FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Koo, J Marshall, DL DePaola, A AF Koo, J Marshall, DL DePaola, A TI Antacid increases survival of Vibrio vulnificus and Vibrio vulnificus phage in a gastrointestinal model SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID OYSTERS CRASSOSTREA-VIRGINICA; LACTIC-ACID BACTERIA; SMALL-INTESTINE; UNITED-STATES; GASTRIC-ACID; GULF-COAST; IN-VITRO; PH; FAMOTIDINE; INFECTIONS AB Viable counts of three strains of Vibrio vulnificus and its phage were determined during exposure to a mechanical gastrointestinal model with or without antacid for 9 h at 37 degreesC. V. vulnificus was eliminated (>4-log reduction) within 30 min in the gastric compartment (pH decline from 5.0 to 3.5). Viable Ti. vulnificus cells delivered from the gastric compartment during the first 30 min of exposure reached 10(6) to 10(8) CFU/ml in the intestinal compartment after 9 h (pH 7.0). Phages were eliminated within 45 min in the gastric compartment (pH decline from 5.1 to 2.5). Less than a 2-log reduction of phage was observed in the intestinal compartment after 9 h (pH 7.0). When the gastric compartment contained antacid V. vulnificus counts decreased slightly (<2 log) during 2 h of exposure (pH decline from 7.7 to 6.0), while counts in the intestinal compartment (pH 7.5) reached 10(7) to 10(9) CFU/ml, Phage numbers decreased 1 log after 2 h in the gastric compartment (pH decline from 7.7 to 5.7) containing antacid and decreased 1 log in the intestinal compartment (pH 7.6) after 9 h. Presence of antacid in the gastric compartment of the model greatly increased the ability of both V. vulnificus and its phage to survive simulated gastrointestinal transit and mag be a factor involved,vith oyster-associated illness. C1 Mississippi State Univ, Dept Food Sci & Technol, Mississippi Agr & Forestry Expt Stn, Mississippi State, MS 39762 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. RP Marshall, DL (reprint author), Mississippi State Univ, Dept Food Sci & Technol, Mississippi Agr & Forestry Expt Stn, Box 9805, Mississippi State, MS 39762 USA. NR 45 TC 28 Z9 30 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2001 VL 67 IS 7 BP 2895 EP 2902 DI 10.1128/AEM.67.7.2895-2902.2001 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 448AV UT WOS:000169605400003 PM 11425699 ER PT J AU Grant, MA Weagant, SD Feng, P AF Grant, MA Weagant, SD Feng, P TI Glutamate decarboxylase genes as a prescreening marker for detection of pathogenic Escherichia coli groups SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; BETA-D-GLUCURONIDASE; SEROTYPE O157-H7; IDENTIFICATION; ANTIGEN; GROWTH; STRAIN; FOODS AB The enzyme glutamate decarboxylase (GAD) is prevalent in Escherichia coli but few strains in the various pathogenic E. coli groups have been tested for GAD. Using PCR primers that amplify a 670-bp segment from the gadA and gadB genes encoding GAD, we examined the distribution of the gadAB genes among enteric bacteria. Analysis of 173 pathogenic E, coli strains, including 125 enterohemorrhagic E. coli isolates of the O157:H7 serotype and its phenotypic variants and 38 isolates of enteropathogenic E. coli, enterotoxigenic E. coli, enteroinvasive E, coli, and other Shiga toxin-producing E, coli (STEC) serotypes, showed that gadAB genes were present in all these strains. Among the 22 non-E, coli isolates tested, only the 6 Shigella spp. carried gadAB, Analysis of naturally contaminated water and food samples using a gadAB-specific DNA probe that was labeled with digoxigenin showed that a gadAB-based assay is as reliable as standard methods that enumerate E. coli organisms on the basis of lactose fermentation. The presence of few E. coli cells initially seeded into produce rinsates could be detected by PCR to gadA/B genes after overnight enrichment. ri multiplex PCR assay using he gadAB primers in combination with primers to Shiga toxin (Stx) genes stx(1) and stx(2) was effective in detecting STEC from the enrichment medium after seeding produce rinsate samples with as few as 2 CFU, The gadAB primers may be multiplexed with primers to other trait virulence markers to specifically identify other pathogenic E. coli groups. C1 US FDA, Pacific Reg Lab NW, Bothell, WA 98021 USA. US FDA, Div Microbiol Studies, Washington, DC 20204 USA. RP Grant, MA (reprint author), US FDA, Pacific Reg Lab NW, 22201 23rd Dr SE, Bothell, WA 98021 USA. NR 28 TC 22 Z9 25 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2001 VL 67 IS 7 BP 3110 EP 3114 DI 10.1128/AEM.67.7.3110-3114.2001 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 448AV UT WOS:000169605400033 PM 11425729 ER PT J AU Chizhikov, V Rasooly, A Chumakov, K Levy, DD AF Chizhikov, V Rasooly, A Chumakov, K Levy, DD TI Microarray analysis of microbial virulence factors SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYMERASE-CHAIN-REACTION; ESCHERICHIA-COLI O157-H7; MULTIPLEX PCR; FOODBORNE DISEASES; BOVINE FECES; RFB LOCUS; O157H7; IDENTIFICATION; STRAINS; GENE AB Hybridization with oligonucleotide microchips (microarrays) was used for discrimination among strains of Escherichia coli and other pathogenic enteric bacteria harboring various virulence factors. Oligonucleotide microchips are miniature arrays of gene-specific oligonucleotide probes immobilized on a glass surface. The combination of this technique with the amplification of genetic material by PCR is a powerful tool for the detection of and simultaneous discrimination among food-borne human pathogens. The presence of six genes (eae-l, slt-I, slt-II,fliC, rfbE, and ipaH) encoding bacterial antigenic determinants and virulence factors of bacterial strains was monitored by multiplex PCR followed by hybridization of the denatured PCR product to the gene-specific oligonucleotides on the microchip. The assay was able to detect these virulence factors in 15 Salmonella, Shigella, and E, coli strains, The results of the chip analysis were confirmed by hybridization of radiolabeled gene-specific probes to genomic DNA from bacterial colonies. In contrast, gel electrophoretic analysis of the multiplex PCR products used for the microarray analysis produced ambiguous results due to the presence of unexpected and uncharacterized bands. Our results suggest that microarray analysis of microbial virulence factors might be very useful for automated identification and characterization of bacterial pathogens. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Rasooly, A (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. EM axr@vm.cfsan.fda.gov NR 28 TC 192 Z9 221 U1 0 U2 17 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JUL PY 2001 VL 67 IS 7 BP 3258 EP 3263 DI 10.1128/AEM.67.7.3258-3263.2001 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 448AV UT WOS:000169605400053 PM 11425749 ER PT J AU Jackson, AJ AF Jackson, AJ TI Evaluation of a limited sampling method used to determine the bioequivalence of highly variable drugs with long half-lives SO BIOPHARMACEUTICS & DRUG DISPOSITION LA English DT Article DE bioequivalence; limited sampling approach; clearance ID UNDER-THE-CURVE; MONTE-CARLO SIMULATIONS; RELATIVE EXTENT; BIOAVAILABILITY AB The usefulness of a limited sampling method (LSM) to determine the bioequivalence of highly variable drugs with long half-lives was investigated. The LSM uses multiple linear regression of observed drug plasma concentrations versus area under the curve (AUC) or C-max (peak plasma concentration) to obtain a best set of coefficients, concentration times and intercept based upon the regression coefficient, R-2, to predict the selected pharmacokinetic parameter (i.e. AUC or C-max). The LSM, used successfully in clinical settings, has also been suggested for data analysis of in vivo bioequivalence studies. Because the method has not yet been thoroughly tested under many conditions likely to be encountered in bioequivalence studies, a further investigation of the method's applicability to bioequivalence determination was undertaken. In the present study, training and test data sets incorporating various levels of intrasubject variability in clearance (CL) with different ratios for fraction absorbed (Fa) of test and reference drug formulations were used to further evaluate the applicability of the limited sampling method (LSM) to the evaluation of bioequivalence for drugs with long half-lives of elimination. Both simulated (a one-compartment pharmacokinetic (PK) model with first-order elimination) and experimental data were used in the study. The results indicated that the determination of bioequivalence using the LSM was significantly influenced by the ratio of Fa(test)/Fa(reference) and by the level of intrasubject error (variability) in CL. Therefore, use of the LSM to determine bioequivalence of drugs with long half-lives and highly variable in CL seems suitable only for formulations that have point estimates of Fa(test)/Fa(reference) within the range of 0.9-1.10. Because the Fa ratio range would have to be verified through use of observed data obtained from a pilot study, the practical utility of the LSM in the determination of bioequivalence would be severely limited. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20857 USA. RP Jackson, AJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Gener Drugs, Div Bioequivalence, Rockville, MD 20857 USA. NR 9 TC 4 Z9 4 U1 1 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0142-2782 J9 BIOPHARM DRUG DISPOS JI Biopharm. Drug Dispos. PD JUL PY 2001 VL 22 IS 5 BP 179 EP 190 DI 10.1002/bdd.275 PG 12 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 501ZK UT WOS:000172717700001 PM 11745920 ER PT J AU Hotchkiss, CE Stavisky, R Nowak, J Brommage, R Lees, CJ Kaplan, J AF Hotchkiss, CE Stavisky, R Nowak, J Brommage, R Lees, CJ Kaplan, J TI Levormeloxifene prevents increased bone turnover and vertebral bone loss following ovariectomy in cynomolgus monkeys SO BONE LA English DT Article; Proceedings Paper CT 2nd Joint Meeting of the American-Society-for-Bone-and-Mineral-Research/International-Bone-and-Mi neral-Society CY DEC 01-06, 1998 CL SAN FRANCISCO, CALIFORNIA SP Amer Soc Bone & Mineral Res, Int Bone & Mineral Soc DE levormeloxifene; selective estrogen receptor modulator (SERM); monkey; osteoporosis; ovariectomy ID HORMONE REPLACEMENT THERAPY; ESTROGEN-RECEPTOR MODULATOR; POSTMENOPAUSAL WOMEN; SERUM-CHOLESTEROL; MINERAL DENSITY; PARATHYROID HORMONE-(1-34); MACACA-FASCICULARIS; RHESUS-MONKEYS; RALOXIFENE; MASS AB Levormeloxifene, a nonsteroidal selective estrogen receptor modulator (SERM), has been evaluated for its effects on bone in cynomolgus monkeys (Macaca fascicularis). Adult female monkeys were imported from Indonesia and randomized into six groups of 25-28 animals each (n = 158). Animals in one group were sham ovariectomized (sham) and received vehicle. Animals in the remaining five groups were ovariectomized and received either vehicle (ovx); 17 beta -estradiol at 0.016 mg/kg (est); or levormeloxifene at 0.5 (Ll), I (L2), or 5 (L3) mg/kg. Lumbar spine and whole body bone mass were measured by dual-energy X-ray absorptiometry (DXA) pretreatment and at 6 and 12 months following the initiation of treatment. Bone mass at the femoral neck was measured by peripheral quantitative computed tomography (pQCT) at 0 and 12 months. Serum markers of bone turnover, including bone-specific alkaline phosphatase (BSAP), osteocalcin (BGP), tartrate-resistant acid phosphatase (TRAP), and urinary collagen C-terminal extension peptides (CrossLaps), were measured at 0, 6, and 12 months. Ovariectomy resulted in an increase in these markers; the increase was prevented by estradiol or levormeloxifene. Estradiol or levormeloxifene inhibited loss of lumbar spine bone mineral density (BMD) following ovariectomy compared with untreated monkeys (ovx -5.0%; sham -0.4%; est +0.2%; Ll -3.6%, L2 -2.0%, L3 -2.5%). Estradiol, but not levormeloxifene, prevented loss of BMD at the femoral neck (ovx -7.4%; sham -3.1%; est -3.6%; Ll -8.0%, L2 -6.5%, L3 -7.8%), and whole body bone mineral content (BMC) (ovx -7.6%; sham -1.9%, est -2.9%; Ll -6.2%, L2 -6.1%, L3 -6.7%). Bone loss at each site was correlated with bone turnover as measured by serum and urine biomarkers. There was no dose effect of levormeloxifene. (C) 2001 by Elsevier Science Inc. All rights reserved. C1 Wake Forest Univ, Bowman Gray Sch Med, Comparat Med Sect, Winston Salem, NC 27157 USA. Novo Nordisk AS, Preclin Dev, Pathol, Malov, Denmark. RP Hotchkiss, CE (reprint author), Natl Ctr Toxicol Res, Bionet Corp, Mail Code 915,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 54 TC 20 Z9 21 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 8756-3282 J9 BONE JI Bone PD JUL PY 2001 VL 29 IS 1 BP 7 EP 15 DI 10.1016/S8756-3282(01)00465-3 PG 9 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 458WX UT WOS:000170219400002 PM 11472885 ER PT J AU Tucker, GT Houston, JB Huang, SM AF Tucker, GT Houston, JB Huang, SM TI Optimizing drug development: strategies to assess drug metabolism/transporter interaction potential - towards a consensus SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article C1 Univ Sheffield, Royal Hallamshire Hosp, Div Clin Sci, Molec pharmacol & Pharmacogenet, Sheffield S10 2JF, S Yorkshire, England. Univ Manchester, Sch Pharm & Pharmaceut Sci, Manchester M13 9PL, Lancs, England. US FDA, Ctr Drug Evaluat & Res, OCBP, Rockville, MD 20852 USA. RP Tucker, GT (reprint author), Univ Sheffield, Royal Hallamshire Hosp, Div Clin Sci, Molec pharmacol & Pharmacogenet, Sheffield S10 2JF, S Yorkshire, England. EM G.T.Tucker@sheffeld.ac.uk NR 0 TC 93 Z9 98 U1 0 U2 4 PU BLACKWELL PUBLISHING PI OXFORD PA 9600 GARSINGTON RD, OXFORD OX4 2DQ, OXON, ENGLAND SN 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD JUL PY 2001 VL 52 IS 1 BP 107 EP 117 DI 10.1046/j.0306-5251.2001.temp.1441.x PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 450AN UT WOS:000169719500015 PM 11453898 ER PT J AU Turesky, RJ Parisod, V Huynh-Ba, T Langouet, S Guengerich, FP AF Turesky, RJ Parisod, V Huynh-Ba, T Langouet, S Guengerich, FP TI Regioselective differences in C-8- and N-oxidation of 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline by human and rat liver microsomes and cytochromes p450 1A2 SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID HETEROCYCLIC AROMATIC-AMINES; METABOLIC-ACTIVATION; ESCHERICHIA-COLI; COOKED FOODS; DRUG-METABOLISM; CARCINOGENS; CANCER; PURIFICATION; ENZYMES; CHROMATOGRAPHY AB The metabolism of the mutagen 2-amino-3,8-dimethylimidazo [4,5-f]quinoxaline (MeIQx) was investigated with human and rat liver microsomes, recombinant human cytochrome P450 1A2 (P450 1A2) expressed in Escherichia coli cells, and rat P450 1A2. Human liver microsomes and human P450 1A2 catalyzed the oxidation of the exocyclic amine group of MeIQx to form the genotoxic product 2-(hydroxyamino)-3,8-dimethylimidazo [4,5-f]quinoxaline (HONH-MeIQx). Human P450 1A2 also catalyzed the oxidation of CB-methyl group of MeIQx to form a-amino(8-hydroxymethyl)-3-methylimidazo [4,5-f]quinoxaline (8-CH2OH-IQx), 2-amino-3-methylimidazo[4,5-f] quinoxaline-8-carbaldehyde (IQx-8-CHO), and 2-amino-3-methylimidazo [4,5-f]quinoxaline-8-carboxylic acid [IQx-8-COOH). Thus, chemically stable CB-oxidation products of MeIQx may be useful biomarkers of P450 1A2 activity in humans. Rat liver microsomes were 10-15-fold less active than the human counterpart at both N-oxidation and C-8-oxidation of MeIQx when expressed as nanomoles of product formed per minute per nanomoles of P450 1A2. Differences in regioselective oxidation of MeIQx were also observed with human and rat liver microsomes and the respective P450 1A2 orthologs. In contrast to human liver microsomes and P450 1A2, rat liver microsomes and purified rat P4501A2 were unable to catalyze the oxidation of MeIQx to the carboxylic derivative IQx-8-COOH, an important detoxication product formed in humans. However, rat liver microsomes and rat P4501A2, but not human liver microsomes or human P450 1A2, extensively catalyzed ring oxidation at the C-5 position of MeIQx to form the detoxication product 2-amino-3,8-dimethyl-5-hydroxyimidazo [4,5-f]quinoxaline (5-HO-MeIQx). There are important differences between human and rat P450 1A2, both in catalytic activities and oxidation pathways of MeIQx, that may affect the biological activity of this carcinogen and must be considered when assessing human health risk. C1 Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne 26, Switzerland. Univ Rennes 1, Fac Pharm, INSERM, U456, F-35043 Rennes, France. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Ctr Mol Toxicol, Nashville, TN 37232 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Turesky, RJ (reprint author), Nestec Ltd, Nestle Res Ctr, Vers Chez Les Blanc, CH-1000 Lausanne 26, Switzerland. RI Langouet, Sophie/I-2776-2015 NR 38 TC 25 Z9 25 U1 0 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JUL PY 2001 VL 14 IS 7 BP 901 EP 911 DI 10.1021/tx010035s PG 11 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 454YP UT WOS:000169999600016 PM 11453738 ER PT J AU Feng, P Dey, M Abe, A Takeda, T AF Feng, P Dey, M Abe, A Takeda, T TI Isogenic strain of Escherichia coli O157 : H7 that has lost both Shiga toxin 1 and 2 genes SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; SEROTYPE O157-H7; MULTIPLEX PCR; IDENTIFICATION; CATTLE AB An Escherichia coli O157:H7 strain isolated from a patient with hemorrhagic colitis was found to exhibit two slightly different colony morphology types on differential medium, Each morphological type, designated TT12A and TT12B, was isolated, and serological testing using various assays confirmed that both strains carried the O157 and the H7 antigens, Biochemical testing showed that the strains had identical profiles on AP120E analysis and, like typical O157:H7 strains, did not ferment sorbitol or exhibit P-glucuronidase activity. Analysis with a multiplex PCR assay showed that TT12B did not carry the gene for either Shiga toxin 1 (Stx1) or Stx2, whereas these genes were present in TT12A and the toxins were produced. Apart from that, both strains carried the +93 gusA mutation, the duster I ehxA gene for enterohemolysin, and the eae gene for gamma -intimin, which are all characteristics of the O157:H7 serotype. Phenotypic assays confirmed that both strains exhibited enterohemolysin activity and the attachment and effacing lesion on HeLa cells. Multilocus enzyme electrophoresis analysis showed that the strains are closely related genetically and belong in the same clonal group. Pulsed-field gel electrophoresis (PFGE) typing of XbaI-digested genomic DNA revealed that the two strains differed by two bands but shared 90% similarity and clustered in the same clade, All other non-Stx-producing O157:H7 strains examined clustered in a major clade that was distinct from that of Stx-producing O157:H7 strains. The findings that TT12B was identical to TT12A, except for Stx production, and its PFGE profile is also more closely related to that of Stx-producing O157:H7 strains suggest that TT12B was derived from TT12A by the loss of both stx genes. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. Kitasato Inst, Dept Bacteriol, Tokyo, Japan. Natl Childrens Med Res Ctr, Dept Infect Dis Res, Tokyo 154, Japan. RP Feng, P (reprint author), US FDA, Div Microbiol Studies, HFS-516,200 C St SW, Washington, DC 20204 USA. EM pfeng@cisan.fda.gov NR 22 TC 37 Z9 39 U1 0 U2 2 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD JUL PY 2001 VL 8 IS 4 BP 711 EP 717 DI 10.1128/CDLI.8.4.711-717.2001 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 449UN UT WOS:000169705700008 PM 11427416 ER PT J AU Rex, JH Walsh, TJ Nettleman, M Anaissie, EJ Bennett, JE Bow, EJ Carillo-Munoz, AJ Chavanet, P Cloud, GA Denning, DW de Pauw, BE Edwards, JE Hiemenz, JW Kauffman, CA Lopez-Berestein, G Martino, P Sobel, JD Stevens, DA Sylvester, R Tollemar, J Viscoli, C Viviani, MA Wu, T AF Rex, JH Walsh, TJ Nettleman, M Anaissie, EJ Bennett, JE Bow, EJ Carillo-Munoz, AJ Chavanet, P Cloud, GA Denning, DW de Pauw, BE Edwards, JE Hiemenz, JW Kauffman, CA Lopez-Berestein, G Martino, P Sobel, JD Stevens, DA Sylvester, R Tollemar, J Viscoli, C Viviani, MA Wu, T TI Need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material ID ACQUIRED-IMMUNODEFICIENCY-SYNDROME; LIPOSOMAL AMPHOTERICIN-B; PLACEBO-CONTROLLED TRIAL; MULTICENTER RANDOMIZED TRIAL; LIVER-TRANSPLANT RECIPIENTS; FUNGAL-INFECTIONS; DOUBLE-BLIND; CRYPTOCOCCAL MENINGITIS; NEUTROPENIC PATIENTS; DISSEMINATED HISTOPLASMOSIS AB Studies of invasive fungal infections have been and remain difficult to implement. Randomized clinical trials of fungal infections are especially slow and expensive to perform because it is difficult to identify eligible patients in a timely fashion, to prove the presence of the fungal infection in an unequivocal fashion, and to evaluate outcome in a convincing fashion. Because of these challenges, licensing decisions for antifungal agents have to date depended heavily on historical control comparisons and secondary advantages of the new agent. Although the availability of newer and potentially more effective agents makes these approaches less desirable, the fundamental difficulties of trials of invasive fungal infections have not changed. Therefore, there is a need for alternative trial designs and evaluation strategies for therapeutic studies of invasive mycoses, and this article summarizes the possible strategies in this area. C1 Univ Texas, Sch Med, Ctr Study Emerging & Reemerging Pathogens, Dept Internal Med,Div Infect Dis, Houston, TX USA. Univ Texas, MD Anderson Canc Ctr, Dept Bioimmunotherapy, Houston, TX 77030 USA. NCI, Infect Dis Sect, Pediat Branch, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. US FDA, Div Antiviral Drug Prod, Rockville, MD 20857 USA. Virginia Commonwealth Univ, Div Gen Internal Med, Richmond, VA USA. Univ Arkansas Med Sci, Div Hematol Oncol, Little Rock, AR 72205 USA. Univ Alabama, Birmingham, AL USA. Harbor UCLA Med Ctr, Dept Med, Div Infect Dis, Torrance, CA 90509 USA. Stanford Univ, Santa Clara Valley Med Ctr, Div Infect Dis, San Jose, CA USA. Florida Hosp Med Ctr, Walt Disney Mem Canc Inst, Orlando, FL 32803 USA. Vet Adm Med Ctr, Ann Arbor, MI 48105 USA. Wayne State Univ, Sch Med, Harper Hosp, Detroit Med Ctr, Detroit, MI USA. Univ Manitoba, Hlth Sci Ctr, Winnipeg, MB, Canada. Asesoria Cient & Invest Aplicada, Dept Microbiol, Barcelona, Spain. Hosp Bocage, Dept Infect Dis, Dijon, France. Univ Manchester, Sch Med, N Manchester Gen Hosp, Dept Infect & Trop Dis, Manchester, Lancs, England. Univ Nijmegen Hosp, Dept Hematol, NL-6500 HB Nijmegen, Netherlands. Univ La Sapienza, Dept Human Biopathol, Rome, Italy. Univ Genoa, Genoa, Italy. Ist Igiene & Med Prevent, Milan, Italy. European Org Res & Treatment Canc, Cent Off, Brussels, Belgium. Huddinge Univ Hosp, Stockholm, Sweden. RP Rex, JH (reprint author), 6431 Fannin,1728 JFB, Houston, TX 77030 USA. OI Denning, David/0000-0001-5626-2251 NR 108 TC 38 Z9 39 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 JUL 1 PY 2001 VL 33 IS 1 BP 95 EP 106 DI 10.1086/320876 PG 12 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 439GB UT WOS:000169101500022 PM 11389501 ER PT J AU Powers, JH AF Powers, JH TI Counterpoint: Alternative trial designs for antifungal drugs - Time to talk SO CLINICAL INFECTIOUS DISEASES LA English DT Editorial Material C1 US FDA, Div Special Pathogen & Immunol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NIAID, NIH, Bethesda, MD 20892 USA. RP Powers, JH (reprint author), 9201 Corp Blvd,HFD-590, Rockville, MD 20850 USA. NR 6 TC 6 Z9 6 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 JUL 1 PY 2001 VL 33 IS 1 BP 107 EP 109 DI 10.1086/320895 PG 3 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 439GB UT WOS:000169101500023 PM 11389502 ER PT J AU Carbone, KM AF Carbone, KM TI Borna disease virus and human disease SO CLINICAL MICROBIOLOGY REVIEWS LA English DT Review ID PERIPHERAL-BLOOD MONONUCLEAR; CHRONIC-FATIGUE-SYNDROME; CENTRAL-NERVOUS-SYSTEM; LINKED-IMMUNOSORBENT-ASSAY; POLYMERASE-CHAIN-REACTION; MENTAL-HEALTH WORKERS; HUMAN BRAIN-TISSUE; INFECTED-RATS; PSYCHIATRIC-PATIENTS; AFFECTIVE-DISORDERS AB mThe biology of Borna disease vints (BDV) strongly supports the likelihood of human infection with BDV or a variant of BDV. Thus far, the evidence supporting BDV infection in humans has initiated much controversy among basic and clinical scientists; only time and additional research wilt support or refute the hypothesis of human BDV infection. Until an assay of acceptable specificity and sensitivity has been developed validated and used to document human BDV infection, scientists cannot reasonably begin to associate BDV infection with specific disease syndromes. Clinical studies seeking causal associations between BDV infection and specific diseases must ensure the proper identification of the BDV infection status of patients and control subjects by using a validated, highly sensitive, and highly specific assay for series of assays). For clinical studies, a highly sensitive "screening" test followed by a highly specific confirmatory test will be of significant benefit. Although it is possible to formulate hypotheses about the clinical outcomes of human BDV infection based on animal model work, to dare no human disease has been causally linked to human BDV infection. Scientists all over the world are actively pursuing these issues, and with continuing advances in clinical and basic BDV research, the answers cannot be far away. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Carbone, KM (reprint author), US FDA, Ctr Biol Evaluat & Res, HFM 460,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 129 TC 50 Z9 63 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0893-8512 J9 CLIN MICROBIOL REV JI Clin. Microbiol. Rev. PD JUL PY 2001 VL 14 IS 3 BP 513 EP + DI 10.1128/CMR.14.3.513-527.2001 PG 16 WC Microbiology SC Microbiology GA 451RB UT WOS:000169814100004 PM 11432811 ER PT J AU Muth, MK Nardinelli, C Beach, RH AF Muth, MK Nardinelli, C Beach, RH TI The marketplace for dietary supplements: Recent studies SO DRUG INFORMATION JOURNAL LA English DT Article; Proceedings Paper CT Workshop on Pharmacoeconomics of Botanicals and the Public Health - Economic Implications for a Changing Health Care Environment in the New Millennium CY MAR 08-09, 1999 CL ARLINGTON, VIRGINIA SP Drug Informati Assoc DE dietary supplements; marketplace; labeling; product claims AB To aid in supporting its mission under the Dietary Supplement Health and Education Act of 1994 (DSHEA), the Food and Drug Administration sponsored studies on producers and consumers of dietary supplements, and the range of dietary supplement products available in the marketplace. From these recently completed studies, this paper describes characteristics of the dietary supplement industry and summarizes label information from selected products offered for sale in retail stores, mail-order catalogs, and Internet sites. In addition, we provide examples of recent uses of the dietary supplement market information from these studies. C1 Res Triangle Inst, Ctr Regulatory Econ & Policy, Res Triangle Pk, NC 27709 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Muth, MK (reprint author), Res Triangle Inst, Ctr Regulatory Econ & Policy, 3040 Cornwallis Rd, Res Triangle Pk, NC 27709 USA. NR 9 TC 2 Z9 2 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 JUL-SEP PY 2001 VL 35 IS 3 BP 973 EP 983 PG 11 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 465YK UT WOS:000170617400034 ER PT J AU Wear, KA AF Wear, KA TI A stratified model to predict dispersion in trabecular bone SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID ULTRASOUND VELOCITY; CANCELLOUS BONE; HIP FRACTURE; IN-VITRO; HUMAN CALCANEUS; ACOUSTIC-WAVES; PHASE-VELOCITY; OS CALCIS; ATTENUATION; DENSITY AB Frequency-dependent phase velocity (dispersion) has previously been measured in trabecular bone by several groups. In contrast to most biologic tissues, phase velocity in trabecular bone tends to decrease with frequency. A stratified model, consisting of alternating layers of bone and marrow (in vivo) or water (in vitro), has been employed in an attempt to explain this phenomenon. Frequency-dependent phase velocity was measured from 300 to 700 kHz in 1) phantoms consisting of regularly spaced thin parallel layers of polystyrene sheets in water and 2) 30 calcaneus samples in vitro. For the polystyrene phantoms, the agreement between theory and experiment was good. For the calcaneus samples, the model has some limited usefulness (uncertainty of about 5%) in predicting average phase velocity. More importantly, the model seems to perform consistently well for predicting the frequency dependence of phase velocity in calcaneus. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-142, Rockville, MD 20852 USA. NR 40 TC 53 Z9 55 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 JUL PY 2001 VL 48 IS 4 BP 1079 EP 1083 DI 10.1109/58.935726 PG 5 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 452RX UT WOS:000169873500028 PM 11477766 ER PT J AU Chowdhury, BA Meyer, RJ AF Chowdhury, BA Meyer, RJ TI Role of mometasone furoate nasal spray as an adjunct treatment of acute sinusitis SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Letter C1 US FDA, Div Pulm & Allergy Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Chowdhury, BA (reprint author), US FDA, Div Pulm & Allergy Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 3 TC 1 Z9 2 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 2001 VL 108 IS 1 BP 148 EP 148 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 458AN UT WOS:000170171200028 PM 11447403 ER PT J AU Wilson, P Stewart, A Flournoy, V Zito, SW Vancura, A AF Wilson, P Stewart, A Flournoy, V Zito, SW Vancura, A TI Liquid chromatographic determination of nystatin in pharmaceutical preparations SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE AB A rapid, reversed-phase liquid chromatographic method was developed for the assay of nystatin in the bulk drug and a variety of dosage forms. Analysis was performed on a Symmetry C-18 reversed-phase column using a mobile phase of methanol-water-dimethylformamide (DMF; 55 + 30 + 15, v/v/v), with detection by UV at 305 nm. Quantitation is based on the sum of the peak areas of the 2 major isomers of nystatin. The linearity of the assay was determined for a concentration range of 0.05 to 0.2 mg/mL (correlation coefficient > 0.999). Accuracies and precision showed good reproducibility. C1 NRL, US FDA, Jamaica, NY 11433 USA. CDER, US FDA, Laurel, MD 20708 USA. St Johns Univ, Jamaica, NY 11439 USA. RP Wilson, P (reprint author), NRL, US FDA, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 7 TC 4 Z9 4 U1 2 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 JUL-AUG PY 2001 VL 84 IS 4 BP 1050 EP 1055 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 457EG UT WOS:000170123700009 PM 11501904 ER PT J AU Mossoba, MM Adam, M Lee, T AF Mossoba, MM Adam, M Lee, T TI Rapid determination of total trans fat content - An attenuated total reflection infrared spectroscopy international collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID GAS-CHROMATOGRAPHY AB Interest in trans fat labeling has prompted efforts to develop new, more efficient methods for rapidly and accurately determining trans fat content of foods. A novel and rapid (5 min) attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopic procedure was recently developed and applied to food products. This procedure was voted official method AOCS Cd 14d-99 by the American Oil Chemists' Society in 1999 after testing in a 12 laboratory international collaborative study. The results of the study are described in this paper. Analytical ATR-FTIR results exhibited high accuracy in the range 5-40% trans; results tended to have <2% high bias relative to the gravimetrically determined values. The precision of this internal reflection method was found to be superior to the precision of transmission infrared official methods. It is recommended that the applicability of the ATR-FTIR method be limited to trans levels of >5% (as percent of total fat). C1 US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, Washington, DC 20204 USA. Lipton, Baltimore, MD 21229 USA. Abbott Labs, Ross Prod Div, Columbus, OH 43216 USA. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support, HFS-717,200 C St SW, Washington, DC 20204 USA. NR 12 TC 19 Z9 20 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 JUL-AUG PY 2001 VL 84 IS 4 BP 1144 EP 1150 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 457EG UT WOS:000170123700021 PM 11501916 ER PT J AU Katz, R Wagner, HN Fauntleroy, M Kuwert, T Frank, R AF Katz, R Wagner, HN Fauntleroy, M Kuwert, T Frank, R TI The use of imaging as biomarkers in drug development: Regulatory issues worldwide SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article C1 Pharmacia Corp, Dept Expt Med, Peapack, NJ 07977 USA. Univ Erlangen Nurnberg, Clin Nucl Med, Nurnberg, Germany. US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. RP Frank, R (reprint author), Pharmacia Corp, Dept Expt Med, Peapack, NJ 07977 USA. NR 0 TC 1 Z9 1 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 JUL PY 2001 SU S BP 118S EP 118S PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 450FC UT WOS:000169730000021 ER PT J AU Beger, RD Wilkes, JG AF Beger, RD Wilkes, JG TI Developing C-13 NMR quantitative spectrometric data-activity relationship (QSDAR) models of steroid binding to the corticosteroid binding globulin SO JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN LA English DT Article DE computer modeling; corticosteroid binding globulin; QSDAR; CoSA; CoSASA; C-13 NMR ID AUTOMATED STRUCTURE EVALUATION; MOLECULAR-FIELD ANALYSIS; CHEMICAL-SHIFTS; CHROMATOGRAPHIC RETENTION; SIMILARITY-MATRICES; NEURAL NETWORKS; PREDICTION; VALIDATION; QSAR AB We have developed four quantitative spectrometric data-activity relationship (QSDAR) models for 30 steroids binding to corticosteroid binding globulin, based on comparative spectral analysis (CoSA) of simulated C-13 nuclear magnetic resonance (NMR) data. A QSDAR model based on 3 spectral bins had an explained variance (r(2)) of 0.80 and a cross-validated variance (q(2)) of 0.78. Another QSDAR model using the 3 atoms from the comparative structurally assigned spectral analysis (CoSASA) of simulated C-13 NMR on a steroid backbone template gave an explained variance (r(2)) of 0.80 and a cross-validated variance (q(2)) of 0.73. Positions 3 and 14 from the steroid backbone template have correlations with the relative binding activity to corticosteroid binding globulin that are greater than 0.52. The explained correlation and cross-validated correlation of these QSDAR models are as good as previously published quantitative structure-activity relationship (QSAR), self-organizing map (SOM) and electrotopological state (E-state) models. One reason that the cross-validated variance of QSDAR models were as good as the other models is that simulated C-13 NMR spectral data are more accurate than the errors introduced by the assumptions and approximations used in calculated electrostatic potentials, E-states, HE-states, and the molecular alignment process of QSAR modeling. The QSDAR models developed provide a rapid, simple way to predict the binding activity of a steroid to corticosteroid binding globulin. 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 28 TC 21 Z9 21 U1 0 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0920-654X J9 J COMPUT AID MOL DES JI J. Comput.-Aided Mol. Des. PD JUL PY 2001 VL 15 IS 7 BP 659 EP 669 DI 10.1023/A:1011959120313 PG 11 WC Biochemistry & Molecular Biology; Biophysics; Computer Science, Interdisciplinary Applications SC Biochemistry & Molecular Biology; Biophysics; Computer Science GA 475DN UT WOS:000171146800004 PM 11688946 ER PT J AU Rodriguez-Saona, LE Giusti, MM Durst, RW Wrolstad, RE AF Rodriguez-Saona, LE Giusti, MM Durst, RW Wrolstad, RE TI Development and process optimization of red radish concentrate extract as potential natural red colorant SO JOURNAL OF FOOD PROCESSING AND PRESERVATION LA English DT Article ID ANTHOCYANIN PIGMENT COMPOSITION; ANTIOXIDANT ACTIVITY; FRUIT JUICES AB Red radish concentrate extracts produced from two radish cultivars, red-skinned cv. Fuego and red-fleshed cv. Chinese Red Meat, were evaluated as potential sources of natural colorants. Unit operations were developed and optimized. Anthocyanins were extracted using a modified abrasive peeler or a hammermill for cultivars Fuego and Red Meat, respectively. The anthocyanin extract was further purified by standard juice processing operations and concentrated by conventional evaporative technology and/or direct osmosis. Anthocyanin recoveries of 80-90% as compared to solvent/resin purification were obtained. Anthocyanins extracted from epidermal tissue resulted in juices with fairly low initial degrees Brix (1.3 degrees), which facilitated juice concentration to levels of 17 degrees Brix containing 400 mg anthocyanin/100 mL concentrate. Radish concentrate provided color similar to FD&C Red #40. Sensory analysis showed that the combined use of conventional evaporation and direct osmosis, Improved aroma attributes. Radish concentrate extracts represent a promising natural alternative to the use of FD&C Red #40. C1 Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Wrolstad, RE (reprint author), Oregon State Univ, Dept Food Sci & Technol, 100 Wiegand Hall, Corvallis, OR 97331 USA. RI Giusti, Maria/B-3367-2012; Rodriguez-Saona, Luis/A-8557-2013; OI Giusti, Maria /0000-0002-2348-3530 NR 27 TC 26 Z9 29 U1 1 U2 17 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 USA SN 0145-8892 J9 J FOOD PROCESS PRES JI J. Food Process Preserv. PD JUL PY 2001 VL 25 IS 3 BP 165 EP 182 DI 10.1111/j.1745-4549.2001.tb00452.x PG 18 WC Food Science & Technology SC Food Science & Technology GA 459LP UT WOS:000170252100001 ER PT J AU Brackett, RE Schuman, JD Ball, HR Scouten, AJ AF Brackett, RE Schuman, JD Ball, HR Scouten, AJ TI Thermal inactivation kinetics of Salmonella spp. within intact eggs heated using humidity-controlled air SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ENTERITIDIS; PASTEURIZATION; SHELL AB The heat resistance of six strains of Salmonella (including Enteritidis, Heidelberg, and Typhimurium) in liquid whole egg and shell eggs was determined. Decimal reduction times (D-values) of each of the six strains were determined in liquid whole egg heated at 56.7 degreesC within glass capillary tubes immersed in a water bath. D-values ranged from 3.05 to 4.09 min, and significant differences were observed between the strains tested (alpha = 0.05). In addition, approximately 7 log(10) CFU/g of a six-strain cocktail was inoculated into the geometric center of raw shell eggs and the eggs heated at 57.2 degreesC using convection currents of humidity-controlled air. D-values of the pooled salmonellae ranged from 5.19 to 6.12 min within the center of intact shell eggs. A heating period of 70 min or more resulted in no surviving salmonellae being detected (i.e., an 8.7-log reduction per egg). C1 Univ Georgia, Ctr Food Safety & Qual Enhancement, Griffin, GA 30223 USA. Michael Foods Inc, Egg Prod Co, Gaylord, MN 55334 USA. RP Brackett, RE (reprint author), US FDA, CFSAN, 200 C St SW, Washington, DC 20204 USA. NR 17 TC 10 Z9 10 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 JUL PY 2001 VL 64 IS 7 BP 934 EP 938 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 450WH UT WOS:000169767500003 PM 11456199 ER PT J AU Lee, YJ Shacter, E AF Lee, YJ Shacter, E TI Fas aggregation does not correlate with Fas-mediated apoptosis SO JOURNAL OF IMMUNOLOGY LA English DT Article ID PROTEIN-KINASE-C; INDUCED CELL-DEATH; AUTOIMMUNE LYMPHOPROLIFERATIVE SYNDROME; SIGNALING COMPLEX DISC; JURKAT T-CELLS; LYMPHOMA-CELLS; TNF RECEPTOR; CD95 FAS/APO-1; ACTIVATION; LYMPHOCYTES AB Cross-linking of cell surface Fas molecules by Fas ligand or by agonistic anti-Fas Abs induces cell death by apoptosis. We found that a serine protease inhibitor, N-tosyl-L-lysine chloromethyl ketone (TLCK), dramatically enhances Fas-mediated apoptosis in the human T cell line Jurkat and in various B cell lines resistant to Fas-mediated apoptosis. The enhancing effect of TLCK is specific to Fas-induced cell death, with no effect seen on TNF-alpha or TNF-related apoptosis-inducing ligand-induced apoptosis. TLCK treatment had no effect on Fas expression levels on the cell surface, and neither promoted death-inducing signaling complex formation nor decreased expression levels of cellular inhibitors of apoptosis (FLICE inhibitory protein, X chromosome-linked inhibitor of apoptosis, and Bcl-2). Activation of the Fas-mediated apoptotic pathway by anti-Fas Ab is accompanied by aggregation of Fas molecules to form oligomers that are stable to boiling in SDS and beta -NM. Fas aggregation is often considered to be required for Fas-mediated apoptosis. However, sensitization of cells to Fas-mediated apoptosis by TLCK or other agents (cycloheximide, protein kinase C inhibitors) causes less Fas aggregation during the apoptotic process compared with that in nonsensitized cells. These results show that Fas aggregation and Fas-mediated apoptosis are not directly correlated and may even be inversely correlated. C1 Ctr Biol & Evaluat & Res, Div Therapeut Prot, Immunol Lab, Food & Drug Adm, Bethesda, MD 20892 USA. RP Lee, YJ (reprint author), NINDS, Surg Neurol Branch, Biochem Sect, NIH, Bldg 10,Room 4N258, Bethesda, MD 20892 USA. NR 48 TC 24 Z9 24 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2001 VL 167 IS 1 BP 82 EP 89 PG 8 WC Immunology SC Immunology GA 471VJ UT WOS:000170949100013 PM 11418635 ER PT J AU Wang, JH Shelly, L Miele, L Boykins, R Norcross, MA Guan, E AF Wang, JH Shelly, L Miele, L Boykins, R Norcross, MA Guan, E TI Human notch-1 inhibits NF-kappa B activity in the nucleus through a direct interaction involving a novel domain SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL DEVELOPMENT; TRANSCRIPTION FACTOR; SIGNALING PATHWAY; NEOPLASTIC LESIONS; ANKYRIN REPEATS; HUMAN HOMOLOG; DNA-BINDING; DROSOPHILA; EXPRESSION; RECEPTOR AB Notch participates in diverse cell fate decisions throughout embryonic development and postnatal life. Members of the NF-kappaB/Rel family of transcription factors are involved in the regulation of a variety of genes important for immune function. The biological activity of the NF-kappaB transcription factors is controlled by I kappaB proteins. Our previous work demonstrated that an intracellular, constitutively active form of human Notch-1/translocation-associated Notch homologue-1 (Notch(IC)) functions as an I kappaB molecule with specificity for the NF-kappaB p50 subunit and physically interacts with NF-kappaB in T cells. In the current study, we investigated the roles of different domains of Notch(IC) in the regulation of NF-kappaB-directed gene expression and NF-kappab DNA binding activity. We found that Notch(IC) localizes to the nucleus and that a region in the N-terminal portion of Notch(IC), not the six ankyrin repeats, is responsible for the inhibitory effects of Notch on NF-kappaB-directed gene expression and NF-kappaB DNA binding activity. The N-terminal portion of Notch(IC) inhibited p50 DNA binding and interacted specifically with p50 subunit, not p65 of NF-kappaB. The interaction between Notch and NF-kappaB indicates that in addition to its role in the development of the immune system, Notch-1 may also have critical functions in the immune response, inflammation, viral infection, and apoptosis through control of NF-kappaB-mediated gene expression. C1 NIH, US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot,Lab Gene Regulat, Bethesda, MD 20892 USA. RP Wang, JH (reprint author), NIH, US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot,Lab Gene Regulat, Bldg 29B,Room 4E12,HFM-541,8800 Rockville Pike, Bethesda, MD 20892 USA. FU NCI NIH HHS [1R01CA84065-01] NR 72 TC 81 Z9 85 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUL 1 PY 2001 VL 167 IS 1 BP 289 EP 295 PG 7 WC Immunology SC Immunology GA 471VJ UT WOS:000170949100040 PM 11418662 ER PT J AU Quintero, EJ Langille, SE Weiner, RM AF Quintero, EJ Langille, SE Weiner, RM TI The polar polysaccharide capsule of Hyphomonas adhaerens MHS-3 has a strong affinity for gold SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE Hyphomonas; metal-sequestration; capsule; exopolysaccharide; gold ID PLACER-GOLD; BACTERIA; MARINE; CAULOBACTERS; NOV AB Select groups of bacteria, including prothescate species, have an unusual capacity to sequester gold and bioconcentrate it to very high levels. Hyphomonas adhaerens MHS-3 (MHS-3) is one such species, as demonstrated by Energy Dispersive Spectroscopy. Transmission electron microscopy revealed that the binding site was specific on the polar polysaccharide capsule. A capsuleless mutant and periodate-treated wild type did not sequester gold. The gold may interact with the same sites in the capsule that naturally adhere MHS-3 to surfaces in the marine environment. C1 Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Santa Maria La Antigua, Dept Ciencias Biol, Panama City, Panama. RP Univ Maryland, Dept Cell Biol & Mol Genet, College Pk, MD 20742 USA. NR 30 TC 8 Z9 8 U1 1 U2 2 PU SPRINGER HEIDELBERG PI HEIDELBERG PA TIERGARTENSTRASSE 17, D-69121 HEIDELBERG, GERMANY SN 1367-5435 EI 1476-5535 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD JUL PY 2001 VL 27 IS 1 BP 1 EP 4 DI 10.1038/sj.jim.7000143 PG 4 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 473QA UT WOS:000171055800001 PM 11598803 ER PT J AU Hansen, LB AF Hansen, LB TI A stable gas chromatography-mass spectrometry analysis system to characterize Ma Huang products found in health foods and supplements SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article DE Ma Huang profile; Ephedrines; health foods; diet supplements; gas chromatography; mass spectrometry; chi-square evaluation ID EPHEDRINE AB Herbal mixtures containing Ma Huang are of significant interest because of their popularity regardless of their potential health hazards. In spite of reports of health problems and even several deaths, these products are still frequently recommended for use. The complex nature of the commercial supplement mixtures has posed a problem in both their qualitative and quantitative analysis. A gas chromatographic procedure has been developed to evaluate authenticity of Ma Huang mixtures. Mass spectrometric identification of the six major alkaloid ephedrine components and application of chi-square evaluation of the chromatographic profile allows a determination to be made regarding the nature of the origin of the mixture. For comparison, a standard mixture was prepared that approximates a typical Ma Huang composition based on average amounts of each alkaloid component reported in the literature. The system is temperature stable and allows simultaneous analysis for caffeine and other components of the commercial supplements. Several samples of commercial herbal products were analyzed by the procedure, and their composition is evaluated and discussed. (C) 2001 Wiley-Liss, Inc. and the American Pharmaceutical Association J Pharm Sci 90:943-948, 2001. C1 Food & Drug Adm, Dallas, TX 75204 USA. RP Hansen, LB (reprint author), Food & Drug Adm, 3032 Bryan St, Dallas, TX 75204 USA. NR 14 TC 18 Z9 18 U1 1 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD JUL PY 2001 VL 90 IS 7 BP 943 EP 948 DI 10.1002/jps.1045 PG 6 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 452FH UT WOS:000169846500012 PM 11458341 ER PT J AU Anderson, DL Cunningham, WC Capar, SG Baratta, EJ Mackill, P AF Anderson, DL Cunningham, WC Capar, SG Baratta, EJ Mackill, P TI Nuclear methods for food analysis at the US Food and Drug Administration SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article; Proceedings Paper CT 5th International Conference on Methods and Applications of Radioanalytical Chemistry (MARC-V) CY APR 09-14, 2000 CL KAILUA-KONA, HAWAII SP Amer Nucl Soc Top ID NEUTRON-ACTIVATION ANALYSIS; CERAMIC GLAZES; IMPORTED FOODS; UNITED-STATES; TOTAL DIET; RADIONUCLIDES; IDENTIFICATION; SPECTROMETRY; PGAA; LEAD AB An overview of radioanalytical techniques used in support of research, monitoring programs, and field assignments directed by the U. S. Food and Drug Administration's Center for Food Safety and Applied Nutrition (CFSAN) is presented. The Winchester Engineering and Analytical Center annually determines radionuclide concentrations in 260 Total Diet Study foods, approximately 80 imported foods, and a selection of domestic foods collected near U. S. nuclear power plants. Radioanalytical techniques used at CFSAN's neutron activation analysis laboratory at the National Institute of Standards and Technology are discussed along with applications for research, quality control, and special projects. C1 FDA, Elemental Res Branch, Washington, DC 20204 USA. FDA, Winchester, MA 01890 USA. Winchester Engn & Anal Ctr, Winchester, MA 01890 USA. RP Anderson, DL (reprint author), FDA, Elemental Res Branch, HFS 338, Washington, DC 20204 USA. NR 32 TC 4 Z9 5 U1 0 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD JUL PY 2001 VL 249 IS 1 BP 29 EP 32 PG 4 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 465XZ UT WOS:000170616400006 ER PT J AU Anderson, DL Capar, SG AF Anderson, DL Capar, SG TI Identification of lead in metal food can seams using Co-57 RXRFS SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article; Proceedings Paper CT 5th International Conference on Methods and Applications of Radioanalytical Chemistry (MARC-V) CY APR 09-14, 2000 CL KAILUA-KONA, HAWAII SP Amer Nucl Soc Top ID CERAMIC GLAZES; SPECTROMETRY AB Radioisotope-induced X-ray fluorescence spectrometry procedures developed for screening solder for Ph are described. By using Co-57 as an excitation source, food cans with Pb-soldered seams were easily distinguished from other types of metal cans. Limits of detection (3 sigma) for Ph in metal food can seams were 0.1 and 0.3 mg Pb/cm(2) for count times of 1 hour and 3 minutes, respectively. Pb/Sn ratios were determined for commercial solders containing 0.6% to 84% Pb. Pb content was quantified as low as 0.07%, and Bi and Sb content could be determined for some commercial solders. C1 US FDA, Elemental Res Branch, Washington, DC 20204 USA. RP Anderson, DL (reprint author), US FDA, Elemental Res Branch, HFS-338,200 C St SW, Washington, DC 20204 USA. NR 6 TC 2 Z9 2 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD JUL PY 2001 VL 249 IS 1 BP 77 EP 81 PG 5 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 465XZ UT WOS:000170616400013 ER PT J AU Wear, KA Armstrong, DW AF Wear, KA Armstrong, DW TI Relationships among calcaneal backscatter, attenuation, sound speed, hip bone mineral density, and age in normal adult women SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID HUMAN TRABECULAR BONE; ULTRASONIC BACKSCATTER; QUANTITATIVE ULTRASOUND; CANCELLOUS BONE; MECHANICAL-PROPERTIES; FREQUENCY-DEPENDENCE; OS CALCIS; FRACTURE; VELOCITY; COEFFICIENTS AB The present study was undertaken in order to investigate the use of calcaneal ultrasonic backscatter for the application of diagnosis of osteoporosis. Broadband ultrasonic attenuation (BUA), speed of sound (SOS), the average backscatter coefficient (ABC), and the hip bone mineral density (BMD) were measured in calcanea in 47 women (average age: 58 years, standard deviation: 13 years). All three ultrasound variables had comparable correlations with hip BMD (around 0.5). As reported previously by others, BUA and SOS were rather highly correlated with each other. The logarithm of the ABC was only moderately correlated with the other two. The three ultrasound parameters exhibited similar moderate negative correlations with age. These results taken collectively suggest that the ABC may carry important diagnostic information independent of that contained in BUA and SOS and, therefore, may be useful as an adjunct measurement in the diagnosis of osteoporosis. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. Natl Naval Med Ctr, Endocrinol Clin, Bethesda, MD 20889 USA. RP US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 46 TC 26 Z9 32 U1 0 U2 1 PU ACOUSTICAL SOC AMER AMER INST PHYSICS PI MELVILLE PA STE 1 NO 1, 2 HUNTINGTON QUADRANGLE, MELVILLE, NY 11747-4502 USA SN 0001-4966 EI 1520-8524 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD JUL PY 2001 VL 110 IS 1 BP 573 EP 578 DI 10.1121/1.1378343 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 452FD UT WOS:000169846100052 PM 11508981 ER PT J AU Hiller, L Lowery, JC Davis, JA Shore, CJ Striplin, DT AF Hiller, L Lowery, JC Davis, JA Shore, CJ Striplin, DT TI Nutritional status classification in the Department of Veterans Affairs SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID HOSPITALIZED-PATIENTS; SURGICAL PATIENTS; NECK-CANCER; WEIGHT-LOSS; MALNUTRITION; DIAGNOSIS; OUTCOMES; JUDGMENT; CARE; INDICATORS AB The Department of Veterans Affairs (VA) Nutrition Status Classification scheme uses clinical data that are routinely collected on admission or shortly thereafter for quick inpatient nutrition screening. In this scheme, patients are assigned to 1 of 4 classification levels according to 7 individual indicators. The indicators include nutrition history, unintentional weight loss as a percent of usual body weight, percent of ideal body weight, diet, diagnosis, albumin, and total lymphocyte count. After ratings (1 to 4) are assigned to each of the 7 indicators, overall nutritional status for each patient is determined by an algorithm. The VA classification system includes many of the same criteria used in other nutritional status classifications. Where it differs is in the greater emphasis on the use of objective criteria and in the rigorous evaluation of reliability and validity that went into its development. Because of these extra measures, the VA classification can be used for prioritizing workload, as well as for determining staff requirements and for comparing workload and productivity across health care facilities. So that others might benefit from using this system, this article provides information on how the classification scheme was developed and explains how it is used. C1 VA Ctr Practice Management & Outcomes Res, Ann Arbor, MI 48113 USA. James A Haley VA Hosp, Tampa, FL USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Dept Vet Affairs, Clin Nutr Program, Washington, DC USA. Dept Vet Affairs, Comp Program, Washington, DC USA. RP Lowery, JC (reprint author), VA Ctr Practice Management & Outcomes Res, POB 130170, Ann Arbor, MI 48113 USA. NR 54 TC 7 Z9 7 U1 0 U2 0 PU AMER DIETETIC ASSOC PI CHICAGO PA 216 W JACKSON BLVD #800, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD JUL PY 2001 VL 101 IS 7 BP 786 EP 792 DI 10.1016/S0002-8223(01)00196-1 PG 7 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 460MY UT WOS:000170312400017 PM 11478477 ER PT J AU Sapirstein, W Chandeysson, P Wentz, C AF Sapirstein, W Chandeysson, P Wentz, C TI The Food and Drug Administration approval of endovascular grafts for abdominal aortic aneurysm: An 18-month retrospective SO JOURNAL OF VASCULAR SURGERY LA English DT Editorial Material ID RUPTURE; REPAIR C1 US FDA, Rockville, MD 20850 USA. RP Sapirstein, W (reprint author), US FDA, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 6 TC 22 Z9 22 U1 0 U2 0 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 JUL PY 2001 VL 34 IS 1 BP 180 EP 183 DI 10.1067/mva.2001.116440 PG 4 WC Surgery; Peripheral Vascular Disease SC Surgery; Cardiovascular System & Cardiology GA 452CR UT WOS:000169840000045 PM 11436096 ER PT J AU Scharf, O Golding, H King, LR Eller, N Frazier, D Golding, B Scott, DE AF Scharf, O Golding, H King, LR Eller, N Frazier, D Golding, B Scott, DE TI Immunoglobulin G3 from polyclonal human immunodeficiency virus (HIV) immune globulin is more potent than other subclasses in neutralizing HIV type 1 SO JOURNAL OF VIROLOGY LA English DT Article ID ANTIBODY-TITERS CORRELATE; COMPLEMENT-MEDIATED LYSIS; HUMAN MONOCLONAL-ANTIBODY; HIV-1/SIV CHIMERIC VIRUS; ENVELOPE GLYCOPROTEIN; CELL-LINE; HYPERIMMUNE IMMUNOGLOBULIN; SEGMENTAL FLEXIBILITY; PASSIVE-IMMUNIZATION; IGG SUBCLASSES AB Passive antibody prophylaxis against human immunodeficiency virus type 1 (HIV-1) has been accomplished in primates, suggesting that this strategy may prove useful in humans. While antibody specificity is crucial for neutralization, other antibody characteristics, such as subclass, have not been explored. Our objective was to compare the efficiencies of immunoglobulin G (IgG) subclasses from polyclonal human HIV immune globulin (HMG) in the neutralization of HIV-1 strains differing in coreceptor tropism. IgG1, IgG2, and IgG3 were enriched from HIVIG by using protein A-Sepharose, All three subclasses bound major HIV-1 proteins, as shown by Western blot assay and enzyme-linked immunosorbent assay. In HIV-1 fusion assays using X4, R5, or X4R5 envelope-expressing effector cells, IgG3 more efficiently blocked fusion, In neutralization assays with cell-free viruses using X4 (W, IIIB), R5 (BaL), and X4R5 (DH123), a similar hierarchy of neutralization was found: IgG3 > IgG1 > IgG2. IgG3 has a longer, more flexible hinge region than the other subclasses. To test whether this is important, IgG1 and IgG3 were digested with pepsin to generate F(ab '), fragments or with papain to generate Fab fragments. IgG3(ab '), fragments were still more efficient in neutralization than F(ab '), of IgG1. However, Fab fragments of IgG3 and IgG1 demonstrated equivalent neutralization capacities and the IgG3 advantage was lost. These results suggest that the IgG3 hinge region confers enhanced HIV-neutralizing ability. Enrichment and stabilization of IgG3 may therefore lead to improved HIVIG preparations. The results of this study have implications for the improvement of passive immunization with polyclonal or monoclonal antibodies and suggest that HIV-1 vaccines which induce high-titer IgG3 responses could be advantageous. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Scott, DE (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bldg 29,Room 232,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 45 TC 52 Z9 52 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 JUL PY 2001 VL 75 IS 14 BP 6558 EP 6565 DI 10.1128/JVI.75.14.6558-6565.2001 PG 8 WC Virology SC Virology GA 445JK UT WOS:000169454200034 PM 11413323 ER PT J AU Lay, JO AF Lay, JO TI MALDI-TOF mass spectrometry of bacteria SO MASS SPECTROMETRY REVIEWS LA English DT Review DE MALDI; TOF; mass spectrometry; bacteria; chemotaxonomy; DNA; proteins ID ASSISTED-LASER-DESORPTION/IONIZATION; PERFORMANCE LIQUID-CHROMATOGRAPHY; CHAIN-REACTION PRODUCTS; ESCHERICHIA-COLI; RAPID IDENTIFICATION; WHOLE CELLS; HELICOBACTER-PYLORI; PROTEIN EXPRESSION; MS ANALYSIS; PEPTIDES AB The development of MALDI-TOF mass spectrometry methods for the characterization of bacteria is reviewed and discussed. The general use of MALDI for the characterization of large biomolecules led directly to obvious applications involving the analysis of isolated bacterial proteins. More surprising was the observation that MALDI-TOF mass spectrometry could be applied directly to crude cellular fractions or cellular suspensions and that the resulting data from such complex mixtures could provide evidence for chemotaxonomic classification. Versatility and the rapidity of analysis led to the rapid development of a number of MALDI-TOF methods involving bacteria. Examples of some of the applications covered in this review are the analysis of bacterial RNA and DNA, the detection of recombinant proteins, the characterization of targeted or unknown proteins, bacterial proteomics, the detection of virulence markers, and the very rapid characterization of bacteria at the genus, species, and strain level. The demonstrated capability of taxonomic classification at the strain level, using unprocessed cells, opens the possibility that MALDI-TOF and similar mass spectrometry approaches may contribute significantly to fulfilling emerging needs for the development of near real-time methods for the characterization of bacteria. (C) 2002 John Wiley Sons, Inc.dagger C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Lay, JO (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 71 TC 321 Z9 330 U1 20 U2 105 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0277-7037 J9 MASS SPECTROM REV JI Mass Spectrom. Rev. PD JUL-AUG PY 2001 VL 20 IS 4 BP 172 EP 194 DI 10.1002/mas.10003.abs PG 23 WC Spectroscopy SC Spectroscopy GA 517DE UT WOS:000173595200002 PM 11835305 ER PT J AU Popke, EJ Allen, RR Pearson, EC Hammond, TG Paule, MG AF Popke, EJ Allen, RR Pearson, EC Hammond, TG Paule, MG TI Differential effects of two NMDA receptor antagonists on cognitive-behavioral development in nonhuman primates SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE remacemide; MK-801; N-methyl-D-aspartate (NMDA); fast sodium channels; operant behavior; learning; motivation ID OPERANT TEST BATTERY; PROGRESSIVE RATIO; RHESUS-MONKEYS; ANTICONVULSANT REMACEMIDE; MARIJUANA SMOKE; PERFORMANCE; MK-801; ACID; ACQUISITION; GLUTAMATE AB The present experiment examined effects of chronic exposure to remacemide (an N-methyl-D-aspartate [NMDA] antagonist which also blocks fast sodium channels) or MK-801 (which blocks NMDA receptors, exclusively) on teaming and motivation in young rhesus monkeys. Remacemide (20 or 50 mg/kg/day) or MK-801 (0.1 or 1.0 mg/kg/day) was administered every day to separate groups of animals via orogastric gavage for up to 2 years. Immediately prior to dosing, 5 days per week (M-F), throughout the 2-year dosing period, an incremental repeated acquisition (IRA) task was used to assess learning and a progressive ratio (PR) task was used to assess motivation. The results indicate an effect of 50 mg/kg/day remacemide to impair learning (IRA) which persisted even after drug treatment was discontinued. MK-801 had no effect on teaming but transiently increased motivation. Because the effects of remacemide occurred independently of changes in motivation or response rates, they are likely due to specific cognitive impairments and are not due to an inability of subjects to fulfill the motoric requirements of the task. The fact that MK-801 did not alter learning suggests that NMDA antagonism alone may be insufficient to produce learning deficits in young monkeys and that such deficits may rely on the ancillary blockade of fast sodium channels. (C) 2001 Elsevier Science Inc. All rights reserved. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, US FDA, HFT132, Jefferson, AR 72079 USA. Peak Stat Serv, Evergreen, CO 80439 USA. Astra Zeneca, Safey Assessment, Loughborough LE11 5RH, Leics, England. RP Paule, MG (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, US FDA, HFT132, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 34 TC 25 Z9 26 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2001 VL 23 IS 4 BP 319 EP 332 DI 10.1016/S0892-0362(01)00156-8 PG 14 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 460KG UT WOS:000170306300002 PM 11485835 ER PT J AU Popke, EJ Allen, RR Pearson, EC Hammond, TG Paule, MG AF Popke, EJ Allen, RR Pearson, EC Hammond, TG Paule, MG TI Differential effects of two NMDA receptor antagonists on cognitive-behavioral performance in young nonhuman primates II SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE remacemide; MK-801; N-methyl-D-aspartate (NMDA); fast sodium channels; operant behaviors; color and position discrimination; short-term memory; Rhesus monkeys ID ANTICONVULSANT REMACEMIDE; MARIJUANA SMOKE; RHESUS-MONKEYS; RAT; GLUTAMATE; EXPOSURE; PROFILE; BATTERY; BINDING; CORTEX AB The present experiment examined the effects of chronic exposure to remacemide (an NMDA antagonist that also blocks fast sodium channels) or MK-801 (which blocks NMDA receptors more selectively) on the acquisition of color and position discrimination and shortterm memory behavior in juvenile rhesus monkeys. Throughout the 2-year dosing period, a conditioned position responding (CPR) task was used to assess color and position discrimination and a delayed matching-to-sample (DMTS) task was used to assess memory. Chronic exposure to high doses of either drug delayed the acquisition of accurate color and position discrimination without altering response rates. In the case of MK-801, these effects abated within 6 months of the start of treatment. In the case of remacemide, the effects persisted for 17 months of dosing. Neither compound significantly altered performance of the short-term memory task at any time point or at any dose tested. The fact that the effects of remacemide on behavioral performance were more persistent than those seen for MK-801 suggests that tolerance may develop to the behavioral effects of MK-801, which does not develop to the effects of remacemide. Alternatively, these results may suggest that the concurrent antagonism of NMDA receptors and fast sodium channels may have more profound consequences for behavior than does the antagonism of NMDA receptors alone. (C) 2001 Elsevier Science Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Peak Stat Serv, Evergreen, CO 80439 USA. Astra Zeneca, Safety Assessment, Loughborough LE11 5RH, Leics, England. RP Paule, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 29 TC 26 Z9 26 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD JUL-AUG PY 2001 VL 23 IS 4 BP 333 EP 347 DI 10.1016/S0892-0362(01)00138-6 PG 15 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA 460KG UT WOS:000170306300003 PM 11485836 ER PT J AU Choi, ST Jin, ZZ Ying, ZL AF Choi, ST Jin, ZZ Ying, ZL TI Goodness-of-fit tests for semiparametric models with multiple event-time data SO STATISTICA SINICA LA English DT Article DE counting process; Cox regression; empirical Bayes; goodness of fit; martingale; multiple event times; Poisson process; random effect AB A counting process approach to multiple event times modeled by an Andersen-Gill-type extension of the Cox proportional hazards regression model is considered. Tests for checking the validity of such a model against a general frailty model are proposed. These tests axe derived from a class of statistics that are connected to Robbins' empirical Bayes estimation of Poisson means. We show that these tests axe consistent against any alternative as specified by a nondegenerate frailty. A simple graphical method is introduced to visually check the appropriateness of model assumptions. Simulation studies axe reported and a real life example is presented. A similar test for checking the gamma frailty assumption is also introduced. C1 US FDA, Rockville, MD 20850 USA. Columbia Univ, Joseph L Mailman Sch Publ Hlth, Div Biostat, New York, NY 10032 USA. Columbia Univ, Dept Stat, New York, NY 10027 USA. RP Choi, ST (reprint author), US FDA, 9201 Corp Blvd, Rockville, MD 20850 USA. NR 20 TC 4 Z9 4 U1 0 U2 0 PU STATISTICA SINICA PI TAIPEI PA C/O DR H C HO, INST STATISTICAL SCIENCE, ACADEMIA SINICA, TAIPEI 115, TAIWAN SN 1017-0405 J9 STAT SINICA JI Stat. Sin. PD JUL PY 2001 VL 11 IS 3 BP 723 EP 736 PG 14 WC Statistics & Probability SC Mathematics GA 461VX UT WOS:000170385100017 ER PT J AU Lee, SJ Sa, P AF Lee, SJ Sa, P TI Tolerance limits as a continuous assessment tool SO TOTAL QUALITY MANAGEMENT LA English DT Article ID WEIGHTED MOVING AVERAGE; EWMA CONTROL CHARTS; SCHEMES AB Non-parametric tolerance limits are used to make sure that production will not be outside specifications for non-normal populations. They are constructed usually at the beginning of a process run. These limits do not reflect changes of tolerance level over the lifetime of the process. This article proposes the continuous assessment of process tolerance. The procedure utilizes the exponentially weighted moving average method and provides evidence of process tolerance over the lifetime of the process. The resulting tolerance limits are shown to be narrower on average and exhibit considerably lower variability than the non-parametric limits commonly used. The sample size required for these tolerance limits can also be reduced by a considerable amount over time. C1 Univ N Florida, Dept Math & Stat, Jacksonville, FL 32224 USA. US FDA, CDER, Div Biometr 3, Jacksonville, FL 32224 USA. Univ W Florida, Pensacola, FL 32514 USA. RP Sa, P (reprint author), Univ N Florida, Dept Math & Stat, Jacksonville, FL 32224 USA. NR 29 TC 3 Z9 3 U1 0 U2 1 PU ROUTLEDGE PI HANTS PA CUSTOMER SERVICES DEPT, RANKINE RD, BASINGSTOKE, HANTS RG24 8PR, ENGLAND SN 0954-4127 J9 TOTAL QUAL MANAGE JI Total Qual. Manage. PD JUL PY 2001 VL 12 IS 4 BP 491 EP 510 PG 20 WC Management SC Business & Economics GA 444PA UT WOS:000169407600007 ER PT J AU Latendresse, JR Newbold, RR Weis, CC Delclos, KB AF Latendresse, JR Newbold, RR Weis, CC Delclos, KB TI Polycystic kidney disease induced in F-1 Sprague-Dawley rats fed para-nonylphenol in a soy-free, casein-containing diet SO TOXICOLOGICAL SCIENCES LA English DT Article DE polycystic kidney; nonylphenol; soy-free diet; endocrine disruptor ID PHYTOESTROGEN CONTENT; INHIBITION; GENISTEIN; TOXICITY; EXPOSURE; PROTEIN; LEVEL; CELLS AB para-Nonylphenol (NP; CAS #84852-15-3); an alkylphenol with a 9-carbon olefin side chain, is widely used in the manufacture of nonionic surfactants, lubricant additives, polymer stabilizers, and antioxidants, Due to its wide commercial use and putative endocrine activity in humans and wildlife, the NTP elected to assess its effects on reproduction in multigenerational studies. To avoid known estrogenic activity of phytoestrogens in soy and alfalfa, a soy- and alfalfa-free, casein-containing diet was used in a range-finding study to determine the doses of NP to be tested further. NP was administered to Sprague-Dawley rats in the diet at 0, 5, 25, 200, 500, 1000, or 2000 ppm to F-0 dams beginning on gestation-day 7, The F-1 pups were weaned at postnatal day (PND) 21, and their exposure via diet was continued at the same dose level as their respective dams. Pup weights from birth through weaning were not significantly different from controls in any dose group, but the average weight of both sexes was significantly less compared to controls, beginning with the PND 28 weighing. The F-1 rats were sacrificed on PND 50 (n = 15, 3 pups of each sex from 5 litters for all dose groups). Terminal body weights of males and females in the 2000-ppm dose group were 74% and 85% of controls, respectively. Severe polycystic kidney disease (PKD) was present in 100% of the 2000 ppm-exposed male and female rats. At 1000 ppm, 67% of males and 53% of females had mild to moderate PKD versus none of either sex in the control and lower-dose groups. The no-adverse-effect level (NOAEL) for PKD was determined to be 500 ppm. Previous studies with comparable duration and route of exposure, but using soy-containing diets, reported either no or only mild PKD at 2000 ppm NP. We conclude that the renal toxicity of NP is highly dependent on the diet on which the animals are maintained, The potential interaction of diet and test compounds on nonreproductive as well as reproductive endpoints should be considered when contemplating the use of special diets formulated to minimize exogenous "hormone" content for the study of the effects of putative endocrine disruptive chemicals. C1 Pathol Associates Int, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Dev Endocrinol Sect, Reprod Toxicol Grp, Lab Toxicol,Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Latendresse, JR (reprint author), Pathol Associates Int, Natl Ctr Toxicol Res, POB 26,3900 NCTR Rd, Jefferson, AR 72079 USA. RI Latendresse, John/A-9215-2009 NR 36 TC 24 Z9 24 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUL PY 2001 VL 62 IS 1 BP 140 EP 147 DI 10.1093/toxsci/62.1.140 PG 8 WC Toxicology SC Toxicology GA 444KQ UT WOS:000169399000017 PM 11399801 ER PT J AU Leakey, A Hirst, R La Brooy, J AF Leakey, A Hirst, R La Brooy, J TI Problems in assaying neutrophil activators - Response from Leakey et al. SO TRENDS IN MICROBIOLOGY LA English DT Letter ID HELICOBACTER-PYLORI; PROTEIN C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. James Cook Univ N Queensland, Dept Med, Townsville, Qld 4811, Australia. James Cook Univ N Queensland, Dept Microbiol & Immunol, Townsville, Qld 4811, Australia. RP Leakey, A (reprint author), US FDA, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE LONDON PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0966-842X J9 TRENDS MICROBIOL JI Trends Microbiol. PD JUL PY 2001 VL 9 IS 7 BP 315 EP 315 DI 10.1016/S0966-842X(01)02037-6 PG 1 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 451QJ UT WOS:000169812500012 ER PT J AU Kapley, A Lampel, K Purohit, HJ AF Kapley, A Lampel, K Purohit, HJ TI Rapid detection of Salmonella in water samples by multiplex polymerase chain reaction SO WATER ENVIRONMENT RESEARCH LA English DT Article DE water analysis; polymerase chain reaction; multiplex polymerase chain reaction; etiological agents; genetic diversity; Salmonella; spv; invA; phoE; 16s rRNA ID VIRULENCE REGION; PCR; TYPHIMURIUM; GENE; STRAINS; SPP. AB A rapid protocol for detecting Salmonella species in water samples using the polymerase chain reaction (PCR) technique is described in this paper. Salmonellae, the etiological agents for typhoid fever, salmonellosis, and gastrointestinal infections, require more than 30 hours to be detected in water samples using current standard protocols. In epidemic conditions, where detection time is crucial, the multiplex PCR protocol developed can give results within 5 hours of collection of water samples. This latter protocol uses a gradient temperature program that allows simultaneous amplification of five different loci in a single reaction. The target loci used were invA, phoE, spvA, spvB, and 16s rDNA gene. The selected primers in the reactions allow the detection of a broad range of pathogenic Salmonella, whereas 16s rRNA locus was included as a reaction control for raw water samples devoid of Salmonella. The protocol has been successfully tried on standard strains and on samples collected from river water. C1 Natl Environm Engn Res Inst, Nagpur 440020, Maharashtra, India. US FDA, Washington, DC 20204 USA. RP Purohit, HJ (reprint author), Natl Environm Engn Res Inst, Nagpur 440020, Maharashtra, India. NR 21 TC 20 Z9 20 U1 0 U2 3 PU WATER ENVIRONMENT FEDERATION PI ALEXANDRIA PA 601 WYTHE ST, ALEXANDRIA, VA 22314-1994 USA SN 1061-4303 J9 WATER ENVIRON RES JI Water Environ. Res. PD JUL-AUG PY 2001 VL 73 IS 4 BP 461 EP 465 DI 10.2175/106143001X139515 PG 5 WC Engineering, Environmental; Environmental Sciences; Limnology; Water Resources SC Engineering; Environmental Sciences & Ecology; Marine & Freshwater Biology; Water Resources GA 494ME UT WOS:000172285800010 ER PT J CA FDA Wound Healing Clin Focus Grp TI Guidance for industry: Chronic cutaneous ulcer and burn wounds - developing products for treatment SO WOUND REPAIR AND REGENERATION LA English DT Article C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 13 TC 2 Z9 4 U1 0 U2 0 PU WILEY-BLACKWELL PI HOBOKEN PA 111 RIVER ST, HOBOKEN 07030-5774, NJ USA SN 1067-1927 EI 1524-475X J9 WOUND REPAIR REGEN JI Wound Repair Regen. PD JUL-AUG PY 2001 VL 9 IS 4 BP 258 EP 268 PG 11 WC Cell Biology; Dermatology; Medicine, Research & Experimental; Surgery SC Cell Biology; Dermatology; Research & Experimental Medicine; Surgery GA 479PZ UT WOS:000171413900002 ER PT J AU Weir, JP AF Weir, JP TI Regulation of herpes simplex virus gene expression SO GENE LA English DT Review DE herpesviruses; gene regulation; virus-host cell interactions; transcription ID RNA-POLYMERASE-II; TRANSCRIPTIONAL CONTROL SIGNALS; CYCLIN-DEPENDENT KINASES; EARLY PROTEIN VMW110; DOWNSTREAM ACTIVATION SEQUENCE; OPEN READING FRAME; HOST-CELL FACTOR; DNA-REPLICATION; BINDING-PROTEIN; INFECTED-CELLS AB Expression of the more than 80 individual genes of herpes simplex virus 1 (HSV-1) takes place in a tightly regulated sequential manner that was first described over 20 years ago. Investigations since that time have focused on understanding the mechanisms that regulate this orderly and efficient expression of viral genes. This review examines recent findings that have shed light on how this process is regulated during productive infection of the cell. Although the story is still not complete, several aspects of HSV gene expression are now clearer as a result of these findings. In particular, several new functions have recently been ascribed to some of the known viral regulatory proteins. The results indicate that the viral gene expression is regulated through transcriptional as well as post-transcriptional mechanisms. In addition, it has become increasingly clear that the virus has evolved specific functions to interact with the host cell in order to divert and redirect critical host functions for its own needs. Understanding the interactions of HSV and the host cell during infection will be essential for a complete understanding of how viral gene expression is regulated. Future challenges in the field will be to develop a complete understanding of the mechanisms that temporally regulate virus gene expression, and to identify and characterize the relevant interactions between the virus and the distinctive cell types normally infected by the virus. Published by Elsevier Science B.V. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Rockville, MD 20852 USA. RP Weir, JP (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. NR 124 TC 66 Z9 70 U1 1 U2 7 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD JUN 27 PY 2001 VL 271 IS 2 BP 117 EP 130 DI 10.1016/S0378-1119(01)00512-1 PG 14 WC Genetics & Heredity SC Genetics & Heredity GA 460LN UT WOS:000170309200001 PM 11418233 ER PT J AU Throckmorton, DC AF Throckmorton, DC TI Future trials of antiplatelet agents in cardiac ischemia. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material ID PLACEBO-CONTROLLED TRIALS; ACTIVE-CONTROL TRIALS; DESIGN; EQUIVALENCE; INTEGRIN; ISSUES C1 US FDA, Rockville, MD 20857 USA. RP Throckmorton, DC (reprint author), US FDA, Rockville, MD 20857 USA. NR 16 TC 4 Z9 5 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 21 PY 2001 VL 344 IS 25 BP 1937 EP 1939 DI 10.1056/NEJM200106213442509 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 443VJ UT WOS:000169362100009 PM 11419432 ER PT J AU Tomazic-Jezic, VJ Merritt, K Umbreit, TH AF Tomazic-Jezic, VJ Merritt, K Umbreit, TH TI Significance of the type and the size of biomaterial particles on phagocytosis and tissue distribution SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE biomaterials; particles; tissue distribution; histology; immune responses ID MACROPHAGES IN-VITRO; BONE-RESORPTION; POLYMETHYLMETHACRYLATE PARTICLES; STIMULATED MACROPHAGES; INFLAMMATORY RESPONSE; PARTICULATE DEBRIS; SURFACE-AREA; RECRUITMENT; OSTEOBLASTS; EXPOSURE AB Particulates generated by dissolution or wear of injected or implanted biomaterials may migrate into various tissues and lead to activation of the host's inflammatory and immune responses. The purpose of this study was to evaluate the relevance of size and chemical composition of biomaterial particles on the pattern of particle distribution in host tissues. Adult female B6C3F1 mice were injected intraperitoneally with polymethylmethacrylate (PMMA) particles (size 1.4 and 6.4 mu in diameter) and polystyrene (PS) particles (size 1.2, 5.2, and 12.5 mu in diameter), and euthanized 1, 7 and 28 days later. Peritoneal exudate cells (PECs) were collected and the number of cells and percentage of actively phagocytic cells was determined. Macroscopic examination of the tissues in the peritoneal cavity peritoneum revealed visible accumulations of the colored PS particles in the adipose tissues adjacent to the spleen and pancreas, and caudal to the stomach. Distribution of the FS particles appeared similar regardless of the particle size. The location of PMMA particles, which were not colored, could not be distinguished from host tissue and could not be observed in this manner. Intensive phagocytosis of the small and medium sized particles by peritoneal macrophages was observed on day 1, and was diminishing by day 7 after injection. The largest PS particles (12.5 CL) were not engulfed bp the peritoneal macrophages. Histological examination of the spleen, lymph nodes, and the adjacent adipose tissues revealed a marked difference in the deposition patterns of the two polymers used. PS particles, regardless of size, were accumulated primarily in the white adipose tissues adjacent to the spleen and pancreas gland, but very few particles were observed in the splenic tissue. On the other hand, mice injected with PMMA particles of either size had enlarged and activated spleens with marked deposits of particles in the red pulp. These results indicate that these PS and PMMA particles induce different patterns and intensities of the host response. The chemical makeup of the particle is more important in the distribution pattern than is the size of the particle. (C) 2001 John Wiley & Sons, Inc. C1 Food & Drug Admin, Ctr Devices & Radiol Hlth, Div Life Sci, Rockville, MD 20852 USA. RP Tomazic-Jezic, VJ (reprint author), Food & Drug Admin, Ctr Devices & Radiol Hlth, Div Life Sci, HFZ-112,12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 21 TC 48 Z9 49 U1 0 U2 3 PU JOHN WILEY & SONS INC PI NEW YORK PA 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD JUN 15 PY 2001 VL 55 IS 4 BP 523 EP 529 DI 10.1002/1097-4636(20010615)55:4<523::AID-JBM1045>3.0.CO;2-G PG 7 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 423VZ UT WOS:000168199600010 PM 11288080 ER PT J AU Kotenko, SV Izotova, LS Mirochnitchenko, OV Esterova, E Dickensheets, H Donnelly, RP Pestka, S AF Kotenko, SV Izotova, LS Mirochnitchenko, OV Esterova, E Dickensheets, H Donnelly, RP Pestka, S TI Identification, cloning, and characterization of a novel soluble receptor that binds IL-22 and neutralizes its activity SO JOURNAL OF IMMUNOLOGY LA English DT Article ID INTERFERON-GAMMA RECEPTOR; ALPHA-BETA RECEPTOR; SIGNAL-TRANSDUCTION; FUNCTIONAL-CHARACTERIZATION; MOLECULAR-CLONING; INDUCIBLE FACTOR; CYTOKINE; PROTEINS; INTERLEUKIN-10; EXPRESSION AB (W)ith the use of a partial sequence of the human genome, we identified a gene encoding a novel soluble receptor belonging to the class II cytokine receptor family. This gene is positioned on chromosome 6 in the vicinity of the IFNGR1 gene in a head-to-tall orientation. The gene consists of six exons and encodes a 231-aa protein with a 21-aa leader sequence. The secreted mature protein demonstrates 34% amino acid identity to the extracellular domain of the IL-22R1 chain. Cross-linking experiments demonstrate that the protein binds IL-22 and prevents binding of IL-22 to the functional cell surface IL-22R complex, which consists of two subunits, the IL-22R1 and the IL-10R2(c). chains. Moreover, this soluble receptor, designated IL-22-binding protein (BP), is capable of neutralizing IL-22 activity. In the presence of the IL-22BP, IL-22 is unable to induce Stat activation in IL-22-responsive human lung carcinoma A549 cells. IL-22BP also blocked induction of the suppressors of cytokine signaling-3 (SOCS-3) gene expression by IL-22 in HepG2 cells. To further evaluate IL-22BP action, we used hamster cells expressing a modified IL-22R complex consisting of the intact IL-10R2(c) and the chimeric IL-22R1/gamma R1 receptor in which the IL-22R1 intracellular domain was replaced with the IFN-gamma R1 intracellular domain. In these cells, IL-22 activates biological activities specific for IFN-gamma, such as up-regulation of MHC class I Ag expression. The addition of IL-22BP neutralizes the ability of IL-22 to induce Stat activation and MHC class I Ag expression in these cells. Thus, the soluble receptor designated IL-22BP inhibits IL-22 activity by binding IL-22 and blocking its interaction with the cell surface IL-22R complex. C1 Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Kotenko, SV (reprint author), Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. FU NCI NIH HHS [R01-CA46465, 1P30-CA72720]; NIAID NIH HHS [R01 AI36450, R01 AI43369] NR 31 TC 131 Z9 139 U1 0 U2 7 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD JUN 15 PY 2001 VL 166 IS 12 BP 7096 EP 7103 PG 8 WC Immunology SC Immunology GA 471VH UT WOS:000170949000012 PM 11390454 ER PT J AU Benton, KA Misplon, JA Lo, CY Brutkiewicz, RR Prasad, SA Epstein, SL AF Benton, KA Misplon, JA Lo, CY Brutkiewicz, RR Prasad, SA Epstein, SL TI Heterosubtypic immunity to influenza A virus in mice lacking IgA, all Ig, NKT cells, or gamma delta T cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID A VIRUS; MONOCLONAL-ANTIBODIES; DEFICIENT MICE; B-CELLS; HETEROTYPIC IMMUNITY; NUCLEOPROTEIN GENE; RESPIRATORY-TRACT; MURINE INFLUENZA; LYMPHOCYTES-T; MUTANT MICE AB The mechanisms of broad cross-protection to influenza viruses of different subtypes, termed heterosubtypic immunity, remain incompletely understood. We used knockout mouse strains to examine the potential for heterosubtypic immunity in mice lacking IgA, all Ig and B cells, NKT cells (CD1 knockout mice), or gamma delta T cells. Mice were immunized with live influenza A virus and compared with controls immunized with unrelated influenza B virus. IgA(-/-) mice survived full respiratory tract challenge with heterosubtypic virus that was lethal to controls. IgA(-/-) mice also cleared virus from the nasopharynx and lungs following heterosubtypic challenge limited to the upper respiratory tract, where IgA has been shown to play an important role. Ig(-/-) mice controlled the replication of heterosubtypic challenge virus in the lungs. Acute depletion of CD4(+) or CD8(+) T cell subsets abrogated this clearance of virus, thus indicating that both CD4(+) and CD8(+) T cells are required for protection in the absence of Ig. These results in Ig(-/-) mice indicate that CD4(+) T cells can function by mechanisms other than providing help to B cells for the generation of Abs. Like wild-type mice, CD1(-/-) mice and gamma delta (-/-) mice survived lethal heterosubtypic challenge. Acute depletion of CD4(+) and CD8(+) cells abrogated heterosubtypic protection in gamma delta (-/-) mice, but not B6 controls, suggesting a contribution of gamma delta T cells. Our results demonstrate that the Ab and cellular subsets deficient in these knockout mice are not required for heterosubtypic protection, but each may play a role in a multifaceted response that as a whole is more effective than any of its parts. C1 US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Cellular & Gene Therapies,Mol Immunol Lab, Bethesda, MD 20852 USA. NIAID, Viral Dis Lab, Cellular Biol Sect, NIH, Bethesda, MD 20892 USA. NIAID, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. Indiana Univ, Sch Med, Dept Microbiol & Immunol, Walther Oncol Ctr, Indianapolis, IN 46202 USA. RP Benton, KA (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Therapeut Res & Review, Div Cellular & Gene Therapies,Mol Immunol Lab, 1401 Rockville Pike,HFM-521, Bethesda, MD 20852 USA. NR 72 TC 97 Z9 103 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 JUN 15 PY 2001 VL 166 IS 12 BP 7437 EP 7445 PG 9 WC Immunology SC Immunology GA 471VH UT WOS:000170949000054 PM 11390496 ER PT J AU Sapirstein, W Zuckerman, B Dillard, J AF Sapirstein, W Zuckerman, B Dillard, J TI Intracoronary radiotherapy for restenosis - Reply SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20850 USA. RP Sapirstein, W (reprint author), US FDA, Rockville, MD 20850 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JUN 7 PY 2001 VL 344 IS 23 BP 1796 EP 1796 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 439TL UT WOS:000169133600022 ER PT J AU Schwetz, BA AF Schwetz, BA TI Oral therapy for CMV retinitis 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 28 Z9 28 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 6 PY 2001 VL 285 IS 21 BP 2705 EP 2705 DI 10.1001/jama.285.21.2705 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 437HG UT WOS:000168985800005 PM 11386912 ER PT J AU Schwetz, BA AF Schwetz, BA TI Labeling changes for Orlaam 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 28 Z9 28 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 6 PY 2001 VL 285 IS 21 BP 2705 EP 2705 DI 10.1001/jama.285.21.2705 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 437HG UT WOS:000168985800006 PM 11386912 ER PT J AU Schwetz, BA AF Schwetz, BA TI Safety of aristolochic acid 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 28 Z9 28 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 6 PY 2001 VL 285 IS 21 BP 2705 EP 2705 DI 10.1001/jama.285.21.2705 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 437HG UT WOS:000168985800004 PM 11386912 ER PT J AU Moore, MA Kaplan, DS Picciolo, GL Wallis, RR Kowolik, MJ AF Moore, MA Kaplan, DS Picciolo, GL Wallis, RR Kowolik, MJ TI Effect of cellulose acetate materials on the oxidative burst of human neutrophils SO JOURNAL OF BIOMEDICAL MATERIALS RESEARCH LA English DT Article DE neutrophils; cellulose acetate; hemodialysis; oxidative response; biocompatibility ID CHRONIC-HEMODIALYSIS PATIENTS; DEPENDENT CHEMI-LUMINESCENCE; POLYMORPHONUCLEAR LEUKOCYTES; DIALYSIS MEMBRANES; ACCELERATES APOPTOSIS; STREPTOCOCCUS-MUTANS; ETHYLENE-GLYCOL; IN-VITRO; GM-CSF; GLYCEROL AB Following adverse clinical events involving seven patients undergoing renal dialysis using 12-year-old cellulose acetate hemodialyzers, this in vitro study was proposed in an effort to characterize the inflammatory response to the constituent cellulose acetate (CA) fiber materials. Chemiluminescence (CL) and apoptosis assays were used to determine whether human neutrophils were activated by CA fiber materials and/or are sensitive to degradation/alteration of these fibers over time. Furthermore, the study examined in vitro assays with human neutrophils using a CA film, the solvents used in the film preparation and CA resin. The film could be cut to identical sized pieces in an effort to compare hemodialysis material effects in standardized amounts. For the CL assays, 60-min exposure was followed by secondary stimulation with n-formyl-met-leu-phe (fMLP) or phorbol-12-myristate-13-acetate (PMA). Short-term exposure (60-min postintroduction to CA materials) increased the inflammatory response as measured by the respiratory burst of neutrophils (p less than or equal to .05), with CA fiber exposure significantly compared with cells alone. There was a trend toward an increased response with exposure to older fibers with secondary PMA stimulation. Apoptosis was increased 12% with exposure to the more aged fibers versus 2% with the new fibers. The fiber storage component, glycerol, significantly inhibited the oxidative response (p less than or equal to .001; greater than or equal to 80% suppression with concentrations of 5-20%). The solvents used in film preparation, N,N-dimethylacetamide and tetrahydrofuran, produced greater than a 70% and 60% suppression, respectively, of CL activity for all concentrations greater than or equal to1%. More work is needed to determine the specific nature of the interaction of inflammatory cells with CA materials, but early evidence suggests that neutrophils are activated by CA and display an altered response to more aged fibers. (C) 2001 John Wiley & Sons, Inc. C1 Indiana Univ, Sch Dent, Dept Periodont, Indianapolis, IN 46202 USA. US FDA, Ctr Devices & Radiol Hlth, Div Mech & Mat Sci, Rockville, MD 20852 USA. RP Moore, MA (reprint author), Roche Diagnost Corp, Roche Mol Biochem, 9115 Hague Rd,POB 50414, Indianapolis, IN 46250 USA. EM michelle.moore@roche.com NR 48 TC 10 Z9 11 U1 0 U2 4 PU JOHN WILEY & SONS INC PI HOBOKEN PA 111 RIVER ST, HOBOKEN, NJ 07030 USA SN 0021-9304 J9 J BIOMED MATER RES JI J. Biomed. Mater. Res. PD JUN 5 PY 2001 VL 55 IS 3 BP 257 EP 265 DI 10.1002/1097-4636(20010605)55:3<257::AID-JBM1013>3.0.CO;2-H PG 9 WC Engineering, Biomedical; Materials Science, Biomaterials SC Engineering; Materials Science GA 414QG UT WOS:000167677200001 PM 11255178 ER PT J AU Ahmad, SR Singer, SJ Leissa, BG AF Ahmad, SR Singer, SJ Leissa, BG TI Congestive heart failure associated with itraconazole SO LANCET LA English DT Article AB Itraconazole is a synthetic antifungal agent approved in the USA far the treatment of onychomycosis and serious systemic fungal infections. Animal and clinical pharmacology studies suggest negative inotropic effects with itraconazole. Data from the US Food and Drug Administration's Adverse Event Reporting System suggest that use of itraconazole is associated with congestive heart failure. We summarise the details of 58 cases suggestive of congestive heart failure in association with the use of itraconazole. Labelling of itraconazole has been changed to alert physicians to this new finding. C1 US FDA, Off Postmkt Drug Risk Assessment, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Special Pathogen & Immunol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Ahmad, SR (reprint author), US FDA, Off Postmkt Drug Risk Assessment, Ctr Drug Evaluat & Res, HFD-430,Room 15B-08,5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 80 Z9 86 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD JUN 2 PY 2001 VL 357 IS 9270 BP 1766 EP 1767 DI 10.1016/S0140-6736(00)04891-1 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 440BN UT WOS:000169156200019 PM 11403818 ER PT J AU Astor, BC Kaczmarek, RG Hefflin, B Daley, WR AF Astor, BC Kaczmarek, RG Hefflin, B Daley, WR TI Hospital characteristics and mortality following aortic valve replacement. SO AMERICAN JOURNAL OF EPIDEMIOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0002-9262 J9 AM J EPIDEMIOL JI Am. J. Epidemiol. PD JUN 1 PY 2001 VL 153 IS 11 SU S MA 184 BP S63 EP S63 PG 1 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 437RB UT WOS:000169006400178 ER PT J AU Wysowski, DK Corken, A Gallo-Torres, H Talarico, L Rodriguez, EM AF Wysowski, DK Corken, A Gallo-Torres, H Talarico, L Rodriguez, EM TI Postmarketing reports of QT prolongation and ventricular arrhythmia in association with cisapride and food and drug administration regulatory actions SO AMERICAN JOURNAL OF GASTROENTEROLOGY LA English DT Article ID TORSADES-DE-POINTES; INTERVAL; CLARITHROMYCIN; IMPACT AB OBJECTIVE: To describe the postmarketing safety data used in the risk assessment of cisapride and to summarize the regulatory actions of the Food and Drug Administration (FDA). METHODS: The FDA analyzed reports of patients who developed QT prolongation, torsades de pointes, and ventricular arrhythmia in association with the use of cisapride to assess probable etiology and risk factors. RESULTS: While cisapride was being marketed from 1993-1999, the FDA received reports of the following patients: 117 who developed QT prolongation; 107, torsades de pointes; 16, polymorphic ventricular tachycardia; 18, ventricular fibrillation; 27, ventricular tachycardia; 25, cardiac arrest; 16, serious (unspecified) arrhythmia; and 15, sudden death; for a total of 341 individual patients affected, following use of cisapride. Eighty (23%) of the 341 patients died. Deaths were directly or indirectly associated with an arrhythmic event. Factors that suggested an association with cisapride included a temporal relationship between use of cisapride and arrhythmia, the absence of identified risk factors and other explanations for arrhythmia in some patients, and cases of positive dechallenge and rechallenge. In most individuals, the arrhythmia occurred in the presence of risk factors (other drugs and/or medical conditions). CONCLUSIONS: Postmarketing reports and pharmacokinetic and electrophysiological data provided evidence that cisapride is associated with the occurrence of QT prolongation and torsades de pointes. The risk of fatal arrhythmia with cisapride was believed to outweigh the benefit for the approved indication, treatment of nocturnal heartburn due to gastroesophageal reflux disease, leading to the drug's discontinuation in the United States. (C) 2001 by Am. Cell. of Gastroenterology. C1 US FDA, Div Drug Risk Evaluat 1, Off Post Mkt Drug Risk Assessment, Rockville, MD 20857 USA. US FDA, Div Gastrointestinal & Coagulat Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Wysowski, DK (reprint author), US FDA, Div Drug Risk Evaluat 1, Off Post Mkt Drug Risk Assessment, Parklawn Bldg,Room 15B-08,HFD-430, Rockville, MD 20857 USA. NR 29 TC 130 Z9 135 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0002-9270 J9 AM J GASTROENTEROL JI Am. J. Gastroenterol. PD JUN PY 2001 VL 96 IS 6 BP 1698 EP 1703 DI 10.1016/S0002-9270(01)02490-X PG 6 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 440XB UT WOS:000169201000005 PM 11419817 ER PT J AU Hsueh, HM Liu, JP Chen, JJ AF Hsueh, HM Liu, JP Chen, JJ TI Unconditional exact tests for equivalence or noninferiority for paired binary endpoints SO BIOMETRICS LA English DT Article DE asymptotic test; confidence interval; correlated binary endpoints; exact confidence interval; exact p-value; two one-sided tests ID IMPROVED CONFIDENCE-INTERVALS; BINOMIAL PROPORTIONS; NON-INFERIORITY; SAMPLE-SIZE; DIFFERENCE; DESIGN AB Problems of establishing equivalence or noninferiority between two medical diagnostic procedures involve comparisons of the response rates between correlated proportions. When the sample size is small the asymptotic tests may not be reliable. This article proposes an unconditional exact test procedure to assess equivalence or noninferiority. Two statistics, a sample-based test statistic and a restricted maximum likelihood estimation (RMLE)-based test statistic, to define the rejection region of the exact test are considered. We show the p-value of the proposed unconditional exact tests can be attained at the boundary point of the null hypothesis. Assessment of equivalence is often based on a comparison of the confidence limits with the equivalence limits. We also derive the unconditional exact confidence intervals on the difference of the two proportion means for the two test statistics. A typical data set of comparing two diagnostic procedures is analyzed using the proposed unconditional exact and asymptotic methods. The p-value from the unconditional exact tests is generally larger than the p-value from the asymptotic tests. In other words, an exact confidence interval is generally wider than the confidence interval obtained from an asymptotic test. C1 Natl Hlth Res Inst, Div Biostat Res, Taipei, Taiwan. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Hsueh, HM (reprint author), Natl Hlth Res Inst, Div Biostat Res, Taipei, Taiwan. OI Liu, Jen-pei/0000-0002-9565-1812; HSUEH, HUEY-MIIN/0000-0003-0536-9440 NR 15 TC 30 Z9 31 U1 0 U2 4 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 2001 VL 57 IS 2 BP 478 EP 483 DI 10.1111/j.0006-341X.2001.00478.x PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 437QY UT WOS:000169006100021 PM 11414572 ER PT J AU DiGirolamo, AM Grummer-Strawn, LM Fein, S AF DiGirolamo, AM Grummer-Strawn, LM Fein, S TI Maternity care practices: Implications for breastfeeding SO BIRTH-ISSUES IN PERINATAL CARE LA English DT Article; Proceedings Paper CT 127th Annual Meeting of the American-Public-Health-Association CY NOV 07-10, 1999 CL CHICAGO, ILLINOIS SP Amer Public Hlth Assoc ID 10 STEPS; POLICIES; DISEASE AB Background: Many United Starts mothers never breastfeed their infants or do so for very short periods. The Baby-Friendly Hospital Initiative was developed to help make breastfeeding the norm in birthing environments, and consists of specific recommendations for maternity care practices. The objective of the current study was to assess the impact of the type and number of Baby-Friendly practices experienced on breastfeeding. Methods: A longitudinal mail survey (1993-1994) was administered to women prenatally through 12 months postpartum. The study focused on the 1085 women with prenatal intentions to breastfeed for more than 2 months who initiated breastfeeding, using data from the prenatal and neonatal periods. Predictor variables included indicators of the absence of specific Baby-Friendly practices (late breastfeeding initiating, introduction of supplements, no rooming-in, not breastfeeding on demand, use of pacifiers), and number of Baby-Friendly practices experienced. The main outcome measure was breastfeeding termination before 6 weeks. Results: Only 7 percent of mothers experienced all five Baby-Friendly practices. The strongest risk factors for early breastfeeding termination were late breastfeeding initiating and supplementing the infant. Compared with mothers experiencing all five Baby-Friendly practices, mothers experiencing none were approximately eight times more likely to stop breastfeeding early. Additional practices decreased the risk for early termination. Conclusion: Increased Baby-Friendly Hospital Initiative practices improve the chances of breastfeeding beyond 6 weeks. The need to work with hospitals to increase adoption of these practices in illustrated by the small proportion of mothers who experienced all five practices measured in this study. C1 CDCP, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30341 USA. US FDA, Consumer Studies Branch, US Dept Hlth & Human Serv, Washington, DC 20204 USA. RP Grummer-Strawn, LM (reprint author), CDCP, Natl Ctr Chron Dis Prevent & Hlth Promot, Mailstop K-25,4770 Buford Hwy NE, Atlanta, GA 30341 USA. NR 20 TC 82 Z9 85 U1 0 U2 3 PU BLACKWELL SCIENCE 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 JUN PY 2001 VL 28 IS 2 BP 94 EP 100 DI 10.1046/j.1523-536X.2001.00094.x PG 7 WC Nursing; Obstetrics & Gynecology; Pediatrics SC Nursing; Obstetrics & Gynecology; Pediatrics GA 435HU UT WOS:000168872000004 PM 11380380 ER PT J AU Yang, MH Kunugita, N Kitagawa, K Kang, SH Coles, B Kadlubar, FF Katoh, T Matsuno, K Kawamoto, T AF Yang, MH Kunugita, N Kitagawa, K Kang, SH Coles, B Kadlubar, FF Katoh, T Matsuno, K Kawamoto, T TI Individual differences in urinary cotinine levels in Japanese smokers: Relation to genetic polymorphism of drug-metabolizing enzymes SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID CIGARETTE-SMOKING; NICOTINE; CYP2A6; EXPOSURE; BIOMARKERS; FREQUENCY; DELETION; TOLUENE; REGION; CYP1A1 AB Urinary cotinine, one of the main metabolites of nicotine, has been widely used as a biomarker for assessment of direct or passive exposure to cigarette smoke. However, there is wide variation of the cotinine level among smokers who smoke the same number of cigarettes. To use urinary cotinine as a proper exposure-biomarker for cigarette smoke, interindividual variations of cotinine formation must be considered. Therefore, we studied the effects of genetic polymorphisms in drug metabolic enzymes on urinary cotinine levels among 190 male Japanese smokers (ages 19-66 years; mean, 40.6 years). Genetic polymorphisms in cytochrome P-450s (CYP1A1, CYP2A6, CYP2E1), and aldehyde dehydrogenase 2 (ALDH2) were determined by analyzing DNA isolated from peripheral blood. Cotinine in morning spot urine was analyzed by high-performance liquid chromatography. Lifestyle, i.e., smoking, alcohol consumption, and intake of coffee or tea, was examined using a questionnaire. The number of cigarettes smoked and CYP2A6 polymorphism were significantly associated with the urinary cotinine level, Especially, the urinary cotinine levels was drastically lower in CYP2A6-deleted homozygous (CYP2A6*4/*4) subjects than in CYP2A6*1 allele-positive subjects. The polymorphism in the CYP2E1 5'-flanking region was related to the urinary cotinine level in intermediate smokers (who smoke 11-20 cigarettes/day; P < 0.01). Polymorphisms in CYP1A1 or ALDH2, and consumption of alcohol, coffee, or tea were not associated with the urinary cotinine level. C1 Univ Occupat & Environm Hlth, Dept Environm Hlth, Yahatanishi Ku, Kitakyushu, Fukuoka 8078555, Japan. Univ Occupat & Environm Hlth, Sch Hlth Sci, Kitakyushu, Fukuoka 8078555, Japan. Univ Occupat & Environm Hlth, Res Ctr Commun Use, Kitakyushu, Fukuoka 8078555, Japan. Seoul Natl Univ, Dept Prevent Med, Seoul 110799, South Korea. Ewha Womans Univ, Dept Stat, Seoul 120750, South Korea. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Kawamoto, T (reprint author), Univ Occupat & Environm Hlth, Dept Environm Hlth, Yahatanishi Ku, 1-1 Iseigakoka, Kitakyushu, Fukuoka 8078555, Japan. EM kawamott@med.uoeh-u.ac.jp NR 27 TC 44 Z9 45 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD JUN PY 2001 VL 10 IS 6 BP 589 EP 593 PG 5 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 442BU UT WOS:000169266000003 PM 11401907 ER PT J AU Poirier, LA Wise, CK Delongchamp, RR Sinha, R AF Poirier, LA Wise, CK Delongchamp, RR Sinha, R TI Blood determinations of S-adenosylmethionine, S-adenosylhomocysteine, and homocysteine: Correlations with diet SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MODERATE FOLATE-DEPLETION; ADENOSYL-L-METHIONINE; CHOLINE-DEVOID DIET; DNA METHYLATION; PLASMA HOMOCYSTEINE; METHYLENETETRAHYDROFOLATE REDUCTASE; SEX-DIFFERENCES; RENAL-FAILURE; BREAST-CANCER; COLON-CANCER AB An increasing number of both clinical and experimental studies have shown an association between deficiencies of the dietary sources of physiological methyl groups and cancer formation. The critical metabolic intermediate in a determination of methylation status is S-adenosylmethionine (SAM), the body's chief physiological methyl donor. The present study examined the erythrocyte levels of SAM and of its demethylated metabolite S-adenosylhomocysteine (SAH) in 66 normal subjects (33 men and 33 women), whose blood had been drawn at days 0, 7 and 14 of an experimental period during which they were fed a fixed diet. The plasma levels of homocysteine (HCys) were also determined in the same individuals at the same time points. In addition, the subjects had completed a food frequency questionnaire (FFQ) describing their usual dietary habits before being placed on the dietary regimen. The blood levels of SAM, SAH, and HCys were compared with the dietary intakes of folate, vitamin B-6, fats, and calories, both prior to using the FFQ and during the experimental period. The results indicated that the intraindividual differences were very low, but the interindividual differences were large for the values of SAM, SAH, SAM: SAH ratios, and HCys. Interestingly, the blood levels of SAM and HCys were higher in men than in women and generally showed the expected correlations with folate intake i.e., positive for SAM and negative for HCys. The intakes of folate (276 mug/days) and B-6 (1.87 mg/days) during the 2-week experimental period were relatively low compared with the usual intakes of these vitamins (375 and 2.06 mg/day for folate and B-6, respectively) but correlated well with each other during both periods of the study. Surprisingly, both men and women showed a significant rise in erythrocyte SAM:SAH ratios as a function of age. In addition, the combined results from men and women, even adjusted for gender, showed significant correlations between HCys and both weight and body mass index. On the other hand, during the experimental period of the study, blood SAM levels were inversely correlated with the intakes of both fat and calories when the data for both men and women were combined and adjusted for gender. The blood determinations of SAM and related compounds showed a high degree of reproducibility over time and thus appear to provide a practical marker of methylation status for the assessment of cancer risk from dietary, environmental, and genetic factors. C1 NCI, Environm Epidemiol Branch, Epidemiol & Biostat Program, NIH, Bethesda, MD 20892 USA. US FDA, Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Sinha, R (reprint author), NCI, Environm Epidemiol Branch, Epidemiol & Biostat Program, NIH, Execut Plaza S,6130 Execut Blvd, Bethesda, MD 20892 USA. RI Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [Y01-CP3-0553] NR 67 TC 59 Z9 60 U1 0 U2 8 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 JUN PY 2001 VL 10 IS 6 BP 649 EP 655 PG 7 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 442BU UT WOS:000169266000011 PM 11401915 ER PT J AU Bross, PF Beitz, J Chen, G Chen, XH Duffy, E Kieffer, L Roy, S Sridhara, R Rahman, A Williams, G Pazdur, R AF Bross, PF Beitz, J Chen, G Chen, XH Duffy, E Kieffer, L Roy, S Sridhara, R Rahman, A Williams, G Pazdur, R TI Approval summary: Gemtuzumab ozogamicin in relapsed acute myeloid leukemia SO CLINICAL CANCER RESEARCH LA English DT Article ID MONOCLONAL-ANTIBODIES; CYTOSINE-ARABINOSIDE; PROGENITOR CELLS; STEM-CELLS; CHEMOTHERAPY; ANTIGENS; EXPRESSION; THERAPY; CANCER; ADULTS AB Purpose: Gemtuzumab ozogamicin (Mylotarg; Wyeth Laboratories, Philadelphia, PA) consists of a semisynthetic derivative of calicheamicin, a cytotoxic antibiotic linked to a recombinant monoclonal antibody directed against the CD33 antigen present on leukemic myeloblasts in most patients with acute myeloid leukemia (AML). In this study, me review the preclinical and clinical profiles of this immunoconjugate and the regulatory review that led to marketing approval by the United States Food and Drug Administration. Experimental Design: From the literature and manufacturer's data, we review the activity, tolerability, and pharmacokinetics of gemtuzumab ozogamicin in preclinical and Phase I studies and ifs activity, efficacy, and side effects in three Phase 2 trials of 142 patients with relapsed AML. Results: In Phase I studies, the major toxicity was myelosuppression, especially neutropenia and thrombocytopenia, resulting from the expression of CD33 on myeloid progenitor cells. The Phase 2 dose was 9 mg/m(2) infused i.v. over 4 h, repeated on day 14. A minority of patients experienced acute infusion-related symptoms, usually transient and occasionally requiring hospitalization. The complete response (CR) rate with full recovery of hematopoiesis was 16%. A subset of patients [CRs with incomplete platelet recovery (CRps)] mas identified with blast clearance and neutrophil recovery but incomplete platelet recovery. The duration of responses of CRps appeared to be similar to those of the CRs, although the numbers were small. The question of the equivalence of these response groups was a central issue in the review of this new drug application (NDA). After considerable discussion, the Oncology Drugs Advisory Committee recommended allowing inclusion of CRps resulting in an overall response rate in the Phase 2 studies of 30%. In the subgroup of patients over 60 years of age, the overall response rate was 26%. Response duration was difficult to establish because of the high prevalence of postremission therapies. Tolerability and ease of administration may be improved compared with conventional chemotherapy, except for hepatotoxicity, with 31% of patients exhibiting abnormal liver enzymes. One patient died of liver failure in the Phase 2 trials. Conclusions: Marketing approval of gemtuzumab ozogamicin was granted on May 17, 2000 by the United States Food and Drug Administration under the Accelerated Approval regulations. Gemtuzumab ozogamicin is indicated for the treatment of patients with CD33 positive AML in first relapse who are 60 years of age or older and who are not considered candidates for cytotoxic chemotherapy. The approved dose was 9 mg/m(2) i.v. over 4 h and repeated in 14 days. Completion of the ongoing studies of gemtuzumab ozogamicin in relapsed AML and initiation of randomized clinical trials comparing the effects of gemtuzunab ozogamicin in combination with conventional induction chemotherapy to conventional chemotherapy alone on survival are mandated to confirm clinical benefit under the accelerated approval Subpart H regulations. Postmarketing reports of fatal anaphylaxis, adult respiratory distress syndrome (ARDS), and hepatotoxicity, especially venoocclusive disease (VOD) in patients treated with gemtuzumab ozogamicin, with and without associated hematopoietic stem cell transplantation (HSCT), have required labeling revisions and the initiation of a registration surveillance program. Tumor lysis and ARDS have been reported in patients with leukocytes above 30,000/ml treated with gemtuzumab ozogamicin; therefore, the reduction of leukocyte counts to below 30,000/ml is recommended prior to treatment. Patients should be carefully monitored for acute hypersensitivity, hypoxia, and delayed hepatotoxicity following treatment with gemtuzumab ozogamicin. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20852 USA. RP Bross, PF (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, HFD 150,1451 Rockville Pike, Rockville, MD 20852 USA. NR 23 TC 444 Z9 466 U1 6 U2 27 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 2001 VL 7 IS 6 BP 1490 EP 1496 PG 7 WC Oncology SC Oncology GA 442XQ UT WOS:000169310600002 PM 11410481 ER PT J AU Gutman, SI AF Gutman, SI TI FDA's role in the regulation of laboratory tests: An update on ASRs, IVDs, OTCs, CLIA waivers, & the SACGT report SO CLINICAL CHEMISTRY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER ASSOC CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S MA 3403 BP S28 EP S28 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400070 ER PT J AU O'Leary, TJ AF O'Leary, TJ TI The impact of FDA regulations on the clinical laboratory SO CLINICAL CHEMISTRY 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 CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S BP S28 EP S29 PN 2 PG 2 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400072 ER PT J AU Sliva, C AF Sliva, C TI FDA's new waiver criteria SO CLINICAL CHEMISTRY 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 CLINICAL CHEMISTRY PI WASHINGTON PA 2101 L STREET NW, SUITE 202, WASHINGTON, DC 20037-1526 USA SN 0009-9147 J9 CLIN CHEM JI Clin. Chem. PD JUN PY 2001 VL 47 IS 6 SU S BP S34 EP S34 PN 2 PG 1 WC Medical Laboratory Technology SC Medical Laboratory Technology GA 437MX UT WOS:000168996400092 ER PT J AU Zoon, KC AF Zoon, KC TI Regulation of new biomedical technologies: the next frontier - Editorial overview SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Editorial Material C1 US FDA, Biol Res Ctr, Rockville, MD 20852 USA. RP Zoon, KC (reprint author), US FDA, Biol Res Ctr, Room 418,Bldg 29,8800 Rockville Pk, Rockville, MD 20852 USA. EM zoon@cber.fda.gov NR 2 TC 1 Z9 1 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD JUN PY 2001 VL 12 IS 3 BP 297 EP 298 DI 10.1016/S0958-1669(00)00214-7 PG 2 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 440GG UT WOS:000169167100011 ER PT J AU Smith, HA Klinman, DM AF Smith, HA Klinman, DM TI The regulation of DNA vaccines SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID INDUCE AUTOIMMUNE-DISEASE; CPG MOTIFS; TISSUE DISTRIBUTION; IMMUNE-RESPONSES; INTERFERON-GAMMA; MALARIA VACCINE; SAFETY; IMMUNIZATION; MICE; VIRUS AB The framework for regulating DNA vaccines has been in place since the first clinical trial was initiated in the mid-1990s. American and European regulatory guidance has evolved on the basis of insights provided by ongoing preclinical and clinical studies. These include analyses of the safety of DNA vaccines in normal volunteers, and recent data concerning the tissue distribution, persistence, and integration potential of DNA plasmids. C1 US FDA, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Smith, HA (reprint author), US FDA, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 38 TC 35 Z9 38 U1 1 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD JUN PY 2001 VL 12 IS 3 BP 299 EP 303 DI 10.1016/S0958-1669(00)00215-9 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 440GG UT WOS:000169167100012 PM 11404109 ER PT J AU Friedmann, T Noguchi, P Mickelson, C AF Friedmann, T Noguchi, P Mickelson, C TI The evolution of public review and oversight mechanisms in human gene transfer research: joint roles of the FDA and NIH SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review AB The federal government is critically examining its responsibilities and opportunities for bringing the new field of gene therapy to fruition and for assuring public confidence in this new area of biomedicine. The evolving mechanisms for review and regulation in human gene transfer studies in the United States are being enhanced by increasingly effective interactions between the Food and Drug Administration and the National Institutes of Health. C1 Univ Calif San Diego, Sch Med, Program Human Gene Therapy, Ctr Genet Mol, La Jolla, CA 92093 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. MIT, Biosafety Off, Cambridge, MA 02139 USA. RP Friedmann, T (reprint author), Univ Calif San Diego, Sch Med, Program Human Gene Therapy, Ctr Genet Mol, La Jolla, CA 92093 USA. NR 6 TC 7 Z9 7 U1 0 U2 2 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD JUN PY 2001 VL 12 IS 3 BP 304 EP 307 DI 10.1016/S0958-1669(00)00216-0 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 440GG UT WOS:000169167100013 PM 11404110 ER PT J AU Stein, KE Webber, KO AF Stein, KE Webber, KO TI The regulation of biologic products derived from bioengineered plants SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID TRANSGENIC PLANTS; TOBACCO PLANTS; GLYCOSYLATION; PROTEINS; VACCINES AB Recently, there has been a large increase in the number and types of biological products - from therapeutic antibodies to vaccines for the prevention of infectious diseases - that are produced in bioengineered plant systems. We anticipate that this technology will be used increasingly on a commercial scale for the manufacture of human and animal products. These production systems have the capacity to produce very large quantities of products at lower costs and with reduced risks compared with mammalian systems. C1 Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Off Therapeut Res & Review, Bethesda, MD 20892 USA. RP Stein, KE (reprint author), Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Off Therapeut Res & Review, 29 Lincoln Dr, Bethesda, MD 20892 USA. NR 13 TC 19 Z9 19 U1 0 U2 0 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD JUN PY 2001 VL 12 IS 3 BP 308 EP 311 DI 10.1016/S0958-1669(00)00217-2 PG 4 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 440GG UT WOS:000169167100014 PM 11404111 ER PT J AU Bloom, ET AF Bloom, ET TI Xenotransplantation: regulatory challenges SO CURRENT OPINION IN BIOTECHNOLOGY LA English DT Review ID PORCINE ENDOGENOUS RETROVIRUS; LIVER SUPPORT SYSTEM; BIOARTIFICIAL LIVER; HUMAN-CELLS; INFECTION AB During 1999-2000, the US government published three xenotransplantation policy/guidance documents, one by the Public Health Service and two by the Food and Drug Administration (FDA). The FDA also held two public meetings of the xenotransplantation subcommittee of the Biological Response Modifiers Advisory Committee to discuss particular issues in xenotransplantation. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Rockville, MD 20852 USA. RP Bloom, ET (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, HFM-518,1401 Rockville Pike, Rockville, MD 20852 USA. NR 21 TC 8 Z9 8 U1 0 U2 1 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0958-1669 J9 CURR OPIN BIOTECH JI Curr. Opin. Biotechnol. PD JUN PY 2001 VL 12 IS 3 BP 312 EP 316 DI 10.1016/S0958-1669(00)00218-4 PG 5 WC Biochemical Research Methods; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 440GG UT WOS:000169167100015 PM 11404112 ER PT J AU White, DG McDermott, PF AF White, DG McDermott, PF TI Biocides, drug resistance and microbial evolution SO CURRENT OPINION IN MICROBIOLOGY LA English DT Review ID GRAM-NEGATIVE BACTERIA; STAPHYLOCOCCUS-AUREUS; ANTIBIOTIC-RESISTANCE; PSEUDOMONAS-AERUGINOSA; ESCHERICHIA-COLI; ANTIMICROBIAL AGENTS; TRICLOSAN; BIOFILMS; DISINFECTANTS; ANTISEPTICS AB Antimicrobial biocides are widely used in critical human health situations in which rigorous infection control is needed. Increasingly, biocidal agents are being marketed for home use, although there is little evidence that they significantly improve home hygiene. Biocide resistance mechanisms share many themes With antibiotic resistance mechanisms. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP White, DG (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 43 TC 37 Z9 40 U1 6 U2 29 PU CURRENT BIOLOGY LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 1369-5274 J9 CURR OPIN MICROBIOL JI Curr. Opin. Microbiol. PD JUN PY 2001 VL 4 IS 3 BP 313 EP 317 DI 10.1016/S1369-5274(00)00209-5 PG 5 WC Microbiology SC Microbiology GA 440HA UT WOS:000169168800014 PM 11378485 ER PT J AU Myers, MJ Farrell, DE Howard, KD Kawalek, JC AF Myers, MJ Farrell, DE Howard, KD Kawalek, JC TI Identification of multiple constitutive and inducible hepatic cytochrome P450 enzymes in market weight swine SO DRUG METABOLISM AND DISPOSITION LA English DT Article ID DRUG-METABOLIZING-ENZYMES; LIVER-MICROSOMES; PIGS; HYDROXYLATION; PURIFICATION; HEPATOCYTES; EXPRESSION; ISOZYMES; GENE; RATS AB Constitutive swine enzymes analogous to human/rat cytochrome P450 (CYP) isoforms 1A2, 2A6, 2B1/2/6, 2D6, 2E1, 3A1, and 4A1/3 were detected by Western blot analysis. Swine 2E1 has a molecular weight greater than rat 2E1; swine 2B2 has a molecular weight similar to human 2B6. An induction cocktail containing beta -naphthoflavone, phenobarbital, and dexamethasone induced immunoreactive homologs of 1A1, 1A2, 2B1, 2B2, 3A1, and 3A2. Although the P450 content was increased by induction, there was no difference in the Soret lambda (max). Swine 1A1 has a lower molecular weight than swine 1A2 and rat 1A1. A swine 2B1 homolog was seen after induction, with a molecular weight that was lower than rat 2B1 but higher than swine 2B2. Induction did not augment swine 2B2 levels. The 3A homologs have molecular weights similar to their rodent counterparts. Following induction, swine 3A1 levels increased and were accompanied by the appearance of swine 3A2. Induction had no effect on expression of 2A6, 2B6, 2D6, 2E1, or 4A1/3. Enzyme induction increased the specific activities (nmol/min/mg) of substrates specific for 1A (7 of 7 substrates tested), 2A (2/2), 2B (5/5), 2C (1/3), 2D (3/4), 2E (3/3), 3A (3/5), and 4A (1/1). Although the specific activities of the 28 substrates increased, the turnover number for hydroxylation of chlorzoxazone was unchanged and that of p-nitrophenol and aniline were depressed in induced pigs. These results show that swine CYP isoforms are similar to those identified in human and rodents, but they are also different in many ways. C1 US FDA, Ctr Vet Med, Div Anim Res, Res Off, Laurel, MD 20708 USA. RP Myers, MJ (reprint author), US FDA, Ctr Vet Med, Div Anim Res, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 42 TC 62 Z9 71 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 JUN PY 2001 VL 29 IS 6 BP 908 EP 915 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 437TG UT WOS:000169009200021 PM 11353762 ER PT J AU Morris, SM Pipkin, JL Hinson, WG Shaddock, JG Tolleson, WH Young, JF Casciano, DA AF Morris, SM Pipkin, JL Hinson, WG Shaddock, JG Tolleson, WH Young, JF Casciano, DA TI Decreased in vitro interaction between p53 and nuclear stress proteins in the p53-deficient mouse SO ELECTROPHORESIS LA English DT Article DE p53; p53-deficient mouse; nuclear stress proteins ID HEAT-SHOCK PROTEINS; POLYACRYLAMIDE GELS; MAMMARY-TUMOR; MUTATED P53; MUTANT P53; DNA-DAMAGE; CELL-LINE; IN-VITRO; GELDANAMYCIN; COMPLEXES AB In a previous study, the strength of the interaction between the nuclear stress proteins (sps) 25a, 70i, 72c, and 90 and the tumor suppressor protein p53 was determined by an in vitro fluorescence binding assay. The relative binding of the individual sps with p53, derived from the bone marrow of transgenic mice heterozygous at the p53 locus (p53+/-), was reduced compared to the interaction of sps and p53 derived from wild-type (p53+/-) mice. In order to determine if the genotype of the p53 donor or the genotype of the sp donor determined the binding efficiency, p53 expression was induced by retinoic acid and sp synthesis by bleomycin. P53 derived from either wildtype or heterozygous animals was cross-reacted with nuclear sps obtained from either wild-type or heterozygous animals. Each of the sps, 25a, 70i, 72c, and 90, bound to wild-type p53 with a similar efficiency, irrespective of the genotype of the sp donor mouse @53+/+ or p53+/-). In contrast, when the sp interaction with p53 obtained from the heterozygous mouse was measured, the relative value of the fluorescence complex was significantly reduced. The data suggest that the strength of the interaction between p53 and nuclear sps is related to the genotype of the p53 donor, and not to the genotype of the animals from which the sps are derived. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Facil & Engn, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Morris, SM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 46 TC 2 Z9 2 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 2001 VL 22 IS 10 BP 2092 EP 2097 DI 10.1002/1522-2683(200106)22:10<2092::AID-ELPS2092>3.0.CO;2-Q PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 451GA UT WOS:000169791700028 PM 11465510 ER PT J AU Stancato, LF Petricoin, EF AF Stancato, LF Petricoin, EF TI Fingerprinting of signal transduction pathways using a combination of anti-phosphotyrosine immunoprecipitations and two-dimensional polyacrylamide gel electrophoresis SO ELECTROPHORESIS LA English DT Article DE protein immunoprecipitation; phosphotoyrosine; proteomics; two-dimensional polyacrylamide gel electrophoresis ID CYTOKINE-REGULATED PROTEINS; PHOSPHORYLATED PROTEINS; IDENTIFICATION; TYROSINE; CELLS AB Virtually all known cellular processes involve modulation of cellular signaling pathways via changes in protein phosphorylation. With genomics efforts more than doubling the number of proteins available for analysis, a major challenge will be to identify unknown phosphoproteins as they exist in the normal or diseased intracellular environment. Recent advances in proteomic technology have made it possible to examine changes in protein expression with much greater resolution than was previously possible. in this report, we describe a rapid and reproducible method for identifying phosphoproteins upregulated in response to activation of cell surface receptors. Phosphotyrosine-containing proteins were immunoprecipitated from IFN alpha- or IL2-treated primary human lymphocyte extracts using a novel anti-phosphotyrosine immunoprecipitation technique. This technique takes advantage of differing antibody affinities for epitopes on native versus denatured proteins. Following separation from the immunopellets, phosphoproteins are resolved by two-dimensional polyacrylamide gel electrophoresis. With this method, we identified known proteins phosphorylated in response to IL2 or IFN alpha using both silver staining and Western blotting for protein detection/identification. The silver-stained immunoprecipitation profile serves as a fingerprint for phosphorylation events that occur in response to cytokine treatment. By merging these techniques with mass spectrometric microsequencing, new capabilities are achieved. It will then be possible to identify novel signaling proteins that are activated in response to a variety of stimuli, including receptor activation, disease progression, etc. C1 US FDA, Ctr Biol Evaluat & Res, Tissue Proteom Unit, Div Therapeut Prod, Bethesda, MD USA. Eli Lilly & Co, Res Triangle Pk, NC USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Tissue Proteom Unit, Div Therapeut Prod, Bethesda, MD USA. NR 9 TC 27 Z9 27 U1 0 U2 1 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JUN PY 2001 VL 22 IS 10 BP 2120 EP 2124 DI 10.1002/1522-2683(200106)22:10<2120::AID-ELPS2120>3.0.CO;2-9 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 451GA UT WOS:000169791700032 PM 11465514 ER PT J AU Dietrich, DR O'Brien, E Stack, ME Heussner, AH AF Dietrich, DR O'Brien, E Stack, ME Heussner, AH TI Species- and sex-specific renal cytotoxicity of Ochratoxin A and B in vitro SO EXPERIMENTAL AND TOXICOLOGIC PATHOLOGY LA English DT Article DE ochratoxin; cytotoxicity; in vitro ID BALKAN ENDEMIC NEPHROPATHY; PRIMARY CULTURE; RAT; TOXICITY; CELLS; KIDNEY; GROWTH; MOUSE; PIGS AB Four different cell models were chosen for comparison of OTA and OTB toxicity: primary porcine (PKC), rat (RPTC) and human renal proximal epithelial cells (HKC) from both sexes and a porcine renal cell line: LLC-PK1. Culture conditions were tested and optimized for each respective cell type (species/sex and origin). All cell types were characterized for epithelial origin and growth patterns and following optimization of dosing strategies and assay procedures, a strict study design was implemented to avoid systemic variations. Due to possible sensitivity differences, three simple endpoints were chosen to provide basic data for interspecies comparison: neutral red uptake, MTT reduction and cell number. Of the endpoints tested neutral red appeared the most sensitive, although all three parameters yielded comparable EC50's. Sex-differences were observed between male and female HKC cells following 96 h exposure to OTA, with HKC(m) being more sensitive than HKC(f). No sex-difference was observed in PKC cells, however, the PKC were approximately 3 and 10 times more sensitive than HKC(m) and HKC(f), respectively, to OTA and OTB. Interestingly, the CI95 of the Ec(50) values obtained for OTA (15.5-16.5 muM) and OTB (17.0-21.0 muM) were comparable in the PKC cells, in contrast, OTB had lower cytotoxicity than OTA in HKC and LLC-PK1 (approx. 2-fold) and no effects in RPTC. Overall. HKC(m) were nearly as sensitive as PKC towards OTA, followed by RPTC, LLC-PK1 and HKC(f), thus suggesting a sex specific sensitivity in humans towards OTA induced cytotoxicity. C1 Univ Konstanz, D-78464 Constance, Germany. US FDA, Washington, DC 20204 USA. RP Dietrich, DR (reprint author), Univ Konstanz, Jacob Burckhardt Str 25, D-78464 Constance, Germany. NR 41 TC 34 Z9 34 U1 0 U2 4 PU URBAN & FISCHER VERLAG PI JENA PA BRANCH OFFICE JENA, P O BOX 100537, D-07705 JENA, GERMANY SN 0940-2993 J9 EXP TOXICOL PATHOL JI Exp. Toxicol. Pathol. PD JUN PY 2001 VL 53 IS 2-3 BP 215 EP 225 DI 10.1078/0940-2993-00184 PG 11 WC Pathology; Toxicology SC Pathology; Toxicology GA 455QU UT WOS:000170039000017 PM 11484842 ER PT J AU Collins, TFX Sprando, RL Black, TN Shackelford, ME Bryant, MA Olejnik, N Ames, MJ Rorie, JI AF Collins, TFX Sprando, RL Black, TN Shackelford, ME Bryant, MA Olejnik, N Ames, MJ Rorie, JI TI Multigenerational evaluation of sodium fluoride in rats SO FOOD AND CHEMICAL TOXICOLOGY LA English DT Article DE sodium fluoride; reproduction; multigeneration; rat ID DEVELOPMENTAL TOXICITY; AFFECT SPERMATOGENESIS; BONE; REPRODUCTION; MICE; OSTEOPOROSIS AB Since the mid 1940s, fluoride has been added to tap water in American communities in an effort to reduce the incidence of dental caries in the population. When the levels of fluoride in drinking water were tested and set, water was the only measurable source of fluoride for most communities. Now, adults and children ingest fluoride with foods and beverages prepared with fluoridated water, and they are exposed to fluoride-containing dental products. As a result, exposure to fluoride is greater than had been anticipated. In the early 1990s, the existing reproductive studies were reviewed in several reports and were considered to be inadequate to determine potential reproductive or developmental hazards. The effects of sodium fluoride ingestion at 0, 25, 100, 175 or 250 ppm in drinking water measured in rats throughout three generations are reported here. Feed and fluid consumption, body weights and clinical signs were recorded at regular intervals. Decreased fluid consumption observed at 175 and 250 ppm was attributed to decreased palatability and did not affect reproduction. No cumulative effects were observed in the three generations. Mating, fertility and survival indices were not affected. organ-to-body-weight ratios and organ-to-brain weight ratios were not affected. Sodium fluoride up to 250 ppm did not affect reproduction in rats. Published by Elsevier Science Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Collins, TFX (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 36 TC 21 Z9 22 U1 2 U2 5 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 JUN PY 2001 VL 39 IS 6 BP 601 EP 613 DI 10.1016/S0278-6915(00)00172-1 PG 13 WC Food Science & Technology; Toxicology SC Food Science & Technology; Toxicology GA 436UG UT WOS:000168953800011 PM 11346491 ER PT J AU Li, Y Brackett, RE Shewfelt, RL Beuchat, LR AF Li, Y Brackett, RE Shewfelt, RL Beuchat, LR TI Changes in appearance and natural microflora on iceberg lettuce treated in warm, chlorinated water and then stored at refrigeration temperature SO FOOD MICROBIOLOGY LA English DT Article ID PARTIALLY PROCESSED LETTUCE; FRESH-CUT VEGETABLES; MICROBIAL-FLORA; SHELF-LIFE; QUALITY; STORAGE; FRUITS; STABILITY; BACTERIA; GROWTH AB The objective of this study was to determine the effect of warm, chlorinated water on the survival and subsequent growth of naturally occurring microorganisms and visual quality of fresh-cut iceberg lettuce. After dipping cut lettuce leaves in water containing 20 mg l(-1) free chlorine for 90s at 50 degreesC, samples were stored at 5 or 15 degreesC for up to 18 or 7 days, respectively. Populations of aerobic mesophiles, psychrotrophs, Enterobacteriaceae, lactic acid bacteria, and yeasts and molds were determined. The visual appearance and development of brown discoloration were monitored. Treatment of lettuce in warm (50 degreesC) chlorinated water delayed browning of lettuce. Shelf life of lettuce stored at 5 degreesC, as determined by subjective evaluation of color and general appearance, was about 5 days longer than that of lettuce stored at 15 degreesC. Treatment in warm (50 degrees) wafer, with or without 20 mg l(-1) chlorine, and in chlorinated water at 20 degrees C significantly (alpha = 0.05) reduced the initial population of mesophilic aerobic microflora by 1.73-1.96 log(10) cfu g(-1). Populations increased, regardless of treatment, as storage time at 5 degreesC and 15 degreesC increased. The same trends were observed in populations of psychrotrophs and Enterobacteriaceae. Yeast populations increased slightly in lettuce stored at 5 degreesC but were consistently about 3 logs lower than mesophilic aerobes. Populations of molds and lactic acid bacteria were less than 2 log(10) cfu g(-1) throughout storage at 5 or 15 degreesC. Results suggest that hear (50 degreesC) treatment may have delayed browning and reduced initial populations of some groups of micro-organisms naturally occurring on iceberg lettuce but enhanced microbial growth during subsequent storage. (C) 2001 Academic Press. C1 Univ Georgia, Dept Food Sci & Technol, Ctr Food Safety, Griffin, GA 30223 USA. US FDA, Off Plant Dairy Foods & Beverages, Washington, DC 20204 USA. RP Beuchat, LR (reprint author), Univ Georgia, Dept Food Sci & Technol, Ctr Food Safety, Griffin, GA 30223 USA. NR 43 TC 84 Z9 87 U1 0 U2 11 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0740-0020 J9 FOOD MICROBIOL JI Food Microbiol. PD JUN PY 2001 VL 18 IS 3 BP 299 EP 308 DI 10.1006/fmic.2001.0401 PG 10 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA 443FH UT WOS:000169329800008 ER PT J AU Montoya-Delgado, LE Irony, TZ Pereira, CAD Whittle, MR AF Montoya-Delgado, LE Irony, TZ Pereira, CAD Whittle, MR TI An unconditional exact test for the Hardy-Weinberg equilibrium law: Sample-space ordering using the Bayes factor SO GENETICS LA English DT Article ID DISEQUILIBRIUM; POLYMORPHISMS; COEFFICIENT AB Much forensic inference based upon DNA evidence is made assuming that the Hardy-Weinberg equilibrium (HWE) is Valid for the genetic loci being used. Several statistical tests to detect and measure deviation from HWE have been devised, each having advantages and limitations. The limitations become more obvious when testing for deviation within multiallelic DNA loci is attempted. Here we present an exact test for HWE in the biallelic case, based on the ratio of weighted likelihoods under the null and alternative hypotheses, the Bayes factor. This test does not depend on asymptotic results and minimizes a linear combination of type I and type II errors. By ordering the sample space using the Ba)ies factor, we also define a significance (evidence) index, P value, using the weighted likelihood under the null hypothesis. We compare it to the conditional exact test for the case of sample size n = 10. Using the idea under the method of chi (2) partition, the test is used sequentially to test equilibrium in the multiple allele case and then applied to two short tandem repeat loci, using a real Caucasian data bank, showing its usefulness. C1 Genom Engn Mol Ltda, BR-01332903 Sao Paulo, SP, Brazil. Univ Cauca, Popayan, Cauca, Colombia. US FDA, Ctr Devices & Radiol Hlth, Div Biostat, Rockville, MD 20850 USA. Univ Sao Paulo, Inst Matemat & Estatist, BR-05008090 Sao Paulo, SP, Brazil. RP Whittle, MR (reprint author), Genom Engn Mol Ltda, Rua Itapeva 500,Cj 5AB, BR-01332903 Sao Paulo, SP, Brazil. NR 40 TC 23 Z9 23 U1 0 U2 1 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JUN PY 2001 VL 158 IS 2 BP 875 EP 883 PG 9 WC Genetics & Heredity SC Genetics & Heredity GA 442FY UT WOS:000169275600034 PM 11404348 ER PT J AU Shuren, JE AF Shuren, JE TI The modern regulatory administrative state: A response to changing circumstances SO HARVARD JOURNAL ON LEGISLATION LA English DT Article ID IMPROVING AMERICAN JUSTICE; AGENCY INTERPRETATIONS; JUDICIAL DEFERENCE; CHEVRON; LAW; GOVERNMENT; STATUTES; PROPOSAL AB In the landmark case Chevron, U.S.A. v. National Resource Defense Council, Inc., the Supreme Court articulated a deferential standard for reviewing an agency's interpretations of statutory language within that agency's area of concern as long as Congress was silent or ambiguous on the matter and the agency's interpretation was reasonable. Using the Food and Drug Administration as a primary case study, Dr Shuren contends that one of the main reasons for granting agencies broad judicial deference in the implementation of statutory mandates is that agencies are the governmental entities best equipped to respond to changing circumstances. Dr Shuren contends that courts should grant sufficient deference to agencies' modifications of prior statutory interpretations in order to ensure adequate agency flexibility to meet new challenges within existing statutory delegations of authority. C1 US FDA, Off Policy Planning & Legislat, Rockville, MD 20857 USA. RP Shuren, JE (reprint author), US FDA, Off Policy Planning & Legislat, Rockville, MD 20857 USA. NR 90 TC 18 Z9 18 U1 0 U2 0 PU HARVARD LAW SCHOOL PI CAMBRIDGE PA PUBLICATIONS CTR, CAMBRIDGE, MA 02138 USA SN 0017-808X J9 HARVARD J LEGIS JI Harv. J. Legis. PD SUM PY 2001 VL 38 IS 2 BP 291 EP 329 PG 39 WC Law SC Government & Law GA 457HJ UT WOS:000170130800001 ER PT J AU Taylor, DR AF Taylor, DR TI Hepatitis C virus and interferon resistance: It's more than just PKR SO HEPATOLOGY LA English DT Editorial Material ID NONSTRUCTURAL 5A PROTEIN; TYROSINE PHOSPHORYLATION; KINASE; SENSITIVITY; NS5A; REPLICATION; EXPRESSION; REPRESSION; REGION; 1B C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Taylor, DR (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,Room 1D-02,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 14 TC 12 Z9 13 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2001 VL 33 IS 6 BP 1547 EP 1549 DI 10.1053/jhep.2001.25447 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 436LN UT WOS:000168937500026 PM 11391546 ER PT J AU Jaeschke, H Gujral, JS Bucci, TJ Farhood, A AF Jaeschke, H Gujral, JS Bucci, TJ Farhood, A TI Mechanism of hepatocyte death after ischemia: Apoptosis versus necrosis - Reply SO HEPATOLOGY LA English DT Letter ID LIVER ISCHEMIA; CELL-DEATH; RAT-LIVER; IN-VIVO; ACTIVATION; INHIBITION C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Pathol Associates Inc, Jefferson, AR USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Houston, TX USA. RP Jaeschke, H (reprint author), Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. NR 13 TC 1 Z9 1 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD JUN PY 2001 VL 33 IS 6 BP 1556 EP 1557 DI 10.1053/jhep.2001.25449 PG 2 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 436LN UT WOS:000168937500031 ER PT J AU Umehara, H Goda, S Imai, T Nagano, Y Minami, Y Tanaka, T Okazaki, T Bloom, ET Domae, N AF Umehara, H Goda, S Imai, T Nagano, Y Minami, Y Tanaka, T Okazaki, T Bloom, ET Domae, N TI Fractalkine, a CX3C-chemokine, functions predominantly as an adhesion molecule in monocytic cell line THP-1 SO IMMUNOLOGY AND CELL BIOLOGY LA English DT Article DE cell adhesion; endothelial cells; fractalkine; integrin; THP-1 cells ID ENDOTHELIAL-CELLS; FIRM ADHESION; CHEMOKINE; FLOW; ACTIVATION; MECHANISMS; CX(3)CR1; AVIDITY; BETA-1; MCP-1 AB A newly identified CX3C-chemokine, fractalkine, expressed on activated endothelial cells plays an important role in leucocyte adhesion and migration. Co-immobilized fractalkine with fibronectin or intercellular adhesion molecule-1 enhanced adhesion of THP-1 cells, which express the fractalkine receptor (CX(3)CR1), compared with that observed for each alone. That adherence was fractalkine-dependent and was confirmed in blocking studies. However, soluble fractalkine induced little chemotaxis in THP-1 cells in comparison to monocyte chemotstatic protein-1 (MCP-1), which induced a strong chemotactic response. Moreover, the membrane form of fractalkine expressed on ECV304 cells reduced MCP-1 mediated chemotaxis of THP-1 cells. These results indicate that fractalkine may function as an adhesion molecule between monocytes and endothelial cells rather than as a chemotactic factor. C1 Osaka Dent Univ, Dept Internal Med, Osaka 5731121, Japan. Kan Res Inst, Kyoto, Japan. Kobe Univ, Dept Biomed Regulat & Parasitol, Sch Med, Kobe, Hyogo 657, Japan. Univ Occupat & Environm Hlth, Dept Internal Med 1, Sch Med, Kitakyushu, Fukuoka, Japan. Kyoto Univ, Dept Hematol & Oncol, Grad Sch Med, Kyoto, Japan. US FDA, Div Cellular & Gene Therapies, Ctr Biol Evaluat Res, Bethesda, MD USA. RP Umehara, H (reprint author), Osaka Dent Univ, Dept Internal Med, 8-1 Kuzuha Hanazono Cho, Osaka 5731121, Japan. NR 18 TC 63 Z9 70 U1 0 U2 1 PU BLACKWELL SCIENCE ASIA PI CARLTON PA 54 UNIVERSITY ST, P O BOX 378, CARLTON, VICTORIA 3053, AUSTRALIA SN 0818-9641 J9 IMMUNOL CELL BIOL JI Immunol. Cell Biol. PD JUN PY 2001 VL 79 IS 3 BP 298 EP 302 DI 10.1046/j.1440-1711.2001.01004.x PG 5 WC Cell Biology; Immunology SC Cell Biology; Immunology GA 450RM UT WOS:000169756900014 PM 11380684 ER PT J AU Zaitseva, M King, LR Manischewitz, J Dougan, M Stevan, L Golding, H Golding, B AF Zaitseva, M King, LR Manischewitz, J Dougan, M Stevan, L Golding, H Golding, B TI Human peripheral blood T cells, monocytes, and macrophages secrete macrophage inflammatory proteins 1 alpha and 1 beta following stimulation with heat-inactivated Brucella abortus SO INFECTION AND IMMUNITY LA English DT Article ID BETA-CHEMOKINES; HIV-1 INFECTION; B-ABORTUS; LIPOPOLYSACCHARIDE LPS; ANTIBODY-RESPONSES; IN-VITRO; V3 LOOP; INDIVIDUALS; ANTIGEN; CD4(+) AB Heat-killed Brucella abortus (HBa) has been proposed as a carrier for therapeutic vaccines for individuals with immunodeficiency, due to its abilities to induce interleukin-2 (IL-2) and gamma interferon (IFN-gamma) in both CD4(+) and CD8(+) T cells and to upregulate antigen-presenting cell functions (including IL-12 production). In the current study, we investigated the ability of HBa or lipopolysaccharide isolated from HBa (LPS-Ba) to elicit beta -chemokines, known to bind to the human immunodeficiency virus type 1 (HIV-1) coreceptor CCRS and to block viral cell entry. It was found that human peripheral blood mononuclear cells secreted beta -chemokines following stimulation with HBa, and this effect could not be blocked by anti-IFN-gamma neutralizing antibodies. Among purified T cells, macrophage inflammatory protein lo and Ip (MIP-1 alpha and MIP-1 beta, respectively) secretion was observed primarily in human CD8(+) T cells. The kinetics of beta -chemokine induction in T cells were slow (3 to 4 days). The majority of beta -chemokine-producing CD8(+) T cells also produced IFN-gamma following HBa stimulation, as determined by triple-color intracellular staining. A significant number of CD8(+) T cells contained stored MIP-1 beta that was released after HBa stimulation. Both HBa and LPS-Ba stimulated high levels of MIP-la and MIP-IP production in elutriated monocytes and even higher levels in macrophages. In these cells, beta -chemokine mRNA was upregulated within 30 min and proteins were secreted within 4 h of stimulation. The monocyte- and macrophage-derived beta -chemokines were sufficient to block CCR5-dependent HIV-1 envelope-mediated cell fusion. These data suggest that, in addition to the ability of HBa to elicit antigen-specific humoral and cellular immune responses, HBa-conjugated HIV-1 proteins or peptides would also generate innate chemokines with antiviral activity that could limit local viral spread during vaccination in vivo. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Golding, B (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, HFM-345,Bldg 29,Room 232,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 38 TC 16 Z9 17 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD JUN PY 2001 VL 69 IS 6 BP 3817 EP 3826 DI 10.1128/IAI.69.6.3817-3826.2001 PG 10 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 433WU UT WOS:000168784300039 PM 11349047 ER PT J AU Verthelyi, D AF Verthelyi, D TI Sex hormones as immunomodulators in health and disease SO INTERNATIONAL IMMUNOPHARMACOLOGY LA English DT Review DE estrogen; dehydroepiandrosterone sulphate; cytokines; systemic lupus erythematosus ID SYSTEMIC-LUPUS-ERYTHEMATOSUS; ESTROGEN REPLACEMENT THERAPY; T-CELL CLONES; AUTOIMMUNE-DISEASE; PERIPHERAL-BLOOD; IMMUNE-SYSTEM; MURINE LUPUS; B-CELLS; MENSTRUAL-CYCLE; DISCOID LUPUS AB In addition to their effects on sexual differentiation and reproduction, sex hormones influence the immune system. This results in a gender dimorphism in the immune function with females having higher immunoglobulin levels and mounting stronger immune responses following immunization or infection than males. The greater immune responsiveness in females is also evident in their increased susceptibility to autoimmune diseases. However, a clear understanding of the myriad of effects that sex hormones have on the immune system is lacking. Studies in normal mice show that estrogen treatment induces polyclonal B cell activation with increased expression of autoantibodies characteristic of autoimmune diseases. Several mechanisms appear to contribute to the break in tolerance and the increase in plasma cell activity including a reduction of the mass of the bone marrow and the thymus, the emergence of sites of extrameduallary hematopoiesis and altered susceptibility of B cells to cell death. In addition, sex hormone levels in both humans and experimental models correlated with the activity of their cytokine-secreting cells indicating that sex hormones influence the cytokine milieu and suggesting that altered sex hormonal levels in autoimmune patients contribute to the skewed cytokine milieu characteristic of systemic lupus erythematosus (SLE). While sex hormones alone do not cause autoimmune disease, abnormal hormone levels may provide the stage for other factors (genetic, infectious) to trigger disease. Understanding the physiology of the interaction between sex hormones and immune function and its potential pathological consequences may provide insight into the autoimmune diseases and new directions for their treatment. Published by Elsevier Science B.V. C1 US FDA, Retroviral Immunol Sect, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Verthelyi, D (reprint author), US FDA, Retroviral Immunol Sect, Ctr Biol Evaluat & Res, Bldg 29A,Rm 3 D 2, Bethesda, MD 20892 USA. NR 90 TC 203 Z9 212 U1 0 U2 12 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1567-5769 J9 INT IMMUNOPHARMACOL JI Int. Immunopharmacol. PD JUN PY 2001 VL 1 IS 6 BP 983 EP 993 DI 10.1016/S1567-5769(01)00044-3 PG 11 WC Immunology; Pharmacology & Pharmacy SC Immunology; Pharmacology & Pharmacy GA 441LB UT WOS:000169230900002 PM 11407317 ER PT J AU Hayes, JR McIntosh, AC Qaiyumi, S Johnson, JA English, LL Carr, LE Wagner, DD Joseph, SW AF Hayes, JR McIntosh, AC Qaiyumi, S Johnson, JA English, LL Carr, LE Wagner, DD Joseph, SW TI High-frequency recovery of quinupristin-dalfopristin-resistant Enterococcus faecium isolates from the poultry production environment SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID VIRGINIAMYCIN AB The occurrence of resistance to the streptogramin quinupristin-dalfopristin in Enterococcus faecium isolates from chickens on the Eastern Seaboard, was evaluated. Quinupristin-dalfopristin resistance was found in 51 to 78% of E. faecium isolates from the food production environment. The high level of resistance in this organism suggests that this reservoir of resistance may compromise the therapeutic potential of quinupristin-dalfopristin. C1 Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. Univ Maryland, Dept Biol Resources Engn, College Pk, MD 20742 USA. Univ Maryland, Sch Med, Vet Affairs Maryland Hlth Care Syst, Baltimore, MD 21201 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Joseph, SW (reprint author), Univ Maryland, Dept Mol Genet & Cell Biol, College Pk, MD 20742 USA. NR 11 TC 26 Z9 26 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD JUN PY 2001 VL 39 IS 6 BP 2298 EP 2299 DI 10.1128/JCM.39.6.2298-2299.2001 PG 2 WC Microbiology SC Microbiology GA 439ED UT WOS:000169097100044 PM 11376075 ER PT J AU White, RM AF White, RM TI Correct fluorouracil (5-FU) half-life comparator for a 5-FU prodrug plus a dihydropyrimidine dehydrogenase inhibitor SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID S-1 C1 US FDA, Rockville, MD 20857 USA. RP White, RM (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 3 Z9 3 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JUN 1 PY 2001 VL 19 IS 11 BP 2970 EP 2970 PG 1 WC Oncology SC Oncology GA 438BN UT WOS:000169034000028 PM 11387375 ER PT J AU Lathers, CM AF Lathers, CM TI Role of veterinary medicine in public health: Antibiotic use in food animals and humans and the effect on evolution of antibacterial resistance SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article AB Veterinary public health is another frontier in the fight against human disease. The veterinary public health scope includes the control and eradication of zoonoses, diseases that are naturally transmitted between vertebrate animals and man. These diseases pose a continuous hazard to the health and welfare of the public. More than 100 diseases are categorized as zoonoses, including salmonellosis. It is important to understand how antibiotics are used in humans and in food animals and how these uses affect the evolution of antibacterial resistance. Appropriate use of antibiotics for food animals will preserve th e long-term efficacy of existing antibiotics, support animal health and welfare, and limit the risk of transfer of antibiotic resistance to humans. An understanding of the epidemiology of antimicrobial resistance allows development of preventive strategies to limit existing resistance and to avoid emergence of new strains of resistant bacteria. Risk assessments are being used by the Center for Veterinary Medicine at the U.S. Food and Drug Administration as regulatory fools to assess potential risk to humans resulting from antibiotic use in food-producing animals and to then develop microbial safety policies to protect the public health. The veterinary public health scope, in addition to the control and eradication of zoonoses, also includes the development and supervision of food hygiene practices, laboratory and research activities, and education of the public. Thus, it may be seen that there are many ways in which veterinary medicine plays a very important role in public health. C1 Ctr Vet Med, Off New Anim Drug Evaluat, US FDA, Rockville, MD 20855 USA. RP Lathers, CM (reprint author), Ctr Vet Med, Off New Anim Drug Evaluat, US FDA, Room 390,HFV-100,7500 Standish Pl, Rockville, MD 20855 USA. NR 19 TC 20 Z9 21 U1 2 U2 18 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 2001 VL 41 IS 6 BP 595 EP 599 DI 10.1177/00912700122010474 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 436RC UT WOS:000168948200001 PM 11402627 ER PT J AU Roe, B Teisl, MF Rong, HP Levy, AS AF Roe, B Teisl, MF Rong, HP Levy, AS TI Characteristics of consumer-preferred labeling policies: Experimental evidence from price and environmental disclosure for deregulated electricity services SO JOURNAL OF CONSUMER AFFAIRS LA English DT Article ID MISSING INFORMATION; HEALTH CLAIM; DISPLAYS; CHOICE; INTERPRET; INFERENCE AB This study gauges how different information disclosure policies impact consumer understanding, performance, and satisfaction during the choice of a deregulated electricity supplier, and it explores how the market share of each firm responds to different policies in a hypothetical market. Compulsory disclosure of detailed price and environmental attribute information yields high consumer satisfaction and minimizes most types of information processing errors. The implications for disclosure policy and firm-level market share are discussed. C1 Ohio State Univ, Dept Agr Environm & Dev Econ, Columbus, OH 43210 USA. Univ Maine, Dept Resource Econ & Policy, Orono, ME USA. US FDA, Consumer Studies Branch, Washington, DC 20204 USA. RP Roe, B (reprint author), Ohio State Univ, Dept Agr Environm & Dev Econ, Columbus, OH 43210 USA. RI Roe, Brian/A-7386-2009; OI Roe, Brian/0000-0003-4228-2889; teisl, mario/0000-0002-2021-9208 NR 33 TC 14 Z9 14 U1 1 U2 3 PU AMER COUNCIL CONSUMER INTEREST PI AMES PA 415 S DUFF AVE, STE C, AMES, IA 50010-6600 USA SN 0022-0078 J9 J CONSUM AFF JI J. Consum. Aff. PD SUM PY 2001 VL 35 IS 1 BP 1 EP 26 PG 26 WC Business; Economics SC Business & Economics GA 510WA UT WOS:000173229200001 ER PT J AU Wilkening, V AF Wilkening, V TI Proposed changes in USA regulations for food labeling SO JOURNAL OF FOOD COMPOSITION AND ANALYSIS LA English DT Article; Proceedings Paper CT 24th National Nutrient Databank Conference CY JUL 27-29, 2000 CL ST PAUL, MINNESOTA SP Univ Minnesota, Nutrit Coordinating Ctr DE nutrition labeling; trans fatty acids; sugars AB On November 17, 1999 the United States (U.S.A.) Food and Drug Administration (FDA) published a proposed rule that would allow for the declaration of trans fatty acids in nutrition labeling and would limit trans fatty acids wherever saturated fat limits are placed on nutrient content or health claims. Specifically, FDA proposed that the amount of trans fat be included with that of saturated fat. The combined amount would be followed by an asterisk referring to a footnote specifying the amount of trans fats included in the total value. In addition, the agency proposed that the percent Daily Value shown be based on the combined amount of saturated and trans fatty acids. Other options for declaring trans fatty acids were discussed and comments requested. FDA also published a notice on June 26, 2000, requesting comment on a Citizen Petition that requested: (1) the declaration of added sugars in nutrition labeling, (2) the development of a Daily Value for added sugars so that consumers would be informed of the proportion of a reasonable day's intake of added sugars that was provided by a serving of food, and (3) the revision of criteria pertaining to nutrient content and health claims to take added sugars into account. (C) 2001 Academic Press. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, Washington, DC 20204 USA. RP Wilkening, V (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Nutr Prod Labeling & Dietary Supplements, Washington, DC 20204 USA. NR 3 TC 5 Z9 5 U1 1 U2 3 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0889-1575 J9 J FOOD COMPOS ANAL JI J. Food Compos. Anal. PD JUN PY 2001 VL 14 IS 3 BP 309 EP 314 DI 10.1006/jfca.2001.0998 PG 6 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 473XP UT WOS:000171074700012 ER PT J AU Fu, T Stewart, D Reineke, K Ulaszek, J Schlesser, J Tortorello, M AF Fu, T Stewart, D Reineke, K Ulaszek, J Schlesser, J Tortorello, M TI Use of spent irrigation water for microbiological analysis of alfalfa sprouts SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; VEGETABLE SPROUTS; SALMONELLA; SEEDS; CARCASSES; SURVIVAL; RINSE AB Numerous outbreaks of foodborne illness have been linked to the consumption of raw sprouts. Sprout producers have been advised by the Food and Drug Administration to include microbiological testing of spent irrigation water during production as part of an overall strategy to enhance the safety of sprouts. Alfalfa sprouts and irrigation water were analyzed to show the feasibility of using irrigation water for monitoring the microbiological safety of sprouts. Sprouts and water were produced and harvested from both commercial-scale (rotary drum) and consumer-scale (glass jars) equipment. Rapid increases of aerobic mesophiles occurred during the first 24 h of sprouting, with maximum levels achieved after 48 to 72 h. The counts in irrigation water were on average within approximately 1 log of their respective counts in the sprouts. Similar results were obtained for analysis of Escherichia coli O157:H7 in irrigation water and sprouts grown from artificially inoculated seeds. Testing of spent irrigation water indicated the contamination status of alfalfa sprouts grown from seeds associated with outbreaks of Salmonella infection. C1 US FDA, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Tortorello, M (reprint author), US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. FU FDA HHS [FD-0004331] NR 19 TC 40 Z9 41 U1 0 U2 13 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 2001 VL 64 IS 6 BP 802 EP 806 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 439XK UT WOS:000169142700008 PM 11403129 ER PT J AU Juneja, VK Novak, JS Eblen, BS McClane, BA AF Juneja, VK Novak, JS Eblen, BS McClane, BA TI Heat resistance of Clostridium perfringens vegetative cells as affected by prior heat shock SO JOURNAL OF FOOD SAFETY LA English DT Article ID THERMAL INACTIVATION; SPORES; PATHOGENS; VEHICLES; PROTEINS; MEMBRANE AB This study quantified the heat resistance and the effects of a heat shock on the subsequent heat resistance of 10 strains of Clostridium perfringens. Beef gravy samples inoculated with vegetative cells of the pathogen were subjected to sublethal heating at 48C for 10 min, and then heated to a final temperature of 58C using a submerged-coil heating apparatus. Heat-treated samples were spiral plated on Shahidi-Ferguson Perfringens agar to determine surviving bacterial population. No correlation between the heat resistance and the origin of the C. perfringens could be established due to significant variations in the hear resistance among strains. inactivation kinetics of both heat-shocked and nonheat-shocked samples exhibited log-linear decline in the number of surviving cells with time. D-values at 58C for C. perfringens vegetative cells ranged from 1.21 to 1.60 min. Heat shocking allowed the organism to survive longer and the increase in heat resistance tvas as high as 1.5 fold. Also, heat shock resulted in the overexpression of proteins exhibiting epitopic and size similarity to E. coli GroEL and B. subtilis small acid soluble proteins. Increased heat resistance due to heat shock must be considered while designing cooking/reheating regimes that ensure safety of ready-to-eat foods contaminated with high numbers of C. perfringens vegetative cells. C1 USDA ARS, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20250 USA. Univ Pittsburgh, Sch Med, Dept Mol Genet & Biochem, Pittsburgh, PA 15261 USA. RP Juneja, VK (reprint author), USDA ARS, Eastern Reg Res Ctr, 600 E Mermaid Lane, Wyndmoor, PA 19038 USA. NR 32 TC 9 Z9 9 U1 0 U2 2 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 USA SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD JUN PY 2001 VL 21 IS 2 BP 127 EP 139 DI 10.1111/j.1745-4565.2001.tb00312.x PG 13 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 451WN UT WOS:000169825600005 ER PT J AU Rabbani, PI Alam, HZ Chirtel, SJ Duvall, RE Jackson, RC Ruffin, G AF Rabbani, PI Alam, HZ Chirtel, SJ Duvall, RE Jackson, RC Ruffin, G TI Subchronic toxicity of fish oil concentrates in male and female rats SO JOURNAL OF NUTRITIONAL SCIENCE AND VITAMINOLOGY LA English DT Article DE subchronic toxicity; fish oil concentrates; n-3 fatty acids ID POLYUNSATURATED FATTY-ACIDS; LOW-DENSITY LIPOPROTEINS; LDL RECEPTOR ACTIVITY; CARDIOVASCULAR-DISEASE; PLASMA-LIPIDS; HEART-DISEASE; MENHADEN OIL; OMEGA-3 PUFA; CORN-OIL; LIVER AB There are an overwhelming number of reports indicating the beneficial effects of fish oil supplements in human and animal nutrition. The purpose of this study, second in a series, was to evaluate the effects, particularly those that may be harmful, of high-dose, long-term consumption of fish oil concentrates (FOC) using male and female rats. One hundred and twenty male and 120 female rats were gavaged daily with oils and oil mixtures in a volume equal to 0.5% body weight (5 mL/kg/d) for 13 weeks. The administered oils were corn oil, pure menhaden oil (MO), pure MaxEPA(R) fish oil or different mixtures of corn oil with MO. The stability and the homogeneity of the dosing solutions were tested under study conditions. The animals received isocaloric and isonitrogenous diets throughout. Food and pure water were supplied ad libitum. At the end of the in-life phase of the study, the animals were anaesthetized with CO2 and humanely killed by exsanguination. Blood and other tissues were prepared for various clinical, histopathological and laboratory tests. Some beneficial effects of FOC, such as reduction in total serum cholesterol, in rats were confirmed. However, we also observed a significant reduction in absolute amount of serum HDL and a significant increase in relative liver and spleen weights in both sexes with the high dose of FOC. High doses of FOC (5 mL/kg/d) reduced serum iron and vitamin E concentrations. A reduction in osmotic fragility of RBC as well as an increase in RBC deformity were also observed in rats treated with high doses of FOC. These rats showed a significant overall increase in WBC count. We conclude that in rats, subchronic consumption of high levels of FOC can be beneficial but may also be harmful because of induction of clinical abnormalities including increased red cell deformity, increased relative liver and spleen weights, and reduced serum HDL, iron and vitamin E concentrations. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Rabbani, PI (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-308,200 C St SW, Washington, DC 20204 USA. NR 69 TC 7 Z9 9 U1 2 U2 5 PU CENTER ACADEMIC PUBL JAPAN PI TOKYO PA 4-16 YAYOI 2-CHOME, BUNKYO-KU, TOKYO, 113, JAPAN SN 0301-4800 J9 J NUTR SCI VITAMINOL JI J. Nutr. Sci. Vitaminol. PD JUN PY 2001 VL 47 IS 3 BP 201 EP 212 PG 12 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 459MM UT WOS:000170254200004 PM 11575575 ER PT J AU Mitchell, JP Dennis, GJ Rider, LG AF Mitchell, JP Dennis, GJ Rider, LG TI Juvenile dermatomyositis presenting with anasarca: A possible indicator of severe disease activity SO JOURNAL OF PEDIATRICS LA English DT Article ID COMPLEMENT AB Juvenile dermatomyositis is a rare autoimmune disease characterized by inflammation of the muscle, skin, and other organs. Although localized edema is a common feature of juvenile dermatomyositis, generalized edema has been reported infrequently. We describe a patient with juvenile dermatomyositis presenting with anasarca and note that generalized edema has been associated with severe disease activity. C1 Walter Reed Army Med Ctr, Dept Rheumatol & Clin Immunol, Washington, DC 20307 USA. Ctr Biol Evaluat & Res, Food & Drug Adm, Washington, DC USA. RP Mitchell, JP (reprint author), Walter Reed Army Med Ctr, Dept Rheumatol & Clin Immunol, 6900 Georgia Ave NW,Ward 77, Washington, DC 20307 USA. OI Rider, Lisa/0000-0002-6912-2458 NR 12 TC 21 Z9 26 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD JUN PY 2001 VL 138 IS 6 BP 942 EP 945 DI 10.1067/mpd.2001.113363 PG 4 WC Pediatrics SC Pediatrics GA 440LH UT WOS:000169176400037 PM 11391348 ER PT J AU Whittaker, P Tufaro, PR Rader, JI AF Whittaker, P Tufaro, PR Rader, JI TI Iron and folate in fortified cereals SO JOURNAL OF THE AMERICAN COLLEGE OF NUTRITION LA English DT Article DE iron; folate; fortification; cereals ID DIETARY IRON; CAROTID ATHEROSCLEROSIS; MYOCARDIAL-INFARCTION; FOOD FORTIFICATION; COLORECTAL-CANCER; RISK; DEFICIENCY; STORES; ANEMIA; HEMOCHROMATOSIS AB Background: Fortification of cereal-grain products was introduced in 1941 when iron and three vitamins were added to flour and bread. Ready-to-eat cereals were fortified at about the same rime. These fortifications have contributed to increased dietary iron intake and reductions in iron deficiency anemia in the US. In 1996, FDA finalized rules for fortification of specific enriched cereal-grain products with folic acid. This measure was instituted to increase the folate intakes of women of child-bearing age and thereby reduce the risk of having a pregnancy affected with a neural tube birth defect. However, with recent increases in fortification, public health officials in the US are concerned that excess intake of specific nutrients such as iron and folic acid may result in toxic manifestations. Objective: Our objective was to measure iron and total folate content in breakfast cereals and compare assay to label values for % Daily Value. We also determined by weight the amount of a ready-to-eat breakfast cereal adults would eat and compared this to the labeled serving size, for which the reference amount for this cereal per eating occasion was 1 cup or 30 g. Design: Twenty-nine breakfast cereals were analyzed for iron content using the bathophenanthroline reaction. Twenty-eight cereals were analyzed for total folate, utilizing a microbiological assay with tri-enzyme digestion. Serving size quantities were estimated in seventy-two adults who regularly ate breakfast cereal and were asked to fill a 16 or 22 cm round bowl with the amount of cereal that they would consume for breakfast. Results: When the labeled value was compared to the assayed value for iron content 21 of the 29 breakfast cereals were 120% or more of the label value and 8 cereals were 150% or more of the label value. Overall, analyzed values for iron ranged from 80% to 190% of label values. Analyzed values for folate ranged from 98% to 320% of label values. For 14 of 28 cereals, analyzed values exceeded label declarations by more than 150%. Bran-containing cereals contained the highest amounts of folate relative to their label declarations. The median analyzed serving size for the breakfast cereal was 47 g for females, 61 g for males with a combined median of 56 g as compared to the label value of 30 g. Conclusions: Analyzed values of iron and folic acid in breakfast cereals were considerably higher than labeled values. For adults, the amount of cereal actually consumed was approximately 200% of the labeled serving size. When the quantity of cereal consumed is more than the labeled serving size and when the levels of iron acid folate are higher than declared, the intake of both will be significantly greater than the labeled values. It will be important to continue monitoring serum ferritin and folate levels in NHANES TV, since daily consumption of breakfast cereals may contribute to excessive intakes of iron and folate. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Whittaker, P (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW,HFS-236, Washington, DC 20204 USA. NR 43 TC 52 Z9 53 U1 2 U2 16 PU AMER COLL NUTRITION PI NEW YORK PA C/O HOSP. JOINT DIS. 301 E. 17TH ST., NEW YORK, NY 10003 USA SN 0731-5724 J9 J AM COLL NUTR JI J. Am. Coll. Nutr. PD JUN PY 2001 VL 20 IS 3 BP 247 EP 254 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 448KH UT WOS:000169625700007 PM 11444421 ER PT J AU Mossoba, MM Kramer, JKG Fritsche, J Yurawecz, MP Eulitz, KD Ku, Y Rader, JI AF Mossoba, MM Kramer, JKG Fritsche, J Yurawecz, MP Eulitz, KD Ku, Y Rader, JI TI Application of standard addition to eliminate conjugated linoleic acid and other interferences in the determination of total trans fatty acids in selected food products by infrared spectroscopy SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE infrared; standard addition; trielaidin; trans fats ID RAPID-DETERMINATION; HUMAN-MILK; GAS-CHROMATOGRAPHY; HYDROGENATED OILS; ADIPOSE-TISSUE; ISOMERS AB A novel and rapid (5 min) attenuated total reflection-fourier transform infrared (ATR-FTIR) spectroscopic method AOCS Cd 14d-99 for the determination of total isolated trans fatty acids, which absorb at 966 cm(-1), was recently developed, collaboratively studied, and applied to food products containing 1-50% trans fat (as percentage of total fat). Attempts to apply the ATR-FTIR method to biological matrices of low trans fat and/or low total fat content, and to dairy and other products were not satisfactory due to interfering 1R absorptions in the trans region. One group of interfering compounds with absorption bands near 985 and 948 cm(-1) was the cis/trans positional isomers of conjugated linoleic acid (CLA) found in dairy and meat products from ruminants at levels of <1% (as percentage of total fat). In the present study, we modified the ATR-FTIR method to overcome matrix interferences. This modification, which consisted of applying the standard addition technique to the ATR-FTIR determination, was also applied to several food products, namely, dairy products, infant formula and salad oil dressing, which successfully eliminated interfering absorbances that impacted on accuracy. The presence of <1% CLA in two butter and two cheese products containing 6.8, 7.5, 8.5, and 10.4% trans fatty acids (as a percentage of total fat) would have led to errors of -11.6, 10.4, 17.6 and 34.6%, respectively, in trans fat measurements had the standard addition technique not been used. The applicability of ATR-FTIR to the quantitation of food products is discussed. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Off Sci Anal & Support, Washington, DC 20204 USA. US FDA, Off Nutr Prod Labeling & Dietary Supplements, Washington, DC 20204 USA. Agr & Agri Food Canada, Food Res Program, Guelph, ON N1G 5C9, Canada. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Mail Stop HFS-717,200 C St SW, Washington, DC 20204 USA. NR 31 TC 11 Z9 13 U1 0 U2 11 PU AMER OIL CHEMISTS SOC A O C S PRESS PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0003-021X J9 J AM OIL CHEM SOC JI J. Am. Oil Chem. Soc. PD JUN PY 2001 VL 78 IS 6 BP 631 EP 634 DI 10.1007/s11746-001-0317-9 PG 4 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA 446KU UT WOS:000169513100014 ER PT J AU Burgess, TM Meyer, EK Bataller, N AF Burgess, TM Meyer, EK Bataller, N TI Practitioner report involving intravenous use of vitamin K-1 prompts label review and revision SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Ctr Vet Med, Div Surveillance, Rockville, MD 20855 USA. US Pharmacopeia, Vet Practitioners Reporting Program, Rockville, MD 20852 USA. RP Burgess, TM (reprint author), US FDA, Ctr Vet Med, Div Surveillance, 7500 Standish Pl, Rockville, MD 20855 USA. NR 11 TC 2 Z9 2 U1 0 U2 0 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD JUN 1 PY 2001 VL 218 IS 11 BP 1767 EP 1770 DI 10.2460/javma.2001.218.1767 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA 437JV UT WOS:000168989300058 PM 11394826 ER PT J AU Balish, E Warner, T Pierson, CJ Bock, DM Wagner, RD AF Balish, E Warner, T Pierson, CJ Bock, DM Wagner, RD TI Oroesophageal candidiasis is lethal for transgenic with combined natural killer and T-cell defects SO MEDICAL MYCOLOGY LA English DT Article DE Candida albicans; candidiasis; natural killer cells; T-cells ID CONGENITALLY IMMUNODEFICIENT MICE; SYSTEMIC CANDIDIASIS; GASTROINTESTINAL CANDIDIASIS; SCID MICE; FUNGAL-INFECTIONS; ALBICANS; MUCOSAL; SUSCEPTIBILITY; OROPHARYNGEAL; COLONIZATION AB Germfree transgenic epsilon 26 (Tg epsilon 26) mice, which express the full-length human CD3 epsilon gene, have combined defects in natural killer (NK) cells and T cells were found to be extremely susceptible to oroesophageal (palate, tongue, esophagus) and gastric (cardia-antrum section) candidiasis, The gnotobiotic Tge26 mice die, apparently from severe oroesophageal candidiasis, within 2-4 weeks after their alimentary tracts are colonized with Candida albicans. The Tge26 mice manifest resistance to acute systemic candidiasis (intravenous injection) and to systemic candidiasis of endogenous origin for the first 2 weeks after their alimentary tracts are colonized with C, albicans, Granulocyte depletion data suggest that granulocytes, in the absence of functional NK cells and T cells, can protect Tg epsilon 26 mice from acute systemic candidiasis and from systemic candidiasis of endogenous origin, for at least 14 days after alimentary tract colonization. Granulocytes and macrophages, in the absence of NK cells and T cells, are unable to protect Tg epsilon 26 mice from lethal oroesophageal candidiasis and systemic candidiasis of endogenous origin which was evident in moribund Tg epsilon 26 mice 2-4 weeks after colonization, Thus, non-T cells (i.e., NK cells) and T cells play important roles in resistance to oroesophageal and systemic (acute and of endogenous origin) candidiasis. C1 Univ Wisconsin, Sch Med, Dept Surg, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Med Microbiol & Immunol, Madison, WI 53706 USA. Univ Wisconsin, Sch Med, Dept Surg Pathol, Madison, WI 53706 USA. Natl Ctr Toxicol Res, Dept Microbiol, Jefferson, AR 72079 USA. RP Balish, E (reprint author), Univ Wisconsin, Sch Med, Dept Surg, 1300 Univ Ave,4638 MSC, Madison, WI 53706 USA. FU NIDCR NIH HHS [DE-09659] NR 41 TC 26 Z9 27 U1 0 U2 0 PU B I O S SCIENTIFIC PUBLISHERS LTD PI OXFORD PA 9 NEWTEC PLACE, MAGDALEN RD, OXFORD OX4 1RE, ENGLAND SN 1369-3786 J9 MED MYCOL JI Med. Mycol. PD JUN PY 2001 VL 39 IS 3 BP 261 EP 268 DI 10.1080/714031024 PG 8 WC Infectious Diseases; Mycology; Veterinary Sciences SC Infectious Diseases; Mycology; Veterinary Sciences GA 451BM UT WOS:000169781300004 PM 11446529 ER PT J AU Wittenberg, G Bastings, E Scales, C Good, D AF Wittenberg, G Bastings, E Scales, C Good, D TI Evolution of TMS motor maps during recovery after stroke SO NEUROIMAGE LA English DT Meeting Abstract C1 Wake Forest Univ, Sch Med, Dept Neurol, Winston Salem, NC 27109 USA. US FDA, Rockville, MD 20857 USA. Wake Forest Univ, Sch Med, Dept Neurosurg, Winston Salem, NC 27109 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S1281 EP S1281 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106301280 ER PT J AU Yen, YF Bastings, E Burdette, J Scales, C Greenberg, J Wittenberg, G Good, D Pons, T AF Yen, YF Bastings, E Burdette, J Scales, C Greenberg, J Wittenberg, G Good, D Pons, T TI Longitudinal evaluation of activation of primary motor cortex with fMRI on subcortical stroke patients during recovery SO NEUROIMAGE LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Dept Med Engn, Winston Salem, NC 27157 USA. US FDA, Rockville, MD 20857 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Radiol, Winston Salem, NC 27157 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Neurol, Winston Salem, NC 27157 USA. Wake Forest Univ, Bowman Gray Sch Med, Dept Neurosurg, Winston Salem, NC 27157 USA. NR 0 TC 0 Z9 1 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 1053-8119 J9 NEUROIMAGE JI Neuroimage PD JUN PY 2001 VL 13 IS 6 SU S BP S853 EP S853 PN 2 PG 1 WC Neurosciences; Neuroimaging; Radiology, Nuclear Medicine & Medical Imaging SC Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA 439HQ UT WOS:000169106300852 ER PT J AU Cote, CJ Notterman, DA Karl, HW Weinberg, JA McCloskey, C AF Cote, CJ Notterman, DA Karl, HW Weinberg, JA McCloskey, C TI Adverse sedation events in pediatrics - Reply SO PEDIATRICS LA English DT Letter C1 Northwestern Univ, Sch Med, Childrens Mem Hosp, Chicago, IL 60614 USA. New York Presbyterian Hosp, Div Crit Care Med, New York, NY USA. Princeton Univ, Dept Mol Biol, Princeton, NJ 08544 USA. Univ Washington, Sch Med, Dept Pediat Anesthesiol, Childrens Hosp, Seattle, WA USA. Univ Tennessee, Dept Pediat, Coll Med, Memphis, TN 38163 USA. Lebonheur Childrens Med Ctr, Dept Emergency Serv, Memphis, TN USA. US FDA, Ctr Drug Evaluat & Res, Off Postmkt Drug Risk Assessment, Div Drug Risk Evaluat 2, Washington, DC 20204 USA. RP Cote, CJ (reprint author), Northwestern Univ, Sch Med, Childrens Mem Hosp, Chicago, IL 60614 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2001 VL 107 IS 6 BP 1494 EP 1495 PG 2 WC Pediatrics SC Pediatrics GA 439HJ UT WOS:000169105500074 ER PT J AU Zanardi, LR Haber, P Mootrey, GT Niu, MT Wharton, M AF Zanardi, LR Haber, P Mootrey, GT Niu, MT Wharton, M CA VAERS Working Grp TI Intussusception among recipients of rotavirus vaccine: Reports to the vaccine adverse event reporting system SO PEDIATRICS LA English DT Article DE intussusception; rotavirus vaccine; Vaccine Adverse Event Reporting System; vaccine safety ID INFECTION; CHILDREN; VAERS; EPIDEMIOLOGY; ADENOVIRUS; CHILDHOOD AB Background. Rotavirus vaccine was licensed on August 31, 1998, and subsequently recommended for routine use among infants. To assess rare adverse events, postlicensure surveillance was conducted. Objective. To describe the cases of intussusception among rotavirus vaccine recipients reported to the Vaccine Adverse Event Reporting System from October 1998 through December 1999. Setting and Participants. Infants vaccinated with rotavirus vaccine in the United States. Outcome Measures. Intussusception confirmed by radiology, surgery, or autopsy report with medical record documentation or confirmed by a primary health care provider. Results. There were 98 confirmed cases of intussusception after vaccination with rotavirus vaccine reported to the Vaccine Adverse Event Reporting System; 60 of these developed intussusception within 1 week after vaccination. Based on calculations using vaccine distribution data and intussusception incidence rates from 2 separate databases, an estimated 7 to 16 cases would have been expected to occur in the week after vaccination by chance alone. Conclusion. Using a passive surveillance system for vaccine adverse events, we observed at least a fourfold increase over the expected number of intussusception cases occurring within 1 week of receipt of rotavirus vaccine. Other studies were initiated to further define the relationship between rotavirus vaccine and intussusception. In light of these and other data, the rotavirus vaccine manufacturer voluntarily removed its product from the market, and the recommendation for routine use of rotavirus vaccine among US infants has been withdrawn. C1 Ctr Dis Control & Prevent, Child Vaccine Preventable Dis Branch, Epidemiol & Surveillance Div, Natl Immunizat Program, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Epidemiol Intellegence Serv Program, Epidemiol Program Off, Atlanta, GA 30333 USA. US FDA, Vaccine Safety Branch, Div Epidemiol, Off Biostat & Epidemiol, Rockville, MD 20857 USA. RP Zanardi, LR (reprint author), Ctr Dis Control & Prevent, Child Vaccine Preventable Dis Branch, Epidemiol & Surveillance Div, Natl Immunizat Program, 1600 Clifton Rd,E-61, Atlanta, GA 30333 USA. NR 24 TC 57 Z9 58 U1 0 U2 0 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JUN PY 2001 VL 107 IS 6 AR e97 DI 10.1542/peds.107.6.e97 PG 6 WC Pediatrics SC Pediatrics GA 439HJ UT WOS:000169105500012 PM 11389295 ER PT J AU Takamatsu, N Kim, ON Welage, LS Idkaidek, NM Hayashi, Y Barnett, J Yamamoto, R Lipka, E Lennernas, H Hussain, A Lesko, L Amidon, GL AF Takamatsu, N Kim, ON Welage, LS Idkaidek, NM Hayashi, Y Barnett, J Yamamoto, R Lipka, E Lennernas, H Hussain, A Lesko, L Amidon, GL TI Human jejunal permeability of two polar drugs: Cimetidine and ranitidine SO PHARMACEUTICAL RESEARCH LA English DT Article DE intestinal permeability; drug absorption; cimetidine; ranitidine; biopharmaceutic classification system ID SMALL-INTESTINE; PERFUSION; ABSORPTION; PLASMA AB Purpose. To determine the human jejunal permeability of cimetidine and ranitidine using a regional jejunal perfusion approach, and to integrate such determinations with previous efforts to establish a baseline correlation between permeability and fraction dose absorbed in humans for soluble drugs. Methods. A sterile multi-channel perfusion tube, Loc-I-Gut (R), was inserted orally and positioned in the proximal region of the jejunum. A solution containing cimetidine or ranitidine and phenylalanine, propranolol, PEG 400, and PEG 4000 was perfused through a 10 cm jejunal segment in 6 and 8 subjects, respectively. Results. The mean P-eff (+/- se) of cimetidine and ranitidine averaged over both phases were 0.30 (0.045) and 0.27 (0.062) x 10(-4) cm/s, respectively, and the differences between the two were found to be statistically insignificant. The mean permeabilities for propranolol, phenylalanine, and PEG 400 averaged over both phases and studies were 3.88 (0.72), 3.36 (0.50), and 0.56 (0.08) x 10(-4) cm/s, respectively. The differences in permeability for a given marker were not significant between phases or between the two studies. Conclusions. The 10-fold lower permeabilities found for cimetidine and ranitidine in this study, compared to propranolol and phenylalanine, appear to be consistent with their less than complete absorption in humans. C1 Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. Yamanouchi Pharmaceut Co Ltd, Shizuoka, Japan. Sookmyung Womens Univ, Seoul 140742, South Korea. Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. Univ Michigan Hosp, Serv Pharm, Ann Arbor, MI 48109 USA. Jordan Univ Sci & Technol, Irbid, Jordan. Nagoya City Univ, Aichi, Japan. Univ Michigan, Sch Med, Ann Arbor, MI USA. Ono Pharmaceut Co Ltd, Osaka 618, Japan. Pfizer Global R&D, Ann Arbor, MI 48105 USA. Uppsala Univ, Sch Pharm, Uppsala, Sweden. US FDA, CDER, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20852 USA. RP Amidon, GL (reprint author), Univ Michigan, Coll Pharm, 428 Church St, Ann Arbor, MI 48109 USA. FU FDA HHS [FD014]; NCRR NIH HHS [M01RR00042] NR 14 TC 39 Z9 41 U1 0 U2 3 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 JUN PY 2001 VL 18 IS 6 BP 742 EP 744 DI 10.1023/A:1011020025338 PG 3 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 452AJ UT WOS:000169834700004 PM 11474776 ER PT J AU Silvers, LE Ellenberg, SS Wise, RP Varricchio, FE Mootrey, GT Salive, ME AF Silvers, LE Ellenberg, SS Wise, RP Varricchio, FE Mootrey, GT Salive, ME TI The epidemiology of fatalities reported to the Vaccine Adverse Event Reporting System 1990-1997 SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE epidemiology; VAERS (Vaccine Adverse Event Reporting System); fatalities; deaths; reports; vaccination; immunization; vaccine safety surveillance; SIDS (Sudden Infant Death Syndrome); reporting rates ID INFANT DEATH SYNDROME; IMMUNIZATION; VAERS; RISK AB Purpose To examine the fatalities reported to the federally administered Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system, in its first 7 years. Methods The working data set included variables such as demographic information, dates of vaccination, adverse event onset and death, vaccines administered, and vaccination facility data. Frequencies for these data and state reporting rates were calculated. Results A total of 1266 fatalities were reported to VAERS during July 1990 through June 1997. The number of death reports peaked in 1992-1993 and then declined. The overall median age of cases was 0.4 years, with a range of 1 day to 104 years. Nearly half of the deaths were attributed to sudden infant death syndrome (SIDS). Conclusions The trend of decreasing numbers of deaths reported to VAERS since 1992-1993 follows that observed for SIDS overall for the US general population following implementation of the 'Back to Sleep' program. These data may support findings of past controlled studies showing that the association between infant vaccination and SIDS is coincidental and not causal. VAERS reports of death after vaccination may be stimulated by the temporal association, rather than by any causal relationship. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Bethesda, MD USA. CDCP, Vaccine Safety & Dev Branch, Epidemiol & Surveillance Div, Natl Immunizat Program, Atlanta, GA USA. RP Silvers, LE (reprint author), POB 34889, Bethesda, MD 20827 USA. NR 20 TC 15 Z9 15 U1 0 U2 0 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 JUN-JUL PY 2001 VL 10 IS 4 BP 279 EP 285 DI 10.1002/pds.619 PG 7 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 490PR UT WOS:000172060700001 PM 11760487 ER PT J AU Godar, DE Wengraitis, SP Shreffler, J Sliney, DH AF Godar, DE Wengraitis, SP Shreffler, J Sliney, DH TI UV doses of Americans SO PHOTOCHEMISTRY AND PHOTOBIOLOGY LA English DT Article ID DIFFERENT OUTDOOR ACTIVITIES; WAVELENGTH DEPENDENCE; ULTRAVIOLET-RADIATION; ACTION SPECTRUM; SKIN-CANCER; HAIRLESS MICE; B TREATMENT; EXPOSURE; PHOTOCARCINOGENESIS; DOSIMETER AB The UV doses of Americans were never measured, but are needed for assessing the risks of UV-related health effects. We calculated these doses using a novel approach, The Environmental Protection Agency's (EPA) National Human Activity Pattern Survey (NHAPS) recorded the activity profiles of 9386 Americans over 24 months to assess their exposure to environmental pollutants, one of which is UV radiation. NHAPS used randomized telephone interviews to get their previous day's minute-by-minute activities. From NHAPS we extracted only the outdoor-daylight data of the northern and southern indoor workers (95%), stratifying by season, sex and age (0-21, 22-40, 41-59 and 60+ years) to find the average time Americans spend outdoors. Knowing the total daylight time and that while outdoors Americans are exposed to about 30% of the available solar UV (on a horizontal plane), we calculated their percent ambients, The average American's percent ambients are 2.6 and 2.5% for northern and southern females, respectively, and 3.5 and 3.6% for northern and southern males, respectively. Men over 40 years of age have the highest ambients (4%). From their ambients we calculated their annual doses using seasonal averages of UV measurements taken daily for over 2 years by EPA Brewer spectrophotometers located in four quadrants of the United States: Atlanta, GA; Boston, MA; Bozeman, MT and Riverside, CA. The average erythemal UV doses of Americans are about 25 000 J/m(2)/year, 22 000 for females and 28 000 for males, or 33 000 J/m(2)/year including a conservative continental U.S. vacation (7800 J/m(2)). Thus, we can now assess the risks of UV-related health effects for Americans. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. USA, Ctr Hlth Promot & Prevent Med, Aberdeen Proving Ground, MD USA. US EPA, Natl Exposure Res Lab, Res Triangle Pk, NC 27711 USA. RP Godar, DE (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12709 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 44 TC 82 Z9 83 U1 1 U2 6 PU AMER SOC PHOTOBIOLOGY PI AUGUSTA PA BIOTECH PARK, 1021 15TH ST, SUITE 9, AUGUSTA, GA 30901-3158 USA SN 0031-8655 J9 PHOTOCHEM PHOTOBIOL JI Photochem. Photobiol. PD JUN PY 2001 VL 73 IS 6 BP 621 EP 629 DI 10.1562/0031-8655(2001)073<0621:UDOA>2.0.CO;2 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 441TY UT WOS:000169246700007 PM 11421067 ER PT J AU Olsen, AR Gecan, JS Ziobro, GC Bryce, JR AF Olsen, AR Gecan, JS Ziobro, GC Bryce, JR TI Regulatory action criteria for filth and other extraneous materials V. Strategy for evaluating hazardous and nonhazardous filth SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Review ID TURTLE-ASSOCIATED SALMONELLOSIS; TRIBOLIUM-CASTANEUM HERBST; ESCHERICHIA-COLI O157-H7; MUSCA-DOMESTICA DIPTERA; SUBSTITUTED PARA-BENZOQUINONES; GERMAN-COCKROACH ORTHOPTERA; INNER-CITY CHILDREN; COMMON HOUSE ROACH; MICROANALYTICAL QUALITY; BLATTELLA-GERMANICA AB The U.S. Food and Drug Administration (FDA) uses regulatory action criteria for filth and extraneous materials to evaluate adulteration of food products. The criteria are organized into three categories: health hazards, indicators of insanitation, and natural or unavoidable defects. The health hazard category includes criteria for physical, chemical, and microbiological hazards associated with filth and extraneous materials. The health hazard category encompasses criteria for HACCP (Hazard Analysis and Critical Control Point) hazards and HACCP contributing factors. The indicators of insanitation category includes criteria for visibly objectionable contaminants, contamination from commensal pests, and other types of contamination that are associated with insanitary conditions in food processing and storage facilities. The natural or unavoidable category includes criteria for harmless, naturally occurring defects and contaminants. A decision tree is presented for the sequential application of regulatory action criteria for filth and extraneous materials associated with each category and with each type of filth or extraneous material in the three categories. This final report of a series in the development of a transparent science base for a revised FDA regulatory policy in the area of filth and extraneous materials in food includes a comprehensive list of the references that form the science base for the FDA regulatory policy. C1 US FDA, Microanalyt Branch, Washington, DC 20204 USA. RP Olsen, AR (reprint author), US FDA, Microanalyt Branch, 200 C St,SW,HFS 315, Washington, DC 20204 USA. NR 458 TC 25 Z9 26 U1 0 U2 10 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0273-2300 EI 1096-0295 J9 REGUL TOXICOL PHARM JI Regul. Toxicol. Pharmacol. PD JUN PY 2001 VL 33 IS 3 BP 363 EP 392 DI 10.1006/trph.2001.1472 PG 30 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 445PX UT WOS:000169467400010 PM 11407939 ER PT J AU Haseman, JK Bailer, AJ Kodell, RL Morris, R Portier, K AF Haseman, JK Bailer, AJ Kodell, RL Morris, R Portier, K TI Statistical issues in the analysis of low-dose endocrine disruptor data SO TOXICOLOGICAL SCIENCES LA English DT Article AB The National Institute of Environmental Health Sciences (NIEHS) and the U,S, Environmental Protection Agency (U.S. EPA) recently cosponsored the Endocrine Disrupters Low-Dose Peer Review. The purpose of this meeting was to examine data supporting the presence or absence of low-dose effects of endocrine disrupters in specific studies and then to evaluate the likelihood and significance of these and/or other potential low-dose effects for humans. All invited speakers agreed to provide their raw data in advance of the meeting to a Statistics Subpanel, which was asked to reevaluate the authors' experimental design, data analysis, and interpretation of experimental results, The purpose of this statistical reevaluation was to provide an independent assessment of the experimental design and data analysis used in each of the studies and to identify key statistical issues relevant to the evaluation and interpretation of the data. This paper presents a summary of the Statistics Subpanel's evaluation. Specific examples are presented to illustrate problems that arose in the experimental design and data analysis of certain studies, The statistical principles and issues that are discussed in this paper are not unique to endocrine disrupter studies and should provide important guidelines regarding appropriate experimental design and statistical analysis for other types of laboratory investigations. C1 NIEHS, Biostat Branch, Res Triangle Pk, NC 27709 USA. Miami Univ, Dept Math & Stat, Oxford, OH 45056 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Univ Florida, Dept Stat, Gainesville, FL 32611 USA. Analyt Sci Inc, Durham, NC 27713 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Miami Univ, Dept Math & Stat, Oxford, OH 45056 USA. RP Haseman, JK (reprint author), NIEHS, Biostat Branch, POB 12233, Res Triangle Pk, NC 27709 USA. NR 9 TC 31 Z9 31 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD JUN PY 2001 VL 61 IS 2 BP 201 EP 210 DI 10.1093/toxsci/61.2.201 PG 10 WC Toxicology SC Toxicology GA 438XJ UT WOS:000169079300003 PM 11353128 ER PT J AU Jensen, E Egan, SK Canady, RA Bolger, PM AF Jensen, E Egan, SK Canady, RA Bolger, PM TI Dietary exposures to persistent organic pollutants SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article; Proceedings Paper CT 36th Annual Conference on Theories and Practices in Toxicology and Risk Assessment CY APR 15-18, 2002 CL CINCINNATI, OHIO SP AFRL/HEST, NHRC/TD, USACEHR, Army Ctr Hlth Promot & Prevent Med, AF Off Sci Res, US EPA, Natl Ctr Environm Assessment-Cincinnati, Agcy Toxic Substances Dis Registry, Natl Inst Occup Safety & Hlth, US FDA, Natl Res Council, Natl Acad Sci DE dietary exposure assessment; persistent organic pollutants AB As one of the main components of risk assessment, exposure assessment plays a key role in evaluating risk. Many different scenarios can be developed to estimate the risk from exposure to chemicals such as persistent organic pollutants (POPS). The US Food and Drug Administration (FDA)'s Center for Food Safety and Applied Nutrition (CFSAN) is primarily interested in POPS as humans may be exposed to these compounds through food. Examples of POPS found in food include dioxins, polychlorinated biphenyls (PCBs), polybrominated diphenyl ethers, and some pesticide chemicals. This overview discusses various sources of data that CFSAN has used to estimate dietary exposure to POPS, and provides an example of a recent calculation of an estimate for dietary exposure for consumers in the USA to dioxins in the food supply. C1 US FDA, College Pk, MD 20740 USA. RP Bolger, PM (reprint author), US FDA, HFS-355,5100 Paint Branch Pkwy, College Pk, MD 20740 USA. NR 5 TC 6 Z9 6 U1 0 U2 4 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUN PY 2001 VL 17 IS 5-10 BP 157 EP 162 DI 10.1191/0748233701th104oa PG 6 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 634CB UT WOS:000180321500003 PM 12539860 ER PT J AU Carrington, CD Bolger, PM AF Carrington, CD Bolger, PM TI Methods for projecting long-term dietary exposure from short-term survey data for environmental contaminants SO TOXICOLOGY AND INDUSTRIAL HEALTH LA English DT Article; Proceedings Paper CT 36th Annual Conference on Theories and Practices in Toxicology and Risk Assessment CY APR 15-18, 2002 CL CINCINNATI, OHIO SP AFRL/HEST, NHRC/TD, USACEHR, Army Ctr Hlth Promot & Prevent Med, AF Off Sci Res, US EPA, Natl Ctr Environm Assessment-Cincinnati, Agcy Toxic Substances Dis Registry, Natl Inst Occup Safety & Hlth, US FDA, Natl Res Council, Natl Acad Sci DE Chronic Dietary Assessment AB Public health risk assessments often involve dietary exposures over long periods of time. However, most information about dietary consumption habits comes from short-term surveys that are conducted for periods of three days or less. When employed for characterizing long-term exposures, short-term surveys are likely to underestimate the number of persons consuming a particular food, while overestimating the amount consumed by each individual. Direct application of short-term data is particularly misleading for foods that are consumed infrequently. If a more accurate population estimate for chronic dietary intake is needed for a risk assessment, then two general techniques may be considered. The first method is simpler, while the second is more accurate. Both methods require information about the size of the population consuming the food over the long-term period. The simpler fractional adjustment method reduces consumption across the entire distribution by the ratio of consumer population sizes. Since this method will tend to underestimate high-end exposures and overestimate low-end exposures, it is most useful as a quick bounding exercise. Since short-term surveys are better at characterizing the behavior of frequent consumers, a second method employs an exponential function to reduce the low end of the population distribution by a greater amount than the high end. If available, additional information may be used to select the parameter values for the exponential adjustment. Otherwise, an uncertainty range may be used for the parameter values. Since the frequency-based method is more complex, it is most valuable when used as part of a chronic exposure simulation. Examples of both methods are given for the estimation of chronic wine consumption. C1 US FDA, Ctr Food Safety & Appl Nutr, College Pk, MD 20740 USA. RP Carrington, CD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 5100 Paint Branch Ave, College Pk, MD 20740 USA. NR 6 TC 1 Z9 1 U1 0 U2 0 PU ARNOLD, HODDER HEADLINE PLC PI LONDON PA 338 EUSTON ROAD, LONDON NW1 3BH, ENGLAND SN 0748-2337 J9 TOXICOL IND HEALTH JI Toxicol. Ind. Health PD JUN PY 2001 VL 17 IS 5-10 BP 176 EP 179 DI 10.1191/0748233701th109oa PG 4 WC Public, Environmental & Occupational Health; Toxicology SC Public, Environmental & Occupational Health; Toxicology GA 634CB UT WOS:000180321500005 PM 12539862 ER PT J AU Ball, R AF Ball, R TI Biochemical decompression of hydrogen by naturally occurring bacterial flora in pigs: What are the implications for human hydrogen diving? SO UNDERSEA & HYPERBARIC MEDICINE LA English DT Editorial Material C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20857 USA. RP Ball, R (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Rockville, MD 20857 USA. NR 2 TC 2 Z9 2 U1 0 U2 0 PU UNDERSEA & HYPERBARIC MEDICAL SOC INC PI KENSINGTON PA 10531 METROPOLITAN AVE, KENSINGTON, MD 20895 USA SN 1066-2936 J9 UNDERSEA HYPERBAR M JI Undersea Hyperb. Med. PD SUM PY 2001 VL 28 IS 2 BP 55 EP 56 PG 2 WC Marine & Freshwater Biology; Medicine, Research & Experimental SC Marine & Freshwater Biology; Research & Experimental Medicine GA 526HA UT WOS:000174123300001 PM 11908695 ER PT J AU Tor-Agbidye, J Blythe, LL Craig, AM AF Tor-Agbidye, J Blythe, LL Craig, AM TI Correlation of endophyte toxins (ergovaline and lolitrem B) with clinical disease: Fescue foot and perennial ryegrass staggers SO VETERINARY AND HUMAN TOXICOLOGY LA English DT Article ID INFECTED TALL FESCUE; SHEEP; PERFORMANCE; TOXICOSIS; GRASSES; CATTLE; FLUID; LAMBS; SEED AB Fescue fool, summer syndrome, reproductive problems, and ryegrass staggers are all diseases of livestock related to endophyte toxins in pasture grasses. Range finding experiments and case studies of fescue foot relative to ergovaline toxin found in endophyte infected tall fescue and lolitrem B present in endophyte infected perennial ryegrass were conducted. Within 42 dof initiating a feeding trial with chopped tall fescue straw containing 825 ppb ergovaline and at environmental temperatures of 15.9 C clinical signs of fescue foot were seen in cattle. Sheep on tall fescue pastures in November consuming feed with 540 ppb ergovaline and at environmental temperatures of 7.8 C developed fescue foot in 21 d while sheep on the adjacent field in the previous 2 mo with environmental temperatures of 16.6 C and 12.8 C and 458 ppb ergovaline in the pasture grasses did not. In a field outbreak of rescue foot affecting 42/425 feeder lambs in November, the ergovaline of sample pasture grasses had a mean concentration of 813 ppb. Perennial ryegrass staggers was seen in 42/237 feeder lambs when mean lolitrem B in the sampled grass was 2135 ppb. Overgrazing both tall fescue and ryegrass fields increased probability of clinical disease since the highest levels of toxin were found in the crowns and basal leaf sheaths of tall fescue and perennial ryegrass respectively. Based on these findings, ergovaline dietary levels of 400 to 750 ppb to cattle and 500 to 800 ppb to sheep and lolitrem B levels of 1800 to 2000 ppb in feed for both species are approximated threshold values for disease. Cold environmental temperatures are equally important to toxin concentrations in precipitating fescue foot disease. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Oregon State Univ, Coll Vet Med, Corvallis, OR 97331 USA. Oregon State Univ, Coll Vet Med, Dept Biomed Sci, Corvallis, OR 97331 USA. RP Tor-Agbidye, J (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Craig, A. Morrie/J-5857-2013 NR 30 TC 65 Z9 66 U1 0 U2 25 PU COMPARATIVE TOXICOLOGY LAB PI MANHATTAN PA KANSAS STATE UNIV, MANHATTAN, KS 66506-5606 USA SN 0145-6296 J9 VET HUM TOXICOL JI Vet. Human Toxicol. PD JUN PY 2001 VL 43 IS 3 BP 140 EP 146 PG 7 WC Toxicology; Veterinary Sciences SC Toxicology; Veterinary Sciences GA 434CE UT WOS:000168796900003 PM 11383653 ER PT J AU Tsang, RSW Law, DKS Tsai, CM Ng, LK AF Tsang, RSW Law, DKS Tsai, CM Ng, LK TI Detection of the lst gene in different serogroups and LOS immunotypes of Neisseria meningitidis SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Neisseria meningitidis; lst; lipooligosaccharide ID LACTO-N-NEOTETRAOSE; LIPOOLIGOSACCHARIDES; SIALYLTRANSFERASE; GONORRHOEAE; DISEASE AB The sialylation of the lipooligosaccharide (LOS) of Nesseria meningitidis is mediated by the LOS sialyltransferase enzyme encoded by the Ist gene. PCR using four sets of primers that targeted to different regions of the Ist gene was used to survey the distribution of ist in different serogroups and LOS immunotypes of N. meningitidis as well as other Neisseria species. While the Ist gene was found in N. meningitidis strains regardless of their capsular serogroup and LOS structures, the gene is also found in N. gonorrhoeae, N. lactamica, N. polysaccharea, and N. subflava biovar subflava. The presence of the Ist gene in these organisms and the sialylation of their LOS antigens were discussed. (C) 2001 Federation of European Microbiological Societies. Published by Elsevier Science B.V. All rights reserved. C1 Hlth Canada, Natl Microbiol Lab, Populat & Publ Hlth Branch, Winnipeg, MB, Canada. US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Tsang, RSW (reprint author), Hlth Canada, Natl Microbiol Lab, Populat & Publ Hlth Branch, Winnipeg, MB, Canada. NR 12 TC 7 Z9 7 U1 0 U2 0 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 30 PY 2001 VL 199 IS 2 BP 203 EP 206 DI 10.1111/j.1574-6968.2001.tb10675.x PG 4 WC Microbiology SC Microbiology GA 442GA UT WOS:000169275800009 PM 11377868 ER PT J AU Collins, JM AF Collins, JM TI Inter-species differences in drug properties SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article ID PHARMACOKINETICS AB There has been a clear trend towards decreased reliance upon animal studies and increased emphasis upon experiments with human-derived tissues. Nonetheless, we continue to need investigations of interspecies differences for two principal reasons: (1) to prospectively design experiments so that the animal species most similar to humans can be chosen, on a case-by-case basis, for each drug; (2) to properly evaluate and interpret data obtained from the experiments ("risk assessment"). Four core examples derived from the work in our FDA laboratory are used to illustrate these points. For paclitaxel, different metabolites were formed in humans and rats, which makes metabolic drug-drug interaction studies in rats irrelevant. For zidovudine (AZT), rapid glucuronidation in humans produced a much shorter half-life than expected from studies in animals, which have negligible glucuronidation. The toxicology and efficacy of both parent drug and metabolite need to be assessed in cases such as iododeoxydoxorubicin, in which the parent molecule is the dominant circulating species in mice, but patients have more than 10-fold greater exposure to the metabolite compared with the parent. While rats have highly-active arylamine N-acetyltransferases. dogs totally lack this enzyme family, and humans have intermediate amounts. For some situations, we've suggested that it can be desirable to inhibit NAT to make the human exposure more similar to dogs. In conclusion, although the ratio of animal:human data is decreasing, our ability to use animal data effectively for drug development has actually increased. Continued focus should be placed upon the application of comparative interspecies data for prospective design of animal experiments and retrospective interpretation of animal findings in terms of the potential for human risk and benefit. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Lab Clin Pharmacol, Rockville, MD 20850 USA. RP Collins, JM (reprint author), US FDA, Lab Clin Pharmacol, 4 Res Court,Rm 314, Rockville, MD 20850 USA. NR 7 TC 28 Z9 29 U1 0 U2 3 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 MAY 16 PY 2001 VL 134 IS 3 BP 237 EP 242 DI 10.1016/S0009-2797(01)00158-2 PG 6 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA 438LB UT WOS:000169053900002 PM 11336972 ER PT J AU McGinnis, TJ AF McGinnis, TJ TI Significant FDA approvals in 2000 SO AMERICAN FAMILY PHYSICIAN LA English DT Editorial Material C1 US FDA, Off Policy, Rockville, MD 20857 USA. RP McGinnis, TJ (reprint author), US FDA, Off Policy, Rockville, MD 20857 USA. NR 0 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 MAY 15 PY 2001 VL 63 IS 10 BP 2061 EP 2064 PG 4 WC Primary Health Care; Medicine, General & Internal SC General & Internal Medicine GA 435GM UT WOS:000168869100012 PM 11388719 ER PT J AU Gautier, JC Holzhaeuser, D Markovic, J Gremaud, E Schilter, B Turesky, RJ AF Gautier, JC Holzhaeuser, D Markovic, J Gremaud, E Schilter, B Turesky, RJ TI Oxidative damage and stress response from ochratoxin A exposure in rats SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Article DE ochratoxin A; oxidative stress; haem oxygenase-1; 8-oxodG; MDA; vitamin E oxidation; free radicals ID CHROMATOGRAPHY MASS-SPECTROMETRY; VITAMIN-E; LIPID-PEROXIDATION; ALPHA-TOCOPHEROL; FERRIC NITRILOTRIACETATE; HEME OXYGENASE; RENAL CARCINOGEN; MAMMALIAN-CELLS; STRAND BREAKS; FREE-RADICALS AB Ochratoxin A (OTA) is a mycotoxin found in some cereal and grain products. It is a potent renal carcinogen in male rats, although its mode of carcinogenic action is not known. Oxidative stress may play a role in OTA-induced toxicity and carcinogenicity. In this study, we measured several chemical and biological markers that are associated with oxidative stress response to determine if this process is involved in OTA-mediated toxicity in rats. Treatment of male rats with OTA (up to 2 mg/kg per os, 24 h exposure) did not increase the formation of biomarkers of oxidative damage such as the lipid peroxidation marker malondialdehyde in rat plasma, kidney, and liver, or the DNA damage marker 8-oxo-7,8-dihydro-2'deoxyguanosine in kidney DNA. However, OTA treatment (1 mg/kg) did result in a 22% decrease in alpha -tocopherol plasma levels and a 5-fold increase in the expression of the oxidative stress responsive protein haem oxygenase-1. specifically in the kidney. The selective alteration of these latter two markers indicates that OTA does evoke oxidative stress, which may contribute at least in part to OTA renal toxicity and carcinogenicity in rats during long-term exposure. (C) 2001 Elsevier Science Inc. C1 Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne, Switzerland. RP Turesky, RJ (reprint author), Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 45 TC 120 Z9 123 U1 0 U2 7 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. PD MAY 15 PY 2001 VL 30 IS 10 BP 1089 EP 1098 DI 10.1016/S0891-5849(01)00507-X PG 10 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 431WL UT WOS:000168654700004 PM 11369498 ER PT J AU Wang, T Shankar, K Bucci, TJ Warbritton, A Mehendale, HM AF Wang, T Shankar, K Bucci, TJ Warbritton, A Mehendale, HM TI Diallyl sulfide inhibition of CYP2E1 does not rescue diabetic rats from thioacetamide-induced mortality SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article DE tissue repair; toxic outcome; diabetes; bioactivation; CYP2E1 ID ACETAMINOPHEN-INDUCED LETHALITY; TISSUE-REPAIR RESPONSE; LIVER-INJURY; INDUCED HEPATOTOXICITY; REGENERATION; CHLORDECONE; COLCHICINE; NECROSIS; MIREX; MODEL AB Previously we have shown that hepatotoxicity of thioacetamide (TA) was increased in streptozotocin (STZ)-induced diabetic (DB) rats due to combined effects of enhanced bioactivation-based liver injury of TA and compromised liver tissue repair response. We have also shown that TA is primarily bioactivated by hepatic CYP2E1. The present study was done to further investigate the importance of liver tissue repair in determining the final outcome of hepatotoxicity. STZ-induced DB rats were pretreated with a CYP2E1 inhibitor, diallyl sulfide (DAS), to decrease the bioactivation-based liver injury of TA. The treatments were as follows: DB/DAS/TA, DB/corn oil/TA, and DB/DAS/saline. Nondiabetic (non-DB) rats received the same treatments as controls. A dose of TA (300 mg/kg ip), which was nonlethal in non-DB rats, caused 92 and 90% mortality in DB/DAS/TA and DB/corn oil/TA groups, respectively. At various times (0-60 h) after treatment, liver injury was assessed by plasma alanine aminotransferase and histopathology. Cell proliferation was evaluated by [H-3]thymidine incorporation and immunohistochemical staining of proliferating cell nuclear antigen (PCNA). In the DB/DAS/TA rats, DAS pretreatment markedly reduced the CYP2E1-dependent liver injury of TA compared to that in DB/corn oil/TA rats. However, subsequent hepatic DNA synthesis in both DB groups was inhibited approximately 50%. PCNA analysis showed a corresponding decrease in cell-cycle progression. This compromised tissue repair response in DB rats was insufficient to compensate for cell loss, resulting in progression of liver injury and culminating in high mortality in both DB groups. Furthermore, non-DB rats were pretreated with a CYP2E1 inducer, isoniazid, to increase the bioactivation-based TA liver injury equal to the liver injury observed in DB/DAS/TA rats. Despite equal injury up to 36 h following TA treatment, the tissue repair response in the non-DB rats was highly stimulated to compensate for liver injury and led to 70% survival in this group. These studies underscore the importance of adequate and timely tissue repair in compensating for liver injury and protecting from lethality. (C) 2001 Academic Press. C1 Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. RP Mehendale, HM (reprint author), Univ Louisiana Monroe, Coll Pharm, Dept Toxicol, 700 Univ Ave, Monroe, LA 71209 USA. FU NIEHS NIH HHS [ES-9870, ES-08604] NR 28 TC 24 Z9 25 U1 0 U2 1 PU ACADEMIC PRESS INC 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 MAY 15 PY 2001 VL 173 IS 1 BP 27 EP 37 DI 10.1006/taap.2001.9165 PG 11 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 438NT UT WOS:000169060500004 PM 11350212 ER PT J AU Uppoor, VRS AF Uppoor, VRS TI Regulatory perspectives on in vitro (dissolution)/in vivo (bioavailability) correlations SO JOURNAL OF CONTROLLED RELEASE LA English DT Article; Proceedings Paper CT 6th European Symposium on Controlled Drug Delivery CY APR 12-14, 2000 CL NOORDWIJK AAN ZEE, NETHERLANDS SP Alza Corp, Inst Biomed Technol, Univ Twente, Janssen Pharmaceut, Novartis Pharma AG, NV Organon Akzo Nobel, Sam Yang Corp AB In vitro dissolution has been extensively used as a quality control tool for solid oral dosage forms. In several cases, however, it is not known whether one can predict the in vivo performance of these products from in vitro dissolution data. In an effort to minimize unnecessary human testing, investigations of in vitro/in vivo correlations (IVIVC) between in vitro dissolution and in vivo bioavailability are increasingly becoming an integral part of extended release (ER) drug product development. This increased activity in developing IVIVCs indicates the value of IVIVCs to the pharmaceutical industry. Because of the scientific interest and the associated utility of IVIVC as a Valuable tool, the US Food and Drug Administration has published a Guidance in September 1997, entitled Extended Release Oral Dosage Forms: Development, Evaluation and Application of In Vitro/In Vivo Correlations. A predictive IVIVC enables in vitro dissolution to serve as a surrogate for in viva bioequivalence testing. IVIVCs can be used in place of biostudies that may otherwise be required to demonstrate bioequivalence, when certain preapproval and postapproval changes are made in formulation, equipment, manufacturing process or in the manufacturing site. IVIVC development could lead to improved product quality (more meaningful dissolution specifications) and decreased regulatory burden (reduced biostudy requirements). This article will discuss in derail the FDA Guidance which deals with the development, evaluation methods and criteria, and applications of IVIVCs. From a regulatory point of view, the applications of IVIVC to grant biowaivers and to set dissolution specifications for ER oral dosage forms will be presented. Additionally, since the principles of IVIVC are considered to be similar for non-oral dosage forms, the guidance for oral extended release products may be applied for non-oral products as well. While the principles are likely to be the same, it is an interesting challenge to look at appropriate methods for dissolution testing and for development of in vitro/in vivo correlations for products such as injectable depot formulations. (C) 2001 Elsevier Science B.V. All rights reserved. C1 US FDA, CDER, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. RP Uppoor, VRS (reprint author), US FDA, CDER, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 5 TC 63 Z9 68 U1 1 U2 11 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-3659 J9 J CONTROL RELEASE JI J. Control. Release PD MAY 14 PY 2001 VL 72 IS 1-3 BP 127 EP 132 DI 10.1016/S0168-3659(01)00268-1 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 445MZ UT WOS:000169462800013 PM 11389991 ER PT J AU You, SY Falgout, B Markoff, L Padmanabhan, R AF You, SY Falgout, B Markoff, L Padmanabhan, R TI In vitro RNA synthesis from exogenous dengue viral RNA templates requires long range interactions between 5 '- and 3 '-terminal regions that influence RNA structure SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID STEM-LOOP STRUCTURE; YELLOW-FEVER VIRUS; PUTATIVE METHYLTRANSFERASE DOMAIN; BORNE ENCEPHALITIS-VIRUS; FLAVIVIRUS GENOMIC RNA; MINUS-STRAND SYNTHESIS; SMALL NUCLEAR RNAS; SECONDARY STRUCTURE; 3'-UNTRANSLATED REGION; MESSENGER-RNA AB Viral replicases of many positive-strand RNA viruses are membrane-bound complexes of cellular and viral proteins that include viral RNA-dependent RNA polymerase (RdRP). The in vitro RdRP assay system that utilizes cytoplasmic extracts from dengue viral-infected cells and exogenous RNA templates was developed to understand the mechanism of viral replication in vivo. Our results indicated that in vitro RNA synthesis at the 5'-untranslated region (UTR) required the presence of the 5'-terminal region (TR) and the two cyclization (CYC) motifs suggesting a functional interaction between the TRs. In this study, using a psoralen-UV crosslinking method and an in vitro RdRP assay, we analyzed structural determinants for physical and functional interactions. Exogenous RNA templates that were used in the assays contained deletion mutations in the 5'-TR and substitution mutations in the 3'-stem-loop structure including those that would disrupt the predicted pseudoknot structure. Our results indicate that there is physical interaction between the 5'-TR and 3'-UTR that requires only the CYC motifs. RNA synthesis at the 3'-UTR, however, requires long range interactions involving the 5'-UTR, CYC motifs, and the 3'-stem-loop region that includes the tertiary pseudoknot structure. C1 Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, Kansas City, KS 66160 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Rockville, MD 20852 USA. RP Padmanabhan, R (reprint author), Univ Kansas, Med Ctr, Dept Biochem & Mol Biol, 3901 Rainbow Blvd, Kansas City, KS 66160 USA. FU NIAID NIH HHS [AI-32078, AI-45623] NR 81 TC 138 Z9 142 U1 2 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 11 PY 2001 VL 276 IS 19 BP 15581 EP 15591 DI 10.1074/jbc.M010923200 PG 11 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 431GH UT WOS:000168623100005 PM 11278787 ER PT J AU Young, JF Wosilait, WD Luecke, RH AF Young, JF Wosilait, WD Luecke, RH TI Analysis of methylmercury disposition in humans utilizing a PBPK model and animal pharmacokinetic data SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID METHYL-MERCURY; TISSUE DISTRIBUTION; GUINEA-PIG; COMPUTER-MODEL; EXPOSURE; GROWTH; BLOOD; BIOTRANSFORMATION; TOXICOKINETICS; ACCUMULATION AB Physiologically based pharmacokinetic (PBPK) models are excellent tools to aid in the extrapolation of animal data to humans. When the late of the chemical is the same among species bring compared, animal data can appropriately be considered as a model for human exposure. For methylmercury exposure, sufficient data exist to allow comparison of numerous mammalian species to humans. PBPK model validation entails obtaining blood and tissue concentrations of the parent chemical and metabolite(s) at various times following a known exposure. From ethical and practical considerations, human tissue concentrations following a known exposure to an environmental toxicant are scarce. While animal-to-human extrapolation demands that sufficient human data exist to validate the model, the validation requirements are less stringent if multiple animal models are utilized within a single model template. A versatile PBPK model was used to analyze the distribution and elimination of methylmercury and its metabolite, inorganic mercury. Uniquely, the model is formed in a generic way from a single basic template during the initial program compilation. Basic parameters are defined for different PBPK models for mammalian species that span a relatively large range of sizes. In this article, the analyser include 12 species (mouse. hamster, rat, guinea pig, cat rabbit, monkey sheep, pig, gear, cow, and human), Allometric (weight-based) correlations of tissue binding coefficients, metabolism rate constants, and elimination parameters for both methylmercury and inorganic mercury are presented for species for which sufficient data are available. The resulting human model, in accord with the animal models, predicts relatively high inorganic mercury levels in the kidneys long alter the disappearance of methylmercury from the blood. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Univ Missouri, Sch Med, Dept Pharmacol, Columbia, MO 65212 USA. Univ Missouri, Dept Chem Engn, Columbia, MO 65212 USA. RP Young, JF (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jyoung@nctr.ida.gov NR 45 TC 35 Z9 37 U1 3 U2 10 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 325 CHESTNUT ST, SUITE 800, PHILADELPHIA, PA 19106 USA SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. Toxicol. Env. Health Part A PD MAY 11 PY 2001 VL 63 IS 1 BP 19 EP 52 DI 10.1080/152873901750128344 PG 34 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 427VG UT WOS:000168425700002 PM 11346132 ER PT J AU Yancy, H Ayers, SL Farrell, DE Day, A Myers, MJ AF Yancy, H Ayers, SL Farrell, DE Day, A Myers, MJ TI Differential cytokine mRNA expression in swine whole blood and peripheral blood mononuclear cell cultures SO VETERINARY IMMUNOLOGY AND IMMUNOPATHOLOGY LA English DT Article DE reverse transcriptase-polymerase chain reaction; PBMC; whole blood; IL-2; IL-6; IL-8; IL-10 ID GENE-EXPRESSION; TNF-ALPHA; ASSAY AB The kinetics of interleukin-2 (IL-2), IL-6, IL-8 and IL-10 gene expression in concanavalin A (Con A)-activated whole blood (WB) and peripheral blood mononuclear cell (PBMC) cultures were examined using reverse transcriptase-polymerase chain reaction (RT-PCR). Unstimulated PBMC or WE cultures failed to show increases in basal cytokine PCR amplicon levels for any cytokine examined. PBMC cultures demonstrated peak expression of IL-2, IL-6, IL-8 and IL-10 mRNA levels at 12, 24, 24 and 6 h, respectively. WE cultures exhibited peak IL-2, IL-6, IL-8 and IL-10 mRNA levels at 24, 12, 6 and 24 h, respectively. PBMC cultures consistently exhibited higher levels of IL-2 mRNA at all times examined than did WE cultures. WE cultures consistently had higher levels of IL-6 mRNA than PBMC cultures. IL-8 and IL-10 protein levels in PBMC cultures were first detected 12 h after stimulation and continued to increase in concentration through 48 h. In WE cultures, 1L-8 and IL-10 protein levels were first noted at 12 and 6 h, respectively. WE culture IL-8 and IL-10 levels quickly reached equilibrium after being detected and remained at levels lower than those noted in PBMC cultures. These results show WE cultures represent an approach with reduced cost and time when compared to traditional cell culture and isolation methods. It may also produce an in vitro test system that more closely resembles in vivo conditions. Published by Elsevier Science B.V. C1 US FDA, Div Anim Res, Ctr Vet Med, Laurel, MD 20708 USA. Howard Univ, Dept Biol, Washington, DC 20017 USA. Ctr Vet Med, Div Anim & Food Microbiol, Laurel, MD 20708 USA. Howard Univ, Dept Microbiol, Washington, DC 20017 USA. RP Myers, MJ (reprint author), US FDA, Div Anim Res, Ctr Vet Med, 8404 Muirkirk Rd, Laurel, MD 20708 USA. NR 13 TC 20 Z9 20 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-2427 J9 VET IMMUNOL IMMUNOP JI Vet. Immunol. Immunopathol. PD MAY 10 PY 2001 VL 79 IS 1-2 BP 41 EP 52 DI 10.1016/S0165-2427(01)00247-1 PG 12 WC Immunology; Veterinary Sciences SC Immunology; Veterinary Sciences GA 434BY UT WOS:000168796300004 PM 11356249 ER PT J AU Chapman, LE Bloom, ET AF Chapman, LE Bloom, ET TI Clinical xenotransplantation SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material ID PORCINE ENDOGENOUS RETROVIRUS; BIOARTIFICIAL LIVER; NO EVIDENCE; HUMAN-CELLS; INFECTION; TRANSPLANTATION; XENOGRAFTS; RECIPIENTS; TISSUE; RISK C1 CDC, HIV AIDS & Retrovirol Branch, Div HIV STD & TB Lab Res, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapy, Lab Immunol & Virol, Bethesda, MD USA. RP Chapman, LE (reprint author), CDC, HIV AIDS & Retrovirol Branch, Div HIV STD & TB Lab Res, Natl Ctr Infect Dis, Mailstop G-19,1600 Clifton Rd, Atlanta, GA 30333 USA. NR 31 TC 12 Z9 13 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 9 PY 2001 VL 285 IS 18 BP 2304 EP 2306 DI 10.1001/jama.285.18.2304 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 427NB UT WOS:000168411200002 PM 11343460 ER PT J AU Monroe, JJ Manjanatha, RG Skopek, TR AF Monroe, JJ Manjanatha, RG Skopek, TR TI Extent of CpG methylation is not proportional to the in vivo spontaneous mutation frequency at transgenic loci in Big Blue (TM) rodents SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE Big Blue; CpG; 5-methylcytosine; spontaneous mutation; methylation; deamination ID HUMAN GENETIC-DISEASE; LACI GENE; CYTOSINE METHYLATION; N-NITROSOUREA; P53 GENE; DNA; MICE; BASE; DINUCLEOTIDE; RATS AB The lad transgene used in the Big Blue (TM) (BB) mouse and rat mutation assays typically displays spontaneous mutation frequencies in the 5 x 10(-5) range. Recently, the bone marrow and bladder of the Big Blue (TM) rat were reported to have, by an order of magnitude, the lowest spontaneous mutation frequencies ever observed for lad in a transgenic animal, approaching the value for endogenous targets such as hprt (similar to 10(-6)). Since spontaneous mutations in transgenes have been attributed in part to deamination of 5-methylcytosine in CpG sequences, we have investigated the methylation status of the lad transgene in bone marrow of BE rats and compared it to that present in other tissues including liver, spleen, and breast. The first 400 bases of the lacI gene were investigated using bisulfite genomic sequencing since this region contains the majority of both spontaneous and induced mutations. Surprisingly, all the CpG cytosines in the lacI sequence were fully methylated in all the tissues examined from both 2- and 14-week-old rats. Thus, there is no correlation between 5-methylcytosine content at CpG sites in lacI and the frequency of spontaneous mutation at this marker. We also investigated the methylation status of another widely used transgenic mutation target, the cll gene. The CpG sites in cll in BE rats were fully methylated while those in BE mice were partially methylated teach site approximately 50% methylated). Since spontaneous mutation frequency at cll is comparable in rat and mouse, the methylation status of CpG sequences in this gene also does not correlate with spontaneous frequency. We conclude that other mechanisms besides spontaneous deamination of 5-methylcytosine at CpG sites are driving spontaneous mutation at BE transgenic loci. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Merck Res Labs, Dept Genet & Cellular Toxicol, W Point, PA 19486 USA. US FDA, Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. RP Monroe, JJ (reprint author), Merck Res Labs, Dept Genet & Cellular Toxicol, WP45-333, W Point, PA 19486 USA. NR 38 TC 20 Z9 20 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0027-5107 J9 MUTAT RES-FUND MOL M JI Mutat. Res.-Fundam. Mol. Mech. Mutagen. PD MAY 9 PY 2001 VL 476 IS 1-2 BP 1 EP 11 DI 10.1016/S0027-5107(01)00081-1 PG 11 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 430XC UT WOS:000168599900001 PM 11336978 ER PT J AU Ainsworth, M Bhamarapravati, N Batson, A Bishai, D Moran-Carpentier, O Casabona, J Clemens, J Collins, C El Habib, R Forsythe, S Goldenthal, K Kunanusont, C Longini, IM Mahoney, R Mastro, TD Ndumbe, P Pallangyo, K Rowley, J Sadoff, J Shin, SI Pratt, D Stanton, BF Suraratdecha, C Teixeira, PR van den Bussche, I Vandermissen, W Walsh, JA Whittington, D Widdus, R AF Ainsworth, M Bhamarapravati, N Batson, A Bishai, D Moran-Carpentier, O Casabona, J Clemens, J Collins, C El Habib, R Forsythe, S Goldenthal, K Kunanusont, C Longini, IM Mahoney, R Mastro, TD Ndumbe, P Pallangyo, K Rowley, J Sadoff, J Shin, SI Pratt, D Stanton, BF Suraratdecha, C Teixeira, PR van den Bussche, I Vandermissen, W Walsh, JA Whittington, D Widdus, R CA WHO-UNAIDS Consultat TI Future access to HIV vaccines - Report from a WHO-UNAIDS Consultation, Geneva, 2-3 October 2000 SO AIDS LA English DT Article DE HIV vaccines; vaccine trials; vaccine access; vaccine delivery ID EFFICACY; PREVALENCE; ACCEPTANCE; INFECTION; EPIDEMICS; COHORTS; TRIALS; DESIGN AB Results from the first phase III efficacy trial of an HIV vaccine will be available within the next 2-3 years. Thus, it is imperative to start planning now to address how any effective vaccines should be used. In the absence of definitive information on the characteristics of the first generation of HIV vaccines, the following assumptions were made: the vaccine will (i) have only low to moderate efficacy ton the order of 50%); (ii) not be inexpensive ton the order of 10 to 30 US $ per dose); (iii) require multiple doses; and, (iv) at least initially, be available in limited quantities. A vaccine with that profile would not be suitable for general use in all countries, and it might have to be initially targeted to populations at higher risk of HIV infection. These populations will differ from region to region, according to the epidemiological situation. In most high and middle income countries potential target groups for an initial HIV immunization programme would include intravenous drug users, gay men, commercial sex workers, and high-risk heterosexuals, as well as healthcare workers exposed to blood. In sub-Saharan Africa, future HIV immunization programmes might include larger segments of the population. In order to plan future vaccination programmes it is important to estimate the need (size of target population) and the demand (uptake in target populations) for future HIV vaccines. In addition to the public sector demand for an HIV vaccine (to be used in public health programmes), there will also be a private sector demand driven by the willingness and ability of individuals and employers to pay for the vaccine. HIV vaccines would need to be delivered as part of comprehensive HIV prevention packages, including behavioral and health promotion interventions. This would be especially important with vaccines of moderate efficacy, in order to prevent increased risk behavior among Vaccine recipients. To avoid false expectations, the vaccine message would need to be recast as part of the total prevention strategy, rather than the "magic bullet" that people have come to expect. Initial deployment of HIV vaccines could proceed through targeted vaccination campaigns, drawing from experience with other vaccines. These campaigns would be complex and expensive, and would require full participation and collaboration from all levels of the community, as well as considerable strengthening of the infrastructures required for vaccine delivery. Current candidate vaccines in phase III trials may not be appropriate for much of Africa and South Asia, two areas most in need of an HIV vaccine. Credible international efforts ("push and pull" mechanisms) are needed to create incentives for the industry to develop vaccines for these regions. Feasible financing mechanisms may have to be established to cover the cost of production and delivery of vaccines, in order to ensure equitable access to HIV vaccines around the world. In parallel to the deployment of the initial vaccine, additional bridging studies and effectiveness trials may be needed to expand vaccine use. Research should also continue at an increased pace to develop new generations of more effective vaccines, especially vaccines appropriate to Africa. Achieving these goals will require real political commitment from government and international organizations, to be materialized in specific actions and budget allocations. The daunting challenge of making future effective vaccines accessible to all populations in need will require a sustained collaborative effort on the part of all parties involved. C1 WHO, WHO UNAIDS HIV Vaccine Initiat, CH-1211 Geneva 27, Switzerland. World Bank, Washington, DC 20433 USA. Mahidol Univ, Bangkok 10700, Thailand. Johns Hopkins Sch Publ Hlth, Baltimore, MD 21205 USA. Int Federat Pharmaceut Manufacturers Assoc, Geneva, Switzerland. Ctr Epidemiol Studies HIV AIDS, Barcelona, Spain. Int Vaccine Inst, Seoul, South Korea. AIDS Vaccine Advocacy Coalit, San Francisco, CA 94143 USA. Aventis Pasteur, Marcy Letoile, France. Wellcome Trust Res Labs, Nairobi, Kenya. US FDA, Bethesda, MD 20014 USA. Minist Publ Hlth, Bangkok, Thailand. Emory Univ, Atlanta, GA 30322 USA. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Univ Yaounde, Yaounde, Cameroon. Muhimbili Med Ctr, Dar Es Salaam, Tanzania. W Virginia Univ, Morgantown, WV 26506 USA. Sukhotai Thammathirat Open Univ, Nonthaburi, Thailand. Minist Hlth, Brasilia, DF, Brazil. European Community AIDS Vaccine Task Force, Brussels, Belgium. SmithKline Beecham Biol, Rixensart, Belgium. Univ N Carolina, Chapel Hill, NC 27599 USA. Int AIDS Vaccine Initiat, Geneva, Switzerland. RP Ainsworth, M (reprint author), WHO, WHO UNAIDS HIV Vaccine Initiat, CH-1211 Geneva 27, Switzerland. NR 28 TC 19 Z9 20 U1 0 U2 7 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD MAY 4 PY 2001 VL 15 IS 7 BP W27 EP W44 PG 18 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 431HU UT WOS:000168626400022 ER PT J AU Oshima, Y Puri, RK AF Oshima, Y Puri, RK TI Characterization of a powerful high affinity antagonist that inhibits biological activities of human interleukin-13 SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID COLONY-STIMULATING FACTOR; CELL CARCINOMA-CELLS; RECEPTOR-ALPHA CHAIN; COMMON GAMMA-CHAIN; HUMAN GLIOMA-CELLS; HUMAN B-CELLS; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; IL-13 RECEPTOR; ATOPIC-DERMATITIS AB Interleukin-13 (IL-13), a predominantly Th2-derived cytokine, appears to play a central pathological role in asthma, atopic dermatitis, allergic rhinitis, some parasitic infections, and cancer. We hypothesized that an IL-13 antagonist may have profound therapeutic utility in these conditions. We, therefore, mutagenized human IL-13 in which Glu at position 13 was substituted by a Lys residue. This highly purified recombinant IL-13 variant, IL-13E13K, bound with 4-fold higher affinity to the IL-13 receptor than wild-type IL-13 but retained no detectable proliferative activity on the TF-1 hematopoietic cell line. IL-13E13K competitively inhibited IL-13- and IL-4-dependent TF-1 proliferation. It also inhibited IL13-induced STAT-B (signal transduction and activator of transducer-6) activation in immune cells and cancer cells and reversed IL-13-induced inhibition of CD14 expression on human primary monocytes. These results demonstrate that high affinity binding and signal generation can be uncoupled efficiently in a ligand receptor interaction. These results also suggest that IL-13E13K may be a useful antagonist for the treatment of allergic, inflammatory, and parasitic diseases or even malignancies in which IL-13 plays a central role. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, 29 Lincoln Dr,NIH Bldg 29B,Rm 2NN10, Bethesda, MD 20892 USA. NR 61 TC 22 Z9 23 U1 0 U2 0 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 4 PY 2001 VL 276 IS 18 BP 15185 EP 15191 DI 10.1074/jbc.M010159200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 429QQ UT WOS:000168528800088 PM 11278629 ER PT J AU Deb, TB Su, L Wong, L Bonvini, E Wells, A David, M Johnson, GR AF Deb, TB Su, L Wong, L Bonvini, E Wells, A David, M Johnson, GR TI Epidermal growth factor (EGF) receptor kinase-independent signaling by EGF SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ACTIVATED PROTEIN-KINASE; TYROSINE KINASE; HEMATOPOIETIC-CELLS; DNA-SYNTHESIS; MICE LACKING; PHOSPHORYLATION; EXPRESSION; HETERODIMERIZATION; PROLIFERATION; TRANSDUCTION AB The ErbB family of receptors, which includes the epidermal growth factor receptor (EGFR), ErbB2, ErbB3, and ErbB4, mediate signaling by EGF-like polypeptides, To better understand the role of the EGFR tyrosine kinase, we analyzed signaling by a kinase-inactive EGFR (K721M) in ErbB-devoid 32D cells. K721M alone exhibited no detectable signaling capacity, whereas coexpression of K721M with ErbB2, but not ErbB3 or ErbB4, resulted in EGF-dependent mitogen-activated protein kinase (MAPK) activation. The kinase activity, but not tyrosine phosphorylation, of ErbB2 was required for EGF-induced MAPK activation. The presence of tyrosine phosphorylation sites in K721M was not a requisite for signaling, indicating that transphosphorylation of K721M by ErbB2 was not an essential mechanism of receptor activation. Conversely, the mutated kinase domain of K721M (residues 648-973) and tyrosine phosphorylation of at least one of the receptors were necessary. EGF was found to activate the pro-survival protein kinase Akt in stable cell lines expressing K721M and ErbB2 but, unlike cells expressing wild-type EGFR, was incapable of activating signal transducers and activators of transcription (STAT) or driving cell proliferation. These results demonstrate that EGFR-ErbB2 oligomers are potent activators of MAPK and Akt, and this signaling does not require EGFR kinase activity. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. Univ Calif San Diego, Ctr Canc, La Jolla, CA 92093 USA. Univ Calif San Diego, Div Biol, La Jolla, CA 92093 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. Univ Pittsburgh, Dept Pathol, Pittsburgh, PA 15261 USA. RP Johnson, GR (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bldg 29A,Rm 3B-16,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Wells, Alan/0000-0002-1637-8150 NR 38 TC 49 Z9 51 U1 0 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD MAY 4 PY 2001 VL 276 IS 18 BP 15554 EP 15560 DI 10.1074/jbc.M100928200 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 429QQ UT WOS:000168528800135 PM 11279155 ER PT J AU Grajkowski, A Wilk, A Chmielewski, MK Phillips, LR Beaucage, SL AF Grajkowski, A Wilk, A Chmielewski, MK Phillips, LR Beaucage, SL TI The 2-(N-formyl-N-methyl)aminoethyl group as a potential phosphate/thiophosphate protecting group in solid-phase oligodeoxyribonucleotide synthesis SO ORGANIC LETTERS LA English DT Article ID PHOSPHATE PROTECTION; CHLORIDE AB [GRAPHICS] The 2-(N-formyl-N-methyl)aminoethyl deoxyribonucleoside phosphoramidite 1 has been synthesized and used in the solid-phase synthesis of an octadecathymidylic acid as a cost-efficient monomer for potential application in the preparation of therapeutic oligonucleotides, The 2-(N-formyl-N-methyl)aminoethyl group can be cleaved from oligonucleotides according to a unique thermolytic cyclodeesterification process at pH 7.0. In addition to being cost-effective, the use of 1 simplifies oligonucleotide postsynthesis processing by eliminating the utilization of concentrated ammonium hydroxide in oligonucleotide deprotection. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. NCI, Biol Tresting Branch, Dev Therapeut Program, Frederick, MD 21701 USA. RP Beaucage, SL (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 10 TC 23 Z9 23 U1 0 U2 6 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 1523-7060 J9 ORG LETT JI Org. Lett. PD MAY 3 PY 2001 VL 3 IS 9 BP 1287 EP 1290 DI 10.1021/ol0156852 PG 4 WC Chemistry, Organic SC Chemistry GA 427GA UT WOS:000168395400011 PM 11348216 ER PT J AU Schwetz, BA AF Schwetz, BA TI Two ophthalmic solutions 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 MAY 2 PY 2001 VL 285 IS 17 BP 2186 EP 2186 DI 10.1001/jama.285.17.2186 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 424WC UT WOS:000168256100008 PM 11325309 ER PT J AU Schwetz, BA AF Schwetz, BA TI New diabetes glucose test 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 MAY 2 PY 2001 VL 285 IS 17 BP 2186 EP 2186 DI 10.1001/jama.285.17.2186 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 424WC UT WOS:000168256100007 PM 11325309 ER PT J AU Schwetz, BA AF Schwetz, BA TI Famotidine labeling change 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 MAY 2 PY 2001 VL 285 IS 17 BP 2186 EP 2186 DI 10.1001/jama.285.17.2186 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 424WC UT WOS:000168256100009 PM 11325309 ER PT J AU Sapirstein, W AF Sapirstein, W TI Designing trials for testing prosthetic cardiac valves: A Food and Drug Administration perspective SO AMERICAN HEART JOURNAL LA English DT Article; Proceedings Paper CT 20th Congress of the European-Society-of-Cardiology CY AUG, 1998 CL VIENNA, AUSTRIA SP European Soc Cardiol C1 US FDA, Div Cardiovasc Resp & Neurol Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Sapirstein, W (reprint author), US FDA, Div Cardiovasc Resp & Neurol Devices, Off Device Evaluat, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 3 TC 5 Z9 5 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD MAY PY 2001 VL 141 IS 5 BP 861 EP 863 DI 10.1067/mhj.2001.114980 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 427YC UT WOS:000168433500026 PM 11320379 ER PT J AU Brinton, LA Lubin, JH Burich, MC Colton, T Brown, SL Hoover, RN AF Brinton, LA Lubin, JH Burich, MC Colton, T Brown, SL Hoover, RN TI Cancer risk at sites other than the breast following augmentation mammoplasty SO ANNALS OF EPIDEMIOLOGY LA English DT Article DE breast implants; cancer; incidence; epidemiology ID GENETICALLY SUSCEPTIBLE STRAINS; SILICONE GEL; MULTIPLE-MYELOMA; UNITED-STATES; LOS-ANGELES; IMPLANTS; WOMEN; MAMMAPLASTY; ASSOCIATION; PLASMACYTOMAS AB PURPOSE: There has been limited investigation of cancer risk other than breast cancer among patients with breast implants, despite some clinical and laboratory evidence suggesting links with certain cancer sites, including hematopoietic and connective tissue malignancies. METHODS: A retrospective cohort study of 13,488 patients who received cosmetic breast implants at 18 plastic surgery practices in six geographic areas was conducted to assess long-term health effects. After an average of 12 years of follow-up, questionnaires were administered to subjects located and alive (78% of eligible population). Attempts were made to obtain death certificates for deceased subjects and medical verification for all reported cancers. Expected numbers of cancers were derived using general population cancer incidence rates and an internal comparison series of 3936 patients who received other types of plastic surgery at the same practices as the implant patients. RESULTS: A total of 359 malignancies was observed versus 295.95 expected based on general population rates, resulting in a standardized incidence ratio (SIR) of 1.21 [95% confidence interval (CI) 1.1-1.4]. Individual malignancies for which incidence was significantly elevated inducted cancers of the stomach (SIR = 2.65), cervix (SIR = 3.18), vulva (SIR = 2.51), brain (SIR = 2.16), and leukemia (SIR = 2.19). No excess risks were observed for other hematopoietic malignancies, including multiple myeloma. The internal analyses, however, based on cancer rates derived among the comparison patients, showed no increased cancer risk among the implant patients [relative risk (RR) = 1.00, 95% CI 0.8-1.2], as well as no statistically significant elevations for most individual sites. Cervical cancer continued to be elevated (RR = 1.78), although to a lesser extent than in the external analyses, while the risk for respiratory cancers was higher (RR = 2.40). Non-significant elevations in risk persisted in this analysis for liver cancer (RR = 2.65), brain cancer (RR = 2.83), and leukemia (RR = 1.83). Many of the cancers showing excesses were defined on the basis of death certificates, requiring caution in interpretation. The histologies of the leukemias were quite varied, which makes a biologic relationship appear unlikely. However, respiratory cancers showed some evidence of increasing risk with follow-up time and both respiratory and brain cancers were elevated in the mortality analyses. CONCLUSIONS: Although excesses of cervical and vulvar cancer among implant patients might he attributable to lifestyle factors, reasons for excesses of respiratory and brain cancers were less apparent. Ann Epidemiol 2001;11:248-256. (C) 2001 Elsevier Science Inc. All rights reserved. C1 NCI, Environm Epidemiol Branch, Epidemiol & Biostat Program, Bethesda, MD 20892 USA. Boston Univ, Dept Epidemiol & Biostat, Boston, MA 02215 USA. ABT Associates Inc, Chicago, IL USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Brinton, LA (reprint author), NCI, Environm Epidemiol Branch, Epidemiol & Biostat Program, 6120 Execut Blvd,Room 7068, Bethesda, MD 20892 USA. RI Brinton, Louise/G-7486-2015 OI Brinton, Louise/0000-0003-3853-8562 NR 43 TC 42 Z9 42 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 1047-2797 J9 ANN EPIDEMIOL JI Ann. Epidemiol. PD MAY PY 2001 VL 11 IS 4 BP 248 EP 256 DI 10.1016/S1047-2797(00)00223-4 PG 9 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA 422FD UT WOS:000168107100005 PM 11306343 ER PT J AU Hebert, AM Strohmaier, J Whitman, MC Chen, T Gubina, E Hill, DM Lewis, MS Kozlowski, S AF Hebert, AM Strohmaier, J Whitman, MC Chen, T Gubina, E Hill, DM Lewis, MS Kozlowski, S TI Kinetics and thermodynamics of beta 2-microglobulin binding to the alpha 3 domain of major histocompatibility complex class I heavy chain SO BIOCHEMISTRY LA English DT Article ID MHC CLASS-I; INDUCED CONFORMATIONAL CHANGE; PROTEIN-PROTEIN INTERACTIONS; CELL-SURFACE EXPRESSION; PEPTIDE BINDING; HUMAN BETA(2)-MICROGLOBULIN; T-CELLS; MOLECULES; ANTIGEN; RECOGNITION AB The major histocompatibility complex (MHC) class I molecule plays a crucial role in cytotoxic lymphocyte function. Functional class I MHC exists as a heterotrimer consisting of the MHC class I heavy chain, an antigenic peptide fragment, and beta2-microglobulin (beta 2m). beta 2m has been previously shown to play an important role in the folding of the MHC heavy chain without continued beta 2m association with the MHC complex. Therefore, beta 2m is both a structural component of the MHC complex and a chaperone-like molecule for MHC folding. In this study we provide data supporting a model in which the chaperone-like role of beta 2m is dependent on initial binding to only one of the two beta 2m interfaces with class 1 heavy chain. beta2-Microglobulin binding to an isolated alpha3 domain of the class I MHC heavy chain accurately models the biochemistry and thermodynamics of beta 2m-driven refolding. Our results explain a 1000-fold discrepancy between beta 2m binding and refolding of MHC1. The biochemical study of the individual domains of complex molecules is an important strategy for understanding their dynamic structure and multiple functions. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Ab, Bethesda, MD 20892 USA. NIH, Mol Interact Resource, Div Bioengn & Phys Sci, Off Res Serv, Bethesda, MD 20892 USA. RP Kozlowski, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Ab, 8800 Rockville Pike,Bldg 29B-3NN08,HFM-561, Bethesda, MD 20892 USA. NR 59 TC 17 Z9 17 U1 0 U2 1 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 1 PY 2001 VL 40 IS 17 BP 5233 EP 5242 DI 10.1021/bi002392s PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 427YV UT WOS:000168435100015 PM 11318646 ER PT J AU Kawakami, K Taguchi, J Murata, T Puri, RK AF Kawakami, K Taguchi, J Murata, T Puri, RK TI The interleukin-13 receptor alpha 2 chain: an essential component for binding and internalization but not for interleukin-13-induced signal transduction through the STAT6 pathway SO BLOOD LA English DT Article ID CARCINOMA CELL-LINES; COMMON GAMMA-CHAIN; PSEUDOMONAS EXOTOXIN; FUNCTIONAL COMPONENT; (IL)-13 BINDING; TYROSINE KINASE; IL-13 RECEPTOR; B-CELLS; T-CELLS; PROTEIN AB The interleukin-13 receptor (IL-13R) complex is composed of 2 different chains, IL-13R alpha1 (also known as IL-13R alpha') and IL-13R alpha2 (also known as IL-13R alpha). For a functional IL-13 receptor, the IL-13R alpha1 chain forms a productive complex with the primary IL-4 binding protein (IL-4R alpha also known as IL-4R beta). However, the function of the IL-13R alpha2 chain is not clear even though this chain binds IL-13 with high affinity. This study demonstrates that IL-13R alpha2 can undergo internalization after binding to ligand without causing activation of its signaling pathways. These conclusions were drawn on the basis of (1) internalization of I-125-IL-13 in Chinese hamster ovarian (CHO-K1) and T98G glioblastoma cells transiently transfected with the IL-13Ra2 chain; (2) a recombinant chimeric fusion protein comprising IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin) is specifically cytotoxic to IL-13R alpha2-transfected CHO-K1 cells in a gene dose-dependent manner, whereas cells transfected with vector alone were not sensitive; and (3) IL-13 did not cause activation of signal transduction and activation of transcription 6 (STAT6) in IL-13R alpha2-transfected cells. IL-13 efficiently caused activation of STAT6 protein in cells transfected with the IL-13R alpha1 and IL-4R alpha chains, and IL-13R alpha2 inhibited this activation. Taken together, these observations indicate that internalization of IL-13R alpha2 is signal independent and that this property of IL-13R alpha2 can be exploited for receptor-directed cancer therapy. (Blood, 2001;97:2673-2679) (C) 2001 by The American Society of Hematology. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bldg 29B,Rm 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 39 TC 162 Z9 174 U1 0 U2 4 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 MAY 1 PY 2001 VL 97 IS 9 BP 2673 EP 2679 DI 10.1182/blood.V97.9.2673 PG 7 WC Hematology SC Hematology GA 429KP UT WOS:000168516200023 PM 11313257 ER PT J AU Igarashi, H Kuwata, N Kiyota, K Sumita, K Suda, T Ono, S Bauer, SR Sakaguchi, N AF Igarashi, H Kuwata, N Kiyota, K Sumita, K Suda, T Ono, S Bauer, SR Sakaguchi, N TI Localization of recombination activating gene 1/green fluorescent protein (RAG1/GFP) expression in secondary lymphoid organs after immunization with T-dependent antigens in rag1/gfp knockin mice SO BLOOD LA English DT Article ID B-CELL DEVELOPMENT; BONE-MARROW; GERMINAL CENTER; CLONAL DELETION; LYMPHOCYTES-B; LIGHT-CHAIN; RECEPTOR; MATURATION; DIVERSIFICATION; PROLIFERATION AB Secondary rearrangements of immunoglobulin gene segments that generate a new antibody repertoire in peripheral B cells have been described as receptor revision and occur by as yet unknown mechanisms. To determine the importance of recombination activating gene (RAG) expression in receptor revision, heterozygous rag1/green fluorescent protein (gfp) knockin mice were used to examine the location of RAG1 expression in the germinal centers (GCs) of lymphoid follicles after immunization with a variety of T-cell-dependent antigens. Immunization of rag1/gfp heterozygous mice or rag1 homozygous knockout mice reconstituted with rag1/gfp heterozygous spleen cells caused the down-regulation of RAG1/GFP signal in GCs. Although some RAG1/GFP(+) cells appeared in regions surrounding the peanut agglutinin (PNA)(+)GL-7(+) GC area, RAG1/GFP(+) cells did not accumulate in the central region. in addition, the stimulation of spleen B cells with anti-mu antibody plus interleukin-4 (IL-4) or with anti-CD40 monoclonal antibody plus IL-7 did not induce GFP signals at detectable levels in vitro. These results clearly demonstrate that RAG1 re-expression either does not occur or is at extremely low levels in antigen-driven B cells in GCs of secondary lymphoid follicles, suggesting that other mechanisms may mediate the gene rearrangements observed in receptor revision. (Blood. 2001;97:2680-2687) (C) 2001 by The American Society of Hematology. C1 Kumamoto Univ, Sch Med, Inst Mol Embryol & Genet, Dept Immunol, Kumamoto 8600811, Japan. Kumamoto Univ, Sch Med, Inst Mol Embryol & Genet, Dept Pediat, Kumamoto 8600811, Japan. Kumamoto Univ, Sch Med, Inst Mol Embryol & Genet, Dept Cell Differentiat, Kumamoto 8600811, Japan. Osaka Univ, Sch Med, Ctr Biomed Res, Suita, Osaka 565, Japan. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. RP Sakaguchi, N (reprint author), Kumamoto Univ, Sch Med, Inst Mol Embryol & Genet, Dept Immunol, 2-2-1 Honjo, Kumamoto 8600811, Japan. RI Bauer, Steven/G-5559-2012; Suda, Toshio/H-6761-2013; OI Suda, Toshio/0000-0001-7540-1771; Bauer, Steven/0000-0003-2831-846X NR 48 TC 34 Z9 34 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 MAY 1 PY 2001 VL 97 IS 9 BP 2680 EP 2687 DI 10.1182/blood.V97.9.2680 PG 8 WC Hematology SC Hematology GA 429KP UT WOS:000168516200024 PM 11313258 ER PT J AU Strickler, HD Goedert, JJ Butel, JS Daniel, R Freymuth, F Gibbs, A Griffiths, DJ Jablons, D Jasani, B Jones, C Lednicky, JA Miller, CW Radu, C Richards, WG Shah, KV You, L Corson, JM Gerwin, B Harris, C Sugarbaker, DJ Egan, W Lewis, AM Krause, PR Peden, K Levine, AS Melnick, S Cosentino, M da Costa, M Devairrakam, V Ji, J Palefsky, J Rasmussen, L Shea, K Wacholder, S Waters, D Wright, T AF Strickler, HD Goedert, JJ Butel, JS Daniel, R Freymuth, F Gibbs, A Griffiths, DJ Jablons, D Jasani, B Jones, C Lednicky, JA Miller, CW Radu, C Richards, WG Shah, KV You, L Corson, JM Gerwin, B Harris, C Sugarbaker, DJ Egan, W Lewis, AM Krause, PR Peden, K Levine, AS Melnick, S Cosentino, M da Costa, M Devairrakam, V Ji, J Palefsky, J Rasmussen, L Shea, K Wacholder, S Waters, D Wright, T CA Int SV40 Working Grp TI A multicenter evaluation of assays for detection of SV40 DNA and results in masked mesothelioma specimens SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID HUMAN-BRAIN-TUMORS; LARGE-T-ANTIGEN; HUMAN PLEURAL MESOTHELIOMA; POLYMERASE-CHAIN-REACTION; SIMIAN VIRUS 40; SV40-LIKE SEQUENCES; POLIO VACCINES; CHOROID-PLEXUS; SIMIAN-VIRUS-40; EXTRACTION AB This nine-laboratory multicenter investigation was designed to assess the sensitivity, specificity, and reproducibility of previously described assays for detection of SV40 DNA with three goals, i.e., (a) to compare methods for testing human tissues, (b) to examine the ability of these methods to detect SV40 in human mesotheliomas, and (c) to uncover assay differences that could explain conflicting findings in some past investigations. Each laboratory received, in a masked fashion, paired replicate DNA samples extracted from 25 fresh frozen mesotheliomas (50 samples) and one from each of 25 normal human lungs. Interspersed were masked positive (titrations of the SV40 genome) and negative control samples. Preliminary studies confirmed the adequacy of the samples for testing high molecular weight double-stranded linear DNA targets. All 15 PCR-based assays detected 5,000 copies or less of the SV40 genome spiked into 2 mug of WI-38 DNA. A high level of specificity and reproducibility was found among the PCR assays performed in most laboratories. However, none of the selected normal human lung tissue or the 25 mesothelioma tumor specimens obtained from archival samples at a single center was reproducibly positive for the presence of SV40 DNA. Further studies are needed to reconcile these results with previous reports of detection of SV40 DNA in tumor specimens. C1 Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10461 USA. NCI, Viral Epidemiol Branch, NIH, Bethesda, MD USA. Brigham & Womens Hosp, Div Thorac Surg, Boston, MA 02115 USA. Baylor Coll Med, Dept Mol Virol & Microbiol, Houston, TX 77030 USA. Johns Hopkins Univ, Dept Mol Microbiol & Immunol, Baltimore, MD USA. Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. Hosp Univ Caen, Lab Virol Humaine & Mol, Caen, France. Univ Wales Coll Cardiff, Coll Med, Dept Pathol, Cardiff, S Glam, Wales. UCL, Windeyer Inst Med Sci, Wohl Vir Ctr, London, England. Univ Calif San Francisco, Thorac Oncol Lab, San Francisco, CA 94143 USA. Univ Calif Los Angeles, Cedars Sinai Res Inst, Dept Med, Los Angeles, CA USA. Brigham & Womens Hosp, Dept Pathol, Boston, MA 02115 USA. NCI, Human Carcinogenesis Lab, NIH, Bethesda, MD 20892 USA. US FDA, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Univ Pittsburgh, Sch Med, Pittsburgh, PA USA. NCI, Div Canc Control & Populat Sci, NIH, Bethesda, MD 20892 USA. BBI Biotech Res Labs, Gaithersburg, MD USA. Res Triangle Inst, Rockville, MD USA. Sci Applicat Int Corp, Frederick, MD USA. NCI, Biostat Branch, NIH, Bethesda, MD 20892 USA. Columbia Univ, Coll Phys & Surg, Dept Pathol, New York, NY USA. RP Strickler, HD (reprint author), Albert Einstein Coll Med, Dept Epidemiol & Social Med, 1300 Morris Pk Ave,Belfer Bldg 1308-B, Bronx, NY 10461 USA. NR 52 TC 68 Z9 70 U1 0 U2 2 PU AMER ASSOC CANCER RESEARCH PI PHILADELPHIA PA 615 CHESTNUT ST, 17TH FLOOR, PHILADELPHIA, PA 19106-4404 USA SN 1055-9965 J9 CANCER EPIDEM BIOMAR JI Cancer Epidemiol. Biomarkers Prev. PD MAY PY 2001 VL 10 IS 5 BP 523 EP 532 PG 10 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA 433CM UT WOS:000168737800015 PM 11352864 ER PT J AU DeVries, JW Keagy, PM Hudson, CA Rader, JI AF DeVries, JW Keagy, PM Hudson, CA Rader, JI TI AACC collaborative study of a method for determining total folate in cereal products - Microbiological assay using trienzyme extraction (AACC method 86-47) SO CEREAL FOODS WORLD LA English DT Article ID TRI-ENZYME EXTRACTION; FOOD FOLATE AB Regulations published in 1996 by the U.S. Food and Drug Administration require that folic acid be added to a wide range of enriched cereal-grain products, including breads, rolls and buns, wheat flours, corn meals, rice, noodles, and macaroni. Mandatory folic acid fortification of cereal-grain products has emphasized the need for validated methods for determining total folate content in foods, particularly cereal products. When the fortification regulations were finalized, no official methods for folate analysis in cereal-grain products were in place. A microbiological assay protocol utilizing a trienzyme extraction procedure was revised to have the conjugase (gamma-glutamyl-carboxy-peptidase) treatment follow a protease treatment, to include the use of cryoprotected inoculum, and to include the spectrophotometric standardization of the standard and optional use of microtiter plates. The draft protocol was prepared in the AOAC format. Thirteen laboratories participated in a collaborative study of 10 required and 10 optional samples of cereal-grain products, including flour, bread, cookies, baking mixes, ready-to-eat breakfast cereals, and snack foods. While the majority of the participating laboratories performed the assay using the standard test tube method, some used the microtiter plate option. The relative standard deviation between laboratories (RSDR) ranged from 2 to 22% for 16 fortified samples compared with expected values of 11 to 20%. RSDR values were higher (i.e., 28-53%) for four unfortified cereal-grain samples. The Youden pair technique was used to estimate within-laboratory relative standard deviations (RSDr), which ranged from 2 to 13% for fortified samples and from 14 to 21% for pairs that included at least one unfortified sample. Based on the results of this collaborative study, the microbiological assay with trienzyme extraction is recommended for Official First Action status with AOAC and First Approval status with AACC. C1 Gen Mills, Medall Labs, Minneapolis, MN 55427 USA. USDA, Western Reg Res Ctr, Albany, CA 94710 USA. US FDA, Ctr Food Safety & Nutr, Bethesda, MD 20205 USA. RP DeVries, JW (reprint author), Gen Mills, Medall Labs, Minneapolis, MN 55427 USA. NR 19 TC 19 Z9 19 U1 1 U2 7 PU AMER ASSOC CEREAL CHEMISTS PI ST PAUL PA 3340 PILOT KNOB RD, ST PAUL, MN 55121-2097 USA SN 0146-6283 J9 CEREAL FOOD WORLD JI Cereal Foods World PD MAY PY 2001 VL 46 IS 5 BP 216 EP 219 PG 4 WC Food Science & Technology SC Food Science & Technology GA 436MJ UT WOS:000168939400006 ER PT J AU Hayward, DG Holcomb, J Glidden, R Wilson, P Harris, M Spencer, V AF Hayward, DG Holcomb, J Glidden, R Wilson, P Harris, M Spencer, V TI Quadrupole ion storage tandem mass spectrometry and high-resolution mass spectrometry: complementary application in the measurement of 2,3,7,8-chlorine substituted dibenzo-p-dioxins and dibenzofurans in US foods SO CHEMOSPHERE LA English DT Article; Proceedings Paper CT 19th Symposium on Halgenated Organic Pollutants and Pops - DIOXIN '99 CY SEP 12-17, 1999 CL VENICE, ITALY DE polychlorinated dibenzo-p-dioxin; polychlorinated dibenzofuran; US food; tandem mass spectrometry; high-resolution mass spectrometry ID UNITED-STATES; SAMPLES; POLYCHLORODIBENZOFURANS; FURANS; FISH; TCDD AB The US Food and Drug Administration has simultaneously utilized both high-resolution mass spectrometry (HRMS) and quadrupole ion storage tandem mass spectrometry (QISTMS) in the measurement of polychlorinated dibenzo-p-dioxins/dibenzofurans (PCDD/Fs) in 147 food samples collected in 1998 and 1999 in the US. In 1998, 20 egg samples, six scallop, 10 blue crab, eight American lobster, 10 pollack: 15 striped bass, five rockfish, 10 crawfish, seven aqua-cultured and 13 wild-caught salmon, along with 19 cream and 18 mozzarella cheese samples were measured for PCDD/Fs. QISTMS provided limits of detection (LODs) close to those produced using HRMS for many congeners in 56 samples analyzed by both techniques in 1998 and three salmon and three striped bass collected in 1999. The I-TEQs of the mean levels for measured congeners in 40 samples of fish and shellfish and 16 cheese and eggs from 1998 analyzed by HRMS and QISTMS were 0.99 and 1.1 ng/kg wet weight, respectively. The I-TEQ for mean congener levels in the 40 fish and shellfish measured by HRMS was 1.4 ng/kg wet weight. A higher sample throughput with greater data quality at a lower cost is achievable by using both QISTMS and HRMS. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 US FDA, Washington, DC 20204 USA. US FDA, Jefferson, AR 72079 USA. RP Hayward, DG (reprint author), US FDA, Washington, DC 20204 USA. NR 17 TC 20 Z9 20 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0045-6535 J9 CHEMOSPHERE JI Chemosphere PD MAY-JUN PY 2001 VL 43 IS 4-7 BP 407 EP 415 DI 10.1016/S0045-6535(00)00388-X PG 9 WC Environmental Sciences SC Environmental Sciences & Ecology GA 430VU UT WOS:000168596800003 PM 11372820 ER PT J AU Rieves, D AF Rieves, D TI The cells of asthma SO CHEST LA English DT Editorial Material ID INFLAMMATION C1 US FDA, CBER, Rockville, MD 20852 USA. RP Rieves, D (reprint author), US FDA, CBER, 1401 Rockville Pike,HPM-57, Rockville, MD 20852 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU AMER COLL CHEST PHYSICIANS PI NORTHBROOK PA 3300 DUNDEE ROAD, NORTHBROOK, IL 60062-2348 USA SN 0012-3692 J9 CHEST JI Chest PD MAY PY 2001 VL 119 IS 5 BP 1299 EP 1300 DI 10.1378/chest.119.5.1299 PG 2 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 432TH UT WOS:000168711400002 PM 11348929 ER PT J AU Ball, R Braun, MM Mootrey, GT AF Ball, R Braun, MM Mootrey, GT CA Vaccine Adverse Event Reporting Syst Working Grp TI Safety Data on Meningococcal Polysaccharide Vaccine from the Vaccine Adverse Event Reporting System SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID GROUP-A; SEROLOGICAL EVALUATION; C VACCINE; GROUP-Y; IMMUNOGENICITY; IMMUNIZATION; CHILDREN AB Recent recommendations by the Centers for Disease Control and Prevention's Advisory Committee on Immunization Practices may lead to the increased use of the meningococcal polysaccharide vaccine. The Vaccine Adverse Event Reporting System (VAERS) is useful for the detection of previously unrecognized reactions and for the monitoring of known reactions. Limitations of VAERS include underreporting and the inability to establish a causal relationship between vaccination and adverse events in most cases. From July 1990 through 31 October 1999, 110 adverse events were reported after receipt of meningococcal vaccine alone. Thirteen (12%) were serious, including 6 injection site reactions, 3 allergic reactions, 1 case of Guillain-Barre syndrome, and 3 miscellaneous events. Fever (30%), headache (17%), dizziness (15%), injection site hypersensitivity (13%), urticaria (12%), and paresthesia (10%) were among the most common events reported. Fever and injection site and allergic reactions are most likely causally linked to the vaccine. That there were few reports of serious adverse events, with >6 million doses having been distributed, and no clear signal of a previously unrecognized serious reaction is reassuring with regard to the safety of meningococcal vaccine. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol, Rockville, MD 20852 USA. Ctr Dis Control & Prevent, Natl Immunizat Program, Epidemiol & Surveillance Div, Vaccine Safety & Dev Act, Atlanta, GA 30333 USA. RP Ball, R (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Div Epidemiol, HFM-220,1401 Rockville Pike, Rockville, MD 20852 USA. EM BallR@cber.fda.gov NR 30 TC 12 Z9 14 U1 0 U2 0 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD MAY 1 PY 2001 VL 32 IS 9 BP 1273 EP 1280 DI 10.1086/319982 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 429LF UT WOS:000168517900027 PM 11303261 ER PT J AU Allaben, WT Bucher, JR Howard, PC AF Allaben, WT Bucher, JR Howard, PC TI International conference on the toxicology of fumonisin: Introduction SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Editorial Material C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Inst Environm Hlth Sci, Res Triangle Pk, NC USA. RP Allaben, WT (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 2 TC 4 Z9 4 U1 0 U2 0 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2001 VL 109 SU 2 BP 237 EP 237 PG 1 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 434PF UT WOS:000168824500008 ER PT J AU Voss, KA Riley, RT Norred, WP Bacon, CW Meredith, FI Howard, PC Plattner, RD Collins, TFX Hansen, DK Porter, JK AF Voss, KA Riley, RT Norred, WP Bacon, CW Meredith, FI Howard, PC Plattner, RD Collins, TFX Hansen, DK Porter, JK TI An overview of rodent toxicities: Liver and kidney effects of fumonisins and Fusarium moniliforme SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT ILSI North America International Conference on the Toxicology of Fumonisin CY JUN 28-30, 1999 CL ARLINGTON, VIRGINIA DE developmental toxicology; fumonisins; Fusarium moniliforme (= F. verticillioides); hepatotoxicity; nephrotoxicity; sphingolipids ID SPRAGUE-DAWLEY RATS; HUMAN ESOPHAGEAL CANCER; CULTURE MATERIAL; EQUINE LEUKOENCEPHALOMALACIA; SUBCHRONIC TOXICITY; F-MONILIFORME; IN-VIVO; DEVELOPMENTAL TOXICITY; SPHINGOLIPID DEPLETION; LIPID-PEROXIDATION AB Fumonisins are produced by Fusarium moniliforme (= F. verticillioides) and other Fusarium that grow on corn worldwide. They cause fatal toxicoses of horses and swine. Their effects in humans are unclear, but epidemiologic evidence suggests that consumption of fumonisin-contaminated corn contributes to human esophageal cancer in southern Africa and China. Much has been learned from rodent studies about fumonisin B-1 (FB1), the most common homologue. FB, is pearly absorbed and rapidly eliminated in feces. Minor amounts are retained in liver and kidneys. Unlike other mycotoxins, fumonisins cause the same liver cancer promotion and subchronic (studies less than or equal to 90 days) liver and kidney effects as F. moniliforme. FB1 induces apoptosis of hepatocytes and of proximal tubule epithelial cells. More advanced lesions in both organs are characterized by simultaneous cell loss (apoptosis and necrosis) and proliferation (mitosis). Microscopic and other findings suggest that an imbalance between cell loss and replacement develops, a condition favorable for carcinogenesis. On the molecular level, fumonisins inhibit ceramide synthase, and disrupt sphingolipid metabolism and, theoretically, sphingolipid-mediated regulatory processes that influence apoptosis and mitosis. Liver sphingolipid effects and toxicity are correlated, and ceramide synthase inhibition occurs in liver and kidney at doses below their respective no-observed-effect levels. FB1 does not cross the placenta and is not teratogenic in vivo in rats, mice, or rabbits, but is embryotoxic at high, maternally toxic doses. These data have contributed to preliminary risk evaluation and to protocol development for carcinogenicity and chronic toxicity studies of FB1 in rats and mice. C1 USDA ARS, Richard B Russell Agr Res Ctr, Toxicol & Mycotoxin Res Unit, Athens, GA 30605 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. USDA, Agr Res Serv, Natl Ctr Agr Utilizat Res, Peoria, IL USA. US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD USA. RP Voss, KA (reprint author), USDA ARS, Richard B Russell Agr Res Ctr, Toxicol & Mycotoxin Res Unit, 950 Coll Stn Rd, Athens, GA 30605 USA. NR 124 TC 106 Z9 110 U1 1 U2 6 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2001 VL 109 SU 2 BP 259 EP 266 DI 10.2307/3435017 PG 8 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 434PF UT WOS:000168824500012 PM 11359694 ER PT J AU Howard, PC Eppley, RM Stack, ME Warbritton, A Voss, KA Lorentzen, RJ Kovach, RM Bucci, TJ AF Howard, PC Eppley, RM Stack, ME Warbritton, A Voss, KA Lorentzen, RJ Kovach, RM Bucci, TJ TI Fumonisin B-1 carcinogenicity in a two-year feeding study using F344 rats and B6C3F(1) mice SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT ILSI North America International Conference on the Toxicology of Fumonisin CY JUN 28-30, 1999 CL ARLINGTON, VIRGINIA DE fumonisin B-1; hepatocarcinogenicity; renal carcinoma; rodent bioassay ID FUSARIUM-MONILIFORME; ESOPHAGEAL CANCER; F-MONILIFORME; MYCOTOXINS; TOXICITY; TRANSKEI; RESTRICTION; MORTALITY; CULTURES; CORN AB Fumonisin B-1 (FB1) is a mycotoxin isolated from Fusarium fungi that contaminate crops worldwide. A previous study demonstrated that FB1 promoted preneoplastic foci in initiated rats and induced hepatocellular carcinomas in ED IX rats at 50 parts per million (ppm), but fundamental dose-response data were not available to assist in setting regulatory guidelines for this mycotoxin. To provide this information, female and male F344/N/Nctr BR rats and B6C3F(1)/Nctr BR; mice were fed for two years a powdered NIH-31 diet containing the following concentrations of FB1: female rats, 0, 5, 15, 50, and 100 ppm; male rats, 0, 5, 15, 50, and 150 ppm; female mice, 0, 5, 15, 50, and 80 ppm; male mice, 0, 5, 15, 80, and 150 ppm. FB1 was not tumorigenic in female F344 rats with doses as high as 100 ppm. Including FB, in the diets of male rats induced renal tubule adenomas and carcinomas in 0/48, 0/40, 9/48, and 15/48 rats at 0, 5, 15, 50, and 150 ppm, respectively. Including up to 150 ppm FB1 in the diet of male mice did not affect tumor incidence. Hepatocellular adenomas and carcinomas were induced by FBI in the female mice, occurring in 5/47, 3/48, 1/48, 19/47, and 39/45 female mice that consumed diets containing 0, 5, 15. 50, and 80 ppm FB1, respectively. This study demonstrates that FB1 is a rodent carcinogen that induces renal tubule tumors in male F344 rats and hepatic tumors in female B6C3F(1) mice. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Pathol Associates Int, Jefferson, AR USA. USDA, Agr Res Serv, Athens, GA USA. RP Howard, PC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd,HFT-110, Jefferson, AR 72079 USA. NR 38 TC 104 Z9 107 U1 0 U2 7 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2001 VL 109 SU 2 BP 277 EP 282 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 434PF UT WOS:000168824500014 PM 11359696 ER PT J AU Howard, PC Warbritton, A Voss, KA Lorentzen, RJ Thurman, JD Kovach, RM Bucci, TJ AF Howard, PC Warbritton, A Voss, KA Lorentzen, RJ Thurman, JD Kovach, RM Bucci, TJ TI Compensatory regeneration as a mechanism for renal tubule carcinogenesis of fumonisin B(1) in the F344/N/Nctr BR rat SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT ILSI North America International Conference on the Toxicology of Fumonisin CY JUN 28-30, 1999 CL ARLINGTON, VA DE apoptosis; fumonisin B(1); renal tubule; rodent bioassay ID DOMINANTLY INHERITED CANCER; FUSARIUM-MONILIFORME; EKER RAT; SPHINGOLIPID METABOLISM; TSC2 GENE; HUMAN KERATINOCYTES; CELL-PROLIFERATION; ESOPHAGEAL CANCER; F344 RATS; LIVER AB Fumonisin B(1) (FB(1)) is a fungal metabolite of Fusarium verticillioides (= F. moniliforme), a fungus that grows on many crops worldwide. Previous studies demonstrated that male ED IX rats consuming diets containing 50 ppm fumonisin B1 developed hepatocellular carcinomas. In our recent studies, diets containing FB1 at 50 ppm or higher concentrations induced renal tubule carcinomas in male F344/N/Nctr BR rats and hepatocellular carcinomas in female B6C3F(1)/Nctr BR mice. The carcinogenicity of FB(1) in rats and mice is not due to DNA damage, as several laboratories have demonstrated that FB(1) is not a genotoxin. FB, induces apoptosis in cells in vitro. Including FB(1) in the diets of rats results in increased hepatocellular and renal tubule epithelial cell apoptosis. In studies with F344/N/Nctr BR rats consuming diets containing up to 484 ppm FB(1) for 28 days, female rats demonstrated more sensitivity than male rats in the induction of hepatocellular apoptosis and mitosis. Conversely, induction of renal tubule apoptosis and regeneration were more pronounced in male than in female rats. Induction of renal tubule apoptosis and hyperplasia correlated with the incidence of renal tubule carcinomas that developed in the 2-year feeding study with FB, in the F344/N/Nctr BR rats. The data are consistent with the hypothesis that the induction Of renal tubule carcinomas in male rats could be partly due to the continuous compensatory regeneration of renal tubule epithelial cells in response to the induction of apoptosis by fumonisin B(1). C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Pathol Associates Int, Jefferson, AR USA. USDA, Agr Res Serv, Athens, GA USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Howard, PC (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd,HFT-110, Jefferson, AR 72079 USA. EM phoward@nctr.fda.gov NR 59 TC 46 Z9 46 U1 0 U2 2 PU US DEPT HEALTH HUMAN SCIENCES PUBLIC HEALTH SCIENCE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SCIENCES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD MAY PY 2001 VL 109 SU 2 BP 309 EP 314 DI 10.2307/3435023 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 434PF UT WOS:000168824500018 PM 11359700 ER PT J AU Jensen, E Bolger, M AF Jensen, E Bolger, M TI Exposure assessment of dioxins/furans consumed in dairy foods and fish SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE dioxin; exposure assessment; dairy; seafood ID UNITED-STATES; P-DIOXINS; DIBENZOFURANS; DDE AB Dioxins/furans are ubiquitous environmental contaminants whose primary route of human exposure occurs via the consumption of fatty foods of animal origin. The US FDA conducted a market basket survey of dairy products and commercial fish and shellfish to obtain data on levels of 17 dioxin/furan congeners (2, 3, 7, 8-congeners) in the US. The dairy products sampled included various cheeses (American, cheddar, Swiss, cottage), ice cream, yogurt, butter, and milk. The finfish and shellfish (molluscs and crustacea) sampled are those marine species consumed in the greatest amounts and include canned tuna, shrimp, cod, blue crab, and oysters. Catfish was sampled because it is the dominant aquaculture species. Samples were collected in 1995/96 and analysis for 17 dioxin/furan congeners was performed by high-resolution gas chromatography following extraction and clean-up. Limits of detection (LOD) and quantitation (LOQ) for each congener in each food were reported. Point estimates of exposure were calculated using a 3- day (1-day diary plus 2-day recall) food consumption survey for eaters-only and for the general population (USDA/CSFII, 1989-92). Toxicity equivalency factors (TEFs) developed by the World Health Organization (1997) were used to derive overall dioxin/furan toxicity equivalents (TEQ) for each sample food. Mean estimates of TEQ exposure for each food were derived using five values for non-detects (ND = 0; ND = 1/2 LOD or LOQ; ND = LOD or LOQ) on both a total sample and eaters-only basis. Using zero and the LOD provide lower and upper bounds on the range of estimated exposure, respectively. The bounds on mean dioxin intakes (pg/person/ day) calculated for consumers of specific foods were estimated as follows (using zero or LOD for non-detects): butter (0.5-11), cheese (1.6-3.2), ice cream (4-19), yogurt (0.8-28), catfish (148-150), fish (other than catfish) (0.03-9), crustacea (32-35), mollusks (16.1-16.6), and shrimp (0.09-4.5). Exposure estimates derived by the five ND-methods are strongly dependent on the LOD and LOQ and represent upper bound estimates of exposure. Uncertainty in the exposure estimates is reduced with refinements in the analytical method. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Jensen, E (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-246,200 C St SW, Washington, DC 20204 USA. NR 10 TC 30 Z9 32 U1 2 U2 9 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD MAY PY 2001 VL 18 IS 5 BP 395 EP 403 DI 10.1080/02652030010024465 PG 9 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 432TA UT WOS:000168710700004 PM 11358181 ER PT J AU Camire, ME Ausman, LM Decker, E Larick, D Nielsen, SS Patrick, R Peterson, D Regenstein, J Schaller, D Solberg, M Whiting, R Zawel, S AF Camire, ME Ausman, LM Decker, E Larick, D Nielsen, SS Patrick, R Peterson, D Regenstein, J Schaller, D Solberg, M Whiting, R Zawel, S TI IFT research needs report - Diet and health research needs SO FOOD TECHNOLOGY LA English DT Article AB This report highlights specific research needs, to aid organizations in prioritizing and distributing research funding. The report comprises three sections, the first of which appears in this issue. The others will be published in future issues. C1 Univ Maine, Orono, ME 04469 USA. Tufts Univ, Medford, MA 02155 USA. Univ Massachusetts, Amherst, MA 01003 USA. N Carolina State Univ, Raleigh, NC 27695 USA. Purdue Univ, W Lafayette, IN 47907 USA. Louisiana State Univ, Baton Rouge, LA 70803 USA. Univ Minnesota, Minneapolis, MN 55455 USA. Cornell Univ, Ithaca, NY 14853 USA. Rutgers State Univ, Piscataway, NJ 08855 USA. US FDA, Rockville, MD 20857 USA. Grocery Manufacturers Amer, Washington, DC 20007 USA. RP Camire, ME (reprint author), Univ Maine, Orono, ME 04469 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 USA SN 0015-6639 J9 FOOD TECHNOL-CHICAGO JI Food Technol. PD MAY PY 2001 VL 55 IS 5 BP 189 EP 191 PG 3 WC Food Science & Technology SC Food Science & Technology GA 434CB UT WOS:000168796600007 ER PT J AU Turkeltaub, PC AF Turkeltaub, PC TI Performance standards for allergen skin testing - An approach to proficiency testing SO IMMUNOLOGY AND ALLERGY CLINICS OF NORTH AMERICA LA English DT Article ID ERYTHEMA; EXTRACTS; POTENCY AB Performance standards and proficiency testing are essential to improve the diagnostic use of clinical allergy testing. An allergy skin test method is prescribed whose performance standards and analytic performance (accuracy, precision, sensitivity) have been established. Its application in clinical practice to evaluating proficiency of percutaneous in intracutaneous allergy testing is discussed. Because of the large variability in cutaneous testing methods, many of which have not been optimized, it is important to compare validated skin tests methods with defined standards and analytic performance with any other proposed skin test method to determine the relative diagnostic safety and efficacy. C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Div Allergen Prod & Parasitol, Rockville, MD 20857 USA. RP Turkeltaub, PC (reprint author), 9112 Fall River Lane, Potomac, MD 20854 USA. NR 24 TC 2 Z9 2 U1 1 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0889-8561 J9 IMMUNOL ALLERGY CLIN JI Immunol. Allerg. Clin. North Am. PD MAY PY 2001 VL 21 IS 2 BP 321 EP + DI 10.1016/S0889-8561(05)70209-5 PG 9 WC Allergy; Immunology SC Allergy; Immunology GA 443DW UT WOS:000169326100009 ER PT J AU Miller, MA AF Miller, MA TI Gender-based differences in the toxicity of pharmaceuticals - The Food and Drug Administration's perspective SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the American-College-of-Toxicology CY NOV 12-15, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Coll Toxicol DE FDA perspective; gender; pharmaceuticals; toxicity ID RISK FACTOR AB Women experience more adverse reactions to treatment with therapeutic drugs than men. Theories proposed to explain this include overdosing, different pharmacokinetics and pharmacodynamics, women are more likely to report adverse events than men, or women take more medications than men. Food and Drug Administration (FDA) Office of Women's Health (OWH) funds research to promote including women in clinical trials and understanding the biology of sex-related differences in the safety of FDA-regulated products. Including women in clinical trials advances the understanding of drug efficacy and safety in women by providing information on drug dosing, pharmacokinetics, and pharmacodynamics. A Baysian statistical analysis of sex differences in adverse events showed that although about the same number of adverse events were reported for men and,women, those reported for women were more serious. One example of a sex difference in the toxicity of pharmaceuticals is the drug-induced cardiac arrhythmia, torsades de point. OWH funded studies in animals and humans to investigate the mechanism behind this sex difference. These studies demonstrated that shortening the QT interval increases the risk of developing torsades and that androgens protect against torsades by slowing cardiac repolarization and prolonging the QT interval. Understanding the mechanisms behind other reported sex-related differences in adverse drug effects requires additional research, The preliminary studies conducted to date suggest that this sex-related difference is likely to be a multifactorial problem requiring information from several fields of study. Ideally, individuals at risk for developing an adverse event should be identified prior to therapeutic intervention, The OWH plans to fund more studies to investigate the role of hormonal variations on drug metabolism and drug-drug interactions. Animal and in vitro model systems are needed to fully understand the mechanism of how gender influences drug toxicity. C1 US FDA, Off Womens Hlth, Sci Programs, Rockville, MD 20857 USA. RP Miller, MA (reprint author), US FDA, Off Womens Hlth, Sci Programs, Parklawn Bldg Room 1665,Mail Stop HF-8,5600 Fishe, Rockville, MD 20857 USA. NR 11 TC 55 Z9 57 U1 0 U2 2 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 2001 VL 20 IS 3 BP 149 EP 152 DI 10.1080/109158101317097728 PG 4 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 455NE UT WOS:000170032300006 PM 11488556 ER PT J AU Slikker, W Scallet, AC Doerge, DR Ferguson, SA AF Slikker, W Scallet, AC Doerge, DR Ferguson, SA TI Gender-based differences in rats after chronic dietary exposure to genistein SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article; Proceedings Paper CT 21st Annual Meeting of the American-College-of-Toxicology CY NOV 12-15, 2000 CL SAN DIEGO, CALIFORNIA SP Amer Coll Toxicol DE behavior; gender-based; genistein; morphometry; pharmacokinetics ID ENDOCRINE DISRUPTION; SOY ISOFLAVONES; RESEARCH NEEDS; HUMANS; DIETHYLSTILBESTROL; ESTRADIOL; EXCRETION; WILDLIFE; HEALTH; PLASMA AB Gender-based differences can be observed from pharmacokinetic, behavioral, or anatomical assessments. No single assessment tool will provide a complete answer, but the use of a variety of indices, each with known gender-related outcome differences, can reveal agent-induced gender-based alterations. In a series of initial range-finding studies in rats conducted at the National Center for Toxicological Research (NCTR), the effects of dietary exposure to the weak estrogen, genistein, have been assessed using a number of techniques with validated gender-related outcome measures. The findings indicated that (1) the internal dose of genistein was higher in females than males after equivalent dietary exposure and this was consistent with the faster rate of genistein elimination in males; (2) in behavioral assessments, males and females in the high-dose dietary genistein group consumed more of a sodium-flavored solution; however, no genistein-related changes were observed in open field or running wheel activity, play behavior, or intake of a saccharin-flavored solution; and (3) dose-related alterations of the volume of the sexually dimorphic nucleus of the medial preoptic area were observed in genistein-exposed male rats but not females. These observations describe the utility of a variety of gender-based assessment tools and indicate that dose-related effects of developmental and chronic dietary exposure to genistein can be observed in the rodent. Additional studies, perhaps in nonhuman primates, are necessary to further predict the effect(s) of genistein on human gender-based development. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Slikker, W (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 31 TC 20 Z9 23 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAY-JUN PY 2001 VL 20 IS 3 BP 175 EP 179 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 455NE UT WOS:000170032300010 PM 11488560 ER PT J AU Laserson, KF Kenyon, AS Kenyon, TA Layloff, T Binkin, NJ AF Laserson, KF Kenyon, AS Kenyon, TA Layloff, T Binkin, NJ TI Substandard tuberculosis drugs on the global market and their simple detection SO INTERNATIONAL JOURNAL OF TUBERCULOSIS AND LUNG DISEASE LA English DT Article DE tuberculosis; treatment; drug quality; thin-layer chromatography; pharmaceutical management; drugs; drug-resistant TB ID THIN-LAYER CHROMATOGRAPHY; DEVELOPING-COUNTRIES; COUNTERFEIT DRUGS; BIOAVAILABILITY; RESISTANCE; EPIDEMIC; QUALITY; DEATHS AB SETTING: The prevalence of substandard anti-tuberculosis drugs is unknown. To maximize the effectiveness of tuberculosis (TB) control efforts, simple, inexpensive drug quality screening methods are needed. DESIGN: Isoniazid (INH) and rifampin (RMP) single- and fixed-dose combination (FDC) formulations were collected from selected TB programs and pharmacies in Colombia, Estonia, India, Latvia, Russia and Vietnam. Samples were screened using a recently developed thin-layer chromatography (TLC) kit. All abnormal samples and a 40% random sample of normal formulations were further analyzed using confirmatory techniques. Samples outside of 85% to 115% of stated content, and/or containing compounds other than the stated drug, were defined as being substandard. RESULTS: Overall, 10% (4/40) of all samples, including 13% (4/30) RMP samples, contained <85% of stated content. More FDCs (5/24, 21%) than single-drug samples (2/16, 13%) were substandard. A comparison of TLC with the confirmatory analysis for RMP analysis showed a sensitivity of 100% (4/4), a specificity of 92% (24/26), a positive predictive value (PPV) of 67% (4/6), and a negative predictive value (NPV) of 100% (24/24), An analysis of INH showed a specificity of 90% (9/10). However, sensitivity, PPV, and NVP could not be determined. CONCLUSION: A substantial number of anti-tuberculosis drugs from several countries, in particular FDCs, were found to be substandard. Such drugs map contribute to the creation of drug-resistant TB. TLC is an effective, convenient, and inexpensive method for the detection of substandard drugs. C1 Ctr Dis Control & Prevent, Natl Ctr HIV STD & TB Prevent, Div TB Eliminat, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Epidemiol Program Off, Div Appl Publ Hlth Training, Epidem Intelligence Serv, Atlanta, GA USA. US FDA, Div Testing & Appl Analyt Dev, St Louis, MO USA. BOTUSA Project, Gaborone, Botswana. RP Laserson, KF (reprint author), Ctr Dis Control & Prevent, Natl Ctr HIV STD & TB Prevent, Div TB Eliminat, 1600 Clifton Rd MS E10, Atlanta, GA 30333 USA. NR 33 TC 49 Z9 51 U1 1 U2 7 PU INT UNION AGAINST TUBERCULOSIS LUNG DISEASE (I U A T L D) PI PARIS PA 68 BOULEVARD SAINT-MICHEL,, 75006 PARIS, FRANCE SN 1027-3719 J9 INT J TUBERC LUNG D JI Int. J. Tuberc. Lung Dis. PD MAY PY 2001 VL 5 IS 5 BP 448 EP 454 PG 7 WC Infectious Diseases; Respiratory System SC Infectious Diseases; Respiratory System GA 426QH UT WOS:000168359500009 PM 11336276 ER PT J AU Turnipseed, SB Roybal, JE Pfenning, AP Gonzales, SA Hurlbut, JA Madson, MR AF Turnipseed, SB Roybal, JE Pfenning, AP Gonzales, SA Hurlbut, JA Madson, MR TI LC/MS confirmation of ionophores in animal feeds SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHIC DETERMINATION; ELECTROSPRAY MASS-SPECTROMETRY; COLLISION-INDUCED DISSOCIATION; MONENSIN; SALINOMYCIN; NARASIN; IONIZATION; EGGS AB A liquid chromatographic/mass spectrometric (LC/MS) electrospray confirmation method has been developed to confirm 4 ionophores (monensin, lasalocid, salinomycin, and narasin) in a variety of animal feeds using a single quadrupole mass spectrometer, The sodium ions of these compounds are dominant in the electrospray mass spectrum, Using optimized "in-source" collision induced dissociation, characteristic fragment ions seen previously using MS/MS can be observed. The drugs were extracted from the feed matrix using hexane-ethyl acetate and isolated using a silica solid-phase extraction cartridge. These ionophores were confirmed in both medicated feeds and nonmedicated feeds fortified with these drugs at the 1-50 ppm level. In addition, this method was used to confirm residues of monensin in a nonmedicated feed that was collected from a feed mill immediately after the production of a similar feed that was medicated with high levels of monensin. C1 US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. Denver Dist Lab, Denver, CO 80225 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. NR 15 TC 20 Z9 21 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 MAY-JUN PY 2001 VL 84 IS 3 BP 640 EP 647 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000005 PM 11417625 ER PT J AU Black, RE Hurley, FJ Havery, DC AF Black, RE Hurley, FJ Havery, DC TI Occurrence of 1,4-dioxane in cosmetic raw materials and finished cosmetic products SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID GAS-CHROMATOGRAPHIC DETERMINATION; GC-MS; ASSAY AB Surveys of cosmetic raw materials and finished products for the presence of the carcinogen 1,4-dioxane have been conducted by the U,S, Food and Drug Administration since 1979, Analytical methods are described for the determination of 1,4-dioxane in ethoxylated cosmetic raw materials and cosmetic finished products. 1,4-Dioxane was isolated by azeotropic atmospheric distillation and determined by gas chromatography using n-butanol as an internal standard, A solid-phase extraction procedure based on a previously published method for the determination of 1,4-dioxane in cosmetic finished products was also used. l,4-Dioxane was found in ethoxylated raw materials at levels up to 1410 ppm, and at levels up to 279 ppm in cosmetic finished products. Levels of l,4-dioxane in excess of 85 ppm in children's shampoos indicate that continued monitoring of raw materials and finished products is warranted. C1 US FDA, Washington, DC 20204 USA. RP Black, RE (reprint author), US FDA, 200 C ST SW, Washington, DC 20204 USA. NR 22 TC 24 Z9 26 U1 3 U2 18 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 2001 VL 84 IS 3 BP 666 EP 670 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000008 PM 11417628 ER PT J AU Wisneski, HH AF Wisneski, HH TI Determination of coumarin in fragrance products by capillary gas chromatography with electron capture detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SPECIES-DIFFERENCES; MASS-SPECTROMETRY; METABOLISM; RAT; HEPATOTOXICITY; COSMETICS; TOXICITY; GERBIL AB A gas chromatographic (GC) method is described for the determination of coumarin in fragrance products. Coumarin was tentatively identified by retention time and confirmed by GC/mass spectrometry, The amount of coumarin was determined by external standard, The method was validated by conducting recovery studies from fortified fragrance products at several concentrations. Recoveries of coumarin ranged from 99 to 110%, with a relative standard deviation of 3.24, The method was used to survey a variety of fragrance products purchased in the metropolitan Washington, DC area, for coumarin, Seventy one percent of the products were found to contain coumarin at concentrations ranging from 0.002 to 0.61%. C1 US FDA, Washington, DC 20204 USA. RP Wisneski, HH (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. NR 32 TC 5 Z9 7 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 2001 VL 84 IS 3 BP 689 EP 692 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000012 PM 11417632 ER PT J AU Gay, ML White, KD Obermeyer, WR Betz, JM Musser, SM AF Gay, ML White, KD Obermeyer, WR Betz, JM Musser, SM TI Determination of ephedrine-type alkaloids in dietary supplements by LC/MS using a stable-isotope labeled internal standard SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MA-HUANG; PSEUDOEPHEDRINE C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Amer Herbal Prod Assoc, Silver Spring, MD USA. RP Gay, ML (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 12 TC 27 Z9 27 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2001 VL 84 IS 3 BP 761 EP 769 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000020 PM 11417640 ER PT J AU Whitaker, TB Hagler, WM Johansson, AS Giesbrecht, FG Trucksess, MW AF Whitaker, TB Hagler, WM Johansson, AS Giesbrecht, FG Trucksess, MW TI Distribution among sample test results when testing shelled corn lots for fumonisin SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID AFLATOXIN; PEANUTS AB The statistical distribution known as the compound gamma function was studied for suitability in describing the distribution of sample test results associated with testing lots of shelled corn for fumonisin, Thirty-two 1.1 kg test samples were taken from each of 16 contaminated lots of shelled corn. An observed distribution consisted of 32 sample fumonisin test results for each lot. The mean fumonisin concentration, c, and the variance, s(2), among the 32 sample fumonisin test results along with the parameters for the compound gamma function were determined for each of the 16 observed distributions. The 16 observed distributions of sample fumonisin test results were compared with the compound gamma function using the Power Divergence test, The null hypothesis that the observed distribution could have resulted from sampling a family of compound gamma distributions was not rejected at the 5% significance level for 15 of the 16 lots studied, Parameters of the compound gamma distribution were calculated from the 32-fumonisin sample test results using the method of moments. Using regression analysis, equations were developed that related the parameters of the compound gamma distribution to fumonisin concentration and the variance associated with a fumonisin test procedure. An operating characteristic curve was developed for a fumonisin sampling plan to demonstrate the use of the compound gamma function. C1 N Carolina State Univ, USDA ARS, Raleigh, NC 27695 USA. N Carolina State Univ, Mycotoxin Lab, Raleigh, NC 27695 USA. N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. US FDA, Washington, DC 20204 USA. RP Whitaker, TB (reprint author), N Carolina State Univ, USDA ARS, Campus Box 7625, Raleigh, NC 27695 USA. NR 18 TC 5 Z9 6 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 2001 VL 84 IS 3 BP 770 EP 776 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000021 PM 11417641 ER PT J AU Carlson, M Thompson, RD AF Carlson, M Thompson, RD TI Identification of allantoin, uric acid, and indoxyl sulfate as biochemical indicators of filth in food packaging by LC SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHY; INSECT INFESTATION AB A liquid chromatographic (LC) method was developed for the determination of allantoin, uric acid, and indoxyl sulfate in mammalian urine contaminated packaging material including paper bagging, corrugated cardboard, graybeard, and burlap bagging. The procedure involves solvent extraction and isolation of the 3 analytes by reversed-phase LC with ultraviolet detection at 225 nm for allantoin and 286 nm for uric acid and indoxyl sulfate. The composition of authentic mammalian urine such as mouse, rat, cat, dog, and human were also determined with regard to the 3 compounds of interest. A linear concentration range of 0.11-20.4, 0.02-10.0, and 0.04-30.0 mug/mL was obtained for allantoin, uric acid, and indoxyl sulfate, respectively. Limits of detection (LOD) and quantitation (LOQ) were 0.0104 and 0.0345 mug/mL for allantoin; 0.0018 and 0.0060 mug/mL for uric acid; and 0.0049 and 0.0165 mug/mL for indoxyl sulfate, respectively. Interday relative standard deviation values for a mixture of standard allantoin, uric acid, and indoxyl sulfate (n = 5) were 0.97, 0.80, and 0.94%, respectively. Analyte composition for 5 types of authentic mammalian urine varied from 0.14-6.88 mg/mL allantoin; 0.08-0.57 mg/mL uric acid; and 0.03-0.78 mg/mL indoxyl sulfate. Analyte content for 8 samples including 2 samples each for paper, cardboard, graybeard, and burlap bagging each contaminated with mouse or rat urine ranged from < LOD to 4598 mug/gm allantoin; < LOD to 202 mug/gm uric acid; and 17.5 to 616 mug/gm indoxyl sulfate. Recoveries of allantoin, uric acid, and indoxyl sulfate from 11 fortified samples (4 types) for both mouse and rat urine ranged from 28.2 to 114.1% for allantoin; 32.6 to 123.4% for uric acid; and 52.6 to 118.2% for indoxyl sulfate. C1 US FDA, Minneapolis, MN 55401 USA. RP Carlson, M (reprint author), 7801 48th Ave N, New Hope, MN 55428 USA. NR 12 TC 1 Z9 2 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 MAY-JUN PY 2001 VL 84 IS 3 BP 782 EP 788 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000023 PM 11417643 ER PT J AU Satchithanandam, S Fritsche, J Rader, JI AF Satchithanandam, S Fritsche, J Rader, JI TI Extension of AOAC Official Method 996.01 to the analysis of Standard Reference Material (SRM) 1846 and infant formulas SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ESSENTIAL FATTY-ACIDS AB There is currently no official method for the analysis of fatty acids (including trans fatty acids) in infant formulas. AOAC Official Method 996.01 for Fat Analysis in Cereal Products was extended to the analysis of milk-based infant formula Standard Reference Material (SRM)1846 to determine its applicability for use with infant formulas. Following the analysis of SRM 1846, 2 infant formulas, one milk-based liquid and one soy-based powdered infant formula, were analyzed for total fatty acid composition. Fatty acid methyl esters were prepared and analyzed by gas chromatography, The results of the analysis of SRM 1846 show that the mean analyzed values were highly reproducible as indicated by low coefficients of variation (CV), The CVs were <5% for the major fatty acids. Mean analyzed values for individual fatty acids in SRM 1846 were within +/- 1 standard deviation of the certificate values, The analyzed value for total fat as triglycerides (26.27 +/- 0.25%) agreed well with the certificate value(27.1 +/- 0.59%). Analyses of infant formulas showed that the concentrations of linoleic acid and fat meet the requirements for such formulas. C1 US FDA, Off Nutr Prod Labeling & Dietary Supplements, Washington, DC 20204 USA. RP Satchithanandam, S (reprint author), US FDA, Off Nutr Prod Labeling & Dietary Supplements, HFS-840,200 C St SW, Washington, DC 20204 USA. NR 6 TC 5 Z9 6 U1 1 U2 4 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2001 VL 84 IS 3 BP 805 EP 813 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000025 PM 11417645 ER PT J AU Thompson, RD AF Thompson, RD TI Determination of phenolic disinfectant agents in commercial formulations by liquid chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID ELECTROCHEMICAL DETECTION; TRICLOSAN; COLUMN AB Using liquid chromatography (LC), a convenient and versatile method was developed for the assay of disinfectant products containing the commonly used phenolic agents, alone or in combination, including phenol, P-phenylphenol, 4-t-amylphenol, 4-chloro-3,5-dimethylphenol (PCMX), 2-benzyl-4-chlorophenol, and triclosan. The procedure involves a simple dilution or dissolution of the product aliquot or portion followed by membrane filtration and LC, The method was applied to 19 different products representing 17 manufacturers and containing from one to 4 phenolic agents. Chromatography was performed using a Zorbax SB-C-18 column, acetonitrile-0.05M KH2PO4 (55 + 45, v/v) pH 3.00, as mobile phase and UV detection at 280 nm, The intralaboratory precision of the product assays ranged form 0.34-5.35% (n = 5) and recoveries via fortification varied from 96.1-103.8%. The limits of quantitation (LOQ) and detection (LOD) ranged from 5.58 x 10(-5) to 2.50 x 10(-4) mg/ml and from 1.76 x 10(-5) to 0.67 x 10(-4) mg/mL, respectively, for the 6 analytes, The response for all analytes was observed to be linear for at least a 50-fold range in concentration (0.001-0.05 mg/mL), The proposed method provides an efficient means for the isolation and quantitation of these phenolic compounds. C1 US FDA, Minneapolis, MN 55401 USA. RP Thompson, RD (reprint author), 1425 W 28th St 611, Minneapolis, MN 55408 USA. NR 21 TC 16 Z9 16 U1 3 U2 8 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 2001 VL 84 IS 3 BP 815 EP 822 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000026 PM 11417646 ER PT J AU Hight, SC AF Hight, SC TI Determination of lead and cadmium in ceramicware leach solutions by graphite furnace atomic absorption spectroscopy: Method development and interlaboratory trial SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB This method was developed to improve sensitivity and eliminate time consuming, evaporative pre-concentration in AOAC Method 973.82 and American Society for Testing and Materials method C738 for testing foodware. The method was developed using leach solutions obtained by leaching 9 differently decorated ceramic vessels with 4% acetic acid for 24 h at room temperature. Lead and cadmium concentrations in leach solutions were 0.005-17 600 and 0.0004-0.500 mug/mL, respectively. Concentrations were determined using peak area, phosphate chemical modifier (8.3 mug PO4-3), and a standard curve for quantitation. Optimized pre-atomization and atomization temperatures were 1300 and 1800 degreesC, respectively, for Pb and 1100 and 1700 degreesC, respectively, for Cd. Characteristic masses (m(o) were 10 and 0.4 pg for Pb and Cd, respectively. Precision of repeated analyses of calibration solutions was less than or equal to3% relative standard deviation. Precision of duplicate leach solution analyses on different days was 0-9% relative difference. Recovery from fortified leach solutions was 96-106%. Results obtained by this method agreed 92-110% with those of confirmatory analyses. Results of certified reference material solutions agreed 94-100% with certificate values. Pb and Cd limits of quantitation (LOQ) were 0.005 and 0.0005 mug/mL, respectively. Results from 3 trial laboratories for 4 leach solutions containing Pb and Cd concentrations of 0.017-1.47 and <0.0005-0.0864 mug/mL, respectively, agreed 84-102% with results of the author. Two attributes of this method were noteworthy: (1) Background absorbance due to organic matter was entirely absent from atomization profiles, making the use of short pre-atomization hold times (2 s) possible. (2) Instrument precision was excellent and only one determination per solution was needed. Acceptance criteria for quality control measurements and a practical procedure for estimating the method LOQ during routine regulatory analyses are described. C1 US FDA, HFS 338, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Hight, SC (reprint author), US FDA, HFS 338, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 16 TC 4 Z9 6 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 MAY-JUN PY 2001 VL 84 IS 3 BP 861 EP 872 PG 12 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000030 PM 11417650 ER PT J AU Horwitz, W Jackson, T Chirtel, SJ AF Horwitz, W Jackson, T Chirtel, SJ TI Examination of proficiency and control recovery data from analyses for pesticide residues in food: Sources of variability SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB We examined a number of large proficiency and control databases supporting the values reported for pesticide residues in agricultural commodities at fractions of a part per million (mg/kg), The average recovery from > 100 000 recovery records in 13 databases was 94%. The overall average single-value relative standard deviation (RSD) of the reported recoveries was 17% at a mean concentration (C) of about 10(-7) (0.1 mg/kg), The average apparent HORRAT value (RSD found/RSDR predicted from the Horwitz formula [2*C-0.1505]) was 0.8. Analysis of variance indicated that about 60-70% of the variance could not be associated with any particular factor or combination of factors-analyte, commodity, method, laboratory, concentration, database, or their interactions. The most predominant factor, analyte, and its third-order interaction with laboratory and concentration contributed most of the assignable variance. These findings suggested that most of the variability of trace analysis for pesticide residues is "random" in the sense of being inherent and not assignable to specific factor fluctuations. C1 US FDA, Ctr Food Safety & Appl Nutr, HFS 500, Washington, DC 20204 USA. Calif Dept Food & Agr, Sacramento, CA 95832 USA. US FDA, Ctr Food Safety & Appl Nutr, Div Math, Washington, DC 20204 USA. RP Horwitz, W (reprint author), AOAC INT, 481 N Frederick Ave, Gaithersburg, MD 20877 USA. NR 14 TC 8 Z9 8 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAY-JUN PY 2001 VL 84 IS 3 BP 919 EP 935 PG 17 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000035 PM 11417655 ER PT J AU McClure, FD Lee, JK AF McClure, FD Lee, JK TI Procedures for estimating confidence intervals for selected method performance parameters SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Procedures for estimating confidence intervals (sigma (2)(r)) for the repeatability variance to laboratory reproducibility variance (sigma (2)(R) = sigma (L) + sigma (2)(r)), laboratory component (sigma (2)(L)), and their, corresponding standard deviations sigma (r), sigma (R), and sigma (L), respectively, are presented. In addition, Cls for the ratio of the repeatability component to the reproducibility variance (sigma (2)(r)/sigma (2)(R)) and the ratio of the laboratory component to the reproducibility variance (sigma (2)(L)/sigma (2)(R)) are also presented. C1 US FDA, US Dept HHS, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support,Div Math, Washington, DC 20204 USA. RP McClure, FD (reprint author), US FDA, US Dept HHS, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support,Div Math, 200 C St SW, Washington, DC 20204 USA. NR 4 TC 2 Z9 2 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 2001 VL 84 IS 3 BP 940 EP 946 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000037 PM 11417657 ER PT J AU McClure, FD AF McClure, FD TI A statistical model to evaluate analyte homogeneity for a material SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An underlying assumption for collaborative studies is that the analyte variation among test samples of the material (i.e., matrix and analyte concentration combination) under study has a negligible influence on the estimates of precision for the method. This assumption is expected to be fulfilled when the material under study is prepared (i.e., thoroughly mixed) such that the analyte is distributed uniformly throughout the matrix. Statistical design and intra-class correlation analysis procedures are proposed to assess the similarity or agreement among analytical results among- and within-containers for single and multiple occasions of use (e,g,, collaborative and proficiency studies). C1 US FDA, US Dept HHS, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support,Div Math, Washington, DC 20204 USA. RP McClure, FD (reprint author), US FDA, US Dept HHS, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support,Div Math, 200 C St SW, Washington, DC 20204 USA. NR 10 TC 2 Z9 2 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 MAY-JUN PY 2001 VL 84 IS 3 BP 947 EP 954 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 442DY UT WOS:000169271000038 PM 11417658 ER PT J AU Zhang, MJ Li, XX Pang, XW Ding, L Wood, O Clouse, K Hewlett, I Dayton, AI AF Zhang, MJ Li, XX Pang, XW Ding, L Wood, O Clouse, K Hewlett, I Dayton, AI TI Identification of a potential HIV-induced source of bystander-mediated apoptosis in T cells: Upregulation of TRAIL in primary human macrophages by HIV-1 Tat SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE HIV; Tat; TRAIL; apoptosis; macrophage ID HUMAN-IMMUNODEFICIENCY-VIRUS; BLOOD MONONUCLEAR-CELLS; BCL-2 GENE-EXPRESSION; FAS LIGAND; INFECTED PERSONS; CROSS-LINKING; UP-REGULATION; APO-2 LIGAND; DEATH DOMAIN; LYMPH-NODES AB The induction of apoptosis in T cells by bystander cells has been repeatedly implicated as a mechanism contributing to the T cell depletion seen in HIV infection. It has been shown that apoptosis could be induced in T cells from asymptomatic HIV-infected individuals in a Fas-independent, TNF-related apoptosis-inducing ligand (TRAIL)-dependent manner if the cells were pretreated with anti-CD3. it has also been shown that T cells from HIV-infected patients were even more sensitive to TRAIL induction of apoptosis than they were to Fas induction. Recently, it has been reported that in an HIV-1 SCID-Hu model, the vast majority of the T cell apoptosis is not associated with p24 and is therefore produced by bystander effects. Furthermore, few apoptotic cells were associated with neighboring cells which were positive for either Fas ligand or TNF. However, most of the apoptotic cells were associated with TRAIL-positive cells. The nature of these TRAIL-positive cells was undetermined. Here, we report that HIV infection of primary human macrophages switches on abundant TRAIL production both at the RNA and protein levels. Furthermore, more macrophages produce TRAIL than are infected by HIV, indicating that a bystander mechanism may, at least in part, upregulate TRAIL. Exogenously supplied HIV-1 Tat protein upregulates TRAIL production by primary human macrophages to an extent indistinguishable from infection. The results suggest a model in which HIV-1-infected cells produce extracellular Tat protein, which in turn upregulates TRAIL in macrophages which then can induce apoptosis in bystander T cells. Copyright (C) 2001 National Science Council. ROC and S. Karger AG, Basel. C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20182 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Off Therapeut Res & Review, Rockville, MD 20182 USA. RP Zhang, MJ (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Emerging & Transfus Transmitted Dis, HFM 315,1401 Rockville Pike, Rockville, MD 20182 USA. NR 52 TC 78 Z9 82 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 MAY-JUN PY 2001 VL 8 IS 3 BP 290 EP 296 DI 10.1007/BF02256603 PG 7 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA 436RF UT WOS:000168948700008 PM 11385301 ER PT J AU Christiansen, JS Bengtsson, BA Thorner, MO Hintz, R Sonksen, PH Cohen, P Clemmons, D Strasburger, CJ Carlsson, L Tanaka, T Robinson, I Jorgensen, JO Johannson, G Clayton, PE Cowell, CT Malozowski, SN Hankinson, S Yee, D Baxter, R Swerdlow, A Rosenfeld, R Fradkin, JE Nishi, Y Monson, JP van den Berghe, G Carroll, PV Takala, J van der Lely, AJ Pollak, MN LeRoith, D Tachibana, K Kappelgaard, AM Langbakke, I Lippe, B Wilton, P Stein, P Salazar, DE Maneatis, T Blethen, SL Cutler, GB Blum, WF Svanberg, E Gertner, JM Shimatsu, A Takahashi, H AF Christiansen, JS Bengtsson, BA Thorner, MO Hintz, R Sonksen, PH Cohen, P Clemmons, D Strasburger, CJ Carlsson, L Tanaka, T Robinson, I Jorgensen, JO Johannson, G Clayton, PE Cowell, CT Malozowski, SN Hankinson, S Yee, D Baxter, R Swerdlow, A Rosenfeld, R Fradkin, JE Nishi, Y Monson, JP van den Berghe, G Carroll, PV Takala, J van der Lely, AJ Pollak, MN LeRoith, D Tachibana, K Kappelgaard, AM Langbakke, I Lippe, B Wilton, P Stein, P Salazar, DE Maneatis, T Blethen, SL Cutler, GB Blum, WF Svanberg, E Gertner, JM Shimatsu, A Takahashi, H CA Growth Hormone Soc TI Critical evaluation of the safety of recombinant human growth hormone administration: Statement from the growth hormone research society SO JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM LA English DT Article C1 Aarhus Kommune Hosp, DK-8000 Aarhus, Denmark. Sahlgrens Univ Hosp, Stockholm, Sweden. Univ Virginia, Hlth Sci Ctr, Dept Med, Charlottesville, VA 22908 USA. Stanford Univ, Med Ctr, Stanford, CA 94305 USA. Univ Calif Los Angeles, Matell Childrens Hosp, Los Angeles, CA 90024 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. Natl Inst Med Res, London NW7 1AA, England. Royal Manchester Childrens Hosp, Manchester M27 1HA, Lancs, England. US FDA, Rockville, MD 20857 USA. Harvard Univ, Sch Publ Hlth, Cambridge, MA 02138 USA. Univ Texas, Hlth Sci Ctr, Austin, TX USA. London Sch Hyg & Trop Med, London WC1, England. Oregon Hlth Sci Univ, Portland, OR 97201 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Hiroshima Redc Cross Hosp, Hiroshima, Japan. Katholieke Univ Leuven, Louvain, Belgium. Erasmus Univ, Med Ctr, Rotterdam, Netherlands. Kanagawa Childrens Med Ctr, Kanagawa, Japan. Novo Nordisk AS, Copenhagen, Denmark. Bristol Myers Squibb Co, New York, NY 10154 USA. Genentech Inc, S San Francisco, CA 94080 USA. Eli Lilly & Co, Indianapolis, IN 46285 USA. Kyoto Natl Hosp, Kyoto, Japan. Kanazawa Med Univ, Kanazawa, Ishikawa, Japan. RP Thorner, MO (reprint author), Univ Virginia, Hlth Sci Ctr, Dept Med, Box 800466, Charlottesville, VA 22908 USA. RI Pollak, Michael/G-9094-2011; Baxter, Robert/F-3927-2012 OI Pollak, Michael/0000-0003-3047-0604; Baxter, Robert/0000-0001-5061-2142 NR 4 TC 82 Z9 87 U1 0 U2 2 PU ENDOCRINE SOC PI CHEVY CHASE PA 8401 CONNECTICUT AVE, SUITE 900, CHEVY CHASE, MD 20815-5817 USA SN 0021-972X J9 J CLIN ENDOCR METAB JI J. Clin. Endocrinol. Metab. PD MAY PY 2001 VL 86 IS 5 BP 1868 EP 1870 PG 3 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 432ZV UT WOS:000168731600004 ER PT J AU Stewart, DS Reineke, KF Ulaszek, JM Tortorello, ML AF Stewart, DS Reineke, KF Ulaszek, JM Tortorello, ML TI Growth of Salmonella during sprouting of alfalfa seeds associated with salmonellosis outbreaks SO JOURNAL OF FOOD PROTECTION LA English DT Article ID ESCHERICHIA-COLI O157-H7; VEGETABLE SPROUTS; EFFICACY AB Growth of Salmonella was assessed during sprouting of naturally contaminated alfalfa seeds associated with two outbreaks of salmonellosis. Salmonella was determined daily in sprouts and sprout rinse water samples by a three-tube most probable number (MPN) procedure and a commercial enzyme immunoassay (EIA). Growth of Salmonella in the sprouts was reflected in the rinse water, and the MPNs of the two samples were generally in agreement within approximately 1 log. The results from EIA testing of sprouts and water samples were also in agreement. The pathogen was present in the seed at less than 1 MPN/g, and it increased in number to maximum population levels of 10(2) to 10(3) MPN/g in one seed lot and 10(2) to 10(4) MPN/g in the other seed lot. Maximum populations of the pathogen were apparent by day 2 of sprouting. These results show the ability of the pathogen to grow to detectable levels during the sprouting process, and they provide support for the recommendation to test the sprout water for the presence of pathogens 48 h after starting seed sprouting. The effectiveness of a 10-min, 20,0000-mug/ml (ppm) calcium hypochlorite treatment of the outbreak-associated seeds was studied. For both seed lots, the hypochlorite treatment caused a reduction, but not elimination, of Salmonella contamination in the finished sprouts. These results confirm the need to test each production batch for the presence of pathogens, even after 20,000 mug/ml (ppm) hypochlorite treatment of seeds, so that contaminated product is not distributed. C1 IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Summit Argo, IL 60501 USA. RP Tortorello, ML (reprint author), US FDA, 6502 S Archer Rd, Summit Argo, IL 60501 USA. FU FDA HHS [FD-0004331] NR 22 TC 67 Z9 69 U1 2 U2 18 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC 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 2001 VL 64 IS 5 BP 618 EP 622 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 428XZ UT WOS:000168488100005 PM 11357873 ER PT J AU Hammack, TS Amaguana, RM Andrews, WH AF Hammack, TS Amaguana, RM Andrews, WH TI An improved method for the recovery of Salmonella serovars from orange juice using universal preenrichment broth SO JOURNAL OF FOOD PROTECTION LA English DT Article ID OUTBREAK; SELENITE; FOODS AB The relative effectiveness of three methods for the recovery of Salmonella serovars from orange juice was determined. One method, a modified Bacteriological Analytical Manual (BAM) procedure consisted of preenrichment in lactose broth at 35 degreesC for 24 h, selective enrichment, and selective plating. Another method, a National Centers for Disease Control and Prevention (CDC 1) procedure, consisted of direct enrichment in tetrathionate broth at 35 degreesC for 24 and 48 h, followed by selective plating. The third method (also from CDC and designated CDC 2) consisted of preenrichment in Universal Preenrichment (UP) broth at 35 degreesC for 24 h, selective enrichment, and selective plating. In 10 experiments encompassing five different Salmonella serovars and 200 test portions per broth, the CDC 1 method recovered 141 Salmonella-positive test portions, the BAM method recovered 151, and the CDC 2 method recovered 171. In 2 of the 10 experiments, with two different Salmonella serovars, the BAM recovered significantly fewer (P < 0.05) Salmonella-positive test portions than did the CDC 2 method. On the basis of the above results, the second phase of this study focused on a comparison of the effectiveness of the BAM-recommended lactose broth and the CDC 2-recommended UP broth as preenrichment media for the recovery of Salmonella serovars from pasteurized and unpasteurized orange juice. Subsequent culture treatment of the two preenrichments was identical so that the effect of other variables (e.g., different selective enrichment media, various incubation temperatures, and different selective plating agars) on the relative performance of these two preenrichment media was excluded. In one of nine experiments, with pasteurized orange juice, lactose broth recovered significantly fewer (P < 0.05) Salmonella-positive test portions than did UP broth. For the combined results of the nine pasteurized orange juice experiments (180 test portions per broth), lactose broth recovered 99 Salmonella-positive test portions, and UP broth recovered 116. In three of seven experiments, with unpasteurized orange juice, lactose broth recovered significantly fewer (P < 0.05) Salmonella-positive test portions than did UP broth. For the combined results of the seven unpasteurized orange juice experiments (140 test portions per broth), lactose broth recovered 73 Salmonella-positive test portions, and UP broth recovered 117. For both pasteurized and unpasteurized orange juice, the total number of Salmonella-positive test portions recovered with UP broth was significantly greater than the number recovered with lactose broth. These results indicate that UP broth is a more effective enrichment broth for the recovery of Salmonella from orange juice than is lactose broth. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, Washington, DC 20204 USA. RP Hammack, TS (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Microbiol Studies, 200 C St SW HFS-516, Washington, DC 20204 USA. NR 23 TC 17 Z9 17 U1 0 U2 4 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC 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 2001 VL 64 IS 5 BP 659 EP 663 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 428XZ UT WOS:000168488100012 PM 11347996 ER PT J AU Ellison, RK Malnati, E DePaola, A Bowers, J Rodrick, GE AF Ellison, RK Malnati, E DePaola, A Bowers, J Rodrick, GE TI Populations of Vibrio parahaemolyticus in retail oysters from Florida using two methods SO JOURNAL OF FOOD PROTECTION LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; THERMOLABILE HEMOLYSIN; VULNIFICUS; GENE; INFECTIONS; MODELS; PROBE; BAY; TRH AB Vibrio parahaemolyticus is a naturally occurring estuarine bacterium that is often associated with gastroenteritis in humans following consumption of raw molluscan shellfish. A number of studies have investigated the environmental distribution of V: parahaemolyticus, but little is known about the levels of this organism during distribution of oysters or at the point of consumption. Duplicate samples of shellstock oysters were collected monthly (September 1997 to May 1998) from the same four restaurants and three wholesale seafood markets in the Gainesville, Fla. area and analyzed for total V. parahaemolyticus densities using two methods: a standard MPN method (BAM-MPN) and a new direct plating procedure (direct-VPAP). Both methods employed an alkaline phosphatase-labeled DNA probe (VPAP) targeting the species-specific thermolabile hemolysin (tlh) gene to confirm suspect colonies as V. parahaemolyticus. The highest monthly geometric mean V, parahaemolyticus density was observed in October of 1997 (similar to3,000/g) with similarly high values during September and November of 1997. From December 1997 to May 1998 mean densities were generally less than 100/g, falling to similar to 10/g in February and March. A strong correlation (r = 0.78) between the direct-VPAP and BAM-MPN methods for determining V. parahaemolyticus densities in market-level oysters was observed. The direct-VPAP method was more rapid and precise while the BAM-MPN was more sensitive and may better recover stressed cells. The utilization of the VPAP probe for identification of V. parahaemolyticus sharply reduced the labor for either method compared to biochemical identification techniques used in earlier V. parahaemolyticus surveys. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. US FDA, Div Math & Stat, Washington, DC 20204 USA. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. NR 31 TC 20 Z9 27 U1 1 U2 3 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC 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 2001 VL 64 IS 5 BP 682 EP 686 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 428XZ UT WOS:000168488100016 PM 11348000 ER PT J AU Kothary, MH Babu, US AF Kothary, MH Babu, US TI Infective dose of foodborne pathogens in volunteers: A review SO JOURNAL OF FOOD SAFETY LA English DT Article ID ENTEROPATHOGENIC ESCHERICHIA-COLI; ORAL CHOLERA VACCINE; COLONIZATION FACTOR ANTIGENS; VIBRIO-CHOLERAE; CRYPTOSPORIDIUM-PARVUM; SHIGELLA-FLEXNERI; CAMPYLOBACTER-JEJUNI; HEALTHY-VOLUNTEERS; MILK IMMUNOGLOBULIN; CHALLENGE MODEL AB Risk assessment and impact of foodborne pathogens on the health of different populations was one of the goals identified in the Presidential Food Safety Initiative three-year plan. This entailed estimation of dose-response relationship for foodborne pathogens to humans, either by feeding studies or from outbreak. For certain pathogens, such as Listeria monocytogenes and Escherichia coli O157. H7, there are no feeding studies due to ethical reasons, and the results from outbreaks are normally used to estimate the infectious dose. The focus of this review is to compile dose-response information in volunteers for several foodborne pathogens including Salmonella, Shigella spp., Campylobacter jejuni, Vibrio spp., Escherichia coli, Cryptosporidium parvum and Entamoeba coli. The infectious dose for different serovars of Salmonella and strains of E. coli was quite large (> 10(5) organisms), while the infectious dose for some Shigella spp. seemed to be as low as less than 10 organisms. Toxigenic V, cholerae (O1 and O139 serotypes) were infective at a dose of 10(4) organisms, a non-O1 strain was infective at a much higher dose (10(6) organisms). C. jejuni, C. parvum and Entamoeba coli appeared to have infectious doses as low as 500 organisms, 10 oocysts, and 1 cyst, respectively. The infectious dose and the dose response are dependent upon the strains used, and the age and physical condition of the individuals, and can therefore show wide variations. In addition, since many of the volunteer studies are carried out by feeding the organisms in a nonfood matrix after neutralizing the stomach acidity, results obtained may not reflect the true dose response. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment HFS327, Washington, DC 20204 USA. RP Kothary, MH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Virulence Assessment HFS327, 200 C St,SW, Washington, DC 20204 USA. NR 71 TC 123 Z9 126 U1 4 U2 37 PU FOOD NUTRITION PRESS INC PI TRUMBULL PA 6527 MAIN ST, P O BOX 374, TRUMBULL, CT 06611 USA SN 0149-6085 J9 J FOOD SAFETY JI J. Food Saf. PD MAY PY 2001 VL 21 IS 1 BP 49 EP 73 DI 10.1111/j.1745-4565.2001.tb00307.x PG 25 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 440JP UT WOS:000169172400004 ER PT J AU Azzam, HS DeJarnette, JB Huang, K Emmons, R Park, CS Sommers, CL El-Khoury, D Shores, EW Love, PE AF Azzam, HS DeJarnette, JB Huang, K Emmons, R Park, CS Sommers, CL El-Khoury, D Shores, EW Love, PE TI Fine tuning of TCR signaling by CD5 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CELL ANTIGEN RECEPTOR; T-CELLS; THYMOCYTE SELECTION; NEGATIVE REGULATION; TRANSGENIC MICE; B-CELLS; TYROSINE; TRANSDUCTION; ACTIVATION; COMPLEX AB Current data indicate that CD5 functions as an inhibitor of TCR signal transduction. Consistent with this role, thymocyte selection in TCR transgenic/CD5(-/-) mice is altered in a manner suggestive of enhanced TCR signaling. However, the impact of CD5 deletion on thymocyte selection varies depending on the transgenic TCR analyzed, ranging from a slight to a marked shift from positive toward negative selection. An explanation for the variable effect of CD5 on selection is suggested by the observation that CD5 surface expression is regulated by TCR signal intensity during development and CD5 surface levels on mature thymocytes and T cells parallel the avidity of the positively selecting TCR/MHC/ligand interaction. In this study, we generated mice that overexpress CD5 during thymocyte development (CD5-tg), and then examined the effect of CD5 overexpression or CD5 deletion (CD5(-/-)) on selection of thymocytes that express the same TCR transgenes. The results demonstrate that the effect on thymocyte selection of altering CD5 expression depends on the avidity of the selecting interaction and, consequently, the level of basal (endogenous) CD5 surface expression. Substitution of endogenous CD5 with a transgene encoding a truncated form of the protein failed to rescue the CD5(-/-) phenotype, demonstrating that the cytoplasmic domain of CD5 is required for its inhibitory function. Together, these results indicate that inducible regulation of CD5 surface expression during thymocyte selection functions to fine tune the TCR signaling response. C1 NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. RP Love, PE (reprint author), NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. NR 37 TC 155 Z9 156 U1 0 U2 5 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAY 1 PY 2001 VL 166 IS 9 BP 5464 EP 5472 PG 9 WC Immunology SC Immunology GA 487YH UT WOS:000171906500018 PM 11313384 ER PT J AU Yao, L Setsuda, J Sgadari, C Cherney, B Tosato, G AF Yao, L Setsuda, J Sgadari, C Cherney, B Tosato, G TI Interleukin-18 expression induced by Epstein-Barr virus-infected cells SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Article DE Burkitt lymphoma; interferon gamma; angiogenesis; latent membrane protein-1; tumor regression ID IFN-GAMMA PRODUCTION; NECROSIS IN-VIVO; INTERFERON-GAMMA; B-CELLS; T-CELLS; LYMPHOPROLIFERATIVE DISEASE; INDUCIBLE PROTEIN-10; CYTOKINE PRODUCTION; TUMOR-REGRESSION; CXC CHEMOKINES AB Human Epstein-Barr virus (EBV)-negative Burkitt lymphomas cells usually grow as malignant subcutaneous tumors in athymic mice, but these tumors regress when the Burkitt cells are injected in conjunction with EBV-positive lymphoblastoid cells or when the Burkitt cells are transfected with the EBV latent membrane protein-1 (LMP-I) gene. Tumor regression is mediated, in part, by murine interferon gamma (IFN-y) and the IFN-gamma -induced murine chemokine IFN-gamma -inducible protein-10 (IP-10), The mechanisms by which EBV-LIMP-1 promotes the expression of IFN-y has remained unclear. Here we show that murine interleukin (IL)-18 was consistently expressed in regressing Burkitt tumors but was either expressed at low levels or absent from progressively growing Burkitt tumors. By immunohistochemical methods, IL-18 protein was visualized in regressing but not in progressively growing Burkitt tumors, In contrast, IL-12 p35 and IL-12 p40 were only rarely expressed in regressing Burkitt tumors. In splenocyte cultures, EBV-infected lymphoblastoid cells and LMP-1-transfected Burkitt cells promoted the expression of IL-18 but not the expression of IL-12 p35 and IL-12 p40. A neutralizing antibody directed at murine IL-18 reduced murine IP-10 expression induced by EBV-immortalized cells in splenocyte cultures. These results pro,ide evidence for IL-18 expression in response to a viral latency protein and suggest that IL-18 may play an important role as an endogenous inducer of IFN-gamma expression, thereby contributing to tumor regression. C1 NCI, Dept Transplantat Immunol, Med Branch, DCS,NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD USA. Ist Super Sanita, Virol Lab, I-00161 Rome, Italy. RP Yao, L (reprint author), NCI, Dept Transplantat Immunol, Med Branch, DCS,NIH, Bldg 10,Room 12C07, Bethesda, MD 20892 USA. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 30 TC 12 Z9 12 U1 0 U2 3 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 2001 VL 69 IS 5 BP 779 EP 784 PG 6 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 434GM UT WOS:000168806800014 PM 11358987 ER PT J AU Sun, H Manger, TJ Muzik, O Collins, JM Shields, AF AF Sun, H Manger, TJ Muzik, O Collins, JM Shields, AF TI Biodistribution and metabolism of F-18-FMAU: PET studies. 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 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 2001 VL 42 IS 5 SU S MA 308 BP 82P EP 83P PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900309 ER PT J AU Yaes, RJ AF Yaes, RJ TI A simple method of estimating radiation tolerance doses for radiopharmaceutical therapy. SO JOURNAL OF NUCLEAR MEDICINE LA English DT Meeting Abstract C1 US FDA, Div Med Imaging & Radiopharmaceut Drug Prod, 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 2001 VL 42 IS 5 SU S MA 1041 BP 247P EP 247P PG 1 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 434NG UT WOS:000168821900940 ER PT J AU Baratta, EJ Mackill, P AF Baratta, EJ Mackill, P TI Determination of isotopic uranium in food and water SO JOURNAL OF RADIOANALYTICAL AND NUCLEAR CHEMISTRY LA English DT Article; Proceedings Paper CT 5th International Conference on Methods and Applications of Radioanalytical Chemistry (MARC-V) CY APR 09-14, 2000 CL KAILUA-KONA, HAWAII SP Amer Nucl Soc Top ID IMPORTED FOODS; UNITED-STATES; RADIONUCLIDES AB The U.S. Food and Drug Administration (FDA) conducts surveys of foods both domestic and imported for the presence of radioactivity. It does not routinely analyze for the actinides, specifically uranium, as it has been shown by previously by studies as reported by WELFORD and others that the concentration in food is very low. This was the result of a "Tri-City" study. However, at specific sites, the FDA has been requested to analyze for uranium. The concern is that either 'enriched' or 'depleted' uranium has been introduced into the environment and possibly contaminated the food supply. In addition some concern has been raised that water from wells or other sources used for processing food may contain uranium, both natural, depleted or enriched. This paper will discuss the methodology for the determination of isotopic uranium, specifically for uranium-238 (depleted) and/or uranium-235 (enriched) in the analyses of food and water samples and the results of these surveys. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Baratta, EJ (reprint author), US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. NR 11 TC 3 Z9 3 U1 1 U2 3 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0236-5731 J9 J RADIOANAL NUCL CH JI J. Radioanal. Nucl. Chem. PD MAY PY 2001 VL 248 IS 2 BP 473 EP 475 DI 10.1023/A:1010617200963 PG 3 WC Chemistry, Analytical; Chemistry, Inorganic & Nuclear; Nuclear Science & Technology SC Chemistry; Nuclear Science & Technology GA 446MA UT WOS:000169516000036 ER PT J AU Brown, SL Pennello, G Berg, WA Soo, MS Middleton, MS AF Brown, SL Pennello, G Berg, WA Soo, MS Middleton, MS TI Silicone gel breast implant rupture, extracapsular silicone, and health status in a population of women SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE breast implants; breast prostheses; silicone; fibromyalgia; adverse events ID CONNECTIVE-TISSUE DISEASES; SYMPTOMATIC WOMEN; FIBROMYALGIA; AUTOANTIBODIES; DISORDERS; PROFILE; RISK AB Objective. To assess whether breast implant rupture or extracapsular silicone are associated with selected symptoms of self-reported physician-diagnosed connective tissue disease (CTD). Methods. Women with silicone gel breast implants responded to a questionnaire that included questions on health status, satisfaction with implants, symptoms of CTD, and physician-diagnosed disease. These women then had magnetic resonance imaging (MRI) of their breasts to determine the status of the implants with respect to rupture and extracapsular silicone. Results. Women with breast implant rupture diagnosed by MRI were no more likely to report a diagnosis of selected CTD than those with intact implants or those with implants of indeterminate status. Women with extracapsular silicone (silicone gel outside of the fibrous scar that forms around breast implants) were more likely to report having fibromyalgia (FM, p = 0.004) or other CTD, which included dermatomyositis, polymyositis, Hashimoto's thyroiditis, mixed CTD, pulmonary fibrosis, eosinophilic fasciitis, and polymyalgia (p = 0.008) than other women in the study. The association with FM remained statistically significant when adjusted for multiple comparisons (7 diagnoses) and implant age, implant location, or implant manufacturer (p < 0.05 in all cases), but became of border line statistical significance when adjusted for multiple comparisons and self-perceived health status (p = 0.094) or self-perceived rupture status (p = 0.051), The association with other CTD remained statistically significant when adjusted Tor multiple comparisons and implant location or implant manufacturer, but became borderline or insignificant when adjusted for multiple comparisons and for implant age (p = 0.051), self-perceived health status (p = 0.434), or self-perceived rupture status (p = 0.145). Logistic regression was used to compute odds ratios of self-reported diagnoses comparing women with and without extracapsular silicone. The odds ratios were 2.8 (95% CI 1.2 to 6.3) for FM, and 2.6 (95% CI 0.8 to 8.5) for other CTD after adjustment far implant age, implant location, implant manufacturer, implant type, self-perceived health, self-perceived rupture status, and site of surgery practice. Conclusion. These data suggest an association between extracapsular silicone. from ruptured silicone breast implants and FM. If this association persists in other studies, women with silicone gel breast implants should be informed of the potential risk of developing fibromyalgia if their breast implants rupture and the silicone gel escapes the fibrous scar capsule. C1 US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Univ Maryland, Sch Med, Dept Radiol, Div Breast Imaging, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Greenebaum Canc Ctr, Baltimore, MD 21201 USA. Duke Univ, Med Ctr, Duke S Hosp, Dept Radiol, Durham, NC USA. Univ Calif San Diego, Sch Med, Dept Radiol, San Diego, CA 92103 USA. RP Brown, SL (reprint author), US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, 1350 Piccard Dr,HFZ-541, Rockville, MD 20850 USA. RI Soo, Mary/B-1580-2017 NR 27 TC 73 Z9 75 U1 0 U2 6 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2001 VL 28 IS 5 BP 996 EP 1003 PG 8 WC Rheumatology SC Rheumatology GA 428XX UT WOS:000168487900013 PM 11361228 ER PT J AU Huber, AM Hicks, JE Lachenbruch, PA Perez, MD Zemel, LS Rennebohm, RM Wallace, CA Lindsley, CB Passo, MH Ballinger, SH Bowyer, SL Reed, AM White, PH Katona, IM Miller, FW Rider, LG Feldman, BM AF Huber, AM Hicks, JE Lachenbruch, PA Perez, MD Zemel, LS Rennebohm, RM Wallace, CA Lindsley, CB Passo, MH Ballinger, SH Bowyer, SL Reed, AM White, PH Katona, IM Miller, FW Rider, LG Feldman, BM CA Juvenile Dermatomyositis Dis Activ TI Validation of the childhood health assessment questionnaire iu the juvenile idiopathic myopathies SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE juvenile idiopathic inflammatory myopathy; juvenile dermatomyositis; outcome assessment; physical function assessment; validation; measurement ID INFLAMMATORY MYOPATHIES; DISEASE-ACTIVITY; DAMAGE INDEXES; DERMATOMYOSITIS; RESPONSIVENESS; CHILDREN; MYOSITIS AB Objective. To examine the validity of the Childhood Health Assessment Questionnaire (CHAQ) in patients with juvenile idiopathic inflammatory myopathy (IIM). Methods. One hundred fifteen patients were enrolled in a multicenter collaborative study, during which subjects were assessed twice, 7-9 months apart. Physical function was measured using the CHAQ. Internal reliability was assessed using adjusted item-total correlations and item endorsement rates. Construct validity was assessed by comparing predicted and actual correlations of the CHAQ with other measures of physical function and disease activity. Responsiveness was assessed by calculating effect size (ES) and standardized response mean (SRM) in a group of a priori defined "improvers." Results. Item-total correlations were high (r(s) range = 0.35-0.81), suggesting all items were related to overall physical function. Manual muscle testing and the Childhood Myositis Assessment Scale correlated moderate to strongly with the CHAQ (r(s) = -0.64 and -0.75. both p < 0.001). Moderate correlations were also seen with the physician global assessment of disease activity (r(s) = 0.58, p < 0.001). parent global assessment of overall health (r(s) = -0.65, p < 0.001). Steinbrocker function class (r(s) = 0.69, p < 0.001), and global skin activity (r(s) = 0.40, p < 0.001), while global disease damage and skin damage had low correlations (r(s) = 0.13 and 0.07, p 0.17). Responsiveness of the CHAQ was high. with ES = 1.05 and SRM = 1.20. Conclusion. In this large cohort of patients with juvenile IIM, the CHAQ exhibited internal reliability, construct validity and strong responsiveness. We conclude that the CHAQ is a valid measure of physical function in juvenile IIm, appropriate for use in therapeutic trials, and potentially in the clinical carl of these patients. C1 Hosp Sick Children, Div Rheumatol, Dept Pediat, Toronto, ON M5G 2X8, Canada. Univ Toronto, Dept Publ Hlth Sci, Toronto, ON, Canada. NIAMSD, Ctr Clin, NIH, Bethesda, MD 20892 USA. NIAMSD, Arthritis & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. US FDA, Div Biostat, Bethesda, MD 20014 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Baylor Coll Med, Texas Childrens Hosp, Houston, TX 77030 USA. Univ Connecticut, Connecticut Childrens Med Ctr, Hartford, CT 06112 USA. Ohio State Univ, Columbus Childrens Hosp, Columbus, OH 43210 USA. Univ Washington, Childrens Hosp, Seattle, WA 98195 USA. Univ Kansas, Kansas City, KS 66103 USA. Univ Cincinnati, Childrens Hosp, Cincinnati, OH USA. Indiana Univ, James Whitcomb Riley Hosp Children, Indianapolis, IN USA. Univ N Carolina, Chapel Hill, NC USA. Childrens Natl Med Ctr, Washington, DC 20010 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Feldman, BM (reprint author), Hosp Sick Children, Div Rheumatol, Dept Pediat, 555 Univ Ave, Toronto, ON M5G 2X8, Canada. RI Feldman, Brian/A-8586-2011; OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 19 TC 75 Z9 75 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2001 VL 28 IS 5 BP 1106 EP 1111 PG 6 WC Rheumatology SC Rheumatology GA 428XX UT WOS:000168487900032 PM 11361197 ER PT J AU Woodworth, TG Furst, DE Strand, V Kempeni, J Fenner, H Lau, CS Miller, F Day, R Lipani, J Brooks, P AF Woodworth, TG Furst, DE Strand, V Kempeni, J Fenner, H Lau, CS Miller, F Day, R Lipani, J Brooks, P TI Standardizing assessment of adverse effects in rheumatology clinical trials. Status of OMERACT Toxicity Working Group March 2000: Towards a common understanding of comparative toxicity/safety profiles for antirheumatic therapies SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT 20th Congress of the International-League-of-Associations-for-Rheumatology CY AUG 26-30, 2000 CL EDMONTON, CANADA SP Int League Assoc Rheumatol DE adverse effects; rheumatic diseases; clinical trials; antirheumatic therapies AB This paper describes the background and current status of an OMERACT facilitated effort to improve the consistency of adverse event reporting in rheumatology clinical trials, The overall goal is the development of an adverse event assessment tool that would provide a basis for use of common terminology and improve the consistency of reporting severity of side effects within rheumatology clinical trials and during postmarketing surveillance. The resulting Rheumatology Common Toxicity Criteria Index encompassed the following organ systems: allergic/immunologic, cardiac, ENT, gastrointestinal, musculoskeletal, neuropsychiatric, ophthalmologic, pulmonary and skin/integument. Before this tool is widely accepted, its validity, consistency, and feasibility need to be assessed in clinical trials. C1 Pfizer Inc, Dept Clin Sci, Groton, CT 06340 USA. Virginia Mason Med Ctr, Seattle, WA 98101 USA. Fujisawa Pharmaceut, Neustadt, Germany. US FDA, Ctr Biol Evaluat & Review, Bethesda, MD 20014 USA. Univ New S Wales, Kensington, NSW 2033, Australia. Univ Queensland, Brisbane, Qld, Australia. RP Woodworth, TG (reprint author), Pfizer Inc, Dept Clin Sci, Bldg 260,Eastern Point Rd, Groton, CT 06340 USA. OI Day, Richard/0000-0002-6045-6937 NR 0 TC 27 Z9 28 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD MAY PY 2001 VL 28 IS 5 BP 1163 EP 1169 PG 7 WC Rheumatology SC Rheumatology GA 428XX UT WOS:000168487900044 PM 11361207 ER PT J AU Mullendore, JL Sobsey, MD Shieh, YSC AF Mullendore, JL Sobsey, MD Shieh, YSC TI Improved method for the recovery of hepatitis A virus from oysters SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE cell culture; detection; hepatitis A; oyster; PCR ID CLAMS MERCENARIA-MERCENARIA; A VIRUS; INDICATOR BACTERIA; NORWALK-VIRUS; PCR; CONSUMPTION AB Hepatitis A is one of the major infectious diseases epidemiologically associated with worldwide shellfish consumption. Molecular detection using polymerase chain reaction (PCR) to detect hepatitis A virus (HAV) in contaminated shellfish can be hindered by low virus recoveries during the concentration process and by natural PCR inhibitors in shellfish. This study evaluated and modified two major steps of a processing procedure for virus concentration from oysters: acid adsorption-elution and solvent extraction. With the addition of second and third elutions, the acid adsorption-elution step doubled the recovery to 46% of HAV seeded initially. Extraction with chloroform or chloroform-butanol resulted in lower HAV detection limits by reverse transcription-PCR (RT-PCR)-oligoprobing than extraction with the fluorocarbon, Freon. These results led to the following modified procedure: HAV was acid adsorbed at pH 4.8, eluted first with 0.05 M glycine, second with 0.5 M threonine, PEG-precipitated twice, chloroform-extracted twice. RNA-extracted. and RT-PCR(single round) amplified. Using the modified procedure, HAV was detected by RT-PCR in all trials with a seeding density of greater than or equal to 1 plaque forming unit (PFU)/g of oyster, and in which the equivalent detection limit was 0.33 PFU of HAV seeded per RT- PCR reaction (corresponding to 111 PCR units). The method developed is capable of detecting low levels of HAV in oysters environmentally contaminated. (C) 2001 Elsevier Science B.V. All rights reserved. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. Univ N Carolina, Dept Environm Sci & Engn, Chapel Hill, NC 27599 USA. RP Shieh, YSC (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. NR 23 TC 63 Z9 67 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD MAY PY 2001 VL 94 IS 1-2 BP 25 EP 35 DI 10.1016/S0166-0934(01)00263-4 PG 11 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 431CP UT WOS:000168614600004 PM 11337037 ER PT J AU Takefman, DM Wong, S Maudru, T Peden, K Wilson, CA AF Takefman, DM Wong, S Maudru, T Peden, K Wilson, CA TI Detection and characterization of porcine endogenous retrovirus in porcine plasma and porcine factor VIII SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; HUMAN-CELLS; NO EVIDENCE; HOST-RANGE; PIG; INFECTION; TROPISM; IDENTIFICATION; INTERFERENCE; INACTIVATION AB The pig genome contains porcine endogenous retroviruses (PERVs) capable of infecting human cells. Detection of infectious retrovirus in porcine peripheral blood mononuclear cells and endothelial cells suggested to us that pig plasma is likely to contain PERV, Both PERV env sequences and viral reverse transcriptase (RT) activity were detected in all plasma samples isolated from four NIH minipigs. To detect infectious virus from plasma, we performed a culture assay using three cell lines of feline, swine, and human origin that had previously been shown to be permissive for PERV, Infectious virus was successfully cultured from all four NIH minipig plasmas on the swine cell line ST-IOWA. Using RT-PCR with env-specific primers, we could detect expression of PERV class C envelope in the supernatant of ST-IOWA cells that had been exposed to each pig plasma. We next examined a pig plasma derivative, Hyate:C (porcine factor VIII), and found evidence of PERV particles, since all six lots examined were positive for PERV RNA and RT activity. However, infectious virus could not be detected in clinical lots of Hyate:C, suggesting that the manufacturing process might reduce the load of infectious virus to levels below detectable limits of the assay, Detection of infectious virus in porcine plasma confirms and extends the previous findings that certain porcine cells express PERV when manipulated in vitro and clearly demonstrates that there are porcine cells that express infectious PERV constitutively in vivo. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD 20892 USA. RP Wilson, CA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bldg 29B,Room NN11,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 29 TC 32 Z9 35 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 2001 VL 75 IS 10 BP 4551 EP 4557 DI 10.1128/JVI.75.10.4551-4557.2001 PG 7 WC Virology SC Virology GA 425UD UT WOS:000168309300009 PM 11312325 ER PT J AU Bacon, DJ Szymanski, CM Burr, DH Silver, RP Alm, RA Guerry, P AF Bacon, DJ Szymanski, CM Burr, DH Silver, RP Alm, RA Guerry, P TI A phase-variable capsule is involved in virulence of Campylobacter jejuni 81-176 SO MOLECULAR MICROBIOLOGY LA English DT Article ID HEAT-STABLE ANTIGENS; ESCHERICHIA-COLI K1; SURFACE HYDROPHOBICITY; HELICOBACTER-PYLORI; POLYSIALIC ACID; LIPOPOLYSACCHARIDES; GENE; PLASMID; CELLS; CAMPYLOBACTER-JEJUNI-81-176 AB Campylobacter jejuni strain 81-176 (HS36, 23) synthesizes two distinct glycan structures, as visualized by immunoblotting of proteinase K-digested whole-cell preparations. A site-specific insertional mutant in the kpsM gene results in loss of expression of a high-molecular-weight (HMW) glycan (apparent M-r 26 kDa to > 85 kDa) and increased resolution of a second ladder-like glycan (apparent M-r 26-50 kDa). The kpsM mutant of 81-176 is no longer typeable in either HS23 or HS36 antisera, indicating that the HMW glycan structure is the serodeterminant of HS23 and HS36. Both the kpsM-dependent HMW glycan and the kpsM-independent ladder-like structure appear to be capsular in nature, as both are attached to phospholipid rather than lipid A. Additionally, the 81-176 kpsM gene can complement a deletion in Escherichia coli kpsM, allowing the expression of an alpha2,8 polysialic acid capsule in E. coli. Loss of the HMW glycan in 81-176 kpsM also increases the surface hydrophobicity and serum sensitivity of the bacterium. The kpsM mutant is also significantly reduced in invasion of INT407 cells and reduced in virulence in a ferret diarrhoeal disease model. The expression of the kpsM-dependent capsule undergoes phase variation at a high frequency. C1 USN, Med Res Ctr, Enter Dis Dept, Silver Spring, MD 20910 USA. US FDA, Laurel, MD USA. Univ Rochester, Dept Microbiol, Rochester, NY USA. Astra Zeneca Boston, Waltham, MA USA. RP Guerry, P (reprint author), USN, Med Res Ctr, Enter Dis Dept, 503 Robert Grant Ave, Silver Spring, MD 20910 USA. RI Guerry, Patricia/A-8024-2011 FU NIAID NIH HHS [AI39615, AI43559] NR 41 TC 184 Z9 186 U1 1 U2 7 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2001 VL 40 IS 3 BP 769 EP 777 DI 10.1046/j.1365-2958.2001.02431.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 433FE UT WOS:000168748300023 PM 11359581 ER PT J AU Boucher, PE Yang, MS Stibitz, S AF Boucher, PE Yang, MS Stibitz, S TI Mutational analysis of the high-affinity BvgA binding site in the fha promoter of Bordetella pertussis SO MOLECULAR MICROBIOLOGY LA English DT Article ID RNA-POLYMERASE; TRANSCRIPTIONAL ACTIVATION; VIRULENCE GENES; LOCUS AB In order to define a consensus binding sequence for the response regulator BvgA, we have undertaken a systematic analysis of contributions made by each nucleotide within the heptad half-sites that are present in an inverted orientation at the promoter for the fha operon. Using in vitro binding assays, we examined the full complement of 21 single point mutations symmetrically arranged in this heptad repeat, Both gel shift and nitrocellulose filter-binding assays provided evidence that nucleotides at positions 3 (thymidine), 4 (cytosine) and 7 (adenine) in the binding heptad contribute substantially to sequence-specific recognition by BvgA, Furthermore, a T to A conversion at position 6 reduced binding. Selected binding site mutations were introduced into a modified fha promoter and examined for their effects on BvgA activation of promoter activity in vivo, Only those substitutions most severely affecting binding in vitro affected promoter activity in vivo, The in vivo effects of substitutions that had a significant effect on binding in vitro but did not severely affect in vivo promoter activity under standard culture conditions could be detected in vivo either in combination with additional substitutions or from their effect on the sensitivity of the mutant promoters to modulation by magnesium sulphate. C1 US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Boucher, PE (reprint author), US FDA, Div Bacterial Parasit & Allergen Prod, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 18 TC 19 Z9 19 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0950-382X J9 MOL MICROBIOL JI Mol. Microbiol. PD MAY PY 2001 VL 40 IS 4 BP 991 EP 999 DI 10.1046/j.1365-2958.2001.02442.x PG 9 WC Biochemistry & Molecular Biology; Microbiology SC Biochemistry & Molecular Biology; Microbiology GA 441JG UT WOS:000169226800021 PM 11401705 ER PT J AU Ball, LK Ball, R Pratt, RD AF Ball, LK Ball, R Pratt, RD TI An assessment of thimerosal use in childhood vaccines SO PEDIATRICS LA English DT Article; Proceedings Paper CT National Vaccine Advisory Committee Worlkshop on Thimerosal in Vaccines CY AUG 11, 1999 CL BETHESDA, MARYLAND DE thimerosal; thiomersal; merthiolate; vaccine; immunization; mercury; methylmercury; ethylmercury; adverse event; risk assessment ID METHYLMERCURY; MERCURY; THIOMERSAL; VACCINATION; EXPOSURE AB Background. On July 7, 1999, the American Academy of Pediatrics and the US Public Health Service issued a joint statement calling for removal of thimerosal, a mercury-containing preservative, from vaccines. This action was prompted in part by a risk assessment from the Food and Drug Administration that is presented here. Methods. The risk assessment consisted of hazard identification, dose-response assessment, exposure assessment, and risk characterization. The literature was reviewed to identify known toxicity of thimerosal, ethylmercury (a metabolite of thimerosal) and methylmercury (a similar organic mercury compound) and to determine the doses at which toxicity occurs. Maximal potential exposure to mercury from vaccines was calculated for children at 6 months old and 2 years, under the US childhood immunization schedule, and compared with the limits for mercury exposure developed by the Environmental Protection Agency (EPA), the Agency for Toxic Substance and Disease Registry, the Food and Drug Administration, and the World Health Organization. Results. Delayed-type hypersensitivity reactions from thimerosal exposure are well-recognized. Identified acute toxicity from inadvertent high-dose exposure to thimerosal includes neurotoxicity and nephrotoxicity. Limited data on toxicity from low-dose exposures to ethylmercury are available, but toxicity may be similar to that of methylmercury. Chronic, low-dose methylmercury exposure may cause subtle neurologic abnormalities. Depending on the immunization schedule, vaccine formulation, and infant weight, cumulative exposure of infants to mercury from thimerosal during the first 6 months of life may exceed EPA guidelines. Conclusion. Our review revealed no evidence of harm caused by doses of thimerosal in vaccines, except for local hypersensitivity reactions. However, some infants may be exposed to cumulative levels of mercury during the first 6 months of life that exceed EPA recommendations. Exposure of infants to mercury in vaccines can be reduced or eliminated by using products formulated without thimerosal as a preservative. C1 US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, HFM 475, Rockville, MD 20852 USA. US FDA, Div Epidemiol, Off Biostat & Epidemiol, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Ball, LK (reprint author), US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, HFM 475, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 51 TC 191 Z9 200 U1 4 U2 34 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2001 VL 107 IS 5 BP 1147 EP 1154 DI 10.1542/peds.107.5.1147 PG 8 WC Pediatrics SC Pediatrics GA 427NA UT WOS:000168411100047 PM 11331700 ER PT J AU Wattigney, WA Mootrey, GT Braun, MM Chen, RT AF Wattigney, WA Mootrey, GT Braun, MM Chen, RT TI Surveillance for poliovirus vaccine adverse events, 1991 to 1998: Impact of a sequential vaccination schedule of inactivated poliovirus vaccine followed by oral poliovirus vaccine SO PEDIATRICS LA English DT Article DE inactivated poliovirus vaccine; oral poliovirus vaccine; vaccine adverse event surveillance ID REPORTING-SYSTEM VAERS; INFANT-DEATH-SYNDROME; UNITED-STATES; IMMUNIZATION; DIPHTHERIA; EPIDEMIOLOGY; SAFETY AB Background. The elimination of wild-virus-associated poliomyelitis in the Western Hemisphere in 1991 and rapid progress in global polio eradication efforts changed the risk-benefit ratio associated with the exclusive use of oral poliovirus vaccine (OPV) for routine immunization. These changes, plus the November 1987 development of an enhanced-potency inactivated poliovirus vaccine (IPV), which poses no risk of vaccine-associated paralytic poliomyelitis (VAPP), resulted in a change in polio immunization policy in the United States. In September 1996, the Centers for Disease Control and Prevention recommended that IPV replace OPV for the first 2 doses in a sequential poliovirus vaccine schedule. The Vaccine Adverse Event Reporting System (VAERS), a passive surveillance system for adverse events after receipt of any US-licensed vaccine, is used to monitor postlicensure vaccine safety. Postlicensure surveillance of vaccines is important to identify new, rare, or delayed-onset adverse reactions not detected in prelicensure clinical trials or when new vaccine schedules are adopted. Through continual monitoring of adverse events and identification of potential vaccine risks, VAERS can serve as an important resource to ensure continued public acceptance of vaccines. We compared VAERS reports after the receipt of IPV to reports after OPV in infants from 1991 through 1998. Comparisons included reports listing IPV and OPV coadministered with other vaccines. Methods. Annual reporting rates per 100 000 doses distributed within 3 severity categories (fatal, nonfatal serious, less serious) were examined. Distributions of severity categories by vaccine type, age, and time period (pre- and postrecommendation) were constructed. Safety profiles (distribution of 21 symptom groupings) for IPV and OPV reports were compared. Analysis was restricted to reports for infants 1 to 3 months old and 4 to 6 months old, corresponding generally to first- and second-dose recipients. Any notable increase in a severity or safety category for IPV compared with OPV was followed up by examining the frequency of specific symptoms, reporting source, and date of vaccination. An important limitation of VAERS is that reports do not necessarily represent adverse events caused by vaccines. In many cases, the events are temporal associations only. Results. The annual rates of VAERS reports per 100 000 vaccine doses distributed by severity category, 1991 to 1998, were in general similar for reports after IPV compared with those after OPV. The reporting rates for poliovirus vaccine did not increase materially with the shift to IPV usage. The relative frequencies of symptoms in the fatal and nonfatal serious categories for 1998 vaccine administrations were similar to 1997 reports. Severity profiles for IPV and OPV reports in infants 1 to 3 months old and 4 to 6 months old, corresponding to first- and second- dose recipients, were remarkably similar. The frequency of symptoms listed on IPV reports categorized as fatal or serious was examined by age, vaccine combinations, and time period, and the distribution of symptoms was similar for ages 1 to 3 months and 4 to 6 months. In the postrecommendation period, the 10 most frequent symptoms reported with IPV were also reported with OPV in either similar or lower relative frequency. During the postrecommendation period, safety profiles for infants 4 to 6 months old showed a 2.5% higher proportion in the allergic reaction category for IPV than for OPV, but none of the allergic reaction reports indicated anaphylaxis. In general, the distribution of symptom groupings was not markedly different for IPV compared with OPV. No cases of VAPP were reported after the administration of IPV, whereas 5 VAPP cases were reported after the administration of OPV. Conclusions. Although VAERS is subject to the limitations of most passive surveillance systems, the large number of reports and national coverage provide a unique database for monitoring vaccine safety. There was a marked increase of IPV reports in VAERS after 1996, consistent with implementation of the Advisory Committee on Immunization Practices recommendation for the sequential IPV/OPV poliovirus vaccination schedule. Given the increased use of IPV, a review of potential adverse events in VAERS compared IPV with OPV reports both before and after the introduction of the sequential vaccination schedule. Vaccine safety surveillance indicated no adverse events patterns of potential concern following the use of IPV in infants after the introduction of the sequential vaccination schedule. Ongoing surveillance is documenting a decrease in VAPP. These findings provide useful information to support the Advisory Committee on Immunization Practices recommendation, made in 1999, to shift to an all-IPV schedule. C1 Ctr Dis Control & Prevent, Natl Immunizat Program, Atlanta, GA 30341 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Wattigney, WA (reprint author), Ctr Dis Control & Prevent, Natl Immunizat Program, 4770 Buford Hwy NE,Mailstop K-47, Atlanta, GA 30341 USA. NR 36 TC 16 Z9 20 U1 1 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAY PY 2001 VL 107 IS 5 AR e83 DI 10.1542/peds.107.5.e83 PG 7 WC Pediatrics SC Pediatrics GA 427NA UT WOS:000168411100020 PM 11331733 ER PT J AU Bortnichak, EA Wise, RP Salive, ME Tilson, HH AF Bortnichak, EA Wise, RP Salive, ME Tilson, HH TI Proactive safety surveillance SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE proactive safety surveillance; pharmacovigilance; pharmacoepidemiology; drug safety; product safety screening strategies; exploratory data analysis; signal detection AB Growth in health information systems presents opportunities to enhance postmarketing safety surveillance of medical products. Spontaneous suspected side effect reports provide the foundation, but we need to 'proactively' improve their quality and our strategies to seek signals. In our more familiar 'reactive' mode, we examine hypotheses from inquiries or publicity. Such responsive evaluations remain essential but may miss latent information on unsuspected risks. Efficient techniques to disclose hidden clusters and associations may emerge through adaptation of approaches from industrial quality control and other disciplines. Data-driven techniques like exploratory analysis, control charts, and time series modeling may help in sifting through accumulated data and in screening consecutive submissions to discern hints of new product hazards or of more specific understanding about previously identified potential side effects. We also need to cultivate non-spontaneous data for hypothesis generation as well as testing, the systematic epidemiologic evaluation of questions and concerns. This hypothesis testing function will assume greater importance if proactive safety surveillance methods yield larger numbers of putatively positive findings. Whether from spontaneous reports or other sources, signals that could have arisen by chance alone usually represent only clues to potential hazards until or unless they can be verified through independent studies. Copyright (C) 2001 John Wiley & Sons, Ltd. C1 Berlex Labs Inc, Corp Epidemiol & Publ Hlth Evaluat, Montville, NJ USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ N Carolina, Chapel Hill, NC 27515 USA. RP Bortnichak, EA (reprint author), Sanofi Synthelabo Inc, 90 Pk Ave,8th Floor, New York, NY 10016 USA. NR 21 TC 8 Z9 8 U1 2 U2 2 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 MAY PY 2001 VL 10 IS 3 BP 191 EP 196 DI 10.1002/pds.587 PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 458UA UT WOS:000170211900002 PM 11501330 ER PT J AU Uhl, K Honig, P AF Uhl, K Honig, P TI Risk management of marketed drugs: FDA and the interface with the practice of medicine SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Editorial Material ID HOSPITALIZED-PATIENTS; ADVERSE EVENTS; PHYSICIANS C1 US FDA, Off Postmkt Drug Risk Assessment, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Uhl, K (reprint author), US FDA, Off Postmkt Drug Risk Assessment, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 19 TC 13 Z9 13 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 MAY PY 2001 VL 10 IS 3 BP 205 EP 208 DI 10.1002/pds.594 PG 4 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA 458UA UT WOS:000170211900004 PM 11501332 ER PT J AU Hoshaw, SJ Klein, PJ Clark, BD Cook, RR Perkins, LL AF Hoshaw, SJ Klein, PJ Clark, BD Cook, RR Perkins, LL TI Breast implants and cancer: Causation, delayed detection, and survival SO PLASTIC AND RECONSTRUCTIVE SURGERY LA English DT Article ID AUGMENTATION MAMMAPLASTY; SILICONE IMPLANTS; UNITED-STATES; LOS-ANGELES; WOMEN; RISK; GEL; RECONSTRUCTION; MAMMOGRAPHY; MASTECTOMY AB Concern for many women with breast implants has been focused on three topics: cancer (both breast and other cancers), delayed detection of breast cancer, and increased breast cancer recurrence or decreased length of survival. In this study, a qualitative review of the literature on these subjects was conducted, coupled with a metaanalysis of the risk for breast cancer or other cancers (excluding that of the breast). Researchers have consistently found no persuasive evidence of a causal association between breast implants and any type of cancer. The metaanalysis results obtained by combining the epidemiology studies support the overall conclusion that breast implants do not pose any additional risk for breast cancer (relative risk, 0.72; 95% confidence interval, 0.61 to 0.85) or for other cancers (relative risk, 1.03; 95% confidence interval, 0.87 to 1.24). This analysis suggests that breast implants may confer a protective effect against breast cancer. Women with implants should be reassured by the consistency of scientific studies which have uniformly determined that, compared with women without implants, they are not at increased risk for cancer, are not diagnosed with later-stage breast malignancies, are not at increased risk for breast cancer recurrence, and do not have a decreased length of survival. C1 RRC Consulting LLC, Midland, MI USA. Dow Corning Corp, Div FDA Regulatory Affarirs & Womens Hlth Issues, Midland, MI USA. Dow Corning Corp, Div Epidemiol, Midland, MI USA. RP Hoshaw, SJ (reprint author), Dow Corning Corp, Mael C01272, Midland, MI 48686 USA. NR 93 TC 39 Z9 40 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0032-1052 J9 PLAST RECONSTR SURG JI Plast. Reconstr. Surg. PD MAY PY 2001 VL 107 IS 6 BP 1393 EP 1408 DI 10.1097/00006534-200105000-00012 PG 16 WC Surgery SC Surgery GA 426JE UT WOS:000168345400012 PM 11335807 ER PT J AU Palinkas, LA Reed, HL Reedy, KR Van Do, N Case, HS Finney, NS AF Palinkas, LA Reed, HL Reedy, KR Van Do, N Case, HS Finney, NS TI Circannual pattern of hypothalamic-pituitary-thyroid (HPT) function and mood during extended antarctic residence SO PSYCHONEUROENDOCRINOLOGY LA English DT Article DE mood; cold; thyroid; circannual rhythms; thyrotropin-releasing hormone; Antarctica ID SEASONAL AFFECTIVE-DISORDER; HYPOTHYROIDISM; DEPRESSION; LIGHT; PHOTOTHERAPY; PREVALENCE; THYROXINE; SYMPTOMS; HORMONE; THERAPY AB The seasonal variation in thyroid function and mood was examined in 10 men and two women who spent the 1997 or 1998 austral winter at McMurdo Station, Antarctica. Serum samples of TSH, free T-3 and free T-4 were collected each month over a 10-month period (October-August), along with responses to the Profile of Mood States (POMS) and the Center for Epidemiologic Studies - Depression (CES-D) Scale. Both TSH and mood (a summary score created from the POMS depression, anger, fatigue and confusion subscales) exhibited a circannual pattern with peaks during the months of November and July and a trough during the months of March and April. High levels of tension-anxiety and confusion were preceded by declines in free T-3 and T-4. However, increases in tension-anxiety and total mood disturbance also preceded a decline in free T-3 levels, suggesting a feedback of mood on T-3 levels. Levels of free T-4 were independently associated with preceding increases in anger scores, These results support the hypothesis that the symptoms characteristic of the winter-over syndrome is a state of relative CNS hypothyroidism. This model of seasonal variation in thyroid function and mood also has implications for an understanding of potential mechanisms underlying the association between latitude and SAD or S-SAD. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Univ Calif San Diego, Dept Family & Prevent Med, La Jolla, CA 92093 USA. Madigan Army Med Ctr, Dept Med, Endocrine Serv, Tacoma, WA 98431 USA. US FDA, Rockville, MD 20857 USA. Western Maryland Coll, Dept Exercise Sci & Phys Educ, Westminster, MD 21157 USA. RP Palinkas, LA (reprint author), Univ Calif San Diego, Dept Family & Prevent Med, 9500 Gilman Dr, La Jolla, CA 92093 USA. NR 37 TC 20 Z9 24 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0306-4530 J9 PSYCHONEUROENDOCRINO JI Psychoneuroendocrinology PD MAY PY 2001 VL 26 IS 4 BP 421 EP 431 DI 10.1016/S0306-4530(00)00064-0 PG 11 WC Endocrinology & Metabolism; Neurosciences; Psychiatry SC Endocrinology & Metabolism; Neurosciences & Neurology; Psychiatry GA 420QR UT WOS:000168016100006 PM 11259861 ER PT J AU Hansen, DK Grafton, TF Melnyk, S James, SJ AF Hansen, DK Grafton, TF Melnyk, S James, SJ TI Lack of embryotoxicity of homocysteine thiolactone in mouse embryos in vitro SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE whole embryo culture; homocysteine; teratogenicity; embryotoxicity; folic acid; cystathionine ID NEURAL-TUBE DEFECTS; CYSTATHIONINE-BETA-SYNTHASE; ASPARTATE RECEPTOR ANTAGONISTS; AMNIOTIC-FLUID; PLASMA HOMOCYSTEINE; REDUCTASE GENOTYPE; SPINA-BIFIDA; RAT EMBRYOS; METABOLISM; METHIONINE AB Recent work from humans and chick embryos has suggested that homocysteine may play a role in producing neural tube defects (NTDs). In an effort to determine if homocysteine is able to produce NTDs in mammalian embryos, mouse embryos were explanted on CD 8 and cultured for 44 h. When either homocysteine or homocysteine thiolactone was added to the culture medium, treated embryos developed as well as controls and had closed neural tubes. Homocysteine thiolactone was also microinjected into the amniotic sac of mouse embryos. Again, development proceeded normally with no significant increase in the number of embryos with open neural tubes at the end of the culture period. HPLC analysis of embryonic thiols 24 h after microinjection revealed a significant increase in embryonic cystathionine levels. These data suggest that homocysteine does not produce NTDs in mouse embryos cultured in vitro and that early organogenesis-stage embryos are able to metabolize homocysteine. (C) 2001 Elsevier Science Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Hansen, DK (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 33 TC 24 Z9 25 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAY-JUN PY 2001 VL 15 IS 3 BP 239 EP 244 DI 10.1016/S0890-6238(01)00133-2 PG 6 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 441QW UT WOS:000169241900003 PM 11390167 ER PT J AU Hard, GC Howard, PC Kovatch, RM Bucci, TJ AF Hard, GC Howard, PC Kovatch, RM Bucci, TJ TI Rat kidney pathology induced by chronic exposure to fumonisin B1 includes rare variants of renal tubule tumor SO TOXICOLOGIC PATHOLOGY LA English DT Article DE adenoma; apoptosis; atypical tubule hyperplasia; carcinoma; metastases; mycotoxin; nephrotoxicity ID SPRAGUE-DAWLEY RATS; CELL CARCINOMA; SPHINGOLIPID METABOLISM; HUMAN KERATINOCYTES; B-1; APOPTOSIS; MYCOTOXINS; INDUCTION; DIMETHYLNITROSAMINE; CLASSIFICATION AB The carcinogenicity of fumonisin B-1 (FB1), a worldwide contaminant of corn produced by Fusaria species of fungi, has been tested recently in 2-year feeding studies in Fischer F344 rats and B6C3F1 mice. Inclusion of FB1 at 50 and 80 ppm in the diet induced liver tumors in female mice, and at 50 and 150 ppm induced renal tumors in male rats (22). In the present study, the kidneys from the rat bioassay were examined to characterize the various histopathological changes associated with renal tumor induction. In all high-dose (150 ppm) and mid-dose (50 ppm) male rats, and to a lesser extent in high-dose (100 ppm) female rats, there was evidence of sustained nephrotoxicity manifested as basophilia, apoptosis, cell regeneration, and simple tubule hyperplasia, affecting proximal convoluted tubules in the deep cortex, extending into the outer region of the outer stripe of outer medulla. A further alteration consisted of sporadic areas of interstitial hyalinization in deep cortex, suggestive of expanded basement membrane, coupled with tubule atrophy. The continued presence of nephrotoxicity throughout chronic exposure to FB1 suggested that renal tumor development may have been an outcome of sustained cell loss and compensatory regeneration. In some cases, preneoplastic tubules or incipient renal tumors presented an immature or fetal form in association with interstitial hyalinization. The renal tubule tumors induced by FB1 were typified by a rare, highly malignant, anaplastic variant capable of growth by infiltration. Of the 10 renal tubule tumors diagnosed in the mid-dose males, and the 16 in the high-dose males, 8 and 10, respectively, were graded as carcinomas. Anaplastic variants represented 50% of the mid-dose carcinomas and 80% of the high-dose carcinomas. One of the anaplastic carcinomas in a mid-dose male was a true sarcomatoid phenotype not previously recorded in the rodent. Metastatic invasion of the lung occurred with 25% of the mid-dose carcinomas and 50% of the high-dose carcinomas. It was speculated that FB1 may have been influencing the growth characteristics of the induced renal tumors via its inhibitory action on the synthesis of sphingolipids, which in turn, participate in regulating cell contact, growth, and differentiation, or alternatively by affecting cell adhesion molecules. C1 Amer Hlth Fdn, Valhalla, NY 10595 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Pathol Associates Int, Jefferson, AR 72079 USA. RP Hard, GC (reprint author), Amer Hlth Fdn, 1 Dana Rd, Valhalla, NY 10595 USA. NR 40 TC 27 Z9 30 U1 0 U2 3 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 2001 VL 29 IS 3 BP 379 EP 386 DI 10.1080/019262301316905345 PG 8 WC Pathology; Toxicology SC Pathology; Toxicology GA 558CZ UT WOS:000175949700013 PM 11442024 ER PT J AU Dragan, YP Bidlack, WR Cohen, SM Goldsworthy, TL Hard, GC Howard, PC Riley, RT Voss, KA AF Dragan, YP Bidlack, WR Cohen, SM Goldsworthy, TL Hard, GC Howard, PC Riley, RT Voss, KA TI Implications of apoptosis for toxicity, carcinogenicity, and risk assessment: Fumonisin B-1 as an example SO TOXICOLOGICAL SCIENCES LA English DT Article DE apoptosis; fumonisin; mycotoxins; kidney cancer; liver cancer; regeneration; carcinogenesis ID ESOPHAGEAL CANCER AREAS; FUSARIUM-MONILIFORME; CELL-PROLIFERATION; RAT-LIVER; N-NITROSOMETHYLBENZYLAMINE; CULTURE MATERIAL; PROMOTING ACTIVITY; IN-VIVO; MYCOTOXINS; CORN AB The rates of cell proliferation and cell loss in conjunction with the differentiation status of a tissue are among the many factors contributing to carcinogenesis. Nongenotoxic (non-DNA reactive) chemicals may affect this balance by increasing proliferation through direct mitogenesis or through a regenerative response following loss of cells through cytotoxic (oncotic) or apoptotic necrosis. In a recent NTP study in Fischer rats and B6C37F(1) mice, the mycotoxin fumonisin B-1 caused renal carcinomas in male rats and liver cancer in female mice. In an earlier study in male ED-IS rats, fumonisin B-1 caused hepatic toxicity and hepatocellular carcinomas. An early effect of fumonisin B-1 exposure in these target organs is apoptosis. However, there is also some evidence of oncotic necrosis following fumonisin B-1 administration, especially in the liver. Induction of apoptosis may be a consequence of ceramide synthase inhibition and disruption of sphingolipid metabolism by fumonisin B-1. Fumonisin B-1 is not genotoxic in bacterial mutagenesis screens or in the rat liver unscheduled DNA-synthesis assay, Fumonisin B-1 may be the first example of an apparently nongenotoxic (non-DNA reactive) agent producing tumors through a mode of action involving apoptotic necrosis, atrophy, and consequent regeneration. C1 Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, Omaha, NE 68198 USA. Ohio State Univ, James Canc Ctr, Columbus, OH 43210 USA. Calif State Polytech Univ Pomona, Coll Agr, Pomona, CA 91768 USA. Integrated Lab Syst Inc, Div Hlth Sci, Res Triangle Pk, NC 27709 USA. Amer Hlth Fdn, Valhalla, NY 10595 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. USDA, Toxicol & Mycotoxin Res Unit, Athens, GA 30604 USA. RP Cohen, SM (reprint author), Univ Nebraska, Med Ctr, Dept Pathol & Microbiol, 983135 Nebraska Med Ctr, Omaha, NE 68198 USA. NR 93 TC 76 Z9 77 U1 1 U2 9 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAY PY 2001 VL 61 IS 1 BP 6 EP 17 DI 10.1093/toxsci/61.1.6 PG 12 WC Toxicology SC Toxicology GA 423YD UT WOS:000168204600003 PM 11294969 ER PT J AU Lachenbruch, PA AF Lachenbruch, PA TI Comparisons of two-part models with competitors SO STATISTICS IN MEDICINE LA English DT Article ID ROBUSTNESS AB Two-part models arise when there is a clump of 0 observations in a distribution of continuous nonnegative responses. Several methods for comparing two such distributions are available. These include the straightforward application of the z-test (or t-test), the Wilcoxon-Mann-Whitney rank sum test, the Kolmogorov-Smirnov test, and three tests that use a 2 degree of freedom chi (2) test based on the sum of the test for equality of proportions and a conditional chi (2) test for the continuous responses. This conditional test may be the z-test, the rank sum test, or the chi (2) corresponding to the Kolmogorov-Smirnov test. This study compares the size and power of several of these methods. All tests have the appropriate distribution under the null hypothesis if the distribution of the continuous part has finite moments. If it does not, the z-test has no power to detect any alternatives. It is found that the 2 d.f. tests are superior to the others when the larger proportion of 0 values corresponds to the population with the larger mean. If the reverse holds, the difference in the proportion of zeros reinforces the difference in means and some single-part models (the rank sum or Kolmogorov-Smirnov) do best. In those cases, the two-part models are not far behind, although statistically significantly poorer with respect to power. Published in 2001 by John Wiley & Sons, Ltd. C1 US FDA, CDER, Div Biostat & Epdicemiol, Rockville, MD 20852 USA. RP Lachenbruch, PA (reprint author), US FDA, CDER, Div Biostat & Epdicemiol, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 12 TC 55 Z9 55 U1 0 U2 2 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 APR 30 PY 2001 VL 20 IS 8 BP 1215 EP 1234 DI 10.1002/sim.790 PG 20 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 425XX UT WOS:000168317900006 PM 11304737 ER PT J AU Lachenbruch, PA AF Lachenbruch, PA TI Power and sample size requirements for two-part models SO STATISTICS IN MEDICINE LA English DT Article AB Two-part models assume the data has a probability mass at zero and a continuous response for values greater than 0. We construct tests based on the proportion of zeros and the difference among the positive values of a response giving rise to a two degree of freedom chi (2) test. This note gives the non-centrality parameter and finds the power for the test. The power is compared to the simulation results in a recent paper. We derive sample size calculations. We note that some modifications of this procedure may provide better tests if the non-zero responses are discrete. Published in 2001 by John Wiley & Sons, Ltd. C1 US FDA, CDER, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, Rockville, MD 20852 USA. RP Lachenbruch, PA (reprint author), US FDA, CDER, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, 140 Rockville Pike, Rockville, MD 20852 USA. NR 9 TC 19 Z9 19 U1 0 U2 5 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 APR 30 PY 2001 VL 20 IS 8 BP 1235 EP 1238 DI 10.1002/sim.812 PG 4 WC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Medicine, Research & Experimental; Statistics & Probability SC Mathematical & Computational Biology; Public, Environmental & Occupational Health; Medical Informatics; Research & Experimental Medicine; Mathematics GA 425XX UT WOS:000168317900007 PM 11304738 ER PT J AU Lee, CJ Wang, TR Frasch, CE AF Lee, CJ Wang, TR Frasch, CE TI Immunogenicity in mice of pneumococcal glycoconjugate vaccines using pneumococcal protein carriers SO VACCINE LA English DT Article DE polysaccharide; glycoconjugate; pneumococcal protein ID STREPTOCOCCUS-PNEUMONIAE; CONJUGATE VACCINES; TYPE-19F POLYSACCHARIDE; PROTECTIVE IMMUNITY; ANTIBODY-RESPONSES; PNEUMOLYSIN; INFECTION; AVIDITY; BINDING; STANDARDIZATION AB Antibody response and protective immunity were evaluated in mice immunized with pneumococcal glycoconjugate vaccines using two pneumococcal protein carriers. Mice injected with type 9V polysaccharide (PS) conjugated to inactivated pneumolysin (Ply) or autolysin (Aly) produced high levels of IgG and IgM antibodies to both the PS and the protein carrier. Higher PS antibody titers to the pneumococcal PS conjugates were measured by ELISA using PS-Ply or PS-tetanus toroid (TT) conjugate as a coating antigen compared with PS mixed with methylated human serum albumin. Type 9V PS (10 mug) inhibited most of the 9V IgM and IgG antibody binding to the 9V-TT coated plate. In contrast, absorption with 19F PS did not inhibit 9V antibody binding. The avidity index of Ige antibodies in the: 9V PS-Ply serum was 55.5 +/- 0.9. compared with 47.8 +/- 1.4 for 9V PS-Aly serum. Thus. high avidity of serum antibodies in conjugate-immunized mice can provide more effective functional activity for protection against pneumococcal infection. Mice immunized with these glycoconjugates exhibited rapid bacterial clearance from blood and provided cross-protection against challenge with heterologous serotypes of virulent pneumococci. These results reveal that conjugates using pneumococcal protein carriers can induce opsonophagocytic activity to destroy homologous and heterologous pneumococci. indicating that such conjugates can confer broader protective immunity than conjugates using nonpneumococcal proteins. Published by Elsevier Science Ltd. C1 US FDA, Ctr Biol Evaluat & Res, NIH, Bethesda, MD 20892 USA. RP Lee, CJ (reprint author), US FDA, Ctr Biol Evaluat & Res, NIH, Bldg 29,Room 405,1401 Rockville Pike, Bethesda, MD 20892 USA. NR 43 TC 15 Z9 18 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 APR 30 PY 2001 VL 19 IS 23-24 BP 3216 EP 3225 DI 10.1016/S0264-410X(01)00033-0 PG 10 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 430NA UT WOS:000168579000023 PM 11312018 ER PT J AU Guiso, N Boursaux-Eude, C Weber, C Hausman, SZ Sato, H Iwaki, M Kamachi, K Konda, T Burns, DL AF Guiso, N Boursaux-Eude, C Weber, C Hausman, SZ Sato, H Iwaki, M Kamachi, K Konda, T Burns, DL TI Analysis of Bordetella pertussis isolates collected in Japan before and after introduction of acellular pertussis vaccines SO VACCINE LA English DT Article DE Bordetella pertussis; acellular vaccines; Japan ID B-OLIGOMER; TOXIN; STRAINS; MODEL AB Because of recent concern that whole-cell pertussis vaccination can drive antigenic divergence of circulating isolates of Bordetella pertussis. we compared 12 clinical isolates of B. pertussis collected in Japan, the first country to introduce acellular pertussis vaccines, with the vaccine strain. We used pulsed-field gel electrophoresis. sequencing of ptx and pm genes and expression of fimbriae. Most of the isolates collected before or after introduction of acellular vaccine possess similar restriction patterns. They contain ptx genes and pm alleles similar to the vaccine strain and to European isolates collected before the introduction of vaccination. Two recently collected isolates exhibiting a different pulsed-field gel electrophoresis pattern possess ptxS1 and pm alleles similar to the alleles harbored by European isolates circulating currently. Our preliminary results suggest that, if acellular pertussis antigenic divergence exists, it is likely to be a slow or rare process. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 Inst Pasteur, Ctr Natl Reference Bordetelles, Unite Bordetella, Paris, France. Natl Inst Infect Dis, Dept Bacterial & Blood Prod, Tokyo, Japan. US FDA, Ctr Biol Evaluat & Res, Lab Resp & Special Pathogens, Bethesda, MD USA. RP Guiso, N (reprint author), Inst Pasteur, Ctr Natl Reference Bordetelles, Unite Bordetella, Paris, France. NR 22 TC 26 Z9 28 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD APR 30 PY 2001 VL 19 IS 23-24 BP 3248 EP 3252 DI 10.1016/S0264-410X(01)00013-5 PG 5 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 430NA UT WOS:000168579000026 PM 11312021 ER PT J AU Oshima, Y Puri, RK AF Oshima, Y Puri, RK TI A novel interleukin-13 (IL-13) antagonist that blocks the biological activity of human IL-13 in immune and nonimmune cells SO FASEB JOURNAL LA English DT Article DE pleiotropic cytokine; inflammatory disease ID RECEPTOR-ALPHA CHAIN; HIGH-AFFINITY INTERLEUKIN-4; REED-STERNBERG CELLS; HUMAN GLIOMA-CELLS; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; SIGNAL-TRANSDUCTION; CARCINOMA-CELLS; ERYTHROPOIETIN RECEPTOR; PROLIFERATIVE ACTIVITY AB The pleiotropic cytokine interleukin-13 (IL-13) plays a major role in the pathogenesis of inflammatory diseases, including allergic rhinitis, atopic dermatitis, allergic asthma, and malignancies. Therefore, specific inhibitors of IL-13 may have important clinical applications. We have previously produced a super agonist of IL-13 (termed IL-13R112D) by single amino acid substitution changing Arg to Asp at position 112. In an effort to create a cell-selective IL-13 agonist, we performed a second mutation in the IL-13R112D molecule substituting Lys for Glu at position 13. Unexpectedly, rather than an agonist, this novel double mutein (IL-13 DM, termed IL-13E13KR112D, turned out to be an IL-13 antagonist. It competes for I-125-IL-13 binding sites as effectively as wtIL-13. Designation of IL-13E13KR112D as an IL-13 antagonist is supported further by a second assay involving a fusion protein consisting of the bacterial cytotoxic molecule PE38QQR as well as wtIL-13 (IL-13-PE38QQR or IL-13 cytotoxin). IL-13E13KR112D neutralizes the cytotoxic activity of IL-13 cytotoxin exhibited in U251 and PM-RCC cancer cell lines. In addition, IL-13E13KR112D inhibits the proliferative activity of wtIL-13 in TF-1 and L1236 hematopoietic cell lines, neutralizes wtIL-13 induced inhibition of CD14 expression on primary monocytes, and prevents wtIL-13 induced activation of signal transducer and activator of transcription (STAT-6) protein in KSY-1 and THP-1 cell lines. Thus, IL-13E13KR112D may be a useful agent for the study of interaction between IL-13 and its cognate receptors and may contribute to the development of new treatments for inflammatory diseases, even malignancies, in which IL-13 plays a central role. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,NIH, 29 Lincoln Dr,NIH Bldg 29B,Room 2NN10, Bethesda, MD 20892 USA. EM puri@cber.fda.gov NR 66 TC 6 Z9 6 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 APR 27 PY 2001 VL 15 IS 6 BP 1469 EP + DI 10.1096/fj.00-0711fje PG 23 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 519BV UT WOS:000173705800007 PM 11387260 ER PT J AU Shallow, S Samuel, M McNees, A Rothrock, G Vugia, D Fiorentino, T Marcus, R Hurd, S Mshar, P Phan, Q Cartter, M Hadler, J Farley, M Baughman, W Segler, S Lance-Parker, S MacKenzie, W McCombs, K Blake, P Morris, JG Hawkins, M Roche, J Smith, K Besser, J Swanson, E Stenzel, S Medus, C Moore, K Zansky, S Hibbs, J Morse, D Smith, P Cassidy, M McGivern, T Shiferaw, B Cieslak, P Kohn, M Jones, T Craig, A Moore, W CDC AF Shallow, S Samuel, M McNees, A Rothrock, G Vugia, D Fiorentino, T Marcus, R Hurd, S Mshar, P Phan, Q Cartter, M Hadler, J Farley, M Baughman, W Segler, S Lance-Parker, S MacKenzie, W McCombs, K Blake, P Morris, JG Hawkins, M Roche, J Smith, K Besser, J Swanson, E Stenzel, S Medus, C Moore, K Zansky, S Hibbs, J Morse, D Smith, P Cassidy, M McGivern, T Shiferaw, B Cieslak, P Kohn, M Jones, T Craig, A Moore, W CDC TI Preliminary FoodNet data on the incidence of foodborne illnesses - Selected sites, United States, 2000 (Reprinted from MMWR, vol 50, pg 241-246, 2001) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 Calif Emerging Infect Program, Sacramento, CA 95814 USA. Calif Dept Hlth Serv, Sacramento, CA 95814 USA. Yale Univ, Sch Med, New Haven, CT USA. Connecticut State Dept Publ Hlth, Hartford, CT 06134 USA. Emory Univ, Sch Med, Atlanta, GA USA. Vet Affairs Med Ctr, Atlanta, GA 30033 USA. Georgia Dept Human Resources, Atlanta, GA 30303 USA. Univ Maryland, Dept Epidemiol & Prevent, Baltimore, MD 21201 USA. Maryland Dept Hlth & Mental Hyg, Baltimore, MD 21201 USA. Minnesota Dept Hlth, Minneapolis, MN 55414 USA. New York State Dept Hlth, Albany, NY 12237 USA. Oregon Hlth Dept Human Serv, Salem, OR 97310 USA. Tennessee Dept Hlth, Nashville, TN 37247 USA. US Food Safety & Inspect Serv, Off Publ Hlth & Sci, USDA, Washington, DC 20250 USA. US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. CDC, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. CDC, Parasit Dis Epidemiol Branch, Div Parasit Dis, Atlanta, GA 30333 USA. CDC, Off Director, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Shallow, S (reprint author), Calif Emerging Infect Program, Sacramento, CA 95814 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 25 PY 2001 VL 285 IS 16 BP 2071 EP 2073 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 422QW UT WOS:000168131600010 ER PT J AU Lester, DS Olds, JL AF Lester, DS Olds, JL TI Biomedical imaging: 2001 and beyond SO ANATOMICAL RECORD LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Lester, DS (reprint author), US FDA, Rockville, MD 20857 USA. RI Olds, James/D-2867-2011 NR 6 TC 2 Z9 4 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 0003-276X J9 ANAT REC JI Anat. Rec. PD APR 15 PY 2001 VL 265 IS 2 BP 35 EP 36 DI 10.1002/ar.1056 PG 2 WC Anatomy & Morphology SC Anatomy & Morphology GA 417PJ UT WOS:000167843100001 PM 11323768 ER PT J AU Husain, SR Joshi, BH Puri, RK AF Husain, SR Joshi, BH Puri, RK TI Interleukin-13 receptor as a unique target for anti-glioblastoma therapy SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE glioblastoma; interleukin-13 receptor; IL-13 toxin; in vivo tumor model; tumor regression ID CELL CARCINOMA-CELLS; CIRCULARLY PERMUTED INTERLEUKIN-4; KAPOSIS-SARCOMA CELLS; PSEUDOMONAS EXOTOXIN; PHASE-I; ANTITUMOR-ACTIVITY; FUSION-PROTEIN; CANCER-CELLS; BRAIN-TUMORS; IMMUNOTOXIN AB Surgery, radiotherapy and chemotherapy have minimally altered survival of glioblastoma patients. We explored a specific approach for glioblastoma therapy in which cellular interleukin-13 (IL-13) receptors were targeted by an IL-13 cytotoxin. A wide array of human glioblastoma cell lines expressing the receptor for IL-13 were effectively killed by an IL-13 cytotoxin, a chimeric protein composed of human IL-13 and a mutated form of Pseudomonas exotoxin (termed IL13-PE38QQR or IL-13 toxin). Daily (qd) intratumoral injections of IL-13 toxin (50 and 100 mug/kg/day) for 5 consecutive days into subcutaneous human U251 glioblastoma tumors (approx. 30 mm(2)) in nude mice resulted in complete regression of tumors in 4/5 and 5/5 mice, respectively. Tumor regression persisted for at least 221 days postimplantation. Three alternate day injections (qod) of IL-13 toxin (250 mug/kg/day) into other subcutaneous U87 glioblastoma tumors also produced durable complete responses (CR) in all 5 mice. Twice daily (bid) intraperitoneal injections of IL-13 toxin at 25 or 50 mug/kg/dose for 5 days (total doses = 10) regressed U251 tumors by 45% and 58% with 1/5 and 2/5 CRs, respectively, on day 54. Intraperitoneal administration of IL-13 toxin with an identical schedule at a dose of 50 mug/kg injected into mice bearing U87 xenografts reduced tumor burden by one-half on day 36. Similar doses (25 or 50 mug/kg) with a daily schedule (qd x 5) by the intravenous route also suppressed growth of U251 subcutaneous tumors by 75% and 81% with 1/6 CR in either group by day 34. All mice tolerated therapy well without any visible signs of toxicity. On the basis of these studies, we have initiated a Phase I clinical trial using IL13-PE38QQR in patients with recurrent glioblastoma. Published 2001 Wiley-Liss, Inc.(dagger). C1 NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bethesda, MD 20892 USA. RP Puri, RK (reprint author), NIH, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res,Food & Drug Adm, Bldg 29B,Room 2nn10,29 Lincoln Dr,MSC 4555, Bethesda, MD 20892 USA. NR 36 TC 91 Z9 98 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 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD APR 15 PY 2001 VL 92 IS 2 BP 168 EP 175 DI 10.1002/1097-0215(200102)9999:9999<::AID-IJC1182>3.0.CO;2-N PG 8 WC Oncology SC Oncology GA 414GA UT WOS:000167656800002 PM 11291041 ER PT J AU Guan, E Wang, JH Norcross, MA AF Guan, E Wang, JH Norcross, MA TI Identification of human macrophage inflammatory proteins 1 alpha and 1 beta as a native secreted heterodimer SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID MONOCYTE CHEMOATTRACTANT PROTEIN-1; BETA-CHEMOKINES; H-1-NMR SPECTROSCOPY; PLATELET FACTOR-4; CRYSTAL-STRUCTURE; NMR ASSIGNMENTS; CCR5 EXPRESSION; T-CELLS; RESOLUTION; DIMER AB Chemokines are secreted proteins that function as chemoattractants for leukocytes. The chemokines macrophage inflammatory protein 1 alpha and 1 beta (MIP-1 alpha and MIP-1 beta) now have been shown to be secreted from activated human monocytes and peripheral blood lymphocytes (PBLs) as a heterodimer. Immunoprecipitation and immunoblot analysis revealed that antibodies to either MIP-1 alpha or MIP-1 beta precipitated a protein complex containing both MIP-1 alpha and MIP-1 beta under normal conditions from culture supernatants and lysates of these cells. Mass spectrometry of the complexes, precipitated from the culture supernatants of monocytes and PBLs, revealed the presence of NH2-terminal truncated MIP-1 alpha (residues 5-70) together with either intact MIP-1 beta or NH2-terminal truncated MIP-1 beta (residues 3-69), respectively. The secreted MIP-1 alpha/beta heterodimers were dissociated into their component monomers under acidic conditions. Exposure of monocytes or PBLs to monensin induced the accumulation of heterodimers composed of NH2-terminal truncated MTP-1 alpha and full-length MIP-1 beta in the Golgi complex. The mixing of recombinant chemokines in vitro demonstrated that heterodimerization of MIP-1 alpha and MIP-1 beta is specific and that it occurs at physiological conditions, pH 7.4, and in the range of nanomolar concentrations. The data presented here provide the first biochemical evidence for the existence of chemokine heterodimers under natural conditions. Formation of heterodimers of MIP-1 alpha/beta may have an impact on intracellular signaling events that contribute to CCR5 and possibly to other chemokine receptor functions. C1 NIH, Lab Gene Regulat, Div Therapeut Prot, Ctr Biol Evaluat & Res,US FDA,HFM 535, Bethesda, MD 20892 USA. RP Guan, E (reprint author), NIH, Lab Gene Regulat, Div Therapeut Prot, Ctr Biol Evaluat & Res,US FDA,HFM 535, Bldg 29B,Rm 4E12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 33 TC 43 Z9 43 U1 1 U2 2 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD APR 13 PY 2001 VL 276 IS 15 BP 12404 EP 12409 DI 10.1074/jbc.M006327200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 421UK UT WOS:000168081800128 PM 11278300 ER PT J AU Paweletz, CP Charboneau, L Bichsel, VE Simone, NL Chen, T Gillespie, JW Emmert-Buck, MR Roth, MJ Petricoin, EF Liotta, LA AF Paweletz, CP Charboneau, L Bichsel, VE Simone, NL Chen, T Gillespie, JW Emmert-Buck, MR Roth, MJ Petricoin, EF Liotta, LA TI Reverse phase protein microarrays which capture disease progression show activation of pro-survival pathways at the cancer invasion front SO ONCOGENE LA English DT Article DE laser capture microdissection; protein microarrays; apoptosis; Akt; mitogen activated protein kinase; tumor progression ID PROSTATIC INTRAEPITHELIAL NEOPLASIA; GLYCOGEN-SYNTHASE KINASE-3; NERVE GROWTH-FACTOR; PROTEOMIC ANALYSIS; GENE-EXPRESSION; APOPTOSIS; AKT; IMMUNOASSAY; SPECIFICITY; ARRAYS AB Protein arrays are described for screening of molecular markers and pathway targets in patient matched human tissue during disease progression. In contrast to previous protein arrays that immobilize the probe, our reverse phase protein array immobilizes the whole repertoire of patient proteins that represent the state of individual tissue cell populations undergoing disease transitions. A high degree of sensitivity, precision and linearity was achieved, making it possible to quantify the phosphorylated status of signal proteins in human tissue cell subpopulations, Using this novel protein microarray we have longitudinally analysed the state of pro-survival checkpoint proteins at the microscopic transition stage from patient matched histologically normal prostate epithelium to prostate intraepithelial neoplasia (PIN) and then to invasive prostate cancer. Cancer progression was associated with increased phosphorylation of Akt (P < 0.04), suppression of apoptosis pathways (P < 0.03), as well as decreased phosphorylation of ERK (P < 0.01), At the transition from histologically normal epithelium to PIN we observed a statistically significant surge in phosphorylated Akt (P < 0.03) and a concomitant suppression of downstream apoptosis pathways which proceeds the transition into invasive carcinoma. C1 NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Tissue Prote Unit, Bethesda, MD 20892 USA. NCI, Canc Prevent Studies Branch, NIH, Bethesda, MD 20892 USA. NCI, Pathogenet Unit, Pathol Lab, NIH, Bethesda, MD 20892 USA. NCI, Canc Genome Anat Project, Off Director, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. RP Liotta, LA (reprint author), NCI, Pathol Lab, NIH, Bldg 10, Bethesda, MD 20892 USA. RI Delehanty, James/F-7454-2012 NR 39 TC 643 Z9 673 U1 5 U2 27 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0950-9232 J9 ONCOGENE JI Oncogene PD APR 12 PY 2001 VL 20 IS 16 BP 1981 EP 1989 DI 10.1038/sj.onc.1204265 PG 9 WC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Oncology; Cell Biology; Genetics & Heredity GA 421CD UT WOS:000168043800006 PM 11360182 ER PT J AU Bocharov, AV Vishnyakova, TG Baranova, IN Patterson, AP Eggerman, TL AF Bocharov, AV Vishnyakova, TG Baranova, IN Patterson, AP Eggerman, TL TI Characterization of a 95 kDa high affinity human high density lipoprotein-binding protein SO BIOCHEMISTRY LA English DT Article ID RECEPTOR CLASS-B; SCAVENGER RECEPTOR; SR-BI; CLONING; CELLS; EXPRESSION; SITES; IDENTIFICATION; CHOLESTEROL; MUTATIONS AB A new human 95 kDa high density lipoprotein (HDL)-binding protein (HBP) corresponding to a high affinity HDL-binding site with K-d = 1.67 mug/mL and a capacity of 13.4 ng/mg was identified in human fetal hepatocytes. The HDL binding with the 95 kDa HBP plateaus at 2.5-5 mug/mL under reducing and nonreducing conditions. The association of HDL3 with the 95 kDa HBP plateaued in 15-30 min while dissociation was complete in 30 min. HDL3, apoA-I, and apoA-II were recognized by the 95 kDa HBP while low density lipoproteins (LDL) and tetranitromethane-modified HDL were not. The 95 kDa HBP predominantly resides on the surface of cells since trypsin treatment of HepG2 cells eliminated nearly 70% of HDL binding. All studied human cells and cell lines (HepG2, Caco-2, HeLa, fibroblasts, SKOV-3, PA-I) demonstrated the presence of the 95 kDa protein. Both RT-PCR and Western blotting for HB-2/ALCAM were negative in human fetal hepatocytes while Gp96/GRP94 was clearly differentiated from the 95 kDa HBP by two-dimensional electrophoretic mobility. Moreover, deglycosylation of HepG2 membrane preparations did not affect either HDL binding to the 95 kDa HBP or its size, while in contrast it affected the molecular weights of HB-2/ALCAM and SR-BI/CLA-1. We conclude that the 95 kDa HBP is a new HDL receptor candidate widely expressed in human cells and cell lines. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapy, OTRR, Bethesda, MD 20892 USA. NHLBI, NIH, Bethesda, MD 20892 USA. RP Bocharov, AV (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapy, OTRR, 8800 Rockville Pike,NIH Campus Bldg 29B,Room 2NN1, Bethesda, MD 20892 USA. NR 33 TC 13 Z9 13 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0006-2960 J9 BIOCHEMISTRY-US JI Biochemistry PD APR 10 PY 2001 VL 40 IS 14 BP 4407 EP 4416 DI 10.1021/bi001503k PG 10 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 423VL UT WOS:000168198400024 PM 11284697 ER PT J AU Luo, WH Li, H Zhang, Y Ang, CYW AF Luo, WH Li, H Zhang, Y Ang, CYW TI Determination of formaldehyde in blood plasma by high-performance liquid chromatography with fluorescence detection SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE formaldehyde ID TISSUES AB An HPLC method was developed for the determination of formaldehyde in human blood plasma. The method was based on the determination of the fluorescent product of the chemical reaction between formaldehyde and ampicillin. A 0.2-ml aliquot of blood plasma was reacted directly with ampicillin under acidic and heating conditions. The reaction product was extracted from the matrix with diethyl ether and analyzed by reversed-phase HPLC with fluorescence detection. Recoveries of spiked formaldehyde at the low ppm (mug/ml) level were between 93% and 102% with relative standard deviations less than 8%. The limits of detection and quantitation of formaldehyde in blood plasma samples were 0.46 mug/ml and 0.87 mug/ml, respectively. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Shantou Univ Med Coll, Cent Lab, Shantou 515031, Guangdong, Peoples R China. US FDA, Natl Ctr Toxicol Res, US Dept HHS, Div Chem, Jefferson, AR 72079 USA. RP Luo, WH (reprint author), Shantou Univ Med Coll, Cent Lab, Xin Lin Rd 22, Shantou 515031, Guangdong, Peoples R China. NR 11 TC 50 Z9 57 U1 2 U2 17 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-4347 J9 J CHROMATOGR B JI J. Chromatogr. B PD APR 5 PY 2001 VL 753 IS 2 BP 253 EP 257 DI 10.1016/S0378-4347(00)00552-1 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 417CB UT WOS:000167816900010 PM 11334338 ER PT J AU Schwetz, BA AF Schwetz, BA TI New formulation of Tripedia 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, HF-1,5600 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 APR 4 PY 2001 VL 285 IS 13 BP 1696 EP 1696 DI 10.1001/jama.285.13.1696 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 415FR UT WOS:000167710600003 PM 11277810 ER PT J AU Schwetz, BA AF Schwetz, BA TI Drug for esophagitis and GERD 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, HF-1,5600 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 APR 4 PY 2001 VL 285 IS 13 BP 1696 EP 1696 DI 10.1001/jama.285.13.1696 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 415FR UT WOS:000167710600004 PM 11277810 ER PT J AU Schwetz, BA AF Schwetz, BA TI Artificial skin for grafts 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, HF-1,5600 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 APR 4 PY 2001 VL 285 IS 13 BP 1696 EP 1696 DI 10.1001/jama.285.13.1696 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 415FR UT WOS:000167710600005 PM 11277810 ER PT J AU Vercruysse, J Holdsworth, P Letonja, T Barth, D Conder, G Hamamoto, K Okano, K AF Vercruysse, J Holdsworth, P Letonja, T Barth, D Conder, G Hamamoto, K Okano, K TI International harmonisation of Anthelmintic Efficacy Guidelines SO VETERINARY PARASITOLOGY LA English DT Article DE Anthelmintic Guidelines; international hormonisation AB The "International Go-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 the present paper is to present the guidelines established by the working group on Anthelmintic Efficacy Guidelines: (1) efficacy of anthelmintics: general requirements (VICH GL7); (2) efficacy of anthelmintics: specific recommendations for bovines (VICH GL12); (3) efficacy of anthelmintics: specific recommendations for ovines (VICH GL13); (4) efficacy of anthelmintics: specific recommendations for caprines (VICH GL14). 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) 2001 Elsevier Science B.V. All rights reserved. C1 State Univ Ghent, Fac Med Vet, Dept Parasitol, B-9820 Merelbeke, Belgium. Avcare, Canberra, ACT 2601, Australia. US FDA, USA Ctr Vet Med, Rockville, MD 20855 USA. Merial GMBH, Katrinehof Res Ctr, D-83101 Rohrdorf Lauterbah, Germany. Pfizer Inc, Div Cent Res, Groton, CT 06340 USA. MAFF, Natl Vet Assay Lab, Kokubunji, Tokyo 1858511, Japan. Itohpia Nihonbashi SA BLDG, Fujisawa Pharmaceut Co Ltd, Div Chem, Sales Dept,Chuo Ku, Tokyo 1030012, Japan. RP Vercruysse, J (reprint author), State Univ Ghent, Fac Med Vet, Dept Parasitol, Salisburylaan 133, B-9820 Merelbeke, Belgium. NR 2 TC 94 Z9 96 U1 0 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0304-4017 J9 VET PARASITOL JI Vet. Parasitol. PD APR 2 PY 2001 VL 96 IS 3 BP 171 EP 193 DI 10.1016/S0304-4017(00)00443-X PG 23 WC Parasitology; Veterinary Sciences SC Parasitology; Veterinary Sciences GA 434HE UT WOS:000168808400001 PM 11240092 ER PT J AU Anderson, DL Lindstrom, RM AF Anderson, DL Lindstrom, RM TI Development of a beam facility for thermal neutron capture prompt gamma-ray activation analysis. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Elemental Res Branch, HFS 388, Washington, DC 20204 USA. Natl Inst Stand & Technol, Div Analyt Chem, Gaithersburg, MD 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 1 PY 2001 VL 221 MA 166-NUCL BP U88 EP U88 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824800526 ER PT J AU Ang, CYW Cui, Y AF Ang, CYW Cui, Y TI Ultrasonic extraction and HPLC analysis of flavonoids, naphthodianthrones, and phloroglucinols in Hypericum perforatum. 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. EM cang@nctr.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 57-AGFD BP U28 EP U28 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700055 ER PT J AU Betenbaugh, MJ Lawrence, SM Coleman, TA Huddleston, KA Vann, WF Lee, YC Pitts, LR Tomiya, N AF Betenbaugh, MJ Lawrence, SM Coleman, TA Huddleston, KA Vann, WF Lee, YC Pitts, LR Tomiya, N TI Identification and characterization of sialic acid pathway genes through bioinformatics. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Johns Hopkins Univ, Dept Chem Engn, Baltimore, MD 21218 USA. Human Genome Sci, Prot Dev, Rockville, MD USA. US FDA, Lab Bacterial Toxins & Bacterial Polysaccharides, Rockville, MD USA. Johns Hopkins Univ, Baltimore, MD 21218 USA. EM beten@jhu.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 261-BIOT BP U150 EP U150 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700733 ER PT J AU Carson, MC Heller, DN Reeves, VB AF Carson, MC Heller, DN Reeves, VB TI Use of LC/MSN for multiresidue regulatory confirmation of veterinary drug residues in food products of animal origin. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. EM mcarson@cvm.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 116-AGRO BP U64 EP U64 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700254 ER PT J AU Castleman, AW Card, D Folmer, D Wisniewski, E Stairs, J Hurley, S Dermota, T AF Castleman, AW Card, D Folmer, D Wisniewski, E Stairs, J Hurley, S Dermota, T TI Studies of cluster dynamics and coulomb explosion in intense optical fields. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Penn State Univ, Dept Chem Phys, University Pk, PA 16802 USA. USA, Washington, DC 20310 USA. US FDA, Rockville, MD 20857 USA. Penn State Univ, Dept Chem, University Pk, PA 16802 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 1 PY 2001 VL 221 MA 375-PHYS BP U290 EP U290 PN 2 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PJ UT WOS:000168824801697 ER PT J AU Cui, Y Reed, LN Ang, CYW AF Cui, Y Reed, LN Ang, CYW TI Supercritical fluid extraction and high-performance liquid chromatographic determination of phloroglucinols in St. John's wort (Hypericum perforatum L.). SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Div Chem, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. EM YCui@NCTR.FDA.GOV NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 56-AGFD BP U28 EP U28 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700054 ER PT J AU Fang, H Tong, WD Shi, LM Perkins, R Hong, HX Xie, Q Tu, MH Branham, W Sheehan, DM AF Fang, H Tong, WD Shi, LM Perkins, R Hong, HX Xie, Q Tu, MH Branham, W Sheehan, DM TI "Four-phase" approach for priority setting of xenoestrogens. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. EM hfang@nctr.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 234-COMP BP U436 EP U436 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824702998 ER PT J AU Frasch, CE Lee, CH AF Frasch, CE Lee, CH TI Use of physical and chemical methods for characterization of multivalent pneumococcal conjugate vaccines. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. EM frasch@cber.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 47-BIOT BP U115 EP U115 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700524 ER PT J AU Holder, CL Rushing, LG Billedeau, SM Siitonen, PH Miller, DW AF Holder, CL Rushing, LG Billedeau, SM Siitonen, PH Miller, DW TI Analysis of ethynyl estradiol in Casein Meal irradiated using electron-capture gas chromatography. 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. EM Cholder@nctr.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 58-AGFD BP U28 EP U28 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700056 ER PT J AU Krynitsky, AJ Wong, JW Halverson, CA Schenck, FJ Podhorniak, LV Stafford, CJ AF Krynitsky, AJ Wong, JW Halverson, CA Schenck, FJ Podhorniak, LV Stafford, CJ TI LC/MS as a practical tool for developing residue enforcement methods. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US EPA, EPA Environm Sci Ctr, Ft George G Meade, MD 20755 USA. US Dept Treasury, Bur Alcohol Tobacco & Firearms, Washington, DC 20226 USA. US FDA, Rockville, MD 20857 USA. EM Krynitsky.Alexander@epa.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 124-AGRO BP U65 EP U66 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700262 ER PT J AU Snellings, SL Takenaka, NE Kim, Y Miller, DW AF Snellings, SL Takenaka, NE Kim, Y Miller, DW TI Confirmation of a colorimetric indole method in shrimp by GC-MS. 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. EM SNELLINGS@NCTR.FDA.GOV NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 59-AGFD BP U28 EP U28 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824700057 ER PT J AU Wang, K Weida, T Goodwin, TE Perkins, R Sheehan, DM Compadre, CM AF Wang, K Weida, T Goodwin, TE Perkins, R Sheehan, DM Compadre, CM TI Does kepone really exist?. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Arkansas Med Sci, Biomed Visualizat Ctr, Little Rock, AR 72205 USA. ROW Sci, Rockville, MD USA. Hendrix Coll, Dept Chem, Conway, AR USA. Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. EM wangkun@exchange.uams.edu NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 195-ENVR BP U475 EP U476 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824703212 ER PT J AU Xie, Q Tong, W Fang, H Hong, HX Perkins, R Sheehan, DM AF Xie, Q Tong, W Fang, H Hong, HX Perkins, R Sheehan, DM TI Pharmacophore models for identification of environmental estrogens. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, ROW Sci Inc, Computat Chem Grp, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. EM qxie@nctr.fda.gov NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 1 PY 2001 VL 221 MA 33-CINF BP U283 EP U283 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA 434PH UT WOS:000168824702148 ER PT J AU Wagner, RF Beiden, SV Metz, CE AF Wagner, RF Beiden, SV Metz, CE TI Continuous versus categorical data for ROC analysis: Some quantitative considerations SO ACADEMIC RADIOLOGY LA English DT Article DE diagnostic radiology, observer performance; receiver operating characteristic curve (ROC) ID CONTAMINATED BINORMAL MODEL; OPERATING CHARACTERISTIC ANALYSIS; MAXIMUM-LIKELIHOOD-ESTIMATION; EXPERIMENTAL-DESIGN; RATING DATA; CURVES; MULTIREADER; VALIDATION; DEGENERACY; SIZE AB Rationale and Objectives. Several authors have encouraged the use of a quasi-continuous rating scale for data collection in receiver operating characteristic (ROC) curve analysis of diagnostic modalities, rather than rating scales based on five to seven ordinal categories or levels of suspicion. Although many investigators have gone over to this method, a discussion of the issues continues. The present work provides a quantitative analysis from the viewpoint of measurement science. Materials and Methods. A simple model of the effect of data discretization or quantization on the measurement of the variance of noisy data was developed. Then Monte Carlo simulations of multiple-reader. multiple-case ROC experiments were performed and analyzed in terms of components-of-variance models to investigate the effect of data quantization in that more complex setting. Results. For single-reader studies, discretization into five categories can reduce the precision of ROC measurements by a large amount, The effect may be attenuated in multireader studies. Conclusion, More precise measurements of diagnostic detection performance and thus more efficient use of resources are served by good measurement methods. These are promoted by the use of a quasi-continuous raring scale in ROC studies. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. Univ Chicago, Dept Radiol, Kurt Rossmann Labs, Chicago, IL 60637 USA. RP Wagner, RF (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, HFZ-142, Rockville, MD 20857 USA. FU NCI NIH HHS [R01-CA62362]; NIGMS NIH HHS [R01-GM57622] NR 30 TC 49 Z9 49 U1 1 U2 3 PU ASSOC UNIV RADIOLOGISTS PI OAK BROOK PA 820 JORIE BLVD, OAK BROOK, IL 60523-2251 USA SN 1076-6332 J9 ACAD RADIOL JI Acad. Radiol. PD APR PY 2001 VL 8 IS 4 BP 328 EP 334 DI 10.1016/S1076-6332(03)80502-0 PG 7 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA 433QG UT WOS:000168770800006 PM 11293781 ER PT J AU Alayash, AI Patel, RP Cashon, RE AF Alayash, AI Patel, RP Cashon, RE TI Redox reactions of hemoglobin and myoglobin: Biological and toxicological implications SO ANTIOXIDANTS & REDOX SIGNALING LA English DT Review ID LOW-DENSITY-LIPOPROTEIN; OXIDATIVE CROSS-LINKING; HYDROGEN-PEROXIDE; ENDOTHELIAL-CELLS; NITRIC-OXIDE; FERRYL INTERMEDIATE; MYOCARDIAL ISCHEMIA; SIGNAL-TRANSDUCTION; HUMAN METHEMOGLOBIN; CEREBRAL VASOSPASM AB Direct cytotoxic effects associated with hemoglobin (Hb) or myoglobin (Mb) have been ascribed to redox reactions (involving either one- or two-electron steps) between the heme group and peroxides. These interactions are the basis of the pseudoperoxidase activity of these hemoproteins and can be cytotoxic when reactive species are formed at relatively high concentrations during inflammation and typically lead to cell death. Peroxides relevant to biological systems include hydrogen peroxide, lipid hydroperoxides, and peroxynitrite. Reactions between Hb/Mb and peroxides form the ferryl oxidation state of the protein, analogous to compounds I and II formed in the catalytic cycle of many peroxidase enzymes. This higher oxidation state of the protein is a potent oxidant capable of promoting oxidative damage to most classes of biological molecules. Free iron, released from Hb, also has the potential to promote oxidative damage via classical "Fenton" chemistry. It has become increasingly evident that Hb/Mb redox reactions or their by-products play a critical role in the pathophysiology of some disease states. This review briefly discusses the reactions of Hb/Mb with biological peroxides, potential cytotoxicity and the impact of these interactions on modulation of cell signaling pathways regulated by these reactive species. Also discussed in this article is the role of heme-protein chemistry in relation to the toxicity of hemoproteins. C1 US FDA, CBER, Bethesda, MD 20892 USA. Univ Alabama, Ctr Free Rad Biol, Birmingham, AL 35294 USA. Univ Maine, Dept Biochem Microbiol & Mol Biol, Orono, ME 04469 USA. Univ Alabama, Dept Pathol, Birmingham, AL 35294 USA. RP US FDA, CBER, NIH Campus,Bldg 29,Rm 112, Bethesda, MD 20892 USA. EM Alayash@cber.fda.gov OI Patel, Rakesh/0000-0002-1526-4303 NR 98 TC 138 Z9 144 U1 1 U2 20 PU MARY ANN LIEBERT, INC PI NEW ROCHELLE PA 140 HUGUENOT STREET, 3RD FL, NEW ROCHELLE, NY 10801 USA SN 1523-0864 EI 1557-7716 J9 ANTIOXID REDOX SIGN JI Antioxid. Redox Signal. PD APR PY 2001 VL 3 IS 2 BP 313 EP 327 DI 10.1089/152308601300185250 PG 15 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 532WW UT WOS:000174498900012 PM 11396484 ER PT J AU Moody, JD Freeman, JP Doerge, DR Cerniglia, CE AF Moody, JD Freeman, JP Doerge, DR Cerniglia, CE TI Degradation of phenanthrene and anthracene by cell suspensions of Mycobacterium sp strain PYR-1 SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; PYRENE-DEGRADING BACTERIUM; SPHINGOMONAS-YANOIKUYAE B1; RING FISSION-PRODUCTS; MICROBIAL-METABOLISM; FLUORANTHENE; MINERALIZATION; IDENTIFICATION; BIODEGRADATION; BENZOPYRENE AB Cultures of Mycobacterium sp. strain PYR-1 were dosed with anthracene or phenanthrene and after 14 days of incubation had degraded 92 and 90% of the added anthracene and phenanthrene, respectively. The metabolites were extracted and identified by UV-visible light absorption, high-pressure liquid chromatography retention times, mass spectrometry, H-1 and C-13 nuclear magnetic resonance spectrometry, and comparison to authentic compounds and literature data. Neutral-pH ethyl acetate extracts from anthracene-incubated cells showed four metabolites, identified as cis-1,2-dihydroxy-1,2-dihydroanthracene, 6,7-benzocoumarin, 1-methoxy-2-hydroxyanthracene, and 9,10-anthraquinone. A novel anthracene ring fission product was isolated from acidified culture media and was identified as 3-(2-carboxyvinyl)naphthalene-2-carboxylic acid. 6,7-Benzocoumarin was also found in that extract. When Mycobacterium sp. strain PYR-1 was grown in the presence of phenanthrene, three neutral metabolites were identified as cis- and trans-9,10-dihydroxy-9,10-dihydrophenanthrene and cis-3,4-dihydroxy-3,4 dihydrophenanthrene. Phenanthrene ring fission products, isolated from acid extracts, were identified as 2,2'-diphenie acid, 1-hydroxynaphthoic acid, and phthalic acid. The data point to the existence, next to already known routes for both gram-negative and gram-positive bacteria, of alternative pathways that might be due to the presence of different dioxygenases or to a relaxed specificity of the same dioxygenase for initial attack on polycyclic aromatic hydrocarbons. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 58 TC 150 Z9 161 U1 10 U2 36 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 2001 VL 67 IS 4 BP 1476 EP 1483 DI 10.1128/AEM.67.4.1476-1483.2001 PG 8 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 417ZN UT WOS:000167865500012 PM 11282593 ER PT J AU Zhao, SH White, DG Ge, BL Ayers, S Friedman, S English, L Wagner, D Gaines, S Meng, JH AF Zhao, SH White, DG Ge, BL Ayers, S Friedman, S English, L Wagner, D Gaines, S Meng, JH TI Identification and characterization of integron-mediated antibiotic resistance among shiga toxin-producing Escherichia coli isolates SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID HEMOLYTIC-UREMIC SYNDROME; MOBILE GENE CASSETTES; HEMORRHAGIC COLITIS; UNITED-STATES; O157-H7; FOOD; ANIMALS; HUMANS; INFECTIONS; FOSFOMYCIN AB A total of 50 isolates of Shiga toxin-producing Escherichia coli (STEC), including 29 O157:H7 and 21 non-O157 STEC strains, were analyzed for antimicrobial susceptibilities and the presence of class 1 integrons. Seventy-eight (n = 39) percent of the isolates exhibited resistance to two or more antimicrobial classes. Multiple resistance to streptomycin, sulfamethoxazole, and tetracycline was most often observed. Class 1 integrons were identified among nine STEC isolates, including serotypes O157:H7, O111:H11, O111:H8, O111:NM, O103:H2, O45:H2, O26:H11, and O5:MM. The majority of the amplified integron fragments were 1 kb in size with the exception of one E. coli O111:H8 isolate which possessed a 2-kb amplicon. DNA sequence analysis revealed that the integrons identified within the O111:H11, O111:NM, O45:H2, and O26:H11 isolates contained the aadA gene encoding resistance to streptomycin and spectinomycin, Integrons identified among the O157:H7 and O103:H2 isolates also possessed a similar aadA gene. However, DNA sequencing revealed only 86 and 88% homology, respectively. The 2-kb integron of the E. coli O111:HS isolate contained three genes, dfrXII, aadA2, and a gene of unknown function, orfF,which were 86, 100, and 100% homologous, respectively, to previously reported gene cassettes identified in integrons found in Citrobacter freundii and Klebsiella pneumoniae, Furthermore, integrons identified among the O157:H7 and O111:NM strains were transferable via conjugation to another strain of E. coli O157:H7 and to several strains of Hafnia alvei. To our knowledge, this is the first report of integrons and antibiotic resistance gene cassettes in STEC, in particular E. coli O157:H7. C1 US FDA, CVM, Res Off, Div Anim & Food Microbiol, Laurel, MD 20708 USA. Univ Maryland, Dept Nutr & Food Sci, College Pk, MD 20742 USA. RP Zhao, SH (reprint author), US FDA, CVM, Res Off, Div Anim & Food Microbiol, 8401 Muirkirk Rd, Laurel, MD 20708 USA. EM szhao@cvm.fda.gov NR 35 TC 141 Z9 151 U1 0 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 EI 1098-5336 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 2001 VL 67 IS 4 BP 1558 EP 1564 DI 10.1128/AEM.67.4.1558-1564.2001 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 417ZN UT WOS:000167865500024 PM 11282605 ER PT J AU Cutlip, RC Miller, JM Hamir, AN Peters, J Robinson, MM Jenny, AL Lehmkuhl, HD Taylor, WD Bisplinghoff, FD AF Cutlip, RC Miller, JM Hamir, AN Peters, J Robinson, MM Jenny, AL Lehmkuhl, HD Taylor, WD Bisplinghoff, FD TI Resistance of cattle to scrapie by the oral route SO CANADIAN JOURNAL OF VETERINARY RESEARCH-REVUE CANADIENNE DE RECHERCHE VETERINAIRE LA English DT Article ID TRANSMISSION AB Early epidemiological information indicated that bovine spongiform encephalopathy (BSE) originated from scrapie in sheep. The question arose if scrapie in North America would induce a BSE-like disease in cattle. Six years ago, we reported that brain tissue from sheep with scrapie caused a neurologic disease when injected directly into the brains of cattle, but the disease induced was different from BSE as it occurs in the United Kingdom and Europe. Here, we report that cattle fed raw brain or meat and bone meal and tallow prepared from sheep with scrapie remained normal for 8 years after exposure. This work indicates that cattle are highly resistant to North American scrapie by the oral route. C1 ARS, Natl Anim Dis Ctr, USDA, Ames, IA 50010 USA. Cornell Univ, Coll Vet Med, Dept Biomed Serv, Ithaca, NY 14853 USA. US FDA, Div Human Food Safety HFV150, Ctr Vet Med, Rockville, MD 20855 USA. Vet Serv, USDA, Natl Vet Serv Labs, Ames, IA 50010 USA. RP Cutlip, RC (reprint author), ARS, Natl Anim Dis Ctr, USDA, 2300 Dayton Rd,POB 70, Ames, IA 50010 USA. NR 6 TC 18 Z9 18 U1 0 U2 2 PU CANADIAN VET MED ASSOC PI OTTAWA PA 339 BOOTH ST ATTN: KIMBERLY ALLEN-MCGILL, OTTAWA, ONTARIO K1R 7K1, CANADA SN 0830-9000 J9 CAN J VET RES JI Can. J. Vet. Res.-Rev. Can. Rech. Vet. PD APR PY 2001 VL 65 IS 2 BP 131 EP 132 PG 2 WC Veterinary Sciences SC Veterinary Sciences GA 428XW UT WOS:000168487800008 PM 11346258 ER PT J AU Kadlubar, FF AF Kadlubar, FF TI James A. Miller (1915-2000) - In memoriam SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Biographical-Item C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NR 0 TC 2 Z9 3 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD APR PY 2001 VL 14 IS 4 BP 335 EP 337 DI 10.1021/tx010499q PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 424XZ UT WOS:000168260400001 PM 11304119 ER PT J AU Lopez, AS Dodson, DR Arrowood, MJ Orlandi, PA da Silva, AJ Bier, JW Hanauer, SD Kuster, RL Oltman, S Baldwin, MS Won, KY Nace, EM Eberhard, ML Herwaldt, BL AF Lopez, AS Dodson, DR Arrowood, MJ Orlandi, PA da Silva, AJ Bier, JW Hanauer, SD Kuster, RL Oltman, S Baldwin, MS Won, KY Nace, EM Eberhard, ML Herwaldt, BL TI Outbreak of cyclosporiasis associated with basil in Missouri in 1999 SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID IMPORTED RASPBERRIES; EXTRACTION; INFECTIONS; PATHOGEN AB During the summer of 1999, an outbreak of cyclosporiasis occurred among attendees of 2 events held on 24 July in different counties in Missouri. We conducted retrospective cohort studies of the 2 clusters of cases, which comprised 62 case patients. The chicken pasta salad served at one event (relative risk [RR], 4.25; 95% confidence interval [CI], 1.80-10.01) and the tomato basil salad served at the other event (RR, 2.95; 95% CI, 1.72-5.07) were most strongly associated with illness. The most likely vehicle of infection was fresh basil, which was included in both salads and could have been grown either in Mexico or the United States. Leftover chicken pasta salad was found to be positive for Cyclospora DNA by means of polymerase chain reaction analysis, and 1 sporulated Cyclospora oocyst was found by use of microscopy. This is the second documented outbreak of cyclosporiasis in the United States linked to fresh basil and the first US outbreak for which Cyclospora has been detected in an epidemiologically implicated food item. C1 Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Atlanta, GA 30341 USA. Missouri Dept Hlth, Jefferson City, MO USA. Missouri State Publ Hlth Lab, Jefferson City, MO USA. Franklin Cty Hlth Dept, Union, MO USA. St Louis Cty Dept Hlth, Clayton, MO USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Dallas Dist Off, Off Regulatory Affairs, Dallas, TX USA. RP Herwaldt, BL (reprint author), Ctr Dis Control & Prevent, Div Parasit Dis, Natl Ctr Infect Dis, Mailstop F-22,4770 Buford Highway NE, Atlanta, GA 30341 USA. NR 19 TC 62 Z9 68 U1 0 U2 6 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 APR 1 PY 2001 VL 32 IS 7 BP 1010 EP 1017 DI 10.1086/319597 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 414EY UT WOS:000167654100003 PM 11264028 ER PT J AU Feigal, D AF Feigal, D TI Who's on first? What's on second? SO CONTROLLED CLINICAL TRIALS LA English DT Editorial Material ID IMMUNODEFICIENCY-VIRUS INFECTION; CD4 CELL COUNTS; CONTROLLED TRIAL; CUBIC MILLIMETER; CLINICAL-TRIALS; DIDANOSINE; ZIDOVUDINE; AIDS C1 US FDA, Rockville, MD 20857 USA. RP Feigal, D (reprint author), US FDA, Rockville, MD 20857 USA. NR 8 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0197-2456 J9 CONTROL CLIN TRIALS JI Controlled Clin. Trials PD APR PY 2001 VL 22 IS 2 BP 139 EP 141 DI 10.1016/S0197-2456(01)00115-5 PG 3 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA 421TE UT WOS:000168079000006 PM 11306152 ER PT J AU Misbin, RI AF Misbin, RI TI Placebo-controlled trials in type 2 diabetes SO DIABETES CARE LA English DT Editorial Material C1 US FDA, Div Endocrine & Met Drug Prod, Rockville, MD 20857 USA. RP Misbin, RI (reprint author), 5727 Crawford Dr, Rockville, MD 20851 USA. NR 9 TC 4 Z9 4 U1 1 U2 1 PU AMER DIABETES ASSOC PI ALEXANDRIA PA 1660 DUKE ST, ALEXANDRIA, VA 22314 USA SN 0149-5992 J9 DIABETES CARE JI Diabetes Care PD APR PY 2001 VL 24 IS 4 BP 773 EP 774 DI 10.2337/diacare.24.4.773 PG 2 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 415BX UT WOS:000167701600033 PM 11315847 ER PT J AU Morris, LA Aikin, KJ AF Morris, LA Aikin, KJ TI The "pharmacokinetics" of patient communications SO DRUG INFORMATION JOURNAL LA English DT Article DE patient communications; informed consent; patient education; psychology; information processing ID CORRECTING MENTAL MODELS; INDIVIDUAL-DIFFERENCES; WORKING-MEMORY; DISCOURSE COMPREHENSION; ORGANIZATIONAL SIGNALS; RISK COMMUNICATIONS; HAZARDOUS PROCESSES; TEXT COMPREHENSION; INSTRUCTIONAL TEXT; EXPOSITORY TEXT AB The safe and effective use of pharmaceuticals often depends on patients' understanding the drug's risks, benefits, and directions for use. This information is often communicated in printed materials. However limits on the patient's willingness and ability to process this information make communications problematic. We review how patients process written information. We postulate that processing drug information is similar to drug pharmacokinetics. It is not the information presented to a patient that matters, rather it is the interaction of the patient with the materials that determines the nature and amount of information communicated. C1 Louis A Morris & Associates, Dix Hills, NY 11746 USA. US FDA, Rockville, MD 20857 USA. RP Morris, LA (reprint author), Louis A Morris & Associates, 8 Norman Court, Dix Hills, NY 11746 USA. NR 88 TC 6 Z9 6 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 2001 VL 35 IS 2 BP 509 EP 527 PG 19 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 433JV UT WOS:000168757000022 ER PT J AU Weng, TS AF Weng, TS TI Evaluation of diagnostic tests: Measuring degree of agreement and beyond SO DRUG INFORMATION JOURNAL LA English DT Article DE diagnosis; kappa; agreement; prevalence; accuracy ID PSYCHIATRIC-DIAGNOSIS; ACCURACY; RELIABILITY; KAPPA AB When evaluating a new diagnostic test against a less than perfect "gold standard, " the kappa coefficient of agreement K is often inappropriately used as a measure of "diagnostic accuracy, " which frequently leads to paradoxical findings. In this paper, K is expressed as a function of disease prevalence and diagnostic accuracy (subject to Youden's index > 0), whereby necessary and sufficient conditions, given the accuracy rates, are derived to aid in locating the maximizer of kappa Paradoxical behavior of K can thus be detected in the light of diagnostic accuracy. Attempts are made to clarify, the subtle difference between "diagnostic accuracy" and "diagnostic reliability. " The implication of this difference is then assessed from a regulatory perspective. In order to extend the idea of K beyond its originally intended use, the maximum likelihood method, coupled with the Expectation-Maximization algorithm, is proposed as a remedial option, not for measuring diagnostic agreement or reliability but, rather, for evaluating diagnostic accuracy. Some illustrative examples adapted from published data are provided. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Biostat, Rockville, MD 20850 USA. RP Weng, TS (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Div Biostat, 1350 Piccard Dr, Rockville, MD 20850 USA. NR 18 TC 3 Z9 3 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 APR-JUN PY 2001 VL 35 IS 2 BP 577 EP 588 PG 12 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 433JV UT WOS:000168757000029 ER PT J AU Neriishi, K Nakashima, E Delongchamp, RR AF Neriishi, K Nakashima, E Delongchamp, RR TI Persistent subclinical inflammation among A-bomb survivors SO INTERNATIONAL JOURNAL OF RADIATION BIOLOGY LA English DT Article ID ERYTHROCYTE SEDIMENTATION-RATE; T-CELLS; IRRADIATION; DISEASES; MICE AB Purpose: To investigate the associations between inflammation tests and radiation dose in A-bomb survivors. Subjects and methods: Subjects were A-bomb survivors who underwent inflammation tests of leukocyte counts, neutrophil counts, erythrocyte sedimentation rate, corrected erythrocyte sedimentation rate, alpha -1 globulin, alpha -2 globulin and sialic acid between 1988 and 1992. Associations with radiation dose (DS86) were analyzed by regression analysis and heterogeneity among inflammatory diseases, anaemia at examination, or history of cancer was also tested. Results: The associations with radiation dose were statistically significant for leukocyte counts (71.0 mm(-3) Gy(-1), p=0.015), erythrocyte sedimentation rate (1.58 mm h(-1) Gy(-1), p=0.0001), corrected erythrocyte sedimentation rate (1.14 mm h(-1) Gy(-1), p=0.0001), alpha -1 globulin (0.0057 g dl(-1) Gy(-1), p=0.0001), alpha -2 globulin (0.0128 g dl(-1) Gy(-1), p=0.0001), and sialic acid (1.2711 mg dl(-1) Gy(-1), p = 0.0001) but not for neutrophil counts (29.9 mm(-3) Gy(-1), p=0.17). Heterogeneity was not statistically significant. Among inflammatory diseases, associations were the strongest for chronic thyroiditis and chronic liver diseases. Conclusions: This study suggests statistically significant association between inflammation in A-bomb survivors and radiation dose of during 1988-1992. The association might contribute, as an epigenetic and/or bystander effect, to development of several radiation-induced disorders. C1 Radiat Effects Res Fdn, Dept Clin Studies, Hiroshima 7320815, Japan. Radiat Effects Res Fdn, Dept Stat, Hiroshima 7320815, Japan. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Neriishi, K (reprint author), Radiat Effects Res Fdn, Dept Clin Studies, 5-2 Hijiyama Pk, Hiroshima 7320815, Japan. NR 21 TC 64 Z9 68 U1 0 U2 4 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0955-3002 J9 INT J RADIAT BIOL JI Int. J. Radiat. Biol. PD APR PY 2001 VL 77 IS 4 BP 475 EP 482 PG 8 WC Biology; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Life Sciences & Biomedicine - Other Topics; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA 420GX UT WOS:000167998200006 PM 11304439 ER PT J AU Fleischman, GJ Bator, C Merker, R Keller, SE AF Fleischman, GJ Bator, C Merker, R Keller, SE TI Hot water immersion to eliminate Escherichia coli O157 : H7 on the surface of whole apples: Thermal effects and efficacy SO JOURNAL OF FOOD PROTECTION LA English DT Article AB The effect of hot water immersion on both the reduction of Escherichia coli O157:H7 on the apple surface and internal temperatures of the apple was assessed in this study. Microbial reductions were measured experimentally, whereas internal temperatures were calculated through a mathematical analysis of experimental heat transfer data obtained from the apples. A method was developed to provide a purely surface-based inoculation of E. coli O157:H7. Rinsing produced no reduction, and treatments at 80 and 95 degreesC produced reductions of more than 5 logs in 15 s or less. The heat transfer analysis based on experimental data was used to calculate surface heat transfer coefficients and predict temperatures throughout the apple. The analysis indicated a low heat transfer rate. Although it reduces thermal degradation, a low heat transfer rate precludes thermal-based reduction of any internalized microorganisms. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. IIT, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Fleischman, GJ (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Ave, Summit Argo, IL 60501 USA. FU FDA HHS [FD-000431] NR 17 TC 21 Z9 21 U1 1 U2 3 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC 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 2001 VL 64 IS 4 BP 451 EP 455 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 419CU UT WOS:000167932400004 PM 11307878 ER PT J AU Tournas, VH Stack, ME AF Tournas, VH Stack, ME TI Production of alternariol and alternariol methyl ether by Alternaria alternata grown on fruits at various temperatures SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LIQUID-CHROMATOGRAPHIC DETERMINATION; MYCO-TOXIN PRODUCTION; NATURAL OCCURRENCE; MONOMETHYL ETHER; TENUAZONIC ACID; MYCOTOXINS; TOMATOES; APPLES; MUTAGENICITY AB Two toxigenic strains of the fungus Alternaria alternata (ATCC 56836 and ATCC 66868) were grown on surface-disinfected, fresh, ripe fruits and tested for the production of alternariol (AOH) and alternariol methyl ether (AME). Examined fruits included strawberries, red and green seedless grapes; concord grapes; red delicious, golden delicious, and gala apples; and blueberries. After inoculation, fruits were incubated at 4, 10 degreesC, or room temperature (approximately 21 degreesC) for up to 3 weeks. At weekly intervals, duplicate samples were analyzed for AOH and AME by using liquid chromatography. Results indicated that A. alternata and its metabolites were not a major problem in strawberries due to the presence of fast-growing molds like Rhizopus and Botrytis that outgrew and possibly inhibited Alternaria. Both Alternaria strains showed limited growth on apples, although fast-growing molds were not present after surface disinfection; AOH and AME were produced only by the ATCC 56836 strain on the golden delicious and gala varieties, (ranging from <0.1 to 5 g/g and <0.1 to 14 g/g for AOH and AME, respectively). Restricted growth of both strains without toxin production occurred in blueberries, whereas moderate growth and AOH (<0.1 to 3.336 g/g) and AME (<0.1 to 1,716 g/g) production took place in grapes. C1 US FDA, Div Nat Prod, Washington, DC 20204 USA. RP Tournas, VH (reprint author), US FDA, Div Nat Prod, 200 C St SW, Washington, DC 20204 USA. NR 25 TC 40 Z9 41 U1 0 U2 11 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC 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 2001 VL 64 IS 4 BP 528 EP 532 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 419CU UT WOS:000167932400017 PM 11307891 ER PT J AU Myers, MJ Friedman, SL Farrell, DE Dove-Pettit, DA Bucker, MF Kelly, S Madzo, S Campbell, W Wang, RF Paine, D Cerniglia, CE AF Myers, MJ Friedman, SL Farrell, DE Dove-Pettit, DA Bucker, MF Kelly, S Madzo, S Campbell, W Wang, RF Paine, D Cerniglia, CE TI Validation of a polymerase chain reaction method for the detection of rendered bovine-derived materials in feedstuffs SO JOURNAL OF FOOD PROTECTION LA English DT Article ID CREUTZFELDT-JAKOB-DISEASE; VARIANT CJD; BSE AB This study validated a polymerase chain reaction-based method for the detection of a specific bovine mitochondrial gene derived from rendered bovine tissues and admired with complete animal feed. Four laboratories participated in this effort: one state laboratory and three Food and Drug Administration (FDA) laboratories, including one FDA field laboratory. The protocol used a statistical approach of 90% probability, with a 95% confidence interval for determining acceptable rates of false-positive and false-negative samples. Each participating laboratory analyzed 30 samples of feed each containing 0, 0.125, and 2.0% bovine meat and bone meal (BMBM), for a total of 90 feed samples. The samples were randomized such that the analysts were unaware of the true identity of the test samples. The results demonstrated that all laboratories met the acceptance criteria established for this protocol. The overall rates of false-negative results were 0.83% (1/120) at the level of 0.125% BMBM and 1.67% (2/120) at the level of 2% BMBM. The overall rate of false-negative results for all levels of BMBM was 1.25% (3/240). The rate for false-positive results was 0.83%. C1 US FDA, Div Anim Res, Res Off, Ctr Vet Med, Laurel, MD 20708 USA. Commonwealth Virginia, Div Consolidated Lab Serv, Dept Gen Serv, Richmond, VA 23219 USA. US FDA, Off Regulatory Affairs, Denver Dist Off, Denver Fed Ctr, Denver, CO 80225 USA. US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Myers, MJ (reprint author), US FDA, Div Anim Res, Res Off, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 9 TC 36 Z9 37 U1 0 U2 0 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC 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 2001 VL 64 IS 4 BP 564 EP 566 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 419CU UT WOS:000167932400025 PM 11307899 ER PT J AU Castelo, MM Jackson, LS Hanna, MA Reynolds, BH Bullerman, LB AF Castelo, MM Jackson, LS Hanna, MA Reynolds, BH Bullerman, LB TI Loss of fuminosin B(1) in extruded and baked corn-based foods with sugars SO JOURNAL OF FOOD SCIENCE LA English DT Article DE fumonisin; corn; extrusion; glucose ID FUMONISIN B-1; FUSARIUM-MONILIFORME; ESOPHAGEAL CANCER; STABILITY; TEMPERATURE; MYCOTOXINS; RATS; RECOVERY; TOXICITY; AFRICA AB The objective of this work was to determine the effect of added sugars on fumonisin B(1) (FB(1)) levels in baked corn muffins and extruded corn grits. Muffins containing added glucose had significantly lower FB(1) levels than muffins with sucrose, fructose, or no added sugar. Extrusion cooking of the grits resulted in significant (p< 0.05) reductions of FB(1) in all treatments relative to unextruded controls, but use of glucose resulted in greater reductions of FB(1) (45.3 to 71%) than did the use of fructose (29.5 to 53%) or sucrose (19.2 to 39%). When extrusion conditions were optimized, 92.1% loss of FB(1) was found when grits were extruded with glucose. Adding glucose to thermally processed food can result in a substantial reduction in FB(1) levels. C1 Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL USA. Lopez Foods Inc, Oklahoma City, OK USA. Univ Nebraska, Dept Biol Syst Engn, Lincoln, NE USA. IIT, Natl Ctr Food Safety & Technol, Summit Argp, IL USA. RP Bullerman, LB (reprint author), Univ Nebraska, Dept Food Sci & Technol, Lincoln, NE 68583 USA. EM lbullerman1@unl.edu NR 29 TC 30 Z9 31 U1 1 U2 2 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD APR PY 2001 VL 66 IS 3 BP 416 EP 421 DI 10.1111/j.1365-2621.2001.tb16120.x PG 6 WC Food Science & Technology SC Food Science & Technology GA 444QA UT WOS:000169410000009 ER PT J AU Hoag, SW Hussain, AS AF Hoag, SW Hussain, AS TI The impact of formulation on bioavailability: Summary of workshop discussion SO JOURNAL OF NUTRITION LA English DT Article; Proceedings Paper CT Conference on Bioavailability of Nutrients and Other Bioactive Components from Dietary Supplements CY JAN 05-06, 2000 CL BETHESDA, MARYLAND SP Off Dietary Supplements, Natl Inst Hlth & Life Sci Res Off, Amer Soc Nutr Sci ID VITRO C1 Univ Maryland, Baltimore, MD 21201 USA. US FDA, Washington, DC 20204 USA. RP Hoag, SW (reprint author), Univ Maryland, Baltimore, MD 21201 USA. NR 3 TC 7 Z9 7 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 APR PY 2001 VL 131 SU 4 BP 1389S EP 1391S PG 3 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 423HU UT WOS:000168170600014 PM 11285360 ER PT J AU Attie, KM Bengtsson, BA Blethen, SL Blum, W Cameron, F Carel, JC Carlsson, L Chipman, JJ Christiansen, JS Clayton, P Clemmons, DR Cohen, P Drop, S Fujieda, K Ghigo, E Hintz, RL Ho, K Ilondo, MM Jasper, H Jesussek, B Kappelgaard, AM Laron, Z Lippe, BM Malozowski, S Mullis, PE de Muinck-Keizer-Schrama, S Nishi, Y Parks, JS Phelps, C Ranke, M Robinson, I Rosenfeld, RG Rose, S Saenger, P Saggese, G Savage, M Shalet, S Sizonenko, PC Strasburger, C Tachibana, K Tanaka, T Thorner, MO Wikland, KA Zadik, Z AF Attie, KM Bengtsson, BA Blethen, SL Blum, W Cameron, F Carel, JC Carlsson, L Chipman, JJ Christiansen, JS Clayton, P Clemmons, DR Cohen, P Drop, S Fujieda, K Ghigo, E Hintz, RL Ho, K Ilondo, MM Jasper, H Jesussek, B Kappelgaard, AM Laron, Z Lippe, BM Malozowski, S Mullis, PE de Muinck-Keizer-Schrama, S Nishi, Y Parks, JS Phelps, C Ranke, M Robinson, I Rosenfeld, RG Rose, S Saenger, P Saggese, G Savage, M Shalet, S Sizonenko, PC Strasburger, C Tachibana, K Tanaka, T Thorner, MO Wikland, KA Zadik, Z CA Growth Hormone Res Soc TI Consensus guidelines for the diagnosis and treatment of growth hormone (GH) deficiency in childhood and adolescence: Summary statement of the GH Research Society (Reprinted from J Clin Endocrinol Metab, vol 85, pg 3990-3993, 2000) SO JOURNAL OF PEDIATRIC ENDOCRINOLOGY & METABOLISM LA English DT Reprint C1 Genentech Inc, S San Francisco, CA 94080 USA. Univ Gothenburg, Sahlgrenska Hosp, Gothenburg, Sweden. Eli Lilly Res Labs, Bad Homburg, Germany. Royal Childrens Hosp, Parkville, Vic 3052, Australia. Hop St Vincent de Paul, F-75674 Paris, France. Eli Lilly Res Labs, Indianapolis, IN USA. Aarhus Kommune Hosp, Dept Med, DK-8000 Aarhus C, Denmark. Royal Manchester Childrens Hosp, Manchester M27 1HA, Lancs, England. Univ N Carolina, Chapel Hill, NC USA. Mattell Childrens Hosp, Los Angeles, CA USA. Sophia Childrens Hosp, Rotterdam, Netherlands. Hokkaido Univ, Sch Med, Sapporo, Hokkaido 060, Japan. Univ Turin, Turin, Italy. Lawson Wilkins Pediat Endocrine Soc, Stanford, CA USA. Garvan Inst Med Res, Sydney, NSW, Australia. Novo Nordisk AS, DK-2880 Bagsvaerd, Denmark. CONICET, CEDIE, RA-1033 Buenos Aires, DF, Argentina. Ferring GmbH, Kiel, Germany. Schneider Childrens Med Ctr Israel, Petah Tiqwa, Israel. Pharmacia & Upjohn Inc, Los Angeles, CA USA. US FDA, Rockville, MD 20857 USA. Univ Bern, Inselspital, CH-3010 Bern, Switzerland. Sophia Kinderziekenhuls, Rotterdam, Netherlands. Hiroshima Red Cross Hosp, Hiroshima, Japan. Emory Univ, Sch Med, Atlanta, GA USA. Ferring Pharmaceut AS, Copenhagen, Denmark. Univ Tubingen, Tubingen, Germany. Natl Inst Med Res, London NW7 1AA, England. Oregon Hlth Sci Univ, Portland, OR 97201 USA. Univ Tennessee, Memphis, TN USA. Albert Einstein Coll Med, New York, NY USA. Univ Pisa, Pisa, Italy. St Bartholomews Hosp, Sch Med, London, England. Christie Hosp, Manchester, Lancs, England. Hop Univ Cantonal Enfants, Geneva, Switzerland. Univ Munich, Munich, Germany. Kanagawa Childrens Ctr, Yokohama, Kanagawa, Japan. Natl Childrens Med Res Ctr, Tokyo 154, Japan. Univ Virginia, Hlth Sci Ctr, Charlottesville, VA USA. Pediat Growth Ctr, Gothenburg, Sweden. Kaplan Hosp, IL-76100 Rehovot, Israel. RP Attie, KM (reprint author), Aarhus Kommune Hosp, Dept Med, DK-8000 Aarhus C, Denmark. RI Parks, John/F-8570-2011; Albertsson-Wikland, Kerstin/D-3843-2012; Cameron, Fergus/N-9535-2015 NR 5 TC 0 Z9 0 U1 0 U2 2 PU FREUND PUBLISHING HOUSE LTD PI LONDON PA STE 500, CHESHAM HOUSE, 150 REGENT ST, LONDON W1R 5FA, ENGLAND SN 0334-018X J9 J PEDIATR ENDOCR MET JI J. Pediatr. Endocrinol. Metab. PD APR PY 2001 VL 14 IS 4 BP 377 EP 382 PG 6 WC Endocrinology & Metabolism; Pediatrics SC Endocrinology & Metabolism; Pediatrics GA 421XJ UT WOS:000168088600003 ER PT J AU Strand, V Lassere, M van der Heijde, D Johnson, K Boers, M AF Strand, V Lassere, M van der Heijde, D Johnson, K Boers, M TI Recent rheumatoid arthritis clinical trials using radiographic endpoints - Updated research agenda SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT OMERACT 5th International Consensus Conference on Outcome Measures in Rheumatology CY MAY 04-07, 2000 CL TOULOUSE, FRANCE DE rheumatoid arthritis; radiographs; radiographic scoring methods ID PROGRESSION; ISSUES; METAANALYSIS AB Recent randomized controlled trials of traditional and newly developed therapies provide evidence that we have interventions that potentially slow or prevent structural damage in active rheumatoid arthritis, as measured using radiography. These trials also provide a unique opportunity for exploratory data analysis to generate hypotheses apropos the pathogenesis and determinants of radiographic progression and functional disability; they also facilitate further study of the methodological issues regarding imaging measurement. C1 Stanford Univ, Div Immunol, San Francisco, CA USA. St George Hosp, Dept Rheumatol, Sydney, NSW, Australia. Univ Hosp Maastricht, Dept Rheumatol, Maastricht, Netherlands. Limburgs Univ Ctr, Diepenbeek, Belgium. US FDA, CDER, Rockville, MD 20857 USA. VU Univ Hosp, Dept Clin Epidemiol, Amsterdam, Netherlands. RP Strand, V (reprint author), 306 Ramona Rd, Portola Valley, CA 94028 USA. NR 16 TC 10 Z9 10 U1 0 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 2001 VL 28 IS 4 BP 887 EP 889 PG 3 WC Rheumatology SC Rheumatology GA 416YT UT WOS:000167808600039 PM 11327271 ER PT J AU Lassere, MND van der Heijde, D Johnson, KR AF Lassere, MND van der Heijde, D Johnson, KR TI Foundations of the minimal clinically important difference for imaging SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT OMERACT 5th International Consensus Conference on Outcome Measures in Rheumatology CY MAY 04-07, 2000 CL TOULOUSE, FRANCE DE smallest detectable difference; randomized controlled trials; minimum clinically important difference ID RHEUMATOID-ARTHRITIS AB This article develops a generic conceptual framework for defining and validating the concept of minimal clinically important difference. We propose 3 approaches. The first uses statistical descriptions of the population ("distribution based"), the second relies on experts ("opinion based"), and a third is based on sequential hypothesis formation and testing ("predictive/data driven based"). The first 2 approaches serve as proxies for the third, which is an experimentally driven approach, asking such questions as "What carries the least penalty?" or "What imparts the greatest gain?" As an experimental approach, it has the expected drawbacks, including the need for greater resources, and the need to tolerate trial and error en route. compared to the other 2 models. C1 St George Hosp, Dept Rheumatol, Sydney, NSW, Australia. Univ Hosp Maastricht, Dept Rheumatol, Maastricht, Netherlands. Limburgs Univ Ctr, Diepenbeek, Belgium. US FDA, CDER, Rockville, MD 20857 USA. RP Lassere, MND (reprint author), St George Hosp, Dept Rheumatol, Kogarah, NSW 2217, Australia. NR 5 TC 25 Z9 25 U1 0 U2 0 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 2001 VL 28 IS 4 BP 890 EP 891 PG 2 WC Rheumatology SC Rheumatology GA 416YT UT WOS:000167808600040 PM 11327272 ER PT J AU Lassere, MND van der Heijde, D Johnson, KR Boers, M Edmonds, J AF Lassere, MND van der Heijde, D Johnson, KR Boers, M Edmonds, J TI Reliability of measures of disease activity and disease damage in rheumatoid arthritis: Implications for smallest detectable difference, minimal clinically important difference, and analysis of treatment effects in randomized controlled trials SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT OMERACT 5th International Consensus Conference on Outcome Measures in Rheumatology CY MAY 04-07, 2000 CL TOULOUSE, FRANCE DE minimal clinically important difference; reliability; randomized controlled trials; articular assessment; health status; radiographs ID HEALTH ASSESSMENT QUESTIONNAIRE; COLLEGE-OF-RHEUMATOLOGY; OBSERVER VARIATION; RADIOGRAPHIC PROGRESSION; RADIOLOGICAL PROGRESSION; QUANTITATIVE ASSESSMENT; ARTICULAR INDEXES; DISABILITY INDEX; SPANISH VERSION; PAIN SCALES AB We evaluate measurement properties of common rheumatoid arthritis (RA) assessments. Included are a comprehensive literature review and new data on the reliability and smallest detectable difference (SDD) for different classes of these measures. We found that certain common measures such as joint counts, pain, and patient global all had poor reliability and showed large SDD compared to multi-item measures of physical/psychological function or compared to radiographic measures. We discuss the implications of these findings on the use of composite endpoints such as the ACR20 or the EULAR responder index in RA clinical trials, particularly the introduction of misclassification bias that arises from differential measurement error, Finally, we consider generically how the concept of the SDD might or might not relate to the concept of the minimal clinically important difference. C1 St George Hosp, Dept Rheumatol, Sydney, NSW, Australia. Univ Hosp Maastricht, Dept Rheumatol, Maastricht, Netherlands. Limburgs Univ Ctr, Diepenbeek, Belgium. US FDA, CDER, Rockville, MD 20857 USA. VU Univ Hosp, Dept Clin Epidemiol, Amsterdam, Netherlands. RP Lassere, MND (reprint author), St George Hosp, Dept Rheumatol, Kogarah, NSW 2217, Australia. NR 84 TC 68 Z9 69 U1 2 U2 4 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 2001 VL 28 IS 4 BP 892 EP 903 PG 12 WC Rheumatology SC Rheumatology GA 416YT UT WOS:000167808600041 PM 11327273 ER PT J AU Lassere, MND van der Heijde, D Johnson, K Bruynesteyn, K Molenaar, E Boonen, A Verhoeven, A Emery, P Boers, M AF Lassere, MND van der Heijde, D Johnson, K Bruynesteyn, K Molenaar, E Boonen, A Verhoeven, A Emery, P Boers, M TI Robustness and generalizability of smallest detectable difference in radiological progression SO JOURNAL OF RHEUMATOLOGY LA English DT Article; Proceedings Paper CT OMERACT 5th International Consensus Conference on Outcome Measures in Rheumatology CY MAY 04-07, 2000 CL TOULOUSE, FRANCE DE minimal clinically important difference; reliability; measurement error; radiographic scoring; rheumatoid arthritis ID RHEUMATOID-ARTHRITIS; RADIOGRAPHS AB The smallest detectable difference (SDD) reflects that component of a measure statistically attributable to error from the measurement process itself. As such it is an irreducible component of the inherent variability in measurements in clinical trials and will affect their design, whether randomized or observational. Even though the application of the SDD concept to assaying radiographs in rheumatoid arthritis is relatively new and not well understood, systematic work on the influences of radiographic SDD can be done. This report describes the effects of a number of clinical aspects of the disease and operational aspects of trials on the values of the SDD of radiographic progression data. We show that if conditions affecting SDD are known and kept constant across datasets, the SDD of radiological progression from one study may be generalizable to other studies. However, if any one condition varies, the SDD is distinctly unrobust and cannot be generalized to other studies. C1 St George Hosp, Dept Rheumatol, Kogarah, NSW 2217, Australia. Univ Hosp Maastricht, Dept Rheumatol, Maastricht, Netherlands. Limburg Univ Ctr, Diepenbeek, Belgium. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. VU Univ Hosp, Dept Clin Epidemiol, Amsterdam, Netherlands. VU Univ Hosp, Dept Rheumatol, Amsterdam, Netherlands. Univ Leeds, Rheumatol Res Unit, Leeds, W Yorkshire, England. RP Lassere, MND (reprint author), St George Hosp, Dept Rheumatol, Kogarah, NSW 2217, Australia. NR 10 TC 30 Z9 30 U1 1 U2 1 PU J RHEUMATOL PUBL CO PI TORONTO PA 920 YONGE ST, SUITE 115, TORONTO, ONTARIO M4W 3C7, CANADA SN 0315-162X J9 J RHEUMATOL JI J. Rheumatol. PD APR PY 2001 VL 28 IS 4 BP 911 EP 913 PG 3 WC Rheumatology SC Rheumatology GA 416YT UT WOS:000167808600043 PM 11327275 ER PT J AU Choma, TJ Chwirut, D Polly, DW AF Choma, TJ Chwirut, D Polly, DW TI Biomechanics of long segment fixation: Hook patterns and rod strain SO JOURNAL OF SPINAL DISORDERS LA English DT Article DE spine; biomechanics; mechanical stress; kyphosis; internal fixators ID COTREL-DUBOUSSET INSTRUMENTATION; SCHEUERMANNS DISEASE; SURGICAL-MANAGEMENT; PEDICLE SCREW; SPINE; SCOLIOSIS; IMPLANTS; FUSION AB This is an in vitro study of the mechanical effects of varying hook attachment patterns in long segment kyphotic deformity. In such cases, the optimal implant bulk, fatigue life, and construct rigidity to reliably achieve fusion are still unquantified. Rod strains were measured for multiple laminar hook patterns in a synthetic thoracic spine test bed. Stresses were calculated from strain data. The model displayed similar flexion bending stiffness to the thoracic spine. None of the hook patterns significantly changed overall construct stiffness. Greatest rod strains were seen when utilizing away-facing apical hooks. This model was too stiff to detect differences in construct stiffness. Nonetheless, rod stress analysis showed that for multisegment thoracic constructs, particularly with fixed kyphosis, minimizing apical hooks will minimize rod strain. If periapical hooks are necessary, orienting the hooks toward the apex will minimize rod strain. C1 Walter Reed Army Med Ctr, Orthopaed Surg Serv, Washington, DC 20307 USA. US FDA, Div Mech & Mat Sci, Rockville, MD 20857 USA. RP Polly, DW (reprint author), Walter Reed Army Med Ctr, Orthopaed Surg Serv, Washington, DC 20307 USA. OI Choma, Theodore/0000-0002-9194-8563 NR 42 TC 4 Z9 6 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0895-0385 J9 J SPINAL DISORD JI J. Spinal Disord. PD APR PY 2001 VL 14 IS 2 BP 125 EP 132 DI 10.1097/00002517-200104000-00006 PG 8 WC Clinical Neurology; Orthopedics SC Neurosciences & Neurology; Orthopedics GA 420KA UT WOS:000168003100006 PM 11285424 ER PT J AU Schott, HC Ewart, SL Walker, RD Dwyer, RM Dietrich, S Eberhart, SW Kusey, J Stick, JA Derksen, FJ AF Schott, HC Ewart, SL Walker, RD Dwyer, RM Dietrich, S Eberhart, SW Kusey, J Stick, JA Derksen, FJ TI An outbreak of salmonellosis among horses at a veterinary teaching hospital SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Article ID FIELD GEL-ELECTROPHORESIS; PLASMID PROFILE ANALYSIS; RISK-FACTORS; EQUINE SALMONELLOSIS; CHROMOSOMAL DNA; INFECTION; FECES; TYPHIMURIUM; PREVALENCE; ANATUM C1 Michigan State Univ, Coll Vet Med, Dept Large Anim Clin Sci, E Lansing, MI 48824 USA. Michigan State Univ, Coll Vet Med, Dept Microbiol, E Lansing, MI 48824 USA. Michigan State Univ, Coll Vet Med, Anim Hlth Diagnost Lab, E Lansing, MI 48824 USA. Univ Kentucky, Coll Agr, Dept Vet Sci, Maxwell H Gluck Equine Res Ctr, Lexington, KY 40546 USA. State Michigan Dept Community Hlth, Mol Biol Sect, Lansing, MI 48909 USA. US FDA, Ctr Vet Med, Div Anim & Food Microbiol, Res Off, Laurel, MD 20708 USA. RP Schott, HC (reprint author), Michigan State Univ, Coll Vet Med, Dept Large Anim Clin Sci, E Lansing, MI 48824 USA. NR 35 TC 54 Z9 55 U1 1 U2 7 PU AMER VETERINARY MEDICAL ASSOC PI SCHAUMBURG PA 1931 N MEACHAM RD SUITE 100, SCHAUMBURG, IL 60173-4360 USA SN 0003-1488 J9 J AM VET MED ASSOC JI J. Am. Vet. Med. Assoc. PD APR 1 PY 2001 VL 218 IS 7 BP 1152 EP + DI 10.2460/javma.2001.218.1152 PG 9 WC Veterinary Sciences SC Veterinary Sciences GA 415KK UT WOS:000167720400029 PM 11318368 ER PT J AU Swann, JP AF Swann, JP TI Pharmaceutical innovation: Revolutionizing human health. SO JOURNAL OF THE HISTORY OF MEDICINE AND ALLIED SCIENCES LA English DT Book Review C1 US FDA, Hist Off, Rockville, MD 20857 USA. RP Swann, JP (reprint author), US FDA, Hist Off, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 1 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 0022-5045 J9 J HIST MED ALL SCI JI J. Hist. Med. Allied Sci. PD APR PY 2001 VL 56 IS 2 BP 196 EP 200 PG 5 WC Health Care Sciences & Services; History & Philosophy Of Science SC Health Care Sciences & Services; History & Philosophy of Science GA 433VD UT WOS:000168780700015 ER PT J AU Martinez, MN Pedersoli, WM Ravis, WR Jackson, JD Cullison, R AF Martinez, MN Pedersoli, WM Ravis, WR Jackson, JD Cullison, R TI Feasibility of interspecies extrapolation in determining the bioequivalence of animal products intended for intramuscular administration SO JOURNAL OF VETERINARY PHARMACOLOGY AND THERAPEUTICS LA English DT Article ID AMPICILLIN-SULBACTAM COMBINATION; COMPARATIVE PHARMACOKINETICS; BIOAVAILABILITY; DISSOLUTION; HUMANS; DRUGS; SHEEP; VETERINARY; TABLETS; CURVE AB To examine the validity of extrapolating parenteral product bioequivalence determinations across target animal species, the relative bioavailability of two injectable formulations of ampicillin trihydrate (Polynex(R), a water-based suspension, and Ampi-kel 10(R), an oil-based suspension) was examined in calves, sheep and swine. Employing products recognized to be bioinequivalent provided an opportunity to explore potential species-by-formulation interactions. As compared with Polyflex(R), Ampi-kel 10(R) exhibited lower area under the curve (AUC) estimates but higher peak concentrations in all target animal species. Nevertheless, marked interspecies differences were noted in the width and bounds of the confidence intervals about the differences in treatment means. Potential physiological and physico-chemical reasons for these findings are discussed. C1 US FDA, Div Therapeut Drugs Food Anim, CVM, MPNII, Rockville, MD 20852 USA. US FDA, Div Anim Res, CVM, OR, Laurel, MD 20708 USA. Auburn Univ, Sch Pharm, Dept Pharmacal Sci, Auburn, AL 36849 USA. RP Martinez, MN (reprint author), US FDA, Div Therapeut Drugs Food Anim, CVM, MPNII, Rockville, MD 20852 USA. NR 34 TC 10 Z9 10 U1 0 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0140-7783 J9 J VET PHARMACOL THER JI J. Vet. Pharmacol. Ther. PD APR PY 2001 VL 24 IS 2 BP 125 EP 135 DI 10.1046/j.1365-2885.2001.00316.x PG 11 WC Pharmacology & Pharmacy; Veterinary Sciences SC Pharmacology & Pharmacy; Veterinary Sciences GA 452ZZ UT WOS:000169890900008 PM 11442787 ER PT J AU Holmes, H Davis, G Heath, A Hewlett, I Lelie, N AF Holmes, H Davis, G Heath, A Hewlett, I Lelie, N TI An international collaborative study to establish the 1st international standard for HIV-1 RNA for use in nucleic acid-based techniques SO JOURNAL OF VIROLOGICAL METHODS LA English DT Article DE HIV-1 RNA; nucleic acid-based techniques; NAT; international standard ID VIRUS TYPE-1 RNA; PLASMA; QUANTIFICATION; INFECTION; MARKERS; BLOOD AB Twenty-six laboratories from 10 different countries participated in a collaborative study to establish the 1st International Standard for HIV-1 RNA for use in nucleic acid-based techniques (NAT). Three candidate preparations were tested all based on genotype B viruses. The candidates were tested by each laboratory at a range of dilutions in four independent assays and the results collated and analysed statistically. All three candidates gave results that were tightly grouped, with little difference between the results from different laboratories or from the use of different assays. Studies of relative potency showed good agreement between laboratories. There were no significant differences between five commercial assay types, except that candidate XX showed a slightly lower potency compared to YY and ZZ with a single commercial assay. The reason for this was not established. Degradation studies showed that the freeze-dried preparations were stable at - 20, 4 and 20 degreesC for 26 weeks, the longest period studied, but that they became difficult to reconstitute after 3 weeks at 45 degreesC and 9 weeks at 37 degreesC. As a result of the study, the World Health Organisation (WHO) Expert Committee on Biological Standardisation (ECBS) established the preparation referred to as candidate YY(NIBSC Code No. 97/656) as the 1st International Standard for HIV-1 RNA for use with NAT with an assigned potency of 100 000 International Units per vial. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Natl Inst Biol Stand & Controls, Div Retrovirol, Potters Bar EN6 3QG, Herts, England. Natl Inst Biol Stand & Controls, Div Informat, Potters Bar EN6 3QG, Herts, England. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Netherlands Blood Transfus Serv, Cent Lab, Viral Diagnost Lab, NL-1066 CX Amsterdam, Netherlands. RP Holmes, H (reprint author), Natl Inst Biol Stand & Controls, Div Retrovirol, Blanche Lane S Mimms, Potters Bar EN6 3QG, Herts, England. NR 21 TC 67 Z9 71 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-0934 J9 J VIROL METHODS JI J. Virol. Methods PD APR PY 2001 VL 92 IS 2 BP 141 EP 150 DI 10.1016/S0166-0934(00)00283-4 PG 10 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Virology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Virology GA 409HR UT WOS:000167378700005 PM 11226561 ER PT J AU Mao, Q Ray, SC Laeyendecker, O Ticehurst, JR Strathdee, SA Vlahov, D Thomas, DL AF Mao, Q Ray, SC Laeyendecker, O Ticehurst, JR Strathdee, SA Vlahov, D Thomas, DL TI Human immunodeficiency virus seroconversion and evolution of the hepatitis C virus quasispecies SO JOURNAL OF VIROLOGY LA English DT Article ID INJECTING DRUG-USERS; HYPERVARIABLE REGION; COINFECTED PATIENTS; NATURAL-HISTORY; LIVER-DISEASE; INFECTION; BLOOD; HEMOPHILIACS; BALTIMORE; FIDELITY AB When chronic hepatitis C virus (HCV) infections are complicated by acquisition of human immunodeficiency virus (HIV), liver disease appears to accelerate and serum levels of HCV RNA may rise. We hypothesized that HIV might affect the HCV quasispecies by decreasing both complexity (if HIV-induced immunosuppression lessens pressure for selecting HCV substitutions) and the ratio of nonsynonymous (d(N)) to synonymous (d(S)) substitutions, because d(N) may be lower (if there is less selective pressure). To test this hypothesis, we studied the evolution of HCV sequences in 10 persons with chronic HCV infection who seroconverted to HIV and, over the next 3 years, had slow or rapid progression of HIV-associated disease. From each subject, four serum specimens were selected with reference to HIV seroconversion: (i) more than 2 years prior, (ii) less than 2 years prior, (iii) less than 2 years after, and (iv) more than 2 years after. The HCV quasispecies in these specimens was characterized by generating clones containing I kb of cDNA that spanned the E1 gene and the E2 hypervariable region 1 (HVR1), followed by analysis of clonal frequencies (via electrophoretic migration) and nucleotide sequences. We examined 1,320 cDNA clones (33 per time point) and 287 sequences (median of 7 per time point). We observed a trend toward lower d(N)/d(S) after HIV seroconversion in 7 of 10 subjects and lower d(N)/d(S) in those with rapid HIV disease progression. However, the magnitude of these differences was small. These results are consistent with the hypothesis that HIV infection alters the HCV quasispecies, but the number of subjects and observation time may be too low to characterize the full effect. C1 Johns Hopkins Med Inst, Dept Med, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA. Johns Hopkins Med Inst, Dept Epidemiol, Baltimore, MD 21205 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Third Mil Med Univ, SW Hosp, Chongqing, Peoples R China. RP Thomas, DL (reprint author), 1147 Ross Bldg,720 Rutland Ave, Baltimore, MD 21205 USA. RI Laeyendecker, Oliver/B-9331-2009; Strathdee, Steffanie/B-9042-2009; Ray, Stuart/B-7527-2008; Ticehurst, John/I-7532-2012; OI Ray, Stuart/0000-0002-1051-7260; Laeyendecker, Oliver/0000-0002-6429-4760 FU Intramural NIH HHS [Z99 AI999999]; NIDA NIH HHS [DA 12568, DA 04334, DA 10627, R01 DA004334, R01 DA012568, R37 DA004334, R56 DA004334, R56 DA012568] NR 38 TC 42 Z9 44 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 2001 VL 75 IS 7 BP 3259 EP 3267 DI 10.1128/JVI.75.7.3259-3267.2001 PG 9 WC Virology SC Virology GA 410YX UT WOS:000167469600021 PM 11238852 ER PT J AU Debrabant, A Bastien, P Dwyer, DM AF Debrabant, A Bastien, P Dwyer, DM TI A unique surface membrane anchored purine-salvage enzyme is conserved among a group of primitive eukaryotic human pathogens SO MOLECULAR AND CELLULAR BIOCHEMISTRY LA English DT Article DE human pathogen; protozoan parasite; class-I nuclease; pulsed field gel electrophoresis; genome; chromosome ID LEISHMANIA-DONOVANI PROMASTIGOTES; 3'-NUCLEOTIDASE NUCLEASE ACTIVITY; CLASS-I NUCLEASE; CRITHIDIA-LUCILIAE; TRYPANOSOMA-BRUCEI; LOCALIZATION; EXPRESSION; 5'-NUCLEOTIDASE; PURIFICATION; AMASTIGOTES AB Previously, we isolated and characterized the gene encoding the 3'-Nucleotidase/Nuclease (Ld3'NT/NU) from the human pathogen, Leishmania donovani. This unique cell surface enzyme has been shown to be involved in the salvage of host-derived purines, which are essential for the survival of this important protozoan parasite. In this report, we assessed whether the 3'-Nucleotidase/Nuclease was conserved amongst other pathogenic Leishmania and related trypanosomatid parasites. Results of pulsed field gel electrophoresis and Southern blotting showed that a Ld3'NT/NU gene homolog was present in each of the visceral and cutaneous Leishmania species tested (i.e. isolates of L. donovani, L. infantum, L. tropica, L. major and L. mexicana, respectively). Further, results of colorimetric assays using 3'-adenosine monophosphate as substrate demonstrated that each of these organisms also expressed significant levels of 3'-nucleotidase enzyme activity. In addition, we showed that a Ld3'NT/NU gene homolog was expressed in each of these Leishmania species as a > 40 kDa 3'-nucleotidase enzyme activity. A Ld3'NT/NU gene homolog was also identified in two Crithidia species (C. fasciculata and C. luciliae) and Leptomonas seymouri but was only marginally detectable in Trypanosoma brucei, Trypanosoma cruzi and Phytomonas serpens. Cumulatively, results of this study showed that an Ld3'NT/NU homolog was conserved amongst pathogenic Leishmania sp. which suggests that this enzyme must play an critical role in purine salvage for all members of this group of human pathogens. C1 NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Bethesda, MD USA. Fac Med, Parasitol Lab, CNRS, UMR 5093, Montpellier, France. RP Dwyer, DM (reprint author), NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bldg 4,Room 126,4 Ctr Dr MSC 0425, Bethesda, MD 20892 USA. RI Bastien, Patrick/F-5904-2013 NR 30 TC 13 Z9 14 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0300-8177 J9 MOL CELL BIOCHEM JI Mol. Cell. Biochem. PD APR PY 2001 VL 220 IS 1-2 BP 109 EP 116 DI 10.1023/A:1010809420104 PG 8 WC Cell Biology SC Cell Biology GA 429WQ UT WOS:000168541300014 PM 11451370 ER PT J AU Khan, SA Khan, AA Nawaz, MS DePaola, A Andrews, A Cerniglia, CE AF Khan, SA Khan, AA Nawaz, MS DePaola, A Andrews, A Cerniglia, CE TI DNA packaging and developmental intermediates of a broad host range Vibrio vulnificus bacteriophage 71A-6 SO MOLECULAR AND CELLULAR PROBES LA English DT Article DE bacteriophage; capsid-assembly; procapsid; capsid-DNA complex; DNA packaging ID ESCHERICHIA-COLI; SCAFFOLDING PROTEIN; CAPSID PROTEIN; T7 CAPSIDS; IN-VITRO; LAMBDA; PHAGE; ELECTROPHORESIS; PURIFICATION; POLYMERASE AB The structural intermediates in the capsid assembly and DNA packaging pathway of Vibrio vulnificus bacteriophage 71A-6, a rod-shaped double-stranded DNA podovirus, were isolated by ultracentrifugation and studied by electron microscopy, SDS-PAGE and pulsed-field gel electrophoretic analysis. Bacteriophage 71A-6 synthesized rod-shaped capsids (mean length = 200 +/- 8 nm; mean width = 47 +/- 3 nm; n = 50) during its development. Several host proteins that probably help in the assembly and maturation of the capsids were attached to these capsids as spherical structures. A capsid-DNA or DNA packaging complex that consisted of the mature capsids, DNA and a 42(.)5-kDa protein was also isolated. The size of the capsids increased in length and decreased in width (mean length = 220 +/- 8 nm; mean width = 45 +/- 3 nm; n = 50) either during or after the DNA packaging. The capsid fractions contained about 12 phage structural proteins and eight host proteins. At least three proteins were tentatively identified: a 38(.)5-kDa major capsid protein, a 35(.)2-kDa tail protein and 42(.)5-kDa packaging initiator or terminator protein. The size of the bacteriophage 71A-6 genome was determined to be 143(.)0-kb by pulsed-field gel electrophoresis. The total mass of all the mature phage proteins corresponded to only 14(.)0% of the coding capacity of phage genome. (C) 2001 Academic Press. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. US FDA, Natl Ctr Toxicol Res, Dept Pathol, Jefferson, AR 72079 USA. RP Nawaz, MS (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 37 TC 4 Z9 4 U1 1 U2 2 PU ACADEMIC PRESS 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 2001 VL 15 IS 2 BP 61 EP 69 DI 10.1006/mcpr.2000.0344 PG 9 WC Biochemical Research Methods; Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Cell Biology GA 422AL UT WOS:000168095700001 PM 11292322 ER PT J AU Jaffee, IS AF Jaffee, IS TI Implantable middle ear hearing devices - Food and Drug Administration review process SO OTOLARYNGOLOGIC CLINICS OF NORTH AMERICA LA English DT Article; Proceedings Paper CT 3rd International Symposium on Electronic Implants in Otology and Conventional Hearing Aids CY JUN, 2000 CL BIRMINGHAM, ENGLAND AB This article presents an overview of the role of the Food and Drug Administration in reviewing new devices and then explains this process in some detail as it applies to implantable middle ear hearing devices. The role of the Food and Drug Administration is to protect the patient and physician by reviewing devices for safety and effectiveness before they are made available for general use. C1 US FDA, Ctr Devices & Radiol Hlth, Ear Nose & Throat Devices Branch, Rockville, MD 20857 USA. RP Jaffee, IS (reprint author), HFZ 460, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 0 TC 2 Z9 3 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 0030-6665 J9 OTOLARYNG CLIN N AM JI Otolaryngol. Clin. N. Am. PD APR PY 2001 VL 34 IS 2 BP 515 EP + DI 10.1016/S0030-6665(05)70346-7 PG 4 WC Otorhinolaryngology SC Otorhinolaryngology GA 445KC UT WOS:000169455800016 PM 11382584 ER PT J AU Krause, PR Klinman, DM AF Krause, PR Klinman, DM TI Disseminated rashes and varicella vaccine SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Letter DE varicella vaccine; disseminated rashes ID STRAIN C1 US FDA, Ctr Biol Evaluat & Res, Div Virol Prod, Bethesda, MD 20205 USA. RP Krause, PR (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Virol Prod, Bethesda, MD 20205 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD APR PY 2001 VL 20 IS 4 BP 467 EP 468 DI 10.1097/00006454-200104000-00031 PG 2 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 421HJ UT WOS:000168058700030 PM 11332687 ER PT J AU Hanna, GM AF Hanna, GM TI Direct enantiomeric purity determination of the chiral anesthetic drug bupivacaine by H-1 NMR spectroscopy SO PHARMAZIE LA English DT Article ID MAGNETIC-RESONANCE SPECTROSCOPY; LIQUID-CHROMATOGRAPHIC RESOLUTION; ALPHA-1-ACID GLYCOPROTEIN COLUMN; MEDICINAL CHEMISTRY; STATIONARY PHASE; OPTICAL PURITY; STEREOCHEMISTRY; METABOLISM; SEPARATION AB The direct determination of the enantiomeric purity of the chiral anaesthetic drug bupivacaine has been developed using H-1 NMR (400 MHz) spectroscopy with a chiral solvating agent. Optimization of experimental conditions in terms of temperature, substrate concentration and solvating agent to substrate molar ratio provided two significant signal splittings for chiral recognition resulting from diastereomeric solvation. Based on the relative intensities of the aliphatic methyl resonances assigned to (S)-(-)- and (R)-(+)-bupivacaine, the analysis of synthetic mixtures of the enantiomers by the proposed NMR method resulted in assay values which agreed closely with the known quantities of each enantiomer in the mixtures tested. The mean PSD recovery values for the (R)-(+)-enantiomer was 100.0 +/- 0.6% of added antipode (n = 7). The optically pure enantiomers were used to establish the minimum sensitivity of the NMR spectroscopic method of chiral analysis. C1 US FDA, Dept Hlth & Human Serv, NE Reg Lab, Jamaica, NY 11433 USA. RP Hanna, GM (reprint author), US FDA, Dept Hlth & Human Serv, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 27 TC 2 Z9 2 U1 0 U2 1 PU GOVI-VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCHER VERLAG GINNHEIMER STRASSE 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD APR PY 2001 VL 56 IS 4 BP 314 EP 317 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 420PZ UT WOS:000168014500009 PM 11338671 ER PT J AU Anderson, V Carneiro, M Bulterys, M Douglas, G Polliotti, B Slikker, W AF Anderson, V Carneiro, M Bulterys, M Douglas, G Polliotti, B Slikker, W TI Perinatal infections: HIV and co-infections in the placenta and therapeutic interventions - A workshop report SO PLACENTA LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; TO-CHILD TRANSMISSION; EXPOSURE; MOTHER; ZIDOVUDINE C1 SUNY Hlth Sci Ctr, Dept Pathol, Brooklyn, NY 11203 USA. Maternidad Concepc Palacios, Miami, FL 33102 USA. CDC, NCHSTP, Atlanta, GA 30333 USA. Univ Calif Davis, Davis, CA 95616 USA. Univ Rochester, Med Ctr, Rochester, NY 14642 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Anderson, V (reprint author), SUNY Hlth Sci Ctr, Dept Pathol, 450 Clarkson Ave, Brooklyn, NY 11203 USA. NR 16 TC 4 Z9 7 U1 0 U2 0 PU W B SAUNDERS CO LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0143-4004 J9 PLACENTA JI Placenta PD APR PY 2001 VL 22 SU A BP S34 EP S37 DI 10.1053/plac.2001.0641 PG 4 WC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology SC Developmental Biology; Obstetrics & Gynecology; Reproductive Biology GA 430YK UT WOS:000168602900008 PM 11312626 ER PT J AU Liu, PT AF Liu, PT TI Extremely small sample size in some toxicity studies: An example from the rabbit eye irritation test SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article DE multiple screening; sensitivity; specificity; false positive; false negative; mixture binomial; Bayes' theorem; regulatory decisions ID CARCINOGENICITY AB The conventional sample-size equations based on either the precision of estimation or the power of testing a hypothesis may not be appropriate to determine sample size for a "diagnostic" testing problem, such as the eye irritant Draize test. When the animals' responses to chemical compounds are relatively uniform and extreme and the objective is to classify a compound as either irritant or nonirritant, the test using just two or three animals may be adequate. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Math, Washington, DC 20204 USA. RP Liu, PT (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Math, 200 C St NW, Washington, DC 20204 USA. NR 20 TC 1 Z9 1 U1 0 U2 3 PU ACADEMIC PRESS INC 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 2001 VL 33 IS 2 BP 187 EP 191 DI 10.1006/rtph.2000.1445 PG 5 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA 433VQ UT WOS:000168781700009 PM 11350201 ER PT J AU Marti, GE Stetler-Stevenson, N Bleesing, JJH Fleisher, TA AF Marti, GE Stetler-Stevenson, N Bleesing, JJH Fleisher, TA TI Introduction to flow cytometry SO SEMINARS IN HEMATOLOGY LA English DT Editorial Material ID WHOLE-BLOOD LYSIS; LYMPHOCYTE SUBSETS; FLUORESCENCE SENSITIVITY; PERIPHERAL-BLOOD; REFERENCE RANGES; CELL SUBSETS; LIGHT; ENUMERATION; CAUCASIANS; POPULATION C1 US FDA, Flow & Image Cytometry Sect, Lab Med & Mol Genet, Div Cell & Gene Therapies,CBER, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Pathol Lab, Bethesda, MD 20892 USA. NIH, Dept Lab Med, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Marti, GE (reprint author), US FDA, Flow & Image Cytometry Sect, Lab Med & Mol Genet, Div Cell & Gene Therapies,CBER, Bldg 29B,Room 2NN08,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 36 TC 15 Z9 15 U1 2 U2 14 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0037-1963 J9 SEMIN HEMATOL JI Semin. Hematol. PD APR PY 2001 VL 38 IS 2 BP 93 EP 99 DI 10.1053/shem.2001.21921 PG 7 WC Hematology SC Hematology GA 423NM UT WOS:000168182400001 PM 11309691 ER PT J AU Mathur, S Constable, PD Eppley, RM Tumbleson, ME Smith, GW Tranquilli, WJ Morin, DE Haschek, WM AF Mathur, S Constable, PD Eppley, RM Tumbleson, ME Smith, GW Tranquilli, WJ Morin, DE Haschek, WM TI Fumonisin B-1 increases serum sphinganine concentration but does not alter serum sphingosine concentration or induce cardiovascular changes in milk-fed calves SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Society-of-Toxicology CY MAR 22, 2000 CL PHILADELPHIA, PENNSYLVANIA SP Soc Toxicol DE fumonisin; sphingosine; sphinganine; sphingolipid; cardiovascular toxicity; metabolic acidosis ID CULTURE MATERIAL; EQUINE LEUKOENCEPHALOMALACIA; SPHINGOLIPID METABOLISM; DIETARY FUMONISIN; PULMONARY-EDEMA; CORN SCREENINGS; RENAL TOXICITY; SWINE; EXPOSURE; DISRUPTION AB Fumonisin B-1 is the most toxic and commonly occurring form of a group of mycotoxins that alter sphingolipid biosynthesis and induce leukoencephalomalacia in horses and pulmonary edema in pigs. Purified fumonisin B-1 (1 mg/kg, iv, daily) increased serum sphinganine and sphingosine concentrations and decreased cardiovascular function in pigs within 5 days. We therefore examined whether the same dosage schedule of fumonisin B-1 produced a similar effect in calves. Ten milk-fed male Holstein calves were instrumented to obtain blood and cardiovascular measurements. Treated calves (n = 5) were administered purified fumonisin B-1 at 1 mg/kg, iv, daily for 7 days and controls (n = 5) were administered 10 ml 0.9% NaCl, iv, daily. Each calf was euthanized on day 7. In treated calves, serum sphinganine concentration increased from day 3 onward (day 7, 0.237 +/- 0.388 mu mol/l; baseline, 0.010 +/- 0.007 mu mol/l; mean +/- SD), whereas, serum sphingosine concentration was unchanged (day 7, 0.044 +/- 0.065 mu mol/l; baseline, 0.021 +/- 0.025 mu mol/l). Heart rate, cardiac output, stroke volume, mean arterial pressure, mean pulmonary artery pressure, pulmonary artery wedge pressure, central venous pressure, plasma volume, base-apex electrocardiogram, arterial Po,, and systemic oxygen delivery were unchanged in treated and control calves. Fumonisin-treated calves developed metabolic acidosis (arterial blood pH, 7.27 +/- 0.11; base excess, -9.1 +/- 7.6 mEq/l), but all survived for 7 days. We conclude that calves are more resistant to fumonisin B-1 cardiovascular toxicity than pigs. C1 Univ Illinois, Coll Vet Med, Dept Vet Clin Med, Urbana, IL 61802 USA. Univ Illinois, Coll Vet Med, Dept Vet Biosci, Urbana, IL 61802 USA. Univ Illinois, Coll Vet Med, Dept Vet Pathobiol, Urbana, IL 61802 USA. US FDA, Washington, DC 20204 USA. RP Constable, PD (reprint author), Univ Illinois, Coll Vet Med, Dept Vet Clin Med, 1008 W Hazelwood Dr, Urbana, IL 61802 USA. NR 21 TC 15 Z9 15 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 APR PY 2001 VL 60 IS 2 BP 379 EP 384 DI 10.1093/toxsci/60.2.379 PG 6 WC Toxicology SC Toxicology GA 414KU UT WOS:000167666400022 PM 11248151 ER PT J AU Mathur, S Constable, PD Eppley, RM Waggoner, AL Tumbleson, ME Haschek, WM AF Mathur, S Constable, PD Eppley, RM Waggoner, AL Tumbleson, ME Haschek, WM TI Fumonisin B-1 is hepatotoxic and nephrotoxic in milk-fed calves SO TOXICOLOGICAL SCIENCES LA English DT Article; Proceedings Paper CT 39th Annual Meeting of the Society-of-Toxicology CY MAR 22, 2000 CL PHILADELPHIA, PENNSYLVANIA SP Soc Toxicol DE fumonisin; sphingosine; sphinganine; sphingolipid; hepatotoxicity; cholesterol; nephrotoxicity; proximal renal tubules ID BILE-ACID CONCENTRATIONS; B-1-CONTAINING CULTURE MATERIAL; SPRAGUE-DAWLEY RATS; FUSARIUM-MONILIFORME; DIETARY FUMONISIN; PULMONARY-EDEMA; EQUINE LEUKOENCEPHALOMALACIA; COLOSTRAL TRANSFER; HEPATIC-FUNCTION; GROWING BARROWS AB Fumonisins are a group of mycotoxins that alter sphingolipid biosynthesis and induce leukoencephalomalacia in horses and pulmonary edema in pigs. Experimental administration of fumonisin induces hepatotoxicity in all species, including cattle, as well as nephrotoxicity in rats, rabbits, and sheep. We investigated the hepatotoxicity and nephrotoxicity of fumonisin B-1 to calves. Ten milk-fed male Holstein calves aged 7 to 14 days were instrumented to obtain blood and urine. Treated calves (n = 5) were administered fumonisin B-1 at 1 mg/kg, iv, daily and controls (n = 5) 10 ml 0.9% NaCl, iv, daily until euthanized on day 7. Fumonisin B-1-treated calves were lethargic and had decreased appetite from day 4 onward, serum biochemical evidence of severe liver and bile duct injury, and impaired hepatic function. Treated calves also had biochemical evidence of renal injury that functionally involved the proximal convoluted tubules. Sphinganine and sphingosine concentrations in liver, kidney, lung, heart, and skeletal muscle were increased in treated calves. Sphinganine, but not sphingosine, concentration was increased in brains of treated calves. Zn fumonisin B-1-treated calves, hepatic lesions were characterized by disorganized hepatic cords, varying severity of hepatocyte apoptosis, hepatocyte proliferation, and proliferation of bile ductular cells. Renal lesions in treated calves consisted of vacuolar change, apoptosis, karyomegaly, and proliferation of proximal renal tubular cells, as well as dilation of proximal renal tubules, which contained cellular debris and protein. This is the first report of fumonisin B-1-induced renal injury and organ sphingolipid alterations in cattle. C1 Univ Illinois, Coll Vet Med, Dept Vet Clin Med, Urbana, IL 61802 USA. Univ Illinois, Coll Vet Med, Dept Vet Pathobiol, Urbana, IL 61802 USA. Univ Illinois, Coll Vet Med, Dept Vet Biosci, Urbana, IL 61802 USA. US FDA, Washington, DC 20204 USA. RP Constable, PD (reprint author), Univ Illinois, Coll Vet Med, Dept Vet Clin Med, 1008 W Hazelwood Dr, Urbana, IL 61802 USA. NR 60 TC 34 Z9 35 U1 0 U2 5 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD APR PY 2001 VL 60 IS 2 BP 385 EP 396 DI 10.1093/toxsci/60.2.385 PG 12 WC Toxicology SC Toxicology GA 414KU UT WOS:000167666400023 PM 11248152 ER PT J AU Stewart, SFC AF Stewart, SFC TI Effects of transducer, velocity, Doppler angle, and instrument settings on the accuracy of color Doppler ultrasound SO ULTRASOUND IN MEDICINE AND BIOLOGY LA English DT Article DE color Doppler accuracy; Doppler ultrasound phantom; color Doppler ultrasound ID BLOOD-FLOW; PHANTOM; BIAS AB The accuracy of a commercial color Doppler ultrasound (US) system was assessed in vitro using a rotating torus phantom, The phantom consisted of a thin rubber tube filled with a blood-mimicking fluid, joined at the ends to form a torus, The torus was mounted on a disk suspended in water, and rotated at constant speeds by a motor. The torus fluid was shown in a previous study to rotate as a solid body, so that the actual fluid velocity was dependent only on the motor speed and sample volume radius. The fluid velocity could, thus, be easily compared to the color Doppler-derived velocity. The effects of instrument settings, velocity and the Doppler angle was assessed in four transducers: a 2.0-MHz phased-array transducer designed for cardiac use, a 4.0-MHz curved-array transducer designed for general thoracic use, and two linear transducers designed for vascular use (one 4.0 MHz and one 6.0 MHz), The color Doppler accuracy was found to be significantly dependent on the transducer used, the pulse-repetition frequency and wall-filter frequency, the actual fluid velocity and the Doppler angle (p < 0.001 by analysis of variance). In particular, the phased array and curved array were observed to be significantly more accurate than the two linear arrays,The torus phantom was found to provide a sensitive measure of color Doppler accuracy. Clinicians need to be aware of these effects when performing color Doppler US exams. <(c)> 2001 World Federation for Ultrasound in Medicine & Biology. C1 US FDA, Hydrodynam & Acoust Branch, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Stewart, SFC (reprint author), US FDA, Hydrodynam & Acoust Branch, Ctr Devices & Radiol Hlth, 9200 Corp Blvd,HFZ-132, Rockville, MD 20850 USA. NR 18 TC 23 Z9 23 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0301-5629 J9 ULTRASOUND MED BIOL JI Ultrasound Med. Biol. PD APR PY 2001 VL 27 IS 4 BP 551 EP 564 DI 10.1016/S0301-5629(01)00357-X PG 14 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA 434JA UT WOS:000168810300011 PM 11368866 ER PT J AU Paweletz, CP Liotta, LA Petricoin, EF AF Paweletz, CP Liotta, LA Petricoin, EF TI New technologies for biomarker analysis of prostate cancer progression: Laser capture microdissection and tissue proteomics SO UROLOGY LA English DT Article; Proceedings Paper CT National-Cancer-Institute Workshop CY 1999 CL ROCKVILLE, MARYLAND SP NCI ID ANTIGEN; ASSAY AB The widespread use of serum markers during cancer screenings has led to the belief that there may be tumor markers yet to be discovered that offer better specificity and sensitivity than prostate-specific antigen (PSA). Proteomics, the analysis and characterization of global protein modifications, will add to our understanding of gene function and aid in biomarker and/or therapeutic target discovery. in the past, most proteomic studies were either performed using turner cell lines or homogenized bulk tissue. Unfortunately, these approaches may not accurately reflect molecular events that take place in the actual ductal epithelium that change as a consequence of the malignant process. This report describes alternative proteomic-based approaches aimed at the identification of protein markers in the actual premalignant and frankly malignant epithelium. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Tissue Proteom Unit, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Tissue Proteom Unit, Bldg 29A,Room 2B02,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 17 TC 90 Z9 106 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD APR PY 2001 VL 57 IS 4A SU S BP 160 EP 163 DI 10.1016/S0090-4295(00)00964-X PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 423HT UT WOS:000168170400030 PM 11295617 ER PT J AU Beitz, J AF Beitz, J TI Trial endpoints for drug approval in oncology: Chemoprevention SO UROLOGY LA English DT Article; Proceedings Paper CT National-Cancer-Institute Workshop CY 1999 CL ROCKVILLE, MARYLAND SP NCI AB As with other drugs, new drug applications for marketing approval of chemopreventive drugs must include data from adequate and well-controlled clinical trials that demonstrate effectiveness and safety for the intended use. This article summarizes the regulatory requirements for traditional marketing approval, as well as for approval under the accelerated approval regulations. Unlike traditional approval, accelerated approval is based on a surrogate endpoint that is reasonably likely to predict clinical benefit. Discussions with the Food and Drug Administration (FDA) regarding the validity of trial endpoints that may serve as surrogates for clinical benefit for accelerated approval should take place as early as possible in drug development. Meetings with the FDA to discuss these issues may be requested throughout the clinical development of a new drug. C1 US FDA, Off Postmkt Drug Assessment, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Beitz, J (reprint author), US FDA, Off Postmkt Drug Assessment, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, 5600 Fishers Lane,HFD-430, Rockville, MD 20857 USA. NR 2 TC 3 Z9 4 U1 0 U2 2 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD APR PY 2001 VL 57 IS 4A SU S BP 213 EP 215 DI 10.1016/S0090-4295(00)00977-8 PG 3 WC Urology & Nephrology SC Urology & Nephrology GA 423HT UT WOS:000168170400043 PM 11295630 ER PT J AU Keegan, P Loughman, BE AF Keegan, P Loughman, BE TI Early clinical trials of chemopreventive and biologic agents: Designs, populations and endpoints SO UROLOGY LA English DT Article; Proceedings Paper CT National-Cancer-Institute Workshop CY 1999 CL ROCKVILLE, MARYLAND SP NCI ID PROSTATE-CANCER; MOUSE AB The optimal design for initial clinical trials of chemopreventive agents for cancer has not been determined. A single design is unlikely to be the model for chemoprevention of cancer, even for prevention of a single subtype of cancer, because of the heterogeneity of drugs under investigation and the variety of biologic effects being targeted. Factors that are important in designing initial clinical trials include the proposed mechanisms of drug action, the ability and types of assays available to detect that activity or pharmacodynamic effect, and the extent of prior clinical experience. In this article. we present a discussion of the factors to be considered in initial activity studies, followed by a specific example of early clinical assessment of a noncytotoxic agent (R-flurbiprofen, E-7869) as a potential chemopreventive agent for prostate cancer. C1 US FDA, Off Therapeut, Ctr Biol Evaluat & Res, Div Clin Trials Design & Anal, Rockville, MD 20852 USA. Loma Linda Univ, Encore Pharmaceut Inc, Dept Med, Loma Linda, CA USA. RP Keegan, P (reprint author), US FDA, Off Therapeut, Ctr Biol Evaluat & Res, Div Clin Trials Design & Anal, 1401 Rockville Pike,HFM-570, Rockville, MD 20852 USA. NR 5 TC 8 Z9 8 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0090-4295 J9 UROLOGY JI UROLOGY PD APR PY 2001 VL 57 IS 4A SU S BP 216 EP 219 DI 10.1016/S0090-4295(00)00978-X PG 4 WC Urology & Nephrology SC Urology & Nephrology GA 423HT UT WOS:000168170400044 PM 11295631 ER PT J AU Engelfriet, CP Reesink, HW Krusius, T Wendel, S Fontao-Wendel, R Hoffer, I Medgyesi, G Tadokoro, K Pisacka, M Kuhnl, P Schwartz, DWM Mayr, WR Schonitzer, D Lin, CK James, V Castel, A Hazenberg, CAM Letowska, M Solheim, BG Guerts, M Ghosh, S Flanagan, P Epstein, J Safwenberg, J Riccardi, D Sirchia, G AF Engelfriet, CP Reesink, HW Krusius, T Wendel, S Fontao-Wendel, R Hoffer, I Medgyesi, G Tadokoro, K Pisacka, M Kuhnl, P Schwartz, DWM Mayr, WR Schonitzer, D Lin, CK James, V Castel, A Hazenberg, CAM Letowska, M Solheim, BG Guerts, M Ghosh, S Flanagan, P Epstein, J Safwenberg, J Riccardi, D Sirchia, G TI The use of the computer cross-match SO VOX SANGUINIS LA English DT Editorial Material C1 Netherlands Red Cross, Blood Transfus Serv Sanquin, Cent Lab, NL-1066 CX Amsterdam, Netherlands. Blood Bank N Holland Sanquin, NL-1066 CX Amsterdam, Netherlands. Finnish Red Cross & Blood Transfus Serv, Lab Serv, FIN-00310 Helsinki, Finland. Hosp Sirio Libanes Blood Bank, BR-01308050 Sao Paulo, Brazil. Hungarian Natl Blood Transfus Serv, Budapest Reg Blood Transfus Ctr, Budapest, Hungary. Tokyo Western Blood Ctr JRCS, Tachikawa, Tokyo 1900014, Japan. Inst Haematol & Blood Transfus, Head Reference Lab Immunohaematol, Prague 12820 2, Czech Republic. Univ Hamburg, Chirurg Klin, Abt Transfus Med Transplantat Immunol, D-20246 Hamburg, Germany. Univ Vienna, Clin Blood Grp Serol & Transfus Med, A-1090 Vienna, Austria. Univ Kliniken Innsbruck, Landeskrankenhaus, Zent Inst Bluttransfus, A-6020 Innsbruck, Austria. Univ Kliniken Innsbruck, Landeskrankenhaus, Immunol Abt, A-6020 Innsbruck, Austria. Hong Kong Red Cross Blood Transfus Serv, Kowloon, Hong Kong, Peoples R China. Natl Blood Serv, Trent Ctr, Sheffield, S Yorkshire, England. Bronovo Hosp, Dept Clin Chem & Haematol, NL-2597 AX The Hague, Netherlands. Inst Hematol & Blood Transfus, Warsaw, Poland. Univ Oslo, Natl Hosp, NO-0027 Oslo, Norway. New Zealand Blood Serv, Auckland, New Zealand. US FDA, Rockville, MD 20852 USA. Univ Hosp, Dept Clin Immunol & Transfus Med, SE-75185 Uppsala, Sweden. Osped Maggiore, I-20122 Milan, Italy. RP Engelfriet, CP (reprint author), Netherlands Red Cross, Blood Transfus Serv Sanquin, Cent Lab, Plesmanlaan 125, NL-1066 CX Amsterdam, Netherlands. NR 4 TC 4 Z9 7 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0042-9007 J9 VOX SANG JI Vox Sang. PD APR PY 2001 VL 80 IS 3 BP 184 EP 192 DI 10.1046/j.1423-0410.2001.00032.x PG 9 WC Hematology SC Hematology GA 443CG UT WOS:000169321400009 PM 11449959 ER PT J AU Holada, K Simak, J Vostal, JG AF Holada, K Simak, J Vostal, JG TI Platelets and red cells in PrPSc propagation in human beings - Reply SO LANCET LA English DT Letter ID SPLEEN C1 US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Hematol,Lab Cellular Hematol, Bethesda, MD 20892 USA. RP Holada, K (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Div Hematol,Lab Cellular Hematol, 8800 Rockville Pike, Bethesda, MD 20892 USA. RI Simak, Jan/C-1153-2011 NR 4 TC 0 Z9 0 U1 0 U2 2 PU LANCET LTD PI LONDON PA 84 THEOBALDS RD, LONDON WC1X 8RR, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD MAR 31 PY 2001 VL 357 IS 9261 BP 1044 EP 1044 DI 10.1016/S0140-6736(05)71618-4 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 416QK UT WOS:000167791500053 ER PT J AU Myers, CS Contreras, MA Chang, MCJ Rapoport, SI Appel, NM AF Myers, CS Contreras, MA Chang, MCJ Rapoport, SI Appel, NM TI Haloperidol downregulates phospholipase A(2) signaling in rat basal ganglia circuits SO BRAIN RESEARCH LA English DT Article DE haloperidol; phospholipase; arachidonic acid; dopamine; schizophrenia; autoradiography ID MAGNETIC-RESONANCE SPECTROSCOPY; FATTY-ACID INCORPORATION; DOPAMINE-RECEPTORS; BRAIN INCORPORATION; PREFRONTAL CORTEX; SIGMA-RECEPTOR; DRUG-TREATMENT; D-2 RECEPTORS; SCHIZOPHRENIA; STRIATUM AB Our laboratory has developed an in vivo method to quantitatively evaluate phospholipase A(2) (PLA(2))-mediated signal transduction in brain regions of rodents. In this method, quantitative autoradiography is used to identify brain uptake of intravenously injected, radiolabeled arachidonic acid ([H-3]AA). Dopamine D-2 receptors are coupled to G-proteins that activate PLA(2), releasing AA from the stereospecifically numbered (sn) 2 position of phospholipids, and regional [H-3]AA uptake is proportional to the rate of release. In the present experiment, the D, antagonist haloperidol (1.0 mg/kg i.p.) or the drug vehicle was administered to male adult rats for 21 days. Rats were infused 3 days later with 1.75 mCi/kg [H-3]AA (i.v.), anesthetized and decapitated 20 min after infusion onset, and brains were processed for quantitative autoradiography. Chronic haloperidol significantly decreased [H-3]AA incorporation in two primary dopaminergic basal ganglia-frontal cortex circuits, the mesocorticolimbic and nigrostriatal systems, while insignificant changes in AA incorporation were noted in other brain regions. These results suggest that one mechanism by which haloperidol exerts its effect is by downregulating D-2-mediated PLA(2) signaling involving AA release in basal ganglia-frontal cortex circuitry. Published by Elsevier Science B.V. C1 NIA, Sect Brain Physiol & Metab, NIH, Bethesda, MD USA. US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Appl Pharmacol Res, Laurel, MD USA. RP Myers, CS (reprint author), Univ Maryland, Maryland Psychiat Res Ctr, POB 21247, Baltimore, MD 21228 USA. NR 44 TC 11 Z9 12 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD MAR 30 PY 2001 VL 896 IS 1-2 BP 96 EP 101 DI 10.1016/S0006-8993(01)02014-5 PG 6 WC Neurosciences SC Neurosciences & Neurology GA 419KL UT WOS:000167947900012 PM 11277978 ER PT J AU Santamaria, A Galvan-Arzate, S Lisy, V Ali, SF Duhart, HM Osorio-Rico, L Rios, C St'astny, F AF Santamaria, A Galvan-Arzate, S Lisy, V Ali, SF Duhart, HM Osorio-Rico, L Rios, C St'astny, F TI Quinolinic acid induces oxidative stress in rat brain synaptosomes SO NEUROREPORT LA English DT Article DE 2-amino-5-phosphonovaleric acid; brain regions; glutathione; oxidative stress; quinolinic acid; rat brain synaptosomes ID INDUCED LIPID-PEROXIDATION; NERVOUS-SYSTEM; FREE-RADICALS; NEUROTOXICITY; GLUTAMATE; GLUTATHIONE; MEDIATORS; MEMBRANES; ISCHEMIA; BINDING AB The oxidative action of quinolinic acid (QUIN), and the protective effects of glutathione (GSH), and 2-amino-5-phosphonovaleric acid (APV), were tested in rat brain synaptosomes, Reactive oxygen species (ROS) formation was quantified after the exposure of synaptosomes to increasing concentrations of QUIN (25-500 muM) The potency of QUIN to induce lipid peroxidation (LP) was tested as a regional index of thiobarbituric acid-reactive substances (TBARS) production, and the antioxidant actions of both GSH (50 muM) and APV (250 muM) on QUIN-induced LP were evaluated in synaptosomes prepared from different brain regions. QUIN induced concentration-dependent increases in ROS formation and TBARS in all regions analyzed, but increased production of fluorescent peroxidized lipids only in the striatum and the hippocampus, whereas both GSH and APV decreased this index. These results suggest that the excitotoxic action of QUIN involves regional selectivity in the oxidative status of brain synaptosomes, and may be prevented by substances exhibiting antagonism at the NMDA receptor. NeuroReport 12:871-874 (C) 2001 Lippincott Williams & Wilkins. C1 Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Dept Neurochem, Mexico City 14269, DF, Mexico. Acad Sci Czech Republ, Inst Physiol, Dept Mol Neurobiol, CZ-14220 Prague 4, Czech Republic. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. Prague Psychiat Ctr, Prague 18103 8, Czech Republic. RP Santamaria, A (reprint author), Natl Inst Neurol & Neurosurg Manuel Velasco Suare, Dept Neurochem, Insurgentes Sur 3877, Mexico City 14269, DF, Mexico. NR 25 TC 71 Z9 73 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0959-4965 J9 NEUROREPORT JI Neuroreport PD MAR 26 PY 2001 VL 12 IS 4 BP 871 EP 874 DI 10.1097/00001756-200103260-00049 PG 4 WC Neurosciences SC Neurosciences & Neurology GA 411MW UT WOS:000167504700048 PM 11277599 ER PT J CA CDC TI Blood and hair mercury levels in young children and women of childbearing age - United States, 1999 (Reprinted from MMWR, vol 50, pg 140, 2001) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. RP US FDA, Ctr Food Safety & Appl Nutr, Rockville, MD 20857 USA. NR 10 TC 0 Z9 0 U1 0 U2 2 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 21 PY 2001 VL 285 IS 11 BP 1436 EP 1437 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 410VQ UT WOS:000167462100011 ER PT J AU Tan, W Chen, GF Xing, DY Song, CY Kadlubar, FF Lin, DX AF Tan, W Chen, GF Xing, DY Song, CY Kadlubar, FF Lin, DX TI Frequency of CYP2A6 gene deletion and its relation to risk of lung and esophageal cancer in the Chinese population SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article DE lung cancer; esophageal cancer; CYP2A6; genetic polymorphism ID GLUTATHIONE S-TRANSFERASES; HUMAN LIVER-MICROSOMES; CYTOCHROME-P450 2A6 CYP2A6; COUMARIN 7-HYDROXYLATION; (+)-CIS-3,5-DIMETHYL-2-(3-PYRIDYL)THIAZOLIDIN-4-ONE HYDROCHLORIDE; NITROSAMINE METABOLISM; N-NITROSAMINES; C-OXIDATION; NICOTINE; SUSCEPTIBILITY AB Cytochrome P450 2A6 (CYP2A6) plays an important role in the oxidation of nicotine and in the activation of tobacco-related carcinogens, such as N-nitrosodimethylamine, N-nitrosodiethylamine and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone. It has been suggested that individuals with defective CYP2A6 alleles are at a lower risk of becoming smokers and of developing lung and other tobacco-related cancers. We examined the relationship between the CYP2A6 gene deletion and susceptibility to lung and esophageal cancer in a Chinese population via a hospital-based case-control study. The CYP2A6 gene deletion was determined by a PCR-based approach in 326 healthy controls, 149 patients with esophageal squamous-cell carcinoma and 151 patients with lung cancer, The allele frequency of the CYP2A6*4 deletion was 8.6% among controls compared with 8.4% among cases with esophageal squamous-cell carcinoma (p = 0.29) or 13.2% among cases with lung cancer (p < 0.01). Individuals who harbored at least one CYP2A6*4 deletion allele were at a I-fold increased risk of developing lung cancer (95% confidence interval [CI] = 1.2-3.2) compared with those without a defective CYP2A6 allele, This effect was mainly limited to squamous-cell carcinoma and to non-smokers, although a joint effect of CYP2A6 deletion and tobacco smoking on lung cancer risk was observed among heavy smokers. The overall risk of esophageal cancer did not appear to be associated with this CYP2A6 genetic polymorphism (odds ratio [OR] = 1.2, 95% CI = 0.7-2.1). However, stratified analysis suggested an excess risk with borderline significance (OR = 2.1; 95% CI = 1.0-4.5) related to the CYP2A6*4 allele among nonsmokers. The distribution of CYP2A6 genotype frequency was not significantly different (p = 0.40) between smokers (n = 174) and non-smokers (n = 152) in this study population, Our results demonstrate that the CYP2A6 gene deletion is associated with an increased risk of lung and esophageal cancer but not with a reduced tendency to smoke. (C) 2001 Wiley-Liss. Inc. C1 Chinese Acad Med Sci, Inst Canc, Dept Etiol & Carcinogenesis, Beijing 100021, Peoples R China. Peking Union Med Coll, Beijing, Peoples R China. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AK USA. RP Lin, DX (reprint author), Chinese Acad Med Sci, Inst Canc, Dept Etiol & Carcinogenesis, Beijing 100021, Peoples R China. NR 41 TC 90 Z9 101 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0020-7136 J9 INT J CANCER JI Int. J. Cancer PD MAR 20 PY 2001 VL 95 IS 2 BP 96 EP 101 DI 10.1002/1097-0215(20010320)95:2<96::AID-IJC1017>3.0.CO;2-2 PG 6 WC Oncology SC Oncology GA 408CR UT WOS:000167309400004 PM 11241319 ER PT J AU Yaes, RJ AF Yaes, RJ TI Late normal tissue injury from permanent interstitial implants SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE biologically effective dose; hot spots; I-125; Pd-103; Au-198; prostate implants ID INCOMPLETE-REPAIR MODEL; LINEAR-QUADRATIC MODEL; DOSE-RATE; TARGETED RADIOTHERAPY; IRRADIATION; MORBIDITY; BRACHYTHERAPY; SURVIVAL; THERAPY AB Purpose: To develop a simple method of calculating biologically effective doses in high-dose regions of permanent interstitial implants. Methods and Materials: The incomplete repair model is used to clarify the relationship between dose, D, and biologically effective dose (BED), for permanent interstitial implants. The relationship is used to ascertain the BED at high-dose regions that may occur in I-125, Pd-103, and Au-198 prostate implants. Results: The relationship between D and BED is nonlinear and is given by BED(D) = D + D-2/D-lambda, where D-lambda = [(t(lambda)/t(mu)) + 1](alpha/beta), t(lambda) and t(mu) are the half-lives of the isotope and of sublethal damage repair respectively and alpha/beta is the alpha:beta ratio, Idealized geometrically identical I-125, Pd-103, and Au-198 prostate implants with minimum target dose (MTD) of 160 Gy, 120 Gy, and 64 Gy, respectively; are considered. The BED for Pd-103 and Au-198 Will b, less than the BED for I-125, for doses up to about 2.5 times the MTD. For higher doses, the BED for Pd-103 may be significantly higher than for I-125. Conclusion: Permanent interstitial implants using short-lived isotopes may have regions with very high biologically effective doses. (C) 2001 Elsevier Science Inc. C1 US FDA, Ctr Drug Evaluat & Res, Div Med Imaging & Radiopharmaceut Drug Prod, Rockville, MD 20857 USA. RP Yaes, RJ (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Med Imaging & Radiopharmaceut Drug Prod, HFD-160,5600 Fishers Lane, Rockville, MD 20857 USA. NR 23 TC 7 Z9 7 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD MAR 15 PY 2001 VL 49 IS 4 BP 1163 EP 1169 DI 10.1016/S0360-3016(00)01425-5 PG 7 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA 408LG UT WOS:000167327200030 PM 11240260 ER PT J AU DiCarlo, CD Chenault, VM Borst, DE AF DiCarlo, CD Chenault, VM Borst, DE TI Lens crystallins of the normal and diabetic Fat Sand Rat Psammomys obesus. SO INVESTIGATIVE OPHTHALMOLOGY & VISUAL SCIENCE LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ASSOC RESEARCH VISION OPHTHALMOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0146-0404 J9 INVEST OPHTH VIS SCI JI Invest. Ophthalmol. Vis. Sci. PD MAR 15 PY 2001 VL 42 IS 4 SU S MA 1594 BP S294 EP S294 PG 1 WC Ophthalmology SC Ophthalmology GA 427EP UT WOS:000168392101584 ER PT J AU Tsuyuki, S Horvath-Arcidiacono, JA Bloom, ET AF Tsuyuki, S Horvath-Arcidiacono, JA Bloom, ET TI Effect of redox modulation on xenogeneic target cells: The combination of nitric oxide and thiol deprivation protects procine endothelial cells from lysis by IL-2-Activated human NK cells SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; TUMOR-NECROSIS-FACTOR; DELAYED XENOGRAFT REJECTION; T-CELL; E-SELECTIN; POSSIBLE INVOLVEMENT; MEDIATED CYTOTOXICITY; TRANSPLANT RECIPIENTS; ADHESION MOLECULES; MONONUCLEAR-CELLS AB Evidence suggests that NK cells contribute to the pathogenesis of delayed rejection of vascularized xenografts, and NK cells have been suggested to participate in hyperacute xenograft rejection. Endothelial cells have been shown to be the primary target of the recipient's immune responses that mediate both hyperacute and delayed xenograft rejection. Under conditions of oxidative stress induced by thiol deprivation, but not under normal conditions, pretreatment of porcine aortic endothelial cells (PAECs) with the NO donor, S-nitroso-N-acetyl-penicillamine, dramatically inhibited killing of PAEC target cells by IL-2-activated human NK cells. This same combined treatment reduced both surface expression and mRNA levels of E-selectin, Moreover, anti-E-selectin mAb, but not Ab to VCAM-1, protected PAEC from lysis by human IL-2-activated NK cells in a dose-dependent manner. These findings Suggest that expression of porcine E-selectin is important for the cytotoxicity of PAEC mediated by activated human NK cells and mag be involved in the redox-mediated modulation of that cytotoxicity. It is known that NF-kappaB activation is required for transcription of E-selectin, and the current data show that the suppression of E-selectin expression by S-nitroso-N-acetyl-penicillamine pretreatment and thiol deprivation was associated with reduced NF-kappaB DNA-binding activity in PAEC. These data suggest that the regulation of porcine E-selectin may be important for modulating delayed xenograft rejection and that manipulation of cellular redox systems may provide a means to protect xenogeneic endothelial cells from NK cell-mediated cytotoxicity. C1 US FDA, Lab Immunol & Virol HFM518, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Bloom, ET (reprint author), US FDA, Lab Immunol & Virol HFM518, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 79 TC 16 Z9 17 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 2001 VL 166 IS 6 BP 4106 EP 4114 PG 9 WC Immunology SC Immunology GA 410JW UT WOS:000167437700063 PM 11238660 ER PT J AU Waynant, RW Ilev, IK Gannot, I AF Waynant, RW Ilev, IK Gannot, I TI Mid-infrared laser applications in medicine and biology SO PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY OF LONDON SERIES A-MATHEMATICAL PHYSICAL AND ENGINEERING SCIENCES LA English DT Article; Proceedings Paper CT Discussion Meeting on Semiconductor Light Sources for Mid-Infrared Applications CY JUL 19-20, 2000 CL LONDON, ENGLAND DE mid-infrared; medicine; biology; 'fingerprint' region; fibres; waveguides ID FLEXIBLE WAVE-GUIDES; RADIATION C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. Tel Aviv Univ, Fac Engn, Dept Biomed Engn, IL-69978 Tel Aviv, Israel. RP Waynant, RW (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-134,12725 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 6 TC 78 Z9 82 U1 3 U2 16 PU ROYAL SOC LONDON PI LONDON PA 6 CARLTON HOUSE TERRACE, LONDON SW1Y 5AG, ENGLAND SN 1364-503X J9 PHILOS T ROY SOC A JI Philos. Trans. R. Soc. Lond. Ser. A-Math. Phys. Eng. Sci. PD MAR 15 PY 2001 VL 359 IS 1780 BP 635 EP 644 PG 10 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA 412LR UT WOS:000167556900022 ER PT J AU Becker, K Southwick, K Reardon, J Berg, R MacCormack, JN AF Becker, K Southwick, K Reardon, J Berg, R MacCormack, JN TI Histamine poisoning associated with eating tuna burgers SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article AB Context Histamine poisoning occurs when persons ingest fish in which bacteria have converted histidine to histamine, a process that usually can be controlled by storage at low temperatures. From 1994 to 1997, North Carolina averaged 2 cases annually; however, from July 1998 to February 1999, a total of 22 cases of histamine fish poisoning were reported. Objectives To examine the increase in histamine case reports, identify risk factors for poisoning, and develop recommendations for prevention. Design and Setting Case series evaluated in North Carolina from July 1998 to February 1999, Subjects Reported case-patients with 2 of the following symptoms within 2 hours of eating tuna: rash, facial flushing, vomiting, diarrhea, dyspnea, a tight feeling in the throat, headache, or a metallic or peppery taste in the mouth. Results Twenty cases occurred during 5 outbreaks, and there were 2 single occurrences. Of the 22 persons affected, 19 (86%) sought emergency medical care. All case-patients ate tuna: 18 ate tuna burgers, 2 ate salad containing tuna, and 2 ate filets, Tuna samples (available from 3 outbreaks) had histamine levels above the Food and Drug Administration regulatory level of 50 ppm (levels were between 213 and 3245 ppm). In 19 cases, the tuna used to prepare burgers or salads was frozen and thawed more than once before serving. Violations of recommended temperature controls were identified in 2 of the 5 restaurants, accounting for 14 (64%) cases. Conclusions Tuna burgers, a relatively new menu item in restaurants, were associated with an increase in histamine poisoning cases in North Carolina. Tuna ground for burgers can be susceptible to both temperature fluctuations and bacterial contamination. C1 Ctr Dis Control & Prevent, Raleigh, NC USA. N Carolina Dept Hlth & Human Serv, Raleigh, NC USA. N Carolina Dept Agr & Consumer Serv, Raleigh, NC USA. US FDA, Atlanta, GA USA. RP Becker, K (reprint author), US Dept HHS, Off Int & Refugee Hlth, 5600 Fishers Ln,Parklawn Bldg,Room 18-105, Rockville, MD 20857 USA. NR 26 TC 49 Z9 53 U1 0 U2 7 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 14 PY 2001 VL 285 IS 10 BP 1327 EP 1330 DI 10.1001/jama.285.10.1327 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA 408QK UT WOS:000167339000025 PM 11255388 ER PT J AU Brorson, KA Hamilton, E Mustafa, M Stein, KE AF Brorson, KA Hamilton, E Mustafa, M Stein, KE TI Role of aromatic V regions residues in polysaccharide : Ig binding SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1024 EP A1024 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201792 ER PT J AU Calvo, MS Mackertich, SK Barton, CN Park, YK Armstrong, DW Schultz, RG AF Calvo, MS Mackertich, SK Barton, CN Park, YK Armstrong, DW Schultz, RG TI Nutrient intakes in US Naval Academy Midshipmen (Midn): Comparisons to dietary reference intakes (DRIs) and to national intakes in comparable age groups. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. USN Acad, Annapolis, MD 21402 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 8 PY 2001 VL 15 IS 5 BP A982 EP A982 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201546 ER PT J AU Chango, A Pogribny, IP Pogribna, M James, JS AF Chango, A Pogribny, IP Pogribna, M James, JS TI Tissue-specific promoter methylation and expression in the reduced folate carrier gene. 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 8 PY 2001 VL 15 IS 5 BP A736 EP A736 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454200133 ER PT J AU Cook, KK Jenkins, MY Grundel, E Mitchell, GV AF Cook, KK Jenkins, MY Grundel, E Mitchell, GV TI Tissue concentrations of vitamin K vary in rats fed diets containing reduced or adequate levels of vitamin E and supplemented with gamma-tocopherol SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Laurel, MD 20708 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 8 PY 2001 VL 15 IS 5 BP A958 EP A958 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201412 ER PT J AU Graham, LJ Veri, MC DeBell, KE Rawat, R Jen, S Bonvini, E Rellahan, BL AF Graham, LJ Veri, MC DeBell, KE Rawat, R Jen, S Bonvini, E Rellahan, BL TI 70Z/3 Cbl promotes PLCgamma1 phosphorylation in T lymphocytes by a distinct pathway SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1042 EP A1042 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201902 ER PT J AU Hashemi, RR Tyler, AA Tyler, NR Slikker, W Paule, MG AF Hashemi, RR Tyler, AA Tyler, NR Slikker, W Paule, MG TI Mining bio-data: The modified rough sets approach SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Arkansas, Little Rock, AR 72204 USA. Natl Univ Ireland Univ Coll Cork, Sch Med, Cork, Ireland. 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 8 PY 2001 VL 15 IS 5 BP A913 EP A913 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201151 ER PT J AU Lathers, CM AF Lathers, CM TI New scientific role for clinical pharmacologists: Endocrine disruptors. Impact on human health, wildlife and the environment. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, CVM, Rockville, MD 20855 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 8 PY 2001 VL 15 IS 5 BP A1226 EP A1226 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454202955 ER PT J AU Lee, CJ Frasch, CE AF Lee, CJ Frasch, CE TI Antibody avidity and protective immunity elicited by pneumococcal type 9V conjugate vaccines. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 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 8 PY 2001 VL 15 IS 5 BP A1034 EP A1034 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201851 ER PT J AU Muthukkumar, S Stein, KE AF Muthukkumar, S Stein, KE TI Modulation of B cell growth by dendritic cells SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1031 EP A1031 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201836 ER PT J AU Pogribna, M Melnyk, M Pogribny, IP Chango, A James, SJ AF Pogribna, M Melnyk, M Pogribny, IP Chango, A James, SJ TI Abnormal folate/methionine metabolism in children with Down syndrome (DS) 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 8 PY 2001 VL 15 IS 5 BP A955 EP A955 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201395 ER PT J AU Potvin, S Bertrand, B Calvo, MS Ferland, G AF Potvin, S Bertrand, B Calvo, MS Ferland, G TI Phylloquinone content of commonly used herbs, spices and condiments: an unexpected significant source of vitamin K SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Montreal, Montreal, PQ H3C 3J7, Canada. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A958 EP A958 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201409 ER PT J AU Rellahan, B Graham, L DeBell, K Veri, C Novello, C Bonvini, E AF Rellahan, B Graham, L DeBell, K Veri, C Novello, C Bonvini, E TI A direct interaction between Cbl and PLCgamma1 negatively regulates PLCgamma1 activity SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 8 PY 2001 VL 15 IS 5 BP A1042 EP A1042 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201899 ER PT J AU Veri, MC DeBell, K Rawat, R Miscia, S Di Baldassarre, A Rellahan, B Graham, L Noviello, C Wange, R Bonvini, E AF Veri, MC DeBell, K Rawat, R Miscia, S Di Baldassarre, A Rellahan, B Graham, L Noviello, C Wange, R Bonvini, E TI Membrane microdomain-dependent regulation of phospholipase Cgamma-1 activation in T lymphocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Immunol Lab, DMA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Ist Morfol Umana Normale, Chieti, Italy. NIA, Biol Chem Lab, GRC, NIH, Baltimore, MD 21224 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 8 PY 2001 VL 15 IS 5 BP A1042 EP A1042 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201903 ER PT J AU Wiesenfeld, PW Babu, US Collins, TFX Sprando, R Flynn, TJ Black, T Olejnik, N AF Wiesenfeld, PW Babu, US Collins, TFX Sprando, R Flynn, TJ Black, T Olejnik, N TI Dietary alpha-linolenic acid (ALA) alters blood and tissue lipid profiles of pregnant and F1 generation Sprague-Dawley rats. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 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 8 PY 2001 VL 15 IS 5 BP A993 EP A993 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410TA UT WOS:000167454201615 ER PT J AU Babu, U Wiesenfeld, P Collins, TFX Raybourne, RB Sprando, R Flynn, T Black, T Olejnik, N AF Babu, U Wiesenfeld, P Collins, TFX Raybourne, RB Sprando, R Flynn, T Black, T Olejnik, N TI High flaxseed and flaxseed meal cause fatty acid changes in spleen cells and slight decrease in CMI SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A645 EP A645 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103702 ER PT J AU Bae, MA Rhee, H Song, BJ AF Bae, MA Rhee, H Song, BJ TI Cytotoxic mechanism of Troglitazone, a widely-used drug for type II non-insulin dependent diabetes SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIAAA, NIH, Rockville, MD 20852 USA. US FDA, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A507 EP A507 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102900 ER PT J AU Calvo, MS Gundberg, CM Barton, CN Park, YMK AF Calvo, MS Gundberg, CM Barton, CN Park, YMK TI Utility of serum undercarboxylated osteocalcin to assess vitamin K status in nutrition surveys. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. Yale Univ, Sch Med, New Haven, CT USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A620 EP A620 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103552 ER PT J AU Caudill, M Wang, J Collins, M Swendseid, M Santos, J Pogribny, I Melnyk, S James, J AF Caudill, M Wang, J Collins, M Swendseid, M Santos, J Pogribny, I Melnyk, S James, J TI Alterations in S-adenosylhomocysteine (SAH) and DNA hypomethylation in tissues from mice heterozygous for the cystationine beta synthase (CBS) gene. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Calif State Polytech Univ Pomona, Pomona, CA 91768 USA. Univ Calif Los Angeles, Sch Publ Hlth, Los Angeles, CA 90024 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A611 EP A611 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103503 ER PT J AU El Yazal, J Rao, SN Slikker, W AF El Yazal, J Rao, SN Slikker, W TI Three-dimensional quantitative structure-analysis relationship (QSAR) of organophosphorus compounds SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Mol Simulat Inc, St Louis, MO 63141 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A556 EP A556 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103180 ER PT J AU Esfandiari, F Miller, JW Green, R Pogribny, IP James, SJ AF Esfandiari, F Miller, JW Green, R Pogribny, IP James, SJ TI Overexpression of the methylated DNA binding protein, MBD2, in livers from a folate- and methionine-deficient rat cancer model SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Calif Davis, Med Ctr, Sch Med, 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 7 PY 2001 VL 15 IS 4 BP A284 EP A284 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438101620 ER PT J AU Ferland, G Calvo, MS Bertrand, B Potvin, S AF Ferland, G Calvo, MS Bertrand, B Potvin, S TI Mediterranean diet and cardiovascular disease: Is there a role for vitamin E? SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Montreal, Montreal, PQ H3C 3J7, Canada. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A394 EP A394 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102253 ER PT J AU Juarez, E Diaz, M Whittaker, PV Rosado, JL AF Juarez, E Diaz, M Whittaker, PV Rosado, JL TI Digestibility of different sources of iron added to corn masa flour and corn tortilla. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Inst Med Sci & Nutr, Mexico City, DF, Mexico. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A634 EP A634 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103635 ER PT J AU Karmazyn, Y Principato, M Robl, M Pontzer, C Abe, R AF Karmazyn, Y Principato, M Robl, M Pontzer, C Abe, R TI Evaluation of morphological changes and induction of apoptosis in lymphoid tissue of young mice after ingestion of staphylococcal enterotoxin B SO FASEB JOURNAL LA English DT Meeting Abstract C1 Univ Maryland, College Pk, MD 20742 USA. US FDA, Laurel, MD 20708 USA. Res Inst Biol Sci, Noda, Chiba, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A371 EP A371 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102126 ER PT J AU Leak, LV Petricoin, EF Liotta, LA Jones, M AF Leak, LV Petricoin, EF Liotta, LA Jones, M TI Proteomic analysis of lymph and plasma during cardiopulmonary bypass SO FASEB JOURNAL LA English DT Meeting Abstract C1 Howard Univ, Washington, DC 20059 USA. US FDA, Div Therapeut Prod, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. NHLBI, Lab Anim Med & Surg, NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A38 EP A38 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438100209 ER PT J AU Max, EE Bernstein, RM Mills, FC AF Max, EE Bernstein, RM Mills, FC TI Effects of IL-4 and CD40 stimulation on the activity of immunoglobulin gene enhancers and promoters. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A699 EP A699 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438104014 ER PT J AU Pogribny, IP Jernigan, S James, JS AF Pogribny, IP Jernigan, S James, JS TI Reduction of DNA methyltransferase capacity by DNA lesions 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 7 PY 2001 VL 15 IS 4 BP A401 EP A401 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102289 ER PT J AU Principato, M Gamez, F Grenade, C Gamez, D Kothary, M Abe, R AF Principato, M Gamez, F Grenade, C Gamez, D Kothary, M Abe, R TI Staphylococcal enterotoxin B-mediated immune activation in the absence of V beta-specific expansion in aged mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Laurel, MD 20708 USA. Univ Maryland, Laurel, MD 20708 USA. Res Inst Biol Sci, Noda, Chiba, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A371 EP A371 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438102127 ER PT J AU Whittaker, P Stewart, EL Turner, EA Diaz, M Rosado, JL Dunkel, VC AF Whittaker, P Stewart, EL Turner, EA Diaz, M Rosado, JL Dunkel, VC TI In vitro prediction of iron bioavailability for tortilla fortification SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. SUSTAIN, Washington, DC 20036 USA. Inst Nacl Nutr Salvador Zubiran, Mexico City 14000, DF, Mexico. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A634 EP A634 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103637 ER PT J AU Whittaker, P Tufaro, PR Dunkel, VC Rader, JI AF Whittaker, P Tufaro, PR Dunkel, VC Rader, JI TI Fortification of iron and folate in breakfast cereals SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 2 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 7 PY 2001 VL 15 IS 4 BP A624 EP A624 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 410KA UT WOS:000167438103580 ER PT J AU Schwetz, BA AF Schwetz, BA TI Proposal for public disclosure about clinical trials 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 3 Z9 3 U1 1 U2 2 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 7 PY 2001 VL 285 IS 9 BP 1146 EP 1146 DI 10.1001/jama.285.9.1146 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 406BH UT WOS:000167194700008 PM 11231734 ER PT J AU Schwetz, BA AF Schwetz, BA TI New measures to manage risks associated with Accutane 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 3 Z9 3 U1 1 U2 2 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 7 PY 2001 VL 285 IS 9 BP 1146 EP 1146 DI 10.1001/jama.285.9.1146 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 406BH UT WOS:000167194700005 PM 11231734 ER PT J AU Schwetz, BA AF Schwetz, BA TI New first-line therapy for advanced breast cancer 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 3 Z9 3 U1 1 U2 2 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 7 PY 2001 VL 285 IS 9 BP 1146 EP 1146 DI 10.1001/jama.285.9.1146 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 406BH UT WOS:000167194700006 PM 11231734 ER PT J AU Schwetz, BA AF Schwetz, BA TI New suppository for ulcerative proctitis 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 3 Z9 3 U1 1 U2 2 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 7 PY 2001 VL 285 IS 9 BP 1146 EP 1146 DI 10.1001/jama.285.9.1146 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 406BH UT WOS:000167194700007 PM 11231734 ER PT J AU Koehler, KM Baumgartner, RN Garry, PJ Allen, RH Stabler, SP Rimm, EB AF Koehler, KM Baumgartner, RN Garry, PJ Allen, RH Stabler, SP Rimm, EB TI Association of folate intake and serum homocysteine in elderly persons according to vitamin supplementation and alcohol use SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE homocysteine; tHcy; folate; folic acid; dietary intake; vitamin supplements; alcohol; coffee; tea; vitamin B-12; methylmalonic acid; elderly ID CORONARY HEART-DISEASE; PLASMA TOTAL HOMOCYSTEINE; NUTRITION EXAMINATION SURVEY; FOLIC-ACID FORTIFICATION; HORDALAND HOMOCYSTEINE; HISTORY QUESTIONNAIRE; COFFEE CONSUMPTION; RISK FACTOR; COBALAMIN DEFICIENCY; ATHEROSCLEROSIS RISK AB Background: The serum total homocysteine concentration (tHcy), an indicator of folate status and a possible risk factor for vascular disease, is elevated with impaired renal function and poor vitamin B-12 status, which are common in the elderly. Objective: Our objective was to determine the association between tHcy; folate intake, alcohol consumption, and other lifestyle factors in elderly persons. Design: This cross-sectional study used linear regression to model changes in tHcy. Subjects were 278 men and women aged 66-94 y studied in 1993. Results: Total folate intake was negatively associated with tHcy in models adjusted for age, sex, serum creatinine, and serum albumin. We found an interaction between food folate intake and supplement use. Food folate intake had an inverse dose-response relation with tHcy that was Limited to nonusers of supplements. Predicted tHcy was 1.5 mu mol/L lower in users of supplements containing folate and vitamin B-12 than in nonusers and was independent of food folate intake. We found a positive dose-response relation of coffee and tea intake with tHcy, a positive association for alcohol intake of greater than or equal to 60 drinks/mo compared with low intake, and an interaction of alcohol use with folate intake and supplement use. Compared with alcohol users, nonusers had higher predicted tHcy and a lower inverse dose-response relation of food folate intake with tHcy. Conclusions: The inverse association between folate intake and tHcy was strongest among nonusers of supplements and among alcohol drinkers. Identifying modifiable factors related to tHcy, a possible risk factor for vascular disease, is especially important in elderly persons. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Univ New Mexico, Sch Med, Clin Nutr Program, Albuquerque, NM 87131 USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Univ Colorado, Hlth Sci Ctr, Dept Biochem Biophys & Genet, Denver, CO 80262 USA. Harvard Univ, Sch Publ Hlth, Dept Epidemiol, Boston, MA 02115 USA. Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA. Harvard Univ, Sch Med, Boston, MA 02115 USA. Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA. RP Koehler, KM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-728,200 C St SW, Washington, DC 20204 USA. FU NCRR NIH HHS [M01RR00997]; NIA NIH HHS [AG09834, AG02049, AG10149] NR 59 TC 59 Z9 65 U1 0 U2 4 PU AMER SOC CLINICAL NUTRITION PI BETHESDA PA 9650 ROCKVILLE PIKE, SUBSCRIPTIONS, RM L-3300, BETHESDA, MD 20814-3998 USA SN 0002-9165 J9 AM J CLIN NUTR JI Am. J. Clin. Nutr. PD MAR PY 2001 VL 73 IS 3 BP 628 EP 637 PG 10 WC Nutrition & Dietetics SC Nutrition & Dietetics GA 404QJ UT WOS:000167111900022 PM 11237942 ER PT J AU Pae, WE Kormos, RL Greene, PS Sapirstein, W AF Pae, WE Kormos, RL Greene, PS Sapirstein, W TI Database: Relevant or not SO ANNALS OF THORACIC SURGERY LA English DT Article; Proceedings Paper CT 5th International Conference on Circulatory Support Devices for Severe Cardiac Failure CY SEP 15-17, 2000 CL NEW YORK, NEW YORK AB Progress in the field of ventricular assist devices requires a more rigorous and systematic method of collecting outcomes data. A worldwide registry of device implants and results is proposed. With widespread participation, data from this registry would improve the identification of risk factors and complications, and allow for the creation of predictive models that would enhance patient selection. Professional societies should lead the development of a registry in close partnership with government and industry. Data collection using the Web, with rigorous security measures to protect patient privacy, would offer numerous advantages in efficiency and immediacy of communication for all participants. (C) 2001 by The Society of Thoracic Surgeons. C1 Penn State Univ, Milton S Hershey Med Ctr, Div Cardiothorac Surg, Dept Surg, Hershey, PA 17033 USA. Presbyterian Univ Hosp, Baltimore, MD USA. Johns Hopkins Hosp, Baltimore, MD 21287 USA. US FDA, Div Cardiovasc & Resp Devices, Rockville, MD 20857 USA. RP Pae, WE (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Div Cardiothorac Surg, Dept Surg, MC H165,500 Univ Dr, Hershey, PA 17033 USA. NR 8 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0003-4975 J9 ANN THORAC SURG JI Ann. Thorac. Surg. PD MAR PY 2001 VL 71 IS 3 SU S BP S204 EP S209 DI 10.1016/S0003-4975(00)02632-1 PG 6 WC Cardiac & Cardiovascular Systems; Respiratory System; Surgery SC Cardiovascular System & Cardiology; Respiratory System; Surgery GA 412KW UT WOS:000167554400036 PM 11265864 ER PT J AU Ibrahim, S Peggins, J Knapton, A Licht, T Aszalos, A AF Ibrahim, S Peggins, J Knapton, A Licht, T Aszalos, A TI Influence of beta-adrenergic antagonists, H1-receptor blockers, analgesics, diuretics, and quinolone antibiotics on the cellular accumulation of the anticancer drug, daunorubicin: P-glycoprotein modulation SO ANTICANCER RESEARCH LA English DT Article DE drug classes; multidrug resistance; P-glycoprotein; daunorubicin ID BLOOD-BRAIN-BARRIER; MULTIDRUG-RESISTANCE; CLINICAL-TRIALS; PHARMACOKINETICS; EXPRESSION; BIOAVAILABILITY; SINGLE; FORMULATIONS; CELLS; GENE AB Background: Treatment of patients with several drugs simultaneously may result in modulation of the naturally expressed P-glycoprotein (Pgp) at different tissues. With this possibility in mind, we have assessed the ability of different classes of drugs to modulate Pgp function in vitro. Modulation of the Pgp function was studied at in vitro drug concentrations comparable to therapeutic blood levels of the drugs. Materials and Methods: Human blood brain barrier endothelial cells and human colon adenocarcinoma cells were transduced or transfected with the multidrug resistance gene (MDR1) to express Pgp. The uptake of fluorescent substrates of Pgp, Rhodamine 123 and daunorubicin, into these cells and NIH3T3/MDR1 and MDCK/MDR1 cells was measured by flow cytometry and in monolayers in the presence and absence of the different drugs. Results: From the tested six H-1-receptor blockers, seven beta-adrenergic antagonists, four analgesics, ten diuretics and five quinolons, five drugs inhibited Pgp at therapeutic blood levels and two at somewhat higher concentrations. Significant synergism for blocking Pgp could be demonstrated for several drugs. Conclusion: We conclude that administration of several drugs which modulate the function of Pgp to patients may adversely affect the natural function of this efflux pump and malt cause drug-drug interactions induced side effects. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. US FDA, Div Appl Pharmacol Res, Rockville, MD 20857 USA. NCI, NIH, Bethesda, MD 20892 USA. RP Ibrahim, S (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, HFD 860,5600 Fishers Lane, Rockville, MD 20857 USA. NR 48 TC 13 Z9 14 U1 0 U2 3 PU INT INST ANTICANCER RESEARCH PI ATHENS PA EDITORIAL OFFICE 1ST KM KAPANDNTIOU-KALAMOU RD KAPANDRITI, POB 22, ATHENS 19014, GREECE SN 0250-7005 J9 ANTICANCER RES JI Anticancer Res. PD MAR-APR PY 2001 VL 21 IS 2A BP 847 EP 856 PG 10 WC Oncology SC Oncology GA 437UQ UT WOS:000169012300004 PM 11396174 ER PT J AU Goldstein, C Lee, MD Sanchez, S Hudson, C Phillips, B Register, B Grady, M Liebert, C Summers, AO White, DG Maurer, JJ AF Goldstein, C Lee, MD Sanchez, S Hudson, C Phillips, B Register, B Grady, M Liebert, C Summers, AO White, DG Maurer, JJ TI Incidence of class 1 and 2 integrases in clinical and commensal bacteria from livestock, companion animals, and exotics SO ANTIMICROBIAL AGENTS AND CHEMOTHERAPY LA English DT Article ID CLASS-I INTEGRONS; ESCHERICHIA-COLI; GENE CASSETTES; MOLECULAR CHARACTERIZATION; RESISTANCE GENE; BETA-LACTAMASE; ELEMENTS; SITE; RECOMBINATION; ACINETOBACTER AB Many pathogenic and commensal organisms are multidrug resistant due to exposure to various antibiotics. Often, this antimicrobial resistance is encoded by integrons that occur on plasmids or that are integrated into the bacterial chromosome. Integrons are commonly associated with bacterial genera in the family Enterobacteriaceae, We determined that class 1 integrases were present in approximately 46% of the isolates from the family Enterobacteriaceae; class 2 integrases were present only among Escherichia coli and Salmonella isolates. Seven percent of veterinary isolates were positive for class 3 integrase by DNA-DNA hybridization but could not be confirmed to be positive by PCR. None of the veterinary isolates possessed the class 4 integrase gene. The distribution of these integrase genes was variable within the members of the family Enterobacteriaceae when some or all integrase classes were absent from a particular genus. There was also considerable variability in the distribution of these integrases within a species, depending on the animal host. Unlike the class 1 integrases, the other integrase class, intI2, appears to be more restricted in its distribution among the members of the family Enterobacteriaceae. There is also considerable variability in the distribution of the class 1 integrases within E. coli strains isolated from different food animals. The class 1 integrases are the most widely disseminated of the four classes among the members of the family Enterobacteriaceae from both the clinical and normal flora of animals. This is the first report to closely examine the distribution of class 2 integrases in members of the family Enterobacteriaceae isolated in the United States. C1 Univ Georgia, Dept Avian Med, Athens, GA 30602 USA. Univ Georgia, Dept Med Microbiol & Parasitol, Athens, GA 30602 USA. Univ Georgia, Dept Microbiol, Athens, GA 30602 USA. US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Maurer, JJ (reprint author), Univ Georgia, Dept Avian Med, Athens, GA 30602 USA. OI Summers, Anne/0000-0003-4258-9696 NR 34 TC 181 Z9 201 U1 3 U2 16 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0066-4804 J9 ANTIMICROB AGENTS CH JI Antimicrob. Agents Chemother. PD MAR PY 2001 VL 45 IS 3 BP 723 EP 726 DI 10.1128/AAC.45.3.723-726.2001 PG 4 WC Microbiology; Pharmacology & Pharmacy SC Microbiology; Pharmacology & Pharmacy GA 405AJ UT WOS:000167134800013 PM 11181350 ER PT J AU Blair, RM Fang, H Gaylor, D Sheehan, DM AF Blair, RM Fang, H Gaylor, D Sheehan, DM TI Threshold analysis of selected dose-response data for endocrine active chemicals SO APMIS LA English DT Article DE dose-response; endocrine disrupter; endogenous dose; Michaelis-Menten; non-hormone controlled background; risk assessment; threshold ID RISK ASSESSMENT; DEVELOPMENTAL TOXICITY; MECHANISTIC MODEL; GENE-EXPRESSION; RAT; ESTROGEN; HEALTH; DIOXIN; MICE; HORMONES AB Using a biologically relevant mathematical model, the Michaelis-Menten equation, we examined published data from endocrine active chemicals for evidence of no-threshold dose-response curves. Data were fit to a modified Michaelis-Menten equation which accounted for total background response. Subsequently, the data sets were analyzed using non-linear regression in order to estimate the four parameters of interest (non-hormone controlled background (B-nh), maximum response (R-max) endogenous hormone level (D-0), and the dose at which a half-maximal response was observed (ED50)) and to determine the fit to the fully modified Michaelis-Menten equation. Subsequently, response data were adjusted to account for B-nh and then normalized to R-max while dose data were adjusted to account for D-0 and then normalized to the ED50. This data set was combined into a single, composite data set and fit to the fully modified Michaelis-Menten equation. We examined 31 data sets (24 endpoints) from studies on 9 different chemical/hormone treatments. Twenty-six of the data sets fit the modified Michaelis-Menten equation with high multiple correlation coefficients (r>0.90). The normalized data demonstrated a good fit to the modified Michaelis-Menten equation. These results indicate that a variety of biological responses fit the modified Michaelis-Menten equation, which does not have a threshold dose term. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Sheehan, DM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT-130, Jefferson, AR 72079 USA. NR 44 TC 8 Z9 8 U1 0 U2 2 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PD MAR PY 2001 VL 109 IS 3 BP 198 EP 208 DI 10.1034/j.1600-0463.2001.090303.x PG 11 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 440LN UT WOS:000169176900003 PM 11430497 ER PT J AU Falkow, SJ Formal, SB Kopecko, DJ AF Falkow, SJ Formal, SB Kopecko, DJ TI Louis S. Baron - Deceased member SO ASM NEWS LA English DT Biographical-Item C1 Stanford Univ, Stanford, CA 94305 USA. 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 AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD MAR PY 2001 VL 67 IS 3 BP 164 EP 165 PG 2 WC Microbiology SC Microbiology GA 408UG UT WOS:000167345600016 ER PT J AU Hartung, T Aaberge, I Berthold, S Carlin, G Charton, E Coecke, S Fennrich, S Fischer, M Gommer, M Halder, M Haslov, K Jahnke, M Montag-Lessing, T Poole, S Schechtman, L Wendel, A Werner-Felmayer, G AF Hartung, T Aaberge, I Berthold, S Carlin, G Charton, E Coecke, S Fennrich, S Fischer, M Gommer, M Halder, M Haslov, K Jahnke, M Montag-Lessing, T Poole, S Schechtman, L Wendel, A Werner-Felmayer, G TI Novel pyrogen tests based on the human fever reaction - The report and recommendations of ECVAM Workshop 43 SO ATLA-ALTERNATIVES TO LABORATORY ANIMALS LA English DT Review ID LIMULUS AMEBOCYTE LYSATE; TUMOR-NECROSIS-FACTOR; MONOCYTOID CELL-LINES; HUMAN WHOLE-BLOOD; SALMONELLA-TYPHIMURIUM PORINS; STAPHYLOCOCCAL-ENTEROTOXIN-A; SILKWORM LARVAE PLASMA; ENDOGENOUS PYROGEN; BACTERIAL PYROGENS; MONONUCLEAR-CELLS AB This is the report of the forty-third of a series of workshops organised by the European Centre for the Validation of Alternative Methods (ECVAM). ECVAM's main goal, as defined in 1993 by its Scientific Advisory Committee, is to promote the scientific and regulatory acceptance of alternative methods which are of importance to the biosciences, and which reduce, refine or replace the use of laboratory animals. One of the first priorities set by ECVAM was the implementation of procedures which would enable it to become well informed about the state of the art of non-animal test development and validation, and the potential for the possible incorporation of alternative tests into regulatory procedures. It was decided that this would best be achieved by the organisation of ECVAM workshops onspecific topics, at which small groups of invited experts would review the current status of various types of in vitro tests and their potential uses, and make recommendations about the best ways forward (1). The workshop on novel pyrogen tests based on the human fever reaction was held in Konstanz, Germany, on 16-20 January 2000, under the chairmanship of the local organiser. Thomas Hartung (University of Konstanz). The participants came from industry, academia and national control authorities (in Europe and the United States), and their expertise extended to pharmacology and toxicology, quality control and quality assurance, immunology, biochemistry, microbiology, laboratory animal science, human medicine, and the development of in vitro assays as alternatives to animal testing, including the pertinent regulatory procedures. The objectives of the workshop were: to identify the need for new pyrogen tests; to review the current status of the development of new pyrogen tests; to evaluate the capabilities of the new pyrogen tests and to give recommendations for further development; to identify regulatory requirements and to give recommendations for promotion to regulatory acceptance; and to summarise the EU project "Human(e) Pyrogen Test" (QLRT-1999 00811; see Appendix 1). The outcome of the discussions and the recommendations agreed by the workshop participants as individuals are summarised in this report. C1 Univ Innsbruck, Inst Med Chem & Biochem, A-6020 Innsbruck, Austria. US FDA, Ctr Drug Evaluat & Res, Off Testin & Res, Rockville, MD 20857 USA. Natl Inst Biol Stand & Controls, Div Endocrinol, Potters Bar EN6 3QG, Herts, England. Pharma Hameln GmbH, D-31789 Hameln, Germany. Statens Serum Inst, Anal & Control Dept, DK-2300 Copenhagen, Denmark. Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. Paul Ehrlich Inst, D-63225 Langen, Germany. Commiss European Communities, Joint Res Ctr, ECVAM, Inst Hlth & Consumer Protect, I-21020 Ispra, VA, Italy. Council Europe, European Directorate Qual Med, F-67029 Strasbourg 1, France. Med Prod Agcy, S-75103 Uppsala, Sweden. Milenia Biotec, D-61231 Bad Nauheim, Germany. Natl Inst Publ Hlth, Dept Vaccinol, N-0403 Oslo, Norway. Univ Konstanz, D-78457 Constance, Germany. RP Hartung, T (reprint author), Commiss European Communities, Joint Res Ctr, ECVAM, Inst Hlth & Consumer Protect, TP 580, I-21020 Ispra, VA, Italy. NR 189 TC 58 Z9 61 U1 0 U2 4 PU FRAME PI NOTTINGHAM PA RUSSELL & BURCH HOUSE 96-98 NORTH SHERWOOD ST, NOTTINGHAM NG1 4EE, NOTTS, ENGLAND SN 0261-1929 J9 ATLA-ALTERN LAB ANIM JI ATLA-Altern. Lab. Anim. PD MAR-APR PY 2001 VL 29 IS 2 BP 99 EP 123 PG 25 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 420VN UT WOS:000168026100009 PM 11262757 ER PT J AU Frasch, CE Concepcion, NF AF Frasch, CE Concepcion, NF TI Induction of group 17 specific antibodies by pneumococcal type 17F and 17A polysaccharide vaccines SO BIOLOGICALS LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; CONJUGATE VACCINE; STANDARDIZATION; ASSAY AB Pneumococcal capsular polysaccharide group 17 contains two distinct serotypes, 17F and 17A. Pneumococcal group 17 is present in the licensed 23 valent polysaccharide vaccines. One such vaccine contains type 17A, while the other vaccine contains type 17F. The purpose of these studies was to determine the extent of cross-protection that could be expected, as both type 17F and 17A cause disease. The antibody responses of one group of adults to a vaccine containing type 17F was compared to that of another group that received a type 17A containing vaccine. By ELISA the 17A vaccine induced more cross-reactive antibodies. Opsonophagocytic antibodies are a good predictor of protection and both vaccines induced antibodies opsonic for both 17F and 17A. We conclude that either 17F or 17A will provide similar protection against group 17 disease. C1 CBER, Div Bacterial Prod, Lab bacterial Polysaccharides, Rockville, MD 20852 USA. RP Frasch, CE (reprint author), CBER, Div Bacterial Prod, Lab bacterial Polysaccharides, 1401 Rockville Pike,HFM-428, Rockville, MD 20852 USA. NR 15 TC 2 Z9 2 U1 0 U2 1 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 1045-1056 J9 BIOLOGICALS JI Biologicals PD MAR PY 2001 VL 29 IS 1 BP 11 EP 16 DI 10.1006/biol.2001.0272 PG 6 WC Biochemical Research Methods; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA 457TF UT WOS:000170152400004 PM 11482888 ER PT J AU Liu, Q Chi, GYH AF Liu, Q Chi, GYH TI On sample size and inference for two-stage adaptive designs SO BIOMETRICS LA English DT Article DE adaptive design; adjusted confidence intervals; adjusted p-value; conditional error; exact inference; Fisher's combination test; point estimate; sample size adjustment; type I error rate ID CLINICAL-TRIALS; INTERIM ANALYSES AB Proschan and Hunsberger (1995, Biometrics 51, 1315-1324) proposed a two-stage adaptive design that maintains the Type I error rate. For practical applications, a two-stage adaptive design is also required to achieve a desired statistical power while limiting the maximum overall sample size. In our proposal, a two-stage adaptive design is comprised of a main stage and an extension stage, where the main stage has sufficient power to reject the null under the anticipated effect size and the extension stage allows increasing the sample size in case the true effect size is smaller than anticipated. For statistical inference, methods for obtaining the overall adjusted p-value, point estimate and confidence intervals are developed. An exact two-stage test procedure is also outlined for robust inference. C1 Cephalon Inc, Clin Biostat, W Chester, PA 19380 USA. US FDA, Div Biometr 1, CDER, Rockville, MD 20857 USA. RP Liu, Q (reprint author), Cephalon Inc, Clin Biostat, 145 Brandywine Pkwy, W Chester, PA 19380 USA. NR 7 TC 61 Z9 61 U1 0 U2 2 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 MAR PY 2001 VL 57 IS 1 BP 172 EP 177 DI 10.1111/j.0006-341X.2001.00172.x PG 6 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA 409GW UT WOS:000167376900022 PM 11252594 ER PT J AU Mondoro, TH Ryan, BB Hrinczenko, BW Schechter, AN Vostal, JG Alayash, AI AF Mondoro, TH Ryan, BB Hrinczenko, BW Schechter, AN Vostal, JG Alayash, AI TI Biological action of nitric oxide donor compounds on platelets from patients with sickle cell disease SO BRITISH JOURNAL OF HAEMATOLOGY LA English DT Article DE nitric oxide; platelets; sickle cell anaemia ID IIB-IIIA COMPLEX; ACTIVATED PLATELETS; OXYGEN-AFFINITY; RELAXING FACTOR; ENDOTHELIUM; NO; ERYTHROCYTES; THROMBOSPONDIN; PROSTACYCLIN; METABOLITES AB Several lines of evidence point to the potential role of nitric oxide (NO) in the pathophysiology, as well as in the therapy, of sickle cell disease (SCD). In this study, we compared the effects of NO on platelets from normal individuals and from patients with SCD. Three NO donors were used to deliver NO to platelets: sodium 2-(N, N-diethylamino)-diazenolate-2-oxide (DEANO), S-nitrosocysteine (CysNO) and sodium trioxdintrate (OXINO or Angeli's salt). ADP-induced platelet aggregation, CD62P expression, PAC-1 binding and calcium elevation were evaluated in paired studies of normal and SCD subjects. DEANO significantly reduced aggregation in SCD platelets compared with normal platelets. DEANO similarly reduced the extent of CD62P expression in SCD platelets. All NO donors reduced PAC-1 binding, but there were no significant differences between platelets from normal or SCD subjects. Calcium elevation, as induced by ADP, was not altered by the presence of NO donors. However, when platelets were stimulated with thrombin, there was an increased initial response of SCD platelets compared with normal platelets. Taken together, these data suggest that the mode of NO delivery to platelets may produce various physiological responses and the optimization of NO delivery may contribute to reducing platelet aggregation in sickle cell disease. C1 US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Bethesda, MD 20892 USA. NIDDKD, Biol Chem Lab, NIH, Bethesda, MD USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Plasma Derivat, Bldg 29,Room 112,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Schechter, Alan N/0000-0002-5235-9408 NR 31 TC 18 Z9 18 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0007-1048 J9 BRIT J HAEMATOL JI Br. J. Haematol. PD MAR PY 2001 VL 112 IS 4 BP 1048 EP 1054 DI 10.1046/j.1365-2141.2001.02623.x PG 7 WC Hematology SC Hematology GA 424YV UT WOS:000168262300029 PM 11298605 ER PT J AU Fang, H Tong, WD Shi, LM Blair, R Perkins, R Branham, W Hass, BS Xie, Q Dial, SL Moland, CL Sheehan, DM AF Fang, H Tong, WD Shi, LM Blair, R Perkins, R Branham, W Hass, BS Xie, Q Dial, SL Moland, CL Sheehan, DM TI Structure-activity relationships for a large diverse set of natural, synthetic, and environmental estrogens SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID RECEPTOR-BINDING-SITE; IN-VITRO ASSAYS; POLYCHLORINATED HYDROXYBIPHENYLS; INDUCTION; CHEMICALS; LIGANDS; ANALOGS; IDENTIFICATION; METABOLITES; AFFINITIES AB Understanding structural requirements for a chemical to exhibit estrogen receptor (ER) binding has been important in various fields. This knowledge has been directly and indirectly applied to design drugs for human estrogen replacement therapy, and to identify estrogenic endocrine disrupters. This paper reports structure-activity relationships (SARs) based on a total of 230 chemicals, including both natural and xenoestrogens. Activities were generated using a validated ER competitive binding assay, which covers a 10(6)-fold range. This study is focused on identification of structural commonalities among diverse ER ligands. It provides an overall picture of how xenoestrogens structurally resemble endogenous 17 beta -estradiol (E-2) and the synthetic estrogen diethylstilbestrol (DES). On the basis of SAR analysis, five distinguishing criteria were found to be essential for xenoestrogen activity, using E-2 as a template: (1) H-bonding ability of the phenolic ring mimicking the 3-OH, (2) H-bond donor mimicking the 17 beta -OH and O-O distance between 3- and 17 beta -OH, (3) precise steric hydrophobic centers mimicking steric 7 alpha- and 11 beta -substituents, (4) hydrophobicity, and (5) a ring structure. The S-position H-bonding ability of phenols is a significant requirement for ER binding. This contributes as both a H-bond donor and acceptor, although predominantly as a donor. However, the 17 beta -OH contributes as a H-bond donor only. The precise space (the size and orientation) of steric hydrophobic bulk groups is as important as a 17 beta -OH. Where a direct comparison can be made, strong estrogens tend to be more hydrophobic, A rigid ring structure favors ER binding. The knowledge derived from this study is rationalized into a set of hierarchical rules that will be useful in guidance for identification of potential estrogens. C1 ROW Sci Inc, Jefferson, AR 72079 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 52 TC 318 Z9 328 U1 3 U2 32 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 2001 VL 14 IS 3 BP 280 EP 294 DI 10.1021/tx000208y PG 15 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 415LT UT WOS:000167723600004 PM 11258977 ER PT J AU Concepcion, NF Frasch, CE AF Concepcion, NF Frasch, CE TI Pneumococcal type 22F polysaccharide absorption improves the specificity of a pneumococcal-polysaccharide enzyme-linked immunosorbent assay SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID STREPTOCOCCUS-PNEUMONIAE; CELL-WALL; CAPSULAR POLYSACCHARIDE; CONJUGATE VACCINE; C-POLYSACCHARIDE; ANTIBODIES; STANDARDIZATION; IMMUNOGENICITY; CHILDREN; LINKAGE AB The specificity of the immune response to the 23-valent pneumococcal-polysaccharide (PS) vaccine in healthy adults and to a pneumococcal conjugate vaccine in infants was examined by measuring immunoglobulin G (IgG) antibody titers by enzyme-linked immunosorbent assay (ELISA) and the opsonophagocytosis assay. ELISA measures total antipneumococcal IgG titers including the titers of functional and nonfunctional antibodies, while the opsonophagocytosis assay measures only functional-antibody titers, Twenty-four pairs of pre- and post-pneumococcal vaccination sera from adults were evaluated (ELISA) for levels of IgG antibodies against serotypes 4, 6B, 9V, 14, 18C, 19F, and 23F. Twelve of the pairs were also examined (opsonophagocytosis assay) for their functional activities. The correlation coefficients between assay results for most types ranged from 0.75 to 0.90, but the correlation coefficient was only about 0.6 for serotypes 4 and 19F. The specificities of these antibodies were further examined by the use of competitive ELISA inhibition, A number of heterologous polysaccharides (types 11A, 12F, 15B, 22F, and 33A) were used as inhibitors. Most of the sera tested showed cross-reacting antibodies, in addition to those removed by pneumococcal C PS absorption. Our data suggest the presence of a common epitope that is found on most pneumococcal PS but that is not absorbed by purified C PS. Use of a heterologous pneumococcal PS (22F) to adsorb the antibodies to the common epitope increased the correlation between the IgG ELISA results and the opsonophagocytosis assay results. The correlation coefficient improve from 0.66 to 0.92 for type 4 and from 0.63 to 0.80 for type 19F. These common epitope antibodies were largely absent in infants at 7 months of age, suggesting the carbohydrate nature of the epitope. C1 CBER, Div Bacterial Prod, Lab Bacterial Polysaccharides, Rockville, MD 20852 USA. RP Frasch, CE (reprint author), CBER, Div Bacterial Prod, Lab Bacterial Polysaccharides, 1401 Rockville Pike,HFM-428, Rockville, MD 20852 USA. NR 23 TC 211 Z9 217 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAR PY 2001 VL 8 IS 2 BP 266 EP 272 DI 10.1128/CDLI.8.2.266-272.2001 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 409FF UT WOS:000167373300009 PM 11238206 ER PT J AU Atkinson, AJ Colburn, WA DeGruttola, VG DeMets, DL Downing, GJ Hoth, DF Oates, JA Peck, CC Schooley, RT Spilker, BA Woodcock, J Zeger, SL AF Atkinson, AJ Colburn, WA DeGruttola, VG DeMets, DL Downing, GJ Hoth, DF Oates, JA Peck, CC Schooley, RT Spilker, BA Woodcock, J Zeger, SL CA Biomarkers Definitions Working Grp TI Biomarkers and surrogate endpoints: Preferred definitions and conceptual framework SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Editorial Material ID END-POINTS; CARDIOVASCULAR-DISEASE; CLINICAL-TRIALS; RISK-FACTORS; MARKERS; OUTCOMES C1 NIH, Off Sci Policy, Bethesda, MD 20892 USA. NIH, Warren G Magnuson Clin Ctr, Bethesda, MD 20892 USA. MDS Harris Inc, Phoenix, AZ USA. Harvard Univ, Sch Publ Hlth, Boston, MA 02115 USA. Univ Wisconsin, Dept Biostat, Madison, WI USA. Axys Pharmaceut, S San Francisco, CA USA. Vanderbilt Univ, Dept Med, Nashville, TN USA. Georgetown Univ, Ctr Drug Dev Sci, Washington, DC USA. Univ Colorado, Hlth Sci Ctr, Dept Med, Denver, CO 80262 USA. Pharmaceut Res & Manufacturers Amer, Washington, DC USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Dept Biostat, Baltimore, MD 21205 USA. RP Downing, GJ (reprint author), NIH, Off Sci Policy, Bldg 1,Rm 218,1 Ctr Dr, Bethesda, MD 20892 USA. NR 28 TC 1607 Z9 1658 U1 16 U2 171 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 MAR PY 2001 VL 69 IS 3 BP 89 EP 95 DI 10.1067/mcp.2000.113989 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 413ZQ UT WOS:000167641800001 ER PT J AU Tabor, E AF Tabor, E TI Hepatocellular carcinoma: global epidemiology SO DIGESTIVE AND LIVER DISEASE LA English DT Article ID HEPATITIS-C VIRUS; PRIMARY LIVER-CANCER; B-VIRUS; CORE PROMOTER; ALCOHOLIC CIRRHOSIS; HIGH PREVALENCE; HCV INFECTION; VIRAL GENOMES; UNITED-STATES; BLOOD-DONORS C1 US FDA, CBER, OBRR, Rockville, MD 20852 USA. RP Tabor, E (reprint author), US FDA, CBER, OBRR, HFM 300,1401 Rockville Pike, Rockville, MD 20852 USA. EM tabor@cber.fda.gov NR 41 TC 37 Z9 38 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 1590-8658 J9 DIGEST LIVER DIS JI Dig. Liver Dis. PD MAR PY 2001 VL 33 IS 2 BP 115 EP 117 DI 10.1016/S1590-8658(01)80062-1 PG 3 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 423VY UT WOS:000168199500001 PM 11346135 ER PT J AU Dorman, DC Allen, SL Byczkowski, JZ Claudio, L Fisher, JE Fisher, JW Harry, GJ Li, AA Makris, SL Padilla, S Sultatos, LG Mileson, BE AF Dorman, DC Allen, SL Byczkowski, JZ Claudio, L Fisher, JE Fisher, JW Harry, GJ Li, AA Makris, SL Padilla, S Sultatos, LG Mileson, BE TI Methods to identify and characterize developmental neurotoxicity for human health risk assessment. III: Pharmacokinetic and pharmacodynamic considerations SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE developmental neurotoxicity; pharmacodynamics; pharmacokinetics; physiologically based pharmacokinetic modeling; rat ID BLOOD-BRAIN-BARRIER; GENDER-RELATED DIFFERENCES; PLASMA-PROTEIN BINDING; DEVELOPING RAT-BRAIN; SPRAGUE-DAWLEY RATS; TRANS-RETINOIC ACID; HEAT-SHOCK-PROTEIN; HUMAN-BREAST MILK; LACTATIONAL TRANSFER; 2-METHOXYACETIC ACID AB We review pharmacokinetic and pharmacodynamic factors that should be considered in the design and interpretation of developmental neurotoxicity studies. Toxicologic effects on the developing nervous system depend on the delivered dose, exposure duration, and developmental stage at which exposure occurred. Several pharmacokinetic processes (absorption, distribution, metabolism, and excretion) govern chemical disposition within the dam and the nervous system of the offspring. in addition, unique physical features such as the presence or absence of a placental barrier and the gradual development of the blood-brain barrier influence chemical disposition and thus modulate developmental neurotoxicity. Neonatal exposure may depend on maternal pharmacokinetic processes and transfer of the xenobiotic through the milk, although direct exposure may occur through other routes (e.g., inhalation). Measurement of the xenobiotic in milk and evaluation of biomarkers of exposure or effect following exposure can confirm or characterize neonatal exposure. Physiologically based pharmacokinetic and pharmacodynamic models that incorporate these and other determinants can estimate tissue dose and biologic response following in utero or neonatal exposure. These models can characterize dose-response relationships and improve extrapolation of results from animal studies to humans. In addition, pharmacologic data allow an experimenter to determine whether exposure to the lest chemical is adequate, whether exposure occurs during critical periods of nervous system development, whether route and duration of exposure are appropriate, and whether developmental neurotoxicity can be differentiated from direct actions of the xenobiotic. C1 ARCADIS Geraghty & Miller, Millersville, MD 21108 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. Zeneca Cent Toxicol Lab, Macclesfield, Cheshire, England. Mt Sinai Sch Med, Div Environm & Occupat Med, New York, NY USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Georgia, Dept Environm Hlth Sci, Athens, GA 30602 USA. Natl Inst Environm Hlth Sci, Neurotoxicol Grp, Res Triangle Pk, NC USA. Monsanto Co, Metab & Safety Evaluat Newstead Lab, St Louis, MO USA. US EPA, Off Prevent Pesticides & Tox Subst, Washington, DC 20460 USA. US EPA, Div Neurotoxicol, Res Triangle Pk, NC 27711 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Dept Pharmacol & Toxicol, Newark, NJ 07103 USA. RP Dorman, DC (reprint author), ARCADIS Geraghty & Miller, 1131 Benfield Blvd,Suite A, Millersville, MD 21108 USA. NR 181 TC 26 Z9 26 U1 3 U2 3 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 MAR PY 2001 VL 109 SU 1 BP 101 EP 111 DI 10.2307/3434851 PG 11 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 412KQ UT WOS:000167553900011 PM 11250810 ER PT J AU Kim, CS Sandberg, JA Slikker, W Binienda, Z Schlosser, PM Patterson, TA AF Kim, CS Sandberg, JA Slikker, W Binienda, Z Schlosser, PM Patterson, TA TI Quantitative exposure assessment: application of physiologically-based pharmacokinetic (PBPK) modeling of low-dose, long-term exposures of organic acid toxicant in the brain SO ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY LA English DT Article; Proceedings Paper CT Annual Meeting of the Society-for-Risk-Analysis CY 1999 CL ATLANTA, GEORGIA SP Soc Risk Analy DE physiologically-based pharmacokinetic (PBPK) modeling; low-dose; long-term exposures; brain ID RABBIT BRAIN; 2,4-D; RATS; DOSIMETRY AB Our objective was to construct a physiologically-based pharmacokinetic (PBPK) model describing the kinetic behavior of 2,4-dichlorophenoxyacetic acid (2:4-D) on rats after long-term exposures to low doses. Our study demonstrated the model's ability to simulate uptake of 2,4-D in discrete areas of, the rat brain. The model was derived from the generic PBPK model that was first developed for high-dose, single exposures of 2,4-D to rats or rabbits (Kim, C.S., Gargas, M.L., Andersen, M.E., 1994. Pharmacokinetic modeling of 2,4-dichlorophenoxyacetic acid (2,4-D) in rats and rabbits brain following single dose administration. Toxicol. Lett. 74, 189-201; Kim, C.S., Slikker, W., Jr., Binienda, 2., Gargas, M.L., Andersen, M.E., 1995. Development of a physiologically based pharmacokinetic (PBPK) model for 2,4-dichlorophenoxyacetic acid (2,4-D) dosimetry in discrete areas of the brain following a single intraperitoneal or intravenous dose. Neurotox. Teratol. 17, 111-120.), to which a subcutaneous (hypodermal) compartment was incorporated for low-dose, long-term infusion. It consisted of two body compartments, along with compartments for venous and arterial blood, cerebrospinal fluid, brain plasma and six brain regions. Uptake of the toxin was membrane-limited by the blood-brain barrier with clearance from the brain provided by cerebrospinal fluid 'sink' mechanisms. This model predicted profiles of 2,4-D levels in brain and blood over a 28-day period that compared well with concentrations measured in vivo with rats that had been given 2,4-D (1 or 10 mg/kg per day) with [C-14]-2,4-D subcutaneously (s.c.) for 7, 14, or 28 days, respectively. This PBPK model should be an effective tool for evaluating the target tissue doses that may produce the neurotoxicity of organic acid toxicants after low-dose, long-term exposures to contaminated foods or the environment. (C) 2001 Elsevier Science B.V. All rights reserved. C1 US FDA, Div Toxicol Res HFS 506, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Natl Ctr Toxicol Res, Div Neurotoxicol HFT 132, Jefferson, AR 72079 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. RP Kim, CS (reprint author), US FDA, Div Toxicol Res HFS 506, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 17 TC 35 Z9 35 U1 2 U2 4 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1382-6689 J9 ENVIRON TOXICOL PHAR JI Environ. Toxicol. Pharmacol. PD MAR PY 2001 VL 9 IS 4 BP 153 EP 160 DI 10.1016/S1382-6689(01)00060-6 PG 8 WC Environmental Sciences; Pharmacology & Pharmacy; Toxicology SC Environmental Sciences & Ecology; Pharmacology & Pharmacy; Toxicology GA 427FA UT WOS:000168393100004 ER PT J AU Bernstein, PS Khachik, F Carvalho, LS Muir, GJ Zhao, DY Katz, NB AF Bernstein, PS Khachik, F Carvalho, LS Muir, GJ Zhao, DY Katz, NB TI Identification and quantitation of carotenoids and their metabolites in the tissues of the human eye SO EXPERIMENTAL EYE RESEARCH LA English DT Article; Proceedings Paper CT Annual Meeting of the Association-for-Research-in-Vision-and-Ophthalmology CY MAY 10-15, 1998 CL FT LAUDERDALE, FLORIDA SP Assoc Res Vis & Ophthalmol DE carotenoid; lutein; zeaxanthin; age-related macular degeneration; cataract; oxidation products; metabolites; uvea; macular pigment; antioxidants ID HUMAN MACULAR PIGMENT; HUMAN PLASMA; HUMAN RETINA; STRUCTURAL ELUCIDATION; CATARACT-EXTRACTION; OXIDATION-PRODUCTS; MONKEY RETINAS; IN-VIVO; LUTEIN; ZEAXANTHIN AB There is increasing evidence that the macular pigment carotenoids. lutein and zeaxanthin. may play an important role in the prevention of age-related macular degeneration, cataract, and other blinding disorders. Although it is well known that the retina and lens are enriched in these carotenoids, relatively little is known about carotenoid levels in the uveal tract and in other ocular tissues. Also, the oxidative metabolism and physiological functions of the ocular carotenoids are not fully understood. Thus, we have set out to identify and quantify the complete spectrum of dietary carotenoids and their oxidative metabolites in a systematic manner in all tissues of the human eye in order to gain better insight into their ocular physiology. Human donor eyes were dissected, and carotenoid extracts from ocular tissues [retinal pigment epithelium/choroid (RPE/choroid), macula, peripheral retina, ciliary body, iris, lens, vitreous, cornea, and sclera] were analysed by high-performance liquid chromatography (HPLC). Carotenoids were identified and quantified by comparing their chromatographic and spectral profiles with those of authentic standards. Nearly all ocular structures examined with the exception of vitreous. cornea, and sclera had quantifiable levels of dietary (3R, 3'R.6'R)-lutein, zeaxanthin, their geometrical (E/Z) isomers, as well as their metabolites. (3R,3'S,6'R)-lutein (3'-epilutein) and 3-hydroxy-beta,epsilon -caroten-3'-one. In addition. human ciliary body revealed the presence of monohydroxycarotenoids and hydrocarbon carotenoids, while only the latter group was detected in human RPE/choroid. Uveal structures (iris, ciliary body, and RPE/choroid) account for similar to 50 % of the eye's total carotenoids and similar to 30 % of the lutein and zeaxanthin. In the iris. these pigments are likely to play a role in filtering out phototoxic short-wavelength visible Light, while they are more likely to act as antioxidants in the ciliary body. Both mechanisms, light screening and antioxidant, may be operative in the RPE/choroid in addition to a possible Function of this tissue in the transport of dihydroxycarotenoids from the circulating blood to the retina. This report lends further support for the critical role of lutein, zeaxanthin, and other ocular carotenoids in protecting the eye from light-induced oxidative damage and aging. (C) 2001 Academic Press. C1 Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, Salt Lake City, UT 84132 USA. Univ Maryland, Dept Chem & Biochem, Joint Inst Food Safety & Appl Nutr, College Pk, MD 20742 USA. RP Bernstein, PS (reprint author), Univ Utah, Sch Med, Dept Ophthalmol & Visual Sci, Moran Eye Ctr, 50 N Med Dr, Salt Lake City, UT 84132 USA. RI Khachik, Frederick/C-5055-2009 FU NEI NIH HHS [EY-11600] NR 41 TC 221 Z9 232 U1 2 U2 21 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0014-4835 J9 EXP EYE RES JI Exp. Eye Res. PD MAR PY 2001 VL 72 IS 3 BP 215 EP 223 DI 10.1006/exer.2000.0954 PG 9 WC Ophthalmology SC Ophthalmology GA 409QE UT WOS:000167393700002 PM 11180970 ER PT J AU Humphreys, SH Carrington, C Bolger, M AF Humphreys, SH Carrington, C Bolger, M TI A quantitative risk assessment for fumonisins B-1 and B-2 in US corn SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE mycotoxins; exposure assessment; Monte Carlo simulation; nephrotoxicity ID FUSARIUM-MONILIFORME; ESOPHAGEAL CANCER; CULTURE MATERIAL; MYCOTOXINS; MAIZE; RATS; LEUKOENCEPHALOMALACIA; TOXICITY; TRANSKEI; AREAS C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Humphreys, SH (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 43 TC 15 Z9 15 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD MAR PY 2001 VL 18 IS 3 BP 211 EP 220 DI 10.1080/02652030010021486 PG 10 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 410ZT UT WOS:000167474100002 PM 11304030 ER PT J AU Kodell, RL Young, JF Delongchamp, RR Turturro, A Chen, JJ Gaylor, DW Howard, PC Zheng, Q AF Kodell, RL Young, JF Delongchamp, RR Turturro, A Chen, JJ Gaylor, DW Howard, PC Zheng, Q TI A mechanistic approach to modelling the risk of liver tumours in mice exposed to fumonisin B-1 in the diet SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE MVK model; non-genotoxic; sphingolipid metabolism; compensatory proliferation ID CARCINOGENESIS AB Data from the National Toxicology Program's carcinogenesis study of fumonisin B-1 in B6C3F(1) mice, conducted at the National Center for Toxicological Research, were used to fit the Moolgavkar-Venzon-Knudson (MVK) two-stage, clonal-expansion model of carcinogenesis. In addition to tumour data from the conventional 2-year bioassay, the study included data on tissue weights, cell proliferation, cell death, and sphingolipid metabolism in primary target organs. The model was used to predict 2-year liver tumour rates in female and male mice based on differences among dose groups in the effect of fumonisin B-1 on the growth of normal tissue and on the proliferation of preneoplastic cells as a compensatory response to sphinganine-induced cell death. Fumonisin B-1 was assumed to be non-genotoxic, i.e. the model did not include any effect of fumonisin B-1 on either of the two mutation rates of the MVK model. The model was able to reproduce reasonably well the observed tumour rates in both female and male mice, predicting substantially increased rates above background only at the highest doses of fumonisin B-1 in females. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Kodell, RL (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 15 TC 10 Z9 10 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD MAR PY 2001 VL 18 IS 3 BP 237 EP 253 DI 10.1080/02652030010021972 PG 17 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 410ZT UT WOS:000167474100005 PM 11304033 ER PT J AU Delongchamp, RR Young, JF AF Delongchamp, RR Young, JF TI Tissue sphinganine as a biomarker of fumonisin-induced apoptosis SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE sphingolipid synthesis; fumonisin B-1; cancer mechanism AB NCTR measured sphinganine concentrations in the livers of mice and in the livers and kidneys of rats in conjunction with a tumour bioassay. In our model of the tumour incidence, target-tissue levels of sphinganine serve as a biomarker for a dose response of fumonisin B-1 on cell death. Initially we questioned the utility of sphinganine levels in this role because they were highly variable when compared across time points. In spite of this concern, a conceptual framework and data are presented that support the use of sphinganine as a biomarker for a dose response of fumonisin B-1 on cell death. This framework is reasonably consistent with observed sphinganine concentrations in the examined tissues, the literature on fumonisin's effects on sphingolipid synthesis, and our hypothesized mechanism through which fumonisin B-1 increases age-specific tumour incidence. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Delongchamp, RR (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 12 TC 16 Z9 17 U1 1 U2 7 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD MAR PY 2001 VL 18 IS 3 BP 255 EP 261 DI 10.1080/02652030118953 PG 7 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 410ZT UT WOS:000167474100006 PM 11304034 ER PT J AU Chen, ZT Karaplis, AC Ackerman, SL Pogribny, IP Melnyk, S Lussier-Cacan, S Chen, MF Pai, A John, SWM Smith, RS Bottiglieri, T Bagley, P Selhub, J Rudnicki, MA James, SJ Rozen, R AF Chen, ZT Karaplis, AC Ackerman, SL Pogribny, IP Melnyk, S Lussier-Cacan, S Chen, MF Pai, A John, SWM Smith, RS Bottiglieri, T Bagley, P Selhub, J Rudnicki, MA James, SJ Rozen, R TI Mice deficient in methylenetetrahydrofolate reductase exhibit hyperhomocysteinemia and decreased methylation capacity, with neuropathology and aortic lipid deposition SO HUMAN MOLECULAR GENETICS LA English DT Article ID DNA METHYLTRANSFERASE GENE; CORONARY-ARTERY DISEASE; ENDOTHELIAL-CELL INJURY; COMMON MUTATION; S-ADENOSYLHOMOCYSTEINE; RISK FACTOR; PLASMA HOMOCYSTEINE; VASCULAR-DISEASE; FOLIC-ACID; FOLATE AB Hyperhomocysteinemia, a risk factor for cardiovascular disease, is caused by nutritional and/or genetic disruptions in homocysteine metabolism. The most common genetic cause of hyperhomocysteinemia is the 677C-->T mutation in the methylenetetrahydrofolate reductase (MTHFR) gene. This variant, with mild enzymatic deficiency, is associated with an increased risk for neural tube defects and pregnancy complications and with a decreased risk for colon cancer and leukemia. Although many studies have reported that this variant is also a risk factor for vascular disease, this area of investigation is still controversial. Severe MTHFR deficiency results in homocystinuria, an inborn error of metabolism with neurological and vascular complications. To investigate the in vivo pathogenetic mechanisms of MTHFR deficiency, we generated mice with a knockout of Mthfr. Plasma total homocysteine levels in heterozygous and homozygous knockout mice are 1.,6- and 10-fold higher than those in wild-type littermates, respectively. Both heterozygous and homozygous knockouts have either significantly decreased S-adenosylmethionine levels or significantly increased S-adenosylhomocysteine levels, or both, with global DNA hypomethylation. The heterozygous knockout mice appear normal, whereas the homozygotes are smaller and show developmental retardation with cerebellar pathology. Abnormal lipid deposition in the proximal portion of the aorta was observed in older heterozygotes and homozygotes, alluding to an atherogenic effect of hyperhomocysteinemia in these mice. C1 McGill Univ, Dept Biol, Montreal, PQ H3A 1B1, Canada. McGill Univ, Dept Human Genet & Pediat, Montreal, PQ H3A 1B1, Canada. McGill Univ, Dept Med, Montreal, PQ H3A 1B1, Canada. McGill Univ, Dept Pathol, Montreal, PQ H3A 1B1, Canada. Jackson Lab, Bar Harbor, ME 04609 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Clin Res Inst Montreal, Montreal, PQ H2W 1R7, Canada. Inst Metab Dis, Dallas, TX 75226 USA. Tufts Univ, Jean Mayer USDA Human Nutr Res Ctr Aging, Boston, MA 02111 USA. McMaster Univ, Inst Mol Biol & Biotechnol, Hamilton, ON L8S 4K1, Canada. RP Rozen, R (reprint author), McGill Univ, Montreal Childrens Hosp, 4060 St Catherine W,Room 242, Montreal, PQ H3Z 2Z3, Canada. RI Bagley, Pamela/N-1906-2015 OI Bagley, Pamela/0000-0002-1214-7814 NR 61 TC 361 Z9 378 U1 2 U2 11 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0964-6906 J9 HUM MOL GENET JI Hum. Mol. Genet. PD MAR 1 PY 2001 VL 10 IS 5 BP 433 EP 443 DI 10.1093/hmg/10.5.433 PG 11 WC Biochemistry & Molecular Biology; Genetics & Heredity SC Biochemistry & Molecular Biology; Genetics & Heredity GA 407FB UT WOS:000167260600001 PM 11181567 ER PT J AU Wear, KA AF Wear, KA TI Ultrasonic attenuation in human calcaneus from 0.2 to 1.7 MHz SO IEEE TRANSACTIONS ON ULTRASONICS FERROELECTRICS AND FREQUENCY CONTROL LA English DT Article ID BOVINE CANCELLOUS BONE; QUANTITATIVE ULTRASOUND; TRABECULAR BONE; HIP FRACTURE; MECHANICAL-PROPERTIES; MINERAL DENSITY; DISEASED LIVER; OS CALCIS; IN-VITRO; VELOCITY AB Ultrasonic attenuation has been demonstrated to be a useful measurement in the diagnosis of osteoporosis. Most studies have employed ultrasound in a range of frequencies from about 200 kHz-300 kHz to 600 kHz-1 MHz, and many have assumed a linear dependence of attenuation on frequency. In order to investigate the attenuation properties of human calcaneus at higher frequencies, 16 defatted human calcanea were interrogated in vitro using two matched pairs of transducers with center frequencies of 500 kHz and 2.25 MHz. The linear dependence of attenuation on frequency seems to extend up to at least 1.7 MHz. The correlation between attenuation coefficient and frequency from 200 kHz to 1.7 MHz was r = 0.999 (95% confidence interval, CI, = 0.998 - 1.00), The measurements: suggest that some deviations from linear frequency dependence of attenuation may occur at lower frequencies (below 400 kHz), however. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP US FDA, Ctr Devices & Radiol Hlth, HFZ 142, Rockville, MD 20852 USA. EM kaw@cdrh.fda.gov NR 51 TC 54 Z9 58 U1 0 U2 2 PU IEEE-INST ELECTRICAL ELECTRONICS ENGINEERS INC PI PISCATAWAY PA 445 HOES LANE, PISCATAWAY, NJ 08855-4141 USA SN 0885-3010 EI 1525-8955 J9 IEEE T ULTRASON FERR JI IEEE Trans. Ultrason. Ferroelectr. Freq. Control PD MAR PY 2001 VL 48 IS 2 BP 602 EP 608 DI 10.1109/58.911743 PG 7 WC Acoustics; Engineering, Electrical & Electronic SC Acoustics; Engineering GA 411PJ UT WOS:000167508200027 PM 11370374 ER PT J AU Flynn, KM Delclos, KB Newbold, RR Ferguson, SA AF Flynn, KM Delclos, KB Newbold, RR Ferguson, SA TI Behavioral responses of rats exposed to long-term dietary vinclozolin SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE fungicide; endocrine disrupter; androgen ID SEX-DIFFERENCES; TESTOSTERONE PROPIONATE; SACCHARIN PREFERENCE; GONADAL-HORMONES; PLAY; FUNGICIDE; DIFFERENTIATION; DEFEMINIZATION; ANTIANDROGEN; METABOLITES AB Vinclozolin is a fungicide used on food crops with human exposure estimated at similar to2 mug/kg/day from ingestion; occupational exposure, however, may be greater. The metabolites of vinclozolin have been reported to act as antiandrogens and have adverse effects on reproductive physiology and behavior in animals. Here, pregnant rats were fed soy-free diets containing 0, 10, 150, or 750 ppm of vinclozolin (approximately 0, 0.8, 12, and 60 mg/kg/day for an adult) beginning on gestational day 7, and offspring were continued on these diets through sacrifice at postnatal day 77. Male and female offspring were assessed for changes in several nonreproductive sexually dimorphic behaviors: open field and running wheel locomotor activity, play behavior, and consumption of saccharin- and sodium chloride-flavored solutions. There was a significant interaction of sex with vinclozolin exposure on running wheel activity, which indicated that females in the high-dose exposure group were hypoactive compared to same-sex controls. There was a significant overall effect of vinclozolin exposure on fluid consumption, and high-dose animals showed increased intake of the saccharin solution and decreased intake of plain water while saccharin was available. Effects were more pronounced in females, which drank 40.8% more saccharin than control females, whereas males drank 6.2% more than control males. There were no effects of vinclozolin treatment on play behavior or sodium solution intake. Gestational duration, total and live pups per litter, litter sex ratios, and birth weight were also not significantly affected, nor were body weight and food intake for dams and offspring. These results indicate that long-term dietary exposure to vinclozolin does not have severe toxicological consequences on the nonreproductive behaviors measured here. However, exposure may cause subtle alterations in locomotor activity and consumption of saccharin-flavored solution. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Inst Environm Hlth Sci, 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,HFT-132, Jefferson, AR 72079 USA. NR 32 TC 21 Z9 21 U1 1 U2 2 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD MAR PY 2001 VL 49 IS 3 BP 1658 EP 1665 DI 10.1021/jf0008893 PG 8 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 437AE UT WOS:000168967400097 PM 11312911 ER PT J AU Wisneski, HH AF Wisneski, HH TI Determination of musk ambrette, musk xylol, and musk ketone in fragrance products by capillary gas chromatography with electron capture detection SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID NITRO MUSKS; GUINEA-PIGS; FRESH-WATER; TAMA RIVER; RAT-LIVER; XYLENE; CONTACT; PHOTOSENSITIVITY; PHOTOALLERGY; TOXICITY AB A gas chromatographic method using a capillary column with electron capture detection was developed for the simultaneous determination of 3 nitromusk fragrance ingredients: musk ambrette (MA), musk xylol (MX), and musk ketone (MK), in fragrance products. The accuracy of the method was determined by recovery of each nitromusk from fortified fragrance products at 3 different concentrations. Recoveries ranged from 95.0 to 105.9% for MA, 88.4 to 102.5% for MX, and 93.7 to 103.7% for MK. The method was used to Survey 30 fragrance products purchased in the Washington, DC, area for each of the nitromusks, MA was not found in any of the products, MX was found in 9 products at levels ranging from 0.001 to 0.22%; MK was found in 8 products at levels ranging from 0.023 to 0.45%. The presence of MX and MK was confirmed by gas chromatography/mass spectrometry in many of the fragrance products. C1 US FDA, Washington, DC 20204 USA. RP Wisneski, HH (reprint author), US FDA, 200 C St,SW, Washington, DC 20204 USA. NR 37 TC 6 Z9 6 U1 1 U2 3 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2001 VL 84 IS 2 BP 376 EP 381 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 418PU UT WOS:000167901200010 PM 11324601 ER PT J AU Ekholm, DF Hirshfield, IN AF Ekholm, DF Hirshfield, IN TI Rapid methods to enumerate Escherichia coli in foods using 4-methylumbelliferyl-beta-D-glucuronide SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB Three methods to enumerate Escherichia coli in food were compared. They were based on AOAC methods using lauryl tryptose broth (LST) medium, LST-4-methylumbelliferyl-beta -D-glucuronide (MUG) medium, and a proposed method using regular LST in combination with E, coli (EC)-MUG medium. An efficacious and cost-effective method is needed that can detect E. coli and does not produce false presumptive positives. We tested 170 cheeses, 40 frozen processed seafood samples, 210 tree nuts, and 40 other samples. The method of choice for enumerating E. coli depends on the commodity itself. For a product, such as hard cheese or processed seafood, with a history of being negative for E. coli and other lactose-fermenting organisms, the proposed method using regular LST/EC-MUG is a good choice, These samples were seldom presumptive positive in the primary LST medium. If gas was produced, EC-MUG was an effective secondary medium. No false positives (fluorescence) or negatives were detected in EC-MUG medium. For a product with a history of being positive for E, coli and/or other lactose fermenting organisms, such as tree nutmeats or cheeses that are ripened by bacteria or mold, the method using LST-MUG is the method of choice. A presumptive positive in the LST-MUG medium was highly correlative with the biochemical tests that confirmed a sample contain E. coli, For samples spiked with E. coli, the results from each of these 3 methods were identical, and were consistent in enumerating E. coli. C1 US FDA, NE Reg Lab, Jamaica, NY 11433 USA. St Johns Univ, Jamaica, NY 11439 USA. RP Ekholm, DF (reprint author), US FDA, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 7 TC 4 Z9 4 U1 1 U2 2 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 2001 VL 84 IS 2 BP 407 EP 415 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 418PU UT WOS:000167901200014 PM 11324605 ER PT J AU Low, NH McLaughlin, MA Page, SW Canas, BJ Brause, AR Low, NH AF Low, NH McLaughlin, MA Page, SW Canas, BJ Brause, AR Low, NH TI Identification of hydrolyzed inulin syrup and high-fructose corn syrup in apple juice by capillary gas chromatography - PVM 4 : 1999 SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A peer-verified, gas chromatographic (GC) method is presented for the identification of hydrolyzed inulin syrup (HIS) and high-fructose corn syrup (HFCS) in apple juice. The procedure involves determining the Brix value of the apple juice or apple juice concentrate and preparing a dilution of the test sample to 5.5 degrees Brix. A 100 muL aliquot of the 5.5 degrees Brix test solution is then freeze-dried in a GC autosampler vial. The su,oars in the freeze-dried residue are converted to trimethylsilyl derivatives, by the addition of an appropriate silylation reagent, and the vial is heated at 75 degreesC for 30 min. After derivatization, the solution is introduced into a gas chromatograph where the analytes are separated on a 30 m, 0.25 mm id DB-5 column. The method can use hydrogen, helium, or nitrogen as the carrier gas. The analytes and marker compounds are measured by use of a flame ionization detector. Commercial apple juice concentrates were diluted with one of the 2 syrups at 2 revels. Dilution was ascertained by the presence of retrograde sugar markers found in the 2 sugar syrups. An 3 laboratories involved in the study were able to identify the correct diluent in the blind, randomly coded, apple juice test portions. The levels of dilution in the test portions were 0, 6.9% (HIS), 16.0% (HIS), 8.1% (HFCS), and 17.0% (HFCS). No false positive results were reported. Quantitative conclusions can be drawn when the same syrup is used for dilution and as a reference standard. C1 Univ Saskatchewan, Dept Appl Microbiol & Food Sci, Saskatoon, SK S7N 5A8, Canada. US FDA, Ctr Food Safety & Appl Nutr, Div Nat Prod, Washington, DC 20204 USA. Columbia Inc, Analyt Chem Serv, Columbia, MD 21045 USA. RP Low, NH (reprint author), Univ Saskatchewan, Dept Appl Microbiol & Food Sci, 51 Campus Dr, Saskatoon, SK S7N 5A8, Canada. NR 7 TC 3 Z9 3 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 2001 VL 84 IS 2 BP 486 EP 492 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 418PU UT WOS:000167901200024 PM 11324615 ER PT J AU Thompson, RD Quaife, JT AF Thompson, RD Quaife, JT TI Liquid chromatographic determination of methyl anthranilate in artificially flavored nonalcoholic beverages SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID RESIDUES AB A liquid chromatographic method was developed that provides a simple and rapid means of determining methyl anthranilate (MA) in carbonated and noncarbonated, artificial grape-flavored, nonalcoholic beverages. The proposed procedure, which was applied to 12 different products, uses a Nova-Pak C-18 column, a mobile phase containing acetonitrile-0.025M KH2PO4 (40 + 60), pH 3.00, and UV detection at 220 nm. Assay values ranged from 0.35 to 16.6 mug MA/mL. The intralaboratory precision (relative standard deviation) for the products ranged from 0.51 to 2.23% (n = 5), and recoveries via fortification ranged from 83.6 to 102.4%. The limits of quantitation and detection were 0.00417 and 0.00125 mug/mL, respectively, and the analyte response was linear over a 100-fold concentration range(0.0001-0.01 mg/mL). C1 US FDA, Minneapolis, MN 55401 USA. RP Thompson, RD (reprint author), 1425 W 28th St,611, Minneapolis, MN 55408 USA. NR 19 TC 4 Z9 4 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 MAR-APR PY 2001 VL 84 IS 2 BP 493 EP 497 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 418PU UT WOS:000167901200025 PM 11324616 ER PT J AU Baratta, EJ Easterly, DG AF Baratta, EJ Easterly, DG TI Determination of iodine-131 at low levels in milk: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB The official method for the determination of iodine-131 in milk has a lower limit of detection (LLD) of 10 pCi/L (0.37 Bq/L), The Nuclear Regulatory Commission had recommended that a method claiming to have an LLD of <0.3 pCi/L (<1.1E-02 Bq/L) be used. That method, which is capable of measuring iodine-131 below the level of detection of the Official Method, was collaboratively studied. The method uses a palladium iodide precipitate to concentrate the iodine-131 and measures (counts) its 364 keV gamma energy in coincidence with the beta decay or with a low-background beta-counting system. The study was performed by using 3 concentrations of iodine-131 in milk: 2.6, 5.0, and 8.0 pCi/L (9.62E-02, 1.85E-01, and 2.96E-01 Bq/L, respectively). Eleven laboratories agreed to participate in the study. Eight laboratories submitted data for the study, The averages of the results were 2.68, 5.30, and 8.12 pCi/L (9.92E-02, 1.96E-01, and 3.00E-01 Bq/L, respectively), respectively, The intra- and interlaboratory variations were acceptable, The method was adopted First Action by AOAC INTERNATIONAL. C1 US FDA, Winchester, MA 01890 USA. US EPA, Las Vegas, NV 89193 USA. RP Baratta, EJ (reprint author), US FDA, 109 Holton St, Winchester, MA 01890 USA. NR 6 TC 0 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 MAR-APR PY 2001 VL 84 IS 2 BP 507 EP 511 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 418PU UT WOS:000167901200027 PM 11324618 ER PT J AU Centola, DT Ayoub, KI Lao, NT Lu, HTC Page, BFJ AF Centola, DT Ayoub, KI Lao, NT Lu, HTC Page, BFJ TI Variables affecting simulated use determination of residual ethylene oxide in medical devices SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB In autumn 1993, AAMI/ST/WG 63, Sterilization Residuals Working Group undertook the task of studying factors involved in determining the amount of residual ethylene oxide in medical devices after sterilization and developing a protocol for controlling the relevant variables. The protocol was evaluated by conducting a round robin study consisting of 8 participating laboratories from around the country, Results of this round robin study demonstrated the range over which results may vary despite controls placed on the time and temperature at which determinations were conducted. The data from the study suggest that small, random variations in technique during short sample extraction times can lead to variability in the results. Variables such as initial water temperature, oven temperature, weighing of sample, and length of extraction should be carefully controlled. inherent variations in the material composition of similar devices are possible contributing factors, The efforts of this working group and the subsequent evaluation and discussion of its findings are presented. C1 Duo TEK Inc, Div STS, Sterilizat Tech Serv, Rush, NY 14343 USA. Tyco Healthcare Kendall, De Land, FL 32721 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. Barry Page Consulting, Garner, NC 27529 USA. RP Centola, DT (reprint author), Micoban Prod Co, 11515 Vanstory Dr, Huntersville, NC 28078 USA. NR 8 TC 8 Z9 8 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 2001 VL 84 IS 2 BP 512 EP 518 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA 418PU UT WOS:000167901200028 PM 11324619 ER PT J AU Rothmann, MD El Barmi, H AF Rothmann, MD El Barmi, H TI Stochastic processes involving random deletion SO JOURNAL OF APPLIED PROBABILITY LA English DT Article DE nonhomogeneous Poisson processes; random deletion; weighted distributions AB We consider a system where units having magnitudes arrive according to a nonhomogeneous Poisson process, remain there for a random period and then depart. Eventually, at any point in time only a portion of those units which have entered the system remain. Of interest are the finite time properties and limiting behaviors of the distribution of magnitudes among the units present in the system and among those which have departed from the system. We will derive limiting results for the empirical distribution of magnitudes among the active (departed) units. These results are also shown to extend to systems having stages or steps through which units must proceed. Examples are given to illustrate these results. C1 Univ Iowa, Iowa City, IA 52242 USA. Kansas State Univ, Dept Stat, Manhattan, KS 66506 USA. RP Rothmann, MD (reprint author), US FDA, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 5 TC 1 Z9 1 U1 0 U2 0 PU APPLIED PROBABILITY TRUST PI SHEFFIELD PA THE UNIVERSITY, SCHOOL MATHEMATICS STATISTICS, SHEFFIELD S3 7RH, ENGLAND SN 0021-9002 J9 J APPL PROBAB JI J. Appl. Probab. PD MAR PY 2001 VL 38 IS 1 BP 95 EP 107 PG 13 WC Statistics & Probability SC Mathematics GA 428XG UT WOS:000168486500008 ER PT J AU Brown, EW LeClerc, JE Li, BG Payne, WL Cebula, TA AF Brown, EW LeClerc, JE Li, BG Payne, WL Cebula, TA TI Phylogenetic evidence for horizontal transfer of mutS alleles among naturally occurring Escherichia coli strains SO JOURNAL OF BACTERIOLOGY LA English DT Article ID EVOLUTIONARY GENETICS; SALMONELLA-ENTERICA; POPULATIONS; SEQUENCE; RECOMBINATION; POLYMORPHISM; MUTATION; DNA; DIVERSITY; GENOME AB MutS mutators accelerate the bacterial mutation rate 100- to 1,000-fold and relax the barriers that normally restrict homeologous recombination. These mutators thus afford the opportunity for horizontal exchange of DNA between disparate strains, While much is known regarding the mutS phenotype, the evolutionary structure of the mutS(+) gene in Escherichia coli remains unclear. The physical proximity of mutS to an adjacent polymorphic region of the chromosome suggests that this gene itself may be subject to horizontal transfer and recombination events. To test this notion, a phylogenetic approach was employed that compared gene phylogeny to strain phylogeny, making it possible to identify E. coli strains in which mutS alleles have recombined. Comparison of mutS phylogeny against predicted E. coli "whole chromosome" phylogenies (derived from multilocus enzyme electrophoresis and mdh sequences) revealed striking levels of phylogenetic discordance among mutS alleles and their respective strains. We interpret these incongruences as signatures of horizontal exchange among mutS alleles. Examination of additional sites surrounding mutS also revealed incongruous distributions compared to E. coli strain phylogeny, This suggests that other regional sequences are equally subject to horizontal transfer, supporting the hypothesis that the 61.5-min mutS-rpoS region is a recombinational hot spot within the E. coli chromosome. Furthermore, these data are consistent with a mechanism for stabilizing adaptive changes promoted by mutS mutators through rescue of defective mutS alleles with wild-type sequences. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol Res & Evaluat HFS235, Mol Biol Branch, Washington, DC 20204 USA. RP Cebula, TA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol Res & Evaluat HFS235, Mol Biol Branch, 200 C St SW, Washington, DC 20204 USA. NR 54 TC 52 Z9 54 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAR PY 2001 VL 183 IS 5 BP 1631 EP 1644 DI 10.1128/JB.183.5.1631-1644.2001 PG 14 WC Microbiology SC Microbiology GA 401TD UT WOS:000166943600016 PM 11160094 ER PT J AU Hallab, N Merritt, K Jacobs, JJ AF Hallab, N Merritt, K Jacobs, JJ TI Metal sensitivity in patients with orthopaedic implants SO JOURNAL OF BONE AND JOINT SURGERY-AMERICAN VOLUME LA English DT Review ID ALLERGIC CONTACT-DERMATITIS; TOTAL JOINT REPLACEMENT; TOTAL HIP-REPLACEMENT; INVITRO LYMPHOCYTE-TRANSFORMATION; LEUKOCYTE MIGRATION-INHIBITION; T-CELL-CLONES; CORROSION PRODUCTS; INDUCED AUTOIMMUNITY; TITANIUM IMPLANTS; CROSS-REACTIVITY C1 Rush Presbyterian St Lukes Med Ctr, Dept Orthopaed Surg, Chicago, IL 60612 USA. US FDA, Rockville, MD 20852 USA. RP Hallab, N (reprint author), Rush Presbyterian St Lukes Med Ctr, Dept Orthopaed Surg, 1653 W Congress Pkwy, Chicago, IL 60612 USA. EM nhallab@rush.edu NR 115 TC 410 Z9 420 U1 2 U2 30 PU JOURNAL BONE JOINT SURGERY INC PI NEEDHAM PA 20 PICKERING ST, NEEDHAM, MA 02192 USA SN 0021-9355 J9 J BONE JOINT SURG AM JI J. Bone Joint Surg.-Am. Vol. PD MAR PY 2001 VL 83A IS 3 BP 428 EP 436 PG 9 WC Orthopedics; Surgery SC Orthopedics; Surgery GA 411MH UT WOS:000167503500017 PM 11263649 ER PT J AU Salotra, P Sreenivas, G Pogue, GP Lee, N Nakhasi, HL Ramesh, V Negi, NS AF Salotra, P Sreenivas, G Pogue, GP Lee, N Nakhasi, HL Ramesh, V Negi, NS TI Development of a species-specific PCR assay for detection of Leishmania donovani in clinical samples from patients with kala-azar and post-kala-azar dermal leishmaniasis SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; VISCERAL LEISHMANIASIS; CUTANEOUS LEISHMANIASIS; KINETOPLAST DNA; BLOOD-SAMPLES; DIAGNOSIS; PARASITES; IDENTIFICATION; AMPLIFICATION; ANTIGENS AB We have developed a PCR assay that is capable of amplifying kinetoplast DNA (kDNA) of Leishmania donovani in a species-specific manner among Old World leishmanias. With Indian strains and isolates of L. donovani the assay was sensitive enough to detect kDNA in an amount equivalent to a single parasite or less. The extreme sensitivity of the assay was reflected in its ability to detect parasite DNA from small volumes of peripheral blood of patients with kala-azar (KA) and from skin lesions from patients with post-KA dermal leishmaniasis (PKDL). A total of 107 clinical leishmaniasis samples were analyzed. Of these 102 (95.3%) were positive by PCR. The test provided a diagnosis of KA with 96% sensitivity using patient whole-blood samples instead of bone marrow or spleen aspirates that are obtained by invasive procedures. The assay was also successful in the diagnosis of 45 of 48 PKDL cases (93.8%). Cross-reactions with pathogens prevalent in the area of endemicity, viz., Mycobacterium tuberculosis, Mycobacterium leprae, and Plasmodium spp., could be ruled out. Eighty-one control samples, including dermal scrapings from healthy portions of skin from patients with PKDL were all negative. Two of twenty controls from the area of endemicity were found positive by PCR assay; however, there was a good possibility that these two were asymptomatic carriers since they were serologically positive for KA. Thus, this PCR assay represents a tool for the diagnosis of KA and PKDL in Indian patients in a noninvasive manner, with simultaneous species identification of parasites in clinical samples. C1 ICMR, Inst Pathol, Mol Biol Lab, New Delhi 110029, India. Safdarjung Hosp, Dept Dermatol, New Delhi 110029, India. Safdarjung Hosp, Dept Med, New Delhi 110029, India. US FDA, Ctr Biol Evaluat & Res, Div Emerging & Transfus Transmitted Dis, Rockville, MD 20852 USA. RP Salotra, P (reprint author), ICMR, Inst Pathol, Mol Biol Lab, Safdarjung Hosp Campus,POB 4909, New Delhi 110029, India. NR 39 TC 114 Z9 116 U1 1 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2001 VL 39 IS 3 BP 849 EP 854 DI 10.1128/JCM.39.3.849-854.2001 PG 6 WC Microbiology SC Microbiology GA 408FY UT WOS:000167316900004 PM 11230394 ER PT J AU Koch, WH Sullivan, PS Roberts, C Francis, K Downing, R Mastro, TD Nkengasong, J Hu, D Masciotra, S Schable, C Lal, RB AF Koch, WH Sullivan, PS Roberts, C Francis, K Downing, R Mastro, TD Nkengasong, J Hu, D Masciotra, S Schable, C Lal, RB TI Evaluation of United States-licensed human immunodeficiency virus immunoassays for detection of group M viral variants SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID GROUP-O; DIVERSE HUMAN; TYPE-1; HIV-1; ANTIBODY; INFECTIONS; SUBTYPES; DONORS; PLASMA; BLOOD AB Six Food and Drug Administration (FDA)-licensed human immunodeficiency virus type 1 (HIV-1) and HIV-1/2 immunoassays, including five enzyme immunoassays and one rapid test, were challenged with up to 250 serum samples collected from various global sites. The serum samples were from individuals known to be infected with variants of HIV-1 including group M subtypes A, B, B', C, D, E, F, and G and group O. All immunoassays detected the vast majority of samples tested. Three samples produced low signal over cutoff values in one or more tests: a clade B sample, an untypeable sample with a low antibody titer, and a group O sample. It is concluded that HIV-1 immunoassays used in the United States are capable of detecting most HIV-1 group M variants. C1 Hosp Italiano Buenos Aires, Secc Infectiol, Buenos Aires, DF, Argentina. Hosp Italiano Buenos Aires, Cent Lab, Buenos Aires, DF, Argentina. Projet RETRO CI, Abidjan, Cote Ivoire. HIV AIDS Collaborat, Nonthaburi, Thailand. Uganda Virus Res Inst, Entebbe, Uganda. Ctr Dis Control & Prevent, Atlanta, GA USA. Natl Ctr Infect Dis, Div AIDS STD & TB Lab Res, Atlanta, GA USA. Natl Ctr HIV STD & TB Prevent, Div HIV AIDS Prevent, Atlanta, GA USA. US FDA, Ctr Biol Evaluat & Res, Off Blood Res & Review, Rockville, MD 20857 USA. RP Koch, WH (reprint author), Roche Mol Syst, 1145 Atlantic Ave, Alameda, CA 94501 USA. RI Sullivan, Patrick/A-9436-2009; OI Sullivan, Patrick/0000-0002-7728-0587 NR 30 TC 22 Z9 24 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2001 VL 39 IS 3 BP 1017 EP 1020 DI 10.1128/JCM.39.3.1017-1020.2001 PG 4 WC Microbiology SC Microbiology GA 408FY UT WOS:000167316900030 PM 11230420 ER PT J AU Santos, N Volotao, EM Soares, CC Albuquerque, MCM da Silva, FM de Carvalho, TRB Pereira, CFA Chizhikov, V Hoshino, Y AF Santos, N Volotao, EM Soares, CC Albuquerque, MCM da Silva, FM de Carvalho, TRB Pereira, CFA Chizhikov, V Hoshino, Y TI Rotavirus strains bearing genotype G9 or P[9] recovered from Brazilian children with diarrhea from 1997 to 1999 SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID POLYMERASE CHAIN-REACTION; PORCINE ROTAVIRUS; UNITED-STATES; MOLECULAR CHARACTERIZATION; VP4 GENOTYPES; P-TYPE; SEROTYPE; IDENTIFICATION; PCR; EMERGENCE AB Human rotavirus strains belonging to genotype G9 or P[9] were detected in a collection of stool specimens from children with diarrhea in two cities of the state of Rio de Janeiro, Brazil, between March 1997 and December 1999. G9 strains were first detected in April 1997 and remained prevalent until the end of the study, at a frequency of 15.9% (n = 157). A high percentage of VP7 nucleotide (99.0 to 99.5%) and deduced amino acid identity (98.6 to 99.1%) was found between three randomly selected Brazilian G9 strains and the American G9 strain US1205. A novel G9:P[4] genotype combination was detected in addition to G9:P[8] and G9:P[6], demonstrating that this G genotype may undergo constant genetic reassortment in nature. The P[9] rotavirus strains constituted 10.2%, the majority of which were detected between April and July 1997. The RNA electrophoretic migration pattern of the G3:P[9] strains resembled that of AU-1 virus (G3:P3[9]), suggesting a genetic similarity between the Brazilian G3:P[9] strains and the Japanese virus, which is similar to a feline rotavirus genetically. C1 Univ Fed Rio de Janeiro, Inst Microbiol, Dept Virol, BR-21941590 Rio De Janeiro, Brazil. Univ Fed Fluminense, Dept Microbiol, BR-24300000 Niteroi, RJ, Brazil. US FDA, Ctr Biol Evaluat & Res, Kensington, MD 20895 USA. NIH, Infect Dis Lab, Bethesda, MD 20892 USA. RP Santos, N (reprint author), Univ Fed Rio de Janeiro, Inst Microbiol, Dept Virol, Cidade Univ,CCS-Bl I, BR-21941590 Rio De Janeiro, Brazil. RI Santos, Norma/H-6986-2015 OI Santos, Norma/0000-0002-5123-9172 NR 37 TC 76 Z9 78 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD MAR PY 2001 VL 39 IS 3 BP 1157 EP 1160 DI 10.1128/JCM.39.3.1157-1160.2001 PG 4 WC Microbiology SC Microbiology GA 408FY UT WOS:000167316900058 PM 11230448 ER PT J AU Royce, ME Hoff, PM Dumas, P Lassere, Y Lee, JJ Coyle, J Ducharme, MP De Jager, R Pazdur, R AF Royce, ME Hoff, PM Dumas, P Lassere, Y Lee, JJ Coyle, J Ducharme, MP De Jager, R Pazdur, R TI Phase I and pharmacokinetic study of exatecan mesylate (DX-8951f): A novel camptothecin analog SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID EPITHELIAL OVARIAN-CANCER; CONTINUAL REASSESSMENT METHOD; METASTATIC COLORECTAL-CANCER; POTENT ANTITUMOR-ACTIVITY; DNA TOPOISOMERASE-I; FLUOROURACIL FAILURE; RANDOMIZED TRIAL; TUMOR-CELLS; NUDE-MICE; TOPOTECAN AB Purpose: to determine the maximum-tolerated dose (MTD), dose-limiting toxicity (DLT), pharmacokinetic (PK) profile, and recommended phase II dose of Exatecan mesylate (DX-8951f) when administered as a 24-hour continuous infusion every 3 weeks to patients with solid tumors. Patients and Methods: Twenty-two patients with advanced solid tumors, ail previously treated, and with performance status less than or equal to 2, were entered. The starting dose of DX-8951f was 0.15 mg/m(2); the dose was escalated according to the modified continual reassessment method. The drug was administered until disease progression or until unacceptable toxic effects occurred. Results: Seven dose escalations were completed, and a total of 53 courses were delivered (median, two courses; range, one to eight courses) during the study. At doses 1.2 mg/m(2) and lower, toxicities were mostly grade 1, primarily hematologic. In the initial cohort of three patients treated at 2.4 mg/m(2), grade 2 hematologic toxicity was observed. Of the six additional patients entered at 2.4 mg/m(2), three had grade 3 or 4 granulocytopenia. At doses higher than 2.4 mg/m(2), DLT granulocytopenia was observed. Nonhematologic toxicities, including nausea, vomiting, diarrhea, fatigue, and alopecia, were mild to moderate. Neither complete nor partial responses were observed, but four patients had stable disease. The PK profile of DX-8951f seemed linear at the doses administered. The plasma clearance, total volume of distribution, and terminal elimination half-life were approximately 3 L/h, 40 L, and 14 hours, respectively. Conclusion: The DLT of this DX-8951f schedule was granulocytopenia for minimally pretreated patients, and both granulocytopenia and thrombocytopenia for heavily pretreated patients. The MTD for both minimally and heavily pretreated patients was 2.4 mg/m(2). DX-8951f seems to have a linear PK profile on the basis of single-dose administration. The recommended phase II dose with this schedule is 2.4 mg/m(2) for minimally pretreated patients. A lower dose should be used for heavily pretreated patients. J Clin Oncol 19:1493-1500. (C) 2001 by American Society of Clinical Oncology. C1 Univ Texas, MD Anderson Canc Ctr, Sect Gastrointestinal Med Oncol, Houston, TX 77030 USA. Daiichi Pharmaceut Corp, Montvale, NJ USA. Phoenix Int Life Sci, Montreal, PQ, Canada. US FDA, Rockville, MD 20857 USA. RP Hoff, PM (reprint author), Univ Texas, MD Anderson Canc Ctr, Sect Gastrointestinal Med Oncol, Box 78,1515 Holcombe Blvd, Houston, TX 77030 USA. NR 32 TC 30 Z9 30 U1 0 U2 2 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAR 1 PY 2001 VL 19 IS 5 BP 1493 EP 1500 PG 8 WC Oncology SC Oncology GA 408LB UT WOS:000167326700034 PM 11230496 ER PT J AU Li, Y Brackett, RE Chen, JR Beuchat, LR AF Li, Y Brackett, RE Chen, JR Beuchat, LR TI Survival and growth of Escherichia coli O157 : H7 inoculated onto cut lettuce before or after heating in chlorinated water, followed by storage at 5 or 15 degrees C SO JOURNAL OF FOOD PROTECTION LA English DT Article ID LISTERIA-MONOCYTOGENES; ICEBERG LETTUCE; MICROBIOLOGICAL SAFETY; PHENOLIC METABOLISM; MODIFIED ATMOSPHERE; FRESH PRODUCE; ALFALFA SEEDS; TEMPERATURE; VEGETABLES; VIABILITY AB This study determined the effects of mild heat and chlorine treatment followed by storage for up to 18 days at 5 degreesC or 7 days at 15 degreesC on the survival and growth of Escherichia coli O157:H7 inoculated onto fresh-cut iceberg lettuce. The efficacy of treatment with 20 ppm chlorine in killing the pathogen on lettuce at 50 degreesC was determined. Treatment of lettuce with 20 ppm chlorine at either 20 or 50 degreesC did not result in significantly greater reductions in populations of E. coli O157:H7 compared to respective treatments in water without chlorine. The pathogen steadily decreased in viability on treated lettuce throughout subsequent storage at 5 degreesC for 18 days. The population increased by 2.3 to 3.2 log(10) CFU/g within 2 days, then continued to increase at a slower rate through 7 days of storage at 15 degreesC. At 4 and 7 days, significantly (alpha = 0.05) higher populations were reached on lettuce that had been treated at 50 degreesC, compared to respective samples that had been treated at 20 degreesC, regardless of the presence of 20 ppm chlorine in the treatment water. Treatment of lettuce with 20 ppm chlorine at 50 or 20 degreesC before or after inoculation with E. coli O157:H7 did not have a marked influence on behavior of the pathogen during subsequent storage at 5 or 15 degreesC. C1 Univ Georgia, Ctr Food Safety, 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 31 TC 80 Z9 83 U1 0 U2 6 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC PI DES MOINES PA 6200 AURORA AVE SUITE 200W, DES MOINES, IA 50322-2863 USA SN 0362-028X J9 J FOOD PROTECT JI J. Food Prot. PD MAR PY 2001 VL 64 IS 3 BP 305 EP 309 PG 5 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 408LC UT WOS:000167326800004 PM 11252471 ER PT J AU Barton, MB Moore, S Shtatland, E Bright, R AF Barton, MB Moore, S Shtatland, E Bright, R TI The relation of household income to mammography utilization in a prepaid health care system SO JOURNAL OF GENERAL INTERNAL MEDICINE LA English DT Article DE mammography; socioeconomical status; managed care ID PREVENTIVE CARE; UNITED-STATES; WOMEN; COVERAGE; INSURANCE; ONTARIO; BARRIER; BREAST; CANCER; OLDER AB Managed care organizations should be expected to provide equivalent access to preventive and screening services to all members. We studied mammography in 1,667 women members of one HMO who had an overall utilization rate of 84.9%. Significant correlates of mammography utilization included age, estimated household income, and division of the managed care organization in which the member was enrolled. Each $10,000 increment of income increased mammography rates by 2.5 percentage points (95% confidence interval [CI], 1.4% to 3.6%), independent of age and division. Our findings suggest that coverage for mammography services is not sufficient to ensure equivalent use of screening across income groups. C1 Harvard Univ, Sch Med, Dept ambulatory Care & Prevent, Boston, MA 02215 USA. Harvard Pilgrim Hlth Care, Boston, MA USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Barton, MB (reprint author), Harvard Univ, Sch Med, Dept ambulatory Care & Prevent, 126 Brookline Ave,Suite 200, Boston, MA 02215 USA. RI Bright, Roselie/D-2240-2016 NR 18 TC 9 Z9 9 U1 1 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0884-8734 J9 J GEN INTERN MED JI J. Gen. Intern. Med. PD MAR PY 2001 VL 16 IS 3 BP 200 EP 203 DI 10.1111/j.1525-1497.2001.00228.x PG 4 WC Health Care Sciences & Services; Medicine, General & Internal SC Health Care Sciences & Services; General & Internal Medicine GA 418DD UT WOS:000167873700009 PM 11318916 ER PT J AU Parshikov, IA Freeman, JP Lay, JO Moody, JD Williams, AJ Beger, RD Sutherland, JB AF Parshikov, IA Freeman, JP Lay, JO Moody, JD Williams, AJ Beger, RD Sutherland, JB TI Metabolism of the veterinary fluoroquinolone sarafloxacin by the fungus Mucor ramannianus SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE biotransformation; fluoroquinolones; Mucor ramannianus; sarafloxacin ID MICROBIOLOGICAL TRANSFORMATION; GLOEOPHYLLUM-STRIATUM; ENROFLOXACIN; DEGRADATION; CHROMATOGRAPHY; IDENTIFICATION; HYDROCHLORIDE; CIPROFLOXACIN; BACTERIA; SOIL AB To investigate the microbial biotransformation of veterinary fluoroquinolones, Mucor ramannianus was grown in sucrose/peptone broth with sarafloxacin for 18 days. Cultures were extracted with ethyl acetate and extracts were analyzed by liquid chromatography. The two metabolites (26% and 15% of the A(280), respectively) were identified by mass and H-1 nuclear magnetic resonance spectra as N-acetylsarafloxacin and desethylene-N-acetylsarafloxacin, The biological formation of desethylene-N-acetylsarafloxacin has not been previously observed. C1 US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Div Microbiol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011; OI Lay, Jackson/0000-0003-3789-2527; Parshikov, Igor/0000-0003-1466-1128 NR 20 TC 20 Z9 20 U1 0 U2 10 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD MAR PY 2001 VL 26 IS 3 BP 140 EP 144 DI 10.1038/sj.jim.7000077 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 420HZ UT WOS:000168000700007 PM 11420653 ER PT J AU Malozowski, S Green, L AF Malozowski, S Green, L TI Premature thelarche in girls after growth hormone therapy - Reply SO JOURNAL OF PEDIATRICS LA English DT Letter C1 US FDA, CDER, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. US FDA, CDER, Div Drug Risk Evaluat 2, Rockville, MD 20857 USA. RP Malozowski, S (reprint author), US FDA, CDER, Div Metab & Endocrine Drug Prod, HFD-510, Rockville, MD 20857 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-ELSEVIER PI NEW YORK PA 360 PARK AVENUE SOUTH, NEW YORK, NY 10010-1710 USA SN 0022-3476 EI 1097-6833 J9 J PEDIATR-US JI J. Pediatr. PD MAR PY 2001 VL 138 IS 3 BP 449 EP 449 DI 10.1067/mpd.2001.109105 PG 1 WC Pediatrics SC Pediatrics GA 413BZ UT WOS:000167591200036 ER PT J AU Hayakawa, T Chang, MCJ Rapoport, SI Appel, NM AF Hayakawa, T Chang, MCJ Rapoport, SI Appel, NM TI Selective dopamine receptor stimulation differentially affects [H-3] arachidonic acid incorporation, a surrogate marker for phospholipase A(2)-mediated neurotransmitter signal transduction, in a rodent model of Parkinson's disease SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID CEREBRAL GLUCOSE-UTILIZATION; SUBSTANTIA NIGRA LESIONS; RAT-BRAIN; SUBTHALAMIC NUCLEUS; FATTY-ACIDS; AUTORADIOGRAPHIC LOCALIZATION; CHOLINERGIC STIMULATION; UNANESTHETIZED RATS; QUINPIROLE BINDING; STRIATAL NEURONS AB Our laboratory has developed a technique whereby radiolabeled long-chain fatty acids are injected intravenously in awake rats to pulse-label brain lipids, mainly phospholipids, to measure regional brain lipid metabolism by autoradiography. The brain incorporation of [H-3] arachidonic acid ([H-3]AA), a polyunsaturated fatty acid, may reflect regional changes in neurotransmitter signal transduction using phospholipase A(2). Using this radiotracer, we examined the brain dopamine system in rats with a chronic unilateral 6-hydroxydopamine lesion of the substantia nigra pars compacta, a model of Parkinson's disease. Four weeks after lesioning, rats received either vehicle; SKF38393 or quinpirole (LY-171,555) (D-1- and D-2-dopamine-like agonists, respectively); or (+)-butaclamol (D-1/D-2 antagonist) followed by either vehicle, SKF38393, or quinpirole. They then were infused with [H-3] AA and their brains processed for autoradiography. SKF38393 increased [H-3] AA incorporation into the lesioned side compared with the intact side in the caudate putamen, somatosensory and motor cortices and subthalamic nucleus, but decreased incorporation in the ipsilateral ventrolateral thalamus. Quinpirole increased ipsilateral [H-3] AA incorporation in the caudate putamen and somatosensory and motor cortices, and decreased it in the ventrolateral thalamus. (+)-Butaclamol blocked this effect. The data suggest up-regulation in basal ganglia and cortical dopamine circuits mediated by phospholipase A(2) ipsilateral to the substantia nigra lesion. C1 NIA, Neurosci Lab, NIH, Bethesda, MD 20892 USA. Tokyo Med & Dent Univ, Dept Neurosurg, Bunkyo Ku, Tokyo, Japan. US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Appl Pharmcol Res, Laurel, MD USA. RP Appel, NM (reprint author), NIDA, Div Treatment Res & Dev, NIH, 6001 Execut Blvd,Room 4123,MSC 9551, Bethesda, MD 20892 USA. NR 60 TC 37 Z9 37 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 MAR PY 2001 VL 296 IS 3 BP 1074 EP 1084 PG 11 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 404TD UT WOS:000167116000054 PM 11181943 ER PT J AU Al-qahtani, JM McLean, IW Weiblinger, RP Ediger, MN AF Al-qahtani, JM McLean, IW Weiblinger, RP Ediger, MN TI Preliminary in vitro study of the histological effects of low fluence 193-nm excimer laser irradiation of corneal tissue SO JOURNAL OF REFRACTIVE SURGERY LA English DT Article ID ABLATION; LIGHT; INCISIONS; SURFACE; LENS; NM AB PURPOSE: To determine if moderate numbers of low fluence, 193-nm excimer laser pulses modify or damage the corneal stroma. METHODS: The corneal epithelium of fresh bovine eyes was scraped off and the exposed stroma was irradiated with 200 low fluence laser pulses from an argon fluoride excimer laser. This process was performed on five eyes each at two laser fluences, 10 mJ/cm(2) and 30 mJ/cm(2). The ten irradiated and three control (unirradiated) corneas were sectioned and studied by electron microscopy. The maximum and minimum thickness of the anterior layer of randomly oriented collagen fibers was measured using electron microscopy. RESULTS: The mean maximum thickness of the anterior randomly oriented layer of collagen was 1.23 +/- 0.45 mum in the control corneas, 0.67 +/- 0.32 mum in the corneas irradiated at 10 mJ/cm(2), and 0.10 +/- 0.12 mum in the corneas irradiated at 30 mJ/cm(2). The mean thickness of corneal stroma removed was 0.7 mum at a fluence of 10 mJ/cm(2) and 1.1 mum at a fluence of 30 mJ/cm(2). A thin, electron-dense pseudomembrane was present at both fluences. CONCLUSION: We report removal of bovine corneal stroma at 10 mJ/cm(2)-below the previously reported ablation threshold of 20 mJ/cm(2). C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. King Fahd Hosp Univ, Alkhobar, Saudi Arabia. USAF, Inst Pathol, Dept Ophthalm Pathol, Washington, DC 20330 USA. RP Ediger, MN (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy,Rm 200,HFZ-134, Rockville, MD 20857 USA. NR 17 TC 1 Z9 1 U1 0 U2 2 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-597X J9 J REFRACT SURG JI J. Refractive Surg. PD MAR-APR PY 2001 VL 17 IS 2 BP 105 EP 109 PG 5 WC Ophthalmology; Surgery SC Ophthalmology; Surgery GA 413WT UT WOS:000167635100003 PM 11310758 ER PT J AU Gaigalas, AK Li, L Henderson, O Vogt, R Barr, J Marti, G Weaver, J Schwartz, A AF Gaigalas, AK Li, L Henderson, O Vogt, R Barr, J Marti, G Weaver, J Schwartz, A TI The development of fluorescence intensity standards SO JOURNAL OF RESEARCH OF THE NATIONAL INSTITUTE OF STANDARDS AND TECHNOLOGY LA English DT Article DE fluorescence intensity; quantitative fluorescence; standards ID FLOW-CYTOMETRY; QUANTITATION AB The use of fluorescence as an analytical technique has been growing over the last 20 years. A major factor in inhibiting more rapid growth has been the inability to make comparable fluorescence intensity measurements across laboratories. NIST recognizes the need to develop and provide primary fluorescence intensity standard (FIS) reference materials to the scientific and technical communities involved in these assays. The critical component of the effort will be the cooperation between the Federal laboratories, the manufacturers, and the technical personnel who will use the fluorescence intensity standards. We realize that the development and use of FIS will have to overcome many difficulties. However, as we outline in this article, the development of FIS is feasible. C1 Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. Ctr Dis Control, Atlanta, GA 30333 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. US FDA, CDER, Laurel, MD USA. Ctr Quantitat Cytometry, San Juan, PR USA. RP Gaigalas, AK (reprint author), Natl Inst Stand & Technol, Gaithersburg, MD 20899 USA. NR 21 TC 35 Z9 36 U1 1 U2 5 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPERINTENDENT DOCUMENTS,, WASHINGTON, DC 20402-9325 USA SN 1044-677X J9 J RES NATL INST STAN JI J. Res. Natl. Inst. Stand. Technol. PD MAR-APR PY 2001 VL 106 IS 2 BP 381 EP 389 PG 9 WC Instruments & Instrumentation; Physics, Applied SC Instruments & Instrumentation; Physics GA 435JA UT WOS:000168872700002 PM 27500028 ER PT J AU Kerr, LN Boivin, WS Hamilton, SL Mailhot, SA O 'Malley, LG Boyd, SM Pierdominici, VJB Bushar, HF AF Kerr, LN Boivin, WS Hamilton, SL Mailhot, SA O 'Malley, LG Boyd, SM Pierdominici, VJB Bushar, HF TI Comparison of ISO/FDA and ASTM condom water leak test methods SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE condom; water leak test; defects; ASTM; FDA; ISO AB This research compares the ISO/FDA and ASTM water leak test methods for detecting defects in latex and synthetic condoms. Detection rates of standardized defects are quantified for four condom materials. The overall detection rate of the ISO/FDA method (53.4%) averages 12.3% higher than the ASTM method (41.1%) and is higher for each of the four condom materials, Detection rates for both test methods vary significantly by condom material. The ISO/FDA method is effective in detecting 30 mum laser defects in polyurethane and latex condoms (79.9 and 69.7%, respectively), but is not very effective in baggy and high elongation condoms (24.4 and 39.7%). Due to the limited number of condoms tested, only four combinations of material, defect type, and hole location showed statistically significant differences in detection rates for ISO/FDA versus ASTM methods. Data produced by this research may help harmonize the ASTM and ISO/FDA water leak test methods. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20850 USA. RP Kerr, LN (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA. NR 11 TC 1 Z9 1 U1 1 U2 3 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 MAR PY 2001 VL 29 IS 2 BP 192 EP 198 PG 7 WC Materials Science, Characterization & Testing SC Materials Science GA 411LK UT WOS:000167501400009 ER PT J AU Kerr, LN Chaput, MP Boyd, SM Galevi, EA Millward, PA AF Kerr, LN Chaput, MP Boyd, SM Galevi, EA Millward, PA TI Characterization and creation of defects in condoms SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE condoms; water leak test; defects; defect creation; characterization; latex; synthetic; polyurethane; holes; slits AB Defects in condoms were examined, then characterized and compared with defects introduced using various techniques. Eighty-five percent of the condom defects examined were classified as either a hole (void in material) or a slit (puncture). Laser drilling and puncturing with a 160 mum diameter acupuncture needle artificially introduced similar types of defects. Microscopic examination of the created defects, before and after FDA water leak testing, showed that this test method does not increase the size of preexisting microscopic defects. Examination also showed that these creation techniques generated reproducible defects within a condom type, with the size of acupuncture needle defects varying less than laser-drilled defects. Results of water leak testing showed that the leakage characteristics of defects are affected by the material type, the condom shape and size, the type of defect and the defect size, and the presence of lubricant. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Kerr, LN (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA. NR 9 TC 1 Z9 1 U1 2 U2 3 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 MAR PY 2001 VL 29 IS 2 BP 214 EP 219 PG 6 WC Materials Science, Characterization & Testing SC Materials Science GA 411LK UT WOS:000167501400012 ER PT J AU Wear, KA AF Wear, KA TI A numerical method to predict the effects of frequency-dependent attenuation and dispersion con speed of sound estimates in cancellous bone SO JOURNAL OF THE ACOUSTICAL SOCIETY OF AMERICA LA English DT Article ID ULTRASOUND ATTENUATION; TRABECULAR BONE; HIP FRACTURE; QUANTITATIVE ULTRASOUND; MECHANICAL-PROPERTIES; HUMAN CALCANEUS; GROUP-VELOCITY; OS CALCIS; IN-VITRO; DENSITY AB Many studies have demonstrated that time-domain speed-of-sound (SOS) measurements in calcaneus are predictive of osteoporotic fracture risk. However, there is a lack of standardization fur this measurement. Consequently, different investigators using different measurement systems and analysis algorithms obtain disparate quantitative values for calcaneal SOS, impairing and often precluding meaningful comparison and/or pooling of measurements. A numerical method has been developed to model the effects of frequency-dependent attenuation and dispersion on transit-time-based SOS estimates. The numerical technique is based on a previously developed linear system analytic model for Gaussian pulses propagating through linearly attenuating, weakly dispersive media. The numerical approach is somewhat more general in that it can be used to predict the effects of arbitrary pulse shapes and dispersion relationships. The numerical technique, however, utilizes several additional assumptions (compared with the analytic model) which would be required for the practical task of correcting existing clinical databases. These include a single dispersion relationship for all calcaneus samples, a simple linear model relating phase velocity to broadband ultrasonic attenuation, and a constant calcaneal thickness. Measurements on a polycarbonate plate and 30 human calcaneus samples were in good quantitative agreement with numerical predictions. In addition, the numerical approach predicts that in cancellous bone, frequency-dependent attenuation tends to be a greater contributor to variations ire transit-time-based SOS estimates than dispersion. This approach may be used to adjust previously acquired individual measurements so that SOS data recorded with different devices using different algorithms may be compared in a meaningful fashion. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, HFZ-142,12720 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 29 TC 18 Z9 18 U1 1 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0001-4966 J9 J ACOUST SOC AM JI J. Acoust. Soc. Am. PD MAR PY 2001 VL 109 IS 3 BP 1213 EP 1218 DI 10.1121/1.1344161 PG 6 WC Acoustics; Audiology & Speech-Language Pathology SC Acoustics; Audiology & Speech-Language Pathology GA 409DM UT WOS:000167369300033 PM 11303934 ER PT J AU Weindruch, R Keenan, KP Carney, JM Fernandes, G Feuers, RJ Floyd, RA Halter, JB Ramsey, JJ Richardson, A Roth, GS Spindler, SR AF Weindruch, R Keenan, KP Carney, JM Fernandes, G Feuers, RJ Floyd, RA Halter, JB Ramsey, JJ Richardson, A Roth, GS Spindler, SR TI Caloric restriction mimetics: Metabolic interventions SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT Caloric-Restriction-Clinical-Implications-Advisory-Group Meeting CY MAR 08-10, 1999 CL BETHESDA, MD SP Calor Restrict Clin Implicat Advisory Grp ID GLYCATION END-PRODUCTS; BUTYL-ALPHA-PHENYLNITRONE; MITOCHONDRIAL PROTON LEAK; UNCOUPLING PROTEIN HOMOLOG; FREE-RADICAL PRODUCTION; SPIN-TRAPPING COMPOUND; FATTY-ACID-COMPOSITION; LOWERS BLOOD-GLUCOSE; AGE-RELATED INCREASE; MALE FISCHER-344 RAT AB Caloric restriction (CR) retards diseases and aging in laboratory rodents and is now being tested in nonhuman primates. One way to apply these findings to human health is to identify and test agents that may mimic critical actions of CR. Panel 2 focused on two outcomes of CR, reduction of oxidative stress and improved glucoregulation, for which candidate metabolic mimics exist. It was recommended that studies on oxidative stress should emphasize mitochondrial function and to test the efficacy of nitrone and other antioxidants in mimicking CR's effects. Studies should also focus on the long-term effects of compounds known to lower circulating glucose and insulin concentrations or to increase insulin sensitivity. Also, four other developing areas were identified: intermediary metabolism, response to infection, stress responses, and source of dietary fat. These areas are important because either they hold promise for the discovery of new mimetics or they need to be explored prior to initiation of CR trials in humans. Other recommendations were that transgenic approaches and adult-onset CR should be emphasized in future studies. C1 Univ Wisconsin, Dept Med, Madison, WI 53706 USA. Merck Res Labs, West Point, PA USA. Centaur Pharmaceut Inc, Sunnyvale, CA USA. Univ Texas, Hlth Sci Ctr, Dept Med, San Antonio, TX 78284 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Oklahoma Med Res Fdn, Free Rad Biol & Aging Res Program, Oklahoma City, OK 73104 USA. Univ Michigan, Geriatr Ctr, Ann Arbor, MI 48109 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53706 USA. Univ Texas, Hlth Sci Ctr, Dept Physiol, San Antonio, TX 78284 USA. Gerontol Res Ctr, Mol Physiol & Genet Sect, Baltimore, MD USA. Univ Calif Riverside, Dept Biochem, Riverside, CA 92521 USA. RP Weindruch, R (reprint author), Univ Wisconsin, VA Hosp, Dept Med, GRECC-4D,2500 Overlook Terrace, Madison, WI 53706 USA. EM rhweindr@facstaff.wisc.edu NR 162 TC 101 Z9 106 U1 0 U2 4 PU OXFORD UNIV PRESS INC PI CARY PA JOURNALS DEPT, 2001 EVANS RD, CARY, NC 27513 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2001 VL 56 SI SI BP 20 EP 33 PG 14 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 422KX UT WOS:000168118000003 PM 12088209 ER PT J AU Poehlman, ET Turturro, A Bodkin, N Cefalu, W Heymsfield, S Holloszy, J Kemnitz, J AF Poehlman, ET Turturro, A Bodkin, N Cefalu, W Heymsfield, S Holloszy, J Kemnitz, J TI Caloric restriction mimetics: Physical activity and body composition changes SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article; Proceedings Paper CT Caloric-Restriction-Clinical-Implications-Advisory-Group Meeting CY MAR 08-10, 1999 CL BETHESDA, MARYLAND SP Calor Restrict Clin Implicat Advisory Grp ID RESTING METABOLIC-RATE; ADIPOSE-TISSUE CELLULARITY; CORONARY HEART-DISEASE; EXERCISING MALE-RATS; ALL-CAUSE MORTALITY; FOOD RESTRICTION; ENERGY-EXPENDITURE; DIETARY RESTRICTION; LEISURE-TIME; CYNOMOLGUS MONKEYS AB As the only paradigm that has consistently increased life span and inhibited the onset and/or progression of disease, dietary restriction has multiple effects on a variety of organ systems. In this brief review, the goal of the panel was to attempt to understand the role of changes in physical activity and body composition as possible modulators of the lift: span in experimental animals and humans. We focus on whether changes in exercise behavior and body composition produce similar changes as those found in dietary restriction and whether these changes can be used to either replace or enhance the beneficial effects of dietary restriction. The complexity of the two stimuli is emphasized in our report, with suggestions offered on how to better interpret existing research. Our panel briefly examines evidence in experimental animals and humans about the specific contributions of each of these factors to altering life span and age-related pathologies. We also discuss additional animal studies and/or human intervention studies that could be performed to clarify these issues. Finally, we provide suggested avenues for future research in this area of changes in physical activity and body composition as dietary restriction mimetics. C1 Univ Vermont, Dept Med, Burlington, VT 05405 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Univ Maryland, Dept Physiol, Obes & Diabet Res Ctr, Baltimore, MD 21201 USA. St Lukes Roosevelt Hosp, New York, NY 10025 USA. Columbia Univ Coll Phys & Surg, New York, NY 10032 USA. Washington Univ, Sch Med, Sect Appl Physiol, Div Geriatr & Gerontol, St Louis, MO USA. Univ Wisconsin, Dept Physiol, Madison, WI 53706 USA. Univ Wisconsin, Wisconsin Reg Primate Res Ctr, Madison, WI 53706 USA. RP Poehlman, ET (reprint author), Univ Vermont, Dept Med, Given Bldg C-247, Burlington, VT 05405 USA. NR 74 TC 30 Z9 30 U1 0 U2 2 PU GERONTOLOGICAL SOCIETY AMER PI WASHINGTON PA 1275 K STREET NW SUITE 350, WASHINGTON, DC 20005-4006 USA SN 1079-5006 J9 J GERONTOL A-BIOL JI J. Gerontol. Ser. A-Biol. Sci. Med. Sci. PD MAR PY 2001 VL 56 SI SI BP 45 EP 54 PG 10 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA 422KX UT WOS:000168118000005 PM 12088211 ER PT J AU Levy, DD Cebula, TA AF Levy, DD Cebula, TA TI Fidelity of replication of repetitive DNA in mutS and repair proficient Escherichia coli SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE replication fidelity; repetitive DNA; mutator; microsatellite; frameshift mutagenesis ID SHUTTLE VECTOR PLASMID; MISMATCH-REPAIR; FRAMESHIFT MUTATIONS; MICROSATELLITE INSTABILITY; ANTIGENIC VARIATION; GENOME SEQUENCE; CODON USAGE; REPEATS; GENE; DEFICIENT AB Replication fidelity is not constant among strains within a species or at all genetic loci within a genome. Altered fidelity of replication may affect patterns of pathogenesis and the evolution of these strains. We have been studying replication fidelity in Escherichia coli, both in laboratory attenuated strains and in food-borne pathogens. To understand the altered patterns of mutagenesis at the molecular level, we used a shuttle vector plasmid with a tRNA mutational marker gene which had been altered to include homopolymeric runs of five, seven and nine [G:C] pairs, as well as non-repetitive DNA. Replication of the plasmid in mutS strains resulted in a 20-fold increase in mutant progeny plasmids. The mutations were almost all (>90%) frameshift mutations, while base substitution mutations were rare. Most mutations were insertions or deletions of one or two [G:C] pairs in the longest homopolymeric runs. Larger deletions (5 to >70 bp), also targeted to the repetitive sequence, were likewise common. Mutations increased exponentially with the length of the homopolymeric run. These patterns of mutation, including unexpectedly high levels in repair proficient strains, led to an examination of the E. coli K-12 genome for homopolymeric DNA. This sequence motif was found to be rare, particularly in genes and open reading frames. Amino acid homotrimers were found to avoid usage of homopolymeric codons, even when they are preferred among synonymous codons in E. coli. There appears to be active selection against tandem direct nucleotide repeats in the E. coli genome, correlated with the inability of the organism to accurately replicate such sequence. Published by Elsevier Science B.V. C1 US FDA, Mol Biol Branch HFS237, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Cebula, TA (reprint author), US FDA, Mol Biol Branch HFS237, Ctr Food Safety & Appl Nutr, 200 C St, Washington, DC 20204 USA. NR 57 TC 16 Z9 16 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 1 PY 2001 VL 474 IS 1-2 BP 1 EP 14 DI 10.1016/S0027-5107(00)00169-X PG 14 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 411HM UT WOS:000167492500001 PM 11239958 ER PT J AU Domon, OE McGarrity, LJ Bishop, M Yoshioka, M Chen, JJ Morris, SM AF Domon, OE McGarrity, LJ Bishop, M Yoshioka, M Chen, JJ Morris, SM TI Evaluation of the genotoxicity of the phytoestrogen, coumestrol, in AHH-1 TK+/- human lymphoblastoid cells SO MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS LA English DT Article DE coumestrol; human lymphoblastoid cells; TK mutations; loss-of-heterozygosity ID INTRACHROMOSOMAL HOMOLOGOUS RECOMBINATION; MAMMALIAN-CELLS; BREAST-CANCER; P53 PROTEIN; MUTATIONS; TOPOISOMERASE; MICRONUCLEUS; INDUCTION; APOPTOSIS; MUTAGENICITY AB Coumestrol, a phytoestrogen found in high levels in alfalfa and red clover, is of concern since endocrine disorders have been observed in farm animals exposed to high levels of phytoestrogens. Previous studies found that coumestrol was an effective inducer of DNA strand breaks, micronuclei, and mutations in the Hypoxanthine phosphoribosyl transferase (HPRT) gene of Chinese hamster ovary cells. In the experiments presented here, we extended the previous studies to examine the effect of coumestrol exposure on AHH-1 TK+/- human lymphoblastoid cells. Micronuclei were induced with the highest frequency occurring at day ? after exposure. Flow cytometric analysis of annexin V-FITC-7-aminoactinomycin D stained cells indicated that the primary pathway of cell death was by apoptosis. Mutations were induced in the Thymidine Kinase (TK) gene and were due primarily to the induction of clones with the slow-growth phenotype. Subsequent molecular analysis revealed the loss of exon 4 in the coumestrol-induced clones. indicative of loss-of heterozygosity and consistent with a proposed inhibition of topoisomerase-II activity as a mechanism of action for coumestrol. Taken together, these results suggest that coumestrol exhibits both mutagenic and clastogenic properties in cultured human lymphoblastoid cells. Published by Elsevier Science B.V. C1 US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Div Biometry & Risk Assessment, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Morris, SM (reprint author), US FDA, Div Genet & Reprod Toxicol, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 37 TC 18 Z9 18 U1 1 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 1 PY 2001 VL 474 IS 1-2 BP 129 EP 137 DI 10.1016/S0027-5107(00)00170-6 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 411HM UT WOS:000167492500013 PM 11239970 ER PT J AU Meyer, MC Straughn, AB Mhatre, RM Shah, VP Chen, ML Williams, RL Lesko, LJ AF Meyer, MC Straughn, AB Mhatre, RM Shah, VP Chen, ML Williams, RL Lesko, LJ TI Variability in the bioavailability of phenytoin capsules in males and females SO PHARMACEUTICAL RESEARCH LA English DT Article DE phenytoin; bioavailability; human; pharmacokinetics; gender; menstrual cycle ID PHARMACOKINETICS; EPILEPSY AB Purpose. To determine inter-lot and intra-subject variability in the bioavailability of the 100 mg extended phenytoin sodium capsules. In addition, to determine the effect of gender and menstrual cycle on phenytoin bioavailability. Methods. Three different lots of extended phenytoin sodium capsules wen given to 12 healthy male and 12 healthy female subjects in a crossover fashion. One of the lots was also given a second time to each subject. Plasma phenytoin was determined, using an HPLC assay, in samples collected over a 73-hr period after each dose. Results.The mean Cmax for the four administrations ranged from 1.71-1.79 mug/ml and mean AUC(0-infinity) values from ranged 53.0-54.1 mug,hr/ml. The elimination half-life was 3 hr shorter, and the AUC(0-infinity) adjusted for the mg/kg dose was 30% lower for females. Average bioequivalence was demonstrated between the three lots for both Cmax and AUC(0-infinity) based on the BE limit of 80-125%. Further, all confidence intervals of AUC(0-infinity) fell within the limit of 90-111%. There were no differences in the confidence limits for Cmax and AUC(0-infinity) determined separately for males and females. Also, there was no difference in the mean Cmax or AUC(0-infinity) for females when analyzed as a function of the week of their menstrual cycle. Individual bioequivalence was demonstrated between three lots of phenytoin using the constant-scaled method, but not the reference-scaled method. Conclusions. There was very little difference in the bioavailability of the three lots of phenytoin. Females exhibited a lower AUC(0-infinity) than males after adjustment of dose for body weight, but their inclusion in the study did not affect the assessment of bioequivalence. When dose was not adjusted for body weight, no difference in AUC(0-infinity) was seen between males and females. C1 Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Meyer, MC (reprint author), Univ Tennessee, Coll Pharm, Dept Pharmaceut Sci, Memphis, TN 38163 USA. NR 13 TC 16 Z9 16 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 2001 VL 18 IS 3 BP 394 EP 397 DI 10.1023/A:1011075502215 PG 4 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA 446NL UT WOS:000169519300023 PM 11442282 ER PT J AU Doerge, DR Churchwell, MI Chang, HC Newbold, RR Delclos, KB AF Doerge, DR Churchwell, MI Chang, HC Newbold, RR Delclos, KB TI Placental transfer of the soy isoflavone genistein following dietary and gavage administration to Sprague Dawley rats SO REPRODUCTIVE TOXICOLOGY LA English DT Article DE soy; isoflavones; genistein; placental transfer; mass spectrometry ID CHROMATOGRAPHY-MASS-SPECTROMETRY; IN-VITRO; BREAST-CANCER; MAMMARY-GLAND; HUMAN HEALTH; EXPOSURE; PHYTOESTROGENS; ESTROGEN; MECHANISMS; CELLS AB Genistein, the principal soy isoflavone, has estrogenic activity and is widely consumed for putative beneficial health effects. The goal of the present study was to measure placental transfer of genistein in rats as a possible route of developmental exposure. Pregnant Sprague-Dawley rats were administered genistein orally, either by diet or by gavage. Concentrations of genistein aglycone and conjugates were measured in maternal and offspring serum and brain using HPLC with isotope dilution electrospray tandem mass spectrometry. Although fetal or neonatal serum concentrations of total genistein were approximately 20-fold lower than maternal serum concentrations, the biologically active genistein aglycone concentration was only 5-fold lower. Fetal brain contained predominately genistein aglycone at levels similar to those in the maternal brain. These studies show that genistein aglycone crosses the rat placenta and can reach fetal brain from maternal serum genistein levels that are relevant to those observed in humans. (C) 2001 Elsevier Science Inc. All rights reserved. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NIEHS, Dev Endocrinol Sect, Reprod Toxicol Grp, Lab Toxicol,Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. FU PHS HHS [224-93-0001] NR 24 TC 81 Z9 82 U1 1 U2 4 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0890-6238 J9 REPROD TOXICOL JI Reprod. Toxicol. PD MAR-APR PY 2001 VL 15 IS 2 BP 105 EP 110 DI 10.1016/S0890-6238(01)00108-3 PG 6 WC Reproductive Biology; Toxicology SC Reproductive Biology; Toxicology GA 424ET UT WOS:000168219700001 PM 11297868 ER PT J AU Vandenberg, JD Sandvol, LE Jaronski, ST Jackson, MA Souza, EJ Halbert, SE AF Vandenberg, JD Sandvol, LE Jaronski, ST Jackson, MA Souza, EJ Halbert, SE TI Efficacy of fungi for control of Russian wheat aphid (Homoptera : Aphididae) in irrigated wheat SO SOUTHWESTERN ENTOMOLOGIST LA English DT Article ID BEAUVERIA-BASSIANA; PAECILOMYCES-FUMOSOROSEUS; CEREAL APHIDS; SOUTHWESTERN IDAHO; ENTOMOPHTHORALES; BLASTOSPORES; REGISTRATION; FORMULATION; HYMENOPTERA; LEPIDOPTERA AB Field plots of irrigated spring and winter wheat, Triticum aestivum L., in southeastern Idaho, were infested with the Russian wheat aphid, Diuraphis noxia (Mordvilko) (Homoptera: Aphididae) and later treated with spores of Brauveria bassiana (Balsamo) Vuillemin or Paecilomyces fumosoroseus (Wize) Brown and Smith at rates of 2.5 or 5 x 10(13) spores/ha. Small plots (1.4 to 6.6 m(2)) were treated with a backpack sprayer in 1995-1998 and large plots (470 m(2)) were treated using an overhead irrigation system in 1997 and 1998. In 1995, Russian wheat aphid densities rose to an average of over 120 Russian wheat aphids per tiller in control plots compared to an average of less than 30 Russian wheat aphids per tiller in all fungus-treated plots 33 days after the first treatment. Smaller, significant reductions were observed within 14 days of treatment with B. bassiana in 1996 and 1997. Low Russian wheat aphid infestation rates, averaging less than 1 Russian wheat aphid per tiller, made significant differences impossible to detect. Significant reductions in both Russian wheat aphid densities and the percentage of tiller infestation were observed in large-plot experiments two weeks after application of a high rate of B. bassiana in spring (1997) and winter wheat (1998). Fungus-treated Russian wheat aphids suffered 32-83% mycosis when field-treated tillers were incubated in the laboratory. Persistence of fungal inocula of either species, measured by estimating CFUs obtained from washed leaf segments, decreased by 10- to 1000-fold within 3 to 5 days. C1 ARS, USDA, US Plant Soil & Nutr Lab, Ithaca, NY 14853 USA. Univ Idaho, Aberdeen Res & Extens Ctr, Aberdeen, ID 83210 USA. Mycotech Corp, Butte, MT 59701 USA. ARS, USDA, Natl Ctr Agr Utilizat Res, Peoria, IL 61604 USA. FDACS Div Plant Ind, Gainesville, FL 32614 USA. RP Vandenberg, JD (reprint author), ARS, USDA, US Plant Soil & Nutr Lab, Tower Rd, Ithaca, NY 14853 USA. NR 26 TC 24 Z9 33 U1 1 U2 3 PU SOUTHWESTERN ENTOMOLOGICAL SOC PI DALLAS PA 17360 COIT RD, DALLAS, TX 75252-6599 USA SN 0147-1724 J9 SOUTHWEST ENTOMOL JI Southw. Entomol. PD MAR PY 2001 VL 26 IS 1 BP 73 EP 85 PG 13 WC Entomology SC Entomology GA 427JC UT WOS:000168400200007 ER PT J AU Tor-Agbidye, J Yamamoto, B Bowyer, JF AF Tor-Agbidye, J Yamamoto, B Bowyer, JF TI Seizure activity and hyperthermia potentiate the increases in dopamine and serotonin extracellular levels in the Amygdala during exposure to d-amphetamine SO TOXICOLOGICAL SCIENCES LA English DT Article DE seizures; neurotoxicity; amphetamine; amygdala; dopamine; serotonin ID RAT BASOLATERAL AMYGDALA; DORSAL RAPHE NUCLEUS; CAUDATE-PUTAMEN; NEURONAL DEGENERATION; REGIONAL DISTRIBUTION; TYROSINE-HYDROXYLASE; GLUTAMATE RELEASE; PERIRHINAL CORTEX; NERVE-TERMINALS; 5-HT3 RECEPTOR AB Behavioral stereotypy, hyperthermia, and convulsive activity produced by exposure to multiple doses of d-amphetamine (AMPH) were related to changes in the extracellular levels of dopamine and serotonin (5-HT) in the amygdala, using the technique of microdialysis in awake and freely moving rats. Hyperactivity and stereotypy, as well as increases in microdialysis dopamine levels ranging from 100-300% of pre-AMPH basal microdialysate levels (BL), occurred during exposure to 3 doses of 2.5 mg/kg (3 x 2.5 mg/kg) AMPH. Three doses of 5 mg/kg produced a more intense stereotypic behavior as well as hyperthermia, and resulted in large increases in the peak dopamine levels (700% BL) while 5-HT levels were increased to a lesser extent (300% BL). The highest doses tested of 3 x 15 mg/kg produced convulsive activity, seizures, intense stereotypy and hyperthermia with peak microdialysate dopamine (1300% BL) and 5-HT levels (1800% BL) that were 2-fold and 6-fold greater, respectively, than those at the 3 x 5-mg/kg doses. Microdialysate glutamate levels were not changed by AMPH exposure. Rats that did not become hyperthermic when dosed with 15 mg/kg AMPH in a cold environment (10 degreesC) exhibited some hyperactivity and stereotypic behavior, but not overt convulsive behavior. Dopamine and 5-HT levels in these rats were significantly reduced by about 75% and 60%, respectively, compared to the room-temperature group. Inclusion of 2 muM tetrodotoxin (TTX) in the microdialysis buffer significantly reduced the 15-mg/kg AMPH-induced increases in dopamine by 30% and the increase in 5-HT levels by 70% at room temperature. These results indicate that a smaller portion of the dopamine release evoked by doses of AMPH that induce seizure activity is neuronal impulse-dependent while the majority of 5-HT released is impulse-dependent. Irrespective of impulse activity, the hyperthermia alone markedly potentiated dopamine release but had a lesser effect on 5-HT release. Thus, there are differences in the regulation of dopamine and serotonin release in the amygdala from high doses of AMPH, which are known to produce neurotoxicity. Further studies are necessary to determine the impact of these differences in release on AMPH neurotoxicity. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Case Western Reserve Univ, Dept Psychiat, Cleveland, OH 44106 USA. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. NR 56 TC 3 Z9 4 U1 0 U2 2 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD MAR PY 2001 VL 60 IS 1 BP 103 EP 111 DI 10.1093/toxsci/60.1.103 PG 9 WC Toxicology SC Toxicology GA 407HY UT WOS:000167267200014 PM 11222877 ER PT J AU Ghedin, E Debrabant, A Engel, JC Dwyer, DM AF Ghedin, E Debrabant, A Engel, JC Dwyer, DM TI Secretory and endocytic pathways converge in a dynamic endosomal system in a primitive protozoan SO TRAFFIC LA English DT Article DE endocytic pathway; GFP chimeras; Leishmania; secretory pathway; trafficking ID LEISHMANIA-DONOVANI; MEMBRANE; GOLGI; SURFACE; PARASITES; TRYPANOSOMATIDS; ORGANIZATION; AMASTIGOTE; LYSOSOMES; TRANSPORT AB Leishmania are a group of primitive eukaryotic trypanosomatid protozoa that are apically polarized with a flagellum at their anterior end. Surrounding the base of the flagellum is the flagellar reservoir that constitutes the site for endocytosis and exocytosis in these organisms. In the present study, we define a novel multivesicular tubular compartment involved in the intracellular trafficking of macromolecules in Leishmania. This dynamic structure appears to subtend the flagellar reservoir and extends towards the posterior end of the cell. Functional domains of several surface-expressed proteins, such as the gp63 glycosyl phosphatidyl inositol anchor and the 3' nucleotidase/nuclease transmembrane domain were fused to green fluorescent protein. These chimeric proteins were found to traffic through the secretory pathway and, while reaching their intended destinations, also accumulated within the intracellular tubular compartment. Using various compounds that are efficient fluid-phase markers used to track endocytosis in higher eukaryotes, we showed that this tubular compartment constitutes an important station in the endocytic pathway of these cells. Based on our functional observations of its role in the trafficking of expressed proteins and endocytosed markers, this compartment appears to have properties similar to endosomes of higher eukaryotes. C1 NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, Bethesda, MD 20892 USA. US FDA, Lab Parasite Biol & Biochem, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Univ Calif San Francisco, Vet Adm Med Ctr, Dept Pathol, San Francisco, CA 94121 USA. RP Dwyer, DM (reprint author), NIAID, Cell Biol Sect, Parasit Dis Lab, Div Intramural Res,NIH, 9000 Rockville Pike, Bethesda, MD 20892 USA. NR 30 TC 54 Z9 54 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 1398-9219 J9 TRAFFIC JI Traffic PD MAR PY 2001 VL 2 IS 3 BP 175 EP 188 DI 10.1034/j.1600-0854.2001.020304.x PG 14 WC Cell Biology SC Cell Biology GA 465TG UT WOS:000170605600004 PM 11260523 ER PT J AU Balaban, N Rasooly, A AF Balaban, N Rasooly, A TI Analytical chromatography for recovery of small amounts of staphylococcal enterotoxins from food SO INTERNATIONAL JOURNAL OF FOOD MICROBIOLOGY LA English DT Article DE analytical chromatography; staphylococcal enterotoxins; sample preparation ID ASSAY KIT TECRA; T-CELLS; TOXIN GENE; PURIFICATION; SEPARATION; MILK; MICE AB Sample preparation is an important element in the detection of toxins in food samples. In this work, a simple analytical sample preparation method for recovery of small amount of staphylococcal enterotoxin B (SEB) and staphylococcal enterotoxin A (SEA) in food samples was developed. Cation exchanger carboxymethylcellulose (CM) was used for small-scale batch chromatography isolation of SEE from infant formula and from mushrooms spiked with SEE. The resulting materials were analyzed for SEB by Western immunoblotting. Nearly all of the extraneous substances in the sample were removed by this procedure with no significant loss of the toxin. Using this method, even small amounts of SE (0.75 ng/g) can be recovered and immunologically analyzed by Western blotting or by ELISA with a very low background. Because this method is effective, rapid, simple and inexpensive, it has the potential to be a general method for the preparation of samples used for analysis of SEs. (C) 2001 Elsevier Science B.V. All rights reserved. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. Univ Calif Davis, Dept Med Pathol, Davis, CA 95616 USA. RP Rasooly, A (reprint author), US FDA, Div Microbiol Studies, Washington, DC 20204 USA. NR 25 TC 28 Z9 28 U1 0 U2 9 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 FEB 28 PY 2001 VL 64 IS 1-2 BP 33 EP 40 DI 10.1016/S0168-1605(00)00439-6 PG 8 WC Food Science & Technology; Microbiology SC Food Science & Technology; Microbiology GA 407AA UT WOS:000167248200004 PM 11252509 ER PT J AU Racoosin, JA Feeney, J Burkhart, G Boehm, G AF Racoosin, JA Feeney, J Burkhart, G Boehm, G TI Mortality in antiepileptic drug development programs SO NEUROLOGY LA English DT Article ID SUDDEN UNEXPLAINED DEATH; UNEXPECTED DEATH; RISK-FACTORS; EPILEPSY; COHORT AB Background: Pooled data from New Drug Applications (NDAs) submitted to the U.S. Food and Drug Administration (FDA) provide an opportunity to study the incidence of and risk factors for rare events. Objective: To examine the incidence and causes of mortality in patients with epilepsy participating in clinical trials of antiepileptic drugs (AEDs); and to examine the incidence of and risk factors for sudden unexplained death in such patients. Methods: Exposure data and death narratives were obtained from the NDAs of five recently reviewed AEDs. Deaths were classified as sudden unexplained, accidental, or other cause using the 1993 Burroughs-Wellcome expert panel criteria, and mortality rates were calculated for each category. Add-on trials were analyzed separately from monotherapy initiation trials. Results: Among 9,144 patients in the add-on trial database, the all-cause and sudden unexplained mortality rates were 9.1 and 3.8 deaths per 1,000 person-years (124 and 52 deaths in 13,617.1 person-years of drug exposure). Sixty-five percent of all deaths were related to the underlying epilepsy. Of the examined risk factors, only age was associated with the incidence of sudden unexplained death. Among 1,293 patients in the monotherapy initiation trials, the all-cause and sudden unexplained mortality rates were 7.1 and 0 deaths per 1,000 person-years (7 and 0 deaths in 982.5 person-years of drug exposure). Conclusions: A large proportion of the deaths in the add-on cohort was attributable to epilepsy-related causes. Mortality due to sudden death in the add-on cohort falls into the high end of the reported range for patients with epilepsy. The difference in mortality due to sudden death between the add-on and monotherapy initiation cohorts suggests that disease severity is the primary determining factor for risk of sudden unexplained death. C1 US FDA, Div Neuropharmacol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Racoosin, JA (reprint author), 5600 Fishers Lane,HFD 120, Rockville, MD 20857 USA. NR 12 TC 32 Z9 33 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0028-3878 J9 NEUROLOGY JI Neurology PD FEB 27 PY 2001 VL 56 IS 4 BP 514 EP 519 PG 6 WC Clinical Neurology SC Neurosciences & Neurology GA 405HT UT WOS:000167154500018 PM 11222797 ER PT J AU Kamstrup, S Verthelyi, D Klinman, DM AF Kamstrup, S Verthelyi, D Klinman, DM TI Response of porcine peripheral blood mononuclear cells to CpG-containing oligodeoxynucleotide SO VETERINARY MICROBIOLOGY LA English DT Article DE PBMC; CpG; oligodeoxynucleotides; immunostimulation; pigs ID BACTERIAL-DNA; IMMUNE-RESPONSES; IN-VITRO; B-CELLS; IMMUNOSTIMULATORY OLIGODEOXYNUCLEOTIDES; INTERFERON-GAMMA; CUTTING EDGE; MOTIFS; OLIGONUCLEOTIDES; ACTIVATION AB Exposure to bacterial DNA generates a "danger signal" that stimulates cellular elements of the mammalian immune system to proliferate and/or secrete cytokines. Stimulation is critically dependent on hexameric motifs that contain an unmethylated CpG dinucleotide: these are commonly found in bacterial but not vertebrate DNA. Different motifs are optimally stimulatory in different species. This work examines whether oligodeoxynucleotides (ODNs) containing CpG motifs stimulate peripheral blood mononuclear cells from pigs. Results show that pigs respond to CpG ODN by proliferating and secreting IL-6, IL-12 and TNF-alpha. By screening a large panel (>100) of ODNs, the palindromic hexamer 'ATCGAT' was identified as being optimally active in all animals examined (N = 10). These findings are the first to establish the immunostimulatory activity of CpG ODN in pigs, and suggest that the therapeutic uses envisioned for these ODNs (as vaccine adjuvants and immunoprotective agents) may be applicable to husbandry animals. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Danish Vet Inst Virus Res, Dept Pathobiol & Diagnost, DK-4771 Lindholm, Kalvehave, Denmark. US FDA, Ctr Biol Evaluat & Res, Retroviral Immunol Sect, Bethesda, MD 20892 USA. RP Kamstrup, S (reprint author), Danish Vet Inst Virus Res, Dept Pathobiol & Diagnost, DK-4771 Lindholm, Kalvehave, Denmark. NR 32 TC 87 Z9 91 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1135 J9 VET MICROBIOL JI Vet. Microbiol. PD FEB 26 PY 2001 VL 78 IS 4 BP 353 EP 362 DI 10.1016/S0378-1135(00)00300-X PG 10 WC Microbiology; Veterinary Sciences SC Microbiology; Veterinary Sciences GA 407HH UT WOS:000167265800006 PM 11182501 ER PT J AU Trauth, JA Seidler, FJ Ali, SF Slotkin, TA AF Trauth, JA Seidler, FJ Ali, SF Slotkin, TA TI Adolescent nicotine exposure produces immediate and long-term changes in CNS noradrenergic and dopaminergic function SO BRAIN RESEARCH LA English DT Article DE adolescence; nicotine; catecholamine; dopamine; norepinephrine ID RAT-BRAIN REGIONS; SMOKING CESSATION; PRENATAL EXPOSURE; NERVOUS-SYSTEM; FETAL NICOTINE; IN-VIVO; CATECHOLAMINE; RELEASE; ADULTHOOD; INFUSIONS AB Animal studies have only recently begun to address whether nicotine evokes unique or persistent effects on brain structure or function during adolescence, the period in which smokers typically begin their habit. In the current study, we examined the impact of adolescent nicotine treatment on catecholaminergic synaptic function in rats infused with nicotine on postnatal days 30-47.5. using a paradigm that reproduces the plasma levels of nicotine found in smokers. We assessed norepinephrine and dopamine content, turnover (an index of neural activity), and the response to an acute challenge dose of nicotine. In the midbrain, the region most closely associated with addiction, both norepinephrine and dopamine turnover were activated during the infusion period, an effect not seen in any other region for norepinephrine, and only in the striatum for dopamine. In the immediate post-infusion period (PN50-60), there was a decrement in midbrain catecholamine turnover restricted to males, whereas there was a later-emerging (PN80) activation of these pathways, Again, this pattern was nor observed in any other region: the cerebral cortex showed post-treatment increases in turnover without gender selectivity, the striatum showed late-emerging deficits in dopamine turnover and the hippocampus displayed a profound deficit in noradrenergic activity that was limited to females. We also assessed the catecholaminergic response to an acute challenge with nicotine (0.3 mg/kg s.c.). The midbrain once more displayed unique properties: there was initial suppression of responses followed by post-treatment rebound elevations that were more prominent in males and eventual deficits: that, in the case of dopamine, were selective for males. With the exception of the cerebellum, other regions showed the initial loss of response during the infusion period but no persistent changes in responsiveness. The current results indicate that adolescent nicotine produces immediate and long-term changes in CNS catecholaminergic systems. with regional targeting and gender selectivity corresponding to the changes seen previously in nicotinic receptor upregulation or indices of cell damage. These effects may underlie long-term behavioral changes associated with adolescent nicotine exposure. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Durham, NC 27710 USA. Natl Ctr Toxicol Res, Div Neurotoxicol SFA, Neurochem Lab, Jefferson, AR 72079 USA. RP Slotkin, TA (reprint author), Duke Univ, Med Ctr, Dept Pharmacol & Canc Biol, Box 3813, Durham, NC 27710 USA. NR 73 TC 96 Z9 102 U1 1 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0006-8993 J9 BRAIN RES JI Brain Res. PD FEB 23 PY 2001 VL 892 IS 2 BP 269 EP 280 DI 10.1016/S0006-8993(00)03227-3 PG 12 WC Neurosciences SC Neurosciences & Neurology GA 403BJ UT WOS:000167022400006 PM 11172774 ER PT J AU Purucker, M Malozowski, S AF Purucker, M Malozowski, S TI Asthma, corticosteroids, and growth. SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter ID CHILDREN C1 US FDA, Rockville, MD 20857 USA. RP Purucker, M (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 3 Z9 3 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 22 PY 2001 VL 344 IS 8 BP 607 EP 607 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 403LU UT WOS:000167044600012 PM 11221624 ER PT J AU Orloff, DG AF Orloff, DG TI Use of surrogate endpoints: A practical necessity in lipid-altering and antiatherosclerosis drug development SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT International Symposium on Atherosclerosis CY JUN 27, 2000 CL STOCKHOLM, SWEDEN ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; CARDIOVASCULAR-DISEASE; ARTERY DISEASE; SECONDARY PREVENTION; ATHEROSCLEROSIS; RISK; TRIGLYCERIDE; HYPERTRIGLYCERIDEMIA; ASSOCIATION AB Apparently favorable effects of antiatherosclerosis drugs as assessed by changes in surrogate markers of cardiovascular disease risk are frequently relied upon for drug approval and labeling. Surrogates must be biologically plausible and adequately validated but are, by definition, imperfect as predictors of ultimate outcome (i.e., serious morbidity and mortality). Surrogate markers utilized in the study of drugs for the treatment of atherosclerotic cardiovascular disease may be classified as laboratory/biochemical, anatomic/morphologic, and functional. The places for various surrogates in all three categories in the development of lipid altering drugs are discussed, (C)2001 by Excerpta Medico, Inc. C1 US FDA, Rockville, MD 20857 USA. RP Orloff, DG (reprint author), US FDA, Room 14B-45,HFD-510,5600 Fishers Lane, Rockville, MD 20857 USA. NR 31 TC 10 Z9 10 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 FEB 16 PY 2001 VL 87 IS 4A SI SI BP 35A EP 41A PG 7 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 405ZW UT WOS:000167191300006 PM 11243603 ER PT J AU Unger, EF AF Unger, EF TI Experimental evaluation of coronary collateral development SO CARDIOVASCULAR RESEARCH LA English DT Review DE blood flow; collateral circulation; coronary circulation; microcirculation; regional blood flow ID FIBROBLAST-GROWTH-FACTOR; CELL NUCLEAR ANTIGEN; BLOOD-FLOW MEASUREMENTS; MYOCARDIAL ANGIOGENESIS; INTRACORONARY INJECTION; ISCHEMIC MYOCARDIUM; CAPILLARY PERFUSION; SWINE MYOCARDIUM; PORCINE HEARTS; GENE-TRANSFER AB During the last decade, there has been great interest in the potential use of biologic agents and mechanical techniques to enhance myocardial collateral development. Available experimental methods to detect the effects of interventions designed to improve collateral function include assessment of vascular cell proliferation, quantification of vessel number and size, appraisal of myocardial perfusion, and evaluation of myocardial function. The purpose of this review is to discuss the various experimental approaches for the evaluation of coronary collateral development, highlighting the relative strengths and limitations of the commonly used animal models and methods of assessment. Published by Elsevier Science B.V. C1 US FDA, Div Clin Trial Design & Anal, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Unger, EF (reprint author), US FDA, Div Clin Trial Design & Anal, Off Therapeut Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NR 44 TC 34 Z9 39 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0008-6363 J9 CARDIOVASC RES JI Cardiovasc. Res. PD FEB 16 PY 2001 VL 49 IS 3 BP 497 EP 506 DI 10.1016/S0008-6363(00)00285-6 PG 10 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 404HX UT WOS:000167092300002 PM 11166263 ER PT J AU Goodman, JL AF Goodman, JL TI The diagnosis of Lyme disease: Good news, bad news SO AMERICAN JOURNAL OF MEDICINE LA English DT Editorial Material ID POLYMERASE CHAIN-REACTION; BORRELIA-BURGDORFERI; ERYTHEMA MIGRANS; SERODIAGNOSIS; URINE C1 Univ Minnesota, Sch Med, Dept Med, Div Infect Dis, Minneapolis, MN 55455 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Goodman, JL (reprint author), Box 250 Mayo,420 Delaware St, Minneapolis, MN 55455 USA. NR 19 TC 0 Z9 0 U1 1 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 650 AVENUE OF THE AMERICAS, NEW YORK, NY 10011 USA SN 0002-9343 J9 AM J MED JI Am. J. Med. PD FEB 15 PY 2001 VL 110 IS 3 BP 236 EP 238 DI 10.1016/S0002-9343(00)00742-7 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 401UL UT WOS:000166946600016 PM 11182116 ER PT J AU Kozuch, P Hoff, PM Hess, K Adams, J Newman, RA Lee, F Pazdur, R AF Kozuch, P Hoff, PM Hess, K Adams, J Newman, RA Lee, F Pazdur, R TI Phase I bioequivalency study of MitoExtra and mitomycin C in patients with solid tumors SO CANCER LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the American-Society-of-Clinical-Oncology CY MAY 20-23, 2000 CL NEW ORLEANS, LOUISIANA SP Amer Soc Clin Oncol DE phase I; solid tumors; cancer; pharmacokinetics; MitoExtra; mitomycin C ID CYCLODEXTRIN; HYPERSENSITIVITY; POLYSORBATE-80; FORMULATIONS; IRRITATION; BINDING; HUMANS; DYES; RAT AB BACKGROUND. This study compares serum pharmacokinetics, urinary excretion patterns, and relative bioequivalencies of single doses of MitoExtra (ME; SuperGen, San Ramon, Ca) and mitomycin C (MMC). METHODS. Thirty-five patients were entered into this open-label, single-institution, crossover study with 2 treatment arms. Each patient received alternating courses of ME and MMC as 15 mg/m(2) single intravenous doses via a short intravenous infusion. Patients were sequentially assigned to receive either ME or MMC as their first treatment course. The courses were given in 6-week intervals and could be repeated up to 4 times in patients with responding disease. Pharmacokinetic parameters were analyzed during the first two courses of therapy. RESULTS, The noncompartmental pharmacokinetic analysis conducted on serum and urine data obtained from patients who received both ME and MMC indicates that the kinetic disposition of these two formulations is similar. This is evident when the mean (+/- standard deviation) values of the various pharmacokinetic parameters are compared. There were no significant differences in any of the kinetic parameters obtained between treatments in all patients examined. The statistical evaluation conducted on the 25 patients that completed both arms of the 2-way pharmacokinetic crossover demonstrates that ME is bioequivalent to MMC. Hematologic and nonhematologic toxicities were similar between the two treatments. There were three clinically significant infusion-related complications associated with MMC administration and none associated with ME. CONCLUSIONS. The similar pharmacokinetics of MMC and ME suggest complete release of MMC from the hydroxypropyl-B-cyclodextrin carrier contained in the ME formulation. Further studies are needed to define the pharmacodynamics, toxicity, and efficacy of this drug-carrier complex. (C) 2001 American Cancer Society. C1 Univ Texas, MD Anderson Canc Ctr, Dept Gastrointestinal Med Oncol, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Biostat, Houston, TX 77030 USA. Univ Texas, MD Anderson Canc Ctr, Dept Expt Therapeut, Houston, TX 77030 USA. SuperGen Pharmaceut, San Ramon, CA USA. US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Hoff, PM (reprint author), 1515 Holcombe Blvd,Box 78, Houston, TX 77030 USA. NR 26 TC 3 Z9 4 U1 0 U2 4 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0008-543X J9 CANCER JI Cancer PD FEB 15 PY 2001 VL 91 IS 4 BP 815 EP 821 PG 7 WC Oncology SC Oncology GA 403TD UT WOS:000167057800028 PM 11241251 ER PT J AU Cohen, MH Rothmann, M AF Cohen, MH Rothmann, M TI Gemcitabine and cisplatin for advanced, metastatic bladder cancer SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter ID DOXORUBICIN; TRIAL C1 US FDA, Rockville, MD 20857 USA. RP Cohen, MH (reprint author), US FDA, Rockville, MD 20857 USA. NR 5 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD FEB 15 PY 2001 VL 19 IS 4 BP 1229 EP 1229 PG 1 WC Oncology SC Oncology GA 406MH UT WOS:000167219400041 PM 11181690 ER PT J AU Verthelyi, D Ishii, KJ Gursel, M Takeshita, F Klinman, DM AF Verthelyi, D Ishii, KJ Gursel, M Takeshita, F Klinman, DM TI Human peripheral blood cells differentially recognize and respond to two distinct CpG motifs SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOSTIMULATORY DNA-SEQUENCES; IFN-GAMMA PRODUCTION; BACTERIAL-DNA; SYNTHETIC OLIGONUCLEOTIDES; IN-VITRO; B-CELL; OLIGODEOXYNUCLEOTIDES; ACTIVATION; ADJUVANTS; MURINE AB Oligodeoxynucleotides (ODN) that contain unmethylated CpG dinucleotides trigger a strong innate immune response in vertebrates. CpG ODN show promise as vaccine adjuvants, anti-allergens, and immunoprotective agents in animal models. Their transition to clinical use requires the identification of motifs that are optimally stimulatory in humans. Analysis of hundreds of novel ODN resulted in the identification and characterization of two structurally distinct "clusters" of immunostimulatory CpG ODN, One cluster ("D") preferentially stimulates IFN-gamma production by NK cells, whereas the other ("K") stimulates cell proliferation and the production of IL-6 and IgM by monocytes and B cells. The distinct immunostimulatory properties of K and D ODN can improve the design of CpG-based products to achieve specific: therapeutic goals. 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,Room 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 NR 28 TC 361 Z9 388 U1 4 U2 13 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 2001 VL 166 IS 4 BP 2372 EP 2377 PG 6 WC Immunology SC Immunology GA 400QA UT WOS:000166882000029 PM 11160295 ER PT J AU Chen, JJZ Smith, L Pfeifer, GP Holmquist, GP AF Chen, Junjian Z. Smith, Leslie Pfeifer, Gerd P. Holmquist, Gerald P. TI Fluorescence-based directed termination PCR: direct mutation characterization without sequencing SO NUCLEIC ACIDS RESEARCH LA English DT Article AB We describe a fluorescence-based directed termination PCR (fluorescent DT-PCR) that allows accurate determination of actual sequence changes without dideoxy DNA sequencing. This is achieved using near infrared dye-labeled primers and performing two PCR reactions under low and unbalanced dNTP concentrations. Visualization of resulting termination fragments is accomplished with a dual dye Li-cor DNA sequencer. As each DT-PCR reaction generates two sets of terminating fragments, a pair of complementary reactions with limiting dATP and dCTP collectively provide information on the entire sequence of a target DNA, allowing an accurate determination of any base change. Blind analysis of 78 mutants of the supF reporter gene using fluorescent DT-PCR not only correctly determined the nature and position of all types of substitution mutations in the supF gene, but also allowed rapid scanning of the signature sequences among identical mutations. The method provides simplicity in the generation of terminating fragments and 100% accuracy in mutation characterization. Fluorescent DT-PCR was successfully used to generate a UV-induced spectrum of mutations in the supF gene following replication on a single plate of human DNA repair-deficient cells. We anticipate that the automated DT-PCR method will serve as a cost-effective alternative to dideoxy sequencing in studies involving large-scale analysis for nucleotide sequence changes. C1 City Hope Natl Med Ctr, Dept Biol, Duarte, CA 91010 USA. City Hope Natl Med Ctr, Beckman Res Inst, Duarte, CA 91010 USA. RP Chen, JJZ (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jjchen@nctr.fda.gov FU [CA69449]; [ES06070/CA84469] FX Funding for this work was provided by grants CA69449 to G.P.H. and ES06070/CA84469 to G.P.P. NR 9 TC 1 Z9 1 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0305-1048 J9 NUCLEIC ACIDS RES JI Nucleic Acids Res. PD FEB 15 PY 2001 VL 29 IS 4 AR e17 DI 10.1093/nar/29.4.e17 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA V17WN UT WOS:000207967400003 PM 11160937 ER PT J AU Ellis, CE Schwartzberg, PL Grider, TL Fink, DW Nussbaum, RL AF Ellis, CE Schwartzberg, PL Grider, TL Fink, DW Nussbaum, RL TI alpha-Synuclein is phosphorylated by members of the Src family of protein-tyrosine kinases SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID LONG-TERM POTENTIATION; T-CELL ACTIVATION; A-BETA COMPONENT; ALZHEIMERS-DISEASE; C-SRC; PARKINSONS-DISEASE; SYNAPTIC VESICLES; MUTATION; IDENTIFICATION; ASSOCIATION AB alpha -Synuclein (alpha -Syn) is implicated in the pathogenesis of Parkinson's Disease, genetically through missense mutations linked to early onset disease and pathologically through its presence in Lewy bodies. alpha -Syn is phosphorylated on serine residues; however, tyrosine phosphorylation of alpha -Syn has not been established (1, 2). A comparison of the protein sequence between Synuclein family members revealed that all four tyrosine residues of alpha -Syn are conserved in all orthologs and beta -Syn paralogs described to date, suggesting that these residues may be of functional importance (3). For this reason, experiments were performed to determine whether alpha -Syn could be phosphorylated on tyrosine residue(s) in human cells. Indeed, alpha -Syn is phosphorylated within 2 min of pervanadate treatment in alpha -Syn-transfected cells. Tyrosine phosphorylation occurs primarily on tyrosine 125 and was inhibited by PP2, a selective inhibitor of Src protein-tyrosine kinase (PTK) family members at concentrations consistent with inhibition of Src function (4). Finally, we demonstrate that alpha -Syn can be phosphorylated directly both in cotransfection experiments using c-Src and Fyn expression vectors and in in vitro kinase assays with purified kinases. These data suggest that alpha -Syn can be a target for phosphorylation by the Src family of PTKs. C1 NHGRI, Genet Dis Res Branch, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Stem Cell Biol Neurotroph Factors, Bethesda, MD 20892 USA. RP Nussbaum, RL (reprint author), NHGRI, Genet Dis Res Branch, NIH, 49 Convent Dr,MSC 4472, Bethesda, MD 20892 USA. NR 42 TC 89 Z9 92 U1 0 U2 1 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD FEB 9 PY 2001 VL 276 IS 6 BP 3879 EP 3884 DI 10.1074/jbc.M010316200 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 401HB UT WOS:000166921200023 PM 11078745 ER PT J AU Wysowski, DK Pitts, M Beitz, J AF Wysowski, DK Pitts, M Beitz, J TI Depression and suicide in patients treated with isotretinoin 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 2 TC 35 Z9 35 U1 0 U2 1 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 8 PY 2001 VL 344 IS 6 BP 460 EP 460 DI 10.1056/NEJM200102083440616 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 399FH UT WOS:000166800600023 PM 11221610 ER PT J AU Falk, LA Ball, LK AF Falk, LA Ball, LK TI Current status and future trends in vaccine regulation - USA SO VACCINE LA English DT Article; Proceedings Paper CT ECPI World Vaccine Congress CY SEP 27-29, 1999 CL GENEVA, SWITZERLAND DE vaccine; regulation; immunization AB In regulating vaccines, the US Food and Drug Administration (FDA) is governed by the Code of Federal Regulations. These regulations serve as the framework for product characterization, as well as preclinical and clinical testing strategies. Novel vaccine approaches such as combination vaccines, vectored vaccines, new adjuvants, and novel delivery systems pose unique regulatory challenges for the FDA. If US licensure is sought, communication with the FDA throughout the clinical development of a product is essential to identify and implement the appropriate strategies for demonstrating the safety and effectiveness of a new product. (C) 2001 Published by Elsevier Science Ltd. C1 US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Falk, LA (reprint author), US FDA, Div Vaccines & Related Prod Applicat, Off Vaccines Res & Review, Ctr Biol Evaluat & Res, FDA HFM 481,1401 Rockville Pike, Rockville, MD 20852 USA. NR 15 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD FEB 8 PY 2001 VL 19 IS 13-14 BP 1567 EP 1572 DI 10.1016/S0264-410X(00)00353-4 PG 6 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 402NN UT WOS:000166995200002 PM 11166876 ER PT J AU Hastings, KL AF Hastings, KL TI Pre-clinical methods for detecting the hypersensitivity potential of pharmaceuticals: regulatory considerations SO TOXICOLOGY LA English DT Article; Proceedings Paper CT 8th Summer School in Immunotoxicology Preclinical Methods for Detecting the Potential Hypersensitivity of Pharmaceuticals CY OCT 04-06, 1999 CL DIVONNE LES BAINS, FRANCE DE drug allergy; systemic hypersensitivity; animal models; hazard identification ID LYMPH-NODE ASSAY; DRUG HYPERSENSITIVITY; IMMUNOTOXICITY; SENSITIZATION; DISPOSITION; ALLERGENS AB Immune-based systemic hypersensitivities account for a significant number of adverse drug reactions. There appear to be no adequate nonclinical models to predict systemic hypersensitivity to small molecular weight drugs. Although there are very good methods For detecting drugs that can induce contact sensitization. these have not been successfully adapted for prediction of systemic hypersensitivity. Several factors have made the development of adequate models difficult. The term systemic hypersensitivity encompases many discrete immunopathologies. Each type of immunopathology presumably is the result of a specific cluster of immunologic and biochemical phenomena. Certainly other factors. such as genetic predisposition. metabolic idiosynerasies. and concomitant diseases. further complicate the problem. Therefore, it mag; be difficult to find common mechanisms upon which to construct adequate models to predict specific types or systemic hypersensitivity reactions. There is some reason to hope. however that adequate methods could be developed for at least identifying drugs that have the potential to produce signs indicative of a general hazard for immune-based reactions. (C) 2001 Published by Elsevier Science Ireland Ltd. All rights reserved. C1 US FDA, Ctr Drug Evaluat & Res, Div Special Pathogen & Immunol Drug Prod, Rockville, MD 20857 USA. RP Hastings, KL (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Special Pathogen & Immunol Drug Prod, 5600 Fishers Lane, Rockville, MD 20857 USA. OI Hastings, Kirk/0000-0002-4616-4444 NR 17 TC 9 Z9 11 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0300-483X J9 TOXICOLOGY JI Toxicology PD FEB 2 PY 2001 VL 158 IS 1-2 BP 85 EP 89 DI 10.1016/S0300-483X(00)00412-1 PG 5 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 403HE UT WOS:000167035800011 PM 11164997 ER PT J AU Baratta, EJ AF Baratta, EJ TI Reference materials for the radionuclide program - performance evaluation samples SO ACCREDITATION AND QUALITY ASSURANCE LA English DT Article; Proceedings Paper CT International Conference on Metrology - Trends and Applications in Calibration and Testing Laboratories CY MAY 16-18, 2000 CL JERUSALEM, ISRAEL DE reference materials; radionuclides; food samples ID IMPORTED FOODS; UNITED-STATES AB The U.S. Food and Drug Administration's (FDA) Radionuclides in Food Program was reinstituted in 1973, expanded in 1975 and again in 1990, to its present status. The need for reference materials for radionuclides in food samples was recognized as early as 1962. There were no available reference materials for these types of samples at that time. The materials developed to assure that the results being obtained were acceptable were primarily milk, water and food. The radionuclides of interest were iodine-131, cesium-137 and other short-lived radionuclides found in fission products. These were first issued through the then Health. Education and Welfare Department's Analytical Quality Control Program and, later, in 1970 through the Environmental Protection Agency (EPA). In November 1998, the EPA discontinued this program. The FDA is proposing to reinstitute part of this program, as a primary laboratory, traceable to the National Institute of Technology (NIST) and included in this, the FDA proposes to supply the States and/or their contractors with low-level standards and with milk- and water intercomparison samples. It will also use these results: where possible as collaborative studies to validate some of the more recent methods adopted by the American Society for Testing and Materials (ASTM), American Public Health Association (APHA) and Association of Official Analytical Chemists International (AOAC, Int'l.) The FDA will also supply low-level standards to compliment these programs as did the EPA. It is expected that these samples will serve as performance evaluation samples for the States programs. C1 US FDA, Winchester, MA 01890 USA. RP Baratta, EJ (reprint author), US FDA, 109 Holton St, Winchester, MA 01890 USA. NR 9 TC 0 Z9 0 U1 2 U2 5 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0949-1775 J9 ACCREDIT QUAL ASSUR JI Accredit. Qual. Assur. PD FEB PY 2001 VL 6 IS 2 BP 84 EP 86 DI 10.1007/s007690000242 PG 3 WC Chemistry, Analytical; Instruments & Instrumentation SC Chemistry; Instruments & Instrumentation GA 402PM UT WOS:000166997400011 ER PT J AU Myers, MR AF Myers, MR TI Calculation of Brownian particle transmission in long, wide channels SO AICHE JOURNAL LA English DT Article ID LAMINAR-FLOW; TRANSPORT AB The transport of Brownian particles in channels which are long and wide compared ro their height is addressed The cross-sectional shape of the channel is assumed to be slowly varying, but otherwise arbitrary A solution to the convective-diffusive equation with reaction-rare boundary condition was obtained by locally incorporating the modified Graetz solution in a flat channel. The solution was evaluated asymptotically for the eases of a channel with a maximum height occurring at an endpoint and at an interior maximum. The asymptotic method was applied in two example geometries: the calibration apparatus used to determine reaction-rate constants for virus adsorption to lares barriers, and overlapping pores in a nucleation-track membrane. The asymptotic expressions compared well with finite-element calculations in the examples. The utility Of the asymptotic approach lies in rapid estimation of particle transmission through a channel us a function of geometric and physical parameters. 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 12 TC 0 Z9 0 U1 1 U2 2 PU AMER INST CHEMICAL ENGINEERS PI NEW YORK PA 3 PARK AVE, NEW YORK, NY 10016-5901 USA SN 0001-1541 J9 AICHE J JI AICHE J. PD FEB PY 2001 VL 47 IS 2 BP 250 EP 255 DI 10.1002/aic.690470203 PG 6 WC Engineering, Chemical SC Engineering GA 403BT UT WOS:000167023200002 ER PT J AU Birnkrant, D AF Birnkrant, D TI Streamlining the process & regulatory issues SO AIDS LA English DT Article; Proceedings Paper CT 1st International Conference on Microbicides for the Prevention of HIV and STI Transmission CY MAR 13-15, 2000 CL WASHINGTON, D.C. SP Off AIDS Res, NIH, Int AIDS Soc C1 US FDA, Washington, DC 20204 USA. RP Birnkrant, D (reprint author), US FDA, Washington, DC 20204 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0269-9370 J9 AIDS JI Aids PD FEB PY 2001 VL 15 SU 1 BP S68 EP S69 DI 10.1097/00002030-200102001-00098 PG 2 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 404JW UT WOS:000167095100093 PM 11407326 ER PT J AU Califf, RM Ellenberg, SS AF Califf, RM Ellenberg, SS TI Statistical approaches and policies for the operations of Data and Safety Monitoring Committees SO AMERICAN HEART JOURNAL LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; CLINICAL-TRIALS; HEART-FAILURE; MORTALITY; SURVIVAL; BREAST C1 Duke Clin Res Inst, Durham, NC USA. US FDA, Div Biostat & Epidemiol, Rockville, MD 20857 USA. RP Califf, RM (reprint author), Duke Clin Res Inst, Durham, NC USA. NR 22 TC 7 Z9 7 U1 0 U2 2 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0002-8703 J9 AM HEART J JI Am. Heart J. PD FEB PY 2001 VL 141 IS 2 BP 301 EP 305 DI 10.1067/mhj.2001.113152 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA 399QF UT WOS:000166823300022 PM 11174347 ER PT J AU Teisl, MF Bockstael, NE Levy, A AF Teisl, MF Bockstael, NE Levy, A TI Measuring the welfare effects of nutrition information SO AMERICAN JOURNAL OF AGRICULTURAL ECONOMICS LA English DT Article DE cost of ignorance; labeling; nutrition; value of information ID IDEAL DEMAND SYSTEM; ELASTICITIES; MODELS AB Cost/benefit analysis justifies regulations altering the amount of health-related information presented to consumers. The current method of benefit analysis, the cost of avoided illness, is limited; it assumes the benefits of health-related information are adequately represented by changes in illnesses. The manuscript develops a benefit estimation method to measure the welfare impacts of providing nutrient information. Nutrient labeling significantly affects purchase behavior but may not lead to increased consumption of healthy foods. Nutrient labeling may increase welfare without any change in health risk. Thus, the cost of avoided illness approach can underestimate the social benefits of providing nutrient information. C1 Univ Maine, Dept Resource Econ & Policy, Orono, ME 04469 USA. Univ Maryland, Dept Agr & Resource Econ, College Pk, MD 20742 USA. US FDA, Div Market Studies, Consumer Studies Branch, Rockville, MD 20857 USA. RP Teisl, MF (reprint author), Univ Maine, Dept Resource Econ & Policy, Orono, ME 04469 USA. OI teisl, mario/0000-0002-2021-9208 NR 22 TC 57 Z9 58 U1 1 U2 10 PU BLACKWELL PUBLISHERS PI MALDEN PA 350 MAIN STREET, STE 6, MALDEN, MA 02148 USA SN 0002-9092 J9 AM J AGR ECON JI Am. J. Agr. Econ. PD FEB PY 2001 VL 83 IS 1 BP 133 EP 149 DI 10.1111/0002-9092.00142 PG 17 WC Agricultural Economics & Policy; Economics SC Agriculture; Business & Economics GA 403AZ UT WOS:000167021500010 ER PT J AU Gooch, JA DePaola, A Kaysner, CA Marshall, DL AF Gooch, JA DePaola, A Kaysner, CA Marshall, DL TI Evaluation of two direct plating methods using nonradioactive probes for enumeration, of Vibrio parahaemolyticus in oysters SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID THERMOSTABLE DIRECT HEMOLYSIN; CHESAPEAKE BAY; THERMOLABILE HEMOLYSIN; WATERS AB Oysters (Crassostrea virginica) were collected monthly from May 1998 to April 1999 from Mobile Bay, Ala,, and analyzed to determine Vibrio parahaemolyticus densities at zero time and after 5, 10, and 24 h of postharvest storage at 26 degreesC. After 24 h of storage at 26 degreesC, oysters were transferred to a refrigerator at 3 degreesC and then analyzed 14 to 17 days later. The V. parahaemolyticus numbers were determined by the most-probable-number procedure using alkaline phosphatase-labeled DNA probe VPAP, which targets the species-specific thermolabile hemolysin gene (tlh), to identify suspect isolates (MPN-VPAP procedure), Two direct plating methods, one using a VPAP probe (Direct-VPAP) and one using a digoxigenin-labeled probe (Direct-VPDig) to identify suspect colonies, were compared to "the MPN-VPAP procedure. The results of the Direct-VPAP and Direct-VPDig techniques were highly correlated (r = 0.91), as were the results of the Direct-VPAP and MPN-VPAP procedures (r = 0.91), The correlation between the Direct-VPDig and MPN-VPAP results was 0.85, The two direct plating methods in which nonradioactive DNA probes were used were equivalent to the MPN-VPAP procedure for identification of total V. parahaemolyticus, and they were more rapid and less labor-intensive. C1 NOAA, US Dept Commerce, NOS, Ctr Coastal Environm Hlth & Biomol Res, Charleston, SC 29412 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. US FDA, Seafood Prod Res Ctr, Bothell, WA 98021 USA. Mississippi State Univ, Dept Food Sci & Technol, Mississippi State, MS 39762 USA. RP Gooch, JA (reprint author), NOAA, US Dept Commerce, NOS, Ctr Coastal Environm Hlth & Biomol Res, 219 Ft Johnson Rd, Charleston, SC 29412 USA. NR 22 TC 42 Z9 55 U1 2 U2 8 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD FEB PY 2001 VL 67 IS 2 BP 721 EP 724 DI 10.1128/AEM.67.2.721-724.2001 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA 399ZR UT WOS:000166844600030 PM 11157236 ER PT J AU Suydam, LA AF Suydam, LA TI The FDA and public health SO ASM NEWS LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0044-7897 J9 ASM NEWS JI ASM News PD FEB PY 2001 VL 67 IS 2 BP 60 EP 61 PG 2 WC Microbiology SC Microbiology GA 400XU UT WOS:000166898600002 ER PT J AU Kawasaki, K Yin, JJ Subczynski, WK Hyde, JS Kusumi, A AF Kawasaki, K Yin, JJ Subczynski, WK Hyde, JS Kusumi, A TI Pulse EPR detection of lipid exchange between protein-rich raft and bulk domains in the membrane: Methodology development and its application to studies of influenza viral membrane SO BIOPHYSICAL JOURNAL LA English DT Article ID ELECTRON-SPIN-RESONANCE; PHOSPHATIDYLCHOLINE-CHOLESTEROL MEMBRANES; OXYGEN-TRANSPORT PARAMETER; ALKYL CHAIN UNSATURATION; RECONSTITUTED MEMBRANES; MOLECULAR-ORGANIZATION; LATERAL DIFFUSION; CELL-MEMBRANES; LABEL; VIRUS AB A pulse saturation-recovery electron paramagnetic resonance (EPR) method has been developed that allows estimation of the exchange rates of a spin-labeled lipid between the bulk domain and the protein-rich membrane domain, in which the rate of collision between the spin label and molecular oxygen is reduced (slow-oxygen transport domain, or SLOT domain). It is based on the measurements of saturation-recovery signals of a lipid spin label as a function of concentrations of both molecular oxygen and the spin label. Influenza viral membrane, one of the simplest paradigms for the study of biomembranes, showed the presence of two membrane domains with slow and fast collision rates with oxygen (a 16-fold difference) at 30 degreesC. The outbound rate from and the inbound rate into the SLOT domain (or possibly the rate of the domain disintegration and formation) were estimated to be 7.7 x 10(4) and 4.6 x 10(4) s(-1), (15 mus residency time), respectively, indicating that the SLOT domain is highly dynamic and that the entire SLOT domain represents about one-third of the membrane area. Because the oxygen transport rate in the SLOT domain is a factor of two smaller than that in purple membrane, where bacteriorhodopsin is aggregated, we propose that the SLOT domain in the viral membrane is the cholesterol-rich raft domain stabilized by the trimers of hemagglutinin and/or the tetramers of neuraminidase. C1 Nagoya Univ, Grad Sch Sci, Dept Biol Sci, Nagoya, Aichi 4648602, Japan. Natl Inst Biosci & Human Technol, Tsukuba, Ibaraki 3058566, Japan. US FDA, Instrumentat & Biophys Branch, Washington, DC 20204 USA. Med Coll Wisconsin, Biophys Res Inst, Natl Biomed EPR Ctr, Milwaukee, WI 53226 USA. Jagiellonian Univ, Inst Mol Biol, Dept Biophys, PL-31120 Krakow, Poland. Japan Sci & Technol Cooperat, Exploratory Res Advancement Technol Org, Kusumi Membrane Org Project, Nagoya, Aichi 4600012, Japan. RP Kusumi, A (reprint author), Nagoya Univ, Grad Sch Sci, Dept Biol Sci, Nagoya, Aichi 4648602, Japan. RI Yin, Jun Jie /E-5619-2014 FU NCRR NIH HHS [RR01008]; NIGMS NIH HHS [GM22923, GM27665] NR 59 TC 71 Z9 72 U1 1 U2 7 PU BIOPHYSICAL SOCIETY PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0006-3495 J9 BIOPHYS J JI Biophys. J. PD FEB PY 2001 VL 80 IS 2 BP 738 EP 748 PG 11 WC Biophysics SC Biophysics GA 398PP UT WOS:000166765100016 PM 11159441 ER PT J AU Goncalves, LL Beland, FA Marques, MM AF Goncalves, LL Beland, FA Marques, MM TI Synthesis, characterization, and comparative P-32-postlabeling efficiencies of 2,6-dimethylaniline-DNA adducts SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID METHYLATED ANILINES PRESENT; DNA-ADDUCTS; AROMATIC-AMINES; TOBACCO-SMOKE; AZIDE/SOLVENT SELECTIVITIES; HEMOGLOBIN ADDUCTS; AQUEOUS-SOLUTION; INVITRO REACTION; CIGARETTE-SMOKE; NITRENIUM AB 2,6-Dimethylaniline (2,6-diMeA) is a ubiquitous environmental pollutant that is used in industry as a synthetic intermediate. It is also found in tobacco smoke and as a major metabolite of lidocaine. Although the potential carcinogenicity of 2,6-diMeA in humans is presently uncertain, this aromatic amine has been classified as a rodent carcinogen. In addition, it is known to form hemoglobin adducts in humans, which indicates a profile of metabolic activation similar to that of typical arylamine carcinogens. Like other aromatic amines, 2,6-diMeA has been shown to yield N-(deoxyguanosin-8-yl)-2,6-dimethylaniline (dG-C8-2,6-diMeA) as a major DNA adduct in vitro. In this study, we show that 8,6-diMeA yields an unusual pattern of DNA adducts. In addition to dG-C8-2,6-diMeA, we have isolated two new adducts, 4-(deoxyguanosin-N-2-yl)-2,6-dimethylaniline (dG-N-2-2,6-diMeA) and 4-(deoxyguanosin-O-6-yl)-2,6-dimethylaniline (dG-O-6-2,6-diMeA), from the reaction of N-acetoxy-2,6-dimethylaniline with deoxyguanosine. A similar reaction conducted with deoxyadenosine yielded 4-( deoxyadenosin-N-6-yl)-2,6-dimethylaniline (dA-N-6-2,6-diMeA). All four adducts were detected in DNA reacted with N-acetoxy-2, 6-dimethylaniline, with the relative yields being 46% for dA-N-6-2,6-diMeA, 22% for dG-N-2-2,6-diMeA, 20% for dG-O-6-2,6-diMeA, and 12% for dG-C8-2,6-diMeA. This product profile contrasts markedly with the usual pattern of adducts obtained with aromatic amines, where C8-substituted deoxyguanosine products typically predominate. We further analyzed the kinetics of the T-4 polynucleotide kinase (PNK)-catalyzed phosphorylation of the C8 and N-2 deoxyguanosine S'-phosphate adducts from 2,6-diMeA. The kinetic parameters obtained with these two structurally different adducts are compared to those determined with the parent nucleotide (dG3'p), and with (+/-)-anti-10-(deoxyguanosin-N-2-yl)-7,8,9,10-tetrahydrobenzo[a]pyrene 3'-phosphate, the major adduct derived from the environmental pollutant benzo[a]pyrene. The results indicate that all the adducts were labeled with lower efficiencies than dG3'p, stressing the likely underestimation of adduct levels in typical P-32- postlabeling protocols. Nonetheless, the N-2 adducts derived from 2,6-diMeA and benzo[a]pyrene were both labeled with higher efficiencies than the C8 adduct derived from 2,6-diMeA, with the benzo[a]pyrene adduct being the best substrate for PNK. Thus, the data suggest that N-2 adducts from dG3'p are intrinsically better substrates than their C8 analogues for PNK, and that bulkier aromatic fragments may favor the enzyme-substrate interaction during the labeling step. 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. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110, Jefferson, AR 72079 USA. EM fbeland@nctr.fda.gov; matilde.marques@ist.utl.pt RI Marques, M. Matilde/E-2535-2012; Goncalves, Luisa/A-4120-2016; OI Marques, M. Matilde/0000-0002-7526-4962; Goncalves, Luisa/0000-0002-3654-8612; Goncalves, Luisa/0000-0002-2385-7395 NR 46 TC 22 Z9 22 U1 0 U2 2 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 2001 VL 14 IS 2 BP 165 EP 174 DI 10.1021/tx0002031 PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 405FM UT WOS:000167147500003 PM 11258965 ER PT J AU Averbuch, M Katzper, M AF Averbuch, M Katzper, M TI Gender and response to placebo analgesia. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Div Analges Drugs, Rockville, MD 20857 USA. Tel Aviv Med Ctr, Tel Aviv, Israel. NR 0 TC 0 Z9 0 U1 0 U2 2 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 2001 VL 69 IS 2 SU S BP P1 EP P1 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 408PA UT WOS:000167333500002 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 in vivo antiangiogenesis agents using the surrogate event of delayed wound healing. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Off Postmarketing Drug Risk Assessment, Rockville, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2001 VL 69 IS 2 SU S BP P46 EP P46 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 408PA UT WOS:000167333500176 ER PT J AU Hamman, MA Wang, Z Honig, P Collins, J Lesko, L Huang, SM Hall, SD AF Hamman, MA Wang, Z Honig, P Collins, J Lesko, L Huang, SM Hall, SD TI Effects of acute and chronic Saint John's wort (SJW) administration on fexofenadine (FEX) disposition. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Div Clin Pharmacol, Indianapolis, IN USA. US FDA, Ctr Drug Evaluat & Res, 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 2001 VL 69 IS 2 SU S BP P53 EP P53 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 408PA UT WOS:000167333500206 ER PT J AU Lau, SWJ Venitz, J AF Lau, SWJ Venitz, J TI Clinical consequences of in vitro estradiol (E-2) binding to sex hormone binding globulin (SHBG) and albumin (ALB). SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. Virginia Commonwealth Univ, Richmond, VA USA. RI Perez , Claudio Alejandro/F-8310-2010 OI Perez , Claudio Alejandro/0000-0001-9688-184X NR 0 TC 0 Z9 0 U1 0 U2 2 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 2001 VL 69 IS 2 SU S BP P55 EP P55 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 408PA UT WOS:000167333500213 ER PT J AU Robbie, GJ Jeong, H Marroum, PJ Venitz, J AF Robbie, GJ Jeong, H Marroum, PJ Venitz, J TI Sensitivity analysis of bioequivalence parameters of parent drug and metabolite. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Univ Illinois, Chicago, IL USA. Med Coll Virginia, Richmond, VA 23298 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 2001 VL 69 IS 2 SU S BP P36 EP P36 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 408PA UT WOS:000167333500140 ER PT J AU Rosebraugh, CJ Yasuda, SU Pezzullo, JC Honig, PK Flockhart, DA Woosley, RL AF Rosebraugh, CJ Yasuda, SU Pezzullo, JC Honig, PK Flockhart, DA Woosley, RL TI National survey of clinical pharmacology (CP) education in medical schools and internal medicine residency programs. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Georgetown Univ, Med Ctr, Div Clin Pharmacol, Washington, DC 20007 USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 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 FEB PY 2001 VL 69 IS 2 SU S BP P93 EP P93 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 408PA UT WOS:000167333500361 ER PT J AU Rosebraugh, CJ Honig, PK Corken, A Flowers, C Mease, M Toyer, D Chen, M Flockhart, DA AF Rosebraugh, CJ Honig, PK Corken, A Flowers, C Mease, M Toyer, D Chen, M Flockhart, DA TI Improving the quality of adverse drug reaction reporting by 4th year medical students with a 15-minute intervention. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Georgetown Univ, Ctr Educ & Res Therapeut, Washington, DC USA. NR 0 TC 0 Z9 0 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 FEB PY 2001 VL 69 IS 2 SU S BP P93 EP P93 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 408PA UT WOS:000167333500362 ER PT J AU Sekar, VJ Gobburu, J AF Sekar, VJ Gobburu, J TI Modeling and simulation in drug development: Application to a drug for an unmet need. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Off Clin Pharm & Biopharm, 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 2001 VL 69 IS 2 SU S BP P90 EP P90 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 408PA UT WOS:000167333500352 ER PT J AU Sekar, VJ Kong, LH Wang, D Rajagopalan, P AF Sekar, VJ Kong, LH Wang, D Rajagopalan, P TI Exposure-response (E-R) assessments as tools for dose selection of anti-HIV drugs. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Office Clin Pharm & Biopharm, Rockville, MD 20857 USA. Univ Georgia, Sch Pharm, Athens, GA 30602 USA. Bayer Corp, W Haven, CT 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 2001 VL 69 IS 2 SU S BP P90 EP P90 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 408PA UT WOS:000167333500353 ER PT J AU Tandon, V Rajagopalan, P Cherstniakova, SA Chiang, N Vocci, F Elkashef, A Mojsiak, J Haigney, M Cantilena, LR AF Tandon, V Rajagopalan, P Cherstniakova, SA Chiang, N Vocci, F Elkashef, A Mojsiak, J Haigney, M Cantilena, LR TI Pharmacokinetics of multiple escalating doses of GBR12909 in healthy volunteers. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Uniformed Serv Univ Hlth Sci, Natl Inst Drug Abuse, Bethesda, MD 20814 USA. US FDA, Bethesda, MD 20014 USA. 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 2001 VL 69 IS 2 SU S BP P61 EP P61 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 408PA UT WOS:000167333500237 ER PT J AU Wang, Z Gorski, JC Honig, P Collins, J Lesko, L Huang, SM Hall, SD AF Wang, Z Gorski, JC Honig, P Collins, J Lesko, L Huang, SM Hall, SD TI St. John's Wort (SJW) alters CYP3A but not CYP1A2 or CYP2C9 activity in vivo. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Indiana Univ, Sch Med, Div Clin Pharmacol, Indianapolis, IN USA. Ctr Drug Evaluat & Res, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0009-9236 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 2001 VL 69 IS 2 SU S BP P71 EP P71 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 408PA UT WOS:000167333500276 ER PT J AU Salice, CJ Rokous, JS Kane, AS Reimschuessel, R AF Salice, CJ Rokous, JS Kane, AS Reimschuessel, R TI New nephron development in goldfish (Carassius auratus) kidneys following repeated gentamicin-induced nephrotoxicosis SO COMPARATIVE MEDICINE LA English DT Article ID HEXACHLOROBUTADIENE; REGENERATION; LIGHT; FISH AB Renal development in mammalian kidneys can only be studied in embryonic animals. Hence, research in this area is hampered by the need to maintain pregnant animals and by the small size of the embryonic kidney. Here, we describe a goldfish (Carassius auratus) model for studying renal repair and nephron development in an adult animal. Previous studies have indicated that chemically induced nephrotoxicosis in goldfish is followed by new nephron development. We tested the hypothesis that new nephron development is not a one-time only event and, thus, will occur after repeated nephrotoxic events. We used repeated injections of gentamicin (50 mg/kg of body weight), a nephrotoxic antibiotic, which has been used as a model nephrotoxicant to study renal repair. Fish were allowed either a recovery period of 9 or 24 weeks between injections. In both experiments, new nephrons developed after each injection of gentamicin, supporting our hypothesis. Nephron development occurring after a 9-week recovery period was similar to development observed after a 24-week recovery period; therefore, the shorter experimental paradigm appears sufficient and can save time and money. Future research using this fish nephrogenesis model may identify the genes responsible for nephron neogenesis, Such information is a prerequisite for developing alternative renal replacement therapies based on the induction of de novo nephrogenesis in diseased kidneys. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Reimschuessel, R (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 20 TC 36 Z9 37 U1 0 U2 1 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI MEMPHIS PA 9190 CRESTWYN HILLS DR, MEMPHIS, TN 38125 USA SN 0023-6764 J9 COMPARATIVE MED JI Comparative Med. PD FEB PY 2001 VL 51 IS 1 BP 56 EP 59 PG 4 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA 414BL UT WOS:000167646000011 PM 11926303 ER PT J AU Roper, E Weinberg, W Watt, FM Land, H AF Roper, E Weinberg, W Watt, FM Land, H TI P19(ARF)-independent induction of p53 and cell cycle arrest by Raf in murine keratinocytes SO EMBO REPORTS LA English DT Article ID MOUSE EPIDERMAL-CELLS; SKIN CARCINOGENESIS; ONCOGENIC RAS; MALIGNANT PROGRESSION; PREMATURE SENESCENCE; TUMOR SUPPRESSION; GENE DOSAGE; GROWTH; DIFFERENTIATION; P21(CIP1) AB In tumorigenesis of the skin, activated Ras co-operates with mutations that inactivate the tumour suppressor p53, but the molecular basis for this co-operation remains unresolved. Here we show that activation of the Raf/MAP kinase pathway in primary mouse keratinocytes leads to a p53 and p21(Cip1)-dependent cycle arrest and to terminal differentiation. Raf activation in keratinocytes lacking p53 or p21(Cip1) genes leads to expression of differentiation markers, but the cells do not cease to proliferate. Thus, loss of p53 or p21(Cip1) function is necessary to disable growth-inhibitory Raf/MAP kinase signalling. Activation of oncogenes, including Ras, has been reported to stabilize and activate p53 via induction of the tumour suppressor p19(ARF). However, the response to Raf in p19(ARF-/-) keratinocytes was indistinguishable from wild-type controls. Thus, p19(ARF) is not essential for Raf-induced p53 induction and cell cycle arrest in keratinocytes, indicating that oncogenes engage p53 activity via multiple mechanisms. C1 Imperial Canc Res Fund, London WC2A 3PX, England. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Land, H (reprint author), Univ Rochester, Med Ctr, Ctr Canc Biol, 601 Elmwood Ave,Box 633, Rochester, NY 14642 USA. OI Watt, Fiona/0000-0001-9151-5154 NR 25 TC 48 Z9 50 U1 0 U2 0 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1469-221X J9 EMBO REP JI EMBO Rep. PD FEB PY 2001 VL 2 IS 2 BP 145 EP 150 DI 10.1093/embo-reports/kve020 PG 6 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA 405BX UT WOS:000167138300017 PM 11258707 ER PT J AU Gujral, JS Bucci, TJ Farhood, A Jaeschke, H AF Gujral, JS Bucci, TJ Farhood, A Jaeschke, H TI Mechanism of cell death during warm hepatic ischemia-reperfusion in rats: Apoptosis or necrosis? SO HEPATOLOGY LA English DT Article ID PRESERVATION INJURY; ENDOTHELIAL-CELL; KUPFFER CELLS; IN-VIVO; ISCHEMIA/REPERFUSION INJURY; LIVER ISCHEMIA; TUNEL ASSAY; NEUTROPHILS; ACTIVATION; MICE AB Reperfusion injury can cause liver dysfunction after cold storage and warm ischemia, Recently it has been suggested that more than 50% of hepatocytes and sinusoidal endothelial cells (SEC) are undergoing apoptosis during the first 24 hours of reperfusion. The aim of our study was to quantify apoptotic and necrotic hepatocytes and apoptotic SEC after 60 or 120 minutes of warm, partial no-flow ischemia and 0 to 24 hours reperfusion in male SD rats. Apoptotic cells were identified by TUNEL assay in combination with morphological criteria. After 60 minutes of ischemia and 1 hour of reperfusion there was a significant increase of apoptotic hepatocytes (0.7 +/- 0.1% vs. 0.3 +/- 0.1% in controls) and SEC (1.5 +/- 0.6% vs. 0.3 +/- 0.1% in controls). The number of apoptotic SEC and hepatocytes was not different from controls at 6 hours or 24 hours of reperfusion. In contrast, the number of necrotic hepatocytes was quantified as 12 +/- 2% at 1 hour, 34 +/- 6% at 6 hours, and 57 +/- 11% at 24 hours. These results correlated with the increase in plasma ALT levels at these time points. Longer (120 min) ischemia times did not affect the number of apoptotic cells but increased hepatocellular necrosis to 58 +/- 4% at 6 hours reperfusion. No significant increase in caspase-3 activity and processing was detectable in any of these livers. Moreover, the caspase inhibitor Z-Asp-cmk (2 mg/kg IV) had no significant effect on reperfusion injury. Our results suggest that only a small minority of SEC and hepatocytes undergo apoptosis after 60 to 120 minutes of warm ischemia followed by 0 to 24 hours of reperfusion. Oncotic necrosis appears to be the principal mechanism of cell death for both cell types. C1 Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Little Rock, AR 72205 USA. Pathol Associates Inc, Jefferson, AR USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Texas, Hlth Sci Ctr, Dept Pathol, Houston, TX USA. RP Jaeschke, H (reprint author), Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, 4301 W markham St,Mailslot 638, Little Rock, AR 72205 USA. FU NIEHS NIH HHS [ES-06091] NR 50 TC 246 Z9 257 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 0270-9139 J9 HEPATOLOGY JI Hepatology PD FEB PY 2001 VL 33 IS 2 BP 397 EP 405 DI 10.1053/jhep.2001.22002 PG 9 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA 397QF UT WOS:000166705800010 PM 11172341 ER PT J AU Rodriguez-Saona, LE Khambaty, FM Fry, FS Calvey, EM AF Rodriguez-Saona, LE Khambaty, FM Fry, FS Calvey, EM TI Rapid detection and identification of bacterial strains by Fourier transform near-infrared spectroscopy SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE FT-NIR spectroscopy; bacterial strains; PCA and classification ID IR SPECTROSCOPY; SPECTRA; CLASSIFICATION; POLYPEPTIDES; PROTEINS; RAMAN AB The use of Fourier transform near-infrared (FT-NIR) spectroscopy and multivariate pattern recognition techniques for the rapid detection and identification of bacterial contamination in liquids was evaluated. The complex biochemical composition of bacteria yields FT-NIR vibrational transitions (overtone and combination bands) that can be used for classification and identification. Bacterial suspensions (Escherichia coli HB101, E. coli ATCC 43888, E. coli 1224; Bacillus amyloliquifaciens, Pseudomonas aeruginosa, Bacillus cereus, and Listeria innocua) were filtered to harvest the cells and eliminate the matrix, which has a strong NIR signal. FT-NIR measurements were done using a diffuse reflection-integrating sphere. Principal component analysis showed tight clustering of the bacterial strains at the information-rich spectral region of 6000-4000 cm(-1). The method reproducibly distinguished between different E. coli isolates and conclusively identified the relationship between a new isolate and one of the test species. This methodology may allow for the rapid assessment of potential bacterial contamination in liquids with minimal sample preparation. C1 US FDA, Washington, DC 20204 USA. Univ Maryland, Dept Biochem & Chem, Joint Inst Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Calvey, EM (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. RI Rodriguez-Saona, Luis/A-8557-2013 NR 28 TC 74 Z9 78 U1 5 U2 30 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD FEB PY 2001 VL 49 IS 2 BP 574 EP 579 DI 10.1021/jf000776j PG 6 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 404XP UT WOS:000167127900008 PM 11261995 ER PT J AU Reeves, JB McCarty, GW Reeves, VB AF Reeves, JB McCarty, GW Reeves, VB TI Mid-infrared diffuse reflectance spectroscopy for the quantitative analysis of agricultural soils SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE mid-infrared; DRIFTS; soil; quantitative analysis ID PARTICLE-SIZE MORPHOLOGY; CARBOHYDRATE SYSTEMS; SAMPLE DILUTION; NITROGEN; SPECTRA AB Soil samples were analyzed conventionally and by mid-infrared diffuse reflectance spectroscopy for total C, total N, pH, and measures of biological activity. Ground, non KBr diluted, samples (n = 180) from experimental plots (two locations, three replicate plots, under plow and no-till practices, three rates of N fertilizer, and from five depths) were scanned from 4000 to 400 cm(-1) (4-cm(-1) resolution, 64 co-added scans) on a DigiLab FTS-60 Fourier transform spectrometer using a custom-made linear sample transport (50 by 2 mm sample area scanned). Results using partial least-squares regression showed that accurate calibrations can be developed for the determination of a number of compositional parameters: total C, total N, pH, and many measures of biological activity. In general, the results achieved using mid-infrared spectra were at least as accurate as those found previously using near-infrared spectra and were sometimes significantly better, that is, pH. C1 ANRI, AMBL, Beltsville, MD 20705 USA. ANRI, EQL, Beltsville, MD 20705 USA. US FDA, CVM, Rockville, MD 20855 USA. RP Reeves, JB (reprint author), ANRI, AMBL, Bldg 306,BARC E, Beltsville, MD 20705 USA. NR 30 TC 91 Z9 92 U1 3 U2 21 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD FEB PY 2001 VL 49 IS 2 BP 766 EP 772 DI 10.1021/jf0011283 PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA 404XP UT WOS:000167127900039 PM 11262026 ER PT J AU Brenner, RJ Focks, DA Lele, SR Horowitz, E Rice, V Milne, DE Anderson, MC Togias, A AF Brenner, RJ Focks, DA Lele, SR Horowitz, E Rice, V Milne, DE Anderson, MC Togias, A TI Procedures for estimating spatial/temporal risks using cockroach trap counts and polyclonal ELISA assays for cockroach antigens SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Florida, USDA ARS, Gainesville, FL 32611 USA. Univ Alberta, Edmonton, AB, Canada. US FDA, Kensington, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY, INC PI ST LOUIS PA 11830 WESTLINE INDUSTRIAL DR, ST LOUIS, MO 63146-3318 USA SN 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2001 VL 107 IS 2 SU S MA 396 BP S120 EP S120 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 405RE UT WOS:000167172300395 ER PT J AU Cardinale, EJ Boykins, RA Soldatova, LN Slater, JE AF Cardinale, EJ Boykins, RA Soldatova, LN Slater, JE TI Matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry in the analysis of allergen vaccines SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2001 VL 107 IS 2 SU S MA 65 BP S19 EP S19 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 405RE UT WOS:000167172300066 ER PT J AU Doekes, G Van Niftrik, M Portengen, L Tomazic-Jezic, VJ Chen, ZP Nij, EIT De Wind, S Heederik, DJ AF Doekes, G Van Niftrik, M Portengen, L Tomazic-Jezic, VJ Chen, ZP Nij, EIT De Wind, S Heederik, DJ TI Measurement of latex proteins in low-volume airborne samples and glove extracts with a sandwich EIA using polyclonal rabbit anti-latex IgG SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Univ Utrecht, Inst Risk Assessment Sci, Utrecht, Netherlands. US FDA, CDRH, Rockville, MD 20857 USA. Berufsgenossenschaftliches Inst, Bochum, Germany. 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2001 VL 107 IS 2 SU S MA 438 BP S132 EP S132 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 405RE UT WOS:000167172300437 ER PT J AU Hsieh, LS Moharram, RM Martin, BM Slater, JE AF Hsieh, LS Moharram, RM Martin, BM Slater, JE TI Latex allergen detection and epitope mapping using microarray technology SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NIH, Bethesda, MD 20892 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2001 VL 107 IS 2 SU S MA 382 BP S115 EP S115 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 405RE UT WOS:000167172300381 ER PT J AU Patterson, ML Slater, JE AF Patterson, ML Slater, JE TI Preliminary studies for the standardization of cockroach extracts SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2001 VL 107 IS 2 SU S MA 190 BP S55 EP S55 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 405RE UT WOS:000167172300190 ER PT J AU Poley, GE Slater, JE AF Poley, GE Slater, JE TI Presentation with avocado enhances murine IgG responses to suboptimal nasal doses of non-ammoniated latex proteins. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Childrens Natl Med Ctr, Washington, DC 20010 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2001 VL 107 IS 2 SU S MA 383 BP S116 EP S116 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 405RE UT WOS:000167172300382 ER PT J AU Solanki, MD Slater, JE AF Solanki, MD Slater, JE TI The effects of lipopolysaccharide (LPS) on airway responses in mice depends upon the route of airway administration SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2001 VL 107 IS 2 SU S MA 571 BP S174 EP S174 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 405RE UT WOS:000167172300569 ER PT J AU Soldatova, LN Luong, TN Marcovic-Housley, Z Morrow, KS Mueller, UR Slater, JE AF Soldatova, LN Luong, TN Marcovic-Housley, Z Morrow, KS Mueller, UR Slater, JE TI Biological activity of glycosylation and active site mutants of honeybee venom hyaluronidase SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Univ Basel, CH-4003 Basel, Switzerland. Zieglerspital, Bern, Switzerland. NR 0 TC 1 Z9 2 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 FEB PY 2001 VL 107 IS 2 SU S MA 730 BP S222 EP S222 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA 405RE UT WOS:000167172300726 ER PT J AU Sutherland, MF Drew, AC Suphioglu, C Rolland, J Slater, JE Ohehir, RE AF Sutherland, MF Drew, AC Suphioglu, C Rolland, J Slater, JE Ohehir, RE TI Hev 5: Production of specific monoclonal antibodies and recombinant expression without maltose binding protein SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 Monash Univ, Prahran, Vic, Australia. US FDA, Rockville, MD 20857 USA. RI O'Hehir, Robyn/H-3627-2011 OI O'Hehir, Robyn/0000-0002-3489-7595 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 0091-6749 J9 J ALLERGY CLIN IMMUN JI J. Allergy Clin. Immunol. PD FEB PY 2001 VL 107 IS 2 SU S MA 385 BP S116 EP S117 PG 2 WC Allergy; Immunology SC Allergy; Immunology GA 405RE UT WOS:000167172300384 ER PT J AU Schmitt, MP Drazek, ES AF Schmitt, MP Drazek, ES TI Construction and consequences of directed mutations affecting the hemin receptor in pathogenic Corynebacterium species SO JOURNAL OF BACTERIOLOGY LA English DT Article ID IRON TRANSPORT; HAEMOPHILUS-INFLUENZAE; SHIGELLA-DYSENTERIAE; ESCHERICHIA-COLI; DIPHTHERIA-TOXIN; YERSINIA-PESTIS; BINDING-PROTEIN; BACTERIA; HEMOGLOBIN; LOCUS AB Genes encoding an ATP-binding cassette transporter system involved in hemin iron utilization from Corynebacterium ulcerans were cloned and characterized. The genes are homologous to a hemin transport system previously identified in Corynebacterium diphtheriae. Disruption of the hmuT gene, which encodes the putative hemin receptor, resulted in greatly reduced ability of C. ulcerans to use hemin or hemoglobin as an iron source. Inactivation of hmuT in C. diphtheriae by site-specific recombination had no effect on hemin utilization, which suggests that C. diphtheriae has an additional system for transporting hemin. C1 US FDA, Ctr Biol Evaluat & Res, DBPAP, Lab Bacterial Toxins, Bethesda, MD 20892 USA. RP Schmitt, MP (reprint author), US FDA, Ctr Biol Evaluat & Res, DBPAP, Lab Bacterial Toxins, 880 Rockville Pike,Bldg 29,Room 108, Bethesda, MD 20892 USA. NR 32 TC 26 Z9 27 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD FEB PY 2001 VL 183 IS 4 BP 1476 EP 1481 DI 10.1128/JB.183.4.1476-1481.2001 PG 6 WC Microbiology SC Microbiology GA 397LM UT WOS:000166697200044 PM 11157965 ER PT J AU Mesmer, MZ Flurer, RA AF Mesmer, MZ Flurer, RA TI Determination of bromethalin in commercial rodenticides found in consumer product samples by HPLC-UV-vis spectrophotometry and HPLC-negative-ion APCI-MS SO JOURNAL OF CHROMATOGRAPHIC SCIENCE LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; IONIZATION MASS-SPECTROMETRY; BRODIFACOUM; INGESTION C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Mesmer, MZ (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 14 TC 6 Z9 6 U1 2 U2 5 PU PRESTON PUBLICATIONS INC PI NILES PA 7800 MERRIMAC AVE PO BOX 48312, NILES, IL 60648 USA SN 0021-9665 J9 J CHROMATOGR SCI JI J. Chromatogr. Sci. PD FEB PY 2001 VL 39 IS 2 BP 49 EP 53 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 400LX UT WOS:000166874000002 PM 11245225 ER PT J AU Shahabuddin, M Sears, JF Khan, AS AF Shahabuddin, M Sears, JF Khan, AS TI No evidence of infectious retroviruses in measles virus vaccines produced in chicken embryo cell cultures SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID REVERSE-TRANSCRIPTASE ACTIVITY; ENDOGENOUS AVIAN RETROVIRUS; POLYMERASE CHAIN-REACTION; MURINE LEUKEMIA VIRUSES; REPLICATION-COMPETENT; SARCOMA VIRUSES; GENE-SEQUENCES; HUMAN GENOME; FAMILY; EXPRESSION AB All vaccines that are prepared in chicken embryo fibroblasts (CEFs) contain a low level of particle-associated reverse transcriptase (RT) activity, which is produced from the avian cell substrate. The RNAs present in the particles have sequence homology to viral DNAs belonging to the ancient endogenous avian virus (EAV) family or to the avian sarcoma-leukosis virus (ALV)-related subgroup E endogenous virus loci. Although no replication-competent retrovirus has been associated with the RT activity produced from CEFs, there have been some theoretical safety concerns regarding potential consequences of integration of EAV and ALV sequences in human DNA, which may result from nonproductive infection with replication-defective particles or infection with EAV and ALV pseudotypes bearing measles virus envelopes. To address these possibilities, we have analyzed EAV and ALV particles in a measles virus vaccine equivalent (MVVE) preparation, obtained from a U.S. manufacturer, for integration and for replication in human peripheral blood mononuclear cells (PBMCs), The results show the absence of EAV and ALV integrants in DNA prepared from MWE-inoculated human cells by direct DNA PCR and Alu PCR assays and no propagation of retrovirus in 18-day cultures of MVVE-inoculated human PBMCs by a highly sensitive PCR-based RT assay. These results provide further confidence regarding the safety of chicken RT activity in live viral vaccines and support the continued use of chick-cell-derived vaccines in humans. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Retrovirus Res, Rockville, MD 20852 USA. RP Khan, AS (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Lab Retrovirus Res, HFM-454,1401 Rockville Pike, Rockville, MD 20852 USA. NR 39 TC 12 Z9 12 U1 0 U2 3 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 2001 VL 39 IS 2 BP 675 EP 684 DI 10.1128/JCM.39.2.675-684.2001 PG 10 WC Microbiology SC Microbiology GA 398VA UT WOS:000166776100043 PM 11158127 ER PT J AU D'Souza, DH Brackett, RE AF D'Souza, DH Brackett, RE TI Aflatoxin B-1 degradation by Flavobacterium aurantiacum in the presence of reducing conditions and seryl and sulfhydryl group inhibitors SO JOURNAL OF FOOD PROTECTION LA English DT Article ID CADMIUM; BACTERIA AB This study was undertaken to determine the effects of reducing conditions (L-cysteine) and seryl (phenylmethylsulfonyl fluoride) and sulfhydryl (divalent cadmium) group inhibitors on aflatoxin B-1 (AFB1) degradation by Flavobacterium aurantiacum. High-performance liquid chromatography was used to determine AFB1 concentrations in 72-h cultures of F. aurantiacum. The addition of 0.1, 1, or 10 mM L-cysteine did not have any significant effect on AFB1 degradation by these cultures after incubation for 4, 24, or 48 h (P > 0.05). The addition of 0.1 mM phenylmethylsulfonyl fluoride did not significantly decrease AFB1 degradation (P > 0.05), but 1 mM phenylmethylsulfonyl fluoride significantly decreased AFB1 degradation after 4, 24, and 48 h of incubation (P less than or equal to 0.05). No significant difference in AFB1 degradation was obtained with 0.1 mM Cd2+ after 4, 24, or 48 h of incubation (P > 0.05). The addition of 1 and 10 mM Cd2+ significantly decreased AFB1 degradation compared with the cells containing AFB1 alone after 4 and 24 h (P less than or equal to 0.05). The addition of chelators, 1 mM EDTA and 1 mM o-phenanthroline, did not result in removal of inhibition of AFB1 degradation observed with 1 and 10 mM Cd2+. Higher concentration of chelators (>1 mM) are necessary to overcome the inhibitory effect. Further work on the cellular fractions and/or crude enzyme preparations is necessary to determine if indeed sulfhydryl and seryl groups of the enzymes are involved in AFB1 degradation (by maintaining either the structure or function of the enzyme). C1 Univ Georgia, Ctr Food Safety & Qual Enhancement, Dept Food Sci & Technol, Griffin, GA 30223 USA. RP Brackett, RE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 13 TC 22 Z9 22 U1 2 U2 3 PU INT ASSOC MILK FOOD ENVIRONMENTAL SANITARIANS, INC 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 2001 VL 64 IS 2 BP 268 EP 271 PG 4 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 402ZL UT WOS:000167018000023 PM 11271780 ER PT J AU Muskhelishvili, L Thompson, PA Kusewitt, DF Wang, C Fadlubar, FF AF Muskhelishvili, L Thompson, PA Kusewitt, DF Wang, C Fadlubar, FF TI In situ hybridization and immunohistochemical analysis of cytochrome P4501B1 expression in human normal tissues SO JOURNAL OF HISTOCHEMISTRY & CYTOCHEMISTRY LA English DT Article DE cytochrome p450; CYP1B1; in situ hybridization; immunohistochemistry ID MESSENGER-RNA; HUMAN CYP1B1; 1B1; ENZYMES; CELLS; CDNA AB Cytochrome P450 1B1 (CYP1B1) is a recently cloned dioxin-inducible form of the cytochrome P450 supergene family of xenobiotic-metabolizing enzymes. CYP1B1 is constitutively expressed mainly in extrahepatic tissues and is inducible by aryl hydrocarbon receptor ligands. Human CYP1B1 is involved in activation of chemically diverse human procarcinogens, including polycyclic aromatic hydrocarbons and some aromatic amines, as well as the endogenous hormone 17 beta -estradiol. The metabolism of 17 beta -estradiol by CYP1B1 forms 4-hydroxyestradiol, a product believed to be important in estrogen-induced carcinogenesis. Although the distribution of CYP1B1 mRNA and protein in a number of human normal tissues has been well documented, neither the cells expressing CYP1B1 in individual tissue nor the intracellular localization of the enzyme has been thoroughly characterized. In this study, using nonradioactive in situ hybridization and immunohistochemistry, we examined the cellular localization of CYP1B1 mRNA and protein in a range of human normal tissues. CYP1B1 mRNA and protein were expressed in most samples of parenchymal and stromal tissue from brain, kidney, prostate, breast, cervix, uterus, ovary, and lymph nodes. In most tissues, CYP1B1 immunostaining was nuclear. However, in tubule cells of kidney and secretory cells of mammary gland, immunoreactivity for CYP1B1 protein was found in both nucleus and cytoplasm. This study demonstrates for the first time the nuclear localization of CYP1B1 protein. Moreover, the constitutive expression and wide distribution of CYP1B1 mRNA and protein in many human normal tissues suggest functional roles for CYP1B1 in the bioactivation of xenobiotic procarcinogens and endogenous substrates such as estrogens. C1 Pathol Associates Int, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. RP Muskhelishvili, L (reprint author), Pathol Associates Int, 3900 NCTR Rd,MC 923, Jefferson, AR 72079 USA. RI Kusewitt, Donna/E-8107-2011 NR 22 TC 104 Z9 109 U1 0 U2 9 PU HISTOCHEMICAL SOC INC PI SEATTLE PA UNIV WASHINGTON, DEPT BIOSTRUCTURE, BOX 357420, SEATTLE, WA 98195 USA SN 0022-1554 J9 J HISTOCHEM CYTOCHEM JI J. Histochem. Cytochem. PD FEB PY 2001 VL 49 IS 2 BP 229 EP 236 PG 8 WC Cell Biology SC Cell Biology GA 397VF UT WOS:000166717900010 PM 11156691 ER PT J AU Imam, SZ Newport, GD Itzhak, Y Cadet, JL Islam, F Slikker, W Ali, SF AF Imam, SZ Newport, GD Itzhak, Y Cadet, JL Islam, F Slikker, W Ali, SF TI Peroxynitrite plays a role in methamphetamine-induced dopaminergic neurotoxicity: evidence from mice lacking neuronal nitric oxide synthase gene or overexpressing copper-zinc superoxide dismutase SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE copper zinc superoxide dismutase; dopamine; methamphetamine; neurotoxicity; nitric oxide synthase; peroxynitrite ID TRANSGENIC MICE; 7-NITROINDAZOLE; INHIBITOR; PROTECTS; RELEASE; BRAIN; DRUGS AB The use of methamphetamine (METH) leads to neurotoxic effects in mammals. These neurotoxic effects appear to be related to the production of free radicals. To assess the role of peroxynitrite in METH-induced dopaminergic, we investigated the production of 3-nitrotyrosine (3-NT) in the mouse striatum. The revels of 3-NT increased in the striatum of wild-type mice treated with multiple doses of METH (4 x 10 mg/kg, 2 h interval) as compared with the controls. However, no significant production or 3-NT was observed either in the striata of neuronal nitric oxide synthase knockout mice (nNOS -/-) or copper-zinc superoxide dismutase overexpressed transgenic mice (SOD-Tg) treated with similar doses of METH. The dopaminergic damage induced by METH treatment was also attenuated in nNOS-/- or SOD-TS mice. These data further confirm that METH causes its neurotoxic effects via the production of peroxynitrite. C1 US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, Jefferson, AR 72079 USA. Hamdard Univ, Neurotoxicol Lab, Dept Med Elementol & Toxicol, New Delhi, India. Univ Miami, Sch Med, Dept Psychiat & Behav Sci, Miami, FL USA. NIDA, Mol Neurosci Sect, Intramural Res Program, Baltimore, MD USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Div Neurotoxicol, HFT-132,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 20 TC 82 Z9 85 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD FEB PY 2001 VL 76 IS 3 BP 745 EP 749 DI 10.1046/j.1471-4159.2001.00029.x PG 5 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 397UG UT WOS:000166715300012 PM 11158245 ER PT J AU Weir, JP AF Weir, JP TI Infection of human NT2 cells and differentiated NT-neurons with herpes simplex virus and replication-incompetent herpes simplex virus vectors SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE herpes simplex virus; cell culture model; thymidine-kinase mutants; herpes simplex virus vectors ID GENE-EXPRESSION; THYMIDINE KINASE; TRIGEMINAL GANGLIA; LATENCY; ESTABLISHMENT; INVITRO; MUTANT; LINE; TRANSCRIPTION; REACTIVATION AB The human embryonal carcinoma cell line NT2 differentiates irreversibly into postmitotic neuron-like cells following treatment with retinoic acid. These differentiated NT-neurons resemble central nervous system (CNS) neurons and are characterized by development of dendrites and axons and the expression of neuron-specific markers. Because of their unique biological characteristics, NT-neurons were investigated for their utility as a system for studying the replication of herpes simplex virus (HSV) in the neuron and for evaluating characteristics of HSV vectors designed for gene delivery to the neuron. Virus replication in differentiated NT-neurons was significantly reduced and delayed relative to replication in undifferentiated NT2 cells. Replication of thymidine-kinase (tk) deficient HSV was further impaired in NT-neurons, reflecting the behavior of tk-negative virus in primary neurons in vitro and ganglia in vivo. Furthermore, replication-incompetent HSV vectors were capable of infecting NT-neurons, expressing a foreign gene, and persisting in a recoverable state for at least 2 weeks following delivery. These results suggest that differentiated NT-neurons can provide a continuous source of human, post-mitotic neurons-like cells for the study of HSV biology and HSV vector development. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Weir, JP (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. NR 31 TC 7 Z9 7 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD FEB PY 2001 VL 7 IS 1 BP 43 EP 51 DI 10.1080/135502801300069656 PG 9 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA 472QZ UT WOS:000170997600006 PM 11519481 ER PT J AU Young, JF Gough, BJ Suber, RL Gaylor, DW AF Young, JF Gough, BJ Suber, RL Gaylor, DW TI Correlation of blood cholinesterase levels with toxicity of sarin in rats SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID PHARMACOKINETICS AB The dose-mortality response curve for sarin when administered to pregnant rats is extremely steep. The pregnant animal either died during the treatment or survived with no observable fetal toxicity. Animals that died displayed many symptoms characteristic of anticholinesterase toxicity. The present study was conducted to determine whether the maternal deaths, clinical observations, and/or weight loss could be correlated with baseline blood cholinesterase levels in individual animals. Cholinesterase levels (plasma and erythrocyte) were obtained prior to, during, and following treatment of nonpregnant rats by gavage with 380 mug/kg/d sarin for 10 d. After the first dose, there was a drop in the plasma cholinesterase levels, which then remained low throughout the dosing period. There was a statistically significant correlation between body weight loss and plasma cholinesterase levels of the sarin dosed animals. The surviving animals also had lower plasma cholinesterase levels and lower body weights, both of which recovered on the cessation of dosing. The erythrocyte cholinesterase levels were not different between treated and nontreated rats. Neither plasma or erythrocyte baseline cholinesterase levels nor relative or absolute cholinesterase decline values could be used as predictors of mortality from sarin administration in rats. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RJR Nabisco Inc, Bowman Gray Tech Ctr, Winston Salem, NC USA. RP Young, JF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 16 TC 8 Z9 8 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 1528-7394 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD FEB PY 2001 VL 62 IS 3 BP 161 EP 174 DI 10.1080/009841001458280 PG 14 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 398BH UT WOS:000166734500002 PM 11212943 ER PT J AU Law, LMJ Duncan, R Esmaili, A Nakhasi, HL Hobman, TC AF Law, LMJ Duncan, R Esmaili, A Nakhasi, HL Hobman, TC TI Rubella virus E2 signal peptide is required for perinuclear localization of capsid protein and virus assembly SO JOURNAL OF VIROLOGY LA English DT Article ID STRUCTURAL PROTEINS; GOLGI; GLYCOPROTEIN; PARTICLES; CELLS; EXPRESSION; CONTAINS; COMPLEX; INVITRO AB The rubella virus (RV) structural proteins capsid, E2, and El are synthesized as a polyprotein precursor. The signal peptide that initiates translocation of E2 into the lumen of the endoplasmic reticulum remains attached to the carboxy terminus of the capsid protein after cleavage by signal peptidase. Among togaviruses, this feature is unique to RV. The E2 signal peptide has previously been shown to function as a membrane anchor for the capsid protein. In the present study, we demonstrate that this domain is required for RV glycoprotein-dependent localization of the capsid protein to the juxtanuclear region and subsequent virus assembly at the Golgi complex. C1 Univ Alberta, Dept Cell Biol, Edmonton, AB T6G 2H7, Canada. US FDA, Ctr Biol Evaluat & Res, Lab Bacterial Parasit & Uncovent Agents, Bethesda, MD 20892 USA. RP Hobman, TC (reprint author), Univ Alberta, Dept Cell Biol, Edmonton, AB T6G 2H7, Canada. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 20 TC 23 Z9 26 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 2001 VL 75 IS 4 BP 1978 EP 1983 DI 10.1128/JVI.75.4.1978-1983.2001 PG 6 WC Virology SC Virology GA 397LK UT WOS:000166697000042 PM 11160697 ER PT J AU Honchel, R Rosenzweig, BA Thompson, KL Blanchard, KT Furst, SM Stoll, RE Sistare, FD AF Honchel, R Rosenzweig, BA Thompson, KL Blanchard, KT Furst, SM Stoll, RE Sistare, FD TI Loss of palindromic symmetry Tg.AC mice with a nonresponder phenotype SO MOLECULAR CARCINOGENESIS LA English DT Article DE transgenic mice; zeta-globin; S1 nuclease; v-Ha-ras ID TRANSGENIC MICE; SKIN TUMORS; GENE; CARCINOGENESIS; EXPRESSION; BIOASSAYS; PROMOTER; LINE; DNA AB The Tg.AC transgenic mouse carries the v-Ha-ras oncogene under the control of the zeta -globin promoter and is currently being used in a short-term carcinogenesis assay for safety testing of pharmaceuticals. A subset of hemizygous Tg.AC mice was found to be nonresponsive to the tumor promoter 12-O-tetradecanoylphorbol-13-acetate, which characteristically induces skin papillomas in these mice with repeated dermal applications. We previously showed that responder and nonresponder hemizygous Tg.AC mice carry about 40 copies of transgene but that the nonresponders had lost a 2-kb BamHI fragment containing the zeta -globin promoter sequence. The present restriction enzyme and S1 nuclease digestion experiments strongly suggested that the 2-kb BamHI fragment resulted from the orientation of two transgenes in an inverted repeat formation. Two subsets of nonresponder Tg.AC mice were identified. Restriction enzyme and S1 nuclease digestion experiments suggested that one nonresponder genotype was produced by a large deletion of one or more near complete copies of transgene sequence and the other genotype was produced by a small deletion near the apex of the "head-to-head" juncture of the inverted repeat. Polymerase chain reaction amplification, cloning, and sequencing results confirmed the palindromic orientation of transgene in Tg.AC mice. Our results indicated that, despite the presence of multiple copies of transgene in a direct repeat orientation, loss of symmetry in the palindromic array of transgene sequence results in the loss of the responder phenotype in Tg.AC mice. Published 2001 Wiley-Liss. Inc.(dagger) C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Off Testing & Res,Off Pharmaceut Sci, Laurel, MD 20708 USA. Boehringer Ingelheim Pharmaceut Inc, Dept Toxicol & Safety Assessment, Ridgefield, CT 06877 USA. RP Sistare, FD (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Off Testing & Res,Off Pharmaceut Sci, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 21 TC 19 Z9 20 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 0899-1987 J9 MOL CARCINOGEN JI Mol. Carcinog. PD FEB PY 2001 VL 30 IS 2 BP 99 EP 110 DI 10.1002/1098-2744(200102)30:2<99::AID-MC1018>3.0.CO;2-7 PG 12 WC Biochemistry & Molecular Biology; Oncology SC Biochemistry & Molecular Biology; Oncology GA 407PR UT WOS:000167280400003 PM 11241757 ER PT J AU Ball, R Ball, LK Wise, RP Braun, MM Beeler, JA Salive, ME AF Ball, R Ball, LK Wise, RP Braun, MM Beeler, JA Salive, ME TI Stevens-Johnson syndrome and toxic epidermal necrolysis after vaccination: Reports to the vaccine adverse event reporting system SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article DE Stevens-Johnson syndrome; toxic epidermal necrolysis; vaccine; adverse event; safety ID ERYTHEMA MULTIFORME AB We conducted a telephone survey of reports of Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) to the Vaccine Adverse Event Reporting System. We identified six cases of SJS or TEN after vaccination without other obvious triggers, suggesting that SJS and TEN might very rarely be caused by vaccination. Confirmation of this hypothesis will likely require controlled studies. C1 US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Vaers Working Grp, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Off Vaccine Res & Review, Vaers Working Grp, Rockville, MD 20852 USA. RP Ball, R (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Biostat & Epidemiol, Vaers Working Grp, HFM-220,1401 Rockville Pike, Rockville, MD 20852 USA. NR 14 TC 31 Z9 32 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 FEB PY 2001 VL 20 IS 2 BP 219 EP 223 DI 10.1097/00006454-200102000-00022 PG 5 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA 402UL UT WOS:000167006500021 PM 11224848 ER PT J AU Hanna, GM Lau-Cam, CA AF Hanna, GM Lau-Cam, CA TI A simple method for the identification and assay of iopamidol and iothalamate meglumine in pharmaceutical samples based on proton nuclear magnetic resonance spectroscopy SO PHARMAZIE LA English DT Article AB A proton nuclear magnetic resonance (PMR) spectroscopic method is described for the direct assay and identification of the triiodinated radiographic contrast agents iopamidol (nonionic type) and iothalamate meglumine (ionic type) in commercial solutions and as a bulk material. Samples were prepared by simply diluting an injectable solution with or dissol ving a powdered sample in D2O. Sodium acetate was added to serve as an internal standard. Quantitations were based on the resonance signals for the protons of the CH3-CO-group at 1.58 ppm (iopamidol) or 2.25 ppm (iothalamate), CH3-N-group at 2.38 ppm (meglumine) and CH3-CO-group at 1.92 ppm (acetate). The mean +/-SD (n = sets of 10 samples each) recovery of iopamidol, iothalamic acid and meglumine from synthetic mixtures with the internal standard were 99.6 +/- 0.63. 99.7 +/- 0.66 and 99.9 +/- 1.18%, respectively; with the values ranging from 98.7-100.9% for iopamidol and iothalamate, and from 98.3-100.8% for meglumine. C1 US FDA, Dept Hlth & Human Serv, NE Reg Lab, Jamaica, NY 11433 USA. St Johns Univ, Coll Pharm & Allied Hlth Profess, Jamaica, NY 11439 USA. RP Hanna, GM (reprint author), US FDA, Dept Hlth & Human Serv, NE Reg Lab, 158-15 Liberty Ave, Jamaica, NY 11433 USA. NR 21 TC 2 Z9 2 U1 0 U2 0 PU GOVI-VERLAG GMBH PI ESCHBORN PA PHARMAZEUTISCHER VERLAG GINNHEIMER STRASSE 26, D-65760 ESCHBORN, GERMANY SN 0031-7144 J9 PHARMAZIE JI Pharmazie PD FEB PY 2001 VL 56 IS 2 BP 152 EP 155 PG 4 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA 401CB UT WOS:000166908400008 PM 11234344 ER PT J AU Gaylor, DW Kodell, RL AF Gaylor, DW Kodell, RL TI Dose-response trend tests for tumorigenesis adjusted for differences in survival and body weight across doses SO TOXICOLOGICAL SCIENCES LA English DT Article DE dose response; tumorigenesis; trend test; body weight; Poly-3 ID CARCINOGENICITY; TOXICITY AB A relationship between rodent body weight and tumor incidence for some tissue/organ sites has been demonstrated in many studies. It is not uncommon for a chemical tested for carcinogenicity to also affect body weight due to toxicity and/or food consumption. In such cases, comparisons of tumor incidence may be biased by body weight differences across dose groups. A simple procedure was investigated for reducing this bias. This procedure divides the animals into a few groups on the basis of body weight. Body weight at 12 months was used, before the appearance of a tumor was likely to affect body weight. Statistics for dose-response trend tests are calculated within body weight strata and pooled to obtain an overall dose-response trend test. This procedure is analogous to stratifying animals on the basis of age at the time of removal from a study to account for differences in ages of animals across dose groups that can affect comparisons of tumor incidence. In this paper, differences in survival times of animals were adjusted by the Poly-3 technique used by the National Toxicology Program. This technique does not require the assignment of cause of death. Several examples from rodent chronic bioassays were investigated, where the high dose group had reduced body weights and associated reductions in tumor incidence. When we analyzed the data by body weight strata, some positive dose-response trends for tumor incidence were demonstrated. In one case, the body weight adjusted analysis indicated that a negative dose-response trend in tumor incidence was a real effect in addition to a body weight reduction. These examples indicate that it is important to consider the effects of body weight changes as low as 10%, and perhaps less, as possibly being caused by chemicals in 2-year bioassays for carcinogenesis. The simple procedure of analyzing tumor incidence within body weight strata can reduce the bias introduced by body weight differences across dose groups. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Gaylor, DW (reprint author), Sci Int Inc, 13815 Abinger Court, Little Rock, AR 72212 USA. NR 14 TC 8 Z9 8 U1 6 U2 10 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 J9 TOXICOL SCI JI Toxicol. Sci. PD FEB PY 2001 VL 59 IS 2 BP 219 EP 225 DI 10.1093/toxsci/59.2.219 PG 7 WC Toxicology SC Toxicology GA 396LR UT WOS:000166638300005 PM 11158714 ER PT J AU Horvath-Arcidiacono, JA Bloom, ET AF Horvath-Arcidiacono, JA Bloom, ET TI Characterization of human killer cell reactivity against porcine target cells: differential modulation by cytokines SO XENOTRANSPLANTATION LA English DT Article DE cytokine; cytotoxicity; interleukin; natural killer cells; T cells ID ANTI-PIG CYTOTOXICITY; CD4(+) T-CELLS; HUMAN NK CELLS; ENDOTHELIAL-CELLS; XENOGRAFT REJECTION; IN-VITRO; MEDIATED REJECTION; MONONUCLEAR-CELLS; INTERFERON-GAMMA; LYMPHOCYTES-T AB The cytotoxic cell response to porcine cells by human lymphocytes, and the modulation of cytolytic cellular activity by human cytokines were investigated. Human peripheral blood mononuclear cells (PBMC) and purified lymphocyte subsets were co-cultured with fresh irradiated porcine stimulator cells and examined for the development of lyric activity and for their proliferative response. Porcine target cells included a new cell fine, MS-PBMC-J2 (designated J2; SLA-DR+MHC class I(+)CD2(+)CD3(-)CD8(+)CD16(+)CD45(+)), aortic and microvascular endothelial cells. Initial results showed that natural killer (NK) cells were fivefold more efficient in killing porcine target cells compared with T cells, IL-12 augmented the killing of porcine target cells by human NK cells beyond that induced by stimulation with cells alone. In contrast, IL-2 and IL-15 often induced substantial human NK cell mediated killing of porcine target cells, including endothelial cells in the case of IL-2 where such targets were examined, even in the absence of stimulator cells. Finally, neither IL-18 nor IL-8 had any effect beyond background on NK cell mediated killing of porcine target cells. These findings show that cytokines that would be produced in a xenograft setting clearly modulate the ability of human cytolytic cells Co kill porcine targets. In addition, fresh unstimulated human NK cells lysed J2 and porcine aortic endothelial cells, but not porcine microvascular endothelial cells, suggesting the possibility of rapid attack of xenografts by NK cells, and differential susceptibility of endothelial cells from different vascular structures to this attack. C1 US FDA, Lab Cellular Immunol HFM518, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Bloom, ET (reprint author), US FDA, Lab Cellular Immunol HFM518, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 61 TC 10 Z9 10 U1 0 U2 3 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0908-665X J9 XENOTRANSPLANTATION JI Xenotransplantation PD FEB PY 2001 VL 8 IS 1 BP 62 EP 74 DI 10.1034/j.1399-3089.2001.00078.x PG 13 WC Medicine, Research & Experimental; Transplantation SC Research & Experimental Medicine; Transplantation GA 403DD UT WOS:000167026500007 PM 11208192 ER PT J AU Pletnikov, MV Rubin, SA Carbone, KM Moran, TH Schwartz, GJ AF Pletnikov, MV Rubin, SA Carbone, KM Moran, TH Schwartz, GJ TI Neonatal Borna disease virus infection (BDV)-induced damage to the cerebellum is associated with sensorimotor deficits in developing Lewis rats SO DEVELOPMENTAL BRAIN RESEARCH LA English DT Article DE Borna; cerebellum; motor coordination; development; rat ID ACOUSTIC STARTLE RESPONSE; PREPULSE INHIBITION; PSYCHIATRIC-PATIENTS; NERVOUS-SYSTEM; MOTOR BEHAVIOR; ADULT-RATS; SCHIZOPHRENIA; PERSISTENT; HEMICEREBELLECTOMY; HABITUATION AB Neonatal Borna disease virus (BDV) infection of the brain produces developmental damage to the cerebellum in Lewis rats, with minimal classical inflammatory responses. In the present study, we assessed the consequences of this damage by measuring motor coordination and postural skills in developing (postnatal days 3 to 30) Lewis rats that were neonatally infected with BDV. Neonatal BDV infection-induced motor impairments were selective and correlated with the time course of BDV damage to cerebellar development. BDV-induced motor deficits were not seen until the end of postnatal week 2. By postnatal week 3, BDV-infected rats had deficits in negative geotropism, fore- and hind limb placing and grasping. BDV-infected rats also exhibited deficits in the ability to hold on to a bar and to cross a suspended bar. Neonatal BDV infection induced impairments in the acoustic startle response. Compared to controls, neonatally BDV-infected rats exhibited attenuated habituation of the acoustic startle at postnatal day (PND) 23 and decreased startle responsiveness at PND 30. Prepulse inhibition of the acoustic startle remained unaltered in BDV-infected rats. The data demonstrate that neonatal BDV brain infection of rats can be a valuable animal model system for studying the relationship between abnormal brain development and resultant behavioral deficits. Further studies of this model may elucidate specific pathogenic mechanisms that that may have implications in the study of neurodevelopmental human disorders. (C) 2001 Elsevier Science B.V. All rights reserved. C1 Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Baltimore, MD 21205 USA. US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viral Dis, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. RP Pletnikov, MV (reprint author), Johns Hopkins Univ, Sch Med, Dept Psychiat & Behav Sci, Ross 618,720 Rutland Ave, Baltimore, MD 21205 USA. NR 57 TC 18 Z9 18 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-3806 J9 DEV BRAIN RES JI Dev. Brain Res. PD JAN 31 PY 2001 VL 126 IS 1 BP 1 EP 12 DI 10.1016/S0165-3806(00)00119-X PG 12 WC Developmental Biology; Neurosciences SC Developmental Biology; Neurosciences & Neurology GA 402UA UT WOS:000167005500001 ER PT J AU Schwieterman, WD Weiss, KD Tiwari, J Siegel, JP AF Schwieterman, WD Weiss, KD Tiwari, J Siegel, JP TI Changes in trial parameters SO LANCET LA English DT Letter C1 USDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Schwieterman, WD (reprint author), USDA, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 1 TC 0 Z9 0 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 JAN 27 PY 2001 VL 357 IS 9252 BP 314 EP 314 DI 10.1016/S0140-6736(05)71764-5 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 397JW UT WOS:000166693400062 PM 11214164 ER PT J AU Remaley, AT Stonik, JA Demosky, SJ Neufeld, EB Bocharov, AV Vishnyakova, TG Eggerman, TL Patterson, AP Duverger, NJ Santamarina-Fojo, S Brewer, HB AF Remaley, AT Stonik, JA Demosky, SJ Neufeld, EB Bocharov, AV Vishnyakova, TG Eggerman, TL Patterson, AP Duverger, NJ Santamarina-Fojo, S Brewer, HB TI Apolipoprotein specificity for lipid efflux by the human ABCAI transporter SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article DE Tangier disease; HDL; ABCAI; ABC transporters ID BINDING CASSETTE TRANSPORTER-1; TANGIER-DISEASE; A-I; CELLULAR CHOLESTEROL; REMOVAL; PHOSPHOLIPIDS; MACROPHAGES; MUTATIONS AB ABCAI, a member of the ATP binding cassette family, mediates the efflux of excess cellular lipid to HDL and is defective in Tangier disease. The apolipoprotein acceptor specificity for Lipid efflux by ABCAI was examined in stably transfected Hela cells, expressing a human ABCAI-GFP fusion protein. ApoA-I and all of the other exchangeable apolipoproteins tested (apoA-II, apoA-IV, apoC-I, apoC-II, apoC-III, apoE) showed greater than a threefold increase in cholesterol and phospholipid efflux from ABCAI-GFP transfected cells compared to control cells. Expression of ABCAI in Hela cells also resulted in a marked increase in specific binding of both apoA-I (Kd = 0.60 mug/mL) and apoA-II (Kd = 0.58 mug/mL) to a common binding site. In summary, ABCAI-mediated cellular binding of apolipoproteins and lipid efflux is not specific for only apoA-I but can also occur with other apolipoproteins that contain multiple amphipathic helical domains. (C) 2001 Academic Press. C1 NHLBI, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Aventis Pharma, Dept Genom, Every, France. RP Remaley, AT (reprint author), NHLBI, NIH, Bldg 10,7H115,10 Ctr Dr, Bethesda, MD 20892 USA. NR 30 TC 216 Z9 222 U1 0 U2 7 PU ACADEMIC PRESS INC 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 JAN 26 PY 2001 VL 280 IS 3 BP 818 EP 823 DI 10.1006/bbrc.2000.4219 PG 6 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 397LN UT WOS:000166697300035 PM 11162594 ER PT J AU Kotenko, SV Izotova, LS Mirochnitchenko, OV Esterova, E Dickensheets, H Donnelly, RP Pestka, S AF Kotenko, SV Izotova, LS Mirochnitchenko, OV Esterova, E Dickensheets, H Donnelly, RP Pestka, S TI Identification of the functional interleukin-22 (IL-22) receptor complex - The IL-10R2 chain (IL-10R beta) is a common chain of both the IL-10 and IL-22 (IL-10-related T cell-derived inducible factor, IL-TIF) receptor complexes SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID DIFFERENTIATION-ASSOCIATED GENE; HUMAN-MELANOMA DIFFERENTIATION; INTERFERON-GAMMA RECEPTOR; TRANSGENIC MICE; CANDIDATE GENE; PROTEIN-KINASE; ASTHMA; EXPRESSION; LINKAGE; HYPERRESPONSIVENESS AB Interleukin-10 (IL-10)-related T cell-derived inducible factor (IL-TIF; provisionally designated IL-22) is a cytokine with limited homology to IL-10, We report here the identification of a functional IL-TIF receptor complex that consists of two receptor chains, the orphan CRF2-9 and IL-10R2, the second chain of the IL-10 receptor complex. Expression of the CRF2-9 chain in monkey COS cells renders them sensitive to IL-TIF, However, in hamster cells both chains, CRF2-9 and IL-10R2, must be expressed to assemble the functional IL-TIF receptor complex. The CRF2-9 chain (or the IL-TIF-R1 chain) is responsible for Stat recruitment. Substitution of the CRF2-9 intracellular domain with the IFN-gamma R1 intracellular domain changes the pattern of IL-TIF-induced Stat activation. The CRF2-9 gene is expressed in normal liver and kidney, suggesting a possible role for IL-TIF in regulating gene expression in these tissues. Each chain, CRF2-9 and IL-10R2, is capable of binding IL-TIF independently and can be cross-linked to the radiolabeled IL-TIF, However, binding of IL-TIF to the receptor complex is greater than binding to either receptor chain alone. Sharing of the common IL-10R2 chain between the IL-10 and IL-TIF receptor complexes is the first such case for receptor complexes with chains belonging to the class II cytokine receptor family, establishing a novel paradigm for IL-10-related ligands similar to the shared use of the gamma common chain (gamma (c)) by several cytokines, including IL-2, IL-4, IL-7, IL-9, and IL-15, C1 Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prot, Bethesda, MD 20892 USA. RP Kotenko, SV (reprint author), Robert Wood Johnson Med Sch, Dept Mol Genet & Microbiol, Piscataway, NJ 08854 USA. FU NCI NIH HHS [1P30-CA72720, R01-CA46465]; NIAID NIH HHS [R01-AI36450, R01-AI43369] NR 41 TC 251 Z9 271 U1 0 U2 4 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0021-9258 J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 26 PY 2001 VL 276 IS 4 BP 2725 EP 2732 DI 10.1074/jbc.M007837200 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA 398YV UT WOS:000166784800059 PM 11035029 ER PT J AU Sapirstein, W Zuckerman, B Dillard, J AF Sapirstein, W Zuckerman, B Dillard, J TI FDA approval of coronary-artery brachytherapy SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Editorial Material C1 US FDA, Rockville, MD 20850 USA. RP Sapirstein, W (reprint author), US FDA, Rockville, MD 20850 USA. NR 4 TC 42 Z9 45 U1 0 U2 0 PU MASSACHUSETTS MEDICAL SOC PI WALTHAM PA WALTHAM WOODS CENTER, 860 WINTER ST,, WALTHAM, MA 02451-1413 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 25 PY 2001 VL 344 IS 4 BP 297 EP 299 DI 10.1056/NEJM200101253440410 PG 3 WC Medicine, General & Internal SC General & Internal Medicine GA 394WA UT WOS:000166545200010 PM 11172159 ER PT J AU Boxwell, D Haverkos, H Kukich, S Struble, K Jolson, H AF Boxwell, D Haverkos, H Kukich, S Struble, K Jolson, H TI Serious adverse events attributed to nevirapine regimens for postexposure prophylaxis after HIV exposures - Worldwide, 1997-2000 (Reprinted from MMWR, vol 49, pg 1153-1156, 2001) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint C1 US FDA, Off Postmkt Drug Risk Assessment, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Antiviral Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. CDC, Prevent & Evaluat Branch, Div Healthcare Qual Promot, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Boxwell, D (reprint author), US FDA, Off Postmkt Drug Risk Assessment, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 11 TC 7 Z9 7 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 24 PY 2001 VL 285 IS 4 BP 402 EP 403 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 394CG UT WOS:000166506000010 ER PT J AU Roberts, DW Churchwell, MI Beland, FA Fang, JL Doerge, DR AF Roberts, DW Churchwell, MI Beland, FA Fang, JL Doerge, DR TI Quantitative analysis of etheno-2 '-deoxycytidine DNA adducts using on-line immunoaffinity chromatography coupled with LC/ES-MS/MS detection SO ANALYTICAL CHEMISTRY LA English DT Article ID IONIZATION MASS-SPECTROMETRY; VINYL-CHLORIDE; LIQUID-CHROMATOGRAPHY; BASE ADDUCTS; LIVER; CELLS; 1,N-6-ETHENODEOXYADENOSINE; PERFORMANCE; CARBON; HPLC AB Etheno DNA adducts, including 3,N-4-etheno-2'-deoxycytidine (etheno-dC), are promutagenic lesions present in normal animal and human tissues. These DNA adducts are believed to be important in the etiology of cancer. Existing methods for quantifying etheno-dC use P-32. postlabeling, Although highly sensitive, postlabeling requires the use of an energetic radioisotope and considerable time and effort. The new methodology reported here permits automated quantitication of trace levels of etheno-dC in crude DNA hydrolysates on the order of 5 adducts in 10(8) normal nucleotides from 100-mug samples of DNA. This was accomplished by using on-line immunoaffinity chromatography, a reverse-phase LC separation on graphitized carbon, tandem mass spectrometric detection, and an isotopically labeled internal standard. The automated procedures permitted analysis of 4 DNA hydrolysates/hr. The sensitivity using immunoaffinity cleanup was approximately 100-fold greater than that observed when using a silica-based trapping system. The validated method was applied to the analysis of etheno-dC in commercial calf thymus DNA, untreated mouse liver, and untreated rat liver DNA, The demonstrated level of performance suggests future applicability of this method in studies of cancer in humans and experimental animals. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 23 TC 33 Z9 35 U1 0 U2 5 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0003-2700 J9 ANAL CHEM JI Anal. Chem. PD JAN 15 PY 2001 VL 73 IS 2 BP 303 EP 309 DI 10.1021/ac000866n PG 7 WC Chemistry, Analytical SC Chemistry GA 391QE UT WOS:000166366000025 PM 11199982 ER PT J AU Tran, ST Shrake, A AF Tran, ST Shrake, A TI The folding of alpha-1-proteinase inhibitor: Kinetic vs equilibrium control SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE alpha-1-proteinase inhibitor; alpha-1 antitrypsin; serine protease inhibitor; protein folding; kinetically controlled protein folding; equilibrium controlled protein folding; guanidine-HC1-induced protein unfolding/refolding ID ALPHA-1-ANTITRYPSIN DEFICIENCY; HUMAN ALPHA(1)-ANTITRYPSIN; CONFORMATIONAL-CHANGES; SERPIN INHIBITION; STABILITY; MECHANISM; LIVER; INCREASE; DISEASE; DEFECT AB Previous folding studies of alpha -1-proteinase inhibitor (alpha (1)-PI), which regulates the activity of the serine protease human neutrophil elastase, show an intermediate state at similar to1.5 M guanidine-HCl (Gu), For the normal form of alpha (1)-PI, we demonstrate the reversible formation of the same stable distribution of monomeric and polymeric intermediates after similar to1 h in 1.5 M Gu at similar to 23 degreesC from fully folded or fully unfolded alpha (1)-PI at similar final total concentrations and show that the stable distribution of monomeric and polymeric intermediates conforms with the law of mass action. We attribute these observations to an apparent equilibrium among intermediates. Our CD data are compatible with the intermediates having slightly relaxed structures relative to that of fully folded alpha (1)-PI and, thus, with the polymeric intermediates having a loop-sheet structure. Furthermore, we observe that the rates of folding (fast and slow terms) from the intermediate state are the same as those from the fully unfolded state, thereby supporting the contention that this intermediate state is on the folding pathway. We attribute the tendency of the Z mutant protein to polymerize/aggregate to an increased rate of the monomeric intermediate to form the apparent equilibrium distribution of intermediate species relative to its rate of folding to give intact alpha (1)-PI. (C) 2001 Academic Press. C1 US FDA, Div Hematol, Off Blood Res & Rev, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Shrake, A (reprint author), US FDA, CBER, HFM-345,1401 Rockville Pike,Suite 200 N, Rockville, MD 20852 USA. NR 44 TC 5 Z9 5 U1 0 U2 1 PU ACADEMIC PRESS INC 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 2001 VL 385 IS 2 BP 322 EP 331 DI 10.1006/abbi.2000.2186 PG 10 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA 393VP UT WOS:000166490600011 PM 11368013 ER PT J AU Bull, TE AF Bull, TE TI The form of an internal reorientational correlation function SO CHEMICAL PHYSICS LA English DT Article ID MODEL-FREE APPROACH; RELAXATION; WATER AB A non-Markovian, non-linearly coupled quantum stochastic dynamics model was used to investigate the reorientational correlation function of the internal motion of a methyl group attached to a large molecule. The values for the parameters used were determined by comparing angular momentum correlation functions calculated from the stochastic model to results of a molecular dynamics simulation. The results show that the correlation function has a rapid short time decay due to inertial effects, followed by a slower, exponential tail. Thus if there is significant inertial motion it is necessary to have at least two order parameters as well as two correlation times, one each for the overall and the internal motion, in order to accurately describe the system. The model can also explain data of Lee and McClung that cannot be explained with a Markovian model. (C) 2001 Elsevier Science B.V. All rights reserved. C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Biophys Lab, Bethesda, MD 20892 USA. RP Bull, TE (reprint author), CBER HFM 419, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 12 TC 0 Z9 0 U1 2 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0301-0104 J9 CHEM PHYS JI Chem. Phys. PD JAN 15 PY 2001 VL 263 IS 2-3 BP 327 EP 331 DI 10.1016/S0301-0104(00)00380-3 PG 5 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA 395LZ UT WOS:000166583000011 ER PT J AU Frykman, G Williams, G Pazdur, R AF Frykman, G Williams, G Pazdur, R TI Conflicting phase II efficacy data for Doxil SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Letter C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Frykman, G (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 1 TC 1 Z9 1 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD JAN 15 PY 2001 VL 19 IS 2 BP 596 EP 596 PG 1 WC Oncology SC Oncology GA 394QD UT WOS:000166534000046 PM 11208859 ER PT J AU Meredith, JM Bennett, C Scallet, AC AF Meredith, JM Bennett, C Scallet, AC TI A practical three-dimensional reconstruction method to measure the volume of the sexually-dimorphic central nucleus of the medial preoptic area (MPOC) of the rat hypothalamus SO JOURNAL OF NEUROSCIENCE METHODS LA English DT Article DE sexually dimorphic nuclei; medial preoptic area (MPOC); computer imaging; volumetric analysis; morphology; morphometry ID FEMALE RATS; 3-DIMENSIONAL RECONSTRUCTION; PITUITARY-RESPONSIVENESS; POSTNATAL INFLUENCE; NEONATAL EXPOSURE; DIFFERENTIATION; BRAIN; HORMONE; DIETHYLSTILBESTROL; PERIOD AB Published estimates of the volume of the sexually-dimorphic central nucleus of the medial preoptic area (MPOC) have been quite variable both within and between laboratories. To obtain MPOC volume, most experimenters began with a two-dimensional (2-D) approach. They outlined the MPOC on each of several individual sections; then they added up the area contained on each section and multiplied the total by the section thickness. A 3-D reconstruction approach, although promising, has been somewhat impractical until recently due to the requirements for highly specialized software and massive computing support. Here. we describe the application of commercially-available PC-based software to measure MPOC volume by 3-D reconstruction. Male and female Sprague-Dawley rats, 24 or 50 days of age, were pel fusion-fixed with 10% neutral phosphate-buffered formaldehyde. Following processing and embedding, a series of 20-mum sagittal paraffin sections were cut and mounted onto slides. After staining with cresyl violet, they were digitized using a microscope-mounted video camera connected to a frame-grabber in a Pentium-class computer. (MCID-M5 +). In addition to the MPOC. the anterior commissure, fornix, paraventricular nucleus, medial division of the bed nucleus of the stria terminalis, third ventricle and the bed nucleus of the anterior commissure were identified on the screen image and outlined using a computer mouse. These outlines were then aligned and rendered in 3-D with a solid overlay. The additional areas, such as anterior commissure, form landmarks within 3-D space to improve the accuracy with which the MPOC may be located and outlined. The reconstruction provides a striking illustration of the geometric relations between the structures of the anterior hypothalamus in the male and female rat. Moreover, the volumes determined from the overlays were reproducible between repeated studies in our laboratory. Our volume measurements confirm the sexual dimorphism previously reported for MPOC volumes, and provide a relatively quick, accurate and reliable protocol that should be useful in future experimental studies of environmental estrogenic compounds. (C) 2001 Elsevier Science B.V. All rights reserved. C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Scallet, AC (reprint author), US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, 3900 NCTR Dr, Jefferson, AR 72079 USA. NR 29 TC 10 Z9 10 U1 1 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-0270 J9 J NEUROSCI METH JI J. Neurosci. Methods PD JAN 15 PY 2001 VL 104 IS 2 BP 113 EP 121 DI 10.1016/S0165-0270(00)00331-9 PG 9 WC Biochemical Research Methods; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA 395UG UT WOS:000166599200001 PM 11164237 ER PT J AU Beland, FA Muschel, RJ Schwab, M Ito, N AF Beland, FA Muschel, RJ Schwab, M Ito, N TI Untitled SO CANCER LETTERS LA English DT Editorial Material C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Univ Penn, Sch Med, Dept Pathol, Philadelphia, PA 19104 USA. Deutsch Krebsforschungszentrum, D-6900 Heidelberg, Germany. Nagoya City Univ, Sch Med, Nobuyuki Ho, Nagoya, Aichi 467, Japan. RP Beland, FA (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCI IRELAND LTD PI CLARE PA CUSTOMER RELATIONS MANAGER, BAY 15, SHANNON INDUSTRIAL ESTATE CO, CLARE, IRELAND SN 0304-3835 J9 CANCER LETT JI Cancer Lett. PD JAN 10 PY 2001 VL 162 IS 1 BP 1 EP 1 DI 10.1016/S0304-3835(00)00682-0 PG 1 WC Oncology SC Oncology GA 428BA UT WOS:000168440200001 ER PT J AU Pollard, AJ Frasch, C AF Pollard, AJ Frasch, C TI Development of natural immunity to Neisseria meningitidis SO VACCINE LA English DT Review DE Neisseria meningitidis; epidemic potential; nasopharyngeal ID OUTER-MEMBRANE PROTEIN; MANNOSE-BINDING PROTEIN; B MENINGOCOCCAL DISEASE; T-CELL RESPONSES; SERUM BACTERICIDAL ACTIVITY; JUVENILE RHESUS-MONKEYS; ESCHERICHIA-COLI K92; SEROGROUP-B; VESICLE VACCINE; CAPSULAR POLYSACCHARIDE AB Although meningococcal disease is rare in industrialized nations, Neisseria meningitidis holds a prominent position amongst pediatric infections because of the dramatic clinical presentation of the disease, high mortality, epidemic potential and the recent disappearance of many other important infectious diseases in developed countries through improvements in public health and vaccination. The precise nature of natural immunity to meningococci remains unknown, although a complex interaction between the organism and nasopharyngeal mucosal barrier, innate immune mechanisms and acquired immunity is involved. Study of the mechanisms of natural immunity may provide the key to development of vaccines that can reduce the burden of disease in early childhood. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 British Columbias Childrens Hosp, Div Infect Dis & Immunol, British Columbia Res Inst Childrens & Womens Hlth, Vancouver, BC V5Z 4H4, Canada. Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD USA. RP Pollard, AJ (reprint author), British Columbias Childrens Hosp, Div Infect Dis & Immunol, British Columbia Res Inst Childrens & Womens Hlth, 950 W 28th Ave,Room 375, Vancouver, BC V5Z 4H4, Canada. NR 250 TC 85 Z9 90 U1 2 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0264-410X J9 VACCINE JI Vaccine PD JAN 8 PY 2001 VL 19 IS 11-12 BP 1327 EP 1346 DI 10.1016/S0264-410X(00)00333-9 PG 20 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 394HB UT WOS:000166517000002 PM 11163654 ER PT J AU Nass, PH Elkins, KL Weir, JP AF Nass, PH Elkins, KL Weir, JP TI Protective immunity against herpes simplex virus generated by DNA vaccination compared to natural infection SO VACCINE LA English DT Article DE herpes simplex virus; DNA vaccination; knockout mice ID CELL-DEFICIENT MICE; GENETIC IMMUNIZATION; HSV-1 CHALLENGE; GENITAL HERPES; GLYCOPROTEIN-B; VACCINES; RESPONSES; EXPRESSION; KERATITIS; DISEASE AB To evaluate the utility of plasmid DNA vaccination against disease caused by herpes simplex virus (HSV), we compared the strength of protection against lethal challenge following natural virus infection with that following vaccination with a plasmid encoding HSV glycoprotein go (gD-DNA). We further determined the cellular basis of each type of protection using lymphocyte deficient knockout mice. Establishment of immunity to HSV using live virus immunization required CD8 (+) T cells and B cells, but not CD4(+) or gamma/delta (+) T cells, and was related to specific antibody levels: surprisingly, CD4 knockout mice had large quantities of IgG anti-HSV serum antibodies. Establishment of immunity to HSV using gD-DNA immunization approached the strength of that generated following sublethal infection, but was dependent on alpha/beta (+) CD4(+) T cells, CD8(+). T cells, B cells, and even partially on gamma/delta (+) T cells, and not strictly correlated with antibody levels. (C) 2001 Elsevier Science Ltd. All rights reserved. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Lab DNA Viruses, Rockville, MD 20852 USA. US FDA, Lab Mycobacteria, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Weir, JP (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Lab DNA Viruses, HFM-457,1401 Rockville Pike, Rockville, MD 20852 USA. NR 31 TC 25 Z9 31 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 8 PY 2001 VL 19 IS 11-12 BP 1538 EP 1546 DI 10.1016/S0264-410X(00)00380-7 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA 394HB UT WOS:000166517000028 PM 11163680 ER PT J AU Henney, JE AF Henney, JE TI Nominations for advisory panels SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Henney, JE (reprint author), US FDA, HF-1,14-71,5600 Fishers Ln, 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 JAN 3 PY 2001 VL 285 IS 1 BP 34 EP 34 DI 10.1001/jama.285.1.34 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 387GH UT WOS:000166114500006 PM 11150092 ER PT J AU Henney, JE AF Henney, JE TI New combination drug for HIV SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Henney, JE (reprint author), US FDA, HF-1,Room 14-71,5600 Fishers Ln, 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 JAN 3 PY 2001 VL 285 IS 1 BP 34 EP 34 DI 10.1001/jama.285.1.34 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 387GH UT WOS:000166114500005 PM 11150092 ER PT J AU Henney, JE AF Henney, JE TI Devices for in-stent restenosis SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT News Item C1 US FDA, Rockville, MD 20857 USA. RP Henney, JE (reprint author), US FDA, HF-1,Room 14-71,5600 Fishers Ln, 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 JAN 3 PY 2001 VL 285 IS 1 BP 34 EP 34 DI 10.1001/jama.285.1.34 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 387GH UT WOS:000166114500004 PM 11150092 ER PT J AU Oliver, JF Ostroff, SM AF Oliver, JF Ostroff, SM TI Preventing Vibrio parahaemolyticus infection SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Atlanta, GA USA. RP Oliver, JF (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 1 TC 1 Z9 1 U1 0 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 JAN 3 PY 2001 VL 285 IS 1 BP 42 EP 43 DI 10.1001/jama.285.1.42 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA 387GH UT WOS:000166114500019 PM 11150104 ER PT B AU Witters, D Portnoy, S Casamento, J Ruggera, P Bassen, H AF Witters, D Portnoy, S Casamento, J Ruggera, P Bassen, H GP IEEE IEEE TI Medical device EMI: FDA analysis of incident reports, and recent concerns for security systems and wireless medical telemetry SO 2001 IEEE EMC INTERNATIONAL SYMPOSIUM, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Electromagnetic Compatibility CY AUG 13-17, 2001 CL MONTREAL, CANADA SP IEEE, EMC Soc ID PACEMAKERS AB FDA has evaluated reports of medical device malfunctions caused by electromagnetic interference (EMI), performed device testing, and developed standardized test procedures. Over 500 incident reports are suspected to be attributable to EMI affecting cardiac devices. More than 80 of these reports involve cardiac and other medical device interactions with electronic security systems. EMI presents a risk to patient safety and medical device effectiveness that is likely to continue as the use of electromagnetic energy in the medical device environment increases (e.g., cell phones, security systems). Recent developments can reduce these risks, such as the allocation of dedicated frequency bands for the new wireless medical telemetry service (WMTS) designed to protect transmissions of patient vital signs from interference by other intentional transmitters. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Witters, D (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-6569-0 PY 2001 BP 1289 EP 1291 PG 3 WC Engineering, Electrical & Electronic SC Engineering GA BT07Y UT WOS:000171881500256 ER PT B AU Silberberg, JL AF Silberberg, JL GP IEEE IEEE TI Achieving medical device EMC: The role of regulations, standards, guidelines and publications SO 2001 IEEE EMC INTERNATIONAL SYMPOSIUM, VOLS 1 AND 2 LA English DT Proceedings Paper CT IEEE International Symposium on Electromagnetic Compatibility CY AUG 13-17, 2001 CL MONTREAL, CANADA SP IEEE, EMC Soc ID ELECTROMAGNETIC-INTERFERENCE; CELLULAR PHONES; HOSPITALS; FIELDS; EQUIPMENT AB Many organizations around the world are currently working to improve EMC of electrical and electronic medical devices. Anecdotal evidence indicates that medical device manufacturers and healthcare providers are becoming increasingly knowledgeable and diligent regarding medical device EMI and EMC. Existing and new wireless services and other sources of EMD continue to proliferate; however at the same time, there is continuing development of regulations, standards, guidelines and publications that are intended to help prevent EMI and promote EMC and that can be applied to the safe use of RF sources and medical devices in hospitals. This paper provides a critical overview of the impact of such regulations, standards, guidelines and publications and their role in minimizing EMI malfunctions in healthcare. It also provides a bibliography that lists many of these important works. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Silberberg, JL (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 115 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA BN 0-7803-6569-0 PY 2001 BP 1298 EP 1303 PG 6 WC Engineering, Electrical & Electronic SC Engineering GA BT07Y UT WOS:000171881500258 ER PT S AU Wear, KA AF Wear, KA BE Yuhas, DE Schneider, SC TI A model to predict dispersion in cancellous bone SO 2001 IEEE ULTRASONICS SYMPOSIUM PROCEEDINGS, VOLS 1 AND 2 SE ULTRASONICS SYMPOSIUM LA English DT Proceedings Paper CT IEEE International Ultrasonic Symposium CY OCT 07-10, 2001 CL ATLANTA, GA SP Ultrason, Ferrelect, & Frequency Control Soc ID ULTRASONIC VELOCITY; TRABECULAR BONE; HUMAN CALCANEUS; ACOUSTIC-WAVES; PHASE-VELOCITY; HIP FRACTURE; OS CALCIS; ATTENUATION; DENSITY; SPEED AB In contrast to most biologic tissues, phase velocity in cancellous bone tends to decrease with frequency. A stratified model, consisting of alternating layers of bone and marrow (in vivo) or water (in vitro), has been employed to study this phenomenon. Phase velocity was measured from 300-700 kHz in phantoms consisting of regularly-spaced parallel polystyrene sheets in water, and 30 calcanea in vitro. For the phantoms, the agreement between theory and experiment was good. For the calcanea, the model performs well for predicting the frequency dependence of phase velocity. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Wear, KA (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. NR 26 TC 1 Z9 1 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1051-0117 BN 0-7803-7177-1 J9 ULTRASON PY 2001 BP 1217 EP 1220 PG 4 WC Acoustics; Engineering, Electrical & Electronic; Physics, Applied; Physics, Condensed Matter SC Acoustics; Engineering; Physics GA BU75C UT WOS:000176890800263 ER PT B AU Brown, DG AF Brown, DG BE Cohen, CJ TI The evaluation of computer-aided diagnosis systems: An FDA perspective SO 30TH APPLIED IMAGERY PATTERN RECOGNITION WORKSHOP, PROCEEDINGS: ANALYSIS AND UNDERSTANDING OF TIME VARYING IMAGERY LA English DT Proceedings Paper CT 30th Annual Applied Imagery Pattern Recognition Workshop (AIPR 2001) CY OCT 10-12, 2001 CL WASHINGTON, D.C. SP IEEE Comp Soc, Tech Comm Pattern Anal & Machine Intelligence AB Computer-aided diagnosis (CADx) systems have begun a successful transition from academic research to commercial implementation. FDA approval of CADx for PAP smear reading in 1995 and for breast cancer detection in 1998 were major milestones in this process. As Agency experience with these devices has increased, a consensus is emerging concerning factors to be considered in the evaluation required during the approval process. Key elements determining the nature of the proof of safety and effectiveness required by the Agency include the intrinsic level of risk associated with the device and the medical condition that it is meant to address, the precise claims made for the device, and the degree of oversight exercised over its use. The Agency expects that an increasing number of CADx devices will be submitted to it in the future and that guidelines will have to be formulated to assist manufacturers in navigating the approval process. C1 US FDA, Ctr Dev & Radiol Hlth, Rockville, MD 20857 USA. RP Brown, DG (reprint author), US FDA, Ctr Dev & Radiol Hlth, Rockville, MD 20857 USA. NR 3 TC 1 Z9 1 U1 0 U2 0 PU IEEE COMPUTER SOC PI LOS ALAMITOS PA 10662 LOS VAQUEROS CIRCLE, PO BOX 3014, LOS ALAMITOS, CA 90720-1264 USA BN 0-7695-1245-3 PY 2001 BP 17 EP 20 DI 10.1109/AIPR.2001.991197 PG 4 WC Computer Science, Artificial Intelligence; Computer Science, Cybernetics; Engineering, Biomedical; Imaging Science & Photographic Technology SC Computer Science; Engineering; Imaging Science & Photographic Technology GA BT89D UT WOS:000174364500003 ER PT J AU Yu, LX Ellison, CD Conner, DP Lesko, LJ Hussain, AS AF Yu, LX Ellison, CD Conner, DP Lesko, LJ Hussain, AS TI Influence of drug release properties of conventional solid dosage forms on the systemic exposure of highly soluble drugs SO AAPS PHARMSCI LA English DT Article DE small intestinal transit; dissolution; disintegration; absorption modeling; bioequivalence ID IN-VIVO DISSOLUTION; ABSORPTION; TRANSIT; MODEL; CLASSIFICATION; HUMANS AB This study was designed to theoretically investigate the influence of drug release properties, characterized by the disintegration of a solid dosage form and dissolution of drug particles, on the systemic exposure of highly soluble drugs in immediate release products. An absorption model was developed by considering disintegration of a solid dosage form, dissolution of drug particles, gastrointestinal transit flow, and intestinal absorption processes. The absorption model was linked to a conventional pharmacokinetic model to evaluate the effect of disintegration and dissolution on the peak exposure (C-max) and total exposure of area under the curve (AUC). Numerical methods were used to solve the model equations. The simulations show that the effect of disintegration of a dosage form and dissolution of drug particles depend on the permeability of a drug, with a low-permeability drug having a greater effect. To provide similar exposure to an oral solution formulation, a solid dosage form containing a low-permeability drug would need to dissolve more rapidly than a solid dosage form containing a high-permeability drug. It was shown theoretically for poorly permeable drugs that the disintegration rate constant has to be greater than 9 hour(-1) (equivalent to approximately 90% in 30 minutes) to make both AUC and C-max ratios higher than .9, ensuring the confidence interval of .80 to 1.25. The rapid in vitro release requirement of at least 85% dissolved in 30 minutes is sufficient for highly soluble and highly permeable drugs. However, for highly soluble and poorly permeable drugs, the appropriate in vitro release requirement seems to be 90% dissolved in 30 minutes. C1 US FDA, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Yu, LX (reprint author), US FDA, Off Pharmaceut Sci, 5600 Fishers Lane, Rockville, MD 20857 USA. RI Yu, Lawrence/L-6280-2016 NR 16 TC 8 Z9 9 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 2001 VL 3 IS 3 BP art. no. EP 24 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 493GN UT WOS:000172213800011 ER PT J AU Kopleman, SH Augsburger, LL NguyenPho, A Zito, WS Muller, FX AF Kopleman, SH Augsburger, LL NguyenPho, A Zito, WS Muller, FX TI Selected physical and chemical properties of commercial Hypericum perforatum extracts relevant for formulated product quality and performance SO AAPS PHARMSCI LA English DT Article DE Hypericum perforatum; St John's Wort; Nutraceuticals ID ST-JOHNS-WORT; ANTIDEPRESSANT ACTIVITY; HYPERFORIN; STABILITY; DOPAMINE AB Objective. The complex composition-activity relationship of botanicals such as St John's Wort (SJW) presents a major challenge to product development, manufacture, and establishment of appropriate quality and performance standards for the formulated products. As part of a larger study aimed at addressing that challenge, the goals of the present study are to (1) determine and compare the phytochemical profiles of 3 commercial SJW extracts; (2) assess the possible impact of humidity, temperature, and light on their stability; and (3) evaluate several physical properties important to the development of solid dosage forms for these extracts. Methods. An adapted analytical method was developed and validated to determine phytochemical profiles and assess their stability. The extract physical properties measured were particle size (Malvern Mastersizer), flow (Carr's compressibility index; minimum orifice diameter), hygroscopicity (method of Callahan et al), and low-pressure compression physics (method of Heda et al). Results. The phytochemical properties differed greatly among the extracts and were extremely sensitive to changes in storage conditions, with marked instability under conditions of elevated humidity. All extracts exhibited moderate to free-flow properties and were very hygroscopic. Compression properties varied among the extracts and differed from a common use excipient, microcrystalline cellulose. Conclusions. Three commercial sources of SJW extracts exhibited different physical and chemical properties. Standardization to 1 or 2 marker compounds does not ensure chemical equivalence nor necessarily equivalent pharmacological activity. Flow and compression properties appear suitable for automatic capsule-filling machines, but hygroscopicity and the moisture sensitivity of the phytochemical profile are concerns. C1 Univ Maryland, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. US FDA, Div Prod Qual Res, Kensington, MD 20891 USA. St Johns Univ, Dept Pharmaceut Sci, Jamaica, NY 11439 USA. GlaxoSmithKline, Pharmaceut Dev, King Of Prussia, PA 19406 USA. RP Augsburger, LL (reprint author), Univ Maryland, Dept Pharmaceut Sci, 20 N Pine St, Baltimore, MD 21201 USA. NR 35 TC 8 Z9 8 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 2001 VL 3 IS 4 AR 26 PG 18 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 521GV UT WOS:000173831600009 ER PT J AU Zheng, JH Chen, CT Au, JLS Wientjes, MG AF Zheng, JH Chen, CT Au, JLS Wientjes, MG TI Time- and concentration-dependent penetration of doxorubicin in prostate tumors SO AAPS PHARMSCI LA English DT Article DE doxorubicin; delivery; apoptosis; solid tumor ID DRUG-RESPONSE ASSAY; BLADDER TISSUE PHARMACOKINETICS; SOLID TUMORS; IN-VIVO; CANCER-PATIENTS; OVARIAN-CANCER; SPHEROIDS; PACLITAXEL; ANTHRACYCLINES; CHEMOTHERAPY AB The penetration of paclitaxel into multilayered solid tumors is time- and concentration-dependent, a result of the drug-induced apoptosis and changes in tissue composition. This study evaluates whether this tissue penetration property applies to other highly protein-bound drugs capable of inducing apoptosis. The penetration of doxorubicin was studied in histocultures of prostate xenograft tumors and tumor specimens obtained from patients who underwent radical prostatectomy. The kinetics of drug uptake and eff lux in whole tumor histocultures were studied by analyzing the average tumor drug concentration using high-pressure liquid chromatography. Spatial drug distribution in tumors and the drug concentration gradient across the tumors were studied using fluorescence microscopy. The results indicate that drug penetration was limited to the periphery for 12 hours in patient tumors and to 24 hours in the more densely packed xenograft tumors. Subsequently, the rate of drug penetration to the deeper tumor tissue increased abruptly in tumors treated with higher drug concentrations capable of inducing apoptosis (i.e., = 5 mum), but not in tumors treated with lower concentrations. These findings indicate a time- and concentration-dependent penetration of doxorubicin in solid tumors, similar to that of paclitaxel. We conclude that doxorubicin penetration in solid tumors is time- and concentration-dependent and is enhanced by drug-induced cell death. C1 Ohio State Univ, Coll Pharm, Columbus, OH 43210 USA. Ohio State Univ, James Canc Hosp, Columbus, OH 43210 USA. Ohio State Univ, Solove Res Inst, Columbus, OH 43210 USA. US FDA, Rockville, MD 20850 USA. Natl Hlth Res Inst, Div Biotechnol & Pharmaceut Res, Taipei 221, Taiwan. RP Wientjes, MG (reprint author), Ohio State Univ, Coll Pharm, 500 W 12th Ave, Columbus, OH 43210 USA. RI Chen, Chiung-Tong/D-2075-2010 NR 35 TC 27 Z9 27 U1 2 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 2001 VL 3 IS 2 AR 15 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 478ZF UT WOS:000171378900006 ER PT J AU Maloney, EM Wilks, R Hisada, M Hanchard, B Cranston, B Jack, N Edwards, J Bartholomew, C Morgan, O Biggar, R Manns, A AF Maloney, EM Wilks, R Hisada, M Hanchard, B Cranston, B Jack, N Edwards, J Bartholomew, C Morgan, O Biggar, R Manns, A TI HTLV-I infection in family members of patients with ATL, TSP and ID: Results from the Jamaica and Trinidad family studies. SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. Univ W Indies, Kingston 7, Jamaica. Med Res Fdn Trinidad & Tobago, Port Of Spain, Trinid & Tobago. NR 0 TC 1 Z9 1 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. PY 2001 VL 17 SU 1 BP S38 EP S38 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300127 ER PT J AU Wilks, R Braham, J LaGrenade, L Hanchard, B Morgan, OSC Miley, WJ Goebel, PB Cranston, B Manns, A AF Wilks, R Braham, J LaGrenade, L Hanchard, B Morgan, OSC Miley, WJ Goebel, PB Cranston, B Manns, A TI HTLV-I associated diseases in three generations of a Jamaican family SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Meeting Abstract C1 Univ W Indies, Kingston 7, Jamaica. NCI, Viral Epidemiol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Sci Applicat Int Corp, Frederick, MD 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 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PY 2001 VL 17 SU 1 BP S45 EP S45 PG 1 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA 446EE UT WOS:000169499300155 ER PT J AU Strizheva, GD Carsillo, T Kruger, WD Sullivan, EJ Ryu, JH Henske, EP AF Strizheva, GD Carsillo, T Kruger, WD Sullivan, EJ Ryu, JH Henske, EP TI The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis SO AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE LA English DT Article ID HIPPEL-LINDAU-DISEASE; GERMLINE MUTATIONS; UNRELATED PATIENTS; SOMATIC MOSAICISM; GENE TSC1; LYMPHANGIOLEIOMYOMATOSIS; COMPLEX; PRODUCT; CANCER; NEUROFIBROMATOSIS AB Lymphangiomyomatosis (LAM) is a progressive and often fatal interstitial lung disease characterized by a diffuse proliferation of abnormal smooth muscle cells in the lungs. LAM is of unusual interest biologically because it affects almost exclusively young women. LAM can occur as an isolated disorder (sporadic LAM) or in association with tuberous sclerosis complex (TSC). Because only a minority of women with TSC develops symptomatic LAM, we hypothesized that a relationship might exist between the type of germline TSC1 or TSC2 gene mutation and the risk of developing LAM. We examined all 41 exons of the TSC2 gene and 21 coding exons of the TSC1 gene for mutations in a group of 14 women with both TSC and LAM using single-strand conformation polymorphism analysis. Seven mutations were found in TSC2 and one in TSC1. Of the seven patients with TSC2 mutations, two had the same in-frame exon 40 deletion and one had an exon 41 missense change. We conclude that germline mutations in the extreme carboxy-terminus of tuberin can result in LAM. Further studies will be required to determine whether mutations in exons 40 and 41 are associated with an increased incidence and/or severity of LAM in women with TSC. C1 Fox Chase Canc Ctr, Philadelphia, PA 19111 USA. Russian State Med Univ, Dept Mol Biol, Moscow 117437, Russia. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Mayo Clin, Div Pulm & Crit Care Med & Internal Med, Rochester, MN USA. RP Henske, EP (reprint author), Fox Chase Canc Ctr, 7701 Burholme Ave, Philadelphia, PA 19111 USA. RI kruger, warren/A-6407-2008 OI kruger, warren/0000-0002-4990-3695 FU NHLBI NIH HHS [HL 60746] NR 34 TC 74 Z9 74 U1 0 U2 3 PU AMER THORACIC SOC PI NEW YORK PA 1740 BROADWAY, NEW YORK, NY 10019-4374 USA SN 1073-449X J9 AM J RESP CRIT CARE JI Am. J. Respir. Crit. Care Med. PD JAN PY 2001 VL 163 IS 1 BP 253 EP 258 PG 6 WC Critical Care Medicine; Respiratory System SC General & Internal Medicine; Respiratory System GA 394TV UT WOS:000166540100042 PM 11208653 ER PT J AU Caruso, JA Heitkemper, DT B'Hymer, C AF Caruso, JA Heitkemper, DT B'Hymer, C TI An evaluation of extraction techniques for arsenic species from freeze-dried apple samples SO ANALYST LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; PLASMA-MASS-SPECTROMETRY; ATOMIC-ABSORPTION SPECTROMETRY; HYDRIDE GENERATION; DIMETHYLARSINIC ACID; SEAFOOD PRODUCTS; SPECIATION; METABOLISM; DIGESTION; RABBITS AB The extraction of arsenic from freeze-dried apples and subsequent determination of individual arsenic species by HPLC-ICP-MS is described. Solvent extraction with sonication using various aqueous and aqueous/solvent mixtures was initially evaluated by measuring total arsenic extracted by ICP-MS. A two step procedure using overnight treatment with alpha -amylase enzyme followed by sonication for 6 h with 40 : 60 acetonitrile-water was found to provide good extraction efficiency. The concentration of arsenic extracted was compared with the concentration of total arsenic in the samples determined using ICP-MS after microwave digestion in order to calculate extraction efficiency. Individual arsenic species in the extracts were measured using HPLC-ICP-MS. The three most abundant arsenic species found were arsenite, arsenate and dimethylarsinic acid. Total arsenic concentrations in the freeze-dried apple samples ranged from 8.2 to 80.9 mug kg(-1) As, dry mass. By HPLC-ICP-MS, the relative amount of inorganic arsenic in the samples ranged from 73 to 90% of the sum of the arsenic species detected in each sample. C1 Univ Cincinnati, Dept Chem, Cincinnati, OH 45221 USA. US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. RP Caruso, JA (reprint author), Univ Cincinnati, Dept Chem, Mail Locat 0172, Cincinnati, OH 45221 USA. FU NIEHS NIH HHS [ES04908] NR 27 TC 68 Z9 74 U1 2 U2 14 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD,, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 J9 ANALYST JI Analyst PY 2001 VL 126 IS 2 BP 136 EP 140 DI 10.1039/b009825f PG 5 WC Chemistry, Analytical SC Chemistry GA 399ME UT WOS:000166816300002 PM 11235091 ER PT J AU Vela, NP Heitkemper, DT Stewart, KR AF Vela, NP Heitkemper, DT Stewart, KR TI Arsenic extraction and speciation in carrots using accelerated solvent extraction, liquid chromatography and plasma mass spectrometry SO ANALYST LA English DT Article ID ATOMIC-ABSORPTION SPECTROMETRY; MEMBRANE HYDRIDE GENERATION; SEAFOOD PRODUCTS; ICP-MS; ION CHROMATOGRAPHY; UNITED-STATES; SEPARATION; FOOD; DIET; EXCRETION AB Arsenic present in freeze-dried carrots was extracted using accelerated solvent extraction (ASE). Several parameters, including selection of the dispersing agent, extraction time, number of extraction cycles, particle size and extraction temperature, were evaluated to optimize the ASE method. Filtering and treatment with C-18 SPE cartridges were also evaluated as part of the sample preparation procedure before speciation analysis. The method was validated by spiking single arsenical and mixed arsenical standards on the dispersing agent and on portions of freeze-dried carrot prior to extraction. LC-ICP-MS was used to determine individual arsenic species in the carrot extracts. A weak anion-exchange column was used for the separation of As(iii), As(v), monomethylarsonic acid (MMA), dimethylarsinic acid and arsenobetaine. Optimized sample preparation conditions were applied to the extraction of arsenic in nine freeze-dried carrot samples. Total arsenic concentration in the carrot samples ranged from less than 20 ng g(-1) to 18.7 mug g(-1), dry mass. Extraction efficiency, defined as the ratio of the sum of individual arsenic species concentrations to total arsenic, ranged from 80 to 102% for freeze-dried carrots with arsenic concentrations greater than the limit of quantitation. Inorganic As(iii) and As(v) were the only species found in samples that contained less than 400 ng g(-1) total arsenic. MMA and an unidentified arsenic compound were present in some of the samples with higher total arsenic content. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45237 USA. Belcan TechServ, Cincinnati, OH 45249 USA. RP Vela, NP (reprint author), US FDA, Forens Chem Ctr, 6751 Steger Dr, Cincinnati, OH 45237 USA. NR 40 TC 78 Z9 79 U1 2 U2 20 PU ROYAL SOC CHEMISTRY PI CAMBRIDGE PA THOMAS GRAHAM HOUSE, SCIENCE PARK, MILTON RD,, CAMBRIDGE CB4 0WF, CAMBS, ENGLAND SN 0003-2654 J9 ANALYST JI Analyst PY 2001 VL 126 IS 7 BP 1011 EP 1017 DI 10.1039/b102420p PG 7 WC Chemistry, Analytical SC Chemistry GA 450ZW UT WOS:000169775600006 PM 11478628 ER PT J AU Lesko, LJ Atkinson, AJ AF Lesko, LJ Atkinson, AJ TI Use of biomarkers and surrogate endpoints in drug development and regulatory decision making: Criteria, validation, strategies SO ANNUAL REVIEW OF PHARMACOLOGY AND TOXICOLOGY LA English DT Review DE regulatory review; clinical endpoints ID CLINICAL-TRIALS; END-POINTS; GENE; THERAPY; MARKERS; ATHEROSCLEROSIS; HYPERTENSION; PHARMACOLOGY; INTEGRATION; MICROARRAY AB In the future, biomarkers will play an increasingly important role in all phases of drug development, including regulatory review. However, only a few of these biomarkers will become established well enough to serve in regulatory decision making as surrogate endpoints, thereby substituting for traditional clinical endpoints. Even generally accepted surrogate endpoints are unlikely to capture all the therapeutic benefits and potential adverse effects a drug will have in a diverse patient population. Accordingly, combinations of biomarkers probably will be needed to provide a more complete characterization of the spectrum of pharmacologic response. In the future, pharmacogenomic approaches, including those based on differential expression of gene arrays, will provide panels of relevant biomarkers that can be expected to transform the drug development process. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Lesko, LJ (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. NR 57 TC 236 Z9 242 U1 2 U2 15 PU ANNUAL REVIEWS PI PALO ALTO PA 4139 EL CAMINO WAY, PO BOX 10139, PALO ALTO, CA 94303-0139 USA SN 0362-1642 J9 ANNU REV PHARMACOL JI Annu. Rev. Pharmacol. Toxicol. PY 2001 VL 41 BP 347 EP 366 DI 10.1146/annurev.pharmtox.41.1.347 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 428AR UT WOS:000168439400014 PM 11264461 ER PT J AU Blair, RM Fang, H Gaylor, D Sheehan, DM AF Blair, RM Fang, H Gaylor, D Sheehan, DM TI Threshold analysis of selected dose-response data for endocrine active chemicals SO APMIS LA English DT Article; Proceedings Paper CT International Workshop on Hormones and Endocrine Disrupters in Food and Water: Possible Effects on Human Health CY MAY 27-30, 2000 CL RIGS HOSP, COPENHAGEN, DENMARK HO RIGS HOSP DE dose-response; endocrine disruptor; endogenous dose; Michaelis-Menten; non-hormone controlled background; risk assessment; threshold ID RISK ASSESSMENT; DEVELOPMENTAL TOXICITY; MECHANISTIC MODEL; GENE-EXPRESSION; RAT; ESTROGEN; HEALTH; DIOXIN; MICE; HORMONES AB Using a biologically relevant mathematical model, the Michaelis-Menten equation, we examined published data from endocrine active chemicals for evidence of no-threshold dose-response curves. Data were fit to a modified Michaelis-Menten equation which accounted for total background response. Subsequently, the data sets were analyzed using non-linear regression in order to estimate the four parameters of interest (non-hormone controlled background (B-nh), maximum response (R-max), endogenous hormone level (D-0), and the dose at which a half-maximal response was observed (ED50)) and to determine the fit to the fully modified Michaelis-Menten equation. Subsequently, response data were adjusted to account for B-nh and then normalized to R-max, while dose data were adjusted to account for D-0 and then normalized to the ED50. This data set was combined into a single, composite data set and fit to the fully modified Michaelis-Menten equation. We examined 31 data sets (24 endpoints) from studies on 9 different chemical/hormone treatments. Twenty-six of the data sets fit the modified Michaelis-Menten equation with high multiple correlation coefficients (r>0.90). The normalized data demonstrated a good fit to the modified Michaelis-Menten equation. These results indicate that a variety of biological responses fit the modified Michaelis-Menten equation, which does not have a threshold dose term. C1 US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Sheehan, DM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, 3900 NCTR Rd,HFT-130, Jefferson, AR 72079 USA. NR 44 TC 0 Z9 0 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S528 EP S538 PG 11 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500100 ER PT J AU Jegou, B Soto, A Sundlof, S Stephany, R Meyer, H Leffers, H Korner, W Bollmer, G McLachlan, J Daxenberger, A Bergman, A Brock, J Sundlof, S Morris, I Pescovitz, O Skakkebaek, N AF Jegou, B Soto, A Sundlof, S Stephany, R Meyer, H Leffers, H Korner, W Bollmer, G McLachlan, J Daxenberger, A Bergman, A Brock, J Sundlof, S Morris, I Pescovitz, O Skakkebaek, N TI General discussion - Existing guidelines for the use of meat hormones and other food additives in Europe and USA SO APMIS LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RI Jegou, Bernard/I-4742-2015 NR 1 TC 2 Z9 3 U1 0 U2 0 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S551 EP S556 PG 6 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500103 ER PT J AU Sheehan, D Foster, P Risbridger, G Pflieger-Bruss, S Larsen, P Keizer-Schrama, SD AF Sheehan, D Foster, P Risbridger, G Pflieger-Bruss, S Larsen, P Keizer-Schrama, SD TI Effects of phthalate esters on the developing reproductive tract of male rats - Discussion SO APMIS LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Sheehan, D (reprint author), US FDA, Rockville, MD 20857 USA. RI Risbridger, Gail/B-8655-2008 OI Risbridger, Gail/0000-0003-3089-4028 NR 0 TC 0 Z9 0 U1 0 U2 1 PU MUNKSGAARD INT PUBL LTD PI COPENHAGEN PA 35 NORRE SOGADE, PO BOX 2148, DK-1016 COPENHAGEN, DENMARK SN 0903-4641 J9 APMIS JI APMIS PY 2001 VL 109 SU 103 BP S276 EP S277 PG 2 WC Immunology; Microbiology; Pathology SC Immunology; Microbiology; Pathology GA 456UW UT WOS:000170101500057 ER PT J AU Nakhasi, HL Ramanujam, M Atreya, CD Hobman, TC Lee, N Esmaili, A Duncan, RC AF Nakhasi, HL Ramanujam, M Atreya, CD Hobman, TC Lee, N Esmaili, A Duncan, RC TI Rubella virus glycoprotein interaction with the endoplasmic reticulum calreticulin and calnexin SO ARCHIVES OF VIROLOGY LA English DT Article ID SUBGENOMIC MESSENGER-RNA; HEPATITIS-C VIRUS; STRUCTURAL PROTEINS; INTRACELLULAR-TRANSPORT; MOLECULAR CHAPERONE; ENVELOPE GLYCOPROTEINS; RETENTION SIGNAL; E2 GLYCOPROTEIN; QUALITY-CONTROL; COS CELLS AB Very little is known about the cellular factors that are required for the maturation of rubella virus glycoproteins (E2 and E1) in the endoplasmic reticulum of the infected cell. In the present study, we established the interaction of the ER chaperone proteins, calreticulin and calnexin. with the RV El and E2 proteins in cells stably expressing the viral proteins. The interaction between E2 and calnexin was significantly higher than with calreticulin. In pulse-chase experiments, the half-life of the E2-calnexin was >45 min, whereas the half-life of the calreticulin-E2 interaction was similar to 10 min. Tunicamycin and castanosper mine treatments altered the mobilities of intracellular El and E2, due to either lack of oligosaccharide ligand addition or trimming of terminal glucose residues, respectively. Further, the drug treatments resulted in a loss of El and E2 interaction with calreticulin or calnexin, thereby demonstrating that the interaction is through monoglucosylated forms of RV proteins. These studies suggest that the interaction of RV glycoproteins with the ER chaperone proteins is essential for their maturation in the endoplasmic reticulum. C1 Univ Alberta, Dept Cell Biol, Edmonton, AB, Canada. US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viral Dis, Div Viral Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, DETTD,Div Allergen Prod & Parasitol, Lab Parasit Biol & Biochem, Bethesda, MD 20892 USA. RP Nakhasi, HL (reprint author), US FDA, Ctr Biol Evaluat & Res, DETTD,Div Allergen Prod & Parasitol, Lab Parasit Biol & Biochem, HFM-310,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 46 TC 12 Z9 13 U1 0 U2 0 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 2001 VL 146 IS 1 BP 1 EP 14 DI 10.1007/s007050170186 PG 14 WC Virology SC Virology GA 398NZ UT WOS:000166763700001 PM 11266204 ER PT J AU Feldman, SA Crim, RL Audet, SA Beeler, JA AF Feldman, SA Crim, RL Audet, SA Beeler, JA TI Human respiratory syncytial virus surface glycoproteins F, G and SH form an oligomeric complex SO ARCHIVES OF VIROLOGY LA English DT Article ID RECOMBINANT VACCINIA VIRUS; MOUTH-DISEASE VIRUS; FUSION GLYCOPROTEIN; CELL-FUSION; HEMAGGLUTININ-NEURAMINIDASE; ATTACHMENT GLYCOPROTEIN; HEPARAN-SULFATE; G-PROTEIN; IDENTIFICATION; INFECTION AB In order to study structural associations, RSV surface glycoproteins were evaluated using heparin agarose affinity chromatography (HAAC). When RSV-infected cell lysate was analyzed by HAAC, all three surface glycoproteins, (F, G and SH), were eluted. Similarly, when separate lysates from Vero cells infected with vaccinia recombinants expressing F (vvF), G (vvG) and SH (vvSH) proteins were subjected to HAAC, only vvF and vvG expressed proteins bound to heparin, whereas vvSH expressed protein did not bind. When lysates from vvF, vvG and vvSH-infected Vero cells were mixed prior to HAAC, only F and G bound heparin. In contrast, following co-infection of Vero cells with vvF, vvG and vvSH, all three proteins were detected subsequent to HAAC. Following HAAC of A2-infected cell lysate and lysate from vvF, vvG and vvSH co-infected Vero cells, two high molecular weight complexes of 175 Kd and 210 Kd, respectively, were identified that reacted with anti-F, anti-G and anti-SH antisera. In addition, anti-SH antiserum was able to co-precipitate RSV F, G and SH. Using HAAC and a NaCl step gradient we demonstrated that a fraction of RSV F, G and SH eluted at higher salt concentrations than either purified F or G protein. Taken together, these data suggest that RSV F, G and SH glycoproteins can form an oligomeric complex within infected cells and this complex has a higher affinity for heparin than either G or F protein alone. C1 US FDA, Ctr Biol Evaluat & Res, Lab Pediat & Resp Viruses, Bethesda, MD USA. RP Beeler, JA (reprint author), US FDA, Ctr Biol Evaluat & Res, Bldg 29A,3B-05,HFM 463,1401 Rockville Pike, Rockville, MD 20852 USA. NR 44 TC 19 Z9 22 U1 0 U2 2 PU SPRINGER-VERLAG WIEN PI VIENNA PA SACHSENPLATZ 4-6, PO BOX 89, A-1201 VIENNA, AUSTRIA SN 0304-8608 J9 ARCH VIROL JI Arch. Virol. PY 2001 VL 146 IS 12 BP 2369 EP 2383 DI 10.1007/s007050170009 PG 15 WC Virology SC Virology GA 504DU UT WOS:000172842700009 PM 11811686 ER PT J AU Alayash, AI AF Alayash, AI TI Is there a need for blood substitutes in the new millennium and what should we expect in the way of safety and efficacy? A research perspective - Editorial comment SO ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY LA English DT Editorial Material ID NITRIC-OXIDE; HEMOGLOBIN C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 13 TC 5 Z9 5 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1073-1199 J9 ARTIF CELL BLOOD SUB JI Artif. Cells Blood Substit. Immobil. Biotechnol. PY 2001 VL 29 IS 1 BP 1 EP 3 DI 10.1081/BIO-100001251 PG 3 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Materials Science, Biomaterials SC Biotechnology & Applied Microbiology; Engineering; Materials Science GA 407HV UT WOS:000167266900001 PM 11280680 ER PT J AU Alayash, AI AF Alayash, AI TI Oxidative mechanisms of hemoglobin-based blood substitutes SO ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY LA English DT Article DE hemoglobin; blood substitutes; oxidative stress ID CROSS-LINKED HEMOGLOBIN; HYDROGEN-PEROXIDE; POLYOXYETHYLENE CONJUGATE; FERRYL INTERMEDIATE; HEME DEGRADATION; MYOGLOBIN; FERRYLHEMOGLOBIN; GENE; OXYHEMOGLOBIN; AUTOXIDATION AB Chemically or genetically altered cell-free hemoglobin (Hb) has been developed as an oxygen carrying therapeutic. Site-directed modifications are introduced and serve to stabilize the protein molecules in a tetrameric and/or a polymeric functional form. Direct cytotoxic effects associated with cell-free Hb have been ascribed to redox reactions (involving either I or 2 electron steps) between the heme group and peroxides. These interactions are the basis of the pseudoperoxidase activity of Hb and can be cytotoxic when reactive species are formed at relatively high concentrations during inflammation and typically lead to cell death. Peroxides relevant to biological systems include hydrogen peroxide (H2O2), lipid hydroperoxides (LOOH), and peroxynitrite (ONOO-). Reactions between Hb and peroxides form the ferryl oxidation state of the protein, analogous to compounds I and II formed in the catalytic cycle of many peroxidase enzymes. This higher oxidation state of the protein is a potent oxidant capable of promoting oxidative damage to most classes of biological molecules. Further complications are thought to arise through the disruption of key signaling pathways resulting from alteration of or destruction of important physiological mediators. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, NIH Campus,Bldg 29,Rm 112, Bethesda, MD 20892 USA. NR 40 TC 18 Z9 19 U1 1 U2 7 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1073-1199 J9 ARTIF CELL BLOOD SUB JI Artif. Cells Blood Substit. Immobil. Biotechnol. PY 2001 VL 29 IS 6 BP 415 EP 425 DI 10.1081/BIO-100108547 PG 11 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Materials Science, Biomaterials SC Biotechnology & Applied Microbiology; Engineering; Materials Science GA 509JX UT WOS:000173145600001 PM 11795628 ER PT S AU Dornish, M Kaplan, D Skaugrud, O AF Dornish, M Kaplan, D Skaugrud, O BE Hunkeler, D Cherrington, A Prokop, A Rajotte, R TI Standards and guidelines for biopolymers in tissue-engineered medical products - ASTM alginate and chitosan standard guides SO BIOARTIFICIAL ORGANS III: TISSUE SOURCING, IMMUNOISOLATION, AND CLINICAL TRIALS SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Bioartificial Organs III - Tissue Sourcing, Immunoisoloation, and Clinical Trials CY OCT 07-11, 2000 CL DAVOS, SWITZERLAND SP Bellevue Asset Management, European Community Cost 840 Encapsulat Network, Fonds Natl Suisse, Inotech Encapsulat AG, Juvenile Diabetes Fdn Int, NIH, Natl Sci Fdn, Nisco Engn, Novartis Pharmaceut Canada Inc, Pronova Biomed, United Engn Fdn DE ASTM; tissue-engineered medical products; TEMPS; alginate; chitosan; standardization ID VESICOURETERAL REFLUX; DELIVERY; CELLS; TRANSPLANTATION; BIOMATERIALS; REGENERATION; HEPATOCYTES; IMPLANTS; PANCREAS; CANINES AB The American Society for Testing and Materials (ASTM) is making a concerted effort to establish standards and guidelines for the entire field of tissue-engineered medical products (TEMPS). Safety, consistency. and functionality of biomaterials used as matrices, scaffolds, and immobilizing agents in TEMPS are a concern. Therefore, the ASTM has established a number of task groups to produce standards and guidelines for such biomaterials. Alginate is a naturally occurring biomaterial used for immobilizing living cells to form an artificial organ, such as encapsulated pancreatic islets. In order to aid in successful clinical applications and to help expedite regulatory approval, the alginate used must be fully documented. The ASTM alginate guide gives information on selection of testing methodologies and safety criteria. Critical parameters such as monomer content, molecular weight, and viscosity, in addition to more general parameters, such as dry matter content, heavy metal content. bioburden, and endotoxin content are described in the ASTM document. In a like manner, the characterization parameters for chitosan, a bioadhesive polycationic polysaccharide, are described in a separate guide. For chitosan, the degree of deacetylation is of critical importance. Control of protein content and, hence, potential for hypersensitivity, endotoxin content, and total bioburden are important in chitosan preparations for TEMPS. Together these two guides represent part of the effort on behalf of the ASTM and other interested parties to ensure quality and standardization in TEMPS. C1 Pronova Biomed AS, N-0349 Oslo, Norway. US FDA, Ctr Devices & Radiol Hlth, Div Mech & Mat Sci, Rockville, MD 20857 USA. RP Dornish, M (reprint author), Pronova Biomed AS, Gaustadalleen 21, N-0349 Oslo, Norway. NR 43 TC 66 Z9 71 U1 1 U2 16 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-342-4 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 2001 VL 944 BP 388 EP 397 PG 10 WC Engineering, Biomedical; Multidisciplinary Sciences; Transplantation SC Engineering; Science & Technology - Other Topics; Transplantation GA BT69D UT WOS:000173774500033 PM 11797688 ER PT J AU Moody, JD Heinze, TM Cerniglia, CE AF Moody, JD Heinze, TM Cerniglia, CE TI Fungal transformation of the tricyclic antidepressant amoxapine: Identification of N-carbomethoxy compounds formed as artifacts by phosgene in chloroform used for the extraction of metabolites SO BIOCATALYSIS AND BIOTRANSFORMATION LA English DT Article DE chloroform; phosgene; N-carbomethoxy compounds; amoxapine; C. elegans; microbial biotransformation ID CUNNINGHAMELLA-ELEGANS; MAMMALIAN METABOLITES; BIOTRANSFORMATION; ANTIHISTAMINES AB The biotransformation of the antidepressant drug amoxapine by Cunninghamella elegans formed three metabolites, 7-hydroxyamoxapine, N-formyl-7-hydroxyamoxapine, and N-formylamoxapine; two other compounds were only present when chloroform was used in the extraction process. All five of the compounds were separated by reversed-phase HPLC, then analyzed by H-1 NMR and mass spectrometry, and by C-13 NMR when sample quantities permitted. The artifacts were identified as N-carbomethoxy-7-hydroxyamoxapine and N-carbomethoxyamoxapine. Phosgene is a decomposition product of chloroform that can form carbomethoxy compounds at the secondary nitrogen of a piperazine ring in an alcoholic solution. Since N-carbomethoxy compounds were not observed when ethyl acetate was used for extraction of the culture medium, they were considered artifacts and not metabolites. These findings suggest that chloroform should be tested for the formation of phosgene before using it to extract any compound with a piperazine ring or any other amine-containing structure. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, 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 12 TC 2 Z9 2 U1 0 U2 2 PU HARWOOD ACAD PUBL GMBH PI READING PA C/O STBS LTD, PO BOX 90, READING RG1 8JL, BERKS, ENGLAND SN 1024-2422 J9 BIOCATAL BIOTRANSFOR JI Biocatal. Biotransform. PY 2001 VL 19 IS 2 BP 155 EP 161 DI 10.3109/10242420109003642 PG 7 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology GA 458BM UT WOS:000170173400005 ER PT J AU Kodell, RL Chen, JJ AF Kodell, RL Chen, JJ TI Inferring effects on tumor frequencies and times to observation in the analysis of tumor multiplicity data SO BIOMETRICAL JOURNAL LA English DT Article DE chemoprevention; initiation-promotion; likelihood ratio; logrank; negative binomial; phototoxicity; skin painting; Weibull ID CANCER CHEMOPREVENTION EXPERIMENTS; STATISTICAL-ANALYSIS; TRANSGENIC MOUSE; MODELS; CARCINOGENICITY; INHIBITION; SACRIFICE; RISK; MICE AB A sequential likelihood-ratio strategy for analyzing tumor multiplicity data from animal bioassays is described and illustrated. The likelihood function is composed of a negative binomial component for the number of induced tumors per animal and a Weibull component for the time to observation of such tumors. The method can distinguish whether differences in tumor responses between treatment groups are due to differences in numbers of induced tumors or to differences in times to observation of such tumors. Although adapted from the underlying model of KOKOSKA (KOKOSKA, 1987, Biometrics 43, 525-534; KOKOSKA et al., 1993, Anticancer Research 13, 1357-1364), the proposed testing methodology can give different results from the Kokoska method, as is shown in an example with real data. Several extensions of the model are described. C1 Natl Ctr Toxicol Res, US FDA, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 24 TC 2 Z9 2 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2001 VL 43 IS 4 BP 447 EP 460 DI 10.1002/1521-4036(200108)43:4<447::AID-BIMJ447>3.0.CO;2-J PG 14 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 471FP UT WOS:000170918100004 ER PT J AU Lu, HL Huque, M AF Lu, HL Huque, M TI Understanding on the pooled test for controlled clinical trials SO BIOMETRICAL JOURNAL LA English DT Article DE pooled tests; type I error rate; interaction tests; power; clinical trial AB Several independent clinical trials are usually conducted to demonstrate and support the evidence of the efficacy of a new drug. When not all the trials demonstrate a treatment effect because-of a lack of statistical significant finding, the sponsor sometimes conducts a post hoc pooled test and uses the pooled result as extra statistical evidence. In this paper, we study the extent of type I error rate inflation with the post hoc pooled analysis and the power of interaction test in assessing the homogeneity of the trials with respect to treatment effect size. We also compare the power of several test procedures with or without pooled test involved and discuss the appropriateness of pooled tests under different alternative hypotheses. C1 US FDA, CDER, Off Biostat, Div 3, Rockville, MD 20857 USA. NR 8 TC 2 Z9 2 U1 0 U2 0 PU AKADEMIE VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0323-3847 J9 BIOMETRICAL J JI Biom. J. PY 2001 VL 43 IS 7 BP 909 EP 923 PG 15 WC Mathematical & Computational Biology; Statistics & Probability SC Mathematical & Computational Biology; Mathematics GA 496XV UT WOS:000172424400009 ER PT S AU Ilev, IK Waynant, RW AF Ilev, IK Waynant, RW BE Gannot, I Gulyaev, YV Papazoglou, TG VanSwol, CFP TI Ultraviolet, visible and infrared laser delivery using laser-to-fiber coupling via a grazing-incidence-based hollow taper SO BIOMONITORING AND ENDOSCOPY TECHNOLOGIES SE Proceedings of SPIE LA English DT Proceedings Paper CT Conference on Biomonitoring and Endoscopy Technologies CY JUL 05-06, 2000 CL AMSTERDAM, NETHERLANDS SP European Opt Soc, SPIE, European Laser Assoc DE laser radiation delivery; hollow taper; optical fiber; grazing incidence AB We present a novel all-optical-waveguide method for ultraviolet (UV), visible (VIS) and infrared (IR) laser delivery including a lens-free method of laser-to-fiber coupling using a simple uncoated glass hollow taper. Based on the grazing incidence effect, the hollow taper provides a way of direct launching, without any intermediate focussing elements, high power laser radiation into delivery fibers. Because of the mutual action of the nearly parallel laser excitation, the mode coupling process, and mode filtering effect, the hollow taper serves as a mode converter that transforms the highly multimode profile of the input laser emission into a high-quality Gaussian-shaped profile at the taper output. When the grazing incidence effect of the taper is applied to laser delivery, the maintenance of high reflectance coefficients in a wide spectral regions allows to utilize the same uncoated hollow taper for laser radiation in the UV, VIS and IR ranges. Applying the experimental hollow-taper-based delivery systems, we obtain high laser-to-taper and taper-to-fiber coupling efficiencies. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP US FDA, Ctr Devices & Radiol Hlth, HFZ-134, Rockville, MD 20857 USA. NR 17 TC 1 Z9 1 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-3814-6 J9 PROC SPIE PY 2001 VL 4158 BP 97 EP 104 DI 10.1117/12.413782 PG 8 WC Engineering, Biomedical; Medical Laboratory Technology; Optics; Surgery SC Engineering; Medical Laboratory Technology; Optics; Surgery GA BS04B UT WOS:000168412400013 ER PT J AU Brorson, K Swann, PG Lizzio, E Maudru, T Peden, K Stein, KE AF Brorson, K Swann, PG Lizzio, E Maudru, T Peden, K Stein, KE TI Use of a quantitative product-enhanced reverse transcriptase assay to monitor retrovirus levels in mAb cell-culture and downstream processing SO BIOTECHNOLOGY PROGRESS LA English DT Article ID MONOCLONAL-ANTIBODIES; VIRUS; REMOVAL; PCR; CHROMATOGRAPHY; SIGNALS; MICE AB Murine hybridoma cells used in the production of monoclonal antibodies (mAb's) produce endogenous type C retrovirus particles. Regulatory agencies require a demonstration that mAb's intended for human use are free of retrovirus with an adequate margin of safety. This is usually achieved by validation 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 this report, we assess the utility of the TaqMan fluorogenic 5'-nuclease Product-Enhanced Reverse Transcriptase (TM-PERT) assay for measuring reverse transcriptase (RT) activity in cell-culture samples and RT removal by models of processing steps. The levels of RT activity contained in laboratory-scale cell-culture harvests (10(8)-10(13) pU/ mL) were substantially above the detection limit of the TM-PERT assay (similar to 10(6) pU/ mL). The nature of the RT activity from cell culture was complex, but the bulk of RT activity in clarified mAb harvests appears to be contained in large molecular weight viral particles. In laboratory-scale chromatographic runs, sufficient RT activity was present in mAb-containing eluates to accurately calculate its log(10) reduction value (LRV), typically between 2 and 4 log(10) per step. Monoclonal antibody purified using a model purification scheme consisting of three serial columns contained some residual RT activity near the limit of detection. The data indicate that the TM-PERT assay, because it is quantitative and highly sensitive and can be used to analyze a large number of samples in a short period, is ideally suited to investigate and optimize retrovirus clearance in purification processes. C1 US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Brorson, K (reprint author), US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, 29 Lincoln Dr, Bethesda, MD 20892 USA. NR 36 TC 23 Z9 25 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 8756-7938 J9 BIOTECHNOL PROGR JI Biotechnol. Prog. PD JAN-FEB PY 2001 VL 17 IS 1 BP 188 EP 196 DI 10.1021/bp000153q PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 399QX UT WOS:000166824800021 PM 11170498 ER PT J AU Bichsel, VE Liotta, LA Petricoin, EF AF Bichsel, VE Liotta, LA Petricoin, EF TI Cancer proteomics: From biomarker discovery to signal pathway profiling SO CANCER JOURNAL LA English DT Article DE proteomics; cancer; microdissection; signaling; pharmacoproteomics ID LASER CAPTURE MICRODISSECTION; POLYACRYLAMIDE-GEL ELECTROPHORESIS; TRANSITIONAL-CELL CARCINOMAS; PROSTATE-SPECIFIC ANTIGEN; GENE-EXPRESSION PATTERNS; MAMMARY EPITHELIAL-CELLS; ACID-BINDING PROTEIN; LOW-FEMTOMOLE LEVEL; MASS-SPECTROMETRY; IN-VITRO AB In the post-genomic era of science, the field of proteomics promises the discovery of new molecular targets for therapy, biomarkers for early detection, and new endpoints for therapeutic efficacy and toxicity. Patient-specific targeted therapeutics with reduced toxicity and increased efficacy, the ultimate goal for rational drug development, can only be achieved if direct analyses of the tissue cells in the actual human malignancy are analyzed. To that end, technologies such as Laser Capture Microdissection (LCM), is providing unparalleled access to the purified diseased human cells directly from tissue specimens. However, limited availability of patient material is a challenge towards the development of new highly sensitive proteomic methodologies. Two-dimensional gel electrophoresis (2D-PAGE), still the mainstay of most proteomic analysis of disease, is being complemented, and in some instances replaced by new exciting approaches to multiparametric protein characterization. The use of rapid, high throughput mass spectrometric-based fingerprints of peptides and proteins may prove to be Valuable for new molecular classification of human tumors and disease stages. Coupled with LCM, high-density protein arrays, antibody arrays, and small molecular arrays, could have a substantial impact on proteomic profiling of human malignancies. Finally, detailed real-time knowledge about the states of intracellular signaling circuitry and pathways in the normal and malignant cells before, during and after thera py will yield invaluable information about mechanism of action and efficacy of existing and novel therapeutics for the treatment of human cancer. C1 US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prod, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Therapeut Prod, Bethesda, MD 20892 USA. NR 82 TC 104 Z9 118 U1 0 U2 5 PU JONES AND BARTLETT PUBLISHERS PI SUDBURY PA 40 TALL PONE DR, SUDBURY, MA 01776 USA SN 1528-9117 J9 CANCER J JI Cancer J. Sci. Am. PD JAN-FEB PY 2001 VL 7 IS 1 BP 69 EP 78 PG 10 WC Oncology SC Oncology GA 406LV UT WOS:000167218400009 PM 11269650 ER PT J AU Wiese, FW Thompson, PA Kadlubar, FF AF Wiese, FW Thompson, PA Kadlubar, FF TI Carcinogen substrate specificity of human COX-1 and COX-2 SO CARCINOGENESIS LA English DT Article ID APC(DELTA-716) KNOCKOUT MICE; ENDOPEROXIDE-H SYNTHASE-1; PROSTAGLANDIN G/H SYNTHASE-1; INTESTINAL POLYP DEVELOPMENT; DOCOSAHEXAENOIC ACID DHA; MUTAGENIC ACTIVATION; MEDIATED METABOLISM; AROMATIC-AMINES; MESSENGER-RNA; EXPRESSION AB The activation of carcinogenic aromatic and heterocyclic amines and benzo[a]pyrene-7,8-diol to intracellular electrophiles by prostaglandin H synthase (COX) is well documented for ovine sources of this enzyme. Here, the arachidonic acid-dependent activation of substrates by human (h)COX-1 and-2 is examined, utilizing recombinant enzymes. The COX-dependent activation of benzidine (BZ), 4-aminobiphenyl, (+)benzo[a]pyrene-7,8-diol, (+)benzo[a]pyrene-7,8-diol, 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline (MeIQx), 2-amino-3-methylimidazo [4,5-f]quinoline (IQ), 2-amino-1-methyl-6-phenylimidazo [4,5-b] pyridine (PhIP), and 4,4'-methylenebis (2-chloroaniline) (MOCA) is assessed by means of COX-catalyzed, covalent DNA binding. The hCOX isozymes activated all substrates tested, activation varied from barely detectable for IQ (0.76 and 1.52 pmol bound/mg DNA for COX-1 and -2, respectively) to a high of 65 and 117 pmol bound/mg DNA for COX-1 and -2, respectively, for the activation of MOCA, BZ, which is an excellent peroxidase substrate, did not exhibit high DNA binding levels in hCOX assays and this phenomenon was found to be due to high levels of binding to protein, which effectively competed with the DNA for binding in the assay, The demonstrated ability of the COX enzymes to activate a variety of environmental and dietary carcinogens indicates a potential role for COX in the activation pathway of aromatic and heterocyclic amines and polycyclic hydrocarbons at extra-hepatic sites during early or late stages of carcinogenesis. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Div Toxicol, Little Rock, AR 72205 USA. RP Kadlubar, FF (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. NR 49 TC 65 Z9 74 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 2001 VL 22 IS 1 BP 5 EP 10 DI 10.1093/carcin/22.1.5 PG 6 WC Oncology SC Oncology GA 396BW UT WOS:000166617300002 PM 11159734 ER PT J AU Gautier, JC Richoz, J Welti, DH Markovic, J Gremaud, E Guengerich, FP Turesky, RJ AF Gautier, JC Richoz, J Welti, DH Markovic, J Gremaud, E Guengerich, FP Turesky, RJ TI Metabolism of ochratoxin A: Absence of formation of genotoxic derivatives by human and rat enzymes SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID PROSTAGLANDIN-H SYNTHASE; HUMAN CYTOCHROME-P450 1A2; DNA ADDUCT FORMATION; LIPID-PEROXIDATION; STRAND BREAKS; MICROSOMAL CYTOCHROME-P-450; OMEGA-HYDROXYLATION; KIDNEY MICROSOMES; RENAL CARCINOGEN; SEX-DIFFERENCES AB Ochratoxin A (OTA) is a potent renal carcinogen in male rats, although its made of carcinogenicity is not known. The metabolism and covalent binding of OTA to DNA were investigated in vitro viith cytochromes P450, glutathione S-transferases, prostaglandin K-synthase, and horseradish peroxidase. Incubation of OTA with rat or human liver microsomes fortified with NADPH resulted in formation of 4-(R)-hydroxyochratoxin A at low rates [10-25 pmol min(-1) (mg of protein)(-1)]. There was no evidence of OTA metabolism and glutathione conjugate formation with rat, mouse, or human kidney microsomes or postmitochondrial supernatants (S-9) [ < 5 pmol. min(-1) (mg of protein)(-1)]. Recombinant human cytochromes P450 (P450) 1A1 and 3A4 formed 4-(R)-hydroxyochratoxin A at low rates [0.08 and 0.06 pmol min(-1) (pmol of P450)(-1), respectively]; no oxidation products of OTA were detected with recombinant human P450 1A2 or 2E1 or rat P450 1A2 or 2C11 [<0.02 pmol min(-1) (pmol of P450)(-1)]. Prostaglandin H-synthase produced small amounts of an apolar product [33 pmol min(-1) (mg of protein)(-1)], and OTA products were not formed with horseradish peroxidase. There was no evidence of DNA adduct formation when [H-3]OTA was incubated with these enzyme systems in the presence of calf thymus DNA (<20 adducts/10(9) DNA bases); however, these enzymes catalyzed DNA adduct formation with the genotoxins aflatoxin B-1, 2-amino-3-methylimidazo[4,5-f]quinoline, benzo[a]pyrene, and pentachlorophenol. There was also no detectable [H-3]-OTA bound in vivo to kidney DNA of male Fischer-344 rats treated orally with [H-3]OTA (1 mg/kg, 100 mCi/mmol, 24 h exposure, <2.7 adducts/10(9) DNA bases), based upon liquid scintillation counting. However, P-32-postlabeling experiments did show evidence of DNA lesions with total adduct levels ranging from 31 to 71 adducts/10(9) DNA bases, while adducts in untreated rat kidney ranged from 6 to 24 adducts/10(9) DNA bases. These results do not support the premise that OTA or metabolically activated species covalently bind to DNA and suggest that the P-32-postlabeled lesions are due to products derived from OTA-mediated cytotoxicity. C1 Vanderbilt Univ, Sch Med, Ctr Mol Toxicol, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Biochem, Nashville, TN 37232 USA. Nestec Ltd, Nestle Res Ctr, CH-1000 Lausanne, Switzerland. RP Turesky, RJ (reprint author), Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 67 TC 75 Z9 76 U1 0 U2 3 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 JAN PY 2001 VL 14 IS 1 BP 34 EP 45 DI 10.1021/tx000070j PG 12 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 393ZW UT WOS:000166500400005 PM 11170506 ER PT J AU Yang, YC Yan, J Churchwell, M Beger, R Chan, PC Doerge, DR Fu, PP Chou, MW AF Yang, YC Yan, J Churchwell, M Beger, R Chan, PC Doerge, DR Fu, PP Chou, MW TI Development of a P-32-postlabeling/HPLC method for detection of dehydroretronecine-derived DNA adducts in vivo and in vitro SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID PYRROLIZIDINE ALKALOID MONOCROTALINE; PROTEIN CROSS-LINKS; AROMATIC-HYDROCARBONS; CARCINOGENIC ACTIVITY; MASS-SPECTROMETRY; LIVER MICROSOMES; MAMMALIAN-CELLS; RAT-LIVER; IN-VITRO; METABOLITE AB Pyrrolizidine alkaloids are naturally occurring genotoxic chemicals produced by a large number of plants. Metabolism of pyrrolizidine alkaloids in vivo and in vitro generates dehydroretronecine (DHR) as a common reactive metabolite. In this study, we report the development of a P-32-postlabeling/HPLC method for detection of (i) two DHR-3'-dGMP and four DHR-3'-dAMP adducts and (ii) a set of eight DHR-derived DNA adducts in vitro and in vivo. The approach involves (1) synthesis of DHR-3'-dGMP, DHR-3'-dAMP, and DHR-3',5'-dG-bisphosphate standards and characterization of their structures by mass and H-1 NMR spectral analyses, (2) development of optimal conditions for enzymatic DNA digestion, adduct enrichment, and P-32-postlabeling, and (3) development of optimal HPLC conditions. Using this methodology, we have detected eight DHR-derived DNA adducts, including the two epimeric DHR-3',5'-dG-bisphosphate adducts both in vitro and in vivo. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 72 TC 38 Z9 39 U1 1 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 JAN PY 2001 VL 14 IS 1 BP 91 EP 100 DI 10.1021/tx000149o PG 10 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 393ZW UT WOS:000166500400011 PM 11170512 ER PT J AU Yang, YC Yan, J Doerge, DR Chan, PC Fu, PP Chou, MW AF Yang, YC Yan, J Doerge, DR Chan, PC Fu, PP Chou, MW TI Metabolic activation of the tumorigenic pyrrolizidine alkaloid, riddelliine, leading to DNA adduct formation in vivo SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID RAT-LIVER MICROSOMES; HAMSTER OVARY CELLS; S-PHASE SYNTHESIS; IN-VITRO; AROMATIC-HYDROCARBONS; CARCINOGENIC ACTIVITY; INVIVO TREATMENT; CROSS-LINKING; INVITRO; MOUSE AB Riddelliine is a representative naturally occurring genotoxic pyrrolizidine alkaloid. We have studied the mechanism by which riddelliine induces hepatocellular tumors in vivo. Metabolism of riddelliine by liver microsomes of F344 female rats generated riddelliine N-oxide and dehydroretronecine (DHR) as major metabolites. Metabolism was enhanced when liver microsomes from phenobarbital-treated rats were used. Metabolism in the presence of calf thymus DNA resulted in eight DNA adducts that were identical to those obtained from the reaction of DHR with calf thymus DNA. Two of these adducts were identified as DHR-modified 7-deoxyguanosin-N-2-yl epimers (DHR-3'-dGMP); the other six were DHR-derived DNA adducts, but their structures were not characterized. A similar DNA adduct profile was detected in the livers of female F344 rats fed riddelliine, and a dose-response relationship was obtained for the level of the total (eight) DHR-derived DNA adducts and the level of the DHR-3'-dGMP adducts. These results suggest that riddelliine induces liver tumors in rats through a genotoxic mechanism and the eight DHR-derived DNA adducts are likely to contribute to liver tumor development. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Chou, MW (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 67 TC 62 Z9 63 U1 2 U2 12 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0893-228X J9 CHEM RES TOXICOL JI Chem. Res. Toxicol. PD JAN PY 2001 VL 14 IS 1 BP 101 EP 109 DI 10.1021/tx000150n PG 9 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA 393ZW UT WOS:000166500400012 PM 11170513 ER PT J AU Sacks, LV Pendle, S Orlovic, D Andre, M Popara, M Moore, G Thonell, L Hurwitz, S AF Sacks, LV Pendle, S Orlovic, D Andre, M Popara, M Moore, G Thonell, L Hurwitz, S TI Adjunctive salvage therapy with inhaled aminoglycosides for patients with persistent smear-positive pulmonary tuberculosis SO CLINICAL INFECTIOUS DISEASES LA English DT Article ID MULTIDRUG-RESISTANT TUBERCULOSIS; HUMAN-IMMUNODEFICIENCY-VIRUS; INFECTED PATIENTS; CYSTIC-FIBROSIS; SUSCEPTIBILITY; OUTBREAK; BACILLI; TRIAL AB A proportion of patients with drug-resistant and drug-susceptible tuberculosis (TB) have sputum that is smear and culture positive for Mycobacterium tuberculosis for a prolonged period of time, despite conventional therapy. Among such patients with refractory TB, an unblinded, observational study was undertaken that used conventional TB therapy and adjunctive aerosol aminoglycosides. Patients with persistent smear- and culture-positive sputum for M. tuberculosis (despite greater than or equal to2 months of optimal systemic therapy) were selected for adjunctive treatment via inhalation with aminoglycosides, and microbiological responses were monitored. Thirteen of 19 patients converted to smear negativity during the study: 6 of 7 with drug-susceptible TB and 7 of 12 with drug-resistant TB. Among patients with drug-susceptible TB, the median time to sputum conversion was 23 days, a shorter time than for a population of historical control patients. Recurrent infection was not observed. Adjunctive aerosol aminoglycosides may expedite sterilization of sputum among certain patients with refractory TB and diminish the risk of transmission. C1 Sizwe Trop Dis Hosp, Johannesburg, South Africa. RP Sacks, LV (reprint author), Ctr Drug Evaluat & Res, Div Special Pathogens, 9201 Corp Blvd,HFD 590, Rockville, MD 20850 USA. NR 21 TC 34 Z9 34 U1 0 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 2001 VL 32 IS 1 BP 44 EP 49 DI 10.1086/317524 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA 385PF UT WOS:000166012300008 PM 11118385 ER PT J AU Chen, ML Lesko, L Williams, RL AF Chen, ML Lesko, L Williams, RL TI Measures of exposure versus measures of rate and extent of absorption SO CLINICAL PHARMACOKINETICS LA English DT Review ID NUMERICAL DECONVOLUTION; DRUG ABSORPTION; INPUT FUNCTIONS; BIOEQUIVALENCE; AREA; RELEASE; BIOAVAILABILITY; METRICS; CURVE; PHARMACODYNAMICS AB Regulatory assessment of bioavailability and bioequivalence in the US frequently rc lies on measures of rate and extent of absorption. Rate of absorption is not only difficult to measure but also bears little clinical relevance. This paper proposes that measures of bioavailability and bioequivalence for drugs that achieve their therapeutic effects after entry into the systemic circulation are best expressed in terms of early [partial area under the concentration-time curve (AUC)], peak plasma or serum drug concentration and total AUC exposure for a plasma or serum concentration-time profile. With suitable documentation, these systemic exposure measures can be related to efficacy and tolerability outcomes. The early measure is recommended for an immediate release drug product where a better control of drug absorption is needed, for example to ensure rapid onset of a therapeutic effect or to avoid an adverse reaction from a fast input rate. The 3 systemic exposure measures for bioavailability and bioequivalence studies can provide critical links between product quality and clinical outcome and thereby reduce the current emphasis on rate of absorption. C1 US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci HFD350, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. US Pharmacopia, Rockville, MD USA. RP Chen, ML (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci HFD350, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 48 TC 38 Z9 39 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 2001 VL 40 IS 8 BP 565 EP 572 DI 10.2165/00003088-200140080-00001 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 465GC UT WOS:000170580400001 PM 11523723 ER PT J AU Chen, ML Lesko, LJ AF Chen, ML Lesko, LJ TI Individual bioequivalence revisited SO CLINICAL PHARMACOKINETICS LA English DT Review ID BY-FORMULATION INTERACTION; VARIABILITY; CRITERION AB For decades, the establishment of bioequivalence has generally relied on the comparison of population averages between the test and reference formulations. In the early 1990s, individual bioequivalence was proposed to ensure that an individual could be switched from the reference product to the test product with unchanged efficacy and safety. Since 1997, the US Food and Drug Administration (FDA) has published three guidance documents on the proposed criterion and statistical methodology for the individual bioequivalence approach. From a scientific stand-point, the individual bioequivalence criterion appears to offer several advantages for some drug products compared with the average criterion. It allows comparison of intraindividual variances, scaling the bioequivalence criterion to the reference variability and detection of an important subject-by-formulation interaction if it exists. Based on these considerations, the FDA has recently recommended replicate study designs for modified release dosage forms and highly variable drug products. The. new criterion also promotes inclusion of a heterogeneous population of volunteers in bioequivalence studies. Despite all the advantages of the individual bioequivalence approach, questions remain on the optimal use of replicate study designs and the proposed criterion for evaluation of bioequivalence between formulations. In the finalised guidance documents, therefore, the FDA maintains the average bioequivalence criterion while allowing other criteria under certain circumstances. Collection and analysis of bioequivalence data from replicate study designs may permit further assessment and resolution of these questions. C1 US FDA, CDER, OCPB, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Lesko, LJ (reprint author), US FDA, CDER, OCPB, Off Pharmaceut Sci, HFD-850,Woodmont II,1451 Rockville Pike,Room 3016, Rockville, MD 20857 USA. NR 31 TC 23 Z9 26 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 2001 VL 40 IS 10 BP 701 EP 706 DI 10.2165/00003088-200140100-00001 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 489EB UT WOS:000171978100001 PM 11707058 ER PT J AU Gobburu, JVS Marroum, PJ AF Gobburu, JVS Marroum, PJ TI Utilisation of pharmacokinetic-pharmacodynamic modelling and simulation in regulatory decision-making SO CLINICAL PHARMACOKINETICS LA English DT Review ID CLINICAL-TRIALS; PERSPECTIVE; RESPONSES; DESIGNS; AGENTS AB Modelling and simulation (M&S) play an important role in regulatory decision making that affects both the public and industry. Technological advances in various fields related to drug development call for more focus on ways to optimise current drug development practices. Recognition of the potential of M&S by regulatory agencies inevitably has a substantial impact on drug development. The objective of the current review is to present the various regulatory initiatives for application of M&S to clinical drug development. The relevant parts of the various recommendations issued by the US Food and Drug Administration (FDA), Via guidance documents and advisory committee meeting proceedings, are highlighted. Application of M&S to a variety of activities, such as integrating pharmacokinetic-pharmacodynamic knowledge across a new drug application and designing efficient trials, is discussed. Some of the challenges that Pharmaceutical institutions currently face when implementing M&S projects, such as team structure, communication with regulators, training and time constraints, are also presented, and solutions are proposed. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Div Pharmacometr, Rockville, MD 20852 USA. US FDA, Div Pharmaceut Evaluat 1, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Gobburu, JVS (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Div Pharmacometr, 1451 Rockville Pike,Room 5088,HFD-860, Rockville, MD 20852 USA. NR 46 TC 37 Z9 38 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 2001 VL 40 IS 12 BP 883 EP 892 DI 10.2165/00003088-200140120-00001 PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 512CN UT WOS:000173303700001 PM 11735607 ER PT J AU Razzaghi, M Kodell, RL AF Razzaghi, M Kodell, RL TI An extension of the EM algorithm for optimization of constrained likelihood: An application in toxicology SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE incomplete data problems; mixture models; Lagrange multiplier; likelihood ratio; risk assessment ID MAXIMUM-LIKELIHOOD AB Since its introduction in the mid 1970's, the EM algorithm has found a widespread popularity for solving the likelihood equations. Several investigators have used the algorithm in a variety of problems with incomplete information to obtain maximum likelihood estimates in numerous applications. The algorithm, however, becomes inappropriate when the underlying equations are subject to some constraints. Although an extension has been proposed to derive solutions when the parameters are subject to a set of linear constraints, the evaluation of likelihood equations from incomplete data when the equations are subject to a nonlinear constraint is still an open problem. Here, we consider a mixture model, a classical example of incomplete data, and discuss the problem of maximum likelihood estimation of the model parameters when the parameters have to satisfy a nonlinear constraint. An extension of the EM algorithm based on the celebrated Lagrange multiplier will be proposed to solve the equations. An application of the methodology in animal bioassay experiments for risk assessment of toxic substances will be described and data from a toxicological experiment will be used to illustrate the results. C1 Bloomsburg Univ Penn, Dept Math Comp Sci & Stat, Bloomsburg, PA 17815 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 9 TC 1 Z9 1 U1 0 U2 1 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 2001 VL 30 IS 11 BP 2317 EP 2327 DI 10.1081/STA-100107688 PG 11 WC Statistics & Probability SC Mathematics GA 500JR UT WOS:000172624000007 ER PT J AU Wiesenfeld, PW Babu, US O'Donnell, MW AF Wiesenfeld, PW Babu, US O'Donnell, MW TI Effect of long-chain fatty acids in the culture medium on fatty acid composition of WEHI-3 and J774A.1 cells SO COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY B-BIOCHEMISTRY & MOLECULAR BIOLOGY LA English DT Article DE lipid; polyunsaturated fatty acids; macrophage; in vitro; WEHI-3; J774A.1; linoleic acid; alpha-linolenic acid; eicosapentaenoic acid; docosahexaenoic acid ID RAT PERITONEAL-MACROPHAGES; PROSTAGLANDIN SYNTHESIS; ANTILISTERIAL; INVITRO; N-3 AB As a first step in determining the mechanism of action of specific fatty acids on immunological function of macrophages, a comparative study of the: effect of long-chain polyunsaturated fatty acids (PUFA) in the medium was conducted in two macrophage cell lines, J774A.1 and WEHI-3. The baseline fatty-acid profiles of the two cell lines differed in the % distribution of saturated (SFA) and unsaturated fatty acids (UFA). J774A,1 cells had a higher % of SFA (primarily palmitic acid) than WEHI-3 cells. Conversely, WEHI-3 cells had a higher % of UFA (primarily oleic acid) than 5773A.1 cells. Neither cell line had detectable amounts of alpha -linolenic acid (ALA) or eicosapentalnoic acid (EPA). The most abundant polyunsaturated fatty acid in both cells lines was arachidonic acid (AA). The efficiency of transport of fatty acids from the medium to the macrophages by two delivery vehicles (BSA complexes and ethanolic suspensions) was compared. Overall, fatty acids were transported satisfactorily by both delivery systems. Alpha-linolenic acid and doscosahexenoic acid (DHA) were transported more efficiently by the ethanolic suspension system. Linoleic acid (LA) was taken up more completely than ALA, and DHA was taken up more completely than EPA by both cell cultures and delivery systems. A dose-response effect was demonstrated for LA, ALA, EPA and DHA in both J774A.1 and WEHI-3 cells. Addition of polyunsaturated fatty acids (PUFA) to the cell cultures modified the total lipid fatty acid composition of the cells. The presence of ALA in the culture medium resulted in a significant decrease in AA in both cell lines. The omega-3/omega-6 fatty acid ratio (omega -3/omega -6), polyunsaturated/saturated fatty acid ratio (P/S), and unsaturation index (UI) increased directly with the amount of PUFA and omega -3 fatty acid provided in the medium. The results indicate that the macrophage cell lines have similar, but not identical, fatty acid profiles that may be the result of differences in fatty acid metabolism. These distinctions could in turn produce differences in immunological function. The ethanol fatty-acid delivery system, when compared with the fatty acid-BSA complex system, is preferable for measurement of dose-response effects, because the cellular fatty acid content increased in proportion to the amount of fatty acid provided in the medium. Similar dose-response results were observed in a previous in vivo study using flaxseed, rich in ALA, as a source of PUFA. (C) 2001 Elsevier Science Inc. All rights reserved, C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Wiesenfeld, PW (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Murikirk Rd,Mod 1,HFS-842, Laurel, MD 20708 USA. NR 21 TC 14 Z9 15 U1 1 U2 7 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 1096-4959 J9 COMP BIOCHEM PHYS B JI Comp. Biochem. Physiol. B-Biochem. Mol. Biol. PD JAN PY 2001 VL 128 IS 1 BP 123 EP 134 DI 10.1016/S1096-4959(00)00305-5 PG 12 WC Biochemistry & Molecular Biology; Zoology SC Biochemistry & Molecular Biology; Zoology GA 396EX UT WOS:000166624300013 PM 11163311 ER PT J AU Lewis, CJ AF Lewis, CJ TI Comment: Regulatory environment for dietary supplements and botanicals targeted to weight loss SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Editorial Material C1 US FDA, Off Nutrit Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Lewis, CJ (reprint author), US FDA, Off Nutrit Prod Labeling & Dietary Supplements, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU CRC PRESS LLC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 USA SN 1040-8398 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2001 VL 41 IS 1 BP 43 EP 44 DI 10.1080/20014091091724 PG 2 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 390KF UT WOS:000166293700007 PM 11152046 ER PT J CA Food Drug Adm TI Guidance for the clinical evaluation of weight-control drugs SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review C1 US FDA, Div Metab & Endocrine Drug Prod, Rockville, MD 20857 USA. RP US FDA, Div Metab & Endocrine Drug Prod, 5600 Fishers Lane,HFD-510, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU TAYLOR & FRANCIS INC PI PHILADELPHIA PA 520 CHESTNUT STREET, STE 850, PHILADELPHIA, PA 19106 USA SN 1040-8398 EI 1549-7852 J9 CRIT REV FOOD SCI JI Crit. Rev. Food Sci. Nutr. PY 2001 VL 41 IS 1 BP 91 EP 94 PG 4 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 390KF UT WOS:000166293700011 ER PT J AU Kawakami, K Kawakami, M Puri, RK AF Kawakami, K Kawakami, M Puri, RK TI Overexpressed cell surface interleukin-4 receptor molecules can be successfully targeted for antitumor cytotoxin therapy SO CRITICAL REVIEWS IN IMMUNOLOGY LA English DT Article; Proceedings Paper CT 10th International Symposium on the Immunobiology of Proteins and Peptides CY SEP 12-16, 2000 CL TAHOE CITY, CALIFORNIA SP Allergan, Allergene, Baxter Healthcare Corp, Int Bioimmune Syst, Multiple Peptidy Syst, Wyeth Lederle Vaccines DE immunotherapy; cpIL4-PE; preclinical development; clinical trial ID RECOMBINANT HUMAN INTERLEUKIN-4; COMMON GAMMA-CHAIN; CIRCULARLY PERMUTED INTERLEUKIN-4; BREAST-CARCINOMA CELLS; ALPHA-CHAIN; PSEUDOMONAS EXOTOXIN; SIGNAL-TRANSDUCTION; CHIMERIC PROTEIN; KAPOSIS-SARCOMA; IL-2 RECEPTOR AB A variety of human solid cancer cell lines and primary cell cultures has been reported to overexpress high-affinity receptors (R) for interleukin-4 (IL-4), a pleiotropic immunoregulatory cytokine. The significance of IL-4R expression is not known; however, IL-4 is able to upregulate adhesion molecules, inhibit cell proliferation, and mediate signal transduction in tumor cell lines. To target IL-4R, we produced a chimeric protein composed of a circular permuted IL-4 and a mutated form of Pseudomonas exotoxin [termed IL4(38-37)PE38KDEL or cpIL4-PE]. The recombinant cpIL4-PE was highly cytotoxic to cancer cells, but not toxic to normal B cells, T cells, monocytes, and CD34(+), even though these cells express detectable numbers of IL-4R. The cytotoxicity was specific because excess of recombinant IL-4 neutralized the cpIL4-PE effect. To further develop this molecule, in vivo antitumor activity was tested in animal models of human cancer. This agent showed remarkable antitumor activity in AIDS-Kaposi's sarcoma, glioblastoma multiforme, and breast cancer models in immunodeficient animals. cpIL4-PE caused partial or complete regression of established human tumors. Preclinical efficacy and toxicity studies provided a therapeutic window in which this cancer-targeted agent could be used. On the basis of these studies, we initiated a Phase I clinical trial for the treatment of recurrent glioblastoma multiforme. Our preliminary clinical results suggest that cpIL4-PE has antitumor activity against the deadliest form of brain tumors, without detectable toxicity to normal brain tissues. Thus, IL-4 receptors represent novel targets for cancer cytotoxin therapy. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Mol Tumor Biol, Rockville, MD 20852 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, Rockville, MD 20852 USA. NR 74 TC 57 Z9 63 U1 0 U2 0 PU BEGELL HOUSE INC PI NEW YORK PA 79 MADISON AVE, SUITE 1205, NEW YORK, NY 10016-7892 USA SN 1040-8401 J9 CRIT REV IMMUNOL JI Crit. Rev. Immunol. PY 2001 VL 21 IS 1-3 BP 299 EP 310 PG 12 WC Immunology SC Immunology GA 480ZM UT WOS:000171493400021 PM 11642612 ER PT J AU Provost, MC Meyers, CM AF Provost, MC Meyers, CM TI New technologies for patients with end-stage renal disease: The US regulatory perspective SO DIALYSIS, DIALYZERS AND SORBENTS: WHERE ARE WE GOING? SE CONTRIBUTIONS TO NEPHROLOGY LA English DT Article ID BLOOD; HEMODIALYSIS C1 US FDA, Ctr Devices & Radiol Hlth,Off Device Evaluat, Gastroenterol & Renal Devices Branch, Div Reprod Abdominal & Radiol Devices, Rockville, MD 20850 USA. RP Provost, MC (reprint author), US FDA, Ctr Devices & Radiol Hlth,Off Device Evaluat, Gastroenterol & Renal Devices Branch, Div Reprod Abdominal & Radiol Devices, 9200 Corp Blvd,HFZ-470, Rockville, MD 20850 USA. NR 29 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0302-5144 J9 CONTRIB NEPHROL JI Contrib.Nephrol. PY 2001 VL 133 BP 10 EP 22 PG 13 WC Urology & Nephrology SC Urology & Nephrology GA BS74N UT WOS:000171041100002 ER PT J AU Herrmann, PC Liotta, LA Petricoin, EF AF Herrmann, PC Liotta, LA Petricoin, EF TI Cancer proteomics: The state of the art SO DISEASE MARKERS LA English DT Article DE proteomics; laser capture microdissection; cancer; signal transduction ID LASER CAPTURE MICRODISSECTION; MASS-SPECTROMETRY; 2-DIMENSIONAL ELECTROPHORESIS; DIFFERENTIAL EXPRESSION; TAILORED THERAPY; CELL CARCINOMA; IN-VITRO; PROTEIN; IDENTIFICATION; TISSUE AB Now that the human genome has been determined, the field of proteomics is ramping up to tackle the vast protein networks that both control and are controlled by the information encoded by the genome. The study of proteomics should yield an unparalleled understanding of cancer as well as an invaluable new target for therapeutic intervention and markers for early detection. This rapidly expanding field attempts to track the protein interactions responsible for all cellular processes. By careful analysis of these systems, a detailed understanding of the molecular causes and consequences of cancer should emerge. A brief overview of some of the cutting edge technologies employed by this rapidly expanding field is given, along with specific examples of how these technologies are employed. Soon cellular protein networks will be understood at a level that will permit a totally new paradigm of diagnosis and will allow therapy tailored to individual patients and situations. C1 US FDA, Tissue Proteom Unit, Div Therapeut Prod, Ctr Biol Evaluat Res,Clin Proteom Program, Bethesda, MD 20892 USA. NCI, Pathol Lab, Clin Prote Program, NIH, Bethesda, MD 20892 USA. RP Petricoin, EF (reprint author), US FDA, Tissue Proteom Unit, Div Therapeut Prod, Ctr Biol Evaluat Res,Clin Proteom Program, Bldg 29A,Room 2B02,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 50 TC 41 Z9 44 U1 0 U2 0 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 2 BP 49 EP 57 PG 9 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 491LG UT WOS:000172109400003 PM 11673651 ER PT J AU Paweletz, CP Trock, B Pennanen, M Tsangaris, T Magnant, C Liotta, LA Petricoin, EF AF Paweletz, CP Trock, B Pennanen, M Tsangaris, T Magnant, C Liotta, LA Petricoin, EF TI Proteomic patterns of nipple aspirate fluids obtained by SELDI-TOF: Potential for new biomarkers to aid in the diagnosis of breast cancer SO DISEASE MARKERS LA English DT Article ID IONIZATION MASS-SPECTROMETRY; RISK; RADIATION; CYTOLOGY; ANTIGEN; HISTORY AB Nipple aspirate fluid (NAF) has been used for many years as a potential non-invasive method to identify markers for breast cancer risk or early detection. Because individual markers have not been optimal, we are exploring the use of surface enhanced laser desorption and ionization time of flight (SELDI-TOF) mass spectrometry to identify patterns of proteins that might define a proteomic signature for breast cancer. SELDI-TOF was used to analyze a study set of NAF samples that included 12 women with breast cancer and 15 healthy controls (the latter included three women with an abnormal mammogram but subsequent normal biopsy). In this preliminary report, we present data showing that SELDI analysis of NAF is rapid, reproducible, and capable of identifying protein signatures that appear to differentiate NAF samples from breast cancer patients and healthy controls, including those with an abnormal mammogram who were later proven to be biopsy normal. C1 US FDA, CBER, Div Therapeut Prot, Tissue Prote, Bethesda, MD 20892 USA. NCI, Pathol Lab, NIH, Bethesda, MD 20892 USA. Georgetown Univ, Dept Chem, Washington, DC 20057 USA. Johns Hopkins Univ, Dept Urol, Baltimore, MD 21287 USA. Georgetown Univ, Dept Surg, Washington, DC 20007 USA. Sibley Hosp, Dept Surg, Washington, DC 20010 USA. RP Petricoin, EF (reprint author), US FDA, CBER, Div Therapeut Prot, Tissue Prote, Bethesda, MD 20892 USA. NR 24 TC 206 Z9 237 U1 1 U2 5 PU IOS PRESS PI AMSTERDAM PA NIEUWE HEMWEG 6B, 1013 BG AMSTERDAM, NETHERLANDS SN 0278-0240 J9 DIS MARKERS JI Dis. Markers PY 2001 VL 17 IS 4 BP 301 EP 307 PG 7 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Medicine, Research & Experimental; Pathology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Research & Experimental Medicine; Pathology GA 514HZ UT WOS:000173434400011 PM 11790897 ER PT B AU Gagne, RM Shope, TB AF Gagne, RM Shope, TB BE Malone, JF Boyle, G Teunen, D Marsh, DM TI Regulatory initiatives and framework in the USA: Interventional radiology SO DOSE AND IMAGE QUALITY IN DIGITAL IMAGING AND INTERVENTIONAL RADIOLOGY (DIMOND) LA English DT Proceedings Paper CT Workshop on Dose and Image Quality in Digital Imaging and Interventional Radiology CY JUN 24-26, 1999 CL DUBLIN, IRELAND ID CARDIAC-CATHETERIZATION; SKIN INJURIES; RADIODERMATITIS; FLUOROSCOPY; EXPOSURE; ABLATION AB Therapeutic procedures using interventional radiology equipment as the imaging tool are often the only available treatment for serious, life-threatening conditions. Many of these procedures require extended periods of radiation exposure often at one location on the patient. As a result. the US Food and Drug Administration (FDA) continues to receive reports of radiation-induced injuries to the skin in patients undergoing some of these therapeutic procedures. The regulatory scheme applicable to interventional radiology equipment in the US is described including federal, state and local aspects. and the impact of professional and non-governmental organisations. Current activities within the I;DA and other organisations which have or will affect the use, maintenance and manufacture of interventional radiology equipment are also described. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Gagne, RM (reprint author), US FDA, Ctr Devices & Radiol Hlth, 9200 Corp Blvd, Rockville, MD 20850 USA. NR 28 TC 0 Z9 0 U1 0 U2 0 PU RAMTRANS PUBLISHING PI ASHFORD PA PO BOX NO 7, ASHFORD TN23 1YW, KENT, ENGLAND BN 1-870965-78-7 PY 2001 BP 13 EP 18 PG 6 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA BS29T UT WOS:000169387600002 ER PT J AU Koti, KM AF Koti, KM TI On a primary efficacy endpoint SO DRUG INFORMATION JOURNAL LA English DT Article DE paired data; ANOVA; Wilcoxon test; P-value; statistical bias AB In some confirmatory clinical trials, data on the number of episodes of a particular type during baseline and treatment phase periods are collected. The primary efficacy variable proposed by the sponsor to compare the test drug with placebo is Y=(B - T)/(B + T), where B and T are x-day rates of episodes for baseline and the treatment phase, respectively In this article, it is argued that this efficacy variable does not have clinical interpretation as required by the International Conference on Harmonization (ICH) E9 guidelines (I). It is claimed that the difference D = B - T would be a natural and legitimate efficacy endpoint as it represents a reduction in the frequency of episodes. The relative difference RD = D/B is also examined for its feasibility It is indicated that using Y as the dependent variable instead of D (or RD) lowers the p-values for the pooled t-test and the Wilcoxon lest. It is concluded that the proposed efficacy variable Y is obscurant in nature and introduces statistical bias in favor of the test drug. The arguments against the use of the response variable Y are also valid for clinical trials designed to increase the rate of an outcome. C1 US FDA, Rockville, MD 20857 USA. RP Koti, KM (reprint author), US FDA, HFD-710,Room 15B45,5600 Fishers Lane, Rockville, MD 20857 USA. NR 8 TC 3 Z9 3 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 2001 VL 35 IS 1 BP 157 EP 162 PG 6 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 406NW UT WOS:000167222900018 ER PT J AU Clements, CJ Ball, LK Ball, R Pratt, RD AF Clements, CJ Ball, LK Ball, R Pratt, RD TI Thiomersal in vaccines - Is removal warranted? SO DRUG SAFETY LA English DT Article ID METHYLMERCURY; THIMEROSAL; EXPOSURE; MERCURY AB The mercury-based vaccine preservative thiomersal has come under scrutiny in recent months because of its presence in certain vaccines that provide the foundation of childhood immunisation schedules. Over the past decade new vaccines have been added to the recommended childhood schedule, and the relatively smaller bodyweight of infants has led to concern that the cumulative exposure of mercury from infant vaccines may exceed certain guidelines for the human consumption of mercury. In the US, government agencies and professional societies have recently recommended that thiomersal be removed altogether from vaccines. Some involved in developing vaccine policy feel that the evidence to support these safety concerns has not risen to the level required for such a response. This apparent divergence of opinion has left healthcare professionals and the public with uncertainty about the potential health effects from low level exposure to thiomersal as well as the necessity of removing thiomersal from vaccines. At present, scientific investigation has not found conclusive evidence of harm from thiomersal in vaccines. As a precautionary measure, efforts are under way to remove or replace thiomersal from vaccines and providers should anticipate the availability of more vaccine products that are thiomersal-free over the coming years. C1 WHO, Expanded Programme Immunisat Vaccines & Biol, Dept Vaccines & Biol, CH-1211 Geneva 27, Switzerland. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. RP Clements, CJ (reprint author), WHO, Expanded Programme Immunisat Vaccines & Biol, Dept Vaccines & Biol, CH-1211 Geneva 27, Switzerland. NR 41 TC 7 Z9 9 U1 2 U2 5 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 2001 VL 24 IS 8 BP 567 EP 574 DI 10.2165/00002018-200124080-00001 PG 8 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy; Toxicology GA 457AW UT WOS:000170115800001 PM 11480489 ER PT J AU Brown, P Will, RG Bradley, R Asher, DM Detwiler, L AF Brown, P Will, RG Bradley, R Asher, DM Detwiler, L TI Bovine spongiform encephalopathy and variant Creutzfeldt-Jakob disease: Background, evolution, and current concerns SO EMERGING INFECTIOUS DISEASES LA English DT Article ID GREAT-BRITAIN; MOUSE SCRAPIE; HUMAN HEALTH; TRANSMISSION; HUMANS; MICE; BSE; CJD; UK; EPIDEMIC AB The epidemic of bovine spongiform encephalopathy (BSE) in the United Kingdom, which began in 1986 and has affected nearly 200,000 cattle, is waning to a conclusion, but leaves in its wake an outbreak of human Creutzfeldt-Jakob disease, most probably resulting from the consumption of beef products contaminated by central nervous system tissue. Although averaging only 10-15 cases a year since its first appearance in 1994, its future magnitude and geographic distribution (in countries that have imported infected British cattle or cattle products, or have endogenous BSE) cannot yet be predicted. The possibility that large numbers of apparently healthy persons might be incubating the disease raises concerns about iatrogenic transmissions through instrumentation (surgery and medical diagnostic procedures) and blood and organ donations. Government agencies in many countries continue to implement new measures to minimize this risk. C1 NINDS, NIH, Cent Nervous Syst Studies Lab, Bethesda, MD 20892 USA. Western Gen Hosp, Natl Creutzfeldt Jakob Dis Surveillance Unit, Edinburgh EH4 2XU, Midlothian, Scotland. Cent Vet Lab, Addlestone, Surrey, England. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20857 USA. USDA, Anim & Plant Hlth Inspect Serv, Robbinsville, NJ USA. RP Brown, P (reprint author), NINDS, NIH, Cent Nervous Syst Studies Lab, Bldg 36,Room 4A-05,36 Convent Dr,MSC 4122, Bethesda, MD 20892 USA. EM brownp@ninds.nih.gov NR 49 TC 138 Z9 150 U1 1 U2 14 PU CENTERS DISEASE CONTROL PI ATLANTA PA 1600 CLIFTON RD, ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PD JAN-FEB PY 2001 VL 7 IS 1 BP 6 EP 16 PG 11 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 403EG UT WOS:000167029200002 PM 11266289 ER PT J AU Liang, AP Koopmans, M Doyle, MP Bernard, DT Brewer, CE AF Liang, AP Koopmans, M Doyle, MP Bernard, DT Brewer, CE TI Teaming up to prevent foodborne disease SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 CDCP, Atlanta, GA 30333 USA. Natl Inst Publ Hlth & Environm, NL-3720 BA Bilthoven, Netherlands. Univ Georgia, Athens, GA 30602 USA. Natl Food Processors Assoc, Washington, DC 20005 USA. US FDA, Washington, DC 20204 USA. RP Liang, AP (reprint author), CDCP, MS G24, Atlanta, GA 30333 USA. NR 2 TC 2 Z9 3 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PY 2001 VL 7 IS 3 SU S BP 533 EP 534 PG 2 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 459BW UT WOS:000170230800012 PM 11485650 ER PT J AU Naimi, T Ringwald, P Besser, R Thompson, S AF Naimi, T Ringwald, P Besser, R Thompson, S TI Antimicrobial resistance SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. Minnesota Dept Hlth, Minneapolis, MN USA. WHO, CH-1211 Geneva, Switzerland. US FDA, Rockville, MD 20857 USA. RP Naimi, T (reprint author), Ctr Dis Control & Prevent, 1600 Clifton Rd,Mailstop C12, Atlanta, GA 30333 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PY 2001 VL 7 IS 3 SU S BP 548 EP 548 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 459BW UT WOS:000170230800027 PM 11485665 ER PT J AU Krause, PR AF Krause, PR TI Adventitious agents and vaccines SO EMERGING INFECTIOUS DISEASES LA English DT Editorial Material C1 US FDA, Bethesda, MD 20892 USA. RP Krause, PR (reprint author), US FDA, Bldg 29A,Room 1C16,HRM-457,29 Lincoln Dr, Bethesda, MD 20892 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU CENTER DISEASE CONTROL PI ATLANTA PA ATLANTA, GA 30333 USA SN 1080-6040 J9 EMERG INFECT DIS JI Emerg. Infect. Dis PY 2001 VL 7 IS 3 SU S BP 562 EP 562 PG 1 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA 459BW UT WOS:000170230800035 PM 11485673 ER PT J AU Torous, DK Hall, NE Dertinger, SD Diehl, MS Illi-Love, AH Cederbrant, K Sandelin, K Bolcsfoldi, G Ferguson, LR Pearson, A Majeska, JB Tarca, JP Hewish, DR Doughty, L Fenech, M Weaver, JL Broud, DD Gatehouse, DG Hynes, GM Kwanyuen, P McLean, J McNamee, JP Parenteau, M Van Hoof, V Vanparys, P Lenarczyk, M Siennicka, J Litwinska, B Slowikowska, MG Harbach, PR Johnson, CW Zhao, S Aaron, CS Lynch, AM Marshall, IC Rodgers, B Tometsko, CR AF Torous, DK Hall, NE Dertinger, SD Diehl, MS Illi-Love, AH Cederbrant, K Sandelin, K Bolcsfoldi, G Ferguson, LR Pearson, A Majeska, JB Tarca, JP Hewish, DR Doughty, L Fenech, M Weaver, JL Broud, DD Gatehouse, DG Hynes, GM Kwanyuen, P McLean, J McNamee, JP Parenteau, M Van Hoof, V Vanparys, P Lenarczyk, M Siennicka, J Litwinska, B Slowikowska, MG Harbach, PR Johnson, CW Zhao, S Aaron, CS Lynch, AM Marshall, IC Rodgers, B Tometsko, CR TI Flow cytometric enumeration of micronucleated reticulocytes: High transferability among 14 laboratories SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE micronucleus test; genotoxicity; flow cytometry; interlaboratory; validation ID PERIPHERAL-BLOOD; ACRIDINE-ORANGE; ERYTHROCYTES; ASSAY; INTEGRATION; TOXICOLOGY; CELLS AB This laboratory previously described a single-laser flow cytometric method, which effectively resolves micronucleated erythrocyte populations in rodent peripheral blood samples. Even so, the rarity and variable size of micronuclei make it difficult to configure instrument settings consistently and define analysis regions rationally to enumerate the cell populations of interest. Murine erythrocytes from animals infected with the malaria parasite Plasmodium berghei contain a high prevalence of erythrocytes with a uniform DNA content. This biological model for micronucleated erythrocytes offers a means by which the micronucleus analysis regions can be rationally defined, and a means for controlling interexperimental variation. The experiments described herein were performed to extend these studies by testing whether malaria-infected erythrocytes could also be used to enhance the transferability of the method, as well as control intra- and interlaboratory variation. For these studies, blood samples from mice infected with malaria, or treated with vehicle or the clastogen methyl methanesulfonate, were fixed and shipped to collaborating laboratories for analysis. After configuring instrumentation parameters and guiding the position of analysis regions with the malaria-infected blood samples, micronucleated reticulocyte frequencies were measured (20,000 reticulocytes per sample). To evaluate both intra- and interlaboratory variation, five replicates were analyzed per day, and these analyses were repeated on up to five separate days. The data of 14 laboratories presented herein indicate that transferability of this flow cytometric technique is high when instrumentation is guided by the biological standard Plasmodium berghei. (C) 2001 Wiley-Liss, Inc. C1 Litron Labs, Rochester, NY 14620 USA. Abbott Labs, Chicago, IL USA. AstraZeneca, Sodertalje, Sweden. Auckland Canc Soc, Auckland, New Zealand. Boehringer Ingelheim Pharmaceut Inc, Ridgefield, CT 06877 USA. CSIRO, Clayton, Vic 3168, Australia. US FDA, CDER, Laurel, MD USA. GlaxoWellcome, Res Triangle Pk, NC USA. Hlth Canada, Ottawa, ON K1A 0L2, Canada. Janssen Pharmaceut, B-2340 Beerse, Belgium. Natl Inst Hyg, PL-00791 Warsaw, Poland. Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA. SmithKline Beecham, Welwyn Garden City, Herts, England. Texas Tech Univ, Lubbock, TX 79409 USA. RP Torous, DK (reprint author), Litron Labs, 1351 Mt Hope Ave, Rochester, NY 14620 USA. RI Ferguson, Lynnette/F-5989-2011; Diehl, Moritz/K-9537-2015; OI McNamee, James/0000-0003-2772-3455 FU NIEHS NIH HHS [N43-ES-05460] NR 15 TC 40 Z9 53 U1 0 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 2001 VL 38 IS 1 BP 59 EP 68 DI 10.1002/em.1051 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 461CN UT WOS:000170347500008 PM 11473389 ER PT J AU Brown, EW LeClerc, JE Kotewicz, ML Cebula, TA AF Brown, EW LeClerc, JE Kotewicz, ML Cebula, TA TI Three R's of bacterial evolution: How replication, repair, and recombination frame the origin of species SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE horizontal transfer; Escherichia coli; DNA replication; recombination; molecular evolution; methyl-directed mismatch repair; phylogeny ID PATHOGENIC ESCHERICHIA-COLI; HORIZONTAL GENE-TRANSFER; VARIABLE MUTATION-RATES; DNA-POLYMERASE-I; NATURAL-POPULATIONS; MOLECULAR EVOLUTION; NUCLEOTIDE-SEQUENCE; COMMENSAL BACTERIA; SALMONELLA; CONSEQUENCES AB The genetic diversity of bacteria results not only from errors in DNA replication and repair but from horizontal exchange and recombination of DNA sequences from similar and disparate species as well. New individuals carrying adaptive changes are thus being spawned constantly among the population at large. When new selection pressures appear, these are the individuals that survive, at the expense of the general population, to forge new populations. Depending on the severity and uniqueness of the selection pressure, this could lead to new speciation. It is becoming more and more evident that, as nucleotide sequences of numerous loci from many bacterial strains continue to amass, horizontal transfer has played a key role in configuring the Escherichia coli chromosome. Here, we examine views, both old and new, for the role of recombination in the evolution of bacterial chromosomes. We present novel phylogenetic evidence for horizontal transfer of three genes involved in DNA replication and repair (mutS, uvrD, and polA). These data reveal a prominent role for horizontal transfer in the evolution of genes known to play a key role in the fidelity of DNA replication and, thus, ultimate survival of the organism. Our data underscore that recombination plays both a diversifying and a homogenizing role in defining the structure of the E. coli genome. Published 2001 Wiley-Liss, Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol, Washington, DC 20204 USA. RP Cebula, TA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Mol Biol, HFS-235,200 C St SW, Washington, DC 20204 USA. NR 79 TC 19 Z9 20 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 2001 VL 38 IS 2-3 BP 248 EP 260 DI 10.1002/em.1079 PG 13 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 489XG UT WOS:000172017400024 PM 11746762 ER PT J AU Whittaker, P Seifried, HE San, RHC Clarke, JJ Dunkel, VC AF Whittaker, P Seifried, HE San, RHC Clarke, JJ Dunkel, VC TI Genotoxicity of iron chelators in L5178Y mouse lymphoma cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE iron chelators; iron toxicity; thalassemia; mutagenicity; mouse lymphoma assay ID DEXRAZOXANE ICRF-187; CLINICAL USE; THALASSEMIA; TOXICITY; DEFERIPRONE; MODULATION; MUTATIONS; EFFICACY; THERAPY; LOCUS AB To further study the mechanism of observed iron mutagenicity and cellular toxicity, a number of different iron chelators were evaluated to select a compound that was not mutagenic and had limited toxicity to mouse lymphoma cells. A series of iron chelators including those used clinically, those under development for clinical applications, and those used in nonclinical applications were evaluated. The mutagenic activity of the iron chelators was assessed in L5178Y mouse lymphoma cells. Eight of the 12 iron chelators that were tested induced mutagenic responses both with and without The addition of S9. Among those chelators used clinically or developed for clinical use, the only compound that did not induce a mutagenic response was the starch deferoxamine conjugate. In contrast, deferoxamine mesylate showed the highest toxicity in this group of chemicals and the concentrations leading to toxicity and mutagenicity between the activated and nonactivated assays were not significantly different. The other three chelators that were not mutagenic were Na(2)EDTA, phyfic acid, and ferrozine, Environ. Mol. Mutagen. 38:347-356, 2001. Published 2001 Wiley-Liss, Inc. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. BioReliance Corp, Rockville, MD USA. NCI, NIH, Bethesda, MD 20892 USA. RP Whittaker, P (reprint author), US FDA HFS236, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. FU NCI NIH HHS [N01-CB-87106] NR 32 TC 10 Z9 10 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 2001 VL 38 IS 4 BP 347 EP 356 DI 10.1002/em.10033 PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 510QJ UT WOS:000173218500011 PM 11774367 ER PT J AU Prival, MJ AF Prival, MJ TI Evaluation of the TOPKAT system for predicting the carcinogenicity of chemicals SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE SAR; computational toxicology; carcinogenicity; TOPKAT ID RODENT CARCINOGENICITY; 30 CHEMICALS; MUTAGENICITY; PROGRAM; STATE AB The TOPKAT computer-based system for predicting chemical carcinogens was evaluated by determining its ability to predict the carcinogenicity of chemicals tested by the National Toxicology Program. TOPKAT was not effective in identifying potential rodent carcinogens and noncarcinogens in the data set analyzed. The chemicals in the TOPKAT database of known carcinogens and non-carcinogens that the software identifies as most "similar" to unknown chemicals are illustrated using six examples. These "similar" chemicals generally bear no apparent relationship to the chemical of interest with regard to metabolism or potential mechanism of carcinogenicity. Published 2001 Wiley-Liss, Inc. C1 US FDA, Genet Toxicol Branch, Washington, DC 20204 USA. RP Prival, MJ (reprint author), US FDA, Genet Toxicol Branch, HFS-236,200 C St SW, Washington, DC 20204 USA. NR 12 TC 23 Z9 25 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 2001 VL 37 IS 1 BP 55 EP 69 DI 10.1002/1098-2280(2001)37:1<55::AID-EM1006>3.0.CO;2-5 PG 15 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 400AU UT WOS:000166847100007 PM 11170242 ER PT J AU Chen, T Mittelstaedt, RA Aidoo, A Hamilton, LP Beland, FA Casciano, DA Heflich, RH AF Chen, T Mittelstaedt, RA Aidoo, A Hamilton, LP Beland, FA Casciano, DA Heflich, RH TI Comparison of hprt and lacl mutant frequency with DNA adduct formation in N-hydroxy-2-acetylaminoflourene-treated Big Blue((R)) rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE P-32-postlabeling; liver; spleen lymphocytes; bone marrow; transgene ID IN-VIVO MUTAGENICITY; BLUE(TM) B6C3F1 MICE; ETHYL-N-NITROSOUREA; TRANSGENIC MICE; FISCHER-344 RATS; HEPATOCARCINOGEN 2-ACETYLAMINOFLUORENE; INHALATION EXPOSURE; SPLENIC LYMPHOCYTES; MUTATION ANALYSIS; SHUTTLE VECTORS AB N-Hydroxy-2-acetylaminofluorene (N-OH-AAF) is the proximate carcinogenic metabolite of the powerful rat liver carcinogen 2-acetylaminofluorene. In this study, transgenic Big Blue(R) rats were used to examine the relationship between in vivo mutagenicity and DNA adduct formation by N-OH-AAF in the target liver compared with that in nontarget tissues. Male rats were given one, two, or four doses of 25 mg N-OH-AAF/kg body weight by i.p. injection at 4-day intervals, and groups of treated and control rats were euthanized up to 10 weeks after beginning the dosing. Mutant frequencies were measured in the spleen lymphocyte hprt gene, and loci mutant frequencies were determined in the liver and spleen lymphocytes. At 6 weeks after beginning the dosing, the hprt mutant frequency in spleen lymphocytes from the four-dose group was 16.5 x 10(-6) compared with 3.2 x 10(-6) in control animals. Also at 6 weeks, rats given one, two, or four doses of N-OH-AAF had loci mutant frequencies in the liver of 97.6, 155.6, and 406.8 x 10(-6), respectively, compared with a control frequency of 25.7 x 10(-6) rats given four doses had loci mutant frequencies in spleen lymphocytes of 55.8 x 10(-6) compared with a control Frequency of 20.4 x 10(-6). Additional rats were evaluated for DNA adduct formation in the liver, spleen lymphocytes, and bone marrow by P-32-postlabeling. Adduct analysis was conducted 1 day after one, two, and four treatments with N-OH-AAF, 5 days after one treatment, and 9 days after two treatments. N-(Deoxyguanosin-8-yl)-2-aminofluorene was the major DNA adduct identified in all the tissues examined. Adduct concentrations increased with total dose to maximum values in samples token 1 day after two doses, and remained essentially the same after Four doses. In samples taken after Four doses, adduct levels were 103, 28, and 7 fmol/mug of DNA in liver, spleen lymphocytes, and bone marrow, respectively. The results indicate that the extent of both DNA adduct formation and mutant induction correlates with the organ specificity For N-OH-AAF carcinogenesis in the rat. Environ. Mol. Mutagen. 37:195-202, 2001. Published 2001 Wiley-Liss, Inc.dagger C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Chen, T (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 48 TC 11 Z9 11 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 2001 VL 37 IS 3 BP 195 EP 202 DI 10.1002/em.1028 PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 429TD UT WOS:000168532300003 PM 11317337 ER PT J AU Chen, T Mittelstaedt, RA Shelton, SD Dass, SB Manjanatha, MG Casciano, DA Heflich, RH AF Chen, T Mittelstaedt, RA Shelton, SD Dass, SB Manjanatha, MG Casciano, DA Heflich, RH TI Gene- and tissue-specificity of mutation in Big Blue (R) rats treated with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE lacl; hprt; transgene; spleen lymphocyte; liver; frameshift ID DIHYDROFOLATE-REDUCTASE MUTANTS; LAMBDA/LACI TRANSGENIC RATS; ENDOGENOUS HPRT GENE; HAMSTER OVARY CELLS; ESCHERICHIA-COLI; MOLECULAR ANALYSIS; DNA-SEQUENCE; B6C3F1 MOUSE; LACI GENE; HA-RAS AB In a previous study, we Found that treating transgenic Big Blue(R) rats with the hepatocarcinogen N-hydroxy-2-acetylaminofluorene (N-OH-AAF) produced the same major DNA adduct in the target liver and the nontarget spleen lymphocytes and bone marrow cells, induced loci mutants in the liver, and induced much lower frequencies of lad and hprt mutants in spleen lymphocytes. In the present study, sequence analysis was conducted on loci DNA and hprt cDNA from the mutants, to determine the mutational specificity of N-OH-AAF in the rat. All the mutation spectra From N-OH-AAF-treated rats differed significantly from corresponding mutation profiles From untreated animals (P = 0.02 to P < 0.0001). Although there were similarities among the mutational patterns derived From N-OH-AAF-treated rats (e.g., G:C --> T:A transversion was the most common mutation in all mutation sets), there were significant differences in the patterns of basepair substitution and frameshift mutation between the liver and spleen lymphocyte loci mutants (P = 0.02) and between the spleen lymphocyte loci and hprt mutants (P = 0.04). Also, multiplex PCR analysis of genomic DNA From the hprt mutants indicated that 12% of mutants from treated rats had major deletions in the hprt gene; no corresponding incidence of large deletions was evident among loci mutations. All the mutation profiles reflect the general mutational specificity of the major DNA adduct Formed by N-OH-AAF. The differences between N-OH-AAF mutation in the endogenous gene and transgene can be partially explained by the structures of the two genes. The tissue-specificity of the mutation spectra may contribute to targeting tumor formation to the liver. Environ. Mol. Mutagen. 37:203-214, 2001. Published 2001 Wiley-Liss, Inc.dagger C1 Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. RP Chen, T (reprint author), Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 41 TC 12 Z9 12 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 2001 VL 37 IS 3 BP 203 EP 214 DI 10.1002/em.1029 PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 429TD UT WOS:000168532300004 PM 11317338 ER PT J AU Malling, HV Delongchamp, RR AF Malling, HV Delongchamp, RR TI Direct separation of in vivo and in vitro am3 revertants in transgenic mice carrying the phiX174 am3, cs70 vector SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE phiX174; transgenic; mice; revertants; ENU; spleen ID ETHYL-N-NITROSOUREA; SPONTANEOUS MUTATION; MUTAGENESIS; SINGLE; PHI-X174; BASEPAIR; SYSTEMS AB Target genes in most transgenic systems have higher spontaneous mutation frequencies than do endogenous mammalian genes. Spontaneous mutations in transgenes predominantly arise from three sources. (1) mutations fixed in the animals, (2) mutations arising from replication errors caused by damage to the DNA that may have occurred in vivo or in vitro and then was fixed during amplification of the vector in vitro, and (3) mutations arising during replication of non-revertant phages in non-permissive bacteria. An assay based on single bursts was developed to directly distinguish between the in vivo and in vitro origins of revertants. The sire of the aliquot is determined by mutant frequency and is adjusted so that ideally no more than 10 to 20% of the aliquots contain a bacterial cell transformed with a mutant phage. Mutations are detected as revertants of an amber mutation (am3) in phiX174 am3, cs70. The minimum burst size of non-revertant phiX174 am3, cs70 From splenic DNA on a permissive bacterial strain was larger than 30 plaque-forming units (pfu). Based on this observation, a burst size of 31 plaque-forming revertants was chosen as the minimum burst size of a fixed mutation. The single burst assay was tested on DNA from spleens of animals that were treated with 150 mg/kg 1-ethyl-1-nitrosurea. Only the fraction of aliquots with single bursts of revertants (> 30) increased in the treated animals compared to the controls. In contrast, there was no difference between treated and control animals For revertant frequencies calculated for burst sizes less than or equal to 30 pfu. Among the spontaneous mutations, only 30% were caused by mutations fixed in animals (i.e. burst size > 30 pfu). Total average revertant Frequency measured in DNA from treated animals was less than twofold more than the average spontaneous frequency (P = 0.048). When frequencies were based on burst sizes > 30, there was a 4.6-fold increase among treated animals compared with controls (P = 0.026). The single burst-assay resulted in a more sensitive test for mutagenicity because it eliminated noise from invitro mutations. Published 2001 Wiley-Liss, Inc.(+) C1 NIEHS, Mammalian Mutagenesis Grp, Environm Toxicol Program, Toxicol Lab, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Malling, HV (reprint author), NIEHS, Mammalian Mutagenesis Grp, Environm Toxicol Program, Toxicol Lab, MD F106,POB 12233, Res Triangle Pk, NC 27709 USA. NR 17 TC 12 Z9 12 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 2001 VL 37 IS 4 BP 345 EP 355 DI 10.1002/em.1042 PG 11 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 450DR UT WOS:000169726700009 PM 11424185 ER PT J AU Delongchamp, RR Valentine, CR Malling, HV AF Delongchamp, RR Valentine, CR Malling, HV TI Estimation of the average burst size of Phi X174 am3, cs70 for use in mutation assays with transgenic mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE Phi X174 am3; cs70; transgenic mice; mutation assay; plaque count; burst size AB In mutation assays using transgenic mice, with recoverable vectors such as Phi X174 am3, cs70, mutations originate from two sources: (1) in vivo mutations, that is, mutations that were fixed in the mouse, or (2) ex vivo mutations, that is, mutations that were Fixed during recovery or plating. When a bacteriophage infects a bacterium, ii multiplies and bursts the cell, releasing a number of phages referred to as the burst size. Our method for distinguishing between in vivo mutations and ex vivo mutations estimates the average number of bursts, the denominator of in vivo mutant Frequencies, by dividing the total plaque-forming units (PFU) by the average number of phages in a burst. Herein, we outline a probability model relating observed plaque counts to the burst size and present the statistical method used to estimate the burst size. The average size of a single burst from nonrevertant phages was estimated in eight studies under the conditions of our mutation assay. The average burst size was stable across studies at 182.5 plaques per burst (standard error, 14.25). The probability that a burst is a specific size was approximated by a negative binomial distribution, which implies a Poisson-Pascal distribution for the observed plaque counts. The observed plaque counts were adequately Fit by this approximation. Published 2001 Wiley-Liss, Inc.(+) C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NIEHS, Mammalian Genet Grp, Toxicol Lab, Res Triangle Pk, NC 27709 USA. RP Delongchamp, RR (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT-20,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 5 TC 7 Z9 7 U1 0 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 2001 VL 37 IS 4 BP 356 EP 360 DI 10.1002/em.1043.abs PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 450DR UT WOS:000169726700010 PM 11424186 ER PT J AU Fritsche, S Rumsey, TS Yurawecz, MP Ku, Y Fritsche, J AF Fritsche, S Rumsey, TS Yurawecz, MP Ku, Y Fritsche, J TI Influence of growth promoting implants on fatty acid composition including conjugated linoleic acid isomers in beef fat SO EUROPEAN FOOD RESEARCH AND TECHNOLOGY LA English DT Article DE beef; conjugated linoleic acid isomers; fatty acid composition; growth promoting implants; trans fatty acids ID PERFORMANCE LIQUID-CHROMATOGRAPHY; GAS-CHROMATOGRAPHY; PRODUCTION SYSTEM; BODY-COMPOSITION; ADIPOSE-TISSUE; STEERS; MILK; MUSCLE; SEPARATION; LIPIDS AB The influence of the growth promoting implants Synovex (SYN), Ralgro (RAL), and Revalor (REV) on the fatty acid profiles of subcutaneous fat, intramuscular fat, and phospholipids of 32 beef steers (eight steers per treatment, and eight controls) was studied. Fatty acid compositions and profiles of conjugated linoleic acid (CLA) isomers were determined by a combination of GC and triple-column Ag+-HPLC. Only small differences could be observed between the different treatment groups. The amount of saturated fatty acids relative to monounsaturated fatty acids was increased by all growth promoting implants in subcutaneous fat (P < 0.1) and also by SYN in intramuscular far. RAL led to slightly higher amounts of trans fatty acids in subcutaneous and intramuscular fat (P < 0.1). REV-implanted steers showed some significant differences in their profiles of polyunsaturated fatty acids compared to control steers. CLA content and isomeric distribution in subcutaneous fat were affected by SYN, which reduced amounts of total CLA (0.42 mg/g fat vs. 0.53 mg/g in control steers, P < 0.001) and decreased the proportions of the primary 18:2 c9t11 isomer (73% of total CLA for SYN vs. 77-78% for all other treatment groups). Slight increases of c9t11 CLA in intramuscular fat were observed in RAL- and REV-implanted steers (P < 0.1). Most differences in fatty acid composition observed in this study were probably due to shifts in the storage lipid/membrane lipid ratio. C1 US FDA, Washington, DC 20204 USA. USDA ARS, Growth Biol Lab, Beltsville, MD 20705 USA. RP Fritsche, S (reprint author), Unilever Res Labs Vlaardingen, Olivier van Noortlaan 120, NL-3133 AT Vlaardingen, Netherlands. NR 50 TC 30 Z9 33 U1 0 U2 2 PU SPRINGER-VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 1438-2377 J9 EUR FOOD RES TECHNOL JI Eur. Food Res. Technol. PY 2001 VL 212 IS 6 BP 621 EP 629 DI 10.1007/s002170100323 PG 9 WC Food Science & Technology SC Food Science & Technology GA 448UC UT WOS:000169647500001 ER PT J AU Stan, AC Casares, S Brumeanu, TD Klinman, DM Bona, CA AF Stan, AC Casares, S Brumeanu, TD Klinman, DM Bona, CA TI CpG motifs of DNA vaccines induce the expression of chemokines and MHC class II molecules on myocytes SO EUROPEAN JOURNAL OF IMMUNOLOGY LA English DT Article DE myocyte; antigen presentation; chemokine; MHC class-II; DNA vaccine ID ANTIGEN-PRESENTING CELLS; CYTOTOXIC T-LYMPHOCYTES; HUMAN MYOBLASTS; INTERFERON-GAMMA; DENDRITIC CELLS; BACTERIAL-DNA; GENETIC IMMUNIZATION; MYASTHENIA-GRAVIS; SCHWANN-CELLS; MUSCLE-CELLS AB Determining how an immune response is initiated after in vivo transfection of myocytes with plasmids encoding foreign antigens is essential to understand the mechanisms of intramuscular (i.m.) genetic immunization. Since myocytes are facultative antigen-presenting cells lacking MHC class II and co-stimulatory molecules, it was assumed that their unique role upon DNA vaccination is to synthesize and secrete the protein encoded by the plasmid. Here we describe that i.m. injection of unmethylated CpG motifs induced the expression of chemokines (monocyte chemotactic protein-1) and MHC class II molecules on myocytes. Our results indicate that immunostimulatory DNA sequences (CpG motifs) of DNA vaccines augment synthesis of chemokine by myocytes with subsequent recruitment of inflammatory cells secreting IFN-gamma, a potent cytokine that up-regulates the expression of MHC class II molecules on myocytes. A myoblast cell line triple transfected with plasmids encoding MHC class II molecules and an immunodominant CD4 T cell epitope of influenza virus presented the endogenously synthesized peptide and activated specific T cells. These findings suggest that one mechanism for the immunogenicity of DNA vaccines consists in the presentation of peptides to CD4 T cells by in vivo plasmid-transfected myocytes. C1 CUNY Mt Sinai Sch Med, Dept Microbiol, New York, NY 10029 USA. Hannover Med Sch, Inst Neuropathol, D-3000 Hannover, Germany. US FDA, Div Viral Prod, Lab Retrovirol & Immunol, CBER, Bethesda, MD 20014 USA. RP Bona, CA (reprint author), CUNY Mt Sinai Sch Med, Dept Microbiol, 1 Gustave L Levy Pl, New York, NY 10029 USA. NR 43 TC 31 Z9 33 U1 0 U2 0 PU WILEY-V C H VERLAG GMBH PI BERLIN PA PO BOX 10 11 61, D-69451 BERLIN, GERMANY SN 0014-2980 J9 EUR J IMMUNOL JI Eur. J. Immunol. PD JAN PY 2001 VL 31 IS 1 BP 301 EP 310 DI 10.1002/1521-4141(200101)31:1<301::AID-IMMU301>3.0.CO;2-K PG 10 WC Immunology SC Immunology GA 393UH UT WOS:000166487700034 PM 11265647 ER PT S AU Anadon, A Appelgren, LE Arnold, D Boisseau, J Boobis, AR Kinabo, LDB McLean, JG MacNeil, JD Miller, MA Palermo-Neto, J Martinez, JLR Soback, SS Stephany, RW AF Anadon, A Appelgren, LE Arnold, D Boisseau, J Boobis, AR Kinabo, LDB McLean, JG MacNeil, JD Miller, MA Palermo-Neto, J Martinez, JLR Soback, SS Stephany, RW GP WHO TI A meeting of the Joint FAO/WHO Expert Committee on Food Additives was held at WHO Headquarters, Geneva, from 15 to 24 February 2000 SO EVALUATION OF CERTAIN VETERINARY DRUG RESIDUES IN FOOD SE WHO TECHNICAL REPORT SERIES LA English DT Article; Proceedings Paper CT Meeting of the Joint FAO/WHO Expert Committee on Food Additives CY FEB 15-24, 2000 CL GENEVA, SWITZERLAND SP FAO, WHO C1 Univ Complutense Madrid, Fac Vet Med, Dept Toxicol & Pharmacol, Madrid, Spain. Swedish Univ Agr Sci, Fac Vet Med, Dept Pharmacol & Toxicol, S-75007 Uppsala, Sweden. Fed Inst Hlth Protect Consumers & Vet Med, Berlin, Germany. French Food Safety Agcy, Natl Agcy Vet Med Prod, Fougeres, France. Univ London Imperial Coll Sci Technol & Med, Div Med, Sect Clin Pharmacol, Sch Med, London, England. Sokoine Univ Agr, Dept Vet Physiol Biochem Pharmacol & Toxicol, Morogoro, Tanzania. Canadian Food Inspect Agcy, Ctr Vet Drugs Residues, Hlth Anim Lab, Saskatoon, SK, Canada. US FDA, Off Womens Hlth, Rockville, MD USA. Univ Fed Sao Paulo, Sch Vet Med, Appl Pharmacol & Toxicol Lab, Dept Pathol, Sao Paulo, Brazil. Minist Agr & Anim Husbandry, Natl Lab Vet Sci, Toxicol & Residues Sect, San Jose, Costa Rica. Natl Inst Publ Hlth & Environm, Lab Residue Anal, Bilthoven, Netherlands. RP Anadon, A (reprint author), Univ Complutense Madrid, Fac Vet Med, Dept Toxicol & Pharmacol, Madrid, Spain. RI Palermo-Neto, Joao/C-6086-2012 NR 182 TC 0 Z9 0 U1 0 U2 0 PU WORLD HEALTH ORGANIZATION PI GENEVA PA 1211 27 GENEVA, SWITZERLAND SN 0512-3054 BN 92-4-120900-3 J9 WHO TECH REP SER PY 2001 VL 900 BP 1 EP 96 PG 96 WC Food Science & Technology; Public, Environmental & Occupational Health; Toxicology SC Food Science & Technology; Public, Environmental & Occupational Health; Toxicology GA BS92L UT WOS:000171392000001 ER PT J AU Komolprasert, V McNeal, TP Agrawal, A Adhikari, C Thayer, DW AF Komolprasert, V McNeal, TP Agrawal, A Adhikari, C Thayer, DW TI Volatile and non-volatile compounds in irradiated semi-rigid crystalline poly(ethylene terephthalate) polymers SO FOOD ADDITIVES AND CONTAMINANTS LA English DT Article DE PET; poly( ethylene terephthalate); volatiles; non-volatiles; irradiation ID PRODUCTS AB In this study two different semi-rigid crystalline and oriented polyethylene terephthalate materials were used and were irradiated at 25-kGy dose at room temperature by using a caesium (137) radiator. Volatile and nonvolatile compounds present in the irradiated materials were identified and quantified. The qualitative results obtained from HS/GC/TCD/FID analysis at room temperature showed volatiles could not be identified. The HS/GC/MSD analysis performed at 106 degreesC showed that the irradiation generated 668-742 mug/kg formic acid, 868-922 mug/kg acetic acid, 17-32 mug/kg 1,3-dioxolane, and 47-71 mug/kg 2-methyl-1,3-dioxolane based on PET weight. The results obtained from the thermal desorption and GC/MSD performed at 200 degreesC showed that 10-12 mg/kg acetaldehyde, 479-975 mug/kg 1,3-dioxolane, and 6.6-11.2 mg/kg methyl-1, 3-dioxolane were detected after irradiation. The concentrations of the two dioxolanes found from thermal desorption were much higher than those observed in the HS, although formic and acetic acids were not detected. It is possible that the formic and acetic acids produced by irradiation underwent further reactions with ethylene glycol during thermal desorption to form the dioxolanes. The soluble solid extracted from various PET specimens before and after irradiation were in a range of 0.67-0.78%. PET cyclic trimer is the major component and is present at 0.41-0.50%, accounting for more than 50% of the percent total solid in PET. Statistically, irradiation did not increase the soluble solid and cyclic trimer. The overall results suggest that 25-kGy irradiation had a significant effect on increasing the volatile but not the non-volatile compounds detected in the PET specimens. C1 IIT, Natl Ctr Food Safety & Technol, Chicago, IL 60616 USA. US FDA, Div Food Proc & Packaging, Summit Argo, IL 60501 USA. US FDA, Off Premarket Approval, Div Prod Manufacture & Use, Washington, DC 20204 USA. Continental PET Technol Inc, Bedford, NH 03110 USA. ARS, USDA, Wyndmoor, PA 19038 USA. RP Komolprasert, V (reprint author), IIT, Natl Ctr Food Safety & Technol, Chicago, IL 60616 USA. FU FDA HHS [FD-000431] NR 8 TC 16 Z9 16 U1 1 U2 5 PU TAYLOR & FRANCIS LTD PI LONDON PA 11 NEW FETTER LANE, LONDON EC4P 4EE, ENGLAND SN 0265-203X J9 FOOD ADDIT CONTAM JI Food Addit. Contam. PD JAN PY 2001 VL 18 IS 1 BP 89 EP 101 DI 10.1080/02652030010006096 PG 13 WC Chemistry, Applied; Food Science & Technology; Toxicology SC Chemistry; Food Science & Technology; Toxicology GA 390WQ UT WOS:000166322300010 PM 11212551 ER PT J AU Levitt, JA Wehr, HM AF Levitt, JA Wehr, HM TI The importance of international activities to the work of the Food and Drug Administration's Center for Food Safety and Applied Nutrition SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. CFSAN, Off Constituent Operat, Washington, DC USA. RP Levitt, JA (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 2 TC 1 Z9 1 U1 0 U2 1 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2001 VL 56 IS 1 BP 1 EP 9 PG 9 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 425AD UT WOS:000168265400001 PM 11942346 ER PT J AU Schwetz, BA AF Schwetz, BA TI Remarks of the acting principal deputy commissioner of food and drugs SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT 44th Annual Educational Conference of the Food-and-Drug-Law-Institute CY APR 18-19, 2001 CL WASHINGTON, D.C. SP Food & Drug Law Inst C1 US FDA, Washington, DC 20204 USA. RP Schwetz, BA (reprint author), US FDA, Washington, DC 20204 USA. NR 17 TC 0 Z9 0 U1 0 U2 2 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2001 VL 56 IS 2 BP 123 EP 129 PG 7 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 466JD UT WOS:000170641700002 PM 12022189 ER PT J AU Suydam, LA Kubic, MJ AF Suydam, LA Kubic, MJ TI FDA's implementation of FDAMA: An interim balance sheet SO FOOD AND DRUG LAW JOURNAL LA English DT Article; Proceedings Paper CT 44th Annual Educational Conference of the Food-and-Drug-Law-Institute CY APR 18-19, 2001 CL WASHINGTON, D.C. SP Food & Drug Law Inst C1 US FDA, Off Publ Affairs, Rockville, MD 20857 USA. RP Suydam, LA (reprint author), US FDA, Off Publ Affairs, Rockville, MD 20857 USA. NR 7 TC 3 Z9 4 U1 0 U2 2 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA SN 1064-590X J9 FOOD DRUG LAW J JI Food Drug Law J. PY 2001 VL 56 IS 2 BP 131 EP 135 PG 5 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 466JD UT WOS:000170641700003 PM 12022190 ER PT J AU Levitt, JA AF Levitt, JA TI FDA's foods program 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 24 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 2001 VL 56 IS 3 BP 255 EP 266 PG 12 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 506FJ UT WOS:000172958900002 PM 11944638 ER EF