women's Studies GA 546YB UT WOS:000175303000057 ER PT J AU Zheng, Q AF Zheng, Q TI Statistical and algorithmic methods for fluctuation analysis with SALVADOR as an implementation SO MATHEMATICAL BIOSCIENCES LA English DT Article; Proceedings Paper CT Annual Conference of the Society-for-Mathematical-Biology CY JUL 16-19, 2001 CL HILO, HAWAII SP Soc Math Biol DE fluctuation experiment; directed mutation controversy; Fisher's information; estimation of mutation rate ID LURIA-DELBRUCK DISTRIBUTION; MUTATION-RATES; DIRECTED MUTATION; ESCHERICHIA-COLI; MUTANTS; POPULATIONS; NUMBER; EVOLUTION AB This paper aims at removing certain long-standing impediments to more effective and widespread use of fluctuation analysis. The paper presents a method of constructing confidence intervals for mutation rates using data from fluctuation experiments. The method was inspired by a rediscovery of a little-known, not fully developed method of Lea and Coulson; substantial modifications have been made both to enhance computational efficiency and to widen the scope of the original method's applicability. A computer package named SALVADOR is presented that can be used for Monte Carlo simulation, for point and interval estimation of mutation rates, and for exploration of various hypotheses spawned by the directed mutation controversy. In addition to the maximum likelihood method, methods of considerable historical interest are also examined and included in SALVADOR to help the reader compare and assess some of the most popular methods for estimating mutation rates. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Zheng, Q (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT-20,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 29 TC 42 Z9 43 U1 0 U2 5 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 APR PY 2002 VL 176 IS 2 BP 237 EP 252 AR PII S0025-5564(02)00087-1 DI 10.1016/S0025-5564(02)00087-1 PG 16 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA 542DN UT WOS:000175028400005 PM 11916511 ER PT J AU White, DG Zhao, SH Simjee, S Wagner, DD McDermott, PF AF White, DG Zhao, SH Simjee, S Wagner, DD McDermott, PF TI Antimicrobial resistance of foodborne pathogens SO MICROBES AND INFECTION LA English DT Article DE antibiotic resistance; food borne pathogens ID ESCHERICHIA-COLI O157; YERSINIA-ENTEROCOLITICA; ANTIBIOTIC-RESISTANCE; CAMPYLOBACTER-JEJUNI; LISTERIA-MONOCYTOGENES; UNITED-STATES; IN-VITRO; STRAINS; FOOD; SUSCEPTIBILITIES AB Emergence of bacterial antimicrobial resistance has become a serious problem worldwide. While much of the resistance observed in human medicine is attributed to inappropriate use in humans, there is increasing evidence that antimicrobial use in animals selects for resistant foodborne pathogens that may be transmitted to humans as food contaminants. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP White, DG (reprint author), US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. NR 50 TC 125 Z9 142 U1 2 U2 10 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2002 VL 4 IS 4 BP 405 EP 412 AR PII S1286-4579(02)01554-X DI 10.1016/S1286-4579(02)01554-X PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 544KU UT WOS:000175157400003 PM 11932191 ER PT J AU Hall, RH AF Hall, RH TI Biosensor technologies for detecting microbiological foodborne hazards SO MICROBES AND INFECTION LA English DT Article DE biosensing techniques; pathogen; biotechnology; food microbiology ID SURFACE-PLASMON RESONANCE; SALMONELLA-TYPHIMURIUM; RAPID DETECTION; REAL-TIME; FOOD; IMMUNOSENSORS; PATHOGENS; PRINCIPLES; TRANSDUCER; AFFINITY AB The convergence of molecular biology and miniaturized instrumentation has accelerated development of biosensors with the specifications necessary to support pathogen reduction and quality programs in the food supply. Advances in optoelectronics, thin layer deposition, and microfabrication have provided many options for achieving microbiological detection goals. Some promising technologies are reviewed. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 US FDA, Ctr Food Safety & Appl Nutr, DVA, Washington, DC 20204 USA. RP Hall, RH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, DVA, HFS 327,200 C St SW, Washington, DC 20204 USA. NR 46 TC 57 Z9 58 U1 0 U2 8 PU EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER PI PARIS CEDEX 15 PA 23 RUE LINOIS, 75724 PARIS CEDEX 15, FRANCE SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD APR PY 2002 VL 4 IS 4 BP 425 EP 432 AR PII S1286-4579(02)01556-3 DI 10.1016/S1286-4579(02)01556-3 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 544KU UT WOS:000175157400005 PM 11932193 ER PT J AU McCardell, BA Sathyamoorthy, V Michalski, J Lavu, S Kothary, M Livezey, J Kaper, JB Hall, R AF McCardell, BA Sathyamoorthy, V Michalski, J Lavu, S Kothary, M Livezey, J Kaper, JB Hall, R TI Cloning, expression and characterization of the CHO cell elongating factor (Cef) from Vibrio cholerae O1 SO MICROBIAL PATHOGENESIS LA English DT Article DE CHO; elongation; cytotonic; Vibrio; Pichia expression ID ENTEROTOXIN ACE; VACCINE STRAIN; CVD103-HGR; TOXIN; SEQUENCE; PROTEINS AB CHO cell-elongating factor (Cef) is a recently identified putative virulence factor of Vibrio cholerae. Our previous studies show that this 85 kDa protein elongates CHO cells, causes fluid accumulation in suckling mice and has esterase activity. In this study, the cef gene was cloned in Escherichia coli using a yeast vector and subsequently expressed in the yeast Pichia pastoris. The cef genes from V. cholerae candidate vaccine strains JBK 70 and CVD 103-HgR were sequenced and found to be nearly identical (100 and 99.9% respectively) with an open reading frame (ORF) from the published sequence of V. cholerae N16961. Cloned toxin was purified to homogeneity in 3 steps using anion exchange, hydrophobic interaction and gel filtration chromatography. The size of cloned Cef on SDS-PAGE gels was 114 kDa. The increased size was probably due to glycosylation by the yeast since cloned protein reacted strongly with a glycoprotein stain. The cloned protein could not be directly sequenced, but when treated with trypsin, yielded a protein fragment with an amino acid sequence that matched the sequence predicted for the Cef protein. The purified cloned protein had esterase and CHO cell activity, but no suckling mouse activity. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 US FDA, Div Virulence Assessment, Washington, DC 20204 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP McCardell, BA (reprint author), US FDA, Div Virulence Assessment, Washington, DC 20204 USA. OI Kaper, James/0000-0003-0715-2907 NR 22 TC 3 Z9 8 U1 0 U2 2 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0882-4010 J9 MICROB PATHOGENESIS JI Microb. Pathog. PD APR PY 2002 VL 32 IS 4 BP 165 EP 172 DI 10.1006/mpat.2001.0492 PG 8 WC Immunology; Microbiology SC Immunology; Microbiology GA 565QW UT WOS:000176381800002 PM 12079406 ER PT J AU Ge, B Larkin, C Ahn, S Jolley, M Nasir, M Meng, J Hall, RH AF Ge, B Larkin, C Ahn, S Jolley, M Nasir, M Meng, J Hall, RH TI Identification of Escherichia coli O157 : H7 and other enterohemorrhagic serotypes by EHEC-hlyA targeting, strand displacement amplification, and fluorescence polarization SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE rapid detection; enterohemorrhagic E coli; strand displacement amplification; fluorescence polarization ID HEMOLYTIC-UREMIC SYNDROME; MYCOBACTERIUM-TUBERCULOSIS DNA; SHIGA TOXIN; HEMORRHAGIC COLITIS; UNITED-STATES; DIARRHEA; OUTBREAK; STRAINS; CONTAMINATION; INFECTION AB Human disease caused by enterohemorrhagic E. coli O157:H7 and other serotypes (EHEC) has been associated with bovine fecal contamination of food and the environment. The range of serotypes, low infectious dose, and numerous transmission vehicles for EHEC render development of detection methods for this pathogen complex. In this study, the hemolysin gene (EHEC-hlyA) was targeted with oligonucleoticles, and probe-target hybrids were amplified using strand displacement amplification (SDA). Amplicons were resolved in the complete reaction mix through changes in the fluorescence polarization (FP) of a fluorescein-labeled detector probe hybridized to the amplicons during amplification. Results combining EHEC-hlyA, SDA, and FP were obtained within 35 min of reaction initiation. The test specificity was determined on EHEC strains representing 13 serotypes (49 isolates); and control uropathogenic, commensal, and other organisms (10 isolates). Statistical analysis of results indicated a sensitivity in the reaction vessel to 4.3 bacteria (95% confidence interval), and a specificity for EHEC (n=59) at 100% (P=5.11 E-17; i.e. Pmuch less than0.05). Detection based on combining EHEC-hlyA, SDA, and FP was compatible with water sources directly associated with human infection (drinking and recreational Supplies), and bovine drinking trough water representing an environmental matrix linked to the maintenance of an EHEC animal reservoir. (C) 2002 Elsevier Science Ltd. C1 US FDA, CFSAN, DVA, Washington, DC 20204 USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Diachemix Corp, Grayslake, IL 60030 USA. RP Hall, RH (reprint author), US FDA, CFSAN, DVA, HFS 327,200 C St SW, Washington, DC 20204 USA. NR 35 TC 15 Z9 18 U1 1 U2 5 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0890-8508 J9 MOL CELL PROBE JI Mol. Cell. Probes PD APR PY 2002 VL 16 IS 2 BP 85 EP 92 DI 10.1006/mcpr.2001.0389 PG 8 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 568RH UT WOS:000176556200001 PM 12030758 ER PT J AU Christopher, SA Melnyk, S James, SJ Kruger, WD AF Christopher, SA Melnyk, S James, SJ Kruger, WD TI S-adenosylhomocysteine, but not homocysteine, is toxic to yeast lacking cystathionine beta-synthase SO MOLECULAR GENETICS AND METABOLISM LA English DT Article ID PLASMA TOTAL HOMOCYSTEINE; SACCHAROMYCES-CEREVISIAE; CARDIOVASCULAR-DISEASE; HORDALAND-HOMOCYSTEINE; DNA HYPOMETHYLATION; METABOLISM; ADENOSYLMETHIONINE; INHIBITION; CYSTEINE; TISSUES AB Elevated plasma homocysteine is associated with a variety of diseases in humans including coronary heart disease, stroke, peripheral vascular disease, and birth defects. However, the mechanism by which plasma homocysteine affects cells is unknown. We have examined the growth of isogenic wild-type and cystathionine beta-synthase (CBS) deficient yeast in response to homocysteine and its immediate metabolic precursor, S-adenosylhomocysteine (SAH). CBS deficient yeast export significantly more homocysteine into the media than wild-type yeast and have elevated internal pools of homocysteine and SAH. We found that 5 mM homocysteine added to the media had very little effect on the growth of wild-type or CBS deficient yeast, although intracellular homocysteine concentrations increased five- to tenfold. In contrast, as little as 25 muM S-adenosylhomocysteine inhibited the growth of CBS deficient yeast, but had no effect on wild-type yeast. Measurements of the intracellular S-adenosylmethionine (SAM) and SAH indicate that CBS deficient yeast contain reduced SAM/SAH ratios relative to wild-type, and this ratio is further reduced by adding SAH to the media. Growth inhibition by SAH in CBS deficient yeast can be totally reversed by addition of SAM to the media, indicating that the ratio and not absolute level is critical for cell growth. These results suggest that CBS plays a key role in the regulation of the SAM/SAH ratio inside cells and that excessive perturbations of this ratio can inhibit growth. We hypothesize that elevated extracellular homocysteine present in humans may reflect an altered intracellular SAM/SAH ratio and that this may be related to disease pathogenesis. (C) 2002 Elsevier Science (USA). All rights reserved. C1 Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Fox Chase Canc Ctr, Div Populat Sci, 7701 Burholme Ave, Philadelphia, PA 19111 USA. EM wd_kruger@fccc.edu RI kruger, warren/A-6407-2008 OI kruger, warren/0000-0002-4990-3695 FU NCI NIH HHS [CA06927]; NHLBI NIH HHS [HL57299] NR 27 TC 20 Z9 21 U1 0 U2 0 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1096-7192 EI 1096-7206 J9 MOL GENET METAB JI Mol. Genet. Metab. PD APR PY 2002 VL 75 IS 4 BP 335 EP 343 AR PII S1096-7192(02)00003-3 DI 10.1016/S1096-7192(02)00003-3 PG 9 WC Endocrinology & Metabolism; Genetics & Heredity; Medicine, Research & Experimental SC Endocrinology & Metabolism; Genetics & Heredity; Research & Experimental Medicine GA 552QP UT WOS:000175631300006 PM 12051965 ER PT J AU Feigal, DW AF Feigal, DW TI FDA public health notification: Reducing radiation risk from computed tomography for pediatric and small adult patients SO PEDIATRIC RADIOLOGY LA English DT Article ID HELICAL CT C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Feigal, DW (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 16 TC 30 Z9 31 U1 0 U2 0 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0301-0449 J9 PEDIATR RADIOL JI Pediatr. Radiol. PD APR PY 2002 VL 32 IS 4 BP 314 EP 316 DI 10.1007/s00247-002-0687-6 PG 3 WC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging SC Pediatrics; Radiology, Nuclear Medicine & Medical Imaging GA 547UN UT WOS:000175350800022 ER PT J AU Roman, DG Rodriguez, WJ Roberts, R Orloff, DG Murphy, D AF Roman, DG Rodriguez, WJ Roberts, R Orloff, DG Murphy, D TI Early evidence of the public health impact generated by the Pediatric Rule SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 US FDA, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 687 BP 118A EP 118A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714600688 ER PT J AU Cooper, WO Staffa, JA Renfrew, JW Graham, DJ Ray, WA AF Cooper, WO Staffa, JA Renfrew, JW Graham, DJ Ray, WA TI Systemic corticosteroid use among children enrolled in TennCare SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Vanderbilt Univ, Nashville, TN USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 756 BP 130A EP 130A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714600757 ER PT J AU Harris, PL West, A Rodriguez, W Kaplan, EI AF Harris, PL West, A Rodriguez, W Kaplan, EI TI High prevalence of GA beta HS in elementary school, low income, immigrant children SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Washington, DC 20010 USA. Catholic Univ Amer, Sch Nurse Practitioner Program, Washington, DC 20064 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Minnesota, Minneapolis, MN USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 926 BP 159A EP 159A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714600926 ER PT J AU Englert, RP Shacter, EB AF Englert, RP Shacter, EB TI Effects on mode of cell death in B lymphoma cells induced by different oxidants SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 USUHS, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 2750 BP 472A EP 472A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714602748 ER PT J AU Alexander, JJ Colangelo, PM Cooper, CK Roberts, R Rodriguez, WJ Murphy, D AF Alexander, JJ Colangelo, PM Cooper, CK Roberts, R Rodriguez, WJ Murphy, D TI Amoxicillin (AMOX) for post-exposure inhalation anthrax (PEIA) in pediatrics: FDA perspective SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 2776 BP 476A EP 476A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714602774 ER PT J AU Hirschfield, S Alexander, J Birenbaum, D Johann-Liang, R Rodriguez, W Shetty, D Murphy, D AF Hirschfield, S Alexander, J Birenbaum, D Johann-Liang, R Rodriguez, W Shetty, D Murphy, D TI Extrapolation (extrapol) from adult efficacy data in pediatric therapeutics (ped ther): FDA analysis of current evidence SO PEDIATRIC RESEARCH LA English DT Meeting Abstract C1 US FDA, CDER, Off Pediat, Rockville, MD 20857 USA. RI Hirschfeld, Steven/E-2987-2016 OI Hirschfeld, Steven/0000-0003-0627-7249 NR 0 TC 0 Z9 0 U1 0 U2 1 PU INT PEDIATRIC RESEARCH FOUNDATION, INC PI BALTIMORE PA 351 WEST CAMDEN ST, BALTIMORE, MD 21201-2436 USA SN 0031-3998 J9 PEDIATR RES JI Pediatr. Res. PD APR PY 2002 VL 51 IS 4 SU S MA 2786 BP 478A EP 478A PN 2 PG 1 WC Pediatrics SC Pediatrics GA 536RA UT WOS:000174714602784 ER PT J AU Williams, RL Adams, WP Poochikian, G Hauck, WW AF Williams, RL Adams, WP Poochikian, G Hauck, WW TI Content uniformity and dose uniformity: Current approaches, statistical analyses, and presentation of an alternative approach, with special reference to oral inhalation and nasal drug products SO PHARMACEUTICAL RESEARCH LA English DT Review DE inhalation drug products; nasal drug products; content uniformity; dose uniformity; tolerance intervals ID BIOEQUIVALENCE AB This article reviews current and proposed approaches to content uniformity testing. In addition, the article proposes an approach that allows regulatory agencies and compendia to clearly state allowable consumer risk. Further, the article suggests that producers be allowed to control producer risk through selection of numbers of units and testing tiers. The approach facilitates risk communication to practitioners and patients/consumers, which is impeded with current approaches, and reduces regulatory and compendial burden. C1 Thomas Jefferson Univ, Biostat Sect, Philadelphia, PA 19107 USA. US Pharmacopeia, Rockville, MD 20852 USA. US FDA, Off New Drug Chem, Ctr Drug Evaluat & Res, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Hauck, WW (reprint author), Thomas Jefferson Univ, Biostat Sect, Philadelphia, PA 19107 USA. NR 32 TC 14 Z9 14 U1 1 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD APR PY 2002 VL 19 IS 4 BP 359 EP 366 AR UNSP 0724-8741/02/0400-0359/0 DI 10.1023/A:1015114821387 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 549QT UT WOS:000175457000001 PM 12033365 ER PT J AU Vath, P Wamer, WG Falvey, DE AF Vath, P Wamer, WG Falvey, DE TI Photochemistry and phototoxicity of aloe emodin SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID EXCITED SINGLET-STATE; MOLECULAR-OXYGEN; QUANTUM YIELDS; HYPERICIN; ELECTRON; DNA; PHOTONUCLEASES; KINETICS; RADICALS; AGENT AB Photochemical pathways leading to the phototoxicity of the aloe vera constituent aloe emodin were studied. The results indicate a photochemical mechanism involving singlet oxygen to be the most likely pathway responsible for the observed phototoxicity. Aloe emodin was found to efficiently generate singlet oxygen when irradiated with UV light (phi(Delta) = 0.56 in acetonitrile). The survival of human skin fibroblast cells in the presence of aloe emodin was found to decrease upon irradiation with UV light. A further decrease in cell survival was observed in DO compared with H2O, suggesting the involvement of singlet oxygen as the primary pathway. Laser flash photolysis experiments were also carried out on aloe emodin alone and in the presence of various biological substrates. Aloe emodin proved to be relatively photostable ((D = 1 x 10(-4)) and a poor photo-oxidant (E*(red) = +1.02 V). Only absorption bands caused by the triplet state of aloe emodin (lambda(max) = 480 nm) and the aloe emodin conjugate base lambda(max) = 520 nm) were observed in the transient spectra. C1 Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Falvey, DE (reprint author), Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. RI Falvey, Daniel/B-7817-2009 NR 27 TC 19 Z9 23 U1 0 U2 8 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 APR PY 2002 VL 75 IS 4 BP 346 EP 352 DI 10.1562/0031-8655(2002)075<0346:PAPOAE>2.0.CO;2 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 542HY UT WOS:000175038500004 PM 12003123 ER PT J AU Gaylor, DW Kodell, RL AF Gaylor, DW Kodell, RL TI A procedure for developing risk-based reference doses SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE probabilistic reference dose (RfD); risk estimation; uncertainty factors ID UNCERTAINTY FACTORS; HEALTH RISKS AB Reference doses (RfDs) for toxic substances based on a no observed adverse effect level (NOAEL) or lowest observed adverse effect level (LOAEL) are established to restrict human exposures to only nontoxic or minimally toxic levels. In order to calculate a risk-based RfD, for the point of departure it is necessary to replace a NOAEL or LOAEL by a benchmark dose (BMD) estimated to be associated with a specified level of estimable risk in or near the low end of an experimental dose range. Then the RfD is calculated by dividing the BMD by a series of uncertainty factors. Among these uncertainty factors is one for interindividual sensitivity, typically assigned a value of 10. If information is available on interindividual sensitivity, this default factor can be replaced with a factor expected to provide protection for a specified proportion of a population. Examination of published databases suggests interindividual effects often to be approximately log-normal. For example, in order to illustrate the procedure for establishing a risk-based RfD, a standard deviation of the logarithm (base e) of individual sensitivity of 1.7 was selected, i.e., a factor of 5.5. This value is near the upper range of values reported in the literature (D. Hattis et al., 1999, in Characterizing Human Variability in the Risk Assessment Process, ILSI Press, Washington, DC). Using this information in combination with an RfD based on a benchmark dose associated with a specified level of risk, the risk at the RfD can be estimated. For example, a benchmark dose associated with a risk of 10% divided by 60, to account for interindividual variation, is expected to limit risk at the RfD to about 1 in 10,000. If the standard deviation of the logarithm (base e) of individual sensitivity is 1.2, a more typical value, the divisor is approximately 20. These would replace an RfD having an unknown risk based on the LOAEL divided by 100. Or, an RfD with a specified level of risk could be estimated. The estimate of risk can be improved for a specific case by replacing an overall estimate of the standard deviation for interindividual variability by an estimate of the standard deviation for a particular class of chemicals and/or biological endpoint, if available. Risks can be substantially lower for smaller values of interindividual variability. Determination of an RfD still would require an additional uncertainty factor for animal to human extrapolation. (C) 2002 Elsevier Science (USA). C1 Sci Int Inc, Alexandria, VA 22314 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gaylor, DW (reprint author), Sci Int Inc, Alexandria, VA 22314 USA. NR 13 TC 24 Z9 24 U1 1 U2 2 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD APR PY 2002 VL 35 IS 2 BP 137 EP 141 DI 10.1006/rtph.2002.1533 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 566JY UT WOS:000176425700001 PM 12051999 ER PT J AU Hope, BK Baker, AR Edel, ED Hogue, AT Schlosser, WD Whiting, R McDowell, RM Morales, RA AF Hope, BK Baker, AR Edel, ED Hogue, AT Schlosser, WD Whiting, R McDowell, RM Morales, RA TI An overview of the Salmonella Enteritidis risk assessment for shell eggs and egg products SO RISK ANALYSIS LA English DT Article DE microbial risk assessment; Salmonella; shell eggs; human health; probabilistic assessment ID UNITED-STATES; FOODBORNE DISEASE; INFECTIONS; TYPHIMURIUM; OUTBREAKS; GROWTH; HENS AB This article summarizes a quantitative microbial risk assessment designed to characterize the public health impact of consumption of shell eggs and egg products contaminated with Salmonella Enteritidis (SE). This risk assessment's objectives were to: (1) establish the baseline risk of foodborne illness from SE, (2) identify and evaluate potential risk mitigation strategies, and (3) identify data gaps related to future research efforts. The risk assessment model has five modules. The Egg Production module estimates the number of eggs produced that are SE-contaminated. Shell Egg Processing, Egg Products Processing, and Preparation & Consumption modules estimate the increase or decrease in the numbers of SE organisms in eggs or egg products as they pass through storage, transportation, processing, and preparation. A Public Health Outcomes module then calculates the incidence of illnesses and four clinical outcomes, as well as the cases of reactive arthritis associated with SE infection following consumption. The baseline model estimates an average production of 2.3 million SE-contaminated shell eggs/year of the estimated 69 billion produced annually and predicts an average of 661,633, human illnesses per year from consumption of these eggs. The model estimates approximate to 94% of these cases recover without medical care, 5% visit a physician, an additional 0.5% are hospitalized, and 0.05% result in death. The contribution of SE from commercially pasteurized egg products was estimated to be negligible. Five mitigation scenarios were selected for comparison of their individual and combined effects on the number of human illnesses. Results suggest that mitigation in only one segment of the farm-to-table continuum will be less effective than several applied in different segments. Key data gaps and areas for future research include the epidemiology of SE on farms, the bacteriology of SE in eggs, human behavior in food handling and preparation, and human responses to SE exposure. C1 USDA, Food Safety & Inspect Serv, Washington, DC 20250 USA. USDA, Food Safety & Inspect Serv, Ft Collins, CO USA. USDA, Food Safety & Inspect Serv, College Stn, TX USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. USDA, Anim & Plant Hlth Inspect Serv, Riverdale, MD USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Hope, BK (reprint author), Oregon Dept Environm Qual, 1030 SE 54th Ave, Portland, OR USA. NR 31 TC 54 Z9 54 U1 0 U2 7 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 APR PY 2002 VL 22 IS 2 BP 203 EP 218 DI 10.1111/0272-4332.00023 PG 16 WC Public, Environmental & Occupational Health; Mathematics, Interdisciplinary Applications; Social Sciences, Mathematical Methods SC Public, Environmental & Occupational Health; Mathematics; Mathematical Methods In Social Sciences GA 552PU UT WOS:000175629400003 PM 12022671 ER PT J AU Weaver, JL Broud, DD McKinnon, K Germolec, DR AF Weaver, JL Broud, DD McKinnon, K Germolec, DR TI Serial phenotypic analysis of mouse peripheral blood leukocytes SO TOXICOLOGY MECHANISMS AND METHODS LA English DT Article DE leukocyte; mouse; peripheral blood; phenotypic analysis; repeat sampling ID FLOW-CYTOMETRY; INTERLABORATORY EVALUATION; LYMPHOCYTE; QUANTIFICATION; INJURY; CELLS; MICE AB Repeated phenotypic analysis of mouse peripheral blood leukocytes over short periods of time (2 weeks) has been difficult because of the very limited volumes of blood available under guidelines of the Institutional Animal Care and Use Committee. The loss of leukocytes and variations among laboratories during conventional flow cytometry sample preparation based on lysing and repeated washing have been limiting factors when measuring multiple parameters in small samples. We describe a method of phenotypic analysis using a no-lyse, no-wash staining technique combined with fluorescent triggering for data collection that can be performed on volumes of 20 muL or less of whole blood per set of markers in one tube. This method allows repeated phenotypic analysis of peripheral whole blood from mice. Fluorescent triggering with anti-CD45-PE/Cy5 antibody allows high-quality phenotypic data to be collected for CD4, CD8, TcR-beta, CD45R (B220), CD11b, and Gr-1 epitopes on leukocytes from mouse peripheral blood without lysis. The markers selected cover the major populations in peripheral mouse blood. Reproducibility and time-course data are presented for sampling periods as long as 4 weeks. Data produced by flow cytometers manufactured by two different companies show well-correlated results. An instrument equipped with a gated amplifier or a photomultiplier tube suitable for Cy7 conjugates could measure additional parameters. Because of interference from unlysed erythrocytes, scatter parameters are not useful for identifying cell populations with this method. C1 US FDA, Div Appl Pharmacol Res, Off Testing & Res, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. Celera Genom Inc, Rockville, MD USA. NIEHS, Toxicol Lab, Natl Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Weaver, JL (reprint author), US FDA, Div Appl Pharmacol Res, Off Testing & Res, Ctr Drug Evaluat & Res, MOD-1,8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 13 TC 6 Z9 8 U1 0 U2 2 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1537-6524 J9 TOXICOL MECH METHOD JI Toxicol. Mech. Methods PD APR-JUN PY 2002 VL 12 IS 2 BP 95 EP 118 DI 10.1080/10517230290075341 PG 24 WC Toxicology SC Toxicology GA 555MX UT WOS:000175798800001 PM 20021196 ER PT J AU Bonnel, RA Villalba, ML Karwoski, CB Beitz, J AF Bonnel, RA Villalba, ML Karwoski, CB Beitz, J TI Aseptic meningitis associated with rofecoxib SO ARCHIVES OF INTERNAL MEDICINE LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; IBUPROFEN AB Rofecoxib is a nonsteroidal anti-inflammatory drug that is reported to act by selectively inhibiting cyclooxygenase-2. A review and analysis of reports sent to the Spontaneous Reporting System of the Food and Drug Administration, Rockville, Md, suggest that aseptic meningitis is associated with rofecoxib use. To our knowledge, there have been no published reports of aseptic meningitis occurring in association with rofecoxib use to date. We report 5 serious cases of aseptic meningitis associated with rofecoxib use. C1 US FDA, Ctr Drug Evaluat & Res, Off Postmkt Drug Risk Assessment, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Div Antiinflammatory Analges & Ophthalm Drug Prod, Rockville, MD 20857 USA. RP Bonnel, RA (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Postmkt Drug Risk Assessment, 560 Fishers Ln,Room 15B-23,HFD-430, Rockville, MD 20857 USA. NR 17 TC 22 Z9 23 U1 0 U2 0 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 MAR 25 PY 2002 VL 162 IS 6 BP 713 EP 715 DI 10.1001/archinte.162.6.713 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 530YL UT WOS:000174387100013 PM 11911727 ER PT J AU Apte, UM Limaye, P Bucci, TJ Mehendale, HM AF Apte, UM Limaye, P Bucci, TJ Mehendale, HM TI Molecular mechanisms of enhanced liver regeneration upon toxic challenge in diet restricted SO FASEB JOURNAL LA English DT Meeting Abstract C1 NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. NCTR, Pathol Associates Inc, Jefferson, AR 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 22 PY 2002 VL 16 IS 5 BP A945 EP A946 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593901224 ER PT J AU Constable, PD Waggoner, AL Tumbleson, ME Smith, GW Foreman, JH Eppley, RM Haschek, WM AF Constable, PD Waggoner, AL Tumbleson, ME Smith, GW Foreman, JH Eppley, RM Haschek, WM TI Sphingolipid alterations following intravenous fumonisin B-1 administration to horses: correlation with neurotoxicity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Illinois, Urbana, IL 61801 USA. USFDA, Washington, DC 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 22 PY 2002 VL 16 IS 5 BP A887 EP A887 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593900892 ER PT J AU Huang, LYC Aliberti, J Inoue, S Mikolajczyk, M Golding, B AF Huang, LYC Aliberti, J Inoue, S Mikolajczyk, M Golding, B TI Role of dendritic cell-derived IFN-gamma in response to a microbial stimulus SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, CBER, DH, Rockville, MD 20852 USA. NIAID, LPD, NIH, 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 22 PY 2002 VL 16 IS 5 BP A1230 EP A1230 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593902794 ER PT J AU Jung, JI Khachik, F Kim, EJ Park, JHY AF Jung, JI Khachik, F Kim, EJ Park, JHY TI Lycopene inhibits cell growth and decreases the levels of ErbB2 and ErbB3 in human colon cancer HT-29 cells. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Hallym Univ, Div Life Sci, Chunchon 20072, South Korea. Univ Maryland, Joint Inst Food Safety & Appl Nutr, Dept Chem & Biochem, College Pk, MD 20742 USA. RI Khachik, Frederick/C-5055-2009 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 22 PY 2002 VL 16 IS 5 BP A1006 EP A1006 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593901550 ER PT J AU Limaye, PB Apte, UM Bucci, TJ Mehendale, HM AF Limaye, PB Apte, UM Bucci, TJ Mehendale, HM TI Involvement of calpain and phospholipase A2 in progression of liver injury initiated by toxic insult. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NE Louisiana Univ, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. NCTR, Pathol Associates Int, Jefferson, AR USA. NR 0 TC 1 Z9 1 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 22 PY 2002 VL 16 IS 5 BP A946 EP A946 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593901225 ER PT J AU Shankar, K Vaidya, VS Manautou, JE Ronis, MJ Corton, JC Bucci, TJ Mehendale, HM AF Shankar, K Vaidya, VS Manautou, JE Ronis, MJ Corton, JC Bucci, TJ Mehendale, HM TI Activation of PPAR-alpha: A protective mechanism against acetaminophen hepatotoxicity in diabetes. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NE Louisiana Univ, Monroe, LA 71209 USA. Univ Connecticut, Storrs, CT USA. Arkansas Childrens Hosp, Inst Res, Little Rock, AR 72202 USA. CIIT Ctr Hlth Res, Res Triangle Pk, NC USA. NCTR, Pathol Associates Int, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 1 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 22 PY 2002 VL 16 IS 5 BP A945 EP A945 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593901223 ER PT J AU Vaidya, VS Shankar, K Chen, MZ Lock, EA Bucci, TJ Mehendale, HM AF Vaidya, VS Shankar, K Chen, MZ Lock, EA Bucci, TJ Mehendale, HM TI Tissue repair as a mechanism of protection from acute renal failure. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NE Louisiana Univ, Monroe, LA 71209 USA. Syngenta, Cent Toxicol Lab, Macclesfield, Cheshire, England. NCTR, Pathol Associates Int, Jefferson, AR 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 22 PY 2002 VL 16 IS 5 BP A957 EP A957 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593901287 ER PT J AU Wang, JH Guan, E Roderiquez, G Calvert, V Alvarez, R Norcross, M AF Wang, JH Guan, E Roderiquez, G Calvert, V Alvarez, R Norcross, M TI Ligand-independent, tyrosine phosphorylation dependent sequestration of CXCR4 in human primary monocytes-macrophages SO FASEB JOURNAL LA English DT Meeting Abstract C1 CBER, DTP, 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 22 PY 2002 VL 16 IS 5 BP A901 EP A902 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593900977 ER PT J AU Wray-Cahen, D Karanian, JW Carmody, KB Vossoughi, J Abii, PO Pritchard, WF AF Wray-Cahen, D Karanian, JW Carmody, KB Vossoughi, J Abii, PO Pritchard, WF TI Female pigs recover more rapidly from general anesthesia with isoflurane than males SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Laurel, MD 20708 USA. Biomed Res Fdn, Washington, DC 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 22 PY 2002 VL 16 IS 5 BP A836 EP A837 PN 2 PG 2 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 534PC UT WOS:000174593900617 ER PT J AU Baldwin, A Wiley, EB Alayash, A AF Baldwin, A Wiley, EB Alayash, A TI Comparison of effects of two hemoglobin-based oxygen carriers on intestinal integrity and microvascular leakage SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Arizona, Tucson, AZ USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 1 Z9 1 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 20 PY 2002 VL 16 IS 4 BP A511 EP A511 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533602830 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 FASEB JOURNAL LA English DT Meeting Abstract C1 Emory Univ, Rollins Sch Publ Hlth, Atlanta, GA 30322 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Ctr Dis Control & Prevent, Div Nutr & Phys Act, Atlanta, GA USA. RI Martorell, Reynaldo /I-2539-2012 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 20 PY 2002 VL 16 IS 4 BP A607 EP A607 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533603375 ER PT J AU Esfandiari, F Miller, JW Green, R Cotterman, RF Pogribny, IP James, SJ AF Esfandiari, F Miller, JW Green, R Cotterman, RF Pogribny, IP James, SJ TI Hepatic methyl-CpG-binding protein 2 (MeCP2) is reduced in rats fed a tumorigenic methyl-deficient diet SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif Davis, Sacramento, CA 95817 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 20 PY 2002 VL 16 IS 4 BP A264 EP A264 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601461 ER PT J AU Ge, H Chuang, E Zhao, SP Temenak, JJ Ching, WM AF Ge, H Chuang, E Zhao, SP Temenak, JJ Ching, WM TI Comparative genomics of Rickettsia prowazekii strains of Madrid E and Breinl by DNA microarray SO FASEB JOURNAL LA English DT Meeting Abstract C1 NMRC, Silver Spring, MD USA. NCI, NIH, Gaithersburg, MD USA. US FDA, CBER, Rockville, MD 20857 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 20 PY 2002 VL 16 IS 4 BP A531 EP A531 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533602945 ER PT J AU Jakubzick, CV Kunkel, S Joshi, BH Puri, RK Hogaboam, C AF Jakubzick, CV Kunkel, S Joshi, BH Puri, RK Hogaboam, C TI Interleukin-13 fusion cytotoxin arrests Schistosoma mansoni egg-induced pulmonary granuloma formation in mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Michigan, Dept Pathol, Ann Arbor, MI 48109 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Bethesda, MD USA. RI hogaboam, cory /M-3578-2014 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 20 PY 2002 VL 16 IS 4 BP A601 EP A601 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533603340 ER PT J AU Lathers, CM AF Lathers, CM TI Clinical pharmacology of antimicrobial use in humans and animals. SO FASEB JOURNAL LA English DT Meeting Abstract C1 FDA Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 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 20 PY 2002 VL 16 IS 4 BP A179 EP A179 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533600996 ER PT J AU Leak, LV Petricoin, EF Liotta, LA Jones, M Krutzell, H AF Leak, LV Petricoin, EF Liotta, LA Jones, M Krutzell, H TI Lymphatic endothelium: Protein profiles during quiescence and proliferation SO FASEB JOURNAL LA English DT Meeting Abstract C1 Howard Univ, Washington, DC 20059 USA. US FDA, Div Therapeut Prod, Bethesda, MD 20014 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Anim Med & Surg, 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 20 PY 2002 VL 16 IS 4 BP A514 EP A514 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533602849 ER PT J AU Melnyk, S Jernigan, S Christopher, SA Kruger, W James, SJ AF Melnyk, S Jernigan, S Christopher, SA Kruger, W James, SJ TI S-adenosylhomocysteine, but not homocysteine, is toxic to yeast lacking cystathionine beta synthase (CBS) activity SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Fox Chase Canc Ctr, Div Populat Sci, Philadelphia, PA 19111 USA. RI kruger, warren/A-6407-2008 OI kruger, warren/0000-0002-4990-3695 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 20 PY 2002 VL 16 IS 4 BP A267 EP A267 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601479 ER PT J AU Melnyk, S Jernigan, S James, SJ AF Melnyk, S Jernigan, S James, SJ TI Storage stability of S-adenosylmethionine (SAM), S-adenosylhomocysteine (SAH), and adenosine (Ado) in plasma and serum SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI kruger, warren/A-6407-2008 OI kruger, warren/0000-0002-4990-3695 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 20 PY 2002 VL 16 IS 4 BP A267 EP A267 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601478 ER PT J AU Pogribna, M Pogribny, IP James, SJ AF Pogribna, M Pogribny, IP James, SJ TI Centromeric DNA hypomethylation in ovaries of folate/methyl deficient rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 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 20 PY 2002 VL 16 IS 4 BP A267 EP A267 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601477 ER PT J AU Whittaker, P Dunkel, VC Seifried, HE Clarke, JJ San, RHC AF Whittaker, P Dunkel, VC Seifried, HE Clarke, JJ San, RHC TI Evaluation of iron chelators for assessing the mechanism of genotoxicity of iron compounds. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. NCI, Bethesda, MD 20892 USA. BioReliance, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 2002 VL 16 IS 4 BP A271 EP A271 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 533MG UT WOS:000174533601501 ER PT J AU Khaidakov, M Manjanatha, MG Aidoo, A AF Khaidakov, M Manjanatha, MG Aidoo, A TI Molecular analysis of mitochondrial DNA mutations from bleomycin-treated rats SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE mutation; deletion; mitochondrial DNA; bleomycin ID DOUBLE-STRAND CLEAVAGE; OXIDATIVE DAMAGE; CELLS; DELETIONS; CANCER; AGE; MULTIPLE; MUTANTS; GENOME; TUMORS AB In our previous studies, we have shown the mutagenicity of bleomycin (BLM) at the nuclear hprt locus. In the present study we have analyzed mutagenic effects of BLM in mitochondrial. DNA (mtDNA) using short extension-PCR (SE-PCR) method for detection of low-copy deletions. Fisher 344 rats were treated with a single dose of BLM and total DNA preparations from splenic lymphocytes were processed in SE-PCR assay. Spontaneous deletions were typically flanked by direct repeats (78.5%), while the in BLM-treated group, direct repeats were found in only 46.6% of breakpoints. The ratio between deletions based on direct repeats and random sequence deletions changed from 3.67 in control group to 0.87 in BLM-treated animals, which corresponds to an approximate 1.7-fold increase in the deletion mutation frequency. Furthermore, 62.5% of deletions not flanked by direct repeats in the treated group contained cleavage sites for BLM. The localization of breakpoints was not entirely random. We have found four clusters containing deletions from both groups indicative of deletion hot spots. The results indicate that BLM exposure may be associated with the induction of mtDNA mutations, and suggest the utility of SE-PCR method for evaluating drug-induced genotoxicity. (C) 2002 Published by Elsevier Science B.V. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson Labs, Jefferson, AR 72079 USA. RP Khaidakov, M (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson Labs, Jefferson, AR 72079 USA. NR 50 TC 4 Z9 4 U1 0 U2 1 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 20 PY 2002 VL 500 IS 1-2 BP 1 EP 8 AR PII S0027-5107(01)00270-6 DI 10.1016/S0027-5107(01)00270-6 PG 8 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 532VB UT WOS:000174494800001 PM 11890929 ER PT J AU Talarico, L AF Talarico, L TI Anticoagulants for prophylaxis and treatment of thromboembolic events - Response SO BLOOD LA English DT Letter C1 US FDA, Div Gastrointestinal & Coagulat Drug Prod, Ctr Drug Evaluat & Res, GICDP, Rockville, MD 20857 USA. RP Talarico, L (reprint author), US FDA, Div Gastrointestinal & Coagulat Drug Prod, Ctr Drug Evaluat & Res, GICDP, HFD 180, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC HEMATOLOGY PI WASHINGTON PA 1900 M STREET. NW SUITE 200, WASHINGTON, DC 20036 USA SN 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 2002 VL 99 IS 6 BP 2279 EP 2280 DI 10.1182/blood.V99.6.2279 PG 2 WC Hematology SC Hematology GA 530KA UT WOS:000174355800070 PM 11902143 ER PT J AU Powers, JH Ross, DB Brittain, E Albrecht, R Goldberger, MJ AF Powers, JH Ross, DB Brittain, E Albrecht, R Goldberger, MJ TI The United States Food and Drug Administration and noninferiority margins in clinical trials of antimicrobial agents SO CLINICAL INFECTIOUS DISEASES LA English DT Letter C1 US FDA, Off Drug Evaluat 4, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Powers, JH (reprint author), 9201 Corp Blvd,HFD-590, Rockville, MD 20850 USA. NR 4 TC 19 Z9 19 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAR 15 PY 2002 VL 34 IS 6 BP 879 EP 881 DI 10.1086/339803 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 525BL UT WOS:000174047300029 PM 11850875 ER PT J AU Zaitseva, M Kawamura, T Loomis, R Goldstein, H Blauvelt, A Golding, H AF Zaitseva, M Kawamura, T Loomis, R Goldstein, H Blauvelt, A Golding, H TI Stromal-derived factor 1 expression in the human thymus SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HEMATOPOIETIC PROGENITOR CELLS; MEDULLARY EPITHELIAL-CELLS; SCID-HU MOUSE; DENDRITIC CELLS; NEGATIVE SELECTION; HUMAN THYMOCYTES; APOPTOTIC CELLS; HIV-1 INFECTION; BONE-MARROW; EBI1-LIGAND CHEMOKINE AB Stromal-derived factor-1 (SDF-1), the only known ligand for the chemokine receptor CXCR4, is broadly expressed in cells of both the immune and central nervous systems, and it can induce the migration of resting leukocytes and hemopoletic progenitors. SDF-1 mRNA was previously detected in human thymus-derived stromal cells, but its role in thymopoiesis was unknown. Here we show that SDF-1 is expressed in medullar epithelial cells forming Hassall's corpuscles (HQ). In search of the cell type that may be attracted by SDF-1(+) cells in the medulla, we determined that dendritic cells (DC) could be found in situ in close proximity to SDF-1(+) epithelial cells in HC. In HIV-1-infected SCID-hu thymuses, DC contained apoptotic cells and were located within enlarged HC. It was further demonstrated that uptake of apoptotic thymocytes by immature DC induced an increase in CXCR4 expression and SDF-1-mediated chemotaxis. Our data suggest a role for SDF-1 in the elimination of apoptotic thymocytes. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. Yeshiva Univ Albert Einstein Coll Med, Dept Microbiol & Immunol, Bronx, NY 10461 USA. RP Zaitseva, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29B,Room 3G21,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 45 TC 35 Z9 36 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 MAR 15 PY 2002 VL 168 IS 6 BP 2609 EP 2617 PG 9 WC Immunology SC Immunology GA 529BP UT WOS:000174280400006 PM 11884424 ER PT J AU Juang, YT Solomou, EE Rellahan, B Tsokos, GC AF Juang, YT Solomou, EE Rellahan, B Tsokos, GC TI Phosphorylation and O-linked glycosylation of Elf-1 leads to its translocation to the nucleus and binding to the promoter of the TCR zeta-chain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID TRANSCRIPTION FACTOR ELF-1; T-LYMPHOCYTES; PROTEIN; GENE; EXPRESSION; ACTIVATION; ENHANCER; CELLS; GLYCOPROTEINS; AP-1 AB Elf-1, a member of the E 26-specific transcription factor family with a predicted molecular mass of 68 kDa, is involved in the transcriptional regulation of several hematopoietic cell genes. We demonstrate that Elf-1 exists primarily as a 98-kDa form in the nucleus and as an 80-kDa form in the cytoplasm. Phosphorylation and O-linked glycosylation contribute to the increased posttranslational molecular mass of Elf-1. The 98-kDa Elf-1 is released from the cytoplasm tethering retinoblastoma protein and moves to the nucleus, where it binds to the promoter of the TCR zeta-chain gene. Finally, the cytoplasmic 98-kDa form enters the proteasome pathway and undergoes degradation. In conclusion, different forms of Elf-1 are the products of posttranslational modifications that determine its subcellular localization, activity, and metabolic degradation. C1 Walter Reed Army Inst Res, Dept Cellular Injury, Silver Spring, MD 20910 USA. Uniformed Serv Univ Hlth Sci, Dept Med, Bethesda, MD 20814 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Tsokos, GC (reprint author), Walter Reed Army Inst Res, Dept Cellular Injury, Bldg 503,Room 1A32,503 Robert Grant Rd, Silver Spring, MD 20910 USA. FU NIAID NIH HHS [AI-42782, AI-49954, R01 AI-42269] NR 25 TC 56 Z9 59 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 MAR 15 PY 2002 VL 168 IS 6 BP 2865 EP 2871 PG 7 WC Immunology SC Immunology GA 529BP UT WOS:000174280400038 PM 11884456 ER PT J AU McDermott, PF Bodeis, SM English, LL White, DG Walker, RD Zhao, SH Simjee, S Wagner, DD AF McDermott, PF Bodeis, SM English, LL White, DG Walker, RD Zhao, SH Simjee, S Wagner, DD TI Ciprofloxacin resistance in Campylobacter jejuni evolves rapidly in chickens treated with fluoroquinolones SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 101st General Meeting of the American-Society-for-Microbiology CY MAY, 2001 CL ORLANDO, FLORIDA SP Ameri Soc Microbiol ID QUINOLONE RESISTANCE AB Fluoroquinolones are commonly used to treat gastroenteritis caused by Campylobacter species. Domestically acquired fluoroquinolone-resistant Campylobacter infection has been documented recently in the United States. It has been proposed that the increase in resistance is due, in part, to the use of fluoroquinolones in poultry. In separate experiments, the effects of sarafloxacin and enrofloxacin treatment of Campylobacter jejuni-infected chickens on the development of ciprofloxacin resistance were measured. Fecal samples were collected before and after treatment and were cultured for C. jejuni. When enrofloxacin or sarafloxacin was used at US Food and Drug Administration-approved doses in broiler chickens, resistance developed rapidly and persisted in C. jejuni. MICs of ciprofloxacin increased from a base of 0.25 mug/mL to 32 mug/mL within the 5-day treatment time frame. These results show that the use of these drugs in chickens rapidly selects for resistant Campylobacter organisms and may result in less effective fluoroquinolone therapy for cases of human campylobacteriosis acquired from exposure to contaminated chicken. C1 US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. RP McDermott, PF (reprint author), US FDA, Ctr Vet Med, Res Off, Div Anim & Food Microbiol, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 13 TC 118 Z9 123 U1 0 U2 7 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 MAR 15 PY 2002 VL 185 IS 6 BP 837 EP 840 DI 10.1086/339195 PG 4 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 527WD UT WOS:000174210200016 PM 11920303 ER PT J AU Fang, GC Chang, CN Wu, YS Lu, SC Fu, PPC Chang, SC Cheng, CD Yuen, WH AF Fang, GC Chang, CN Wu, YS Lu, SC Fu, PPC Chang, SC Cheng, CD Yuen, WH TI Concentration of atmospheric particulates during a dust storm period in central Taiwan, Taichung SO SCIENCE OF THE TOTAL ENVIRONMENT LA English DT Article DE total suspended particulate; fugitive dust; dust-storm; PM2.5; PM2.5-10; particulate matter ID PM2.5; SITE; TSP AB In this study we monitored concentrations of particles in central Taiwan using PS-1 (GPSI PUF Sampler) and Model 310 Universal Air Sampler(TM) (UAS(TM)) from 02/23/2001 to 03/12/2001 at two sampling sites. During this period, an Asian dust storm moved across central Taiwan from 3/3 to 3/6. The total ambient air particle concentrations during the dust storm period were than compared with previous data from this region. In general, the average total suspended particulate (TSP) concentration order was during dust storm period > after dust storm period > non-dust storm period at both HKITT (traffic) and THUC (rural) sampling sites. The ratio of PM2.5/PM10 was 60% before and after the dust storm period. However, this ratio was decreased to less than 50% during the dust storm. This demonstrates that the coarse particulate concentrations (PM2.5-10) increased during the dust storm period. In contrast the increase of ambient air particles concentrations after the Taiwan Chi-Chi Earthquake were mainly due to fine particles (PM2.5). And, the increased of ambient air particles concentrations after dust storm period were mainly coarse particle (PM2.5-10) concentrations in central Taiwan. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Hungkuang Inst Technol, Air Tox & Environm Anal Lab, Taichung 433, Taiwan. Tunghai Univ, Dept Environm Sci, Taichung 407, Taiwan. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Hsiuping Int Technol, Dept Chem Engn, Taichung 412, Taiwan. RP Fang, GC (reprint author), Hungkuang Inst Technol, Air Tox & Environm Anal Lab, Sha Lu, Taichung 433, Taiwan. NR 8 TC 28 Z9 29 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0048-9697 J9 SCI TOTAL ENVIRON JI Sci. Total Environ. PD MAR 15 PY 2002 VL 287 IS 1-2 BP 141 EP 145 AR PII S0048-9697(01)00996-2 DI 10.1016/S0048-9697(01)00996-2 PG 5 WC Environmental Sciences SC Environmental Sciences & Ecology GA 525MW UT WOS:000174076400013 ER PT J AU Starke, PR Chowdhury, BA AF Starke, PR Chowdhury, BA TI Efficacy of intranasal corticosteroids for acute sinusitis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. RP Starke, PR (reprint author), US FDA, Div Pulm & Allergy Drug Prod, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 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 13 PY 2002 VL 287 IS 10 BP 1261 EP 1261 DI 10.1001/jama.287.10.1261 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 529YU UT WOS:000174329500012 PM 11886305 ER PT J AU Freedberg, DI AF Freedberg, DI TI An alternative method for pucker determination in carbohydrates from residual dipolar couplings: A solution NMR study of the fructofuranosyl ring of sucrose SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID CROSS-CORRELATED RELAXATION; LIQUID-CRYSTALLINE MEDIUM; SOLID-STATE NMR; STRUCTURE REFINEMENT; MOLECULAR ALIGNMENT; SUGAR PUCKER; MACROMOLECULES; PROTEINS; PSEUDOROTATION; SPECTROSCOPY AB A simple solution NMR method is presented for pucker determination of five-membered rings using only residual dipolar couplings obtained in a single liquid crystalline medium, DMPC/DHPC bicelles (DMPC = dimyristoylphosphatidylcholine; DHPC = dihexanoylphosphatidylcholine). The method was applied to determine the pucker of the fructofuranosyl ring of sucrose. The results indicate a fructofuranosyl pucker phase in the 20degrees-70degrees range. The pucker phases are in agreement with those from previous NMR and optical spectroscopic studies and, importantly, do not rely on empirically parametrized Karplus curves. Furthermore, the analysis implies more than one stable pucker phase and rapid ring interconversion in this range. The present results suggest that using residual dipolar couplings alone can reveal multiple conformations present in solution. Hence, when a sufficient number of residual dipolar coupling constants is measured, the outcome is a robust, reliable, and independent route for determining carbohydrate and nucleic acid structure by NMR spectroscopy. C1 US FDA, Biophys Lab, CBER, Bethesda, MD 20892 USA. RP Freedberg, DI (reprint author), US FDA, Biophys Lab, CBER, 29 Lincoln Dr,Bldg 29,HFM-419, Bethesda, MD 20892 USA. NR 49 TC 44 Z9 44 U1 0 U2 8 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD MAR 13 PY 2002 VL 124 IS 10 BP 2358 EP 2362 DI 10.1021/ja010981v PG 5 WC Chemistry, Multidisciplinary SC Chemistry GA 532HZ UT WOS:000174469600058 PM 11878992 ER PT J AU Bebak-Williams, J Bullock, G Carson, MC AF Bebak-Williams, J Bullock, G Carson, MC TI Oxytetracycline residues in a freshwater recirculating system SO AQUACULTURE LA English DT Article DE oxytetracycline; residues; recirculating system; rainbow trout; antibiotics ID OXOLINIC ACID; FISH FARMS; MARINE-SEDIMENTS; RAINBOW-TROUT; SEA-WATER; PERSISTENCE AB When oxytetracycline (OTC) medicated feed is fed to fish in a recirculating aquaculture system, antibiotic residues could accumulate in fish tissue, water, biofilter sand and sediment to a greater extent than in single pass or serial reuse aquaculture systems. In two trials, oxytetracycline-medicated feed (3 g active ingredient per pound of feed) was fed to adult rainbow trout at 1% b.w. per day for 10 days. OTC residues were assayed in fish muscle (with skin attached), water, sediment (e.g., fish feces, uneaten feed) and biofilter sand. For both trials, oxytetracycline was detected during the 10 days of treatment in all matrices assayed. In trout muscle, OTC concentrations increased to an average of 1.8 etag/g by day 10 of treatment and then declined to <0.2 μg/g by 21 days posttreatment. For water entering and exiting the biofilter, OTC concentrations increased to 0.5 μg/ml by day 10 and was not detectable (<0.001 mug/ml) by 21 days post-treatment. For biofilter sand, OTC concentration was approximately 14 mug/g by day 10 and decreased to < 2 μg/g by 21 days posttreatment. In sediment samples, OTC concentrations increased to 1900 μg/g by day 10 and declined to <2 mug/g by 21 days post-treatment. In this system, OTC concentrations in trout muscle were well below 2 mug/g by 21 days after withdrawal of the drug. After input of medicated feed to the system was stopped, OTC concentrations in water, sediment and the biofilter declined and did not increase during the post-treatment period. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Inst Freshwater, Shepherdstown, WV 25443 USA. US FDA, Div Residue Chem, Ctr Vet Med, Laurel, MD 20708 USA. RP Bebak-Williams, J (reprint author), Inst Freshwater, POB 1889, Shepherdstown, WV 25443 USA. NR 18 TC 22 Z9 23 U1 1 U2 10 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0044-8486 J9 AQUACULTURE JI Aquaculture PD MAR 11 PY 2002 VL 205 IS 3-4 BP 221 EP 230 AR PII S0044-8486(01)00690-1 DI 10.1016/S0044-8486(01)00690-1 PG 10 WC Fisheries; Marine & Freshwater Biology SC Fisheries; Marine & Freshwater Biology GA 533WT UT WOS:000174553800002 ER PT J AU Whiting, RC Bagi, LK AF Whiting, RC Bagi, LK TI Modeling the lag phase of Listeria monocytogenes SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article; Proceedings Paper CT 3rd International Conference on Predictive Modelling in Foods CY SEP 12-15, 2000 CL LEUVEN, BELGIUM DE lag phase; Listeria monocytogenes; temperature ID GROWTH; TEMPERATURE; TIME AB An estimate of the lag phase duration is an important component for predicting the growth of a bacterium and for creating process models and risk assessments. Most current research and data for predictive modeling programs initiated growth studies with cells grown to the stationary phase in a favorable pH, nutrient and temperature environment. In this work, Listeria monocytogenes Scott A cells were grown in brain heart infusion (BHI) broth at different temperatures from 4 to 37 degreesC to the exponential growth or stationary phases. Additional cells were suspended in a dilute broth, desiccated or frozen. These cells were then transferred to BHI broth at various temperatures from 4 to 37 T and the lag phase durations were determined by enumerating cells at appropriate time intervals. Long lag phases were observed for cells initially grown at high temperatures and transferred to low temperatures. In general, exponential growth cells had the shortest lag phases, stationary phase and starved cells had longer, frozen cells had slightly longer and desiccated cells had the longest lag phases. These data were from immediate temperature transitions. When a computer-controlled water bath linearly changed the temperature from 37 to 5 degreesC over a 3.0- or 6.0-h period, the cells had short lags and grew continuously with declining growth rates. Transitions of 0.75 or 1.0 h had 20-h lag phases, essentially that of immediate transitions. When the transition was 1.5 h, an intermediate pattern of less than I log of growth followed by no additional growth for 20 h occurred. Published by Elsevier Science B.V. C1 USDA ARS, Microbial Food Safety Res Unit, Wyndmoor, PA 19038 USA. RP Whiting, RC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 8 TC 40 Z9 44 U1 5 U2 8 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 11 PY 2002 VL 73 IS 2-3 BP 291 EP 295 AR PII S0168-1605(01)00662-6 DI 10.1016/S0168-1605(01)00662-6 PG 5 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 533HQ UT WOS:000174523900019 PM 11934036 ER PT J AU Colman, E Hedin, R Swann, J Orloff, D AF Colman, E Hedin, R Swann, J Orloff, D TI A brief history of calcitonin SO LANCET LA English DT Article ID ESTABLISHED OSTEOPOROSIS; CALCIUM METABOLISM; SALMON-CALCITONIN; FRACTURE; TRIAL C1 US FDA, Div Metab & Endocrine Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Drug Risk Evaluat 1, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Colman, E (reprint author), US FDA, Div Metab & Endocrine Drug Prod, Ctr Drug Evaluat & Res, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 15 TC 13 Z9 13 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 MAR 9 PY 2002 VL 359 IS 9309 BP 885 EP 886 DI 10.1016/S0140-6736(02)07949-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 529YV UT WOS:000174329600033 PM 11897305 ER PT J AU Isaacsohn, J Black, D Troendle, A Orloff, D AF Isaacsohn, J Black, D Troendle, A Orloff, D TI The impact of the National Cholesterol Education Program Adult Treatment Panel III guidelines on drug development SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT 14th Symposium on Drugs Affecting Lipid Management (DALM 2001) CY SEP 10, 2001 CL NEW YORK, NEW YORK AB In the newest guidelines of the National Cholesterol Education Program (NCEP) Adult Treatment Panel (ATP) III, more intensive low-density lipoprotein cholesterol-lowering therapy, together with more attention to other lipid and lipoprotein parameters, are recommended for a larger group of dyslipidemic patients than was covered under ATP I and ATP III. A discussion to evaluate how future drug development might be affected by these new guidelines took place at the 14th International Symposium on Drugs Affecting Lipid Metabolism (DALM) conference, held in New York in September 2001. These discussions involved how to develop new lipid-lowering drugs in an era in which so much compelling evidence demonstrates the benefits of statins. Also covered were issues related to the development of drugs with triglyceride indications and whether the proportion of patients achieving NCEP guidelines should be included in the label of lipid-lowering drugs. Additional topics discussed included: (1) the possibility of incorporating a non-high-density lipoprotein cholesterol (HDL-C) indication for lipid-lowering drugs, (2) the possibility of obtaining indications for lipid-lowering drugs specifically in patients with diabetes, (3) the place of combination lipid-lowering drug therapy in drug development, and (4) whether drugs could be approved to increase levels of HDL-C in patients with isolated low HDL-C. (C) 2002 by Excerpta Medica, Inc. C1 Medpace LLC, Cincinnati, OH 45212 USA. Med Res Labs Int, Highland Hts, KY USA. US FDA, Rockville, MD 20857 USA. RP Isaacsohn, J (reprint author), Medpace LLC, 4850 Smith Rd, Cincinnati, OH 45212 USA. NR 1 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD MAR 7 PY 2002 VL 89 IS 5A SI SI BP 45C EP 49C AR PII S0002-9149(02)02228-2 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 531BL UT WOS:000174395000006 PM 11900719 ER PT J AU White, DG McDermott, PF Meng, JH AF White, DG McDermott, PF Meng, JH TI Resistant bacteria in retail meats and antimicrobial use in animals - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID UNITED-STATES; SALMONELLA; TYPHIMURIUM C1 US FDA, Laurel, MD 20708 USA. Univ Maryland, College Pk, MD 20742 USA. RP White, DG (reprint author), US FDA, Laurel, MD 20708 USA. NR 4 TC 1 Z9 1 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD MAR 7 PY 2002 VL 346 IS 10 BP 778 EP 779 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 527UA UT WOS:000174205000017 ER PT J AU Schwetz, BA AF Schwetz, BA TI Warning on Serzone SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commiss Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commiss Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 8 Z9 8 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 6 PY 2002 VL 287 IS 9 BP 1103 EP 1103 DI 10.1001/jama.287.9.1103-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 527KV UT WOS:000174186000004 PM 11879090 ER PT J AU Schwetz, BA AF Schwetz, BA TI New indication for Gleevec SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commiss Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commiss Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 8 Z9 8 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 6 PY 2002 VL 287 IS 9 BP 1103 EP 1103 DI 10.1001/jama.287.9.1103-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 527KV UT WOS:000174186000005 PM 11879090 ER PT J AU Schwetz, BA AF Schwetz, BA TI Treatment for psoriatic arthritis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commiss Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commiss Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 8 Z9 8 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 6 PY 2002 VL 287 IS 9 BP 1103 EP 1103 DI 10.1001/jama.287.9.1103-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 527KV UT WOS:000174186000007 PM 11879090 ER PT J AU Schwetz, BA AF Schwetz, BA TI Drug for pediatric liver disease SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commiss Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commiss Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 8 Z9 8 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 6 PY 2002 VL 287 IS 9 BP 1103 EP 1103 DI 10.1001/jama.287.9.1103-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 527KV UT WOS:000174186000006 PM 11879090 ER PT J AU Evans, DR Huang, MS Seganish, WM Fettinger, JC Williams, TL AF Evans, DR Huang, MS Seganish, WM Fettinger, JC Williams, TL TI Synthesis, structures, and solution behavior of bis(sulfoxide)-pincer complexes of palladium(II) SO ORGANOMETALLICS LA English DT Article ID KHARASCH ADDITION-REACTION; METAL SULFOXIDE COMPLEXES; RAY CRYSTAL-STRUCTURES; PLATINUM(II) COMPLEXES; ORGANONICKEL(II) COMPLEXES; ASYMMETRIC CATALYSIS; DIMETHYL-SULFOXIDE; BUILDING-BLOCKS; BOND ACTIVATION; PINCER COMPLEX AB Cyclometalation of bis(sulfoxide)-substituted m-xylene derivatives, rac/meso-1,3-((PrS)-Pr-i-(O)CH2)(2)C6H4, occurred readily with Pd(II) using two synthetic routes. The first route utilized [Pd(NCMe)(4)] [(BF4)(2)] as starting material and led to the exclusive isolation of the C-2-symmetric diastereomer [rac-2,6-((PrS)-Pr-i(O)CH2)(2)C6H3Pd(NCMe)][BF4], rac-3, even though spectroscopic measurements confirmed the formation of meso-3. The second palladation pathway used Pd(BF4)Cl(NCPh)(2) and both diastereomers rac- and meso-2,6-((PrS)-Pr-i(O)CH2)(2)C6H3PdCl, racand meso-4, were separable by fractional crystallization. Characterization of the isolated complexes using H-1 and C-13 NMR, FT-IR, and X-ray crystallography illuminated subtle differences between the two diastereomers of 4 and provided a rationale for the greater solution stability of rac-4 relative to meso-4. The source of the instability is due to the stereochemical configuration at sulfur. Additional solution studies, examined by variable temperature H-1 NMR (25 to -130 degreesC), probed the dynamic exchange behavior of the three complexes. In addition, electrospray mass spectrometry experiments of rac-4 in methanol solutions detected the presence of the unsupported mu-chloro-bridged dimer, [2,6-((PrS)-Pr-i(O)CH2))(2)C6H3Pd](2)-mu(2)-Cl. C1 Univ Maryland, Dept Chem & Biochem, College Pk, MD 20742 USA. US FDA, CIFSAN, College Pk, MD 20740 USA. RP Evans, DR (reprint author), Univ Maryland, Dept Chem & Biochem, 5100 Paint Branch Pkwy, College Pk, MD 20742 USA. NR 77 TC 32 Z9 32 U1 0 U2 4 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0276-7333 J9 ORGANOMETALLICS JI Organometallics PD MAR 4 PY 2002 VL 21 IS 5 BP 893 EP 900 DI 10.1021/om0109253 PG 8 WC Chemistry, Inorganic & Nuclear; Chemistry, Organic SC Chemistry GA 527TK UT WOS:000174203400017 ER PT J AU Tuttle, DL Anders, CB Aquino-De Jesus, M Poole, PP Lamers, SL Briggs, DR Pomeroy, SM Alexander, L Peden, KWC Andiman, WA Sleasman, JW Goodenow, MM AF Tuttle, DL Anders, CB Aquino-De Jesus, M Poole, PP Lamers, SL Briggs, DR Pomeroy, SM Alexander, L Peden, KWC Andiman, WA Sleasman, JW Goodenow, MM TI Increased replication of non-syncytium-inducing HIV type 1 isolates in monocyte-derived macrophages is linked to advanced disease in infected children SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; POST-ENTRY LEVEL; T-CELL LINES; CHEMOKINE RECEPTORS; CORECEPTOR USAGE; CCR5 UTILIZATION; NUCLEAR-LOCALIZATION; BIOLOGICAL PHENOTYPE; PRODUCTIVE INFECTION; PROGNOSTIC VALUE AB Non-syncytium-inducing (NSI) strains of HIV-1 prevail among most infected children, including pediatric patients who develop advanced disease, severe immune suppression, and die. A study was designed to address the hypothesis that genotypic and/or phenotypic markers can distinguish NSI viruses isolated during early infection from NSI viruses found in advanced disease. Primary HIV-1 isolates, which were obtained from 43 children, adolescents, and adults who displayed a cross-section of clinical disease and immune suppression but were untreated by protease inhibitor antiretroviral therapy, were characterized for replication phenotype in different cell types. Most individuals (81%) harbored NSI viruses and almost half had progressed to advanced disease or severe immune deficiency. About 51% of NSI isolates produced low levels of p24 antigen (median, 142 pg/ml) in monocyte-derived macrophages (MDMs), 31% produced medium levels (median, 1584 pg/ml), and 17% produced high levels (median, 81,548 pg/ml) (p<0.001). Seven of eight syncytium-inducing isolates also replicated in MDMs and displayed a dual-tropic phenotype that was associated with advanced disease. Replication of NSI viruses in MDMs varied as much as 100- to 1000-fold and was independent of replication in peripheral blood mononuclear cells. Replication in MDMs provided a clear biological feature to distinguish among viruses that were otherwise identical by NSI phenotype, V3 genotype, and CCR5 coreceptor usage. Low-level MDM replication was characteristic of viruses isolated from asymptomatic individuals, including long-term survivors. Enhanced MDM replication was related to morbidity and mortality among patients. Replication levels in MDMs provide a novel prognostic indicator of pathogenic potential by NSI viruses. C1 Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, Gainesville, FL 32610 USA. Yale Univ, Sch Med, Dept Pediat, New Haven, CT 06520 USA. Genegenie Inc, Thibodaux, LA USA. Univ Florida, Coll Med, Dept Pediat, Gainesville, FL 32610 USA. Yale Univ, Sch Med, Dept Epidemiol & Publ Hlth, New Haven, CT 06520 USA. US FDA, Lab Retrovirus Res, Bethesda, MD 20014 USA. RP Goodenow, MM (reprint author), Univ Florida, Coll Med, Dept Pathol Immunol & Lab Med, 1600 SW Archer Rd,Box 100275, Gainesville, FL 32610 USA. FU NCI NIH HHS [CA09126]; NHLBI NIH HHS [HL58005]; NIAID NIH HHS [AI39015]; NICHD NIH HHS [HD32259] NR 82 TC 58 Z9 59 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD MAR PY 2002 VL 18 IS 5 BP 353 EP 362 DI 10.1089/088922202753519133 PG 10 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 531NW UT WOS:000174422300006 PM 11897037 ER PT J AU Delatour, T Guy, PA Stadler, RH Turesky, RJ AF Delatour, T Guy, PA Stadler, RH Turesky, RJ TI 3-nitrotyrosine butyl ester: A novel derivative to assess tyrosine nitration in rat plasma by liquid chromatography-tandem mass spectrometry detection SO ANALYTICAL BIOCHEMISTRY LA English DT Article ID LOW-DENSITY-LIPOPROTEIN; NITRIC-OXIDE; BLOOD SPOTS; PEROXYNITRITE; NITROTYROSINE; FAILURE; QUANTIFICATION; INFLAMMATION; OXIDATION; PEPTIDES AB A novel, sensitive, and specific method is presented for the quantification of endogenous 3-nitrotyrosine in rat plasma based on isotope dilution liquid chromatography-electrospray ionization tandem mass spectrometry, using 3-nitro-2,5,6-d(3)-L-tyrosine as an internal standard. The extraction and cleanup method entails three major steps: protein precipitation, solid-phase extraction with an aminopropyl cartridge, followed by derivatization of 3-nitrotyrosine to the corresponding butyl ester. The analysis of the stable butyl ester derivative circumvented matrix interferences, which were encountered on the analysis of the nonderivatized analyte in plasma, and thus significantly improved sensitivity. The mass spectral acquisition of 3-nitrotyrosine butyl ester was done in the positive ion mode using selected reaction monitoring of two specific transitions. The response was linear over the concentration range 1.4-28.5 nM, and the recoveries of spiked 3-nitrotyrosine in rat plasma exceeded 75%. The detection and quantification limits of 3-nitrotyrosine in rat plasma (165 muL equivalent injected) approached 0.43 and 1.4 nM (0.07 and 0.23 pmol, on column), respectively. This study also addresses the potential artifactual formation of 3-nitrotyrosine, which may lead to an overestimation of the background levels of the biomarker. Solid-phase extraction of 3-nitrotyrosine was required prior to esterification to avoid artifactual nitration of tyrosine. In this context, analysis of eight rat plasma samples showed quantifiable levels in only four of the samples of the order of 1.4-1.5 nM. (C) 2002 Elsevier Science (USA). C1 Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Guy, PA (reprint author), Nestec Ltd, Nestle Res Ctr, Vers Chez Les Blanc, CH-1000 Lausanne 26, Switzerland. NR 35 TC 29 Z9 29 U1 0 U2 5 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-2697 J9 ANAL BIOCHEM JI Anal. Biochem. PD MAR 1 PY 2002 VL 302 IS 1 BP 10 EP 18 DI 10.1006/abio.2001.5521 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 523WX UT WOS:000173981500002 PM 11846371 ER PT J AU Moody, JD Doerge, DR Freeman, JP Cerniglia, CE AF Moody, JD Doerge, DR Freeman, JP Cerniglia, CE TI Degradation of biphenyl by Mycobacterium sp strain PYR-1 SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; META-CLEAVAGE PRODUCT; PSEUDOMONAS-PUTIDA; 2-HYDROXY-6-OXO-6-PHENYLHEXA-2,4-DIENOIC ACID; DEGRADING BACTERIUM; METABOLISM; OXIDATION; TRANSFORMATION; ENZYME; RHA1 AB The metabolism of biphenyl by Mycobacterium sp. PYR-1 was investigated. The Mycobacterium sp. degraded >98% of the biphenyl added within 72 h. Analysis of ethyl acetate extracts of the culture medium by HPLC indicated that benzoic acid was the major metabolite. Other products were 4-hydroxybiphenyl, 4-hydroxybenzoic acid, and 5-oxo-5-phenylpentanoic acid. The metabolites were characterized by mass and H-1 NMR spectrometry. Identification of benzoic acid and 5-oxo-5phenylpentanoic acid indicates that biphenyl degradation by Mycobacterium sp. PYR-1 is generally similar to known pathways. A novel alternative metabolic pathway consisted of monooxygenation at C-4 of biphenyl to give 4-hydroxybiphenyl, with subsequent degradation via ring cleavage to 4-hydroxybenzoic acid. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 40 TC 27 Z9 29 U1 2 U2 7 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD MAR PY 2002 VL 58 IS 3 BP 364 EP 369 DI 10.1007/s00253-001-0878-3 PG 6 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 534VY UT WOS:000174611500015 PM 11935189 ER PT J AU Brorson, K Xu, YA Swann, PG Hamilton, E Mustafa, M de Wit, C Norling, LA Stein, KE AF Brorson, K Xu, YA Swann, PG Hamilton, E Mustafa, M de Wit, C Norling, LA Stein, KE TI Evaluation of a quantitative product-enhanced reverse transcriptase assay to monitor retrovirus in mAb cell-culture SO BIOLOGICALS LA English DT Article ID DNA-POLYMERASE-ALPHA; MONOCLONAL-ANTIBODIES; CALF THYMUS; L1 RETROTRANSPOSONS; PCR; GENOME; SIMIAN-VIRUS-40; QUANTIFICATION; PURIFICATION; ELEMENTS AB Murine hybridoma cells used in the production of monoclonal antibodies (mAbs) produce endogenous type C retrovirus particles. Regulatory agencies require a demonstration that mAbs intended for human use are free of retrovirus with an adequate margin of safety, This is usually achieved by evaluation studies, performed at small scale, to demonstrate that the manufacturing process is capable of removing or inactivating several different model viruses, including a murine retrovirus. In a previous report, we demonstrated the utility of TaqMan fluorogenic 5'-nuclease product-enhanced reverse transcriptase (TM-PERT) assays for measuring reverse transcriptase (RT) activity in laboratory-scale cell-culture samples and RT removal by laboratory-scale models of processing steps. In this report, we evaluate the specificity, accuracy, range, precision and robustness of TM-PERT for this purpose. We find that this assay detects RT activity contained in xenotropic murine leukemia virus (X-MuLV) and CHO cell type C particles and quantifies particle numbers comparably to other assays (e.g. transmission electron microscopy, viral sequence specific TaqMan). Cell derived DNA polymerases appear to contribute only modestly to the assay background and RT activity in clarified cell culture harvests is contained largely in Type C particles. TM-PERT is linear and precise between 10(7) and 10(13) pU/ml, establishing the assay range. The assay is robust in that test article storage condition and DNA/protein content had little impact on assay performance. Thus, TM-PERT appears to be an acceptable assay to measure type C particles in rodent cell culture samples. C1 Ctr Biol Evaluat & Res Food & Drug Adm, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. Genentech Inc, San Francisco, CA 94080 USA. RP Brorson, K (reprint author), Ctr Biol Evaluat & Res Food & Drug Adm, Div Monoclonal Antibodies, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 41 TC 22 Z9 25 U1 0 U2 0 PU ACADEMIC PRESS LTD ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 2002 VL 30 IS 1 BP 15 EP 26 DI 10.1006/biol.2001.0290 PG 12 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 515AH UT WOS:000173472900003 PM 11846426 ER PT J AU Bockstahler, LE Li, Z Nguyen, NY Van Houten, KA Brennan, MJ Langone, JJ Morris, SL AF Bockstahler, LE Li, Z Nguyen, NY Van Houten, KA Brennan, MJ Langone, JJ Morris, SL TI Peptide nucleic acid probe detection of mutations in Mycobacterium tuberculosis genes associated with drug resistance SO BIOTECHNIQUES LA English DT Article ID LIQUID CULTURES; DIFFERENTIATION; IDENTIFICATION; KATG AB The emergence of drug-resistant strains of Mycobacterium tuberculosis is a serious public health problem. Many of the specific gene mutations that cause drug resistance in M. tuberculosis are point mutations. We are developing a PCR-peptide nucleic acid (PNA)-based ELISA as a diagnostic method to recognize point mutations in genes associated with isoniazid and rifampin resistance in M. tuberculosis. Specific point mutation-containing sequences and wild-type sequences of cloned mycobacterial genes were PCR-amplified, denatured, and hybridized with PNA probes bound to microplate wells. Using 15-base PNA probes,, we established the hybridization temperatures (50degreesC-55degreesC) and other experimental conditions suitable for detecting clinically relevant point mutations in the katG and rpoB genes. Hybridization of PCR-amplified sequences that contained these point mutations with complementary mutation-specific PNAs resulted in significant increases in ELISA response compared with hybridization using wild-ope-specific PNAs. Conversely, PCR-amplified wild-type sequences hybridized much more efficiently with wildtype PNAs than with the mutation-specific PNAs. Using the M. tuberculosis cloned genes and PCR-PNA-ELISA format developed here, M. tuberculosis sequences containing point mutations associated with drug resistance can be identified in less than 24 h. C1 US FDA, Rockville, MD 20857 USA. RP Bockstahler, LE (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 17 TC 15 Z9 16 U1 0 U2 0 PU EATON PUBLISHING CO PI NATICK PA 154 E. CENTRAL ST, NATICK, MA 01760 USA SN 0736-6205 J9 BIOTECHNIQUES JI Biotechniques PD MAR PY 2002 VL 32 IS 3 BP 508 EP + PG 5 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 529ZK UT WOS:000174331000006 PM 11926172 ER PT J AU Hung, S Morrison, DR Whittington, LA Fein, SB AF Hung, S Morrison, DR Whittington, LA Fein, SB TI Prepartum work, job characteristics, and risk of cesarean delivery SO BIRTH-ISSUES IN PERINATAL CARE LA English DT Article ID BIRTH-WEIGHT; PRETERM DELIVERY; GESTATIONAL-AGE; PREGNANCY; EMPLOYMENT; WOMEN AB Background: Reducing the rate of cesarean deliveries in the United States is a high priority among public health officials and members of the medical community. Many factors known to contribute to an individual woman's risk of having a cesarean rather than a vaginal delivery are not readily altered by public policy intervention. In this study we explored the effects on type of delivery of prepartum work practices, a category of factors that has a potential to affect the likelihood of cesarean delivery and to be amenable to change. Methods: Data are from U.S. Food and Drug Administrations Infant Feeding Practices Study using questions on mail surveys administered prenatally and at 1 month postpartum. The sample comprised 1194 women who worked during pregnancy. The outcome measure is type of delivery. Predictor variables are characteristics of prepartum work: how far into their pregnancy the women work, number of hours worked, and occupation. Results: For most women, maintaining employment through the third trimester, working long hours, and working in certain occupations are not independently associated with the odds of having a cesarean delivery. However, we found marginally significant evidence that those women who worked more than 40 hours a week in a sales job were more likely to have cesarean deliveries than women who worked in other occupations. Conversely, women working part-time in sales jobs were less likely to have a cesarean delivery. Conclusion: This study provides evidence that prenatal work does not substantially increase the probability of having a cesarean delivery in most occupational categories. C1 George Washington Univ, Georgetown Publ Policy Inst, Washington, DC USA. Cable New Network, Washington, DC USA. US Dept Hlth & Human Serv, Ctr Food Safety & Appl Nutr, Div Market Studies, Food & Drug Adm, College Pk, MD 20740 USA. RP Fein, SB (reprint author), US Dept Hlth & Human Serv, Ctr Food Safety & Appl Nutr, Div Market Studies, Food & Drug Adm, Room 2C-103,HFS-727,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 17 TC 13 Z9 13 U1 0 U2 0 PU BLACKWELL PUBLISHING INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0730-7659 J9 BIRTH-ISS PERINAT C JI Birth-Issue Perinat. Care PD MAR PY 2002 VL 29 IS 1 BP 10 EP 17 DI 10.1046/j.1523-536X.2002.00150.x PG 8 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 522WQ UT WOS:000173920300002 PM 11843785 ER PT J AU Dong, S Fu, PP Shirsat, RN Hwang, HM Leszczynski, J Yu, H AF Dong, S Fu, PP Shirsat, RN Hwang, HM Leszczynski, J Yu, H TI UVA light-induced DNA cleavage by isomeric methylbenz[a]anthracenes SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; ACTIVITY RELATIONSHIP MODEL; PHOTOINDUCED TOXICITY; METABOLIC-ACTIVATION; CARCINOGENESIS; BENZOPYRENE; MECHANISM; QUINONES; CELLS; PHOTOSENSITIZATION AB UVA light-induced DNA single strand cleavage by a set of 12 monomethyl substituted benz[a]anthracenes (MBAs) along with their parent compound, benz[a]anthracene (BA), and the potent carcinogen, 7,12-dimethylbenz [a] anthracene (DMBA), was studied. On the basis of the relative DNA single strand photocleavage efficiency of the fourteen compounds, they are divided into three groups: (1) strong DNA cleavers, 4-MBA, 5-MBA, 6-MBA, 8-MBA, 9-MBA, 10-MBA, and BA; (2) medium DNA cleavers, 1-MBA, 2-MBA, 3-MBA, and 11-MBA; and (3) weak DNA cleavers, 7-MBA, 12-MBA, and DMBA. The relative DNA photocleavage efficiency parallels very well with the energy gap between the highest-occupied-molecular-orbitaI (HOMO) and the lowest-unoccupied-molecular-orbitaI (LUMO) of each MBA, indicating that the DNA cleavage is related to their excited-state properties. The 7 and 12 positions of BA are two unique sites. Methyl substitution at either 7 or 12 (or both) positions lowers the HOMO-LUMO gap and greatly diminishes the DNA photocleavage efficiency. UVA light-induced photodegradation of selected MBAs reveals that methyl substitution at either 7 or 12 (or both) positions greatly enhances the degradation rate. Photodegradation of 7-MBA, 12-MBA, and DMBA yields products that are much less effective in mediating DNA cleavage. Photodegradation of other MBAs, exemplified by 5-MBA, yields a photooxidation product 5-MBA-7,12-quinone which is relatively stable under light and is a stronger DNA photocleaver than 5-MBA itself. The higher efficiency of DNA photocleavage for MBAs with methyl substitution at positions other than 7 or 12 is due, at least in part, to the formation of 7,12-quinone. Light-induced DNA single strand cleavage efficiency for several MBAs parallels the light-induced toxicity observed by other research groups, suggesting that light-induced DNA cleavage of MBAs are the source for phototoxicity. Since some PAHs such as coal tar are used commercially as creams, therapeutic agents, or ointments, or those roofers and asphalt workers that are subject to contamination with PAHs, the combination of PAHs and light (in the skin) may present a greater health risk to humans. C1 Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Jackson State Univ, Dept Biol, Jackson, MS 39217 USA. RP Yu, H (reprint author), Jackson State Univ, Dept Chem, Jackson, MS 39217 USA. FU CCR NIH HHS [RCMI G122RR13459] NR 54 TC 36 Z9 37 U1 3 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 MAR PY 2002 VL 15 IS 3 BP 400 EP 407 DI 10.1021/tx015567n PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 536AR UT WOS:000174679000015 PM 11896688 ER PT J AU Cohen, MH Johnson, JR Li, N Chen, G Pazdur, R AF Cohen, MH Johnson, JR Li, N Chen, G Pazdur, R TI Approval summary: Letrozole in the treatment of postmenopausal women with advanced breast cancer SO CLINICAL CANCER RESEARCH LA English DT Article ID ORAL AROMATASE INHIBITOR; DOUBLE-BLIND; PHASE-I; CGS-20267; TRIAL; EFFICACY; ESTROGEN AB Letrozole (Femara; Novartis Pharmaceuticals Corp., East Hanover, NJ) is a nonsteroidal inhibitor of aromatase enzyme complex. It inhibits the peripheral conversion of circulating androgens to estrogens. In postmenopausal women, letrozole decreases plasma concentrations of estradiol, estrone, and estrone sulfate by 75-95% from baseline with maximal suppression achieved within 2-3 days of treatment initiation. Suppression is dose related, with doses of greater than or equal to0.5 mg giving estrone and estrone sulfate values that were often below assay detection limits. At clinically used dosage, letrozole does not impair adrenal synthesis of glucocorticoids or aldosterone. In 1998, letrozole was approved by the United States Food and Drug Administration (FDA) for the treatment of advanced breast cancer in postmenopausal women, with hormone receptor positive or unknown breast cancer, who had failed one prior antiestrogen treatment (i.e., for "second-line" treatment). Approval was based on two randomized trials comparing tumor RRs of patients receiving 0.5 mg of letrozole, 2.5 mg of letrozole, and either megestrol acetate (MA) or aminoglutethimide. In the megestrol trial, 2.5 mg/day letrozole was superior to 0.5 mg of letrozole and MA (RRs 24, 13, and 16%, respectively), whereas in the aminoglutethimide trial, there was no significant difference in 2.5 mg of letrozole and 0.5 mg of letrozole RRs (20 and 17%). There was a trend toward RR superiority of 2.5 mg of letrozole over aminoglutethimide (P = 0.06). Letrozole (2.5 mg) was the dose chosen for comparison with tamoxifen in the first-line setting. In July 2000, a marketing application for first-line letrozole treatment of postmenopausal women with hormone receptor positive or hormone receptor unknown locally advanced or metastatic breast cancer was submitted to the FDA. A single double-blind, double dummy, randomized, and multicenter trial compared 2.5 mg of letrozole to 20 mg of tamoxifen (456 patients/arm). Letrozole was superior to tamoxifen with regard to time to progression (TTP) and objective response rate (1111). The median TTP for letrozole treatment was 9.9 months [95% confidence interval (CI) 9.1-12.2] versus 6.2 months (95% CI 5.8-8.5) for tamoxifen, P = 0.0001, hazard ratio 0.713, (95% Cl 0.610.84). RR was 32% for letrozole versus 21% for tamoxifen (odds ratio 1.74, 95 % CI 1.29 -2.34, P = 0.0003). Preliminary survival data (survival data are still blinded) indicate that letrozole is unlikely to be worse than tamoxifen. Both treatments were similarly tolerated. On the basis of these results, the United States FDA approved letrozole tablets, 2.5 mg/day, for first-line treatment of postmenopausal women with hormone receptor-positive or hormone receptor-unknown locally advanced or metastatic breast cancer. The manufacturer made a commitment to provide updated information on survival. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod HFD150, Rockville, MD 20857 USA. RP Cohen, MH (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod HFD150, HFD-150,5600 Fishers Lane, Rockville, MD 20857 USA. NR 19 TC 47 Z9 48 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD MAR PY 2002 VL 8 IS 3 BP 665 EP 669 PG 5 WC Oncology SC Oncology GA 531EP UT WOS:000174403300005 PM 11895893 ER PT J AU Cristillo, AD Highbarger, HC Dewar, RL Dimitrov, DS Golding, H Bierer, BE AF Cristillo, AD Highbarger, HC Dewar, RL Dimitrov, DS Golding, H Bierer, BE TI Up-regulation of HIV coreceptor CXCR4 expression in human T lymphocytes is mediated in part by a cAMP-responsive element SO FASEB JOURNAL LA English DT Article DE CXCR4; HIV; cyclic AMP; CREB; chemokine receptors; AIDS ID IMMUNODEFICIENCY-VIRUS TYPE-1; CHEMOKINE RECEPTOR CXCR4; HEMATOPOIETIC PROGENITOR CELLS; DOWN-MODULATION; SURFACE EXPRESSION; CUTTING EDGE; CYCLIC-AMP; INFECTION; ENTRY; REPLICATION AB The chemokine and HIV receptor CXCR4 has been shown to play a role in chemotaxis and HIV-1 entry into T cells. Dibutyryl cAMP (DcAMP), an analog of cAMP, has been shown to increase CXCR4 cell surface expression and HIV-1 infectivity, but the molecular mechanism(s) responsible is unknown. Here we show that DcAMP treatment of purified human T lymphocytes increased transcription of CXCR4 mRNA as well as cell surface and intracellular CXCR4 protein expression. DcAMP-mediated stimulation of human PBL increased T-trophic HIV-1 (X4) fusion and viral replication as measured by syncytia formation and p24 levels, respectively. To determine the region( s) of the CXCR4 promoter required for cAMP responsiveness, truncations and point mutations of the CXCR4 promoter (nucleotides -1098 to +59) fused to luciferase were constructed and transiently transfected into human PBL. Deletional analysis demonstrated that the -1098 to -93 region of the CXCR4 promoter construct could be eliminated; the residual (-93 to +59) promoter retained cAMP responsiveness. Site-directed mutagenesis of a putative cAMP-responsive element (CRE) in the 5' UTR (+41 to +49) significantly and specifically attenuated the ability of DcAMP to drive the minimal CXCR4 promoter. Electrophoretic mobility shift assays demonstrated the formation of a complex between the CREB transcription factor and the putative CXCR4 CRE site. Our findings demonstrate a CRE element within the CXCR4 promoter that regulates CXCR4 transcription in response to changes in cAMP signaling. The cAMP-dependent up-regulation of CXCR4 mRNA results in increased CXCR4 intracellular and cell surface protein expression as well as increased HIV infectivity. C1 NHLBI, Lab Lymphocyte Biol, NIH, Bethesda, MD 20892 USA. NIAID, SAIC AIDS Monitoring Lab, NIH, Bethesda, MD 20892 USA. NCI, Frederick Canc Res & Dev Ctr, NIH, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Bierer, BE (reprint author), NHLBI, Lab Lymphocyte Biol, NIH, Bldg 10,Room 6C208,10 Ctr Dr, Bethesda, MD 20892 USA. EM biererb@nih.gov NR 56 TC 31 Z9 32 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 PY 2002 VL 16 IS 3 AR UNSP 0892-6638/02/0016-0354 DI 10.1096/fj.01-0744com PG 11 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 537JV UT WOS:000174755900027 PM 11874984 ER PT J AU Pletnikov, MV Moran, TH Carbone, KM AF Pletnikov, MV Moran, TH Carbone, KM TI Borna disease virus infection of the neonatal rat: Developmental brain injury model of autism spectrum disorders SO FRONTIERS IN BIOSCIENCE LA English DT Review DE animal model; autism; Borna; brain; development; environment; rat; review ID CENTRAL-NERVOUS-SYSTEM; INFANTILE-AUTISM; POSTNATAL-DEVELOPMENT; ETIOLOGIC FACTOR; GENE-EXPRESSION; IMMUNE-SYSTEM; BDV INFECTION; LEWIS RATS; CELLS; PERSISTENT AB Autism spectrum disorders (ASD) have been the focus of a great deal of research and clinical speculation. This intense interest relates to both the perplexing pathogenesis and devastating consequences of these disorders. One of the obstacles to understanding the pathogenesis of autism and its efficient treatment has been the paucity of animal models that could be used for hypotheses-driven mechanistic studies of abnormal brain and behavior development and for the pre-clinical testing novel pharmacological treatments. The present review provides a detailed analysis of a new animal model of ASD. This model utilizes neonatal Borna disease virus (BDV) infection of the rat brain as a unique experimental teratogen to study the pathogenesis of neurodevelopmental damage. For more than a decade, studies of the BDV animal model have yielded much insight into the pathogenic processes of abnormal brain development and resulting autistic-like behavioral abnormalities in rats. The most recent experiments demonstrate the utility of the BDV model for studying the pathophysiological mechanisms of the gene-environment interaction that determines differential disease outcomes and variability in responses to treatments. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, 720 Rutland Ave,Ross 618, Baltimore, MD 21205 USA. FU NIMH NIH HHS [R01 MH 48948-08A1] NR 96 TC 42 Z9 44 U1 0 U2 1 PU FRONTIERS IN BIOSCIENCE INC PI MANHASSET PA C/O NORTH SHORE UNIV HOSPITAL, BIOMEDICAL RESEARCH CENTER, 350 COMMUNITY DR, MANHASSET, NY 11030 USA SN 1093-9946 J9 FRONT BIOSCI JI Front. Biosci. PD MAR PY 2002 VL 7 BP D593 EP D607 DI 10.2741/pletnik PG 15 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 534RK UT WOS:000174600400002 PM 11861216 ER PT J AU Myers, MJ Baarsch, MJ Murtaugh, MP AF Myers, MJ Baarsch, MJ Murtaugh, MP TI Effects of pentoxifylline on inflammatory cytokine expression and acute pleuropneumonia in swine SO IMMUNOBIOLOGY LA English DT Article ID TUMOR-NECROSIS-FACTOR; ACUTE LUNG INJURY; ALPHA TNF-ALPHA; INFLUENZA-A VIRUS; ACTINOBACILLUS-PLEUROPNEUMONIAE; MESSENGER-RNA; GUINEA-PIGS; LIPOPOLYSACCHARIDE; MACROPHAGES; PIGLETS AB Pentoxifylline, a methylxanthine derivative and nonspecific type 4 phosphodiesterase inhibitor, has been used to improve survival of animals with sepsis and to attenuate lung injury in acute lung inflammation. The purpose of this study was to examine whether pentoxifylline would inhibit the expression of inflammatory cytokines, particularly tumor necrosis factor alpha (TNF), and thereby decrease the pathophysiology of acute porcine pleuropneumonia. E. coli lipopolysaccharide (LPS) and bacterial extracts of A. pleuropneumoniae - induced elevations in TNF mRNA which were fully abrogated by addition of pentoxifylline in both alveolar macrophage and neutrophil cultures. A 30% reduction in the level of LPS-induced interleukin (IL)-1beta mRNA levels also was achieved in macrophages. Pentoxifylline did not affect either IL-1alpha or IL-8 expression in vitro. Pentoxifylline therapy in vivo significantly reduced the number of band neutrophils in swine but did not reduce the pathology associated with pleuropneumonia, including changes in serum zinc, iron, or haptoglobin. Neither did it alter TNF, IL-1, IL-6, or IL-8 expression. Measurement of pentoxifylline and its metabolites in pig sera suggested that efficacious doses of pentoxifylline were probably not achieved in vivo. However, subcutaneous doses of pentoxifylline higher than 25 mg/kg produced transient diarrhea, vomiting, and tremors. These results suggest that pentoxifylline is an effective pharmacological tool for the dissection of cytokine regulation in vitro, but inhibitory concentrations may not be achievable for in vivo pharmacological use in swine. C1 US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD USA. Univ Minnesota, Dept Vet Pathobiol, St Paul, MN 55108 USA. RP Myers, MJ (reprint author), US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD USA. NR 47 TC 10 Z9 11 U1 1 U2 1 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0171-2985 J9 IMMUNOBIOLOGY JI Immunobiology PD MAR PY 2002 VL 205 IS 1 BP 17 EP 34 DI 10.1078/0171-2985-00108 PG 18 WC Immunology SC Immunology GA 540QP UT WOS:000174939900002 PM 11999342 ER PT J AU Farizo, KM Fiddner, S Cheung, AM Burns, DL AF Farizo, KM Fiddner, S Cheung, AM Burns, DL TI Membrane localization of the S1 subunit of pertussis toxin in Bordetella pertussis and implications for pertussis toxin secretion SO INFECTION AND IMMUNITY LA English DT Article ID CARBOXY-TERMINAL PHENYLALANINE; ISLET-ACTIVATING PROTEIN; ESCHERICHIA-COLI; SUBCELLULAR-LOCALIZATION; MONOCLONAL-ANTIBODIES; ENVELOPE PROTEINS; ADP-RIBOSYLATION; GENE; CLONING; SYSTEM AB Pertussis toxin is secreted from Bordetella pertussis with the assistance of the Ptl transport system, a member of the type IV family of macromolecular transporters. The SI subunit and the B oligomer combine to form the holotoxin prior to export from the bacterial cell, although the site of assembly is not known. To better understand the pathway of pertussis toxin assembly and secretion, we examined the subcellular location of the SI subunit, expressed with or without the B oligomer and the Ptl proteins. In wild-type B. pertussis, the majority of the S1 subunit that remained cell associated localized to the bacterial membranes. In mutants of B. pertussis that do not express pertussis toxin and/or the Ptl proteins, full-length S1, expressed from a plasmid, partitioned almost entirely to the bacterial membranes. Several lines of evidence strongly suggest that the SI subunit localizes to the outer membrane of B. pertussis. First, we found that membrane-bound full-length SI was almost completely insoluble in Triton X-100. Second, recombinant SI previously has been shown to localize to the outer membrane of Escherichia coli (J. T. Barbieri, M. Pizza, G. Cortina, and R. Rappuoli, Infect. Immun. 58:999-1003, 1990). Third, the SI subunit possesses a distinctive amino acid motif at its carboxy terminus, including a terminal phenylalanine, which is highly conserved among bacterial outer membrane proteins. By using site-directed mutagenesis, we determined that the terminal phenylalanine is critical for stable expression of the SI subunit. Our findings provide evidence that prior to assembly with the B oligomer and independent of the Ptl proteins, the SI subunit localizes to the outer membrane of B. pertussis. Thus, outer membrane-bound SI may serve as a nucleation site for assembly with the B oligomer and for interactions with the Ptl transport system. C1 US FDA, Ctr Biol Evaluat & Res, Lab Resp & Special Pathogens, Bethesda, MD 20892 USA. RP US FDA, Ctr Biol Evaluat & Res, Lab Resp & Special Pathogens, HFM-434,Bldg29,Room 124,8800 Rockville Pike, Bethesda, MD 20892 USA. EM burns@cber.fda.gov NR 42 TC 13 Z9 16 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 EI 1098-5522 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 2002 VL 70 IS 3 BP 1193 EP 1201 DI 10.1128/IAI.70.3.1193-1201.2002 PG 9 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 522EQ UT WOS:000173883100021 PM 11854200 ER PT J AU Lee, CJ Lee, LH Koizumi, K AF Lee, CJ Lee, LH Koizumi, K TI Polysaccharide vaccines for prevention of encapsulated bacterial infections: Part 1 SO INFECTIONS IN MEDICINE LA English DT Article DE vaccines, polysaccharide, conjugate; Neisseria meningitidis; Streptococcus pneumoniae ID INFLUENZAE TYPE-B; PROTEIN CONJUGATE VACCINE; INVASIVE PNEUMOCOCCAL INFECTIONS; UNITED-STATES; MATERNAL IMMUNIZATION; GROUP-A; STREPTOCOCCUS-PNEUMONIAE; NASOPHARYNGEAL CARRIAGE; NEISSERIA-MENINGITIDIS; MENINGOCOCCAL VACCINES AB Protective immunity to encapsulated bacteria involves an antibody response to a polysaccharide (PS) antigen, interactions with T and B lymphocytes, and host defense mechanisms. PS vaccines, such as those developed against Neisseria meningitidis, Streptococcus pneumoniae, Haemophilus influenzae type b, and Salmonella typhi, prevent infection by inducing an immune response against specific capsular polysaccharides. These vaccines, however, provided little protective immunity in infants and young children. The development of glycoconjugate vaccines overcame many limitations associated with PS vaccines by eliciting a quantitatively and qualitatively different immune response. Alternative strategies intended to enhance an immune response in infants include maternal immunization with PS or conjugate vaccine and hormone treatment during the critical period of neonatal development. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Lee, CJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NR 50 TC 4 Z9 4 U1 0 U2 2 PU SCP COMMUNICATIONS INC PI NEW YORK PA 134 W 29TH ST, NEW YORK, NY 10001-5304 USA SN 0749-6524 J9 INFECT MED JI Infect. Med. PD MAR PY 2002 VL 19 IS 3 BP 127 EP 133 PG 7 WC Infectious Diseases SC Infectious Diseases GA 532DF UT WOS:000174455800011 ER PT J AU Adkinson, NF Essayan, D Gruchalla, R Haggerty, H Kawabata, T Sandler, JD Updyke, L Shear, NH Wierda, D AF Adkinson, NF Essayan, D Gruchalla, R Haggerty, H Kawabata, T Sandler, JD Updyke, L Shear, NH Wierda, D CA The Hlth & Environm Sci Inst Task TI Task Force Report: Future research needs for the prevention and management of immune-mediated drug hypersensitivity reactions SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Article DE adverse drug reactions; drug allergy; drug development; drug hypersensitivity; immunotoxicology ID LYMPH-NODE ASSAY; CD4(+) T-CELLS; RISK ASSESSMENT; AUTOIMMUNE REACTIONS; PENICILLIN ALLERGY; CONTACT ALLERGY; ANIMAL-MODELS; HLA-DR; SENSITIZATION; ANTIGENS AB Immune-mediated drug hypersensitivity reactions (IDHR) have a significant impact on clinical practice, drug development, and public health. However, research to understand IDHR mechanisms and to develop diagnostic and predictive tests has been limited. To stimulate more research, a task force with representatives from the key stakeholders (research clinicians, regulatory scientists, and immunotoxicologists from the pharmaceutical industry) was assembled to identify critical data gaps and opportunities and to make recommendations on how to overcome some of the barriers to IDHR research and address research needs. It is hoped that this report will act as a springboard for future discussions and progress toward increased funding and development of organizational structures for IDHR research. C1 ILSI Hlth & Environm Sci Inst, Washington, DC 20036 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. US FDA, Rockville, MD 20857 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Bristol Myers Squibb Co, Syracuse, NY USA. Pfizer Global Res & Dev, Groton, CT USA. Univ Toronto, Toronto, ON, Canada. Eli Lilly & Co, Greenfield, IN USA. RP Sandler, JD (reprint author), ILSI Hlth & Environm Sci Inst, 1126 16th St NW, Washington, DC 20036 USA. NR 83 TC 48 Z9 51 U1 1 U2 2 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 MAR PY 2002 VL 109 IS 3 BP S461 EP S478 DI 10.1067/mai.2002.122214 PG 18 WC Allergy; Immunology SC Allergy; Immunology GA 534KW UT WOS:000174586400033 PM 11897992 ER PT J AU Carson, MC Bullock, G Bebak-Williams, J AF Carson, MC Bullock, G Bebak-Williams, J TI Determination of oxytetracycline residues in matrixes from a freshwater recirculating aquaculture system SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MULTIPLE TETRACYCLINE RESIDUES; LIQUID-CHROMATOGRAPHIC METHOD; ANIMAL-TISSUES; MILK; CHLORTETRACYCLINE; SHRIMP AB This paper describes related procedures to determine the amount of oxytetracycline (OTC) present in trout tissue (muscle with skin attached), biofilter sand, sediment, and tank water from a recirculating aquaculture system. OTC was extracted from the matrixes by different techniques, depending on complexity of the matrix and desired OTC detection level in that matrix. Listed in order of increasing complexity, OTC was extracted from tank water by dilution with acidic buffer containing ethylenediaminetetraacetic acid (EDTA); from biofilter sand by shaking with 0.1 N HCl; from sediment by homogenization and shaking with buffer/EDTA; and from ground trout by homogenization and shaking with buffer/EDTA (twice), with further cleanup and concentration of the extract on a polymeric solid-phase extraction cartridge. The 4 procedures all used the same reversed-phase gradient chromatography on a polymeric column with UV detection at 350 nm. The lower limit of detection (estimated) and upper limit of validation for each of these 4 matrixes were 0.04-4.0 mug/g (ppm; trout), 0.03-20 ppm (biofilter sand), 1-6000 ppm (sediment), and 0.003-10 ppm (water). Recoveries ranged from 82 to 108%, with relative standard deviation <20% over the applicable concentration ranges. These procedures were used to monitor OTC residues resulting from medicated feed administered to rainbow trout in a recirculating aquaculture system. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Inst Freshwater, Shepherdstown, WV 25443 USA. RP Carson, MC (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 15 TC 10 Z9 10 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 MAR-APR PY 2002 VL 85 IS 2 BP 341 EP 348 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 537XR UT WOS:000174785400005 PM 11990017 ER PT J AU Hammack, TS Johnson, ML Jacobson, AP Andrews, WH AF Hammack, TS Johnson, ML Jacobson, AP Andrews, WH TI Enhanced recovery of Salmonella from apple cider and apple juice with Universal Preenrichment Broth SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID OUTBREAK AB A comparison was made of the relative efficiencies of Universal Preenrichment (UP) broth and lactose broth for the recovery of a variety of Salmonella serovars from pasteurized and unpasteurized apple cider and pasteurized apple juice. Bulk portions of juice were contaminated with single Salmonella serovars at high and low levels of 0.4 and 0.04 CFU/mL, respectively. The juice was aged for a minimum of 5 days at 2-5degreesC. On the day analysis was initiated, each of 20 test portions (25 mL) of the contaminated juice was preenriched in UP broth and in lactose broth. The Bacteriological Analytical Manual Salmonella culture method was followed thereafter. For pasteurized apple cider, UP broth recovered significantly (p < 0.05) more Salmonella-positive test portions than did lactose broth (112 and 75, respectively). For unpasteurized apple cider, UP broth recovered significantly more Salmonella-positive test portions than did lactose broth (326 and 221, respectively). For pasteurized apple juice, UP broth recovered more Salmonella-positive test portions than did lactose broth (93 and 81, respectively). However, this difference was not statistically significant. These results indicate that UP broth should replace lactose broth for the analysis of pasteurized and unpasteurized apple cider and pasteurized apple juice. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, Washington, DC 20204 USA. RP Hammack, TS (reprint author), 5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 18 TC 9 Z9 9 U1 0 U2 0 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 2002 VL 85 IS 2 BP 384 EP 387 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 537XR UT WOS:000174785400011 PM 11990023 ER PT J AU Stewart, DS Reineke, KF Tortorello, ML AF Stewart, DS Reineke, KF Tortorello, ML TI Comparison of assurance gold salmonella EIA, BAX for screening/salmonella, and GENE-TRAK salmonella DLP rapid assays for detection of Salmonella in alfalfa sprouts and sprout irrigation water SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID VEGETABLE SPROUTS; SEEDS AB The Assurance Gold Salmonella EIA, BAX for Screening/Salmonella, and GENE-TRAK Salmonella DLP rapid assays were compared with official cultural methods described in the Bacteriological Analytical Manual (BAM) for analysis of alfalfa sprouts and sprout irrigation water for the presence of Salmonella. The lower limits of detection of 4 serovars of Salmonella cells (S. tennessee, S. muenchen, S. mbandanka, and S. cubana) in pure culture were determined as approximately log(10) 2,5, and 6 for the BAX, GENE-TRAK, and Gold EIA, respectively. Despite its low detection limit, the BAX did not perform as well as the other assays in analyzing contaminated sprouts and sprout irrigation water. For 4 different lots of sprouts and sprout irrigation water samples inoculated with the 4 serovars at low [1-2 colony forming units (CFU/g)] and high (68-180 CFU/g) levels, the BAX detected Salmonella in 58/64 (90.6%) of the samples, compared with 64/64 (100%) by the GENE-TRAK, Gold EIA, and BAM methods. Assay performance was also compared for analysis of naturally contaminated sprouts and sprout irrigation water with 3 lots of alfalfa sprouted seeds associated with different salmonellosis outbreaks. Positive assay results for the naturally contaminated samples were Gold EIA 41, GENE-TRAK 36, BAM 33, and BAX 13. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Tortorello, ML (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 18 TC 13 Z9 14 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 MAR-APR PY 2002 VL 85 IS 2 BP 395 EP 403 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 537XR UT WOS:000174785400013 PM 11990025 ER PT J AU Bird, CB Malone, B Rice, LG Ross, PF Eppley, R Abouzied, MM AF Bird, CB Malone, B Rice, LG Ross, PF Eppley, R Abouzied, MM TI Determination of total fumonisins in corn by competitive direct enzyme-linked immunosorbent assay: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID FUSARIUM-MONILIFORME; EQUINE LEUKOENCEPHALOMALACIA; PULMONARY-EDEMA; SCREENINGS; ELISA; SWINE; FEED AB Fumonisins-mycotoxins produced by some Fusarium species-have been shown to be the causative agent of diseases in horses and other domesticated animals as well as possible carcinogens in humans. A collaborative study was conducted to evaluate the effectiveness of a competitive direct enzyme-linked immunosorbent assay (CD-ELISA) for the determination of total fumonisins (B-1, B-2, and B-3) in corn. The test portion was extracted with methanol-water (7 + 3), filtered, diluted, and tested on the CD-ELISA. Naturally and artificially contaminated corn test portions were sent to 13 collaborators in the United States. Naturally contaminated field test portions were prepared at 3 different levels. Artificially contaminated test portions were spiked at 1.0, 3.0, and 5.0 mg/kg total fumonisins (B-1, B-2, and B-3). Average recoveries of total fumonisins were 120, 100, and 90%, respectively. The relative standard deviations for repeatability ranged from 13.3 to 23.3% and the relative standard deviations for reproducibility ranged from 15.8 to 30.3% across all levels tested. HORRAT values, calculated for each individual sample, ranged from 1.24 to 1.94. This method demonstrated acceptable intra- and interlaboratory precision at the levels tested. C1 Neogen Corp, Lansing, MI 48912 USA. Trilogy Analyt Lab Inc, Washington, MO 63090 USA. Natl Vet Serv Lab, USDA, Anim & Plant Hlth Inspect Serv, Ames, IA 50010 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Bird, CB (reprint author), Neogen Corp, 620 Lesher Pl, Lansing, MI 48912 USA. NR 16 TC 18 Z9 20 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 MAR-APR PY 2002 VL 85 IS 2 BP 404 EP 410 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 537XR UT WOS:000174785400014 PM 11990026 ER PT J AU Raybourne, RB AF Raybourne, RB TI Virulence testing of Listeria mmocytogenes SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 114th AOAC INTERNATIONAL Annual Meeting CY SEP 10-14, 2000 CL PHILADELPHIA, PENNSYLVANIA SP AOAC INT ID TO-CELL SPREAD; MONOCYTOGENES INFECTION; IMMUNOCOMPROMISED MICE; SPORADIC LISTERIOSIS; INTRACELLULAR GROWTH; EPITHELIAL-CELLS; SURFACE PROTEIN; PRFA GENE; PCR; RESISTANCE AB A major problem in understanding foodborne listeriosis from both the basic science and regulatory perspectives revolves around the role played by virulence factors of Listeria monocytogenes and how these interact with host susceptibility to result in the observed incidence of disease. From a mechanistic perspective, this problem has been well investigated, and many virulence components of L. monocytogenes have been discovered. Deletion of these genes results in large reductions in virulence functions in vitro and in vivo. The clonal bacteria and genetically identical hosts necessary to solve the riddles associated with virulence mechanisms are not likely to reflect the natural diversity found among wild populations of L. monocytogenes, including those associated with food. These factors contribute to a major dilemma in risk assessment and risk management of foodborne listeriosis: Although low-level L. monocytogenes contamination of certain foods is relatively common, suggesting widespread exposure, illness is overwhelmingly associated with only a relatively small subpopulation (3 of the 13 L. monocytogenes serotypes) and occurs in only a small proportion of susceptible individuals. Virulence testing based on DNA probes for virulence genes is confounded by the widespread distribution of these genes in food isolates. In terms of the distribution of virulence factors among food isolates of L. monocytogenes, only listeriolysin is well characterized, because P-hemolysis is often used to confirm the presence of L. monocytogenes in foods. The presence of other virulence genes such as those involved in host cell invasion and cell-to-cell spread (inlA and actA) among food isolates has not been extensively investigated. How the presence of these components translates into functional virulence as measured in vivo and in vitro is also unknown. Animal studies and cell culture systems show a range of virulence among food isolates of L. monocytogenes. However, clinical isolates included in such studies are not consistently more virulent than food isolates with no known human disease association. Where multiple serotypes or ribotypes are compared, it has been difficult to demonstrate a consistent pattern of increased virulence associated with any subtype(s) in animal or in vitro studies. Development of model systems that adequately reflect the complexity of the host-pathogen relationship remains a challenge. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Raybourne, RB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 55 TC 16 Z9 18 U1 0 U2 0 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 2002 VL 85 IS 2 BP 516 EP 523 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 537XR UT WOS:000174785400029 PM 11990040 ER PT J AU Zhang, MJ Li, XX Pang, XW Ding, L Wood, O Clouse, KA Hewlett, I Dayton, AI AF Zhang, MJ Li, XX Pang, XW Ding, L Wood, O Clouse, KA Hewlett, I Dayton, AI TI Bcl-2 Upregulation by HIV-1 Tat during infection of primary human macrophages in culture SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE HIV; Tat; Bcl-2; apoptosis; macrophage; HIV-1(BAL) ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; CD4+ T-CELLS; FAS LIGAND; GENE-EXPRESSION; UP-REGULATION; JURKAT CELLS; IN-VIVO; APOPTOSIS; PROTEIN AB The ability of cells of the human monocyte/macrophage lineage to host HIV-1 replication while resisting cell death is believed to significantly contribute to their ability to serve as a reservoir for viral replication in the host. Although macrophages are generally resistant to apoptosis, interruption of anti-apoptotic pathways can render them susceptible to apoptosis. Here we report that HIV-1(BAL) infection of primary human monocyte-derived macrophages (MDM) upregulates the mRNA and protein levels of the anti-apoptic gene, Bcl-2. Furthermore, this upregulation can be quantitatively mimicked by treating MDM with soluble HIV-1 Tat-86 protein. These results suggest that in infecting cells of the monocyte/macrophage lineage, HIV-1 may be benefiting from additional protection against apoptosis caused by specific upregulation of cellular anti-apoptotic genes. Copyright (C) 2002 National Science Council, ROC and S. Karger AG,Basel. C1 US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. US FDA, Div Monoclonal Antibodies, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Dayton, AI (reprint author), US FDA, Div Emerging & Transfus Transmitted Dis, Off Blood Res & Review, Ctr Biol Evaluat & Res, HFM 315,1401 Rockville Pike, Rockville, MD 20852 USA. NR 55 TC 25 Z9 28 U1 0 U2 0 PU KARGER PI BASEL PA ALLSCHWILERSTRASSE 10, CH-4009 BASEL, SWITZERLAND SN 1021-7770 J9 J BIOMED SCI JI J. Biomed. Sci. PD MAR-APR PY 2002 VL 9 IS 2 BP 133 EP 139 PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 537BZ UT WOS:000174738400006 PM 11914580 ER PT J AU Gudemez, E Eksioglu, F Korkusuz, P Asan, E Gursel, I Hasirci, V AF Gudemez, E Eksioglu, F Korkusuz, P Asan, E Gursel, I Hasirci, V TI Chondroitin sulfate-coated polyhydroxyethyl methacrylate membrane prevents adhesion in full-thickness tendon tears of rabbits SO JOURNAL OF HAND SURGERY-AMERICAN VOLUME LA English DT Article DE tendon injuries; adhesion; polyhydroxyethyl methacrylate (pHEMA); chondroitin sulfate; biomaterials ID CHICKENS AB Polyhydroxyethyl methacrylate (pHEMA) membranes coated on one side with chondroitin sulfate (CS) were used to block adhesion physically and to reduce friction between healing flexor tendons and the surrounding tissue in rabbit forepaws after surgical repair. Digits with pHEMA-only, standard tendon sheath repair, and with no sheath repair were the controls. Over 12 weeks the CS-coated membranes were evaluated for joint flexion, adhesion limitation, and tendon healing progress. The membranes initially allowed for better flexion (i.e, for 6 weeks), but their relative superior effectiveness faded afterward. Histology showed that adhesions were less severe and healing was better in the CS-pHEMA membranes at 3 and 6 weeks. If further studies determine precise amounts or thicknesses of CS coats that will maximize its healing properties, CS-pHEMA should prove useful in clinical settings in which restoration of tendon sheath integrity with a minimum of adhesions is not possible. Copyright (C) 2002 by the American Society for Surgery of the Hand. C1 Middle E Tech Univ, Dept Sci Biol, Biotechnol Res Unit, TR-06531 Ankara, Turkey. Kirikkale Univ, Sch Med, Dept Traumat & Orthopaed Surg, Kirikkale, Turkey. Hacettepe Univ, Sch Med, Dept Histol & Embryol, Ankara, Turkey. US FDA, Lab Retroviral Res, Biol Res Ctr, Bethesda, MD 20014 USA. RP Hasirci, V (reprint author), Middle E Tech Univ, Dept Sci Biol, Biotechnol Res Unit, TR-06531 Ankara, Turkey. RI KORKUSUZ, PETEK/I-8321-2013 NR 35 TC 27 Z9 35 U1 0 U2 6 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0363-5023 J9 J HAND SURG-AM JI J. Hand Surg.-Am. Vol. PD MAR PY 2002 VL 27A IS 2 BP 293 EP 306 DI 10.1053/jhsu.2002.31161 PG 14 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 531VE UT WOS:000174437300013 PM 11901389 ER PT J AU Stewart, SFC Bushar, HF AF Stewart, SFC Bushar, HF TI Improved statistical characterization of prosthetic heart valve hydrodynamics using a performance index and regression analysis SO JOURNAL OF HEART VALVE DISEASE LA English DT Article; Proceedings Paper CT 1st Biennial Meeting of the Society-for-Heart-Valve-Disease CY JUN 15-18, 2001 CL LONDON, ENGLAND SP Soc Heart Valve Dis ID PRESSURE AB Background and aims of the study: The ISO 5840 Standard (Cardiovascular implants - Cardiac valves) currently requires a minimum of three test samples per size for hydrodynamic testing. Typically, the only statistical analysis performed is a descriptive analysis, with the mean (+/- SE) given for each size and cardiac output (CO). The study aim was to develop better statistical methods, incorporating regression analysis of a performance index, equal to the effective orifice area divided by the tissue annulus area. The analysis is performed on the full dataset, with size and CO as independent variables. Methods: Hydrodynamic data of Ionescu-Shiley pericardial valves from a published study were used to compare the two analysis methods. Three samples each of size 19, 23 and 27 mm valves were tested at COs of 4.2, 5.6, 7.0 and 8.4 l/min. Descriptive statistics were performed for each size and CO. Regression analysis was also performed on the full dataset. Confidence intervals (CI) were calculated for each statistical method and compared. Results: The regression equation that best fitted the data was: Performance Index (PI) = -1.63 + (0.011 x CO) + (0.167 x size) - (0.0036 x size 2). All four parameter estimates were significantly different from zero (p <0.02). The SE of the mean was 0.015 for COs of 4.2 or 8.4 l/min, and 0.013 for COs of 5.6 or 7.0 l/min, less than that of nine of 12 of the individual descriptive analysis. Cl for the regression analysis were substantially tighter, averaging one-third the width of those of the descriptive statistics. Conclusion: The tighter Cl resulting from the regression analysis allows a better comparison of the PI to an objective performance criterion. Such methods should be considered for inclusion in the new version of the ISO 5840 standard for prosthetic heart valves. C1 US FDA, Off Sci & Technol, Rockville, MD 20850 USA. US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Stewart, SFC (reprint author), US FDA, Hydrodynam & Acoust Branch, 9200 Corp Blvd,HFZ-132, Rockville, MD 20850 USA. NR 13 TC 0 Z9 1 U1 1 U2 6 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD HA6 2ET, ENGLAND SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD MAR PY 2002 VL 11 IS 2 BP 270 EP 274 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 535EL UT WOS:000174632200024 PM 12000171 ER PT J AU Keilholz, U Weber, J Finke, JH Gabrilovich, DI Kast, WM Disis, ML Kirkwood, JM Scheibenbogen, C Schlom, J Maino, VC Lyerly, HK Lee, PP Storkus, W Marincola, F Worobec, A Atkins, MB AF Keilholz, U Weber, J Finke, JH Gabrilovich, DI Kast, WM Disis, ML Kirkwood, JM Scheibenbogen, C Schlom, J Maino, VC Lyerly, HK Lee, PP Storkus, W Marincola, F Worobec, A Atkins, MB TI Immunologic monitoring of cancer vaccine therapy: Results of a workshop sponsored by the Society for Biological Therapy SO JOURNAL OF IMMUNOTHERAPY LA English DT Review DE cancer vaccines; immunologic monitoring; immunotherapy ID T-CELL RESPONSES; COLONY-STIMULATING FACTOR; ENDOTHELIAL GROWTH-FACTOR; HERPES-SIMPLEX VIRUS; NATURAL-KILLER-CELLS; GAMMA-ELISPOT-ASSAY; KAPPA-B ACTIVATION; PHASE-I TRIAL; SIGNAL-TRANSDUCTION MOLECULES; SENSITIVE FLUOROMETRIC ASSAY AB The Society for Biological Therapy held a Workshop last fall devoted to immune monitoring for cancer immunotherapy trials. Participants included members of the academic and pharmaceutical communities as well as the National Cancer Institute and the Food and Drug Administration. Discussion focused on the relative merits and appropriate use of various immune monitoring tools. Six breakout groups dealt with assays of T-cell function, serologic and proliferation assays to assess B cell and T helper cell activity, and enzyme-linked immunospot assay, tetramer, cytokine flow cytometry, and reverse transcription polymerase chain reaction assays of T-cell immunity. General conclusions included: (1) future vaccine studies should be designed to determine whether T-cell dysfunction (tumor-specific and nonspecific) correlated with clinical outcome; (2) tetramer-based assays yield quantitative but not functional data (3) enzyme-linked immunospot assays have the lowest limit of detection (4) cytokine flow cytometry have a higher limit of detection than enzyme-linked immunospot assay, but offer the advantages of speed and the ability to identify subsets of reactive cells; (5) antibody tests are simple and accurate and should be incorporated to a greater extent in monitoring plans; (6) proliferation assays are imprecise and should not be emphasized in future studies; (7) the reverse transcription polymerase chain reaction assay is a promising research approach that is not ready for widespread application; and (8)there is a critical need to validate these assays as surrogates for vaccine potency and clinical effect. Current data and opinion support the use of a functional assay like the enzyme-linked immunospot assay or cytokine flow cytometry in combination with a quantitative assay like tetramers for immune monitoring. At present, assays appear to be most useful as measures of vaccine potency. Careful immune monitoring in association with larger scale clinical trials ultimately may enable the correlation of monitoring results with clinical benefit. C1 Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. UKBF Free Univ, Berlin, Germany. Norris Canc Ctr, Los Angeles, CA USA. Cleveland Clin Fdn, Cleveland, OH USA. H Lee Moffitt Canc Ctr, Tampa, FL USA. Loyola Univ, Ctr Med, Maywood, IL USA. Washington Univ, Seattle, WA USA. Univ Pittsburgh, Inst Canc, Pittsburgh, PA USA. Natl Canc Inst, Bethesda, MD USA. BD Biosci, San Jose, CA USA. Duke Univ, Ctr Med, Durham, NC USA. Stanford Univ, Stanford, CA 94305 USA. US FDA, Rockville, MD 20857 USA. RP Atkins, MB (reprint author), Beth Israel Deaconess Med Ctr, Kirstein Hall Rm 158 330 Brookline Ave, Boston, MA 02215 USA. RI Lyerly, Herbert/B-6528-2014; OI Lyerly, Herbert/0000-0002-0063-4770; Storkus, Walter/0000-0001-8961-4444 NR 271 TC 223 Z9 231 U1 2 U2 8 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 1053-8550 J9 J IMMUNOTHER JI J. Immunother. PD MAR-APR PY 2002 VL 25 IS 2 BP 97 EP 138 DI 10.1097/00002371-200203000-00001 PG 42 WC Oncology; Immunology; Medicine, Research & Experimental SC Oncology; Immunology; Research & Experimental Medicine GA 535TP UT WOS:000174662700001 PM 12074049 ER PT J AU Gursel, I Yagmurlu, F Korkusuz, F Hasirci, V AF Gursel, I Yagmurlu, F Korkusuz, F Hasirci, V TI In vitro antibiotic release from poly(3-hydroxybutyrate-co-3-hydroxyvalerate) rods SO JOURNAL OF MICROENCAPSULATION LA English DT Article DE controlled drug delivery; polyhydroxybutyrate; osteomyelitis; sulperazone; gentamicin (R); encapsulation ID DRUG-DELIVERY SYSTEM; POLY(L-LACTIDE) BONE PLATES; EXPERIMENTAL OSTEOMYELITIS; DEGRADABLE COMPOSITE; INTERNAL-FIXATION; ORTHOPEDIC USE; GENTAMICIN; COPOLYMERS; POLYMERS; CARRIER AB Provision and maintenance of adequate concentrations of antibiotics at infection sites is very important in treating highly resistant infections. For diseases like implant related osteomyelitis (IRO) it is best to provide this locally via implanted drug formulations, as systemic administration of the antibiotic may not be effective due to damaged vasculature. In this study, poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) rods containing 7, 14 and 22% (mol) 3-hydroxyvalerate were loaded with sulbactam:cefoperazone or gentamicin(R) and their antibiotic release behaviours were studied under in vitro conditions in physiological phosphate buffer at room temperature. The release patterns were representative of release from monolithic devices where a rapid early release phase is followed by a slower and prolonged release. With PHBV 22 rods, the latter phase continued for similar to2 months. This duration is critical because a proper antibiotic therapy of IRO requires the minimal effective concentration for at least 6 weeks. After in vitro release, voids with sharp edges were detected on the rods, indicating that the drug crystals dissolved but the polymer did not undergo erosion within this test period. Changing the polymer:drug ratio from 2:1 to 20:1 substantially decreased the drug release rate. A change of polymer type, however, did not lead to any detectable changes in the release patterns. Gentamicin(R) release also followed a similar pattern, except that the concentration of the drug in the release medium exhibited a decrease after long release periods, indicating degradation (or decomposition) of the antibiotic in the release medium. C1 Middle E Tech Univ, Dept Biol Sci, Biotechnol Res Unit, TR-06531 Ankara, Turkey. Biol Res Ctr, US FDA, Lab Retroviral Immunol, Bethesda, MD 20892 USA. Numune State Hosp, Dept Traumat & Orthopaed Surg 3, TR-06100 Ankara, Turkey. Middle E Tech Univ, Ctr Med, TR-06531 Ankara, Turkey. RP Hasirci, V (reprint author), Middle E Tech Univ, Dept Biol Sci, Biotechnol Res Unit, TR-06531 Ankara, Turkey. RI KORKUSUZ, FEZA/I-9501-2013; OI Gursel, Ihsan/0000-0003-3761-1166 NR 34 TC 37 Z9 41 U1 0 U2 7 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK,, ABINGDON OX14 4RN, OXON, ENGLAND SN 0265-2048 J9 J MICROENCAPSUL JI J. Microencapsul. PD MAR-APR PY 2002 VL 19 IS 2 BP 153 EP 164 DI 10.1080/02652040110065413 PG 12 WC Chemistry, Applied; Engineering, Chemical; Pharmacology & Pharmacy SC Chemistry; Engineering; Pharmacology & Pharmacy GA 515BK UT WOS:000173475400002 PM 11837970 ER PT J AU Hussain, M Sarkar, FH Djuric, Z Pollak, MN Banerjee, M Doerge, D Fontana, J Chinni, S Davis, J Forman, J Wood, DP Kucuk, O AF Hussain, M Sarkar, FH Djuric, Z Pollak, MN Banerjee, M Doerge, D Fontana, J Chinni, S Davis, J Forman, J Wood, DP Kucuk, O TI Soy isoflavones in the treatment of prostate cancer. SO JOURNAL OF NUTRITION LA English DT Meeting Abstract C1 Wayne State Univ, Div Hematol & Oncol, Detroit, MI 48202 USA. Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA. Wayne State Univ, Dept Radiat Oncol, Detroit, MI 48202 USA. Wayne State Univ, Dept Urol, Detroit, MI 48202 USA. Wayne State Univ, Ctr Healthcare Effectiveness Res, Detroit, MI 48202 USA. Barbara Ann Karmanos Canc Inst, Detroit, MI USA. VA Med Ctr, Detroit, MI USA. McGill Univ, Dept Med, Montreal, PQ, Canada. McGill Univ, Jewish Gen Hosp, Montreal, PQ H3T 1E2, Canada. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RI Pollak, Michael/G-9094-2011; Djuric, Zora/H-5147-2013 OI Pollak, Michael/0000-0003-3047-0604; Djuric, Zora/0000-0002-8886-8853 NR 0 TC 8 Z9 8 U1 0 U2 2 PU AMER INST NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-3166 J9 J NUTR JI J. Nutr. PD MAR PY 2002 VL 132 IS 3 BP 575S EP 576S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 527ML UT WOS:000174189800053 ER PT J AU Doerge, DR AF Doerge, DR TI Soy and the thyroid: Can the effects of isoflavones observed in rodent studies guide human investigations? SO JOURNAL OF NUTRITION LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 1 TC 1 Z9 1 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 MAR PY 2002 VL 132 IS 3 BP 580S EP 581S PG 2 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 527ML UT WOS:000174189800068 ER PT J AU Paige, JC AF Paige, JC TI The importance of understanding human misuse of veterinary medications SO JOURNAL OF RURAL HEALTH LA English DT Editorial Material C1 US FDA, Div Epidemiol, Rockville, MD 20857 USA. RP Paige, JC (reprint author), US FDA, Div Epidemiol, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL RURAL HEALTH ASSOC PI KANSAS CITY PA ONE WEST ARMOUR BLVD, STE 301, KANSAS CITY, MO 64111 USA SN 0890-765X J9 J RURAL HEALTH JI J. Rural Health PD SPR PY 2002 VL 18 IS 2 BP 309 EP 310 DI 10.1111/j.1748-0361.2002.tb00892.x PG 2 WC Health Care Sciences & Services; Health Policy & Services; Public, Environmental & Occupational Health SC Health Care Sciences & Services; Public, Environmental & Occupational Health GA 588GN UT WOS:000177693900006 PM 12135151 ER PT J AU Mohan, KVK Som, I Atreya, CD AF Mohan, KVK Som, I Atreya, CD TI Identification of a type 1 peroxisomal targeting signal in a viral protein and demonstration of its targeting to the organelle SO JOURNAL OF VIROLOGY LA English DT Article ID SIMIAN ROTAVIRUS SA11; FATTY-ACIDS; ENHANCEMENT; INFECTIVITY; MEMBRANE; SEQUENCE; IMPORT; CELLS; VP4 AB Peroxisomes are unimembrane, respiratory organelles of the cell. Transport of cellular proteins to the peroxisomal matrix requires a type 1 peroxisomal targeting signal (PTS1) which essentially constitutes a tripeptide from the consensus sequence S/T/A/G/C/N-K/R/H-L/I/V/M/A/F/Y. Although PTS-containing proteins have been identified in eukaryotes, prokaryotes, and parasites, viral proteins with such signals have not been identified so far. We report here the first instance of a virus, the rotavirus, which causes infantile diarrhea worldwide, containing a functional C-terminal PTS1 in one of its proteins (VP4). Analysis of 153 rotavirus VP4-deduced amino acid sequences identified five groups of conserved C-terminal PTS1 tripeptide sequences (SKL, CKL, GKL, CRL, and CRI), of which CRL is represented in approximately 62% of the sequences. Infection of cells by a CRL-containing representative rotavirus (SA11 strain) and confocal immunofluorescence analysis revealed colocalization of VP4 with peroxisomal markers and morphological changes of peroxisomes. Further, transient cellular expression of green fluorescent protein (GFP)-fused VP4CRL resulted in transport of VP4 to peroxisomes, whereas the chimera lacking the PTS1 signal, GFP-VP4DeltaCRL, resulted in diffuse cytoplasmic staining, suggesting a CRL-dependent targeting of the protein. The present study therefore demonstrates hitherto unreported organelle involvement, specifically of the peroxisomes, in rotaviral infections as demonstrated by using the SA11 strain of rotavirus and opens a new line of investigation toward understanding viral pathogenesis and disease mechanisms. C1 US FDA, Ctr Biol Evaluat & Res, Sect Viral pathogenesis & Vaccine Adverse React, Lab Pediat & Resp Viral Dis,Div Viral Prod, Bethesda, MD 20892 USA. RP Atreya, CD (reprint author), US FDA, Ctr Biol Evaluat & Res, Sect Viral pathogenesis & Vaccine Adverse React, Lab Pediat & Resp Viral Dis,Div Viral Prod, Bldg 29A,Room 2C-11,HFM-460,NIH Campus,8800 Rock, Bethesda, MD 20892 USA. NR 30 TC 27 Z9 27 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 MAR PY 2002 VL 76 IS 5 BP 2543 EP 2547 DI 10.1128/JVI.76.5.2543-2547.2002 PG 5 WC Virology SC Virology GA 519ZX UT WOS:000173756300053 PM 11836432 ER PT J AU Ge, BL Zhao, SH Hall, R Meng, JH AF Ge, BL Zhao, SH Hall, R Meng, JH TI A PCR-ELISA for detecting Shiga toxin-producing Escherichia coli SO MICROBES AND INFECTION LA English DT Article DE PCR; ELISA; Shiga toxin-producing E. coli ID POLYMERASE-CHAIN-REACTION; RAPID ENUMERATION; EAE-GENE; O157-H7; FOOD; SAMPLES; ASSAY; IDENTIFICATION; SEROTYPE; ALLELE AB A sensitive and specific PCR-ELISA was developed to detect Escherichia coli O157:H7 and other Shiga toxin-producing E. coli (STEC) in food. The assay was based on the incorporation of digoxigenin-labeled dUTP and a biotin-labeled primer specific for Shiga toxin genes during PCR amplification. The labeled PCR products were bound to streptavidin-coated wells of a microtiter plate and detected by an ELISA. The specificity of the PCR was determined using 39 bacterial strains, including STEC, enteropathogenic E. coli, E. coli K12, and Salmonella. All of the STEC strains were positive, and non-STEC organisms were negative. The ELISA detecting system was able to increase the sensitivity of the PCR assay by up to 100-fold, compared with a conventional gel electrophoresis. The detection limit of the PCR-ELISA was 0.1-10 CFU dependent upon STEC serotypes, and genotypes of Shiga toxins. With the aid of a simple DNA extraction system, PrepMan, the PCR-ELISA was able to detect ca. 10(5) CFU of STEC per grain of ground beef without any culture enrichment. The entire procedure took about 6 h. Because of its microtiter plate format, PCR-ELISA is particularly suitable for large-scale screening and compatible with future automation. (C) 2002 Editions scientifiques et medicales Elsevier SAS. All rights reserved. C1 Univ Maryland, Dept Food Sci & Nutr, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Meng, JH (reprint author), Univ Maryland, Dept Food Sci & Nutr, College Pk, MD 20742 USA. NR 24 TC 20 Z9 28 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1286-4579 J9 MICROBES INFECT JI Microbes Infect. PD MAR PY 2002 VL 4 IS 3 BP 285 EP 290 AR PII S1286-4579(02)01540-X DI 10.1016/S1286-4579(02)01540-X PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 539JT UT WOS:000174867300004 PM 11909738 ER PT J AU Menozzi, FD Pethe, K Bifani, P Soncin, F Brennan, MJ Locht, C AF Menozzi, FD Pethe, K Bifani, P Soncin, F Brennan, MJ Locht, C TI Enhanced bacterial virulence through exploitation of host glycosaminoglycans SO MOLECULAR MICROBIOLOGY LA English DT Review ID HEPARIN-BINDING HEMAGGLUTININ; FILAMENTOUS HEMAGGLUTININ; BORDETELLA-PERTUSSIS; NEISSERIA-GONORRHOEAE; CHLAMYDIA-TRACHOMATIS; EPITHELIAL-CELLS; FIBROBLAST GROWTH; RESPIRATORY-TRACT; EUKARYOTIC CELLS; FIMBRIAL SUBUNIT AB Present in the extracellular matrix and membranes of virtually all animal cells, proteoglycans (PGs) are among the first host macromolecules encountered by infectious agents. Because of their wide distribution and direct accessibility, it is not surprising that pathogenic bacteria have evolved mechanisms to exploit PGs for their own purposes, including mediating attachment to target cells. This is achieved through the expression of adhesins that recognize glycosaminoglycans (GAGs) linked to the core protein of PGs. Some pathogens, such as Bordetella pertussis and Chlamydia trachomatis, may express more than one GAG-binding adhesin. Bacterial interactions with PGs may also facilitate cell invasion or systemic dissemination, as observed for Neisseria gonorrhoeae and Mycobacterium tuberculosis respectively. Moreover, pathogenic bacteria can use PGs to enhance their virulence via a shedding of PGs that leads to the release of effectors that weaken the host defences. The exploitation of PGs by pathogenic bacteria is thus a multifaceted mechanistic process directly related to the potential virulence of a number of microorganisms. C1 Inst Pasteur, INSERM, U447, F-59019 Lille, France. Inst Biol Lille, UMR 8526, F-59019 Lille, France. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Menozzi, FD (reprint author), Inst Pasteur, INSERM, U447, Rue Prof Calmette, F-59019 Lille, France. RI SONCIN, Fabrice/A-1475-2009; Pethe, Kevin/D-4505-2011; Pethe, Kevin/L-1199-2013; Pethe, Kevin/F-9495-2015; OI Pethe, Kevin/0000-0003-0297-0150; Soncin, Fabrice/0000-0001-6312-0673 NR 71 TC 56 Z9 58 U1 1 U2 9 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 MAR PY 2002 VL 43 IS 6 BP 1379 EP 1386 DI 10.1046/j.1365-2958.2002.02841.x PG 8 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 536NZ UT WOS:000174710000002 PM 11971262 ER PT J AU Chen, T Harrington-Brock, K Moore, MM AF Chen, T Harrington-Brock, K Moore, MM TI Mutant frequencies and loss of heterozygosity induced by N-ethyl-N-nitrosourea in the thymidine kinase gene of L5178Y/TK+-3.7.2C mouse lymphoma cells SO MUTAGENESIS LA English DT Article ID SISTER-CHROMATID EXCHANGES; TK-/ MUTANTS; MUTATIONS; AGENTS; DNA; MUTAGENICITY; GENOTOXICITY; ABERRATIONS; INDUCTION; REPAIR AB N-ethyl-N-nitrosourea (ENU) is a potent monofunctional ethylating agent that has been found to be mutagenic in a wide variety of organisms from viruses to mammalian germ cells. To elucidate the mutagenicity of ENU at the Tk(+/-) locus of mouse lymphoma cells and to confirm the ability of the mouse lymphoma assay (MLA) to detect both point mutations and large DNA alterations, Tk(+/-) L5178Y cells were exposed to different doses of ENU. Treatment of the cells with ENU resulted in a linear dose response with mutant frequencies of up to 16-fold over control. Evaluation of mutant clone size showed that 36% of the 100 mug/ml ENU-induced clones (66% in control) were small colony mutants and 64% (34% in control) were large colony mutants. DNA isolated from mutants in the control culture and the 100 mug/ml ENU treatment group was analyzed for loss of heterozygesity (LOH) using allele-specific PCR. The majority of the small colony mutants, both ENU-treated (97%) and spontaneous (91%), lost the Tk1b allele. The percentage of allele loss in ENU-Induced large colony mutants was distinctly different from that of the control. Twenty-three percent of ENU-induced large colony mutants lost their Tk1b alleles, whereas 73% of the large colony mutants from the control culture lost the allele (P < 0.001). Overall, 50% of the Tk mutants from the 100 μg/ml ENU-treated cultures (86% in control) showed LOH. Our data indicate that ENU is a potent mutagen in mouse lymphoma cells and that 100 μg/ml ENU induces equal numbers of point mutations and chromosomal mutations. This study serves to verify that the MLA detects both point mutations and chromosomal mutations. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Technol, Jefferson, AR 72079 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27709 USA. RP Chen, T (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Technol, Jefferson, AR 72079 USA. NR 32 TC 23 Z9 28 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 2002 VL 17 IS 2 BP 105 EP 109 DI 10.1093/mutage/17.2.105 PG 5 WC Genetics & Heredity; Toxicology SC Genetics & Heredity; Toxicology GA 531QC UT WOS:000174426000003 PM 11880538 ER PT J AU Morris, SM AF Morris, SM TI A role for p53 in the frequency and mechanism of mutation SO MUTATION RESEARCH-REVIEWS IN MUTATION RESEARCH LA English DT Review DE p53; mutant p53; loss-of-function; p53 knockout ID WILD-TYPE P53; NUCLEOTIDE EXCISION-REPAIR; HUMAN LYMPHOBLASTOID-CELLS; TUMOR-SUPPRESSOR GENE; INTRACHROMOSOMAL HOMOLOGOUS RECOMBINATION; HUMAN OSTEOSARCOMA CELLS; THYMIDINE KINASE LOCUS; EYED UNSTABLE MUTATION; C-TERMINAL DOMAIN; MUTANT P53 AB The tumor suppressor protein. p53, is often referred to as the guardian of the genome. when p53 function is impaired, its ability to preserve genomic integrity is compromised. This may result in an increase in mutation on both a molecular and chromosomal level and contribute to the progression to a malignant phenotype. In order to study the effect of p53 function on the acquisition of mutation, in vitro and in vivo models have been developed in which both the frequency and mechanism of mutation can be analyzed. In human lymphoblastoid cells in which p53 function was impaired, both the spontaneous and induced mutant frequency increased at the autosomal thymidine kinase (TK) locus. The mutant frequency increased to a greater extent in cell lines in which p53 harbored a point mutation than in those lines in which a "null" mutation had been introduced by molecular targeting or by viral degradation indicating a possible "gain-of-function" associated with the mutant protein. Further, molecular analysis revealed that the loss of p53 function was associated with a greater tendency towards loss-of-heterozygosity (LOH) within the TK gene that was due to non-homologous recombination than that found in wild-type cells. Most data obtained from the in vivo models uses the LacI reporter gene that does not efficiently detect mutation that results in LOH. However, studies that have examined the effect of p53 status on mutation in the adenine phosphoribosyl transferase (APRT) gene in transgenic mice also suggest that loss of p53 function results in an increase in mutation resulting from non-homologous recombination. The results of these studies provide clear and convincing evidence that p53 plays a role in modulating the mutant frequency and the mechanism of mutation. In addition, the types of mutation that occur within the p53 gene are also of importance in determining the mutant frequency and the pathways leading to mutation, Published by Elsevier Science B.V. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Morris, SM (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 149 TC 59 Z9 63 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5742 J9 MUTAT RES-REV MUTAT JI Mutat. Res.-Rev. Mutat. Res. PD MAR PY 2002 VL 511 IS 1 BP 45 EP 62 AR PII S1383-5742(01)00075-8 DI 10.1016/S1383-5742(01)00075-8 PG 18 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 547CY UT WOS:000175316500003 PM 11906841 ER PT J AU Bonson, KR Grant, SJ Contoreggi, CS Links, JM Metcalfe, J Weyl, HL Kurian, V Ernst, M London, ED AF Bonson, KR Grant, SJ Contoreggi, CS Links, JM Metcalfe, J Weyl, HL Kurian, V Ernst, M London, ED TI Neural systems and cue-induced cocaine craving SO NEUROPSYCHOPHARMACOLOGY LA English DT Article DE craving; cocaine; cognitive; brain imaging; positron emission tomography (PET); cerebral glucose metabolism ID POSITRON-EMISSION-TOMOGRAPHY; HUMAN PREFRONTAL CORTEX; OBSESSIVE-COMPULSIVE DISORDER; PRIMATE ORBITOFRONTAL CORTEX; ANTERIOR CINGULATE CORTEX; WORKING-MEMORY; HUMAN BRAIN; BASOLATERAL AMYGDALA; HIERARCHICAL ORGANIZATION; SYMPTOM PROVOCATION AB We have extended our previous work investigating the neural correlates of cue-induced cocaine craving through the use of positron emission tomography with greater spatial resolution (<4.6 mm), an evocative script, and a pixel-by-pixel analysis. Craving and cerebral glucose metabolism were measured after presentation of cocaine-related or neutral cues to 11 cocaine abusers. Cocaine cues elicited a higher degree of craving titan has been previously reported and resulted in left hemispheric activation of lateral amygdala, lateral orbitofrontal cortex, and rhinal cortex and right hemispheric activation of dorsolateral prefrontal cortex and cerebellum. The intensity of activation in these areas (except cerebellum), as well its left insula, was also correlated with craving. Deactivation occurred in left ventral pole and left medial prefrontal cortex. The results suggest that induction of drug craving involves a neural network that assigns incentive motivational value to environmental stimuli through the coactivation of brain regions that process information about memories and emotions. (C) 2002 American College of Neuropsychopharmacology. Published by Elsevier Science Inc. C1 Natl Inst Drug Abuse, Brain Imaging Ctr, Baltimore, MD 21224 USA. Johns Hopkins Univ, Sch Publ Hlth, Baltimore, MD 21205 USA. Columbia Univ, Dept Psychol, New York, NY 10027 USA. RP Bonson, KR (reprint author), US FDA, Controlled Substance Staff, HFD-009,5600 Fishers Lane, Rockville, MD 20857 USA. NR 74 TC 281 Z9 294 U1 12 U2 21 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0893-133X J9 NEUROPSYCHOPHARMACOL JI Neuropsychopharmacology PD MAR PY 2002 VL 26 IS 3 BP 376 EP 386 AR PII S0893-133X(01)00371-2 DI 10.1016/S0893-133X(01)00371-2 PG 11 WC Neurosciences; Pharmacology & Pharmacy; Psychiatry SC Neurosciences & Neurology; Pharmacology & Pharmacy; Psychiatry GA 523UU UT WOS:000173976300011 PM 11850152 ER PT J AU Popke, EJ Patton, R Newport, GD Rushing, LG Fogle, CM Allen, RR Pearson, EC Hammond, TG Paule, MG AF Popke, EJ Patton, R Newport, GD Rushing, LG Fogle, CM Allen, RR Pearson, EC Hammond, TG Paule, MG TI Assessing the potential toxicity of MK-801 and remacemide: Chronic exposure in juvenile rhesus monkeys SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE remacemide; MK-801; N-methyl-D-aspartate (NMDA); fast sodium channels; clinical chemistry; hematology; ophthalmology; home-cage behavior; rhesus monkeys ID NMDA RECEPTOR ANTAGONISTS; CENTRAL-NERVOUS-SYSTEM; NONHUMAN-PRIMATES; DOUBLE-BLIND; TOLERABILITY; SAFETY; PHARMACOKINETICS; HYDROCHLORIDE; PERFORMANCE; PERIPHERY AB The present experiment examined the effects of chronic exposure to either 0.1 or 1.0 mg/kg MK-801 [a selective V-methyl-D-aspartate (NMDA) receptor antagonist] or 20.0 or 50.0 mg/kg remacemide (an NMDA receptor antagonist which also blocks fast sodium channels) in juvenile rhesus monkeys, Endpoints were monitored to provide a general index of subjects' health and included measures of clinical chemistry, hematology, ophthalmology, spontaneous home-cage behavior, and peak drug plasma levels. In general, both drugs were well tolerated and produced no treatment-related effects during 2 years of dosing and assessment. Periodic plasma drug level determinations provided limited evidence that both compounds may induce their own metabolism. The present results contrast sharply with previously reported effects of long-lasting impairments in the acquisition of incremental learning and in the development of color and position discrimination in these same subjects. These observations highlight the importance of collecting a broad range of toxicology data, including tests of cognitive function, to make comprehensive assessments of new drug safety, In the present case, the less obvious effects of these drugs on cognition defined the toxicologic response. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, US FDA, Jefferson, AR 72079 USA. Charles River Labs, Jefferson, AR USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR USA. Peak Statist Serv, Evergreen, CO USA. AstraZeneca, Safety Assessment, Loughborough LE11 5RH, Leics, England. RP Paule, MG (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, US FDA, HFT 132 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 28 TC 10 Z9 10 U1 1 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 2002 VL 24 IS 2 BP 193 EP 207 AR PII S0892-0362(02)00206-4 DI 10.1016/S0892-0362(02)00206-4 PG 15 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 555GE UT WOS:000175785600008 PM 11943507 ER PT J AU Hinson, JA Bucci, TJ Irwin, LK Michael, SL Mayeux, PR AF Hinson, JA Bucci, TJ Irwin, LK Michael, SL Mayeux, PR TI Effect of inhibitors of nitric oxide synthase on acetaminophen-induced hepatotoxicity in mice SO NITRIC OXIDE-BIOLOGY AND CHEMISTRY LA English DT Article DE acetaminophen; nitric oxide; peroxynitrite; nitrotyrosine; hepatotoxicity; aminoguanidine ID NITROTYROSINE-PROTEIN ADDUCTS; LIPID-PEROXIDATION; IMMUNOHISTOCHEMICAL LOCALIZATION; GLUTATHIONE-PEROXIDASE; CARBON-TETRACHLORIDE; COVALENT BINDING; HEPATIC-NECROSIS; REACTIVE OXYGEN; PEROXYNITRITE; TOXICITY AB We recently reported that following a toxic dose of acetaminophen to mice, tyrosine nitration occurs in the protein of cells that become necrotic. Nitration of tyrosine is by peroxynitrite, a species formed from nitric oxide (NO) and superoxide. In this manuscript we studied the effects of the NO synthase inhibitors N-monomethyl-L-arginine (L-NMIA), N-nitro-L-arginine methyl ester (NAME), L-N-(1-iminoethyl)lysine (L-NIL), and aminoguanidine on acetaminophen hepatotoxicity. Acetaminophen (300 mg/kg) increased serum nitrate/nitrite and alanine aminotransferase (ALT) levels, indicating increased NO synthesis and liver necrosis, respectively. None of the NO synthase inhibitors reduced serum ALT levels. In fact, L-NMMA, L-NIL, and aminoguanidine significantly augmented acetaminophen hepatotoxicity at 4 h. A detailed time course indicated that aminoguanidine (15 mg/kg at 0 h and 15 mg/kg at 2 h) significantly increased serum ALT levels over that for acetaminophen alone at 2 and 4 h; however, at 6 and 8 h serum ALT levels in the two groups were identical. At 2 h following acetaminophen plus aminoguanidine NO synthesis was significantly increased; however, at 4, 6, and 8 h NO synthesis was significantly decreased. Aminoguanidine also decreased acetaminophen-induced nitration of tyrosine. Acetaminophen alone did not induce lipid peroxidation, but acetaminophen plus aminoguanidine significantly increased hepatic lipid peroxidation (malondialdehyde levels) at 2, 4, and 6 h. These data are consistent with NO having a critical role in controlling superoxide-mediated lipid peroxidation in acetaminophen hepatotoxicity. Thus, acetaminophen hepatotoxicity may be mediated by either lipid peroxidation or by peroxynitrite. (C) 2001 Elsevier Science (USA). C1 Univ Arkansas Med Sci, Coll Med, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Natl Ctr Toxicol Res, Pathol Associates Inc, Jefferson, AR 72079 USA. RP Hinson, JA (reprint author), Univ Arkansas Med Sci, Coll Med, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. FU NIGMS NIH HHS [GM58884] NR 49 TC 59 Z9 63 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 1089-8603 J9 NITRIC OXIDE-BIOL CH JI Nitric Oxide-Biol. Chem. PD MAR PY 2002 VL 6 IS 2 BP 160 EP 167 DI 10.1006/niox.2001.0404 PG 8 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 533MP UT WOS:000174534500006 PM 11890740 ER PT J AU Rodriguez, WJ Schwartz, RH Thorne, MM AF Rodriguez, WJ Schwartz, RH Thorne, MM TI Evaluation of diagnostic tests for influenza in a pediatric practice SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article; Proceedings Paper CT 38th Annual Meeting of the Infectious-Diseases-Society-of-America CY SEP 07-10, 2000 CL NEW ORLEANS, LOUISIANA SP Infect Dis Soc Amer DE influenza; rapid diagnostic test ID INHALED ZANAMIVIR; PREVENTION; EFFICACY; SAFETY AB Introduction. Recent advances in the diagnosis and treatment of influenza virus infections include: (1) rapid bedside diagnosis methods with simple commercially available tests; and (2) Food and Drug Administration approval of treatment for children 1 year of age and older with neuraminidase inhibitor drugs. For proven benefit antivirals should be used within 2 days of onset of symptoms. Objectives. We conducted a performance improvement exercise comparing the sensitivity and specificity of four rapid tests for influenza viruses: (1) Flu OIA (Biostar); (2) Quickvue Influenza Test Quidel); (3) Z Stat Flu (ZymeTx); and (4) Directigen Flu A (Becton Dickinson). Methods. During the 1999 to 2000 epidemic, symptomatic patients seen at the private practice of one of the authors provided specimens collected and processed according to the manufacturer's directions. Throat swabs only were used to collect the specimens for the Z Stat Flu Kit. Directigen was performed immediately, and the others were run in parallel within 12 to 24 h. Specimens were frozen first at -20degreesC for up to 3 days and shipped in transport medium to the Virology Research Laboratory of the Virginia State Health Department for culture where they were stored at -60degreesC until cultured. Some of the samples were processed by a commercial laboratory. Results. Specimens from 116 patients were available for influenza culture; for 88 of these culture was performed at the State Health Department Laboratory, and for 28 culture was performed at a local commercial medical laboratory. Influenza virus (A) was detected in 58 of 116 (50%) specimens, 10 (17%) of these only by direct fluorescent antigen samples. Viral culture-direct fluorescent antigen results were used as the standard. Of the 4 tests Biostar and Z Stat Flu required more technician time (by an average of 2-fold). The 4 tests had sensitivities ranging from 72 to 95%. Z Stat differed significantly in sensitivity from the other three (P = 0.001). The specificities of Directigen, Quickvue, Flu OIA and Z Stat Flu were similar (76 to 86%). The positive predictive value of Directigen, Quickvue and FluOIA and Z Stat ranged from 80 to 86%. The negative predictive value of all 4 tests ranged from 75 to 94%. Z Stat Flu had a lower negative predictive value than the other 3 tests (75%; P 0.001. Conclusion. In this first head-to-head comparison of four rapid diagnostic tests for influenza, Directigen Flu A, Quickvue and Flu OIA appear equivalent in sensitivity, specificity, positive predictive value and negative predictive value. Z Stat Flu was not as sensitive or as efficient as the other three tests. C1 US FDA, US Dept HHS, Ctr Drug Evaluat & Res, Off Review Management,Off Drug Evaluat, Rockville, MD 20857 USA. Fairfax Hosp, INOVA, Falls Church, VA 22046 USA. Adv Pediat, Vienna, VA USA. RP Rodriguez, WJ (reprint author), US FDA, US Dept HHS, Ctr Drug Evaluat & Res, Off Review Management,Off Drug Evaluat, Rockville, MD 20857 USA. NR 11 TC 78 Z9 79 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAR PY 2002 VL 21 IS 3 BP 193 EP 196 DI 10.1097/00006454-200203000-00006 PG 4 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 531WD UT WOS:000174439500004 PM 12005080 ER PT J AU Jackson, AJ AF Jackson, AJ TI Determination of in vivo bioequivalence SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material DE bioequivalence; highly-variable; metrics; cutaneous pharmacokinetics AB The May and June 2001 issues of Pharmaceutical Research contained three articles related to the determination of in vivo Bioequivalence (1-3). The articles discussed: (a) the bioequivalence of highly variable drugs, (b) novel metrics for direct comparison of bioequivalence study plasma curves, and (c) the role of a microemulsion vehicle on cutaneous bioequivalence. An analysis of the relationship and potential impact of these articles on their respective areas of bioequivalence will be addressed in this commentory. C1 FDA, Div Bioequivalence, Off Gener Drugs, CDER, Rockville, MD 20857 USA. RP Jackson, AJ (reprint author), FDA, Div Bioequivalence, Off Gener Drugs, CDER, Rockville, MD 20857 USA. NR 6 TC 2 Z9 2 U1 0 U2 2 PU KLUWER ACADEMIC/PLENUM PUBL PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD MAR PY 2002 VL 19 IS 3 BP 227 EP 228 DI 10.1023/A:1014422430027 PG 2 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 532WA UT WOS:000174497000002 PM 11934226 ER PT J AU Bright, RA Nelson, RC AF Bright, RA Nelson, RC TI Automated support for pharmacovigilance: a proposed system SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE postmarketing surveillance; pharmacovigilance; spontaneous reporting; computing; signal detection AB Governments, manufacturers, and other entities are interested in adverse event surveillance of marketed medical products. FDA's Center for Drug Evaluation and Research redesigned the post-marketing adverse reaction surveillance process to use the advantages of new technology. As part of this effort, a 'Pharmacovigilance Working Group' designed a new strategy for the review and analyses of adverse event reports received by FDA. It created requirements which divided signal detection into five tiers: (1) Single 'urgent' reports would be sent to reviewers' workstations nightly for immediate attention. Reviewers would be able to customize definitions of 'urgent' (events that should not wait for aggregate review). (2) Single urgent reports would be placed in a context matrix containing historical counts of similar events to aid in initial interpretation. (3) In this first level of aggregate review, graphical displays would highlight patterns within all the reports, both urgent and non-urgent, and (4) periodic drug-specific tabled-based reports would display the newly received reports across a pre-defined variety of displays. These four tiers would produce passive and criteria-based results which would be presented to safety reviewers' electronic workstations. (5) Active query capabilities (routine, such as age, sex, and year distributions, as well as ad hoc) would be available for exploring alerted issues. The historical database would be migrated into the new format. All historical and new reaction data would be coded with the new MedDRA (Medical Dictionary for Regulatory Activities) scheme. The strategy was to design a full data capture system which effectively exploits current computing advances and technical performance to automate many aspects of initial adverse event review, supporting more efficient and effective clinical assessment of safety signals. Published in 2002 by John Wiley Sons, Ltd. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RCN Associates Inc, Annapolis, MD 21403 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Bright, RA (reprint author), US FDA, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. RI Bright, Roselie/D-2240-2016 NR 10 TC 10 Z9 10 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAR PY 2002 VL 11 IS 2 BP 121 EP 125 DI 10.1002/pds.684 PG 5 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 544ZV UT WOS:000175192500005 PM 11998536 ER PT J AU Ishibe, N Sinha, R Hein, DW Kulldorff, M Strickland, P Fretland, AJ Chow, WH Kadlubar, FF Lang, NP Rothman, N AF Ishibe, N Sinha, R Hein, DW Kulldorff, M Strickland, P Fretland, AJ Chow, WH Kadlubar, FF Lang, NP Rothman, N TI Genetic polymorphisms in heterocyclic amine metabolism and risk of colorectal adenomas SO PHARMACOGENETICS LA English DT Article DE heterocyclic amines; MelQx; colorectal adenomas; N-acetyltransferases ID ARYLAMINE N-ACETYLTRANSFERASE; UNITED-STATES; COLON-CANCER; RED MEAT; POLYADENYLATION POLYMORPHISM; ACETYLATOR PHENOTYPE; FAMILY HISTORY; COOKING METHOD; WELL-DONE; DIET AB High red meat intake has been linked with an increased risk of colorectal cancer and adenomas. During high temperature cooking of red meats, heterocyclic amines (HCAs) are generated; however, to be carcinogenic, they must be metabolized by enzymes including cytochrome P450 1A2 (CYP1A2) and N-acetyltransferase 1 (NAT1) and/or N-acetyltransferase 2 (NAT2). We have conducted a clinic-based case-control study of colorectal adenomas that focused on assessment of exposure to HCAs (estimated by use of a HCA database and meat cooking module) and modification of these exposures by genetic factors. We have previously reported that intake of MelQx was associated with an increased risk of colorectal adenomas [overall association at 80th percentile, > 27.00 ng/day: odds ratio (OR) = 2.68,95% confidence interval (CI) 1.58-4.55]. Here, we report our evaluation of whether variation in CYP1A2, NAT1 and/or NAT2 modify the association between HCAs and colorectal adenoma formation in 146 cases and 228 frequency-matched controls. The NAT1* 10 allele was associated with a nonsignificant increased risk of colorectal adenomas (OR = 1.43; 95% Cl 0.86-2.36). Further, when we analysed 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MelQx) intake as a categorical variable, we observed a six-fold increase in adenoma risk among rapid NAT1 acetylators who consumed more than 27 ng a day (OR = 6.50; 95% Cl 2.16-19.7), whereas among slow NAT1 acetylators, the increase in risk was two-fold (OR = 2.32; 95% Cl 1.12-4.81). While suggestive, the results were not significantly different from each other on either an additive or multiplicative scale. In contrast, NAT2 genotype and CYP1A2 and NAT2 hepatic activity measured by caffeine urinary metabolites were not associated with adenoma risk, although an increase in risk with rapid CYP1A2 activity could not be ruled out (OR = 1.46; 95% Cl 0.76-2.81). Moreover, there was no evidence that the effect of MeIQx was enhanced among subjects in any subgroup defined by variation in these measures. These results are compatible with the hypothesis that high HCA exposure is associated with an increased risk of colorectal adenomas, particularly in genetically susceptible subgroups. Further study of larger populations is needed to confirm and extend these observations. C1 NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, Bethesda, MD 20892 USA. Univ Louisville, Sch Med, Dept Pharmacol & Toxicol, Louisville, KY 40292 USA. Univ Connecticut, Sch Med, Div Biostat, Dept Community Med & Hlth Care, Farmington, CT USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Environm Hlth Sci, Baltimore, MD USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Ishibe, N (reprint author), NCI, Genet Epidemiol Branch, Div Canc Epidemiol & Genet, NIH, 6120 Execut Blvd,MSC 7236, Bethesda, MD 20892 USA. RI Hein, David/A-9707-2008; Kulldorff, Martin/H-4282-2011; Sinha, Rashmi/G-7446-2015; OI Sinha, Rashmi/0000-0002-2466-7462; Kulldorff, Martin/0000-0002-5284-2993 FU NCI NIH HHS [CA-34627, R01 CA034627, R01 CA034627-16]; NIEHS NIH HHS [ES06052] NR 58 TC 87 Z9 88 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0960-314X J9 PHARMACOGENETICS JI Pharmacogenetics PD MAR PY 2002 VL 12 IS 2 BP 145 EP 150 DI 10.1097/00008571-200203000-00008 PG 6 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy SC Biotechnology & Applied Microbiology; Genetics & Heredity; Pharmacology & Pharmacy GA 540UE UT WOS:000174947200008 PM 11875368 ER PT J AU Katz, DG Dutcher, GA Toigo, TA Bates, R Temple, F Cadden, CG AF Katz, DG Dutcher, GA Toigo, TA Bates, R Temple, F Cadden, CG TI The AIDS Clinical Trials Information Service (ACTIS): A decade of providing clinical trials information SO PUBLIC HEALTH REPORTS LA English DT Article ID PREVENTION; CALLERS; HOTLINE; IMPACT; HEALTH AB The AIDS Clinical Trials Information Service (ACTIS) is a central resource for information about federally and privately funded HIV/AIDS clinical trials. Sponsored by four components of the U.S. Department of Health and Human Services, ACTIS has been a key part of U.S. HIV/AIDS information and education services since 1989. ACTIS offers a toll-free telephone service, through which trained information specialists can provide callers with information about AIDS clinical trials in English or Spanish, and a website that provides access to clinical trials databases and a variety of educational resources. Future priorities include the development of new resources to target diverse and underserved populations. In addition, research needs to be conducted on the use of telephone services vs. Web-based information exchange to ensure the broadest possible dissemination of up-to-date information on HIV infection and clinical trials. C1 NIAID, DMID, NIH, Bethesda, MD 20892 USA. Food & Drug Adm, Off Special Hlth Issues, Washington, DC USA. Aspen Syst Corp, Rockville, MD USA. RP Katz, DG (reprint author), NIAID, DMID, NIH, 6700B Rockledge Dr, Bethesda, MD 20892 USA. NR 17 TC 2 Z9 2 U1 0 U2 0 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAR-APR PY 2002 VL 117 IS 2 BP 123 EP 130 DI 10.1093/phr/117.2.123 PG 8 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 605MC UT WOS:000178680800004 PM 12356996 ER PT J AU Morehouse, KM AF Morehouse, KM TI Food irradiation - US regulatory considerations SO RADIATION PHYSICS AND CHEMISTRY LA English DT Article; Proceedings Paper CT 12th International Meeting on Radiation Processing (IMRP-12) CY MAR 25-30, 2001 CL AVIGNON, FRANCE DE food irradiation; FDA; regulations AB The use of ionizing radiation in food processing has received increased interest as a means of reducing the level of foodborne pathogens. This overview discusses the regulatory issues connected with the use of this technology in the United States. Several recent changes in the FDA's review process are discussed. These include the current policy that utilizes an expedited review process for petitions seeking approval of additives and technologies intended to reduce pathogen levels in food, and the recent USDA rule that eliminates the need for a separate rulemaking process by USDA for irradiation of meat and poultry. Recently promulgated rules and pending petitions before the FDA associated with the use of ionizing radiation for the treatment of foods are also discussed along with the current FDA labeling requirements for irradiated foods and the 1999 advanced notice of proposed rule on labeling, Another issue that is presented is the current status of the approval of packaging materials intended for food contact during irradiation treatment of foods. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Morehouse, KM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 0 TC 42 Z9 43 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-806X J9 RADIAT PHYS CHEM JI Radiat. Phys. Chem. PD MAR PY 2002 VL 63 IS 3-6 BP 281 EP 284 AR PII S0969-806X(01)00514-X DI 10.1016/S0969-806X(01)00514-X PG 4 WC Chemistry, Physical; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical SC Chemistry; Nuclear Science & Technology; Physics GA 535JT UT WOS:000174642000018 ER PT J AU May, JC Rey, L Lee, CJ AF May, JC Rey, L Lee, CJ TI Evaluation of some selected vaccines and other biological products irradiated by gamma rays, electron beams and X-rays SO RADIATION PHYSICS AND CHEMISTRY LA English DT Article; Proceedings Paper CT 12th International Meeting on Radiation Processing (IMRP-12) CY MAR 25-30, 2001 CL AVIGNON, FRANCE DE irradiated vaccines; electron beams; Co-60 gamma irradiation; X-ray ID PROTEIN CONJUGATE VACCINES; CAPSULAR POLYSACCHARIDE; FRAGMENTATION; MICE AB Molecular sizing potency results are presented for irradiated samples of one lot of Haemophilus b conjugate vaccine, pneumococcal polysaccharide type 6B and typhoid vi polysaccharide vaccine. The samples were irradiated (25 kGy) by gamma rays, electron beams and X-rays. IgG and I.-M antibody response in mice test results (ELISA) are given for the Hib conjugate vaccine irradiated at 0degreesC or frozen in liquid nitrogen. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol & Res, Rockville, MD 20852 USA. RP May, JC (reprint author), US FDA, Ctr Biol & Res, HMF-6 73,1401 Rockville Pike, Rockville, MD 20852 USA. NR 15 TC 10 Z9 10 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-806X J9 RADIAT PHYS CHEM JI Radiat. Phys. Chem. PD MAR PY 2002 VL 63 IS 3-6 BP 709 EP 711 AR PII S0969-806X(01)00565-5 DI 10.1016/S0969-806X(01)00565-5 PG 3 WC Chemistry, Physical; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical SC Chemistry; Nuclear Science & Technology; Physics GA 535JT UT WOS:000174642000115 ER PT J AU Buchalla, R Begley, TH Morehouse, KM AF Buchalla, R Begley, TH Morehouse, KM TI Analysis of low-molecular weight radiolysis products in extracts of gamma-irradiated polymers by gas chromatography and high-performance liquid chromatography SO RADIATION PHYSICS AND CHEMISTRY LA English DT Article; Proceedings Paper CT 12th International Meeting on Radiation Processing (IMRP-12) CY MAR 25-30, 2001 CL AVIGNON, FRANCE DE packaging materials; ionizing radiation; radiolysis products ID MASS SPECTROMETRY AB Estimating exposure to radiolysis products of polymers is an important part of the regulatory evaluation of packaging materials for use in food irradiation. However, as Koni Grob recently put it, the comprehensive analysis of migrants is a challenge. This paper discusses some of the analytical difficulties and presents results obtained with extracts of irradiated polystyrene and polyamide-6. The results indicate that headspace or thermal desorption techniques may, in some instances, lead to an overestimation of radiolysis product concentrations. It is concluded that validated analytical methods and a better understanding of the underlying radiation chemistry would greatly facilitate the safety assessment of irradiated packaging materia is. Published by Elsevier Science Ltd. C1 US FDA, Div Prod Manufacture & Use, Washington, DC 20204 USA. RP Buchalla, R (reprint author), US FDA, Div Prod Manufacture & Use, HFS-245,200 C St SW, Washington, DC 20204 USA. NR 6 TC 13 Z9 13 U1 0 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0969-806X J9 RADIAT PHYS CHEM JI Radiat. Phys. Chem. PD MAR PY 2002 VL 63 IS 3-6 BP 837 EP 840 AR PII S0969-806X(01)00642-9 DI 10.1016/S0969-806X(01)00642-9 PG 4 WC Chemistry, Physical; Nuclear Science & Technology; Physics, Atomic, Molecular & Chemical SC Chemistry; Nuclear Science & Technology; Physics GA 535JT UT WOS:000174642000142 ER PT J AU Shi, L Tong, W Fang, H Xie, Q Hong, H Perkins, R Wu, J Tu, M Blair, RM Branham, WS Waller, C Walker, J Sheehan, DM AF Shi, L Tong, W Fang, H Xie, Q Hong, H Perkins, R Wu, J Tu, M Blair, RM Branham, WS Waller, C Walker, J Sheehan, DM TI An integrated "4-phase" approach for setting endocrine disruption screening priorities - Phase I and II predictions of estrogen receptor binding affinity SO SAR AND QSAR IN ENVIRONMENTAL RESEARCH LA English DT Article; Proceedings Paper CT 9th International Workshop on Quantitative Structure-Activity Relationships in Environmental Sciences (QSAR 2000) CY SEP 16-20, 2000 CL BURGAS, BULGARIA DE endocrine disrupting chemicals; estrogens; priority setting; estrogen receptor binding; QSAR ID CONFORMATIONAL COVERAGE; ANTAGONISM; DISCOVERY; MODELS AB Recent legislation mandates the US Environmental Protection Agency (EPA) to develop a screening and testing program for potential endocrine disrupting chemicals (EDCs), of which xenoestrogens figure prominently. Under the legislation, a large number of chemicals will undergo various in vitro and in vivo assays for their potential estrogenicity, as well as other hormonal activities. There is a crucial need for priority setting before this strategy can be effectively implemented. Here we report an integrated computational approach to priority setting using estrogen receptor (ER) binding as an example. This approach rationally integrates different predictive computational models into a "Four-Phase" scheme so that it can effectively identify potential estrogenic EDCs based on their predicted ER relative binding affinity (RBA). The system has been validated using an in-house ER binding assay dataset for 232 chemicals that was designed to have both broad structural diversity and a wide range of binding affinities. When applied to 58,000 chemicals identified by Walker et at. as candidates for endocrine disruption screening, some 9 100 chemicals were predicted to bind to ER. Of these, only 3600 were expected to bind to ER at RBA values up to 100,000-fold less than that of 17beta-estradiol. The method ruled out 83% of the chemicals as non-binders with a very low rate of false negatives. We believe that the same integrated scheme will be equally applicable to endpoints of other endocrine disrupting mechanisms, e.g, androgen receptor binding. C1 ROW Sci Inc, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Sphinz Pharmaceut, Res Triangle Pk, NC 27709 USA. US EPA, TSCA Interagency Testing Comm, Washington, DC 20460 USA. RP Shi, L (reprint author), ROW Sci Inc, 3900 NCTR Rd,MC910, Jefferson, AR 72079 USA. NR 36 TC 49 Z9 50 U1 1 U2 4 PU TAYLOR & FRANCIS LTD PI ABINGDON PA 4 PARK SQUARE, MILTON PARK,, ABINGDON OX14 4RN, OXON, ENGLAND SN 1062-936X J9 SAR QSAR ENVIRON RES JI SAR QSAR Environ. Res. PD MAR PY 2002 VL 13 IS 1 BP 69 EP 88 DI 10.1080/10629360290002235 PG 20 WC Chemistry, Multidisciplinary; Computer Science, Interdisciplinary Applications; Environmental Sciences; Mathematical & Computational Biology; Toxicology SC Chemistry; Computer Science; Environmental Sciences & Ecology; Mathematical & Computational Biology; Toxicology GA 536TM UT WOS:000174718000007 PM 12074393 ER PT J AU McCarty, GW Reeves, JB Reeves, VB Follett, RF Kimble, JM AF McCarty, GW Reeves, JB Reeves, VB Follett, RF Kimble, JM TI Mid-infrared and near-infrared diffuse reflectance spectroscopy for soil carbon measurement SO SOIL SCIENCE SOCIETY OF AMERICA JOURNAL LA English DT Article ID PARTICLE-SIZE MORPHOLOGY; CARBOHYDRATE SYSTEMS; SAMPLE DILUTION; SPECTRA; WHEAT AB The ability to inventory soil C on landscapes is limited by the ability to rapidly measure soil C. Diffuse reflectance spectroscopic analysis in the near-infrared (NIR, 400-2500 nm) and mid-infrared (MIR, 2500-25000 nm) regions provides means for measurement of soil C. To assess the utility of spectroscopy for soil C analysis, we compared the ability to obtain information from these spectral regions to quantify total, organic, and inorganic C in samples representing 14 soil series collected over a large region in the west central United States. The soils temperature regimes ranged from thermic to frigid and the soil moisture regimes from udic to aridic. The soils ranged considerably in organic (0.23-98 g C kg(-1)) and inorganic C content (0.0-65.4 g CO3-C kg(-1)). These soil samples were analyzed with and without an acid treatment for removal of CO3. Both spectral regions contained substantial information on organic and inorganic C in soils studied and MIR analysis substantially outperformed NIR. The superior performance of the MIR region likely reflects higher quality of information for soil C in this region. The spectral signature of inorganic C was very strong relative to Soil organic C. The presence of CO3 reduced ability to quantify organic C using MIR as indicated by improved ability to measure organic C in acidified soil samples. The ability of MIR spectroscopy to quantify C in diverse soils collected over a large geographic region indicated that regional calibrations are feasible. C1 BARC W, Environm Qual Lab, Beltsville, MD 20705 USA. US FDA, Rockville, MD 20857 USA. USDA ARS, Ft Collins, CO 80522 USA. USDA, NRCS, Lincoln, NE USA. RP McCarty, GW (reprint author), BARC W, Environm Qual Lab, Bldg 007,Room 201, Beltsville, MD 20705 USA. NR 23 TC 234 Z9 255 U1 5 U2 78 PU SOIL SCI SOC AMER PI MADISON PA 677 SOUTH SEGOE ROAD, MADISON, WI 53711 USA SN 0361-5995 J9 SOIL SCI SOC AM J JI Soil Sci. Soc. Am. J. PD MAR-APR PY 2002 VL 66 IS 2 BP 640 EP 646 PG 7 WC Soil Science SC Agriculture GA 528ZF UT WOS:000174275000038 ER PT J AU Djuric, Z Lewis, SM Lu, MH Mayhugh, M Naegeli, L Tang, N Hart, RW AF Djuric, Z Lewis, SM Lu, MH Mayhugh, M Naegeli, L Tang, N Hart, RW TI Effect of varying caloric restriction levels on female rat growth and 5-hydroxymethyl-2 '-deoxyuridine in DNA SO TOXICOLOGICAL SCIENCES LA English DT Article DE caloric restriction; oxidative stress; DNA damage; 5-hydroxymethyl-2 '-deoxyuridine; aging; female rats ID GAS-CHROMATOGRAPHY; MASS-SPECTROMETRY; DIETARY-FAT; DAMAGE; 5-(HYDROXYMETHYL)URACIL; CARCINOGENESIS; PROTEIN; MICE AB Caloric restriction has previously been shown to decrease levels of oxidative stress in rats. In this study, we examined the effects of 5 different caloric intake levels on one type of oxidative DNA damage in rat mammary gland, blood, and liver. Animals were fed modified AIN-93G diets to accommodate 10, 20, 30, or 40% calorie restriction (CR), relative to ad libitum (AL) consumption. The intakes of fat, protein, vitamins, and minerals thus remained constant, but total carbohydrate intake decreased. Body weights of the animals at 20 weeks reflected the degree of restriction, but in the first 10 weeks, weight gain in the 10% CR group was not reduced relative to animals fed ad libitum. Levels of 5-hydroxymethyl-2'-deoxyuridine increased with time in mammary gland and nucleated blood cells regardless of CR level, indicating an effect of animal age, despite the fact that the animals were only 7 months old after the 20-week dietary study. In liver, however, there was a trend towards decreased DNA damage levels with time. The effect of diet on levels of 5-hydroxymethyl-2'-deoxyuridine was not statistically significant, indicating no protective effect of restricted dietary carbohydrate. This dietary study differed from previous work in that the modified AIN-93G dietary formulation contains relatively higher levels of fat and vitamins K, E, and B-12, and it has certain added trace minerals. This data raises the question of whether the previously reported effects of caloric restriction on preventing oxidative stress in mammary gland are dependent on the type of dietary formulation used. C1 Wayne State Univ, Barbara Ann Karmanos Canc Inst, Detroit, MI 48118 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Djuric, Z (reprint author), Wayne State Univ, Barbara Ann Karmanos Canc Inst, 100 E Warren, Detroit, MI 48118 USA. RI Djuric, Zora/H-5147-2013 OI Djuric, Zora/0000-0002-8886-8853 NR 28 TC 7 Z9 7 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2002 VL 66 IS 1 BP 125 EP 130 DI 10.1093/toxsci/66.1.125 PG 6 WC Toxicology SC Toxicology GA 524LG UT WOS:000174014300014 PM 11861979 ER PT J AU Lomander, A Schreuders, P Russek-Cohen, E Ali, L AF Lomander, A Schreuders, P Russek-Cohen, E Ali, L TI A method for rapid analysis of biofilm morphology and coverage on glass and polished and brushed stainless steel SO TRANSACTIONS OF THE ASAE LA English DT Article DE biofilms; glass; 316 stainless steel; morphometrics; image analysis ID IMAGE-ANALYSIS; BACTERIAL-GROWTH; MICROSCOPY; SUBSTRATUM; VIABILITY; ADHERENCE; ADHESION; SURFACES AB A tool for the rapid analysis of biofilms, using epifluorescence microscopy and image analysis was developed. The tool allows the evaluation of overall biofilm coverage and biofilm patch morphology. It will provide a quantitative method for identifying relationships between biofilms and their substrates and for identifying the morphology of patches of damaged bacteria. The coverage percentage allows evaluation of the growth of biofilms and will allow the evaluation of the effectiveness of sanitizers and mechanical cleaning methods in removing biofilms from food processing surfaces. The patch morphology is useful for investigating the relationships between surface morphology and biofilm growth and for determining the surface morphology, biofilm shape, and sanitizer effectiveness. The software was tested and validated using biofilms of E. coli K12 on glass, polished 316 stainless steel, and brushed 316 stainless steel. The biofilms were stained with both propidium iodide and SYTO-16. After peforming digital image analysis of both overall coverage and biofilm patch morphometries, it was found that the percentages of living or total biofilm were independent of the substrate material. However, the absolute area of individual biofilm patches varied depending on the substrate material. These areas also showed changes over time. The circularity of the biofilm patches was investigated. At the end of the studies, the shape of most of the biofilm patches in this group was nearly circular. C1 Univ Maryland, Biol Resources Engn Dept, College Pk, MD 20742 USA. Univ Maryland, Anim & Avian Sci Dept, College Pk, MD 20742 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Prod Manafucture & Use, Off Premarket Approval, Washington, DC 20204 USA. RP Schreuders, P (reprint author), Univ Maryland, Biol Resources Engn Dept, College Pk, MD 20742 USA. NR 40 TC 5 Z9 5 U1 0 U2 5 PU AMER SOC AGRICULTURAL ENGINEERS PI ST JOSEPH PA 2950 NILES RD, ST JOSEPH, MI 49085-9659 USA SN 0001-2351 J9 T ASAE JI Trans. ASAE PD MAR-APR PY 2002 VL 45 IS 2 BP 479 EP 487 PG 9 WC Agricultural Engineering SC Agriculture GA 555UU UT WOS:000175812300026 ER PT J AU Simak, J Holada, K D'Agnillo, F Janota, J Vostal, JG AF Simak, J Holada, K D'Agnillo, F Janota, J Vostal, JG TI Cellular prion protein is expressed on endothelial cells and is released during apoptosis on membrane microparticles found in human plasma SO TRANSFUSION LA English DT Article ID SPONGIFORM ENCEPHALOPATHY; PRPC EXPRESSION; HUMAN BLOOD; IN-VITRO; SURFACE; MICE; TISSUES; DISEASE; GENE; COMPONENTS AB BACKGROUND: Blood and plasma of animals experimentally infected with transmissible spongiform encephalopathies (TSEs) can transmit TSE infection by transfusion. A conformational isoform of prion protein (PrPsc) is believed to be the TSE-infectious agent that propagates by converting the cellular prion protein (PrPc) to additional molecules of PrPsc. In orally infected animals, PrPsc accumulates in intestinal endothelial cells. In blood, two thirds of PrPc resides in plasma, but its source is not known. STUDY DESIGN AND METHODS: The expression of PrPc in cultured human umbilical vein endothelial cells (HUVECs) was studied using flow cytometry, immunoblotting, and RT-PCR. Flow cytometry was used to characterize endothelial membrane microparticles (MPs) in cell culture supernatants and in normal human plasma. RESULTS: HUVECs and bovine aorta endothelial cells express PrPc. The number of surface PrPc molecules per cell in HUVECs was 58,000 +/- 2,800. The induction of apoptosis in HUVECs led to a marked release of membrane MPs (60,000-80,000 MPs/10(3) cells) that expressed PrPc and other endothelial antigens. The presence of endothelial cell-derived MPs expressing PrPc was demonstrated in platelet-free human plasma. CONCLUSION: Endothelial cell apoptosis is associated with the release of PrPc-positive MPs. These MPs contribute to the PrPc pool in plasma and may have a role in disseminating TSE infectivity in blood. C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Div Hematol, Bethesda, MD 20892 USA. RP Vostal, JG (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Div Hematol, Bldg 29,Room 323,HFM-335,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 41 TC 54 Z9 56 U1 0 U2 5 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD MAR PY 2002 VL 42 IS 3 BP 334 EP 342 DI 10.1046/j.1537-2995.2002.00072.x PG 9 WC Hematology SC Hematology GA 540BH UT WOS:000174907900010 PM 11961239 ER PT J AU Frazier-Jessen, MR Thompson, CD Brown, R Rawat, R Nordan, RP Feldman, GM AF Frazier-Jessen, MR Thompson, CD Brown, R Rawat, R Nordan, RP Feldman, GM TI NF-kappa B elements contribute to junB inducibility by lipopolysaccharide in the murine macrophage cell line RAW264.7 SO FEBS LETTERS LA English DT Article DE lipopolysaccharide; junB; macrophage; nuclear factor kappa B ID GENE-EXPRESSION; TNF-ALPHA; INDUCTION; DNA; BINDING; ACTIVATION; PROMOTER; SUBUNITS; PROTEINS; P50 AB Macrophages respond to bacterial lipopolysaccharide (LPS) by activating latent cis-acting factors that initiate transcription of immediate early genes. One such immediate early gene, junB, is induced by LPS in macrophages within 30 min. To identify elements that mediate the induction of junB by LPS, upstream and downstream sequences flanking the junB gene were examined by transient expression in the RAW264.7 murine macrophage cell line using a luciferase reporter gene vector containing the junB minimal promoter. A > 10-fold enhancement was associated with a 222 bp region downstream of the junB promoter in response to LPS. Transient reporter assays demonstrated that multiple nuclear factor (NIT) kappaB sites are required for inducibility of junB by LPS in RAW264.7 cells. Electrophoretic mobility shift assays confirmed binding of LPS-induced nuclear proteins included p50/p65 heterodimers at these NF-kappaB sites. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Biochemical Societies. C1 US FDA, Immunobiol Lab,Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Off Therapeut Res & Review, Bethesda, MD 20892 USA. Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. RP Frazier-Jessen, MR (reprint author), US FDA, Immunobiol Lab,Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Off Therapeut Res & Review, HFM-564,Bldg 29A,Room 3C22,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 17 TC 18 Z9 18 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0014-5793 J9 FEBS LETT JI FEBS Lett. PD FEB 27 PY 2002 VL 513 IS 2-3 BP 203 EP 207 AR PII S0014-5793(02)02295-0 DI 10.1016/S0014-5793(02)02295-0 PG 5 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA 534QM UT WOS:000174597900013 PM 11904151 ER PT J AU Pogribny, IP James, SJ AF Pogribny, IP James, SJ TI Reduction of p53 gene expression in human primary hepatocellular carcinoma is associated with promoter region methylation without coding region mutation SO CANCER LETTERS LA English DT Article DE DNA methylation; human; hepatocellular carcinoma; p53 promoter; mutation; gene expression ID TUMOR-SUPPRESSOR GENE; DNA METHYLATION; CPG METHYLATION; MYELOID-LEUKEMIA; CANCER; HYPERMETHYLATION; INACTIVATION; SITES AB Functional inactivation of tumor suppressor genes during tumor progression has been shown to occur by either coding region mutation or promoter region methylation. Because of the functional equivalence of these two mechanisms, loss of tumor suppressor function generally occurs by one or the other mechanism, but rarely by both. Aberrant de novo methylation in most tumor suppressor promoter regions is found within CpG islands that occur near the transcription start site. The p53 promoter region is unique in that it does not contain a CpG island and therefore it is possible that methylation at critical CpG sites may be more important in gene silencing than total CpG methylation density. Other than site-specific aflatoxin B-induced mutations, p53 coding region mutations are not frequently observed in most human primary hepatocellular carcinomas. In the present study, paired samples of human primary liver carcinoma and uninvolved tissue obtained from the same individual were evaluated for site-specific p53 promoter methylation status by methylation sensitive single nucleotide primer extension (Ms-SNuPE) and also for coding region mutations using polymerase chain reaction (PCR)- single strand conformation polymorphism (SSCP). The methylation pattern in the uninvolved tissue was variable at specific CpG sites, whereas the same sites had become highly methylated in tumor tissue from the same individual. Associated with de novo methylation, the level of p53 mRNA was significantly reduced in the tumor DNA relative to the uninvolved tissue DNA. None of the samples exhibited coding region mutations. Given that p53 mutations are rare in primary human liver tumors, these data suggest that transcriptional repression by p53 promoter methylation may contribute to tumor progression. Published by Elsevier Science Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP James, SJ (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 28 TC 49 Z9 53 U1 1 U2 4 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 FEB 25 PY 2002 VL 176 IS 2 BP 169 EP 174 DI 10.1016/S0304-3835(01)00748-0 PG 6 WC Oncology SC Oncology GA 520PJ UT WOS:000173790000007 PM 11804744 ER PT J AU Baladron, V Ruiz-Hidalgo, MJ Bonvini, E Gubina, E Notario, V Laborda, J AF Baladron, V Ruiz-Hidalgo, MJ Bonvini, E Gubina, E Notario, V Laborda, J TI The EGF-like homeotic protein dlk affects cell growth and interacts with growth-modulating molecules in the yeast two-hybrid system SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE dlk; cell growth; tumoral transformation; yeast two-hybrid system; growth factor; growth arrest; GAS1; acrogranin ID ARREST-SPECIFIC GENE; HUMAN-SKIN FIBROBLASTS; IN-SITU HYBRIDIZATION; ADIPOCYTE DIFFERENTIATION; ADIPOSE-CELLS; HUMAN HOMOLOG; EXPRESSION; GAS1; PREF-1; SUPPRESSION AB Levels of dlk, an EGF-like homeotic protein, are critical for several differentiation processes. Because growth and differentiation are, in general, exclusive of each other, and increasing evidence indicates that Dlk1 expression changes in tumorigenic processes, we studied whether dlk could also affect cell growth. We found that, in response to glucocorticoids, Balb/c 3T3 cells with diminished levels of dlk expression develop foci-like cells that have lost contact inhibition, display altered morphology, and grow faster than control cell lines. Balb/c 3T3 cells spontaneously growing more rapidly are also dlk-negative cells. Moreover, screening by the yeast two-hybrid system, using Dlk1 constructs as baits, resulted in the isolation of GAS1 and acrogranin cDNAs. Interestingly, these proteins are cysteine-rich molecules involved in the control of cell growth. Taken together, these observations suggest that dlk may participate in a network of interactions controlling how the cells respond to growth or differentiation signals. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Immunobiol Lab, Rockville, MD 20852 USA. Georgetown Univ, Med Ctr, Dept Radiat Med, Expt Carcinogenesis Lab, Washington, DC 20007 USA. RP Laborda, J (reprint author), Univ Castilla La Mancha, Fac Med, Campus Albacete,Edif Benjamin Palencia S-N, Albacete 02071, Spain. RI Laborda, Jorge/L-5726-2014; Ruiz-Hidalgo, Maria/L-1956-2014; Baladron, Victoriano/L-1758-2014 OI Laborda, Jorge/0000-0002-9210-838X; Baladron, Victoriano/0000-0003-4574-8760 NR 59 TC 38 Z9 39 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 0006-291X J9 BIOCHEM BIOPH RES CO JI Biochem. Biophys. Res. Commun. PD FEB 22 PY 2002 VL 291 IS 2 BP 193 EP 204 DI 10.1006/bbrc.2002.6431 PG 12 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 524AY UT WOS:000173990800001 PM 11846389 ER PT J AU Lathrop, SL Ball, R Haber, P Mootrey, GT Braun, MM Shadomy, SV Ellenberg, SS Chen, RT Hayes, EB AF Lathrop, SL Ball, R Haber, P Mootrey, GT Braun, MM Shadomy, SV Ellenberg, SS Chen, RT Hayes, EB TI Adverse event reports following vaccination for Lyme disease: December 1998-July 2000 SO VACCINE LA English DT Article DE Lyme disease; vaccine adverse event reporting system; major histocompatibility complex; lyme vaccine; adverse events; safety ID BORRELIA-BURGDORFERI; SYSTEM VAERS; ANTIBODY AB Context: The vaccine adverse event reporting system (VAERS) monitors vaccine safety post-licensure. Although events reported to VAERS are not necessarily causally associated with vaccination, VAERS reports can be used to identify possible safety concerns that occur at too low a rate to have been identified prior to Licensure. Objective: To evaluate adverse events following Lyme disease vaccination reported to VAERS during the first 19 months of the vaccine's licensure. Design, setting, and participants: Analysis of all VAERS reports of adverse events following vaccination for Lyme disease in the US from 28 December 1998 to 31 July 2000. Main outcome measure: We evaluated reported adverse events for unexpected patterns in age, gender, time to onset, dose number, and clinical characteristics and compared them to adverse events observed in clinical trials of this vaccine. Results: Over 1,400,000 doses were distributed and 905 adverse events were reported to VAERS, 440 in men and 404 in women, with ages ranging from 10 to 82 years. The majority (56%) of adverse events occurred after administration of the first dose. The most frequently reported adverse events were arthralgia (250), myalgia (195), and pain (157). There were 59 reports coded as arthritis, 34 as arthrosis, 9 as rheumatoid arthritis, and 12 as facial paralysis. Sixty-six (7.4%) events were classified as serious, involving life-threatening illness, hospitalization, prolongation of hospitalization, persistent or significant disability/incapacity, or death. Twenty-two hypersensitivity reactions were reported. Conclusions: Based on reporting to VAERS, we did not detect unexpected or unusual patterns of reported adverse events following Lyme disease vaccine administration, other than hypersensitivity reactions, compared with adverse events observed in clinical trials. Published by Elsevier Science Ltd. C1 Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Ft Collins, CO 80522 USA. Ctr Dis Control & Prevent, Epidem Intelligence Serv, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA 30333 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Hayes, EB (reprint author), Ctr Dis Control & Prevent, Div Vector Borne Infect Dis, Ft Collins, CO 80522 USA. NR 15 TC 45 Z9 45 U1 1 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD FEB 22 PY 2002 VL 20 IS 11-12 BP 1603 EP 1608 AR PII S0264-410X(01)00500-X DI 10.1016/S0264-410X(01)00500-X PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 536DR UT WOS:000174685900017 PM 11858868 ER PT J AU Keane, J Gershon, SK Braun, MM AF Keane, J Gershon, SK Braun, MM TI Tuberculosis and treatment with infliximab - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Boston Univ, Sch Med, Boston, MA 02118 USA. US FDA, Rockville, MD 20852 USA. RP Keane, J (reprint author), Boston Univ, Sch Med, Boston, MA 02118 USA. NR 3 TC 18 Z9 18 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 21 PY 2002 VL 346 IS 8 BP 625 EP 626 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 522ZK UT WOS:000173926700022 ER PT J AU Wilk, A Grajkowski, A Bull, TE Dixon, AM Freedberg, DI Beaucage, SL AF Wilk, A Grajkowski, A Bull, TE Dixon, AM Freedberg, DI Beaucage, SL TI Direct assignment of the absolute configuration of a distinct class of deoxyribonucleoside cyclic N-acylphosphoramidites at phosphorus by M-GOESY nuclear magnetic resonance spectroscopy SO JOURNAL OF THE AMERICAN CHEMICAL SOCIETY LA English DT Article ID STEREOCONTROLLED SYNTHESIS; OLIGO(NUCLEOSIDE PHOSPHOROTHIOATE)S; OLIGONUCLEOTIDES; SYNTHONS; MONOMERS C1 US FDA, Div Therapeut Prot, Bethesda, MD 20892 USA. US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Beaucage, SL (reprint author), US FDA, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 6 Z9 6 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0002-7863 J9 J AM CHEM SOC JI J. Am. Chem. Soc. PD FEB 20 PY 2002 VL 124 IS 7 BP 1180 EP 1181 DI 10.1021/ja017190d PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 524YD UT WOS:000174039700026 PM 11841281 ER PT J AU Petricoin, EF Ardekani, AM Hitt, BA Levine, PJ Fusaro, VA Steinberg, SM Mills, GB Simone, C Fishman, DA Kohn, EC Liotta, LA AF Petricoin, EF Ardekani, AM Hitt, BA Levine, PJ Fusaro, VA Steinberg, SM Mills, GB Simone, C Fishman, DA Kohn, EC Liotta, LA TI Use of proteomic patterns in serum to identify ovarian cancer SO LANCET LA English DT Article AB Background New technologies for the detection of early-stage ovarian cancer are urgently needed. Pathological changes within an organ might be reflected in proteomic patterns in serum. We developed a bioinformatics tool and used it to identify proteomic patterns in serum that distinguish neoplastic from non-neoplastic disease within the ovary. Methods Proteomic spectra were generated by mass spectroscopy (surface-enhanced laser desorption and ionisation). A preliminary "training" set of spectra derived from analysis of serum from 50 unaffected women and 50 patients with ovarian cancer were analysed by an iterative searching algorithm that identified a proteomic pattern that completely discriminated cancer from non-cancer. The discovered pattern was then used to classify an independent set of 116 masked serum samples: 50 from women with ovarian cancer, and 66 from unaffected women or those with non-malignant disorders. Findings The algorithm identified a cluster pattern that, in the training set, completely segregated cancer from non-cancer. The discriminatory pattern correctly identified all 50 ovarian cancer cases in the masked set, including all 18 stage I cases. Of the 66 cases of non-malignant disease, 63 were recognised as not cancer. This result yielded a sensitivity of 100% (95% CI 93-100), specificity of 95% (87-99), and positive predictive, value of 94% (84-99). Interpretation These findings justify a prospective population-based assessment of proteomic pattern technology as a screening tool for all stages of ovarian cancer in high-risk and general populations. C1 US FDA, Natl Inst Hlth Clin Proteom Program, Dept Therapeut Prot, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NCI, Biostat & Data Management Sect, Ctr Canc Res, NIH, Bethesda, MD 20892 USA. Correlog Syst Inc, Bethesda, MD USA. Univ Texas, MD Anderson Canc Ctr, Dept Mol Therapeut, Div Canc Med, Houston, TX 77030 USA. Simone Protect Canc Inst, Lawrenceville, NJ USA. Northwestern Univ, Sch Med, Natl Ovarian Canc Early Detect Program, Chicago, IL USA. RP Petricoin, EF (reprint author), Bldg 29A,Room 2B02,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 20 TC 2086 Z9 2284 U1 10 U2 129 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD FEB 16 PY 2002 VL 359 IS 9306 BP 572 EP 577 DI 10.1016/S0140-6736(02)07746-2 PG 6 WC Medicine, General & Internal SC General & Internal Medicine GA 523FP UT WOS:000173943600011 PM 11867112 ER PT J AU Verthelyi, D Kenney, RT Seder, RA Gam, AA Friedag, B Klinman, DM AF Verthelyi, D Kenney, RT Seder, RA Gam, AA Friedag, B Klinman, DM TI CpG oligodeoxynucleotides as vaccine adjuvants in primates SO JOURNAL OF IMMUNOLOGY LA English DT Article ID BACTERIAL-DNA; CUTANEOUS LEISHMANIASIS; IMMUNOSTIMULATORY DNA; IMMUNE-RESPONSES; B-CELL; MOTIFS; ACTIVATION; TRIGGER; INTERLEUKIN-12; ENHANCER AB Synthetic oligodeoxynucleotides (ODN) containing unmethylated CpG motifs act as immune adjuvants in mice, boosting the humoral and cellular response to coadministered Ags. CpG ODN that stimulate human PBMC are only weakly active in mice. Thus, alternative animal models are needed to monitor the activity and safety of "human" CpG ODN in vivo. This work demonstrates that rhesus macaques recognize and respond to the same CpG motifs that trigger human immune cells. Coadministering CpG ODN with heat-killed Leishmania vaccine provided significantly increased protection of macaques against cutaneous Leishmania infection. These findings indicate that rhesus macaques provide a useful model for studying the in vivo activity of human CpG motifs, and that ODN expressing these motifs act as strong immune adjuvants. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Bacterial Parasit & Allergen Prod, Bethesda, MD 20892 USA. NIAID, Vaccine Res Ctr, NIH, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bldg 29 A,Room 3 D 10, Bethesda, MD 20892 USA. NR 38 TC 132 Z9 141 U1 0 U2 3 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD FEB 15 PY 2002 VL 168 IS 4 BP 1659 EP 1663 PG 5 WC Immunology SC Immunology GA 520FU UT WOS:000173771000021 PM 11823494 ER PT J AU Siegel, JP AF Siegel, JP TI Biotechnology and clinical trials SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT Symposium on Insights on Infection and Immunity CY JAN 19, 2001 CL STANFORD UNIV MED CTR, FAIRCHILD AUDITORIUM, PALO ALTO, CALIFORNIA HO STANFORD UNIV MED CTR, FAIRCHILD AUDITORIUM ID HUMAN MONOCLONAL-ANTIBODY; PLACEBO-CONTROLLED TRIAL; SEPTIC SHOCK; DOUBLE-BLIND; HA-1A AB Not surprisingly, clinical trials have been critically important to developments in the field of biotechnology. Perhaps less expectedly, the clinical trials of biotechnology products have been critically important to recent developments in the field of clinical trials design, conduct, and analysis. This manuscript explores three examples of biotechnology clinical trials-a trial in sepsis, a trial in fibrinolytics in myocardial infarction, and trials in gene therapy-and highlights their contributions to the theory and practice of clinical research. C1 US FDA, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Siegel, JP (reprint author), US FDA, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Woodmont Off Complex,Suite 200S,1401 Rockville Pi, Rockville, MD 20852 USA. NR 23 TC 3 Z9 3 U1 0 U2 2 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 15 PY 2002 VL 185 SU 1 BP S52 EP S57 DI 10.1086/338061 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 517FP UT WOS:000173600700008 PM 11865440 ER PT J AU Staffa, JA Chang, J Green, L AF Staffa, JA Chang, J Green, L TI Cerivastatin and reports of fatal rhabdomyolysis. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Staffa, JA (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 389 Z9 412 U1 3 U2 13 PU MASSACHUSETTS MEDICAL SOC/NEJM 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 14 PY 2002 VL 346 IS 7 BP 539 EP 540 DI 10.1056/NEJM200202143460721 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 521AE UT WOS:000173815300032 PM 11844864 ER PT J AU da Costa, GG Manjanatha, MG Marques, MM Beland, FA AF da Costa, GG Manjanatha, MG Marques, MM Beland, FA TI Induction of lacI mutations in Big Blue rats treated with tamoxifen and alpha-hydroxytamoxifen SO CANCER LETTERS LA English DT Article DE tamoxifen; alpha-hydroxytamoxifen; Big Blue rats; lacI; liver; uterus; DNA adducts; mutagenesis ID DNA ADDUCT FORMATION; LAMBDA/LACI TRANSGENIC RATS; ETHYL-N-NITROSOUREA; BREAST-CANCER; IN-VIVO; HUMAN ENDOMETRIUM; FISCHER-344 RATS; LIVER; IDENTIFICATION; DERIVATIVES AB The antiestrogen tamoxifen is carcinogenic in the liver and uterus of rats. Liver tumors appear to result from sequential hydroxylation and esterification of the a-carbon of tamoxifen followed by DNA adduct formation. The mechanism for the induction of uterine tumors is not known. Big Blue rats were treated by intraperitoneal injection with 21 daily doses of 54 mumol/kg tamoxifen or its proximate carcinogenic metabolite alpha-hydroxytamoxifen. One month after the last treatment, the mutant frequency in the lacl transgene was determined in the liver and uterus. For comparison, the mutant frequency in the hypoxanthine phosphoribosyl transferase (Hprt) gene of spleen lymphocytes was also measured. In the liver, tamoxifen (32 +/- 18 mutants/10(6) plaques; mean +/- SD) and alpha-hydroxytamoxifen (770 +/- 270 mutants/10(6) plaques) caused a significant increase in the mutant frequency of the lacI gene compared to solvent treated controls (10 +/- 10 mutants/10(6) plaques). P-32-Postlabeling analyses of liver DNA indicated three DNA adducts, one each from tamoxifen, N-desmethyltamoxifen, and N,N-didesmethyltamoxifen. Neither tamoxifen nor (x-hydroxytamoxifen caused an increase in the mutant frequency in the lacI gene of the uterus or in the Hprt gene of spleen lymphocytes. These results suggest that induction of endometrial tumors in rats is not due to the genotoxicity of tamoxifen. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Tecn Lisboa, Ctr Quim Estrutural, Inst Super Tecn, P-1049001 Lisbon, Portugal. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 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 RI Marques, M. Matilde/E-2535-2012 OI Marques, M. Matilde/0000-0002-7526-4962 NR 43 TC 14 Z9 14 U1 0 U2 2 PU ELSEVIER IRELAND LTD PI CLARE PA ELSEVIER HOUSE, BROOKVALE PLAZA, EAST PARK SHANNON, CO, CLARE, 00000, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD FEB 8 PY 2002 VL 176 IS 1 BP 37 EP 45 PG 9 WC Oncology SC Oncology GA 517PP UT WOS:000173619400006 ER PT J AU Venable, RM Pastor, RW AF Venable, RM Pastor, RW TI Molecular dynamics simulations of water wires in a lipid bilayer and water/octane model systems SO JOURNAL OF CHEMICAL PHYSICS LA English DT Letter ID ENERGY; TRANSPORT; MEMBRANE; CHANNEL C1 US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20854 USA. RP Venable, RM (reprint author), US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Rockville, MD 20854 USA. NR 16 TC 16 Z9 16 U1 0 U2 3 PU AMER INST PHYSICS PI MELVILLE PA CIRCULATION & FULFILLMENT DIV, 2 HUNTINGTON QUADRANGLE, STE 1 N O 1, MELVILLE, NY 11747-4501 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD FEB 8 PY 2002 VL 116 IS 6 BP 2663 EP 2664 DI 10.1063/1.1434952 PG 2 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 517PD UT WOS:000173618400043 ER PT J AU Schwetz, BA AF Schwetz, BA TI Congenital heart defect devices SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 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 FEB 6 PY 2002 VL 287 IS 5 BP 578 EP 578 DI 10.1001/jama.287.5.578-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 518UR UT WOS:000173686700006 PM 11829678 ER PT J AU Schwetz, BA AF Schwetz, BA TI New contraceptive patch SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 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 FEB 6 PY 2002 VL 287 IS 5 BP 578 EP 578 DI 10.1001/jama.287.5.578-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 518UR UT WOS:000173686700005 PM 11829678 ER PT J AU Schwetz, RA AF Schwetz, RA TI Risk management of Accutane SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Schwetz, RA (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 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 FEB 6 PY 2002 VL 287 IS 5 BP 578 EP 578 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 518UR UT WOS:000173686700004 ER PT J AU Vercruysse, J Holdsworth, P Letonja, T Conder, G Hamamoto, K Okano, K Rehbein, S AF Vercruysse, J Holdsworth, P Letonja, T Conder, G Hamamoto, K Okano, K Rehbein, S TI International harmonisation of anthelmintic efficacy guidelines - (Part 2) SO VETERINARY PARASITOLOGY LA English DT Article DE anthelmintic efficacy; harmonisation; horse; swine; dog; cat; poultry ID PARASITOLOGY WAAVP GUIDELINES; WORLD-ASSOCIATION; ADVANCEMENT AB The "International Co-operation on Harmonisation of Technical Requirements for Registration of Veterinary Medicinal Products (VICH)" is an international programme of co-operation between regulatory authorities and the animal health industries of the European Union, Japan and the United States of America which aims to harmonise the technical requirements for the registration of veterinary medicinal products. Australia and New Zealand participate as active observers. The objective of this second paper is to present additional guidelines established by the Working Group on anthelmintic guidelines: (1) efficacy of anthelmintics: specific recommendations for equine (VICH GL15), (2) efficacy of anthelmintics: specific recommendations for porcine (VICH GL16), (3) efficacy of anthelmintics: specific recommendations for canine (VICH GL19), (4) efficacy of anthelmintics: specific recommendations for feline (VICH GL20) and (5) efficacy of anthelmintics: specific recommendations for poultry (VICH GL21). These guidelines do not consist of rigid stipulations, but make clear recommendations on the minimal standards needed. To the veterinary profession, livestock producers and animal owners, harmonisation should mean quicker access to safer and more effective veterinary anthelmintics. In general, products should be relatively more affordable because of the reduction in registration costs and efficient use of resources by the regulatory authorities. (C) 2002 Elsevier Science B.V. All rights reserved. C1 State Univ Ghent, Fac Med Vet, Dept Parasitol & Parasit Dis, B-9820 Merelbeke, Belgium. Avcare, Canberra, ACT 2601, Australia. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Pfizer Inc, Global Res & Dev, Groton, CT 06340 USA. Minist Agr Forestry & Fisheries, Natl Vet Assay Lab, Kokubunji, Tokyo 1858511, Japan. Takeda Schering Plough Anim Hlth KK, Mkt & Business Dept Div, Dept Mkt, Chiyoda Ku, Tokyo 1020075, Japan. Merial GMBH, Kathrinenhof Res Ctr, D-83101 Rohrdorf Lauterbach, Germany. RP Vercruysse, J (reprint author), State Univ Ghent, Fac Med Vet, Dept Parasitol & Parasit Dis, Salisburylaan 133, B-9820 Merelbeke, Belgium. NR 4 TC 31 Z9 33 U1 0 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4017 J9 VET PARASITOL JI Vet. Parasitol. PD FEB 4 PY 2002 VL 103 IS 4 BP 277 EP 297 DI 10.1016/S0304-4017(01)00615-X PG 21 WC Parasitology; Veterinary Sciences SC Parasitology; Veterinary Sciences GA 514DG UT WOS:000173422400001 PM 11777607 ER PT J AU Gillespie, JW Best, CJM Bichsel, VE Cole, KA Greenhut, SF Hewitt, SM Ahram, M Gathright, YB Merino, MJ Strausberg, RL Epstein, JI Hamilton, SR Gannot, G Baibakova, GV Calvert, VS Flaig, MJ Chuaqui, RF Herring, JC Pfeifer, J Petricoin, EF Linehan, WM Duray, PH Bova, GS Emmert-Buck, MR AF Gillespie, JW Best, CJM Bichsel, VE Cole, KA Greenhut, SF Hewitt, SM Ahram, M Gathright, YB Merino, MJ Strausberg, RL Epstein, JI Hamilton, SR Gannot, G Baibakova, GV Calvert, VS Flaig, MJ Chuaqui, RF Herring, JC Pfeifer, J Petricoin, EF Linehan, WM Duray, PH Bova, GS Emmert-Buck, MR TI Evaluation of non-formalin tissue fixation for molecular profiling studies SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID PARAFFIN-EMBEDDED TISSUE; POLYMERASE CHAIN-REACTION; GENE-EXPRESSION PATTERNS; HOUSEKEEPING GENE; RNA; AMPLIFICATION; CANCER; OPTIMIZATION; SPECIMENS; ETHANOL AB Using a general strategy for evaluating clinical tissue specimens, we found that 70% ethanol fixation and paraffin embedding is a useful method for molecular profiling studies. Human prostate and kidney were used as test tissues. The protein content of the samples was analyzed by one-dimensional gel electrophoresis, immunoblot, two-dimensional gel electrophoresis, and layered expression scanning. In each case, the fixed and embedded tissues produced results similar to that obtained from snap-frozen specimens, although the protein quantity was somewhat decreased. Recovery of mRNA was reduced in both quantity and quality in the ethanol-fixed samples, but was superior to that obtained from formalin-fixed samples and sufficient to perform reverse transcription polymerase chain reactions. Recovery of DNA from ethanol-fixed specimens was superior to formalin-fixed samples as determined by one-dimensional gel electrophoresis and polymerase chain reaction. In conclusion, specimens fixed in 70% ethanol and embedded in paraffin produce good histology and permit recovery of DNA, mRNA, and proteins sufficient for several downstream molecular analyses. Complete protocols and additional discussion of relevant issues are available on an accompanying website (http://cgap-mf.nih.gov/). C1 NCI, Pathol Lab, Pathogenet Unit, Bethesda, MD 20892 USA. NCI, Sci Applicat Int Corp, Frederick, MD 21701 USA. US FDA, Ctr Biolog & Res, Bethesda, MD 20014 USA. NCI, Off Director, CGAP, Bethesda, MD 20892 USA. Johns Hopkins Univ, Dept Pathol, Baltimore, MD USA. Univ Texas, MD Anderson Canc Ctr, Dept Pathol, Houston, TX 77030 USA. Tel Aviv Univ, Sackler Fac Med, IL-69978 Tel Aviv, Israel. Ctr Prostate Dis Res, Rockville, MD USA. NIH, Ctr Informat Technol, Bethesda, MD 20892 USA. NCI, Urol Oncol Branch, Bethesda, MD 20892 USA. RP Emmert-Buck, MR (reprint author), NCI, Pathol Lab, Pathogenet Unit, Rm 2A33,Bldg 10,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Cole, Kristina/M-3922-2015; OI Hewitt, Stephen/0000-0001-8283-1788 NR 31 TC 175 Z9 196 U1 2 U2 10 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2002 VL 160 IS 2 BP 449 EP 457 DI 10.1016/S0002-9440(10)64864-X PG 9 WC Pathology SC Pathology GA 519NZ UT WOS:000173733500009 PM 11839565 ER PT J AU Blease, K Schuh, JM Jakubzick, C Lukacs, NW Kunkel, SL Joshi, BH Puri, RK Kaplan, MH Hogaboam, CM AF Blease, K Schuh, JM Jakubzick, C Lukacs, NW Kunkel, SL Joshi, BH Puri, RK Kaplan, MH Hogaboam, CM TI Stat6-deficient mice develop airway hyperresponsiveness and peribronchial fibrosis during chronic fungal asthma SO AMERICAN JOURNAL OF PATHOLOGY LA English DT Article ID SIGNAL TRANSDUCER; MUCUS PRODUCTION; TH2 CELLS; T-CELLS; STAT6; TRANSCRIPTION; INTERLEUKIN-13; INFLAMMATION; IL-4; DISEASE AB Signal transducer and activator of transcription 6 (Stat6) is critical for Th2-mediated responses during allergic airway disease. To investigate the role of Stat6 in fungus-induced airway hyperresponsiveness and remodeling, Stat6-deficient (Stat6-/-) and Stat6-wildtype (Stat6+/+) mice were sensitized to Aspergillus fumigatus and airway disease was subsequently assessed in both groups at days 21, 30, 38, and 44 after an intratracheal challenge with live A. fumigatus conidia. At all times after conidia, histological analysis revealed an absence of goblet cell hyperplasia and markedly diminished peribronchial inflammation in Stat6-/- mice in contrast to Stat6+/+ mice. Airway hyperresponsiveness and peribronchial fibrosis in Stat6-/- mice were significantly reduced at day 21 after conidia compared with Stat6+/+ mice, but both groups exhibited significant, similar increases in these parameters at all subsequent times after conidia. In separate experiments, IL-13-responsive cells in Stat6-/- mice were targeted via the daily intranasal administration of 200 ng of IL-13-PE38QQR (IL13-PE), comprised of human IL-13 and a derivative of Pseudomonas exotoxin, from days 38 to 44 after the conidia challenge. IL13-PE treatment abolished airway hyperresponsiveness, but not peribronchial fibrosis in Stat6-/- mice. Taken together, these data demonstrate that the chronic development of airway hyperresponsiveness during fungal asthma is IL-13-dependent but Stat6-independent. C1 Univ Michigan, Sch Med, Dept Pathol, Ann Arbor, MI 48109 USA. US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biolog Evaluat & Res, Bethesda, MD 20014 USA. Indiana Univ Sch Med, Dept Immunol & Microbiol, Walther Oncol Ctr, Indianapolis, IN USA. RP Hogaboam, CM (reprint author), Univ Michigan, Sch Med, Dept Pathol, 1301 Catherine Rd, Ann Arbor, MI 48109 USA. RI hogaboam, cory /M-3578-2014 FU NHLBI NIH HHS [1P50 HL 60289, HL 35276, P01 HL 31963, P01 HL031963, R37 HL035276] NR 38 TC 79 Z9 83 U1 0 U2 0 PU AMER SOC INVESTIGATIVE PATHOLOGY, INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3993 USA SN 0002-9440 J9 AM J PATHOL JI Am. J. Pathol. PD FEB PY 2002 VL 160 IS 2 BP 481 EP 490 DI 10.1016/S0002-9440(10)64867-5 PG 10 WC Pathology SC Pathology GA 519NZ UT WOS:000173733500012 PM 11839568 ER PT J AU Berg, WA Nguyen, TK Middleton, MS Soo, MS Pennello, G Brown, SL AF Berg, WA Nguyen, TK Middleton, MS Soo, MS Pennello, G Brown, SL TI MR imaging of extracapsular silicone from breast implants: Diagnostic pitfalls SO AMERICAN JOURNAL OF ROENTGENOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Radiological-Society-of-North-America CY NOV, 2000 CL CHICAGO, ILLINOIS SP Radiolog Soc N Amer ID RUPTURE; US; REMOVAL; WOMEN AB OBJECTIVE. We sought to identify pitfalls in recognition of extracapsular silicone on MR imaging. MATERIALS AND METHODS. Three experienced observers reviewed MR images from 3,59 women with current (n = 320), prior (n = 15), or both current and prior (n = 24) silicone gel implants. Axial and sagittal fast spin-echo T2-weighted images with water suppression, axial inversion-recovery T2-weighted images with water suppression, and axial T2-weighted images with silicone suppression were obtained in a dedicated phased array breast coil on a 1.5-T magnet. Images were reviewed again when only one observer saw extracapsular silicone, and reasons for disagreement were recorded. RESULTS. Rupture was identified in 265 women (77%) with current silicone implants and 378 (55%) of 687 implants. Observers agreed in describing extracapsular silicone in 85 (12%) of 687 breasts with current silicone gel implants, of which 81 (95%) showed definite evidence of rupture on MR imaging. One observer reported extracapsular silicone in another 79 breasts. Confusion over contour deformity due to weakening versus breach of the capsule accounted for 33 (42%) of 79 disagreements. Another 20 (25%) of the 79 disagreements were attributed to poor conspicuity of extracapsular silicone on fast spin-echo T2-weighted images combined with intermittent observer failure to review inversion-recovery images. Subtlety of findings (n = 17, 22%) and technical issues (n = 9, 11%) with failed water suppression of pleural effusion or cysts and ghosting artifacts accounted for remaining disagreements. CONCLUSION. Extracapsular rupture is usually manifest as local spread of silicone in the breast and is not well-depicted on fast spin-echo T2-weighted images. Water-suppressed inversion-recovery T2-weighted images are often needed to identify extracapsular silicone. Distinction of the bulge in the fibrous capsule from herniation through the capsule remains problematic. C1 Univ Maryland, Univ Imaging Ctr, Dept Radiol, Baltimore, MD 21201 USA. Univ Maryland, Univ Imaging Ctr, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Univ Calif San Diego, MRI Inst, Dept Radiol, San Diego, CA 92103 USA. Duke Univ, Med Ctr, Dept Radiol, Durham, NC 27710 USA. US FDA, Div Biostat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Berg, WA (reprint author), Univ Maryland, Univ Imaging Ctr, Dept Radiol, 419 W Redwood St,Ste 110, Baltimore, MD 21201 USA. RI Soo, Mary/B-1580-2017 NR 26 TC 24 Z9 27 U1 1 U2 1 PU AMER ROENTGEN RAY SOC PI RESTON PA 1891 PRESTON WHITE DR, SUBSCRIPTION FULFILLMENT, RESTON, VA 22091 USA SN 0361-803X J9 AM J ROENTGENOL JI Am. J. Roentgenol. PD FEB PY 2002 VL 178 IS 2 BP 465 EP 472 PG 8 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 515GF UT WOS:000173486500038 PM 11804919 ER PT J AU Schroeder, CM Zhao, CW DebRoy, C Torcolini, J Zhao, SH White, DG Wagner, DD McDermott, PF Walker, RD Meng, JH AF Schroeder, CM Zhao, CW DebRoy, C Torcolini, J Zhao, SH White, DG Wagner, DD McDermott, PF Walker, RD Meng, JH TI Antimicrobial resistance of Escherichia coli O157 isolated from humans, cattle, swine, and food SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; ANTIBIOTIC USAGE; ANIMALS; FLUOROQUINOLONES; INFECTIONS; FOSFOMYCIN; ASSAY; DEATH AB A total of 361 Escherichia coli O157 isolates, recovered from humans, cattle, swine, and food during the years 1985 to 2000, were examined to better understand the prevalence of antimicrobial resistance among these organisms. Based on broth microdilution results, 220 (61%) of the isolates were susceptible to all 13 antimicrobials tested. Ninety-nine (27%) of the isolates, however, were resistant to tetracycline, 93 (26%) were resistant to sulfamethoxazole, 61 (17%) were resistant to cephalothin, and 48 (13%) were resistant to ampicillin. Highest frequencies of resistance occurred among swine isolates (n = 70), where 52 (74%) were resistant to sulfamethoxazole, 50 (71%) were resistant to tetracycline, 38 (54%) were resistant to cephalothin, and 17 (24%) were resistant to ampicillin. Based on the presence of Shiga toxin genes as determined by PCR, 210 (58%) of the isolates were identified as Shiga toxin-producing E. coli (STEC). Among these, resistance was generally low, yet 21 (10%) were resistant to sulfamethoxazole and 19 (9%) were resistant to tetracycline. Based on latex agglutination, 189 (52%) of the isolates were identified as E. coli O157:H7, among which 19 (10%) were resistant to sulfamethoxazole and 16 (8%) were resistant to tetracycline. The data suggest that selection pressure imposed by the use of tetracycline derivatives, sulfa drugs, cephalosporins, and penicillins, whether therapeutically in human and veterinary medicine or as prophylaxis in the animal production environment, is a key driving force in the selection of antimicrobial resistance in STEC and non-STEC O157. C1 Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. Penn State Univ, Gastroenter Dis Ctr, University Pk, PA 16802 USA. US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Res Off, Laurel, MD 20708 USA. RP Meng, JH (reprint author), Univ Maryland, Dept Nutr & Food Sci, 3304 Marie Mt Hall, College Pk, MD 20742 USA. EM jm332@umail.umd.edu NR 34 TC 145 Z9 155 U1 0 U2 24 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 FEB PY 2002 VL 68 IS 2 BP 576 EP 581 DI 10.1128/AEM.68.2.576-581.2002 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 517AH UT WOS:000173588600017 PM 11823193 ER PT J AU Landry, RJ Miller, SA Byrnes, GA AF Landry, RJ Miller, SA Byrnes, GA TI Study of filtered light on potential retinal photic hazards with operation microscopes used for ocular surgery SO APPLIED OPTICS LA English DT Article ID EXTRACAPSULAR CATARACT-EXTRACTION; INTRAOCULAR-LENS IMPLANTATION; INDUCED MACULOPATHY; PENETRATING KERATOPLASTY; RECOVERY; DAMAGE AB There have been numerous reports of retinal photic injury from operation microscopes used during cataract surgery. The risk of injury has been associated with the intensity of the light directed into the eye, short-wavelength emission, user technique, exposure time, and direct axial lighting. We evaluated use of light transmission filters to modify a tungsten-halogen light source spectrum to reduce the risk of retinal photic injury. A two-light source filter combination was found with a color profile acceptable for intraocular surgery that reduces the risk of retinal photic injury by a factor of approximately 2.5. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Natl Naval Med Res Inst, Dept Ophthalmol, Bethesda, MD 20889 USA. RP Landry, RJ (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. EM rjl@cdrh.fda.gov NR 19 TC 1 Z9 1 U1 0 U2 1 PU OPTICAL SOC AMER PI WASHINGTON PA 2010 MASSACHUSETTS AVE NW, WASHINGTON, DC 20036 USA SN 1559-128X EI 2155-3165 J9 APPL OPTICS JI Appl. Optics PD FEB 1 PY 2002 VL 41 IS 4 BP 802 EP 804 DI 10.1364/AO.41.000802 PG 3 WC Optics SC Optics GA 515MZ UT WOS:000173500800027 PM 11993928 ER PT J AU Kawakami, M Kawakami, K Puri, RJ AF Kawakami, M Kawakami, K Puri, RJ TI Apoptotic pathways of cell death induced by an interleukin-13 receptor-targeted recombinant cytotoxin in head and neck cancer cells SO CANCER IMMUNOLOGY IMMUNOTHERAPY LA English DT Article DE interleukin-13; cytotoxin; head and neck squamous cell carcinoma; apoptosis; nitric oxide ID PSEUDOMONAS EXOTOXIN; CARCINOMA-CELLS; SIGNAL-TRANSDUCTION; TUMOR-CELLS; PROTEIN; LINES; CASPASES; GROWTH; BCL-2; IL-13 AB Interleukin 13 receptor (IL-13R)-targeted cytotoxin, IL13-PE38QQR, composed of IL-13 and a mutated form of Pseudomonas exotoxin (PE), is found to be highly and specifically cytotoxic to human solid cancer cell lines. However, the mechanism of tumor cell death mediated by IL-13 toxin is still not known. To elucidate the mechanism, we utilized four head and neck cancer cell lines (SCC-25, HN12, KCCT873, and YCUM911), which express high levels of IL-13R, and IL-13 toxin is highly cytotoxic to these cells. We observed chromatin condensation and DNA fragmentation, indicating apoptotic cell death, after treatment with IL-13 toxin, as determined by bis-benzimide staining and DNA ladder assays. However, IL-13 did not induce cell death. Flow cytometric analysis suggested that these cancer cell lines increased the sub-G1/G0 phase DNA population in a dose- and time-dependent manner (ranged between 10 and 30%) after treatment with IL-13 toxin. By Western blot analysis, cleavage of caspase-3 and PARP was observed after treatment with a high concentration of IL-13 toxin, also suggesting apoptotic cell death. In addition, the results of immunofluorescence and RT-PCR assays showed that the apoptosis-regulator, Bcl-2 was downregulated after treatment with IL-13 toxin. while Bax was upregulated. Moreover, significant nitrite production was detected in the HN12 cell line after treatment with IL-13 toxin for 48-96 h. Taken together, our results suggest that IL-13 toxin-induced cytotoxicity is at least partially mediated by the apoptosis and nitric oxide pathways. This information may be useful in developing specific approaches where apoptotic bodies from tumor cells may be used to pulse antigen-presenting cells for immunotherapy of cancer. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Puri, RJ (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 41 TC 24 Z9 25 U1 1 U2 1 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0340-7004 J9 CANCER IMMUNOL IMMUN JI Cancer Immunol. Immunother. PD FEB PY 2002 VL 50 IS 12 BP 691 EP 700 DI 10.1007/s00262-001-0242-6 PG 10 WC Oncology; Immunology SC Oncology; Immunology GA 531LG UT WOS:000174416400006 PM 11862421 ER PT J AU Chang, HF Huffer, DM Chiarelli, MP Blankenship, LR Culp, SJ Cho, BP AF Chang, HF Huffer, DM Chiarelli, MP Blankenship, LR Culp, SJ Cho, BP TI Characterization of DNA adducts derived from syn-benzo[ghi]fluoranthene-3,4-dihydrodiol-5,5a-epoxide and comparative DNA binding studies with structurally-related anti-diolepoxides of benzo[ghi]fluoranthene and benzo[c]phenanthrene SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID REGION DIOL-EPOXIDES; POLYCYCLIC AROMATIC-HYDROCARBONS; TUMOR-INITIATING ACTIVITY; BAY-REGION; FJORD-REGION; DIHYDRODIOL EPOXIDES; MAMMALIAN-CELLS; MOUSE SKIN; 11,12-DIHYDRODIOL 13,14-EPOXIDE; 3,4-DIOL 1,2-EPOXIDES AB This paper reports structural characterization of the adducts and tetraols formed from syn-benzo[ghi]fluoranthene-3,4-dihydrodiol-5,5a-epoxide (syn-B[ghi]FDE, 3) and comparative DNA-binding and mutagenicity studies involving 3, anti-B[ghi]FDE (2), and anti-benzo[c]phenanthrene-11,12-dihydrodiol-13,14-epoxide (anti-BcPDE, 5). The structures of nine DNA adducts and two racemic tetraols derived from 3 have been determined spectroscopically. Similar characterization of adducts obtained from the anti-isomer 2 was described in the preceding paper in this issue [Chang et al. (2002) Chem. Res. Toxicol. 15, 187-197]. The majority of DNA adducts with 3 are those from the trans- or cis-opening of the epoxide at C5a by the exocyclic amino groups of dG, dA, and dC. The diolepoxides 2 and 3 are rigid structure analogues of anti- and syn-BcPDE (5 and 6), respectively, thus serving as models for probing molecular deformity and diol conformation in diolepoxide-DNA interaction. Comparative DNA binding experiments indicate that 57% of 2 and 33% of 3 were converted into DNA adducts, whereas a 71% conversion was observed for 5. In general, lower percentages were observed with denatured calf-thymus DNA. As for base selectivity, 2 showed a greater affinity for dA relative to dG (dA/dG ratio, 0.79) than 3 (0.56) when reacted with native calf-thymus DNA. A much higher dA/dG ratio (1.41) was obtained for 5. The overall dA/dG ratios were lower with denatured DNA, indicating the importance of the secondary structure of DNA for both adduct formation and chemical selectivity. The T-shape pseudo-diaxial diols of 3 appears to have favorable electrostatic interactions with the nearby phosphate backbone in the minor groove of DNA, thereby yielding greater amounts of dG adducts than the pseudo-diequatorial 2. The anti-isomer 2 was found to be seven times more mutagenic than 3, but they are significantly less mutagenic than the nonplanar analogue 5 when tested in Salmonella typhimurium TA 100. C1 Univ Rhode Isl, Dept Biomed Sci, Kingston, RI 02881 USA. Loyola Univ, Dept Chem, Chicago, IL 60626 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Cho, BP (reprint author), Univ Rhode Isl, Dept Biomed Sci, Kingston, RI 02881 USA. NR 50 TC 6 Z9 6 U1 0 U2 1 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 2002 VL 15 IS 2 BP 198 EP 208 DI 10.1021/tx0101346 PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 524VM UT WOS:000174033600013 PM 11849046 ER PT J AU Suzuki, K Yanagi, M Mori-Aoki, A Moriyama, E Ishii, KJ Kohn, LD AF Suzuki, K Yanagi, M Mori-Aoki, A Moriyama, E Ishii, KJ Kohn, LD TI Transfection of single-stranded hepatitis A virus RNA activates MHC class I pathway SO CLINICAL AND EXPERIMENTAL IMMUNOLOGY LA English DT Article DE infectious immunity-virus; MHC; antigen presentation; protein kinases/phosphatases ID NF-KAPPA-B; MAJOR HISTOCOMPATIBILITY COMPLEX; DEPENDENT PROTEIN-KINASE; NECROSIS-FACTOR-ALPHA; GENE-EXPRESSION; A VIRUS; ANTIGEN PRESENTATION; V(D)J RECOMBINATION; IMMUNE-RESPONSES; CDNA CLONE AB Although infection of single-stranded RNA viruses can enhance expression of major histocompatibility complex (MHC) class I genes, the mechanism underlying this process remains unclear. Recent studies have indicated that exposure of non-immune cells to double-stranded deoxyribonucleic acid (DNA) or ribonucleic acid (RNA) of viral origin can directly increase the expression of MHC class I and related molecules without immune cell interaction. In this report, we show that transfection of single-stranded hepatitis A virus RNA into cultured hepatocytes results in the induction of genes for MHC class I, LMP2 and transporter for antigen processing (TAP1), in addition to the generation of viral proteins. We suggest that this stimulatory effect is due to the double-stranded RNA formed during replication of single-stranded viral RNA, and involves both double-stranded, RNA-dependent protein kinase PKR and the secretion of IFNbeta. C1 Natl Inst Infect Dis, Leprosy Res Ctr, Dept Microbiol, Tokyo 1890002, Japan. NIDDKD, Cell Regulat Sect, Metab Dis Branch, NIH, Bethesda, MD USA. Kanazawa Univ, Sch Med, Dept Internal Med, Kanazawa, Ishikawa 920, Japan. Tottori Univ, Sch Med, Dept Internal Med, Tottori 680, Japan. US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. Ohio Univ, Coll Med, Edison Biotechnol Inst, Athens, OH 45701 USA. RP Suzuki, K (reprint author), Natl Inst Infect Dis, Leprosy Res Ctr, Dept Microbiol, 4-2-1 Aoba Cho, Tokyo 1890002, Japan. RI Ishii, Ken/B-1685-2012 OI Ishii, Ken/0000-0002-6728-3872 NR 58 TC 10 Z9 10 U1 0 U2 0 PU BLACKWELL PUBLISHING LTD PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DG, OXON, ENGLAND SN 0009-9104 J9 CLIN EXP IMMUNOL JI Clin. Exp. Immunol. PD FEB PY 2002 VL 127 IS 2 BP 234 EP 242 DI 10.1046/j.1365-2249.2002.01767.x PG 9 WC Immunology SC Immunology GA 548JP UT WOS:000175385100008 PM 11876745 ER PT J AU Chapman, LE Ellis, BA Koster, FT Sotir, M Ksiazek, TG Mertz, GJ Rollin, PE Baum, KF Pavia, AT Christenson, JC Rubin, PJ Jolson, HM Behrman, RE Khan, AS Bell, LJW Simpson, GL Hawk, J Holman, RC Peters, CJ AF Chapman, LE Ellis, BA Koster, FT Sotir, M Ksiazek, TG Mertz, GJ Rollin, PE Baum, KF Pavia, AT Christenson, JC Rubin, PJ Jolson, HM Behrman, RE Khan, AS Bell, LJW Simpson, GL Hawk, J Holman, RC Peters, CJ CA Ribavirin Study Grp TI Discriminators between hantavirus-infected and -uninfected persons enrolled in a trial of intravenous ribavirin for presumptive hantavirus pulmonary syndrome SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID DISEASE AB To provide a potentially therapeutic intervention and to collect clinical and laboratory data during an outbreak of hantavirus pulmonary syndrome (HPS), 140 patients from the United States with suspected HPS were enrolled for investigational intravenous ribavirin treatment. HPS was subsequently laboratory confirmed in 30 persons and not confirmed in 105 persons with adequate specimens. Patients with HPS were significantly more likely than were hantavirus-negative patients to report myalgias from onset of symptoms through hospitalization, nausea at outpatient presentation, and diarrhea and nausea at the time of hospitalization; they were significantly less likely to report respiratory symptoms early in the illness. The groups did not differ with regard to time from the onset of illness to the point at which they sought care; time from onset, hospitalization, or enrollment to death was significantly shorter for patients with HPS. At the time of hospitalization, patients with HPS more commonly had myelocytes, metamyelocytes, or promyelocytes on a peripheral blood smear, and significantly more of them had thrombocytopenia, hemoconcentration, and hypocapnia. Patterns of clinical symptoms, the pace of clinical evolution, and specific clinical laboratory parameters discriminated between these 2 groups. C1 Ctr Dis Control & Prevent, Hantavirus Task Force, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Viral & Rickettsial Zoonoses Branch, Div Viral & Rickettsial Dis, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. Univ New Mexico, Sch Med, Dept Internal Med, Albuquerque, NM 87131 USA. New Mexico Dept Hlth, Santa Fe, NM USA. Univ Utah, Sch Med, Dept Pediat, Salt Lake City, UT USA. Infect Dis Consultants Ltd, Phoenix, AZ USA. US FDA, Rockville, MD 20857 USA. Univ Colorado, Sch Med, Denver, CO USA. RP Chapman, LE (reprint author), Ctr Dis Control & Prevent, Div AIDS STD & TB Lab Res, Mailstop A-12,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 16 TC 26 Z9 27 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD FEB 1 PY 2002 VL 34 IS 3 BP 293 EP 304 DI 10.1086/324619 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 507UF UT WOS:000173049100001 PM 11774075 ER PT J AU Booth, BP Gobburu, JV AF Booth, BP Gobburu, JV TI Considerations in analyzing single-trough samples using mixed-effect modeling. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDER, 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 2002 VL 71 IS 2 BP P21 EP P21 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 527GP UT WOS:000174178600080 ER PT J AU Cantilena, LR Katki, AG Klecker, RW Collins, JM AF Cantilena, LR Katki, AG Klecker, RW Collins, JM TI Targeted inhibition of N-acetyltransferase, type 2 (NAT2) in healthy volunteers. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. US FDA, Bethesda, MD 20014 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 2002 VL 71 IS 2 BP P58 EP P58 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 527GP UT WOS:000174178600214 ER PT J AU Chatterjee, DJ Parekh, A Malinowski, H Hunt, J Sun, H AF Chatterjee, DJ Parekh, A Malinowski, H Hunt, J Sun, H TI Exposure-response factors affecting long-term efficacy: A case study. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract 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 2002 VL 71 IS 2 BP P20 EP P20 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 527GP UT WOS:000174178600073 ER PT J AU Gobburu, JV Lawrence, J AF Gobburu, JV Lawrence, J TI Bayesian approach to nonlinear mixed effects model selection. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract 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 2002 VL 71 IS 2 BP P22 EP P22 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 527GP UT WOS:000174178600081 ER PT J AU Gorski, JC Hamman, MA Wang, Z Vasavada, N Huang, S Hall, SD AF Gorski, JC Hamman, MA Wang, Z Vasavada, N Huang, S Hall, SD TI The effect of St. John's wort on the efficacy of oral contraception. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Indiana Univ, Indianapolis, IN 46204 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 7 Z9 7 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 2002 VL 71 IS 2 BP P25 EP P25 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 527GP UT WOS:000174178600093 ER PT J AU Kim, CY Davit, BM Conner, DP AF Kim, CY Davit, BM Conner, DP TI Demographics of subjects in bioequivalence studies of generic drug products. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDER, 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 2002 VL 71 IS 2 BP P19 EP P19 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 527GP UT WOS:000174178600072 ER PT J AU Lee, SH Sun, H Bashaw, ED Selen, A Lazor, J AF Lee, SH Sun, H Bashaw, ED Selen, A Lazor, J TI The impact of imbalanced design of categorical covariates on model misspecification and parameter distinction between sub-groups in population analysis. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract 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 2002 VL 71 IS 2 BP P22 EP P22 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 527GP UT WOS:000174178600082 ER PT J AU Li, Z Willy, ME AF Li, Z Willy, ME TI Managing the risks of drug-induced liver failure - What is the product labeling telling doctors? SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract 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 2002 VL 71 IS 2 BP P91 EP P91 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 527GP UT WOS:000174178600331 ER PT J AU Nguyen, B Gobburu, J AF Nguyen, B Gobburu, J TI Individual vs. population QT correction: Inferences from a pilot study. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract 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 2002 VL 71 IS 2 BP P22 EP P22 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 527GP UT WOS:000174178600083 ER PT J AU Shaffer, D Butterfield, M AF Shaffer, D Butterfield, M TI Metoclopramide and tardive dyskinesia: A review of the FDA Adverse Event Reporting System. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Durham VAMC, Rockville, MD 20857 USA. Duke Univ, Sch Med, Durham, NC 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 2002 VL 71 IS 2 BP P24 EP P24 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 527GP UT WOS:000174178600091 ER PT J AU Sun, HH Parekh, A Chatterjee, DJ Zhao, HH Pelsor, F Lazor, J Malinowski, H Hunt, J Lesko, L AF Sun, HH Parekh, A Chatterjee, DJ Zhao, HH Pelsor, F Lazor, J Malinowski, H Hunt, J Lesko, L TI The significance of distribution of pharmacokinetic (PK) and pharmacodynamic (PD) variabilities in determining clinical outcomes. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract 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 2002 VL 71 IS 2 BP P75 EP P75 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 527GP UT WOS:000174178600269 ER PT J AU Wang, SJ Hung, HMJ Tsong, Y AF Wang, SJ Hung, HMJ Tsong, Y TI Utility and pitfalls of some statistical methods in active controlled clinical trials SO CONTROLLED CLINICAL TRIALS LA English DT Article DE putative placebo; noninferiority margin; indirect confidence interval comparison; virtual comparison; preservation of control effect; random effects ID PLACEBO-CONTROLLED TRIALS; EQUIVALENCE TRIALS; PRACTICAL ISSUES; DESIGN AB Increasingly often, the study objective in an active controlled clinical trial without a placebo arm is to show that a new treatment is no less effective than the active control treatment within some noninferiority range. Two issues behind this objective are that of whether the new treatment is efficacious relative to a putative placebo and that of whether the new treatment preserves a certain fraction of effect of the active control. To address these issues, two types of statistical analysis methods are employed in recent pharmaceutical applications. In one type of method, a noninferiority margin is determined, and then the relative effect of the new treatment versus the control is compared against the margin to test noninferiority and the efficacy of the new treatment. In the other type of method, a synthetic statistic is constructed to directly estimate or test the effect of the new treatment relative to the putative placebo without resorting to noninferiority argument. Preservation of control effect can also be estimated and tested. These methods carry some crucial assumptions. The effect of active control is often estimated from a collection of historical placebo controlled trials using the random effects modeling of DerSi-monian and Laird. In this work we find that statistical validity of the latter method rests highly on the assumptions that control effect is not reduced in the current active controlled trial population compared to the historical trials and that a normal approximation is appropriate in the random effects modeling. This type of method is very sensitive to departure from these assumptions. In contrast, the former method is ultraconservative in terms of type I error when the assumptions are met and can be anticonservative when control effect is substantially less in the: active controlled trial than estimated from the historical placebo controlled trials. (C) 2002 Elsevier Science Inc. All rights reserved. C1 US FDA, CDER, OB, Div Biometr 2, Rockville, MD 20857 USA. US FDA, CDER, OB, Div Biometr 1, Rockville, MD 20857 USA. RP Wang, SJ (reprint author), US FDA, CDER, OB, Div Biometr 2, HFG-715,9B07,PKLN,5600 Fishers Lane, Rockville, MD 20857 USA. NR 21 TC 61 Z9 63 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD FEB PY 2002 VL 23 IS 1 BP 15 EP 28 DI 10.1016/S0197-2456(01)00155-6 PG 14 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 517BA UT WOS:000173590200002 PM 11852161 ER PT J AU Egan, SK Tao, SSH Pennington, JAT Bolger, PM AF Egan, SK Tao, SSH Pennington, JAT Bolger, PM TI US Food and Drug Administration's total diet study: Intake of nutritional and toxic elements, 1991-96 SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE Total Diet Study (TDS); dietary intakes; nutritional elements; toxic elements; monitoring ID FDA TOTAL DIET; UNITED-STATES; PESTICIDES; CHEMICALS; MINERALS; HISTORY AB The Food and Drug Administration (FDA) has conducted the Total Diet Study (TDS) annually since 1961. The TDS is designed to monitor the US food supply for levels of toxic chemical contaminants (pesticide residues, industrial chemicals and toxic elements) and nutritional elements. Foods are generally collected four times a year, once from each of four regions of the country. The foods are prepared table-ready before being analysed. From the results of the TDS, dietary intakes of these analytes are estimated for selected age- sex groups in the US population. This paper reports on the dietary intake of 10 nutritional and four toxic elements based on measurements made in foods collected in the TDS between 1991 and late 1996. Average daily intakes were estimated for 14 age- sex groups in the US population, as well as the contribution of specific food groups to total intakes. For most nutritional elements, teenage boys and adult males had the highest daily intakes. Intakes by infants were below the intake references for seven of 10 nutritional elements, and young girls and women had inadequate intakes of at least half the nutritional elements. Intakes by children between 2 and 10 years of age, teenage boys, and adult males met or exceeded the reference intakes for the majority of nutritional elements. Intakes by all population groups were well below the reference intakes for all toxic elements. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NIH, Div Nutr Res Coordinat, Bethesda, MD 20892 USA. RP Egan, SK (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 28 TC 67 Z9 73 U1 0 U2 8 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 FEB PY 2002 VL 19 IS 2 BP 103 EP 125 DI 10.1080/02652030110071354 PG 23 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 512AJ UT WOS:000173298700001 PM 11824417 ER PT J AU Weagant, SD Feng, PCH AF Weagant, SD Feng, PCH TI Comparative analysis of a modified rapid presence/absence test and the standard MPN method for detecting Escherichia coli in orange juice SO FOOD MICROBIOLOGY LA English DT Article ID COLIFORMS AB A modified rapid presence/absence test was evaluated and compared to the standard most probable number (MPN) method for detecting Escherichia coli in artificially contaminated orange juice. In each of the four experiments conducted pasteurized and unpasteurized orange juice samples were seeded with one of the three different strains of E. coli, at levels ranging from 0.4 to 6.5 cfu ml(-1). The samples were also seeded with 360-510 cfu ml(-1) of other enteric bacteria to simulate background flora. Samples were analysed by the MPN method for E. coli and by the modified ColiComplete (CC) presence/ absence test in E. coli (EC) broth at 44.5degreesC, after pre-enriching 10 ml of juice samples in Universal Pre-enrichment Broth for 24h (modified CC method). Of the 12 comparative analyses performed E. coli was detected in all 12 tests by the modified CC method and furthermore, showed the presence of E. coli in 59 of the 60 (98.3%) orange juice replicates that were examined In contrast, the standard MPN method was only able to quantify detectable levels of E. coli in eight of 12 tests. The modified CC procedure was faster required less media and reagents, enabled analysis of 10ml samples and was more reliable than the standard MPN method for determining the presence or absence of E. coli in artificially contaminated orange juice. (C) 2002 Elsevier Science Ltd. C1 Pacific Regional Lab, Food & Drug Adm, Bothell, WA 98021 USA. Ctr Food Safety & Appl Nutr, Food & Drug Adm, Washington, DC 20204 USA. RP Weagant, SD (reprint author), 22201 23rd Dr S E, Bothell, WA 98021 USA. EM sweagant@ora.fda.gov NR 13 TC 6 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD FEB PY 2002 VL 19 IS 1 BP 111 EP 115 DI 10.1006/fmic.2001.0460 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 534FD UT WOS:000174573100014 ER PT J AU Park, DL AF Park, DL TI World trade success depends on risk analysis SO FOOD TECHNOLOGY LA English DT Editorial Material C1 US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, Washington, DC 20204 USA. RP Park, DL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, Washington, DC 20204 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 2002 VL 56 IS 2 BP 100 EP 100 PG 1 WC Food Science & Technology SC Food Science & Technology GA 521MY UT WOS:000173845500023 ER PT J AU Kim, K Lawrence, SM Park, J Pitts, L Vann, WF Betenbaugh, MJ Palter, KB AF Kim, K Lawrence, SM Park, J Pitts, L Vann, WF Betenbaugh, MJ Palter, KB TI Expression of a functional Drosophila melanogaster N-acetylneuraminic acid (Neu5Ac) phosphate synthase gene: evidence for endogenous sialic acid biosynthetic ability in insects SO GLYCOBIOLOGY LA English DT Article DE insects; KDN; N-acetylneuraminic acid; sialic acid synthase ID CELL-ADHESION MOLECULE; POLYSIALIC ACID; 2-KETO-3-DEOXY-D-GLYCERO-D-GALACTO-NONONIC ACID; 2-EPIMERASE/N-ACETYLMANNOSAMINE KINASE; HUMAN POLYSIALYLTRANSFERASE; NUCLEOTIDE SULFATE; GOLGI-APPARATUS; CLONING; GLYCOSYLATION; GLYCOPROTEINS AB In this study, we report the first cloning and characterization of a N-acetylneuraminic acid phosphate synthase gene from Drosophila melanogaster, an insect in the protostome lineage. The gene is ubiquitously expressed at all stages of Drosophila development and in Schneider cells. Similar to the human homologue, the gene encodes an enzyme with dual substrate specificity that can use either N-acetylmannosamine 6-phosphate or mannose 6-phosphate to generate phosphorylated forms of both the sialic acids, N-acetylneuraminic acid and 2-keto-3-deoxy-D-glycero-D-galacto-nononic acid, respectively, when expressed in either bacterial or baculoviral expression systems. The identification of a functional sialic acid synthase in Drosophila indicates that insects have the biosynthetic capability to produce sialic acids endogenously. Although sialylation is widely distributed in organisms of the deuterstome lineage, genetic evidence concerning the presence or absence of sialic acid metabolism in organisms of the protostome lineage has been lacking. Homology searches of the Drosophila genome identified putative orthologues of other genes required for sialylation of glycoconjugates. C1 Temple Univ, Dept Biol, Philadelphia, PA 19122 USA. Johns Hopkins Univ, Dept Chem Engn, Baltimore, MD 21218 USA. US FDA, Lab Bacterial Toxins, Bethesda, MD 20892 USA. US FDA, Lab Bacterial Polysaccharides, Bethesda, MD 20892 USA. RP Palter, KB (reprint author), Temple Univ, Dept Biol, Philadelphia, PA 19122 USA. RI Betenbaugh, Michael J./A-3252-2010 OI Betenbaugh, Michael J./0000-0002-6336-4659 NR 66 TC 35 Z9 36 U1 0 U2 3 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD FEB PY 2002 VL 12 IS 2 BP 73 EP 83 DI 10.1093/glycob/12.2.73 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 535KX UT WOS:000174644600007 PM 11886840 ER PT J AU Mahmood, I AF Mahmood, I TI Comparison of different reduced sampling approaches for the estimation of pharmacokinetic parameters for long half-life drugs in patients with renal or hepatic impairment SO INTERNATIONAL JOURNAL OF CLINICAL PHARMACOLOGY AND THERAPEUTICS LA English DT Article DE reduce sampling; Bayesian and population pharmacokinetics; long half-life; renal or hepatic impairment ID PARTIAL AREAS; BIOEQUIVALENCE; POPULATION; DESIGN; EXTENT AB Objective: To compare 3 different reduced sampling approaches (truncated area, population and Bayesian; sampling schedule till 48 or 72 hours) with the extensive sampling for the estimation of pharmacokinetic parameters for long half-life drugs in healthy subjects and in patients with renal or hepatic impairment. Methods: Two drugs (extensively metabolized or extensively excreted) whose half-lives were greater than 30 hours were used in this analysis. Pharmacokinetic parameters such as maximum plasma concentration, clearance and half-life were estimated in healthy subjects and in patients using the above-mentioned 3 reduced sampling approaches and then compared with the extensive sampling. Results: The truncated area method failed to detect the same magnitude of difference in pharmacokinetic parameters between healthy subjects and patient populations that was determined using extensive sampling. On the other hand, the population or Bayesian approach provided the same magnitude of difference in pharmacokinetic parameters between the 2 populations that was observed with extensive sampling. Conclusion: This study indicates that the truncated area method may be a less suitable method to accurately characterize the pharmacokinetics of a long half-life drug either in healthy subjects or in patients with renal or hepatic impairment compared to a population or Bayesian approach. C1 US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut, Woodmont Off Ctr 2, HFD-860,Rockville Pike, Rockville, MD 20852 USA. NR 10 TC 0 Z9 0 U1 0 U2 2 PU DUSTRI-VERLAG DR KARL FEISTLE PI OBERHACHING PA BAJUWARENRING 4, D-82041 OBERHACHING, GERMANY SN 0946-1965 J9 INT J CLIN PHARM TH JI Int. J. Clin. Pharmacol. Ther. PD FEB PY 2002 VL 40 IS 2 BP 53 EP 59 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 521ED UT WOS:000173825200002 PM 11862973 ER PT J AU Bischoff, KM White, DG McDermott, PF Zhao, SH Gaines, S Maurer, JJ Nisbet, DJ AF Bischoff, KM White, DG McDermott, PF Zhao, SH Gaines, S Maurer, JJ Nisbet, DJ TI Characterization of chloramphenicol resistance in beta-hemolytic Escherichia coli associated with diarrhea in neonatal swine SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID TYPHIMURIUM DT104; DRUG-RESISTANCE; FLORFENICOL; GENE; PIGS AB Ninety beta-hemolytic Escherichia coli isolates associated with diarrhea in neonatal pigs from multiple farms in Oklahoma were investigated for known associated disease serotypes, virulence factors, ribotypes, and antimicrobial susceptibility phenotypes. Fifteen different serotypes were observed, with 58% of isolates belonging to groups that produce one of three major enterotoxins: O149, O147, and O139. Thirty percent of the swine E. coli isolates possessed a combination of F4 fimbriae and the heat-labile toxin and heat-stable toxin B enterotoxins. Seventy-three percent of the E. coli isolates were resistant to five or more antibiotics. Interestingly, 53% of swine E. coli isolates exhibited resistance to chloramphenicol (CHL), an antibiotic whose use in food animals has been prohibited in the United States since the mid-1980s. The cmlA gene, which encodes a putative CHL efflux pump, was detected by PCR in 47 of the 48 CHL-resistant isolates, and 4 of these also possessed the cat2 gene, which encodes a chloramphenicol acetyltransferase. The one CHL-resistant isolate that did not contain either cmlA or cat-2 possessed the flo gene, which confers resistance to both florfenicol and CHL. To determine whether CHL-resistant swine E. coli isolates represented dissemination of a clonal strain, all 90 isolates were analyzed by ribotyping. Seventeen distinct E. coli ribogroups were identified, with CHL resistance observed among the isolates in all except one of the major ribogroups. The identification of the cmlA gene among diverse hemolytic enterotoxigenic E. coli strains demonstrates its broad dissemination in the swine production environment and its persistence even in the absence of CHL selection pressure. C1 ARS, So Plains Agr Res Ctr, USDA, College Stn, TX 77845 USA. US FDA, Res Off, Ctr Vet Med, Laurel, MD USA. Univ Georgia, Dept Avian Med, Athens, GA 30602 USA. RP Bischoff, KM (reprint author), ARS, So Plains Agr Res Ctr, USDA, 2881 F-B Rd, College Stn, TX 77845 USA. NR 32 TC 66 Z9 77 U1 0 U2 10 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 FEB PY 2002 VL 40 IS 2 BP 389 EP 394 DI 10.1128/JCM.40.2.389-394.2002 PG 6 WC Microbiology SC Microbiology GA 519NG UT WOS:000173731900012 PM 11825947 ER PT J AU Lathers, CM Schraeder, PL AF Lathers, CM Schraeder, PL TI Clinical pharmacology: Drugs as a benefit and/or risk in sudden unexpected death in epilepsy? SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the American-College-of-Clinical-Pharmacology CY SEP, 2000 CL CHICAGO, ILLINOIS SP Amer Coll Clin Pharmac ID CARDIAC NEURAL DISCHARGE; INDUCED EPILEPTOGENIC ACTIVITY; UNEXPLAINED DEATH; AUTONOMIC DYSFUNCTION; PSYCHOACTIVE AGENTS; MENTAL-RETARDATION; CORONARY-OCCLUSION; PARTIAL SEIZURES; ARRHYTHMIA; SUDEP AB Death may be the consequence of natural or unnatural causes, such as accidents, homicide, and suicide, which have no relationship to the disease of epilepsy. Direct causes of death include status epilepticus, and indirect causes may be head trauma or drowning subsequent to a seizure. When death occurs suddenly and without explanation, the term sudden unexpected unexplained death is used. Unexplained is a term that clinicians and research scientists are working to clarify. Numerous preclinical animal studies have been conducted as models for sudden death and have led to clinical studies in persons with epilepsy. These studies show that sympathetic nerve stimulation, ouabain, or coronary occlusion increased temporal dispersion of recovery of ventricular excitability and led to an underlying electrical instability that predisposed the ventricular myocardium to arrhythmia. Cardiac arrhythmias in an animal model for ouabain-induced toxicity were associated with neural autonomic dysfunction. Neural discharges were characterized by increases, decreases, or no change in the discharge of postganglionic cardiac sympathetic nerves monitored simultaneously, predisposing to cardiac arrhythmia. Stimulation of the sympathetic ventrolateral cardiac nerve produced a shift in the origin of the pacemaker and tachyarrhythmias because the nerve is not uniformly distributed to the various regions of the heart but is localized to the atrioventricular junctional and ventricular regions. Such nonuniform distribution of sympathetic nerves would also contribute to initiation of arrhythmia as a nonuniform neural discharge occurred. Studies examining the physiology and pharmacology of this finding in multiple animal models found that subconvulsant, interictal discharge was associated with autonomic cardiac neural non-uniform discharge and cardiac arrhythmias. As a result of further investigations, Lathers and Schraeder edited a book in 1990 that summarized the clinical problem of sudden unexpected death and epilepsy (SUDEP). The contributors concluded that there was a paucity of clinical data addressing the mechanism of death. Regulatory response resulting from the consequent increased awareness of SUDEP occurred in 1993, when the FDA focused attention of practitioners and pharmaceutical manufacturers on the question of whether use of anticonvulsant drugs contributes to or prevents sudden unexpected death in epileptic persons. The FDA-convened panel of scientists considered the prevalence of sudden unexpected death in patients involved in studies associated with developing new anticonvulsant drugs and reviewed data on the risk of sudden unexpected death in patients taking lamotrigine. The risk of SUDEP was no different from that found in the young epilepsy population in general. Estimated SUDEP rates in patients receiving the new anticonvulsant drugs lamotrigine, gabapentin, topiramate, tigabine, and zonisamide were found to be similar to those in patients receiving standard anticonvulsant drugs, suggesting that SUDEP rates reflect population rates and not a specific drug effect. The FDA required warning labels on the risk of SUDEP in association with the use of each of the above-mentioned drugs. Another effect of bringing SUDEP to the attention of epilepsy researchers has been the expansion of basic science and the development of epidemiological and clinical studies directed at this phenomenon. Results from some of these studies are discussed in this article. (C) 2002 the American College of Clinical Pharmacology. C1 US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. Albert Einstein Med Ctr, Philadelphia, PA 19141 USA. RP Lathers, CM (reprint author), US FDA, Off New Anim Drug Evaluat, Ctr Vet Med, Rockville, MD 20857 USA. NR 119 TC 24 Z9 25 U1 0 U2 0 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD FEB PY 2002 VL 42 IS 2 BP 123 EP 136 DI 10.1177/00912700222011157 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 516CT UT WOS:000173534800001 PM 11831534 ER PT J AU Guo, X Chen, JR Brackett, RE Beuchat, LR AF Guo, X Chen, JR Brackett, RE Beuchat, LR TI Survival of Salmonella on tomatoes stored at high relative humidity, in soil, and on tomatoes in contact with soil SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; LISTERIA-MONOCYTOGENES; RAW TOMATOES; OUTBREAK; CONTAMINATION; MONTEVIDEO; VEGETABLES; PRODUCE; SPROUTS AB Salmonellosis has been linked to the, consumption of several types of raw fruits and vegetables, some of which may have been contaminated with Salmonella before harvesting. The objectives of this study were to investigate water and soil as reservoirs of Salmonella for the contamination of mature green tomato fruits. Salmonella survived for at least 45 days in inoculated moist soil. The population of Salmonella on tomatoes in contact with soil increased by 2.5 log(10) CFU per tomato during storage for 4 days at 20degreesC and remained constant for an additional 10 days. The number of cells inoculated on tomatoes decreased by approximately 4 log(10) CFU per tomato during storage for 14 days at 20degreesC and 70% relative humidity. Fruits in contact with inoculated soil for 1 day at 20degreesC harbored Salmonella only near or on the skin surface. More Salmonella cells were observed in stem scar and subsurface areas of tomatoes as the time of storage increased. PCR fingerprinting revealed that among five Salmonella serotypes in the inoculum, Salmonella Montevideo was the most persistent on tomatoes in contact with inoculated soil and on spot-inoculated tomatoes, followed by Salmonella Poona and Salmonella Michigan. The results of this study demonstrate that an enhanced green fluorescent protein marker can be used to detect cells and monitor the growth of Salmonella in the presence of other microorganisms. Observations on the infiltration of Salmonella into tomato tissues support the contention that preharvest contact of produce with contaminated water or soil exacerbates problems associated with the postharvest removal of pathogens or their accessibility to treatment with sanitizers. C1 Univ Georgia, Ctr Food Safety, Griffin, GA 30223 USA. Univ Georgia, Dept Food Sci & Technol, Griffin, GA 30223 USA. US FDA, Off Plant Dairy Foods & Beverages, Washington, DC 20204 USA. RP Beuchat, LR (reprint author), Univ Georgia, Ctr Food Safety, 1109 Expt St, Griffin, GA 30223 USA. NR 39 TC 82 Z9 83 U1 2 U2 11 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 FEB PY 2002 VL 65 IS 2 BP 274 EP 279 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 520EE UT WOS:000173767000004 PM 11848557 ER PT J AU Goswami, BB Kulka, I Ngo, D Istafanos, P Cebula, TA AF Goswami, BB Kulka, I Ngo, D Istafanos, P Cebula, TA TI A polymerase chain reaction-based method for the detection of hepatitis A virus in produce and shellfish SO JOURNAL OF FOOD PROTECTION LA English DT Article ID VIRION CONCENTRATION METHOD; HUMAN ENTERIC VIRUSES; A VIRUS; NORWALK VIRUS; PCR; OYSTERS; SEQUENCE; TISSUES; LETTUCE; RNA AB Outbreaks of gastroenteritis that are suspected to be of viral origin are on the rise. Thus, there is a need for regulatory agencies entrusted with food safety to develop adequate techniques for the detection of viruses in foods. We have established a general procedure for the detection of hepatitis A virus (HAV) in shellfish that, with minor modifications, is also applicable to fresh produce such as cilantro. Total RNA was isolated from shellfish or cilantro, followed by isolation of poly(A)-containing RNA. Because HAV genomic RNA contains a poly(A) tail, the isolation of poly(A)-containing RNA also enriches HAV genomic RNA. Reverse transcription was used to convert the RNA to cDNA, and then amplification was carried out by polymerase chain reaction (PCR). Reamplification with internal primers was used to improve the quality and the quantity of amplified DNA, allowing for post-PCR analysis such as sequence identification of the viral strain. With this procedure, multiple samples could be analyzed in four working days by a single trained individual. The nominal sensitivity of detection of the procedure was 0.15 TCID50 (50% tissue culture infective dose) per 0.62 g of tissue with a test virus. The direct RNA isolation protocol avoided pitfalls associated with whole-virus purification procedures by replacing virus precipitation steps involving polyethylene glycol and Procipitate with phenol extraction. The method is straightforward and reliable. We successfully used this procedure to detect naturally occurring HAV in clams involved in a gastroenteritis outbreak, as well as in cilantro artificially contaminated with a test virus. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol Res & Evaluat, Washington, DC 20204 USA. RP Goswami, BB (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol Res & Evaluat, HFS-237,200 C St SW, Washington, DC 20204 USA. NR 22 TC 22 Z9 22 U1 0 U2 3 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD FEB PY 2002 VL 65 IS 2 BP 393 EP 402 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 520EE UT WOS:000173767000022 PM 11858194 ER PT J AU Orlandi, PA Lampel, KA South, PK Assar, SK Carter, L Levy, DD AF Orlandi, PA Lampel, KA South, PK Assar, SK Carter, L Levy, DD TI Analysis of flour and food samples for cry9C from bioengineered corn SO JOURNAL OF FOOD PROTECTION LA English DT Article ID MAIZE AB StarLink corn is a variety of yellow corn that has been genetically modified by the insertion of an altered cry9C gene into the plant genome, resulting in expression of the insecticidal Cry9C protein. The U.S. Environmental Protection Agency has approved StarLink corn for use in animal feed but not in food intended for human consumption. Therefore, under the U.S. Food, Drug, and Cosmetic Act, any food intended for human consumption in which the presence of StarLink corn is indicated by the presence of either the Cry9C protein or the cry9C gene would be considered adulterated. Extraction and PCR-based methods were used to detect the presence of the cry9C DNA initially in corn flour and corn meal, and then these methods were extended to the analysis of processed corn products, including taco shells, cereals, baby foods, party snacks,. and chips, for the presence of this modified genetic material. In a survey of 63 products, the cry9C transgene was detected in 4 taco shells. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Levy, DD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-237,200 C St SW, Washington, DC 20204 USA. NR 10 TC 7 Z9 9 U1 0 U2 4 PU INT ASSOC FOOD PROTECTION PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD FEB PY 2002 VL 65 IS 2 BP 426 EP 431 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 520EE UT WOS:000173767000029 PM 11848580 ER PT J AU Takefman, DM Spear, GT Saifuddin, M Wilson, CA AF Takefman, DM Spear, GT Saifuddin, M Wilson, CA TI Human CD59 incorporation into porcine endogenous retrovirus particles: Implications for the use of transgenic pigs for xenotransplantation SO JOURNAL OF VIROLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; HUMAN-COMPLEMENT; HUMAN-CELLS; HUMAN SERUM; PROTEINS CD55; EXPRESSION; INFECTION; INACTIVATION; DESTRUCTION; XENOGRAFTS AB Transgenic pigs have been engineered to express human CD59 (hCD59) in order to suppress hyperacute rejection of xenotransplants in human recipients. In this study, porcine endogenous retrovirus (PERV) was produced in a porcine cell line expressing hCD59 in order to examine the effect of this complement control protein on PERV neutralization by human sera. hCD59 was found to be incorporated into PERV particles produced from engineered ST-IOWA cells. PERV incorporation of hCD59 resulted in a dramatic inhibition of complement-mediated virolysis by human serum. However, incorporation of hCD59 had no effect on neutralization of PERV by human serum, as measured in infectivity assays. Our results suggest that the use of organs from hCD59 transgenic pigs will inhibit complement-mediated virolysis, but will not compromise the protective effects of human sera on the neutralization of PERV particles. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. Rush Univ, Dept Microbiol Immunol, Chicago, IL 60612 USA. RP Wilson, CA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bldg 29B,room 2E12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 28 TC 28 Z9 29 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 FEB PY 2002 VL 76 IS 4 BP 1999 EP 2002 DI 10.1128/JVI.76.4.1999-2002.2002 PG 4 WC Virology SC Virology GA 514TT UT WOS:000173457700049 PM 11799196 ER PT J AU Lu, MH Warbritton, A Tang, N Bucci, TJ AF Lu, MH Warbritton, A Tang, N Bucci, TJ TI Dietary restriction alters cell proliferation in rats: an immunohistochemical study by labeling proliferating cell nuclear antigen SO MECHANISMS OF AGEING AND DEVELOPMENT LA English DT Article DE dietary restriction; cell preoliferation; percent S-phase cells; proliferating cell nuclear antigen labeling; rat ID S-PHASE CELLS; CALORIC RESTRICTION; FOOD-RESTRICTION; ENERGY-INTAKE; LIVER-INJURY; MICE; CARCINOGENESIS; APOPTOSIS; CANCER; NUTRITION AB Dietary restriction (DR) delays the onset of aging and lowers the incidence of both spontaneous and chemically induced cancers. The inhibition of cell proliferation has been suggested as a possible mechanism for this effect. We examined the effect of DR oil cell proliferation in duodenum, forestomach. glandular stomach. and liver tissues of male Fischer 344 rats receiving 60% of the control feed intake For 24 months starting at 16 weeks of age. Rats were sacrificed, when 28 months old. Tissues were collected, histologically prepared, and stained immunohistochemically for proliferating cell nuclear antigen (PCNA). The PCNA-stained nuclei Lire detected in different phases of the cell cycle. A minimum sample of 2000 cells was counted in liver. The percentage of labeled S-phase cells per total cells counted was used as the labeling index for liver. The number of labeled S-phase epithelial cells per 1.1 mm of basement membrane or muscularis mucosa was used as the labeling index for duodenum, forestomach, and glandular stomach. Cell proliferation in glandular stomach and liver tissues was inhibited in rats DR for 24 months; however, Cell proliferation in duodenum and forestomach mucosal tissues was unexpectedly enhanced by DR. These results indicated that while DR inhibits cell proliferation in tissues of rats, it is tissue-dependent. The decreased rate of cell division by DR in the designated tissues could be implicated in lowering the conversion of endogenous DNA damage or lesions to mutation and cancer. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, HFT 130, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Coll Med, Dept Pediat, Little Rock, AR 72205 USA. Pathol Associates Inc, Jefferson, AR 72079 USA. RP Lu, MH (reprint author), US FDA, Natl Ctr Toxicol Res, HFT 130, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 61 TC 8 Z9 8 U1 1 U2 2 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0047-6374 J9 MECH AGEING DEV JI Mech. Ageing Dev. PD FEB PY 2002 VL 123 IS 4 BP 391 EP 400 DI 10.1016/S0047-6374(01)00397-9 PG 10 WC Cell Biology; Geriatrics & Gerontology SC Cell Biology; Geriatrics & Gerontology GA 578NR UT WOS:000177125000012 PM 11744049 ER PT J AU Zhou, G Li, HM DeCamp, D Chen, S Shu, HJ Gong, Y Flaig, M Gillespie, JW Hu, N Taylor, PR Emmert-Buck, MR Liotta, LA Petricoin, EF Zhao, YM AF Zhou, G Li, HM DeCamp, D Chen, S Shu, HJ Gong, Y Flaig, M Gillespie, JW Hu, N Taylor, PR Emmert-Buck, MR Liotta, LA Petricoin, EF Zhao, YM TI 2D differential in-gel electrophoresis for the identification of esophageal scans cell cancer-specific protein markers SO MOLECULAR & CELLULAR PROTEOMICS LA English DT Article ID IMMOBILIZED PH GRADIENTS; 2-DIMENSIONAL ELECTROPHORESIS; MASS-SPECTROMETRY; SAMPLE PREPARATION; MESSENGER-RNA; CURRENT STATE; PROTEOMICS; YEAST AB The reproducibility of conventional two-dimensional (2D) gel electrophoresis can be improved using differential in-gel electrophoresis (DIGE), a new emerging technology for proteomic analysis. In DIGE, two pools of proteins are labeled with 1-(5-carboxypentyl)-1'-propylindocarbocyanine halide (Cy3) N-hydroxy-succinimidyl ester and 1-(5carboxypentyl)-1'-methylindodi-carbocyanine halide (Cy5) N-hydroxysuccinimidyl ester fluorescent dyes, respectively. The labeled proteins are mixed and separated in the same 2D gel. 2D DIGE was applied to quantify the differences in protein expression between laser capture microdissection-procured esophageal carcinoma cells and normal epithelial cells and to define cancer-specific and normal-specific protein markers. Analysis of the 2D images from protein lysates of similar to 250,000 cancer cells and normal cells identified 1038 protein spots in cancer cell lysates and 1088 protein spots in normal cell lysates. Of the detected proteins, 58 spots were up-regulated by >3-fold and 107 were down-regulated by >3-fold in cancer cells. In addition to previously identified down-regulated protein annexin I, tumor rejection antigen (gp96) was found up-regulated in esophageal squamous cell cancer. Global quantification of protein expression between laser capture-microdissected patient-matched cancer cells and normal cells using 2D DIGE in combination with mass spectrometry is a powerful tool for the molecular characterization of cancer progression and identification of cancer-specific protein markers. Molecular & Cellular Proteomics 1:117-124, 2002. C1 Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. Univ Texas, SW Med Ctr, Dept Pharmacol, Dallas, TX 75390 USA. US FDA, Tissue Proteom Unit, Ctr Biol Evaluat & Res, Bethesda, MD 20857 USA. NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20857 USA. NCI, Urol Oncol Branch, Pathol Lab, NIH, Bethesda, MD 20857 USA. NCI, Canc Prevent Studies Branch, NIH, Bethesda, MD 20857 USA. RP Zhao, YM (reprint author), Univ Texas, SW Med Ctr, Dept Biochem, Dallas, TX 75390 USA. RI Li, Hongmei/L-2595-2013 OI Li, Hongmei/0000-0002-4952-1734 NR 25 TC 276 Z9 317 U1 2 U2 18 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 FEB PY 2002 VL 1 IS 2 BP 117 EP 124 DI 10.1074/mcp.M100015-MCP200 PG 8 WC Biochemical Research Methods SC Biochemistry & Molecular Biology GA 654UT UT WOS:000181515000004 PM 12096129 ER PT J AU Shacter, E Weitzman, SA AF Shacter, E Weitzman, SA TI Chronic inflammation and cancer SO ONCOLOGY-NEW YORK LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; DNA-DAMAGE; COLORECTAL-CANCER; POLYMORPHONUCLEAR LEUKOCYTES; ULCERATIVE-COLITIS; LIPID-PEROXIDATION; OXIDATIVE STRESS; REACTIVE OXYGEN; OVARIAN-CANCER; KNOCKOUT MICE AB A substantial body of evidence supports the conclusion that chronic inflammation can predispose an individual to cancer, as demonstrated by the association between chronic inflammatory bowel diseases and the increased risk of colon carcinoma, Chronic inflammation is caused by a variety of factors, including bacterial, viral, and parasitic Infections, chemical irritants, and nondigestible particles, The longer the inflammation persists, the higher the risk of associated carcinogenesis, This review describes some of the underlying causes of the association between chronic inflammation and cancer, Inflammatory mediators contribute to neoplasia by inducing proneoplastic mutations, adaptive responses, resistance to apoptosis, and environmental changes such as stimulation of angiogenesis. All these changes confer a survival advantage to a susceptible cell, In this article, we discuss the contribution of reactive oxygen and nitrogen intermediates, prostaglandins, and inflammatory cytokines to carcinogenesis, A thorough understanding of the molecular basis of inflammation-associated neoplasia and progression can lead to novel approaches to the prevention and treatment of cancer. C1 US FDA, Immunol Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Northwestern Univ, Sch Med, Dept Med, Hematol Oncol Sect, Chicago, IL 60611 USA. RP Shacter, E (reprint author), US FDA, Immunol Lab, Ctr Biol Evaluat & Res, Bldg 29A,Rm 2A-11,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 81 TC 352 Z9 366 U1 5 U2 25 PU P R R INC PI MELVILLE PA 48 SOUTH SERVICE RD, MELVILLE, NY 11747 USA SN 0890-9091 J9 ONCOLOGY-NY JI Oncology-NY PD FEB PY 2002 VL 16 IS 2 BP 217 EP + PG 11 WC Oncology SC Oncology GA 523EY UT WOS:000173942100016 PM 11866137 ER PT J AU Mondoro, TH Vostal, JG AF Mondoro, TH Vostal, JG TI Cold temperatures reduce the sensitivity of stored platelets to disaggregating agents SO PLATELETS LA English DT Article ID AGGREGATION; ACTIVATION; STORAGE; 4-DEGREES-C; ADP AB In this study, we compared the effect of signal transduction inhibitors on fibrinogen binding, aggregation, the activation state of GPIIb-IIIa, and cytosolic calcium levels in cold and room temperature-stored platelets. Cold-stored platelets have a higher sensitivity to agonist-induced aggregation when compared to room temperature-stored platelets. We also found that cold-stored platelets had a significantly higher aggregation response to ADP and epinephrine, while platelets stored at room temperature responded poorly to these agonists (mean values of 61 vs. 18%, n = 14). Four inhibitors were selected to target various signaling pathways. Cold-stored platelets were more resistant to disaggregation by promethazine, prostaglandin D2, yohimbine, and echistatin. The effects of cold temperatures on stored platelets are targeted to activation pathways as there was no spontaneous aggregation or spontaneous fibrinogen binding as measured in this study. PAC-1 binding was not inhibited to the same degree as aggregation or fibrinogen binding responses, suggesting that the disaggregation was not caused by a change in the conformation of GPIIb-IIIa. Cytosolic calcium levels did not decrease in cold-stored platelets after inhibitor addition. The inhibitors are likely acting after the establishment of the GPIIb-IIIa activation state and may affect the post-occupancy signaling by the fibrinogen-occupied integrin. Differences between aggregation and disaggregation responses of cold- and room temperature-stored platelets suggest that cold-stored platelets may have different mechanisms to stabilize platelet aggregates during their formation. C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20892 USA. RP Vostal, JG (reprint author), Bldg 29,Room 321,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 13 Z9 13 U1 1 U2 4 PU CARFAX PUBLISHING PI BASINGSTOKE PA RANKINE RD, BASINGSTOKE RG24 8PR, HANTS, ENGLAND SN 0953-7104 J9 PLATELETS JI Platelets PD FEB PY 2002 VL 13 IS 1 BP 11 EP 20 DI 10.1080/09537100120111586 PG 10 WC Cell Biology; Hematology SC Cell Biology; Hematology GA 517FU UT WOS:000173601100002 PM 11918832 ER PT J AU Engelfriet, CP Reesink, HW Hernandez, JM Sauleda, S O'Riordan, J Prati, D Mozzi, F Lin, CK Cuypers, HT Vranckx, R Yoshizawa, H Tomono, T Flanagan, P Sabino, EC Politis, C Tegtmeier, GE Carasa, MAV Hewlett, IK Yu, MYW Epstein, JS Eglin, R Barbara, J Coste, J Cornillot, C Hyland, CA Heier, HE Jeansson, S Ekermo, B Jarvis, LM Krusius, T Wesberg, S Bird, AR Levicnik-Stezinar, S Mayr-Wohlfart, U Cardoso, MD Koerner, K Kubanek, B Gessner, M Zerlauth, G AF Engelfriet, CP Reesink, HW Hernandez, JM Sauleda, S O'Riordan, J Prati, D Mozzi, F Lin, CK Cuypers, HT Vranckx, R Yoshizawa, H Tomono, T Flanagan, P Sabino, EC Politis, C Tegtmeier, GE Carasa, MAV Hewlett, IK Yu, MYW Epstein, JS Eglin, R Barbara, J Coste, J Cornillot, C Hyland, CA Heier, HE Jeansson, S Ekermo, B Jarvis, LM Krusius, T Wesberg, S Bird, AR Levicnik-Stezinar, S Mayr-Wohlfart, U Cardoso, MD Koerner, K Kubanek, B Gessner, M Zerlauth, G TI Implementation of donor screening for infectious agents transmitted by blood by nucleic acid technology SO VOX SANGUINIS LA English DT Editorial Material ID HEPATITIS-C VIRUS; POLYMERASE-CHAIN-REACTION; LIVER-DISEASE; GENERAL-POPULATION; RISK-FACTORS; B VIRUS; TRANSMISSION; PREVALENCE; SERVICE; ASSAY C1 Blood Transfus Serv Sanquin, Cent Lab, NL-1066 CX Amsterdam, Netherlands. Blood Bank N Holland Sanquin, NL-1066 CX Amsterdam, Netherlands. Banc Teixits, Ctr Transfusio, Barcelona 08035, Spain. Irish Blood Transfus Serv, Natl Blood Ctr, Dublin 8, Ireland. IRCCS Osped Maggiore Milano, Ctr Trasfusionale & Immunol Trapianti, I-20122 Milan, Italy. Hong Kong Red Cross Blood Transfus Serv, Kowloon, Hong Kong, Peoples R China. Sanquin Blood Supply Fdn, Div Diagnost Serv, NL-1066 CX Amsterdam, Netherlands. Inst Publ Hlth, Dept Microbiol, B-1050 Brussels, Belgium. Japanese Red Cross, Plasma Fractionat Ctr, Chitose Shi 0668610, Japan. Hiroshima Univ, Sch Med, Dept Hyg, Minami Ku, Hiroshima 7348551, Japan. New Zealand Blood Serv, Epsom, New Zealand. Fundacao Pro Sangue Hemoctr Sao Paulo, BR-05403000 Sao Paulo, Brazil. George Gennimatas Reg Gen Hosp Athens, Reg Blood Transfus Ctr 3, GR-11527 Athens, Greece. Community Blood Ctr Greater Kansas City, Kansas City, MO 64111 USA. Basque Country Blood Transfus Serv, Galdakao Vizcaya 48960, Spain. US FDA, Off Blood Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. N London Ctr, Natl Transfus Microbiol Labs, London NW9 5BG, England. N London Ctr, Natl Blood Author, London NW9 5BG, England. EFS Pyrenees Mediterranee, F-34094 Montpellier, France. EFS Siege, F-75725 Paris, France. Australian Red Cross Blood Serv, Brisbane, Qld 4000, Australia. Univ Oslo, Ullevaal Hosp, Dept Immunol & Transfus Med, N-0407 Oslo, Norway. Univ Oslo, Ullevaal Hosp, Dept Med Microbiol, N-0407 Oslo, Norway. Linkoping Univ Hosp, Dept Transfus Med, Swedish Soc Transfus Med, Working Grp Transfus Transmitted Dis, S-58185 Linkoping, Sweden. Univ Edinburgh, SNBTS NAT Reference Unit, Edinburgh EH9 1QH, Midlothian, Scotland. Finnish Red Cross Blood Transfus Serv, Helsinki, Finland. Western Prov Blood Transfus Serv, Cape Town, South Africa. Blood Transfus Ctr Slovenia, Ljubljana 1000, Slovenia. German Red Cross Blood Transfus Serv Baden Wurtte, D-89081 Ulm, Germany. Baxter AG, Plasmakontrolle, A-1221 Vienna, Austria. RP Engelfriet, CP (reprint author), Blood Transfus Serv Sanquin, Cent Lab, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands. RI Sabino, Ester/F-7750-2010 OI Sabino, Ester/0000-0003-2623-5126 NR 43 TC 27 Z9 32 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 FEB PY 2002 VL 82 IS 2 BP 87 EP 111 DI 10.1046/j.0042-9007.2001.00147_1.x PG 25 WC Hematology SC Hematology GA 525ML UT WOS:000174075500011 ER PT J AU Golding, B Eller, N Levy, L Beining, P Inman, J Matthews, N Scott, DE Golding, H AF Golding, B Eller, N Levy, L Beining, P Inman, J Matthews, N Scott, DE Golding, H TI Mucosal immunity in mice immunized with HIV-1 peptide conjugated to Brucella abortus SO VACCINE LA English DT Article DE mucosal immunity; Brucella abortus; HIV-1 ID T-CELLS; B-ABORTUS; V3 LOOP; RESPONSES; CARRIER; CD4(+); LIPOPOLYSACCHARIDE; VACCINES AB We have previously shown that a V3-loop peptide from HIV-1 envelope conjugated to heat-inactivated Brucella abortus (Ba) (V3-Ba) is capable of inducing antibodies that neutralize HIV-1 and cytotoxic T cells (CTL) that kill HIV-1-infected targets, even in mice that lack CD4(+) T cells. In this paper we show that intranasal (i.n.) immunization elicits neutralizing antibodies and IFN-gamma-secreting T cells at mucosal surfaces. This approach may protect individuals from HIV-1 infection and reduce transmission from infected individuals to their sexual partners and offspring. (C) 2002 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Hematol,Lab Plasma Derivat, Rockville, MD 20852 USA. NIAID, Immunol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Viral Prod,Lab Retrovirus Res, Rockville, MD 20852 USA. RP Golding, B (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Hematol,Lab Plasma Derivat, Rockville, MD 20852 USA. NR 11 TC 16 Z9 16 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 31 PY 2002 VL 20 IS 9-10 BP 1445 EP 1450 AR PII S0264-410X(01)00477-7 DI 10.1016/S0264-410X(01)00477-7 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 521TW UT WOS:000173858300022 PM 11818165 ER PT J AU Park, H Hung, YC Brackett, RE AF Park, H Hung, YC Brackett, RE TI Antimicrobial effect of electrolyzed water for inactivating Campylobacter jejuni during poultry washing SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE electrolyzed water; chlorine water; hypochlorous acid; chicken; poultry; Campylobacter jejuni ID HYPOCHLOROUS ACID; CHICKEN CARCASSES; ESCHERICHIA-COLI; OXIDIZING WATER; SALMONELLA-TYPHIMURIUM; LISTERIA-MONOCYTOGENES; PATHOGENS; OXIDATION; EFFICACY; SURFACE AB The effectiveness of electrolyzed (EO) water for killing Campylobacter jejuni on poultry was evaluated. Complete inactivation of C. jejuni in pure culture occurred within 10 s after exposure to EO or chlorinated water, both of which contained 50 mg/l of residual chlorine. A strong bactericidal activity was also observed on the diluted EO water (containing 25 mg/l of residual chlorine) and the mean population of C. jejuni was reduced to less than 10 CFU/ml (detected only by enrichment for 48 h) after 10-s treatment. The diluted chlorine water (25 mg/l residual chlorine) was less effective than the diluted EO water for inactivation of C. jejuni. EO water was further evaluated for its effectiveness in reducing C. jejuni on chicken during washing. EO water treatment was equally effective as chlorinated water and both achieved reduction of C. jejuni by about 3 log(10) CFU/g on chicken, whereas deionized water (control) treatment resulted in only I log(10) CFU/g reduction. No viable cells of C. jejuni were recovered in EO and chlorinated water after washing treatment, whereas high populations of C. jejuni (4 log(10) CFU/ml) were recovered in the wash solution after the control treatment. Our study demonstrated that EO water was very effective not only in reducing the populations of C. jejuni on chicken, but also could prevent cross-contamination of processing environments. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Georgia, Coll Agr & Environm Sci, Dept Food Sci & Technol, Griffin, GA 30223 USA. US FDA, Off Plant & Dairy Foods & Beverages, Washington, DC 20204 USA. RP Hung, YC (reprint author), Univ Georgia, Coll Agr & Environm Sci, Dept Food Sci & Technol, Griffin, GA 30223 USA. NR 24 TC 103 Z9 107 U1 3 U2 22 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 JAN 30 PY 2002 VL 72 IS 1-2 BP 77 EP 83 DI 10.1016/S0168-1605(01)00622-5 PG 7 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 518NX UT WOS:000173675700009 PM 11843416 ER PT J AU Liu, JP Hsueh, HM Hsieh, E Chen, JJ AF Liu, JP Hsueh, HM Hsieh, E Chen, JJ TI Tests for equivalence or non-inferiority for paired binary data SO STATISTICS IN MEDICINE LA English DT Article DE asymptotic test; correlated binary endpoints; confidence interval; diagnostic tests; two one-sided tests ID SAMPLE-SIZE; NULL HYPOTHESIS; CLINICAL-TRIALS; MCNEMARS TEST; DESIGN; PROPORTIONS; DIFFERENCE AB Assessment of therapeutic equivalence or non-inferiority between two medical diagnostic procedures often involves comparisons of the response rates between paired binary endpoints. The commonly used and accepted approach to assessing equivalence is by comparing the asymptotic confidence interval on the difference of two response rates with some clinical meaningful equivalence limits. This paper investigates two asymptotic test statistics, a Wald-type (sample-based) test statistic and a restricted maximum likelihood estimation (RMLE-based) test statistic, to assess equivalence or non-inferiority based on paired binary endpoints. The sample size and power functions of the two tests are derived. The actual type I error and power of the two tests are computed by enumerating the exact probabilities in the rejection region. The results show that the RMLE-based test controls type I error better than the sample-based test. To establish an equivalence between two treatments with a symmetric equivalence limit of 0.15, a minimal sample size of 120 is needed. The RMLE-based test without the continuity correction performs well at the boundary point 0. A numerical example illustrates the proposed procedures. Copyright (C) 2002 John Wiley Sons, Ltd. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Hlth Res Inst, Div Biostat & Bioinformat, Taipei, Taiwan. Apex Int Clin Res Co, Stat & Data Management, Taipei, Taiwan. RP Chen, JJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. OI Liu, Jen-pei/0000-0002-9565-1812; HSUEH, HUEY-MIIN/0000-0003-0536-9440 NR 21 TC 53 Z9 55 U1 3 U2 13 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0277-6715 J9 STAT MED JI Stat. Med. PD JAN 30 PY 2002 VL 21 IS 2 BP 231 EP 245 DI 10.1002/sim.1012 PG 15 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 510PV UT WOS:000173217200006 PM 11782062 ER PT J AU Aardema, MJ MacGregor, JT AF Aardema, MJ MacGregor, JT TI Toxicology and genetic toxicology in the new era of "toxicogenomics": impact of "-omics" technologies SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE genetic toxicology; microarrays; gene expression; toxicogenomics; biomarkers ID QUALITY-CONTROL; SACCHAROMYCES-CEREVISIAE; METABOLIC-RESPONSES; MASS-SPECTROMETRY; DNA MICROARRAYS; HUMAN GENOME; EXPRESSION; TOXICITY; DRUG; PHARMACOGENETICS AB The unprecedented advances in molecular biology during the last two decades have resulted in a dramatic increase in knowledge about gene structure and function, an immense database of genetic sequence information, and an impressive set of efficient new technologies for monitoring genetic sequences, genetic variation, and global functional gene expression. These advances have led to a new sub-discipline of toxicology: "toxicogenomics". We define toxicogenomics as "the study of the relationship between the structure and activity of the genome (the cellular complement of genes) and the adverse biological effects of exogenous agents". This broad definition encompasses most of the variations in the current usage of this term, and in its broadest sense includes studies of the cellular products controlled by the genome (messenger RNAs, proteins, metabolites, etc.). The new "global" methods of measuring families of cellular molecules, such as RNA, proteins, and intermediary metabolites have been termed "-omic" technologies, based on their ability to characterize all, or most, members of a family of molecules in a single analysis. With these new tools, we can now obtain complete assessments of the functional activity of biochemical pathways, and of the structural genetic (sequence) differences among individuals and species, that were previously unattainable. These powerful new methods of high-throughput and multi-endpoint analysis include gene expression arrays that will soon permit the simultaneous measurement of the expression of all human genes on a single "chip". Likewise, there are powerful new methods for protein analysis (proteomics: the study of the complement of proteins in the cell) and for analysis of cellular small molecules (metabonomics: the study of the cellular metabolites formed and degraded under genetic control). This will likely be extended in the near future to other important classes of biomolecules such as lipids, carbohydrates, etc. These assays provide a general capability for global assessment of many classes of cellular molecules, providing new approaches to assessing functional cellular alterations. These new methods have already facilitated significant advances in our understanding of the molecular responses to cell and tissue damage, and of perturbations in functional cellular systems. As a result of this rapidly changing scientific environment, regulatory and industrial toxicology practice is poised to undergo dramatic change during the next decade. These advances present exciting opportunities for improved methods of identifying and evaluating potential human and environmental toxicants, and of monitoring the effects of exposures to these toxicants. These advances also present distinct challenges. For example, the significance of specific changes and the performance characteristics of new methods must be fully understood to avoid misinterpretation of data that could lead to inappropriate conclusions about the toxicity of a chemical or a mechanism of action. We discuss the likely impact of these advances on the fields of general and genetic toxicology, and risk assessment. We anticipate that these new technologies will (1) lead to new families of biomarkers that permit characterization and efficient monitoring of cellular perturbations, (2) provide an increased understanding of the influence of genetic variation on toxicological outcomes, and (3) allow definition of environmental causes of genetic alterations and their relationship to human disease. The broad application of these new approaches will likely erase the current distinctions among the fields of toxicology, pathology, genetic toxicology, and molecular genetics. Instead, a new integrated approach will likely emerge that involves a comprehensive understanding of genetic control of cellular functions, and of cellular responses to alterations in normal molecular structure and function. Published by Elsevier Science B.V. C1 Procter & Gamble Co, Miami Valley Labs, Cincinnati, OH 45253 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. RP Aardema, MJ (reprint author), Procter & Gamble Co, Miami Valley Labs, POB 538707, Cincinnati, OH 45253 USA. EM aardema.mj@pg.com NR 64 TC 216 Z9 237 U1 3 U2 57 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 JAN 29 PY 2002 VL 499 IS 1 BP 13 EP 25 DI 10.1016/S0027-5107(01)00292-5 PG 13 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 517TM UT WOS:000173626000003 PM 11804602 ER PT J AU Ahn, H Moon, H Kim, S Kodell, RL AF Ahn, H Moon, H Kim, S Kodell, RL TI A Newton-based approach for attributing tumor lethality in animal carcinogenicity studies SO COMPUTATIONAL STATISTICS & DATA ANALYSIS LA English DT Article DE cause of death; inequality constraint; maximum likelihood; optimization; sacrifice ID TIME; MORTALITY; ONSET; TESTS AB A new Newton-based approach is proposed for finding the global maximum of a nonlinear function subject to various inequality constraints. This method can be applied to nonparametric maximum likelihood estimation problems to attribute tumor lethality in long-term carcinogenicity studies. This method is substantially faster and easier to implement than the Complex Method used in Ahn et al. (2000). This approach is very useful especially when there exist a large number of parameters of interest to be estimated and many nonlinear inequality constraints. A Monte Carlo simulation study is conducted to evaluate the computational efficiency and accuracy of the estimates obtained from the new approach. The advantages of using the Newton-based approach are illustrated with a real data set. (C) 2002 Elsevier Science B.V. All rights reserved. C1 SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Ewha Womans Univ, Dept Math, Seoul 120750, South Korea. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 12 TC 5 Z9 5 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0167-9473 J9 COMPUT STAT DATA AN JI Comput. Stat. Data Anal. PD JAN 28 PY 2002 VL 38 IS 3 BP 263 EP 283 DI 10.1016/S0167-9473(01)00041-X PG 21 WC Computer Science, Interdisciplinary Applications; Statistics & Probability SC Computer Science; Mathematics GA 514GG UT WOS:000173430200002 ER PT J AU Luo, WH Li, H Zhang, Y Ang, CYW AF Luo, WH Li, H Zhang, Y Ang, CYW TI Rapid method for the determination of total 5-methyltetrahydrofolate in blood by liquid chromatography with fluorescence detection SO JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES LA English DT Article DE 5-methyltetrahydrofolate ID FOLATE; ASSAY; SERUM AB A liquid chromatographic method is described for the determination of total 5-methyltetrahydrofolate (5-MTHF) in whole-blood samples. The method was applied to a survey of whole-blood total 5-MTHF levels of women at child-bearing age. To determine whole-blood total 5-MTHF content, a whole-blood sample was frozen and thawed to break red blood cells and the 5-MTHF polyglutamates were released and hydrolyzed into 5-MTHF monoglutamate by endogenous polyglutamates hydrolase in the plasma. In brief, an aliquot of 0.1 ml whole-blood sample was mixed with 0.3 ml 57 mmol/l ascorbic acid and incubated at 37degreesC for 60 min, then diluted with 0.6 ml buffer solution (0.2 mol/l potassium phosphate dibasic and 30 mmol/l mercaptoethanol, pH 8.5). After the sample was heated at 100degreesC for 10 min and centrifuged, the supernatant was analyzed by reversed-phase liquid chromatography with fluorescence detection, The recoveries from spiked samples were from 95 to 105% with within-day and day-to-day relative standard deviations less than 6.5%. The detection limit was estimated to be 30 mmol/l based on three times the noise level (peak to peak). Application of the method to a survey of whole-blood total 5-MTHF levels of women at child-bearing age showed that the method was reliable and suitable for the determination of blood total 5-MTHF. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Shantou Univ, Coll Med, Cent Lab, Shantou 515031, Guangdong, Peoples R China. US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Chem, Jefferson, AR 72079 USA. RP Luo, WH (reprint author), Shantou Univ, Coll Med, Cent Lab, Shantou 515031, Guangdong, Peoples R China. EM whluo@stu.edu.cn NR 17 TC 6 Z9 6 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1570-0232 J9 J CHROMATOGR B JI J. Chromatogr. B PD JAN 25 PY 2002 VL 766 IS 2 BP 331 EP 337 DI 10.1016/S0378-4347(01)00521-7 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 511PN UT WOS:000173274900015 PM 11829002 ER PT J AU Powers, JH Dixon, CA Goldberger, MJ AF Powers, JH Dixon, CA Goldberger, MJ TI Voriconazole versus liposomal amphotericin B in patients with neutropenia and persistent fever. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20850 USA. RP Powers, JH (reprint author), US FDA, Rockville, MD 20850 USA. NR 2 TC 45 Z9 47 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC/NEJM PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 24 PY 2002 VL 346 IS 4 BP 289 EP 290 DI 10.1056/NEJM200201243460414 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 513UR UT WOS:000173398900013 PM 11807157 ER PT J AU Laurenzana, EM Balasubramanian, G Weis, C Blaydes, B Newbold, RR Delclos, KB AF Laurenzana, EM Balasubramanian, G Weis, C Blaydes, B Newbold, RR Delclos, KB TI Effect of nonylphenol on serum testosterone levels and testicular steroidogenic enzyme activity in neonatal, pubertal, and adult rats SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article DE nonylphenol; testosterone; steroidogenesis ID ALKYLPHENOL ETHOXYLATES; REPRODUCTIVE-TRACT; NEWBORN RATS; LEYDIG-CELLS; EXPOSURE; 4-TERT-OCTYLPHENOL; GONADOTROPIN; OCTYLPHENOL; DISRUPTION; EXPRESSION AB Previous dose range-finding studies with nonylphenol (NP) administered to rats in a soy- and alfalfa-free diet showed apparent feminization of several endpoints in male rats at doses of 25 ppm and above. One possible mechanism contributing to these effects is a reduction of testosterone at critical developmental periods. The present study was conducted as an adjunct to a multigeneration study and was designed to examine the effect of NP on testosterone production. Male rats in the F-1 and F-2 generations were exposed through their dams or directly to various dietary doses of NP (0, 25, 200 and 750 ppm) throughout gestation and until sacrifice at either postnatal day 2 (PND2), PND50, or PND140. Male pups in the F, generation were examined only on PND2. At PND2, serum testosterone levels were significantly decreased in all groups exposed to NP in the F-1 generation, but not in the F-2 or F-3 generations. The activity of 17alpha-hydroxylase/C17, 20 lyase (P450c17) in PND2 testicular homogenates was not affected by NP treatment. In F-1 and F-2 PND50 and PND140 rats, NP treatment did not affect serum testosterone levels. The absolute dorsolateral prostate weight was increased in the 200 and 750 ppm dose groups only in the F-1 PND50 rats, however, no significant effects were observed in other male reproductive organs. NP treatment did not affect P450c17 activity in microsomes prepared from testes of F-1 PND50 or PND140 rats. However, P450c17 activity was significantly decreased in testicular microsomes of F-1 PND50 (200 and 750 ppm dose groups) and PND140 (25, 200, and 750 ppm dose groups) rats. A decrease in testicular beta-nicotinamide adenine dinucleotide phosphate (NADPH) P450 reductase was also observed in all PND50 and PND140 NP-exposed rats of the F-1 and F-2 generations. The ability of NP to directly inhibit P450c17 activity in vitro at concentrations of 1-100 muM was also demonstrated. These results indicate that NP call inhibit the activity of enzymes involved in testosterone synthesis, but suggest minimal effects on testosterone or testosterone-dependent endpoints via this mechanism. (C) 2002 Elsevier Science Ireland Ltd. All rights reserved. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Delclos, KB (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd HFT-110, Jefferson, AR 72079 USA. NR 43 TC 25 Z9 34 U1 0 U2 4 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0009-2797 J9 CHEM-BIOL INTERACT JI Chem.-Biol. Interact. PD JAN 22 PY 2002 VL 139 IS 1 BP 23 EP 41 AR PII S0009-2797(01)00291-5 DI 10.1016/S0009-2797(01)00291-5 PG 19 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 522KR UT WOS:000173895600002 PM 11803027 ER PT J AU Feldman, LT Ellison, AR Voytek, CC Yang, L Krause, P Margolis, TP AF Feldman, LT Ellison, AR Voytek, CC Yang, L Krause, P Margolis, TP TI Spontaneous molecular reactivation of herpes simplex virus type 1 latency in mice SO PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA LA English DT Article ID HUMAN TRIGEMINAL GANGLIA; CENTRAL-NERVOUS-SYSTEM; GENE-EXPRESSION; INFECTED NEURONS; VIRULENT-STRAIN; SPINAL GANGLIA; TRANSCRIPTS; RNA; ESTABLISHMENT; INFILTRATION AB Infection of the mouse trigeminal ganglia (TG) is the most commonly used model for the study of herpes simplex virus type 1 (HSV-1) latency. Its popularity is caused, at least in part, by the perception that latent infection can be studied in this system in the absence of spontaneous viral reactivation. However, this perception has never been rigorously tested. To carefully study this issue, the eyes of Swiss-Webster mice were inoculated with HSV-1 (KOS), and 37-47 days later the TG were dissected, serial-sectioned, and probed for HSV-1 ICP4, thymidine kinase, glycoprotein C, and latency-associated transcript RNA by in situ hybridization. Serial sections of additional latently infected TG were probed with HSV-1-specific polyclonal antisera. Analysis of thousands of probed sections revealed abundant expression of viral transcripts, viral protein, and viral DNA replication in about 1 neuron per 10 TG tested. These same neurons were surrounded by a focal white cell infiltrate, indicating the presence of an antigenic stimulus. We conclude that productive cycle viral genes are abundantly expressed in rare neurons of latently infected murine TG and that these events are promptly recognized by an active local immune response. In the absence of detectable infectious virus in these ganglia, we propose the term "spontaneous molecular reactivation" to describe this ongoing process. C1 Univ Calif San Francisco, Med Ctr, Francis I Proctor Fdn, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Med Ctr, Dept Microbiol & Immunol, Los Angeles, CA 90024 USA. Ctr Biol Evaluat & Res, Food & Drug Adm, Bethesda, MD 20892 USA. RP Margolis, TP (reprint author), Univ Calif San Francisco, Med Ctr, Francis I Proctor Fdn, San Francisco, CA 94143 USA. FU NEI NIH HHS [EY02162, EY10008, R01 EY010008, P30 EY002162]; NIAID NIH HHS [R01 AI045679, AI45679] NR 42 TC 157 Z9 161 U1 1 U2 5 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 22 PY 2002 VL 99 IS 2 BP 978 EP 983 DI 10.1073/pnas.022301899 PG 6 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 514PK UT WOS:000173450100079 PM 11773630 ER PT J AU Joshi, BH Leland, P Silber, J Kreitman, RJ Pastan, I Berger, M Puri, RK AF Joshi, BH Leland, P Silber, J Kreitman, RJ Pastan, I Berger, M Puri, RK TI IL-4 receptors on human medulloblastoma tumours serve as a sensitive target for a circular permuted IL-4-Pseudomonas exotoxin fusion protein SO BRITISH JOURNAL OF CANCER LA English DT Article DE medulloblastoma; IL-4 receptor; subunit composition; immunofluorescence ID AFFINITY INTERLEUKIN-4 RECEPTORS; CARCINOMA CELL-LINES; IN-VIVO; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; SIGNAL-TRANSDUCTION; ANTITUMOR-ACTIVITY; INHIBITS GROWTH; SARCOMA-CELLS; CANCER-CELLS AB Cytotoxins directed to interleukin-4 receptors have shown to mediate relatively selective cytotoxicity against a variety of human cancer cells in vitro and in vivo. In an ongoing Phase I clinical trial, a recombinant protein comprised of circularly permuted IL-4 fused to a mutated form of Pseudomonas exotoxin (the fusion protein termed IL-4(38-37)-PE38KDEL or cpIL4-PE) has shown antitumour activity against malignant glioma. Human medulloblastomas are neuroectodermal tumours that occur in children and have a poor prognosis. The goal of this study was to determine whether human medulloblastoma derived cell lines express interleukin-4 receptor and whether interleukin-4 receptor expression is accompanied by sensitivity to cpIL4-PE. Medulloblastoma cell lines express interleukin-4 receptor at the protein and mRNA levels as determined by binding, indirect immunofluorescence and RT-PCR studies. These cells expressed IL-4Ralpha (also known as IL-4Rbeta) and IL-13Ralpha1 (also known as IL-13Ralpha) chains, however common c, a component of the interleukin-4 receptor system in immune cells was not detected. Consistent with the expression of IL-4R, cpIL4-PE was found to be highly and specifically cytotoxic to four of five medulloblastoma cell lines. Susceptibility of medulloblastoma cell lines to cpIL4-PE seemed to correlate closely to the functional IL-4 binding sites in general as demonstrated by I-125-IL-4 binding, but did not seem to correlate with mRNA or cell surface immunoreactive receptor protein expression. The sensitivity of medulloblastoma cells to cpIL4-PE could be eliminated by concurrent incubation with IL-4 or IL-13, but not with IL-2. None of these cell lines showed any change in proliferation upon treatment with exogenous IL-4. These studies establish the interleukin-4 receptor as a medulloblastoma-associated target for possible tumour-directed cancer therapy. Further studies are warranted to investigate interleukin-4 receptor expression in primary medulloblastoma tumours and sensitivity to cpIL-4PE in vitro and in vivo. (C) 2002 The Cancer Research Campaign. C1 US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. NCI, Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Calif San Francisco, Dept Neurosurg, San Francisco, CA 94143 USA. Univ Washington, Dept Neurol Surg, Seattle, WA 98195 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, NIH Bld 29B,Room 2NN10,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 33 TC 23 Z9 25 U1 0 U2 1 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 JAN 21 PY 2002 VL 86 IS 2 BP 285 EP 291 DI 10.1038/sj/bjc/6600034 PG 7 WC Oncology SC Oncology GA 529QR UT WOS:000174310500023 PM 11870521 ER PT J AU Uhl, K Kennedy, D Kweeder, S AF Uhl, K Kennedy, D Kweeder, S TI Medications and breastfeeding SO AMERICAN FAMILY PHYSICIAN LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Team, Rockville, MD 20857 USA. RP Uhl, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Pregnancy Labeling Team, 5600 Fishers Lane,HFD-970, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD FAMILY PHYSICIANS PI KANSAS CITY PA 8880 WARD PARKWAY, KANSAS CITY, MO 64114-2797 USA SN 0002-838X J9 AM FAM PHYSICIAN JI Am. Fam. Physician PD JAN 15 PY 2002 VL 65 IS 2 BP 170 EP 170 PG 1 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 514QQ UT WOS:000173452900002 PM 11820482 ER PT J AU Petrovics, G Bird, T Lehel, C Oravecz, T Anderson, WB AF Petrovics, G Bird, T Lehel, C Oravecz, T Anderson, WB TI Protein kinase C epsilon mediates PMA-induced growth inhibition of low population density NIH 3T3 fibroblasts SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE protein kinase C epsilon; phorbol ester; phorbol 12-myristate-13 acetate; growth inhibition ID CELL-CYCLE ARREST; SIGNAL-TRANSDUCTION; SUBCELLULAR-LOCALIZATION; GENE-EXPRESSION; PKC-EPSILON; ACTIVATION; DELTA; DIFFERENTIATION; P21(CIP1); PHOSPHORYLATION AB Phorbol 12-myristate-13-acetate (PMA), a potent tumor promoter and activator of most protein kinase C (PKC) isotypes, was found to significantly inhibit the growth of low population density (1-5% confluency) NTH 3T3 cells. Higher cell population density (above 10% confluency) provided protection from this growth inhibitory effect of PMA. PMA-induced growth arrest is accompanied by an elevation in the level of p21(Clp1) protein, along with cell cycle arrest at the G1/S transition. Activation of PKC is required for this growth inhibitory response since the pan PKC inhibitor GF109203 blocked this effect of PMA. However, the classical PKC inhibitor G66976 had no effect, strongly suggesting the involvement of novel PKC isotypes (delta and/or epsilon). Overexpression of PKCepsilon, but not PKCdelta, was found to potentiate PMA-induced growth inhibition. Overexpression of a kinase-inactive dominant-negative mutant of PKCepsilon (K437R) decreased the growth inhibitory effect of PMA and also blocked the PMA-induced increase in the level of p21(Clp1) protein. Taken together, these results indicate that PMA has a cell population density-dependent effect on the growth of NIH 3T3 cells and that the PMA growth inhibitory effect at low cell population density is mediated through activation of PKCepsilon. (C) 2001 Elsevier Science. C1 NCI, Cellular Oncol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Anderson, WB (reprint author), NCI, Cellular Oncol Lab, NIH, Bldg 37,Room 3E08,37 Convent Dr, Bethesda, MD 20892 USA. NR 40 TC 3 Z9 3 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 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 15 PY 2002 VL 397 IS 2 BP 217 EP 223 DI 10.1006/abbi.2001.2640 PG 7 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 517LH UT WOS:000173611700012 PM 11795874 ER PT J AU Senturker, S Tschirret-Guth, R Morrow, J Levine, R Shacter, E AF Senturker, S Tschirret-Guth, R Morrow, J Levine, R Shacter, E TI Induction of apoptosis by chemotherapeutic drugs without generation of reactive oxygen species SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE oxidants; apoptosis; cancer; chemotherapy ID MYELOBLASTIC-LEUKEMIA CELLS; AMINO-ACID-RESIDUES; OXIDATIVE STRESS; HYDROGEN-PEROXIDE; CISPLATIN CYTOTOXICITY; SUPEROXIDE-DISMUTASE; THYMOCYTE APOPTOSIS; CANCER-CHEMOTHERAPY; LIPID-PEROXIDATION; CATALASE ACTIVITY AB Studies in a variety of cell types have suggested that cancer chemotherapy drugs induce tumor cell apoptosis in part by inducing formation of reactive oxygen species (ROS). Using human B lymphoma cells as the targets, we have found that apoptosis can be induced in the absence of any detectable oxidative stress. Apoptosis was induced with the chemotherapy drugs VP-16 and cisplatin. To determine whether oxidants are formed as part of the drug-induced apoptotic process, intracellular markers of oxidative stress were examined. These included measurement of (1) protein carbonyl groups by Western blot immunoassay, (2) protein methionine sulfoxide residues by amino acid analysis, (3) protein sulfhydryl oxidation by Western blot immunoassay, (4) F2-isoprostanes by GC/MS, and (5) intracellular ROS production using the oxidant-sensitive dyes DCFDA and dihydrorhodamine 123. Apoptosis was quantified using fluorescence microscopy to assess nuclear morphology. The results show that VP-16 and cisplatin induce extensive apoptosis in the absence of any detectable protein or lipid oxidation, measured in both the cytosolic and mitochondrial compartments of the cell. In contrast, 112021 which kills the cells by nonapoptotic pathways, caused increases in both protein and lipid oxidation. Three different antioxidant compounds (N-acetyl cysteine, Tempol, and MnTBAP) failed to inhibit VP-16-induced apoptosis, while inhibiting H2O2-induced cell death. Only N-acetyl cysteine inhibited cisplatin-induced cell death and this is attributed to its known ability to react directly with and inactivate cisplatin before it enters the cell. The results demonstrate that, at least in B lymphoma cells, chemotherapy-induced apoptosis occurs using a mechanism that does not involve oxidants. (C) 2002 Elsevier Science. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Immunol Lab, Bethesda, MD 20892 USA. NHLBI, Biochem Lab, NIH, Bethesda, MD 20814 USA. Vanderbilt Univ, Sch Med, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. RP Shacter, E (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Immunol Lab, Bethesda, MD 20892 USA. NR 59 TC 43 Z9 51 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0003-9861 J9 ARCH BIOCHEM BIOPHYS JI Arch. Biochem. Biophys. PD JAN 15 PY 2002 VL 397 IS 2 BP 262 EP 272 DI 10.1006/abbi.2001.2681 PG 11 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 517LH UT WOS:000173611700019 PM 11795881 ER PT J AU Schneiderman, E Gratz, SR Stalcup, AM AF Schneiderman, E Gratz, SR Stalcup, AM TI Optimization of preparative electrophoretic chiral separation of ritalin enantiomers SO JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS LA English DT Article DE ritalin; methylphenidate; chiral; preparative; separation; continuous free flow electrophoresis; capillary electrophoresis; deflection angle ID FLOW ZONE ELECTROPHORESIS; DL-THREO-METHYLPHENIDATE; CAPILLARY-ELECTROPHORESIS; PHARMACOKINETICS; PURIFICATION; SIMULATION AB Continuous free flow electrophoresis (CFFE) was applied to the preparative chiral separation of ritalin enantiomers. Sulfated beta-cyclodextrin (sbeta-CD) was used as the chiral additive. Liquid chromatography-mass spectrometry (LC-MS) experiments were applied to study the time averaged concentration of sbeta-CD in the separation chamber. The distribution of sbeta-CD in the separation chamber greatly influenced resolution and the angle of deflection. To optimize the separation, several parameters (methanol, concentration of sbeta-CD in the cathodic wash and in the separation buffer, and the introduction of a low conductivity zone) were investigated. The dependence of the resolution and deflection angles of ritalin enantiomers on the concentration of sbeta-CD in both the separation buffer and in the cathode wash solution appeared to be non-linear. Under close to optimal conditions, resolution of ritalin enantiomers was about 0.8 with an average processing rate of 0.5 mg/h. Overall, the enantiomeric purity of the individual isomers was similar to 83%; however, of the 20 vials containing ritalin, the presence of both enantiomers was only detected in three vials. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Stalcup, AM (reprint author), Univ Cincinnati, Dept Chem, POB 210172, Cincinnati, OH 45221 USA. RI Stalcup, A. M./E-9386-2013 OI Stalcup, A. M./0000-0003-1537-0437 FU NIGMS NIH HHS [GM 59675-01] NR 38 TC 8 Z9 9 U1 0 U2 8 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0731-7085 J9 J PHARMACEUT BIOMED JI J. Pharm. Biomed. Anal. PD JAN 15 PY 2002 VL 27 IS 3-4 BP 639 EP 650 DI 10.1016/S0731-7085(01)00572-6 PG 12 WC Chemistry, Analytical; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 514GK UT WOS:000173430500027 PM 11755764 ER PT J AU Treanor, J Keitel, W Belshe, R Campbell, J Schiff, G Zangwill, K Wolff, M Klimov, A Levandowski, R Lambert, L AF Treanor, J Keitel, W Belshe, R Campbell, J Schiff, G Zangwill, K Wolff, M Klimov, A Levandowski, R Lambert, L TI Evaluation of a single dose of half strength inactivated influenza vaccine in healthy adults SO VACCINE LA English DT Article DE influenza vaccine; healthy adults; dose response ID ANTIBODY-RESPONSE; VIRUS-VACCINE; REACTOGENICITY; A/USSR/77; SERUM AB Because of delays in the manufacturing of the 2000-2001, trivalent inactivated influenza vaccine in the US, there were concerns that there might be shortages of vaccine supply in the US, Therefore, we conducted a prospective, randomized, open-label, multicenter trial at six C academic medical centers in the US, to evaluate the immunogenicity of a half dose of inactivated vaccine in healthy adults. Healthy adults between the ages of 18 and 49 were randomized to receive either a full 0.5 ml (15.5 mug of each HA antigen) dose or a 0.25 ml (7.75 mug of each HA antigen) dose of the 2000-2001 trivalent inactivated influenza vaccine by intramuscular injection. Sera were obtained for assessment of hemagglutination-inhibiting antibody to each of the three strains contained in the vaccine before and 21 days after vaccination. The proportions of individuals achieving a post-vaccination titer of greater than or equal to1:40, the geometric mean titers (GMTs) of post-vaccination antibody, and the proportions of individuals with a four-fold or greater increase in antibody were lower for all three strains in those receiving 0.25 ml of vaccine compared to those receiving 0.5 ml. However, the differences were small for all three antigens. The upper 95% confidence limits for differences between 0.25 and 0.5 ml doses were less than 20% for rates of achieving a titer of greater than or equal to1:40 and four-fold response, and less than 1.5 for the ratios of GMTs between dose groups, for all three vaccine antigens. These results suggest that when vaccine is in short supply, a strategy using a half dose in healthy adults could increase the number of people vaccinated with relatively little adverse impact on vaccine immunogenicity. (C) 2002 Published by Elsevier Science Ltd. C1 Univ Rochester, Infect Dis Unit, Rochester, NY 14642 USA. Baylor Coll Med, Houston, TX 77030 USA. St Louis Univ, St Louis, MO 63103 USA. Univ Maryland, Baltimore, MD 21201 USA. Childrens Hosp, Med Ctr, Cincinnati, OH 45229 USA. Univ Calif Los Angeles, Ctr Vaccine Res, Los Angeles, CA 90024 USA. EMMES Corp, Rockville, MD USA. Ctr Dis Control & Prevent, Atlanta, GA USA. US FDA, Bethesda, MD 20014 USA. NIAID, Bethesda, MD 20892 USA. RP Treanor, J (reprint author), Univ Rochester, Infect Dis Unit, 601 Elmwood Ave, Rochester, NY 14642 USA. FU NCRR NIH HHS [M01 RR 00425, M01 RR0044-40]; NIAID NIH HHS [N01 AI 45250, N01 AI 45249, N01 AI 45252, N01 AI 65313, T32 AI 07524, N01 AI 45251, N01 AI 45248, N01 AI 65316]; PHS HHS [N01 45250] NR 15 TC 55 Z9 56 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 15 PY 2002 VL 20 IS 7-8 BP 1099 EP 1105 AR PII S0264-410X(01)00440-6 DI 10.1016/S0264-410X(01)00440-6 PG 7 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 521TV UT WOS:000173858200016 PM 11803070 ER PT J AU Khan, AA McCarthy, S Wang, RF Cerniglia, CE AF Khan, AA McCarthy, S Wang, RF Cerniglia, CE TI Characterization of United States outbreak isolates of Vibrio parahaemolyticus using enterobacterial repetitive intergenic consensus (ERIC) PCR and development of a rapid PCR method for detection of 03 : K6 isolates SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE enterobacterial repetitive intergenic consensus polymerase chain reaction; nucleotide sequence; molecular detection; Vibrio parahaemolyticus 03 : K6 ID ESCHERICHIA-COLI; SEQUENCES; STRAINS; GENOMES; GENE; TDH; FINGERPRINT; HEMOLYSIN AB Outbreaks of Vibrio parahaemolyticus gastroenteritis in the United States (Texas, New York and Pacific Northwest) in 1997-98 emphasized the need to develop molecular methods for identification and differentiation of these organisms. When outbreak isolates were analyzed for the enterobacterial repetitive intergenic consensus sequences, the Texas and New York outbreak isolates had a specific 850-bp DNA fragment that was absent in Pacific Northwest isolates. The 850-bp polymerase chain reaction (PCR) product was found in isolates of serovar O3:K6, which have an unusual potential to spread and cause infections. To develop a specific molecular detection method for serovar O3:K6, the nucleotide sequence of the 850-bp product was determined. The GenBank blast analysis did not show homology with any known Vibrio spp. gene sequences. Two PCR primers were designed to specifically amplify the unique sequences from serovar O3:K6 isolates. Genomic DNA from 10 Texas, eight New York, and seven Pacific Northwest outbreak isolates of V: parahaemolyticus was assayed by PCR. Texas and New York isolates were positive in the PCR assay, giving a 327-bp PCR product as predicted; however, Pacific Northwest isolates were negative, indicating the absence of the target gene. Texas and New York isolates were all serovar O3:K6; the Pacific Northwest isolates were not. The primers were tested with other Vibrio spp. and other closely related species and no amplification of the 327-bp PCR product was found. The PCR method can be used to specifically identify O3:K6 V. parahaemolyticus isolates in less than 6 h. (C) 2002 Published by Elsevier Science B.V. on behalf of the Federation of European Microbiological Societies. C1 Natl Ctr Toxicol Res, US FDA, Div Microbiol, Jefferson, AR 72079 USA. US FDA, CFSAN, Dauphin Isl, AL 36528 USA. RP Khan, AA (reprint author), Natl Ctr Toxicol Res, US FDA, Div Microbiol, Jefferson, AR 72079 USA. NR 23 TC 39 Z9 42 U1 1 U2 4 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 JAN 10 PY 2002 VL 206 IS 2 BP 209 EP 214 DI 10.1111/j.1574-6968.2002.tb11011.x PG 6 WC Microbiology SC Microbiology GA 517UC UT WOS:000173627600013 PM 11814665 ER PT J AU Bishop, PC Myers, T Robey, R Fry, DW Liu, ET Blagosklonny, MV Bates, SE AF Bishop, PC Myers, T Robey, R Fry, DW Liu, ET Blagosklonny, MV Bates, SE TI Differential sensitivity of cancer cells to inhibitors of the epidermal growth factor receptor family SO ONCOGENE LA English DT Article DE oncogenes; HER1/HER2 inhibitors; EGF; NCI drug screen; signal transduction ID ANTICANCER DRUG SCREEN; BREAST-CANCER; PROGNOSTIC FACTOR; TUMOR-SUPPRESSOR; ONCOGENE; THERAPY; GENE; P53; AMPLIFICATION; EXPRESSION AB Clinical responses to the HER1 (EGF receptor) inhibitors and HER2/neu/ErbB2 inhibitors correlate with high levels of receptor expression. However, a significant subset of patients with high receptor levels appear to be refractory to treatment. We have observed similar results in the 60 cell lines of the NCI Anti-Cancer Drug Screen using a panel of 11 selective HER1 inhibitors. As expected, low HER1-expressing cell lines were insensitive to HER1 inhibitors. In cell lines with high HER1 expression, low concentrations of HER1 inhibitors potently inhibit both HER1 phosphorylation and the mitogen-activated protein kinase (MAPK) pathway. However, this inhibition did not always correlate with cellular arrest. High HER1-expressing cell lines can be subdivided into two groups based on their sensitivity to HER1 inhibitors. In the sensitive group, receptor and growth inhibition was concordant and occurred at submicromolar concentrations of HER1 inhibitors. In the insensitive group, receptor inhibition occurred at a low concentration (<1 mum) but concentrations that were ten times or higher were required for growth inhibition. Also, neither induction of p21 and cyclin D1 nor p53 status could explain the difference between sensitive and insensitive cells. Although EGF activated the MAPK pathway in all cell lines, only drug-sensitive cell lines responded to EGF (accelerated entry from G1 to S) and to HER1 inhibitors (GI arrest) by changes in cell cycling. Furthermore, an EGF-dependent immortalized mammary epithelial cell line was extremely sensitive to a panel of HER1 inhibitors. We infer that independence from mitogen-mediated signaling confers insensitivity to HER1 inhibitors in a large subset of cancer cell lines. C1 NCI, Med Branch, DCS, MB,NIH, Bethesda, MD 20892 USA. US FDA, CBER, OTRR, DCTDA,Oncol Branch, Rockville, MD 20852 USA. NCI, DTP, Rockville, MD USA. Parke Davis Pharmaceut, Ann Arbor, MI USA. Natl Univ Singapore, Singapore Genom Programme, Singapore, Singapore. New York Med Coll, Dept Med, Valhalla, NY 10595 USA. RP Bates, SE (reprint author), NCI, Med Branch, DCS, MB,NIH, Bldg 10,Room 12N226,9000 Rockville Pike, Bethesda, MD 20892 USA. RI Liu, Edison/C-4141-2008 NR 33 TC 79 Z9 83 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD JAN 3 PY 2002 VL 21 IS 1 BP 119 EP 127 DI 10.1038/sj.onc.1205028 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 505AD UT WOS:000172887800012 PM 11791182 ER PT J AU Schwetz, BA AF Schwetz, BA TI Rheumatoid arthritis treatment SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 6 Z9 6 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 JAN 2 PY 2002 VL 287 IS 1 BP 33 EP 33 DI 10.1001/jama.287.1.33-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 506NK UT WOS:000172978500006 PM 11754690 ER PT J AU Schwetz, BA AF Schwetz, BA TI Drug for severe adult sepsis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fushers Ln, Rockville, MD 20857 USA. NR 0 TC 6 Z9 6 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 JAN 2 PY 2002 VL 287 IS 1 BP 33 EP 33 DI 10.1001/jama.287.1.33-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 506NK UT WOS:000172978500004 PM 11754690 ER PT J AU Schwetz, BA AF Schwetz, BA TI Breast tissue ablation device SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Off Commissioner Food & Drugs, Rockville, MD 20857 USA. RP Schwetz, BA (reprint author), US FDA, Off Commissioner Food & Drugs, HF-1,Room 14-71,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 6 Z9 6 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 JAN 2 PY 2002 VL 287 IS 1 BP 33 EP 33 DI 10.1001/jama.287.1.33-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 506NK UT WOS:000172978500005 PM 11754690 ER PT B AU Ilev, IK Waynant, RW AF Ilev, IK Waynant, RW GP IEEE IEEE TI Infrared tissue imaging at on-the-spot laser delivery using an all-optical-waveguide transmitting system SO 2002 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING, PROCEEDINGS LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging CY JUL 07-10, 2002 CL WASHINGTON, D.C. SP IEEE Signal Processing Sco, Engn Med & Biol Soc ID UNCOATED HOLLOW TAPER AB We present experimental results on mid-infrared thermal imaging of micro-scale tissue area irradiated by an all-optical-waveguide laser delivery system. The infrared transmitting system is based on a novel and simple laser delivery technique that includes two key optical elements: a grazing-incidence-based uncoated hollow taper used for direct infrared laser-to-fiber coupling, and a tissue-activated optical fiber probe with a specialty shaped tip. The lens-free all-optical-waveguide transmitting system provides on-the-spot laser delivery into a precise micro-scale tissue area. When an Er:YAG (lambda=2.94 mum) laser is used as a mid-infrared laser source, we obtain infrared thermal images from a small-size tissue area and a single hair. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Ilev, IK (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. NR 7 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-7584-X PY 2002 BP 281 EP 284 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BV15G UT WOS:000178000400070 ER PT B AU Badano, A Gagne, RM Jennings, RJ AF Badano, A Gagne, RM Jennings, RJ GP IEEE IEEE TI Depth-of-interaction effects in columnar phosphors for exponential X-ray absorption SO 2002 IEEE INTERNATIONAL SYMPOSIUM ON BIOMEDICAL IMAGING, PROCEEDINGS LA English DT Proceedings Paper CT IEEE International Symposium on Biomedical Imaging CY JUL 07-10, 2002 CL WASHINGTON, D.C. SP IEEE Signal Processing Sco, Engn Med & Biol Soc AB The depth-dependent blur of phosphor screens have been studied using analytical and numerical methods by a number of investigators. We present an analysis of the effect of depth-of-interaction on the modulation transfer function of columnar phosphor screens. We extend our previously reported results of single x-ray interactions to the study of x-ray beams that exponentially deposit energy in the phosphor. We show that depth dependence of the signal is significant also in columnar phosphors. However, the modulation of high frequencies remains high due to the sharpness of the line-spread function caused by waveguiding of light within the columns. C1 US FDA, Ctr Device & Radiol Hlth, Rockville, MD 20857 USA. RP Badano, A (reprint author), US FDA, Ctr Device & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. OI badano, aldo/0000-0003-3712-6670 NR 8 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-7584-X PY 2002 BP 557 EP 560 PG 4 WC Engineering, Biomedical; Engineering, Electrical & Electronic; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Radiology, Nuclear Medicine & Medical Imaging GA BV15G UT WOS:000178000400140 ER PT B AU Casamento, JP AF Casamento, JP GP IEEE IEEE TI Comparison of magnetic fields emitted from security screening devices with magnetic field immunity standards SO 2002 IEEE INTERNATIONAL SYMPOSIUM ON ELECTROMAGNETIC COMPATIBILITY, VOLS 1 AND 2, SYMPOSIUM RECORD LA English DT Proceedings Paper CT IEEE International Symposium on Electromagnetic Compatibility CY AUG 19-23, 2002 CL MINNEAPOLIS, MN SP IEEE, EMC Soc, Superior EMC, Laird Technologies, Rohde & Schwarz, TUV Prod Serv, Murata Electr NA Inc, ETS Lindgren, Hoolihan EMC Consulting, IBM Engn Solut Serv, Retlif Testing Labs DE security screening; anti-theft systems; pacemakers; implanted cardioverter defibrillator; electronic article surveillance; magnetic field; metal detector ID SURVEILLANCE AB The Food and Drug Administration (FDA) received over 90 problem reports of medical device malfunctions due to electromagnetic interference (EMI) from magnetic field emitting security devices. The FDA took action to alert users and manufacturers of medical devices and security screening devices [7, 8]. These malfunctions were thought to be related to the electromagnetic fields emitted from the security device and judged serious enough by the reporters (clinical users of these devices) to potentially cause patient injuries. Measurements of magnetic field emissions from security, devices reveal that some security screening devices can emit magnetic fields at strengths that exceed the test levels specified in sonic medical device standards. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Casamento, JP (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 15 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-7264-6 PY 2002 BP 937 EP 940 PG 4 WC Engineering, Electrical & Electronic SC Engineering GA BV20F UT WOS:000178146200172 ER PT S AU Waynant, RW Ilev, IK AF Waynant, RW Ilev, IK GP IEEE IEEE TI Delivery of coherent radiation from terahertz to X-rays SO 2002 IEEE/LEOS ANNUAL MEETING CONFERENCE PROCEEDINGS, VOLS 1 AND 2 SE IEEE Lasers and Electro-Optics Society (LEOS) Annual Meeting LA English DT Proceedings Paper CT 15th Annual Meeting of the IEEE-Lasers-and-Electro-Optics-Society CY NOV 10-14, 2002 CL GLASGOW, SCOTLAND SP IEEE Lasers & Electro Opt Soc C1 US FDA, CDRH, Electroopt Branch, Rockville, MD 20857 USA. RP Waynant, RW (reprint author), US FDA, CDRH, Electroopt Branch, HFZ-134,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1092-8081 BN 0-7803-7500-9 J9 IEEE LEOS ANN MTG PY 2002 BP 785 EP 786 PG 2 WC Engineering, Electrical & Electronic; Optics; Physics, Applied SC Engineering; Optics; Physics GA BV68X UT WOS:000179772700391 ER PT J AU Burgess, DJ Hussain, AS Ingallinera, TS Chen, ML AF Burgess, DJ Hussain, AS Ingallinera, TS Chen, ML TI Assuring quality and performance of sustained and controlled release parenterals: Workshop report SO AAPS PHARMSCI LA English DT Article AB This is a summary report of the American Association of Pharmaceutical Scientists, the Food and Drug Administration and the United States Pharmacopoeia co-sponsored workshop on "Assuring Quality and Performance of Sustained and Controlled Release Parenterals." Experts from the pharmaceutical industry, the regulatory authorities and academia participated in this workshop to review, discuss and debate formulation, processing and manufacture of sustained and controlled release parenterals and identify critical process parameters and their control. Areas were identified where research is needed in order to understand the performance of these drug delivery systems and to assist in the development of appropriate testing procedures. Recommendations were made for future workshops, meetings and working groups in this area. C1 Univ Connecticut, Dept Pharmaceut, Storrs, CT 06269 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. InfiMed Therapeut Inc, Framingham, MA 01702 USA. RP Burgess, DJ (reprint author), Univ Connecticut, Dept Pharmaceut, 372 Fairfied Rd, Storrs, CT 06269 USA. NR 0 TC 23 Z9 23 U1 1 U2 4 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1522-1059 J9 AAPS PHARMSCI JI AAPS Pharmsci PY 2002 VL 4 IS 2 AR 7 PG 15 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 584MJ UT WOS:000177470100001 ER PT J AU Fahmy, R Marnane, B Bensley, D Hollenbeck, RG AF Fahmy, R Marnane, B Bensley, D Hollenbeck, RG TI Dissolution test development for complex veterinary dosage forms: Oral boluses SO AAPS PHARMSCI LA English DT Article; Proceedings Paper CT AAPS Pharmaceutics and Drug Delivery Conference CY APR 22-24, 2002 CL ARLINGTON, VIRGINIA SP AAPS DE dissolution; veterinary products; bolus AB Fundamental aspects of electrolyte chemistry were used to design an appropriate dissolution medium with the capacity to maintain sink conditions throughout the test. Dissolution of various bolus dosage forms was studied using USP Apparatus II at various stirring speeds. Complete dissolution of each drug in the designed medium was achieved, and there is evidence that such a dissolution test could be discriminating. This review details the development of potentially discriminating in vitro dissolution tests for veterinary boluses using USP Apparatus II and examines the potential role of such testing during product quality assessments, in the evaluation of postapproval manufacturing changes and for the establishment of the generic equivalence of veterinary products. C1 US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. RP Fahmy, R (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, 7500 Standish Pl,HFV 143, Rockville, MD 20855 USA. NR 5 TC 1 Z9 1 U1 0 U2 2 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1522-1059 J9 AAPS PHARMSCI JI AAPS Pharmsci PY 2002 VL 4 IS 4 AR 35 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 668LM UT WOS:000182293400019 ER PT J AU Martinez, M Rathbone, MJ AF Martinez, M Rathbone, MJ TI Linking human and veterinary health: Trends, directions and initiatives SO AAPS PHARMSCI LA English DT Article; Proceedings Paper CT AAPS Pharmaceutics and Drug Delivery Conference CY APR 22-24, 2002 CL ARLINGTON, VIRGINIA SP AAPS DE communication; globalization; veterinary medicine AB The objective of this brief article is to provide an overview of some of the important harmonization efforts that are currently under way within the animal health community. Topics include: scientific networks and interdisciplinary communication; organizations that address animal-related public health concerns; the role of the veterinary pharmaceutical scientist within human health-oriented professional organizations; recent publications pertaining to veterinary pharmacology, pharmaceutics and therapeutics; and the role of global networking in veterinary product research and development. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. InterAg, Hamilton, New Zealand. RP Martinez, M (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA. NR 2 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 1522-1059 J9 AAPS PHARMSCI JI AAPS Pharmsci PY 2002 VL 4 IS 4 AR 32 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 668LM UT WOS:000182293400016 ER PT J AU Martinez, M Soback, S AF Martinez, M Soback, S TI Introduction: A welcome to the first Special Animal Health Issue of AAPS PharmSci SO AAPS PHARMSCI LA English DT Editorial Material DE veterinary medicine; harmonization ID CARCASS; IMMUNIZATION; TRANSPORT; IMPLANT; GROWTH AB The goal of this special volume is to provide veterinary scientists with state-of-the art reviews in animal health and to inform human health scientists of the various challenges and collaborative opportunities associated with their animal health counterparts. The contributors are highly respected experts, providing invaluable insights into current issues and state-of-the-art advances within veterinary medicine. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. Minist Agr, Kimron Vet Inst, IL-50250 Bet Dagan, Israel. RP Martinez, M (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20855 USA. NR 27 TC 2 Z9 2 U1 0 U2 1 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1522-1059 J9 AAPS PHARMSCI JI AAPS Pharmsci PY 2002 VL 4 IS 4 AR 39 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 668LM UT WOS:000182293400001 ER PT J AU Tollefson, L Flynn, WT AF Tollefson, L Flynn, WT TI Impact of antimicrobial resistance on regulatory policies in veterinary medicine: Status report SO AAPS PHARMSCI LA English DT Article; Proceedings Paper CT AAPS Pharmaceutics and Drug Delivery Conference CY APR 22-24, 2002 CL ARLINGTON, VIRGINIA SP AAPS DE antimicrobial resistance; animal drugs; foodborne disease; veterinary medicine ID ANTIBIOTIC-RESISTANCE; ESCHERICHIA-COLI; SALMONELLA AB Increasing resistance to antimicrobial agents is of growing concern to public health officials worldwide. The concern includes infections acquired in hospitals, community infections acquired in outpatient care settings, and resistant foodborne disease associated with drug use in food-producing animals. In the United States, a significant source of antimicrobial-resistant foodborne infections in humans is the acquisition of resistant bacteria originating from animals, The US Food and Drug Administration's (FDA's) goal in resolving the public health impact arising from the use of antimicrobial drugs in food-producing animals 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's approach to the problem is multipronged and innovative. The strategy includes revision of the pre-approval safety assessment for new animal drug applications, use of risk assessment to determine the human health effect resulting from the use of antimicrobials in food animals, robust monitoring for changes in susceptibilities among foodborne pathogens to drugs that are important both in human and veterinary medicine, research, and risk management. 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 27 TC 6 Z9 6 U1 1 U2 3 PU AMER ASSOC PHARMACEUTICAL SCIENTISTS PI ALEXANDRIA PA 1650 KING ST, STE 200, ALEXANDRIA, VA 22314-2747 USA SN 1522-1059 J9 AAPS PHARMSCI JI AAPS Pharmsci PY 2002 VL 4 IS 4 AR 37 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 668LM UT WOS:000182293400021 ER PT J AU Yu, LX Wang, JT Hussain, AS AF Yu, LX Wang, JT Hussain, AS TI Evaluation of USP apparatus 3 for dissolution testing of immediate release products SO AAPS PHARMSCI LA English DT Article DE dissolution; USP apparatus 2; USP apparatus 3; immediate- release; and product ID DRUG-RELEASE; INVITRO AB We sought to evaluate whether U.S. Pharmacopeia (USP) apparatus 3 can be used as an alternative to USP apparatus 2 for dissolution testing of immediate-release (IR) dosage forms. Highly soluble drugs, metoprolol and ranitidine, and poorly soluble drugs, acyclovir and furosemide, were chosen as model drugs. The dissolution profiles of both innovator and generic IR products were determined using USP apparatus 2 at 50 rpm and apparatus 3 at 5, 15, and 25 dips per minute (dpm). The dissolution profiles from USP apparatus 3 were compared to those from USP apparatus 2 using the f(2) similarity test. The dissolution profile from USP apparatus 3 generally depends on the agitation rate, with a faster agitation rate producing a faster dissolution rate. It was found that USP apparatus 3 at the extreme low end of the possible agitation range, such as 5 dpm, gave hydrodynamic conditions equivalent to USP apparatus 2 at 50 rpm. With appropriate agitation rate, USP apparatus 3 can produce similar dissolution profiles to USP apparatus 2 or distinguish dissolution characteristics for the IR products of metoprolol, ranitidine, and acyclovir. Incomplete dissolution was observed for the furosemide tablets using USP apparatus 3. Although it is primarily designed for the release testing of extended-release products, USP apparatus 3 may be used for the dissolution testing of IR products of highly soluble drugs, such as metoprolol and ranitidine, and some IR products of poorly soluble drugs, such as acyclovir. USP apparatus 3 offers the advantages of avoiding cone formation and mimicking the changes in physiochemical conditions and mechanical forces experienced by products in the gastrointestinal tract. C1 US FDA, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Yu, LX (reprint author), US FDA, Off Pharmaceut Sci, Rockville, MD 20857 USA. RI Yu, Lawrence/L-6280-2016 NR 11 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 1522-1059 J9 AAPS PHARMSCI JI AAPS Pharmsci PY 2002 VL 4 IS 1 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 584MH UT WOS:000177470000001 ER PT J AU Walton, MK AF Walton, MK TI Endpoint considerations for clinical trials SO AMYOTROPHIC LATERAL SCLEROSIS AND OTHER MOTOR NEURON DISORDERS LA English DT Article; Proceedings Paper CT Symposium on Classical and Emergent Measures for Clinical Trials in ALS CY NOV 15-16, 2001 CL OAKLAND, CALIFORNIA C1 US FDA, Ctr Biol Evaluat & Res, Div Clin Trial Design & Anal, Rockville, MD 20857 USA. RP Walton, MK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Clin Trial Design & Anal, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1466-0822 J9 AMYOTROPH LATERAL SC JI Amyotroph. Lateral. Scler. Mot. Neuron Disord. PY 2002 VL 3 SU 1 BP S3 EP S6 PG 4 WC Clinical Neurology SC Neurosciences & Neurology GA 607VA UT WOS:000178810400002 PM 12396791 ER PT J AU Weininger, S AF Weininger, S TI Designing a pulse oximeter safety standard SO ANESTHESIA AND ANALGESIA LA English DT Article AB The development of a safety standard is a time-consuming and complex task. Many factors influence the stringency of the requirements, including history with the products and test methods, safety records, and the intended use of the standard and device. Four primary issues are used to illustrate the complexity of developing a safety standard for today's complicated software-controlled pulse oximeters: Can a patient simulator be used to assess performance? What is meant by motion artifact resistance? What is a safe surface temperature limit for the probe? What default low SpO(2) limit should be required? Under ASTM's new standards development paradigm, ASTM may achieve consensus on the 2001 draft of ASTM F1415 but not publish it, electing instead to submit the standard to ISO for consideration as the internationally harmonized pulse oximeter safety standard. C1 US FDA, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Weininger, S (reprint author), HFZ-141,12720 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0003-2999 J9 ANESTH ANALG JI Anesth. Analg. PD JAN PY 2002 VL 94 IS 1 SU S BP S4 EP S7 PG 4 WC Anesthesiology SC Anesthesiology GA 509NY UT WOS:000173154900002 PM 11900036 ER PT J AU Fedorka-Cray, PJ Englen, MD Gray, JT Hudson, C Headrick, ML AF Fedorka-Cray, PJ Englen, MD Gray, JT Hudson, C Headrick, ML TI Programs for monitoring antimicrobial resistance SO ANIMAL BIOTECHNOLOGY LA English DT Article; Proceedings Paper CT Conference on Antibiotic Use in Aninmal Agriculture CY OCT 16-17, 2000 CL CHICAGE, ILLINOIS ID SALMONELLA-TYPHIMURIUM DT104; CAMPYLOBACTER-JEJUNI INFECTIONS; LEVEL QUINOLONE RESISTANCE; ANTIBIOTIC-RESISTANCE; ANIMAL HUSBANDRY; DRUG-RESISTANCE; UNITED-STATES; SWINE; SUSCEPTIBILITY; CHOLERAESUIS C1 USDA ARS, Russell Res Ctr, Antimicrobial Resistance Res Unit, Athens, GA USA. FDA, Ctr Vet Med, Div Epidemiol, Rockville, MD USA. RP Fedorka-Cray, PJ (reprint author), USDA ARS, Russell Res Ctr, Antimicrobial Resistance Res Unit, Athens, GA USA. NR 90 TC 8 Z9 8 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1049-5398 J9 ANIM BIOTECHNOL JI Anim. Biotechnol. PY 2002 VL 13 IS 1 BP 43 EP 55 DI 10.1081/ABIO-120005769 PG 13 WC Agriculture, Dairy & Animal Science; Biotechnology & Applied Microbiology SC Agriculture; Biotechnology & Applied Microbiology GA 586QG UT WOS:000177595300005 PM 12212943 ER PT J AU McDermott, PF Zhao, S Wagner, DD Simjee, S Walker, RD White, DG AF McDermott, PF Zhao, S Wagner, DD Simjee, S Walker, RD White, DG TI The food safety perspective of antibiotic resistance SO ANIMAL BIOTECHNOLOGY LA English DT Article; Proceedings Paper CT Conference on Antibiotic Use in Aninmal Agriculture CY OCT 16-17, 2000 CL CHICAGE, ILLINOIS ID MOBILE GENE CASSETTES; ESCHERICHIA-COLI; DRUG-RESISTANCE; ANTIMICROBIAL RESISTANCE; UNITED-STATES; BACTERIA; SALMONELLA; INTEGRONS; PLASMIDS; ANIMALS AB Bacterial antimicrobial resistance in both the medical and agricultural fields has become a serious problem worldwide. Antibiotic resistant strains of bacteria are an increasing threat to animal and human health, with resistance mechanisms having been identified and described for all known antimicrobials currently available for clinical use. There is currently increased public and scientific interest regarding the administration of therapeutic and subtherapeutic antimicrobials to animals, due primarily to the emergence and dissemination of multiple antibiotic resistant zoonotic bacterial pathogens. This issue has been the subject of heated debates for many years, however, there is still no complete consensus on the significance of antimicrobial use in animals, or resistance in bacterial isolates from animals, on the development and dissemination of antibiotic resistance among human bacterial pathogens. In fact, the debate regarding antimicrobial use in animals and subsequent human health implications has been going on for over 30 years, beginning with the release of the Swann report in the United Kingdom. The latest report released by the National Research Council (1998) confirmed that there were substantial information gaps that contribute to the difficulty of assessing potential detrimental effects of antimicrobials in food animals on human health. Regardless of the controversy, bacterial pathogens of animal and human origin are becoming increasingly resistant to most frontline antimicrobials, including expanded-spectrum cephalosporins, aminoglycosides, and even fluoroquinolones. The lion's share of these antimicrobial resistant phenotypes is gained from extra-chromosomal genes that may impart resistance to an entire antimicrobial class. In recent years, a number of these resistance genes have been associated with large, transferable, extrachromosomal DNA elements, called plasmids, on which may be other DNA mobile elements, such as transposons and integrons. These DNA mobile elements have been shown to transmit genetic determinants for several different antimicrobial resistance mechanisms and may account for the rapid dissemination of resistance genes among different bacteria. The increasing incidence of antimicrobial resistant bacterial pathogens has severe implications for the future treatment and prevention of infectious diseases in both animals and humans. Although much scientific information is available on this subject, many aspects of the development of antimicrobial resistance still remain uncertain. The emergence and dissemination of bacterial antimicrobial resistance is the result of numerous complex interactions among antimicrobials, microorganisms, and the surrounding environments. Although research has linked the use of antibiotics in agriculture to the emergence of antibiotic-resistant foodborne pathogens, debate still continues whether this role is significant enough to merit further regulation or restriction. C1 US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. RP White, DG (reprint author), US FDA, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. NR 42 TC 69 Z9 76 U1 2 U2 29 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1049-5398 J9 ANIM BIOTECHNOL JI Anim. Biotechnol. PY 2002 VL 13 IS 1 BP 71 EP 84 DI 10.1081/ABIO-120005771 PG 14 WC Agriculture, Dairy & Animal Science; Biotechnology & Applied Microbiology SC Agriculture; Biotechnology & Applied Microbiology GA 586QG UT WOS:000177595300007 PM 12212946 ER PT J AU Meyer, JM Silliman, NP Wang, WJ Siepman, NY Sugg, JE Morris, D Zhang, J Bhattacharyya, H King, EC Hopkins, RJ AF Meyer, JM Silliman, NP Wang, WJ Siepman, NY Sugg, JE Morris, D Zhang, J Bhattacharyya, H King, EC Hopkins, RJ TI Risk factors for Helicobacter pylori resistance in the United States: The surveillance of H-pylori antimicrobial resistance partnership (SHARP) study, 1993-1999 SO ANNALS OF INTERNAL MEDICINE LA English DT Article ID DOUBLE-BLIND; NITROIMIDAZOLE RESISTANCE; ANTIBIOTIC-RESISTANCE; ULCER RECURRENCE; TRIPLE THERAPY; CLARITHROMYCIN; ERADICATION; AMOXICILLIN; MULTICENTER; METRONIDAZOLE AB Background: Pretreatment antimicrobial resistance has an important impact on the efficacy of many Helicobacter pylori treatment regimens. Objective: To estimate the prevalence of H. pylori resistance to antimicrobials in the United States, to characterize risk factors associated with H. pylori antimicrobial resistance, and to explore the association between drug utilization and antimicrobial resistance patterns over time. Design: Meta-analysis using patient-level data. Setting: 20 nationwide trials of H. pylori eradication. Patients: 3624 men and women, each of whom contributed one isolate. Measurements: Rates of H. pylori resistance to clarithromycin, metronidazole, and amoxicillin, according to geographic region, age, sex, study year, ethnicity, ulcer status, test method, and study. Results: Overall resistance to clarithromycin, metronidazole, and amoxicillin was 10.1% (95% CI, 9.1% to 11.1% [360 of 3571 patients]), 36.9% (CI, 35.1% to 38.7% [1063 of 2883 patients]), and 1.4% (CI, 1.0% to 1.8% [48 of 3486 patients]), respectively. In multivariable analyses, multiple risk factors were associated with resistance to individual agents. Clarithromycin resistance was significantly associated with geographic region (P = 0.050), older age (P < 0.001), female sex (P < 0.001), inactive ulcer disease (P < 0.001), and study (P = 0.010). Metronidazole resistance was significantly associated with female sex (P < 0.001), earlier year of study enrollment (P = 0.036), Asian ethnicity (P < 0.001), use of an epsilometer test (P = 0.002), and study (P < 0.001). Amoxicillin resistance was low and was not significantly associated with any risk factor. In the 1990s, when rates for use of oral macrolides and metronidazole were relatively stable, clarithromycin resistance rates were stable and metronidazole resistance rates varied. Conclusions: Clinicians should consider risk factors for antimicrobial resistance when deciding which patients should have susceptibility testing and when choosing appropriate H. pylori treatments in the empirical setting. C1 US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Evaluat 3 HFD880, Rockville, MD 20850 USA. AstraZeneca LP, Wayne, NJ USA. TAP Pharmaceut Prod Inc, Deerfield, IL USA. Abbott Labs, Abbott Pk, IL 60064 USA. Pfizer Cent Res, New York, NY USA. Procter & Gamble Co, Mason, OH USA. RP Meyer, JM (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Pharmaceut Evaluat 3 HFD880, 9201 Corp Blvd,Roo S-402, Rockville, MD 20850 USA. RI King, Eileen/Q-1815-2015 NR 26 TC 134 Z9 146 U1 0 U2 2 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 2002 VL 136 IS 1 BP 13 EP 24 PG 12 WC Medicine, General & Internal SC General & Internal Medicine GA 510BF UT WOS:000173188300002 PM 11777360 ER PT J AU Ruley, KM Reimschuessel, R Trucksis, M AF Ruley, KM Reimschuessel, R Trucksis, M TI Goldfish as an animal model system for mycobacterial infection SO BACTERIAL PATHOGENESIS, PT C SE METHODS IN ENZYMOLOGY LA English DT Review ID IDENTIFICATION; GENES; TUBERCULOSIS; DISEASE C1 Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. Ctr Vet Med Food & Drug Adm, Laurel, MD 20708 USA. RP Ruley, KM (reprint author), Univ Maryland, Sch Med, Ctr Vaccine Dev, Baltimore, MD 21201 USA. NR 16 TC 10 Z9 10 U1 0 U2 2 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 358 BP 29 EP 39 PG 11 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BV73G UT WOS:000179914700003 PM 12474377 ER PT S AU Diachenko, GW Warner, CR AF Diachenko, GW Warner, CR BE Lee, TC Ho, CT TI Potassium bromate in bakery products: Food technology, toxicological concerns, and analytical methodology SO BIOACTIVE COMPOUNDS IN FOODS: EFFECTS OF PROCESSING AND STORAGE SE ACS SYMPOSIUM SERIES LA English DT Article; Proceedings Paper CT Symposium on the Effects of Processing and Storage on Bioactive Compounds CY MAR 26-30, 2000 CL SAN FRANCISCO, CALIFORNIA SP Amer Chem Soc, Div Agr & Food Chem ID FLOW REACTOR DETECTION; PERFORMANCE LIQUID-CHROMATOGRAPHY; BREAD; IMPROVER; RATS; MS AB Potassium bromate, which has been used since 1916 as a dough conditioner, has been found, in some circumstances, to leave bromate residues in retail bakery products. Studies published in 1983 established potassium bromate as an animal carcinogen. Over the past decade, improvements in analytical methodology have made it possible to detect these residues at levels of 5 mug/kg (ppb). Research within laboratories of the baking industry has established that reducing the amount of added potassium bromate, maintaining higher baking temperatures, and using ferrous salts as the nutritive iron supplement will significantly reduce or eliminate bromate residues. FDA surveys have revealed progress towards the goal of eliminating residues; however, more work is required. C1 US FDA, Div Prod Manufacture & Use, Washington, DC 20204 USA. RP Diachenko, GW (reprint author), US FDA, Div Prod Manufacture & Use, Washington, DC 20204 USA. NR 14 TC 2 Z9 2 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 SIXTEENTH ST NW, WASHINGTON, DC 20036 USA SN 0097-6156 BN 0-8412-3765-4 J9 ACS SYM SER PY 2002 VL 816 BP 218 EP 227 PG 10 WC Chemistry, Multidisciplinary; Food Science & Technology SC Chemistry; Food Science & Technology GA BV81A UT WOS:000180109800016 ER PT B AU Miller, SA Beer, JZ Lao, NT Zmudzka, BZ AF Miller, SA Beer, JZ Lao, NT Zmudzka, BZ BE Holick, MF TI Production and persistence of UV-induced tan SO BIOLOGIC EFFECTS OF LIGHT 2001 LA English DT Proceedings Paper CT 6th International Arnold Riki Symposium on the Biologic Effects of Light CY JUN 16-18, 2001 CL BOSTON, MA SP Sci Advisory Comm ID HUMAN-SKIN; MELANIN C1 US FDA, Rockville, MD 20850 USA. RP Miller, SA (reprint author), US FDA, Rockville, MD 20850 USA. NR 22 TC 6 Z9 7 U1 0 U2 0 PU KLUWER ACADEMIC PUBLISHERS PI NORWELL PA 101 PHILIP DRIVE, ASSINIPPI PARK, NORWELL, MA 02061 USA BN 0-7923-7669-2 PY 2002 BP 113 EP 126 PG 14 WC Biophysics; Medicine, General & Internal SC Biophysics; General & Internal Medicine GA BU72C UT WOS:000176835300011 ER PT B AU Goodman, JL AF Goodman, JL BE Knobler, SL Mahmoud, AAF Pray, LA TI Meeting the regulatory and product development challenges for vaccines and other biologics to address terrorism SO BIOLOGICAL THREATS AND TERRORISM, WORKSHOP SUMMARY: ASSESSING THE SCIENCE AND RESPONSE CAPABILITIES LA English DT Proceedings Paper CT Workshop of the Forum on Emerging Infections CY NOV 27-29, 2001 CL WASHINGTON, D.C. SP US Dept Hlth & Human Serv, NIH, US FDA, US Dept Def, US Dept State, US Dept Vet Affairs, UDSA, Amer Soc Microbiol, Bristol Myers Squibb Co, Burroughs Wellcome Fund, Eli Lilly & Co, Pfizer, GlaxoSmithKline, Wyeth Ayerst Labs C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Goodman, JL (reprint author), US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 0-309-08253-6 PY 2002 BP 105 EP 110 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BW72M UT WOS:000182974100019 ER PT B AU Meyerhoff, A AF Meyerhoff, A BE Knobler, SL Mahmoud, AAF Pray, LA TI Meeting the regulatory and product development challenges to address terrorism SO BIOLOGICAL THREATS AND TERRORISM, WORKSHOP SUMMARY: ASSESSING THE SCIENCE AND RESPONSE CAPABILITIES LA English DT Proceedings Paper CT Workshop of the Forum on Emerging Infections CY NOV 27-29, 2001 CL WASHINGTON, D.C. SP US Dept Hlth & Human Serv, NIH, US FDA, US Dept Def, US Dept State, US Dept Vet Affairs, UDSA, Amer Soc Microbiol, Bristol Myers Squibb Co, Burroughs Wellcome Fund, Eli Lilly & Co, Pfizer, GlaxoSmithKline, Wyeth Ayerst Labs C1 US FDA, Off Commissioner, Anti Terrorism Program, Rockville, MD 20857 USA. RP Meyerhoff, A (reprint author), US FDA, Off Commissioner, Anti Terrorism Program, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 0-309-08253-6 PY 2002 BP 139 EP 142 PG 4 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BW72M UT WOS:000182974100026 ER PT B AU Stein, KE AF Stein, KE BE Knobler, SL Mahmoud, AAF Pray, LA TI Regulation and production of recombinant human antibodies SO BIOLOGICAL THREATS AND TERRORISM, WORKSHOP SUMMARY: ASSESSING THE SCIENCE AND RESPONSE CAPABILITIES LA English DT Proceedings Paper CT Workshop of the Forum on Emerging Infections CY NOV 27-29, 2001 CL WASHINGTON, D.C. SP US Dept Hlth & Human Serv, NIH, US FDA, US Dept Def, US Dept State, US Dept Vet Affairs, UDSA, Amer Soc Microbiol, Bristol Myers Squibb Co, Burroughs Wellcome Fund, Eli Lilly & Co, Pfizer, GlaxoSmithKline, Wyeth Ayerst Labs ID ARGENTINE HEMORRHAGIC-FEVER; TOXIN TYPE-A; COMPLEMENTARITY-DETERMINING REGIONS; BACILLUS-ANTHRACIS INFECTION; NEUROTOXIN TYPE-A; BOTULINUM TOXIN; EBOLA-VIRUS; MONOCLONAL-ANTIBODIES; BINDING DOMAIN; GUINEA-PIGS C1 US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Stein, KE (reprint author), US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. NR 83 TC 0 Z9 0 U1 0 U2 2 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 0-309-08253-6 PY 2002 BP 142 EP 147 PG 6 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA BW72M UT WOS:000182974100027 ER PT S AU Ho, C AF Ho, C BE Sollers, JJ Thayer, JF TI Challenges in designing a multi-function patient monitor SO BIOMEDICAL SCIENCES INSTRUMENTATION, VOL 38 SE BIOMEDICAL SCIENCES INSTRUMENTATION LA English DT Proceedings Paper CT 39th Annual Rocky Mountain Bioengineering Symposium/39th International ISA Biomedical Sciences Instrumentation Symposium CY APR 12-14, 2002 CL COPPER MT, CO SP Instrumentat Syst & Automat Soc DE electrocardiography; battery; bioimpedance; ablation; hemodynamics; cardiovascular; respiration; management; combination device AB This article presents a discussion of some challenges in the design of a multi-function patient monitor. The term "multi-function patient monitor" refers to a single medical device that monitors multiple physiological parameters from the same patient. A common configuration of the monitor is a personal computer (PC) platform communicating with several modules each designed to monitor one physiological parameter. Although such an integration of modules allows the modules to access to the display screen, keyboard, power supply and printer of the PC, the integration also involves new design challenges. The foremost challenge is the increased demand on the PCs resources, while another challenge is compatibility among the various modules. Examples of compatibility are electromagnetic compatibility, and clinical compatibility. A well-known example of incompatibility is the non-invasive blood pressure monitor cuff cutting off blood flow to the finger with a pulse oximeter probe, resulting in a Low Signal alarm in the pulse oximeter. Other challenges include clutter on the display screen and confusing alarm annunciation. This article discusses these design challenges and proposes some solutions based on engineering principles, and common sense considerations. Examples will also be drawn from case reports available in the public domain. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Ho, C (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-450, Rockville, MD 20850 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU INSTRUMENT SOC AMER PI RESEARCH TRIANGLE PARK PA 67 ALEXANDER DR, PO BOX 12277, RESEARCH TRIANGLE PARK, NC 27709 USA SN 0067-8856 BN 1-55617-787-9 J9 BIOMED SCI INSTRUM PY 2002 VL 38 BP 71 EP 76 PG 6 WC Engineering, Biomedical; Instruments & Instrumentation SC Engineering; Instruments & Instrumentation GA BX29J UT WOS:000184842900011 PM 12085660 ER PT J AU Chen, JJ Wang, SJ AF Chen, JJ Wang, SJ TI Testing for treatment effects on subsets of endpoints SO BIOMETRICAL JOURNAL LA English DT Article DE bootstrap; multiple endpoints; global test; p-value adjustment; single-step procedure; familywise error rate (FWE); power ID MULTIPLE END-POINTS; CLINICAL-TRIALS; BINARY OUTCOMES AB Multiple endpoints are tested to assess an overall treatment effect and also to identify which endpoints or subsets of endpoints contributed to treatment differences. ne conventional p-value adjustment methods, such as single-step, step-up, or step-down procedures, sequentially identify each significant individual endpoint. Closed test procedures can also detect individual endpoints that have effects via a step-by-step closed strategy. This paper proposes a global-based statistic for testing an a priori number, say, r of the k endpoints, as opposed to the conventional approach of testing one (r = 1) endpoint. The proposed test statistic is an extension of the single-step p-value-based statistic based on the distribution of the smallest p-value. The test maintains strong control of the FamilyWise Error (FWE) rate under the null hypothesis of no difference in any (sub)set of r endpoints among all possible combinations of the k endpoints. After rejecting the null hypothesis, the individual endpoints in the sets that are rejected can be tested further, using a univariate test statistic in a second step, if desired. However, the second step test only weakly controls the FWE. The proposed method is illustrated by application to a psychosis data set. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT 20, Jefferson, AR 72079 USA. US FDA, Ctr Drug Evaluat & Res, Off Biostat, Rockville, MD 20857 USA. NR 27 TC 3 Z9 3 U1 0 U2 2 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2002 VL 44 IS 5 BP 541 EP 557 DI 10.1002/1521-4036(200207)44:5<541::AID-BIMJ541>3.0.CO;2-0 PG 17 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 577NE UT WOS:000177066600002 ER PT J AU Liu, JP Hsueh, H Chen, JJ AF Liu, JP Hsueh, H Chen, JJ TI Sample size requirements for evaluation of bridging evidence SO BIOMETRICAL JOURNAL LA English DT Article DE extrapolation; similarity; equivalence limit; hierarchical model ID ACTIVE-CONTROL TRIALS; PRACTICAL ISSUES; CLINICAL-TRIALS; EQUIVALENCE; BIOEQUIVALENCE; PLACEBO AB This paper addresses issues concerning methodologies on the sample size required for statistical evaluation of bridging evidence for a registration of pharmaceutical products in a new region. The bridging data can be either in the Complete Clinical Data Package (CCDP) generated during clinical drug development for submission to the original region or from a bridging study conducted in the new region after the pharmaceutical product was approved in the original region. When the data are in the CCDP, the randomized parallel dose-response design stratified to the ethnic factors and region will generate internally valid data for evaluating similarity concurrently between the regions for assessment of the ability of extrapolation to the new region. Formula for sample size under this design is derived. The required sample size for evaluation of similarity between the regions can be at least four times as large as that needed for evaluation of treatment effects only. For a bridging study conducted in the new region in which the data of the foreign and new regions are not generated concurrently, a hierarchical model approach to incorporating the foreign bridging information into the data generated by the bridging study is suggested. The sample size required is evaluated. In general, the required sample size for the bridging trials in the new region is inversely proportional to equivalence limits, variability of primary endpoints, and the number of patients of the trials conducted in the original region. C1 Natl Cheng Kung Univ, Dept Stat, Tainan 70101, Taiwan. Natl Hlth Res Inst, Div Biostat & Bioinformat, Taipei, Taiwan. Natl Ctr Toxicol Res, Food & Drug Adm, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Chengchi Univ, Dept Stat, Taipei, Taiwan. OI Liu, Jen-pei/0000-0002-9565-1812; HSUEH, HUEY-MIIN/0000-0003-0536-9440 NR 29 TC 16 Z9 17 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. PY 2002 VL 44 IS 8 BP 969 EP 981 DI 10.1002/bimj.200290008 PG 13 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 630YY UT WOS:000180140400005 ER PT J AU Moon, H Ahn, H Kodell, RL AF Moon, H Ahn, H Kodell, RL TI Extension of Peto's test by attribution of tumor lethality in the absence of cause-of-death information SO BIOMETRICAL JOURNAL LA English DT Article DE bioassay; competing risk; fatal tumor; incidental tumor; sacrifice ID SURVIVAL SACRIFICE EXPERIMENTS; RODENT TUMORIGENICITY EXPERIMENTS; NONPARAMETRIC-ESTIMATION; ANIMAL CARCINOGENICITY; EM ALGORITHM; TIME; ONSET; DISEASE AB A new statistical testing approach is developed for rodent tumorigenicity assays that have a single terminal sacrifice or occasionally interim sacrifices but not cause-of-death data. For experiments that lack cause-of-death data, statistically imputed numbers of fatal tumors and incidental tumors are used to modify Peto's cause-of-death test which is usually implemented using pathologist-assigned cause-of-death information. The numbers of fatal tumors are estimated using a constrained nonparametric maximum likelihood estimation method. A new Newton-based approach under inequality constraints is proposed for finding the global maximum likelihood estimate. In this study, the proposed method is concentrated on data with a single sacrifice experiment without implementing further assumptions. The new testing approach may be more reliable than Peto's test because of the potential for a misclassification of cause-of-death by pathologists. A Monte Carlo simulation study for the proposed test is conducted to assess size and power of the test. Asymptotic normality for the statistic of the proposed test is also investigated. The proposed testing approach is illustrated using a real data set. C1 UT, MD Anderson Canc Ctr, Houston, TX 77030 USA. SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 31 TC 5 Z9 5 U1 0 U2 1 PU AKADEMIE VERLAG GMBH PI BERLIN PA PALISADENSTR 40, D-10243 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2002 VL 44 IS 8 BP 982 EP 1001 DI 10.1002/bimj.200290009 PG 20 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 630YY UT WOS:000180140400006 ER PT J AU Ramasamy, S Nagababu, E Alayash, AI Dumaswala, UJ Rifkind, JM AF Ramasamy, S Nagababu, E Alayash, AI Dumaswala, UJ Rifkind, JM TI The formation of high-spin rhombic heme during heme degradation of human hemoglobin SO BIOPHYSICAL JOURNAL LA English DT Meeting Abstract C1 NIA, NIH, Baltimore, MD 21224 USA. US FDA, Bethesda, MD 20892 USA. Univ Cincinnati, Med Ctr, Hoxworth Blood Ctr, Cincinnati, OH 45267 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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 2002 VL 82 IS 1 MA 2158 BP 443A EP 443A PN 2 PG 1 WC Biophysics SC Biophysics GA 511EY UT WOS:000173252702175 ER PT J AU Egorin, MJ Lagattuta, TF Hamburger, DR Covey, JM White, KD Musser, SM Eiseman, JL AF Egorin, MJ Lagattuta, TF Hamburger, DR Covey, JM White, KD Musser, SM Eiseman, JL TI Pharmacokinetics, tissue distribution, and metabolism of 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin (NSC 707545) in CD2F1 mice and Fischer 344 rats SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE geldanamycin; ansamycin; HSP90; pharmacokinetics ID ANTICANCER DRUG TARGETS; GENE-PRODUCT P185; BENZOQUINOID ANSAMYCINS; MUTANT P53; CELL-CYCLE; IN-VIVO; GELDANAMYCIN DERIVATIVES; GLUCOCORTICOID RECEPTOR; MOLECULAR CHAPERONE; HSP90-BINDING AGENT AB Purpose: 17-(Dimethylaminoethylamino)-17-demethoxygeldanamycin (17DMAG) is an analogue of the benzoquinone ansamycin compound 17-(allylamino)-17-demethoxygeldanamycin (17AAG), which is currently being evaluated in clinical trials. Studies were performed in mice and rats to: (1) define the plasma pharmacokinetics, tissue distribution, and urinary excretion of 17DMAG after i.v. delivery; (2) define the bioavailability of 17DMAG after i.p. and oral delivery; (3) characterize the biliary excretion of 17DMAG after i.v. delivery to rats; and (4) characterize, if possible, any metabolites of 17DMAG observed in plasma, tissue, urine, or bile. Materials and methods: Studies were performed in female, CD2F1 mice or male Fischer 344 rats. In preliminary toxicity studies and subsequent i.v. pharmacokinetic studies in mice, 17DMAG i.v. bolus doses of 33.3, 50, and 75 mg/kg were used. In bioavailability studies, i.p. and oral 17DMAG doses of 75 mg/kg were used. In preliminary toxicity studies in rats, i.v. bolus doses of 10 and 20 mg/kg were used, and in i.v. pharmacokinetic studies 10 mg/kg was used. Compartmental and noncompartmental analyses were applied to the plasma concentration versus time data. In mice and rats, concentrations of 17DMAG were determined in multiple tissues. Urine was collected from mice and rats treated with each of the i.v. doses of 17DMAG mentioned above, and drug excretion was calculated until 24 h after treatment. Biliary excretion of 17DMAG and metabolites was studied in bile duct-cannulated rats given a 10 mg/kg i.v. bolus dose of 17DMAG. 17DMAG metabolites were identified with LC/MS. Results: A 75 mg/kg dose of 17DMAG caused no changes in appearance, appetite, waste elimination, or survival of treated mice as compared to vehicle-treated controls. Bolus i.v. delivery of 17DMAG at 75 mg/kg produced "peak" plasma 17DMAG concentrations between 18 and 24.2 mug/ml in mice killed at 5 min after injection. Sequential reduction in the 17DMAG dose to 50 and 33.3 mg/kg resulted in "peak" plasma 17DMAG concentrations between 9.4 and 14.4, and 8.4 and 10.5 mug/ml, respectively. Plasma 17DMAG AUC increased from 362 to 674 and 1150 mug/ml.min when the 17DMAG dose increased from 33.3 to 50 and 75 mg/kg, respectively, corresponding to a decrease in 17DMAG CLtb from 92 ml/min per kg to 75 and 65 ml/min per kg. Plasma 17DMAG concentration versus time data were best fit by a two-compartment open linear model. No potential 17DMAG metabolites were observed in plasma. 17DMAG bioavailability was 100% and 50% after i.p. and oral delivery. respectively. In rats, an i.v. bolus dose of 10 mg/kg produced peak plasma 17DMAG concentrations between 0.88 and 1.74 mug/ml. Plasma 17DMAG concentrations had fallen below the lower limit of quantitation by 180 min and were best fit by a one-compartment open linear model. The plasma 17DMAG AUC was 104 mug/ml.min, corresponding to a 17DMAG CLtb of 96 ml/min per kg. 17DMAG distributed rapidly to all mouse and rat tissues except brain and testes. Only mouse liver contained materials consistent with potential metabolites of 17DMAG, but their concentrations were below the limit of quantitation of the HPLC assay used. Within the first 24 h after delivery. urinary excretion of 17DMAG by mice and rats accounted or 10.6-14.8% and 12.5-16%. respectively, of the delivered dose. By 15 min after i.v. delivery of 10 mg/kg of 17DMAG, rat bile contained 11 new materials with absorbance similar to that of 17DMAG. Four of these proposed metabolites had an M, of 633, indicating addition of an oxygen. Two of these proposed metabolites had an M-r of 603. implying the loss of one methyl group, and one had an M-r of 589, implying the loss of two methyl groups. The remaining four proposed metabolites had an M-r of 566, 571, 629, and 645. respectively. Biliary excretion of 17DMAG and metabolites accounted for 4.7 +/- 1.4% of the delivered dose. with 17DMAG accounting for 50.7 +/- 3.4% of the biliary excretion. Conclusions: 17DMAG has excellent bioavailability when given i.p. and good bioavailability when given orally. 17DMAG is widely distributed to tissues and is quantitatively metabolized much less than is 17AAG. The pharmacokinetic and metabolite data generated should prove relevant to the design of additional preclinical studies as well as to contemplated clinical trials of 17DMAG and could be useful in their interpretation. C1 Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Med, Div Hematol Oncol, Pittsburgh, PA 15213 USA. Univ Pittsburgh, Sch Med, Dept Pharmacol, Pittsburgh, PA 15213 USA. NCI, Toxicol & Pharmacol Branch, Dev Therapeut Program, Div Canc Treatment & Diag, Bethesda, MD 20892 USA. US FDA, Ctr Food Safety & Appl Nutr, Instrumentat & Biophys Branch, Washington, DC 20204 USA. RP Egorin, MJ (reprint author), Univ Pittsburgh, Inst Canc, Mol Therapeut Drug Discovery Program, Pittsburgh, PA 15213 USA. EM egorinmj@msx.upmc.edu FU NCI NIH HHS [N01-CM07106, 2P30 CA47904] NR 71 TC 111 Z9 118 U1 0 U2 15 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD JAN PY 2002 VL 49 IS 1 BP 7 EP 19 DI 10.1007/s00280-001-0380-8 PG 13 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA 521RY UT WOS:000173856400002 PM 11855755 ER PT J AU Voss, KA Howard, PC Riley, RT Sharma, RP Bucci, TJ Lorentzen, RJ AF Voss, KA Howard, PC Riley, RT Sharma, RP Bucci, TJ Lorentzen, RJ TI Carcinogenicity and mechanism of action of fumonisin B-1: a mycotoxin produced by Fusarium moniliforme (= F-verticillioides) SO CANCER DETECTION AND PREVENTION LA English DT Article DE fumonisin B-1; Fusarium moniliforme (= F verticillioides); carcinogenicity; sphingolipids; tumor necrosis factor alpha ID SPRAGUE-DAWLEY RATS; HUMAN ESOPHAGEAL CANCER; NECROSIS-FACTOR-ALPHA; RISK ASSESSMENT; APOPTOSIS; TOXICITY; LIVER; MICE; SPHINGOLIPIDS; CHINA AB Fumonisins are fungal metabolites and suspected human carcinogens. They inhibit ceramide synthase in vitro, enhance tumor necrosis factor alpha (TNFalpha) production, and cause apoptosis. Fumonisin B-1 (FB1) was fed to rats and mice for 2 years or, in separate studies, given to rats or mice for up to 4 weeks. Kidney tubule adenomas and carcinomas were found in male rats fed greater than or equal to50 ppm, whereas liver adenomas and carcinomas were found in female mice fed greater than or equal to50 ppm for 2 years. In the short-term studies, increases in tissue concentration of the ceramide synthase substrate sphinganine (Sa) and the Sa to sphingosine (So) ratio were correlated with apoptosis. Further, hepatotoxicity was ameliorated in mice lacking either the TNFR1 or the TNFR2 TN-Falpha receptors. Thus, FB1 was carcinogenic to rodents and the findings support the hypothesis that disrupted sphingolipid metabolism and TNFalpha play important roles in its mode of action. (C) 2002 International Society for Preventive Oncology. Published by Elsevier Science Ltd. All rights reserved. C1 USDA ARS, Richard B Russell Agr Res Ctr, Toxicol & Mycotoxin Res Unit, Athens, GA 30604 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Georgia, Coll Vet Med, Dept Physiol & Pharmacol, Athens, GA 30602 USA. Expt Pathol Associates, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Nutr, Washington, DC 20204 USA. RP Voss, KA (reprint author), USDA ARS, Richard B Russell Agr Res Ctr, Toxicol & Mycotoxin Res Unit, POB 5677, Athens, GA 30604 USA. NR 49 TC 51 Z9 52 U1 2 U2 14 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 2002 VL 26 IS 1 BP 1 EP 9 AR PII S0361-090X(02)00011-9 DI 10.1016/S0361-090X(02)00011-9 PG 9 WC Oncology SC Oncology GA 617QU UT WOS:000179373000001 PM 12088196 ER PT J AU Michener, CM Ardekani, AM Petricoin, EF Liotta, LA Kohn, EC AF Michener, CM Ardekani, AM Petricoin, EF Liotta, LA Kohn, EC TI Genomics and proteomics: application of novel technology to early detection and prevention of cancer SO CANCER DETECTION AND PREVENTION LA English DT Review DE molecular-targeted therapies; cancer; laser capture microdissection ID LASER CAPTURE MICRODISSECTION; OVARIAN-CANCER; BREAST-CANCER; GENE-EXPRESSION; CELL-LINES; MONOCLONAL-ANTIBODY; ESTROGEN-RECEPTOR; CARCINOMA; ONCOGENE; TUMORS AB Advances in molecular biology over the past decade have helped to enhance our understanding of the complex interplay between genetic, transcriptional and translational alterations in human cancers. These molecular changes are the basis for an evolving field of high-throughput cancer discovery techniques using microscopic amounts of patient-based materials. Laser capture microdissection allows pure populations of cells to be isolated from both the tumor and stroma in order to identify subtle differences in RNA and protein expression. Comparative, analysis of these alterations between normal, pre-invasive, and invasive tissue using powerful bioinformatics programs has allowed us to identify novel tumor markers, profile complex protein pathways, and develop new molecular-based therapies. Continued refinement of such high-throughput microtechnologies will enable us to rapidly query patient specimens to identify novel methods for early detection, treatment, and follow-up of a wide array of human cancers. (C) 2002 International Society for Preventive Oncology. Published by Elsevier Science Ltd. All rights reserved. C1 NCI, FDA Clin Prote Program, Pathol Lab, Mol Signalling Lab,Ctr Canc Res, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Kohn, EC (reprint author), NCI, FDA Clin Prote Program, Pathol Lab, Mol Signalling Lab,Ctr Canc Res, Bldg 10 Room 2A33, Bethesda, MD 20892 USA. EM kohne@helix.gov NR 57 TC 51 Z9 53 U1 2 U2 6 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 2002 VL 26 IS 4 BP 249 EP 255 AR PII S0361-090X(02)00092-2 DI 10.1016/S0361-090X(02)00092-2 PG 7 WC Oncology SC Oncology GA 612PN UT WOS:000179084800001 PM 12430629 ER PT J AU Sibani, S Melnyk, S Pogribny, IP Wang, W Hiou-Tim, F Deng, LY Trasler, J James, SJ Rozen, R AF Sibani, S Melnyk, S Pogribny, IP Wang, W Hiou-Tim, F Deng, LY Trasler, J James, SJ Rozen, R TI Studies of methionine cycle intermediates (SAM, SAH), DNA methylation and the impact of folate deficiency on tumor numbers in Min mice SO CARCINOGENESIS LA English DT Article ID DEOXYNUCLEOTIDE POOL IMBALANCE; HAMSTER OVARY CELLS; NESTED CASE-CONTROL; COLONIC NEOPLASIA; COLORECTAL-CANCER; DIETARY-FOLATE; FOLIC-ACID; RATS; CARCINOGENESIS; RISK AB Several epidemiological studies have suggested a modulatory effect of dietary folate intake on the risk of colorectal cancer. The molecular basis for this inverse association is not clearly understood, but may involve alterations in DNA methylation. In this study, we examined the levels of methylation intermediates [S-adenosylmethionine (SAM) and S-adenosylhomocysteine (SAH)] and of global DNA methylation in the pre-neoplastic small intestine of Min (multiple intestinal neoplasia) mice. We also studied the effect of folate/choline deficiency on these parameters and on tumor multiplicity in this animal model. In folate-adequate Min mice, we identified positive linear correlations between SAM or SAH and tumor numbers (R-2 = 0.38, P < 0.005; R-2 = 0.26, P = 0.025, respectively). A positive correlation between global DNA hypomethylation and tumor multiplicity was also observed (R-2 = 0.29, P = 0.014). These three biochemical determinants (SAM, SAH and DNA hypomethylation) may, therefore, serve as early markers of cell transformation. Folate/choline deficiency, however, did not produce a consistent effect on tumor numbers in three separate experiments. As an increase in tumor numbers was observed only in folate- and choline-deficient mice with low levels of SAM and DNA hypomethylation, the modulatory role of folate may be dependent on the transformation state of the cell. C1 McGill Univ, Montreal Childrens Hosp, Dept Pediat, Montreal, PQ H3Z 2Z3, Canada. McGill Univ, Montreal Childrens Hosp, Dept Human Genet, Montreal, PQ H3Z 2Z3, Canada. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. McGill Univ, Dept Pharmacol & Therapeut, Montreal, PQ, Canada. RP Rozen, R (reprint author), McGill Univ, Montreal Childrens Hosp, Dept Pediat, 4060 Ste Catherine St W, Montreal, PQ H3Z 2Z3, Canada. NR 36 TC 66 Z9 67 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2002 VL 23 IS 1 BP 61 EP 65 DI 10.1093/carcin/23.1.61 PG 5 WC Oncology SC Oncology GA 511NX UT WOS:000173273400008 PM 11756224 ER PT J AU Langouet, S Paehler, A Welti, DH Kerriguy, N Guillouzo, A Turesky, RJ AF Langouet, S Paehler, A Welti, DH Kerriguy, N Guillouzo, A Turesky, RJ TI Differential metabolism of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine in rat and human hepatocytes SO CARCINOGENESIS LA English DT Article ID HETEROCYCLIC AROMATIC-AMINES; HUMAN CYTOCHROME-P450 1A2; IN-VITRO; MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; LIVER-MICROSOMES; PHIP; ACTIVATION; IDENTIFICATION; CARCINOGEN; DNA AB Metabolism of the carcinogen 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP) has been compared in human and rat hepatocytes. The identities of seven metabolites were confirmed by UV and mass spectroscopy and by co-elution with reference standards using HPLC. In human hepatocytes, the major biotransformation pathway of PhIP was cytochrome P4501A2 (CYP1A2)-mediated N-oxidation to form the genotoxic metabolite 2-(hydroxyamino)-1-methyl-6-phenylimidazo[4,5-b]pyridine (HONH-PhIP), which underwent glucuronidation at the N-2 and N3 positions of PhIP to form stable conjugates. These products combined accounted for as much as 60% of the added PhIP. Direct glucuronidation of PhIP at the N-2 and N3 positions also occurred, accounting for up to 20% of the amount added. Glucuronide and sulfate conjugates of 2-amino-4'-hydroxy-1-methyl-6-phenylimidazo[4,5-b]pyridine (4'-HO-PhIP) were also detected, comprising 5 and 12% of the products, respectively. The CYP1A2 inhibitor furafylline diminished the formation of both HONH-PhIP glucuronide conjugates in a concentration-dependent manner, however, levels of 4'-HO-PhIP were unchanged, indicating that CYP1A2 does not significantly contribute to 4'-hydroxylation of PhIP. Hepatocytes of male rats, both untreated and pretreated with the CYP1A2 inducer 3-methylcholanthrene (3-MC) transformed PhIP into 4'-HO-PhIP as the prominent product. Unconjugated and conjugated 4'-HO-PhIP metabolites combined accounted for 18 and 46% of the PhIP products in untreated and in 3-MC-pretreated rat hepatocytes, respectively. The isomeric glucuronide conjugates of HONH-PhIP combined accounted for 11 and 26% of the PhIP, respectively, in untreated and 3-MC-pretreated hepatocytes. The regioselectivity of glucuronidation of PhIP was different in human and rat hepatocytes. Human liver UDP-glucuronosyltransferases favored conjugation to the N-2 positions of PhIP and HONH-PhIP, while the N3 atom was the preferred site of conjugation for the rat enzymes. Thus, important differences exist between human and rat enzymes in catalytic activity and regioselectivity of PhIP metabolism. Some human hepatocyte populations are more active at transforming PhIP to a genotoxic species than rat hepatocytes pretreated with the potent CYP1A2 inducer 3-MC. C1 Univ Rennes 1, Fac Pharm, INSERM, U456, F-35043 Rennes, France. Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Langouet, S (reprint author), Univ Rennes 1, Fac Pharm, INSERM, U456, F-35043 Rennes, France. RI Langouet, Sophie/I-2776-2015 NR 33 TC 48 Z9 50 U1 2 U2 4 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2002 VL 23 IS 1 BP 115 EP 122 DI 10.1093/carcin/23.1.115 PG 8 WC Oncology SC Oncology GA 511NX UT WOS:000173273400016 PM 11756232 ER PT J AU Lee, N Bertholet, S Debrabant, A Muller, J Duncan, R Nakhasi, HL AF Lee, N Bertholet, S Debrabant, A Muller, J Duncan, R Nakhasi, HL TI Programmed cell death in the unicellular protozoan parasite Leishmania SO CELL DEATH AND DIFFERENTIATION LA English DT Article DE programmed cell death; Leishmania; promastigote; amastigote; Pentostam; amphotericin B ID CYTOCHROME-C RELEASE; MITOCHONDRIAL DEPOLARIZATION; INDUCED APOPTOSIS; IMMUNE-SYSTEM; BCL-2; BAX; DONOVANI; YEAST; PROMASTIGOTES; MACROPHAGES AB In the present study we have demonstrated some features characterizing programmed cell death (PCD) in the unicellular protozoan parasite Leishmania donovani, the causative agent of visceral Leishmaniasis. We report that PCD is initiated in stationary phase cultures of promastigotes and both inactively growing cultures of axenic amastigotes and promastigotes upon treatment with anti Leishmanial drugs (Pentostam and amphotericin B). However, the two cell types respond to antileishmanial drugs differently. The features of PCD in L. donovani promastigotes are nuclear condensation, nicked DNA in the nucleus, DNA ladder formation, increase in plasma membrane permeability, decrease in the mitochondrial membrane potential (DeltaPsim) and induction of a PhiPhiLux (PPL)-cleavage activity. PCD in both stationary phase culture and upon induction by amphotericin B resulted first in the decrease of mitochondrial membrane potential followed by simultaneous change in plasma membrane permeability and Induction of PPL-cleavage activity. Of the total PPL-cleavage activity, several caspase inhibitors inhibited a significant amount (21-34%). Inhibitors of cathepsin or calpain did not inhibit PPL-cleavage activity. Taken together this study demonstrates that the characteristic features of PCD exist in unicellular protozoan Leishmania donovani. The implication of PCD on the Leishmania pathogenesis is discussed. C1 OBRR,CBER, US FDA, LBPUA, DETTD, Bethesda, MD 20892 USA. OVRR, CBER, US FDA,Div Bacterial Parasit & Allergen Prod, Lab Parasit Biol & Biochem, Bethesda, MD 20892 USA. CBER, US FDA, OVRR,Lab Vector Borne Viral Dis, Div Viral Prod, Bethesda, MD 20892 USA. RP Nakhasi, HL (reprint author), OBRR,CBER, US FDA, LBPUA, DETTD, Bldg 29,Rm 222,8800 Rockville Pike, Bethesda, MD 20892 USA. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 63 TC 176 Z9 188 U1 1 U2 6 PU NATURE PUBLISHING GROUP PI LONDON PA MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND SN 1350-9047 J9 CELL DEATH DIFFER JI Cell Death Differ. PD JAN PY 2002 VL 9 IS 1 BP 53 EP 64 DI 10.1038/sj.cdd.4400952 PG 12 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 511GZ UT WOS:000173257400007 PM 11803374 ER PT J AU Miscia, S Marchisio, M Grilli, A Di Valerio, V Centurione, L Sabatino, G Garaci, F Zauli, G Bonvini, E Di Baldassarre, A AF Miscia, S Marchisio, M Grilli, A Di Valerio, V Centurione, L Sabatino, G Garaci, F Zauli, G Bonvini, E Di Baldassarre, A TI Tumor necrosis factor alpha (TNF-alpha) activates Jak1/Stat3-Stat5B signaling through TNFR-1 in human B cells SO CELL GROWTH & DIFFERENTIATION LA English DT Article ID PROTEIN-TYROSINE KINASES; TRANSCRIPTION FACTOR; FACTOR RECEPTOR; JAK FAMILY; U937 CELLS; STAT; TRANSDUCTION; PATHWAYS; CERAMIDE; APOPTOSIS AB The biological actions of tumor necrosis factor alpha (TNF-alpha) are mediated by two cell surface receptors, TNFR-1 and TNFR-2. These receptors do not display protein tyrosine kinase activity. Nevertheless, an early TNF-induced activation of specific tyrosine kinases has been reported as an important cue to the cellular response to this cytokine. Here we present evidence that TNF-alpha induces the activation of the cytoplasmic Janus tyrosine kinases Jak1 and Tyk2 in both human healthy peripheral and lymphoma B cells. This event was accompanied by the recruitment of a specific set of latent cytosolic transcription factors, Stat3 and Stat5b. Furthermore, Jak1 coprecipitated with TNFR-1 after TNF-alpha treatment. These data suggest that at least in human B cells this cytokine can exert its biological effects through the Jak-Stat signaling pathway and that such signals are initiated through an interaction between TNFR-1 and Jak1. C1 Univ Chieti, Sch Med, Dipartimento Biomorfol, Cell Signaling Unit, I-66100 Chieti, Italy. Univ Chieti, Sch Med, Sect Neonatol, I-66100 Chieti, Italy. Univ Roma Tor Vergata, Dipartimento Diagnost Immagini & Radiol Intervent, Rome, Italy. Univ Ferrara, Dept Morphol & Embryol, Sect Human Anat, I-44100 Ferrara, Italy. Univ Trieste, Sch Med, Dept Human Morphol, I-34127 Trieste, Italy. Ctr Biol Evaluat & Res, Immunobiol Lab, Bethesda, MD 20814 USA. RP Miscia, S (reprint author), Univ Chieti, Sch Med, Dipartimento Biomorfol, Cell Signaling Unit, Via Vestini 6, I-66100 Chieti, Italy. OI grilli, alfredo/0000-0002-5746-5007 NR 32 TC 51 Z9 54 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1044-9523 J9 CELL GROWTH DIFFER JI Cell Growth Differ. PD JAN PY 2002 VL 13 IS 1 BP 13 EP 18 PG 6 WC Cell Biology SC Cell Biology GA 516JT UT WOS:000173550700002 PM 11801527 ER PT S AU Onaivi, ES Ali, SF Chirwa, SS Zwiller, J Thiriet, N Akinshola, BE Ishiguro, H AF Onaivi, ES Ali, SF Chirwa, SS Zwiller, J Thiriet, N Akinshola, BE Ishiguro, H BE Ali, SF TI Ibogaine signals addiction genes and methamphetamine alteration of long-term potentiation SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE II: COCAINE, SUBSTITUTED AMPHETAMINES, GHB, AND OPIATES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse II - Cocaine, Substituted Amphetamines, GHB, and Opiates CY AUG 22-24, 2001 CL MAR DEL PLATA, ARGENTINA SP Int Soc Neurochem, Natl Inst Drug Abuse, Argentinian Sectrtary State Prevent Drug Addict & Narcotraffic, Natl Univ Rosario, Sch Biomed & Pharmaceut Sci, SIGMA TAU Hlth Sci, USDA, Natl Ctr Toxicol Res DE ibogaine; pharmacogenomics; pharmacotherapy; psychostimulant; gene chip; addiction; methamphetamine; haplotypes; SNPs; signal transduction; animal model ID IMMEDIATE-EARLY GENES; IN-VIVO; CIGARETTE-SMOKING; HUMAN ALCOHOLISM; CA1 REGION; EXPRESSION; DOPAMINE; RECEPTOR; COCAINE; DRUGS AB The mapping of the human genetic code will enable us to identify potential gene products involved in human addictions and diseases that have hereditary components. Thus, large-scale, parallel gene-expression studies, made possible by advances in microarray technologies, have shown insights into the connection between specific genes, or sets of genes, and human diseases. The compulsive use of addictive substances despite adverse consequences continues to affect society, and the science underlying these addictions in general is intensively studied. Pharmacological treatment of drug and alcohol addiction has largely been disappointing, and new therapeutic targets and hypotheses are needed. As the usefulness of the pharmacotherapy of addiction has been limited, an emerging potential, yet controversial, therapeutic agent is the natural alkaloid ibogaine. We have continued to investigate programs of gene expression and the putative signaling molecules used by psychostimulants such as amphetamine in in vivo and in vitro models. Our work and that of others reveal that complex but defined signal transduction pathways are associated with psychostimulant administration and that there is broad-spectrum regulation of these signals by ibogaine. We report that the actions of methamphetamine were similar to those of cocaine, including the propensity to alter long-term potentiation (LTP) in the hippocampus of the rat brain. This action suggests that there may be a "threshold" beyond which the excessive brain stimulation that probably occurs with compulsive psychostimulant use results in the occlusion of LTP. The influence of ibogaine on immediate early genes (IEGs) and other candidate genes possibly regulated by psychostimulants and other abused substances requires further evaluation in compulsive use, reward, relapse, tolerance, craving and withdrawal reactions. It is therefore tempting to suggest that ibogaine signals addiction gene products. C1 William Paterson Univ, Dept Biol, Wayne, NJ 07470 USA. NIDA, NIH, IRP, Mol Neurobiol Branch, Baltimore, MD 21224 USA. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol Res, Jefferson, AR 72079 USA. Meharry Med Coll, Dept Anat & Physiol, Nashville, TN 37308 USA. INSERM, U338, Ctr Neurochem, Strasbourg, France. Howard Univ, Coll Med, Dept Pharmacol, Washington, DC 20059 USA. RP Onaivi, ES (reprint author), William Paterson Univ, Dept Biol, 300 Pompton Rd, Wayne, NJ 07470 USA. NR 58 TC 12 Z9 14 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-408-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 965 BP 28 EP 46 PG 19 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BU83M UT WOS:000177157600004 PM 12105083 ER PT S AU Baumann, MH Phillips, JM Ayestas, MA Ali, SF Rice, KC Rothman, RB AF Baumann, MH Phillips, JM Ayestas, MA Ali, SF Rice, KC Rothman, RB BE Ali, SF TI Preclinical evaluation of GBR12909 decanoate as a long-acting medication for methamphetamine dependence SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE II: COCAINE, SUBSTITUTED AMPHETAMINES, GHB, AND OPIATES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse II - Cocaine, Substituted Amphetamines, GHB, and Opiates CY AUG 22-24, 2001 CL MAR DEL PLATA, ARGENTINA SP Int Soc Neurochem, Natl Inst Drug Abuse, Argentinian Sectrtary State Prevent Drug Addict & Narcotraffic, Natl Univ Rosario, Sch Biomed & Pharmaceut Sci, SIGMA TAU Hlth Sci, USDA, Natl Ctr Toxicol Res DE methamphetamine; cocaine; pharmacotherapies; drug addiction; DA transporter; GBR-decanoate; GBR12909; psychomotor stimulants ID BIOGENIC-AMINE TRANSPORTERS; MONOAMINE REUPTAKE INHIBITORS; HUMAN DOPAMINE TRANSPORTER; LIGAND-BINDING DOMAINS; ANALOG I-125 RTI-55; RHESUS-MONKEYS; COCAINE-ABUSE; D-AMPHETAMINE; GBR-12909; RAT AB Methamphetamine (METH) abuse is a growing health problem, and no treatments for METH dependence have been identified. The powerful addictive properties of METH are mediated by release of dopamine (DA) from nerve terminals in mesolimbic reward pathways. METH stimulates DA release by acting as a substrate for DA transporter (DAT) proteins, thereby triggering efflux of DA from cells into the synapse. We have shown that blocking DAT activity with high-affinity DA uptake inhibitors, like GBR12909, can substantially reduce METH-evoked DA release in vitro, suggesting GBR12909 may have potential as a pharmacotherapy for METH dependence. The purpose of the present study was to examine the neurobiological effects of a long-acting oil-soluble preparation of GBR12909 (1-[2-[bis(4-fluorophenyl)methoxy]ethyl]-4-(3-hydroxy-3-phenylpropyl) piperazinyl decanoate, or GBR-decanoate). Male rats received GBR-decanoate (480 mg/kg, i.m.) or its oil vehicle, and were tested using a variety of methods one and two weeks later. Ex vivo autoradiography showed that GBR-decanoate decreases DAT binding in DA-rich brain regions. In vivo microdialysis in the nucleus accumbens revealed that GBR-decanoate elevates baseline levels of extracellular DA and antagonizes the ability of METH to evoke DA release. The dopaminergic effects of GBR-decanoate were sustained, lasting for at least two weeks. Rats pretreated with GBR-decanoate displayed enhanced locomotor responses to novelty at one week, but not two weeks, postinjection. Administration of the D-2/D-3 receptor agonist quinpirole (10 and 100 mug/kg, s.c.) decreased locomotor activity and suppressed plasma prolactin levels; quinpirole-induced responses were not altered by GBR-decanoate. Thus, GBR-decanoate is able to elevate basal synaptic DA levels and block METH-evoked DA release in a persistent manner, without significant perturbation of DA receptor function. The findings suggest that GBR-decanoate, or similar long-acting agents, should be evaluated further as potential treatment adjuncts in the management of METH addiction in humans. C1 NIDA, IRP, NIH, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. NIDDK, Med Chem Lab, NIH, Bethesda, MD USA. RP Baumann, MH (reprint author), NIDA, IRP, NIH, Clin Psychopharmacol Sect, 5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 68 TC 12 Z9 12 U1 1 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-408-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 965 BP 92 EP 108 PG 17 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BU83M UT WOS:000177157600009 PM 12105088 ER PT S AU Itzhak, Y Ali, SF AF Itzhak, Y Ali, SF BE Ali, SF TI Behavioral consequences of methamphetamine-induced neurotoxicity in mice: Relevance to the psychopathology of methamphetamine addiction SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE II: COCAINE, SUBSTITUTED AMPHETAMINES, GHB, AND OPIATES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse II - Cocaine, Substituted Amphetamines, GHB, and Opiates CY AUG 22-24, 2001 CL MAR DEL PLATA, ARGENTINA SP Int Soc Neurochem, Natl Inst Drug Abuse, Argentinian Sectrtary State Prevent Drug Addict & Narcotraffic, Natl Univ Rosario, Sch Biomed & Pharmaceut Sci, SIGMA TAU Hlth Sci, USDA, Natl Ctr Toxicol Res DE neurotoxicity; reward; sensitization; psychostimulants; methamphetamine ID TYROSINE-HYDROXYLASE ACTIVITY; TRANSPORTER KNOCKOUT MICE; NITRIC-OXIDE SYNTHASE; DOPAMINE-TRANSPORTER; INCENTIVE-SENSITIZATION; LOCOMOTOR-ACTIVITY; RAT; DEPLETION; STRIATUM; REGIMEN AB Methamphetamine (METH) is a major drug of abuse in the United States. A high dose of METH given to mice and rats causes long-lasting depletion of tyrosine hydroxylase activity, dopamine (DA), and DA-transporter (DAT) binding sites in the striatum. In human METH-abusers, a marked decrease of the DAT in the caudate putamen was observed. Despite intensive investigations of the mechanism associated with METH-induced neurotoxicity, the behavioral consequences of this phenomenon are not clear. We used the mouse model of METH-induced neurotoxicity to investigate the response of the animals to the psychomotor-stimulating effect of METH and the rewarding effect of the drug. Mice pre-exposed to a neurotoxic dose of METH developed a marked sensitization to the psychomotor-stimulating effect of METH, which lasted for more than two months. The rewarding effect of METH was determined by the conditioned place preference (CPP) paradigm. Mice pre-exposed to the neurotoxic dose of METH showed reduced sensitivity to the rewarding effect of METH compared with control animals. While CPP was maintained for three months in the control group, the conditioned response in the METH pre-exposed animals lasted only a few days. These findings indicate that METH neurotoxicity is associated with opposing and long-lasting behavioral outcomes: (a) sensitization to the psychomotor-stimulating effect of the drug and (b) desensitization to the rewarding properties of the drug. These consequences may be relevant to the psychopathology of METH abuse. Sensitization is pertinent to compulsive drug-seeking behavior that is accompanied by desensitization to the rewarding effect of METH. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Psychiat & Behav Sci, 1011 NW 15th St,Gautier Bldg,Room 503, Miami, FL 33136 USA. FU NIDA NIH HHS [DA12867, R01DA08584] NR 26 TC 24 Z9 24 U1 3 U2 7 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-408-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 965 BP 127 EP 135 PG 9 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BU83M UT WOS:000177157600011 PM 12105090 ER PT S AU Binienda, ZK Pereira, F Alper, K Slikker, W Ali, SF AF Binienda, ZK Pereira, F Alper, K Slikker, W Ali, SF BE Ali, SF TI Adaptation to repeated cocaine administration in rats SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE II: COCAINE, SUBSTITUTED AMPHETAMINES, GHB, AND OPIATES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse II - Cocaine, Substituted Amphetamines, GHB, and Opiates CY AUG 22-24, 2001 CL MAR DEL PLATA, ARGENTINA SP Int Soc Neurochem, Natl Inst Drug Abuse, Argentinian Sectrtary State Prevent Drug Addict & Narcotraffic, Natl Univ Rosario, Sch Biomed & Pharmaceut Sci, SIGMA TAU Hlth Sci, USDA, Natl Ctr Toxicol Res DE rat; brain; cocaine; EEG; slow wave; delta frequency ID VENTRAL TEGMENTAL AREA; NUCLEUS-ACCUMBENS; SENSITIZATION; DOPAMINE; EEG; DEPENDENCE; GLUTAMATE AB Quantitative electroencephalogram (EEG) studies in cocaine-dependent human patients show deficits in slow-wave brain activity, reflected in diminished EEG power in the delta and theta frequency bands. In the present study, electrophysiological measures were monitored in 10 nonanesthetized, adult male Sprague-Dawley rats via bipolar, epidural electrodes implanted over the somatosensory cortex. Control electrocorticograms (ECoG) were recorded twice within a two-week interval to establish a baseline. Rats were subsequently injected daily with cocaine HCl at 15 mg/kg, i.p., for two weeks. The ECoG was recorded during a 1-h session one day after the last injection. Total concentrations of dopamine (DA) and its metabolites were assayed in caudate nucleus (CN) and frontal cortex (FC) using HPLC/EC. Compared with controls, marked increases in DA concentrations were observed in both regions. The DA turnover decreased significantly. The power spectra, obtained by use of a fast Fourier transformation, revealed a significant decrease in slow-wave delta frequency bands following repeated exposure to cocaine. These data are consistent with reported findings in humans that repeated exposures to cocaine result in a decrease in slow-wave brain activity. Further studies are necessary to establish whether regional alterations in blood flow and metabolic activity may underlie such observations. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. NYU, Brain Res Labs, Ctr Med, New York, NY 10016 USA. Univ Coimbra, Sch Med, Inst Farmacol & Terapeut Expt, Coimbra, Portugal. RP Binienda, ZK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132, Jefferson, AR 72079 USA. RI Alper, Kenneth/B-5676-2009; OI Pereira, Frederico/0000-0002-9381-3320 NR 18 TC 7 Z9 7 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 1-57331-408-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 965 BP 172 EP 179 PG 8 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BU83M UT WOS:000177157600014 PM 12105093 ER PT S AU Imam, SZ Newport, GD Duhart, HM Islam, F Slikker, W Ali, SF AF Imam, SZ Newport, GD Duhart, HM Islam, F Slikker, W Ali, SF BE Ali, SF TI Methamphetamine-induced dopaminergic neurotoxicity and production of peroxynitrite are potentiated in nerve growth factor differentiated pheochromocytoma 12 cells SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE II: COCAINE, SUBSTITUTED AMPHETAMINES, GHB, AND OPIATES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse II - Cocaine, Substituted Amphetamines, GHB, and Opiates CY AUG 22-24, 2001 CL MAR DEL PLATA, ARGENTINA SP Int Soc Neurochem, Natl Inst Drug Abuse, Argentinian Sectrtary State Prevent Drug Addict & Narcotraffic, Natl Univ Rosario, Sch Biomed & Pharmaceut Sci, SIGMA TAU Hlth Sci, USDA, Natl Ctr Toxicol Res DE methamphetamine; peroxynitrite; oxidative stress; nerve growth factor; dopaminergic neurotoxicity ID NITRIC-OXIDE SYNTHASE; DISMUTASE TRANSGENIC MICE; PC12 CELLS; TYROSINE-HYDROXYLASE; LIPID-PEROXIDATION; SUPEROXIDE; 7-NITROINDAZOLE; PROTECTION; NITRATION; INHIBITOR AB Methamphetamine (METH) is a widely abused psychomotor stimulant known to cause dopaminergic neurotoxicity in rodents, nonhuman primates, and humans. METH administration selectively damages the dopaminergic nerve terminals, which is hypothesized to be due to release of dopamine from synaptic vesicles within the terminals. This process is believed to be mediated by the production of free radicals. The current study evaluates METH-induced dopaminergic toxicity in pheochromocytoma 12 (PC12) cells cultured in the presence or absence of nerve growth factor (NGF). Dopaminergic changes and the formation of 3-nitrotyrosine (3-NT), a marker for peroxynitrite production, were studied in PC12 cell cultures grown in the presence or absence of NGF after different doses of METH (100-1,000 mu). METH exposure did not cause significant alterations in cell viability and did not produce significant dopaminergic changes or 3-NT production in PC12 cells grown in NGF-negative media after 24 hours. However, cell viability of PC12 cells grown in NGF-positive media was decreased by 45%, and significant dose-dependent dopaminergic alteration and 3-NT production were observed 24 hours after exposure to METH. The current study supports the hypothesis that METH acts at the dopaminergic nerve terminals and produces dopaminergic damage by the production of free radical peroxynitrite. C1 US FDA, Div Neurotoxicol, Neurochem Lab, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Jamia Hamdard Hamdard Univ, Neurotoxicol Lab, Dept Med Elementol & Toxicol, New Delhi, India. RP Ali, SF (reprint author), US FDA, Div Neurotoxicol, Neurochem Lab, Natl Ctr Toxicol Res, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 34 TC 11 Z9 12 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 1-57331-408-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 965 BP 204 EP 213 PG 10 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BU83M UT WOS:000177157600017 PM 12105096 ER PT S AU Virmani, A Gaetani, F Imam, S Binienda, Z Ali, S AF Virmani, A Gaetani, F Imam, S Binienda, Z Ali, S BE Ali, SF TI The protective role of L-carnitine against neurotoxicity evoked by drug of abuse, methamphetamine, could be related to mitochondrial dysfunction SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE II: COCAINE, SUBSTITUTED AMPHETAMINES, GHB, AND OPIATES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse II - Cocaine, Substituted Amphetamines, GHB, and Opiates CY AUG 22-24, 2001 CL MAR DEL PLATA, ARGENTINA SP Int Soc Neurochem, Natl Inst Drug Abuse, Argentinian Sectrtary State Prevent Drug Addict & Narcotraffic, Natl Univ Rosario, Sch Biomed & Pharmaceut Sci, SIGMA TAU Hlth Sci, USDA, Natl Ctr Toxicol Res DE L-carnitine; methamphetamine; neurotoxicity ID INDUCED DOPAMINERGIC NEUROTOXICITY; ACETYL-L-CARNITINE; 3-NITROPROPIONIC ACID; NEUROPROTECTIVE ROLE; PEROXYNITRITE; INHIBITOR; 7-NITROINDAZOLE; ANTIOXIDANTS; STRIATUM; RATS AB There is growing evidence that suggests that brain injury after amphetamine and methamphetamine (METH) administration is due to an increase in free radical formation and mitochondrial damage, which leads to a failure of cellular energy metabolism followed by a secondary excitotoxicity. Neuronal degeneration caused by drugs of abuse is also associated with decreased ATP synthesis. Defective mitochondrial oxidative phosphorylation and metabolic compromise also play an important role in atherogenesis, in the pathogenesis of Alzheimer's disease, Parkinson's disease, diabetes, and aging. The energy deficits in the central nervous system can lead to the generation of reactive oxygen and nitrogen species as indicated by increased activity of the free radical scavenging enzymes like catalase and superoxide dismutase. The METH-induced dopaminergic neurotoxicity may be mediated by the generation of peroxynitrite and can be protected by antioxidants selenium, melatonin, and selective nNOS inhibitor, 7-nitroindazole. L-Carnitine (LC) is well known to carry long-chain fatty acyl groups into mitochondria for beta-oxidation. It also plays a protective role in 3-nitropropioinc acid (3-NPA)-induced neurotoxicity as demonstrated in vitro and in vivo. LC has also been utilized in detoxification efforts in fatty acid-related metabolic disorders. In this study we have tested the hypothesis that enhancement of mitochondrial energy metabolism by LC could prevent the generation of peroxynitrite and free radicals produced by METH. Adult male C57BL/6N mice were divided into four groups. Group I served as control. Groups III and IV received LC (100 mg/kg, orally) for one week. Groups 11 and IV received 4 x 10 mg/kg METH i.p. at 2-h intervals after one week of LC administration. LC treatment continued for one more week to groups III and IV. One week after METH administration, mice were sacrificed by decapitation, and striatum was dissected to measure the formation of 3-nitrotyrosine (3-NT) by HPLC/Coularry system. METH treatment produced significant formation of 3-NT, a marker of peroxynitrite generation, in mice striatum. C1 Sigma Tau HealthSci, I-00040 Pomezia, Italy. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Virmani, A (reprint author), Sigma Tau HealthSci, I-00040 Pomezia, Italy. NR 21 TC 39 Z9 48 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 1-57331-408-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 965 BP 225 EP 232 PG 8 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BU83M UT WOS:000177157600019 PM 12105098 ER PT S AU Chera, B Schaecher, KE Rocchini, A Imam, SZ Ray, SK Ali, SF Banik, NL AF Chera, B Schaecher, KE Rocchini, A Imam, SZ Ray, SK Ali, SF Banik, NL BE Ali, SF TI Calpain upregulation and neuron death in spinal cord of MPTP-induced parkinsonism in mice SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE II: COCAINE, SUBSTITUTED AMPHETAMINES, GHB, AND OPIATES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse II - Cocaine, Substituted Amphetamines, GHB, and Opiates CY AUG 22-24, 2001 CL MAR DEL PLATA, ARGENTINA SP Int Soc Neurochem, Natl Inst Drug Abuse, Argentinian Sectrtary State Prevent Drug Addict & Narcotraffic, Natl Univ Rosario, Sch Biomed & Pharmaceut Sci, SIGMA TAU Hlth Sci, USDA, Natl Ctr Toxicol Res DE substantia nigra; dopaminergic neurons; apoptosis; astrocyte; motor neuron ID ACTIVATED NEUTRAL PROTEASE; SUBSTANTIA-NIGRA; DOPAMINERGIC-NEURONS; MONOAMINE-OXIDASE; HUMAN BRAIN; DISEASE; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 1-METHYL-4-PHENYL-1,2,5,6-TETRAHYDROPYRIDINE; NEUROTOXICITY; DEGENERATION AB Parkinson's disease (PD) is a neurodegenerative disorder resulting in slowness, tremors, and imbalance. Treatment of mice with 1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine (MPTP) is one of several models used to mimic PD in humans. Administration of MPTP leads to the production of 1-methyl-4-phenyl-2,3 dihydropyridinium (MPP+). MPP+ is taken up by dopaminergic neurons, causing mitochondrial dysfunction and cell death. Because calpain is involved in neuronal cell death and mitochondrial dysfunction, we examined the level of calpain in neurons in the substantia nigra (SN) and hippocampus of MPTP-treated C57BL/6 mice. Because of the interconnections between spinal cord and upper central nervous system neurons, we examined morphology, calpain activity, and calpain expression in neurons by double immunofluorescence using calpain and neuron marker (NeuN) antibodies. In controls, calpain expression was low in SN, hippocampus, and spinal cord NeuN(+) cells, and the NeuN stain was concentrated around the nucleus. In mice sacrificed 24 h after administration of three 20 mg/kg doses of MPTP, calpain expression was slightly increased in SN and hippocampal neurons and moderately increased in spinal cord neurons. In these animals, the NeuN stain was less concentrated around the nuclear membrane. One week after MPTP treatment, calpain content in NeuN(+) cells was greatly increased in SN, hippocampus, and spinal cord. Morphologically, SN and spinal cord neurons, treated for one week, were necrotic with a granular cytoplasmic NeuN content. Also, MPTP treatment upregulated calpain activity and mRNA level in spinal cord. These data suggest that following MPTP treatment, calpain causes neuronal death in SN as well as in spinal cord. C1 Med Univ S Carolina, Dept Neurol, Charleston, SC 29425 USA. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Banik, NL (reprint author), Med Univ S Carolina, Dept Neurol, POB 250606,Suite 307,96 Jonathan Lucas St, Charleston, SC 29425 USA. FU NINDS NIH HHS [NS-31622, NS-41088, NS-38146] NR 43 TC 21 Z9 22 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 1-57331-408-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 965 BP 274 EP 280 PG 7 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BU83M UT WOS:000177157600024 PM 12105103 ER PT S AU Meyer, JS Ali, SF AF Meyer, JS Ali, SF BE Ali, SF TI Serotonergic neurotoxicity of MDMA (ecstasy) in the developing rat brain SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE II: COCAINE, SUBSTITUTED AMPHETAMINES, GHB, AND OPIATES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse II - Cocaine, Substituted Amphetamines, GHB, and Opiates CY AUG 22-24, 2001 CL MAR DEL PLATA, ARGENTINA SP Int Soc Neurochem, Natl Inst Drug Abuse, Argentinian Sectrtary State Prevent Drug Addict & Narcotraffic, Natl Univ Rosario, Sch Biomed & Pharmaceut Sci, SIGMA TAU Hlth Sci, USDA, Natl Ctr Toxicol Res DE neurotoxicity; 3,4-methylenedioxymethamphetamine; MDMA; ecstasy; brain ID EXPOSURE; 3,4-METHYLENEDIOXYMETHAMPHETAMINE; NEURONS; BINDING; DRUG AB The abused drug 3,4-methylenedioxymethamphetamine (MDMA) damages fine serotonergic fibers and nerve terminals in adult organisms; however, developing animals seem less susceptible to this effect. One proposed hypothesis is that neonates are less sensitive to MDMA neurotoxicity because they fail to show drug-induced hyperthermia. We tested this hypothesis by producing hyperthermia in neonatal rats for 2 hours after each of twice-daily MDMA (10 mg/kg sc) or saline injections given over the period from postnatal day (PD) 1 to 4. Other drug-treated and control litters were maintained at normothermic temperatures after injection. Differential core body temperatures were achieved by placing pups (without the dam) in humidified, thermostatically controlled incubators. Temperatures were monitored with a thermocouple probe at 30-minute intervals. Pups subsequently remained undisturbed until sacrifice at PD 25 and PD 60 for assessment of serotonergic damage by measuring 5-HT transporter (SERT) binding in the hippocampus and neocortex as well as 5-HT and 5-HIAA concentrations (PD 25 only). Neonatal MDMA exposure led to significant reductions in both SERT binding and 5-HT levels in the hippocampus at PD 25, independent of body temperature during treatment. Hippocampal SERT binding increased between PD 25 and PD 60 in both the MDMA and saline groups, but the MDMA-related deficit remained unchanged. Interestingly, the neocortex showed no effect of MDMA at PD 25, but SERT binding was significantly reduced at PD 60. Thus, MDMA can exert serotonergic neurotoxicity in developing animals in the absence of elevated body temperature. Hippocampal serotonergic innervation is damaged early, whereas neocortical effects emerge at a later time. Furthermore, the tendency for serotonergic recovery may be less after neonatal MDMA exposure than exposure of adult animals. C1 Univ Massachusetts, Dept Psychol, Neurosci & Behav Program, Amherst, MA 01003 USA. Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Meyer, JS (reprint author), Univ Massachusetts, Dept Psychol, Neurosci & Behav Program, Tobin Hall, Amherst, MA 01003 USA. OI Meyer, Jerrold/0000-0002-8382-7075 NR 22 TC 21 Z9 21 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 1-57331-408-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 965 BP 373 EP 380 PG 8 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BU83M UT WOS:000177157600034 PM 12105113 ER PT S AU Gough, B Imam, SZ Blough, B Slikker, W Ali, SF AF Gough, B Imam, SZ Blough, B Slikker, W Ali, SF BE Ali, SF TI Comparative effects of substituted amphetamines (PMA, MDMA, and METH) on monoamines in rat caudate - A microdialysis study SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE II: COCAINE, SUBSTITUTED AMPHETAMINES, GHB, AND OPIATES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse II - Cocaine, Substituted Amphetamines, GHB, and Opiates CY AUG 22-24, 2001 CL MAR DEL PLATA, ARGENTINA SP Int Soc Neurochem, Natl Inst Drug Abuse, Argentinian Sectrtary State Prevent Drug Addict & Narcotraffic, Natl Univ Rosario, Sch Biomed & Pharmaceut Sci, SIGMA TAU Hlth Sci, USDA, Natl Ctr Toxicol Res DE paramethoxyamphetamine; MDMA; monoamine; caudate nucleus; microdialysis ID 3,4-METHYLENEDIOXYMETHAMPHETAMINE MDMA; ANALOGS; HYPERTHERMIA; FATALITIES; ECSTASY; RELEASE AB Paramethoxyamphetamine (PMA) is a metboxylated phenethylamine derivative that has been used illicitly in Australia since 1994. PMA is also becoming popular at rave parties in the United States. PMA raised concern when a series of fatalities resulted after its use in South Australia, where it was marketed as "ecstasy," which is the colloquial name for MDMA. In the present study, we evaluated the comparative neurotoxicity of substituted amphetamines in rats. Extracellular levels of dopamine (DA), 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), serotonin (5-HT), and 5-hydroxyindoleacetic acid (5-HIAA) were assayed in the caudate of freely moving rats using microdialysis and HPLC-EC. Dialysates were assayed every 20 minutes for 4 hours after an intraperitoneal (i.p.) injection of PMA (2.5, 5, 10, 20 mg/kg), MDMA (10 and 20 mg/kg), or METH (2.5 mg/kg). METH produced a significant increase in extracellular DA (700%), and significant decreases in extracellular DOPAC and HVA (30% and 50%), with no detectable changes in either 5-HT or 5-HIAA. MDMA produced significant increases in DA (700% at 10 mg/kg and 950% at 20 mg/kg) and decreases in DOPAC (15% for both 10 and 20 mg/kg), and HVA (50% at 10 mg/kg and 35% at 20 mg/kg). MDMA also increased 5-HT (350% at 10, and 575% at 20 mg/kg), and decreased 5-HIAA to 60% for both dose levels. PMA produced no detectable increases in DA at dose levels of 2.5, 5, or 10 mg/kg, but significantly increased DA (975%) at a dose of 20 mg/kg. However, PMA significantly decreased DOPAC at all dose levels (75% at 2.5; 40% at 5; 30% at 10; 10% at 20 mg/kg), with comparable decreases in HVA at all dose levels. PMA also produced significant increases in 5-HT at 10 and 20 mg/kg (350% for both dose levels), with no detectable changes in 5-HT at 2.5 or 5 mg/kg. All dose levels of PMA significantly decreased 5-HIAA (50 to 70%). These data suggest that PMA, like MDMA and METH, is capable of producing dopaminergic and serotonergic neurotoxicity. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Res Triangle Inst, Res Triangle Pk, NC 27709 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, 3900 NCTR Rd,HFT-132, Jefferson, AR 72079 USA. NR 21 TC 37 Z9 37 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 1-57331-408-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 965 BP 410 EP 420 PG 11 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BU83M UT WOS:000177157600037 PM 12105116 ER PT S AU Itzhak, Y Ali, SF AF Itzhak, Y Ali, SF BE Ali, SF TI Repeated administration of gamma-hydroxybutyric acid (GHB) to mice - Assessment of the sedative and rewarding effects of GHB SO CELLULAR AND MOLECULAR MECHANISMS OF DRUGS OF ABUSE II: COCAINE, SUBSTITUTED AMPHETAMINES, GHB, AND OPIATES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Cellular and Molecular Mechanisms of Drugs of Abuse II - Cocaine, Substituted Amphetamines, GHB, and Opiates CY AUG 22-24, 2001 CL MAR DEL PLATA, ARGENTINA SP Int Soc Neurochem, Natl Inst Drug Abuse, Argentinian Sectrtary State Prevent Drug Addict & Narcotraffic, Natl Univ Rosario, Sch Biomed & Pharmaceut Sci, SIGMA TAU Hlth Sci, USDA, Natl Ctr Toxicol Res DE gamma-hydroxybuturic acid; GHB; brain; drug abuse; hypolocomotion; reward ID QUANTITATIVE AUTORADIOGRAPHY; PLACE PREFERENCE; BINDING-SITES; RAT-BRAIN; ABUSE; DRUG; BUTYROLACTONE; 7-NITROINDAZOLE; WITHDRAWAL; RECEPTORS AB Because of the sedative/hypnotic and euphoric effects of gamma-hydroxybutyric acid (GHB), the recreational use of the drug has increased significantly. In the current study we investigated the sedative and rewarding effects of GHB in Swiss Webster mice. Although the acute administration of GHB (200 mg/kg) caused marked hypolocomotion, repeated administration of the drug for 6 or 14 days produced tolerance to this effect. In addition, the administration of GHB 300 mg/kg to naive mice caused catalepsy, which dissipated in mice pre-exposed to GHB (200 mg/kg). Consequently, after repeated treatment with GHB, tolerance developed to both the hypolocomotion and cataleptic effects of the drug. The administration of GHB or its precursor gamma-butyrolactone for 14 days increased the striatal content of dopamine. The sedative effects of GHB may be due to hypodopaminergic activity from inhibition of dopamine release and a subsequent increase in the intraneuronal dopamine level. The rewarding effect of GHB was assessed in the conditioned place preference paradigm. Mice treated repeatedly with 250 mg/kg for 7 days developed conditioned preference for the GHB-paired compartment of the cage, suggesting that the GHB; cue is rewarding. The development of tolerance to the sedative effects of GHB coupled with the rewarding properties of the drug support the abuse potential of GHB. Further studies are necessary to determine the mechanism underlying the development of tolerance to GHB and the rewarding effect of the drug. C1 Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL 33136 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Psychiat & Behav Sci, 1011 NW 15 St,Gautier Bldg,Room 503, Miami, FL 33136 USA. FU NIDA NIH HHS [R01DA08584, DA12867] NR 38 TC 45 Z9 45 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 1-57331-408-0 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 965 BP 451 EP 460 PG 10 WC Cell Biology; Multidisciplinary Sciences; Neurosciences; Pharmacology & Pharmacy SC Cell Biology; Science & Technology - Other Topics; Neurosciences & Neurology; Pharmacology & Pharmacy GA BU83M UT WOS:000177157600041 PM 12105120 ER PT B AU Martin, RL AF Martin, RL GP AWWA AWWA TI International symposium on chlorine dioxide fourth international symposium SO CHLORINE DIOXIDE: THE STATE OF SCIENCE, REGULATORY, ENVIRONMENTAL ISSUES, AND CASE HISTORIES LA English DT Proceedings Paper CT 4th International Symposium on Chlorine Dioxide CY FEB 15-16, 2001 CL LAS VEGAS, NV SP Amer Chem Council, Sodium Chlorite Clorine Dioxide Panel, Awwa Res Fdn AB Since 1995, chlorine dioxide have been approved by FDA for a number of new food uses. The complete regulatory history of chlorine dioxide will be presented. The regulatory process will be discussed as well as several new interventions that FDA has employed since 1995 to speed up the review and approval of additives such as chlorine dioxide. Included in this discussion will be information on our expedited review process, food contact notifications and GRAS notifications. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Premarket Approval, Washington, DC 20204 USA. RP Martin, RL (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Premarket Approval, 200 C St SW, Washington, DC 20204 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU AMER WATER WORKS ASSOC PI DENVER PA 6666 WEST QUINCY AVE, DENVER, CO 80235 USA BN 1-58321-180-2 PY 2002 BP 27 EP 33 PG 7 WC Environmental Sciences; Water Resources SC Environmental Sciences & Ecology; Water Resources GA BV99Y UT WOS:000180629400003 ER PT J AU Kawakami, K Kawakami, M Leland, P Puri, RK AF Kawakami, K Kawakami, M Leland, P Puri, RK TI Internalization property of interleukin-4 receptor a chain increases cytotoxic effect of interleukin-4 receptor-targeted cytotoxin in cancer cells SO CLINICAL CANCER RESEARCH LA English DT Article ID CIRCULARLY PERMUTED INTERLEUKIN-4; BREAST-CARCINOMA CELLS; COMMON GAMMA-CHAIN; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; KAPOSIS-SARCOMA; CYTOSINE DEAMINASE; RECOMBINANT TOXINS; MALIGNANT-CELLS; ALPHA CHAIN AB Although the receptor for interleukin-4 (IL-4R) is highly expressed on solid human cancer cells, its significance and internalization function is still unclear. To address these issues, we reconstituted Chinese hamster ovarian (CHO-K1) cells with various components of the IL-4R by transient transfection and performed internalization assays using radiolabeled IL-4. Radiolabeled IL-4 internalized through the IL-4Ralpha chain in a time-dependent manner. When the IL-4Ralpha chain was cotransfected with the IL-13Ralpha1 or -gamma(c) chain, the IL-4 internalization level was identical to IL-4Ralpha transfectants, suggesting that the IL-4Ralpha chain plays a major role in IL-4 internalization. These results were confirmed by determining the cytotoxicity of a chimeric protein composed of IL-4 and a mutated form of Pseudomonas exotoxin [IL4(38-37)-PE38KDEL] in CHO-K1 cells transfected with increasing concentrations of IL-4Ralpha cDNA. To use the internalization property of the IL-4Ralpha chain in the context of IL-4R-targeted cytotoxin therapy, we transiently transfected pancreatic and brain tumor cells with IL-4Ralpha chain. Surprisingly, these tumor cells acquired 4-75-fold higher binding activity to IL-4 compared with control cells. Consequently, the cytotoxic activity of IL-4 toxin to these cancer cells was enhanced 5-13-fold compared with control cells as assessed by protein synthesis inhibition and clonogenic assays. Taken together, a combination approach that involves transfer of the IL-4Ra, gene and IL-4R-targeted cytotoxin therapy may serve as a novel approach for cancer therapy. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 59 TC 14 Z9 15 U1 1 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 2002 VL 8 IS 1 BP 258 EP 266 PG 9 WC Oncology SC Oncology GA 515WM UT WOS:000173519700037 PM 11801567 ER PT J AU Strome, SE Kawakami, K Alejandro, D Voss, S Kasperbauer, JL Salomao, D Chen, LP Maki, RA Puri, RK AF Strome, SE Kawakami, K Alejandro, D Voss, S Kasperbauer, JL Salomao, D Chen, LP Maki, RA Puri, RK TI Interleukin 4 receptor-directed cytotoxin therapy for human head and neck squamous cell carcinoma in animal models SO CLINICAL CANCER RESEARCH LA English DT Article ID IN-VIVO; PSEUDOMONAS EXOTOXIN; ANTITUMOR-ACTIVITY; TOXIN; RECURRENT; CISPLATIN; INDUCTION; APOPTOSIS; 4-TOXIN; PROTEIN AB Receptors for interleukin 4 (IL-4R) are overexpressed on the surface of various human solid tumors including renal cell carcinoma, glioblastoma, Kaposi's sarcoma, and head and neck squamous cell carcinoma (SCCHN). On the basis of this preferential receptor overexpression, a novel IL-4R-targeted cytotoxin, IL-4 (38-37)-PE38KDEL, was developed in which circularly permuted IL-4 [IL-4 (38-37)] was fused to mutated form of Pseudomonas exotoxin (PE38KDEL). Despite the recognized expression of the IL-4R on SSCHN, the utility of a receptor-specific fusion protein for the treatment of this disease remains unknown. The purpose of this study was to establish the utility of IL-4 (38-37)-PE38KDEL for the treatment of established SSCHN in animal models of human disease. Expression of IL-4R in SCCHN was confirmed by immunohistochemistry with eight of eight tissue sections expressing IL-4R. Protein synthesis inhibition assays demonstrated growth inhibition of two cell lines in IL-4 (38-37)-PE38KDEL in a dose-dependent fashion. In two SCCHN s.c. xenografted nude mouse models, i.p. and intratumoral injection of IL-4 (38-37)-PE38KDEL mediated tumor regression with no visual toxicity observed in any of the animals. Subcultured tumor cells after intratumoral treatment with IL-4 toxin did not develop resistance to the drug. These data demonstrate that IL-4 (38-37)-PE38KDEL is effective in mediating significant antitumor effects in SCCHN and may represent an attractive therapeutic option for patients with advanced cancers of the upper aerodigestive tract. C1 Mayo Clin & Mayo Fdn, Dept Otolaryngol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Immunol, Rochester, MN 55905 USA. Mayo Clin & Mayo Fdn, Dept Pathol, Rochester, MN 55905 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. Neurocrine Biosci, San Diego, CA 92121 USA. RP Strome, SE (reprint author), Mayo Clin & Mayo Fdn, Dept Otolaryngol, 200 1st St SW, Rochester, MN 55905 USA. FU NIDCR NIH HHS [K23 DE 00459-2] NR 19 TC 21 Z9 22 U1 0 U2 0 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 2002 VL 8 IS 1 BP 281 EP 286 PG 6 WC Oncology SC Oncology GA 515WM UT WOS:000173519700040 PM 11801570 ER PT J AU Toerner, JG Cvetkovich, T AF Toerner, JG Cvetkovich, T TI Kawasaki-like syndrome: Abacavir hypersensitivity? SO CLINICAL INFECTIOUS DISEASES LA English DT Letter ID JAPAN C1 US FDA, Div Antiviral Drug Prod, Rockville, MD 20850 USA. RP Toerner, JG (reprint author), US FDA, Div Antiviral Drug Prod, HFD-530,9201 Corp Blvd, Rockville, MD 20850 USA. NR 6 TC 3 Z9 3 U1 1 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 1427 E 60TH ST, CHICAGO, IL 60637-2954 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN 1 PY 2002 VL 34 IS 1 BP 131 EP 132 DI 10.1086/324094 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 498ZM UT WOS:000172543800032 PM 11731962 ER PT J AU Marroum, PJ Gobburu, J AF Marroum, PJ Gobburu, J TI The product label - How pharmacokinetics and pharmacodynamics reach the prescriber SO CLINICAL PHARMACOKINETICS LA English DT Review ID DRUG AB The product label, or package insert, is the 'manual' for the safe and effective use of a drug. Important pharmacokinetic and pharmacodynamic properties of a drug product should appear in the label under specific sections, as required in the Code of Federal Regulations (CFR), using a format and language recommended by the Food and Drug Administration (FDA) in various guidances to the industry. The relevant regulations and guidance documents impacting on how this information is conveyed to the healthcare professional are discussed, with special emphasis on how the new proposed rule will impact upon how information is to be conveyed. With the availability of new clinical pharmacology information not available at the time of approval, package inserts for older drugs should be updated to reflect the new data and recommend the proper dosage regimen, enabling prescribers to optimise drug therapy and minimise possible adverse events. C1 US FDA, Ctr Drug Evaluat & Res, OPS, OCPB,DPE1, Rockville, MD 20857 USA. RP Marroum, PJ (reprint author), US FDA, Ctr Drug Evaluat & Res, OPS, OCPB,DPE1, HFD 860,5600 Fishers Lane,Woodmont 2 Bldg,Room 50, Rockville, MD 20857 USA. NR 16 TC 14 Z9 15 U1 0 U2 2 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2002 VL 41 IS 3 BP 161 EP 169 DI 10.2165/00003088-200241030-00001 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 543ZK UT WOS:000175133600001 PM 11929317 ER PT J AU Ball, R Schwartz, SL AF Ball, R Schwartz, SL TI Kinetic and dynamic models of diving gases in decompression sickness prevention SO CLINICAL PHARMACOKINETICS LA English DT Review ID BUBBLE EVOLUTION; INERT-GAS; BREATHING GAS; OXYGEN; BLOOD; RISK; AIR; LIKELIHOOD; ILLNESS; HUMANS AB Decompression sickness is a complex phenomenon involving gas exchange, bubble dynamics and tissue response. Relatively simple deterministic compartmental models using empirically derived parameters have been the mainstay of the practice for preventing decompression sickness since the early 1900s. Decades of research have improved our understanding of decompression physiology, and the insights incorporated in decompression models have allowed people to dive deeper into the ocean. However, these efforts have not yet, and are unlikely in the near future, to result in a 'universal' deterministic model that can predict when decompression sickness will occur. Divers using current recreational dive computers need to be aware of their limitations. Probabilistic models based on the estimation of parameters using modern statistical methods from large databases of dives offer a new approach and can provide a means of standardisation of deterministic models. Future improvements in decompression practice will depend on continued improvement in understanding the kinetics and dynamics of gas exchange, bubble evolution and tissue response, and the incorporation of this knowledge in risk models whose parameters can be estimated from large databases of human and animal data. C1 USN, Med Res Inst, Decompress Program, Diving & Environm Physiol Dept, Bethesda, MD USA. Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. Int Ctr Toxicol & Med, Rockville, MD USA. RP Ball, R (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, HFM-220, Rockville, MD 20852 USA. NR 75 TC 7 Z9 9 U1 0 U2 1 PU ADIS INTERNATIONAL LTD PI AUCKLAND PA 41 CENTORIAN DR, PRIVATE BAG 65901, MAIRANGI BAY, AUCKLAND 10, NEW ZEALAND SN 0312-5963 J9 CLIN PHARMACOKINET JI Clin. Pharmacokinet. PY 2002 VL 41 IS 6 BP 389 EP 402 DI 10.2165/00003088-200241060-00001 PG 14 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 573PG UT WOS:000176839600001 PM 12074688 ER PT J AU Rosebraugh, CJ Honig, PK Yasuda, SU Pezzullo, JC Woosley, RL AF Rosebraugh, CJ Honig, PK Yasuda, SU Pezzullo, JC Woosley, RL TI Centers for education and research on therapeutics report: Survey of medication errors education during undergraduate and graduate medical education in the United States SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID ADVERSE DRUG EVENTS; CLINICAL-PHARMACOLOGY; HOSPITALIZED-PATIENTS; CORE CURRICULUM; MORTALITY; DISCOVERY; PROGRAMS; STUDENTS; ILLNESS C1 US FDA, Rockville, MD 20857 USA. Georgetown Univ, Dept Pharmacol, Washington, DC USA. Univ Arizona, Coll Med, Tucson, AZ USA. RP Rosebraugh, CJ (reprint author), US FDA, Rm 10B-45,HFD-570,5600 Fishers Lane, Rockville, MD 20857 USA. OI Woosley, Raymond L./0000-0002-2588-328X FU AHRQ HHS [U18HS10385]; NIGMS NIH HHS [T32 GM008386] NR 33 TC 19 Z9 19 U1 0 U2 1 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 JAN PY 2002 VL 71 IS 1 BP 4 EP 10 DI 10.1067/mcp.2002.120676 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 520FN UT WOS:000173770500002 PM 11823752 ER PT J AU Brinker, A Beitz, J AF Brinker, A Beitz, J TI Use of a spontaneous adverse drug events database for identification of unanticipated drug benefits SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Article ID ANGIOGENESIS; STATINS AB We describe an examination of a spontaneous adverse events database in an effort to identify agents with possible hitherto unknown antiangiogenic properties. The surrogate end point was abnormal wound healing. This analysis represents use of this database for identification of a possibly useful in vivo side effect. Through thoughtful choice of end points, we believe spontaneous adverse events databases have the capacity for hypothesis generation in a search for unanticipated beneficial drug properties. C1 US FDA, Ctr Drug Evaluat & Res, Off Postmkt Drug Risk Assessment, Rockville, MD 20857 USA. RP Brinker, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Postmkt Drug Risk Assessment, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 16 TC 12 Z9 12 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 JAN PY 2002 VL 71 IS 1 BP 99 EP 102 DI 10.1067/mcp.2002.120677 PG 4 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 520FN UT WOS:000173770500012 PM 11823762 ER PT J AU Blodgett, RJ AF Blodgett, RJ TI Measuring improbability of outcomes from a serial dilution test SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE MPN; most probable number; improb; crossover; designated interval; rarity AB This article introduces a max, designated, and MPN measure of the rarity of an outcome for serial dilution tests. All three measures divide the likelihood of the specified outcome at its MPN by the likelihood of an outcome with the same design. The max measure divides by. the maximum of the likelihood at their MPN of all outcomes with the same number of positive tubes. The designated measure divides by the likelihood of an outcome that maximizes over a single dilution at a time. The MPN measure divides by the largest likelihood of any outcome at the MPN of the specified outcome. These new measures appear to agree well with improb and are much easier to compute. C1 US FDA, College Pk, MD 20740 USA. NR 11 TC 6 Z9 7 U1 0 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0926 J9 COMMUN STAT-THEOR M JI Commun. Stat.-Theory Methods PY 2002 VL 31 IS 12 BP 2209 EP 2223 DI 10.1081/STA-120017222 PG 15 WC Statistics & Probability SC Mathematics GA 627XR UT WOS:000179962400008 ER PT J AU Zheng, Q AF Zheng, Q TI Computing relations between moments and cumulants SO COMPUTATIONAL STATISTICS LA English DT Article DE symbolic computing; rewrite rule; Kendall's operator; cumulant; moment AB It is sometimes desirable to have easily accessible formulae expressing moments in terms of cumulants and vice versa. This paper offers a Mathematica implementation of two methods for generating such formulae, a method based on Kendall's operator and an elementary method of equating coefficients of generating functions. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Zheng, Q (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 7 TC 1 Z9 1 U1 0 U2 1 PU PHYSICA-VERLAG GMBH & CO PI HEIDELBERG PA TIERGARTENSTRASSE 17, 69121 HEIDELBERG, GERMANY SN 0943-4062 J9 COMPUTATION STAT JI Comput. Stat. PY 2002 VL 17 IS 4 BP 507 EP 515 DI 10.1007/s001800200123 PG 9 WC Statistics & Probability SC Mathematics GA 626MV UT WOS:000179877500005 ER PT J AU Jordan, A AF Jordan, A TI Toxicology of progestogens of implantable contraceptives for women SO CONTRACEPTION LA English DT Article DE progestogen; implant; contraception; levonorgestrel; etonogestrel; nestorone; nomegestrol acetate; toxicology ID NOMEGESTROL ACETATE; CLINICAL-TRIAL; BREAST-CANCER; LIPOPROTEINS; PROGESTERONE; ESTRADIOL; UNIPLANT; RECEPTOR; STEROIDS; CELLS AB There are currently four progestogens used in implantable contraceptives marketed or tested in clinical trials: levonorgestrel in Norplant and Jadelle, etonogestrel (3-keto-desogestrel) in Implanon, nestorone in Elcometrine, and nomegestrol acetate in Uniplant and Surplant, Each progestogen was evaluated for hormonal activity and for safety in a wide variety of tests in vitro and in animals prior to their use in women. All four progestogens underwent pre-clinical testing that generally followed the formal for animal testing of steroidal contraceptives published by the World Health Organization and the US Food and Drug Administration (FDA) [1]. Most of the progestogens have been tested for genotoxicity in bacterial and mammalian cultured cells and in rodents. All were tested for toxicity in short- and long-term toxicology studies in rodents and dogs or monkeys, and all were tested for their effects on reproduction and fetal development. In most cases. the progestogens were tested for carcinogenicity in two rodent species, rats and mice. Early clinical trials in small numbers of women provided additional safety data prior to the exposure of large numbers of women in Phase 3 clinical trials. The published data and data submitted to the FDA demonstrate that the implantable progestogens have no significant or unusual toxicities and have a similar safety profile to the progestogens found in the approved oral contraceptives. (C) 2002 Elsevier Science Inc. All rights reserved. C1 Ctr Drug Evaluat & Res, Div Reprod & Urol Drug Prod, Food & Drug Adm, Rockville, MD USA. RP Jordan, A (reprint author), Ctr Drug Evaluat & Res, Div Reprod & Urol Drug Prod, Food & Drug Adm, Rockville, MD USA. NR 33 TC 13 Z9 15 U1 1 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0010-7824 J9 CONTRACEPTION JI Contraception PD JAN PY 2002 VL 65 IS 1 BP 3 EP 8 AR PII S0010-7824(02)00283-9 DI 10.1016/S0010-7824(01)00283-9 PG 6 WC Obstetrics & Gynecology SC Obstetrics & Gynecology GA 526PE UT WOS:000174138200002 PM 11861049 ER PT J AU Weinberg, WC Denning, MF AF Weinberg, WC Denning, MF TI p21(waf1) control of epithelial cell cycle and cell fate SO CRITICAL REVIEWS IN ORAL BIOLOGY & MEDICINE LA English DT Review DE p21(WAF1); cell cycle; keratinocytes; cyclin-dependent kinase; cell transformation ID DEPENDENT KINASE INHIBITOR; GROWTH-FACTOR-BETA; SQUAMOUS CARCINOMA-CELLS; FAS-MEDIATED APOPTOSIS; PCNA BINDING DOMAINS; HUMAN-MELANOMA CELLS; NF-KAPPA-B; TERMINAL DIFFERENTIATION; HUMAN KERATINOCYTES; SKIN CARCINOGENESIS AB As a broad-acting cyclin-dependent kinase inhibitor, p21(WAF1) occupies a central position in the cell cycle regulation of self-renewing tissues such as oral mucosa and skin. In addition to regulating normal cell cycle progression decisions, p21(WAF1) integrates genotoxic insults into growth arrest and apoptotic signaling pathways that ultimately determine cell fate. As a result of its complex interactions with cell cycle machinery and response to mutagenic agents, p21(WAF1) also has stage-specific roles in epithelial carcinogenesis. Finally, a view is emerging of p21(WAF1) as not merely a cyclin-dependent kinase inhibitor, but also as a direct participant in regulating genes involved in growth arrest, senescence, and aging, thus providing an additional layer of control over matters of the cell cycle. This review discusses these various roles played by p21(WAF1) in cell cycle control, and attempts to relate these to epithelial cell biology, with special emphasis on keratinocytes. (Abbreviations used include the following: Brdu, 5-Bromo-2'-deoxyuridine; cdk, cyclin-dependent kinase; EGF, epidermal growth factor; KIP, kinase inhibitor protein; PCNA, proliferating cell nuclear antigen; and TPA, 12-O-tetradecanoylphorbol-13-acetate.) C1 US FDA, CBER, DMA, Immunobiol Lab, Bethesda, MD 20892 USA. Loyola Univ, Med Ctr, Dept Pathol, Maywood, IL 60153 USA. Loyola Univ, Med Ctr, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. RP Weinberg, WC (reprint author), US FDA, CBER, DMA, Immunobiol Lab, 29 Lincoln Dr,NIH Bldg 29B,Room 3NN04,HFM-564, Bethesda, MD 20892 USA. RI Weinberg, Wendy/A-8920-2009 NR 142 TC 106 Z9 115 U1 0 U2 4 PU INT AMER ASSOC DENTAL RESEARCHI A D R/A A D R PI ALEXANDRIA PA 1619 DUKE ST, ALEXANDRIA, VA 22314-3406 USA SN 1045-4411 J9 CRIT REV ORAL BIOL M JI Crit. Rev. Oral Biol. Med. PY 2002 VL 13 IS 6 BP 453 EP 464 PG 12 WC Dentistry, Oral Surgery & Medicine SC Dentistry, Oral Surgery & Medicine GA 677PC UT WOS:000182815900001 PM 12499239 ER PT J AU Marti, G Abbasi, F Paweletz, C Zenger, V Caporaso, N Petricoin, E AF Marti, G Abbasi, F Paweletz, C Zenger, V Caporaso, N Petricoin, E TI B cell purification: Rossette negative selection for kappa/lambda, PCR and SELDI analysis SO CYTOMETRY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PY 2002 SU 11 BP 104 EP 104 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 544VM UT WOS:000175182400257 ER PT J AU Marti, G Luning, M Dreyfuss, R Zenger, VE Stetler-Stevenson, M Rick, ME AF Marti, G Luning, M Dreyfuss, R Zenger, VE Stetler-Stevenson, M Rick, ME TI Morphometric image analysis in CLL SO CYTOMETRY LA English DT Meeting Abstract C1 US FDA, CBER, Rockville, MD 20857 USA. Gustavus Adolphus Coll, St Peter, MN 56082 USA. NCI, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PY 2002 SU 11 BP 107 EP 107 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 544VM UT WOS:000175182400267 ER PT J AU Vogt, RF Marti, G Gaigalas, A AF Vogt, RF Marti, G Gaigalas, A TI Standard reference materials and NCCLS guidelines for quantitative fluorescence calibration SO CYTOMETRY LA English DT Meeting Abstract C1 Ctr Dis Control, Atlanta, GA 30333 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0196-4763 J9 CYTOMETRY JI Cytometry PY 2002 SU 11 BP 122 EP 122 PG 1 WC Biochemical Research Methods; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 544VM UT WOS:000175182400313 ER PT J AU Keane-Moore, M Coder, D Marti, G AF Keane-Moore, M Coder, D Marti, G TI Public Meeting and Workshop on 'Safety issues pertaining to the clinical application of flow cytometry to human-derived cells' SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT 3rd Biannual Conference on Applications of Flow Cytometry in Blood and Marrow Stem Cell Transplantation CY JUN, 2001 CL QUEBEC CITY, CANADA ID TRANSPLANTATION C1 US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Cellular & Gene Therapy, Bethesda, MD 20892 USA. Int Soc Analyt Cytol, Chair Biosafety Issues Surveillance Comm, Seattle, WA USA. RP Keane-Moore, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Cellular & Gene Therapy, Bethesda, MD 20892 USA. NR 4 TC 5 Z9 5 U1 0 U2 0 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2002 VL 4 IS 1 BP 89 EP 90 DI 10.1080/146532402317251590 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 541MJ UT WOS:000174988100011 PM 11953048 ER PT J AU Marti, GE Zenger, VE Vogt, R Gaigalas, A AF Marti, GE Zenger, VE Vogt, R Gaigalas, A TI Quantitative flow cytometry: history, practice, theory, consensus, inter-laboratory variation and present status SO CYTOTHERAPY LA English DT Article; Proceedings Paper CT 3rd Biannual Conference on Applications of Flow Cytometry in Blood and Marrow Stem Cell Transplantation CY JUN, 2001 CL QUEBEC CITY, CANADA ID FLUORESCENCE CALIBRATION C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Ctr Dis Control & Prevent, Atlanta, GA USA. Natl Inst Stand & Technol, Washington, DC USA. RP Marti, GE (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 8 TC 7 Z9 7 U1 0 U2 5 PU TAYLOR & FRANCIS AS PI OSLO PA CORT ADELERSGT 17, PO BOX 2562, SOLLI, 0202 OSLO, NORWAY SN 1465-3249 J9 CYTOTHERAPY JI Cytotherapy PY 2002 VL 4 IS 1 BP 97 EP 98 DI 10.1080/146532402317251626 PG 2 WC Cell & Tissue Engineering; Biotechnology & Applied Microbiology; Cell Biology; Hematology; Medicine, Research & Experimental SC Cell Biology; Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine GA 541MJ UT WOS:000174988100014 PM 11953051 ER PT J AU Lawrence, J AF Lawrence, J TI Designing group sequential trials with survival endpoints SO DRUG INFORMATION JOURNAL LA English DT Article DE interim analysis; sequential monitoring; sample size estimation; time-dependent rates; G-rho family AB This paper discusses an algorithm to calculate information about the trial that is needed at the design stage implemented as an S-plus function. The function allows the user to specify arbitrary length of accrual, control, and treatment survival distributions; number and timing of interim analyses; stopping boundaries or an alpha-spending function; and which member of the Harrington-Fleming G class of statistics it is. Three examples from real treatment protocols are presented. C1 US FDA, Div Biometr 1, Rockville, MD 20852 USA. RP Lawrence, J (reprint author), US FDA, Div Biometr 1, HFD-710,Room 2030,Woodmont 2,1451 Rockville Pike, Rockville, MD 20852 USA. NR 6 TC 0 Z9 0 U1 0 U2 1 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 2002 VL 36 IS 1 BP 9 EP 15 PG 7 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 528XB UT WOS:000174269100004 ER PT J AU Lawrence, J AF Lawrence, J TI Analysis of combination trials with no placebo arm SO DRUG INFORMATION JOURNAL LA English DT Article DE active control studies; factorial trial AB When two drug products are combined together the traditional design of a trial to investigate the efficacy of the combination product usually, includes four arms: a placebo arm, both monotherapy arms, and the combination arm. For ethical reasons, it is sometimes not possible to include a placebo arm in the study when one drug has already been shown to be effective. In this article, we will specifically look at the case when drug A has already been shown to have a mortality effect relative to placebo from an historical study. A new drug is believed to have a similar effect to drug A, and the effect of the combination of the two drugs is believed to be more effective than drug A alone. A clinical trial is designed with three arms to show these conclusions, but no placebo arm is present. C1 US FDA, Div Biometr 1, Rockville, MD 20852 USA. RP Lawrence, J (reprint author), US FDA, Div Biometr 1, HFD-710 Room 2030,Woodmont 2,1451 Rockville Pike, Rockville, MD 20852 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI FORT WASHINGTON PA 501 OFFICE CENTER DR, STE 450, FORT WASHINGTON, PA 19034-3212 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 2002 VL 36 IS 1 BP 151 EP 156 PG 6 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 528XB UT WOS:000174269100019 ER PT J AU Myers, MJ Farrell, DE Howard, KD Kawalek, JC AF Myers, MJ Farrell, DE Howard, KD Kawalek, JC TI Pig and minipig cytochromes P450 - Response SO DRUG METABOLISM AND DISPOSITION LA English DT Letter ID HEPATOCYTES; CULTURES; ENZYME; LIVER C1 US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA. RP Myers, MJ (reprint author), US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA. NR 13 TC 1 Z9 1 U1 0 U2 3 PU AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0090-9556 J9 DRUG METAB DISPOS JI Drug Metab. Dispos. PD JAN PY 2002 VL 30 IS 1 BP 101 EP 102 PG 2 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 505PU UT WOS:000172925400017 ER PT J AU Kadlubar, FF Minchin, RF Teitel, CH Turesky, RJ Ilett, KF AF Kadlubar, FF Minchin, RF Teitel, CH Turesky, RJ Ilett, KF TI ATP-dependent kinase-catalyzed activation of N-hydroxy hetero-cyclic amines SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 11th North-American-International-Society-for-the-Study-of-Xenobiotics Meeting CY OCT 27-31, 2002 CL ORLANDO, FLORIDA SP N Amer Int Soc Study Xenobiot C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Western Australia, Dept Pharmacol, Perth, WA 6009, Australia. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2002 VL 34 SU 1 MA 53 BP 27 EP 27 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 609WC UT WOS:000178927200053 ER PT J AU Myers, MJ AF Myers, MJ TI Human, pig and minipig cytochrome P450: Why men are not pigs are not minipigs SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 11th North-American-International-Society-for-the-Study-of-Xenobiotics Meeting CY OCT 27-31, 2002 CL ORLANDO, FLORIDA SP N Amer Int Soc Study Xenobiot C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2002 VL 34 SU 1 MA 83 BP 42 EP 42 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 609WC UT WOS:000178927200083 ER PT J AU King, RS Jha, G Churchwell, MI Doerge, DR AF King, RS Jha, G Churchwell, MI Doerge, DR TI Metabolism of the heterocyclic amine 2-amino-alpha-carboline SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 11th North-American-International-Society-for-the-Study-of-Xenobiotics Meeting CY OCT 27-31, 2002 CL ORLANDO, FLORIDA SP N Amer Int Soc Study Xenobiot C1 Univ Rhode Isl, Dept Biomed Sci, Kingston, RI 02881 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2002 VL 34 SU 1 MA 190 BP 95 EP 95 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 609WC UT WOS:000178927200190 ER PT J AU Kawalek, JC Farrell, DE Howard, KD Derr, JA Cope, CV Jackson, J Myers, MJ AF Kawalek, JC Farrell, DE Howard, KD Derr, JA Cope, CV Jackson, J Myers, MJ TI Effect of low doses of pentobarbital in beagles SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 11th North-American-International-Society-for-the-Study-of-Xenobiotics Meeting CY OCT 27-31, 2002 CL ORLANDO, FLORIDA SP N Amer Int Soc Study Xenobiot C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2002 VL 34 SU 1 MA 243 BP 122 EP 122 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 609WC UT WOS:000178927200243 ER PT J AU Kawalek, JC Farrell, DE Howard, KD Niwatananun, K Weiner, M Myers, MJ AF Kawalek, JC Farrell, DE Howard, KD Niwatananun, K Weiner, M Myers, MJ TI Induction of hepatic drug metabolizing enzymes in swine: Effects of classic inducers on CYP1A1 SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 11th North-American-International-Society-for-the-Study-of-Xenobiotics Meeting CY OCT 27-31, 2002 CL ORLANDO, FLORIDA SP N Amer Int Soc Study Xenobiot C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2002 VL 34 SU 1 MA 244 BP 122 EP 122 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 609WC UT WOS:000178927200244 ER PT J AU Gorski, JC Huang, SM Pinto, A Miller, P Desai, M Hall, SD AF Gorski, JC Huang, SM Pinto, A Miller, P Desai, M Hall, SD TI Echinacea alters CYP2C9 activity in vivo SO DRUG METABOLISM REVIEWS LA English DT Meeting Abstract CT 11th North-American-International-Society-for-the-Study-of-Xenobiotics Meeting CY OCT 27-31, 2002 CL ORLANDO, FLORIDA SP N Amer Int Soc Study Xenobiot C1 Indiana Univ, Sch Med, Dept Med, Indianapolis, IN 46202 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Off Commissioner, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2002 VL 34 SU 1 MA 261 BP 131 EP 131 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 609WC UT WOS:000178927200261 ER PT J AU Turesky, RJ AF Turesky, RJ TI Heterocyclic aromatic amine metabolism, DNA adduct formation, mutagenesis, and carcinogenesis SO DRUG METABOLISM REVIEWS LA English DT Article; Proceedings Paper CT 5th International Symposium on the Biological Oxidation of Nitrogen in Organic Molecules CY OCT 04-06, 2001 CL MUNICH, GERMANY ID CHROMATOGRAPHY/MICROELECTROSPRAY MASS-SPECTROMETRY; SISTER-CHROMATID EXCHANGES; HUMAN LYMPHOBLASTOID-CELLS; HUMAN CYTOCHROME-P450 1A2; P-32 POSTLABELING ASSAY; N-ACETOXY DERIVATIVES; SALMONELLA-TYPHIMURIUM; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; NONHUMAN-PRIMATES; ESCHERICHIA-COLI AB Heterocyclic aromatic amines (HAAs) are carcinogenic compounds formed in meats, fish, and poultry prepared under common household cooking practices. Some HAAs are also formed in tobacco smoke condensate. Because of the widespread occurrence of HAAs in these daily staples, health concerns have been raised regarding the potential role of HAAs in the etiology of some human cancers associated with frequent consumption of these products. In this review, the metabolism of HAAs to biologically active metabolites that bind to DNA and provoke mutations and cancer in various biological systems is discussed. Some of the current analytical and molecular methods that are used to measure biomarkers of HAA exposure and genetic damage in experimental animal models and humans are also presented. These biochemical data combined may help to better assess the role that HAAs may have in the development of some common forms of human cancers. C1 Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Turesky, RJ (reprint author), Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 122 TC 88 Z9 89 U1 2 U2 7 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0360-2532 J9 DRUG METAB REV JI Drug Metab. Rev. PY 2002 VL 34 IS 3 BP 625 EP 650 DI 10.1081/DMR-120005665 PG 26 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 589DN UT WOS:000177743100013 PM 12214671 ER PT J AU Ellenberg, SS Braun, MM AF Ellenberg, SS Braun, MM TI Monitoring the safety of vaccines - Assessing the risks SO DRUG SAFETY LA English DT Article ID EVENT-REPORTING-SYSTEM; HEPATITIS-B VACCINATION; LARGE FREQUENCY TABLES; MEASLES-MUMPS-RUBELLA; ROTAVIRUS VACCINATION; MULTIPLE-SCLEROSIS; DATALINK PROJECT; INTUSSUSCEPTION; VAERS; CHILDREN AB The safety of vaccines, particularly the most widely used vaccines to which most children are exposed as infants and toddlers, has always been an extremely high priority for vaccine manufacturers and government agencies. Products intended for healthy people must be held to a high standard of safety assurance. In addition to the intense safety assessments conducted prior to licensure, post-marketing surveillance programmes are essential to identify and study possible risks that occur too rarely to have been identified in pre-licensure studies or that occur in populations not studied in pre-licensure studies. Studying rare risks of vaccines is more complex than for therapeutic products because the exposure is virtually universal for many vaccines, ensuring occurrence simply by chance of many adverse outcomes in temporal association with vaccination. In the US the Vaccine Safety Datalink (VSD), a consortium of managed care organisations, has been established to study more rigourously possible vaccine-associated risks. These risks may be identified through reports to the Vaccine Adverse Event Reporting System (VAERS), the nationwide passive surveillance programme, as well as other sources. The combination of passive surveillance and more structured case-control or cohort studies possible in the VSD has helped to both identify new vaccine risks and to provide reassuring evidence of lack of risk in other situations where concerns have been raised. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Ellenberg, SS (reprint author), US FDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. NR 33 TC 39 Z9 39 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 2002 VL 25 IS 3 BP 145 EP 152 DI 10.2165/00002018-200225030-00001 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 549FV UT WOS:000175434600001 PM 11945111 ER PT J AU Szarfman, A Machado, SG O'Neill, RT AF Szarfman, A Machado, SG O'Neill, RT TI Use of screening algorithms and computer systems to efficiently signal higher-than-expected combinations of drugs and events in the USFDA's spontaneous reports database SO DRUG SAFETY LA English DT Article; Proceedings Paper CT Symposium on Signal Generation CY JUN 25-26, 2001 CL SOUTHAMPTON, ENGLAND ID LARGE FREQUENCY TABLES AB Since 1998, the US Food and Drug Administration (FDA) has been exploring new automated and rapid Bayesian data mining techniques. These techniques have been used to systematically screen the FDA's huge MedWatch database of voluntary reports of adverse drug events for possible events of concern. The data mining method currently being used is the Multi-Item Gamma Poisson Shrinker (MGPS) program that replaced the Gamma Poisson Shrinker (GPS) program we originally used with the legacy database. The MGPS algorithm, the technical aspects of which are summarised in this paper. computes signal scores for pairs, and for higher-order (e.g. triplet, quadruplet) combinations of drugs and events that are significantly more frequent than their pair-wise associations would predict. MGPS generates consistent, redundant. and replicable signals while minimising random patterns. Signals are generated without using external exposure data, adverse event background information, or medical information on adverse drug reactions. The MGPS interface streamlines multiple input-output processes that previously had been manually integrated. The system, however, cannot distinguish between already-known associations and new associations, so the reviewers must filter these events. In addition to detecting possible serious single-drug adverse event problems. MGPS is currently being evaluated to detect possible synergistic interactions between drugs (drug interactions) and adverse events (syndromes), and to detect differences among subgroups defined by gender and by age. such as paediatrics and geriatrics. In the current data, only 3.4% of all 1.2 million drug-event pairs ever reported (with frequencies 1) generate signals [lower 95% confidence interval limit of the adjusted ratios of the observed counts over expected (O/E) counts (denoted EB05) of greater than or equal to2]. The total frequency count that contributed to signals comprised 23% (2.4 million) of the total number. 10.4 million of drug-event pairs reported, greatly facilitating a more focused follow-up and evaluation. The algorithm provides an objective, systematic view of the data alerting reviewers to critically important, new safety signals. The study of signals detected by current methods. signals stored in the Center for Drug Evaluation and Research's Monitoring Adverse Reports Tracking System, and the signals regarding cerivastatin. a cholesterol-lowering drug voluntarily withdrawn from the market in August 2001, exemplify the potential of data mining to improve early signal detection. The operating characteristics of data mining in detecting early safety signals. exemplified by studying a drug recently well characterised by large clinical trials confirms our experience that the signals generated by data mining have high enough specificity to deserve further investigation. The application of these tools may ultimately improve usage recommendations. C1 US FDA, Ctr Drug Evaluat & Res, Off Biostat, Rockville, MD 20857 USA. RP Szarfman, A (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Biostat, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 18 TC 255 Z9 260 U1 0 U2 11 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 2002 VL 25 IS 6 BP 381 EP 392 DI 10.2165/00002018-200225060-00001 PG 12 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 570PU UT WOS:000176667300002 PM 12071774 ER PT J AU Ahmad, SR Kortepeter, C Brinker, A Chen, M Beitz, J AF Ahmad, SR Kortepeter, C Brinker, A Chen, M Beitz, J TI Renal failure associated with the use of celecoxib and rofecoxib SO DRUG SAFETY LA English DT Article ID NONSTEROIDAL ANTIINFLAMMATORY DRUGS; CYCLOOXYGENASE-2 INHIBITION; GASTROINTESTINAL TOXICITY; RHEUMATOID-ARTHRITIS; SELECTIVE INHIBITORS; CONTROLLED TRIAL; ELDERLY PERSONS; COX-2; NEPHROTOXICITY; THERAPY AB Objective: Celecoxib and rofecoxib are two relatively new nonsteroidal anti-inflammatory drugs (NSAIDs) that selectively inhibit the cyclo-oxygenase-2 (COX-2) isoenzyme at therapeutic concentrations. The nephrotoxic potential of selective COX-2 inhibitors has not been clearly established. This study was conducted in order to understand the association-between acute renal failure and the two COX-2 inhibitors celecoxib and rofecoxib. Methods: A search was performed in the US Food and Drug Administration's (FDA) Adverse Event Reporting System (AERS) to identify cases of renal failure submitted to the FDA. A MEDLINE search of the English language literature was also performed to identify published cases of renal failure associated with celecoxib and rofecoxib. Results: One hundred twenty-two and 142 domestic US cases of celecoxib and rofecoxib-associated renal failure, respectively, were identified in the AERS database. The literature search identified 19 cases of acute renal impairment in association with celecoxib and rofecoxib. In addition, drug regulatory authorities in the UK, Canada, and Australia have received about 50 reports of renal failure with celecoxib and rofecoxib. Descriptive statistics of the AERS cases have been summarised in this report. Conclusions: Data from AERS and published case reports suggest that use of both these drugs is associated with renal effects similar to that of conventional nonselective NSAIDs. Physicians should be aware that serious or life-threatening renal failure has been reported in patients with normal or impaired renal function after short-term therapy with celecoxib and rofecoxib. Patients at greatest risk for renal injury are those with pre-existing renal impairment, heart failure, liver dysfunction, those taking diuretics and/or ACE inhibitors, and the elderly. Kidney function should be monitored closely for any signs of potential renal injuries soon after initiating treatment with these agents, especially in high-risk populations. In addition, healthcare practitioners should adequately warn patients of the signs and symptoms of serious renal toxicity, and of the need for them to see their physician promptly if they occur. Celecoxib and rofecoxib are not recommended for use in patients with advanced renal disease. C1 US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Div Drug Risk Evaluat, Rockville, MD 20857 USA. RP Ahmad, SR (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Drug Safety, Div Drug Risk Evaluat, HDF-430,Room 15B-08,5600 Fishers Lane, Rockville, MD 20857 USA. NR 33 TC 71 Z9 78 U1 0 U2 4 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 2002 VL 25 IS 7 BP 537 EP 544 DI 10.2165/00002018-200225070-00007 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 577YU UT WOS:000177091300007 PM 12093311 ER PT J AU Uhl, K Kennedy, DL Kweder, SL AF Uhl, K Kennedy, DL Kweder, SL TI Risk management strategies in the physicians' desk reference product labels for pregnancy category x drugs SO DRUG SAFETY LA English DT Article ID TERATOGENIC RISK; PERCEPTION; SYSTEM; WOMEN AB Background: Drugs that carry a concern for teratogenicity are often classified as pregnancy category X in the drug label and contraindicated for use during pregnancy. Many drug labels can be found in the Physicians' Desk Reference (PDR), a widely used source of drug information by American clinicians and patients. Objective: To review product labelling in the electronic PDR for the pregnancy category X products for pregnancy prevention risk management components in labelling. Methods: The electronic version of the 2001 and 2002 PDR was searched for pregnancy category V products using the full text search feature. All product labels identified were retrieved and reviewed for trade name, generic name, manufacturer and indication. Product labels were manually searched for any pregnancy prevention risk management strategies included in labelling. Those labels that had specific pregnancy prevention risk management strategies were further evaluated. Results: One hundred and seventeen pregnancy category X products were obtained from 2249 products searched in the 2001 PDR database and 124 pregnancy category X products were obtained from the 2150 products in the 2002 PDR database. All pregnancy category X products identified were drug products. The label/package insert for each drug was reviewed to identify risk management strategies for pregnancy prevention. The majority of the labels include as the sole risk management strategy either a black box warning and/or a contraindication for use in women who are or may become pregnant. Only 13 drugs contained specific pregnancy prevention risk management strategies in the label directing the clinician and/or patient, e.g. frequency of pregnancy testing, number and type of contraception methods. Two drugs, bexarotene capsules and gel, were only included in the 2001 PDR. Three drugs, isotretinoin, acitretin, and thalidomide, have formal pregnancy prevention risk management programmes. Conclusion: This study demonstrates the varied risk management approaches in labelling for pregnancy prevention for pregnancy category X drugs. There is a need for consistency in the classification of pregnancy category X products and the pregnancy prevention risk management strategies utilised in the labelling for them. C1 US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Pregnancy Labeling Team, Rockville, MD 20852 USA. RP Uhl, K (reprint author), US FDA, Ctr Drug Evaluat & Res, Off New Drugs, Pregnancy Labeling Team, 1451 Rockville Pike,WOC 2, Rockville, MD 20852 USA. NR 14 TC 18 Z9 19 U1 0 U2 2 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 2002 VL 25 IS 12 BP 885 EP 892 DI 10.2165/00002018-200225120-00006 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 603DH UT WOS:000178543200006 PM 12241129 ER PT B AU Sundlof, SF AF Sundlof, SF BE Burroughs, T Knobler, S Lederberg, J TI Practices and policies to protect human health from antibiotic-resistant pathogens SO EMERGENCE OF ZOONOTIC DISEASES, WORKSHOP SUMMARY: UNDERSTANDING THE IMPACT ON ANIMAL AND HUMAN HEALTH LA English DT Proceedings Paper CT Workshop on the Emergence of Zoonotic Diseases CY JUN 07-08, 2000 CL INST MED, FORUM EMERGING INFECT, WASHINGTON, D.C. SP US Dept HHS, NIH, Ctr Dis Control & Prevent, US FDA, US Dept Def, US Dept State, US Dept Vet Affairs, Abbott Labs, Amer Soc Microbiol, Bristol Myers Squibb Co, Burroughs Welcome Fund, Eli Lilly & Co, Glaxo Wellcome, F Hoffmann La Roche AG, Pfizer, SmithKline Beecham Corp, Wyeth Ayerst Labs HO INST MED, FORUM EMERGING INFECT C1 US Dept HHS, US FDA, Ctr Vet Med, Washington, DC 20201 USA. RP Sundlof, SF (reprint author), US Dept HHS, US FDA, Ctr Vet Med, Washington, DC 20201 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATL ACADEMIES PRESS PI WASHINGTON PA 2101 CONSTITUTION AVE, WASHINGTON, DC 20418 USA BN 0-309-08327-3 PY 2002 BP 35 EP 40 PG 6 WC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences SC Public, Environmental & Occupational Health; Infectious Diseases; Veterinary Sciences GA BX26C UT WOS:000184775900008 ER PT J AU Moore, MM Honma, M Clements, J Harrington-Brock, K Awogi, T Bolcsfoldi, G Cifone, M Collard, D Fellows, M Flanders, K Gollapudi, B Jenkinson, P Kirby, P Kirchner, S Kraycer, J McEnaney, S Muster, W Myhr, B O'Donovan, M Oliver, J Ouldelhkim, MC Pant, K Preston, R Riach, C San, R Shimada, H Stankowski, LF AF Moore, MM Honma, M Clements, J Harrington-Brock, K Awogi, T Bolcsfoldi, G Cifone, M Collard, D Fellows, M Flanders, K Gollapudi, B Jenkinson, P Kirby, P Kirchner, S Kraycer, J McEnaney, S Muster, W Myhr, B O'Donovan, M Oliver, J Ouldelhkim, MC Pant, K Preston, R Riach, C San, R Shimada, H Stankowski, LF TI Mouse lymphoma thymidine kinase gene mutation assay: Follow-up International Workshop on Genotoxicity Test Procedures, New Orleans, Louisiana, April 2000 SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article ID CELLS; LOCUS AB The Mouse Lymphoma Assay (MLA) Workgroup of the International Workshop on Genotoxicity Test Procedures held a second harmonization meeting just prior to the U.S. Environmental Mutagen Society Meeting in New Orleans, LA, in April 2000. The discussion focused on several important aspects of the MLA, including: 1) cytotoxicity measures and their determination, 2) use of a 24-hr treatment, 3) the ability of the assay to detect aneugens, and 4) concentration selection. Prior to the meeting the group developed Microsoft Excel Workbooks for data entry. Ten laboratories entered their data into the workbooks (primarily as coded chemicals). The Excel Workbooks were used to facilitate data analysis by generating an extensive set of graphs that were evaluated by the meeting participants. Based on the Workgroup's previous agreement that a single cytotoxicity measure should be established for both the microwell and soft agar versions of the assay, the Workgroup analyzed the submitted data and unanimously agreed that the relative total growth (RTG) should be used as the cytotoxicity measure for concentration selection and data evaluation. The Workgroup also agreed that the various cytotoxicity measures should be calculated using the same methods regardless of whether the soft agar or microwell version of the assay was used. In the absence of sufficient data to make a definitive determination, the Workgroup continued to endorse the International Committee on Harmonization recommendation for the use of 24-hr treatment and made some specific 24-hr treatment protocol recommendations. The Workgroup recognized the ability of the MLA to detect at least some aneugens and also developed general guidance and requirements for appropriate concentration selection. C1 US FDA, Natl Ctr Toxicol Res, DGRT, Jefferson, AR 72079 USA. Natl Inst Hlth Sci, Div Genet & Mutagenesis, Tokyo 158, Japan. Covance Labs Ltd, Harrogate, N Yorkshire, England. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. Otsuka Pharmaceut Co Ltd, Tokushima 77101, Japan. AstraZeneca, Genet Toxicol, Safety Assessment, R&D, Sodertalje, Sweden. Covance Labs Inc, Vienna, VA USA. AstraZeneca, Safety Assessment, R&D Charnwood, Loughborough, Leics, England. Dow Chem Co USA, Hlth & Environm Res Lab, Midland, MI 48674 USA. Safepharm Labs Ltd, Derby, England. Sitek Res Labs, Rockville, MD USA. F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland. Calvert Preclin Serv Corp, Olyphant, PA USA. Glaxo Wellcome Res & Dev Ltd, Ware, Herts, England. Aventis, Paris, France. Johnson & Johnson Pharmaceut Res & Dev, Spring House, PA USA. Inveresk Res Int Ltd, Tranent, Scotland. BioReliance Corp, Rockville, MD USA. Daiichi Pharmaceut Co Ltd, Dev Res Labs, Edogawa Ku, Tokyo, Japan. RP Moore, MM (reprint author), US FDA, Natl Ctr Toxicol Res, DGRT, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 6 TC 40 Z9 44 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2002 VL 40 IS 4 BP 292 EP 299 DI 10.1002/em.10122 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 632GC UT WOS:000180214700009 PM 12489120 ER PT J AU Valentine, CR Montgomery, BA Miller, SG Delongchamp, RR Fane, BA Malling, HV AF Valentine, CR Montgomery, BA Miller, SG Delongchamp, RR Fane, BA Malling, HV TI Characterization of mutant spectra generated by a forward mutational assay for gene A of Phi X174 from ENU-treated transgenic mouse embryonic cell line PX-2 SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE phiX174; transgenic; ENU; mouse cell; gene A ID ETHYLNITROSOUREA-INDUCED MUTATION; ESCHERICHIA-COLI; ETHYLATING AGENTS; POINT MUTATIONS; SHUTTLE VECTOR; DNA-ADDUCTS; MICE; MUTAGENESIS; SINGLE; BACTERIOPHAGE-PHI-X174 AB The sensitivity of in vivo transgenic mutation assays benefits from the sequencing of mutations, although the large number of possible mutations hinders high throughput sequencing. A forward mutational assay exists for PhiX174 that requires an altered, Functional PhiX174 protein and therefore should have fewer targets (sense, base-pair substitutions) than forward assays that inactivate a protein. We investigated this assay to determine the number of targets and their suitability for detecting a known mutagen, N-ethyl-N-nitrosourea (ENU). We identified 25 target sites and 33 different mutations in PhiX174 gene A after sequencing over 350 spontaneous and ENU-induced mutants, mostly from mouse embryonic cell line PX-2 isolated from mice transgenic for PhiX174 am3, cs70 (line 54). All six types of base-pair substitution were represented among both the spontaneous and ENU-treated mutant spectra. The mutant spectra from cells treated with 200 and 400 mug/ml ENU were both highly different from the spontaneous spectrum (P < 0.000001) but not from each other. The dose trend was significant (P < 0.0001) fora linear regression of mutant Frequencies (R-2 = 0.79), with a ninefold increase in mutant frequency at the 400 mug/ml dose. The spontaneous mutant frequency was 1.9 X 10(-5) and the spontaneous spectrum occurred at 11 target base pairs with 15 different mutations. Thirteen mutations at 12 targets were identified only from ENU-treated cells. Seven mutations had highly significant increases with ENU treatment (P < 0.0001) and 15 showed significant increases. The results suggest that the PhiX174 forward assay might be developed into a sensitive, inexpensive in vivo mutagenicity assay. Published 2002 Wiley-Liss, Inc. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Arizona, Dept Vet Sci & Microbiol, Tucson, AZ 85721 USA. NIEHS, NIH, Res Triangle Pk, NC 27709 USA. RP Valentine, CR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT-120, Jefferson, AR 72079 USA. NR 67 TC 8 Z9 8 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2002 VL 39 IS 1 BP 55 EP 68 DI 10.1002/em.10043 PG 14 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 522EY UT WOS:000173883800008 PM 11813297 ER PT J AU Thompson, PA DeMarini, D Kadlubar, FF McClure, GY Brooks, LR Green, BL Fares, MY Stone, A Josephy, PD Ambrosone, CB AF Thompson, PA DeMarini, D Kadlubar, FF McClure, GY Brooks, LR Green, BL Fares, MY Stone, A Josephy, PD Ambrosone, CB TI Evidence for the presence of mutagenic arylamines in human breast milk and DNA adducts in exfoliated breast ductal epithelial cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT Conference on Breast Cancer and Environmental Mutagens CY SEP 22-25, 2001 CL RES TRIANGLE PK, NORTH CAROLINA SP Environm Mutagen Soc DE DNA adducts; Salmonella mutagenicity; breast milk; aryl amines ID POLYCYCLIC AROMATIC-HYDROCARBONS; RAT MAMMARY-GLAND; CANCER RISK; METABOLIC-ACTIVATION; CIGARETTE-SMOKING; FOOD-PRODUCTS; AMINES; CARCINOGENS; TISSUE; N-ACETYLTRANSFERASE-2 AB Aromatic and heterocyclic amines are ubiquitous environmental mutagens present in combustion emissions, fried meats, and tobacco smoke, and are suspect human mammary carcinogens. To determine the presence of arylamines in breast tissue and fluid, we examined exfoliated breast ductal epithelial cells for DNA adducts and matched human milk samples for mutagenicity. Breast milk was obtained from 50 women who were 4-6 weeks postpartum, and exfoliated epithelial-cell DNA was evaluated for bulky, nonpolar DNA adducts by P-32-postlabeling and thin-layer chromatography. Milk was processed by acid hydrolysis, and the extracted organics were examined in the standard plate-incorporation Ames Salmonella assay using primarily strain YG1024, which detects frameshift mutations and overexpresses aryl amine N-acetyltransferase. DNA adducts were identified in 66% of the specimens, and bulky adducts migrated in a pattern similar to that of 4-aminobiphenyl standards. The distribution of adducts did not vary by NAT2 genotype status. Of whole milk samples, 88% (22/25) had mutagenic activity. Among the samples for which we had both DNA adduct and mutagenicity data, 58% (14/19) of the samples with adducts were also mutagenic, and 85% (11/13) of the mutagenic samples had adducts. Quantitatively, no correlation was observed between the levels of adducts and the levels of mutagenicity. Separation of the milk showed that mutagenic activity was found in 69% of skimmed milk samples but in only 29% of the corresponding milk fat samples, suggesting that the breast milk mutagens were moderately polar molecules. Chemical fractionation showed that mutagenic activity was found in 67% (4/6) of the basic fractions but in only 33% (2/6) of acidic samples, indicating that the mutagens were primarily basic compounds, such as arylamines. Although pilot in nature, this study corroborates previous findings of significant levels of DNA adducts in breast tissue and mutagenicity in human breast milk and indicates that breast milk mutagens may be moderately polar basic compounds, such as arylamines. Published 2002 Wiley-Liss, Inc.(dagger) C1 Mt Sinai Sch Med, DH Ruttenberg Canc Ctr, New York, NY 10029 USA. Univ Arizona, Coll Med, Dept Pathol, Ctr Hlth Sci, Tucson, AZ 85721 USA. US EPA, Div Environm Carcinogenesis, Res Triangle Pk, NC 27711 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Guelph, Dept Chem & Biochem, Guelph, ON N1G 2W1, Canada. RP Ambrosone, CB (reprint author), Mt Sinai Sch Med, DH Ruttenberg Canc Ctr, Box 1130,1 Gustave L Levy Pl, New York, NY 10029 USA. OI Josephy, Philip David/0000-0002-4462-6625 NR 54 TC 33 Z9 33 U1 1 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2002 VL 39 IS 2-3 BP 134 EP 142 DI 10.1002/em.10067 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 532UT UT WOS:000174494000010 PM 11921181 ER PT J AU Gorlewska-Roberts, K Green, B Fares, M Ambrosone, CB Kadlubar, FF AF Gorlewska-Roberts, K Green, B Fares, M Ambrosone, CB Kadlubar, FF TI Carcinogen-DNA adducts in human breast epithelial cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT Conference on Breast Cancer and Environmental Mutagens CY SEP 22-25, 2001 CL RES TRIANGLE PK, NORTH CAROLINA SP Environm Mutagen Soc DE DNA adducts; epithelial cells; breast milk; carcinogens ID AROMATIC-AMINES; HETEROCYCLIC AMINES; CANCER ETIOLOGY; RISK-FACTORS; GENOTOXICITY; ACTIVATION; INVITRO; GUANINE; AGENTS; TISSUE AB Diet and environmental exposures are often regarded as significant etiologic factors in human breast cancer. Chemicals that may be involved in these exposures include heterocyclic amines, aromatic amines, and polycyclic aromatic hydrocarbons, which also serve as strong mammary carcinogens in different animal models. in this study, we chose to quantify the major DNA adducts derived from one member of each of these classes of carcinogens, that is, 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), 4-aminobiphenyl (ABP), and benzo[a]pyrene (B[a]P), respectively, in DNA isolated from exfoliated ductal epithelial cells in human breast milk. Milk was collected from healthy, nonsmoking mothers. The isolated DNA was digested to 3' nucleotides and subjected to P-32-postlabeling. Adduct enrichment was achieved using Oasis Sep-Paks and the analyses were conducted by HPLC using radiometric detection. Critical to the analyses were the syntheses of bis(phosphate) standards for the C8-dG adducts of PhIP and ABP, and the N-2-dG adduct of B[a]P, which were added to each reaction as UV markers. Of the 64 samples analyzed, adducts were found in 3 1 samples. Thirty samples contained detectable levels of PhIP adducts, with a mean value of 4.7 adclucts/10(7) nucleotides; 18 were positive for ABP adducts with a mean value of 4.7 adducts/10(7) nucleotides; and 13 were found to contain B[a]P adducts with a mean level of 1.9 adducts/10(7) nucleotides. These data indicate that women are exposed to several classes of dietary and environmental carcinogens and that these carcinogens react with DNA in breast ductal epithelial cells, the cells from which most breast cancers arise. Published 2002 Wiley-Liss, Inc.(dagger) C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Mt Sinai Sch Med, New York, NY 10029 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, HFT 100,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 37 TC 72 Z9 72 U1 0 U2 2 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2002 VL 39 IS 2-3 BP 184 EP 192 DI 10.1002/em.10060 PG 9 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 532UT UT WOS:000174494000017 PM 11921188 ER PT J AU Chen, T Harrington-Brock, K Moore, MM AF Chen, T Harrington-Brock, K Moore, MM TI Mutant frequency and mutational spectra in the Tk and Hprt genes of N-ethyl-N-nitrosourea-treated mouse lymphoma cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE Tk; Hprt; mouse lymphoma assay; mutant frequency; point mutation; chromosome alteration ID HUMAN LYMPHOBLASTOID-CELLS; HAMSTER OVARY CELLS; L5178Y/TK+/ MOUSE; ESCHERICHIA-COLI; IN-VIVO; 6-THIOGUANINE-RESISTANT LYMPHOCYTES; TRIFLUOROTHYMIDINE-RESISTANT; DROSOPHILA-MELANOGASTER; MOLECULAR ANALYSIS; LOCUS SPECIFICITY AB The mouse lymphoma assay (MLA) utilizing the Tk gene is widely used to identify chemical mutagens. The autosomal location of the Tk gene allows for the detection of a wide range of mutational events, from point mutations to chromosome alterations. However, chemically induced point mutation spectra in the Tk gene of mouse lymphoma cells have not been characterized. In this study, we determined and compared the mutagenicity and mutational spectra of N-ethyl-N-nitrosourea (ENU) in the Tk and Hprt genes of mouse lymphoma cells. Treatment of L5178Y mouse lymphoma cells with 100 mug/ml ENU induced a Tk mutant frequency of 756 X 10(-6) and an Hprt mutant frequency of 311 X 10(-6). Sequence analysis of Tk and Hprt mutant cDNAs showed a similar overall mutation pattern in the two genes with base-pair substitutions accounting for 83% of non-loss of heterozygosity mutations in the Tk gene and 75% of all mutations in the Hprt gene. The most common point mutation induced by ENU was G:C --> A:T transition (36 and 28% of independent mutations detected in the Tk and Hprt genes, respectively). The mutation spectra induced by ENU in both the Tk and Hprt genes were different from the respective patterns produced in mutants from untreated cells. About 9% of Tk and 7% of Hprt mutations from control cells were in-frame deletions, whereas no such mutations were found among the ENU-induced Tk and Hprt mutations. Our results indicate that ENU produces a chemical-specific point mutational profile in the Tk gene of mouse lymphoma cells that is remarkably similar to that found in the X-linked Hprt gene. This study provides evidence that the MLA can be used not only to detect point mutagens but also for analysis of mutational spectra. Published 2002 Wiley-Liss, Inc.(dagger) C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA. RP Chen, T (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-130,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 50 TC 19 Z9 21 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2002 VL 39 IS 4 BP 296 EP 305 DI 10.1002/em.10075 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 570VA UT WOS:000176678200002 PM 12112381 ER PT J AU Dobrovolsky, VN Shaddock, JG Heflich, RH AF Dobrovolsky, VN Shaddock, JG Heflich, RH TI Mutagenicity of gamma-radiation, mitomycin C, and etoposide in the Hprt and Tk genes of Tk(+/-) mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE thymidine kinase; mutation; loss of heterozygosity; Hprt ID MOUSE LYMPHOMA-CELLS; DOUBLE-STRAND BREAK; THYMIDINE KINASE; IONIZING-RADIATION; PERIPHERAL-BLOOD; TRANSGENIC MICE; ORAL ETOPOSIDE; SOMATIC-CELLS; LYMPHOCYTES; MUTATION AB The recently developed Tk(+/)- mouse detects in vivo somatic cell mutation in the endogenous, autosomal Tk gene. To evaluate the sensitivity of this model, we have treated Tk(+/)- mice with three agents that induce DNA damage by different mechanisms, and determined spleen lymphocyte mutant frequencies (MFs) in the autosomal Tk gene and in the X-linked Hprt gene. gamma-Radiation, which produces single- and double-strand breaks by nonspecific oxidative stress, efficiently increased Hprt MF, but not Tk MF. Mitomycin C, which produces bulky DNA monoadducts and crosslinks, was mutagenic in both the Hprt and Tk genes, but the response was greater in the Tk gene. An inhibitor of the ligase function of DNA topoisomerase 11, etoposide, did not increase Hprt MF, and induced a small, but nonsignificant increase in A MF. Combined with previous data, the results indicate that the two genes are differentially sensitive to many agents, and that the A gene is more sensitive than the Hprt gene to some, but not all types of DNA damage. Published 2002 Wiley-Liss, Inc.(dagger) C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod 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. NR 45 TC 7 Z9 8 U1 0 U2 1 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 2002 VL 39 IS 4 BP 342 EP 347 DI 10.1002/em.10074 PG 6 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 570VA UT WOS:000176678200007 PM 12112386 ER PT J AU Hong, HX Tong, WD Fang, H Shi, LM Xie, Q Wu, J Perkins, R Walker, JD Branham, W Sheehan, DM AF Hong, HX Tong, WD Fang, H Shi, LM Xie, Q Wu, J Perkins, R Walker, JD Branham, W Sheehan, DM TI Prediction of estrogen receptor binding for 58,000 chemicals using an integrated system of a tree-based model with structural alerts SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article DE endocrine-disrupting chemicals; estrogen receptor binding; relative binding affinties; risk assessment; structural alerts; tree-based models ID PHARMACOPHORE; ANTAGONISM; ALGORITHMS; DISCOVERY; ALPHA; SET AB A number of environmental chemicals, by mimicking natural hormones, can disrupt endocrine function in experimental animals, wildlife, and humans. These chemicals, called "endocrine-disrupting chemicals" (EDCs), are such a scientific and public concern that screening and testing 58,000 chemicals for EDC activities is now statutorily mandated. Computational chemistry tools are important to biologists because they identify chemicals most important for in vitro and in vivo studies. Here we used a computational approach with integration of two rejection filters, a tree-based model, and three structural alerts to predict and prioritize estrogen receptor (ER) ligands. The models were developed using data for 232 structurally diverse chemicals (training set) with a 10(6) range of relative binding affinities (RBAs); we then validated the models by predicting ER RBAs for 463 chemicals that had ER activity data (testing set). The integrated model gave a lower false negative rate than any single component for both training and testing sets. When the integrated model was applied to approximately 58,000 potential EDCs, 80% (-46,000 chemicals) were predicted to have negligible potential (log RBA < -4.5, with log RBA = 2.0 for estradiol) to bind ER. The ability to process large numbers of chemicals to predict inactivity for ER binding and to categorically prioritize the remainder provides one biologic measure to prioritize chemicals for entry into more expensive assays (most chemicals have no biologic data of any kind). The general approach for predicting ER binding reported here may be applied to other receptors and/or reversible binding mechanisms involved in endocrine disruption. C1 ROW Sci Inc, Jefferson, AR 72079 USA. BASF Corp, Princeton, NJ USA. US EPA, TSCA Interagcy Testing Comm, Washington, DC 20460 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Tong, WD (reprint author), ROW Sci Inc, 3900 NCTR Rd,MC 910, Jefferson, AR 72079 USA. NR 41 TC 103 Z9 110 U1 1 U2 18 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD JAN PY 2002 VL 110 IS 1 BP 29 EP 36 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 521WH UT WOS:000173864000023 PM 11781162 ER PT J AU Takamatsu, N Welage, LS Hayashi, Y Yamamoto, R Barnett, JL Shah, VP Lesko, LJ Ramachandran, C Amidon, GL AF Takamatsu, N Welage, LS Hayashi, Y Yamamoto, R Barnett, JL Shah, VP Lesko, LJ Ramachandran, C Amidon, GL TI Variability in cimetidine absorption and plasma double peaks following oral administration in the fasted state in humans: correlation with antral gastric motility SO EUROPEAN JOURNAL OF PHARMACEUTICS AND BIOPHARMACEUTICS LA English DT Article DE cimetidine; antral motility phase; gastrointestinal motility; gastrointestinal pH; pharmacokinetics; double peaks; secondary maxima; human bioavailability ID PHARMACOKINETICS; BIOAVAILABILITY; KINETICS; TIME; DOGS AB The role of gastrointestinal motility and pH in determining cimetidine bioavailability as well as double peaks in plasma profiles following oral administration, in the quiescent or active phase of antral motility, to humans in the fasted state was examined. Plasma cimetidine-time curves did not show the presence of double peaks in any subject following intravenous administration. The incidence of double peaks was 73% following oral administration and was independent of antral migrating motility complex phase. Further, it was found that oral administration of cimetidine in the quiescent phase resulted in significantly higher bioavailability and in other pharmacokinetic parameters compared to that obtained following administration in the active phase. Excellent linearity in plots of motility peaks vs. plasma peaks with slopes close to unity were evident for both quiescent (r(2) = 0.93) and active phase (r(2) = 0.97) administration. A total of 14 peaks out of 22 (10 subjects, 64%) and 20 out of 27 peaks (11 subjects, 74%), were accounted for in quiescent and active phase oral administration, respectively. The proximal occurrence of plasma peaks to antral motility peaks typical of phase III contractions strongly implies that motility patterns may be responsible for secondary maxima following oral cimetidine administration in the fasted state. (C) 2002 Elsevier Science B.V. All rights reserved. C1 Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. US FDA, Rockville, MD 20857 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. Ono Pharmaceut Co Ltd, Osaka, Japan. Nagoya City Univ, Aichi, Japan. Yamanouchi Pharmaceut Co Ltd, Shizuoka, Japan. FU FDA HHS [FD 01462]; NCRR NIH HHS [M01 RR 00042] NR 29 TC 31 Z9 32 U1 0 U2 6 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0939-6411 J9 EUR J PHARM BIOPHARM JI Eur. J. Pharm. Biopharm. PD JAN PY 2002 VL 53 IS 1 BP 37 EP 47 DI 10.1016/S0939-6411(01)00207-7 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 519RR UT WOS:000173739700006 PM 11777751 ER PT J AU Begley, TH McNeal, TP Biles, JE Paquette, KE AF Begley, TH McNeal, TP Biles, JE Paquette, KE TI Evaluating the potential for recycling all PET bottles into new food packaging SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article; Proceedings Paper CT 2nd International Symposium on Food Packaging - Ensuring the Safety and Quality of Food CY NOV 08-10, 2000 CL VIENNA, AUSTRIA SP Int Life Sci Inst, Int Union Pure & Appl Chem, Vienna Univ Technol, European Commiss DE recycled polymers; food packaging; sorption ID POLY(ETHYLENE-TEREPHTHALATE); MIGRATION; SORPTION AB To evaluate the feasibility of recycling all PET bottles into food packaging, realistic estimates of the maximum concentration of contaminants that might be expected in the polymer are needed. To estimate the maximum concentration of a contaminant that might be in PET from the storage of non-food substances, sorption experiments into two types of PET were performed. These test materials were 0.8 mm thick amorphous PET (a relative sink for contaminants) and commercial PET bottle wall. Using a commercial shampoo containing 1% lindane (C6H6Cl6), the test materials were stored in contact with the shampoo at 20 and 40degrees C for 231 days. This commercial shampoo also represents an extreme case because it contains 7% acetone, a solvent which swells PET, further enhancing sorption of chemicals. Additional sorption experiments into PET were performed by preparing solutions of 10% toluene in Miglyol (a fractionated coconut oil), 10% benzophenone in Miglyol, 5% 2-butoxyethoxy ethanol (2-BE) in 50/50 water/ethanol, and 10% methyl stearate in heptane. Sorption data from the shampoo into PET illustrate Fickian behaviour. Specifically, the amount of sorption at room temperature is similar to40 tilnes less than that at 40degrees C. The amount of lindane sorbed into PET from the shampoo after 231 days was 0.1 and 3.7 mg dm(-2) at 20 and 40degrees C respectively. These values correspond to 28 and 765 mg kg(-1) on a mass/mass basis. All sorptions are within the ranges measured and published by other authors using surrogate contamination testing schemes. Additionally, actual bottles from recycle bins were analysed for the amount of contamination. Results are discussed in terms of potential consumer exposure to non-food contaminants in food containers made of recycled PET and in relation to the surrogate testing methods recommended by the Food and Drug Administration (FDA) for determining the compatibility of a PET recycling process to produce containers suitable for food-contact use. C1 US FDA, Washington, DC 20204 USA. RP Begley, TH (reprint author), US FDA, Washington, DC 20204 USA. NR 19 TC 23 Z9 23 U1 2 U2 12 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. PY 2002 VL 19 SU S BP 135 EP 143 DI 10.1080/02652030110083720 PG 9 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 539XZ UT WOS:000174899400012 PM 11962702 ER PT J AU Laurenzana, EM Weis, CC Bryant, CW Newbold, R Delclos, KB AF Laurenzana, EM Weis, CC Bryant, CW Newbold, R Delclos, KB TI Effect of dietary administration of genistein, nonylphenol or ethinyl estradiol on hepatic testosterone metabolism, cytochrome P-450 enzymes, and estrogen receptor alpha expression SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE genistein; nonylphenol; ethinyl estradiol; cytochromes P450; testosterone metabolism ID SPRAGUE-DAWLEY RATS; HORMONAL-REGULATION; GROWTH-HORMONE; MESSENGER-RNA; TISSUE DISTRIBUTION; MAMMALIAN LIVER; SEX DIFFERENCE; FEMALE RATS; IGF-I; MECHANISMS AB The objective of this study was to examine effects of estrogenic agents of varying potencies (genistein, p-nonylphenol, and ethinyl estradiol) on hepatic testosterone metabolism, cytochrome P-450 (CYP450) enzymes, and ER alpha expression. These endpoints were examined as potential biomarkers of, and contributors to, endocrine disruptive activity. Exposure occurred during critical developmental periods, from gestational day 7 through weaning via the mothers' diet. Thereafter, rats were exposed via their diet to the compounds until puberty (postnatal day 50). Testosterone hydroxylase and 5 alpha -reductase activities, CYP2C and CYP3A levels were determined. In general, the compounds were more active in male rats than female rats. The only effect observed in female rats was at the 250 ppm genistein dose, in which an approximately 40% increase in 5 alpha -reductase activity was observed. In male rats, genistein treatment had mixed effects on testosterone metabolism. The 1250 ppm dose decreased both CYP2C and CYP3A protein levels. Nonylphenol had the most profound effects on testosterone metabolism and CYP450 expression in male rats, with effects occurring at doses as low as 25 ppm. An increase in 5 alpha -reductase activity and a decrease in the formation of 16 alpha -OH-, 2 alpha -OH-testosterone metabolites, CYP2C and CYP3A protein were observed. EE2 decreased the formation of several testosterone metabolites and CYP2C protein. All compounds had some effect on hepatic ERa expression, although a consistent effect was not observed. This study demonstrates that the test compounds can influence hepatic testosterone hydroxylase activity and CYP450 expression, as well as ER alpha expression, although these activities cannot be directly related to estrogenic activity. Published by Elsevier Science Ltd. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Delclos, KB (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 47 TC 46 Z9 49 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 JAN PY 2002 VL 40 IS 1 BP 53 EP 63 DI 10.1016/S0278-6915(01)00095-3 PG 11 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 506CM UT WOS:000172952400007 PM 11731036 ER PT J AU Levitt, JA AF Levitt, JA TI Regulation of dietary supplements: FDA's strategic plan SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP Levitt, JA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. NR 6 TC 7 Z9 7 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 2002 VL 57 IS 1 BP 1 EP 13 PG 13 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 568GF UT WOS:000176533500001 PM 12118474 ER PT J AU Schoonmaker, M Bagley, GP Scanlan, MK AF Schoonmaker, M Bagley, GP Scanlan, MK TI Coordination of federal regulation and payment for new diagnostic tests: A proposed new approach SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 Vysis Inc, Downers Grove, IL USA. Arnold & Porter, Washington, DC 20036 USA. US Hlth Care Financing Adm, Off Clin Stand & Qual, Coverage & Anal Grp, Baltimore, MD 21207 USA. RP Schoonmaker, M (reprint author), US FDA, Rockville, MD 20857 USA. NR 5 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 2002 VL 57 IS 2 BP 195 EP 204 PG 10 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 612UV UT WOS:000179094600003 PM 12436983 ER PT J AU Eng, J Hatch, OG Crawford, LM Troy, DE Anthony, SF Azar, AM AF Eng, J Hatch, OG Crawford, LM Troy, DE Anthony, SF Azar, AM TI The Food and Drug Law Institute's 45th Annual Educational Conference - Keynote addresses SO FOOD AND DRUG LAW JOURNAL LA English DT Editorial Material C1 Eng Consulting LLC, Cooksville, MD USA. US FDA, Rockville, MD 20857 USA. RP Eng, J (reprint author), Eng Consulting LLC, Cooksville, MD 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 2002 VL 57 IS 2 BP 227 EP + PG 18 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 612UV UT WOS:000179094600005 ER PT J AU Ali, SF Oetinger, M Skinner, J Slikker, W Imam, SZ AF Ali, SF Oetinger, M Skinner, J Slikker, W Imam, SZ TI Methamphetamine-induced dopaminergic neurotoxicity in mice: Neuroprotective role of caspases and alterations in p53 and BCL-2 expression SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2002 VL 33 SU 1 MA 308 BP S119 EP S119 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 578AY UT WOS:000177096300308 ER PT J AU Hoke, E Bar-Noy, S Shacter, E AF Hoke, E Bar-Noy, S Shacter, E TI Tumoricidal activities of deferoxamine and doxorubicin: Role of iron SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract CT 9th Annual Meeting of the Oxygen-Society CY NOV 20-24, 2002 CL SAN ANTONIO, TEXAS SP Oxygen Soc C1 Uniformed Serv Univ Hlth Sci, Dept Pediat, Bethesda, MD 20814 USA. US FDA, Biochem Lab, CBER, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 2002 VL 33 SU 2 MA 411 BP S440 EP S441 PG 2 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 614PY UT WOS:000179199600430 ER PT S AU Sievert, MK Pilli, G Liu, Y Sutkowski, EM Seamon, KB Ruoho, AE AF Sievert, MK Pilli, G Liu, Y Sutkowski, EM Seamon, KB Ruoho, AE BE Iyengar, E Hildebrandt, JD TI Photoaffinity labeling of adenylyl cyclase SO G PROTEIN PATHWAYS: PT C, EFFECTOR MECHANISMS SE Methods in Enzymology LA English DT Review ID HUMAN-ERYTHROCYTES; BINDING-SITES; FORSKOLIN; TRANSPORTER; DITERPENE; ACTIVATION; DOMAINS; PEPTIDE C1 Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. GlaxoSmithKline, Philadelphia, PA 19102 USA. US FDA, Div Vaccines & Related Prod Applicat, Rockville, MD 20852 USA. Immunex Res & Dev Corp, Seattle, WA 98101 USA. Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. RP Univ Wisconsin, Sch Med, Dept Pharmacol, Madison, WI 53706 USA. NR 23 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0076-6879 BN 0-12-182246-X J9 METHOD ENZYMOL JI Methods Enzymol. PY 2002 VL 345 BP 188 EP 197 PG 10 WC Biochemical Research Methods; Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA BT06Z UT WOS:000171866300014 PM 11665604 ER PT S AU Gendel, SM AF Gendel, SM BE Fu, TJ Gendel, SM TI Sequence analysis for assessing potential allergenicity SO GENETICALLY ENGINEERED FOODS ASSESSING POTENTIAL ALLERGENICITY SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT Conference on Assessment of the Potential Allergenicity of Genetically Engineered Food CY DEC 05-06, 2000 CL SUMMIT ARGO, IL SP Hlth & Environm Sci Inst, Int Life Sci Inst DE bioinformatic sequence analysis; allergenicity; allergen sequence database ID ACID SUBSTITUTION MATRICES; DATABASE RESOURCES; PROTEIN; INFORMATION AB Sequence analysis plays an important role in assessing the potential allergenicity of proteins used in transgenic foods, particularly for proteins that have not previously been part of the food supply. Sequence comparisons are used to indicate potential unexpected cross reactivity to existing allergens and to assess the potential for developing new sensitivities. Although the concept of using sequence analysis is straightforward, implementing a bioinformatic analysis that is accurate and complete can be complex. Several factors need to be considered, including the design and content of the sequence database, the analysis strategy, and the criteria for evaluating the results. C1 US FDA, Natl Ctr Food Safety & Technol, Biotechnol Studies Branch, Summit Argo, IL 60501 USA. RP Gendel, SM (reprint author), US FDA, Natl Ctr Food Safety & Technol, Biotechnol Studies Branch, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM sgendel@cfsan.fda.gov NR 14 TC 28 Z9 31 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 1-57331-384-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 964 BP 87 EP 98 PG 12 WC Food Science & Technology; Multidisciplinary Sciences SC Food Science & Technology; Science & Technology - Other Topics GA BU76N UT WOS:000176951800005 PM 12023196 ER PT S AU Fu, TJ AF Fu, TJ BE Fu, TJ Gendel, SM TI Digestion stability as a criterion for protein allergenicity assessment SO GENETICALLY ENGINEERED FOODS ASSESSING POTENTIAL ALLERGENICITY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Assessment of the Potential Allergenicity of Genetically Engineered Food CY DEC 05-06, 2000 CL SUMMIT ARGO, ILLINOIS SP Hlth & Environm Sci Inst, Int Life Sci Inst DE digestion stability; food allergens; protein allergenicity assessment; in vitro digestion assays ID SAFETY ASSESSMENT; FOOD ALLERGENS; IMMUNOLOGICAL PROPERTIES; SOYBEAN GLYCININ; IN-VITRO; DIGESTIBILITY; PROTEOLYSIS; HYDROLYSIS; TOMATOES; PEANUT AB Assessing the allergenic potential of transgenic proteins introduced into genetically engineered food remains a critical part of the overall safety assessment of these foods. Stability to digestion has been proposed as one of the steps in the decision tree approach to assess the allergenic potential of transgenic proteins. The validity of digestion stability as a criterion for protein allergenicity assessment, however, has encountered some criticism in recent years. This chapter gives an overview of the rationale behind the use of digestion stability as a criterion for protein allergenicity assessment and reviews the available data that may or may not support its use. The application of in vitro digestion assays for the assessment of allergenic potential of novel proteins and the factors that affect the assay results are also discussed. There is a need to establish standardized assay conditions so that direct comparison of results from different laboratories can be made. Consensus also needs to be reached on relating the measured digestibility to the allergenic potential of proteins. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Fu, TJ (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 37 TC 44 Z9 47 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 1-57331-384-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 964 BP 99 EP 110 PG 12 WC Food Science & Technology; Multidisciplinary Sciences SC Food Science & Technology; Science & Technology - Other Topics GA BU76N UT WOS:000176951800006 PM 12023197 ER PT S AU Gendel, SM AF Gendel, SM BE Fu, TJ Gendel, SM TI Where do we go from here? A discussion summary SO GENETICALLY ENGINEERED FOODS ASSESSING POTENTIAL ALLERGENICITY SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Editorial Material CT Conference on Assessment of the Potential Allergenicity of Genetically Engineered Food CY DEC 05-06, 2000 CL SUMMIT ARGO, ILLINOIS SP Hlth & Environm Sci Inst, Int Life Sci Inst C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60565 USA. RP Gendel, SM (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60565 USA. 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 1-57331-384-X J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2002 VL 964 BP 197 EP 200 PG 4 WC Food Science & Technology; Multidisciplinary Sciences SC Food Science & Technology; Science & Technology - Other Topics GA BU76N UT WOS:000176951800015 PM 12023206 ER PT J AU Lozier, JN Csako, G Mondoro, TH Krizek, DM Metzger, ME Costello, R Vostal, JG Rick, ME Donahue, RE Morgan, RA AF Lozier, JN Csako, G Mondoro, TH Krizek, DM Metzger, ME Costello, R Vostal, JG Rick, ME Donahue, RE Morgan, RA TI Toxicity of a first-generation adenoviral vector in rhesus Macaques SO HUMAN GENE THERAPY LA English DT Article ID NONHUMAN PRIMATE LUNGS; HUMAN FACTOR-IX; GENE-THERAPY; ESCHERICHIA-COLI; HEMOPHILIA-B; IN-VIVO; MEDIATED EXPRESSION; IMMUNE-RESPONSES; VIRAL-ANTIGENS; TISSUE FACTOR AB We constructed a first-generation adenovirus vector (AVC3FIX5) that we used to assess the rhesus macaque as a nonhuman primate model for preclinical testing of hemophilia B gene therapy vectors. Although we succeeded in our primary objective of demonstrating expression of human factor IX we encountered numerous toxic side effects that proved to be dose limiting. Following intravenous administration of AVC3FIX5 at doses of 3.4 x 10(11) vector particles/kg to 3.8 x 10(12) vector particles/kg, the animals in our study developed antibodies against human factor IX, and dose-dependent elevations of enzymes specific for liver, muscle, and lung injury. In addition, these animals showed dose-dependent prolongation of clotting times as well as acute, dose-dependent decreases in platelet counts and concomitant elevation of fibrinogen and von Willebrand factor. These abnormalities may be caused by the direct toxic effects of the adenovirus vector itself, or may result indirectly from the accompanying acute inflammatory response marked by elevations in IL-6, a key regulator of the acute inflammatory response. The rhesus macaque may be a useful animal model in which to evaluate mechanisms of adenovirus toxicities that have been encountered during clinical gene therapy trials. C1 US FDA, Lab Hemostasis, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NHGRI, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NIH, Hematol Serv, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. NHLBI, Rockville, MD USA. NCI, Surg Branch, Bethesda, MD 20892 USA. RP Lozier, JN (reprint author), US FDA, Lab Hemostasis, Div Hematol, Off Blood Res & Review,Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 39 TC 78 Z9 79 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2002 VL 13 IS 1 BP 113 EP 124 DI 10.1089/10430340152712665 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 508ED UT WOS:000173075000006 PM 11779415 ER PT J AU Eggerman, TL Mondoro, TH Lozier, JN Vostal, JG AF Eggerman, TL Mondoro, TH Lozier, JN Vostal, JG TI Adenoviral vectors do not induce, inhibit, or potentiate human platelet aggregation SO HUMAN GENE THERAPY LA English DT Article ID IIB-IIIA COMPLEX; GENE-THERAPY; CYSTIC-FIBROSIS; RECEPTORS; FIBRINOGEN; EXPRESSION; INTEGRINS; INFECTION; SEQUENCE; CELLS AB Adenoviruses are commonly used as vectors in human clinical gene therapy trials. High doses of intravenous adenovirus vectors have been associated with development of thrombocytopenia of undetermined origin. Viral internalization requires the presence cell surface integrins, alpha(v)beta(3) or alpha(v)beta(5), that can blind ligands with a arginine-glycine-aspartic acid (RGD) sequence. This sequence is found in the adenovirus penton base. Platelets express the alpha(v)beta(3) integrin and other integrins that bind the RGD sequence of ligands such as fibrinogen, laminin, vitronectin, and von Willebrand factor (vWF). Platelet aggregation is mediated, in part, by the binding of the RGD sequence of fibrinogen to a platelet surface integrin, glycoprotein IIb/IIIa (GP IIb/IIIa). We investigated whether adenovirus particles could interfere with or potentiate agonist-induced platelet aggregation. Incubation of platelet-rich plasma with adenovirus under stirred conditions did not promote spontaneous aggregation. The addition of physiological platelet agonists, ADP, collagen, or epinephrine, induced platelet aggregation. However, the presence of adenovirus in a wide range of concentrations did not inhibit or potentiate agonist-induced aggregation. These results suggest that the adenovirus-associated thrombocytopenia observed in vivo is independent of a direct effect of the virus on platelet aggregation. C1 US FDA, Lab Cellular Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Cellular & Gene Therapy, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Vostal, JG (reprint author), US FDA, Lab Cellular Hematol, Off Blood Res & Review, Ctr Biol Evaluat & Res, Room 321,Bldg 29,HFM-335,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 21 TC 21 Z9 21 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2002 VL 13 IS 1 BP 125 EP 128 DI 10.1089/10430340152712674 PG 4 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 508ED UT WOS:000173075000007 PM 11779416 ER PT J AU Yamano, S Huang, LY Ding, CT Chiorini, JA Goldsmith, CM Wellner, RB Golding, B Kotin, RM Scott, DE Baum, BJ AF Yamano, S Huang, LY Ding, CT Chiorini, JA Goldsmith, CM Wellner, RB Golding, B Kotin, RM Scott, DE Baum, BJ TI Recombinant adeno-associated virus serotype 2 vectors mediate stable interleukin 10 secretion from salivary glands into the bloodstream SO HUMAN GENE THERAPY LA English DT Article ID ADENOASSOCIATED VIRUS; GENE-TRANSFER; IN-VIVO; TRANSGENE PRODUCTS; AUTOIMMUNE-DISEASE; NONDIVIDING CELLS; SYSTEMIC DELIVERY; HIGH-EFFICIENCY; GROWTH-HORMONE; AAV VECTORS AB We have constructed a recombinant adeno-associated virus serotype 2 vector encoding human interleukin 10 (rAAVhIL10). IL-10 is a potent antiinflammatory/immune cytokine, which has received growing attention for its therapeutic potential. Human IL-10 (hIL-10) production was virus dose dependent after in vitro infection of HSG cells, a human submandibular gland cell line. The vector-derived hIL-10 produced was biologically active, as the medium from rAAVhIL10-infected HSG cells caused a dose-dependent blockade of IL-12 secretion from spleen cells of IL-10 knockout mice challenged with heat-killed Brucella abortus. Administration of rAAVhIL10 (10(10) genomes per gland) to both mouse submandibular glands led to hIL-10 secretion into the bloodstream (similar to1-5 pg/ml), that is, in an endocrine manner, which was stable for similar to2 months. Salivary gland administration of rAAVhIL10 under experimental conditions was more efficacious than intravenous administration (similar to0.5-0.7 pg/ml). Also, hIL-10 was readily secreted in vitro from organ cultures of minced submandibular glands infected with rAAVhIL10, 6 or 8 weeks earlier. Consistent with these results, hIL-10 mRNA was detected by reverse transcription-polymerase chain reaction in submandibular glands of mice infected with rAAVhIL10 but not from control mice. At these doses, little to no hIL-10 was detected in mouse saliva. Using a rAAV serotype 2 vector encoding beta-galactosidase, we observed that the primary parenchymal target cells were ductal. These findings represent the first report of rAAV use to target exocrine glands for systemic secretion of a therapeutic protein, and support the notion that rAAV serotype 2 vectors may be useful in salivary glands for local (periglandular) and systemic gene-based protein therapeutics. C1 NIDCR, GTTB, NIH, Bethesda, MD 20892 USA. US FDA, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NHLBI, Lab Biochem Genet, NIH, Bethesda, MD 20892 USA. RP Baum, BJ (reprint author), NIDCR, GTTB, NIH, 10 Ctr Dr,MSC 1190,Bldg 10,Room 1N113, Bethesda, MD 20892 USA. RI kotin, robert/B-8954-2008; OI Yamano, Seiichi/0000-0003-2056-4359 NR 57 TC 27 Z9 28 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1043-0342 J9 HUM GENE THER JI Hum. Gene Ther. PD JAN PY 2002 VL 13 IS 2 BP 287 EP 298 DI 10.1089/10430340252769806 PG 12 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine GA 515ML UT WOS:000173499600010 PM 11812284 ER PT J AU Delogu, G Li, A Repique, C Collins, F Morris, SL AF Delogu, G Li, A Repique, C Collins, F Morris, SL TI DNA vaccine combinations expressing either tissue plasminogen activator signal sequence fusion proteins or ubiquitin-conjugated antigens induce sustained protective immunity in a mouse model of pulmonary tuberculosis SO INFECTION AND IMMUNITY LA English DT Article ID MYCOBACTERIUM-TUBERCULOSIS; MOLECULAR-CLONING; T-LYMPHOCYTES; IMMUNOGENICITY; RESPONSES; MICE; EFFICACY; VIRULENCE; INJECTION; FAMILY AB DNA vaccination has emerged as a powerful approach in the search for a more efficacious vaccine against tuberculosis. In this study, we evaluated the effectiveness of immunizing with combinations of 10 different tuberculosis DNA vaccines that expressed mycobacterial proteins fused at the N terminus to eukaryotic intracellular targeting sequences. In one vaccine combination, the genes were fused to the tissue plasminogen activator signal sequence (TPA), while in a second combination the same 10 genes were expressed as ubiquitin (Ub)-conjugated proteins. In ex vivo studies in which the secretion of gamma interferon was measured, cellular immune responses were detected in mice vaccinated with either the TPA DNA vaccine combination or the Ub DNA vaccine combination at 7 and 14 days following a low-dose Mycobacterium tuberculosis challenge. Moreover, mice vaccinated with the TPA combination, the Ub combination, and Mycobacterium bovis BCG were able to limit the growth of tubercle bacilli in the lung and spleen after a virulent tuberculous aerosol challenge. Histopathological analyses also showed that mice immunized with the DNA vaccine combinations had substantially improved postinfection lung pathology relative to the naive controls. Finally, in three different long-term experiments, the survival periods following aerogenic challenge were extended as much as sevenfold for vaccinated mice compared to naive controls. Interestingly, in all three experiments, no significant differences were detected in the mean times to death for mice immunized with the TPA combination or the Ub combination relative to the BCG controls. In conclusion, these studies demonstrate the effectiveness of immunization with DNA vaccine combinations against tuberculosis and suggest that further testing of these plasmid cocktails is warranted. C1 US FDA, LMDCI, OVRR, CBER, Bethesda, MD 20892 USA. RP Morris, SL (reprint author), US FDA, LMDCI, OVRR, CBER, HFM-431,Bldg 29,Room 502,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Delogu, Giovanni/I-3701-2012 OI Delogu, Giovanni/0000-0003-0182-8267 NR 40 TC 97 Z9 107 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JAN PY 2002 VL 70 IS 1 BP 292 EP 302 DI 10.1128/IAI.70.1.292-302.2002 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 504FX UT WOS:000172847600040 PM 11748195 ER EF