FN Thomson Reuters Web of Science™ VR 1.0 PT J AU Turnipseed, SB Walker, CC Roybal, JE Pfenning, AP Hurlbut, JA AF Turnipseed, SB Walker, CC Roybal, JE Pfenning, AP Hurlbut, JA TI Confirmation of fluoroquinolones in catfish muscle by electrospray liquid chromatography mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID METABOLITE CIPROFLOXACIN; PIROMIDIC ACIDS; ENROFLOXACIN; DANOFLOXACIN; ANTIBIOTICS; FLUMEQUINE; OFLOXACIN; RESIDUES; CHICKEN; BOVINE AB A multiresidue liquid chromatography/mass spectrometry (LC/MS) confirmation method for fluoroquinolones in catfish muscle was developed by using an electrospray interface. Residues of ciprofloxacin, enrofloxacin, sarafloxacin, and difloxacin were positively identified in catfish muscle fortified at 10-80 ppb as well as in incurred tissue. The extraction procedure is based on an LC method with fluorescence detection for determination of these compounds in catfish. Residues were extracted from catfish muscle with an acidic ethanol solution, and the extracts were cleaned up on a propyl sulfonic acid solid-phase extraction column. Chromatographic conditions were optimized to be compatible with the electrospray interface, internal electrospray voltages were optimized so that 3 fragment ions, in addition to the protonated molecular ion, could be monitored for each residue. To obtain maximum sensitivity, separate MS acquisition programs were developed for ciprofloxacin/enrofloxacin and sarafloxacin/difloxacin pairs. C1 US FDA, Anim Drugs Res Ctr, Denver, CO 80225 USA. US FDA, Denver Dist Lab, Denver, CO 80225 USA. Metropolitan State Coll, Denver, CO 80217 USA. RP Turnipseed, SB (reprint author), US FDA, Anim Drugs Res Ctr, POB 25087, Denver, CO 80225 USA. NR 19 TC 38 Z9 40 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 1998 VL 81 IS 3 BP 554 EP 562 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA ZM875 UT WOS:000073585100011 PM 9606921 ER PT J AU Chase, GW Long, AR Eitenmiller, RR AF Chase, GW Long, AR Eitenmiller, RR TI Liquid chromatographic method for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in soy-based infant formula using a zero-control reference material (ZRM) as a method development tool SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A liquid chromatographic method is described for analysis of all-rac-alpha-tocopheryl acetate, tocopherols, and retinyl palmitate in soy-based infant formula. The vitamins are extracted in isopropyl alcohol and hexane-ethyl acetate without saponification and quantitated by normal-phase chromatography with fluorescence detection. All-rac-alpha-tocopheryl acetate and retinyl palmitate are quantitated isocratically with mobile phases of 0.5% (v/v) and 0.125% (v/v) isopropyl alcohol in hexane, respectively. Recoveries from zero control reference material soy-based formula averaged 97.2% (n = 25) for retinyl palmitate and 100% (n = 25) for all-rac-alpha-tocopheryl acetate, Coefficients of variation ranged from 1.21 to 2.86% for retinyl palmitate and from 1.49 to 5.16% for all-rac-alpha-tocopheryl acetate. The method provides a rapid, specific, and easily controlled assay for analysis of vitamin A and vitamin E in fortified infant formula. Additionally, the method eliminates use of chlorinated solvents. C1 US FDA, Atlant Ctr Nutr Anal, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Chase, GW (reprint author), US FDA, Atlant Ctr Nutr Anal, 60 8th ST, Atlanta, GA 30309 USA. NR 5 TC 12 Z9 12 U1 0 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 MAY-JUN PY 1998 VL 81 IS 3 BP 577 EP 581 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA ZM875 UT WOS:000073585100014 PM 9606923 ER PT J AU Chase, GW Long, AR AF Chase, GW Long, AR TI Liquid chromatographic method for analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in milk-based infant formula using matrix solid-phase dispersion SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID MULTIRESIDUE METHOD; TISSUE AB A liquid chromatographic method is described for analysis of all-rac-alpha-tocopheryl acetate, tocopherols, and retinyl palmitate in milk-based infant formula. The vitamins are extracted from infant formula without saponification by matrix solid-phase dispersion and quantitated by normal-phase chromatography with fluorescence detection. Retinyl palmitate and vitamin E are quantitated isocratically with mobile phases of 0.125% (v/v) and 0.5% (v/v) isopropyl alcohol in hexane, respectively Results were similar to the certified and non-certified ranges for all-rac-alpha-tocopheryl acetate, retinyl palmitate, and tocopherols in the infant formula standard reference material (SRM) 1846. Results also compared favorably with the label declaration on a retail infant formula. Recoveries were determined on an analyte-fortified zero control reference material for milk-based infant formula and averaged 96.8% (n = 30) for retinyl palmitate and 91.5% (n = 25) for all-rac-alpha-tocopheryl acetate. Examination of 5 concentrations for each analyte gave results that were linear (r = 0.999) over the concentration examined, with coefficients of variation ranging from 1.02 to 5.86%. The method provides a rapid, specific, and easily controlled assay for analysis of retinyl palmitate and vitamin E in fortified infant formula. Additionally, the method minimizes solvent use by using only 14 mL solvent per extraction. C1 US Food & Drug Adm, Atlanta Ctr Nutrient Anal, Atlanta, GA 30309 USA. RP Chase, GW (reprint author), US Food & Drug Adm, Atlanta Ctr Nutrient Anal, 60 8th St, Atlanta, GA 30309 USA. NR 12 TC 23 Z9 24 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 1998 VL 81 IS 3 BP 582 EP 586 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA ZM875 UT WOS:000073585100015 PM 9606924 ER PT J AU Stibitz, S AF Stibitz, S TI Mutations affecting the a subunit of Bordetella pertussis RNA polymerase suppress growth inhibition conferred by short C-terminal deletions of the response regulator BvgA SO JOURNAL OF BACTERIOLOGY LA English DT Article ID 2-COMPONENT SENSOR PROTEIN; GRAM-NEGATIVE BACTERIA; ESCHERICHIA-COLI; VIRULENCE FACTORS; CLONING VECTORS; ALPHA-SUBUNIT; ACTIVATION; LOCUS; GENE; PROMOTER AB The effects of short deletions of the C terminus of the BvgA response regulator protein of the BvgAS two-component system were examined in Bordetella pertussis, When present as a single copy in the chromosome, deletions removing as few as two amino acids conferred a completely Bvg(-) phenotype. When provided in trans, on the broad-host-range plasmid pRK290, under the control of the native bvgAS promoter, deletions of two or three amino acids conferred a profound growth inhibition which was dependent on the integrity and activity of the wild-type chromosomal bvgAS locus. It is proposed that this phenotype was the result of an inappropriate interaction of the mutant BvgA protein with the RNA polymerase enzyme, specifically the alpha subunit, Mutant strains in which this growth inhibition was relieved were isolated and characterized. Although most of the suppressor mutations affected either the mutant plasmid copy or the Mild-type chromosomal beg locus, three mutations which affected the alpha subunit of B. pertussis RNA polymerase were also isolated. Two of these resulted in increased levels of the a! subunit, and one caused a substitution of glycine for the aspartic acid residue at position 171, in the N-terminal domain. All three mutations also resulted in a differential phenotype in that expression of fha was essentially normal, but expression of ptx was greatly reduced. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20892 USA. RP Stibitz, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, 8800 Rockville Pike, Bethesda, MD 20892 USA. NR 42 TC 14 Z9 14 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD MAY PY 1998 VL 180 IS 9 BP 2484 EP 2492 PG 9 WC Microbiology SC Microbiology GA ZK570 UT WOS:000073338400029 PM 9573202 ER PT J AU Klutch, M Woerner, AM Marcus-Sekura, CJ Levin, JG AF Klutch, M Woerner, AM Marcus-Sekura, CJ Levin, JG TI Generation of HIV-1/HIV-2 cross-reactive peptide antisera by small sequence changes in HIV-1 reverse transcriptase and integrase immunizing peptides SO JOURNAL OF BIOMEDICAL SCIENCE LA English DT Article DE HIV-1; HIV-2; synthetic peptides; peptide antisera; cross-reactive response; chimeric peptides; reverse transcriptase; integrase; enzyme assays; peptide diagnostics ID IMMUNODEFICIENCY-VIRUS TYPE-1; DNA-BINDING DOMAIN; MONOCLONAL-ANTIBODIES; CRYSTAL-STRUCTURE; ESCHERICHIA-COLI; ANGSTROM RESOLUTION; NATURAL PROTECTION; HTLV-III; H DOMAIN; PROTEIN AB We have generated peptide antisera against selected regions in HIV-1 and HIV-2 reverse transcriptase (RT) and integrase (IN) to investigate the specificity of determinants governing the immune response, Peptides representing homologous regions (>50%) in the N- and C-termini and central portions of HIV-2 these proteins were synthesized and injected into rabbits. HIV-1 and HIV-2 IN peptide antisera inhibited IN-mediated cleavage of an HIV-1 DNA oligonucleotide substrate in a 3' processing assay, while anti-RT or normal sera had no effect. None of the RT sera inhibited RT activity. In Western blots, HIV-2 antisera directed against RT or IN peptides recognized HIV-2. RT and IN proteins, respectively, as expected, but also cross-reacted with the corresponding HIV-1 proteins. By contrast, corresponding HIV-1 antisera were type-specific. In some cases, HIV-1 cross-reactive antisera could be generated by immunization with HIV-1 chimeric peptides with as few as two residues in the HIV-1 sequence changed to the corresponding HIV-2 amino acids. The finding that a type-specific response can be converted to a cross-reactive response suggests alternate strategies for developing new diagnostic reagents which detect HIV-1 and HIV-2. In addition, our results provide a general model for generating HIV peptide vaccines with dual specificity against HIV-1 and HIV-2. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. NICHHD, Mol Genet Lab, NIH, Bethesda, MD 20892 USA. RP Levin, JG (reprint author), NICHD, Mol Genet Lab, NIH, Bldg 6B,Room 216,9000 Rockville Pike, Bethesda, MD 20892 USA. EM judith.levin@nih.gov NR 42 TC 6 Z9 6 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 1998 VL 5 IS 3 BP 192 EP 202 DI 10.1007/BF02253469 PG 11 WC Cell Biology; Medicine, Research & Experimental SC Cell Biology; Research & Experimental Medicine GA ZY858 UT WOS:000074668700005 PM 9678490 ER PT J AU Bogusz, S Cheatham, TE Brooks, BR AF Bogusz, S Cheatham, TE Brooks, BR TI Removal of pressure and free energy artifacts in charged periodic systems via net charge corrections to the Ewald potential SO JOURNAL OF CHEMICAL PHYSICS LA English DT Article ID PARTICLE MESH EWALD; MOLECULAR-DYNAMICS SIMULATIONS; CALCULATING ELECTROSTATIC INTERACTIONS; COMPUTER-SIMULATIONS; BOUNDARY-CONDITIONS; IONIC HYDRATION; WATER; SUMS; TRANSFERABILITY; PROTEINS AB A uniform neutralizing background plasma is employed by default in standard Ewald calculations for net-charged systems. We show here that this plasma leads to serious artifacts in both system energy and pressure, which lead to unrealistic behavior. These artifacts are especially critical to simulations where either net charge or volume is allowed to change. To correct these problems we institute a net-charge correction term that consists of subtracting off the Ewald sum for a single particle with charge equal to the net charge of the full system and an optional Born or Poisson-Boltzmann term. This correction decreases pressure artifacts by three orders of magnitude and allows rapid energy convergence as the cell size increases. The correction term is general, in that it applies to systems of any shape or net charge. The net-charge correction was tested for systems in all three phases of matter: gas, solid and liquid, and found to be markedly superior to standard Ewald in all three cases. In the gas phase, isolated molecular energies are quickly achieved as the cell size increases. In the solid phase the vaporization energy of the NaCl crystal is reproduced using free energy perturbation techniques where a single atom is removed. In the liquid phase, the solvation free energy of Na+ was investigated. It is demonstrated that both the net-charge correction and an energy term twice the size of a Born term is required to obtain optimal free energies of ionic hydration. (C) 1998 American Institute of Physics. C1 NIH, Struct Biol Lab, Div Comp Res & Technol, Bethesda, MD 20892 USA. RP Bogusz, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Biophys Lab, Rockville, MD 20852 USA. NR 42 TC 101 Z9 103 U1 2 U2 23 PU AMER INST PHYSICS PI WOODBURY PA CIRCULATION FULFILLMENT DIV, 500 SUNNYSIDE BLVD, WOODBURY, NY 11797-2999 USA SN 0021-9606 J9 J CHEM PHYS JI J. Chem. Phys. PD MAY 1 PY 1998 VL 108 IS 17 BP 7070 EP 7084 DI 10.1063/1.476320 PG 15 WC Chemistry, Physical; Physics, Atomic, Molecular & Chemical SC Chemistry; Physics GA ZK384 UT WOS:000073315200006 ER PT J AU Weiss, RB Freiman, J Kweder, SL Diehl, LF Byrd, JC AF Weiss, RB Freiman, J Kweder, SL Diehl, LF Byrd, JC TI Hemolytic anemia after fludarabine therapy for chronic lymphocytic leukemia SO JOURNAL OF CLINICAL ONCOLOGY LA English DT Article ID MONOPHOSPHATE; AGENT; 2-CHLORODEOXYADENOSINE; CHLORAMBUCIL; PATIENT AB Purpose: A report of the clinical features, treatment, and outcome of patients who developed hemolytic anemia (HA) temporally associated with fludarabine (Fludara; Berlex Laboratories, Richmond, CA) therapy for chronic lymphocytic leukemia (CLL). Patients and Methods: Data on 24 patients who developed HA related to fludarabine therapy were collected from the Spontaneous Reporting System of the Food and Drug Administration (FDA) and the Walter Reed Army Medical Center (Washington, DC). Results: Seventeen (71%) patients developed HA after either the first, second, or third cycle of this drug. The longest duration of fludarabine therapy before HA occurred was six cycles. The median decline in hematocrit from baseline during the hemolytic episode was 14.1 (range, 8.0 to 28.9) for the 18 patients for whom this information was available. For the 11 patients for wham transfusion requirements were known, the number of transfusions administered ranged between three and 36. Seven (29%) patients died of medical complications associated with the HA. Seven of eight patients who were re-challenged with fludarabine after an episode of HA developed recurrent HA, and three of these patients died. Conclusion: HA associated with fludarabine therapy appears to be uncommon, but it can be severe and fatal, especially if a patient is re-treated with this drug after a previous episode of HA. The mechanism of this toxicity is unknown, but it may be caused by the release of a suppressed auto-antibody to a native red cell antigen. C1 Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. Georgetown Univ, Med Ctr, Vincent T Lombardi Canc Res Ctr, Washington, DC 20007 USA. US FDA, Rockville, MD 20857 USA. Uniformed Serv Univ Hlth Sci, Bethesda, MD 20814 USA. RP Byrd, JC (reprint author), Walter Reed Army Med Ctr, Hematol Oncol Serv, Washington, DC 20307 USA. EM rayweissmd@aol.com NR 26 TC 66 Z9 72 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0732-183X J9 J CLIN ONCOL JI J. Clin. Oncol. PD MAY PY 1998 VL 16 IS 5 BP 1885 EP 1889 PG 5 WC Oncology SC Oncology GA ZL271 UT WOS:000073415900034 PM 9586905 ER PT J AU Ette, EI Sun, H Ludden, TM AF Ette, EI Sun, H Ludden, TM TI Balanced designs in longitudinal population pharmacokinetic studies SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article AB A simulation study was performed using a balanced design to determine the sample size required for accurate and precise estimation of a parameter at a given level of intersubject variability in a longitudinal population pharmacokinetic study. A two-compartment model parameterized in terms of clearance (Cl), volumes of the central (V1) and peripheral (V2) compartments, and intercompartmental clearance (Q) with multiple intravenous bolus inputs was assumed. Six samples were obtained from each subject using the informative profile (block) randomized design. Variability (in terms of coefficient of variation, CV) in model parameters was varied between 30% and 100%, and residual variability was fixed at 15%. Sample sizes ranging from 30 to 1,000 subjects were studied, and a hundred replicate data sets were generated and analyzed with NONMEM for each sample size at each CV. A sample size of 30 was required for accurate and precise estimation of structural model parameters when CV less than or equal to 75%, except for Cl where it is adequate for CV less than or equal to 100%. A sample size of 80 was required for intersubject variability estimation with CV less than or equal to 60%. Robust estimates of variability in CI were obtained with sample sizes of 30 (CV less than or equal to 45%), 60 (CV 60-75%), and 100 (CV greater than or equal to 75%). Positively biased estimates of residual variability were obtained irrespective of sample size at greater than or equal to 60% CV. This indicates that estimates of residual variability obtained in study situations where CV greater than or equal to 60% should be interpreted with caution. In such situations model misspecification may not be the issue, because in this simulation study concentration-time profiles were generated and analyzed with the same model. Although these results should be interpreted within the context of the study, they provide a framework for addressing the issue of sample size in longitudinal population pharmacokinetic study with a balanced sampling design. The result of a population pharmacokinetic study can be anticipated by comparing the results of several simulations in which the various input factors have been varied. (C) 1998 The American College of Clinical Pharmacology. C1 Vertex Pharmaceut, Cambridge, MA 02139 USA. US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. Univ Nebraska, Med Ctr, Coll Pharm, Dept Pharmaceut Sci, Omaha, NE USA. RP Ette, EI (reprint author), Vertex Pharmaceut, 130 Waverly St, Cambridge, MA 02139 USA. NR 9 TC 16 Z9 16 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAY PY 1998 VL 38 IS 5 BP 417 EP 423 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZM668 UT WOS:000073563900005 PM 9602953 ER PT J AU Mesmer, MZ Satzger, RD AF Mesmer, MZ Satzger, RD TI Determination of gamma-hydroxybutyrate (GHB) and gamma-butyrolactone (GBL) by HPLC/UV-VIS spectrophotometry and HPLC/thermospray mass spectrometry SO JOURNAL OF FORENSIC SCIENCES LA English DT Article DE forensic science; gamma-hydroxybutyrate; high-performance liquid chromotography; thermospray liquid chromatography mass spectrometry; substance abuse detection ID ACID AB This laboratory frequently receives samples that are suspected of being gamma-hydroxybutyrate (GHB), its lactone, gamma-butyrolactone (GBL), or a mixture of the two. We have developed an HPLC/UV-VIS spectrophotometric method for the separation and quantitation of GHB and GEL in illegal preparations that are available on the black market. The estimated detection limit is 50 ng injected onto the column. We are also reporting a simple and fast HPLC/thermospray mass spectrometric method for the confirmation of these compounds in illegal preparations. The characteristic mass spectrum for each compound could be obtained from as low as a 5 mu g injection. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45202 USA. RP Mesmer, MZ (reprint author), US FDA, Forens Chem Ctr, 1141 Cent Pkwy, Cincinnati, OH 45202 USA. NR 12 TC 29 Z9 32 U1 3 U2 11 PU AMER SOC TESTING MATERIALS PI W CONSHOHOCKEN PA 100 BARR HARBOR DR, W CONSHOHOCKEN, PA 19428-2959 USA SN 0022-1198 J9 J FORENSIC SCI JI J. Forensic Sci. PD MAY PY 1998 VL 43 IS 3 BP 489 EP 492 PG 4 WC Medicine, Legal SC Legal Medicine GA ZN879 UT WOS:000073692700006 ER PT J AU Mason, LH Willette-Brown, J Anderson, SK Gosselin, P Shores, EW Love, PE Ortaldo, JR McVicar, DW AF Mason, LH Willette-Brown, J Anderson, SK Gosselin, P Shores, EW Love, PE Ortaldo, JR McVicar, DW TI Characterization of an associated 16-kDa tyrosine phosphoprotein required for Ly-49D signal transduction SO JOURNAL OF IMMUNOLOGY LA English DT Article ID NATURAL-KILLER-CELLS; MOLECULES; RECEPTORS; WELL AB Ly-49D is an activating receptor on NK cells that does not become tyrosine phosphorylated upon activation. This report demonstrates that immunoprecipitation of Ly-49D, following pervanadate treatment or specific Ab cross-linking, coprecipitates a 16-kDa tyrosine-phosphorylated protein (pp16), Immunoblotting experiments and data from TCR-zeta/FceRI gamma double knockout mice confirm that pp16 is not TCR-zeta, TCR-eta, or FceRI gamma, Association of pp16 with Ly-49D involves a transmembrane arginine since mutation to leucine (Ly-49D(R54L)) abolishes association with pp16 in transfected P815 cells. In addition, Ly-49D(R54L) transfectants fail to mediate Ca2+ mobilization following Ab cross-linking. Therefore, signaling through Ly-49D on NK cells depends on association with a distinct tyrosine phosphoprotein (pp16) in a manner analogous to that of TCR and FcR. Expression of this novel signaling peptide in both the NK and myeloid lineages indicates that pp16 is likely involved in the signal transduction cascade of additional receptor families. C1 NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. NCI, Intramural Res Support Program, SAIC Frederick, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Washington, DC 20204 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Mason, LH (reprint author), NCI, Expt Immunol Lab, Div Basic Sci, Frederick Canc Res & Dev Ctr, Bldg 560,Room 31-93, Frederick, MD 21702 USA. EM MASON@MAIL.NCIFCRF.GOV RI Anderson, Stephen/B-1727-2012; McVicar, Daniel/G-1970-2015 OI Anderson, Stephen/0000-0002-7856-4266; NR 20 TC 80 Z9 80 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 MAY 1 PY 1998 VL 160 IS 9 BP 4148 EP 4152 PG 5 WC Immunology SC Immunology GA ZJ528 UT WOS:000073225800002 PM 9574512 ER PT J AU McRae, BL Semnani, RT Hayes, MP van Seventer, GA AF McRae, BL Semnani, RT Hayes, MP van Seventer, GA TI Type I IFNs inhibit human dendritic cell IL-12 production and Th1 cell development SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CD4(+) T-CELLS; TUMOR-NECROSIS-FACTOR; RECOMBINANT INTERFERON-ALPHA; GAMMA-PRODUCTION; INTERLEUKIN-12 PRODUCTION; NATURAL-KILLER; LYMPHOKINE PRODUCTION; LYMPHOCYTE-RESPONSES; IMMUNE-RESPONSES; ANTIGEN AB We have investigated the role of type I IFNs (IFN-alpha and -beta) in human T cell differentiation using anti-CD3 mAb and allogeneic, in vitro-derived dendritic cells (DC) as APCs. DC were very efficient activators of naive CD4(+) T cells, providing necessary costimulation and soluble factors to support Th1 differentiation and expansion. Addition of IFN-alpha beta to DC/T cell cultures resulted in induction of T cell IL-10 production and inhibition of IFN-gamma, TNF-alpha, and LT secretion. Diminished T cell IFN-gamma production correlated with IFN-alpha beta-mediated inhibition of the p40 chain of the IL-12 heterodimer secreted by DC. Suppression of p40 IL-12 and IFN-alpha was not due to increased levels of IL-10 in these cultures, and production of IFN-gamma could be restored by exogenous IL-12, These data indicate that type I IFNs inhibit DC p40 IL-12 expression, which is required for development of IFN-gamma-producing CD4+ T cells. Furthermore, when T cells were restimulated without IFN-beta, these cells induced less p40 IL-12 from DC, suggesting that the functional properties of T cells may regulate DC function. Thus, IFN-alpha beta inhibits both IL-12-dependent and independent Th1 cytokine production and provides a mechanism for inhibition of IL-12-mediated immunity in viral infections. C1 Univ Chicago, Comm Immunol, Dept Pathol, Div Biol Sci, Chicago, IL 60637 USA. US FDA, Div Cytokine Biol, Bethesda, MD 20892 USA. RP van Seventer, GA (reprint author), Univ Chicago, Comm Immunol, Dept Pathol, Div Biol Sci, 5841 S Maryland Ave,Room J541A,MC1089, Chicago, IL 60637 USA. EM gvsevent@flowcity.bsd.uchicago.edu FU NIAID NIH HHS [AI34541] NR 56 TC 193 Z9 199 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 MAY 1 PY 1998 VL 160 IS 9 BP 4298 EP 4304 PG 7 WC Immunology SC Immunology GA ZJ528 UT WOS:000073225800022 PM 9574532 ER PT J AU Goletti, D Weissman, D Jackson, RW Collins, F Kinter, A Fauci, AS AF Goletti, D Weissman, D Jackson, RW Collins, F Kinter, A Fauci, AS TI The in vitro induction of human immunodeficiency virus (HIV) replication in purified protein derivative-positive HIV-infected persons by recall antigen response to Mycobacterium tuberculosis is the result of a balance of the effects of endogenous interleukin-2 and proinflammatory and antiinflammatory cytokines SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 4th Conference on Retroviruses and Opportunistic Infections CY JAN 22-31, 1997 CL WASHINGTON, D.C. ID TUMOR-NECROSIS-FACTOR; GROWTH-FACTOR-BETA; ACTIVE TUBERCULOSIS; IMMUNE ACTIVATION; FACTOR-ALPHA; TRANSFORMING GROWTH-FACTOR-BETA-1; PULMONARY TUBERCULOSIS; MONOCYTIC CELLS; TGF-BETA; EXPRESSION AB Coinfection with Mycobacterium tuberculosis and human immunodeficiency virus (HIV) is a serious problem, particularly in developing countries. Recently, M. tuberculosis and purified protein derivative (PPD) were demonstrated to induce HIV replication in CD8 T cell-depleted peripheral blood mononuclear cells from HIV-positive, PPD-positive persons but not in cells from PPD-negative persons. The role of endogenous and exogenous cytokines in modulating M. tuberculosis-induced HIV replication was evaluated. M. tuberculosis-induced HIV replication decreased following simultaneous inhibition of endogenous interleukin (IL)-2, IL-1 beta, and tumor necrosis factor-alpha by the addition of soluble receptors and receptor antagonists or following exogenous IL-10 and transforming growth factor (TGF)-beta. In contrast, neutralization of endogenous IL-10 and TGF-beta augmented M. tuberculosis-induced HIV replication by increasing cellular activation. Thus, the balance between IL-2 and proinflammatory and antiinflammatory cytokines plays a major role in,II. tuberculosis-induced replication of HIV. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mycobacterial Dis & Cellular Immunol, Rockville, MD 20857 USA. RP Fauci, AS (reprint author), NIAID, Immunoregulat Lab, NIH, Bldg 31,Room 7A03, Bethesda, MD 20892 USA. EM afl03@nih.gov OI Goletti, Delia/0000-0001-8360-4376 NR 44 TC 35 Z9 36 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAY PY 1998 VL 177 IS 5 BP 1332 EP 1338 PG 7 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZM264 UT WOS:000073521100026 PM 9593021 ER PT J AU Mahmood, I AF Mahmood, I TI Interspecies scaling: Predicting volumes, mean residence time and elimination half-life. Some suggestions SO JOURNAL OF PHARMACY AND PHARMACOLOGY LA English DT Article ID IN-VITRO DATA; METABOLIC-CLEARANCE; COMPARATIVE PHARMACOKINETICS; PHYSIOLOGICAL TIME; CIPROFLOXACIN; HUMANS; ANIMALS; DRUGS; DOG; DISPOSITION AB Extrapolation of animal data to assess pharmacokinetic parameters in man is an important tool in drug development. Clearance, volume of distribution and elimination half-life are the three most frequently extrapolated pharmacokinetic parameters. Extensive work has been done to improve the predictive performance of allometric scaling for clearance. In general there is good correlation between body weight and volume, hence volume in man can be predicted with reasonable accuracy from animal data. Besides the volume of distribution in the central compartment (V-c), two other volume terms, the volume of distribution by area (V-beta) and the volume of distribution at steady state (Vd(ss)), are also extrapolated from animals to man. This report compares the predictive performance of allometric scaling for V-c, V-beta and Vd(ss) in man from animal data. The relationship between elimination half-life (t1/2) and body weight across species results in poor correlation, most probably because of the hybrid nature of this parameter. To predict half-life in man from animal data, an indirect method (CL=VK, where CL=clearance, V is volume and K is elimination rate constant) has been proposed. This report proposes another indirect method which uses the mean residence time (MRT). After establishing that MRT can be predicted across species, it was used to predict half-life using the equation MRT = 1.44 x t1/2. The results of the study indicate that V, is predicted more accurately than Vp and Vdss in man. It should be emphasized that for first-time dosing in man, V,is a more important pharmacokinetic parameter than Vp or Vdss. Furthermore, MRT can be predicted reasonably well for man and can be used for prediction of half-life. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off Ctr 2, HFD-860,Room 4079,1451 Rockville Pike, Rockville, MD 20852 USA. NR 36 TC 33 Z9 33 U1 0 U2 3 PU ROYAL PHARMACEUTICAL SOC GREAT BRITAIN PI LONDON PA 1 LAMBETH HIGH ST, LONDON SE1 7JN, ENGLAND SN 0022-3573 J9 J PHARM PHARMACOL JI J. Pharm. Pharmacol. PD MAY PY 1998 VL 50 IS 5 BP 493 EP 499 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 174PP UT WOS:000079043800007 PM 9643442 ER PT J AU Prince, DM Welschenbach, MA AF Prince, DM Welschenbach, MA TI Olestra: A new food additive SO JOURNAL OF THE AMERICAN DIETETIC ASSOCIATION LA English DT Article ID SUBJECTS CONSUMING OLESTRA; CHRONIC TOXICITY; FRYING OILS; CARCINOGENICITY; TRIGLYCERIDE AB In 1987, Procter and Gamble Company (Cincinnati, Ohio) petitioned the US Food and Drug Administration (FDA) to amend the food additive regulations to allow sucrose esterified with fatty acids (olestra) to be used as a replacement for conventional fats. The petitioner later restricted its request for use in savory snacks. FDA considered evidence submitted by the petitioner, the opinions of experts, proceedings from the FDA Food Advisory Committee, and public discussion and concluded on January 25, 1996, that olestra was safe for use in savory snacks (eg, salty snacks such as potato chips, corn chips). Olestra is not toxic, carcinogenic, genotoxic, or teratogenic and is neither absorbed nor metabolized by the body, but may be associated with gastrointestinal tract symptoms such as cramping or loose stools. In addition, olestra affects the absorption of fat-soluble vitamins but does not affect the absorption of water-soluble nutrients. The petitioner's studies concluded that when olestra was consumed with foods containing vitamins A, D, E, or K, the fat substitute could have an effect on the absorption of these nutrients. Therefore, FDA is requiring that fat-soluble vitamins lost through absorption be added back to olestra as follows: 170 IU vitamin A per gram olestra, 12 IU vitamin D per gram olestra, 2.8 IU vitamin E per gram olestra, and 8 mu g vitamin K per gram olestra. As part of the conditions of approval FDA is requiring that the food labels of products containing olestra disclose the vitamin compensation and the potential gastrointestinal effects. FDA is also requiring that further studies examining consumption patterns and the effects of olestra on human beings be conducted. C1 US FDA, Off Special Invest, Off Commiss, Rockville, MD 20857 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US PHS, Washington, DC 20201 USA. RP Prince, DM (reprint author), US FDA, Off Special Invest, Off Commiss, HF-5,Room 15-44,5600 Fishers Ln, Rockville, MD 20857 USA. NR 22 TC 10 Z9 12 U1 2 U2 5 PU AMER DIETETIC ASSOC PI CHICAGO PA 120 S RIVERSIDE PLZ, STE 2000, CHICAGO, IL 60606-6995 USA SN 0002-8223 J9 J AM DIET ASSOC JI J. Am. Diet. Assoc. PD MAY PY 1998 VL 98 IS 5 BP 565 EP 569 PG 5 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZL506 UT WOS:000073440300015 PM 9597030 ER PT J AU Thompson, P Lu, JH Kaplan, GG AF Thompson, P Lu, JH Kaplan, GG TI The Cys-rich region of hepatitis A virus cellular receptor 1 is required for binding of hepatitis a virus and protective monoclonal antibody 190/4 SO JOURNAL OF VIROLOGY LA English DT Article ID COFACTOR PROTEIN CD46; A VIRUS; CAPSID PROTEIN; MEASLES-VIRUS; CLEAVAGE; IDENTIFICATION; VACCINE AB The hepatitis A virus cellular receptor 1 (HAVcr-1) cDNA codes for a class I integral membrane glycoprotein, termed havcr-1, of unknown natural function which serves as an African green monkey kidney (AGMK) cell receptor for HAV. The extracellular domain of haver-1 has an N-terminal Cys-rich region that displays homology with sequences of members of the immunoglobulin superfamily, followed by a Thr/Ser/Pro (TSP)-rich region characteristic of mucin-like O-glycosylated proteins. The havcr-1 glycoprotein contains four putative N-glycosylation sites, two in the Cys-rich region and two in the TSP-rich region. To characterize havcr-1 and define region(s) involved in HAV receptor function, we expressed the TSP-rich region in Escherichia coli fused to glutathione S-transferase and generated antibodies (Ab) in rabbits (anti-GST2 Ab), Western blot analysis with anti-GST2 Ab detected 62- and 65-kDa bands in AGMK cells and 59-, 62-, and 65-kDa bands in dog cells transfected with the HAVcr-1 cDNA (cr5 cells) but not in dog cells transfected with the vector alone (DR2 cells). Treatment of AGMK and cr5 cell extracts with peptide-N-glycosidase F resulted in the collapse of the havcr-1-specific bands into a single band of 56 kDa, which indicated that different N-glycosylated forms of haver-1 were expressed in these cells. Treatment of AGMK and cr5 cells with tunicamycin reduced binding of protective monoclonal Ab (MAb) 190/4, which suggested that N-glycans are required for binding of MAb 190/4 to havcr-1. To test this hypothesis, havcr-1 mutants lacking the N-glycosylation motif at the first site (mut1), second site (mut2), and both (mut3) sites were constructed and transfected into dog cells. Binding of MAb 190/4 and HAV to mut1 and mut3 cells was highly reduced, while binding to mut2 cells was not affected and binding to dog cells expressing an havcr-1 construct containing a deletion of the Cys-rich region (d1-cells) was undetectable. HAV-infected cr5 and mut2 cells but not mut1, mut3, d1-, and DR2 cells developed the characteristic cytoplasmic granular fluorescence of HAV-infected cells. These results indicate that the Cys-rich region of havcr-1 and its first N-glycosylation site are required for binding of protective MAb 190/4 and HAV receptor function. C1 US FDA, CBER, Div Viral Prod, Lab Hepatitus Viruses, Bethesda, MD 20892 USA. RP Kaplan, GG (reprint author), US FDA, CBER, Div Viral Prod, Lab Hepatitus Viruses, 8800 Rockville Pike,Bldg 29A-NIH,Rm 1D10,HFM-448, Bethesda, MD 20892 USA. NR 22 TC 25 Z9 27 U1 0 U2 3 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD MAY PY 1998 VL 72 IS 5 BP 3751 EP 3761 PG 11 WC Virology SC Virology GA ZH268 UT WOS:000073090100030 PM 9557657 ER PT J AU Ito, Y Kajkenova, O Feuers, RJ Udupa, KB Desai, VG Epstein, J Hart, RW Lipschitz, DA AF Ito, Y Kajkenova, O Feuers, RJ Udupa, KB Desai, VG Epstein, J Hart, RW Lipschitz, DA TI Impaired glutathione peroxidase activity accounts for the age-related accumulation of hydrogen peroxide in activated human neutrophils SO JOURNALS OF GERONTOLOGY SERIES A-BIOLOGICAL SCIENCES AND MEDICAL SCIENCES LA English DT Article ID SUPEROXIDE-DISMUTASE; SIGNAL TRANSDUCTION; CATALASE; GENERATION; REDUCTASE; SELENIUM; CALCIUM; CELLS AB Background. As assessed by flow cytometry, the increase in hydrogen peroxide in individual neutrophils from old volunteers was significantly greater than in neutrophils from young volunteers. To explain the discrepancy in previous reports that showed reduced superoxide generation with age and our finding, we measured the kinetics of antioxidative enzymes. Methods. Neutrophils were obtained from young (ages 21-34) and old (ages over 65) volunteers. The increase in hydrogen peroxide following stimulation with formyl peptide in individual neutrophils was assessed by how cytometry by using dihydrorhodamine 123. The enzyme kinetics was determined from the best fit curve using Michaelis-Menten equations. Results. Aging was associated with a significant reduction in the V-max for glutathione peroxidase. The decreased activity was not due to selenium deficiency as the serum and neutrophil concentrations were identical with age. Following activation, a significant increase in the K-m was noted in neutrophils from young but not from old volunteers. Conclusions. These results account for the increased intracellular accumulation of hydrogen peroxide as a function of age in stimulated neutrophils. These results provide evidence in humans of an age-related impairment in antioxidative defense mechanisms that support the free radical theory of aging. C1 John L McClellan Mem Vet Hosp, GRECC 182LR, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Anat, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Donald W Reynolds Dept Geriatr, Little Rock, AR 72205 USA. US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Genet Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Dept Hlth & Human Serv, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Lipschitz, DA (reprint author), John L McClellan Mem Vet Hosp, GRECC 182LR, 4300 W 7th St, Little Rock, AR 72205 USA. FU NIA NIH HHS [AG 09458, AG 07473] NR 25 TC 20 Z9 21 U1 0 U2 1 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 MAY PY 1998 VL 53 IS 3 BP M169 EP M175 PG 7 WC Geriatrics & Gerontology; Gerontology SC Geriatrics & Gerontology GA ZM037 UT WOS:000073498400011 PM 9597047 ER PT J AU Tao, CB Mittelstaedt, RA Heflich, RH AF Tao, CB Mittelstaedt, RA Heflich, RH TI DNA sequence flanking the protein coding regions of the rat Hprt gene SO MUTATION RESEARCH-GENOMICS LA English DT Article DE gene mutation; chemical mutagenesis; multiplex PCR; exon; intron; promoter region ID HYPOXANTHINE PHOSPHORIBOSYLTRANSFERASE GENE; EXPRESSION; MUTATION C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Interdisciplinary Toxicol Program, Little Rock, AR 72205 USA. RP Tao, CB (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM tchen@nctr.fda.gov NR 12 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5726 J9 MUTAT RES-GENOMICS JI Mutat. Res.-Genomics PD MAY PY 1998 VL 382 IS 3-4 BP 79 EP 80 PG 2 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA 128LN UT WOS:000076407900001 ER PT J AU Debinski, W Gibo, DM Obiri, NI Kealiher, A Puri, RK AF Debinski, W Gibo, DM Obiri, NI Kealiher, A Puri, RK TI Novel anti-brain tumor cytotoxins specific for cancer cells SO NATURE BIOTECHNOLOGY LA English DT Article DE interleukin 13; glioblastoma; fusion proteins; mutations; tumor specificity; anticancer therapeutics; receptors ID PSEUDOMONAS EXOTOXIN-A; HUMAN INTERLEUKIN-4 RECEPTOR; COMMON GAMMA-CHAIN; HUMAN GLIOMA-CELLS; ADHESION MOLECULE-1; CARCINOMA-CELLS; ENDOTHELIAL-CELLS; TOXIN; EXPRESSION; AERUGINOSA AB The vast majority of brain cancers (gliomas) express a receptor (R) for interleukin 13 (IL13). In order to achieve specific targeting of the IL13R in gliomas, we have mutagenized human (h) IL13. The mutation was made to alter IL13 interaction with the shared functional IL13/4 normal tissue receptor, but not with the glioma-associated receptor. We have thus produced hIL13.E13K (glutamic acid at position 13 changed to lysine) and fused it to derivatives of Pseudomonas exotoin A. The hIL13.E13K-based cytotoxins are less active on normal cells and thus less toxic, and are better antitumor agents compared with the cytotoxins containing nonmutagenized hIL13. C1 Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Neurosurg Sect,Dept Surg, Hershey, PA 17033 USA. US FDA, Ctr Biol Evaluat & Res, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. RP Debinski, W (reprint author), Penn State Univ, Milton S Hershey Med Ctr, Coll Med, Neurosurg Sect,Dept Surg, Hershey, PA 17033 USA. EM wdebinski@psghs.edu NR 44 TC 74 Z9 75 U1 0 U2 4 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1087-0156 J9 NAT BIOTECHNOL JI Nat. Biotechnol. PD MAY PY 1998 VL 16 IS 5 BP 449 EP 453 DI 10.1038/nbt0598-449 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA ZL948 UT WOS:000073489600029 PM 9592393 ER PT J AU Ikeda, H Fernandez, R Wilk, A Barchi, JJ Huang, XL Marquez, VE AF Ikeda, H Fernandez, R Wilk, A Barchi, JJ Huang, XL Marquez, VE TI The effect of two antipodal fluorine-induced sugar puckers on the conformation and stability of the Dickerson-Drew dodecamer duplex [d(CGCGAATTCGCG)](2) SO NUCLEIC ACIDS RESEARCH LA English DT Article ID YEAST TFIIA/TBP/DNA COMPLEX; TRANSCRIPTION FACTOR-IIIA; DOUBLE-HELIX FORMATION; CRYSTAL-STRUCTURE; ANTIVIRAL NUCLEOSIDES; DNA DODECAMER; BINDING-SITE; MINOR-GROOVE; B-FORM; X-RAY AB UV thermal melting studies, CD and NMR spectroscopies were employed to assess the contribution of antipodal sugar conformations on the stability of the canonical B-DNA conformation of the Dickerson-Drew dodecamer duplex {[d(CGCGAATTCGCG)](2), (ODN 1)}. Different oligodeoxynucleotide versions of ODN 1 were synthesized with modified thymidine units favoring distinct sugar conformations by using a 3'-endo (north) 2'-fluoro-2'-deoxyribofuranosyl thymine (1) or a 2'-endo (south) 2'-fluoro-2'-deoxyarabinofuranosyl thymine (2). The results showed that two south thymidines greatly stabilized the double helix, whereas two north thymidines destabilized it by inducing a more A-like conformation in the middle of the duplex. Use of combinations of north and south thymidine conformers in the same oligo destabilized the double helix even further, but without inducing a conformational change. The critical length for establishing a detectable A-like conformation in the middle of a B-DNA ODN appears to be 4 bp. Our results suggest that manipulation of the conformation of DNA in a sequence-independent manner is possible. C1 NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Marquez, VE (reprint author), NCI, Med Chem Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. EM marquezv@dc37a.nci.nih.gov RI Barchi Jr., Joseph/N-3784-2014 NR 52 TC 56 Z9 56 U1 0 U2 7 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 MAY 1 PY 1998 VL 26 IS 9 BP 2237 EP 2244 DI 10.1093/nar/26.9.2237 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZL462 UT WOS:000073435300031 PM 9547286 ER PT J AU Lichtenstein, AH Kennedy, E Barrier, P Danford, D Ernst, ND Grundy, SM Leveille, GA Van Horn, L Williams, CL Booth, SL AF Lichtenstein, AH Kennedy, E Barrier, P Danford, D Ernst, ND Grundy, SM Leveille, GA Van Horn, L Williams, CL Booth, SL TI Dietary fat consumption and health SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT Tufts-University Dialogue Conference on the Role of Fat-Modified Foods in Dietary Change CY DEC 07-09, 1997 CL TUFTS UNIV, BOSTON, MASSACHUSETTS SP Proctor & Gamble Co HO TUFTS UNIV ID NUTRITION EXAMINATION SURVEYS; DEPENDENT DIABETES-MELLITUS; AMERICAN-HEART-ASSOCIATION; HIGH-CARBOHYDRATE DIETS; BREAST-CANCER; RISK-FACTORS; PHYSICAL-ACTIVITY; NATIONAL-HEALTH; ENERGY-INTAKE; COLON-CANCER C1 Tufts Univ, Boston, MA 02111 USA. USDA, Res Educ & Econ, Washington, DC 20250 USA. Amer Diabet Assoc, Alexandria, VA USA. US FDA, Washington, DC USA. NIH, Bethesda, MD 20892 USA. Univ Texas, SW Med Ctr, Dallas, TX USA. Leveille Associates, Denville, NJ USA. Northwestern Univ, Chicago, IL 60611 USA. Amer Hlth Fdn, Valhalla, NY 10595 USA. RP Booth, SL (reprint author), Tufts Univ, 711 Washington St, Boston, MA 02111 USA. NR 143 TC 99 Z9 103 U1 0 U2 19 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 1998 VL 56 IS 5 BP S3 EP S19 PN 2 PG 17 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZR336 UT WOS:000073963900002 PM 9624878 ER PT J AU Porter, D Kris-Etherton, P Borra, S Christ-Erwin, M Novelli, P Foreyt, J Goldberg, J Nabors, LO Schwartz, N Lewis, C Layden, W Novelli, P Economos, C AF Porter, D Kris-Etherton, P Borra, S Christ-Erwin, M Novelli, P Foreyt, J Goldberg, J Nabors, LO Schwartz, N Lewis, C Layden, W Novelli, P Economos, C TI Educating consumers regarding choices for fat reduction SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT Tufts-University Dialogue Conference on the Role of Fat-Modified Foods in Dietary Change CY DEC 07-09, 1997 CL TUFTS UNIV, BOSTON, MASSACHUSETTS SP Proctor & Gamble Co HO TUFTS UNIV ID DIETARY GUIDELINES; DISEASE PREVENTION; HEALTH; COMMUNITY; PROGRAM; ADULTS C1 Tufts Univ, Medford, MA 02155 USA. Lib Congress, Washington, DC 20540 USA. Penn State Univ, University Pk, PA 16802 USA. Int Food Informat Council, Washington, DC USA. Porter Novelli, Washington, DC USA. Baylor Coll Med, Houston, TX 77030 USA. Calorie Control Council, Atlanta, GA USA. Amer Dietet Assoc, Chicago, IL USA. US FDA, Washington, DC 20204 USA. RP Economos, C (reprint author), Tufts Univ, 132 Curtis St, Medford, MA 02155 USA. NR 86 TC 5 Z9 5 U1 0 U2 1 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 1998 VL 56 IS 5 BP S75 EP S92 PN 2 PG 18 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZR336 UT WOS:000073963900008 PM 9624881 ER PT J AU Roberts, SB Pi-Sunyer, FX Dreher, M Hahn, R Hill, JO Kleinman, RE Peters, JC Ravussin, E Rolls, BJ Yetley, E Booth, SL AF Roberts, SB Pi-Sunyer, FX Dreher, M Hahn, R Hill, JO Kleinman, RE Peters, JC Ravussin, E Rolls, BJ Yetley, E Booth, SL TI Physiology of fat replacement and fat reduction: Effects of dietary fat and fat substitutes on energy regulation SO NUTRITION REVIEWS LA English DT Article; Proceedings Paper CT Tufts-University Dialogue Conference on the Role of Fat-Modified Foods in Dietary Change CY DEC 07-09, 1997 CL TUFTS UNIV, BOSTON, MASSACHUSETTS SP Proctor & Gamble Co HO TUFTS UNIV ID HIGH-CARBOHYDRATE DIETS; EATING AD-LIBITUM; FREE-LIVING MEN; FOOD-INTAKE; WEIGHT-LOSS; SUCROSE POLYESTER; COVERT MANIPULATION; MACRONUTRIENT INTAKE; SUBSTRATE OXIDATION; CONTROLLED TRIAL C1 Tufts Univ, Boston, MA 02111 USA. Columbia Univ, St Lukes Roosevelt Hosp, New York, NY USA. Nabisco Foods Grp, E Hanover, NJ USA. Publ Voice Food & Hlth Policy, Washington, DC USA. Univ Colorado, Denver, CO 80202 USA. Massachusetts Gen Hosp, Boston, MA 02114 USA. Procter & Gamble Co, Cincinnati, OH USA. NIH, Phoenix, AZ USA. Penn State Univ, University Pk, PA 16802 USA. US FDA, Washington, DC 20204 USA. RP Booth, SL (reprint author), Tufts Univ, 711 Washington St, Boston, MA 02111 USA. NR 102 TC 35 Z9 36 U1 4 U2 5 PU INT LIFE SCIENCES INST PI LAWRENCE PA 810 EAST 10TH ST SUBSCRIPTION OFFICE, LAWRENCE, KS 66044 USA SN 0029-6643 J9 NUTR REV JI Nutr. Rev. PD MAY PY 1998 VL 56 IS 5 BP S29 EP S41 PN 2 PG 13 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZR336 UT WOS:000073963900004 PM 9624879 ER PT J AU Cardinali, M Jakus, J Shah, S Ensley, JF Robbins, KC Yeudall, WA AF Cardinali, M Jakus, J Shah, S Ensley, JF Robbins, KC Yeudall, WA TI p21(WAF1/Cip1) retards the growth of human squamous cell carcinomas in vivo SO ORAL ONCOLOGY LA English DT Article DE oral cancer; gene therapy; tumour suppressor; cell cycle; p21; WAF1; Cip1; sdi1 ID WILD-TYPE P53; CYCLIN-DEPENDENT KINASES; TGF-BETA; GENE-TRANSFER; DNA-REPLICATION; NECK-CANCER; TUMOR-CELLS; IN-VITRO; RETROVIRAL VECTORS; MEDIATED TRANSFER AB The excessive proliferation exhibited by cancer cells is frequently a result of their failure to adequately regulate cell cycle progression, In the present study, we developed a xenograft model of oral cancer in athymic mice, using squamous carcinoma cell lines and examined the ability of the cyclin-dependent kinase inhibitor p21 (WAF1/Cip1) to retard tumour growth in vivo, using a retroviral delivery system. Human p21 cDNA was cloned by polymerase chain reaction, expressed, and the encoded protein shown to have biological activity in in vitro kinase assays. Amphotropic retrovirus cultures which expressed recombinant p21 were generated and used to treat established squamous cell carcinoma xenografts. Two weeks following onset of treatment, tumours injected with p21 virus producer cells showed a reduction in size between 3- and 10-fold compared with tumours which received control cells which produced control virus alone. The data indicate that recombinant p21 may be of future use for therapeutic intervention in oral cancer. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 NIDR, Oral & Pharyngeal Canc Branch, Bethesda, MD 20892 USA. Wayne State Univ, Div Hematol Oncol, Detroit, MI 48201 USA. RP Cardinali, M (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Clin Trials Design & Anal, Oncol Branch, 1401 Rockville Pike,WOC I HFM-573, Rockville, MD 20852 USA. EM cardinali@al.cber.fda.gov NR 71 TC 30 Z9 31 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0964-1955 J9 ORAL ONCOL JI Oral Oncol. PD MAY PY 1998 VL 34 IS 3 BP 211 EP 218 DI 10.1016/S1368-8375(97)00083-3 PG 8 WC Oncology; Dentistry, Oral Surgery & Medicine SC Oncology; Dentistry, Oral Surgery & Medicine GA ZU714 UT WOS:000074226900009 PM 9692056 ER PT J AU Read, JS Frasch, CE Rich, K Fitzgerald, GA Clemens, JD Pitt, J Pelton, SI Hanson, IC Handelsman, E Diaz, C Fowler, MG AF Read, JS Frasch, CE Rich, K Fitzgerald, GA Clemens, JD Pitt, J Pelton, SI Hanson, IC Handelsman, E Diaz, C Fowler, MG CA Women Infants Transmission Study Grp TI The immunogenicity of Haemophilus influenzae type b conjugate vaccines in children born to human immunodeficiency virus-infected women SO PEDIATRIC INFECTIOUS DISEASE JOURNAL LA English DT Article; Proceedings Paper CT Annual Meeting of the Pediatric-Academic-Society/Ambulatory-Pediatric-Association CY MAY 01-05, 1998 CL NEW ORLEANS, LOUISIANA SP Pediat Acad Soc, Ambulatory Pediat Assoc DE Haemophilus vaccines; bacterial antibodies; acquired immunodeficiency syndrome-related opportunistic infections ID CAPSULAR POLYSACCHARIDE; ANTIBODY-RESPONSES; INFANTS; VACCINATION; IMMUNITY AB Background. Immunocompromise caused by HIV-1 infection increases the importance of receipt of routine childhood vaccines to prevent infections such as invasive Haemophilus influenzae type B (Hib) disease. The objectives of the study were to evaluate the immunogenicity of Hib conjugate vaccines among HIV-infected children according to clinical and immunologic disease progression as well as viral load. Methods. The concentration of antibody to polyribosylribitol phosphate (PRP) was measured at similar to 9 and 24 months of age in plasma specimens from children of HIV-infected women enrolled in the Women and Infants Transmission Study. Results. Among 227 children (35 HIV-infected, 192 uninfected) at the 9-month study visit who were known to have received age-appropriate immunization with CRM197 mutant Corynebacterium diphtheriae protein-conjugated Hib vaccine, geometric mean antibody concentrations were lower among HIV-infected children (1.64 mu g/ml) than among uninfected children (2.70 mu g/ml), although the difference was not statistically significant. Anti-PRP antibody concentrations did not vary significantly among these HIV-infected children with predominantly mild-moderate disease progression according to clinical category, immunologic stage or viral load (P greater than or equal to 0.48). The proportion of children with antibody concentrations greater than or equal to 1.0 mu g/ml did not vary significantly according to HIV infection status (73% uninfected, 74% infected) or, if infected, clinical or immunologic disease progression or viral load. Similar results were obtained among 127 children (17 HIV-infected, 110 uninfected) eligible for analysis at the 24-month study visit. Changes in antibody concentrations over time (between 9 and 24 months of age) did not differ significantly among 10 HIV-infected as compared with 72 uninfected children (P = 0.81). Conclusions. These results suggest that HIV-infected children with predominantly mild-moderate disease progression respond reasonably well in terms of a quantitative antibody response to Hib conjugate vaccines during the first 2 years of life. Research to further characterize the immune response to Hib conjugate vaccines and to further delineate the "durability" of anti-PRP antibody concentrations beyond 2 years of life should be pursued. C1 NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Bethesda, MD 20892 USA. US FDA, Div Bacterial Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. Univ Illinois, Chicago, IL USA. New England Res Inst, Watertown, MA 02172 USA. NICHHD, Epidemiol Branch, Bethesda, MD 20892 USA. NICHHD, WHO Int Collaborating Ctr Clin Evaluat Vaccines D, Div Epidemiol Stat & Prevent Res, Bethesda, MD 20892 USA. Columbia Univ, New York, NY USA. Boston Univ, Sch Med, Boston, MA 02118 USA. Baylor Coll Med, Houston, TX 77030 USA. SUNY Hlth Sci Ctr, Brooklyn, NY 11203 USA. Univ Puerto Rico, San Juan, PR 00936 USA. NIAID, Bethesda, MD 20892 USA. RP Read, JS (reprint author), NICHHD, Pediat Adolescent & Maternal AIDS Branch, NIH, Execut Bldg,Room 4B11F,6100 Execut Blvd MSC 751, Bethesda, MD 20892 USA. EM jr92o@nih.gov NR 29 TC 20 Z9 20 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0891-3668 J9 PEDIATR INFECT DIS J JI Pediatr. Infect. Dis. J. PD MAY PY 1998 VL 17 IS 5 BP 391 EP 397 DI 10.1097/00006454-199805000-00009 PG 7 WC Immunology; Infectious Diseases; Pediatrics SC Immunology; Infectious Diseases; Pediatrics GA ZN324 UT WOS:000073634500008 PM 9613652 ER PT J AU Silverman, BG Daley, WR Rubin, JD AF Silverman, BG Daley, WR Rubin, JD TI The use of infrared ear thermometers in pediatric offices SO PUBLIC HEALTH REPORTS LA English DT Article ID TYMPANIC THERMOMETRY; EMERGENCY; FEVER; CHILDREN AB Objective. To describe the use of infrared (IR) ear thermometers in pediatric and family practice offices. Methods, The authors mailed a questionnaire to 350 randomly selected members of the American Academy of Pediatrics and to 355 randomly selected members of the American Academy of Family Physicians. Results. Of respondents in clinical practice, 78% had used IR ear thermometers at least once in the past; 65% of pediatricians and 64% of family practice physicians were current users. Seventeen percent of pediatric offices and 18% of family practice offices that had used IR ear thermometers had discontinued use. most citing inaccuracy or lack of staff trust in the device. Pediatric offices were less likely than family practice offices to use the device in well neonates and sick neonates and more likely to use it in sick children. Advantages cited included rapid readings, ease of use, and accuracy. Seventy-five percent of current users reported at least one problem, including low readings and lack of staff trust. Conclusions, IR ear thermometers are widely used in pediatric and family practice offices. Some offices limit use of these devices to older children and adults, and most of the offices surveyed report using other devices as a check on the accuracy of IR thermometers. Statements by professional organizations that provide user guidelines and establish appropriate age cutoffs would be helpful. C1 US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, Rockville, MD 20850 USA. Univ Maryland, Sch Med, Dept Pediat, Baltimore, MD 21201 USA. Univ Maryland, Sch Med, Dept Epidemiol & Prevent Med, Baltimore, MD 21201 USA. RP Silverman, BG (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Surveillance & Biometr, HFZ-541,1350 Piccard Dr, Rockville, MD 20850 USA. EM bgs@cdrh.fda.gov OI Silverman, Barbara/0000-0002-0337-4919 NR 14 TC 7 Z9 7 U1 0 U2 1 PU US GOVERNMENT PRINTING OFFICE PI WASHINGTON PA SUPT OF DOCUMENTS, WASHINGTON, DC 20402-9325 USA SN 0033-3549 J9 PUBLIC HEALTH REP JI Public Health Rep. PD MAY-JUN PY 1998 VL 113 IS 3 BP 268 EP 272 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZQ313 UT WOS:000073845800025 PM 9633875 ER PT J AU Ramaiah, SK Soni, MG Bucci, TJ Mehendale, HM AF Ramaiah, SK Soni, MG Bucci, TJ Mehendale, HM TI Diet restriction enhances compensatory liver tissue repair and survival following administration of lethal dose of thioacetamide SO TOXICOLOGY AND APPLIED PHARMACOLOGY LA English DT Article; Proceedings Paper CT 36th Annual Meeting of the Society-of-Toxicology CY MAR 09-13, 1997 CL CINCINNATI, OH SP Soc Toxicol ID CALORIC RESTRICTION; HEPATOCELLULAR REGENERATION; PRETREATED RATS; HEPATOTOXICITY; TOXICITY; INJURY; AUTOPROTECTION; ACETAMINOPHEN; NECROSIS; CANCER AB Diet restriction is known to prevent a plethora of age-associated diseases including cancer. However, the effects of diet restriction on noncancer end points are not known. The objective of this study was to investigate whether diet restriction protects against hepatotoxicity of thioacetamide (TB), and if so, to investigate the underlying mechanism. Male Sprague-Dawley rats (250-275 g) were maintained on 65% of their ad libitum (AL) food consumption for a period of 3 weeks and then treated with a single low dose of 50 mg TA/kg ip. plasma enzymes (ALT and SDH), hepatic glycogen levels, and H-3-thymidine incorporation into hepatocellular nuclear DNA were measured during a time course (0-120 h) after TA administration. fiver sections were examined for histopathology, and cell-cycle progression was assessed by proliferating cell nuclear antigen (PCNA) immunohistochemistry. In Ak rats hepatic necrosis was evident at 12 h, peaked at 36 h, persisted up to 72 h, and was resolved by 96 h. in the diet-restricted (DR) group hepatic necrosis was observed at 12 h, peaked at 24 h, persisted tip 72 h, and was resolved by 96 h, Maximal injury indicated by enzyme elevation occurred in DR rats and was approximately sixfold greater than that observed in the Ak group. Histopathological examination of the liver sections revealed liver injury concordant with plasma enzyme elevations. There was a higher and sustained S-phase synthesis in the DR rats compared to AL group. S-phase stimulation was evident at 36 h, peaked at 48 h, and persisted until 96 h in the DR rats, whereas in the AL rats peak S-phase stimulation occurred at 36 h and subsided by 72 h. PCNA studies revealed a corresponding stimulation of cell-cycle progression indicating highly stimulated compensatory tissue repair. The 14-day lethality experiments (600 mg TA/kg ip) indicated 70% survival in the DR rats compared to 10% survival in the AL group. Although diet restriction increases hepatotoxic injury of TA, it protects from the lethal outcome by enhanced liver tissue repair. Comparison of liver injury and tissue repair employing an equitoxic dose (600 mg TA/kg in AL rats yields similar liver injury as observed with 50 mg TA/kg in DR rats) revealed that in spite of near equal injury up to 36 h, tissue repair response in DR rats is much higher. The compensatory tissue repair allows the DR rats to escape death in contrast to much lower compensation in AL rats leading to progression of liver injury culminating in death. (C) 1998 Academic Press. C1 NE Louisiana Univ, Coll Pharm & Hlth Sci, Div Toxicol, Monroe, LA 71209 USA. NE Louisiana Univ, Coll Pharm & Hlth Sci, Louisiana Inst Toxicol, Monroe, LA 71209 USA. Natl Ctr Toxicol Res, Pathol Associates Int, Jefferson, AR 72079 USA. RP NE Louisiana Univ, Coll Pharm & Hlth Sci, Div Toxicol, Monroe, LA 71209 USA. EM pymehendale@alpha.nlu.edu FU NIEHS NIH HHS [ES-08604] NR 48 TC 29 Z9 29 U1 0 U2 1 PU ACADEMIC PRESS INC ELSEVIER SCIENCE PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0041-008X EI 1096-0333 J9 TOXICOL APPL PHARM JI Toxicol. Appl. Pharmacol. PD MAY PY 1998 VL 150 IS 1 BP 12 EP 21 DI 10.1006/taap.1998.8365 PG 10 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZT328 UT WOS:000074073800002 PM 9630448 ER PT J AU Nishimura, T Newkirk, K Sessions, RB Andrews, PA Trock, BJ Rasmussen, AA Montgomery, EA Bischoff, EK Hanigan, MH Cullen, KJ AF Nishimura, T Newkirk, K Sessions, RB Andrews, PA Trock, BJ Rasmussen, AA Montgomery, EA Bischoff, EK Hanigan, MH Cullen, KJ TI Association between expression of glutathione-associated enzymes and response to platinum-based chemotherapy in head and neck cancer SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT International Conference on Glutathione and Glutathione-Linked Enzymes in Human Cancer and Other Diseases CY OCT 31-NOV 03, 1996 CL HILTON HEAD ISL, SOUTH CAROLINA DE cancer; glutathione-associated enzymes; platinum-based chemotherapy ID SQUAMOUS-CELL CARCINOMA; GAMMA-GLUTAMYL-TRANSPEPTIDASE; S-TRANSFERASES; GENE-EXPRESSION; CISPLATIN; HYBRIDIZATION; AMPLIFICATION; LOCALIZATION; RESISTANCE; INFUSION AB We examined the correlation between response to platinum-based chemotherapy and expression of glutathione S-transferase (GST), gamma-GGT (both by immunohistochemistry) and gamma-GCS (by in situ hybridization) in 51 patients with head and neck cancer, who received a total of 56 courses of chemotherapy. The overall response rate for the 56 chemotherapy treatment courses was 48%. The overall response rate (CR, PR) for patients with low GST scores was 88% (21 of 24), while among the patients with high GST scores, the overall response rate was 19% (6 of 32, P = 0.001). Patients with a low GST score were 4.7 times more likely to respond to chemotherapy than patients with high GST scores. GST scores corresponded to response in 84% of cases. Among 33 patients treated with chemotherapy for relapsed disease, the overall response rate for patients with low GST score was 70% (7 of 10), while among the patients with high GST scores, the overall response rate was 8.7% (2 of 23, P < 0.001). In contrast, both gamma-GCS and gamma-GGT showed a range of expression in these samples, but there was no significant correlation with treatment response. We conclude that GST expression correlates well with response to platinum based chemotherapy in head and neck cancer. (C) 1998 Elsevier Science Ireland Ltd. All rights reserved. C1 Georgetown Univ, Med Ctr, Div Hematol Oncol, Washington, DC 20007 USA. Georgetown Univ, Dept Otolaryngol Head & Neck Surg & Pathol, Washington, DC USA. Kanazawa Univ, Dept Otolaryngol, Kanazawa, Ishikawa 920, Japan. US FDA, Rockville, MD 20857 USA. Georgetown Univ, Vincent T Lombardi Canc Res Ctr, Washington, DC USA. Univ Virginia, Charlottesville, VA USA. RP Cullen, KJ (reprint author), Georgetown Univ, Med Ctr, Div Hematol Oncol, 3800 Reservoir Rd NW, Washington, DC 20007 USA. NR 31 TC 5 Z9 5 U1 0 U2 0 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 APR 24 PY 1998 VL 112 BP 187 EP 198 PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA ZV735 UT WOS:000074335800018 ER PT J AU Pogribny, IP Pogribna, M James, SJ AF Pogribny, IP Pogribna, M James, SJ TI Methylation of a single CpG site within the p53 gene promoter region reduces gene expression. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 460 BP A1389 EP A1389 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500612 ER PT J AU Romanova, L Alexandrov, L Nguyen, M Nordan, R Trepel, J Mushinski, F AF Romanova, L Alexandrov, L Nguyen, M Nordan, R Trepel, J Mushinski, F TI PKC- and IL-3 regulate actin cytoskeleton rearrangements associated with the effects on cell cycle by two distinct pathways: PKC-delta dominates over IL-3 signal. SO FASEB JOURNAL LA English DT Meeting Abstract C1 NCI, NIH, Bethesda, MD 20892 USA. US FDA, CBER, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD APR 24 PY 1998 VL 12 IS 8 SU S MA 543 BP A1404 EP A1404 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 260QN UT WOS:000083961500696 ER PT J AU Kaine, LA Wolnik, KA AF Kaine, LA Wolnik, KA TI Detection of counterfeit and relabeled infant formulas by high-pH anion-exchange chromatography pulsed amperometric detection for the determination of sugar profiles SO JOURNAL OF CHROMATOGRAPHY A LA English DT Article; Proceedings Paper CT 10th Anniversary of the International Ion Chromatography Symposium (IICS 97) CY SEP 14-17, 1997 CL SANTA CLARA, CALIFORNIA DE infant formulas; food analysis; carbohydrates ID OLIGOSACCHARIDES AB High pH anion-exchange separation with pulsed amperometric detection (HPAE-PAD) is used to characterize various milk-based, soy-based, and protein hydrolysate infant formulas based on carbohydrate profiles. Counterfeit and relabeled formulas are compared to authentics. Figures of merit are shown for glucose, fructose, lactose, sucrose, and maltose. (C) 1998 Elsevier Science B.V. C1 US Food & Drug Adm, Cincinnati, OH 45202 USA. RP Kaine, LA (reprint author), US Food & Drug Adm, 1141 Cent Pkwy, Cincinnati, OH 45202 USA. NR 7 TC 16 Z9 16 U1 0 U2 5 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0021-9673 J9 J CHROMATOGR A JI J. Chromatogr. A PD APR 24 PY 1998 VL 804 IS 1-2 BP 279 EP 287 DI 10.1016/S0021-9673(97)01249-1 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZN363 UT WOS:000073638400035 PM 9615407 ER PT J AU Lunn, G Phillips, LR Pacula-Cox, C AF Lunn, G Phillips, LR Pacula-Cox, C TI Reversed-phase high-performance liquid chromatography of 4-(2-pyridyl)-1-piperazinethiocarboxylic acid 2-[1-(pyridyl)ethylidene]hydrazide dihydrochloride (NSC 348977), a synthetic thiosemicarbazone with antitumor activity SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE NSC 348977; thiosemicarbazone ID 2-ACETYLPYRIDINE THIOSEMICARBAZONES; DERIVATIVES; COMPLEXES; INVITRO; AGENTS AB Reversed-phase HPLC conditions for the separation of 4-(2-pyridyl)-1-piperazinethiocarboxylic acid 2-[1-(pyridyl)ethylidene]hydrazide dihydrochloride (NSC 348977, I), a synthetic thiosemicarbazone with antitumor activity, from mouse plasma have been investigated. Following denaturization and precipitation of the spiked plasma with acetonitrile, an aliquot of the supernatant was diluted with aqueous buffer and subjected to analysis on a Nova-Pak C-18 column (150x3.9 mm I.D.) by isocratic elution with 50 mM aqueous potassium phosphate buffer (pH 6.8, containing 1 mM EDTA)-acetonitrile (60:40, v/v). The column effluent was monitored for UV absorption at 310 nm. Problems identified in the sample preparation and separation of I include sensitivity to oxygen, light, non-neutral pH and the presence of metal ions. These factors were seen to adversely influence sample recovery, and attempts were made to find conditions which minimize their effects. (C) 1998 Elsevier Science B.V. C1 NCI, Frederick Canc Res & Dev Ctr, Program Resources Inc Dyncorp, Lab Pharmaceut Chem, Frederick, MD 21702 USA. NCI, Lab Pharmaceut Chem, Dev Therapeut Program, Div Canc Treatment, Frederick, MD 21702 USA. RP Lunn, G (reprint author), US FDA, HFD-530,5600 Fishers Lane, Rockville, MD 20857 USA. FU NCI NIH HHS [N01- CO-74102] NR 20 TC 2 Z9 2 U1 0 U2 2 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 24 PY 1998 VL 708 IS 1-2 BP 217 EP 222 DI 10.1016/S0378-4347(97)00637-3 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZR377 UT WOS:000073968600025 PM 9653965 ER PT J AU Aurecchia, S Orloff, D Sobel, S AF Aurecchia, S Orloff, D Sobel, S TI Regulatory concerns at various phases of drug development SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT VIth World Conference on Clinical Pharmacology and Therapeutics CY AUG, 1996 CL BUENOS AIRES, ARGENTINA SP Int Union Pharm C1 US Food & Drug Adm, Ctr Drug Evaluat & Res, Rockville, MD USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Aurecchia, S (reprint author), Kansas Fdn Clin Pharmcol, 10550 Quivira Rd,Suite 240, Overland Pk, KS 66215 USA. NR 8 TC 3 Z9 3 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 23 PY 1998 VL 81 IS 8A SI SI BP 2F EP 4F DI 10.1016/S0002-9149(98)00250-1 PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZN749 UT WOS:000073678300003 PM 9604895 ER PT J AU Temple, R AF Temple, R TI The challenge of regulating development and approval drugs with pleiotropic action in cardiovascular disease SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT VIth World Conference on Clinical Pharmacology and Therapeutics CY AUG, 1996 CL BUENOS AIRES, ARGENTINA SP Int Union Pharm ID CORONARY HEART-DISEASE; BLOOD-PRESSURE; MORTALITY; STROKE C1 US FDA, Off Drug Evaluat, Rockville, MD 20857 USA. RP Temple, R (reprint author), Kansas Fdn Clin Pharmacol, 10550 Quivira Rd,Suite 240, Overland Pk, KS 66215 USA. NR 10 TC 2 Z9 2 U1 0 U2 1 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 23 PY 1998 VL 81 IS 8A SI SI BP 5F EP 8F DI 10.1016/S0002-9149(98)00249-5 PG 4 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZN749 UT WOS:000073678300005 PM 9604896 ER PT J AU Weintraub, M AF Weintraub, M TI Guidance for industry - Over-the-counter treatment of hypercholesterolemia SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT VIth World Conference on Clinical Pharmacology and Therapeutics CY AUG, 1996 CL BUENOS AIRES, ARGENTINA SP Int Union Pharm C1 US FDA, US Dept HHS, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Weintraub, M (reprint author), Off Training & Commun, Div Commun Management, Drug Informat Branch, HFD-210,5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 23 PY 1998 VL 81 IS 8A SI SI BP 78F EP 78F DI 10.1016/S0002-9149(98)00272-0 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZN749 UT WOS:000073678300040 PM 9604918 ER PT J AU Orloff, DG AF Orloff, DG TI Update on the US Food and Drug Administration regulatory approach to over-the-counter cholesterol-lowering drugs SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Article; Proceedings Paper CT VIth World Conference on Clinical Pharmacology and Therapeutics CY AUG, 1996 CL BUENOS AIRES, ARGENTINA SP Int Union Pharm C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Orloff, DG (reprint author), Care Of Dujovne C, Kansas Fdn Clin Pharmacol, 10550 Quivira Rd,Suite 240, Overland Pk, KS 66215 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 23 PY 1998 VL 81 IS 8A SI SI BP 79F EP 79F DI 10.1016/S0002-9149(98)00273-2 PG 1 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZN749 UT WOS:000073678300041 PM 9604919 ER PT J AU Black, DM Orloff, DG Bilheimer, DW Shepherd, J Olsson, AG Sacks, FM Paoletti, R Catapano, A AF Black, DM Orloff, DG Bilheimer, DW Shepherd, J Olsson, AG Sacks, FM Paoletti, R Catapano, A TI Section III - Should separate endpoint trials be required for all lipid-lowering drugs acting by the same mechanism? Section III discussion SO AMERICAN JOURNAL OF CARDIOLOGY LA English DT Editorial Material C1 Warner Lambert Parke Davis, Parke Davis Pharmaceut Res, Ann Arbor, MI 48105 USA. US FDA, Rockville, MD 20857 USA. Merck Sharp & Dohme Ltd, W Point, NY USA. RP Black, DM (reprint author), Warner Lambert Parke Davis, Parke Davis Pharmaceut Res, Ann Arbor, MI 48105 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0002-9149 J9 AM J CARDIOL JI Am. J. Cardiol. PD APR 23 PY 1998 VL 81 IS 8A SI SI BP 92F EP 94F PG 3 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZN749 UT WOS:000073678300050 ER PT J AU Pierce, LR Gaines, A Varricchio, F Epstein, JS AF Pierce, LR Gaines, A Varricchio, F Epstein, JS TI A dangerous error in the dilution of 25 percent albumin SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US Food & Drug Adm, Rockville, MD 20852 USA. RP Pierce, LR (reprint author), US Food & Drug Adm, Rockville, MD 20852 USA. NR 2 TC 6 Z9 6 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD APR 23 PY 1998 VL 338 IS 17 BP 1226 EP 1227 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZJ376 UT WOS:000073208400013 ER PT J AU Yin, JJ Smith, MJ Eppley, RM Page, SW Sphon, JA AF Yin, JJ Smith, MJ Eppley, RM Page, SW Sphon, JA TI Effects of fumonisin B-1 on lipid peroxidation in membranes SO BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES LA English DT Article DE membrane permeability; fumonisin; lipid peroxidation; electron spin resonance ID FUSARIUM-MONILIFORME; OXYGEN; PHOSPHATIDYLCHOLINE; TOXICITY; RADICALS; METALS; PHOSPHOLIPIDS; INHIBITION; RESONANCE; MECHANISM AB Electron spin resonance (ESR)(1) spill-label oximetry and spin trapping techniques have been used to study the effect of fumonisin B-1 (FB1), an amphipathic mycotoxin on lipid peroxidation in egg yolk phosphatidylcholine (EYPC) bilayers. In the study of the interaction between FB1 and lipid bilayers our results show that fumonisin disturbs the ordering of membranes, enhances oxygen transport in membranes, and also increases membrane permeability. In our model system, lipid peroxidations were initiated by extended incubation of the liposomes, or by inducing Fr2+ ions, UV illumination of H2O2 or ultrasound irradiation. As an indication of the rates of lipid oxidation in EYPC, the consumption of molecular oxygen was studied by monitoring the oxygen concentration in the aqueous phases of the liposomes. Lipid-derived free radicals generated during the oxidation process were measured by a spin trapping method. The incorporation of FB1 in the test samples made the membranes highly susceptible to oxidation. Our results provide the first evidence that the fumonisins appear to increase the rate of oxidation, promote the free radical intermediate production and accelerate the chain reactions associated with lipid peroxidation. The disruption of membrane structure, the enlargement of the relative oxygen diffusion-concentration products, as well as the enhancement effects on membrane permeability, thus provide additional insights into potential mechanisms by which the fumonisins could enhance oxidative stress and cell damage. (C) 1998 Elsevier Science B.V. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Yin, JJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. EM j2y@vm.cfsan.fda.gov RI Yin, Jun Jie /E-5619-2014 NR 44 TC 58 Z9 60 U1 0 U2 3 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0005-2736 J9 BBA-BIOMEMBRANES JI Biochim. Biophys. Acta-Biomembr. PD APR 22 PY 1998 VL 1371 IS 1 BP 134 EP 142 DI 10.1016/S0005-2736(98)00018-2 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA ZJ222 UT WOS:000073191700017 PM 9565668 ER PT J AU Romanova, LY Alexandrov, IA Nordan, RP Blagosklonny, MV Mushinski, JF AF Romanova, LY Alexandrov, IA Nordan, RP Blagosklonny, MV Mushinski, JF TI Cross-talk between protein kinase C-alpha (PKC-alpha) and -delta (PKC-delta): PKC-alpha elevates the PKC-delta protein level, altering its mRNA transcription and degradation SO BIOCHEMISTRY LA English DT Article ID DOWN-REGULATION; PHORBOL ESTER; MESSENGER-RNA; ENDOPLASMIC-RETICULUM; UP-REGULATION; BINDING SITE; CELLS; ISOZYMES; EXPRESSION; PHOSPHORYLATION AB Studies utilizing the overexpression of individual isoforms indicated that both PKC-alpha and -delta promote a number of biological effects, including inhibition of DNA synthesis associated with rearrangements of the actin cytoskeleton in the murine B-cell lymphoma (Baf3), differentiation of the murine promyelocyte line 32D, and activation of MAP kinase in CHO fibroblasts. We postulated that these results reflect some form of cross-regulation between PKC-alpha and -delta rather than their functional redundancy. In this report, we show that overexpression of PKC-alpha in Baf3 and 32D leads to an elevation of the endogenous PKC-delta mRNA and protein levels. The elevated steady-state PKC-delta mRNA level results from a combination of increased PKC-delta transcription and mRNA stability. Upregulation of PKC-delta mRNA by PKC-alpha occurs even after a selective depletion of the PKC-delta protein. In addition, phorbol ester-induced elevation of PKC-delta mRNA and protein levels can be prevented by the PKC inhibitor GF109203X, an indication of the requirement for PKC kinase activity. Inhibition of new protein synthesis by cycloheximide showed that upregulation of PKC-delta mRNA, as opposed to delayed downregulation of the PKC-delta protein, is primarily responsible for the accumulation of this isoform by PKC-alpha. In parental Baf3 and 32D cells and PKC-alpha overexpressers, PKC-alpha and PKC-delta are uniquely involved in cross-regulation, while PKC-epsilon, PKC-eta, and PKC-mu are not. C1 NIH, Natl Canc Inst, Genet Lab, Bethesda, MD 20892 USA. NIH, Natl Canc Inst, Med Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, Bethesda, MD 20892 USA. RP Mushinski, JF (reprint author), NIH, Natl Canc Inst, Genet Lab, Bldg 37,Rm 2B23,37 Convent Dr,MSC 4255, Bethesda, MD 20892 USA. NR 33 TC 44 Z9 45 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 21 PY 1998 VL 37 IS 16 BP 5558 EP 5565 DI 10.1021/bi9731807 PG 8 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZM208 UT WOS:000073515500027 PM 9548940 ER PT J AU Bai, RL Choe, K Ewell, JB Nguyen, NY Hamel, E AF Bai, RL Choe, K Ewell, JB Nguyen, NY Hamel, E TI Direct photoaffinity labeling of cysteine-295 of alpha-tubulin by guanosine 5 '-triphosphate bound in the nonexchangeable site SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID EXCHANGEABLE NUCLEOTIDE SITE; AMINO-ACID-SEQUENCE; DIMER DISSOCIATION; BETA-TUBULIN; FLUORESCENCE ANISOTROPY; PORCINE BRAIN; BINDING SITE; GTP; MICROTUBULES; POLYMERIZATION AB The alpha beta-tubulin heterodimer has two high affinity guanosine 5'-triphosphate binding sites, so that purified tubulin usually contains two molecules of bound guanosine nucleotide. Half this nucleotide is freely exchangeable with exogenous guanine nucleotide, and its binding site has been readily localized to the beta-subunit, The remaining nonexchangeable guanosine 5'-triphosphate can only be released from tubulin by denaturing the protein. We replaced the exchangeable site nucleotide of tubulin with 2'-deoxyguanosine 5'-diphosphate, exposed the resulting tubulin to ultraviolet light, degraded the protein, and isolated ribose-containing peptide derived from the nonexchangeable site. A large cyanogen bromide peptide was recovered, and its further degradation with endoproteinase Glu-C established that cysteine-295 of alpha-tubulin was the major reactive amino acid cross-linked to guanosine by ultraviolet irradiation. C1 NIH, Frederick Canc Res & Dev Ctr, Div Canc Treatment & Diag,Dev Therapeut Program, Lab Drug Discovery Res & Dev, Frederick, MD 21702 USA. NIH, Frederick Canc Res & Dev Ctr, Sci Applicat Int Corp, Frederick, MD 21702 USA. US FDA, Ctr Biol Evaluat & Res, Facil Biotechnol Resources, Bethesda, MD 20892 USA. RP Hamel, E (reprint author), NIH, Bldg 37,Rm 5D02, Bethesda, MD 20892 USA. NR 28 TC 9 Z9 9 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 APR 17 PY 1998 VL 273 IS 16 BP 9894 EP 9897 DI 10.1074/jbc.273.16.9894 PG 4 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZH610 UT WOS:000073128800077 PM 9545331 ER PT J AU Grimley, PM Fang, H Rui, H Petricoin, EF Ray, S Dong, F Fields, KH Hu, RQ Zoon, KC Audet, S Beeler, J AF Grimley, PM Fang, H Rui, H Petricoin, EF Ray, S Dong, F Fields, KH Hu, RQ Zoon, KC Audet, S Beeler, J TI Prolonged STAT1 activation related to the growth arrest of malignant lymphoma cells by interferon-alpha SO BLOOD LA English DT Article ID INDUCED GENE-EXPRESSION; TRANSCRIPTIONALLY ACTIVE STAT1; DOMINANT-NEGATIVE MUTANT; AURIN TRICARBOXYLIC-ACID; REGULATORY FACTOR FAMILY; DAUDI CELLS; TYROSINE-PHOSPHATASE; SIGNAL-TRANSDUCTION; LYMPHOPROLIFERATIVE DISORDERS; TARGETED DISRUPTION AB Multiple biologic effects of interferon-alpha (IFN-alpha), including cell growth inhibition and antiviral protection, are initiated by tyrosine phosphorylation of STAT proteins, Although this signal pathway has been intensively investigated, the relevance of STAT signal persistence has received scant attention. Using paired isogenic lymphoma cells (Daudi), which either are sensitive or resistant to growth inhibition by IFN-alpha, we found comparable initial tyrosine phosphorylation of multiple STAT proteins; however, the phosphorylation durations and associated DNA-binding activities diverged. Phosphorylation and DNA-binding capacity of STAT1 decreased after 4 to 8 hours in resistant cells, as compared with 24 to 32 hours in sensitive cells, whereas phosphorylation of STAT3 and STAT5b was briefer in both lines. Functional significance of the prolonged STAT1 signal, therefore, was explored by experimental interruption of tyrosine phosphorylation, either by premature withdrawal of the IFN-alpha or deferred addition of pharmacologically diverse antagonists: staurosporine (protein kinase inhibitor), phorbol 12-myristate 13-acetate (growth promoter), or aurintricarboxylic acid (ligand competitor). Results indicated that an approximately 18-hour period of continued STAT1 phosphorylation was associated with growth arrest, but that antiviral protection developed earlier, These differences provide novel evidence of a temporal dimension to IFN-alpha signal specificity and show that duration of STAT1 activation may be a critical variable in malignant cell responsiveness to antiproliferative therapy. C1 Uniformed Serv Univ Hlth Sci, Dept Pathol, Bethesda, MD 20814 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. RP Grimley, PM (reprint author), Uniformed Serv Univ Hlth Sci, Dept Pathol, 4301 Jones Bridge Rd, Bethesda, MD 20814 USA. NR 78 TC 35 Z9 35 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 0006-4971 J9 BLOOD JI Blood PD APR 15 PY 1998 VL 91 IS 8 BP 3017 EP 3027 PG 11 WC Hematology SC Hematology GA ZG521 UT WOS:000073012000047 PM 9531615 ER PT J AU Lau, D Yang, S Shmuely, H Turner, K Parsonnet, J AF Lau, D Yang, S Shmuely, H Turner, K Parsonnet, J TI H-pylori detection by immunomagnetic separation in clinical matrices. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 Stanford Univ, Stanford, CA 94305 USA. US FDA, Alameda, CA USA. NR 0 TC 0 Z9 0 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G0805 BP A196 EP A196 DI 10.1016/S0016-5085(98)80798-1 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089600798 ER PT J AU Osato, MS Flamm, RK Utrup, LJ AF Osato, MS Flamm, RK Utrup, LJ TI Helicobacter pylori susceptibility testing: Comparison of E-test and agar dilution methods. SO GASTROENTEROLOGY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Abbott Labs, Abbott Pk, IL 60064 USA. Baylor Coll Med, Houston, TX USA. Vet Affairs Med Ctr, Dept Med, Houston, TX 77030 USA. NR 0 TC 2 Z9 2 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 0016-5085 J9 GASTROENTEROLOGY JI Gastroenterology PD APR 15 PY 1998 VL 114 IS 4 SU S MA G1025 BP A250 EP A250 DI 10.1016/S0016-5085(98)81016-0 PN 2 PG 1 WC Gastroenterology & Hepatology SC Gastroenterology & Hepatology GA ZH263 UT WOS:000073089601016 ER PT J AU Bonder, CS Dickensheets, HL Finlay-Jones, JJ Donnelly, RP Hart, PH AF Bonder, CS Dickensheets, HL Finlay-Jones, JJ Donnelly, RP Hart, PH TI Involvement of the IL-2 receptor gamma-chain (gamma(c)) in the control by IL-4 of human monocyte and macrophage proinflammatory mediator production SO JOURNAL OF IMMUNOLOGY LA English DT Article ID SYNOVIAL-FLUID MACROPHAGES; TUMOR-NECROSIS-FACTOR; INTERLEUKIN-2 RECEPTOR; BLOOD MONOCYTES; ALPHA-CHAIN; INFLAMMATORY ARTHRITIS; MONONUCLEAR PHAGOCYTES; SIGNAL-TRANSDUCTION; B-CELLS; EXPRESSION AB IL-4 has potent anti-inflammatory properties on monocytes and suppresses both IL-1 beta and TNF-alpha production, Well-characterized components of the IL-3 receptor on monocytes include the 140-kDa alpha-chain and the IL-2R gamma-chain, gamma(c), which normally dimerize 1:1 for signaling from the receptor, However, mRNA levels for gamma(c) were very low in 7-day-cultured monocytes. As mRNA levels for gamma(c) declined with culture, so too did the ability of IL-4 to down-regulate LPS-induced TNF-alpha production. In contrast, IL-4 consistently down-regulated IL-1 beta production by cultured monocytes, Immunoprecipitation and Western blot analyses demonstrated that 7-day-cultured monocytes do not express the functionally active 64-kDa gamma(c) protein, This was associated with decreased STAT6 activation by IL-4. Studies with Abs to gamma(c) and an IL-4 mutant that is unable to bind to gamma(c) showed that IL-4 can suppress IL-1 beta but not TNF-alpha production by LPS-stimulated monocytes in the presence of little or no functioning gamma(c), IL-4 also suppressed IL-1 beta but not TNF-alpha production by Mono Mac 6 cells, which express minimal levels of gamma(c). For gamma(c)-expressing LPS/PMA-activated U937 cells, IL-4 decreased both TNF-alpha and IL-1 beta production, These results suggest that functional gamma(c) is not present on in vitro-derived macrophages, and that while some anti-inflammatory responses to IL-4 are lost with this down-regulation of functional gamma(c), others are retained, We conclude that different functional responses to IL-4 by human monocytes and macrophages are regulated by different IL-4 receptor configurations. C1 Flinders Univ S Australia, Sch Med, Dept Microbiol & Infect Dis, Adelaide, SA 5001, Australia. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RP Hart, PH (reprint author), Flinders Univ S Australia, Sch Med, Dept Microbiol & Infect Dis, GPO Box 2100, Adelaide, SA 5001, Australia. EM prue.hart@flinders.edu.au RI Finlay-Jones, John/C-2421-2013 NR 42 TC 29 Z9 30 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 APR 15 PY 1998 VL 160 IS 8 BP 4048 EP 4056 PG 9 WC Immunology SC Immunology GA ZG143 UT WOS:000072970400056 PM 9558115 ER PT J AU Rubin, SA Yednock, TA Carbone, KM AF Rubin, SA Yednock, TA Carbone, KM TI In vivo treatment with anti-alpha(4) integrin suppresses clinical and pathological evidence of Borna disease virus infection SO JOURNAL OF NEUROIMMUNOLOGY LA English DT Article DE alpha(4) integrin; disease; inflammation; virus ID CENTRAL-NERVOUS-SYSTEM; EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS; EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS; ANTIGEN-SPECIFIC LYMPHOCYTES; T-CELLS; ENDOTHELIAL-CELLS; ALPHA(4) INTEGRIN; IMMUNE REACTIVITY; VLA-4; ADHESION AB Borna disease virus (BDV) infection of the rat brain induces a severe T-lymphocyte mediated inflammatory response that parallels the course of clinical Borna disease. In other models of CNS inflammation, the recruitment of T-lymphocytes from the circulation to sites of inflammation is believed to be directed, in part, by the cellular adhesion molecules alpha(4) beta(1) integrin (expressed on T-lymphocytes) and its ligand VCAM-1 (expressed on blood brain barrier endothelium). Since BDV-specific T-lymphocytes are known to express the alpha(4) beta(1), integrin, we examined the effect of in vivo treatment with an anti-alpha(4) integrin monoclonal antibody (GG5/3) on the development of BDV-specific encephalitis and Borna disease. Here, we report that the inhibition of alpha(4) integrin provided significant clinical benefit in slowing the progression of Boma disease. Antibody treatment greatly reduced the immune cell infiltrates in the CNS of BDV-infected animals, but we found that this inhibition of the immune response did not result in enhanced viral levels. (C) 1998 Elsevier Science B.V. C1 US FDA, Ctr Biol Evaluat & Res, OVPR, Bethesda, MD 20892 USA. Johns Hopkins Univ, Sch Med, Dept Med, Baltimore, MD 21205 USA. Athena Neurosci Inc, San Francisco, CA USA. RP Carbone, KM (reprint author), US FDA, Ctr Biol Evaluat & Res, OVPR, 29A,Room 2C-14,8800 Rockville Pike, Bethesda, MD 20892 USA. EM carbonek@al.cber.fda.gov FU NIMH NIH HHS [MH48948]; NINDS NIH HHS [NS289599] NR 37 TC 14 Z9 17 U1 0 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0165-5728 J9 J NEUROIMMUNOL JI J. Neuroimmunol. PD APR 15 PY 1998 VL 84 IS 2 BP 158 EP 163 DI 10.1016/S0165-5728(97)00249-X PG 6 WC Immunology; Neurosciences SC Immunology; Neurosciences & Neurology GA ZR735 UT WOS:000074008500008 PM 9628458 ER PT J AU Heredia, A Vallejo, A Soriano, V Silva, A Mansinho, K Fevereiro, S Mas, A Gutierrez, M Epstein, JS Hewlett, IK AF Heredia, A Vallejo, A Soriano, V Silva, A Mansinho, K Fevereiro, S Mas, A Gutierrez, M Epstein, JS Hewlett, IK TI Phylogenetic analysis of HIV type 2 strains from Portugal SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Letter ID IMMUNODEFICIENCY-VIRUS TYPE-2; SPREAD C1 US FDA, Mol Virol Lab, Divt Transfus & Transmittes Dis, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Inst Salud Carlos III, Serv Infect Dis & Microbiol, Madrid 28029, Spain. Hosp Mil Belern, Lisbon, Portugal. Hosp Egas Moniz, Lisbon, Portugal. Hosp Santa Cruz, Carnaxide, Portugal. RP Heredia, A (reprint author), Inst Human Virol, Lab Viral Immunoregulat, 725 W Lombard St, Baltimore, MD 21201 USA. RI Vallejo, Alejandro/I-5881-2015; Mas, Antonio/F-2505-2011 OI Vallejo, Alejandro/0000-0001-5360-878X; Mas, Antonio/0000-0003-2563-570X NR 11 TC 7 Z9 7 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD APR 10 PY 1998 VL 14 IS 6 BP 471 EP 473 DI 10.1089/aid.1998.14.471 PG 3 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZG357 UT WOS:000072993500001 PM 9566548 ER PT J AU Pine, PS Weaver, JL Oravecz, T Pall, M Ussery, M Aszalos, A AF Pine, PS Weaver, JL Oravecz, T Pall, M Ussery, M Aszalos, A TI A semiautomated fluorescence-based cell-to-cell fusion assay for gp120-gp41 and CD4 expressing cells SO EXPERIMENTAL CELL RESEARCH LA English DT Article ID IMMUNODEFICIENCY-VIRUS TYPE-1; ENVELOPE GLYCOPROTEIN; MONOCLONAL-ANTIBODY; AURINTRICARBOXYLIC ACID; AIDS RETROVIRUS; MEMBRANE-FUSION; HIV-INFECTION; BINDING; RECEPTOR; PROTEIN AB A novel fluorescence-based method was developed to measure HIV envelope glycoprotein (env)-CD4-mediated cell fusion. This method measures the spread of a fluorescent dye as the cytosolic compartments of adjacent cells become contiguous upon cell-to-cell fusion, Calcein-labeled CD4(+) Sup-T1 cells were seeded onto a monolayer of unlabeled TF228.1.16 cells, which stably express env, the gp120-gp41 complex. Changes in the following parameters were measured using a stage-scanning laser microscope: total fluorescent area, average fluorescent area, and average shape factor. Anti-CD4 monoclonal antibodies, anti-Leu3a, and OKT4E were shown to block fusion in a dose-dependent manner, while OKT4 had no effect. Aurin tricarboxylic acid, a compound that interferes with the binding of anti-leu3a mAb and gp120 to CD4(+) human peripheral blood lymphocytes, T20, a peptide that interferes with gp41, and cytochalasin D, a microfilament disrupter, all blocked fusion in a dose-dependent manner. This semiautomated assay can be used to quickly assess the effectiveness of compounds acting at different sites to block CD4 and env initiated cell-to-cell fusion, (C) 1998 Academic Press. C1 US FDA, CDER, Div Appl Pharmacol Res, Laurel, MD 20708 USA. US FDA, CDER, Div Hematol Prod, Bethesda, MD 20708 USA. US FDA, CDER, Antiviral Res Lab, Rockville, MD 20708 USA. RP Pine, PS (reprint author), US FDA, CDER, Div Appl Pharmacol Res, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 40 TC 7 Z9 7 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0014-4827 J9 EXP CELL RES JI Exp. Cell Res. PD APR 10 PY 1998 VL 240 IS 1 BP 49 EP 57 DI 10.1006/excr.1998.3939 PG 9 WC Oncology; Cell Biology SC Oncology; Cell Biology GA ZK186 UT WOS:000073294000006 PM 9570920 ER PT J AU Asafu-Adjaye, EB Shiu, GL AF Asafu-Adjaye, EB Shiu, GL TI Solid-phase extraction-high-perfomance liquid chromatography determination of verapamil and norverapamil enantiomers in urine SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article; Proceedings Paper CT 10th Annual Meeting and Exposition of the American-Association-of-Pharmaceutical-Scientists CY NOV, 1995 CL MIAMI BEACH, FLORIDA SP Amer Assoc Pharm Scientists DE verapamil; norverapamil; enantiomer separation ID CHIRAL STATIONARY-PHASE; RESOLUTION; PLASMA AB A simple, rapid, sensitive and selective method has been developed for the stereospecific determination of verapamil and its metabolite, norverapamil in urine. For sample preparation we utilized a membrane-based solid-phase extraction (SPE) disk consisting of a thin, particle-loaded membrane inserted in a plastic syringe-like barrel. The particles, which may be C-8 or C-18 bonded phase (C-8 in this work), are embedded within a matrix of PTFE (Teflon) fibrils. Overall analyte recoveries were above 85%, even at low concentration of 3.0 ng/ml with reproducibilities (C.V. values) below 13.1%. This method of extraction has the advantage of speed and considerable reduction in solvent volumes compared to conventional SPE and solvent extraction. The separation of all the enantiomers was achieved using a single chiral stationary phase column, the cellulose-based reversed-phase, Chiralcel OD-R. Analyte concentrations of less than 3.0 ng/ml could be quantitated with C.V. values below 14%. Calibration curves were linear in the range 2.5-300 ng/ml. Intra-day and inter-day reproducibilities were 10.5-14.2% at 3 ng/ml, 4.8-9.3% at 138.5 ng/ml and 7.8-10.1% at 280 ng/ml level, respectively, for all the enantiomers. (C) 1998 Elsevier Science B.V. C1 US FDA, Prod Qual Res Lab, DPQR, OPS,CDER, Rockville, MD 20850 USA. RP Asafu-Adjaye, EB (reprint author), US FDA, Prod Qual Res Lab, DPQR, OPS,CDER, 4 Res Court, Rockville, MD 20850 USA. NR 8 TC 22 Z9 22 U1 0 U2 3 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 10 PY 1998 VL 707 IS 1-2 BP 161 EP 167 DI 10.1016/S0378-4347(97)00575-6 PG 7 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZJ706 UT WOS:000073238700020 PM 9613945 ER PT J AU Kimber, I Hilton, J Dearman, RJ Gerberick, GF Ryan, CA Basketter, DA Lea, L House, RV Ladics, GS Loveless, SE Hastings, KL AF Kimber, I Hilton, J Dearman, RJ Gerberick, GF Ryan, CA Basketter, DA Lea, L House, RV Ladics, GS Loveless, SE Hastings, KL TI Assessment of the skin sensitization potential of topical medicaments using the local lymph node assay: An interlaboratory evaluation SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A LA English DT Article ID ALLERGIC CONTACT-DERMATITIS; GUINEA-PIG; BENZOYL PEROXIDE; MAXIMIZATION TEST; VALIDATION; BUEHLER; IDENTIFICATION; TRIAL AB The murine local lymph node assay (LLNA) is a method for the predictive identification of chemicals that have a potential to cause skin sensitization. Activity is measured as a function of lymph node cell (LNC) proliferative responses stimulated by topical application of test chemicals. Those chemicals that induce a threefold or greater increase in LNC proliferation compared with concurrent vehicle controls are classified as skin sensitizers. In the present investigations we have evaluated further the reliability and accuracy of the LLNA. In the context of an international interlaboratory trial the sensitization potentials of six materials with a history of use in topical medicaments have been evaluated: benzoyl peroxide, hydroquinone, penicillin G, streptomycin sulfate, ethylenediamine dihydrochloride, and methyl salicylate. Each chemical was analyzed in the LLNA by all five laboratories. Either the standard LLNA protocol or minor modifications of it were used Benzoyl peroxide and hydroquinone, both human contact allergens, elicited strong LLNA responses in each laboratory. Penicillin G, another material shown previously to cause allergic contact dermatitis in humans, was also positive in all laboratories. Streptomycin sulfate induced equivocal responses, in that this material provoked a positive LLNA response in only one of the five laboratories, and then only at the highest concentration tested. Ethylenediamine dihydrochloride dissolved in a 3:1 mixture of acetone with water, or in 4:1 acetone:olive oil (one laboratory), was uniformly negative. However, limited further testing with the free base of ethylene diamine yielded a positive LLNA response when applied in acetone:olive oil (AOO). Finally, methyl salicylate, a nonsensitizing skin irritant, was negative at all test concentrations in each laboratory. Collectively these data serve to confirm that the local lymph node assay is sufficiently robust to yield equivalent results when performed independently in separate laboratories and indicate also that the LLNA is of value in assessing the skin sensitization potential of topical medicaments. C1 Zeneca Cent Toxicol Lab, Macclesfield SK10 4TJ, Cheshire, England. Unilever Safety & Environm Assurance Ctr, Sharnbrook, Beds, England. IIT, Res Inst, Chicago, IL 60616 USA. DuPont Co Inc, Haskell Lab, Newark, DE 19714 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Procter & Gamble Co, Miami Valley Labs, Cincinnati, OH USA. RP Kimber, I (reprint author), Zeneca Cent Toxicol Lab, Alderley Pk, Macclesfield SK10 4TJ, Cheshire, England. EM IAN.KIMBER@APVXCI.ZENECA.COM NR 38 TC 56 Z9 58 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 0098-4108 J9 J TOXICOL ENV HEAL A JI J. TOXICOL. ENV. HEALTH PT A PD APR 10 PY 1998 VL 53 IS 7 BP 563 EP 579 PG 17 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA ZG770 UT WOS:000073037600004 PM 9561969 ER PT J AU Shores, EW Ono, M Kawabe, T Sommers, CL Tran, T Lui, K Udey, MC Ravetch, J Love, PE AF Shores, EW Ono, M Kawabe, T Sommers, CL Tran, T Lui, K Udey, MC Ravetch, J Love, PE TI T cell development in mice lacking all T cell receptor zeta family members (zeta, eta, and Fc epsilon RI gamma) SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID ANTIGEN RECEPTOR; INTRAEPITHELIAL LYMPHOCYTES; MUTANT MICE; CHAIN; CD3-ZETA; SELECTION; SUBUNIT; GENE; DIFFERENTIATION; CD3-EPSILON AB The zeta family includes zeta, eta, and Fc epsilon RI gamma (Fc gamma). Dimers of the zeta family proteins function as signal transducing subunits of the T cell antigen receptor (TCR), the pre-TCR, and a subset of Fc receptors. In mice lacking zeta/eta chains, T cell development is impaired, yet low numbers of CD4(+) and CD8(+) T cells develop. This finding suggests either that pre-TCR and TCR complexes lacking a zeta family dimer can promote T cell maturation, or that in the absence of zeta/eta, Fc gamma serves as a subunit in TCR complexes. To elucidate the role of zeta family dimers in T cell development, we generated mice lacking expression of all of these proteins and compared their phenotype to mice lacking only zeta/eta or Fc gamma. The data reveal that surface complexes that are expressed in the absence of zeta family dimers are capable of transducing signals required for alpha/beta-T cell development. Strikingly, T cells generated in both zeta/eta(-/-) and zeta/eta(-/-)-Fc gamma(-/-) mice exhibit a memory phenotype and elaborate interferon gamma. Finally, examination of different T cell populations reveals that zeta/eta and Fc gamma have distinct expression patterns that correlate with their thymus dependency. A possible function for the differential expression of zeta family proteins may be to impart distinctive signaling properties to TCR complexes expressed on specific T cell populations. C1 US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. Rockefeller Univ, Lab Mol Genet & Immunol, New York, NY 10021 USA. NCI, Dermatol Branch, NIH, Bethesda, MD 20892 USA. NICHHD, Lab Mammalian Genes & Dev, NIH, Bethesda, MD 20892 USA. RP Shores, EW (reprint author), US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, 1401 Rockville Pike,HFM-538, Rockville, MD 20852 USA. EM shoresew@helix.nih.gov RI kawabe, tsutomu/I-6277-2014 OI kawabe, tsutomu/0000-0002-9319-9930 NR 37 TC 44 Z9 44 U1 0 U2 1 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD APR 6 PY 1998 VL 187 IS 7 BP 1093 EP 1101 DI 10.1084/jem.187.7.1093 PG 9 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA ZH131 UT WOS:000073075900012 PM 9529325 ER PT J AU Copie, V Tomita, Y Akiyama, SK Aota, S Yamada, KM Venable, RM Pastor, RW Krueger, S Torchia, DA AF Copie, V Tomita, Y Akiyama, SK Aota, S Yamada, KM Venable, RM Pastor, RW Krueger, S Torchia, DA TI Solution structure and dynamics of linked cell attachment modules of mouse fibronectin containing the RGD and synergy regions: Comparison with the human fibronectin crystal structure SO JOURNAL OF MOLECULAR BIOLOGY LA English DT Article DE fibronectin; cell adhesion; RGD region; NMR; protein flexibility ID ISOTOPICALLY ENRICHED PROTEINS; SIDE-CHAIN RESONANCES; N-15 NMR RELAXATION; CARBON-J-COUPLINGS; 3-DIMENSIONAL STRUCTURE; C-13-ENRICHED PROTEINS; ROTATIONAL DIFFUSION; C-13 MAGNETIZATION; ADHESIVE FUNCTION; LARGER PROTEINS AB We report the three-dimensional solution structure of the mouse fibronectin cell attachment domain consisting of the linked ninth and tenth type III modules, mFnFn3(9,10). Because the tenth module contains the RGD cell attachment sequence while the ninth contains the synergy region, mFnFn3(9,10) has the cell attachment activity of intact fibronectin. Essentially complete signal assignments and approximately 1800 distance and angle restraints were derived from multidimensional heteronuclear NMR spectra. These restraints were used with a hybrid distance geometry/simulated annealing protocol to generate an ensemble of 20 NMR structures having no distance or angle violations greater than 0.3 Angstrom or 3 degrees. Although the beta-sheet core domains of the individual modules are well-ordered structures, having backbone atom rmsd values from the mean structure of 0.51(+/-0.12) and 0.40(+/-0.07) Angstrom, respectively, the rmsd of the core atom coordinates increases to 3.63(+/-1.41) A when the core domains of both modules are used to align the coordinates. The latter result is a consequence of the fact that the relative orientation of the two modules is not highly constrained by the NMR restraints. Hence, while structures of the beta-sheet core domains of the NMR structures are very similar to the core domains of the crystal structure of hFnFn3(9,10), the ensemble of NMR structures suggests that the two modules form a less extended and more flexible structure than the fully extended rod-like crystal structure. The radius of gyration, R-g, of mFnFn3(9,10) derived from small-angle neutron scattering measurements, 20.5(+/-0.5) Angstrom, agrees with the average R-g calculated for the NMR structures, 20.4 Angstrom, and is ca 1 Angstrom less than the value of R-g calculated for the X-ray structure. The values of the rotational anisotropy, D-parallel to/D-perpendicular to, derived from an analysis of N-15 relaxation data, range from 1.7 to 2.1, and are significantly less than the anisotropy of 2.67 predicted by hydrodynamic modeling of the crystal coordinates. In contrast, hydrodynamic modeling of the NMR coordinates yields anisotropies in the range of 1.9 to 2.7 (average 2.4(+/-0.2)), with NMR structures bent by more than 20 degrees relative the crystal structure having calculated anisotropies in best agreement with experiment. In addition, the relaxation parameters indicate that several loops in mFnFn3(9,10), including the RGD loop, are flexible on the nanosecond to picosecond time-scale. Taken together, our results suggest that, in solution, the Limited set of interactions between the mFnFn3(9,10) modules position the RGD and synergy regions to interact specifically with tell surface integrins, and at the same time permit sufficient flexibility that allows mFnFn3(9,10) to adjust for some variation in integrin structure or environment. (C) 1998 Academic Press Limited. C1 NIDR, Struct Mol Biol Unit, NIH, Bethesda, MD 20892 USA. NIDR, Craniofacial Dev Biol & Regenerat Branch, NIH, Bethesda, MD 20892 USA. US FDA, Biophys Lab, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIST, Ctr Neutron Res, Gaithersburg, MD 20899 USA. RP Copie, V (reprint author), Montana State Univ, Dept Biochem & Chem, Bozeman, MT 59717 USA. OI Yamada, Kenneth/0000-0003-1512-6805 NR 59 TC 129 Z9 130 U1 0 U2 11 PU ACADEMIC PRESS LTD PI LONDON PA 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND SN 0022-2836 J9 J MOL BIOL JI J. Mol. Biol. PD APR 3 PY 1998 VL 277 IS 3 BP 663 EP 682 PG 20 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZK501 UT WOS:000073328800013 PM 9533887 ER PT J AU Ang, CYW Luo, WH McKim, K Hansen, EB Lay, JO Lochmann, R AF Ang, CYW Luo, WH McKim, K Hansen, EB Lay, JO Lochmann, R TI Amoxicillin concentrations in catfish muscle following oral administration of the drug. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 Univ Arkansas, Pine Bluff, AR 71601 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RI Lay, Jackson/G-1007-2011 OI Lay, Jackson/0000-0003-3789-2527 NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0065-7727 J9 ABSTR PAP AM CHEM S JI Abstr. Pap. Am. Chem. Soc. PD APR 2 PY 1998 VL 215 MA 055-AGRO BP U40 EP U41 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414400129 ER PT J AU Begley, T McNeal, TP Franz, R Huber, H Piringer, O AF Begley, T McNeal, TP Franz, R Huber, H Piringer, O TI Evaluation of a virgin polymer layer as a functional barrier to migration for food packaging. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. Fraunhofer Inst Food Technol & Packaging, D-80992 Munich, Germany. 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 2 PY 1998 VL 215 MA 041-AGFD BP U12 EP U12 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414400042 ER PT J AU Chen, ET Pardue, HL AF Chen, ET Pardue, HL TI Fabrication and characterization of novel amperometric biomimetic enzyme sensors SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Devices Radiol Hlth, Rockville, MD 20852 USA. Purdue Univ, Dept Chem, W Lafayette, IN 47907 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 2 PY 1998 VL 215 MA 308-COLL BP U501 EP U501 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414401589 ER PT J AU Gehring, TA Churchwell, MI Gehring, TA Doerge, DR AF Gehring, TA Churchwell, MI Gehring, TA Doerge, DR TI Analysis of malachite green and metabolites in fish fillets using hplc with APCI/MS detection. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU 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 2 PY 1998 VL 215 MA 056-AGRO BP U41 EP U41 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414400130 ER PT J AU Oriani, JA AF Oriani, JA TI US food and drug administration perspective on aquaculture drug residues. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Ctr Vet Med, Rockville, MD 20855 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 2 PY 1998 VL 215 MA 090-AGRO BP U50 EP U51 PN 1 PG 2 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414400164 ER PT J AU Plakas, SM Doerge, DR Turnipseed, SB AF Plakas, SM Doerge, DR Turnipseed, SB TI Disposition and metabolism of malachite green and other therapeutic dyes in fish. SO ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY LA English DT Meeting Abstract C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Anim Drugs Res Ctr, Denver, CO 80225 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 2 PY 1998 VL 215 MA 106-AGRO BP U55 EP U55 PN 1 PG 1 WC Chemistry, Multidisciplinary SC Chemistry GA ZA911 UT WOS:000072414400180 ER PT J AU Mattes, CE Belendiuk, GW Lynch, TJ Brady, RO Dretchen, KL AF Mattes, CE Belendiuk, GW Lynch, TJ Brady, RO Dretchen, KL TI Butyrylcholinesterase: an enzyme antidote for cocaine intoxication SO ADDICTION BIOLOGY LA English DT Review ID PLASMA CHOLINESTERASE ACTIVITY; HUMAN-SERUM CHOLINESTERASE; ECGONINE METHYL-ESTER; DIFFERENTIAL CARDIOVASCULAR SENSITIVITY; INDUCED NEUROMUSCULAR BLOCKADE; URINARY-EXCRETION; ACETYLCHOLINESTERASE PROPHYLAXIS; H-3 WIN-35,428; BINDING-SITES; ANIONIC SITE AB Cocaine-associated toxicity is the result of effects on the cardiovascular and central nervous systems. Since the primary route of cocaine inactivation is enzymatic degradation by butyrylcholinesterase (BChE), we sought to determine if the administration of purified human enzyme would ameliorate the lethal effects of cocaine. While the cardiovascular, autonomic or central nervous systems were unaffected by BChE, the enzyme reduced the adverse effects of cocaine including hypertension, hyperactivity and convulsions. BChE decreased both the brain and blood levels of cocaine and shifted the metabolites towards the production of the inactive product ecgonine methyl ester and away from the physiologically active metabolites, norcocaine and benzoylecgonine. We conclude that BChE would appear to be an ideal antidote in the treatment of cocaine intoxication and has potential therapeutic application. C1 Georgetown Univ, Med Ctr, Dept Pharmacol, Washington, DC 20007 USA. Pharmavene Inc, Rockville, MD USA. US FDA, Rockville, MD 20857 USA. RP Dretchen, KL (reprint author), Georgetown Univ, Med Ctr, Dept Pharmacol, 3900 Reservoir Rd NW, Washington, DC 20007 USA. EM dretchenk@odrge.odr.georgetown.edu NR 105 TC 15 Z9 15 U1 2 U2 2 PU CARFAX PUBL CO PI ABINGDON PA PO BOX 25, ABINGDON, OXFORDSHIRE, ENGLAND OX14 3UE SN 1355-6215 J9 ADDICT BIOL JI Addict. Biol. PD APR PY 1998 VL 3 IS 2 BP 171 EP 188 DI 10.1080/13556219872236 PG 18 WC Biochemistry & Molecular Biology; Substance Abuse SC Biochemistry & Molecular Biology; Substance Abuse GA ZK502 UT WOS:000073328900005 PM 26734822 ER PT J AU Lee, HHC Gerrior, SA Smith, JA AF Lee, HHC Gerrior, SA Smith, JA TI Energy, macronutrient, and food intakes in relation to energy compensation in consumers who drink different types of milk SO AMERICAN JOURNAL OF CLINICAL NUTRITION LA English DT Article DE energy compensation; reduced-fat milk; whole milk; low-fat milk; skim milk; fat intake; carbohydrate intake; energy intake ratio; Continuing Survey of Food Intakes by Individuals; humans ID DIETARY-FAT; CHILDREN; PATTERNS AB To examine whether total fat intake is actually lower in reduced-fat (low-fat and skim) milk drinkers and whether reduced-fat-milk drinkers compensate for energy intake we compared the intakes of foods. energy, and energy-yielding nutrients in reduced-fat-milk drinkers and whole milk drinkers by using the US Department of Agriculture's 1989-1991 nationwide food intake database, the Continuing Survey of Food Intakes by Individuals. This database represents a national stratified sample population of 15 128 individuals. Of the survey population, approximately one-third consumed whole milk, one-third consumed low-fat milk, one-tenth consumed skim milk, and one-tenth consumed mixed types of milk. The data provided the following information: I) total fat intake of reduced-fat-milk drinkers is significantly (P less than or equal to 0.05) lower than that of whole milk drinkers: 2) in general, males but not females compensate for energy by increasing their carbohydrate intake; 3) reduced-fat-milk drinkers consume more fruit and vegetables (P less than or equal to 0.05) and less red meat and sweets (P less than or equal to 0.05) than whole milk drinkers: 4) through their reduction in total fat intake, several age groups of skim milk drinkers have achieved the US dietary goal for fat intake, ie, less than or equal to 30% of energy intake from fat; 5) teenagers compensate for energy intake the least of all age groups; and 6) with advancing age, fewer people drink milk and fewer drink whole milk. The data indicate significant sex differences in energy compensation, that reduced-fat-milk drinkers consume significantly (P less than or equal to 0.05) less fat than whole milk drinkers, and that the US dietary goal for fat intake may be practically achieved by consuming reduced-fat foods such as skim milk and limiting intakes of high-fat foods such as red meat. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Human Nutr Informat Serv, USDA, Washington, DC USA. RP Lee, HHC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW HFS-222, Washington, DC 20204 USA. EM hcl@vm.cfsan.fda.gov NR 25 TC 13 Z9 14 U1 1 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 APR PY 1998 VL 67 IS 4 BP 616 EP 623 PG 8 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZE350 UT WOS:000072783800006 PM 9537608 ER PT J AU Fintor, L Brown, M Fischer, R Suleiman, O Garlinghouse, C Camburn, J Frazier, E Houn, F AF Fintor, L Brown, M Fischer, R Suleiman, O Garlinghouse, C Camburn, J Frazier, E Houn, F TI The impact of mammography quality improvement legislation in Michigan: Implications for the national mammography quality standards act SO AMERICAN JOURNAL OF PUBLIC HEALTH LA English DT Article ID FACILITIES; ASSURANCE AB Objectives. This study examined the impact of state legislation on mammography quality and access in Michigan. Methods. The impact of state legislation was analyzed with respect to utilization, numbers of machines and facilities, and image quality. Results. The legislation had a positive effect on image quality improvement, had no impact on utilization by women aged 50 years and above, and resulted in few facility closures. Conclusions. Michigan's legislative intervention appears to have had a positive effect on efforts to improve mammography quality assurance with implications for other federal and state efforts to achieve quality assurance in health care delivery. C1 NCI, Div Canc Control & Populat Sci, Bethesda, MD 20892 USA. US FDA, Div Mammog Qual & Radiat Programs, Rockville, MD 20857 USA. Michigan Dept Community Hlth, Ctr Chron Dis Prevent & Hlth Promot, Lansing, MI USA. Michigan Dept Consumer & Ind Serv, Bur Hlth Syst, Lansing, MI USA. Ctr Dis Control & Prevent, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA USA. RP Fintor, L (reprint author), Univ Michigan, Sch Med, Div Gen Med, Consortium Hlth Outcomes Innovat & Costeffectiven, 1904 Clin Fac Off Bldg,1414 Catherine St, Ann Arbor, MI 48109 USA. NR 17 TC 7 Z9 7 U1 0 U2 0 PU AMER PUBLIC HEALTH ASSOC INC PI WASHINGTON PA 1015 FIFTEENTH ST NW, WASHINGTON, DC 20005 USA SN 0090-0036 J9 AM J PUBLIC HEALTH JI Am. J. Public Health PD APR PY 1998 VL 88 IS 4 BP 667 EP 671 DI 10.2105/AJPH.88.4.667 PG 5 WC Public, Environmental & Occupational Health SC Public, Environmental & Occupational Health GA ZT681 UT WOS:000074113900029 PM 9551016 ER PT J AU Parchment, RE Gordon, M Grieshaber, CK Sessa, C Volpe, D Ghielmini, M AF Parchment, RE Gordon, M Grieshaber, CK Sessa, C Volpe, D Ghielmini, M TI Predicting hematological toxicity (myelosuppression) of cytotoxic drug therapy from in vitro tests SO ANNALS OF ONCOLOGY LA English DT Article DE CFU-GM; hematotoxicity; in vitro; myelosuppression; neutropenia; phase I clinical trial; prediction model; validation ID HEMATOPOIETIC PROGENITOR CELLS; INVITRO MYELOTOXICITY; MURINE; CANINE; 3'-AZIDO-3'-DEOXYTHYMIDINE; PHARMACOKINETICS; TRIALS AB Several clinical oncology units are studying the roles of in vitro hematotoxicology in phase I evaluations. At the same time, the European Center for the Validation of Alternative Methods (ECVAM) is supporting a validation study of the C FU-GM assay [13]. It is important that these activities be coordinated so that high-performance, optimized technical protocols are used for prospective and retrospective clinical evaluations. The EORTC, the NCI, and ECVAM could provide support for these coordinated efforts. There is an opportunity for medical oncologists involved in early clinical trials to participate in the evaluation of in vitro tests and their clinical application. Fundamental to acceptance of these assays by oncologists and regulatory scientists, they must predict clinical outcome for myelosuppressive agents and then improve phase I design and performance. These achievements would justify more aggressive dose escalation schemes using guidance from in vitro studies without compromising patient safety. Success in predicting neutropenia might also stimulate the research required to understand how to predict other hematologic toxicities, such as thrombocytopenia. The complexity of a validation study in hematotoxicology is that it seeks to predict the level of exposure that causes neutropenia, in contrast to other validation studies that have sought to classify a xenobiotic as toxic or not. It may be that the clinical relevance of a new assay is not just a yes-no answer. This important distinction came from the realization that the xenobiotic tolerance in other organ systems of the body must be the same or greater than marrow in order for myelosuppression to be a clinical consequence of exposure. Pharmacological principles of systemic exposure and toxicity that are integrated into the prediction model provide the links to clinical oncology. It is also important to anticipate future applications of in vitro hematotoxicology. If the maximum tolerated level of drug exposure for human hematopoietic cells can be predicted, then in vitro hematotoxicology could play an important role in new drug discovery. One concept involves screening for compounds that show efficacy at the IC level that predicts maximum tolerated exposure levels in the human [12, 22]. 'Therapeutic index-based' drug discovery has been applied to the tallimustine family with some success [21]. C1 Osped San Giovanni, Dept Oncol, Div Oncol, CH-6500 Bellinzona, Switzerland. Wayne State Univ, Barbara Ann Karmanos Canc Inst, Div Hematol Oncol, Detroit, MI USA. Hammersmith Hosp, Imperial Coll, Sch Med, Dept Haematol, London, England. US FDA, Off Testing & Res, Ctr Drug Evaluat & Res, Laurel, MD USA. RP Ghielmini, M (reprint author), Osped San Giovanni, Dept Oncol, Div Oncol, CH-6500 Bellinzona, Switzerland. NR 23 TC 53 Z9 56 U1 0 U2 1 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PD APR PY 1998 VL 9 IS 4 BP 357 EP 364 DI 10.1023/A:1008245906772 PG 8 WC Oncology SC Oncology GA ZT412 UT WOS:000074083100011 PM 9636825 ER PT J AU Cho-Chung, YS Beaucage, S Bergan, R Marquez, V Neckers, L Torrence, PF AF Cho-Chung, YS Beaucage, S Bergan, R Marquez, V Neckers, L Torrence, PF TI Presentations from the second NIH symposium on therapeutic oligonucleotides - Introduction SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Editorial Material C1 NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, DBS, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. NCI, Tumor Cell Biol Sect, Med Branch, DCS, Bethesda, MD 20892 USA. NIDDK, Biomed Chem Sect, Med Chem Lab, Bethesda, MD 20892 USA. RP Cho-Chung, YS (reprint author), NCI, Cellular Biochem Sect, Tumor Immunol & Biol Lab, DBS, Bldg 10,Room 5B05, Bethesda, MD 20892 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 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD APR PY 1998 VL 8 IS 2 BP 113 EP 114 PG 2 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA ZK996 UT WOS:000073388500005 ER PT J AU Klinman, DM AF Klinman, DM TI Therapeutic applications of CpG-containing oligodeoxynucleotides SO ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT LA English DT Article; Proceedings Paper CT 2nd NIH Symposium on Therapeutic Oligonucleotides - Targeting Transcription Factors and Signaling Pathways CY DEC 05, 1997 CL NIH, MASUR AUDITORIUM, BETHESDA, MARYLAND SP NIH, Interinst Therapeut Oligonucleotide Interest Grp HO NIH, MASUR AUDITORIUM ID CIRCUMSPOROZOITE PROTEIN; INTERFERON-GAMMA; PLASMID DNA; INTERLEUKIN-12; IMMUNIZATION; LYMPHOCYTES; PROTECTION; CYTOKINE; MOTIFS; CELLS C1 US FDA, CBER, Div Viral Prod, Sect Retroviral Immunol, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, CBER, Div Viral Prod, Sect Retroviral Immunol, Bldg 29A,Room 3D10, Bethesda, MD 20892 USA. NR 19 TC 50 Z9 52 U1 0 U2 1 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1087-2906 J9 ANTISENSE NUCLEIC A JI Antisense Nucleic Acid Drug Dev. PD APR PY 1998 VL 8 IS 2 BP 181 EP 184 DI 10.1089/oli.1.1998.8.181 PG 4 WC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Biotechnology & Applied Microbiology; Research & Experimental Medicine GA ZK996 UT WOS:000073388500018 PM 9593061 ER PT J AU Motes, ML DePaola, A Cook, DW Veazey, JE Hunsucker, JC Garthright, WE Blodgett, RJ Chirtel, SJ AF Motes, ML DePaola, A Cook, DW Veazey, JE Hunsucker, JC Garthright, WE Blodgett, RJ Chirtel, SJ TI Influence of water temperature and salinity on Vibrio vulnificus in northern Gulf and Atlantic Coast oysters (Crassostrea virginica) SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID ENVIRONMENT; INFECTIONS; SEAWATER; BAY; IMMUNOASSAY; SHELLSTOCK; SHELLFISH; FEATURES; SEDIMENT; REDUCE AB This study investigated the temperature and salinity parameters associated with waters and oysters linked to food-borne Vibrio vulnificus infections, V. vulnificus was enumerated in oysters collected at three northern Gulf Coast sites and two Atlantic Coast sites from July 1994 through September 1995, Two of these sites, Black Bay, La., and Apalachicola Bay, Fla,, are the source of the majority of the oysters implicated in V, vulnificus cases, Oysters in all Gulf Coast sites exhibited a similar seasonal distribution of V, vulnificus: a consistently large number (median concentration, 2,300 organisms [most probable number] per g of oyster meat) from May through October followed by a gradual reduction during November and December to less than or equal to 10 per g, where it remained from January through mid-March, and a sharp increase in late March and April to summer levels. V. vulnificus was undetectable (<3 per g) in oysters from the North and South Carolina sites for most of the year, An exception occurred when a late summer flood caused a drop in salinity in the North Carolina estuary, apparently causing V. vulnificus numbers to increase briefly to Gulf Coast levels, At Gulf Coast sites, V. vulnificus numbers increased with water temperatures up to 26 degrees C and were constant at higher temperatures. High V. vulnificus levels (>10(3) per g) were typically found in oysters from intermediate salinities (5 to 25 ppt), Smaller V. vulnificus numbers (<10(2) per g) were found at salinities above 28 ppt, typical of Atlantic Coast sites. On 11 occasions oysters were sampled at times and locations near the source of oysters implicated in 13 V. vulnificus cases; the V. vulnificus levels and environmental parameters associated with these samples were consistent with those of other study samples collected from the Gulf Coast from April through November, These findings suggest that the hazard of V. vulnificus infection is not limited to brief periods of unusual abundance of V. vulnificus in Gulf Coast oysters or to environmental conditions that are unusual to Gulf Coast estuaries. C1 US FDA, Div Math, Washington, DC 20204 USA. US FDA, State Cooperat Programs, SE Reg, Baton Rouge, LA 70809 USA. US FDA, SE Reg Lab, Atlanta, GA 30309 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. RP Cook, DW (reprint author), US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. NR 30 TC 161 Z9 165 U1 2 U2 20 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD APR PY 1998 VL 64 IS 4 BP 1459 EP 1465 PG 7 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA ZF412 UT WOS:000072894900046 PM 9546182 ER PT J AU Sutherland, JB Freeman, JP Williams, AJ AF Sutherland, JB Freeman, JP Williams, AJ TI Biotransformation of isoquinoline, phenanthridine, phthalazine, quinazoline, and quinoxaline by Streptomyces viridosporus SO APPLIED MICROBIOLOGY AND BIOTECHNOLOGY LA English DT Article ID PSEUDOMONAS-PUTIDA; MUTAGENICITY; METABOLISM; NITROGEN AB Streptomyces viridosporus T7A (ATCC 39115), during growth in tryptone/yeast extract broth, cometabolized five heterocyclic nitrogen-containing compounds. The metabolites produced from the azaarenes were identified by high-performance liquid chromatography, UV/visible absorption spectroscopy, and mass spectrometry. Isoquinoline was transformed to 1(2H)-isoquinolinone (14%), phenanthridine to 6(5H)-phenanthridinone (25%), phthalazine to 1(2H)-phthalazinone (46%), quinazoline to 2,4(1H,3H)-quinazolinedione (4%), and quinoxaline to 2(1H)-quinoxalinone (8%) and 1-methyl-3(1H)-quinoxalinone (12%). C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol & Chem, Jefferson, AR 72079 USA. RP Sutherland, JB (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol & Chem, Jefferson, AR 72079 USA. EM jsutherland@nctr.fda.gov NR 15 TC 19 Z9 19 U1 1 U2 2 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0175-7598 J9 APPL MICROBIOL BIOT JI Appl. Microbiol. Biotechnol. PD APR PY 1998 VL 49 IS 4 BP 445 EP 449 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA ZN130 UT WOS:000073612900016 ER PT J AU Wiese, FW Chang, HC Lloyd, RV Freeman, JP Samokyszyn, VM AF Wiese, FW Chang, HC Lloyd, RV Freeman, JP Samokyszyn, VM TI Peroxidase-catalyzed oxidation of 2,4,6-trichlorophenol SO ARCHIVES OF ENVIRONMENTAL CONTAMINATION AND TOXICOLOGY LA English DT Article ID PENTACHLOROPHENOL; CHLOROPHENOLS; HEMOGLOBIN; REDUCTION; ADDUCTS AB 2,4,6-Trichlorophenol (TCP) is an environmental contaminant that is toxic, mutagenic, and carcinogenic. We have investigated peroxidase-catalyzed oxidation of TCP as an alternative pathway of TCP bioactivation using horseradish peroxidase (HRP) as a model peroxidase. TCP was shown to function as a reducing substarte for HRP as evidenced by TCP-dependent, HRP-catalyzed reduction of 5-phenyl-4-penten-1-yl hydroperoxide (PPHP) to its corresponding alcohol. In addition, TCP was shown to undergo hydroperoxide (H2O2, ethyl hydroperoxide, or PPHP)-dependent metabolism as evidenced by electronic absorption spectroscopic analysis of reaction mixtures. A single major product was detected by reverse phase HPLC and was identified as 2,6-dichloro-1,4-benzoquinone (2,6-dichloro-2,5-cyclohexadiene-1,4-dione, CAS no. 697-91-6) on the basis of electronic absorption spectroscopy, mass spectrometry, and cochromatography with synthetic standard. In addition, HRP-catalyzed oxidation of TCP yielded EPR-detectable phenoxyl radical intermediates whose EPR spectrum consisted of a 1:2:1 triplet characterized by proton hyperfine coupling constants a(H(3,5)) = 2.35 gauss. Mechanisms for the hydroperoxide-dependent, HRP-catalyzed oxidation of TCP are proposed that are consistent with these results. C1 Univ Arkansas Med Sci, Div Toxicol, Little Rock, AR 72205 USA. US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Memphis, Dept Chem, Memphis, TN 38152 USA. RP Samokyszyn, VM (reprint author), Univ Arkansas Med Sci, Div Toxicol, Little Rock, AR 72205 USA. FU NIEHS NIH HHS [R29ES06765-03] NR 25 TC 25 Z9 27 U1 3 U2 11 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0090-4341 J9 ARCH ENVIRON CON TOX JI Arch. Environ. Contam. Toxicol. PD APR PY 1998 VL 34 IS 3 BP 217 EP 222 PG 6 WC Environmental Sciences; Toxicology SC Environmental Sciences & Ecology; Toxicology GA ZB638 UT WOS:000072492600001 PM 9504966 ER PT J AU Rider, LG Gurley, RC Pandey, JP Garcia-de la Torre, I Kalovidouris, AE O'Hanlon, TP Love, LA Hennekam, RCM Baumbach, LL Neville, HE Garcia, CA Klingman, J Gibbs, M Weisman, MH Targoff, IN Miller, FW AF Rider, LG Gurley, RC Pandey, JP Garcia-de la Torre, I Kalovidouris, AE O'Hanlon, TP Love, LA Hennekam, RCM Baumbach, LL Neville, HE Garcia, CA Klingman, J Gibbs, M Weisman, MH Targoff, IN Miller, FW TI Clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy SO ARTHRITIS AND RHEUMATISM LA English DT Article ID INCLUSION-BODY MYOSITIS; SYSTEMIC LUPUS-ERYTHEMATOSUS; DEPENDENT DIABETES-MELLITUS; SIGNAL RECOGNITION PARTICLE; RHEUMATOID-ARTHRITIS; GENETIC SUSCEPTIBILITY; OLIGONUCLEOTIDE PROBES; IRANIAN JEWS; DISEASE; HLA AB Objective. To describe the clinical, serologic, and immunogenetic features of familial idiopathic inflammatory myopathy (IIM) and to compare these with the features of sporadic IIM. Methods. Clinical signs and symptoms, autoantibodies, HLA-DRB1 and DQA1 alleles, and GM/KM phenotypes were compared among 36 affected and 28 unaffected members of 16 unrelated families in which 2 or more blood relatives developed an IIM. In addition, findings in patients with familiar IIM were compared with those in 181 patients with sporadic IIM, The families included 3 pairs of monozygotic twins with juvenile dermatomyositis, 11 families with other siblings or relatives with polymyositis or dermatomyositis, and 3 families with inclusion body myositis. Results, The clinical features of familial IIM were similar to those of sporadic IIM, although the frequency of myositis-specific autoantibodies tvas lon cr in familial than in sporadic IIM. DRB1*0301 mas a common genetic risk factor for familial and sporadic IIM, but contributed less to the genetic risk of familial IIM (etiologic fraction 0.35 versus 0.51 in sporadic IIM), Homozygosity at the HLA-DQA1 locus was found to be a genetic risk factor unique to familial IIM (57% versus 24% of controls; odds ratio 4.2, corrected P = 0.002), Conclusion. These findings emphasize that 1) familial muscle weakness is not always due to inherited metabolic defects or dystrophies, but may be the result of the development of IIM in several members of the same family, and 2) multiple genetic factors are likely important in the etiology and disease expression of familial IIM, as is also the case for sporadic myositis, but DQA1 homozygosity is a distinct risk factor for familial IIM. C1 US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Med Univ S Carolina, Charleston, SC 29425 USA. Univ Guadalajara, Guadalajara 44430, Jalisco, Mexico. Hosp Gen Occidente SS, Guadalajara, Jalisco, Mexico. US FDA, Ctr Food & Special Nutr, Washington, DC 20204 USA. Amsterdam Med Coll, Dept Pediat, Amsterdam, Netherlands. Amsterdam Med Coll, Inst Human Genet, Amsterdam, Netherlands. Univ Miami, Sch Med, Miami, FL 33152 USA. Univ Colorado, Sch Med, Denver, CO 80202 USA. Denver VA Med Ctr, Denver, CO USA. Louisiana State Univ, Sch Med, New Orleans, LA USA. So Calif Permanente Med Grp, Walnut Creek, CA USA. Univ Calif San Diego, Med Ctr, San Diego, CA 92103 USA. Univ Oklahoma, Med Sci Ctr, VA Med Ctr, Oklahoma City, OK USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. Indiana Univ, VA Med Ctr, Indianapolis, IN 46204 USA. RP Rider, LG (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Monoclonal Antibodies, NIH, Bldg 29B,Room 2G11,HFM-561,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Rider, Lisa/0000-0002-6912-2458; Miller, Frederick/0000-0003-2831-9593 NR 58 TC 35 Z9 36 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD APR PY 1998 VL 41 IS 4 BP 710 EP 719 DI 10.1002/1529-0131(199804)41:4<710::AID-ART19>3.0.CO;2-K PG 10 WC Rheumatology SC Rheumatology GA ZG163 UT WOS:000072972800018 PM 9550481 ER PT J AU Cherney, BW Sgadari, C Kanegane, C Wang, F Tosato, G AF Cherney, BW Sgadari, C Kanegane, C Wang, F Tosato, G TI Expression of the Epstein-Barr virus protein LMP1 mediates tumor regression in vivo SO BLOOD LA English DT Article ID LATENT MEMBRANE-PROTEIN; NF-KAPPA-B; NECROSIS-FACTOR RECEPTOR; BURKITTS-LYMPHOMA; TRANSFORMING PROTEIN; CELL-LINES; ACTIVATION; DOMAIN; BCL-2; TUMORIGENICITY AB By stimulating the expression of murine IP-10 and Mig, CXC chemokines that inhibit neovascularization and cause damage to established tumor vasculature, human B cells immortalized with Epstein-Barr virus (EBV) can promote an effective antitumor response in athymic mice. In the present study, we examined the potential role of EBV in the induction of this antitumor response. Using a panel of EBV+ and EBV- Burkitt lymphoma (BL) cell lines, a significant correlation was detected between the expression of the EBV latency gene LMP1 and the occurrence of spontaneous tumor regression in athymic mice. inoculation of LMP1(+) and LMP1(-) BL cells in the same subcutaneous site resulted in tumors that completely regressed in a manner indistinguishable from that induced by EBV-immortalized B cells. EBV-converted BL30 and BL41 sublines infected with B95-8 virus expressed LMP1, generated tumors that frequently regressed spontaneously, and promoted an effective antitumor response against progressively growing tumors. In contrast, the EBV- BL30 and BL41 cell lines and the EBV-converted BL30 and BL41 infected with P3HR-1 virus did not express LMP1 protein, and generated progressively growing tumors in nude mice. When transfected with the LMP1 gene, BL41 cells produced tumors that regressed spontaneously in most cases, and could induce the regression of tumors derived from BL41 cells transfected with vector alone. Tumors induced by LMP1-expressing cells expressed murine IP-10 and Mig and displayed histological evidence of extensive tumor tissue necrosis and vascular damage. We conclude that the EBV protein LMP1 is likely responsible for the antitumor response elicited by EBV-immortalized cells in athymic mice. This is a US government work. There are no restrictions on its use. C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD USA. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. RP Cherney, BW (reprint author), Ctr Biol Evaluat & Res, Bldg 29A,Room 2D06,1401 Rockville Pike HFM535, Rockville, MD 20852 USA. RI Sgadari, Cecilia/H-4302-2016 OI Sgadari, Cecilia/0000-0003-0364-4912 NR 46 TC 16 Z9 17 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0006-4971 J9 BLOOD JI Blood PD APR 1 PY 1998 VL 91 IS 7 BP 2491 EP 2500 PG 10 WC Hematology SC Hematology GA ZD305 UT WOS:000072671900033 PM 9516150 ER PT J AU Fan, SJ Cherney, B Reinhold, W Rucker, K O'Connor, PM AF Fan, SJ Cherney, B Reinhold, W Rucker, K O'Connor, PM TI Disruption of p53 function in immortalized human cells does not affect survival or apoptosis after taxol or vincristine treatment SO CLINICAL CANCER RESEARCH LA English DT Article ID TUMOR-SUPPRESSOR GENE; DNA-DAMAGE; WILD-TYPE; LINES; MUTATIONS; AGENTS; RADIOSENSITIVITY; SENSITIVITY; CARCINOMA; CANCER AB In the present study, we report our findings on the impact of p53 disruption on the sensitivity of human cell lines to the antimitotic agents Taxol and vincristine. Comparisons of cell survival and apoptosis were made with gamma-irradiation and, in some cases, several other DNA-damaging chemotherapeutic agents, Studies in eight Burkitt's lymphoma and lymphoblastoid cell lines (four wild-type p53 and four mutant p53 cell lines) revealed that the DNA-damaging agents assayed tended to exhibit less growth inhibition in the mutant p53 cell lines compared to the wildtype p53 cell lines, In contrast, no significant correlation was apparent between p53 gene status and the growth-inhibitory potency of Taxol or vincristine in these eight cell lines, We also found that contrary to gamma-irradiation, Taxol and vincristine could induce apoptosis in lymphoma cell lines harboring p53 mutations, These observations were explored further in lymphoblastoid VDSO cells (wild-type p53) from a normal individual and stably transfected VDSO derivatives lacking p53 function due to expression of the human papillomavirus type-16 E6 gene, We found that p53 disruption in VDSO/E6 cells blocked gamma-ray-induced apoptosis and afforded a survival advantage to VDSO/E6 cells compared to control-transfected cells, In contrast, p53 disruption did not affect Taxol-or vincristine-induced apoptosis or survival in VDSO cells, The effect of p53 disruption on Taxol sensitivity was explored further in the breast carcinoma MCF-7 and colon carcinoma HCT-116 cell lines that had been stably transfected with either the human papillomavirus type-16 Ed gene or a dominant-negative mutant p53 gene, Again, in these cell model systems, we found that p53 disruption did not affect the growth-inhibitory potency of Taxol, Taken together, our results suggest that p53 status is not a dominant factor in the mechanism by which antimitotic agents induce apoptosis and reduce survival in immortalized human cell lines. C1 US FDA, Immunol Lab, Bethesda, MD 20892 USA. NCI, Mol Pharmacol Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. RP O'Connor, PM (reprint author), Agouron Pharmaceut Inc, Oncol Res Div, 3565 Gen Atom Ct, San Diego, CA 92121 USA. EM poconnor@agouron.com RI Ain, Kenneth/A-5179-2012 OI Ain, Kenneth/0000-0002-2668-934X NR 32 TC 77 Z9 78 U1 1 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD APR PY 1998 VL 4 IS 4 BP 1047 EP 1054 PG 8 WC Oncology SC Oncology GA ZG200 UT WOS:000072977200028 PM 9563901 ER PT J AU Leber, PD Davis, CS AF Leber, PD Davis, CS TI Threats to the validity of clinical trials employing enrichment strategies for sample selection SO CONTROLLED CLINICAL TRIALS LA English DT Article DE enrichment design; internal validity; external validity; carry-over effect; withdrawal effect; learning effect; unblinding ID ALZHEIMERS-DISEASE; RUN-IN; TACRINE; PHYSOSTIGMINE; ENHANCEMENT; EFFICIENCY; UTILITY; DESIGN; PERIOD AB Subject selection and exclusion criteria employed in typical clinical effectiveness trials of investigational new drugs have two fundamental aims: (1) to ensure that patients entering a study are truly suffering from the condition the drug is intended to treat and (2) to maximize the likelihood that the study will detect an effect of the drug if, in fact, one exists. Typical protocol selection criteria not only specify exacting procedures for establishing and documenting the diagnosis of those recruited for a study but also seek to increase, relative to the prevalence in the general population, the proportion of individuals in the sample likely to respond to pharmacological treatment. Because it is ordinarily impossible to learn prior to extensive clinical experience with a new drug which, if any, patient characteristics reliably predict a consistent treatment response, strategies for sample "enrichment" typically operate by excluding patients (for example, those with very advanced and/or complicated illness, those with serious concomitant illness, those at the extremes of age, those with very mild illness, and so forth) in whom a dependable response to treatment seems unlikely on logical and/or generic grounds. Some studies use positive strategies for sample "enrichment." In studies evaluating drugs intended to treat recurrent episodes of psychiatric illnesses, many protocols recommend selective recruitment of patients with a history of meaningful positive responses to antipsychotic treatment during prior episodes. Sample selection procedures of these kinds impose limits on the generalizability of a study's results (i.e., external validity), but the use of nonrandom patient samples is ordinarily held to have no effect on the internal validity of the results. In short, studies employing highly selected patient samples are, despite their limited external validity, regularly accepted as valid sources of evidence bearing on a drug's effectiveness. There are exceptions, however; this paper describes one in which the use of a seemingly innocuous sample enrichment maneuver proved highly damaging to the ultimate credibility of an important multicenter trial. In particular, exposure to an experimental treatment during an open qualification phase may invalidate drug-placebo comparisons made during a later randomized, blinded, controlled phase. Our review of the trial also reveals that the enrichment maneuver employed probably failed to accomplish its intended aims, selecting patients whose improvements on the outcome variable may be as reasonably ascribed to chance as to drug effect. This is all the more surprising because the method of sample enrichment employed has much in common with those long recommended in the clinical trial literature. (C) Elsevier Science Inc. 1998. C1 Univ Iowa, Dept Prevent Med & Environm Hlth, Iowa City, IA 52242 USA. US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod, Rockville, MD 20857 USA. RP Davis, CS (reprint author), Univ Iowa, Dept Prevent Med & Environm Hlth, 2837 Steindler Bldg, Iowa City, IA 52242 USA. NR 18 TC 73 Z9 73 U1 0 U2 6 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 1998 VL 19 IS 2 BP 178 EP 187 PG 10 WC Medicine, Research & Experimental; Pharmacology & Pharmacy SC Research & Experimental Medicine; Pharmacology & Pharmacy GA ZD740 UT WOS:000072718700006 PM 9551282 ER PT J AU Woodcock, J AF Woodcock, J TI A shift in the regulatory approach SO DRUG INFORMATION JOURNAL LA English DT Article DE off-label use; food and drug administration; promotion; oncology; pediatrics AB This paper highlights the shift in the Food and Drug Administration's (FDA) approach to the off-label use of drugs, including definitions and a discussion of current policies, reasons for the changes, and current initiatives in off-label use. Off-label uses must be studied and effective uses should be labeled. FDA is adopting new strategies to get more uses an the label. C1 US FDA, Dir Ctr Drug Evaluat, Rockville, MD 20857 USA. RP Woodcock, J (reprint author), US FDA, Dir Ctr Drug Evaluat, 5600 Fishers Lane,HFD-1, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI AMBLER PA 321 NORRISTOWN RD, STE 225, AMBLER, PA 19002-2755 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD APR-JUN PY 1998 VL 32 IS 2 BP 367 EP 371 PG 5 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 128GF UT WOS:000076396800006 ER PT J AU Fairweather, WR Bhattacharyya, A Ceuppens, PP Heimann, G Hothorn, LA Kodell, RL Lin, KK Mager, H Middleton, BJ Slob, W Soper, KA Stallard, N Ventre, J Wright, J AF Fairweather, WR Bhattacharyya, A Ceuppens, PP Heimann, G Hothorn, LA Kodell, RL Lin, KK Mager, H Middleton, BJ Slob, W Soper, KA Stallard, N Ventre, J Wright, J TI Biostatistical methodology in carcinogenicity studies SO DRUG INFORMATION JOURNAL LA English DT Article DE carcinogenicity; study design; data analysis; test statistics; literature ID HISTORICAL CONTROL INFORMATION; MULTIPLE TUMOR DATA; ANIMAL CARCINOGENICITY; TUMORIGENICITY EXPERIMENTS; BINOMIAL PROPORTIONS; SINGLE-SACRIFICE; TREND TESTS; RANK-TESTS; DESIGN; SAFETY AB This paper addresses the design, conduct, and statistical analysis of carcinogenicity studies, especially in the context of drug products for human use. It contains suggestions concerning the choice of dose levels, number of animals, methods of slide reading, and the ensuing statistical analysis, focusing an the significance testing approach. The purpose of this document is to describe the current thinking of statisticians and others who work in the area of carcinogenicity studies. The authors represent experience gained in the pharmaceutical industry, regulatory agencies, and academia. C1 US FDA, Ctr Drug Evaluat & Res, Off Epidemiol & Biostat, Div Biometr 2, Rockville, MD 20857 USA. Zeneca Pharmaceut, Macclesfield, Cheshire, England. Univ Hannover, Hannover, Germany. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. Bayer AG, Ctr Drug Res, Preclin & Clin Biostat, D-5600 Wuppertal, Germany. Schering AG, Corp Biometry, D-1000 Berlin, Germany. Natl Inst Publ Hlth & Environm, RIVM, NL-3720 BA Bilthoven, Netherlands. Merck Res Labs, W Point, PA USA. Univ Reading, Med & Pharmaceut Stat Res Unit, Reading, Berks, England. Nycomed, Rensselaer, NY 12144 USA. Quintiles, Bracknell, Berks, England. RP Fairweather, WR (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Epidemiol & Biostat, Div Biometr 2, HFD-700,5600 Fishers Lane, Rockville, MD 20857 USA. NR 90 TC 16 Z9 17 U1 1 U2 5 PU DRUG INFORMATION ASSOCIATION PI AMBLER PA 321 NORRISTOWN RD, STE 225, AMBLER, PA 19002-2755 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD APR-JUN PY 1998 VL 32 IS 2 BP 401 EP 421 PG 21 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 128GF UT WOS:000076396800012 ER PT J AU Ellenberg, SS AF Ellenberg, SS TI Commentary on "Surrogate endpoints in AIDS drug development: Current status," by Christy Chuang-Stein and Ralph DeMasi SO DRUG INFORMATION JOURNAL LA English DT Editorial Material DE HIV/AIDS; markers; clinical outcomes ID CLINICAL-TRIALS; HIV DISEASE; END-POINTS; RNA LEVELS; ZIDOVUDINE; ZALCITABINE; DIDANOSINE; INFECTION; MARKERS AB This paper offers commentary on "Surrogate Endpoints in AIDS Drug Development: Current Status" by Cristy Chuang-Stein and Ralph DeMasi which appears in this issue of the Drug Information Journal. Chuang-Stein and DeMasi pose the question: "Are researchers likely to be misled?" by surrogate endpoints, but the critical question is "How likely are researchers to be misled?" This commentary provides a brief review of AIDS treatments and knowledge, A reasonable strategy for assessing new HN therapies might be to couple studies in pre-AIDS patients using viral load endpoints with studies in more advanced patients that can evaluate effects on clinical progression and mortality in a timely way. Researchers cannot answer the question "how likely" until they have seen marker and clinical data for a wide variety of products. C1 US FDA, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, Rockville, MD 20852 USA. RP Ellenberg, SS (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Biostat & Epidemiol, 1401 Rockville Pike,HFM-210, Rockville, MD 20852 USA. NR 20 TC 0 Z9 0 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI AMBLER PA 321 NORRISTOWN RD, STE 225, AMBLER, PA 19002-2755 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD APR-JUN PY 1998 VL 32 IS 2 BP 449 EP 452 PG 4 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 128GF UT WOS:000076396800016 ER PT J AU Merrill, RA AF Merrill, RA TI The FDA may not regulate tobacco products as "drugs" or as "medical devices" SO DUKE LAW JOURNAL LA English DT Article; Proceedings Paper CT Duke-Law-Journal 1998 Administrative Law Conference CY 1998 CL DURHAM, NORTH CAROLINA SP Duke Law Journal AB Professor Richard Merrill contends that the Federal Food, Drug, and Cosmetic Act does not grant the FDA regulatory authority over cigarettes and smokeless tobacco products. the fact that Congress did not expressly deny the FDA regulatory authority over tobacco cannot, Professor Merrill argues, be used to infer such authority. This inference is particularly inappropriate in the case of tobacco regulation, he maintains, because there is compelling evidence that Congress had no intention of delegating this authority to the FDA. He is unpersuaded that presidential approval legally sanctions the FDA's claim of authority by granting it a superficial political legitimacy. Finally, he reminds us of the FDA's own repeated denials of jurisdiction over tobacco products, and he recalls the numerous times that Congress passed legislation directed at tobacco without granting the FDA any role in its regulation. Professor Merrill's Essay, like the other pieces in this volume, was written after the United States District Court for the Middle District of North Carolina decided Coyne Beahm v. FDA,(1) but before a three judge panel of the United States Court of Appeals for the Fourth Circuit reversed that decision in Brown & Williamson Tobacco Corp. v. FDA.(2) In Coyne Beahm, the District Court held that the Federal Food, Drug, and Cosmetic Act authorized the FDA to regulate tobacco products, but not tobacco advertising. The Fourth Circuit rejected the District Court's jurisdictional ruling and invalidated the FDA's regulations in their entirety. The Clinton Administration has since requested an en banc rehearing before the Fourth Circuit.(3). C1 Univ Virginia, Charlottesville, VA 22903 USA. US FDA, Rockville, MD 20857 USA. RP Merrill, RA (reprint author), Univ Virginia, Charlottesville, VA 22903 USA. NR 18 TC 9 Z9 9 U1 0 U2 4 PU DUKE UNIV PI DURHAM PA SCHOOL LAW BOX 90364, DURHAM, NC 27708-0364 USA SN 0012-7086 J9 DUKE LAW J JI Duke Law J. PD APR PY 1998 VL 47 IS 6 BP 1071 EP 1094 DI 10.2307/1373031 PG 24 WC Law SC Government & Law GA 142DV UT WOS:000077185400002 PM 10557545 ER PT J AU Blaauboer, BJ Balls, M Barratt, M Casati, S Coecke, S Mohamed, MK Moore, J Rall, D Smith, KR Tennant, R Schwetz, BA Stokes, WS Younes, M AF Blaauboer, BJ Balls, M Barratt, M Casati, S Coecke, S Mohamed, MK Moore, J Rall, D Smith, KR Tennant, R Schwetz, BA Stokes, WS Younes, M TI 13th meeting of the Scientific Group on Methodologies for the Safety Evaluation of Chemicals (SGOMSEC): Alternative testing methodologies and conceptuals issues SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 13th Meeting of the Scientific-Group-on-Methodologies-for-the-Safety-Evaluation-of-Chemicals on Alternative Testing Methodologies CY JAN 26-31, 1997 CL JOINT RES CTR, ISPRA, ITALY SP Sci Grp Methodol Safety Evaluat Chem, European Ctr Validat Alternat Methods, US Natl Inst Environm Hlth Sci, Commiss European Communities, Intl Program Chem Safety, US EPA, US FDA HO JOINT RES CTR DE risk assessment; alternative methods; toxicology; in vitro methods; reduction; refinement; replacement; testing; QSAR; PBBK modeling; transgenic models ID TOXICOLOGY; VALIDATION AB Substantial world-wide resources are being committed to develop improved toxicological testing methods that will contribute to better protection of human health and the environment. The development of new methods is intrinsically driven by new knowledge emanating from fundamental research in toxicology, carcinogenesis, molecular biology, biochemistry, computer sciences, and a host of other disciplines. Critical evaluations and strong scientific consensus are essential to facilitate adoption of alternative methods for use in the safety assessment of drugs, chemicals, and other environmental factors. Recommendations to hasten the development of new alternative methods included increasing emphasis on the development of mechanism-based methods, increasing fundamental toxicological research, increasing training on the use of alternative methods, integrating accepted alternative methods into toxicity assessment, internationally harmonizating chemical toxicity classification schemes, and increasing international cooperation to develop, validate, and gain acceptance of alternative methods. C1 Univ Utrecht, RITOX, NL-3508 TD Utrecht, Netherlands. Commiss European Communities, ECVAM, Ispra, Italy. Unilever Environm Safety Lab, Bedford, England. Ain Shams Univ, Dept Community Med, Cairo, Egypt. Inst Evaluating Hlth Risks, Washington, DC 20002 USA. NIEHS, Washington, DC 20002 USA. Univ Calif Berkeley, Sch Publ Hlth, Berkeley, CA 94720 USA. NIEHS, Res Triangle Pk, NC 27709 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. WHO, Int Programme Chem Safety, CH-1211 Geneva, Switzerland. RP Blaauboer, BJ (reprint author), Univ Utrecht, RITOX, POB 80-176, NL-3508 TD Utrecht, Netherlands. NR 11 TC 20 Z9 20 U1 1 U2 3 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1998 VL 106 SU 2 BP 413 EP 418 DI 10.2307/3433790 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WD UT WOS:000075403800003 PM 9599687 ER PT J AU Schwetz, B Gaylor, D AF Schwetz, B Gaylor, D TI Alternative tests: Carcinogenesis as an example SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 13th Meeting of the Scientific-Group-on-Methodologies-for-the-Safety-Evaluation-of-Chemicals on Alternative Testing Methodologies CY JAN 26-31, 1997 CL JOINT RES CTR, ISPRA, ITALY SP Sci Grp Methodol Safety Evaluat Chem, European Ctr Validat Alternat Methods, US Natl Inst Environm Hlth Sci, Commiss European Communities, Intl Program Chem Safety, US EPA, US FDA HO JOINT RES CTR DE carcinogenesis; alternative tests; regulations ID RODENT CARCINOGENICITY; 44 CHEMICALS; POTENCY; RATS; PREDICTION; MICE AB Acceptance of new tests that are alternatives to currently used toxicology tests is a topic of considerable importance in the field of toxicology. Carcinogenicity testing today normally includes 2-year studies in rats and mice of both sexes, following widely accepted procedures for husbandry; selection of dose levels; pathology and toxicity observations; and statistical interpretation of tumor data. These studies are usually preceded by tests for genetic toxicity and subchronic toxicity studies to select dose levels for the 2-year studies. Although these data are used for quantitative risk assessment, the mechanistic basis for effects is usually unknown. The series of studies is very expensive and requires 5 years or more to conduct. Alternative approaches are being developed that would provide more mechanistic information and hopefully would permit decisions to be made about carcinogenic potential without the need to conduct 2-year studies in rats and mice of both sexes. Decisions could be based on a profile of data rather than on the result of one test. Procedures for regulatory acceptance of new approaches for carcinogenicity testing are critical to future progress. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Schwetz, B (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 20 TC 10 Z9 10 U1 0 U2 1 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD APR PY 1998 VL 106 SU 2 BP 467 EP 471 DI 10.2307/3433796 PG 5 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WD UT WOS:000075403800009 PM 9599693 ER PT J AU Kvenberg, JE AF Kvenberg, JE TI Introduction to food safety HACCP SO FOOD CONTROL LA English DT Editorial Material C1 US FDA, US Dept HHS, Washington, DC 20204 USA. RP Kvenberg, JE (reprint author), US FDA, US Dept HHS, 200 C St SW, Washington, DC 20204 USA. NR 0 TC 6 Z9 7 U1 0 U2 0 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD APR-JUN PY 1998 VL 9 IS 2-3 BP 73 EP 74 DI 10.1016/S0956-7135(97)00080-7 PG 2 WC Food Science & Technology SC Food Science & Technology GA ZY583 UT WOS:000074638200001 ER PT J AU Tsai, CM Chen, WH Balakonis, PA AF Tsai, CM Chen, WH Balakonis, PA TI Characterization of terminal NeuNAc alpha 2-3Gal beta 1-4GlcNAc sequence in lipooligosaccharides of Neisseria meningitidis SO GLYCOBIOLOGY LA English DT Article DE Maackia amurensis leukoagglutinin; meningococcal lipooligosaccharide; sialic acid linkage ID LACTO-N-NEOTETRAOSE; LIPOPOLYSACCHARIDE CORE OLIGOSACCHARIDES; OUTER-MEMBRANE PROTEIN; MENINGOCOCCAL LIPOPOLYSACCHARIDES; MONOCLONAL-ANTIBODY; HUMAN-ERYTHROCYTES; MAACKIA-AMURENSIS; HUMAN-NEUTROPHILS; SERUM RESISTANCE; NEURAMINIC ACID AB Group B and C Neisseria meningitidis are the major cause of meningococcal disease in the United States and in Europe, N.meningitidis lipooligosaccharide (LOS), a major surface antigen, can be divided into 12 immunotypes of which L1 through L8 were found among Group B and C organisms, Groups B and C but not Group A may sialylate their LOSs with N-acetylneuraminic acid (NeuNAc) at the nonreducing end because they synthesize CMP-NeuNAc, Using sialic acid-galactose binding lectins as probes in an ELISA format, six of the eight LOS immunotypes (L2, L3, L4, L5, L7, and L8) in Groups B and C bound specifically to Maackia amurensis leukoagglutinin (MAL), which recognizes NeuNAc alpha 2-3Gal beta 1-GlcNAc/Glc sequence, but not to Sambucus nigra agglutinin, which binds NeuNAc alpha 2-6Gal sequence, The combination of SDS-PAGE and MAL-blot analyses revealed that these six LOSs contained only the NeuNAc alpha 2-3Gal beta 1-4GlcNAc trisaccharide sequence in their 4.1 kDa LOS components, which have a common terminal lacto-N-neotetraose (LNnT, Gal beta 1-4GlcNAc beta 1-3Gal beta 1-4Glc) structure when nonsialylated as shown by previous studies. The LOS-lectin binding was abolished when the LOSs were treated with Newcastle disease viral neuraminidase which cleaves alpha 2-->3 linked sialic acid. Methylation analysis of a representative LOS (L2) confirmed that NeuNAc is 2-->3 linked to Gal. Thus, these LOSs structurally mimic certain glycolipids, i.e., paragloboside (LNnT-ceramide) and sialyl-paragloboside and some glycoproteins in having LNnT and N-acetyllactosamine sequences, respectively, with or without alpha 2-->3 linked NeuNAc, The molecular mimicry of the LOSs may play a role in the pathogenesis of N.meningitidis by assisting the organism to evade host immune defenses in man. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20892 USA. RP Tsai, CM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20892 USA. NR 62 TC 10 Z9 10 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0959-6658 J9 GLYCOBIOLOGY JI Glycobiology PD APR PY 1998 VL 8 IS 4 BP 359 EP 365 DI 10.1093/glycob/8.4.359 PG 7 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA ZG228 UT WOS:000072980000007 PM 9499383 ER PT J AU Rosenstein, M AF Rosenstein, M TI Comment on "phantom-derived estimation of effective dose equivalent from x-rays with and without a lead apron" SO HEALTH PHYSICS LA English DT Letter ID DIAGNOSTIC-RADIOLOGY; PROTECTIVE APRONS; PERSONNEL; STAFF C1 Ctr Devices & Radiol Hlth, Gaithersburg, MD 20877 USA. NR 9 TC 2 Z9 2 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 530 WALNUT ST, PHILADELPHIA, PA 19106-3621 USA SN 0017-9078 EI 1538-5159 J9 HEALTH PHYS JI Health Phys. PD APR PY 1998 VL 74 IS 4 BP 489 EP 490 PG 2 WC Environmental Sciences; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Nuclear Science & Technology; Radiology, Nuclear Medicine & Medical Imaging GA ZD057 UT WOS:000072646500014 PM 9525426 ER PT J AU Carrington, CD Bolger, PM AF Carrington, CD Bolger, PM TI Uncertainty and risk assessment SO HUMAN AND ECOLOGICAL RISK ASSESSMENT LA English DT Article C1 US FDA, Ctr Food Safety & Appl Nutr, Contaminants Stand & Monitoring Branch, Washington, DC 20204 USA. RP Carrington, CD (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Contaminants Stand & Monitoring Branch, HFS-308, Washington, DC 20204 USA. NR 7 TC 15 Z9 15 U1 0 U2 2 PU CRC PRESS INC PI BOCA RATON PA 2000 CORPORATE BLVD NW, JOURNALS CUSTOMER SERVICE, BOCA RATON, FL 33431 USA SN 1080-7039 J9 HUM ECOL RISK ASSESS JI Hum. Ecol. Risk Assess. PD APR PY 1998 VL 4 IS 2 BP 253 EP 257 DI 10.1080/10807039891284325 PG 5 WC Biodiversity Conservation; Environmental Sciences SC Biodiversity & Conservation; Environmental Sciences & Ecology GA ZL600 UT WOS:000073450600005 ER PT J AU Chen, I Finn, TM Liu, YQ Qi, GM Rappuoli, R Pizza, M AF Chen, I Finn, TM Liu, YQ Qi, GM Rappuoli, R Pizza, M TI A recombinant live attenuated strain of Vibrio cholerae induces immunity against tetanus toxin and Bordetella pertussis tracheal colonization factor SO INFECTION AND IMMUNITY LA English DT Article ID CELL-MEDIATED-IMMUNITY; ESCHERICHIA-COLI; RESPIRATORY-INFECTION; FILAMENTOUS HEMAGGLUTININ; NIRB PROMOTER; ORAL VACCINE; EXPRESSION; IMMUNIZATION; IMMUNOGENICITY; EFFICACY AB An attenuated strain of Vibro cholerae was used as a carrier for the expression of heterologous antigens such as fragment C from tetanus toxin (TetC) and tracheal colonization factor from Bordetella pertussis (Tcf). In vitro, high levels of protein were obtained when the Escherichia coli nirB promoter was used and the bacteria were grown with low aeration. Intranasal immunization of mice with IEM101 expressing TetC elicited serum vibriocidal activity and induced antibodies against tetanus toxin which were protective against lethal challenge with 10 times the 50% lethal dose of tetanus toxin. Bacterial viability was essential for the induction of anti-TetC antibodies. Intranasal administration of IEM101 expressing Tcf induced a significant reduction in bacterial colonization of the tracheas of mice challenged with wild-type B. pertussis. These data are in agreement with the putative role of Tcf in Bordetella tracheal colonization. In conclusion, we have demonstrated that V. cholerae may be used as a live vector to deliver heterologous antigens in vivo and that protection to both systemic and local challenge may be achieved. C1 Chiron Vaccines Immunobiol Res Inst Siena, IRIS, I-53100 Siena, Italy. Univ Sao Paulo, ICB 2, Dept Microbiol, BR-05508900 Sao Paulo, Brazil. US FDA, Ctr Biol Evaluat & Res, Lab Pertussis, Bethesda, MD 20892 USA. Chinese Acad Prevent Med, Beijing, Peoples R China. RP Rappuoli, R (reprint author), Chiron Vaccines Immunobiol Res Inst Siena, IRIS, Via Fiorentina 1, I-53100 Siena, Italy. EM Rappuoli@IRIS02.BIOCINE.IT OI Chen, Ines/0000-0002-1405-9703 NR 37 TC 20 Z9 20 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD APR PY 1998 VL 66 IS 4 BP 1648 EP 1653 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA ZD630 UT WOS:000072706100052 PM 9529093 ER PT J AU Nightingale, SL AF Nightingale, SL TI New national campaign to help stop tobacco sales to children SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 1 PY 1998 VL 279 IS 13 BP 984 EP 984 DI 10.1001/jama.279.13.984 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZD283 UT WOS:000072669700005 PM 9533484 ER PT J AU Nightingale, SL AF Nightingale, SL TI New rules require financial disclosure SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Lane, Rockville, MD 20857 USA. NR 1 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 1 PY 1998 VL 279 IS 13 BP 984 EP 984 DI 10.1001/jama.279.13.984 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZD283 UT WOS:000072669700004 PM 9533484 ER PT J AU Nightingale, SL AF Nightingale, SL TI New warning for isotretinoin SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD APR 1 PY 1998 VL 279 IS 13 BP 984 EP 984 DI 10.1001/jama.279.13.984 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA ZD283 UT WOS:000072669700006 PM 9533484 ER PT J AU Piringer, O Franz, R Huber, M Begley, TH McNeal, TP AF Piringer, O Franz, R Huber, M Begley, TH McNeal, TP TI Migration from food packaging containing a functional barrier: Mathematical and experimental evaluation SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE migration; functional barrier; diffusion; food packaging; recycled polymers ID RECYCLED POLYMERS; POLY(ETHYLENE-TEREPHTHALATE) AB A model for predicting the functional barrier properties of layered films based on Fickian diffusion is presented along with experimental migration data from layered poly(ethylene terephthalate) films (PET) to test the model. Three-layered coextruded PET films were produced in which the center layer contained model solutes/contaminants and the outer layers were made with virgin material. The contaminants in the center layer were toluene and chlorobenzene. The PET films, which were 400 mu m thick, had barrier layers of 20, 30, 40, and 60 mu m of virgin coextruded PET. The center or core layer had thicknesses between 360 and 280 mu m. The amount of migration was measured into water, 3% acetic acid, and isooctane at temperatures up to 60 degrees C. The measured amount of migration through the different barrier thicknesses was predictable on the basis of the model presented. The effects of diffusion from the center layer to a virgin barrier layer during the coextrusion process must be considered if reliable predictions of migration are to be obtained. C1 FABES Res Inc Anal & Evaluat Mass Transfer, D-80992 Munich, Germany. Fraunhofer Inst Food Technol & Packaging, D-85354 Freising, Germany. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Piringer, O (reprint author), FABES Res Inc Anal & Evaluat Mass Transfer, Schragenhofstr 35, D-80992 Munich, Germany. NR 22 TC 42 Z9 44 U1 0 U2 20 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR PY 1998 VL 46 IS 4 BP 1532 EP 1538 DI 10.1021/jf970771v PG 7 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA ZK354 UT WOS:000073312000059 ER PT J AU Newkirk, DK Benson, RW Howard, PC Churchwell, MI Doerge, DR Roberts, DW AF Newkirk, DK Benson, RW Howard, PC Churchwell, MI Doerge, DR Roberts, DW TI On-line immunoaffinity capture, coupled with HPLC and electrospray ionization mass spectrometry, for automated determination of fumonisins SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE analytical immunology; fumonisins; immunoaffinity; mass spectrometry; immunoassay; site-directed coupling; ELISA; mixtures ID ANTIBODY-BASED ELISA; CORN-BASED FOOD; ENZYME-IMMUNOASSAY; B-1; MYCOTOXINS; B1; CARCINOGENESIS; CHROMATOGRAPHY; TOXICITY; TOXIN AB An automated on-line method for the quantitative detection of fumonisins B-1, B-2, and B-3 and hydrolyzed fumonisin B-1 in corn-based feed was developed using a combination of immunoaffinity capture (IAC)/cleanup, coupled with reversed phase liquid chromatography and electrospray ionization mass spectrometry. Blocking the C2 amine of fumonisin B-1 with 9-fluorenylmethylchloroformate allowed coupling to keyhole limpet hemocyanin through the tricarballylic end, leaving the amino terminus exposed on the immunogenic conjugate after removal of the blocking group. Antiserum had specificity for the C1-C10 fumonisin domain and was used for ELISA and to prepare immunoaffinity columns. The quantitation limit (s/n = 10) for fumonisin B-1 standard was 250 pg using the protonated molecule signal (m/z 722). Similar sensitivity was observed for fumonisins B-2 and B-3 (m/z 706) and hydrolyzed fumonisin B-1 (m/z 406). The on-line IAC/LC/ESI-MS method provided a linear response from the detection limit to 5 ng for fumonisin B-1 and has the capability to analyze low-level contamination of rodent feed samples for fumonisins. The dynamic range can be adjusted as necessary by varying the volume of the sample injected for IAC capture. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Roberts, DW (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 37 TC 27 Z9 29 U1 0 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0021-8561 J9 J AGR FOOD CHEM JI J. Agric. Food Chem. PD APR PY 1998 VL 46 IS 4 BP 1677 EP 1688 DI 10.1021/jf970919a PG 12 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA ZK354 UT WOS:000073312000081 ER PT J AU Merkel, TJ Barros, C Stibitz, S AF Merkel, TJ Barros, C Stibitz, S TI Characterization of the bvgR locus of Bordetella pertussis SO JOURNAL OF BACTERIOLOGY LA English DT Article ID ESCHERICHIA-COLI GENOME; VIR-REPRESSED GENES; NUCLEOTIDE-SEQUENCE; DNA-SEQUENCE; VIRULENCE FACTORS; TRANSPOSON TN501; MERCURIC-RESISTANCE; PLASMID R100; REGION; SYSTEM AB Bordetella pertussis, the causative agent of whooping cough, produces a wide array of factors that are associated with its ability to cause disease. The expression and regulation of these virulence factors is dependent upon the bvg locus (originally designated the vir locus), which encodes two proteins: BvgA, a 23-kDa cytoplasmic protein, and BvgS, a 135-kDa transmembrane protein. It is proposed that BvgS responds to environmental signals and interacts with BvgA, a transcriptional regulator which upon modification by BvgS binds to specific promoters and activates transcription. An additional class of genes is repressed by the bvg locus. Expression of this class, the bvg-repressed genes (vrgs [for vir-repressed genes]), is reduced under conditions in which expression of the aforementioned bvg-activated virulence factors is maximal; this repression is dependent upon the presence of an intact bvgAS locus. We have previously identified a locus required for regulation of all of the known bvg-repressed genes in B. pertussis. This locus, designated bvgR, maps to a location immediately downstream of bvgAS. We have undertaken deletion and complementation studies, as well as sequence analysis, in order to identify the bvgR open reading frame and identify the cis-acting sequences required for regulated expression of bvgR. Studies utilizing transcriptional fusions of bvgR to the gene encoding alkaline phosphatase have demonstrated that bvgR is activated at the level of transcription and that this activation is dependent upon an intact bvgAS locus. C1 NIDR, OIIB, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Merkel, TJ (reprint author), NIDR, OIIB, NIH, Bldg 30,Rm 303,30 Convent Dr,MSC 4350, Bethesda, MD 20892 USA. NR 46 TC 59 Z9 63 U1 0 U2 1 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0021-9193 J9 J BACTERIOL JI J. Bacteriol. PD APR PY 1998 VL 180 IS 7 BP 1682 EP 1690 PG 9 WC Microbiology SC Microbiology GA ZE273 UT WOS:000072775500010 PM 9537363 ER PT J AU McSharry, JM Lurain, NS Drusano, GL Landay, A Manischewitz, J Nokta, M O'Gorman, M Shapiro, HM Weinberg, A Reichelderfer, P Crumpacker, C AF McSharry, JM Lurain, NS Drusano, GL Landay, A Manischewitz, J Nokta, M O'Gorman, M Shapiro, HM Weinberg, A Reichelderfer, P Crumpacker, C TI Flow cytometric determination of ganciclovir susceptibilities of human cytomegalovirus clinical isolates SO JOURNAL OF CLINICAL MICROBIOLOGY LA English DT Article ID INFECTION; RESISTANCE; FOSCARNET AB A flow cytometric assay has been developed for the measurement of susceptibilities to ganciclovir of laboratory strains and clinical isolates of human cytomegalovirus (HCMV). The assay uses fluorochrome-labeled monoclonal antibodies to HCMV immediate-early and late antigens to identify HCMV-infected cells and flow cytometry to detect and quantitate the number of antigen-positive cells. By this assay, the 50 and 90% inhibitory concentrations (IC50 and IC90, respectively) of ganciclovir for the AD169 strain of HCMV were 1.7 and 9.2 mu M, respectively, and the IC50 for the ganciclovir-resistant D6/3/1 derivative of the AD169 strain was greater than 12 mu M. The ganciclovir susceptibilities of 17 HCMV clinical isolates were also dctermined by flow cytometric analysis of the effect of ganciclovir on late-antigen synthesis in HCMV-infected cells. The average IC50 of ganciclovir for drug-sensitive HCMV clinical isolates was 3.79 mu M (+/-2.60). The plaque-reduction assay for these clinical isolates yielded an average IC50 of 2.80 mu M (+/-1.46). Comparison of the results of the flow cytometry assays with those obtained from the plaque-reduction assays demonstrated acceptable bias and precision. Flow cytometric and plaque-reduction analysis of cells infected with ganciclovir-resistant clinical isolates failed to show a reduction in the percentage of late-antigen-positive cells or PFU, even at 96 mu M ganciclovir. The flow cytometric assay for determining ganciclovir susceptibility of HCMV is quantitative, and objective, and potentially automatable, and its results are reproducible among laboratories. C1 Albany Med Coll, Dept Microbiol Mol Genet & Immunol, Albany, NY 12208 USA. Rush Presbyterian St Lukes Med Ctr, Chicago, IL 60153 USA. US FDA, Bethesda, MD 20892 USA. Univ Texas, Med Branch, Galveston, TX 77555 USA. Northwestern Univ, Childrens Mem Hosp, Chicago, IL 60614 USA. Univ Colorado, Med Ctr, Denver, CO 80262 USA. NIH, Bethesda, MD 20892 USA. Beth Israel Deaconess Med Ctr, Boston, MA 02215 USA. RP McSharry, JM (reprint author), Albany Med Coll, Dept Microbiol Mol Genet & Immunol, A-68,47 New Scotland Ave, Albany, NY 12208 USA. EM jim_mcsharry@ccgateway.amc.edu FU NIAID NIH HHS [N01-AI35172, AI30883, AI32367] NR 22 TC 21 Z9 23 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0095-1137 J9 J CLIN MICROBIOL JI J. Clin. Microbiol. PD APR PY 1998 VL 36 IS 4 BP 958 EP 964 PG 7 WC Microbiology SC Microbiology GA ZC324 UT WOS:000072565800019 PM 9542916 ER PT J AU Mahmood, I AF Mahmood, I TI Development of a limited sampling approach in pharmacokinetic studies: Experience with the antiepilepsy drug tiagabine SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article ID UPTAKE INHIBITOR; PERFORMANCE; MODEL; GABA AB A sparse sampling method is proposed to assess pharmacokinetic parameters after a single dose of the antiepilepsy drug tiagabine. Pharmacokinetic parameters obtained from two different pharmacokinetic studies were compared using sparse sampling (7 blood samples) with extensive sampling (15 to 16 blood samples). The results indicated that sparse blood samples taken at appropriate times can be used to estimate pharmacokinetic parameters as accurately as extensive blood samples. In addition, a limited sampling model (LSM) was developed using samples fram 10 subjects at two time points (6 and 8 hours). The model was validated in 40 subjects and provided good population mean estimates of area under the concentration-time curve (AUC) and maximum concentration (C-max). The sparse sampling method described here can be used to assess pharmacokinetic parameters in drug development provided a prior knowledge of the pharmacokinetics of a drug has been obtained front extensive sampling. Further, the LSM described here may be useful in estimating AUC and C-max of tiagabine using two samples in clinical settings. The LSM approach described here can also be used to estimate AUC and C-max of a drug in preclinical toxicokinetic studies without detailed pharmacokinetic studies. (C)1998 The American College of Clinical Pharmacology. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, CDER, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, CDER, Room 479,Woodmont Off Ctr 2,1451 Rockville Pike, Rockville, MD 20852 USA. NR 28 TC 6 Z9 7 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD APR PY 1998 VL 38 IS 4 BP 324 EP 330 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZK356 UT WOS:000073312200004 PM 9590459 ER PT J AU Marti, G Johnsen, H Sutherland, R Serke, S AF Marti, G Johnsen, H Sutherland, R Serke, S TI A convergence of methods for a worldwide standard for CD34+ cell enumeration SO JOURNAL OF HEMATOTHERAPY LA English DT Letter ID FLOW CYTOMETRIC ANALYSIS; BLOOD C1 US FDA, Ctr Biol Evaluat & Res, Div Gene & Cell Therapies, Rockville, MD 20857 USA. Herlev Hosp, Stem Cell Lab, Dept Hematol, DK-2730 Herlev, Denmark. Toronto Gen Hosp, Toronto, ON, Canada. Univ Berlin, Virchow Klinikkum, Berlin, Germany. RP Marti, G (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Gene & Cell Therapies, Rockville, MD 20857 USA. NR 22 TC 18 Z9 19 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1061-6128 J9 J HEMATOTHER JI J. Hematother. PD APR PY 1998 VL 7 IS 2 BP 105 EP 109 DI 10.1089/scd.1.1998.7.105 PG 5 WC Hematology; Medicine, Research & Experimental; Transplantation SC Hematology; Research & Experimental Medicine; Transplantation GA ZL514 UT WOS:000073441200002 PM 9597567 ER PT J AU Jiang, SP Vacchio, MS AF Jiang, SP Vacchio, MS TI Cutting edge: Multiple mechanisms of peripheral T cell tolerance to the fetal "allograft" SO JOURNAL OF IMMUNOLOGY LA English DT Article ID EXTRATHYMIC TOLERANCE; CLONAL ELIMINATION; INDUCED APOPTOSIS; TRANSGENIC MICE; FAS LIGAND; EXPRESSION; DELETION; ANTIGEN; ANERGY; LYMPHOCYTES AB The fetus represents a foreign entity to the maternal immune system, yet this "natural" allograft is not normally rejected, This unique situation provides a physiologic system to evaluate peripheral tolerance in which the maternal immune system is challenged with relatively rare Ags not previously encountered in the thymus, Using H-Y-specific TCR transgenic mice, we demonstrate that T cells specific for fetal Ags decrease in an Ag-specific manner during pregnancy and remain low postpartum, the result of an encounter with fetal cells expressing the appropriate MHC/peptide complexes, The finding that placental trophoblasts can induce Fas-mediated death of T cells is consistent with peripheral clonal deletion as one mechanism of tolerance. The remaining clonotypic T cells are unresponsive to antigenic stimulation, although neither TCR nor coreceptor is down-regulated. Our study demonstrates that specific recognition of fetal allogeneic Ags by maternal T cells results in tolerance induction of reactive T cells via multiple mechanisms. C1 US FDA, Immunol Lab, Div Hematol Prod, Ctr Biol Evaluat & Review, Bethesda, MD 20014 USA. RP Vacchio, MS (reprint author), US FDA, Div Hematol Prod, CBER, 1401 Rockville Pike,Suite 200N HFM 538, Rockville, MD 20852 USA. NR 30 TC 146 Z9 154 U1 0 U2 1 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1998 VL 160 IS 7 BP 3086 EP 3090 PG 5 WC Immunology SC Immunology GA ZD573 UT WOS:000072700100002 PM 9531261 ER PT J AU Goldstein, JS Chen, T Brunswick, M Mostowsky, H Kozlowski, S AF Goldstein, JS Chen, T Brunswick, M Mostowsky, H Kozlowski, S TI Purified MHC class I and peptide complexes activate naive CD8(+) T cells independently of the CD28/B7 and LFA-1/ICAM-1 costimulatory interactions SO JOURNAL OF IMMUNOLOGY LA English DT Article ID LYMPHOCYTES-T; TRANSGENIC MICE; INTERLEUKIN-2 PRODUCTION; IMMUNE-RESPONSE; VIRUS-INFECTION; CLONAL ANERGY; B-CELLS; RECEPTOR; ANTIGEN; REQUIREMENTS AB T cells play a central role in the initiation, maintenance, and regulation of the immune response. Effector responses of T cells are controlled by complex combinations of lymphokines and adhesion/costimulatory molecule signals. To isolate the effects of specific adhesion/costimulatory molecules and to define the minimal molecular requirements of naive CD8(+) T cell activation, we have developed an APC-free system for stimulation of naive CD8(+) T cells. In this report, we demonstrate that immobilized MHC class I-peptide complexes can activate naive CD8(+) T cells from TCR transgenic mice at low cell densities. The CD8(+) T cells were stimulated to proliferate and secrete IL-2 independently of the molecular interactions between CD28/B7.1-B7.2 or LFA-1/ICAM-1 surface receptors. Previous reports have shown that CD28 ligation is necessary for late T cell survival of APC-stimulated naive CD8(+) T cells. Our data suggest that under certain specific conditions of high intensity T cell signaling, early activation and late cell proliferation can occur independently of APC-derived costimulatory signals. C1 US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Cell & Gene Therapy, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Goldstein, JS (reprint author), US FDA, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, 8800 Rockville Pike,Bldg 29B-3NN13,HFM-561, Bethesda, MD 20892 USA. EM goldstein@a1.cber.fda.gov NR 64 TC 26 Z9 26 U1 0 U2 2 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD APR 1 PY 1998 VL 160 IS 7 BP 3180 EP 3187 PG 8 WC Immunology SC Immunology GA ZD573 UT WOS:000072700100014 PM 9531273 ER PT J AU Li, ZM Kelley, C Collins, F Rouse, D Morris, S AF Li, ZM Kelley, C Collins, F Rouse, D Morris, S TI Expression of katG in Mycobacterium tuberculosis is associated with its growth and persistence in mice and guinea pigs SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 97th Annual Meeting of the American-Society-for-Microbiology CY MAY 02-08, 1997 CL MIAMI, FLORIDA SP Amer Soc Microbiol ID CATALASE-PEROXIDASE GENE; DRUG-RESISTANT TUBERCULOSIS; ISONIAZID RESISTANCE; MOLECULAR MECHANISMS; STRAINS; MUTATIONS; VIRULENCE AB The molecular mechanisms associated with the pathogenesis of tuberculosis are not well understood. The present study evaluated the role of catalase-peroxidase as a potential virulence factor for Mycobacterium tuberculosis. Growth and persistence of M. tuberculosis H37Rv in intravenously infected BALB/c mice were compared with katG-deleted, isoniazid-resistant M. tuberculosis H37RvINH(R). Transformation of M. tuberculosis H37Rv (TBkatG) or Mycobacterium intracellulare (MACkatG) genes into M. tuberculosis H37RvINH(R) restored its catalase-peroxidase activities and the ability of the recombinants to persist in spleens of mice and guinea pigs. Transformation with the TBkatG gene with the codon 463 R-->L mutation also restored catalase-peroxidase activity and enhanced persistence. However, transformants with the codon 275 T-->P mutant expressed low levels of enzymatic activity and failed to persist in guinea pig spleen, although they did survive in mouse tissues. These results indicate that KatG contributes to the ability of M. tuberculosis to grow and survive within the infected host tissues. C1 US FDA, CDER, Lab Mycobacteria, Rockville, MD 20857 USA. RP Morris, S (reprint author), US FDA, CDER, Lab Mycobacteria, Bldg 29,Room 416,1401 Rockville Pike, Rockville, MD 20857 USA. NR 33 TC 121 Z9 128 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD APR PY 1998 VL 177 IS 4 BP 1030 EP 1035 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZD747 UT WOS:000072719400026 PM 9534978 ER PT J AU Asada, H Klaus-Kovtun, V Golding, H Katz, SI Blauvelt, A AF Asada, H Klaus-Kovtun, V Golding, H Katz, SI Blauvelt, A TI Human herpesvirus 6 (HHV6) infects dendritic cells (DC) and suppresses HIV replication in co-infected cultures. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 US FDA, Div Viral Prod, Bethesda, MD 20014 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 485 EP 485 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200108 ER PT J AU Zoeteweij, JP Zaitseva, M Klaus-Koytun, V Golding, H Blauvelt, A AF Zoeteweij, JP Zaitseva, M Klaus-Koytun, V Golding, H Blauvelt, A TI Cytokines regulate the HIV co-receptor CXCR4 on cultured human Langerhans cells (cLC). SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 US FDA, Div Viral Prod, Bethesda, MD 20014 USA. NCI, Dermatol Branch, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 498 EP 498 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738200187 ER PT J AU Godar, DE Thomas, DP Lucas, AD AF Godar, DE Thomas, DP Lucas, AD TI Ultraviolet-A1 radiation induces immediate preprogrammed apoptosis of transformed, but not normal, human lymphocytes. SO JOURNAL OF INVESTIGATIVE DERMATOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0022-202X J9 J INVEST DERMATOL JI J. Invest. Dermatol. PD APR PY 1998 VL 110 IS 4 BP 691 EP 691 PG 1 WC Dermatology SC Dermatology GA ZD914 UT WOS:000072738201345 ER PT J AU Zhang, XH Shinzawa, H Shao, L Ishibashi, M Jiang, QH Saito, K Misawa, H Togashi, H Takahashi, T AF Zhang, XH Shinzawa, H Shao, L Ishibashi, M Jiang, QH Saito, K Misawa, H Togashi, H Takahashi, T TI Epidemiological study and genetic analysis of GB virus C infection in general population from an area endemic for hepatitis C SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE GBV-C; HGV; HCV; epidemiology; phylogenetic tree ID POLYMERASE CHAIN-REACTION; GENOME; ASSOCIATION; SEQUENCES; CLONING; PCR AB The aim of this work was to study the prevalence, potential risk factors, clinical and laboratory features of GB virus C (GBV-C) infection in general population from an area endemic for hepatitis C. A reverse transcriptase-polymerase chain reaction (RT-PCR) for detection of GBV-C RNA was used to examine the prevalence of GBV-C RNA in both hepatitis C virus (HCV) endemic (R town) and nonendemic areas (M town) in Yamagata prefecture, Japan. In R town, GBV-C RNA was detected in 23 (2.9%) out of the 800 residents, whereas anti-HCV and HCV-RNA were found in 226 (28.3%) and 163 (20.4%), respectively. The prevalence of GBV-C RNA in R town (2.9%) was higher than that in M town (1.0%), although the difference was not statistically significant. The individuals with anti-HCV had significantly higher frequency of active GBV-C infection than those without anti-HCV in both towns. No evidence indicating that GBV-C infection affected the severity of hepatitis C was obtained. The multivariate analysis revealed that the young anti-HCV positive individuals with a history of blood transfusion had higher incidence of active GBV-C infection. The phylogenetic analysis showed that the GBV-C isolates from both R and M towns were divided into two separate branch groups designated HG and Asia GB groups. (C) 1998 Wiley-Liss, Inc. C1 Yamagata Univ, Sch Med, Dept Internal Med 2, Yamagata 9909598, Japan. US FDA, CDER, Div Biometr 4, Rockville, MD 20857 USA. RP Shinzawa, H (reprint author), Yamagata Univ, Sch Med, Dept Internal Med 2, Yamagata 9909598, Japan. NR 28 TC 3 Z9 3 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD APR PY 1998 VL 54 IS 4 BP 237 EP 242 PG 6 WC Virology SC Virology GA ZE792 UT WOS:000072831400001 PM 9557288 ER PT J AU Gil, C Ruiz-Meana, M Alava, M Yavin, E Aguilera, J AF Gil, C Ruiz-Meana, M Alava, M Yavin, E Aguilera, J TI Tetanus toxin enhances protein kinase C activity translocation and increases polyphosphoinositide hydrolysis in rat cerebral cortex preparations SO JOURNAL OF NEUROCHEMISTRY LA English DT Article DE tetanus toxin; protein kinase C; phorbol ester; neuronal cultures; polyphosphoinositide hydrolysis; phospholipase C; synaptosomes ID DOWN-REGULATION; NEUROTRANSMITTER RELEASE; BOTULINUM NEUROTOXIN; SYNAPSIN-I; BRAIN; CALPAIN; ACTIVATION; SYNAPTOBREVIN; ASSOCIATION; INHIBITION AB Tetanus toxin (TeTx) has been recently demonstrated to be a Zn2+-dependent endopeptidase that cleaves synaptobrevin, a protein in part responsible for neurotransmitter release. Nevertheless, certain aspects of TeTx action, for example, the causal relationship between TeTx and protein kinase C (PKC; EC 2.7.1.37) activity cannot be explained by this cleavage alone, In the present study, primary neurons from fetal rat brain, synaptosomes, and whole slices have been used to examine this issue. Low doses of TeTx (less than or equal to 10(-8) M) caused PKC activity translocation in a manner similar to that produced by 12-O-tetradecanoylphorbol 13-acetate (TPA). TPA (less than or equal to 10(-7) M) caused sustained PKC activity translocation, whereas TeTx produced translocation followed by relocation, depending on the dose and time of exposure. Immunoidentification with a monoclonal antibody recognizing both alpha and beta isoforms revealed that TeTx induced moderate losses of PKC in the cytosolic fraction, without a comparable increase in the particulate fraction, Although moderate losses of activity were also noticed in the cytosolic fraction, the inconsistency with respect to activity translocation may be explained by translocation of additional PKC isoforms that are not identified by the antibody, Comparable levels of water-soluble inositol phosphate-labeled intermediates were obtained after treatment of cerebral cells and/or cortical brain slices with TeTx. Significant increases of 19 and 114% in the watersoluble myo-[2-H-3]inositol-labeled inositol phosphate metabolites were found in cerebral cell culture and brain slices, respectively, after treatment with 10(-8) M TeTx, TeTx (10(-8) M) increased to the same degree the watersoluble inositol phosphate levels as did serotonin (10(-5) M) or carbachol (10(-6) M). It is suggested that part of the signaling cascade of TeTx consists of a component involving inositol phospholipid hydrolysis, which is associated with PKC activity translocation. C1 Univ Autonoma Barcelona, Fac Med, Dept Bioquim & Biol Mol, Bellaterra 08193, Spain. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Weizmann Inst Sci, Dept Neurobiol, IL-76100 Rehovot, Israel. RP Aguilera, J (reprint author), Univ Autonoma Barcelona, Fac Med, Dept Bioquim & Biol Mol, Bellaterra 08193, Spain. RI Gil, Carles/C-7016-2008; Aguilera, Jose/N-6519-2015 OI Aguilera, Jose/0000-0002-9906-8034 NR 46 TC 17 Z9 17 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PD APR PY 1998 VL 70 IS 4 BP 1636 EP 1643 PG 8 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA ZC308 UT WOS:000072564100035 PM 9523581 ER PT J AU Adams, AM Hoberg, EP McAlpine, DF Clayden, SL AF Adams, AM Hoberg, EP McAlpine, DF Clayden, SL TI Occurrence and morphological comparisons of Campula oblonga (Digenea : Campulidae), including a report from an atypical host, the thresher shark, Alopias vulpinus SO JOURNAL OF PARASITOLOGY LA English DT Article AB New host records for Campula oblonga Cobbold, 1858 from the common dolphin. Delphinus delphis L., and from the thresher shark, Alopias vulpinus (Bonnaterre), are reported herein. Campulids have not been reported previously from a host that was not a marine mammal. The excellent condition and small size of the gravid specimen and the diet and natural history of the thresher shark lead us to conclude that the digene was acquired from the consumption of infected fish. Specimens of C. oblonga from these 2 hosts and from harbor porpoises, Phocoena phocoena (L.), and from Dall's porpoises, Phocoenoides dalli (True). are compared, and a wide variation in ranges and values for characters is noted. The synonymy of Campula folium Ozaki. 1935 with C. oblonga is further supported by the apparent effect of the host on the size of the trematodes. Due to the degree of variation in measurements and the numerous factors that may impact these values, we recommend the use of qualitative morphologic characters for the identification of C. oblonga. C1 US FDA, Seafood Prod Res Ctr, Bothell, WA 98041 USA. USDA ARS, Beltsville, MD 20705 USA. New Brunswick Museum, St John, NB E2K 1E5, Canada. Grand Manan Whale & Seabird Res Stn, N Head, Grand Manan E0G 2M0, Canada. RP Adams, AM (reprint author), US FDA, Seafood Prod Res Ctr, POB 3012, Bothell, WA 98041 USA. NR 24 TC 6 Z9 6 U1 0 U2 2 PU AMER SOC PARASITOLOGISTS PI LAWRENCE PA 810 EAST 10TH STREET, LAWRENCE, KS 66044 USA SN 0022-3395 J9 J PARASITOL JI J. Parasitol. PD APR PY 1998 VL 84 IS 2 BP 435 EP 438 DI 10.2307/3284507 PG 4 WC Parasitology SC Parasitology GA ZJ986 UT WOS:000073273600034 PM 9576521 ER PT J AU Mahmood, I AF Mahmood, I TI Integration of in vitro data and brain weight in allometric scaling to predict clearance in humans: Some suggestions SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID INTRINSIC CLEARANCE; PARAMETERS; DRUGS C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off Ctr 2, HFD-860,1451 Rockville Pike, Rockville, MD 20852 USA. NR 11 TC 13 Z9 14 U1 0 U2 0 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD APR PY 1998 VL 87 IS 4 BP 527 EP 529 DI 10.1021/js9702628 PG 3 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA ZF384 UT WOS:000072892100021 PM 9548910 ER PT J AU Allen, LB Siitonen, PH Thompson, HC AF Allen, LB Siitonen, PH Thompson, HC TI Determination of copper, lead, and nickel in edible oils by plasma and furnace atomic spectroscopies SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE atomic absorption spectrometry; edible oils; inductively coupled plasma atomic emission spectrometry; microwave dissolution; trace metals ID ABSORPTION SPECTROSCOPY; VEGETABLE-OILS; SPECTROMETRY; FATS AB An atmospheric pressure microwave digestion procedure is described for the determination of copper, lead, and nickel in edible oils. The digestion procedure is compatible with either inductively coupled plasma atomic emission spectrometry (ICP-AES) or graphite furnace atomic absorption spectrometry (GFAAS). Instrument conditions are specified to allow the simultaneous determination of all three metals for each sample introduction. Method detection limits were element-specific but equal to or less than 50 ng/g with ICP-AES and 30 ng/g with GFAAS. Results from spike and recovery experiments at levels of 50, 100, and 200 ng/g are reported for corn and soybean oil. For soybean oil, recoveries at 100 ng/g were 90, 100, and 106%, respectively, for copper, lead, and nickel with ICP-AES, and 89, 106, and 96%, respectively, with GFAAS. Recoveries for corn oil spiked at 100 ng/g were 93, 95, and 103%, respectively, for copper, lead, and nickel with ICP-AES, and 90, 117, and 100%, respectively, with GFAAS. Day-to-day reproducibility was demonstrated by similar method recoveries and reproducibilities in independent analysis of two canola oil sample sets that were spiked at 100 ng/g. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Allen, LB (reprint author), Univ Wisconsin Parkside, Dept Chem, 900 Wood Rd, Kenosha, WI 53141 USA. NR 10 TC 41 Z9 42 U1 3 U2 31 PU AMER OIL CHEMISTS SOC 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 APR PY 1998 VL 75 IS 4 BP 477 EP 481 DI 10.1007/s11746-998-0250-1 PG 5 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA ZK153 UT WOS:000073290700006 ER PT J AU Steele, JH Blackwell, MJ Andres, CR AF Steele, JH Blackwell, MJ Andres, CR TI The 50th anniversary of the Veterinary Medical Corps Officers of the US Public Health Service SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material C1 US PHS, Vet Category, Washington, DC 20201 USA. US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Andres, CR (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20855 USA. NR 0 TC 4 Z9 4 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 APR 1 PY 1998 VL 212 IS 7 BP 952 EP 954 PG 3 WC Veterinary Sciences SC Veterinary Sciences GA ZF097 UT WOS:000072862300016 PM 9565474 ER PT J AU Oeller, DS AF Oeller, DS TI Veterinary careers in the US Public Health Service Commissioned Corps SO JOURNAL OF THE AMERICAN VETERINARY MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, CVM, Rockville, MD 20855 USA. RP Oeller, DS (reprint author), US FDA, CVM, HFV-133,7500 Standish Pl, Rockville, MD 20855 USA. NR 0 TC 1 Z9 1 U1 1 U2 1 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 1998 VL 212 IS 7 BP 962 EP 965 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA ZF097 UT WOS:000072862300018 PM 9540864 ER PT J AU Wilson, CA Wong, S Muller, J Davidson, CE Rose, TM Burd, P AF Wilson, CA Wong, S Muller, J Davidson, CE Rose, TM Burd, P TI Type C retrovirus released from porcine primary peripheral blood mononuclear cells infects human cells SO JOURNAL OF VIROLOGY LA English DT Article ID MURINE LEUKEMIA-VIRUS; GENE-TRANSFER; COMPLEX AB As part of the evaluation of porcine cells, tissues, and organs intended for transplantation into humans, we investigated the conditions required to induce expression and release of porcine endogenous retrovirus (PoEV) from primary cells, Pigs contain endogenous retroviral sequences encoding infectious retrovirus, yet little is known about the conditions required to activate the expression and release of PoEV from primary cells, We show here that mitogenic activation of peripheral blood mononuclear cells (PBMC) isolated from the National Institutes of Health (NIH) miniature pig and the Yucatan pig resulted in the activation and release of an infectious type C retrovirus, Coculture of activated porcine PBMC with pig or human cell lines resulted in the transfer and expression of PoEV-specific sequences and the establishment of a productive infection. Sequence comparison of portions of the PoEV pol gene expressed in pig cell lines productively infected with virus derived from NIH miniature pig and Yucatan pig PBMC revealed marked similarity, suggesting that one or a few loci may be capable of being activated to yield an infectious virus. These findings demonstrate that the presence of endogenous viruses in source animals needs to be carefully considered when the infectious disease potential of xenotransplantation is being assessed. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD USA. US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Bethesda, MD USA. Univ Washington, Sch Publ Hlth & Community Med, Dept Pathobiol, Seattle, WA 98195 USA. RP Wilson, CA (reprint author), Bldg 29B,Room 2E12,8800 Rockville Pike, Bethesda, MD 20892 USA. NR 27 TC 308 Z9 322 U1 0 U2 6 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0022-538X J9 J VIROL JI J. Virol. PD APR PY 1998 VL 72 IS 4 BP 3082 EP 3087 PG 6 WC Virology SC Virology GA ZC506 UT WOS:000072586900061 PM 9525633 ER PT J AU Gaines, AR Varricchio, F AF Gaines, AR Varricchio, F TI Interferon beta-1b injection site reactions and necroses SO MULTIPLE SCLEROSIS LA English DT Article DE interferon beta-1b adverse events AB We conducted a comprehensive review of selected adverse event reports that were submitted to the Food and Drug Administration (FDA) for interferon beta-1b during the first 30 months following licensure. The adverse events reviewed were injection site reactions, injection site necroses, and non-injection site necroses. These adverse events were selected because of the relative frequency of injection site reactions and because of the severity and sequelae of certain injection site and non-injection site necroses. Our review enabled us to characterize the clinical presentation and the treatment received, which were not described in the package insert or by the IFNB (interferon beta-1b) Multiple Sclerosis Study Group Publication. The time of onset of the adverse events ranged from I - 29 months after initiation of interferon beta-1b treatment, with a mean of 1 month. In general, the more clinically significant adverse events (i.e., injection site necrosis and non-injection site necrosis) developed more slowly than the injection site reactions. Greater than 85% of the adverse events presented with one or two signs/symptoms, although the number of signs/symptoms ranged from I - 8. No predominance of treatments for the adverse events was observed. The most striking finding was that the overall sex ratio, which could be due to reporting artifacts, was 8.1:1 female:male. C1 US FDA, Div Biostat & Epidemiol, Off Estab Licensing & Prod Surveillance, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Gaines, AR (reprint author), US FDA, Div Biostat & Epidemiol, Off Estab Licensing & Prod Surveillance, Ctr Biol Evaluat & Res, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 7 TC 29 Z9 31 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1352-4585 J9 MULT SCLER JI Mult. Scler. PD APR PY 1998 VL 4 IS 2 BP 70 EP 73 PG 4 WC Clinical Neurology; Neurosciences SC Neurosciences & Neurology GA ZJ614 UT WOS:000073234400005 PM 9599336 ER PT J AU Heneine, W Switzer, WM Sandstrom, P Brown, J Vedapuri, S Schable, CA Khan, AS Lerche, NW Schweizer, M Neumann-Haefelin, D Chapman, LE Folks, TM AF Heneine, W Switzer, WM Sandstrom, P Brown, J Vedapuri, S Schable, CA Khan, AS Lerche, NW Schweizer, M Neumann-Haefelin, D Chapman, LE Folks, TM TI Identification of a human population infected with simian foamy viruses SO NATURE MEDICINE LA English DT Article ID T-LYMPHOTROPIC VIRUS; IMMUNODEFICIENCY-VIRUS; REVERSE-TRANSCRIPTASE; PREVALENCE; RETROVIRUS; ANTIBODY; MONKEYS; COLONY AB Studying the transmission of simian retroviruses to humans can help define the importance of these infections to public health. We identified a substantial prevalence (4/231, 1.8%) of infection with simian foamy viruses (SFV) among humans occupationally exposed to nonhuman primates. Evidence of SFV infection included seropositivity, proviral DNA detection and isolation of foamy virus. The infecting SFV originated from an African green monkey (one person) and baboons (three people), These infections have not as yet resulted in either disease or sexual transmission, and may represent benign endpoint infections. C1 Ctr Dis Control & Prevent, HIV & Retrovirol Branch, Atlanta, GA 30333 USA. Ctr Dis Control & Prevent, Immunol & Diagnost Branch, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. US FDA, Ctr Biol Evaluat & Res, Lab Retrovirus Res, Bethesda, MD 20892 USA. Univ Calif Lawrence Livermore Natl Lab, Calif Reg Primate Res Ctr, Simian Retrovirus Lab, Livermore, CA 95616 USA. Univ Freiburg, Dept Virol, D-79104 Freiburg, Germany. RP Heneine, W (reprint author), Ctr Dis Control & Prevent, HIV & Retrovirol Branch, Atlanta, GA 30333 USA. NR 32 TC 161 Z9 163 U1 0 U2 6 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1078-8956 J9 NAT MED JI Nat. Med. PD APR PY 1998 VL 4 IS 4 BP 403 EP 407 DI 10.1038/nm0498-403 PG 5 WC Biochemistry & Molecular Biology; Cell Biology; Medicine, Research & Experimental SC Biochemistry & Molecular Biology; Cell Biology; Research & Experimental Medicine GA ZF531 UT WOS:000072906800033 PM 9546784 ER PT J AU Furuta, RA Wild, CT Weng, YK Weiss, CD AF Furuta, RA Wild, CT Weng, YK Weiss, CD TI Capture of an early fusion-active conformation of HIV-1 gp41 SO NATURE STRUCTURAL BIOLOGY LA English DT Article ID HUMAN-IMMUNODEFICIENCY-VIRUS; SYNTHETIC PEPTIDE; POTENT INHIBITORS; TRANSMEMBRANE GLYCOPROTEIN; VIRAL FUSION; CELL FUSION; INFECTION; DOMAIN; ANTIBODIES; PROTEIN AB Using an inhibitory synthetic peptide (DP-178) from HIV-1 gp31, we have trapped HIV-1 envelope glycoprotein (Env) undergoing conformational changes during virus entry. Our data show that DP-178 binds gp41 and inhibits Env-mediated membrane fusion after gp 120 interacts with cellular receptors, indicating that conformational changes involving the coiled coil domain of gp41 are required for entry. Capture of this fusion-active conformation of Env provides insights into the early events leading to Env-mediated membrane fusion. C1 US FDA, Off Vaccines, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Biotech Res Labs, Gaithersburg, MD 20877 USA. RP Weiss, CD (reprint author), US FDA, Off Vaccines, Ctr Biol Evaluat & Res, Bldg 29,Room 532,HFM-413,291 Lincoln Dr, Bethesda, MD 20892 USA. RI Weiss, Carol/F-6438-2011 OI Weiss, Carol/0000-0002-9965-1289 NR 28 TC 420 Z9 425 U1 1 U2 19 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 1072-8368 J9 NAT STRUCT BIOL JI Nat. Struct. Biol. PD APR PY 1998 VL 5 IS 4 BP 276 EP 279 DI 10.1038/nsb0498-276 PG 4 WC Biochemistry & Molecular Biology; Biophysics; Cell Biology SC Biochemistry & Molecular Biology; Biophysics; Cell Biology GA ZF530 UT WOS:000072906700012 PM 9546217 ER PT J AU Berlin, E Kim, CS McClure, D Banks, MA Peters, RC AF Berlin, E Kim, CS McClure, D Banks, MA Peters, RC TI Brain and heart membrane fatty acid composition in miniature swine fed diets containing corn and menhaden oils SO NUTRITION RESEARCH LA English DT Article; Proceedings Paper CT 16th International Congress of Nutrition CY JUL 27-AUG 01, 1997 CL MONTREAL, CANADA DE n-3 fatty acids; synaptosomes; n-6 fatty acids; membrane fluidity; fish oil; docosahexaenoate ID VITAMIN-E; FLUORESCENCE POLARIZATION; FISH-OIL; N-3; LIVER; FLUIDITY; PLASMA; CELLS; RATS; LIPIDS AB Thirty-six female minipigs, from 4.7-10.6 years old, were fed corn oil (CO) and/or menhaden oil (MO) in diets containing 0, 0.75, or 15% MO and sufficient CO to provide 15% total oil for 6 months. Half the animals were made hypercholesterolemic by feeding them a 13% lard, 2% cholesterol diet for 2 months prior to the experimental feeding period. Samples were taken from the same location in each animal from forebrain, caudate nucleus, cerebellum, and heart to isolate brain synaptosomes and heart plasma membranes. Pretreatment of the minipigs with cholesterol had no effect on the fatty acid composition of the fractions isolated and their membrane fluidity. Despite MO feeding, the long chain n-3 fatty acids were low in the heart plasma membranes compared to heart tissue homogenates from the same animals. Minipigs fed 15% MO showed significant increases in synaptosomal eicosapentaenoate (EPA) and docosapentaenoate (DPA). Docosahexaenoate (DHA) was incorporated into synaptosomes in animals fed 0.75% MO, at concentrations significantly higher than in the CO-fed pigs. Rigs fed 15% MO showed significantly lower brain DHA than those fed CO. The synaptosomal data for the pigs fed the various diets suggest that metabolic synthesis from linolenate, 18:3(n-3), may be a more important source bf brain DHA than diet, but that dietary n-6/n-3 ratios and levels of 18:3(n-3), EPA, DPA and DHA may require careful attention. The fatty acid changes did not affect fluidity determined by fluorescence anisotropy of diphenylhexatriene or its polar derivatives. Published by Elsevier Science Inc. C1 USDA ARS, Beltsville Human Nutr Res Ctr, Metab & Nutr Interact Lab, Beltsville, MD 20705 USA. US Dept HHS, Ctr Food Safety & Appl Nutr, Div Toxicol Res, US FDA, Laurel, MD 20708 USA. RP Peters, RC (reprint author), USDA ARS, Beltsville Human Nutr Res Ctr, Metab & Nutr Interact Lab, Bldg 307,Rm 323,BARC-E,10300 Baltimore Ave, Beltsville, MD 20705 USA. NR 41 TC 3 Z9 3 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0271-5317 J9 NUTR RES JI Nutr. Res. PD APR PY 1998 VL 18 IS 4 BP 751 EP 765 DI 10.1016/S0271-5317(98)00061-X PG 15 WC Nutrition & Dietetics SC Nutrition & Dietetics GA ZH278 UT WOS:000073091200018 ER PT J AU Nakhasi, HL Pogue, GP Duncan, RC Joshi, M Atreya, CD Lee, NS Dwyer, DM AF Nakhasi, HL Pogue, GP Duncan, RC Joshi, M Atreya, CD Lee, NS Dwyer, DM TI Implications of calreticulin function in parasite biology SO PARASITOLOGY TODAY LA English DT Article ID CELL-SURFACE CALRETICULIN; CALCIUM-BINDING PROTEIN; MOLECULAR CHAPERONE; LEISHMANIA; ANTIGEN; LECTIN; GENE; CA2+; OVEREXPRESSION; AUTOANTIGEN AB Calreticulin (CR) is it Ca2+-binding, multifunctional protein. The amazing array of CX-associated functions range from intracellular activities in secondary messenger release, protein folding and the modulation of gene expression to potential interactions with host receptors and signaling machinery and recognition by the host immune system. The multifunctional nature of CA may impact upon the ability of cells to recognize extracellular stimuli and coordinate appropriate responses. Identification of CX isolated from parasites and the conservation of its functions suggests that investigations into the contributions of CA to various aspects of parasite biology should be undertaken because it may reveal information regarding parasite interaction with the host and how the parasite may modulate its response to the host. C1 US FDA, Sect Viral Pathogenesis & Adverse React, Div Viral Prod, OVRR,CBER, Bethesda, MD 20892 USA. NIAID, Cell Biol Sect, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. Biosource Technol, Vacaville, CA 95688 USA. RP Nakhasi, HL (reprint author), US FDA, Sect Viral Pathogenesis & Adverse React, Div Viral Prod, OVRR,CBER, Bethesda, MD 20892 USA. RI Duncan, Robert/I-8168-2015 OI Duncan, Robert/0000-0001-8409-2501 NR 32 TC 33 Z9 36 U1 0 U2 1 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0169-4758 J9 PARASITOL TODAY JI Parasitol. Today PD APR PY 1998 VL 14 IS 4 BP 157 EP 160 DI 10.1016/S0169-4758(97)01180-0 PG 4 WC Parasitology SC Parasitology GA ZD176 UT WOS:000072659000011 PM 17040734 ER PT J AU Page, WF Braun, MM Caporaso, NE AF Page, WF Braun, MM Caporaso, NE TI Twinning, cancer, and genetics SO LANCET LA English DT Letter C1 Natl Acad Sci, Inst Med, Med Follow Up Agcy, Washington, DC 20418 USA. NCI, Bethesda, MD 20892 USA. US FDA, Rockville, MD 20857 USA. RP Page, WF (reprint author), Natl Acad Sci, Inst Med, Med Follow Up Agcy, Washington, DC 20418 USA. NR 5 TC 0 Z9 0 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0140-6736 EI 1474-547X J9 LANCET JI Lancet PD MAR 21 PY 1998 VL 351 IS 9106 BP 910 EP 911 DI 10.1016/S0140-6736(05)70328-7 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZD047 UT WOS:000072645500061 PM 9525399 ER PT J AU Cooney, CA Kodell, RL Moore, SR Wolff, GL AF Cooney, CA Kodell, RL Moore, SR Wolff, GL TI Maternal dietary methyl supplements affect epigenetically regulated, visible expression of the A(vy) gene in viable yellow mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 3686 BP A634 EP A634 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500069 ER PT J AU DeBell, KE Stoica, B DiBaldassarre, A Miscia, S Graham, L Rellahan, B Kurosaki, T Bonvini, E AF DeBell, KE Stoica, B DiBaldassarre, A Miscia, S Graham, L Rellahan, B Kurosaki, T Bonvini, E TI Role of the SRC homology 2 (SH2) domains of phospholipase C gamma 1 (PLC gamma 1) in coupling PLC gamma 1 to the antigen receptor of T and B lymphocytes SO FASEB JOURNAL LA English DT Meeting Abstract C1 Kansai Univ, Suita, Osaka, Japan. Univ Chieti, Chieti, Italy. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RI STOICA, BOGDAN/H-9782-2013 OI STOICA, BOGDAN/0000-0002-2501-6434 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5436 BP A939 EP A939 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501819 ER PT J AU Duarte, CG Zhang, J Ellis, S AF Duarte, CG Zhang, J Ellis, S TI Effects on systolic blood pressure (SBP) and renal pathology (RP) of a radiocontrast agent (RC) and mannitol (M) in aging SHR. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4445 BP A767 EP A767 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500831 ER PT J AU Goldstein, J Chen, T Brunswick, M Mostowsky, H Kozlowski, S AF Goldstein, J Chen, T Brunswick, M Mostowsky, H Kozlowski, S TI Purified MHC class I and peptide complexes activate naive CD8(+) T cells independently of the CD28/B7 and LFA-1/ICAM-1 costimulatory interactions. 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 20 PY 1998 VL 12 IS 5 SU S MA 6301 BP A1089 EP A1089 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502684 ER PT J AU Graham, LJ Stoica, B DeBell, KE Bonvini, E Rellahan, BL AF Graham, LJ Stoica, B DeBell, KE Bonvini, E Rellahan, BL TI The product of the proto-oncogene, c-cbl, regulates PLC gamma 1 activation after T cell receptor engagement. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RI STOICA, BOGDAN/H-9782-2013 OI STOICA, BOGDAN/0000-0002-2501-6434 NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5428 BP A937 EP A937 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501809 ER PT J AU Schaffer, A Zan, H Cerutti, A Max, EE Casali, P AF Schaffer, A Zan, H Cerutti, A Max, EE Casali, P TI The ECS-I gamma sequence upstream of the human Ig S gamma 3 region is a functional promoter. Synergistic activation by CD40L and IL-4 via distinct cis regulatory elements SO FASEB JOURNAL LA English DT Meeting Abstract C1 Cornell Univ, Coll Med, Dept Pathol, New York, NY 10021 USA. US FDA, Bethesda, MD 20892 USA. RI Casali, Paolo/F-6579-2010 NR 0 TC 1 Z9 1 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6121 BP A1058 EP A1058 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502502 ER PT J AU Steinbrecher, A Scott, D Pak, SH Izikson, L Martin, R Jendoubi, M Brocke, S AF Steinbrecher, A Scott, D Pak, SH Izikson, L Martin, R Jendoubi, M Brocke, S TI Partial resistance to experimental autoimmunity in invariant chain deficient mice SO FASEB JOURNAL LA English DT Meeting Abstract C1 NINDS, Neuroimmunol Branch, NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 6081 BP A1051 EP A1051 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006502462 ER PT J AU Tiffany, LJ Riblet, R Stein, KE AF Tiffany, LJ Riblet, R Stein, KE TI Genetic mapping of Sr1, a mouse gene which regulates antibody diversity. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Med Biol Inst, La Jolla, CA 92037 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 5138 BP A887 EP A887 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006501521 ER PT J AU Whittaker, P Dunkel, VC Wolff, GL Bucci, TJ Kusewitt, DF Thurman, JD Warbritton, A AF Whittaker, P Dunkel, VC Wolff, GL Bucci, TJ Kusewitt, DF Thurman, JD Warbritton, A TI Influence of genome on toxic responses to dietary iron overload. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Pathol Associates Int, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 20 PY 1998 VL 12 IS 5 SU S MA 4606 BP A795 EP A795 PN 2 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HD UT WOS:000076006500992 ER PT J AU Remick, D Chancellor, K Pederson, J Zambraski, EJ Sawka, MN Wenger, CB AF Remick, D Chancellor, K Pederson, J Zambraski, EJ Sawka, MN Wenger, CB TI Hyperthermia and dehydration-related deaths associated with intentional rapid weight loss in three collegiate wrestlers - North Carolina, Wisconsin, and Michigan, November-December 1997 (Reprinted from MMWR, vol 47, pg 105-108, 1998) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID EXERCISE C1 Univ Michigan, Ann Arbor, MI 48109 USA. N Carolina Dept Hlth & Human Serv, Raleigh, NC 27611 USA. Franciscan Skemp Healthcare, La Crosse, WI 54601 USA. Rutgers State Univ, Piscataway, NJ 08854 USA. USA, Environm Med Res Inst, Natick, MA 01760 USA. CDC, Div Nutr Phys Act, Natl Ctr Chron Dis Prevent & Hlth Promot, Atlanta, GA 30333 USA. CDC, Off Regulatory Affairs, Atlanta, GA 30333 USA. CDC, Ctr Food Safety & Appl Nutr, US FDA, Atlanta, GA 30333 USA. CDC, Div Environm Hazards & Hlth Effects, Natl Ctr Environm Hlth, Atlanta, GA 30333 USA. RP Remick, D (reprint author), Univ Michigan, Ann Arbor, MI 48109 USA. NR 11 TC 38 Z9 38 U1 1 U2 6 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 18 PY 1998 VL 279 IS 11 BP 824 EP 825 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA ZA943 UT WOS:000072417600010 ER PT J AU Agranovich, I Scott, D Golding, B AF Agranovich, I Scott, D Golding, B TI BA-induced alteration of costimulatory pathway for murine T-cells in vivo includes IL-12 independent component. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, 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 17 PY 1998 VL 12 IS 4 SU S MA 3559 BP A613 EP A613 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403554 ER PT J AU Calvo, MS Park, YK AF Calvo, MS Park, YK TI Protein intake relative to calcium intake in the US: Implications for bone health SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, 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 17 PY 1998 VL 12 IS 4 SU S MA 3178 BP A547 EP A547 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403173 ER PT J AU Cook, KK Mitchell, GV Grundel, E Rader, JI AF Cook, KK Mitchell, GV Grundel, E Rader, JI TI Evaluation of two methods for extraction of vitamin K compounds from margarines and margarine-like products prior to reverse phase HPLC analysis. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Laurel, MD 20708 USA. US FDA, 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 17 PY 1998 VL 12 IS 4 SU S MA 3018 BP A519 EP A519 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403013 ER PT J AU Gao, JL Lee, EJ Westphal, H Elkins, EL Murphy, PM AF Gao, JL Lee, EJ Westphal, H Elkins, EL Murphy, PM TI Impaired host defense against Listeria monocytogenes in mice lacking the high affinity N-formylpeptide receptor SO FASEB JOURNAL LA English DT Meeting Abstract C1 NIH, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3340 BP A575 EP A575 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403335 ER PT J AU Hart, PH Bonder, CS Dickenshets, HL Finlay-Jones, JJ Donnelly, RP AF Hart, PH Bonder, CS Dickenshets, HL Finlay-Jones, JJ Donnelly, RP TI gamma(c) and the control by IL-4 of human macrophage proinflammatory mediator production. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Flinders Univ S Australia, Sch Med, Bedford Pk, SA 5042, Australia. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. RI Finlay-Jones, John/C-2421-2013 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 17 PY 1998 VL 12 IS 4 SU S MA 1734 BP A298 EP A298 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401729 ER PT J AU Herman, E Zhang, J Hasinoff, B Tran, K Chadwick, D Clark, J Ferrans, V AF Herman, E Zhang, J Hasinoff, B Tran, K Chadwick, D Clark, J Ferrans, V TI Comparison of the chronic toxicity of piroxantrone (PXR), losoxantrone (LXR) and doxorubicin (DXR) in spontaneously hypertensive rats (SHR) SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Laurel, MD USA. Univ Manitoba, Winnipeg, MB, Canada. NIH, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 560 BP A96 EP A96 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400561 ER PT J AU Lee, H Gerrior, S AF Lee, H Gerrior, S TI Intakes of fat and cholesterol by consumers who drink whole or reduced-fat milks in the USA. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. USDA, Ctr Nutr Policy & Promot, Washington, DC 20036 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 17 PY 1998 VL 12 IS 4 SU S MA 1307 BP A224 EP A224 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401302 ER PT J AU Lewis, C Wright, J Yetley, E AF Lewis, C Wright, J Yetley, E TI Patterning of measures of folate status from NHANES III. SO FASEB JOURNAL LA English DT Meeting Abstract C1 Ctr Dis Control & Prevent, Hyattsville, MD 20782 USA. US FDA, 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 17 PY 1998 VL 12 IS 4 SU S MA 1328 BP A227 EP A227 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401323 ER PT J AU Mason, L Willette-Brown, J Anderson, S Gosselin, P Shores, E Love, P Ortaldo, J McVicar, D AF Mason, L Willette-Brown, J Anderson, S Gosselin, P Shores, E Love, P Ortaldo, J McVicar, D TI Characterization of an associated 16 kDa tyrosine phosphoprotein required for Ly-49D signal transduction SO FASEB JOURNAL LA English DT Meeting Abstract C1 SAIC, Intramural Res Support Program, DBS, LEI, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NICHD, LMGD, NIH, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU FEDERATION AMER SOC EXP BIOL PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3998 USA SN 0892-6638 J9 FASEB J JI Faseb J. PD MAR 17 PY 1998 VL 12 IS 4 SU S MA 3497 BP A602 EP A602 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403493 ER PT J AU Morris, P Gillam, MP Lensing, S Paule, MG AF Morris, P Gillam, MP Lensing, S Paule, MG TI Acute effects of haloperidol on operant behavior in rhesus monkey offspring exposed to cocaine inutero. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, 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 17 PY 1998 VL 12 IS 4 SU S MA 925 BP A159 EP A159 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400927 ER PT J AU Obermeyer, WR Kuzmycz, YC Warner, CR Garcia-Villanova, B Ellwood, KC AF Obermeyer, WR Kuzmycz, YC Warner, CR Garcia-Villanova, B Ellwood, KC TI A rapid technique for detection of antioxidant activity in dietary constituents. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Univ Granada, Dept Nutr & Food Sci, Granada, Spain. USDA, CSREES, Washington, DC 20250 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 17 PY 1998 VL 12 IS 4 SU S MA 3257 BP A561 EP A561 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403251 ER PT J AU Post, LO Cope, CV Farrell, DE Baker, JD Myers, MJ AF Post, LO Cope, CV Farrell, DE Baker, JD Myers, MJ TI The impact of pleural Actinobacillus pleuropneumoniae (APP) infection and dexamethasone, alone or in combination, on enrofloxacin pharmacokinetics in swine SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, CVM, Div Anim Res, 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 17 PY 1998 VL 12 IS 4 SU S MA 836 BP A143 EP A143 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006400831 ER PT J AU Scott, DE Golding, B Krieg, A Huang, LY AF Scott, DE Golding, B Krieg, A Huang, LY TI Comparative ability of bacterial DNA, LPS, and whole inactivated bacteria to induce a Th1-favoring environment. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20892 USA. Univ Iowa, Iowa City, IA 52292 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 17 PY 1998 VL 12 IS 4 SU S MA 3595 BP A619 EP A619 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006403590 ER PT J AU Varricchio, F Khan, I Jablons, D Puri, R AF Varricchio, F Khan, I Jablons, D Puri, R TI IL-4 receptor expression in solitary fibrous tumor of the pleura SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, CBER, Div Cellular & Gene Therapy, Rockville, MD 20852 USA. US FDA, CBER, Div Biostat & Epidemiol, Rockville, MD 20852 USA. UCSF, Div Thorac Surg, San Francisco, CA 94415 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 17 PY 1998 VL 12 IS 4 SU S MA 1143 BP A196 EP A196 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401141 ER PT J AU Yetley, E Johnson, C Lewis, C AF Yetley, E Johnson, C Lewis, C TI Approaches for assessing iron status: Comparisons between NHANES II and NHANES III. SO FASEB JOURNAL LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. Ctr Dis Control & Prevent, Hyattsville, MD 20782 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 17 PY 1998 VL 12 IS 4 SU S MA 1332 BP A228 EP A228 PN 1 PG 1 WC Biochemistry & Molecular Biology; Biology; Cell Biology SC Biochemistry & Molecular Biology; Life Sciences & Biomedicine - Other Topics; Cell Biology GA 121HC UT WOS:000076006401328 ER PT J AU Ambrosone, CB Freudenheim, JL Sinha, R Graham, S Marshall, JR Vena, JE Laughlin, R Nemoto, T Shields, PG AF Ambrosone, CB Freudenheim, JL Sinha, R Graham, S Marshall, JR Vena, JE Laughlin, R Nemoto, T Shields, PG TI Breast cancer risk, meat consumption and N-acetyltransferase (NAT2) genetic polymorphisms SO INTERNATIONAL JOURNAL OF CANCER LA English DT Article ID HETEROCYCLIC AMINES; FAT AB Although inconsistencies exist, some studies have shown that meat consumption is associated with breast cancer risk. Several heterocyclic amines (HAs), formed in the cooking of meats, are mammary carcinogens in laboratory models. HAs are activated by polymorphic N-acetyltransferase (NAT2) and rapid NAT2 activity may increase risk associated with HAs. We investigated whether ingestion of meat, chicken and fish, as well as particular concentrated sources of HAs, was associated with breast cancer risk, and if NAT2 genotype modified risk. Caucasian women with incident breast cancer (n = 740) and community controls (n = 810) were interviewed and administered a food frequency questionnaire. A subset of these women (n = 793) provided a blood sample. Polymerase chain reaction and restriction fragment length polymorphism analyses were used to determine NAT2 genotype. Consumption of red meats, as well as an index of concentrated sources of HAs, was not associated with increased breast cancer risk, nor did risk vary by NAT2 genotype. In post-menopausal women, higher fish consumption was inversely associated with risk (odds ratio = 0.7; 95% confidence interval, 0.4-1.0); among pre-menopausal women, there was the suggestion of inverse associations between risk and pork and chicken intake. Our results suggest that consumption of meats and other concentrated sources of HAs is not associated with increased breast cancer risk. However, due to the strong biologic plausibility for a role of some HAs in mammary carcinogenesis, and the likely measurement error in evaluation of sources of HAs in this study, further studies of these possible relationships are warranted. (C) 1998 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Mol Endocrinol, Jefferson, AR 72079 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14260 USA. NCI, Div Canc Epidemiol & Genet, Nutr Epidemiol Branch, Rockville, MD USA. Univ Arizona, Div Canc Prevent & Control, Tucson, AZ USA. NCI, Human Carcinogenesis Lab, Bethesda, MD 20892 USA. RP Ambrosone, CB (reprint author), Natl Ctr Toxicol Res, Div Mol Endocrinol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM cambrosone@nctr.fda.gov; peter_g_shields@nih.gov RI Shields, Peter/I-1644-2012; Sinha, Rashmi/G-7446-2015 OI Sinha, Rashmi/0000-0002-2466-7462 FU NCI NIH HHS [CA-62995, CA-11535, CA01633] NR 28 TC 93 Z9 93 U1 1 U2 5 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 16 PY 1998 VL 75 IS 6 BP 825 EP 830 DI 10.1002/(SICI)1097-0215(19980316)75:6<825::AID-IJC2>3.0.CO;2-X PG 6 WC Oncology SC Oncology GA ZA691 UT WOS:000072391400002 PM 9506525 ER PT J AU Kumar, A Dhawan, S Hardegen, NJ Aggarwal, BB AF Kumar, A Dhawan, S Hardegen, NJ Aggarwal, BB TI Curcumin (diferuloylmethane) inhibition of tumor necrosis factor (TNF)-mediated adhesion of monocytes to endothelial cells by suppression of cell surface expression of adhesion molecules and of nuclear factor-kappa B activation SO BIOCHEMICAL PHARMACOLOGY LA English DT Article DE curcumin; adhesion proteins; NF-kappa B; TNF; endothelial cells ID E-SELECTIN EXPRESSION; GENE-EXPRESSION; DIETARY CURCUMIN; TRANSCRIPTIONAL REGULATION; COLON CARCINOGENESIS; PROTEIN-KINASE; IMMUNE-SYSTEM; CYTOKINES; INDUCTION; ALTERS AB Recruitment of leukocytes by endothelial cells and their subsequent migration from the vasculature into the tissue play major roles in inflammation In the present study, we investigated the effect of curcumin, an antiinflammatory agent, on the adhesion of monocytes to human umbilical vein endothelial cells (EC). Treatment of EC with tumor necrosis factor (TNF) for 6 hr augmented the adhesion of monocytes to EC, and this adhesion was due to increased expression of intracellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leukocyte adhesion molecule-1 (ELAM-1). Pretreatment of EC for I hr with curcumin completely blocked their adhesion to monocytes, as well as the cell surface expression of ICAM-1, VCAM-1, and ELAM-1 in EC. Although curcumin inhibited adhesion even when administered 1 hr after TNF treatment, maximum inhibition occurred when added either 1 hr before or at the same time as TNF. As the induction of various adhesion molecules by TNF requires activation of the transcription factor NF-kappa B, the effect of curcumin on the activation of this factor in the EC was also investigated. A 30-min treatment with TNF activated NF-kappa B; the activation was inhibited in a concentration-dependent manner by pretreatment with curcumin, indicating that NF-kappa B inhibition may play a role in the suppression of expression of adhesion molecules in EC. Our results demonstrate that the antiinflammatory properties of curcumin may be attributable, in part, to inhibition of leukocyte recruitment. (C) 1998 Elsevier Science Inc. C1 Univ Texas, MD Anderson Cancer Ctr, Dept Mol Oncol, Cytokine Res Sect, Houston, TX 77030 USA. US FDA, Ctr Biol Evaluat & Res, Lab Immunochem, Div Transfus Transmitted Dis, Bethesda, MD 20892 USA. NIDR, Oral Infect & Immun Branch, NIH, Bethesda, MD 20892 USA. RP Aggarwal, BB (reprint author), Univ Texas, MD Anderson Cancer Ctr, Dept Mol Oncol, Cytokine Res Sect, Houston, TX 77030 USA. RI Aggarwal, Bharat/G-3388-2013 NR 53 TC 161 Z9 171 U1 1 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0006-2952 J9 BIOCHEM PHARMACOL JI Biochem. Pharmacol. PD MAR 15 PY 1998 VL 55 IS 6 BP 775 EP 783 DI 10.1016/S0006-2952(97)00557-1 PG 9 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZC895 UT WOS:000072629800008 PM 9586949 ER PT J AU Kanegane, H Bhatia, K Gutierrez, M Kaneda, H Wada, T Yachie, A Seki, H Arai, T Kagimoto, S Okazaki, M Oh-ishi, T Moghaddam, A Wang, F Tosato, G AF Kanegane, H Bhatia, K Gutierrez, M Kaneda, H Wada, T Yachie, A Seki, H Arai, T Kagimoto, S Okazaki, M Oh-ishi, T Moghaddam, A Wang, F Tosato, G TI Syndrome of peripheral blood T-cell infection with Epstein-Barr virus (EBV) followed by EBV-positive T-cell lymphoma SO BLOOD LA English DT Article ID CD3-NEGATIVE LYMPHOPROLIFERATIVE DISEASE; POLYMERASE CHAIN-REACTION; GRANULAR LYMPHOCYTES; HUMAN THYMOCYTES; VIRAL-DNA; HODGKINS-DISEASE; EXPRESSION; LINE; ASSOCIATION; CARCINOMA AB The role of Epstein-Barr virus (EBV) in the pathogenesis of severe, chronic active EBV infection and its complications is unclear. We investigated two Japanese patients diagnosed with severe, chronic active EBV infection who subsequently developed EBV-positive T-cell lymphoma. The patients displayed abnormally high antibody titers to EBV antigens, and had evidence of peripheral blood CD4(+) T cell infection with EBV, 19 months and 3 months, respectively, before the diagnosis of EBV-positive T-cell lymphoma. The lymphomas were infected with monoclonal EBV and expressed the EBV latency genes EBNA-1, LMP-1, and LMP-2. Genetic studies showed that the virus detected in the T-cell lymphoma was indistinguishable, with respect to type and previously defined LMP-1 and EBNA-1 gene variations, from virus detected in the peripheral blood T cells 19 months earlier. These studies support an important pathogenetic role of T cell infection with EBV in chronic active EBV infection and in the EBV-positive T-cell lymphoma that followed. C1 Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NCI, NIH, Bethesda, MD 20892 USA. Kanazawa Univ, Sch Med, Kanazawa, Ishikawa 920, Japan. Saitama Childrens Med Ctr, Iwatsuki, Saitama, Japan. Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Infect Dis, Boston, MA 02115 USA. RP Tosato, G (reprint author), Ctr Biol Evaluat & Res, Bldg 29A,Room 2D16,HFM-535,1401 Rockville Pike, Rockville, MD 20852 USA. RI Yachie, Akihiro/C-4660-2015 NR 40 TC 85 Z9 87 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 0006-4971 J9 BLOOD JI Blood PD MAR 15 PY 1998 VL 91 IS 6 BP 2085 EP 2091 PG 7 WC Hematology SC Hematology GA ZB156 UT WOS:000072442000031 PM 9490694 ER PT J AU Strickler, HD Burk, R Shah, K Viscidi, R Jackson, A Pizza, G Bertoni, F Schiller, JT Manns, A Metcalf, R Qu, WM Goedert, JJ AF Strickler, HD Burk, R Shah, K Viscidi, R Jackson, A Pizza, G Bertoni, F Schiller, JT Manns, A Metcalf, R Qu, WM Goedert, JJ TI A multifaceted study of human papillomavirus and prostate carcinoma SO CANCER LA English DT Article DE human papillomavirus; prostate carcinoma; benign prostate hypertrophy; polymerase chain reaction; serology ID POLYMERASE CHAIN-REACTION; RISK-FACTORS; CERVICAL-CANCER; UNITED-STATES; HPV DNA; INFECTION; TYPE-16; TISSUE; VIRUS; PCR AB BACKGROUND. The presence of human papillomavirus (HPV) in the prostate and its role in prostate carcinoma are in dispute. To address these issues, two laboratories with extensive HPV experience were selected to test specimens from two populations at different risk for prostate carcinoma, using three different polymerase chain reaction (PCR) assays and two serologic assays for HPV. METHODS, The cases were comprised of 51 African-American (men at high risk far prostate carcinoma) and 15 Italian (men at intermediate risk for prostate carcinoma) men with prostate carcinoma. Controls were 108 African-American men and 40 Italian men with histologically proven benign prostate hypertrophy (BPH). Prostate tissue was obtained from each patient at surgery and immediately frozen in Liquid nitrogen. The PCR primer sets included two (MY09/MY11 and GP5+/GP6+) that amplify different regions of L1 and a third (WD66,67,154/WD72,76) targeted to E6. Sensitivity in the 2 L1 PCR assays was shown to be I HPV DNA genome per 100 cells. Serum antibodies to HPV-16 and HPV-11 virus-like particles (VLPs) were detected using enzyme-linked immunosorbent assays. RESULTS. All available prostate carcinoma tissue specimens (n = 63) and BPH specimens from selected controls (n = 61) were tested by PCR. Human beta-globin DNA could be amplified from all specimens except three carcinomas, but no HPV DNA was detected in any case or control specimens by MY09/MY11 or E6 PCR. Microdissection of 27 carcinoma specimens was conducted to minimize nontumor DNA, but results remained negative by MY09/MY11 and GP5+/GP6+ PCR. In addition, serum specimens in cases (n = 63) and controls (n = 144) showed no differences in their responses against HPV-16 (P = 0.54) or HPV-11 VLPs (P = 0.64). CONCLUSIONS. The findings suggest that HPV is not associated with prostate carcinoma, and that HPV DNA is not at all common in the prostate glands of older men. (C) 1998 American Cancer Society. C1 NCI, Viral Epidemiol Branch, NIH, Rockville, MD 20852 USA. Albert Einstein Coll Med, Canc Res Ctr, New York, NY USA. Johns Hopkins Univ, Sch Hyg & Publ Hlth, Baltimore, MD USA. Howard Univ, Dept Urol, Washington, DC 20059 USA. St Orsola Marcello Malpighi Hosp, Dept Urol, Bologna, Italy. US FDA, Bethesda, MD 20014 USA. RP Strickler, HD (reprint author), NCI, Viral Epidemiol Branch, NIH, 6130 Execut Blvd,EPN Rm 434, Rockville, MD 20852 USA. NR 51 TC 51 Z9 53 U1 0 U2 0 PU WILEY-BLACKWELL PI MALDEN PA COMMERCE PLACE, 350 MAIN ST, MALDEN 02148, MA USA SN 0008-543X J9 CANCER-AM CANCER SOC JI Cancer PD MAR 15 PY 1998 VL 82 IS 6 BP 1118 EP 1125 PG 8 WC Oncology SC Oncology GA ZA556 UT WOS:000072376400016 PM 9506358 ER PT J AU Sengupta, TK Nandy, RK Mukhopadhyay, S Hall, RH Sathyamoorthy, V Ghose, AC AF Sengupta, TK Nandy, RK Mukhopadhyay, S Hall, RH Sathyamoorthy, V Ghose, AC TI Characterization of a 20-kDa pilus protein expressed by a diarrheogenic strain of non-O1/non-O139 Vibrio cholerae SO FEMS MICROBIOLOGY LETTERS LA English DT Article DE Vibrio cholerae; pilus protein; outer membrane protein; intestinal colonization; protective antigen ID OUTER-MEMBRANE PROTEIN; EL-TOR; COLONIZATION FACTOR; PILIN GENE; PURIFICATION; ADHERENCE; FIMBRIAE; TOXIN; O1; SEQUENCE AB A diarrheogenic strain of non-O1/non-O139 Vibrio cholerae (10325) belonging to serogroup O34 was earlier shown to express a new type of pilus composed of a 20-kDa subunit protein. Amino-terminal sequence data (determined up to 20 amino acid residues) of this protein showed it to be different ii om the subunit proteins of other known types of pill of V. cholerae. On the other hand, it showed complete homology with the corresponding sequence of a 22-kDa outer membrane protein (OmpW) of V. cholerae. Expression of 10325 pill was Favored in AKI rather than in NE medium and at 30 degrees C rather than at 37 degrees C. Further, cultural conditions favoring pilus expression also enhanced autoagglutination and adherence properties of strain 10325. An antiserum to the 20-kDa protein induced passive protection against challenge with the parent organism 10325, bur not against V. cholerae O1 strains. Such protection was shown to be mediated by inhibition of intestinal colonization in vivo. (C) 1998 Federation of European Microbiological Societies. Published by Elsevier Science B.V. C1 Bose Inst, Dept Microbiol, Calcutta 700054, W Bengal, India. US FDA, Div Virulence Assessment, Washington, DC 20204 USA. RP Ghose, AC (reprint author), Bose Inst, Dept Microbiol, P-1-12,CIT Scheme VIIM, Calcutta 700054, W Bengal, India. NR 25 TC 8 Z9 8 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 MAR 15 PY 1998 VL 160 IS 2 BP 183 EP 189 DI 10.1111/j.1574-6968.1998.tb12909.x PG 7 WC Microbiology SC Microbiology GA ZB815 UT WOS:000072510800003 PM 9532736 ER PT J AU Mehrotra, PT Donnelly, RP Wong, S Kanegane, H Geremew, A Mostowski, HS Furuke, K Siegel, JP Bloom, ET AF Mehrotra, PT Donnelly, RP Wong, S Kanegane, H Geremew, A Mostowski, HS Furuke, K Siegel, JP Bloom, ET TI Production of IL-10 by human natural killer cells stimulated with IL-2 and/or IL-12 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID HUMAN T-CELLS; INTERFERON-GAMMA-PRODUCTION; TUMOR-NECROSIS-FACTOR; SEVERE COMBINED IMMUNODEFICIENCY; EXPERIMENTAL VIRAL-INFECTIONS; INHIBITS CYTOKINE PRODUCTION; IFN-GAMMA; NK-CELLS; HETERODIMERIC CYTOKINE; FACTOR INTERLEUKIN-12 AB Human NK cell activity can be augmented in vitro by stimulation with IL-2 or IL-12, both of which also induce the production of IFN-gamma, TNF-alpha, and granulocyte-macrophage CSF by NK cells, For the first time, we demonstrate that freshly purified NK cells stimulated with IL-2 proliferated and produced IL-10 in a dose-dependent manner, IL-10 mRNA expression, as detected by semiquantitative reverse transcription-PCR, reached peak levels at 24 h, IL-10 protein was detectable on day 2 and further increased on days 3 and 6 as measured by ELISA, However, IL-12 alone induced neither substantial proliferation nor detectable IL-10 production by fresh NK cells, but it synergized with IL-2 in inducing IL-10 mRNA expression and protein synthesis, IL-10 production by activated NK cells was confirmed by intracytoplasmic cytokine staining by three-color immunofluorescence of CD16(+) and/or CD56(+) NK cells with anti-IL-10 antibody, IL-10 production by NK cells was further confirmed in the NK-like cell line, YT, which constitutively expressed IL-10 mRNA and protein, IL-12 alone did not induce NK proliferation, but it inhibited IL-2-induced proliferation, Neutralization of endogenously produced IL-10 with anti-IL-10 antibodies did not overcome the inhibition of IL-2-induced proliferation by IL-12. Together, these results demonstrate that IL-2 and IL-12 synergize to induce IL-10 production by human NK cells and that IL-12 inhibits IL-2 induced NK cell proliferation by an IL-10-independent mechanism. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Cellular Immunol HFM 518, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Rockville, MD 20852 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Rockville, MD 20852 USA. RP Bloom, ET (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Lab Cellular Immunol HFM 518, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 73 TC 105 Z9 108 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1998 VL 160 IS 6 BP 2637 EP 2644 PG 8 WC Immunology SC Immunology GA ZA798 UT WOS:000072402900012 PM 9510161 ER PT J AU Rellahan, BL Jensen, JP Howcroft, TK Singer, DS Bonvini, E Weissman, AM AF Rellahan, BL Jensen, JP Howcroft, TK Singer, DS Bonvini, E Weissman, AM TI Elf-1 regulates basal expression from the T cell antigen receptor zeta-chain gene promoter SO JOURNAL OF IMMUNOLOGY LA English DT Article ID AP-1 TRANSCRIPTION FACTORS; DNA-BINDING SPECIFICITIES; FAMILY PROTEINS; POTENTIAL ROLE; ALPHA-GENE; ETS; ACTIVATION; ENHANCER; ELEMENTS; SITES AB In mature T cells, limited synthesis of the TCR-zeta subunit is primarily responsible for regulating surface expression of TCRs, Transcription of zeta is directed by a complex promoter that includes two potential binding sites for the Ets family of transcription factors at -52 (2EBS1) and -135 (zEBS2), Mutation of these two sites results in a marked reduction of transcription from this promoter, Using electrophoretic mobility shift analysis, Elf-1 was demonstrated to be the Ets family member that binds to these sites, One site, zEBS1, matches the optimal Elf-1 consensus sequence in eight of nine bases? making it the best match of any known mammalian Elf-1 binding site, A role for Elf-1 in TCR-zeta trans-activation was confirmed by ectopic expression of Elf-1 in COS-7 cells, This resulted in an increase in TCR-zeta promoter activity that mapped to 2EBS1 and zEBS2, Additional support for the involvement of Elf-1 in TCR-zeta trans-activation derives from the finding that a GAL4-Elf-1 fusion protein trans-activated TCR-zeta promoter constructs that had been modified to contain GAL4 DNA binding sites, These results demonstrate that Elf-1 plays an essential role in the trans-activation of a constitutively expressed T cell-specific gene, and that trans-activation occurs in the context of the native promoter in both lymphoid and nonlymphoid cells. Taken together with the existing literature, these data also suggest that the requirement for inducible factors in Elf-1-mediated trans-activation may decrease as the affinity and number of Elf-1 sites increase. C1 US FDA, Ctr Biol Evaluat & Res, Immunobiol Lab, Rockville, MD 20892 USA. NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20892 USA. NCI, Expt Immunol Branch, NIH, Bethesda, MD 20892 USA. RP Rellahan, BL (reprint author), US FDA, Ctr Biol Evaluat & Res, Immunobiol Lab, Bldg 29B,Room 5E16,HFM 564,1401 Rockville Pike, Rockville, MD 20892 USA. EM rellahan@al.cber.fda.gov NR 44 TC 35 Z9 37 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 15 PY 1998 VL 160 IS 6 BP 2794 EP 2801 PG 8 WC Immunology SC Immunology GA ZA798 UT WOS:000072402900032 PM 9510181 ER PT J AU Sahu, SC Eppley, RM Page, SW Gray, GC Barton, CN O'Donnell, MW AF Sahu, SC Eppley, RM Page, SW Gray, GC Barton, CN O'Donnell, MW TI Peroxidation of membrane lipids and oxidative DNA damage by fumonisin B-1 in isolated rat liver nuclei SO CANCER LETTERS LA English DT Article DE fumonisin B-1; DNA damage; lipid peroxidation; oxygen radicals ID FUSARIUM-MONILIFORME; CANCER; CORN; CARCINOGENESIS; HEPATOCYTES; PROMOTION; CELLS AB Fumonisin B-1 (FB1), a contaminant of corn, has been reported to be a hepatocarcinogen in rats. In an attempt to understand its mechanisms of action, a model system of isolated rat liver nuclei was used to determine what effects, if any, FB1 might have on nuclear membrane lipids and DNA. The data suggested that FB1 induced lipid peroxidation concurrently with DNA strand breaks in this in vitro system. Iron and copper had no statistically significant stimulatory effects on these reactions. In addition, the active oxygen scavengers catalase, superoxide dismutase (SOD), mannitol and sodium azide had no significant inhibitory effects on the FB1-induced DNA strand breaks. However, a small but significant reduction in lipid peroxidation by catalase and mannitol was observed. These results suggested that hydroxyl radicals may be the initiators of the nuclear membrane lipid peroxidation, which results in production of peroxyl radicals. In turn, the peroxyl radicals may be responsible for the DNA strand breaks. An alternative explanation is that the hydroxyl radicals, produced close to the DNA-bound metal ions, may induce direct site-specific strand breaks, which are insensitive to the scavengers of active oxygen. (C) 1998 Elsevier Science Ireland Ltd. C1 US FDA, Ctr Food Safety & Appl Nutr, Laurel, MD 20708 USA. RP Sahu, SC (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 29 TC 31 Z9 31 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 MAR 13 PY 1998 VL 125 IS 1-2 BP 117 EP 121 DI 10.1016/S0304-3835(97)00521-1 PG 5 WC Oncology SC Oncology GA ZE238 UT WOS:000072772000018 PM 9566705 ER PT J AU Nightingale, SL AF Nightingale, SL TI Teleconference on natural rubber/latex allergy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 20 Z9 22 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 4 PY 1998 VL 279 IS 9 BP 645 EP 645 DI 10.1001/jama.279.9.645-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YY849 UT WOS:000072192800007 PM 9496968 ER PT J AU Nightingale, SL AF Nightingale, SL TI Tobramycin inhalation product approved for use in cystic fibrosis therapy SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 20 Z9 22 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 4 PY 1998 VL 279 IS 9 BP 645 EP 645 DI 10.1001/jama.279.9.645-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YY849 UT WOS:000072192800005 PM 9496968 ER PT J AU Nightingale, SL AF Nightingale, SL TI Promotional practices of pharmacy benefits management companies SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg, Rockville, MD 20857 USA. NR 0 TC 20 Z9 22 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 4 PY 1998 VL 279 IS 9 BP 645 EP 645 DI 10.1001/jama.279.9.645-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YY849 UT WOS:000072192800004 PM 9496968 ER PT J AU Nightingale, SL AF Nightingale, SL TI Generic substitution SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Article C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 1 TC 20 Z9 22 U1 1 U2 1 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD MAR 4 PY 1998 VL 279 IS 9 BP 645 EP 645 DI 10.1001/jama.279.9.645-a PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YY849 UT WOS:000072192800006 PM 9496968 ER PT J AU Simon, JHM Miller, DL Fouchier, RAM Soares, MA Peden, KWC Malim, MH AF Simon, JHM Miller, DL Fouchier, RAM Soares, MA Peden, KWC Malim, MH TI The regulation of primate immunodeficiency virus infectivity by Vif is cell species restricted: a role for Vif in determining virus host range and cross-species transmission SO EMBO JOURNAL LA English DT Article DE HIV; SIV; Vif; viral infection; zoonosis ID TYPE-1 VIF; VIRION INCORPORATION; MATRIX PROTEIN; T-LYMPHOCYTES; DNA-SYNTHESIS; HIV-1; GENE; MUTANTS; RETROVIRUSES; EXPRESSION AB The primate immunodeficiency virus Vif proteins are essential for replication in appropriate cultured cell systems and, presumably, for the establishment of productive infections in vivo. We describe experiments that define patterns of complementation between human and simian immunodeficiency virus (HIV and SIV) Vif proteins and address the determinants that underlie functional specificity, Using human cells as virus producers, it was found that the HIV-I Vif protein could modulate the infectivity of HIV-1 itself, HIV-2 and SIV isolated from African green monkeys (SIVAGM). In contrast, the Vif proteins of SIVAGM and SIV isolated from Sykes' monkeys (SHVSYK) were inactive for all HIV and SIV substrates in human cells even though, at least for the SIVAGM protein, robust activity could be demonstrated in cognate African green monkey cells, These observations suggest that species-specific interactions between Vif and virus-producing cells, as opposed to between Vif and virus components, may govern the functional consequences of Vif expression in terms of inducing virion infectivity, The finding that the replication of murine leukemia virus could also be stimulated by HIV-1 Vif expression in human cells further supported this notion, We speculate that species restrictions to Vif function may have contributed to primate immunodeficiency virus zoonosis. C1 Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Dept Med, Philadelphia, PA 19104 USA. Univ Penn, Sch Med, Howard Hughes Med Inst, Philadelphia, PA 19104 USA. Univ Alabama, Dept Med, Birmingham, AL 35294 USA. Univ Alabama, Dept Microbiol, Birmingham, AL 35294 USA. Ctr Biol Evaluat & Res Food & Drug Adm, Bethesda, MD 20892 USA. RP Malim, MH (reprint author), Univ Penn, Sch Med, Dept Microbiol, Philadelphia, PA 19104 USA. RI Fouchier, Ron/A-1911-2014; OI Fouchier, Ron/0000-0001-8095-2869; Malim, Michael/0000-0002-7699-2064 FU NIAID NIH HHS [AI38715] NR 52 TC 117 Z9 118 U1 0 U2 1 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0261-4189 J9 EMBO J JI Embo J. PD MAR 2 PY 1998 VL 17 IS 5 BP 1259 EP 1267 DI 10.1093/emboj/17.5.1259 PG 9 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZC380 UT WOS:000072572100009 PM 9482723 ER PT J AU Villalba, L Hicks, JE Adams, EM Sherman, JB Gourley, MF Leff, RL Thornton, BC Burgess, SH Plotz, PH Miller, FW AF Villalba, L Hicks, JE Adams, EM Sherman, JB Gourley, MF Leff, RL Thornton, BC Burgess, SH Plotz, PH Miller, FW TI Treatment of refractory myositis - A randomized crossover study of two new cytotoxic regimens SO ARTHRITIS AND RHEUMATISM LA English DT Article ID IDIOPATHIC INFLAMMATORY MYOPATHIES; PLACEBO-CONTROLLED TRIAL; RHEUMATOID-ARTHRITIS; CLINICAL-TRIAL; AZATHIOPRINE; POLYMYOSITIS; METHOTREXATE; THERAPY; DERMATOMYOSITIS; PREDNISONE AB Objective. To assess the clinical usefulness of 2 novel therapies for treatment-resistant myositis. Methods. Thirty patients with refractory myositis, of whom 25 had an inadequate or no response to previous cytotoxic therapy? were randomized to begin either a combination of weekly oral methotrexate and daily azathioprine (MTX/AZA) or intravenous methotrexate with leucovorin rescue (IV MTX) every 2 weeks for 6 months, Crossover to the alternate therapy occurred according to defined rules; evaluations of muscle strength and functional abilities were performed at the beginning, and after 3 and 6 months, of each treatment. Results. Of the 15 patients initially randomized to oral MTX/AZA, 8 improved with oral therapy and 1 improved with TV MTX during the crossover period, Of the 15 patients initially randomized to IV MTX therapy, 3 improved with the IV therapy and 4 with the oral combination during the crossover period, Although the study lacked the power to directly compare both treatments, intention-to-treat analysis showed a trend in favor of those patients who first received oral combination therapy (P = 0.025). There were 0.09 adverse events per patient-month with oral combination therapy and 0.16 per patient-month with IV therapy (P = 0.09). Conclusion. Combination oral MTX/AZA may benefit patients with treatment-resistant myositis, including those who previously had inadequate responses to either MTX or AZA alone. IV MTX with leucovorin rescue may also benefit some patients with refractory myositis. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. NIH, Ctr Clin, Bethesda, MD 20892 USA. RP Miller, FW (reprint author), US FDA, Ctr Biol Evaluat & Res, N29B,2G11,HFM-561, Bethesda, MD 20892 USA. OI Miller, Frederick/0000-0003-2831-9593 NR 29 TC 94 Z9 97 U1 1 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 1998 VL 41 IS 3 BP 392 EP 399 DI 10.1002/1529-0131(199803)41:3<392::AID-ART3>3.0.CO;2-X PG 8 WC Rheumatology SC Rheumatology GA ZA910 UT WOS:000072414300002 PM 9506565 ER PT J AU Ginn, LR Lin, JP Plotz, PH Bale, SJ Wilder, RL Mbauya, A Miller, FW AF Ginn, LR Lin, JP Plotz, PH Bale, SJ Wilder, RL Mbauya, A Miller, FW TI Familial autoimmunity in pedigrees of idiopathic inflammatory myopathy patients suggests common genetic risk factors for many autoimmune diseases SO ARTHRITIS AND RHEUMATISM LA English DT Article ID POLYMYOSITIS; MYOSITIS; DERMATOMYOSITIS; AUTOANTIBODIES; PREDISPOSITION; PATHOGENESIS; AGGREGATION; MUSCLE; MODELS; MICE AB Objective, To test the hypothesis that many autoimmune diseases share common genetic risk factors and to define the frequency and distribution of autoimmune diseases in relatives of patients with very rare disorders, the idiopathic inflammatory myopathies (IIM). Methods. We evaluated, in a prospective case-control study, consecutive patients with IIM who were referred to our center and ascertained without regard to family history or known risk factors for autoimmunity, and all available family members, We used a standardized assessment to determine the presence and type of autoimmune disease in each subject, A matched comparison group of control subjects without autoimmune disease who were referred to our center and their families were similarly assessed, Results. Autoimmune diseases were significantly increased in prevalence (21.9%) in the 151 first-degree relatives of the 21 IIM probands compared with the prevalence (4.9%) in the 143 relatives of the 21 control probands (odds ratio [OR] by regression analysis 7.9, 95% confidence interval [95% CI] 2.9-21.9, P < 0.001), Women had more autoimmune disease than men (OR by regression analysis 4.6, 95% CI 2.3-9.0) and the odds ratio for autoimmune disease increased 0.02 per year of age, These disorders tended to follow the frequency distribution of autoimmune diseases in the general population, Genetic modeling studies showed that a non-Mendelian polygenic inheritance pattern for autoimmune disease was most consistent with these data, Conclusion. Autoimmune diseases are significantly increased in frequency in first-degree relatives of IIM patients, affect more women than men, increase with age, and are distributed in a pattern similar to that in the general population, Many autoimmune disorders share genes that together act as polygenic risk factors for autoimmunity. C1 US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Miller, FW (reprint author), US FDA, Lab Mol & Dev Immunol, Div Monoclonal Antibodies, Ctr Biol Evaluat & Res, Bldg 29B,Room 2G11,HFM-561,8800 Rockville Pike, Bethesda, MD 20892 USA. OI Miller, Frederick/0000-0003-2831-9593 NR 33 TC 58 Z9 60 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD MAR PY 1998 VL 41 IS 3 BP 400 EP 405 DI 10.1002/1529-0131(199803)41:3<400::AID-ART4>3.0.CO;2-5 PG 6 WC Rheumatology SC Rheumatology GA ZA910 UT WOS:000072414300003 PM 9506566 ER PT J AU Higgins, KM Davidian, M Chew, G Burge, H AF Higgins, KM Davidian, M Chew, G Burge, H TI The effect of serial dilution error on calibration inference in immunoassay SO BIOMETRICS LA English DT Article DE confidence intervals; ELISA; generalized least squares; measurement error; precision profile; variance function estimation ID NONLINEAR CALIBRATION; ASSAYS AB A common practice in immunoassay is the use of sequential dilutions of an initial stock solution of the antigen of interest to obtain standard samples in a desired concentration range. Nonlinear, heteroscedastic regression models are a common framework for analysis, and the usual methods for fitting the model assume that measured responses on the standards are independent. However, the dilution procedure introduces a propagation of random measurement error that may invalidate this assumption. We demonstrate that failure to account for serial dilution error in calibration inference on unknown samples leads to serious inaccuracy of assessments of assay precision such as confidence intervals and precision profiles. Techniques for taking serial dilution error into account based on data from multiple assay runs are discussed and are shown to yield valid calibration inferences. C1 N Carolina State Univ, Dept Stat, Raleigh, NC 27695 USA. US FDA, CDER, QMR Staff, Rockville, MD 20857 USA. Harvard Univ, Sch Publ Hlth, Dept Environm Hlth, Boston, MA 02115 USA. RP Davidian, M (reprint author), N Carolina State Univ, Dept Stat, Box 8203, Raleigh, NC 27695 USA. FU NIAID NIH HHS [R01-AI24643, R01-AI41214] NR 14 TC 25 Z9 25 U1 0 U2 8 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1998 VL 54 IS 1 BP 19 EP 32 DI 10.2307/2533992 PG 14 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA ZF255 UT WOS:000072879200002 PM 9544505 ER PT J AU Zheng, Q AF Zheng, Q TI To use or not to use? Backward equations in stochastic carcinogenesis models SO BIOMETRICS LA English DT Article DE backward equation; carcinogenesis model; characteristic curve; forward equation; hazard function; survival function ID MULTISTAGE MODEL; CANCER; PARAMETERS; HAZARD; TUMOR AB The method based on the Kolmogorov backward equations of Little (1995, Biometrics 51, 1278-1291) for computing hazard functions for the multistage carcinogenesis models fails when model parameters are time-dependent. In addition to suggesting an alternative method based on the Kolmogorov forward equation, this note highlights the interplay of the forward equation, the backward equation, and the characteristic method. Advantages and disadvantages of the forward and backward equations are discussed. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Zheng, Q (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. EM qzheng@nctr.fda.gov NR 25 TC 2 Z9 3 U1 1 U2 1 PU INTERNATIONAL BIOMETRIC SOC PI WASHINGTON PA 808 17TH ST NW SUITE 200, WASHINGTON, DC 20006-3910 USA SN 0006-341X J9 BIOMETRICS JI Biometrics PD MAR PY 1998 VL 54 IS 1 BP 384 EP 388 DI 10.2307/2534024 PG 5 WC Biology; Mathematical & Computational Biology; Statistics & Probability SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology; Mathematics GA ZF255 UT WOS:000072879200034 PM 9544530 ER PT J AU Mahmood, I Chamberlin, N AF Mahmood, I Chamberlin, N TI A limited sampling method for the estimation of AUC and C-max of carbamazepine and carbamazepine epoxide following a single and multiple dose of a sustained-release product SO BRITISH JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article DE carbamazepine; limited sampling; prediction of AUC and C-max ID PHARMACOKINETICS; DOSAGE; MODEL AB Aims The objectives of this study are to develop a model to predict area under the curve (AUG) and maximum plasma concentration (C-max) of carbamazepine (CBZ) and its active metabolite carbamazepine epoxide (CBZE) following single and multiple dose of CBZ using one or mio samples in volunteers. Methods Limited sampling models (LSM) were developed for CBZ and CBZE following 200-800 mg single oral dose and 400-800 mg twice daily dose for 14 days of a sustained-release product (CBZ-SR) to estimate AUC and C-max. The LSM was developed from a training data set of 15 subjects using one blood sample taken at 48 h following a single dose. The model was validated on 60 subjects who received different doses of CBZ. Following multiple dosing, the LSM was developed from a training data set of 10 subjects using the steady state C-min (plasma concentration obtained 5 min before the last CBZ-SR dose). Results The model provided good estimates of AUC and C-max for CBZ and CBZE. The bias and the precision of the predicted AUC and C-max for CBZ and CBZE were less than 10% and 15%, respectively. Similar results were obtained when CBZ was given as multiple dose. Conclusions The method described here may be used to estimate AUC and C-max for CBZ and CBZE without detailed pharmacokinetic studies following single or multiple dose of CBZ. C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off Ctr 2, Rockville, MD 20852 USA. US FDA, Div Pharmacovigilance & Epidemiol, Woodmont Off Ctr 2, Rockville, MD 20852 USA. RP Mahmood, I (reprint author), US FDA, Off Clin Pharmacol & Biopharmaceut, Div Pharmaceut Evaluat 1, Woodmont Off Ctr 2, HFD-860,Room 4079,1451 Rockville Pike, Rockville, MD 20852 USA. NR 17 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 0306-5251 J9 BRIT J CLIN PHARMACO JI Br. J. Clin. Pharmacol. PD MAR PY 1998 VL 45 IS 3 BP 241 EP 246 DI 10.1046/j.1365-2125.1998.00668.x PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YY269 UT WOS:000072130200004 PM 9517367 ER PT J AU Jin, JG Dasari, VR Sistare, FD Kunapuli, SP AF Jin, JG Dasari, VR Sistare, FD Kunapuli, SP TI Distribution of P2Y receptor subtypes on haematopoietic cells SO BRITISH JOURNAL OF PHARMACOLOGY LA English DT Article DE P2Y receptors; P2Y(1) receptors; P2Y(2) receptors; P2Y(4) receptors; P2Y(6) receptors; haematopoietic cell lines; endothelial cells; peripheral blood leukocytes ID URIDINE NUCLEOTIDE RECEPTOR; MONOCYTE PROGENITOR CELLS; EXTRACELLULAR ATP; FUNCTIONAL EXPRESSION; LEUKEMIA-CELLS; CHROMOSOMAL LOCALIZATION; PURINERGIC RECEPTORS; P-2U PURINOCEPTORS; MOLECULAR-CLONING; ADP AB 1 RT-PCR-southern hybridization analyses with radiolabelled P2Y receptor cDNAs as probes indicated that the peripheral blood leukocytes and the human umbilical vein endothelial cells express P2Y(1), P2Y(2), P2Y(4) and P2Y(6) receptors. 2 Of the haematopoietic cell lines tested, promonocytic U937 cells express P2Y(2) and P2Y(6), but not P2Y(1) or P2Y(4); promyelocytic HL-60 cells express the P2Y(1), P2Y(2) and P2Y(6) receptors but not the P2Y(4) receptor; K562 cells express P2Y(1) but not P2Y(2), P2Y(4) or P2Y(6); and Dami cells express P2Y(1), P2Y(2), P2Y(4) and P2Y(6) receptors. 3 Of the peripheral blood leukocytes tested, polymorphonuclear cells express P2Y(4) and P2Y(6) but not P2Y(1) or P2Y(2) receptors; monocytes express P2Y(1), P2Y(2), P2Y(4) and P2Y(6) receptors and lymphocytes express P2Y(1), P2Y(2), P2Y(4) and P2Y(6) receptors. 4 These results suggest a physiological role for different P2Y receptor subtypes in the extracellular nucleotide-mediated stimulation of monocytes, neutrophils, lymphocytes and endothelial cells. C1 Temple Univ, Sch Med, Dept Physiol, Philadelphia, PA 19140 USA. US FDA, Div Res & Testing, Off Testing & Res, Ctr Drug Evaluat & Res, Laurel, MD 20708 USA. RP Kunapuli, SP (reprint author), Temple Univ, Sch Med, Dept Physiol, Philadelphia, PA 19140 USA. NR 47 TC 97 Z9 99 U1 0 U2 4 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0007-1188 J9 BRIT J PHARMACOL JI Br. J. Pharmacol. PD MAR PY 1998 VL 123 IS 5 BP 789 EP 794 DI 10.1038/sj.bjp.0701665 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YZ253 UT WOS:000072235600002 PM 9535005 ER PT J AU Zhang, RW Li, YF Cai, QY Liu, TP Sun, H Chambless, B AF Zhang, RW Li, YF Cai, QY Liu, TP Sun, H Chambless, B TI Preclinical pharmacology of the natural product anticancer agent 10-hydroxycamptothecin, an inhibitor of topoisomerase I SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE anticancer drugs; 10-hydroxycamptothecin; pharmacokinetics; metabolism; topoisomerase I ID TISSUE DISTRIBUTION; GROWTH-INHIBITION; PHARMACOKINETICS; CPT-11; RATS; CELLS AB Purpose: 10-Hydroxycamptothecin (HCPT) is an indole alkaloid isolated from a Chinese tree, Camptotheca acuminata, and has a wide spec?rum of anticancer activity in vitro and in vivo mainly through inhibitory effects on topoisomerase I. HCPT has been shown to be more potent and less toxic than camptothecin and has recently undergone clinical trials. To determine how HCPT might be best used as an anticancer agent, preclinical studies of the pharmacokinetics, tissue distribution, metabolism and elimination of HCPT in rats were undertaken. Methods: HCPT was administered to rats by i.v. bolus injection at doses of 1, 3, and 10 mg/kg body weight. HCPT (lactone and carboxylate) and its metabolites in plasma, urine, feces, and various tissues were quantitated by reversed-phase HPLC. Pharmacokinetic parameters were then estimated. Results: Following i.v. administration at doses of 3 or 10 mg/kg, the plasma concentration-time profile for lactone HCPT could be best described by a three-compartment model, with terminal elimination half-lives of 140.4 and 428.6 min, respectively. A two-compartment model was used to fit the plasma concentration-time curve at 1 mg/kg, with a terminal elimination half-life of 30.5 min. Carboxylate HCPT had a longer half-life than the lactone form of HCPT. During the initial G h after dosing, urinary excretion was the major route of elimination, and fecal excretion became the major route of elimination thereafter. HCPT was widely distributed to various tissues including the enterohepatic system, kidney, and bone marrow. The lactone form of HCPT was detectable in various tissues examined up to 72 h after dosing at all the three test doses. HCPT glucuronides were present in plasma, urine, feces and various tissues. No significant toxicity was observed at doses of 1 or 3 mg/kg. Polyuria and hematuria were observed only during the initial 3 h after dosing at 10 mg/kg. Conclusions: Prolonged elimination of HCPT in vivo may have a significant impact on its therapeutic effects. HCPT is metabolized to its carboxylate form End glucuronides. Dose-dependent toxicity was observed with i.v. administration of HCPT. The results of this study should be useful in the design of future human trials with this anticancer drug. C1 Univ Alabama, Dept Pharmacol & Toxicol, Birmingham, AL 35294 USA. Univ Alabama, Div Clin Pharmacol, Birmingham, AL 35294 USA. Univ Alabama, Ctr Comprehens Canc, Birmingham, AL 35294 USA. US FDA, Ctr Drug Evaluat & Res, OCPB, Div Biopharmaceut Evaluat, Rockville, MD 20857 USA. RP Zhang, RW (reprint author), Univ Alabama, Dept Pharmacol & Toxicol, 1670 Univ Blvd, Birmingham, AL 35294 USA. NR 21 TC 43 Z9 80 U1 0 U2 12 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD MAR PY 1998 VL 41 IS 4 BP 257 EP 267 DI 10.1007/s002800050738 PG 11 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA YW726 UT WOS:000071966600001 PM 9488594 ER PT J AU Moysich, KB Ambrosone, CB Vena, JE Shields, PG Mendola, P Kostyniak, P Greizerstein, H Graham, S Marshall, JR Schisterman, EF Freudenheim, JL AF Moysich, KB Ambrosone, CB Vena, JE Shields, PG Mendola, P Kostyniak, P Greizerstein, H Graham, S Marshall, JR Schisterman, EF Freudenheim, JL TI Environmental organochlorine exposure and postmenopausal breast cancer risk SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID POLYCHLORINATED-BIPHENYLS PCBS; ADIPOSE-TISSUE; HEXACHLOROBENZENE HCB; BLOOD-LEVELS; FEMALE RAT; SERUM; MIREX; EPIDEMIOLOGY; PESTICIDES; TOXICITY AB Environmental exposure to organochlorine compounds has been associated with a potential role in breast cancer etiology, but results from previous investigations yielded inconsistent results. In this case-control study, we examined the effect of 1,1-dichloro-2,2-bis(p-chlorophenyl)ethyl (DDE), hexachlorobenzene (HCB), mirex, and several measures of polychlorinated biphenyls (PCBs) on postmenopausal breast cancer risk. The study sample included 154 primary, incident, histologically confirmed, postmenopausal breast cancer cases and 192 postmenopausal community controls. Usual diet, reproductive and medical histories, and other lifestyle information was obtained by an extensive in person interview. Serum levels (ng/g) of DDE, HCB, mirex, and 73 PCB congeners were determined by gas chromatography with electron capture. PCB exposure was examined as total measured PCB levels, total number of detected PCB peaks, and three PCB congener groups. In the total sample, there was no evidence of an adverse effect of serum levels of DDE [odds ratio (OR), 1.34; 95% confidence interval (CI) 0.71-2.55], HCB (OR, 0.81; 95% CI, 0.43-1.53), or mirex (OR, 1.37; 95% CI, 0.78-2.39). Further, higher serum levels of total PCBs (OR, 1.14; 95% CI, 0.61-2.15), moderately chlorinated PCBs (OR, 1.37; 95% CI, 0.73-2.59), more highly chlorinated PCBs (OR, 1.19; 95% CI, 0.60-2.36), or greater number of detected peaks (OR, 1.34; 95% CI, 0.72-2.47) were not associated with increased risk. There was some indication of a modest increase in risk for women with detectable levels of less chlorinated PCBs (OR, 1.66; 95% CI, 1.07-2.88). Among parous women who had never lactated, there was some evidence for increased risk, associated with having detectable levels of mirex (OR, 2.42; 95% CI, 0.98-4.32), higher serum concentrations of total PCBs (OR, 2.87; 95% CI, 1.01-7.29), moderately chlorinated PCBs (OR, 3.57; 95% CI, 1.10-8.60), and greater numbers of detected PCB congeners (OR, 3.31; 95% CI, 1.04-11.3). These results suggest that an increase in risk of postmenopausal breast cancer associated with environmental exposure to PCBs and mirex, if at all present, is restricted to parous women who had never breast-fed an infant. Future studies should consider lactation history of participants, as well as use similar epidemiological and laboratory methodologies, to ensure comparability of results across studies. C1 SUNY Buffalo, Dept Prevent & Social Med, Sch Med & Biomed Sci, Buffalo, NY 14214 USA. SUNY Buffalo, Toxicol Res Ctr, Buffalo, NY 14214 USA. Univ Arizona, Arizona Canc Ctr, Tucson, AZ 85724 USA. NCI, Bethesda, MD 20892 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Moysich, KB (reprint author), SUNY Buffalo, Dept Prevent & Social Med, Sch Med & Biomed Sci, 270 Farber Hall, Buffalo, NY 14214 USA. EM kmoyisch@ubmedg.buffalo.edu RI Shields, Peter/I-1644-2012; OI Mendola, Pauline/0000-0001-5330-2844; Schisterman, Enrique/0000-0003-3757-641X FU NCI NIH HHS [CA/ES 62995, CA11535] NR 47 TC 130 Z9 133 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 MAR PY 1998 VL 7 IS 3 BP 181 EP 188 PG 8 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA627 UT WOS:000072384000001 PM 9521429 ER PT J AU Palom, Y Lipman, R Musser, SM Tomasz, M AF Palom, Y Lipman, R Musser, SM Tomasz, M TI A mitomycin-N-6-deoxyadenosine adduct isolated from DNA SO CHEMICAL RESEARCH IN TOXICOLOGY LA English DT Article ID ACTIVATED MITOMYCIN-C; CROSS-LINKING; SEQUENCE SPECIFICITY; DT-DIAPHORASE; TUMOR-CELLS; ALKYLATION; MECHANISM; SELECTIVITY; IDENTIFICATION; SPECTROSCOPY AB A minor N-6-deoxyadenosine adduct of mitomycin C (MC) was isolated from synthetic oligonucleotides and calf thymus DNA, representing the first adduct of MC and a DNA base other than guanine. The structure of the adduct (8) was elucidated using submilligram quantities of total available material. UV difference spectroscopy, circular dichroism, and electrospray mass spectroscopy as well as chemical transformations were utilized in deriving the structure of 8. A series of synthetic oligonucleotides was designed to probe the specificities of the alkylation of adenine by MC. The nature and frequency of the oligonucleotide-MC adducts formed under conditions of reductive activation of MC were determined by their enzymatic digestion to the nucleoside level followed by quantitative analysis of the products by HPLC. The analyses indicated the following: (i) (A)(n) sequence is favored over (AT)(n) for adduct formation; (ii) the alkylation favors the duplex structure; (iii) at adenine sites only monofunctional alkylation occurs; (iv) the adenine-to-alkylation frequency in the model oligonucleotides was 0.3-0.6 relative to guanine alkylation at the 5'-ApG sequence but only 0.02-0.1 relative to guanine alkylation at 5'-CpG. The 5'-phosphodiester linkage of the MC-adenine adduct is resistant to snake venom diesterase. The overall ratio of adenine to guanine alkylation in calf thymus DNA was 0.03, indicating that 8 is a minor MC-DNA adduct relative to MC-DNA adducts at guanine residues in the present experimental residues in the present experimental system. However, the HPLC elution time of 8 coincides with that of a major, unknown MC adduct detected previously in mouse mammary tumor cells treated with radiolabeled MC [Bizanek, R., Chowdary, D., Arai, H., Kasai, M., Hughes, C. S., Sartorelli, A. C., Rockwell, S., and Tomasz, M. (1993) Cancer Res. 53, 5127-5134]. Thus, 8 may be identical or closely related to this major adduct formed in vivo. This possibility can now be tested by further comparison. C1 CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. US FDA, Washington, DC 20204 USA. RP Palom, Y (reprint author), CUNY Hunter Coll, Dept Chem, New York, NY 10021 USA. FU NCI NIH HHS [CA28681]; NCRR NIH HHS [RR03037] NR 39 TC 14 Z9 14 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 MAR PY 1998 VL 11 IS 3 BP 203 EP 210 DI 10.1021/tx970205u PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Toxicology SC Pharmacology & Pharmacy; Chemistry; Toxicology GA ZD197 UT WOS:000072661100007 PM 9544618 ER PT J AU Concepcion, N Frasch, CE AF Concepcion, N Frasch, CE TI Evaluation of previously assigned antibody concentrations in pneumococcal polysaccharide reference serum 89SF by the method of cross-standardization SO CLINICAL AND DIAGNOSTIC LABORATORY IMMUNOLOGY LA English DT Article ID INFLUENZAE TYPE-B; LINKED-IMMUNOSORBENT-ASSAY; NEISSERIA-MENINGITIDIS; VACCINE; PREVENTION; DISEASE AB An enzyme-linked immunosorbent assay (ELISA) and the antibody concentrations assigned to different pneumococcal capsular polysaccharide types were used to estimate concentrations of antibody to additional pneumococcal types in reference serum 89SF and to confirm assigned antibody values, This was possible because the slopes of curves of antibody binding to all polysaccharide types evaluated (1, 3, 4, 5, 6B, 7F, 9V, 14, 18C, 19F, and 23F) were similar. The point estimates for total anti-pneumococcal antibody and immunoglobulin G (IgG) antibody determined by cross-standardization by an ELISA based on use of methylated human serum albumin (mHSA) to improve the efficiency of polysaccharide binding to the ELISA plate differed by less than 40% from those reported by Quataert et al. (Clin. Diagn. Lab. Immunol. 2:590-597, 1995) far types 1, 4, 6B, 7F, 9V, 14, 18C, and 23F. However, large differences were found between the assigned values and those obtained by our mHSA ELISA for types 3 and 19F. The mHSA ELISA and the direct polysaccharide coat ELISA may not measure antibodies to the same epitopes on polysaccharides of types 3 and 19F. The functional importance of these different antibody specificities is being investigated. We have thus confirmed the assigned IgG antibody values for most types by a different method and have extended antibody assignments to several additional types. C1 US FDA, Ctr Biol Evaluat & Res, Div Bacterial Prod, Bethesda, MD 20892 USA. RP Frasch, CE (reprint author), Ctr Biol Evaluat & Res, Div Bacterial Prod, 1401 Rockville Pike,Mailstop HFM-428, Rockville, MD 20853 USA. EM frasch@helix.nih.gov NR 18 TC 58 Z9 60 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 1071-412X J9 CLIN DIAGN LAB IMMUN JI Clin. Diagn. Lab. Immunol. PD MAR PY 1998 VL 5 IS 2 BP 199 EP 204 PG 6 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA ZA823 UT WOS:000072405600012 PM 9521143 ER PT J AU Sehat, N Niedwetzki, G AF Sehat, N Niedwetzki, G TI Food labelling in Germany including European union aspects SO FOOD TECHNOLOGY LA English DT Article C1 Handels & Umweltschutzlab GMBH, D-21107 Hamburg, Germany. RP Sehat, N (reprint author), US FDA, Off Food Labeling, 200 C St SW, Washington, DC 20204 USA. NR 0 TC 2 Z9 2 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 MAR PY 1998 VL 52 IS 3 BP 58 EP 61 PG 4 WC Food Science & Technology SC Food Science & Technology GA ZB100 UT WOS:000072435700008 ER PT J AU Pei, ZH Burucoa, C Grignon, B Baqar, S Huang, XZ Kopecko, DJ Bourgeois, AL Fauchere, JL Blaser, MJ AF Pei, ZH Burucoa, C Grignon, B Baqar, S Huang, XZ Kopecko, DJ Bourgeois, AL Fauchere, JL Blaser, MJ TI Mutation in the peb1A locus of Campylobacter jejuni reduces interactions with epithelial cells and intestinal colonization of mice SO INFECTION AND IMMUNITY LA English DT Article ID ESCHERICHIA-COLI; GEL-ELECTROPHORESIS; NUCLEOTIDE-SEQUENCE; POLYACRYLAMIDE GELS; HELA-CELLS; PROTEINS; IDENTIFICATION; ENTERITIS; MEMBRANE; PATHOGENESIS AB Campylobacter jejuni is one of the leading causes of bacterial diarrhea throughout the world. We previously found that PERI is a homolog of cluster 3 binding proteins of bacterial ABC transporters and that a C. jejuni adhesin, cell-binding factor 1 (CBF1), if not identical to, contains PEB1. A single protein migrating at approximately 27 to 28 kDa was recognized by anti-CBF1 and anti-PEB1. To determine the role that the operon encoding PEB1 plays in C. jejuni adherence, peb1A, the gene encoding PEB1, was disrupted in strain 81-176 by insertion of a kanamycin resistance gene through homologous recombination. Inactivation of this operon completely abolished expression of CBF1, as determined by sodium dodecyl sulfate-polyaccrylamide gel electrophoresis (SDS-PAGE) and immunoblotting. In comparison to the wild-type strain, the mutant strain showed 50- to 100-fold less adherence to and 15-fold less invasion of epithelial cells in culture, Mouse challenge studies showed that the rate and duration of intestinal colonization by the mutant were significantly lower and shorter than with the wild-type strain. In summary, PEB1 is identical to a previously identified cell-binding factor, CBF1, in C. jejuni, and the peb1A locus plays an important role in epithelial cell interactions and in intestinal colonization in a mouse model. C1 Vanderbilt Univ, Sch Med, Div Infect Dis, Dept Med, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA. Vet Affairs Med Ctr, Nashville, TN 37212 USA. CHU La Miletrie, Lab Microbiol A, F-86021 Poitiers, France. USN, Med Res Inst, Enter Dis Program, Bethesda, MD USA. US FDA, Lab Enter & Sexually Transmitted Dis, CBER, Rockville, MD 20857 USA. RP Blaser, MJ (reprint author), Vanderbilt Univ, Sch Med, Div Infect Dis, Dept Med, A-3310 Med Ctr N, Nashville, TN 37232 USA. NR 43 TC 122 Z9 135 U1 0 U2 4 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0019-9567 J9 INFECT IMMUN JI Infect. Immun. PD MAR PY 1998 VL 66 IS 3 BP 938 EP 943 PG 6 WC Immunology; Infectious Diseases SC Immunology; Infectious Diseases GA YY565 UT WOS:000072160900009 PM 9488379 ER PT J AU Murata, T Obiri, NI Puri, RK AF Murata, T Obiri, NI Puri, RK TI Structure of and signal transduction through interleukin-4 and interleukin-13 receptors (Review) SO INTERNATIONAL JOURNAL OF MOLECULAR MEDICINE LA English DT Review DE signal transduction; interleukin-4; interleukin-13 receptors ID HUMAN B-CELLS; TUMOR-NECROSIS-FACTOR; JAK-3 JANUS KINASE; COMMON GAMMA-CHAIN; HUMAN GLIOMA-CELLS; IL-4 RECEPTOR; CARCINOMA-CELLS; ALPHA-CHAIN; PSEUDOMONAS EXOTOXIN; HIGH-AFFINITY AB We have recently demonstrated that two different forms of IL-4R exist; classical or alternative. The classical IL-4R is predominantly expressed in hematopoietic cells and consist of IL-4R beta and IL-2R gamma(c) (gamma(c)) chains. On the other hand, alternative form of IL-4R is predominantly expressed in nonhematopoietic cells and consists of IL-4R beta and IL-13R alpha' chains. Moreover, the alternative form of lL-4R is also utilized as a functional component IL-13R complex. It has been shown that the phosphorylation and activation of JAK3 tyrosine kinase is crucial for IL-4 activation of STAT6 in hematopoietic cells. However, we have recently demonstrated that nonhematopoietic cells lack JAK3 expression. We also demonstrated that in these cells, STAT6 activation is mediated through JAK1 and JAK2 tyrosine kinases instead. Furthermore, our results show that IL-4 and IL-13 signals are transmitted through the alternative form of IL-4R in these cells. Thus, major differences exist between hematopoietic and non-hematopoietic cells with regard to structure and signal transduction through IL-4R and IL-13R systems. C1 US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene therapies, Lab Mol Tumor Biol, Bethesda, MD 20892 USA. Yokohama City Univ, Sch Med, Dept Internal Med 1, Yokohama, Kanagawa 236, Japan. RP Puri, RK (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene therapies, Lab Mol Tumor Biol, NIH Bldg 29B,Room 2NN10,29 Lincoln Dr MSC 4555, Bethesda, MD 20892 USA. NR 95 TC 112 Z9 114 U1 0 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1107-3756 J9 INT J MOL MED JI Int. J. Mol. Med. PD MAR PY 1998 VL 1 IS 3 BP 551 EP 557 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA 117DV UT WOS:000075766100005 PM 9852261 ER PT J AU Mangipudy, RS Rao, PS Andrews, A Bucci, TJ Witzmann, FA Mehendale, HM AF Mangipudy, RS Rao, PS Andrews, A Bucci, TJ Witzmann, FA Mehendale, HM TI Dose-dependent modulation of cell death: Apoptosis versus necrosis in thioacetamide hepatotoxicity SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article DE apoptosis; dose response; heat shock protein 70; in situ end labeling; necrosis; thioacetamide; transmission electron microscopy ID HEAT-SHOCK PROTEINS; RAT-LIVER; EXPRESSION; PROLIFERATION; STRESS; HSP70; WITHDRAWAL; MECHANISMS; INHIBITION; ACTIVATION AB Apoptosis is programmed cell death, morphologically and biochemically distinct from necrosis. The objective of the present study was to examine thioacetamide-induced apoptosis over an early time course of 0 to 8 h after administration of a la-fold close range (50, 150, 300, and 600 mg/kg, ip) of thioacetamide (TA). Male Sprague-Dawley rats (200-225 g) were used for the study. The incidence of apoptosis was determined by in situ end labeling, transmission electron microscopy, and charge modification of heat shock protein 70 (Hsp 70). Light microscopic examination of liver sections revealed apoptotic bodies (ABs) as early as 2 h after TA administration A dose-dependent increase in the incidence of ABs was seen with all doses until 4 h. Thereafter, the incidence of ABs continued to increase in a temporal manner with 50 and 150 mg/kg, while a decreased in the rats treated with 300 and 600 mg/kg. Between 4 and 8 h, while necrosis as assessed by serum alanine aminotransferase (ALT) and histopathology declined in the sixfold dose range (50, 150, and 300 mg TA/kg), it increased in a temporal manner with 600 mg TA/kg. Preliminary studies indicate an inverse relation between Hsp 70 abundance and the incidence of apoptosis. Hsp 70 expression was significantly higher in the 600 mg TA/kg group compared to the lower doses. Lowest abundance was recorded in the groups receiving 50 and 150 mg TA/kg, where maximum apoptosis was noted. These findings collectively suggest that although the processes of apoptosis and necrosis are initiated simultaneously the proportion of cells dying via either mechanism seems to be regulated by the dose of TA. Lower doses seem to favor cell death via apoptosis, while higher doses favor cell death via necrosis. Additionally, the inverse relation between Hsp 70 and apoptosis at lower doses suggests a regulatory role for Hsp 70. C1 NE Louisiana Univ, Coll Pharm & Hlth Sci, Div Toxicol, Monroe, LA 71209 USA. Pathol Associates Inc, Natl Ctr Toxicol Res, Jefferson, AR USA. Indiana Univ Purdue Univ, Div Mol Anat, Columbus, IN USA. RP Mehendale, HM (reprint author), NE Louisiana Univ, Coll Pharm & Hlth Sci, Div Toxicol, Monroe, LA 71209 USA. EM pymehendale@alpha.nlu.edu NR 52 TC 15 Z9 16 U1 0 U2 1 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PD MAR-APR PY 1998 VL 17 IS 2 BP 193 EP 212 PG 20 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA ZF718 UT WOS:000072925100007 ER PT J AU Shaikh, B Rummel, N AF Shaikh, B Rummel, N TI Liquid chromatographic determination of chlorothiazide and hydrochlorothiazide diuretic drugs in bovine milk SO JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY LA English DT Article DE chlorothiazide; hydrochlorothiazide; trichlormethiazide; LC; bovine milk; thiazides; diuretics; incurred residue ID URINE AB A liquid chromatographic (LC) procedure was developed for the determination of chlorothiazide (CTZ) and hydrochlorothiazide (HCTZ) in bovine milk. Whole milk was defatted by centrifugation at 4 degrees C. The top layer was treated with lead acetate and acetonitrile, mixed, and centrifuged. The supernatant was extracted with ethyl acetate to remove acetonitrile. The solvent mixture was further treated with sodium tungstate and mixed. The top layer was removed and evaporated to dryness, the residue was dissolved in the mobile phase, and the final extract was analyzed by LC. The LC employed a polymer column, a mobile phase of acetonitrile/tetrahydrofuran in phosphate buffer, and a UV detector. The average recoveries of CTZ from milk fortified at 35, 70, and 140 ppb were 97, 96, and 99%, respectively, with corresponding coefficients of variation (CVs) of 8, 5, and 5%. The average recoveries of HCTZ at 35, 70, and 140 ppb were 87, 91, and 90%, respectively, with CVs of 5, 6, and 5%. The method was validated by assaying milk obtained from cows dosed separately with the two diuretics. CTZ was detected in 8-h (430 ppb) and 24-h (85 ppb) incurred milk samples and HCTZ (47 ppb) only in the 8-h incurred milk samples. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Shaikh, B (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 9 TC 10 Z9 10 U1 0 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 1998 VL 46 IS 3 BP 1039 EP 1043 DI 10.1021/jf970637a PG 5 WC Agriculture, Multidisciplinary; Chemistry, Applied; Food Science & Technology SC Agriculture; Chemistry; Food Science & Technology GA ZC845 UT WOS:000072624200041 ER PT J AU Adam, LA Reeves, VB AF Adam, LA Reeves, VB TI Procedure for detecting and confirming pentobarbital residues in dog food by gas chromatography mass spectrometry SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID SOLID-PHASE EXTRACTION; URINE AB The method described detects and confirms presence of pentobarbital residues in dry, extruded feeds at concentrations of 5-20 ppb. Dried feed is ground to a uniform powder and shaken overnight in methanol. A portion of the methanolic extract is evaporated, and the residue is reconstituted in phosphate-buffered saline. The aqueous extract is cleaned with a solid-phase extraction cartridge designed to extract barbiturate residues from biological matrixes. Dimethyl sulfoxide, tetramethylammonium hydroxide, and iodomethane are added to derivatize pentobarbital. 1,3-Dimethylpentobarbital is then acidified with dilute hydrochloric acid and extracted with isooctane. The organic layer is transferred and evaporated under a stream of nitrogen. The residue is reconstituted in a small volume of ethyl acetate for analysis by gas chromatography/mass spectrometry. The limit of detection is approximately 0.7 ppb. The method was validated with pentobarbital-fortified feed samples containing high concentrations of meat and bone meal. C1 US FDA, Ctr Vet Med, Res Off, Laurel, MD 20708 USA. RP Adam, LA (reprint author), US FDA, Ctr Vet Med, Res Off, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 8 TC 8 Z9 9 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 1998 VL 81 IS 2 BP 359 EP 367 PG 9 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA ZE544 UT WOS:000072804100006 PM 9549069 ER PT J AU Chou, HJ Yates, RL AF Chou, HJ Yates, RL TI A rapid and selective method for determining potential nitrosating agents in cosmetic products by chemiluminescence detection of nitric oxide SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID CHEMI-LUMINESCENCE; ALKYL NITRITES; NITRATE; SUNSCREENS; FOODSTUFFS AB A method was developed for rapid and selective determination of potential nitrosating agents at the part-per-billion level in cosmetic products. These compounds are chemically reduced to nitric oxide, which is determined by its chemiluminescent reaction with ozone. Suspended materials and colors in cosmetic products do not interfere. Hence their removal before analysis is not required. A detection limit of 33 ppb, calculated as nitrite, was obtained. No false-positive interferences were observed from antifoaming agents, several N-nitroso compounds, and nitrate up to 20 ppm. Among cosmetic products surveyed, potential nitrosating agents were found at levels ranging from 113 to 5021 ppb. No consistent relationship was found between levels of potential nitrosating agents and N-nitrosamines in the same products. However, the highest levels of nitrosating agents were most often associated with the highest levels of N-nitrosamines known to be present in the products. C1 US FDA, Washington, DC 20204 USA. RP Chou, HJ (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. NR 24 TC 5 Z9 5 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 1998 VL 81 IS 2 BP 368 EP 372 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA ZE544 UT WOS:000072804100007 PM 9549070 ER PT J AU Cieri, UR AF Cieri, UR TI Determination of reserpine and rescinnamine in Rauwolfia serpentina powders and tablets: Collaborative study SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID LIQUID-CHROMATOGRAPHY AB A liquid chromatographic (LC) method for determining reserpine and rescinnamine in Rauwolfia serpentine powders and tablets, which uses fluorescence detection, was subjected to a collaborative study. The procedure for extraction and purification is a simplified version of that used in the current official method for analysis of these products. LC separations are performed on a normal-phase column. The mobile phase is methanol to which a small volume of an aqueous solution of 1-pentanesulfonic acid sodium salt can be added to achieve desired elution characteristics. Reserpine and rescinnamine elute at approximately the same time but can be individually quantitated by appropriate settings of the fluorescence detector. Reserpine is determined at an excitation wavelength of 280 nm and an emission wavelength of 360 nm, because rescinnamine is completely non-fluorescent at these wavelengths. Rescinnamine is determined at an excitation wavelength of 330 nm and an emission wavelength of 435 nm, because reserpine is completely nonfluorescent at these wavelengths. The following materials were used for the study: one sample of United States Pharmacopeia (USP) standard R. serpentina powder, one tablet type labeled as containing 100 mg R. serpentina and 2 tablet types labeled as containing 50 mg R. serpentina. For each of the 4 materials, 2 pairs of blind duplicates were prepared. Three materials were analyzed in duplicate by 8 laboratories. One of the 2 tablets labeled to contain 50 mg R. serpentina was analyzed only by 7 of 8 participating laboratories. Average combined content of reserpine and rescinnamine was 0.144% for the USP raw material and 0.132, 0.135, and 0.137% for the 3 commercial tablets. Reproducibility relative standard deviation values were 5.72, 5.93, 8.61, and 3.48% and repeatability relative standard deviation values were 2.57, 4.87, 3.19, and 1.99% for the 4 samples. The Associate Referee conducted a study to determine recoveries of reserpine plus rescinnamine by this method from mixtures simulating sample extracts. Average recovery of 15 determinations was 100.1%, with a relative standard deviation of 1.3%. The LC method for determination of reserpine and rescinnamine in R. serpentina powders and tablets has been adopted first action by AOAC INTERNATIONAL. C1 US FDA, Philadelphia, PA 19106 USA. RP Cieri, UR (reprint author), US FDA, 2 & Chestnut Sts, Philadelphia, PA 19106 USA. NR 10 TC 9 Z9 9 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD MAR-APR PY 1998 VL 81 IS 2 BP 373 EP 380 PG 8 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA ZE544 UT WOS:000072804100008 PM 9549071 ER PT J AU Farag, SA AF Farag, SA TI Simultaneous liquid chromatographic analysis of the beta-lactam antibiotics cefazolin, cefadroxil, cephalexin, ampicillin, and cephradine in solution SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A liquid chromatographic method was developed for the determination of nanogram quantities of 5 broad-spectrum structurally related beta-lactam antibiotics (cefazolin, cefadroxil, cephalexin, cephradine, and ampicillin) in solution. The method uses a C-18 reversed-phase column, UV absorption (240 nm) detection, and an aqueous mobile phase containing isopropyl alcohol and acetic acid. Relative resolution between the antibiotic peaks ranged from 1.7 to 5.9 for all peaks. Chromatographic retention times were 2.97, 3.92, 4.57, 5.37, and 6.56 min for cefazolin, cefadroxil, cephalexin, ampicillin, and cephradine, respectively. Accuracy, precision, linearity, and long term analytical reproducibility were determined by statistical analysis. Use of the proposed method to evaluate the degradation of cephradine solutions stored at room temperature illustrated its potential as a stability-indicating assay. C1 US FDA, Ctr Drug Evaluat & Res, Div Testing & Appl Analyt Dev, St Louis, MO 63101 USA. RP Farag, SA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Testing & Appl Analyt Dev, 1114 Mkt St, St Louis, MO 63101 USA. NR 5 TC 22 Z9 22 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 1998 VL 81 IS 2 BP 381 EP 385 PG 5 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA ZE544 UT WOS:000072804100009 PM 9549072 ER PT J AU Chase, GW Reid, AP Eitenmiller, RR Long, AR AF Chase, GW Reid, AP Eitenmiller, RR Long, AR TI Zero control reference materials for infant formula methods development SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A zero control reference material (ZRM) for milk and soy-based infant formula was manufactured and characterized. The ZRM was free of retinyl palmitate and all-rac-alpha-tocopheryl acetate. The composition was similar to commercially available infant formula. The ZRM provides a valuable tool to ascertain method performance. C1 US FDA, Atlanta Ctr Nutr Anal, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Chase, GW (reprint author), US FDA, Atlanta Ctr Nutr Anal, 60 8th St, Atlanta, GA 30309 USA. NR 3 TC 10 Z9 10 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 1998 VL 81 IS 2 BP 453 EP 456 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA ZE544 UT WOS:000072804100018 PM 9549080 ER PT J AU Smallwood, AW Ranieri, TL Satzger, RD AF Smallwood, AW Ranieri, TL Satzger, RD TI Determination of 4-hexylresorcinol in crab meat SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID POLYPHENOL OXIDASE; PROCESSING AID; SHRIMP; PREVENTION; MECHANISM AB A method is described for determining 4-hexylresorcinol in crab meat. 4-Hexylresorcinol is used to prevent melanosis in shrimp, and the same use has been proposed for crab meat. Because 4-hexylresorcinol may be added illegally to crab meat as a preservative, consumer protection requires that residues of the compound be monitored in crab meat. 4-Hexylresorcinol is extracted from crab meat with acetonitrile. After dilution with water, the extract is passed through a C-18 solid-phase extraction column and 4-hexylresorcinol is eluted from the column with ethanol. The compound is determined by reversed-phase liquid chromatography with diode array detection at 206 nm. Limit of quantitation is 1.0 mu g/g. Mean recovery in the range 1-20 mu g/g is 89%, with a relative standard deviation of 6.3. C1 US FDA, Natl Forens Chem Ctr, Cincinnati, OH 45202 USA. RP Smallwood, AW (reprint author), US FDA, Natl Forens Chem Ctr, 1141 Cent Pkwy, Cincinnati, OH 45202 USA. NR 9 TC 6 Z9 6 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 1998 VL 81 IS 2 BP 488 EP 491 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA ZE544 UT WOS:000072804100023 PM 9549084 ER PT J AU Ette, EI Sun, H Ludden, TM AF Ette, EI Sun, H Ludden, TM TI Ignorability and parameter estimation in longitudinal pharmacokinetic studies SO JOURNAL OF CLINICAL PHARMACOLOGY LA English DT Article AB In the analysis of longitudinal pharmacokinetic data, both balanced (equal number of samples per subject) and unbalanced data are used. It is implicitly assumed that the process that caused the missing data can be ignored. A simulation study was performed to determine the effect of ignoring the missing data (i.e., "ignorability") on the accuracy and precision of parameter estimation in longitudinal pharmacokinetic studies. A two-compartment model with multiple intravenous bolus inputs was assumed. Subjects with balanced data sets had six samples, and those with unbalanced data had 1 to 5 samples missing(i.e., supplied in a decreasing order from 5 to I samples). The proportion of subjects with 1 to 5 samples missing varied from 25% to 75% in ct fixed sample size of 100. The effect of ignorability was studied at intersubject variability ranging from 25% to 60% for a drug assumed to be dosed at its elimination half-life. One hundred replicate data sets of 100 subjects each were simulated for each missing data scenario. The accuracy of parameter estimation was not significantly affected by the amount of ignorable missing data at any given level of variability. However, the precision of parameter estimation was affected by the degree of "missingness." C1 Vertex Pharmaceut, Cambridge, MA 02139 USA. US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. Univ Nebraska, Dept Pharmaceut Sci, Omaha, NE 68182 USA. RP Ette, EI (reprint author), Vertex Pharmaceut, 130 Waverly St, Cambridge, MA 02139 USA. NR 5 TC 8 Z9 8 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0091-2700 J9 J CLIN PHARMACOL JI J. Clin. Pharmacol. PD MAR PY 1998 VL 38 IS 3 BP 221 EP 226 PG 6 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZC966 UT WOS:000072637100004 PM 9549660 ER PT J AU Brownell, CR Shiu, GK Croitoru, A AF Brownell, CR Shiu, GK Croitoru, A TI Stability of ergotamine tartrate sublingual tablets SO JOURNAL OF FOOD AND DRUG ANALYSIS LA English DT Article DE ergotamine tartrate tablet; stability AB The high moisture content of ergotamine tartrate sublingual tablets poses potential stability problems and safety concerns. The finished product is confined in a protective aluminum foil and could degrade to generate toxic by-products during moisture evaporation and condensation within the package under some storage conditions. This study was initiated to examine the stability of ergotamine tartrate sublingual tablets under various simulated storage conditions. The physical and chemical stability of the product was evaluated over a period of 12 months. Results indicated that no stability problems arose when the product was stored at constant temperature, either ambient or sub-ambient. Experimental results indicated that storage in an environment where the temperature fluctuated widely might lead to poor product stability and should be avoided. C1 US FDA, Div Prod Qual Res, Off Testing & Res, Rockville, MD 20850 USA. US FDA, Div Chem, Off Gener Drugs, OPS,CDER, Rockville, MD 20850 USA. NR 7 TC 0 Z9 0 U1 0 U2 1 PU NATL LABORATORIES FOODS DRUGS PI NANKANG, TAIPEI PA DEPT HEALTH, EXECUTIVE YUAN, 161-2 KUEN YANG ST DR. ERICK T. SUEN, DEPUTY DIR., NANKANG, TAIPEI, TAIWAN SN 1021-9498 J9 J FOOD DRUG ANAL JI J. Food Drug Anal. PD MAR PY 1998 VL 6 IS 1 BP 405 EP 411 PG 7 WC Food Science & Technology; Pharmacology & Pharmacy SC Food Science & Technology; Pharmacology & Pharmacy GA ZJ677 UT WOS:000073241000002 ER PT J AU Heinitz, ML Johnson, JM AF Heinitz, ML Johnson, JM TI The incidence of Listeria spp., Salmonella spp., and Clostridium botulinum in smoked fish and shellfish SO JOURNAL OF FOOD PROTECTION LA English DT Article ID YERSINIA-ENTEROCOLITICA; SEAFOOD PRODUCTS; PACKAGING METHOD; MONOCYTOGENES; STORAGE; GROWTH; OUTBREAK; HOT; PREVALENCE; BEHAVIOR AB The frequency of occurrence of Listeria spp., Salmonella spp., and Clostridium botulinum in samples of smoked finfish and smoked shellfish was analyzed over a 5-year period. Listeria monocytogenes was isolated from 14% of 1,080 samples. For those samples where the smoke process was known, the incidence of L, monocytogenes was higher in cold-smoked than hot-smoked products (51 of 240 cold-smoked compared to 19 of 215 hot-smoked products). Listeria species other than L. monocytogenes were also detected (in 7.2% of cold-smoked and 3.8% of hot-smoked products). The time and temperature smoke processing guidelines are reviewed for a few state authorities. L, monocytogenes was isolated from 15.2% of the 559 samples of foreign origin. There were four countries for which more than 70 samples were analyzed: Canada, Norway, the Philippines, and the United Kingdom. The occurrence of L. monocytogenes in samples from these four countries was 14.3%, 23.7%, 0%, and 16.1%, respectively. The 521 samples originating in the United States were processed by 194 plants. Thirty-seven plants in 13 states produced contaminated product. Salmonella species were isolated from 5 (3.2%) of 156 samples tested for this organism. All positive samples were of foreign origin (4 from the Philippines and 1 from the United Kingdom). No C. botulinum spores were detected in any of the 201 vacuum-packed samples tested for this organism. C1 US FDA, Minneapolis, MN 55401 USA. US FDA, Bothell, WA 98041 USA. RP Heinitz, ML (reprint author), US FDA, 240 Hennepin Ave, Minneapolis, MN 55401 USA. EM gvl@cu.nih.gov NR 50 TC 62 Z9 65 U1 0 U2 8 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 1998 VL 61 IS 3 BP 318 EP 323 PG 6 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA ZC329 UT WOS:000072566400011 PM 9708303 ER PT J AU Mueller, EP Regnault, WF AF Mueller, EP Regnault, WF TI Replacement heart valves and performance standards SO JOURNAL OF HEART VALVE DISEASE LA English DT Article AB The international use of medical device standards is expanding for both economic and regulatory reasons. It is no longer adequate to have standards that only specify measurement methods and labeling for a product. An effort needs to be put forth between industry, academia and government to promote standards that also include a minimum set of acceptable performance criteria. This will allow for a less subjective evaluation of the conformance of the medical device to the appropriate standard as well as promote a uniform set of minimal performance expectations for a class of products among consumers. C1 US FDA, Dept Mech & Mat Sci, Rockville, MD 20852 USA. RP Mueller, EP (reprint author), US FDA, Dept Mech & Mat Sci, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 10 TC 1 Z9 1 U1 0 U2 1 PU I C R PUBLISHERS PI NORTHWOOD PA CRISPIN HOUSE, 12/A SOUTH APPROACH, MOOR PARK, NORTHWOOD, ENGLAND HA6 2ET SN 0966-8519 J9 J HEART VALVE DIS JI J. Heart Valve Dis. PD MAR PY 1998 VL 7 IS 2 BP 125 EP 129 PG 5 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA ZD080 UT WOS:000072649400002 PM 9587851 ER PT J AU Cerutti, A Zan, H Schaffer, A Bergsagel, L Harindranath, N Max, EE Casali, P AF Cerutti, A Zan, H Schaffer, A Bergsagel, L Harindranath, N Max, EE Casali, P TI CD40 ligand and appropriate cytokines induce switching to IgG, IgA, and IgE and coordinated germinal center and plasmacytoid phenotypic differentiation in a human monoclonal IgM(+)IgD(+) B cell line SO JOURNAL OF IMMUNOLOGY LA English DT Article ID IMMUNOGLOBULIN HEAVY; ISOTYPE SWITCH; SOMATIC MUTATION; HIGH-FREQUENCY; HUMAN TONSIL; IN-VITRO; EXPRESSION; LYMPHOCYTES; TRANSCRIPTS; RECOMBINATION AB B lymphocytes are induced to undergo Ig class switching and a complex phenotypic differentiation by the milieu of the germinal center. Partly as a result of the lack of a suitable in vitro B cell model, the relationship between these processes in the humans has never been formally established in vitro. We have identified a human monoclonal B cell line, CL-01, that expresses surface IgM and IgD and, upon induction with CD40 ligand, IL-4, and IL-10, switches to all seven downstream isotypes, showing typical DNA switch recombination preceded by germline;transcription of targeted C-H regions. In CL-01 cells, switch-inducing stimuli trigger concomitant changes in expression of surface IgD, CD23, CD38, and CD77 that parallel those reported in ex vivo isolated tonsillar centroblasts, centrocytes, and memory B cells. Eventually, in the presence of IL-6, CL-01 cells express CD56 and accumulate cytoplasmic IgG and IgA, both traits of plasmacytoid differentiation. Analysis of transcription and recombination of the Ig H locus in sorted CL-01 cells suggest that Ig class switching begins in centroblasts, it extends to all isotypes in centrocytes, and it is extinct in memory B cells. Thus, we have induced coordinated Ig class switching, progression through germinal center phenotypic stages, and differentiation to memory B cells and plasma cells at the level of a single B clonotype. Our data suggest that these processes are likely regulated by a common maturation program, the activation of which may require CD40 ligand, IL-4, IL-10, and IL-6 only. C1 Cornell Univ, Grad Sch Med Sci, Dept Pathol, Div Mol Immunol, New York, NY 10021 USA. Cornell Univ, Grad Sch Med Sci, Program Immunol, New York, NY 10021 USA. Cornell Univ, Coll Med, Dept Internal Med, Div Hematol, New York, NY 10021 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Casali, P (reprint author), Cornell Univ, Coll Med, Dept Pathol C 312, Div Mol Immunol, 1300 York Ave, New York, NY 10021 USA. EM pcasali@mail.med.cornell.edu RI Casali, Paolo/F-6579-2010; Bergsagel, Peter/A-7842-2011 OI Bergsagel, Peter/0000-0003-1523-7388 FU NCI NIH HHS [CA 68541]; NIAMS NIH HHS [AR 40908, R01 AR040908] NR 44 TC 153 Z9 155 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1998 VL 160 IS 5 BP 2145 EP 2157 PG 13 WC Immunology SC Immunology GA YY124 UT WOS:000072115700016 PM 9498752 ER PT J AU Klinman, DM Sechler, JMG Conover, J Gu, ML Rosenberg, AS AF Klinman, DM Sechler, JMG Conover, J Gu, ML Rosenberg, AS TI Contribution of cells at the site of DNA vaccination to the generation of antigen-specific immunity and memory SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; DIRECT GENE-TRANSFER; PLASMID DNA; CIRCUMSPOROZOITE PROTEIN; IMMUNIZATION; MICE; EXPRESSION; RESPONSES; MUSCLE; ANTIBODY AB Gene gun-mediated DNA vaccination stimulates an immune response characterized by the activation of IgG-secreting B cells and IFN-gamma-secreting T cells, To monitor the contribution of cells at the site of vaccination to this process, transfected skin was periodically removed and grafted onto naive recipients, Immediate removal of vaccinated skin abrogated the development of an immune response, Low-level IgG production was stimulated when the vaccination site was left in place for greater than or equal to 5 h, with the strength of this response increasing the longer the site remained intact (for up to 2 wk), Measurable primary T cell responses were observed in animals whose vaccination site remained in place for greater than or equal to 1 day. Skin grafts transferred 0 to 24 h postvaccination stimulated a primary immune response in naive recipients, Memory B and T cells were generated in animals whose site of vaccination remained intact for 5 to 12 h, Skin transferred within 12 h of vaccination triggered memory B and T cell development in graft recipients, while the removal of skin > 12 h postvaccination did not reduce memory in vaccinated mice. These findings suggest that 1) primary immunity is induced by cells that migrate rapidly from the site of immunization, 2) nonmigratory cells influence the magnitude of this primary response, and 3) migratory cells alone are responsible for the induction of immunologic memory. C1 US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Retroviral Immunol Sect, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Immunol Lab, Bethesda, MD 20892 USA. RP Klinman, DM (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Viral Prod, Retroviral Immunol Sect, Bldg 29A,Rm 3 D 10, Bethesda, MD 20892 USA. EM Klinman@AI.CBER.FDA.GOV NR 34 TC 99 Z9 106 U1 0 U2 0 PU AMER ASSOC IMMUNOLOGISTS PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814 USA SN 0022-1767 J9 J IMMUNOL JI J. Immunol. PD MAR 1 PY 1998 VL 160 IS 5 BP 2388 EP 2392 PG 5 WC Immunology SC Immunology GA YY124 UT WOS:000072115700045 PM 9498781 ER PT J AU Kenney, RT Sacks, DL Gam, AA Murray, HW Sundar, S AF Kenney, RT Sacks, DL Gam, AA Murray, HW Sundar, S TI Splenic cytokine responses in Indian kala-azar before and after treatment SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 01-05, 1996 CL BALTIMORE, MARYLAND SP Amer Soc Trop Med & Hyg ID LEISHMANIA-DONOVANI INFECTIONS; VISCERAL LEISHMANIASIS; INTERFERON-GAMMA; IFN-GAMMA; ANTIMONY; INTERLEUKIN-10; IL-10 AB Cytokine mRNA levels were measured in serial splenic aspirates from 27 patients with visceral leishmaniasis during monotherapy with interferon-gamma (IFN-gamma, n = 9), sodium antimony gluconate (SAG; n = 8), or amphotericin B lipid complex (ABLC; n = 10). At baseline, mRNA for IFN-gamma was detected in 18 (86%) of 21 patients, and mRNA for interleukin (IL)-10 and IL-4 was detected in 21 (100%) and 10 (48%) of 21 patients, respectively. With IFN-gamma treatment alone, levels of IFN-gamma mRNA decreased by day 10 and then returned to baseline levels; IL-10 mRNA levels were high throughout treatment. In the SAG and ABLC groups, levels of IFN-gamma and IL-10 mRNA decreased significantly. Polarized Th2 cell type responses do not appear to develop in Indian kala-azar; instead, there is an initial mixed Th1-Th2 cell picture. With successful treatment and resolution of infection, both components of the immune response appear to involute. C1 FDA, CBER, OVRR, DAPP, Rockville, MD 20852 USA. NIAID, NIH, Bethesda, MD 20892 USA. Cornell Univ Med Coll, New York, NY USA. Banaras Hindu Univ, Inst Med Sci, Varanasi 221005, Uttar Pradesh, India. RP Kenney, RT (reprint author), FDA, CBER, OVRR, DAPP, 1401 Rockville Pike,HFM-416, Rockville, MD 20852 USA. FU NIAID NIH HHS [AI-16963] NR 15 TC 95 Z9 96 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD MAR PY 1998 VL 177 IS 3 BP 815 EP 819 PG 5 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YY555 UT WOS:000072159900047 PM 9498473 ER PT J AU Kenney, RT Sacks, DL Sypek, JP Gam, AA Evans-Davis, K AF Kenney, RT Sacks, DL Sypek, JP Gam, AA Evans-Davis, K TI Solid immunity in a primate model of cutaneous leishmaniasis. SO JOURNAL OF INVESTIGATIVE MEDICINE LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. NIAID, NIH, Bethesda, MD 20892 USA. Genet Inst, Andover, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SLACK INC PI THOROFARE PA 6900 GROVE RD, THOROFARE, NJ 08086 USA SN 1081-5589 J9 J INVEST MED JI J. Invest. Med. PD MAR PY 1998 VL 46 IS 3 SU S BP 216A EP 216A PG 1 WC Medicine, General & Internal; Medicine, Research & Experimental SC General & Internal Medicine; Research & Experimental Medicine GA ZK545 UT WOS:000073335300156 ER PT J AU Salako, QA AF Salako, QA TI Correct use of dose calibrator values - Reply SO JOURNAL OF NUCLEAR MEDICINE LA English DT Letter C1 US FDA, Div Med Imaging & Radiopharmaceut Drug Prod, Rockville, MD 20857 USA. RP Salako, QA (reprint author), US FDA, Div Med Imaging & Radiopharmaceut Drug Prod, Rockville, MD 20857 USA. NR 4 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 MAR PY 1998 VL 39 IS 3 BP 575 EP 576 PG 2 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA ZA974 UT WOS:000072421600044 ER PT J AU Itzhak, Y Gandia, C Huang, PL Ali, SF AF Itzhak, Y Gandia, C Huang, PL Ali, SF TI Resistance of neuronal nitric oxide synthase-deficient mice to methamphetamine-induced dopaminergic neurotoxicity SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID EXCITATORY AMINO-ACIDS; STRIATAL DOPAMINE; IN-VIVO; BEHAVIORAL SENSITIZATION; RAT STRIATUM; RELEASE; AMPHETAMINE; INHIBITION; 7-NITROINDAZOLE; GLUTAMATE AB Methamphetamine (METH) is a powerful psychostimulant that produces dopaminergic neurotoxicity manifested by a decrease in the levels of dopamine, tyrosine hydroxylase activity and dopamine transporter (DAT) binding sites in the nigrostriatal system. We have recently reported that blockade of the neuronal nitric oxide synthase (nNOS) isoform by 7-nitroindazole provides protection against METH-induced neurotoxicity in Swiss Webster mice. The present study was undertaken to investigate the effect of a neurotoxic dose of METH on mutant mice lacking the nNOS gene [nNOS(-/-)] and wild-type controls. In addition, we sought to investigate the behavioral outcome of exposure to a neurotoxic dose of METH. Homozygote nNOS(-/-), heterozygote nNOS(+/-) and wild-type animals were administered either saline or METH (5 mg/kg x 3). Dopamine, DOPAC and HVA levels, as well as DAT binding site levels, were determined in striatal tissue derived 72 h after the last METH injection. This regimen of METH given to nNOS(-/-) mice affected neither the tissue content of dopamine and its metabolites nor the number of DAT binding sites. Although a moderate reduction in the levels of dopamine (35%) and DAT binding sites (32%) occurred in striatum of heterozygote nNOS(+/-) mice, a more profound depletion of the dopaminergic markers (up to 68%) was observed in the wild-type animals. METH-induced hyperthermia was observed in all animal strains examined except the nNOS(-/-) mice. Investigation of the animals' spontaneous locomotor activity before and after administration of the neurotoxic dose of METH (5 mg/kg x 3) revealed no differences. A low dose of METH (1.0 mg/kg) administered to naive animals (nNOS(-/-) and wild-type) resulted in a similar intensity of locomotor stimulation. However, 68 to 72 h after exposure to the high-dose METH regimen, a marked sensitized response to a challenge METH injection was observed in the wild-type mice but not in the nNOS(-/-) mice. Taken together, these results indicate that nNOS(-/-) mice are protected against METH-induced dopaminergic neurotoxicity and locomotor sensitization. It also appears that a partial deficit of dopaminergic transmission in wild-type animals does not prevent the development of sensitization to METH, whereas a deficit in nNOS may attenuate this process. C1 Univ Miami, Sch Med, Dept Biochem & Mol Biol R629, Miami, FL 33101 USA. Univ Miami, Sch Med, Dept Microbiol & Immunol, Miami, FL 33101 USA. Massachusetts Gen Hosp, Dept Med, Cardiovasc Res Ctr, Charlestown, MA USA. Harvard Univ, Sch Med, Charlestown, MA USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Biochem & Mol Biol R629, POB 016129, Miami, FL 33101 USA. FU NIDA NIH HHS [DA08584]; NINDS NIH HHS [NS33335] NR 51 TC 116 Z9 119 U1 0 U2 4 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 1998 VL 284 IS 3 BP 1040 EP 1047 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA532 UT WOS:000072373700030 PM 9495865 ER PT J AU Morris, LA Lechter, K Weintraub, M Bowen, D AF Morris, LA Lechter, K Weintraub, M Bowen, D TI Comprehension testing for OTC drug labels: Goals, methods, target population, and testing environment SO JOURNAL OF PUBLIC POLICY & MARKETING LA English DT Article ID CORRECTING MENTAL MODELS; ORGANIZATIONAL SIGNALS; RISK COMMUNICATIONS; HAZARDOUS PROCESSES; INSTRUCTIONAL TEXT; FTC; GUIDELINES; DECEPTION; BEHAVIOR; RECALL AB Drug products may be switched from precription (Rx) to over-the-counter (OTC) status if labeling can be written that ensures that the label information is comprehensible to ordinary consumers, including persons with low literacy ability, under normal conditions of purchase and use. The Food and Drug Administration has been working with sponsors to develop methods to test consumer comprehension of proposed OTC product labels. The authors discuss several conceptual and operational elements of comprehension testing, focusing on the goals, methods, appropriate target audience, and testing environment. The authors also examine areas in need of further research and debate. As more complex products are considered for OTC status, it is even more important to ensure that OTC labels are comprehensible. As understanding and the validity of methods to evaluate consumer comprehension improve, so should the quality of labels offered to consumers. C1 US FDA, Div Drug Mkt Advertising & Comunicat HFD40, Rockville, MD 20857 USA. US FDA, Off Drug Evaluat 5 HFD500, Rockville, MD 20857 USA. RP Morris, LA (reprint author), US FDA, Div Drug Mkt Advertising & Comunicat HFD40, Rockville, MD 20857 USA. NR 58 TC 14 Z9 14 U1 1 U2 5 PU AMER MARKETING ASSOC PI CHICAGO PA 311S WACKER DR, STE 5800, CHICAGO, IL 60606-6629 USA SN 0743-9156 J9 J PUBLIC POLICY MARK JI J. Public Policy Mark. PD SPR PY 1998 VL 17 IS 1 BP 86 EP 96 PG 11 WC Business SC Business & Economics GA ZR854 UT WOS:000074021300009 ER PT J AU Adam, M Chew, M Wasserman, S McCollum, A McDonald, RE Mossoba, MM AF Adam, M Chew, M Wasserman, S McCollum, A McDonald, RE Mossoba, MM TI Determination of trans fatty acids in hydrogenated vegetable oils by attenuated total reflection infrared spectroscopy: Two limited collaborative studies SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Article DE attenuated total reflection; collaborative study; infrared; trans fatty acid ID ISOMERS AB An attenuated total reflection infrared spectroscopy procedure was collaboratively studied among two sets of five laboratories for quantitating the total trans fatty acid levels in neat (without solvent) hydrogenated vegetable oils, measured as triacylglycerols in one study, and as fatty acid methyl ester derivatives in the other. Unlike the fatty acid methyl esters, the triacylglycerols required no derivatization but had to be melted prior to measurement. To obtain a symmetric absorption band at 966 cm(-1) on a horizontal background, the single-beam spectrum of the trans-containing fat was "ratioed" against that of a refined oil or a reference material that contained only cis double bonds. A single-bounce horizontal attenuated total reflection cell that requires 50 mu L of undiluted test samples was used for oils, melted fats, or their methyl esters. For fatty acid methyl esters, the reproducibility relative standard deviations were in the range of 0.9 to 18.46% for 39.08 to 3.41% trans, determined as methyl elaidate per total fatty acid methyl esters. For five pairs of triacylglycerol blind duplicates, the reproducibility and repeatability relative standard deviations were in the ranges of 1.62 to 18.97%, and 1.52 to 13.26%, respectively, for 39.12 to 1.95% trans, determined as trielaidin per total triacylglycerols. Six pairs of spiked triacylglycerol blind duplicates (quality assurance standards) exhibited high accuracy in the range of 0.53 to 40.69% trans and averaged a low bias of 1.3%. These statistical analysis results were compared to those collaboratively obtained by the recently adopted AOCS Cd14-95 and AOAC 994.34 Infrared Official Methods. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. Lipton, Baltimore, MD 21229 USA. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS-717, Washington, DC 20204 USA. NR 24 TC 9 Z9 9 U1 0 U2 1 PU AMER OIL CHEMISTS SOC 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 MAR PY 1998 VL 75 IS 3 BP 353 EP 358 DI 10.1007/s11746-998-0052-5 PG 6 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA ZD910 UT WOS:000072737600005 ER PT J AU Mossoba, MM Yurawecz, MP Roach, JAG AF Mossoba, MM Yurawecz, MP Roach, JAG TI Confirmation of trans 18 : 1 fatty isomers SO JOURNAL OF THE AMERICAN OIL CHEMISTS SOCIETY LA English DT Letter ID LIQUID-CHROMATOGRAPHY; ACIDS C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. 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 7 TC 0 Z9 0 U1 0 U2 0 PU AMER OIL CHEMISTS SOC 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 MAR PY 1998 VL 75 IS 3 BP 423 EP 423 DI 10.1007/s11746-998-0063-2 PG 1 WC Chemistry, Applied; Food Science & Technology SC Chemistry; Food Science & Technology GA ZD910 UT WOS:000072737600016 ER PT J AU Lopez, H Harris, KM AF Lopez, H Harris, KM TI Ultrasound interactions with free silicone in a tissue-mimicking phantom SO JOURNAL OF ULTRASOUND IN MEDICINE LA English DT Article DE breast ultrasonography; silicone; breast implants; silicone leakage ID BREAST IMPLANT RUPTURE; MAMMOGRAPHY; DIAGNOSIS; US; SPECKLE AB This study attempts to explain the physical basis for the sonographic appearance of different stages of free silicone in breast tissue by laboratory simulations. A tissue-mimicking breast phantom was constructed, into which silicone inclusions were introduced, to simulate various forms of silicone leakage within the body. These simulations suggest that silicone leakage into surrounding body tissues can cause three primary physical interactions with an ultrasound beam: (1) distortions due to changes in speed of sound; (2) refraction, causing a "lens" effect; and (3) multiple scattering, producing the "snowstorm" effect described previously as a signature pattern for detection of silicone migration in breast tissue. C1 US FDA, US Dept HHS, CDRH, DPS,HAB, Rockville, MD 20850 USA. Univ Pittsburgh, Magee Womens Hosp, Sch Med, Pittsburgh, PA 15213 USA. RP Lopez, H (reprint author), US FDA, US Dept HHS, CDRH, DPS,HAB, 9200 Corp Blvd,Mail Code HFZ-132, Rockville, MD 20850 USA. NR 17 TC 6 Z9 6 U1 0 U2 0 PU AMER INST ULTRASOUND MEDICINE PI LAUREL PA SUBSCRIPTION DEPT, 14750 SWEITZER LANE, STE 100, LAUREL, MD 20707-5906 USA SN 0278-4297 J9 J ULTRAS MED JI J. Ultrasound Med. PD MAR PY 1998 VL 17 IS 3 BP 163 EP 170 PG 8 WC Acoustics; Radiology, Nuclear Medicine & Medical Imaging SC Acoustics; Radiology, Nuclear Medicine & Medical Imaging GA YZ096 UT WOS:000072219900006 PM 9514168 ER PT J AU Jackson, AM Ivshina, AV Senko, O Kuznetsova, A Sundan, A O'Donnell, MA Clinton, S Alexandroff, AB Selby, PJ James, K Kuznetsov, VA AF Jackson, AM Ivshina, AV Senko, O Kuznetsova, A Sundan, A O'Donnell, MA Clinton, S Alexandroff, AB Selby, PJ James, K Kuznetsov, VA TI Prognosis of intravesical Bacillus Calmette-Guerin therapy for superficial bladder cancer by immunological urinary measurements: Statistically weighted syndromes analysis SO JOURNAL OF UROLOGY LA English DT Article DE bladder cancer; BCG immunotherapy; pattern recognition; ICAM-1; CD14; TNF; prognosis ID TUMOR-NECROSIS-FACTOR; INTERCELLULAR-ADHESION MOLECULE-1; EVANS BCG THERAPY; INTERFERON-GAMMA; ICAM-1 EXPRESSION; CARCINOMA INSITU; NEURAL NETWORKS; SOLUBLE CD14; FACTOR-ALPHA; CELL-LINES AB Purpose: The goal of this research was to discover new biological indicators in urine which could be used for short-term prognosis of local Bacillus Calmette-Guerin (BCG) therapy outcome in patients with superficial bladder cancer. Patients and Methods: We measured and statistically evaluated soluble immunological molecules in urine from bladder cancer patients (n = 34) receiving BCG intravesically. Urine was collected following each of 6 weekly treatments, processed and assayed. The data base included measurements of interleukin-1 (IL-1), IL-2, IL-4, IL-6, IL-8, IL-10, IL-12, soluble intercellular adhesion molecule-1 (sICAM-1), tumour necrosis factor-alpha (TNF alpha), soluble CD14 (sCD14), interferon-gamma (IFN gamma), CM-CSF, volume of urine and its pH. The clinical response was evaluated by urine histology and random quadrant biopsy 3 months after the start of therapy. Patients were divided into 2 groups, with good and poor therapeutic effect. The initial complete response rate was 62% (21/34). The data base was analyzed using traditional multivariate statistical methods and a pattern recognition method which deals with combinatorial-statistical analysis (statistically weighted syndromes (SWS) method) of the gradated features. The SWS method is capable of identifying robust patterns in small "fuzzy" sets with high dimensional objects and some missing values. Results: Only one parameter gave significant differences at p<0.05, GM-CSF at instillation 6. Repeated measurement analysis of variance, backward stepwise multiple logistic regression and linear discriminant analysis failed to show any significance. However, significant differences in the structure of correlation between features in the groups with and without therapeutic effect were observed and four highly informative variables (the masses of sICAM-1, TNF alpha, sCD14 and pH) relating to 5(th)-6(th) installations were selected by SWS. These features provided accurate individual prediction of therapeutic outcome for all our patients. Cross-validation analysis and computer simulation showed the statistically significant stability of the prediction. Conclusion: We have selected a set of urinary variables that could be considered as a perspective combination of indicators (syndromes) of outcome of pre-operation BCG therapy of patients with superficial bladder cancer. A larger patient database will provide testing and evaluation of the biological and clinical significance of selected features. The computational syndrome-disease approach should be applicable for the solution of decision-making problems for management of cancer. C1 Univ Leeds, Imperial Canc Res Fund, Canc Med Res Unit, Leeds, W Yorkshire, England. Univ Edinburgh, Dept Surg, Edinburgh EH8 9YL, Midlothian, Scotland. Inst Biochem Phys, Moscow, Russia. NCI, Frederick Canc & Dev Ctr, Frederick, MD USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD USA. Russian Acad Sci, Ctr Comp, Moscow, Russia. Univ Trondheim, Canc Res Inst, N-7034 Trondheim, Norway. Beth Israel Hosp, Dept Urol Surg, Boston, MA USA. Dana Farber Canc Inst, Boston, MA 02115 USA. RP Jackson, AM (reprint author), St James Univ Hosp, Imperial Canc Res Fund, Canc Med Res Unit, Beckett St, Leeds LS9 7TF, W Yorkshire, England. RI Jackson, Andrew/I-5929-2013 OI Jackson, Andrew/0000-0003-4739-4804 NR 61 TC 37 Z9 38 U1 0 U2 3 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-5347 J9 J UROLOGY JI J. Urol. PD MAR PY 1998 VL 159 IS 3 BP 1054 EP 1063 DI 10.1016/S0022-5347(01)63835-7 PG 10 WC Urology & Nephrology SC Urology & Nephrology GA YW252 UT WOS:000071913700146 PM 9474231 ER PT J AU Dawson, R Marschall, EG Chan, KC Millard, WJ Eppler, B Patterson, TA AF Dawson, R Marschall, EG Chan, KC Millard, WJ Eppler, B Patterson, TA TI Neurochemical and neurobehavioral effects of neonatal administration of beta-N-methylamino-L-alanine and 3,3 '-iminodipropionitrile SO NEUROTOXICOLOGY AND TERATOLOGY LA English DT Article DE beta-N-methylamino-L-alanine; 3,3 '-iminodipropionitrile; excitatory amino acids; developmental neurotoxicity; amyotrophic lateral sclerosis ID AMYOTROPHIC-LATERAL-SCLEROSIS; CEREBELLAR GRANULE CELLS; SEX-SPECIFIC IMPAIRMENT; GLUTAMATE-TREATED RATS; D-ASPARTATE RECEPTORS; AMINO-ACID RECEPTORS; BLOOD-BRAIN-BARRIER; NERVE GROWTH-FACTOR; MONOSODIUM GLUTAMATE; SPINAL-CORD AB Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease that is characterized by a loss of motor neurons in the spinal cord, brain stem, and cortex The present study examined the neurochemical and neurobehavioral consequences of the neonatal administration of IDPN and BMAA, two neurotoxins previously considered as experimental models of ALS. Sprague-Dawley rat pups (male and female) were injected SC with IDPN or BMAA. The following treatment groups (n = 5-14 per group) were studied: IDPN [100 mg/kg on postnatal days (PNDs) 2, 4, and 6], BMAA-A (500 mg/kg PND 5 only), BMAA-B (500 mg/kg PND 2 and 5), and BMAA-C (100 mg/kg PND 2 and 5). Neurobehavioral testing was performed and the rats were sacrificed at 101 days of age. Monoamine and amino acid content was measured by HPLC in brain regions and the spinal cord. IDPN treatment impaired the righting reflex and decreased forepaw suspension times. BMAA-A and BMAA-B males exhibited an increase in open field behavior. The hindlimb splay of BMAA-A females was increased. Other significant behavioral and endocrine effects were also seen with neonatal IDPN or BMAA treatment. IDPN females had increased spinal cord content of norepinephrine (NE), serotonin, and 5-hydroxyindoleacetic acid (5-HIAA). IDPN males had no alterations in spinal cord content of NE or Glu, but serotonin and 5-HIAA content were increased. BMAA-A and BMAA-B males also had elevated spinal cord 5-HIAA content whereas females were unaffected. Glu and Asp content in the spinal cord was elevated in the female BMAA-C group. Monoamines were also altered in the cerebellum, mediobasal hypothalamus, and hippocampus by IDPN and BMAA treatment. az-Adrenergic binding sites were increased in the spinal cord by IDPN and in the cerebellum by BMAA treatment. The results of this study clearly demonstrated that both IDPN and BMAA given neonatally can produce changes in motor function and spinal cord neurochemistry, although the pattern of the effects is both treatment and sex dependent. Neonatal exposure to either IDPN or BMAA resulted in permanent changes in adult neurochemistry that may be related to reorganizational effects induced by toxin-mediated neuroplasticity in developing neurons. (C) 1998 Elsevier Science Inc. C1 Univ Florida, Coll Pharm, Dept Pharmacodynam, Gainesville, FL 32610 USA. US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Dawson, R (reprint author), Univ Florida, Coll Pharm, Dept Pharmacodynam, JHMHC Box 100487, Gainesville, FL 32610 USA. FU NIA NIH HHS [T32 AG00196] NR 77 TC 18 Z9 19 U1 1 U2 5 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0892-0362 J9 NEUROTOXICOL TERATOL JI Neurotoxicol. Teratol. PD MAR-APR PY 1998 VL 20 IS 2 BP 181 EP 192 DI 10.1016/S0892-0362(97)00078-0 PG 12 WC Neurosciences; Toxicology SC Neurosciences & Neurology; Toxicology GA ZB813 UT WOS:000072510600008 PM 9536463 ER PT J AU Ball, LK Evans, G Bostrom, A AF Ball, LK Evans, G Bostrom, A TI Risky business: Challenges in vaccine risk communication SO PEDIATRICS LA English DT Article; Proceedings Paper CT Annual Meeting of the American-Academy-of-Pediatrics CY OCT 25-30, 1996 CL BOSTON, MASSACHUSETTS SP Amer Acad Pediat ID PERTUSSIS VACCINATION; DECISIONS; BIAS C1 US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, Rockville, MD 20852 USA. US Hlth Resources & Serv Adm, Natl Vaccine Injury Compensat Program, Dept Hlth & Human Serv, Rockville, MD 20857 USA. Georgia Inst Technol, Sch Publ Policy, Atlanta, GA 30332 USA. RP Ball, LK (reprint author), US FDA, Ctr Biol Evaluat & Res, Off Vaccines Res & Review, HFM 475,1401 Rockville Pike, Rockville, MD 20852 USA. NR 52 TC 102 Z9 102 U1 1 U2 18 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 MAR PY 1998 VL 101 IS 3 BP 453 EP 458 DI 10.1542/peds.101.3.453 PG 6 WC Pediatrics SC Pediatrics GA ZA433 UT WOS:000072362800021 PM 9481013 ER PT J AU Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R Peter, G Donowitz, LG Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B Shira, JE Diamond, J O'Connor, ME Packard, JM Reynolds, M Schaeffer, HA Steinhart, CM English, CS Perkins, MT Maruca, R Wilson, JM Wiener, E VanOstenberg, PR Striker, T Raphaely, RC AF Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R Peter, G Donowitz, LG Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR Schwartz, B Shira, JE Diamond, J O'Connor, ME Packard, JM Reynolds, M Schaeffer, HA Steinhart, CM English, CS Perkins, MT Maruca, R Wilson, JM Wiener, E VanOstenberg, PR Striker, T Raphaely, RC TI The revised CDC guidelines for isolation precautions in hospitals: Implications for pediatrics SO PEDIATRICS LA English DT Article AB The Hospital Infection Control Practices Advisory Committee of the US Centers for Disease Control and Prevention and the National Center for Infectious Diseases have issued new isolation guidelines that replace earlier recommendations. Modifications of these guidelines for the care of hospitalized infants and children should be considered specifically as they relate to glove use for routine diaper changing, private room isolation, and common use areas such as playrooms and schoolrooms. These new guidelines replace those provided in the 1994 Red Book and have been incorporated into the 1997 Red Book. C1 Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. Amer Acad Pediat, Comm Hosp Care, Elk Grove Village, IL 60007 USA. Natl Vaccine Program Off, Rockville, MD USA. US FDA, Rockville, MD 20857 USA. Amer Thorac Soc, New York, NY USA. Canadian Paediat Soc, Ottawa, ON, Canada. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. NIH, Bethesda, MD USA. Amer Acad Family Phys, Kansas City, MO 64114 USA. Amer Hosp Assoc, Chicago, IL USA. Natl Assoc Childrens Hosp & Related Inst, Alexandria, VA USA. Joint Commiss Accreditat Healthcare Org, Chicago, IL USA. Amer Acad Pediat, Sect Anesthesiol, Elk Grove Village, IL USA. RP Halsey, NA (reprint author), Amer Acad Pediat, Comm Infect Dis, Elk Grove Village, IL 60007 USA. NR 2 TC 0 Z9 0 U1 0 U2 1 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD MAR PY 1998 VL 101 IS 3 BP art. no. EP e13 PG 4 WC Pediatrics SC Pediatrics GA ZA433 UT WOS:000072362800034 ER PT J AU Endrenyi, L Csizmadia, F Tothfalusi, L Balch, AH Chen, ML AF Endrenyi, L Csizmadia, F Tothfalusi, L Balch, AH Chen, ML TI The duration of measuring partial AUCs for the assessment of bioequivalence SO PHARMACEUTICAL RESEARCH LA English DT Article DE bioequivalence; partial AUC; absorption rate; experimental design; crossover trials ID ABSORPTION RATE; PERFORMANCE; EXTENT AB Purpose. To determine favourable sampling conditions for assessing bioequivalence by the comparison of partial AUCs in the early phase of concentration-time profiles. Methods. Two-period crossover trials were simulated, They assumed a wide range of the ratios of absorption rate constants of the test (T) and reference (R) formulations (k(aT)/k(aR)). Averages and standard deviations of the corresponding ratios of simulated partial AUCs (AUC(pT)/AUC(pR)) were determined together with the statistical power of assessing bioequivalence, i.e., the percentage of simulated trials in which bioequivalence was declared. Results. The power for stating bioequivalence was high when AUG(p) was recorded until the earlier rather than the later of two peaks in each subject. Similarly, power was comparatively high when AUC(p) was measured until the time of the reference peak instead of multiples of this time. Power was high also when AUC(p) was determined until the fixed true, population mean time of the reference formulation instead of multiples of this time. The pattern for the kinetic sensitivity parallelled that found for the power, while the standard deviations changed generally in the opposite direction. Conclusions. The effectiveness (power) of evaluating bioequivalence in the early phase of concentration-time profiles by partial AUCs generally decreases when the duration for measuring the metric is extended. Among the investigated designs, determination of partial AUCs until the earlier of two peaks in each subject is the most powerful. C1 Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. US FDA, Ctr Drug Evaluat & Res, Rockville, MD USA. RP Endrenyi, L (reprint author), Univ Toronto, Dept Pharmacol, Toronto, ON M5S 1A8, Canada. RI Tothfalusi, Laszlo/J-9301-2012 NR 12 TC 15 Z9 15 U1 0 U2 0 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD MAR PY 1998 VL 15 IS 3 BP 399 EP 404 DI 10.1023/A:1011916113082 PG 6 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZG048 UT WOS:000072960400006 PM 9563068 ER PT J AU Eddington, ND Marroum, P Uppoor, R Hussain, A Augsburger, L AF Eddington, ND Marroum, P Uppoor, R Hussain, A Augsburger, L TI Development and internal validation of an in vitro in vivo correlation for a hydrophilic metoprolol tartrate extended release tablet formulation SO PHARMACEUTICAL RESEARCH LA English DT Article DE convolution; metoprolol; validation; dissolution; prediction errors ID DOSAGE FORMS; BIOAVAILABILITY AB Purpose. To develop and validate internally an in vitro-in vivo correlation (IVIVC) for a hydrophilic matrix extended release metoprolol tablet. Methods. In vitro dissolution of the metoprolol tablets was examined using the following methods: Apparatus II, pH 1.2 & 6.8 at 50 rpm and Apparatus I, pH 6.8, at 100 and 150 rpm. Seven healthy subjects received three metoprolol formulations (100 mg): slow, moderate, fast releasing and an oral solution (50 mg). Serial blood samples were collected over 48 hours and analyzed by a validated HPLC assay using fluorescence detection. The fl metric (similarity factor) was used to analyze the dissolution data. Correlation models were developed using pooled fraction dissolved (FRD) and fraction absorbed (FRA) data from various combinations of the formulations. Predicted metoprolol concentrations were obtained by convolution of the in vivo dissolution rates. Prediction errors were estimated for C-max and AUC to determine the validity of the correlation. Results. Apparatus I operated at 150 rpm, and pH of 6.8 was found to be the most discriminating dissolution method. There was a significant linear relationship between FRD and FRA when using either two or three of the formulations. An average percent prediction error for C-max and AUC for all formulations of less than 10% was found for all IVIVC models. Conclusions. The relatively low prediction errors for C-max and AUC observed strongly suggest that the metoprolol IVIVC models are valid. The average percent prediction error of less than 10% indicates that the correlation is predictive and allows the associated dissolution data to be used as a surrogate for bioavailability studies. C1 Univ Maryland, Pharmacokinet Biopharmaceut Lab, Baltimore, MD 21201 USA. Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. US FDA, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Eddington, ND (reprint author), Univ Maryland, Pharmacokinet Biopharmaceut Lab, 100 Penn St,AHB, Baltimore, MD 21201 USA. EM eddingto@pharmacy.ab.umd.edu NR 16 TC 48 Z9 49 U1 1 U2 10 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD MAR PY 1998 VL 15 IS 3 BP 466 EP 473 DI 10.1023/A:1011988601696 PG 8 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZG048 UT WOS:000072960400017 PM 9563079 ER PT J AU Davis, H AF Davis, H TI Use of computerized health claims data to monitor compliance with antibiotic prophylaxis in sickle cell disease SO PHARMACOEPIDEMIOLOGY AND DRUG SAFETY LA English DT Article DE sickle cell anemia; health services research; patient compliance; penicillins ID HEMOGLOBIN SC DISEASE; ORAL PENICILLIN; CHILDREN; ANEMIA AB Objective-To demonstrate how computerized claims data can be used to identify children with sickle cell disease probably having low compliance with antibiotic prophylaxis of pneumococcal disease. Methods-The study included under-5-year-old children with sickle cell disease who were on antibiotic prophylaxis and covered by Medicaid in Michigan (N = 158), Missouri (N = 64), and New York (N = 297). Medicaid pharmacy claims from 10-month periods were used to estimate the total days' supply of antibiotics dispensed for each child. Low compliance was defined as a ratio less than 0.33 for the child's estimated total days' supply of antibiotics divided by days in the child's study period. Two slightly different methods of estimating antibiotic supplies were used to generate a low and high estimate of the percentage of children having low compliance. Results-Low and high estimates of the percentage of children having low compliance were 20% and 25% in Michigan, 19% and 31% in Missouri, and 16% and 24% in New York. With each method of estimating antibiotic supplies, low compliance was not associated with age in any state. Conclusions-Computerized claims data can be used, potentially by Medicaid programs and managed care organizations, to identify children with sickle cell disease who probably have low compliance with antibiotic prophylaxis. (C) 1998 John Wiley & Sons, Ltd. C1 US FDA, Off Epidemiol & Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Davis, H (reprint author), US FDA, Off Epidemiol & Biostat, Ctr Drug Evaluat & Res, 5600 Fishers Lane,Room 15-B-18,HFD-733, Rockville, MD 20857 USA. NR 18 TC 8 Z9 8 U1 0 U2 1 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 1053-8569 J9 PHARMACOEPIDEM DR S JI Pharmacoepidemiol. Drug Saf. PD MAR-APR PY 1998 VL 7 IS 2 BP 107 EP 112 DI 10.1002/(SICI)1099-1557(199803/04)7:2<107::AID-PDS323>3.0.CO;2-G PG 6 WC Public, Environmental & Occupational Health; Pharmacology & Pharmacy SC Public, Environmental & Occupational Health; Pharmacology & Pharmacy GA ZQ366 UT WOS:000073854000004 PM 15073734 ER PT J AU Goldman, SA Kennedy, DL AF Goldman, SA Kennedy, DL TI MEDWATCH: FDA's medical products reporting program - A joint effort toward improved public health SO POSTGRADUATE MEDICINE LA English DT Editorial Material C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Goldman, SA (reprint author), US FDA, Off Commissioner, 5600 Fishers Lane,HF-2,Room 9-57, Rockville, MD 20857 USA. NR 9 TC 5 Z9 5 U1 0 U2 0 PU MCGRAW HILL HEALTHCARE PUBLICATIONS PI MINNEAPOLIS PA 4530 WEST 77TH ST, MINNEAPOLIS, MN 55435-5000 USA SN 0032-5481 J9 POSTGRAD MED JI Postgrad. Med. PD MAR PY 1998 VL 103 IS 3 BP 13 EP 16 PG 4 WC Medicine, General & Internal SC General & Internal Medicine GA ZB003 UT WOS:000072425100002 PM 9519028 ER PT J AU Sheehan, DM AF Sheehan, DM TI The Third International Conference on Phytoestrogens SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Editorial Material C1 US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. RP Sheehan, DM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD MAR PY 1998 VL 217 IS 3 BP 240 EP 240 PG 1 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YX605 UT WOS:000072057300001 ER PT J AU Baker, ME Medlock, KL Sheehan, DM AF Baker, ME Medlock, KL Sheehan, DM TI Flavonoids inhibit estrogen binding to rat alpha-fetoprotein SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT 3rd International Symposium on Phytoestrogens CY DEC 03-06, 1995 CL LITTLE ROCK, ARKANSAS ID 11-BETA-HYDROXYSTEROID DEHYDROGENASE; LIGANDS AB There is considerable interest in the role(s) of plant-derived compounds such as bioflavonoids in regulating steroid hormone action in mammals, and in particular, the possible effects of the bioflavonoids on the growth of steroid-dependent breast and prostate tumors and on possible abnormal development of steroid-sensitive tissues. Studies of the hormone-like actions of bioflavonoids often use fetal or neonatal rats, which contain high levels of serum alpha-fetoprotein (AFP), a protein that binds estradiol with a K-d - 5 x 10(-9) M. Interaction of bioflavonoids with AFP could affect the availability of estrogens to estrogen-responsive cells, as well as the actions of bioflavonoids. These considerations motivated us to study the effect of several flavonoids (quercetin, rutin, naringenin, chrysin, apigenin, kaempferol, myricetin, morin, fisetin) and isoflavonoids (daidzein, genistein) on estrogen binding to rat AFP. We found that naringenin, a flavanone, and quercetin and kaempferol, flavonols, inhibit estrogen binding to AFP with apparent K(d)s of about 5 x 10(-7) M. To our surprise, the two isoflavonoids, daidzein and genistein, have K(d)s of about 5 x 10(-6) M for AFP. This to-fold difference in affinity for AFP between flavonoids and isoflavonoids suggests that AFP has a specificity for the flavonoid structure. Moreover, the affinities of bioflavonoids for rat AFP are sufficiently high to suggest that flavonoids and isoflavonoids could modulate estradiol and estrone binding to rat AFP in vivo, when present at dietary levels. Additionally, the potency of the plant estrogens may be altered by binding to AFP. The flavonoids that we tested have different hydroxyl and glucoside substituents on the A, B, and C rings, which allows us to define some of the spatial requirements for binding to AFP. We find that 5,7-hydroxyl groups in ring A and a 4'-hydroxyl group in ring B are important for binding to AFP. This information, combined with molecular modeling studies, may elucidate the molecular basis for recognition of flavonoids and estrogens by AFP. Also, these findings indicate that the flavonoid levels in the diet need to be considered in studies of the effects of various xenobiotics and endocrine manipulations on experimental animals, particularly during development when serum estrogen binding protein concentrations are often elevated. Finally, bioflavonoids should be useful tools for understanding the variety of estrogen actions initiated by different structural classes of estrogens. C1 US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. Univ Calif San Diego, Dept Med 0623B, La Jolla, CA 92093 USA. Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. RP Sheehan, DM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. OI Baker, Michael/0000-0003-4387-3269 NR 25 TC 28 Z9 29 U1 0 U2 0 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD MAR PY 1998 VL 217 IS 3 BP 317 EP 321 PG 5 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YX605 UT WOS:000072057300012 PM 9492341 ER PT J AU Sheehan, DM AF Sheehan, DM TI Herbal medicines, phytoestrogens and toxicity: Risk: Benefit considerations SO PROCEEDINGS OF THE SOCIETY FOR EXPERIMENTAL BIOLOGY AND MEDICINE LA English DT Article; Proceedings Paper CT 3rd International Symposium on Phytoestrogens CY DEC 03-06, 1995 CL LITTLE ROCK, ARKANSAS ID VENO-OCCLUSIVE DISEASE; ENDOMETRIAL CANCER; BREAST-CANCER; EARLY INFANCY; HEALTH; TEAS; CHILDREN; FORMULA; TOXINS AB There are several suggested health benefits of phytoestrogens, particularly those found in soy products, Herbal medicines are also widely thought to confer health benefits, Additionally, drugs are prescribed to improve human health, but unlike phytoestrogens and herbal medicines, toxicities are defined in experimental animals and monitored in humans before and after marketing, Knowledge of toxicity is crucial to decrease the risk:benefit ratio; this knowledge defines appropriate conditions for use and strategies for development of safer products. However, our awareness of the toxicity of herbal medicines and phytoestrogen-containing foods is dramatically limited compared to drugs, Some aspects of the toxicity of herbal medicines are briefly reviewed; it is concluded that virtually all of our knowledge is derived from human exposures leading to acute toxicities, Importantly, detection of toxicity is sporadic, and little information is available from prior animal experimentation, Additionally, well-organized monitoring of human populations (as occurs for drugs) is virtually nonexistent. Important toxicities with long latencies are particularly difficult to associate with a causative agent during or even after large scale exposures, as exemplified by tobacco smoking and lung cancer; estrogen replacement therapy and endometrial cancer; diethylstilbestrol and reproductive tract cancers; and fetal alcohol exposure and birth defects, These considerations suggest that much closer study in experimental animals and human populations exposed to phytoestrogen-containing products, and particularly soy-based foods, is necessary, Among human exposures, infant soy formula exposure appears to provide the highest of all phytoestrogen doses, and this occurs during development, often the most sensitive life-stage for induction of toxicity, Large, carefully controlled studies in this exposed infant population are a high priority. C1 US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. RP Sheehan, DM (reprint author), US FDA, Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. NR 64 TC 47 Z9 47 U1 0 U2 2 PU BLACKWELL SCIENCE INC PI MALDEN PA 350 MAIN ST, MALDEN, MA 02148 USA SN 0037-9727 J9 P SOC EXP BIOL MED JI Proc. Soc. Exp. Biol. Med. PD MAR PY 1998 VL 217 IS 3 BP 379 EP 385 PG 7 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YX605 UT WOS:000072057300022 PM 9492351 ER PT J AU Picciolo, GL Hellman, KB Johnson, PC AF Picciolo, GL Hellman, KB Johnson, PC TI Meeting report: Tissue engineered medical products standards: The time is ripe SO TISSUE ENGINEERING LA English DT Editorial Material C1 US FDA, InterCtr Tissue Engn Working Grp, Rockville, MD 20850 USA. Pittsburgh Tissue Engn Initiat, Pittsburgh, PA 15219 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1076-3279 J9 TISSUE ENG JI Tissue Eng. PD SPR PY 1998 VL 4 IS 1 BP 5 EP 7 DI 10.1089/ten.1998.4.5 PG 3 WC Cell & Tissue Engineering SC Cell Biology GA ZF720 UT WOS:000072925300003 ER PT J AU Altekruse, SF Swerdlow, DL Wells, SJ AF Altekruse, SF Swerdlow, DL Wells, SJ TI Factors in the emergence of food borne diseases SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID ESCHERICHIA-COLI O157-H7; SALMONELLA-ENTERITIDIS INFECTIONS; HUMAN-IMMUNODEFICIENCY-VIRUS; UNITED-STATES; APPLE CIDER; OUTBREAK; EPIDEMIOLOGY; CHOLERA; BRUCELLOSIS; CALIFORNIA AB Food borne diseases are an important public health problem. Over the past two decades, the epidemiology of food borne diseases has changed rapidly as a consequence of changes in the social environment and the ability of pathogens to adapt to new niches. Several newly recognized pathogens have emerged and well-recognized pathogens have increased in prevalence or become associated with new food vehicles. Several factors have contributed to the changing patterns of food borne diseases, and addressing food borne diseases will require rapid surveillance and effective prevention strategies. This article examines these factors and briefly addresses prevention and control of food borne diseases. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, Atlanta, GA 30333 USA. US FDA, Ctr Dis Control & Prevent, Atlanta, GA USA. USDA, Anim Plant Hlth Inspect Serv, Ctr Epidemiol & Anim Hlth, Ft Collins, CO USA. RP Altekruse, SF (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Foodborne & Diarrheal Dis Branch, Div Bacterial & Mycot Dis, 1600 Clifton Rd A38, Atlanta, GA 30333 USA. NR 78 TC 11 Z9 13 U1 0 U2 3 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1998 VL 14 IS 1 BP 1 EP + PG 16 WC Veterinary Sciences SC Veterinary Sciences GA ZF288 UT WOS:000072882500002 PM 9532663 ER PT J AU Tollefson, L AF Tollefson, L TI Microbial food borne pathogens - Preface SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Editorial Material C1 US FDA, Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20855 USA. RP Tollefson, L (reprint author), US FDA, Ctr Vet Med, Off Surveillance & Compliance, HFV-200,7500 Standish Pl, Rockville, MD 20855 USA. NR 1 TC 0 Z9 0 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 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1998 VL 14 IS 1 BP XIII EP XIV PG 2 WC Veterinary Sciences SC Veterinary Sciences GA ZF288 UT WOS:000072882500001 ER PT J AU Ekperigin, HE Nagaraja, KV AF Ekperigin, HE Nagaraja, KV TI Salmonella SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID PELLETING PROCESS; ENVIRONMENT; INFECTION; TURKEYS AB All food animals are susceptible to infection with Salmonella, a genus of gram negative, nonspore-forming, usually motile, facultative anaerobic bacilli belonging to the family Enterobacteriaceae. Salmonella are differentiated into over 2200 serologically distinct types (serotypes) based on differences in somatic, flagellar, and capsular antigens. Infection with Salmonella may or may not lead to a sometimes fatal salmonellosis, a disease that can remain localized in the gastrointestinal tract as gastro-enteritis, or become generalized as a septicemia and affect several organ systems. Infected food animals that do not develop salmonellosis, and those that recover from the disease, become carriers of Salmonella and serve as sources of infection to humans and other animals. Apart from being a source of Salmonella food poisoning for humans, Salmonella-contaminated food animal carcasses are also a concern because they are a source of antibiotic-resistant Salmonella. C1 US FDA, Ctr Vet Med, Div Anim Feeds, Rockville, MD 20855 USA. Univ Minnesota, Coll Vet Med, Dept Pathobiol, St Paul, MN 55108 USA. RP Ekperigin, HE (reprint author), US FDA, Ctr Vet Med, Div Anim Feeds, Feed Safety Team,HFV-222,7500 Standish Pl, Rockville, MD 20855 USA. NR 29 TC 44 Z9 47 U1 0 U2 5 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1998 VL 14 IS 1 BP 17 EP + PG 15 WC Veterinary Sciences SC Veterinary Sciences GA ZF288 UT WOS:000072882500003 PM 9532664 ER PT J AU Altekruse, SF Swerdlow, DL Stern, NJ AF Altekruse, SF Swerdlow, DL Stern, NJ TI Campylobacter jejuni SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID GUILLAIN-BARRE-SYNDROME; YERSINIA-ENTEROCOLITICA; BROILER-CHICKENS; RISK-FACTORS; PREVALENCE; COLONIZATION; ENTERITIS; POULTRY; SALMONELLA; COLI AB Campylobacter jejuni is the most common food borne bacterial pathogen and leading cause of food borne disease in humans in the United States and other industrialized nations. Approximately four million cases of human campylobacteriosis occur each year in the United States. Although the majority of cases consist of limited diarrheal illness, severe sequelae can affect a small portion of patients with campylobacteriosis that may include reactive arthritis and Guillain-Barre syndrome. Animal reservoirs primarily include poultry (C. jejuni) and swine (C. coli). Pathogen reduction during poultry processing and safe handling of raw poultry in the kitchen are needed to prevent illness. C1 Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Foodborne & Diarrheal Dis Branch, Atlanta, GA 30333 USA. US FDA, Ctr Dis Control & Prevent, Atlanta, GA USA. USDA ARS, Russell Res Ctr, Poultry Microbiol Safety Res Unit, Athens, GA 30613 USA. RP Altekruse, SF (reprint author), Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Foodborne & Diarrheal Dis Branch, 1600 Clifton Rd A38, Atlanta, GA 30333 USA. NR 68 TC 42 Z9 42 U1 0 U2 2 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1998 VL 14 IS 1 BP 31 EP + PG 11 WC Veterinary Sciences SC Veterinary Sciences GA ZF288 UT WOS:000072882500004 PM 9532665 ER PT J AU Godon, KAH Honstead, J AF Godon, KAH Honstead, J TI Transmissible spongiform encephalopathies in food animals - Human food safety and animal feed safety concerns for veterinarians SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID NATURAL SCRAPIE; SUFFOLK SHEEP; PRP GENOTYPE; AGENT; INFECTION; SURVIVAL; DISEASE; TISSUES; BRAIN; VIRUS AB This article presents a brief overview of transmissible spongiform encephalopathies (TSEs) using examples of diseases that provide evidence supporting oral transmission of the agent. Agent theories are described briefly in general terms. Scrapie, bovine spongiform encephalopathy (BSE), chronic wasting disease, and transmissible mink encephalopathy are discussed to improve disease recognition by the food animal practitioner. Control programs for scrapie and BSE are described and the role of the veterinarian in animal feed and human food safety is related to TSEs. C1 US FDA, Ctr Vet Med, Div Epidemiol & Surveillance, Rockville, MD 20855 USA. RP Godon, KAH (reprint author), US FDA, Ctr Vet Med, Div Epidemiol & Surveillance, 7500 Standish Pl, Rockville, MD 20855 USA. NR 35 TC 4 Z9 5 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1998 VL 14 IS 1 BP 49 EP + PG 24 WC Veterinary Sciences SC Veterinary Sciences GA ZF288 UT WOS:000072882500006 PM 9532667 ER PT J AU Miller, MA Paige, JC AF Miller, MA Paige, JC TI Other food borne infections SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID YERSINIA-ENTEROCOLITICA O-3; HUMAN BRUCELLOSIS; UNITED-STATES; SAUDI-ARABIA; CYCLOSPORA; OUTBREAK; PATHOGEN; CRYPTOSPORIDIOSIS; EPIDEMIOLOGY; TRANSMISSION AB This article presents an update of several emerging or reemerging pathogens: Yersinia, Cryptosporidia, Cyclospora, Brucella, and Mycobacterium. All of these zoonotic pathogens show evidence of food borne transmission. Yersiniosis is presented as an emerging pathogen that has as its major route of transmission preparation and consumption of pork products. New evidence is presented that supports the transmission of brucellosis via the food chain, especially through contaminated raw milk and cheese. While TB has limited transmission via raw milk, it is highlighted as a reemerging infection due to the development of multiple drug resistance. Public health veterinarians stand in an excellent position to recognize these emerging diseases and apply intervention strategies to prevent and control these infections in the future. This article is intended to raise their consciousness as to the management and medical practices that can diminish food borne transmission. C1 US FDA, Ctr Vet Med, Div Epidemiol & Surveillance, Rockville, MD 20855 USA. RP Miller, MA (reprint author), US FDA, Ctr Vet Med, Div Epidemiol & Surveillance, 7500 Standish Pl,HFV-218, Rockville, MD 20855 USA. NR 56 TC 11 Z9 11 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1998 VL 14 IS 1 BP 71 EP + PG 20 WC Veterinary Sciences SC Veterinary Sciences GA ZF288 UT WOS:000072882500007 PM 9532668 ER PT J AU Headrick, ML Tollefson, L AF Headrick, ML Tollefson, L TI Food borne disease summary by food commodity SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID LACTIC-ACID DECONTAMINATION; UNITED-STATES; SALMONELLOSIS; OUTBREAK; IDENTIFICATION; MEAT AB Microbial pathogens may be transmitted to humans via food animals and food animal products. A quick reference table is presented to provide easy access to food safety information related to the major food animal product areas. Included in the table are the pathogens, mode of transmission, public health impact, and control and prevention strategies for poultry, beef, dairy products, and pork. C1 US FDA, Ctr Devices & Radiol Hlth, Div Postmarket Surveillance, Rockville, MD 20850 USA. US FDA, Off Surveillance & Compliance, Rockville, MD 20857 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Headrick, ML (reprint author), US FDA, Ctr Devices & Radiol Hlth, Div Postmarket Surveillance, HFZ-541,1350 Piccard Dr, Rockville, MD 20850 USA. NR 34 TC 6 Z9 6 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 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1998 VL 14 IS 1 BP 91 EP + PG 11 WC Veterinary Sciences SC Veterinary Sciences GA ZF288 UT WOS:000072882500008 PM 9532669 ER PT J AU Greenlees, KJ Machado, J Bell, T Sundlof, SF AF Greenlees, KJ Machado, J Bell, T Sundlof, SF TI Food borne microbial pathogens of cultured aquatic species SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID FRESH-WATER FISH; PLESIOMONAS-SHIGELLOIDES; EDWARDSIELLA-TARDA; VIBRIO-VULNIFICUS; HUMANS; INFECTIONS; SALMONELLA; PREVALENCE; SHELLFISH; DISEASES AB This article provides a broad overview of microbial pathogens associated with marine and fresh water aquatic animals, including Vibrio species, Escherichia coli, Streptococcus iniae, Salmonella species, and Edwardsiella tarda. Historically, cultured fish were not considered important vectors of human pathogens. This situation is changing, partly due to increasing animal densities as a consequence of a rapidly growing industry and partly due to increasing awareness by health care providers of pathogens in aquatic species that may result in human illness. Concerns facing the industry are also discussed along with possible solutions. C1 US FDA, Ctr Vet Med, Div Human Food Safety, Rockville, MD 20855 USA. US FDA, Div Anim Feeds, Rockville, MD 20857 USA. US FDA, Div Therapeut Drugs Food Anim, Rockville, MD 20857 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Greenlees, KJ (reprint author), US FDA, Ctr Vet Med, Div Human Food Safety, 7500 Standish Pl, Rockville, MD 20855 USA. NR 46 TC 10 Z9 10 U1 2 U2 7 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1998 VL 14 IS 1 BP 101 EP + PG 13 WC Veterinary Sciences SC Veterinary Sciences GA ZF288 UT WOS:000072882500009 PM 9532670 ER PT J AU Cooper, J Walker, RD AF Cooper, J Walker, RD TI Listeriosis SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID PHAGE-TYPING SYSTEM; MONOCYTOGENES; MILK; RESISTANCE AB Listeria monocytogenes is ubiquitous in nature and is part of the normal flora of the distal portion of the intestinal tract of numerous animal species. Listeriosis is an emerging food borne disease that is responsible for approximately 1,700 cases of human illness each year and 650 deaths. Listeria is the cause of three main disease entities in animals and humans: neural, visceral, and reproductive. Clinical signs associated with the three forms are discussed along with diagnosis, therapy, prevention, and control. C1 US FDA, Ctr Vet Med, Div Human Food Safety, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. Michigan State Univ, Coll Vet Med, Vet Med Ctr A3, Dept Microbiol, E Lansing, MI 48824 USA. RP Cooper, J (reprint author), US FDA, Ctr Vet Med, Div Human Food Safety, Off New Anim Drug Evaluat, Rockville, MD 20855 USA. NR 28 TC 31 Z9 32 U1 0 U2 1 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1998 VL 14 IS 1 BP 113 EP + PG 14 WC Veterinary Sciences SC Veterinary Sciences GA ZF288 UT WOS:000072882500010 PM 9532671 ER PT J AU Tollefson, L Angulo, FJ Fedorka-Cray, PJ AF Tollefson, L Angulo, FJ Fedorka-Cray, PJ TI National surveillance for antibiotic resistance in zoonotic enteric pathogens SO VETERINARY CLINICS OF NORTH AMERICA-FOOD ANIMAL PRACTICE LA English DT Article ID QUINOLONE RESISTANCE; ANTIMICROBIAL AGENTS; VETERINARY-MEDICINE; CAMPYLOBACTER; SALMONELLA; ANIMALS; HEALTH AB Treatment of food-producing animals with antimicrobial agents that are important in human therapy may present a public health risk by the transfer of resistant zoonotic pathogens from animals to humans. Resistant bacteria can diminish the effectiveness of antibiotics and demand the use of more expensive or less safe alternatives. Ln 1996, the Centers for Disease Control (CDC), United States Department of Agriculture (USDA), and Food and Drug Administration (FDA) established the National Antimicrobial Monitoring System to prospectively monitor changes in antimicrobial susceptibilities of zoonotic pathogens from human and animal clinical specimens, healthy farm animals, and carcasses of food-producing animals at slaughter plants. This article describes the development, implementation, and objectives of the monitoring system and presents initial data generated by the system. C1 US FDA, Ctr Vet Med, Off Surveillance & Compliance, Rockville, MD 20855 USA. Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Foodborne & Diarrheal Dis Branch, Atlanta, GA USA. USDA ARS, Natl Anim Dis Ctr, Ames, IA 50010 USA. RP Tollefson, L (reprint author), US FDA, Ctr Vet Med, Off Surveillance & Compliance, HFV-200,7500 Standish Pl, Rockville, MD 20855 USA. NR 17 TC 61 Z9 63 U1 1 U2 4 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0749-0720 J9 VET CLIN N AM-FOOD A JI Vet. Clin. N. Am.-Food Anim. Pract. PD MAR PY 1998 VL 14 IS 1 BP 141 EP + PG 11 WC Veterinary Sciences SC Veterinary Sciences GA ZF288 UT WOS:000072882500012 PM 9532673 ER PT J AU Kessler, J Muller, J Weir, JP AF Kessler, J Muller, J Weir, JP TI Expression of the human immunodeficiency virus gag gene products by a replication-incompetent herpes simplex virus vector SO VIRUS RESEARCH LA English DT Article DE herpes simplex virus vector; human immunodeficiency virus 1 gag gene; pol gene ID DEFECTIVE MUTANTS; HIV-1 GAG; TYPE-1; PARTICLES; IMMUNIZATION; SEQUENCES; DELIVERY; PROTEASE; RELEASE; PR55GAG AB A recombinant replication-incompetent herpes simplex virus vector (vd120/Gag) that expressed the human immunodeficiency virus 1 gag gene and part of the pol gene that encodes the HIV-1 protease was constructed. Examination of cells infected with vd120/Gag revealed the presence of the Gag polyprotein pr55(gag) by 12 h post-infection, as well as abundant levels of the proteolytically processed 24-kDa capsid protein. Analysis of vector-infected cells and culture supernatant indicated that the majority of the 24-kDa protein remained cell-associated. Although the HIV-1 Gag polyprotein was produced in vd120/Gag-infected cells, there was no evidence of HIV virus-like particle production upon examination of vector-infected cells by transmission electron microscopy. (C) 1998 Elsevier Science B.V. All rights reserved. C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Lab DNA Viruses, 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 26 TC 5 Z9 5 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0168-1702 J9 VIRUS RES JI Virus Res. PD MAR PY 1998 VL 54 IS 1 BP 31 EP 38 DI 10.1016/S0168-1702(98)00004-5 PG 8 WC Virology SC Virology GA ZU836 UT WOS:000074240500004 PM 9660069 ER PT J AU Stibitz, S AF Stibitz, S TI Allelic retrieval: a scheme to facilitate the repeated isolation of a specific segment of the Bordetella pertussis chromosome SO GENE LA English DT Article DE bvg locus; allelic exchange; suicide vector; rpsL; sacB ID GRAM-NEGATIVE BACTERIA; SUBTILIS SACB GENE; POSITIVE SELECTION; ESCHERICHIA-COLI; SUICIDE VECTORS; EXCHANGE; MUTAGENESIS; REPLACEMENT; DELETIONS; VIRULENCE AB A plasmid vector was designed, constructed, and used for the repeated retrieval of the bvgA gene from a number of Bordetella pertussis strains that, due to mutations in this gene, exhibited interesting phenotypes regarding the regulation of virulence genes. The vector was used in a scheme called allelic retrieval that exploits two cross-overs between cloned plasmid and native chromosomal sequences flanking the bvgA gene. This scheme is very similar to allelic exchange through the use of plasmid suicide vectors, but in the case presented here, the non-replicating plasmid that has received the chromosomal gene is recovered, rather than being allowed to be lost due to segregation. Incorporation of the counterselectable sacB gene of Bacillus subtilis in place of the plasmid copy of bvgA allows selection, after recovery in Escherichia coli, for only those plasmids that have retrieved the chromosomal bvgA gene. The validity of this approach was demonstrated by the retrieval of bvgA alleles with distinctive physical markers, as well as by the reintroduction of retrieved bvgA alleles to demonstrate that they conferred the expected phenotypes. It is expected that this approach will be applicable to the analysis of other genes in other bacterial species. (C) 1998 Elsevier Science B.V. C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Stibitz, S (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 29 TC 3 Z9 3 U1 1 U2 1 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-1119 J9 GENE JI Gene PD FEB 27 PY 1998 VL 208 IS 2 BP 183 EP 189 DI 10.1016/S0378-1119(97)00643-4 PG 7 WC Genetics & Heredity SC Genetics & Heredity GA ZD054 UT WOS:000072646200010 PM 9524261 ER PT J AU Goldoft, M Stehr-Green, P Hedberg, K Flemming, DW Hall, W Johnson, DR AF Goldoft, M Stehr-Green, P Hedberg, K Flemming, DW Hall, W Johnson, DR TI Adverse ocular reactions following transfusions - United States, 1997-1998 (Reprinted from MMWR, vol 47, pg 49-50, 1998) SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Reprint ID BLOOD C1 St John Hosp, Longview, WA 98632 USA. Washington State Dept Hlth, Seattle, WA USA. Oregon Hlth Div, Portland, OR USA. Michigan Dept Community Hlth, Detroit, MI USA. US FDA, Ctr Biol Evaluat & Res, Ctr Devices & Radiol Hlth, Off Regulatory Affairs, Rockville, MD 20857 USA. CDC, Div Appl Publ Hlth Training, Epidemiol Program Off, Atlanta, GA 30333 USA. CDC, Hosp Infect Program, Natl Ctr Infect Dis, Atlanta, GA 30333 USA. RP Goldoft, M (reprint author), St John Hosp, Longview, WA 98632 USA. NR 5 TC 4 Z9 4 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD FEB 25 PY 1998 VL 279 IS 8 BP 576 EP + PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YX457 UT WOS:000072041900013 ER PT J AU Warren, KJ Boxwell, DE Kim, NY Drolet, BA AF Warren, KJ Boxwell, DE Kim, NY Drolet, BA TI Nevirapine-associated Stevens-Johnson syndrome SO LANCET LA English DT Article ID CONTROLLED TRIAL; ZIDOVUDINE C1 Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. US FDA, Rockville, MD 20857 USA. RP Drolet, BA (reprint author), Med Coll Wisconsin, Dept Dermatol, Milwaukee, WI 53226 USA. NR 5 TC 75 Z9 78 U1 0 U2 2 PU LANCET LTD PI LONDON PA 42 BEDFORD SQUARE, LONDON WC1B 3SL, ENGLAND SN 0140-6736 J9 LANCET JI Lancet PD FEB 21 PY 1998 VL 351 IS 9102 BP 567 EP 567 DI 10.1016/S0140-6736(98)24008-6 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YZ216 UT WOS:000072231900014 PM 9492778 ER PT J AU Ozawa, S Tang, YM Yamazoe, Y Kato, R Lang, NP Kadlubar, FF AF Ozawa, S Tang, YM Yamazoe, Y Kato, R Lang, NP Kadlubar, FF TI Genetic polymorphisms in human liver phenol sulfotransferases involved in the bioactivation of N-hydroxy derivatives of carcinogenic arylamines and heterocyclic amines SO CHEMICO-BIOLOGICAL INTERACTIONS LA English DT Article; Proceedings Paper CT 3rd International Sulfation Workshop CY SEP 22-25, 1996 CL DRYMEN, SCOTLAND DE phenol sulfotransferase; human; liver; pharmacogenetics; reverse-transcriptase polymerase chain reaction; aromatic amine carcinogens ID METABOLIC-ACTIVATION; CYTOSOLIC SULFOTRANSFERASES; PARTIAL-PURIFICATION; THERMAL-STABILITY; MESSENGER-RNA; CDNA; EXPRESSION; ACID; FORM; DNA AB Three related forms of phenol sulfotransferase (PSULT), thermostable ST1A2 (SULT1A2hum) and ST1A3 (SULT1A1hum) and a thermolabile TL-PST (SULT1A3hum), are known to exist in human livers. Thermostable forms, whose activities are polymorphically distributed, have been shown to mediate the bioactivation of carcinogenic N-hydroxy arylamines and heterocyclic amines. To clarify the nature of the sulfation polymorphism, the study compared the expressed levels of ST1A2, ST1A3 and TL-PST mRNAs in human livers by the method of reverse-transcriptase polymerase chain reaction (RT-PCR), utilizing HindIII, BamHI and SnaBI sites which were unique to the above PSULT cDNAs, respectively. Of the PCR products derived from human liver (n = 26), 43-89, < 1-29 and < 1-21% showed the restriction pattern characteristic for ST1A3, ST1A2 and TL-PST cDNAs, respectively, thus indicating that ST1A3 mRNA is the major transcript. Hepatic p-nitrophenol and dopamine sulfation rates ranged from 440-2670 and < 5-460 pmol/min per mg protein in the 26 individuals, respectively. The observed differences in the ST1A3 and TL-PST mRNA levels were consistent with the differences in p-nitrophenol and dopamine sulfations. Relative levels of hepatic ST1A3 mRNA were non-normally distributed and correlated significantly with p-nitrophenol sulfation. In addition, variant forms of ST1A3 mRNA encoding Arg213His and Met223Val were detected in human livers. With regard to Arg213His, 28 individuals who had homozygous (213)Arg alleles, 15 individuals who were heterozygotes and nine homozygous (213)His individuals were found by a newly established genotyping method among 52 human liver samples. Frequency of (223)Val allele was apparently lower than that of (213)His allele, as no homozygous (223)Val individual and only three individuals who were heterozygotes ((223)Met/Val) were observed among 52 individuals. These results suggest that regulation of p-nitraphenol sulfation occurs at the level of gene transcription of ST1A3 which is the major transcript of the three PSULT mRNAs and that a polygenic basis for the apparent genetic polymorphism of sulfation was likely because of the existence of ST1A3 variants. Published by Elsevier Science Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Tohoku Univ, Dept Mol Metab & Toxicol, Sendai, Miyagi 980, Japan. Keio Univ, Sch Med, Dept Pharmacol, Tokyo 160, Japan. John L McClellan Mem Vet Adm Med Ctr, Surg Serv, Little Rock, AR 72205 USA. Arkansas Canc Res Ctr, Div Surg, Little Rock, AR USA. RP Ozawa, S (reprint author), Natl Inst Hlth Sci, Div Pharmacol, Setagaya Ku, 1-18-1 Kamiyoga, Tokyo 1588501, Japan. NR 32 TC 83 Z9 83 U1 0 U2 0 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 FEB 20 PY 1998 VL 109 IS 1-3 BP 237 EP 248 DI 10.1016/S0009-2797(97)00135-X PG 12 WC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy; Toxicology GA ZE613 UT WOS:000072812100020 PM 9566748 ER PT J AU Dass, SB Hammons, GJ Bucci, TJ Heflich, RH Casciano, DA AF Dass, SB Hammons, GJ Bucci, TJ Heflich, RH Casciano, DA TI Susceptibility of C57BL/6 mice to tumorigenicity induced by dimethylnitrosamine and 2-amino-1-methyl-6-phenylimidazo [4,5-b]pyridine in the neonatal bioassay SO CANCER LETTERS LA English DT Article DE strain C57BL/6; neonatal mice; hepatic tumors; P-450 enzymes; dimethylnitrosamine; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ID LIVER-TUMORS; POLYCHLORINATED-BIPHENYLS; MOUSE-LIVER; HEPATOCARCINOGENESIS; ACTIVATION; LUNG; CARCINOGENESIS; PROMOTION; NEWBORN; 4-AMINOBIPHENYL AB Male C57BL/6 neonates were treated on days 8 and 15 with 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP, 6.5 or 26.2 mg/kg) or dimethylnitrosamine (DMN, 2.6 or 10.5 mg/kg). No tumors were seen in PhIP-treated animals at 15 months of age. Liver and lung tumor incidences in DMN-treated animals were 67-79 and 0-7%, respectively. In comparison with data from other strains, our results indicate that (1) neonatally-treated C57BL/6 mice are resistant to the induction of liver and lung tumors by PhIP and lung tumors by DMN and (2) the susceptibility of this strain to induced liver tumors correlates with the activity of hepatic DMN N-demethylase and PhIP N-hydroxylase in the (untreated) neonates. Published by Elsevier Science Ireland Ltd. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Pathol Associates, Jefferson, AR 72079 USA. RP Dass, SB (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 30 TC 6 Z9 6 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 FEB 13 PY 1998 VL 124 IS 1 BP 105 EP 110 DI 10.1016/S0304-3835(97)00462-X PG 6 WC Oncology SC Oncology GA YX725 UT WOS:000072071000015 PM 9500198 ER PT J AU Fritsche, J Steinhart, H Mossoba, MM Yurawecz, MP Sehat, N Ku, Y AF Fritsche, J Steinhart, H Mossoba, MM Yurawecz, MP Sehat, N Ku, Y TI Rapid determination of trans-fatty acids in human adipose tissue - Comparison of attenuated total reflection infrared spectroscopy and gas chromatography SO JOURNAL OF CHROMATOGRAPHY B LA English DT Article DE trans-fatty acids ID HYDROGENATED OILS; ISOMERS; RISK; DISEASE AB A rapid attenuated total reflection (ATR) infrared (IR) spectroscopy procedure was used for quantitating the levels of total trans-fatty acid methyl ester (FAME) derivatives in neat (without solvent) test samples isolated from human adipose tissue. This procedure requires no weighing of the laboratory sample. The single-beam spectrum of the trans-containing FAMEs was 'ratioed' against that of a reference material having only cis double bonds in order to obtain a symmetric absorption band at 966 cm(-1) on a horizontal background, A single reflection ATR diamond cell that requires only about 1 mu l of neat FAMEs was used. The average level of trans-fatty acids in human adipose tissue found by ATR (3.07+/-0.27%) was generally higher than that obtained by gas chromatography (2.59+/-0.20%). Reasons for such a difference are discussed. (C) 1998 Elsevier Science B.V. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. Univ Hamburg, Inst Biochem & Food Chem, D-20146 Hamburg, Germany. RP Mossoba, MM (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 22 TC 19 Z9 22 U1 1 U2 2 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 FEB 13 PY 1998 VL 705 IS 2 BP 177 EP 182 DI 10.1016/S0378-4347(97)00509-4 PG 6 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YY734 UT WOS:000072178500001 PM 9521553 ER PT J AU Prival, MJ Zeiger, E AF Prival, MJ Zeiger, E TI Chemicals mutagenic in Salmonella typhimurium strain TA1535 but not in TA100 SO MUTATION RESEARCH-GENETIC TOXICOLOGY AND ENVIRONMENTAL MUTAGENESIS LA English DT Article DE Salmonella typhimurium; Ames test; TA1535; TA100; base pair substitution mutation ID MAMMALIAN-MICROSOME ASSAY; AMES TEST; CARCINOGENS; MUTATION; DRUGS AB The standard Salmonella mutagenicity test uses two strains of Salmonella typhimurium (TA1535 and TA100) containing the same base pair substitution mutation (hisG46). These strains differ only in that strain TA100 contains the plasmid pKM101, whose mucAB gene products enhance SOS mutagenesis. This makes strain TA100, in general, the more sensitive of the two for mutagen detection, raising the question as to whether or not to include strain TA1535 in the core battery of strains in routine testing. Out of 659 chemicals judged as mutagens in the S. typhimurium assay when subjected to the National Toxicology Program's screening protocol, 36 (5%) were evaluated as positive in strain TA1535 but not in strain TA100. Of these, 23 were judged as negative and 13 as equivocal in strain TA100, and 5 were positive or equivocal in at least one other strain (TA97 or TA98). In general, the data on these chemicals indicate that the absolute increases in revertants per plate induced in strain TA1535 were too small to have been judged as positive if similar increases occurred in strain TA100. which has a much higher spontaneous background. For three chemicals (acetaldehyde oxime, 6-mercaptopurine, and 1,3-butadiene) the absolute increases in revertants in strain TA1535 greatly exceeded those in strain TA100. Evaluation of the reproducibility of these findings and of the mechanisms and relevance of unique TA1535 positives should be useful when decisions are made as to whether this strain should be kept as a part of the core battery of strains in the S. typhimurium assay. (C) 1998 Elsevier Science B.V. C1 US FDA, Genet Toxicol Branch HFS236, Washington, DC 20204 USA. NIEHS, Environm Toxicol Program, Res Triangle Pk, NC 27709 USA. RP Prival, MJ (reprint author), US FDA, Genet Toxicol Branch HFS236, 200 C St SW, Washington, DC 20204 USA. NR 27 TC 18 Z9 18 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 1383-5718 J9 MUTAT RES-GEN TOX EN JI Mutat. Res. Genet. Toxicol. Environ. Mutagen. PD FEB 13 PY 1998 VL 412 IS 3 BP 251 EP 260 DI 10.1016/S1383-5718(97)00196-4 PG 10 WC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology SC Biotechnology & Applied Microbiology; Genetics & Heredity; Toxicology GA ZL336 UT WOS:000073422700006 PM 9600693 ER PT J AU Potter, LS Trussell, J Rarick, L AF Potter, LS Trussell, J Rarick, L TI Emergency postcoital contraception SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 Princeton Univ, Princeton, NJ 08544 USA. US FDA, Rockville, MD 20857 USA. RP Potter, LS (reprint author), Princeton Univ, Princeton, NJ 08544 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD FEB 12 PY 1998 VL 338 IS 7 BP 476 EP 477 DI 10.1056/NEJM199802123380718 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YW122 UT WOS:000071900100030 PM 9463166 ER PT J AU Zhang, MJ Dayton, AI AF Zhang, MJ Dayton, AI TI Tolerance of diverse amino acid substitutions at conserved positions in the nuclear export signal (NES) of HIV-1 Rev SO BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS LA English DT Article ID VIRUS TYPE-1 REV; INFECTIOUS-ANEMIA VIRUS; IMMUNODEFICIENCY-VIRUS; ACTIVATION DOMAIN; EFFECTOR DOMAINS; PROTEINS; IDENTIFICATION AB The effector domain of the Rev protein is a nuclear export signal (NES) that is responsible for transporting Rev and its bound congeners out of the nucleus and into the cytoplasm. Previous work has identified several critical residues in the NES and has led to the belief that NESs of the Rev type are necessarily leucine rich. Here we present the sequences of a large number of functional Rev molecules with NES mutations. The data indicate a previously unreported diversity in allowable residues at a number of positions, including each of the leucine residues previously considered essential. (C) 1998 Academic Press. C1 US FDA, CBER, HFM 315, Div Transfus Transmitted Dis,Lab Mol Virol, Rockville, MD 20852 USA. RP Dayton, AI (reprint author), US FDA, CBER, HFM 315, Div Transfus Transmitted Dis,Lab Mol Virol, 1401 Rockville Pike, Rockville, MD 20852 USA. EM Dayton@A1.cber.fda.gov NR 22 TC 18 Z9 18 U1 0 U2 0 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 FEB 4 PY 1998 VL 243 IS 1 BP 113 EP 116 DI 10.1006/bbrc.1997.8070 PG 4 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YV778 UT WOS:000071862400021 PM 9473489 ER PT J AU Nightingale, SL AF Nightingale, SL TI Health advisory for low-molecular weight heparins and heparinoids SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 10 Z9 10 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 FEB 4 PY 1998 VL 279 IS 5 BP 346 EP 346 DI 10.1001/jama.279.5.346 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YU572 UT WOS:000071731300007 PM 9459455 ER PT J AU Nightingale, SL AF Nightingale, SL TI Guidance on industry-supported scientific and educational activities SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 10 Z9 10 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 FEB 4 PY 1998 VL 279 IS 5 BP 346 EP 346 DI 10.1001/jama.279.5.346 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YU572 UT WOS:000071731300006 PM 9459455 ER PT J AU Nightingale, SL AF Nightingale, SL TI FDA Modernization Act of 1997 SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 10 Z9 10 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 FEB 4 PY 1998 VL 279 IS 5 BP 346 EP 346 DI 10.1001/jama.279.5.346 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YU572 UT WOS:000071731300008 PM 9459455 ER PT J AU Nightingale, SL AF Nightingale, SL TI Two new warnings added to labeling for Mibefradil SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 10 Z9 10 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 FEB 4 PY 1998 VL 279 IS 5 BP 346 EP 346 DI 10.1001/jama.279.5.346 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YU572 UT WOS:000071731300005 PM 9459455 ER PT J AU Kakuda, TN Struble, KA Piscitelli, SC AF Kakuda, TN Struble, KA Piscitelli, SC TI Protease inhibitors for the treatment of human immunodeficiency virus infection SO AMERICAN JOURNAL OF HEALTH-SYSTEM PHARMACY LA English DT Review DE antivirals; compliance; costs; dosage; drug administration; drug interactions; food; HIV infections; human immunodeficiency virus; indinavir sulfate; mechanism of action; nelfinavir mesylate; patient information; pharmacists; pharmacokinetics; resistance; ritonavir; saquinavir mesylate; toxicity ID ORALLY BIOAVAILABLE INHIBITOR; HIV-1 PROTEASE; TYPE-1 PROTEASE; IN-VIVO; PROTEINASE-INHIBITOR; INCREASED RESISTANCE; CRYSTAL-STRUCTURE; RATIONAL DESIGN; DRUG-RESISTANCE; RITONAVIR AB The pharmacology, pharmacokinetics, efficacy, adverse effects, drug interactions, and dosage and administration of protease inhibitors are reviewed. Protease inhibitors are a novel class of drugs used for the treatment of human immunodeficiency virus (HIV) infection. Saquinavir, ritonavir, indinavir, and nelfinavir have been approved in the United States; several other agents are under development. Protease inhibitors selectively block HIV protease, an enzyme involved in the later stages of HIV replication. Various pharmacokinetic differences exist among these agents, including differences in bioavailability, protein binding, and drug interactions. The drugs undergo extensive hepatic metabolism; dosage adjustments should be considered for patients with hepatic dysfunction. Clinical trials have shown protease inhibitors to be effective in reducing HIV RNA levels and increasing CD4+ lymphocyte counts. When protease inhibitors are used in combination with other antiretroviral agents, an additional beneficial effect on these markers occurs. Adverse effects of saquinavir and nelfinavir include mild gastrointestinal disturbances such as diarrhea. Ritonavir is less well tolerated because of gastrointestinal disturbances and circumoral and peripheral paresthesia. Indinavir has been associated with nephrolithiasis and asymptomatic hyperbilirubinemia. The development of resistance to protease inhibitors may be related to suboptimal dosages, noncompliance, or partial compliance. Protease inhibitors are potent and highly selective agents that block a critical step in HIV replication. They are effective and relatively well tolerated, but they are expensive, have extensive drug interaction profiles, and require careful compliance with the prescribed regimen. C1 NIH, Warren G Magnuson Clin Ctr, Dept Pharm, Clin Pharmacokinet Res Lab, Bethesda, MD 20892 USA. US FDA, Div Antiviral Drug Prod, Rockville, MD 20857 USA. RP Piscitelli, SC (reprint author), NIH, Warren G Magnuson Clin Ctr, Dept Pharm, Clin Pharmacokinet Res Lab, 10 Ctr Dr,Bldg 10,Room 1N-257,MSC 1196, Bethesda, MD 20892 USA. EM spisc@nih.gov NR 125 TC 63 Z9 63 U1 1 U2 2 PU AMER SOC HEALTH-SYSTEM PHARMACISTS PI BETHESDA PA 7272 WISCONSIN AVE, BETHESDA, MD 20814 USA SN 1079-2082 J9 AM J HEALTH-SYST PH JI Am. J. Health-Syst. Pharm. PD FEB 1 PY 1998 VL 55 IS 3 BP 233 EP 254 PG 22 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YX156 UT WOS:000072012000010 PM 9492254 ER PT J AU Myers, MR Malinauskas, RA AF Myers, MR Malinauskas, RA TI Effect of orifice-area reduction on flow characteristics during injection through spinal needles SO ANAESTHESIA LA English DT Article DE equipment, needles, spinal ID ANESTHESIA AB A reduction in hole size for certain side-port spinal needles has been advocated in recent reports. While the influence of orifice-area reduction on the aspiration capability of the needle has been studied, the influence on the anaesthetic delivery properties is relatively unknown. As a first step in understanding the effects of hole-size reduction on anaesthetic distribution within the subarachnoid space, we studied flows emanating from isolated needles using computer simulations. Following validation of the numerical model using experimental particle visualisation, trajectories of anaesthetic particles injected through 25G Whitacre needles of various orifice areas were computed and used to determine the orientation and rate of spread of the anaesthetic jet exiting the needle. Two factors impacting the concentration distribution were observed: the rate of spread of the anaesthetic jet increases markedly with decreasing orifice area and the jet alignment shifts toward perpendicular to the needle axis. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Myers, MR (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12721 Twinbrook Pkwy,HFZ-132, Rockville, MD 20852 USA. NR 8 TC 4 Z9 4 U1 0 U2 2 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0003-2409 J9 ANAESTHESIA JI Anaesthesia PD FEB PY 1998 VL 53 IS 2 BP 151 EP 156 DI 10.1046/j.1365-2044.1998.00286.x PG 6 WC Anesthesiology SC Anesthesiology GA YX879 UT WOS:000072088900010 PM 9534638 ER PT J AU Liu, T Lin, Y AF Liu, T Lin, Y TI The epitope stability of Group 1 and Group 2 allergens in mite extracts SO ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY LA English DT Article ID HOUSE-DUST MITE; DER-F-II; DERMATOPHAGOIDES-PTERONYSSINUS; MONOCLONAL-ANTIBODIES; MAJOR ALLERGENS; P-II; PURIFICATION; FARINAE; ELISA; IGE AB Background: Commercial mite allergenic extracts sold in the US are prepared with whole body mites in buffer solutions containing 50% glycerol. Mite extracts were reported to contain large number of proteolytic enzymes and their structural integrity in aqueous solutions have not been evaluated. Objective: To evaluate the epitope stabilities of Group 1 and 2 allergens in two commercial mite extracts used by Center for Biologics Evaluation and Research (CBER) as reference extracts, E5-Dp (Dermatophagoides pteronyssinus) and E5-Df (D. farinae). Methods: Epitope stability was determined by using monoclonal antibodies in a Sandwich ELISA. Samples were stored at four different temperatures and the amounts of Der p 1, Der p 2, Der f 1, and Der f 2 were determined at different time intervals. The overall stability of mite extracts was evaluated by immunoblot and competition ELISA. Results: The epitope stability of these allergens varies: Der f 1 was stable for at least 3 years and Der f 2 for 1 year when stored at 4 degrees C; Der p 1 and 2 were less stable. None of the Group 1 and 2 allergens remained intact when stored at 50 degrees C. Immunoblot and competition ELISA data also showed similar trend of degradation as compared with extracts stored at 4 degrees C for same length of time. Conclusion: With the exception of Der f 1, the amount of detectable epitopes in Group 1 and 2 allergens reduce rapidly after 1 year, especially at elevated temperatures. The changes in allergen composition were also observed by immunoblotting and in relative potency by ELISA competition assay. These findings are highly relavent to the users of CBER's mite extracts as standards. C1 US FDA, CBER HFM422, Div Allergen Prod & Parasitol, Lab Immunobiochem, Rockville, MD 20852 USA. RP Lin, Y (reprint author), US FDA, CBER HFM422, Div Allergen Prod & Parasitol, Lab Immunobiochem, 1401 Rockville Pike, Rockville, MD 20852 USA. NR 21 TC 10 Z9 10 U1 1 U2 4 PU AMER COLL ALLERGY ASTHMA IMMUNOLOGY PI ARLINGTON HTS PA 85 WEST ALGONQUIN RD SUITE 550, ARLINGTON HTS, IL 60005 USA SN 1081-1206 J9 ANN ALLERG ASTHMA IM JI Ann. Allergy Asthma Immunol. PD FEB PY 1998 VL 80 IS 2 BP 177 EP 183 PG 7 WC Allergy; Immunology SC Allergy; Immunology GA YZ485 UT WOS:000072258800007 PM 9494451 ER PT J AU Davis, JC Austin, H Boumpas, D Fleisher, TA Yarboro, C Larson, A Balow, J Klippel, JH Scott, D AF Davis, JC Austin, H Boumpas, D Fleisher, TA Yarboro, C Larson, A Balow, J Klippel, JH Scott, D TI A pilot study of 2-chloro-2 '-deoxyadenosine in the treatment of systemic lupus erythematosus-associated glomerulonephritis SO ARTHRITIS AND RHEUMATISM LA English DT Article ID CHRONIC LYMPHOCYTIC-LEUKEMIA; PROGRESSIVE MULTIPLE-SCLEROSIS; PULSE CYCLOPHOSPHAMIDE; CONTROLLED TRIAL; DEOXYCYTIDINE KINASE; RHEUMATOID-ARTHRITIS; CLADRIBINE; 2-CHLORODEOXYADENOSINE; THERAPY; NEPHRITIS AB Objective. To determine the safety and tolerability, as well as the clinical and immunologic effects, of 2-chloro-2'-deoxyadenosine (2-CdA) in patients with systemic lupus erythematosus-associated glomerulonephritis. Methods. In a phase I study, 12 patients with proliferative lupus nephritis received 2-CdA either in weekly escalating intravenous treatments (0.15 mg/kg/week x 4, 0.1875 mg/kg/week x 4, 0.225 mg/kg/week x 4; n = 5) or in a continuous 7-day infusion (0.05 mg/kg/day; n = 7). Safety, renal improvement, and immunologic effects were evaluated for 12 months. Results. Patients treated with 2-CdA showed peripheral lymphocyte depletion without a significant reduction in neutrophil, monocyte, or platelet numbers or hematocrit levels. Naive and memory T cells were decreased, as were lymphocytes with markers of early and late activation. Peripheral B cell depletion was not associated with significant decreases in serum immunoglobulin levels. Continuous infusion induced better clinical responses than weekly infusions, as evidenced by 1) the percentage of patients showing complete response (43% versus 0%), 2) the percentage with at least 50% reduction in proteinuria (43% versus 20%), 3) the percentage with at least a 50% reduction in urinary dysmorphic red cells (57% versus 0%), and 4) the percentage in whom cellular casts disappeared (43% versus 0%), Several infections occurred; these responded to standard antibiotic therapy. Conclusion. In this pilot study, 2-CdA was safely administered to 12 patients with lupus nephritis. It induced prolonged reductions in lymphocyte populations and may be efficacious in selected patients with lupus nephritis when administered as a continuous infusion. C1 NIAMSD, Arthrit & Rheumatism Branch, NIH, Bethesda, MD 20892 USA. NIDDKD, NIH, Bethesda, MD 20892 USA. NIH, Dept Clin Pathol, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. RP Davis, JC (reprint author), NIAMSD, Arthrit & Rheumatism Branch, NIH, Bldg 10,Room 9S205, Bethesda, MD 20892 USA. NR 45 TC 56 Z9 57 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0004-3591 J9 ARTHRITIS RHEUM JI Arthritis Rheum. PD FEB PY 1998 VL 41 IS 2 BP 335 EP 343 DI 10.1002/1529-0131(199802)41:2<335::AID-ART18>3.0.CO;2-O PG 9 WC Rheumatology SC Rheumatology GA YW210 UT WOS:000071909500017 PM 9485092 ER PT J AU O'Boyle, KP Senter, PD Bhargava, K Chun, S Anthony, G Markowitz, AL Wadler, S AF O'Boyle, KP Senter, PD Bhargava, K Chun, S Anthony, G Markowitz, AL Wadler, S TI Effects of a hybrid recombinant human alpha interferon (A/D) on in vitro cytotoxicity and in vivo localization of monoclonal antibody L6-cytosine deaminase conjugate in a colon cancer model SO CANCER BIOTHERAPY AND RADIOPHARMACEUTICALS LA English DT Article DE colon cancer; cytosine deaminase; 5-fluorouracil; monoclonal antibody; cytotoxicity; and localization ID CYTOSINE DEAMINASE; COLORECTAL-CARCINOMA; FLUOROURACIL; COMBINATION; 5-FLUOROCYTOSINE; GENERATION; 5-FLUOROURACIL; MODULATION; LEUCOVORIN; PRODRUG AB L6 is an IgG2a murine monoclonal antibody which we have demonstrated binds well to HT29 human colon carcinoma cells by flow cytometry, whole cell ELISA, and mixed hemadsorption. In vitro cytotoxicity studies revealed that the monoclonal antibody L6-cytosine deaminase (L6-CD) immunoconjugate plus the nontoxic prodrug, 5-fluorocytosine (5-FC), is equivalent to 5-fluorouracil (5-FU) in its ability to kill HT29 cells. Human alpha-interferon (A/D) was able to enhance this cytotoxic effect. The I.C.(50)'s revealed that very small amounts of L6-CD are needed for this cytotoxic effect (approximately, 5 pg/ml resulted in 50% viability). The limiting factor was the amount of 5-FC employed with L6-CD (3 mu M yielded 50% cell viability). alpha-Interferon (A/D) lowered the requirement of 5-FC to 1 mu M to achieve 50% cell lethality. In vivo biodistribution experiments indicated that 1 mu g of L6-CD is nonspecifically taken up by the liver and spleen and cleared rapidly from the blood. Significant localization of L6-CD to HT29 tumors occurred only when 99 mu g of unlabeled L6-CD was added to 1 mu g of I-125-labeled immunoconjugate injected intravenously. Further augmentation of tumor/blood ratios without reduction in percent injected dose per gram of tumor was possible with the intravenous injection of 100 mu g of anti-idiotypic monoclonal antibody 13B, 24 hours after L6-CD, which bound unreacted L6-CD and cleared it from the blood. The addition of 100,000 U of alpha-interferon (A/D) given intraperitoneally every day increased the clearance of L6-CD by the liver and spleen, but impaired tumor localization (percent injected dose per gram). These studies demonstrated that in vivo localization of the L6-CD conjugate to HT29 tumors could be optimized by injecting excess L6-CD followed by an equal amount of L6 anti-idiotype mAb 13B, 24 hours after L6-CD. C1 US FDA, CBER, Div Monoclonal Antibodies, Rockville, MD 20852 USA. Montefiore Med Ctr, Albert Einstein Canc Ctr, Dept Oncol, Bronx, NY 10467 USA. Albert Einstein Coll Med, Bronx, NY 10467 USA. Bristol Myers Squibb Pharmaceut Res Inst, Seattle, WA 98121 USA. RP O'Boyle, KP (reprint author), US FDA, CBER, Div Monoclonal Antibodies, Bldg 29B,Room 3NN13,HFM-561,1401 Rockville Pike, Rockville, MD 20852 USA. FU NCI NIH HHS [CA 13330-22] NR 22 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 1084-9785 J9 CANCER BIOTHER RADIO JI Cancer Biother. Radiopharm. PD FEB PY 1998 VL 13 IS 1 BP 33 EP 42 DI 10.1089/cbr.1998.13.33 PG 10 WC Oncology; Medicine, Research & Experimental; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Research & Experimental Medicine; Pharmacology & Pharmacy; Radiology, Nuclear Medicine & Medical Imaging GA ZB239 UT WOS:000072451100004 PM 10850340 ER PT J AU DeGeorge, JJ Ahn, CH Andrews, PA Brower, ME Giorgio, DW Goheer, MA Lee-Ham, DY McGuinn, WD Schmidt, W Sun, CJ Tripathi, SC AF DeGeorge, JJ Ahn, CH Andrews, PA Brower, ME Giorgio, DW Goheer, MA Lee-Ham, DY McGuinn, WD Schmidt, W Sun, CJ Tripathi, SC TI Regulatory considerations for preclinical development of anticancer drugs SO CANCER CHEMOTHERAPY AND PHARMACOLOGY LA English DT Article DE antineoplastic agents; toxicity tests; toxicology; guidelines; phase I clinical trials ID I CLINICAL-TRIALS; PHASE-I; MULTIDRUG-RESISTANCE; TRACT ABNORMALITIES; TAMOXIFEN; CANCER; MICE; TOXICOLOGY; ADRIAMYCIN; CISPLATIN AB The entry of new anticancer treatments into phase I clinical trials is ordinarily based on relatively modest preclinical data. This report defines the battery of preclinical tests important for assessing safety under an Investigational New Drug application (IND) and outlines a basis for extrapolating starting doses of investigational anticancer drugs in phase I clinical trials from animal toxicity studies. Types of preclinical studies for the support of marketing of a new anticancer drug are also discussed. This report addresses differences and similarities in the preclinical development of cytotoxic drugs (including photosensitizers and targeted delivery products), drugs used chronically (chemopreventive drugs, hormonal drugs, immunomodulators), and drugs intended to enhance the efficacy (MDR-reversing agents and radiation/chemotherapy sensitizers) or diminish the toxicity of currently used anticancer therapies. Factors to consider in the design of preclinical studies of combination therapies, alternative therapies, and adjuvant therapies in the treatment of cancer, and to support changes in clinical formulations or route of administration, are also discussed. C1 US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, Rockville, MD 20857 USA. RP Andrews, PA (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Oncol Drug Prod, 5600 Fishers Lane HFD-150, Rockville, MD 20857 USA. NR 48 TC 61 Z9 69 U1 0 U2 6 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-5704 J9 CANCER CHEMOTH PHARM JI Cancer Chemother. Pharmacol. PD FEB PY 1998 VL 41 IS 3 BP 173 EP 185 PG 13 WC Oncology; Pharmacology & Pharmacy SC Oncology; Pharmacology & Pharmacy GA YM614 UT WOS:000071082400001 PM 9443633 ER PT J AU Lester, DS Kidder, LH Levin, IW Lewis, EN AF Lester, DS Kidder, LH Levin, IW Lewis, EN TI Infrared microspectroscopic imaging of the cerebellum of normal and cytarabine treated rats SO CELLULAR AND MOLECULAR BIOLOGY LA English DT Article DE infrared imaging; FT-IR spectroscopy; infrared focal-plane arrays; cerebellum; microscopy; neuropathology; histology ID BRAIN-TISSUE AB Conventionally, the diagnosis of neuropathology in a subject requires the identification of a behavioral modification, which provides direction for appropriate histological analyses. However, since the ultimate diagnosis of the pathology largely depends on the initial choice of histological tests, the opportunity exists for inaccurate or insensitive results. An innovative approach using Fourier transform infrared (FT-IR) spectroscopic imaging to diagnose neuropathology should prove useful. This novel method monitors and visualizes the underlying chemistry of the tissue, based on hundreds of vibrational absorption bands that are intrinsic to the sample, As such, it makes no prior assumptions as to the type or degree of pathology. Using this technique, we have spectroscopically imaged cerebellar tissue slices from rats [control subjects and subjects treated with the antineoplastic drug, cytarabine (Ara-C)], and have been able to correlate lipid and protein distributions within distinct cell types in the cerebellum. A further benefit of the technique is that it simultaneously records tens of thousands of independent spectra from different spatial locations within the sample. Thus, a variety of statistical and multivariate techniques can be exploited to characterize large sample areas and to provide robust classification of individual spectral signatures. In comparison to standard histological protocols, FT-IR spectroscopic imaging simultaneously analyzes cell layers and identifies subtle structural and biochemical changes within the sample. We suggest that FT-IR spectroscopic imaging should provide a highly reliable, complementary tool for standard histological tier testing. C1 NIDDKD, Chem Phys Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Laurel, MD 20708 USA. RP Lester, DS (reprint author), NIDDKD, Chem Phys Lab, NIH, 9000 Rockville Pike,Bldg 5,Room B1-38, Bethesda, MD 20892 USA. NR 19 TC 32 Z9 32 U1 0 U2 1 PU C M B ASSOC PI POITIERS PA 40 AVENUE RECTEUR PINEAU, BAT MECANIQUE, 86022 POITIERS, FRANCE SN 0145-5680 J9 CELL MOL BIOL JI Cell. Mol. Biol. PD FEB PY 1998 VL 44 IS 1 BP 29 EP 38 PG 10 WC Biochemistry & Molecular Biology; Cell Biology SC Biochemistry & Molecular Biology; Cell Biology GA ZE327 UT WOS:000072781500005 PM 9551635 ER PT J AU Scheinbaum, MI Eisenach, JC AF Scheinbaum, MI Eisenach, JC TI Placebo response in intractable neuropathic pain. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 Wake Forest Univ, Bowman Gray Sch Med, Winston Salem, NC USA. US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PI27 BP 144 EP 144 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300028 ER PT J AU Chen, ML Lee, SC Ng, MJ Schuirmann, D AF Chen, ML Lee, SC Ng, MJ Schuirmann, D TI Gender analysis of bioequivalence trials. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PI31 BP 145 EP 145 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300032 ER PT J AU Huang, SS Balian, J Marroum, P Mehta, M Lesko, LJ AF Huang, SS Balian, J Marroum, P Mehta, M Lesko, LJ TI Assessment of the quality and quantity of metabolism based drug-drug interaction studies in NDA submissions. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PI37 BP 146 EP 146 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300038 ER PT J AU Spyker, DA Dawson, JM AF Spyker, DA Dawson, JM TI Reporting of equivalence in the current medical literature: Confidence interval calculations. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDRH, Rockville, MD 20850 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PI35 BP 146 EP 146 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300036 ER PT J AU Marroum, P Burnett, A Svadjian, R Uppoor, RS Ajayi, F Yuan, R Lesko, LJ Balian, JD AF Marroum, P Burnett, A Svadjian, R Uppoor, RS Ajayi, F Yuan, R Lesko, LJ Balian, JD TI A survey of drug-drug interaction (DDI) studies. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Off Clin Pharm & Biopharm, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PI39 BP 147 EP 147 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300040 ER PT J AU Mehta, MU Lesko, LJ Ching, ML AF Mehta, MU Lesko, LJ Ching, ML TI Comparison of clinical pharmacology (CP) and biopharmaceutics (BP) studies submitted in NDAS during 1995 and 1997. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Off Clin Pharmacol & Biopharm, CDER, Rockville, MD 20857 USA. SUNY Buffalo, Buffalo, NY 14260 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PI42 BP 147 EP 147 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300043 ER PT J AU Uppoor, RS Marroum, P Burnett, A Ajayi, F Yuan, R Svadjian, R Balian, JD AF Uppoor, RS Marroum, P Burnett, A Ajayi, F Yuan, R Svadjian, R Balian, JD TI Most common interactant drugs in drug-drug interaction (DDI) studies. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Off Clin Pharm & Biopharm, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PI40 BP 147 EP 147 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300041 ER PT J AU Fossler, MJ AF Fossler, MJ TI A pharmacokinetic/pharmacodynamic model of the vasodilatory effects of niacin. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PI97 BP 161 EP 161 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300097 ER PT J AU El-Tahtawy, A Grevel, J Venitz, J Karkowsky, A Parekh, A Taylor, AA AF El-Tahtawy, A Grevel, J Venitz, J Karkowsky, A Parekh, A Taylor, AA TI Dual effect PK/PD modeling of intravenous fenoldopam in moderate hypertensive patients. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. BAST Inc, Austin, TX USA. Virginia Commonwealth Univ, Richmond, VA USA. Neurex Corp, Menlo Pk, CA USA. Baylor Coll Med, Houston, TX 77030 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU NATURE PUBLISHING GROUP PI NEW YORK PA 75 VARICK ST, 9TH FLR, NEW YORK, NY 10013-1917 USA SN 0009-9236 EI 1532-6535 J9 CLIN PHARMACOL THER JI Clin. Pharmacol. Ther. PD FEB PY 1998 VL 63 IS 2 MA PI102 BP 162 EP 162 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300102 ER PT J AU Cantilena, LR Honig, PK AF Cantilena, LR Honig, PK TI QT dispersion as a predictor of proarrhythmia in drug interactions with terfenadine. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 USUHS, Div Clin Pharmacol, Bethesda, MD USA. US FDA, CDER, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PII23 BP 178 EP 178 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300164 ER PT J AU Barditch-Crovo, P Trapnell, CB Ette, E Zacur, H Flexner, C AF Barditch-Crovo, P Trapnell, CB Ette, E Zacur, H Flexner, C TI A pharmacokinetic and pharmacodynamic evaluation of the effect of rifampin and rifabutin on combination oral contraceptives. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. Johns Hopkins Univ, Sch Med, Baltimore, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PII31 BP 180 EP 180 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300173 ER PT J AU Mishina, EV Miller, R Salcoz, C AF Mishina, EV Miller, R Salcoz, C TI Pharmacokinetic/pharmacodynamic (PK/PD) population model linking cortisol production with fluticasone concentration. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PII116 BP 201 EP 201 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300258 ER PT J AU Sun, H Pelsor, F Ette, EI AF Sun, H Pelsor, F Ette, EI TI On covariates (Cov) and parameter (P) estimation in population pharmacokinetic (PPK) studies. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, CDER, Off Clin Pharmacol & Biopharm, Rockville, MD 20857 USA. Vertex Pharmaceut, Cambridge, MA USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PII119 BP 202 EP 202 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300261 ER PT J AU Yuan, R Balian, JD Svadjian, R Uppoor, RS Ajayi, F Burnett, A Lesko, LJ Marroum, P AF Yuan, R Balian, JD Svadjian, R Uppoor, RS Ajayi, F Burnett, A Lesko, LJ Marroum, P TI Role of in vitro metabolic interactions in the conduct of drug-drug interaction (DDI) studies. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Off Clin Pharmacol & Biopharm, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PIII46 BP 218 EP 218 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300326 ER PT J AU Kieffer, LV Takimoto, CH Morrison, GB Cantilena, LR Allegra, CJ Grem, JL Marino, M AF Kieffer, LV Takimoto, CH Morrison, GB Cantilena, LR Allegra, CJ Grem, JL Marino, M TI Development of a pharmacokinetic and pharmacodynamic population model of paclitaxel administered with 5-fluorouracil. SO CLINICAL PHARMACOLOGY & THERAPEUTICS LA English DT Meeting Abstract C1 NCI, USN, Metab Oncol Branch, NIH, Bethesda, MD USA. US FDA, Rockville, MD 20857 USA. WRAIR, Washington, DC USA. USUHS, Bethesda, MD USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 1998 VL 63 IS 2 MA PIII69 BP 224 EP 224 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZA963 UT WOS:000072420300348 ER PT J AU Hasinoff, BB Hellmann, K Herman, EH Ferrans, VJ AF Hasinoff, BB Hellmann, K Herman, EH Ferrans, VJ TI Chemical, biological and clinical aspects of dexrazoxane and other bisdioxopiperazines SO CURRENT MEDICINAL CHEMISTRY LA English DT Review ID CARDIOPROTECTIVE AGENT ICRF-187; SPONTANEOUSLY HYPERTENSIVE RATS; SYRIAN GOLDEN-HAMSTERS; DNA TOPOISOMERASE-II; DOXORUBICIN-INDUCED CARDIOTOXICITY; HYDROXYL RADICAL PRODUCTION; CHRONIC DAUNORUBICIN CARDIOTOXICITY; PERFORMANCE LIQUID-CHROMATOGRAPHY; HEART SUBMITOCHONDRIAL PARTICLES; IRON-ANTHRACYCLINE COMPLEXES AB The bisdioxopiperazine dexrazoxane (ICRF-187) has proven to be clinically very effective in reducing the cardiotoxicity of doxorubicin and other anthracyclines. Doxorubicin is thought to exert its toxicity through iron-based oxygen free radical-induced oxidative stress on the relatively unprotected cardiac muscle. Upon hydrolysis, dexrazoxane forms a compound similar to ethylenediaminetetraacetic acid (EDTA) which, like EDTA, is a strong chelator of iron. Dexrazoxane presumably exerts its cardioprotective effects by either binding free or loosely bound iron, or iron complexed to doxorubicin, thus preventing or reducing site-specific oxygen radical production that damages cellular components. The chemistry, biochemistry, and cell biology of dexrazoxane and other bisdioxopiperazines are discussed. The pre-clinical studies demonstrating the protective effects of dexrazoxane against toxicities caused by doxorubicin, other anthracyclines, bleomycin, alloxan. acetaminophen, and oxygen are also discussed. in vitro and in vivo studies of the cardioprotective and other effects of other bisdioxopiperazines are also covered. Also discussed are the anti-metastatic and radiosensitization effects of razoxane and dexrazoxane. The current clinical status of dexrazoxane in preventing anthracycline-induced toxicities in both adult and pediatric patients is reviewed. C1 Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada. Windleshaw House, Withyham 7N7 4DB, E Sussex, England. US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res, Laurel, MD 20708 USA. NHLBI, Pathol Sect, NIH, Bethesda, MD 20892 USA. RP Hasinoff, BB (reprint author), Univ Manitoba, Fac Pharm, Winnipeg, MB R3T 2N2, Canada. NR 223 TC 111 Z9 112 U1 0 U2 7 PU BENTHAM SCIENCE PUBL LTD PI SHARJAH PA EXECUTIVE STE Y26, PO BOX 7917, SAIF ZONE, 1200 BR SHARJAH, U ARAB EMIRATES SN 0929-8673 J9 CURR MED CHEM JI Curr. Med. Chem. PD FEB PY 1998 VL 5 IS 1 BP 1 EP 28 PG 28 WC Biochemistry & Molecular Biology; Chemistry, Medicinal; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Pharmacology & Pharmacy GA YZ154 UT WOS:000072225700001 PM 9481032 ER PT J AU Contrera, JF DeGeorge, JJ AF Contrera, JF DeGeorge, JJ TI In vivo transgenic bioassays and assessment of the carcinogenic potential of pharmaceuticals SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Review DE transgenic; animal models; ICH; testing guidance; carcinogenicity; bioassay; pharmaceuticals ID TUMOR-SUPPRESSOR GENES; FALSE-POSITIVE RATES; HA-RAS GENE; LIVER-TUMORS; CHEMICAL CARCINOGENS; RISK ASSESSMENT; P53 MUTATIONS; BODY-WEIGHT; LONG-TERM; MICE AB There is general agreement in the scientific community on the need to improve carcinogenicity testing and the assessment of human carcinogenic risk and to incorporate more information on mechanisms and modes of action into the risk assessment process. Advances in molecular biology have identified a growing number of genes such as protooncogenes and tumor-suppressor genes that are highly conserved across species and are associated with a wide variety of human and animal cancers. in vivo transgenic rodent models incorporating such mechanisms are used to identify mechanisms involved in tumor formation and as selective tests for carcinogens. Transgenic methods can be considered an extension of genetic manipulation by selective breeding, which long has been employed in science and agriculture. The use of two rodent species in carcinogenicity testing is especially important for identifying transspecies carcinogens. The capacity of a substance to induce neoplasia across species suggests that the mechanism(s) involved in the induction of the neoplasia are conserved and therefore may have significance for humans. Based on available information there is sufficient experience with some in vivo transgenic rodent carcinogenicity models to support their application as complementary second species studies in conjunction with a single 2-year rodent carcinogenicity study. The optional substitution of a second 2-year rodent carcinogenicity study with an alternative study such as an in vivo transgenic carcinogenicity study is part of the International Conference on Harmonization guidance S1B: Testing for Carcinogenicity of Pharmaceuticals. This guidance is intended to be flexible enough to accommodate a wide range of possible carcinogenicity assessment models currently under consideration or models that may be developed in the future. The use of an in vivo transgenic mouse model in place of a second ii-year mouse study will improve the assessment of carcinogenic risk by contributing insights into the mechanisms of tumorigenesis and potential human relevance not available from a standard 2-year bioassay. II is envisioned that this will stimulate the further development of more efficient and relevant methods for identifying and assessing potential human carcinogenic risk, which will benefit public health. C1 US FDA, Adm Ctr Drug Evaluat & Res, Off Testing & Res, Rockville, MD 20857 USA. US FDA, Adm Ctr Drug Evaluat & Res, Off Rev Management, Rockville, MD 20857 USA. RP Contrera, JF (reprint author), US FDA, Adm Ctr Drug Evaluat & Res, Off Testing & Res, HFD-900,5600 Fishers Lane, Rockville, MD 20857 USA. EM contrerajf@cder.fda.gov NR 82 TC 24 Z9 24 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 EI 1552-9924 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 1998 VL 106 SU 1 BP 71 EP 80 DI 10.2307/3433913 PG 10 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WC UT WOS:000075403700005 PM 9539006 ER PT J AU James, SJ Muskhelishvili, L Gaylor, DW Turturro, A Hart, R AF James, SJ Muskhelishvili, L Gaylor, DW Turturro, A Hart, R TI Upregulation of apoptosis with dietary restriction: Implications for carcinogenesis and aging SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 3rd BELLE Conference on Toxicological Defense Mechanisms and the Shape of Dose-Response Relationships CY NOV 12-14, 1996 CL RES TRIANGLE PK, NORTH CAROLINA SP Biol Effects Low Level Exposures, Advisory Comm DE apoptosis; proliferation; homeostasis; dietary restriction; cancer; aging ID GROWTH-FACTOR-I; CALORIC RESTRICTION; CELL-PROLIFERATION; B6C3F1 MICE; RAT-LIVER; DEATH APOPTOSIS; TUMOR PROMOTERS; CANCER; TUMORIGENESIS; INSULIN AB The maintenance of cell number homeostasis in normal tissues reflects a highly regulated balance between the rates of cell proliferation and cell death. Under pathologic conditions such as exposure to cytotoxic, genotoxic, or nongenotoxic agents, an imbalance in these rates may indicate subsequent risk of carcinogenesis. Apoptotic cell death, as opposed to necrotic cell death, provides a protective mechanism by selective elimination of senescent, preneoplastic, or superfluous cells that could negatively affect normal function and/or promote cell transformation. The relative efficiency or dysfunction of the cell death program could therefore have a direct impact on the risk of degenerative or neoplastic disease. Dietary restriction of rodents is a noninvasive intervention that has been reproducibly shown to retard tumor development and most physiologic indices of aging relative to ad libitum-fed animals. As such, it provides a powerful model in which to study common mechanistic processes associated with both aging and cancer. In a recent study we established that chronic dietary restriction (DR) induces an increase in spontaneous apoptotic rate and a decrease in cell proliferation rate in hepatocytes of 12-month-old B6C3F1 DR mice relative to ad libitum (AL)-fed mice. This diet-induced shift in cell death/proliferation rates was associated with a marked reduction in subsequent development of spontaneous hepatoma and a marked increase in disease-free life span in DR relative to AL-fed mice. These results suggest that total caloric intake may modulate the rates of cell death and proliferation in a direction consistent with a cancer-protective effect in DR mice and a cancer-promoting effect in AL mice. To determine whether the increase in spontaneous apoptotic rate was maintained over the life span of DR mice, apoptotic rates were quantified in 12-, 18-, 24- and 30-month-old DR and AL mice. The rate of apoptosis was elevated with age in both diet groups; however, the rate of apoptosis was significantly and consistently higher in DR mice regardless of age. In double-labeling experiments, an age-associated increase in the glutathione S-transferase-II expression in putative preneoplastic hepatocytes in AL mice was rapidly reduced by apoptosis upon initiation of DR. Thus, interventions that promote a low-level increase in apoptotic cell death may be expected to protect genotypic and phenotypic stability with age. If during tumor promotion an adaptive increase in apoptosis effectively balances the dysregulated increase proliferation, the risk of permanent genetic error and carcinogenesis would be minimized. C1 US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP James, SJ (reprint author), US FDA, Natl Ctr Toxicol Res, Div Biochem Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM jjames@nctr.fda.gov NR 51 TC 38 Z9 38 U1 1 U2 1 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 1998 VL 106 SU 1 BP 307 EP 312 DI 10.2307/3433932 PG 6 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WC UT WOS:000075403700024 PM 9539024 ER PT J AU Frame, LT Hart, RW Leakey, JEA AF Frame, LT Hart, RW Leakey, JEA TI Caloric restriction as a mechanism mediating resistance to environmental disease SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 3rd BELLE Conference on Toxicological Defense Mechanisms and the Shape of Dose-Response Relationships CY NOV 12-14, 1996 CL RES TRIANGLE PK, NORTH CAROLINA SP Biol Effects Low Level Exposures, Advisory Comm DE caloric restriction; dietary restriction; aging; calories; cancer; diet; carcinogenesis; glucocorticoids; life span; longevity; body mass index; adaptation; evolution ID CORTICOTROPIN-RELEASING FACTOR; GROWTH FACTOR-I; NITRIC-OXIDE SYNTHASE; SPRAGUE-DAWLEY RATS; STIMULATES CORTICOSTERONE SECRETION; MODERATE DIETARY RESTRICTION; CORONARY HEART-DISEASE; LIFE-SPAN EXTENSION; OBESE GENE-PRODUCT; RENAL-CELL CANCER AB It has been observed that susceptibility to many degenerative diseases increases concurrently with industrialization and rising living standards. Although epidemiologic studies suggest that specific environmental and dietary factors may be important, caloric intake alone (as reflected in body size) may account for much of the differential risk observed among diverse human populations. it has been suggested from animal studies that caloric intake may be the primary effector for many hormonal, metabolic, physiologic, and behavioral responses that coordinate reproductive strategy to apparent availability of food. When caloric intake is excessive, particularly at critical developmental stages, physiologic priorities are set for body growth and fecundity rather than for endurance and longevity. The converse occurs during periods of famine, thus increasing the probability that sufficient individuals survive to restore the population when conditions improve. Calorically restricted rodents have significantly longer reproductive and total life spans than their ad libitum-fed controls and exhibit a spectrum of biochemical and physiologic alterations that characterize their adaptation to reduced caloric intake. These include reduced stature, hypercorticism in the absence of elevated adrenocorticotropic hormone levels, increased metabolic efficiency, decreased mitogenic response coupled with increased rates of apoptosis, reduced inflammatory response, induction of stress proteins and DNA repair enzymes, altered drug-metabolizing enzyme expression, and modified cell-mediated immune function. The overall profile of these changes is one of improved defense against environmental stress. This has been suggested as the mechanistic basis for the protective effects of low body weight on radiation-and chemically induced cancers in experimental animals. It may also explain the significantly higher thresholds of acute toxicity observed when calorically restricted rodents are exposed to certain lest compounds. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Texas Tech Univ, Lubbock, TX USA. RP Leakey, JEA (reprint author), Natl Ctr Toxicol Res, HFT-020,3900 NCTR Rd, Jefferson, AR 72079 USA. FU PHS HHS [224-86-0001] NR 217 TC 51 Z9 51 U1 1 U2 4 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 1998 VL 106 SU 1 BP 313 EP 324 PG 12 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WC UT WOS:000075403700025 PM 9539025 ER PT J AU Gaylor, DW Bolger, PM Schwetz, BA AF Gaylor, DW Bolger, PM Schwetz, BA TI US Food and Drug Administration perspective of the inclusion of effects of low-level exposures in safety and risk assessment SO ENVIRONMENTAL HEALTH PERSPECTIVES LA English DT Article; Proceedings Paper CT 3rd BELLE Conference on Toxicological Defense Mechanisms and the Shape of Dose-Response Relationships CY NOV 12-14, 1996 CL RES TRIANGLE PK, NORTH CAROLINA SP Biol Effects Low Level Exposures, Advisory Comm DE health risk assessment; regulatory practices; toxicity; US Food and Drug Administration (US FDA) AB A brief overview is provided of some of the general safety and risk assessment procedures used by the different centers of the U.S. Food and Drug Administration (U.S. FDA) to evaluate low-level exposures. The U.S. FDA protects public health by regulating a wide variety of consumer products including foods, human and animal drugs, biologics, and medical devices under the federal Food, Drug, and Cosmetic Act. The diverse legal and regulatory standards in the act allow for the consideration of benefits for some products (e.g., drugs) but preclude them from others (e.g., food additives). When not precluded by statutory mandates (e.g., Delaney prohibition), the U.S. FDA considers both physiologic adaptive responses and beneficial effects. For the basic safety assessment paradigm as presently used, for example in the premarket approval of food additives, the emphasis is on the identification of adverse effects and no observed adverse effect level(s) (NOAEL). Generally, the NOAEL is divided by safety factors to establish an acceptable exposure level. This safely assessment paradigm does not preclude the consideration of effects whether they are biologically adaptive or beneficial at lower dose levels. The flexibility to consider issues such as mechanisms of action and adaptive and beneficial responses depends on the product under consideration. For carcinogenic contaminants and radiation from medical devices, the U.S. FDA considers the potential cancer risk at low exposure levels. This generally involves downward extrapolation from the observed dose-response range. The consideration of adverse effects of other toxicologic end points (e.g., reproductive, immunologic, neurologic, developmental) associated with low exposure levels is also becoming more of a reality (e.g., endocrine disrupters). The evaluation of the biologic effects of low-level exposures to toxic substances must include whether the effect is adverse or a normal physiologic adaptive response and also determine the resiliency of a physiologic system. The public health mandate of the U.S. FDA includes an active research program at the National Center for Toxicological Research and the other U.S. FDA centers to support the regulatory mission of the U.S. FDA. This includes the development of knowledge bases, predictive strategies, and toxicologic studies to investigate effects at the lower end of the dose-response range. Because of the wide diversity of legal and regulatory standards for various products regulated by the U.S. FDA, agency-wide safety and risk assessment procedures and policies generally do not exist. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, Rockville, MD 20857 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Gaylor, DW (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 7 TC 9 Z9 9 U1 0 U2 0 PU US DEPT HEALTH HUMAN SERVICES PUBLIC HEALTH SERVICE PI RES TRIANGLE PK PA NATL INST HEALTH, NATL INST ENVIRONMENTAL HEALTH SERVICES, PO BOX 12233, RES TRIANGLE PK, NC 27709-2233 USA SN 0091-6765 J9 ENVIRON HEALTH PERSP JI Environ. Health Perspect. PD FEB PY 1998 VL 106 SU 1 BP 391 EP 394 DI 10.2307/3433944 PG 4 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA 110WC UT WOS:000075403700036 PM 9539036 ER PT J AU Negiz, A Ramanauskas, P Cinar, A Schlesser, JE Armstrong, DJ AF Negiz, A Ramanauskas, P Cinar, A Schlesser, JE Armstrong, DJ TI Modeling, monitoring and control strategies for high temperature short time pasteurization systems - 1. Empirical model development SO FOOD CONTROL LA English DT Article DE time series models; autoregressive models with exogenous inputs; transfer functions; HTST pasteurization AB Dynamic models of high temperature short time (HTST) pasteurization systems can be developed by using empirical model development paradigms such as transfer functions and times series models. Properly designed experiments that excite all output variables provide good data that enable the development of accurate dynamic models. These models are used in feedback control and statistical process monitoring system design. The methodology for time series model development for HTST pasteurization processes is illustrated by using data collected from a pilot scale HTST pasteurization system. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 IIT, Dept Environm Chem & Engn, Chicago, IL 60616 USA. US Food & Drug Adm, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Negiz, A (reprint author), IIT, Dept Environm Chem & Engn, Chicago, IL 60616 USA. OI Cinar, Ali/0000-0002-1607-9943 NR 19 TC 11 Z9 11 U1 0 U2 4 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD FEB PY 1998 VL 9 IS 1 BP 1 EP 15 DI 10.1016/S0956-7135(97)00012-1 PG 15 WC Food Science & Technology SC Food Science & Technology GA ZK513 UT WOS:000073330000002 ER PT J AU Negiz, A Ramanauskas, P Cinar, A Schlesser, JE Armstrong, DJ AF Negiz, A Ramanauskas, P Cinar, A Schlesser, JE Armstrong, DJ TI Modeling, monitoring and control strategies for high temperature short time pasteurization systems - 2. Lethality-based control SO FOOD CONTROL LA English DT Article DE automatic control; lethality-based control; dairy products pasteurization; HTST pasteurization AB A lethality-based control system was designed to provide accurate control of a high temperature shout time (HTST) pasteurizer and to process milk products with a lethality equivalent of 161 degrees F (71.67 degrees C) or above for 15 s. This control system provides significant flexibility in operating the process and optimizing functional properties of the food components. Multivariable control of an HTST pasteurizer is implemented by using product total lethality to determine the controller set-points. The equation that relates the temperature and flow rate combinations to the product total lethality, 161 degrees F (71.67 degrees C), 15 s, was modified to permit overprocessing levels specified by plant personnel. By using this equation and the set-point value selected for the other variable, set-point values for the temperature or the flow rate controller were computed. The flow and temperature controllers are integrated into a real-time monitoring and control system. The monitoring and control system includes the multivariable controller, the lethality rate calculation module, statistical monitoring of the total lethality, product flow rate, hot wafer outlet temperature, and holding tube exit temperature measurements, and the display screens for visual inspection of the monitoring tools. This study attempted to achieve compliance of the HTST process operation with the recommended Pasteurized Milk Ordinance by providing a margin between the alarm limits of the monitoring chart and the safety limits. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 IIT, Dept Environm Chem & Engn, Chicago, IL 60616 USA. US Food & Drug Adm, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Cinar, A (reprint author), IIT, Dept Environm Chem & Engn, Chicago, IL 60616 USA. OI Cinar, Ali/0000-0002-1607-9943 NR 22 TC 9 Z9 9 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD FEB PY 1998 VL 9 IS 1 BP 17 EP 28 DI 10.1016/S0956-7135(97)00013-3 PG 12 WC Food Science & Technology SC Food Science & Technology GA ZK513 UT WOS:000073330000003 ER PT J AU Negiz, A Ramanauskas, P Cinar, A Schlesser, JE Armstrong, DJ AF Negiz, A Ramanauskas, P Cinar, A Schlesser, JE Armstrong, DJ TI Modeling, monitoring and control strategies for high temperature short time pasteurization systems - 3. Statistical monitoring of product lethality and process sensor reliability SO FOOD CONTROL LA English DT Article DE statistical process control; product safety monitoring; sensor fusion; dairy products pasteurization; autocorrelated process; multivariable process ID CORRELATED OBSERVATIONS; PERFORMANCE AB Statistical process monitoring (SPM) is used in food processing industries to improve productivity and product quality. SPM can also provide information to operators on how close a process is to non-compliance to product safety limits, and carry out periodic checks of sensor accuracy at high frequency. Traditional SPM tools such as Shewhart charts are not appropriate for continuous food processes because of autocorrelation in data. Four alternative SPM techniques are presented and applied to high temperature short time (HTST) dairy pasteurization. The study attempted to achieve compliance of the HTST process operation with the recommended Pasteurized Milk Ordinance by providing a margin between the alarm limits of the monitoring chart and the safety limits. Monitoring of residuals and parameter change detection techniques ave used for monitoring processes with autocorrelated variables. Hotelling's T-2 and residuals of canonical variates techniques are used for monitoring multivariable processes. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 IIT, Dept Environm Chem & Engn, Chicago, IL 60616 USA. US Food & Drug Adm, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Cinar, A (reprint author), IIT, Dept Environm Chem & Engn, Chicago, IL 60616 USA. OI Cinar, Ali/0000-0002-1607-9943 NR 28 TC 11 Z9 11 U1 1 U2 7 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0956-7135 J9 FOOD CONTROL JI Food Control PD FEB PY 1998 VL 9 IS 1 BP 29 EP 47 DI 10.1016/S0956-7135(97)00014-5 PG 19 WC Food Science & Technology SC Food Science & Technology GA ZK513 UT WOS:000073330000004 ER PT J AU Blodgett, RJ Garthright, WE AF Blodgett, RJ Garthright, WE TI Several MPN models for serial dilutions with suppressed growth at low dilutions SO FOOD MICROBIOLOGY LA English DT Article AB Most probable number (MPN) estimates of microbial concentrations from serial dilutions employ a usual model of probabilities of the various possible outcomes. Outcomes challenge the usual model when they occur at markedly different rates from what the usual model predicts. Too many outcomes that suggest suppression of growth at low dilutions have occurred in some foods. These challenge the usual model and suggest new models. This paper provides four new models: growth suppression by a toxicant released from the food product by sample preparation; interference by a non-target species of microbe; disaggregation of clumped microbes at a single dilution step; disaggregation spread evenly over several dilution steps. The assumptions and discussion of how to find the maximum likelihood estimate for the parameters are given. (C) 1998 Academic Press Limited. C1 US FDA, Ctr Food Safety & Appl Nutr, Div Math, Washington, DC 20204 USA. RP Blodgett, RJ (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Div Math, 200 C St,SW, Washington, DC 20204 USA. NR 6 TC 13 Z9 13 U1 0 U2 1 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 FEB PY 1998 VL 15 IS 1 BP 91 EP 99 DI 10.1006/fmic.1997.0144 PG 9 WC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology SC Biotechnology & Applied Microbiology; Food Science & Technology; Microbiology GA ZA446 UT WOS:000072364100011 ER PT J AU Nakashima, Y Hsia, CC Hao, YW Minemura, M Nakashima, O Kojiro, M Tabor, E AF Nakashima, Y Hsia, CC Hao, YW Minemura, M Nakashima, O Kojiro, M Tabor, E TI p53 overexpression in small hepatocellular carcinomas containing two different histologic grades SO INTERNATIONAL JOURNAL OF ONCOLOGY LA English DT Article DE p53 gene; hepatocellular carcinoma ID TUMOR-SUPPRESSOR GENE; MUTATIONS; PROGRESSION; OCCUR; HEPATOCARCINOGENESIS; CANCER; CELLS AB There is evidence to suggest that a focus of less-differentiated hepatocellular carcinoma (HCC) may arise within a pre-existing well-differentiated HCC, eventually replacing it. In the present study, the p53 tumor suppressor gene was analyzed by immunohistochemistry in 31 hepatocellular carcinomas (HCCs) containing two or more regions in the same nodule with different histologic grades. p53 was overexpressed in the nucleus in 13 of 31 HCCs (42%), in seven of which p53 overexpression was seen only in the less-differentiated area of the tumor. This suggests that overexpression of presumed mutant p53 may have contributed to dedifferentiation during the development of HCC. C1 US FDA, Div Transfus Transmitted Dis, Rockville, MD 20852 USA. Kurume Univ, Sch Med, Dept Pathol 1, Kurume, Fukuoka 830, Japan. RP Tabor, E (reprint author), US FDA, Div Transfus Transmitted Dis, HFM-310,1401 Rockville Pike, Rockville, MD 20852 USA. NR 24 TC 7 Z9 7 U1 0 U2 0 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1019-6439 J9 INT J ONCOL JI Int. J. Oncol. PD FEB PY 1998 VL 12 IS 2 BP 455 EP 459 PG 5 WC Oncology SC Oncology GA YT516 UT WOS:000071614900032 PM 9458375 ER PT J AU Kubo, HD Coursey, BM Hanson, WF Kline, RW Seltzer, SM Shuping, RE Williamson, JF AF Kubo, HD Coursey, BM Hanson, WF Kline, RW Seltzer, SM Shuping, RE Williamson, JF TI Report of the ad hoc committee of the AAPM radiation therapy committee on I-125 sealed source dosimetry SO INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS LA English DT Article DE I-125 dosimetry; brachytherapy; dose-rate constant ID I125 SEEDS; WATER AB Purpose: Two developments in I-125-sealed source dosimetry have necessitated swift and accurate implementation of TG-43 dosimetry in clinic: (a) the dosimetry constants of I-125 endorsed by the AAPM Task Group 43 Report result in calculated dose rate that deviates by as much as 15 % from currently accepted dose-rate distributions, and (b) The National Institute of Standards and Technology (NIST) has proposed modifying the I-125 air-kerma strength standard by approximately 10 %. Methods and Materials: The ad hoc committee of AAPM Radiation Therapy Committee describes specific procedures to implement these two developments without causing confusion and mistakes. Conclusions: Confusion and mistakes may be avoided when the following two general steps are taken: 1) STEP L, TG-43 implementation, and 2) STEP II, new air-kerma strength standard implementation when available from NIST. (C) 1998 Elsevier Science Inc. C1 Univ Calif Davis, Ctr Canc, Dept Radiat Oncol, Sacramento, CA 95817 USA. Natl Inst Stand & Technol, Ionizing Radiat Div, Gaithersburg, MD USA. Univ Texas, Md Anderson Canc Ctr, Dept Radiat Phys, Houston, TX 77030 USA. Mayo Clin, Dept Radiat Oncol, Rochester, MN USA. Natl Inst Stand & Technol, Ionizing Radiat Div, Gaithersburg, MD 20899 USA. US FDA, Rockville, MD 20857 USA. Washington Univ, Mallinckrodt Inst Radiol, St Louis, MO USA. RP Kubo, HD (reprint author), Univ Calif Davis, Ctr Canc, Dept Radiat Oncol, Ste G-126,4501 X St, Sacramento, CA 95817 USA. NR 12 TC 32 Z9 32 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0360-3016 J9 INT J RADIAT ONCOL JI Int. J. Radiat. Oncol. Biol. Phys. PD FEB 1 PY 1998 VL 40 IS 3 BP 697 EP 702 DI 10.1016/S0360-3016(97)00767-0 PG 6 WC Oncology; Radiology, Nuclear Medicine & Medical Imaging SC Oncology; Radiology, Nuclear Medicine & Medical Imaging GA YX786 UT WOS:000072077700024 PM 9486622 ER PT J AU Duarte, CG Zhang, J Ellis, S AF Duarte, CG Zhang, J Ellis, S TI Effects of radiocontrast and endothelin administration on systolic blood pressure and renal damage in male spontaneously hypertensive and Wistar Kyoto rats with phentolamine-induced adrenergic blockade SO INVESTIGATIVE RADIOLOGY LA English DT Article DE spontaneously hypertensive rats; radiocontrast; endothelin; phentolamine renal damage ID SYMPATHETIC-NERVES; CONTRAST-MEDIA; MAINTENANCE AB RATIONALE AND OBJECTIVES. The systemic administration of hypertonic solutions may activate the adrenergic system, thus triggering vasomotor reactions that may result in renal failure, In this study the effects of diatrizoate meglumine sodium radiocontrast agent Hypaque-76 on systolic blood pressure (BP) and renal damage were determined in male spontaneously hypertensive (SH) rats and Wistar Kyoto (WKY) rats under adrenergic blockade. METHODS. The systolic BP was measured in ketamine-anesthetized male SH and WKY rats after administration of saline solution, radiocontrast, or endothelin during adrenergic blockade with phentolamine. Then the left kidney mas removed and examined histologically. RESULTS. The fall in systolic BP after phentolamine was not influenced by saline solution or radiocontrast in WKY rats but was restored partially by radiocontrast in SH rats. Endothelin produced an elevation in BP toward baseline levels in both strains. Only moderate renal damage was observed in the kidneys of WKY rats given radiocontrast or endothelin, but very severe damage was produced by these agents in SH rats. CONCLUSIONS. Adrenergic blockade with phentolamine did not prevent the elevation in systolic BP in SH rats by radiocontrast or by endothelin in SH and WKY rats, nor did it protect against renal damage by radiocontrast or by endothelin in SH rats. C1 US FDA, Div Cardiorenal Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. US FDA, Div Res & Testing, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Duarte, CG (reprint author), US FDA, Div Cardiorenal Drug Prod, Ctr Drug Evaluat & Res, HFD-110,5600 Fishers Lane, Rockville, MD 20857 USA. EM duarte@cder.fda.gov NR 31 TC 9 Z9 9 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0020-9996 J9 INVEST RADIOL JI Invest. Radiol. PD FEB PY 1998 VL 33 IS 2 BP 104 EP 112 DI 10.1097/00004424-199802000-00008 PG 9 WC Radiology, Nuclear Medicine & Medical Imaging SC Radiology, Nuclear Medicine & Medical Imaging GA YV625 UT WOS:000071846100008 PM 9493726 ER PT J AU Stoica, B DeBell, KE Graham, L Rellahan, BL Alava, MA Laborda, J Bonvini, E AF Stoica, B DeBell, KE Graham, L Rellahan, BL Alava, MA Laborda, J Bonvini, E TI The amino-terminal Src homology 2 domain of phospholipase C gamma 1 is essential for TCR-induced tyrosine phosphorylation of phospholipase C gamma 1 SO JOURNAL OF IMMUNOLOGY LA English DT Article ID T-CELL RECEPTOR; GROWTH-FACTOR RECEPTOR; SIGNAL-TRANSDUCTION; ANTIGEN RECEPTOR; SH2 DOMAIN; C-GAMMA; PHOSPHATIDYLINOSITOL 3-KINASE; CD2 STIMULATION; EGF RECEPTOR; BINDING-SITE AB TCR engagement activates phospholipase C gamma 1 (PLC gamma 1) via a tyrosine phosphorylation-dependent mechanism. PLC gamma 1 contains a pair of Src homology 2 (SH2) domains whose function is that of promoting protein interactions by binding phosphorylated tyrosine and adjacent amino acids, The role of the PLC gamma 1 SH2 domains in PLC gamma 1 phosphorylation was explored by mutational analysis of an epitope-tagged protein transiently expressed in Jurkat T cells. Mutation of the amino-terminal SH2 domain (SH2(N) domain) resulted in defective tyrosine phosphorylation of PLC gamma 1 in response to TCR/CD3 perturbation. In addition, the PLC gamma 1 SH2(N) domain mutant failed to associate with Grb2 and a 36- to 38-kDa phosphoprotein (p36-38), which has previously been recognized to interact with PLC gamma 1, Grb2, and other molecules involved in TCR signal transduction. Conversely, mutation of the carboxyl-terminal SH2 domain (SH2(C) domain) did not affect TCR-induced tyrosine phosphorylation of PLC gamma 1. Furthermore, binding of p36-38 to PLC gamma 1 was not abrogated by mutations of the SH2(C) domain. In contrast to TCR/CD3 Ligation, treatment of cells with pervanadate induced tyrosine phosphorylation of either PLC gamma 1 SH2(N) or SH2(C) domain mutants to a level comparable with that of the mild-type protein, indicating that pervanadate treatment induces an alternate mechanism of PLC gamma 1 phosphorylation, These data indicate that the SH2(N) domain is required for TCR-induced PLC gamma 1 phosphorylation, presumably by participating in the formation of a complex that promotes the association of PLC gamma 1 with a tyrosine kinase. C1 Ctr Biol Evaluat & Res, Immunobiol Lab, Div Monoclonal Antibodies, OTRR, Bethesda, MD 20892 USA. RP Bonvini, E (reprint author), Ctr Biol Evaluat & Res, Immunobiol Lab, Div Monoclonal Antibodies, OTRR, HFM-564,Natl Inst Hlth Campus,Bldg 29B,Room 3NN10, Bethesda, MD 20892 USA. RI STOICA, BOGDAN/H-9782-2013; Laborda, Jorge/L-5726-2014 OI STOICA, BOGDAN/0000-0002-2501-6434; Laborda, Jorge/0000-0002-9210-838X NR 50 TC 49 Z9 50 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 FEB 1 PY 1998 VL 160 IS 3 BP 1059 EP 1066 PG 8 WC Immunology SC Immunology GA YW269 UT WOS:000071915400002 PM 9570517 ER PT J AU Khan, AA Jones, RA Cerniglia, CE AF Khan, AA Jones, RA Cerniglia, CE TI Rapid method for the detection of genetically engineered microorganisms by polymerase chain reaction from soil and sediments SO JOURNAL OF INDUSTRIAL MICROBIOLOGY & BIOTECHNOLOGY LA English DT Article DE PCR; genetically engineered microorganisms (GEMs); Pseudomonas putida; catechol 2,3-dioxygenase; xylE ID PSEUDOMONAS-PUTIDA; ESCHERICHIA-COLI; 3-PHENYLCATECHOL DIOXYGENASE; ENVIRONMENTAL-SAMPLES; DNA; GENES; EXPRESSION; GENOTYPES; SURVIVAL; BIPHENYL AB A rapid and sensitive method for the detection of genetically engineered microorganisms in soil and sediments has been devised by in vitro amplification of the target DNAs by a polymerase chain reaction. A cloned catechol 2,3-dioxygenase gene located on the recombinant plasmid pOH101 was transferred to Pseudomonas putida MMB2442 by triparental crossing and used as a target organism, For the polymerase chain reaction from soil and sediment samples, the template DNA was released from a 100-mg soil sample. Bacterial seeded soil samples were washed with Tris-EDTA buffer (pH 8.0) and treated with a detergent lysis solution at 100 degrees C, After addition of 1% polyvinylpolypyrrolidine solution, the samples were boiled for 5 min, Supernatant containing nucleic acid was purified with a PCR purification kit. The purified DNA was subjected to polymerase chain reaction, using two specific primers designed for the amplification of catechol 2,3-dioxygenase gene sequences. The detection limit was 10(2) cells per gram of soil. This method is rapid and obviates the need far lengthy DNA purification from soil samples. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Cerniglia, CE (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 22 TC 17 Z9 20 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1367-5435 J9 J IND MICROBIOL BIOT JI J. Ind. Microbiol. Biotechnol. PD FEB PY 1998 VL 20 IS 2 BP 90 EP 94 DI 10.1038/sj.jim.2900489 PG 5 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA ZJ940 UT WOS:000073269000004 PM 9643968 ER PT J AU Sadaie, MR Zamani, M Whang, S Sistron, N Arya, SK AF Sadaie, MR Zamani, M Whang, S Sistron, N Arya, SK TI Towards developing HIV-2 lentivirus-based retroviral vectors for gene therapy: Dual gene expression in the context of HIV-2 LTR and Tat SO JOURNAL OF MEDICAL VIROLOGY LA English DT Article DE gene transfer; promoter/cell specificity; regulatory loops; AIDS ID HUMAN-IMMUNODEFICIENCY-VIRUS; LONG TERMINAL REPEAT; RIBOSOME ENTRY SITE; REGULATORY ELEMENTS; HEMATOPOIETIC-CELLS; TYPE-2 HIV-2; 2 GENES; IN-VIVO; TRANSLATION; INITIATION AB Because of the distinct ability of retroviruses to integrate into the target cell genome and thus achieve long-term expression, retrovirus vectors hold great promise for stable gene transfer. Such vectors derived from human immunodeficiency retroviruses (HIVs) and other lentiviruses are envisioned to possess several advantages, especially for in vivo gene therapy of HIV infection and acquired immunodeficiency syndrome (AIDS) where targeting CD4+ T cells/macrophages and pluripotent non-dividing stem cells would be required. Among these is the ability of HIVs to transduce nondividing cells in contrast to the murine retroviruses which require target cell mitosis. The advantages of the lentivirus vectors will be further enhanced by the development of multigenic vectors carrying more than one gene in a dependent or independent transcriptional unit. Separate from the issue of transduction efficiency, information is needed about the impact of the configuration of the genes in a multigenic vector on their expression. Towards this end, we investigated the expression of genes specifically directed by the HIV-2 LTR and Tat in a prototypic minimal transfer vector. We found that the expression of a gene in a dual gene configuration depended upon its position in the transcriptional unit and that the insertion of an internal translational initiation mechanism improved the expression of the downstream gene. Apparently not sufficiently appreciated previously, these effects were promoter and cell-type dependent. Our data also suggest that the commonly used cellular or viral promoters may be orders of magnitude less effective than HIV-2 LTR in the presence of Tat, and thus may not be useful as internal promoters in the context of the HIV-2 LTR:Tat regulatory loop. (C) 1998 Wiley-Liss, Inc.dagger. C1 NCI, Basic Res Lab, Div Basic Sci, NIH, Bethesda, MD 20892 USA. US FDA, Lab Immunochem, Div Transfus Transmitted Dis, CBER, Rockville, MD 20857 USA. RP Arya, SK (reprint author), NCI, Basic Res Lab, Div Basic Sci, NIH, 37 Convent Dr,Bldg 37,Room 6C24, Bethesda, MD 20892 USA. NR 40 TC 19 Z9 19 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 0146-6615 J9 J MED VIROL JI J. Med. Virol. PD FEB PY 1998 VL 54 IS 2 BP 118 EP 128 PG 11 WC Virology SC Virology GA YV169 UT WOS:000071796300009 PM 9496370 ER PT J AU Lekstrom-Himes, JA Wang, KN Pesnicak, L Krause, PR Straus, SE AF Lekstrom-Himes, JA Wang, KN Pesnicak, L Krause, PR Straus, SE TI The comparative biology of latent herpes simplex virus type 1 and type 2 infections: latency-associated transcript promoter activity and expression in vitro and in infected mice SO JOURNAL OF NEUROVIROLOGY LA English DT Article DE animal models; herpes simplex virus; latency-associated transcripts; virus latency; viral pathogenesis ID HUMAN TRIGEMINAL GANGLIA; NERVE GROWTH-FACTOR; GENITAL HERPES; MESSENGER-RNA; IN-VIVO; INDUCED REACTIVATION; SODIUM-BUTYRATE; PC12 CELLS; GENE; IDENTIFICATION AB HSV-1 and HSV-2 express abundant latency-associated transcripts (LATs) without which these viruses reactivate in animals inefficiently. To further characterize the importance of LATs to the comparative biology of latent HSV-1 and -2 infections, we assessed the relative activities of the viral LAT promoters in vitro using transient transfection assays? and the accumulation of LATs in vivo using a mouse ocular infection model. In vitro, the HSV-2 LAT promoter proved to be six to tenfold more potent than the HSV-1 promoter in driving reporter gene expression. In mice HSV-1 and -2 achieved comparable levels of virus replication in the eye, but HSV-2, grew to higher titers than HSV-1 in trigeminal ganglia and brain. Quantitative-competitive DNA and RNA (RT) PCR and in situ hybridization showed that ganglia latently infected with HSV-2 contained sixfold more copies of DNA (P=0.003), eightfold more LATS (P=0.01), and ninefold more LAT in situ-positive neurons. However, the numbers of LATs per latent genome were equivalent for both viruses. Although the HSV-2 LAT promoter is more potent than the HSV-1 promoter in transient expression assays, the accumulation of HSV-1 and 2 LATs in mouse trigeminal ganglia is comparable. C1 NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Virol, Bethesda, MD 20892 USA. RP Straus, SE (reprint author), NIAID, Med Virol Sect, Clin Invest Lab, NIH, Bldg 10 Room 11N-228,10 Ctr Dr, Bethesda, MD 20892 USA. NR 52 TC 6 Z9 6 U1 0 U2 1 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 1355-0284 J9 J NEUROVIROL JI J. Neurovirol. PD FEB PY 1998 VL 4 IS 1 BP 27 EP 37 PG 11 WC Neurosciences; Virology SC Neurosciences & Neurology; Virology GA YZ339 UT WOS:000072244500002 PM 9531009 ER PT J AU Clausing, P Newport, GD Bowyer, JF AF Clausing, P Newport, GD Bowyer, JF TI Fenfluramine and norfenfluramine levels in brain microdialysate, brain tissue and plasma of rats administered dose of d-fenfluramine known to deplete 5-hydroxytryptamine levels in brain SO JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS LA English DT Article ID INDIVIDUAL-DIFFERENCES; AMPHETAMINE LEVELS; CAUDATE-PUTAMEN; SEROTONIN; RELEASE; DRUG; 5-HT; PHARMACOKINETICS; DEXFENFLURAMINE; NEUROTOXICITY AB The relationship between dose, frontal cortex (brain) microdialysate and brain tissue levels of fenfluramine (FEN) and norfenfluramine (NF), as well as the effect that these levels have on body temperature, was determined after systemic d-FEN. FEP and NF levels were monitored continuously in the microdialysate of adult male Sprague-Dawley rats dosed with 3 x 5 mg/kg s.c. (spaced 2 hr apart), 1 x 2 mg/kg s.c. or 1 x 10 mg/kg i.p. d-FEN (at ambient temperatures of either 23 degrees C or 27 degrees C). Drug concentrations In plasma and brain regions were also determined 1 hr after one or three doses of 5 mg/kg of d-FEN and 1 and 8 hr after 10 mg/kg d-FEN, and the levels of 5-hydroxytryptamine and 5-hydroxyindole acetic acid in the frontal cortex of FEN and controls were determined 4 days after dosing. Peak microdialysate FEN levels occurring between 40 and 60 min after the first dose, were 0.24 +/- 0.07 mu M after 2 mg/kg, 0.33 +/- 0.04 mu M after 5 mg/kg and 1.65 mu M after 10 mg/kg. After multiple doses of 5 mg/kg FEN the time-to-peak level was greater than 80 min with peaks of 0.68 +/- 0.04 mu M after the second dose and 1.20 +/- 0.07 mu M after the third dose. There was a positive correlation between combined (FEN + NF) peak levels in microdialysate and the increase in body temperature after 10 mg/kg d-FEN at 27 degrees C; however, the group mean and peak levels of FEN and NF in microdialysate were statistically the same at either 23 degrees C or 27 degrees C. The indole-depleting effect of d-FEN at 4 days after dosing was exacerbated at 27 degrees C when hyperthermia occurred. Thus, hyperthermia does not affect the pharmacokinetics of d-FEN but pharmacokinetics can influence the degree of hyperthermia in a 27 degrees C environment, Plasma levels, brain extracellular and brain levels of approximately 1 mu M, 2.5 mu M and 50 mu M FEN (respectively), or greater, result from 5-hydroxytryptamine-depleting doses of 5 mg/kg s.c. FEN. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Scantox Biol Labs, DK-4623 Lille Skensved, Denmark. RP Bowyer, JF (reprint author), Natl Ctr Toxicol Res, Div Neurotoxicol, HFT-132, Jefferson, AR 72079 USA. NR 44 TC 18 Z9 18 U1 0 U2 0 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 FEB PY 1998 VL 284 IS 2 BP 618 EP 624 PG 7 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA YW378 UT WOS:000071929100026 PM 9454806 ER PT J AU Califf, RM Abdelmeguid, AE Kuntz, RE Popma, JJ Davidson, CJ Cohen, EA Kleiman, NS Mahaffey, KW Topol, EJ Pepine, CJ Lipicky, RJ Granger, CB Harrington, RA Tardiff, BE Crenshaw, BS Bauman, RP Zuckerman, BD Chaitman, BR Bittl, JA Ohman, EM AF Califf, RM Abdelmeguid, AE Kuntz, RE Popma, JJ Davidson, CJ Cohen, EA Kleiman, NS Mahaffey, KW Topol, EJ Pepine, CJ Lipicky, RJ Granger, CB Harrington, RA Tardiff, BE Crenshaw, BS Bauman, RP Zuckerman, BD Chaitman, BR Bittl, JA Ohman, EM TI Myonecrosis after revascularization procedures SO JOURNAL OF THE AMERICAN COLLEGE OF CARDIOLOGY LA English DT Article ID ACUTE MYOCARDIAL-INFARCTION; QRS SCORING SYSTEM; CREATINE KINASE-MB; TRANSLUMINAL CORONARY ANGIOPLASTY; QUANTITATIVE ANATOMIC FINDINGS; ATHERECTOMY TRIAL CAVEAT; BYPASS GRAFT-SURGERY; CARDIAC TROPONIN-T; SKELETAL-MUSCLE; ELECTROCARDIOGRAPHIC CHANGES AB The detection of elevated cardiac enzyme levels and the occurrence of electrocardiographic (EGG) abnormalities after revascularization procedures have been the subject of recent controversy. This report represents an effort to achieve a consensus among a group of researchers with data on this subject. Creatine kinase (CK) or CK-MB isoenzyme (CK MB) elevations occur in 5% to 30% of patients after a percutaneous intervention and commonly during coronary artery bypass graft surgery (CABG). Although Q wave formation is rare, other ECG changes are common. The rate of detection is highly dependent on the intensity of enzyme and ECG measurement. Because most events occur without the development of a Q wave, the ECG will not definitively diagnose them; even the ECG criteria for Q wave formation signifying an important clinical event have been variable. At least 10 studies evaluating >10,000 patients undergoing percutaneous intervention have demonstrated that elevation of CK or CK MB is associated not only with a higher mortality, but also with a higher risk of subsequent cardiac events and higher cost. Efforts to identify a specific cutoff value below which the prognosis is not impaired have not been successful. Rather, the risk of adverse outcomes increases with any elevation of CK or CK-MB and increases further in proportion to the level of intervention. This information complements similar previous data on CABG. Obtaining preprocedural and postprocedural ECGs and measurement of serial cardiac enzymes after revascularization are recommended. Patients with enzyme levels elevated more than threefold above the upper limit of normal or with ECG changes diagnostic for Q wave myocardial infarction (MI) should be treated as patients with an MI. Patients with more modest elevations should be observed carefully. Clinical trials should ensure systematic evaluation for myocardial necrosis, with attention paid to multivariable analysis of risk factors for poor long-term outcome, to determine the extent to which enzyme elevation is an independent risk factor after considering clinical history, coronary anatomy, left ventricular function and clinical evidence of ischemia. In addition, tracking of enzyme levels in clinical trials is needed to determine whether interventions that reduce periprocedural enzyme elevation also improve mortality. (C) 1998 by the American College of Cardiology. C1 Duke Univ, Med Ctr, Dept Anesthesiol, Durham, NC 27710 USA. Duke Univ, Med Ctr, Dept Med, Div Cardiol, Durham, NC 27710 USA. Henry Ford Hosp & Med Ctr, Detroit, MI USA. Beth Israel Hosp, Boston, MA 02215 USA. Washington Hosp Ctr, Washington, DC 20010 USA. Northwestern Univ, Sch Med, Chicago, IL USA. Sunnybrook Hlth Sci Ctr, Toronto, ON M4N 3M5, Canada. Baylor Coll Med, Methodist Hosp, Houston, TX 77030 USA. Cleveland Clin Fdn, Dept Cardiol, Cleveland, OH 44195 USA. Univ Florida, Coll Med, Gainesville, FL USA. US FDA, Rockville, MD 20857 USA. St Louis Univ, Dept Internal Med, St Louis, MO 63103 USA. Brigham & Womens Hosp, Dept Med, Div Cardiovasc, Boston, MA 02115 USA. RP Duke Clin Res Inst, 2024 W Main St, Durham, NC 27705 USA. EM calif001@mc.duke.edu RI Granger, Christopher/D-3458-2014; OI Granger, Christopher/0000-0002-0045-3291; Topol, Eric/0000-0002-1478-4729 NR 98 TC 419 Z9 436 U1 2 U2 7 PU ELSEVIER SCIENCE INC PI NEW YORK PA 360 PARK AVE SOUTH, NEW YORK, NY 10010-1710 USA SN 0735-1097 EI 1558-3597 J9 J AM COLL CARDIOL JI J. Am. Coll. Cardiol. PD FEB PY 1998 VL 31 IS 2 BP 241 EP 251 DI 10.1016/S0735-1097(97)00506-8 PG 11 WC Cardiac & Cardiovascular Systems SC Cardiovascular System & Cardiology GA YV175 UT WOS:000071796900001 PM 9462562 ER PT J AU Contrera, JF AF Contrera, JF TI Transgenic animals: Refining the two year rodent carcinogenicity study SO LAB ANIMAL LA English DT Article ID MICE; GENE AB Efforts are currently underway to refine the double two-year carcinogenicity tests required for new pharmaceuticals. The International Conference on Harmonization has recently approved the use of short-term studies using transgenic animal models to replace the second two-year study. Transgenic studies use fewer animals, have less spontaneous tumor incidence, and hold the promise of stronger weight-of-evidence and enhanced cross-species extrapolation. C1 US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Rockville, MD 20857 USA. RP Contrera, JF (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, HFD-900,5600 Fishers Lane, Rockville, MD 20857 USA. NR 6 TC 3 Z9 3 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD FEB PY 1998 VL 27 IS 2 BP 30 EP 33 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA YW283 UT WOS:000071916800007 ER PT J AU Seng, JE Allaben, WT Nichols, ML Bryant, BD Ulmer, C Contrera, JF Leakey, JEA AF Seng, JE Allaben, WT Nichols, ML Bryant, BD Ulmer, C Contrera, JF Leakey, JEA TI Putting dietary control to the test: Increasing bioassay sensitivity by reducing variability SO LAB ANIMAL LA English DT Article ID BODY-WEIGHT; CALORIC RESTRICTION; TUMOR-INCIDENCE; MECHANISMS; PATHOLOGY; SURVIVAL; TOXICITY; MICE AB Capitalizing on the relationship between body weight and spontaneous tumor incidence, the authors explain how to use rodent dietary control to standardize background tumor incidence, thus increasing bioassay sensitivity. This may also result in the need for fewer animals in chronic bioassay tests. C1 Natl Ctr Toxicol Res, Div Microbiol & Chem, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Bionet Corp, Jefferson, AR 72079 USA. ROW Sci, Rockville, MD USA. US FDA, Ctr Drug Evaluat, Rockville, MD USA. RP Seng, JE (reprint author), Natl Ctr Toxicol Res, Div Microbiol & Chem, Jefferson, AR 72079 USA. NR 17 TC 8 Z9 8 U1 0 U2 0 PU NATURE AMERICA INC PI NEW YORK PA 345 PARK AVE SOUTH, NEW YORK, NY 10010-1707 USA SN 0093-7355 J9 LAB ANIMAL JI Lab Anim. PD FEB PY 1998 VL 27 IS 2 BP 35 EP 38 PG 4 WC Veterinary Sciences SC Veterinary Sciences GA YW283 UT WOS:000071916800008 ER PT J AU Evans-Davis, KD Dillehay, DL Wargo, DN Webb, SK Talkington, DF Thacker, WL Small, LS Brown, MB AF Evans-Davis, KD Dillehay, DL Wargo, DN Webb, SK Talkington, DF Thacker, WL Small, LS Brown, MB TI Pathogenicity of Mycoplasma volis in mice and rats SO LABORATORY ANIMAL SCIENCE LA English DT Article AB A new species of Mycoplasma, M. volis, was isolated front the respiratory tract of clinically normal field-trapped prairie voles (Microtus ochrogaster) that were to be housed in close proximity to other rodents. To determine the pathogenic potential of the new mycoplasmal isolate, three groups of rodents (Sprague Dawley rats, BALB/c mice, and severe combined immunodeficient [SCID] mice) were intranasally inoculated with 2 x 10(8) color-changing units (CCU) of M. volis and were observed for 4 to 6 weeks. Experimental animals did not manifest clinical signs of disease; however, one experimental SCID mouse was euthanized 5 days after inoculation because of a severe circling disorder, Lung lesions in experimental SD rats ranged from mild to severe bronchial-associated lymphoid tissue (BALT) hyperplasia, Lung lesions in BALB/c and SCID mice ranged from no lesions to mild pneumonia. We were able to isolate M. volis from some control mice, none of which had lung lesions, All mice were seronegative for Sendai virus, mouse hepatitis virus, and M. pulmonis. All immunocompetent experimental animals (BALB/c mice and Sprague Dawley rats) were seropositive for M. volis, All immunocompetent control animals and SCID, mice were seronegative for M. volis. Our data suggest that M. volis is capable of causing microscopic lesions and seroconversion in rats and mice, and therefore these rodents should not be housed in close proximity to voles. C1 Emory Univ, Sch Med, Div Anim Resources, Atlanta, GA USA. Emory Univ, Sch Med, Dept Pathol, Atlanta, GA 30322 USA. Ctr Dis Control & Prevent, Div Bacterial & Mycot Dis, Atlanta, GA USA. Microbiol Associates Inc, Microbiol Lab, Rockville, MD USA. Univ Florida, Dept Infect Dis, Gainesville, FL USA. RP Evans-Davis, KD (reprint author), US FDA, Div Vet Serv, 1401 Rockville Pike HFM-280, Rockville, MD 20852 USA. NR 14 TC 2 Z9 2 U1 0 U2 0 PU AMER ASSOC LABORATORY ANIMAL SCIENCE PI CORDOVA PA 70 TIMBERCREEK DR, SUITE 5, CORDOVA, TN 38018 USA SN 0023-6764 J9 LAB ANIM SCI JI Lab. Anim. Sci. PD FEB PY 1998 VL 48 IS 1 BP 38 EP 44 PG 7 WC Veterinary Sciences; Zoology SC Veterinary Sciences; Zoology GA YY876 UT WOS:000072196000008 PM 9517888 ER PT J AU Stewart, DS Tortorello, ML Gendel, SM AF Stewart, DS Tortorello, ML Gendel, SM TI Evaluation of DNA preparation techniques for detection of the SLT-1 gene of Escherichia coli O157 : H7 in bovine faeces using the polymerase chain reaction SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article ID FECAL SAMPLES; CATTLE; INFECTION; CALVES; FOOD AB The polymerase chain reaction (PCR) has the potential to detect low levels of the human pathogen Escherichia coli O157:H7 in bovine faeces. To improve the utility of PCR for this application, several methods for preparing template DNA from bovine faeces, both directly and after non-selective enrichment, were tested. These were boiling, enzyme treatment, enzyme treatment plus phenol-chloroform extraction, and enzyme treatment plus phenol-chloroform extraction plus Geneclean(R) purification. Of these, the boiling method was the most and had a sensitivity of approximately 3 cfu g(-1) faeces, with an assay time of less than 32 h. The boiling method was also combined with immunomagnetic separation (IMS) to detect E. coli O157:H7 in less than 8 h, but with a sensitivity of approximately 10(3) cfu g(-1) faeces. These methods can be used to prepare template for PCR screening of bovine faeces using any appropriate PCR primers. C1 US FDA, Natl Ctr Food Safety & Technol, Summit, IL 60501 USA. RP Stewart, DS (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit, IL 60501 USA. FU FDA HHS [FD-000431] NR 18 TC 22 Z9 26 U1 1 U2 1 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD FEB PY 1998 VL 26 IS 2 BP 93 EP 97 PG 5 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA ZD425 UT WOS:000072683900002 PM 9569687 ER PT J AU Tran, TT AF Tran, TT TI A blood-free enrichment medium for growing Campylobacter spp. under aerobic conditions SO LETTERS IN APPLIED MICROBIOLOGY LA English DT Article ID JEJUNI AB Detection limits for Campylobacter jejuni strains JH93 and ATCC 29428 in a new blood-free enrichment broth (BFEB) were investigated under aerobic conditions. Cultures of Camp. jejuni were inoculated into 50 mi BFEB containing 10% food homogenate in 50 mi screw-cap tubes. After 24 h enrichment under aerobic conditions, Camp. jejuni were isolated on four selective agar media. The least squares means of the detection limit 50% endpoint (DL50) values were 0.4 (plain BFEB), 0.9 (crabmeat), 1.7 (mushroom), 1.7 (raw milk) and 2.1 (oyster) colony forming units (cfu) 5 g(-1) food. The efficiency of the BFEB was significantly affected (P < 0.05) by food type and bacterial strain. Overall, the BFEB enrichment compared favourably with the existing US Food and Drug Administration method under modified atmosphere. In addition, the BFEB method did not require the use of blood, special equipment or Oxyrase(R) to reduce oxygen tensions. C1 US FDA, Div Microbiol Studies, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Tran, TT (reprint author), US FDA, Div Microbiol Studies, Ctr Food Safety & Appl Nutr, HFS-516,200 C St SW, Washington, DC 20204 USA. NR 14 TC 24 Z9 24 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 0266-8254 J9 LETT APPL MICROBIOL JI Lett. Appl. Microbiol. PD FEB PY 1998 VL 26 IS 2 BP 145 EP 148 PG 4 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA ZD425 UT WOS:000072683900014 PM 9569699 ER PT J AU Sehat, N Yurawecz, MP Roach, JAG Mossoba, MM Kramer, JKG Ku, Y AF Sehat, N Yurawecz, MP Roach, JAG Mossoba, MM Kramer, JKG Ku, Y TI Silver-ion high-performance liquid chromatographic separation and identification of conjugated linoleic acid isomers SO LIPIDS LA English DT Article ID FATTY-ACIDS; DIENE; DERIVATIVES; PRODUCTS; TRIENE AB This is the first report of the application of silver-ion impregnated high-performance liquid chromatography (Ag+-HPLC) to the separation of complex mixtures of conjugated linolenic acid (CLA) isomers present in commercial CLA sources and foods and in biological specimens. This method showed a clear separation of CLA isomers into three groups related to their trans,trans, cis,trans or trans,-cis, and cis,cis configuration of the conjugated double-bond system. In addition, this method separated individual positional isomers of the conjugated diene system within each geometrical isomeric group. Following Ag+-HPLC isolation, gas chromatography (GC)-electron impact mass spectrometry, and GC-direct deposition-Fourier transformed infrared spectroscopy were used to confirm the identity of two major positional isomers in the cis/trans region, i.e., Delta 8,10- and Delta 11,13-octadecadienoic acids, which had not been chromatographically resolved previously. Furthermore, the potential of this method was demonstrated by showing different Ag+-HPLC profiles exhibiting patterns of isomeric distributions for biological specimens from animals fed a diet containing a commercial CLA preparation, as well as for a commercial cheese product. C1 US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling, Washington, DC 20204 USA. Agr Canada, Food Proc Qual Improvement Program, Guelph, ON N1H 8J7, Canada. RP Yurawecz, MP (reprint author), US FDA, Ctr Food Safety & Appl Nutr, Off Food Labeling, HFS-175,200 C St SW, Washington, DC 20204 USA. NR 26 TC 199 Z9 205 U1 2 U2 21 PU AMER OIL CHEMISTS SOC PI CHAMPAIGN PA 1608 BROADMOOR DRIVE, CHAMPAIGN, IL 61821-0489 USA SN 0024-4201 J9 LIPIDS JI Lipids PD FEB PY 1998 VL 33 IS 2 BP 217 EP 221 DI 10.1007/s11745-998-0198-6 PG 5 WC Biochemistry & Molecular Biology; Nutrition & Dietetics SC Biochemistry & Molecular Biology; Nutrition & Dietetics GA YY163 UT WOS:000072119600012 PM 9507244 ER PT J AU Qi, Z AF Qi, Z TI Note on the non-homogeneous Prendiville process SO MATHEMATICAL BIOSCIENCES LA English DT Article; Proceedings Paper CT 157th Annual Meeting of the American-Statistical-Association CY AUG 10-14, 1997 CL ANAHEIM, CALIFORNIA SP Amer Stat Assoc ID MODELS AB By creating an auxiliary process, this note obtains complete solution to the distribution of the non-homogeneous Prendiville process. In addition, an error in the literature of the original Prendiville process is corrected. Published by Elsevier Science Inc. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Qi, Z (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 8 TC 1 Z9 1 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0025-5564 J9 MATH BIOSCI JI Math. Biosci. PD FEB PY 1998 VL 148 IS 1 BP 1 EP 5 PG 5 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA ZK444 UT WOS:000073321500001 ER PT J AU Shah, VP Flynn, GL Yacobi, A Maibach, HI Bon, C Fleischer, NM Franz, TJ Kaplan, SA Kawamoto, J Lesko, LJ Marty, JP Pershing, LK Schaefer, H Sequeira, JA Shrivastava, SP Wilkin, J Williams, RL AF Shah, VP Flynn, GL Yacobi, A Maibach, HI Bon, C Fleischer, NM Franz, TJ Kaplan, SA Kawamoto, J Lesko, LJ Marty, JP Pershing, LK Schaefer, H Sequeira, JA Shrivastava, SP Wilkin, J Williams, RL TI Bioequivalence of topical dermatological dosage forms - Methods of evaluation of bioequivalence SO PHARMACEUTICAL RESEARCH LA English DT Editorial Material C1 US FDA, CDER, Off Pharm Sci, Off Gener Drugs,Div Bioequivalence, Rockville, MD 20857 USA. Univ Michigan, Sch Pharm, Ann Arbor, MI 48109 USA. Taro Pharmaceut Inc, Hawthorne, NY 10532 USA. Univ Calif San Francisco, Med Ctr, Dept Dermatol, San Francisco, CA 94143 USA. Novum Pharmaceut, Pittsburgh, PA 15206 USA. Univ Arkansas, Dept Dermatol, Little Rock, AR 72205 USA. Alpharma Inc, Baltimore, MD 21224 USA. Hlth Protect Branch, Ottawa, ON K1A 1B6, Canada. US FDA, CDER, Off Pharm Sci, Off Clin Pharmacol & Biopharmaceut, Rockville, MD 20857 USA. Univ Paris, Chatenay Malabry, France. LOreal, Clichy, France. Univ Utah, Dept Dermatol, Salt Lake City, UT 84132 USA. Schering Plough Corp, Res Inst, Kenilworth, NJ 07033 USA. US FDA, CDER, Off Drug Evaluat, Div Dermatol & Dent Prod, Rockville, MD 20857 USA. RP Shah, VP (reprint author), US FDA, CDER, Off Pharm Sci, Off Gener Drugs,Div Bioequivalence, Rockville, MD 20857 USA. NR 0 TC 103 Z9 105 U1 0 U2 6 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD FEB PY 1998 VL 15 IS 2 BP 167 EP 171 DI 10.1023/A:1011941929495 PG 5 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA ZA124 UT WOS:000072331300002 PM 9523299 ER PT J AU Cattley, RC DeLuca, J Elcombe, C Fenner-Crisp, P Lake, BG Marsman, DS Pastoor, TA Popp, JA Robinson, DE Schwetz, B Tugwood, J Wahli, W AF Cattley, RC DeLuca, J Elcombe, C Fenner-Crisp, P Lake, BG Marsman, DS Pastoor, TA Popp, JA Robinson, DE Schwetz, B Tugwood, J Wahli, W TI Do peroxisome proliferating compounds pose a hepatocarcinogenic hazard to humans? SO REGULATORY TOXICOLOGY AND PHARMACOLOGY LA English DT Article ID ACTIVATED RECEPTOR-ALPHA; <4-CHLORO-6-(2,3-XYLIDINO)-2-PYRIMIDINYLTHIO>ACETIC ACID WY-14,643; RATS FOLLOWING EXPOSURE; LONG-TERM EXPOSURE; ACYL-COA OXIDASE; DNA-SYNTHESIS; RESPONSE ELEMENT; CLOFIBRIC ACID; FATTY-ACIDS; ELEVATED 8-HYDROXYDEOXYGUANOSINE AB The purpose of the workshop "Do Peroxisome Proliferating Compounds Pose a Hepatocarcinogenic Hazard to Humans?" was to provide a review of the current state of the science on the relationship between peroxisome proliferation and hepatocarcinogenesis. There has been much debate regarding the mechanism by which peroxisome proliferators may induce liver tumors in rats and mice and whether these events occur in humans. A primary goal of the workshop was to determine where consensus might be reached regarding the interpretation of these data relative to the assessment of potential human risks. A core set of biochemical and cellular events has been identified in the rodent strains that are susceptible to the hepatocarcinogenic effects of peroxisome proliferators, including peroxisome proliferation, increases in fatty acyl-CoA oxidase levels, microsomal fatty acid oxidation, excess production of hydrogen peroxide, increases in rates of cell proliferation, and expression and activation of the alpha subtype of the peroxisome proliferator-activated receptor (PPAR-alpha), Such effects have not been identified clinically in liver biopsies from humans exposed to peroxisome proliferators or in in vitro studies with human hepatocytes, although PPAR-alpha is expressed at a very low level in human liver. Consensus was reached regarding the significant intermediary roles of cell proliferation and PPAR-alpha receptor expression and activation in tumor formation. Information considered necessary for characterizing a compound as a peroxisome proliferating hepatocarcinogen include hepatomegaly, enhanced cell proliferation, and an increase in hepatic acyl-CoA oxidase and/or palmitoyl-CoA oxidation levels. Given the lack of genotoxic potential of most peroxisome proliferating agents, and since humans appear likely to be refractive or insensitive to the tumorigenic response, risk assessments based on tumor data may not be appropriate. However, nontumor data on intermediate endpoints would provide appropriate toxicological endpoints to determine a point of departure such as the LED10 or NOAEL which would be the basis for a margin-of-exposure (MOE) risk assessment approach. Pertinent factors to be considered in the MOE evaluation would include the slope of the dose-response curve at the point of departure, the background exposure levels, and variability in the human response. (C) 1998 Academic Press. C1 Int Life Sci Inst, Hlth & Environm Sci Inst, Washington, DC 20036 USA. Chem Ind Inst Toxicol, Res Triangle Pk, NC 27709 USA. Merck Res Labs, W Point, PA 19486 USA. Univ Dundee, Ninewells Hosp, Biomed Res Ctr, Dundee DD1 9SY, Scotland. US EPA, Off Pesticide Programs & Tox Subst, Washington, DC 20460 USA. British Ind Biol Res Assoc, Carshalton SM5 4DS, Surrey, England. Procter & Gamble Co, Miami Valley Labs, Cincinnati, OH 45253 USA. Zeneca Ag Prod, Registrat & Regulatory Affairs, Wilmington, DE 19897 USA. Sanofi Res, Malvern, PA 19355 USA. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Zeneca Cent Toxicol Lab, Macclesfield 50 4TG, Cheshire, England. Univ Lausanne, Inst Biol Anim, CH-1015 Lausanne, Switzerland. RP Robinson, DE (reprint author), Int Life Sci Inst, Hlth & Environm Sci Inst, 1126 16th St NW, Washington, DC 20036 USA. RI Wahli, Walter/B-1398-2009 OI Wahli, Walter/0000-0002-5966-9089 NR 95 TC 180 Z9 181 U1 0 U2 2 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 FEB PY 1998 VL 27 IS 1 BP 47 EP 60 DI 10.1006/rtph.1997.1163 PN 1 PG 14 WC Medicine, Legal; Pharmacology & Pharmacy; Toxicology SC Legal Medicine; Pharmacology & Pharmacy; Toxicology GA ZT330 UT WOS:000074074000007 PM 9629596 ER PT J AU Weiss, K AF Weiss, K TI Safety profile of interferon-alpha therapy SO SEMINARS IN ONCOLOGY LA English DT Review C1 US FDA, Div Clin Trial Design & Anal, Ctr Biol, Rockville, MD 20892 USA. RP Weiss, K (reprint author), US FDA, Div Clin Trial Design & Anal, Ctr Biol, 1401 Rockville Pike,HFM570,Suite 2N,Room 216, Rockville, MD 20892 USA. NR 6 TC 63 Z9 64 U1 0 U2 0 PU W B SAUNDERS CO PI PHILADELPHIA PA INDEPENDENCE SQUARE WEST CURTIS CENTER, STE 300, PHILADELPHIA, PA 19106-3399 USA SN 0093-7754 J9 SEMIN ONCOL JI Semin. Oncol. PD FEB PY 1998 VL 25 IS 1 SU 1 BP 9 EP 13 PG 5 WC Oncology SC Oncology GA YY633 UT WOS:000072167900003 PM 9482535 ER PT J AU Chetty, M Miller, R Seymour, MA AF Chetty, M Miller, R Seymour, MA TI Phenytoin auto-induction SO THERAPEUTIC DRUG MONITORING LA English DT Article DE phenytoin auto-induction; period effect AB Information regarding phenytoin auto-induction is sparse and conflicting. However. confirmation of the presence or absence of auto-induction by phenytoin could have important implications in phenytoin therapy and research. This was an open, randomized, three-way crossover study in which each of the eighteen volunteers received three different formulations of phenytoin, which was allocated in a random order. The period effect between each crossover was determined to assess the effect of the previous exposure to phenytoin on the area under the concentration-time curve (AUC). The point estimate ratio of AUC(o-t) for the third dose relative to the first dose was 81.19% with 90% t-confidence limits of 74.37% to 88.00% and p = 0.3847. The point estimate ratio of AUC(o-infinity) for the third dose relative to the first dose was 76.25% with 90% t-confidence limits of 65.3% to 87.2% and p = 0.7169. These results suggest that the AUC(o-infinity) and AUC(o-t) measured after the third dose of phenytoin was statistically significantly smaller than those measured after the first dose. This decrease in AUC after the third dose of phenytoin is probably caused by enhanced elimination of the drug as a result of enzyme induction. C1 Univ Witwatersrand, Dept Expt & Clin Pharmacol, ZA-2193 Johannesburg, South Africa. US FDA, Dept Biopharmaceut, Washington, DC 20204 USA. Park Davis, Dept Med, Cape Town, South Africa. RP Chetty, M (reprint author), Univ Witwatersrand, Dept Expt & Clin Pharmacol, 7 York St,Parktown, ZA-2193 Johannesburg, South Africa. NR 7 TC 10 Z9 10 U1 0 U2 1 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0163-4356 J9 THER DRUG MONIT JI Ther. Drug Monit. PD FEB PY 1998 VL 20 IS 1 BP 60 EP 62 DI 10.1097/00007691-199802000-00011 PG 3 WC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology SC Medical Laboratory Technology; Pharmacology & Pharmacy; Toxicology GA YV542 UT WOS:000071835500011 PM 9485556 ER PT J AU Epstein, JS AF Epstein, JS TI Serologic test for syphilis: a discredited surrogate test for HIV infection - Reply SO TRANSFUSION LA English DT Letter C1 US FDA, Off Blood Res & Review, Bethesda, MD 20014 USA. RP Epstein, JS (reprint author), US FDA, Off Blood Res & Review, Bethesda, MD 20014 USA. NR 2 TC 0 Z9 0 U1 0 U2 0 PU AMER ASSOC BLOOD BANKS PI BETHESDA PA 8101 GLENBROOK RD, BETHESDA, MD 20814-2749 USA SN 0041-1132 J9 TRANSFUSION JI Transfusion PD FEB PY 1998 VL 38 IS 2 BP 218 EP 218 PG 1 WC Hematology SC Hematology GA ZC744 UT WOS:000072612800018 ER PT J AU Sakatsume, M Stancato, LF David, M Silvennoinen, O Saharinen, P Pierce, J Larner, AC Finbloom, DS AF Sakatsume, M Stancato, LF David, M Silvennoinen, O Saharinen, P Pierce, J Larner, AC Finbloom, DS TI Interferon gamma activation of Raf-1 is Jak1-dependent and p21(ras)-independent SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID SIGNAL-REGULATED KINASE; SERINE THREONINE KINASE; PROTEIN-TYROSINE KINASE; GENE-EXPRESSION; HUMAN-MONOCYTES; CELL-LINES; RECEPTOR; PHOSPHORYLATION; RAS; BINDING AB Signal transduction through the interferon gamma (IFN gamma) receptor involves the formation of a ligand-dependent multimolecular association of receptor chains (alpha and beta), Janus tyrosine kinases (Jak1 and Jak2), and the transcription factor (signal transducers and activators of transcription 1 alpha (STAT1 alpha)) in addition to activation of mitogen-activated protein kinases (MAPK), Interactions between components of the Jak/STAT cascade and the p21(ras)/Raf-1/MAPK cascade are unexplored, Treatment of HeLa cells with IFN gamma resulted in the rapid and transient activation of Raf-1 and MAPK. Parallel activation of cells resulted in essentially no enhancement of p21(ras) activation despite marked enhancement after treatment with epidermal growth factor, In HeLa (E1C3) and fibrosarcoma (U4A) cell lines, both of which are deficient in Jak1 kinase, Raf-1 activation by IFN gamma was absent. Reconstitution of Raf-1 activity was observed only with kinase active Jak1 in both cell lines. In COS cells, transient expression of wild type or kinase-inactive Jak1 coimmunoprecipitated with Raf-1, but activation of Raf-1 activity was only observed in cells expressing kinase-active Jak1. These observations suggest that a kinase-active Jak1 is required for IFN gamma activation of Raf-1 that is p21(ras)-independent. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bethesda, MD 20892 USA. NCI, Cellular & Mol Biol Lab, NIH, Bethesda, MD 20892 USA. Univ Tampere, Inst Med Technol, FIN-33101 Tampere, Finland. RP Finbloom, DS (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, HFM-505,29 Lincoln Dr, Bethesda, MD 20892 USA. EM Finbloom@A1.cbef.fda.gov RI Saharinen, Pipsa/C-9601-2016 OI Saharinen, Pipsa/0000-0003-2652-0584 NR 41 TC 67 Z9 69 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 JAN 30 PY 1998 VL 273 IS 5 BP 3021 EP 3026 DI 10.1074/jbc.273.5.3021 PG 6 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YU621 UT WOS:000071736600071 PM 9446616 ER PT J AU Sze'kely, Z Fabian, P Torday, LL Michejda, CJ Aszalos, A AF Sze'kely, Z Fabian, P Torday, LL Michejda, CJ Aszalos, A TI Binding between the CD4 receptor and polysulfonated azo-dyes. An exploratory theoretical study on action-mechanism SO THEOCHEM-JOURNAL OF MOLECULAR STRUCTURE LA English DT Article DE HIV entry; CD4; gp120; antiviral drug; docking ID IMMUNODEFICIENCY-VIRUS; SURAMIN; CELLS AB The antiviral mechanism of action of the polysulfonated ate-dyes is discussed in this paper. Crucial to the antiviral activity of these dyes is the inhibition of the HIV entry into the host cell, This is a result of the covering strategic areas of the CD4 viral receptor surface. A consistent, mainly electrostatic, interaction model has been established to explain the mode of inhibition activity of Direct Red 79 and Direct Yellow 50, The basis of the model is a dynamic distance matrix of the most important positively charged amino acid side chains within the CD4, which might serve as an electrostatic docking site for the negatively charged sulfonate groups of the ate-dyes. Beside the intrinsic value of interpreting the biological effect, this model might serve as a useful tool for a rational drug design. Published by Elsevier Science B.V. C1 NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. Albert Szent Gyorgyi Med Univ, Dept Med Chem, H-6701 Szeged, Hungary. Agr Biotechnol Ctr, Inst Biochem, H-2101 Godollo, Hungary. Albert Szent Gyorgyi Med Univ, Dept Pharmacol, H-6701 Szeged, Hungary. US FDA, Ctr Drug Evaluat & Res, Div Res & Testing, Washington, DC 20204 USA. RP Sze'kely, Z (reprint author), NCI, Frederick Canc Res & Dev Ctr, ABL Basic Res Program, Frederick, MD 21702 USA. RI Torday, Laszlo/J-7899-2012 OI Torday, Laszlo/0000-0002-2911-5499 NR 12 TC 3 Z9 3 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0166-1280 J9 THEOCHEM-J MOL STRUC JI Theochem-J. Mol. Struct. PD JAN 26 PY 1998 VL 423 IS 1-2 BP 153 EP 159 DI 10.1016/S0166-1280(97)00363-1 PG 7 WC Chemistry, Physical SC Chemistry GA YX314 UT WOS:000072027800014 ER PT J AU Pothuluri, JV Doerge, DR Churchwell, MI Fu, PP Cerniglia, CE AF Pothuluri, JV Doerge, DR Churchwell, MI Fu, PP Cerniglia, CE TI Fungal metabolism of nitrofluoranthenes SO JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES LA English DT Article ID POLYCYCLIC AROMATIC-HYDROCARBONS; CUNNINGHAMELLA-ELEGANS; SALMONELLA-TYPHIMURIUM; 3-NITROFLUORANTHENE; 2-NITROFLUORANTHENE; FLUORANTHENE; MUTAGENICITY; DETOXIFICATION; PHASE; IDENTIFICATION AB Metabolism of 2-nitrofluoranthene (2-NFA), one of the most abundant and genotoxic environmental pollutants in air, and of a mixture of 2-nitrofluoranthene and 3-nitrofluoranthene (3-NFA) was studied using (1) the fungus Cunninghamella elegans ATCC 36112 and (2) rat liver microsomes. The fungal metabolites were separated by reversed-phase high-performance liquid chromatography (HPLC) and identified by (1)H nuclear magnetic resonance (NMR) spectrometry, ultraviolet (UV)-visible spectroscopy, and online atmospheric-pressure chemical ionization/mass spectrometry (APCI/MS). The fungus metabolized 82% of 2-nitro-[(3)H]-fluoranthene to 2-nitrofluoranthene 8-sulfate and 2-nitrofluoranthene 9-sulfate. Metabolism of a mixture of 2- and 3-nitrofluoranthene by C. elegans similarly produced 2-nitrofluoranthene 8- and 9-sulfate and 3-nitrofluoranthene 8- and 9-sulfate as major metabolites. In addition, a glucoside conjugate of 3-hydroxy-2-nitrofluoranthene was tentatively identified by APCI/MS analysis. When rat liver microsomes were incubated with a mixture of 2- and 3-nitrofluoranthene for 1 h, in addition to the trans-7,8- and 9, 10-dihydrodiols reported previously for 2-nitrofluoranthene, several novel metabolites were produced including 2-nitrofluoranthene trans-4,5-dihydrodiol and 2-nitrofluoranthene trans-8,9-dihydrodiol, the trans-4,5-dihydrodiol of 3-nitrofluoranthene, and phenolic products of both 2- and 3-nitrofluoranthene. The fungal metabolism of the 2- and 3-nitrofluoranthene mixture was similar to the metabolism of individual nitrofluoranthenes; however, the mammalian metabolism of the nitrofluoranthene mixture showed differences in regioselectivity at positions C4, C5, C8, and C9. C1 US FDA, Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. RP Pothuluri, JV (reprint author), US FDA, Natl Ctr Toxicol Res, Div Microbiol, HFT-250,3900 NCTR Rd, Jefferson, AR 72079 USA. EM JPothuluri@NCTR.FDA.Gov NR 34 TC 8 Z9 8 U1 0 U2 3 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 JAN 23 PY 1998 VL 53 IS 2 BP 153 EP 174 PG 22 WC Environmental Sciences; Public, Environmental & Occupational Health; Toxicology SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health; Toxicology GA ZB410 UT WOS:000072469700006 PM 9444318 ER PT J AU Misbin, RI Green, L Stadel, BV Gueriguian, JL Gubbi, A Fleming, GA AF Misbin, RI Green, L Stadel, BV Gueriguian, JL Gubbi, A Fleming, GA TI Lactic acidosis in patients with diabetes treated with metformin SO NEW ENGLAND JOURNAL OF MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Misbin, RI (reprint author), US FDA, Rockville, MD 20857 USA. NR 5 TC 228 Z9 236 U1 1 U2 12 PU MASS MEDICAL SOC PI BOSTON PA 10 SHATTUCK, BOSTON, MA 02115 USA SN 0028-4793 J9 NEW ENGL J MED JI N. Engl. J. Med. PD JAN 22 PY 1998 VL 338 IS 4 BP 265 EP 266 DI 10.1056/NEJM199801223380415 PG 2 WC Medicine, General & Internal SC General & Internal Medicine GA YT358 UT WOS:000071594100024 PM 9441244 ER PT J AU Franzoso, G Carlson, L Poljak, L Shores, EW Epstein, S Leonardi, A Grinberg, A Tran, T Scharton-Kersten, T Anver, M Love, P Brown, K Siebenlist, U AF Franzoso, G Carlson, L Poljak, L Shores, EW Epstein, S Leonardi, A Grinberg, A Tran, T Scharton-Kersten, T Anver, M Love, P Brown, K Siebenlist, U TI Mice deficient in nuclear factor (NF)-kappa B/p52 present with defects in humoral responses, germinal center reactions, and splenic microarchitecture SO JOURNAL OF EXPERIMENTAL MEDICINE LA English DT Article ID NF-KAPPA-B; CANDIDATE PROTOONCOGENE BCL-3; DNA-BINDING; ONCOPROTEIN BCL-3; IMMUNE-RESPONSE; P50 HOMODIMERS; LYMPHOID MALIGNANCIES; TARGETED DISRUPTION; DENDRITIC CELLS; PRECURSOR P105 AB p52 is a subunit of nuclear factor (NF)-kappa B transcription factors, most closely related to p50. Previously, we have shown that p52, but not p50 homodimers can form transactivating complexes when associated with Bcl-3, an unusual member of the I kappa B family. To determine nonredundant physiologic roles of p52, we generated mice deficient in p52. Null mutant mice were impaired in their ability to generate antibodies to T-dependent antigens, consistent with an absence of B cell follicles and follicular dendritic cell networks in secondary lymphoid organs, and an inability to form germinal centers. Furthermore, the splenic marginal zone was disrupted. These phenotypes are largely overlapping with those observed in Bcl-3 knockout animals, but distinct from those of p50 knockouts, supporting the notion of a physiologically relevant complex of p52 homodimers and Bcl-3. Adoptive transfer experiments further su that such a complex may be critical in accessory cell functions during antigen-specific immune reactions. Possible roles of p52 and Bcl-3 are discussed that may underlie the oncogenic potential of these proteins, as evidenced by recurrent chromosomal translocations of their genes in lymphoid tumors. C1 NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 USA. NICHHD, Genet Mol Lab, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Hematol Prod, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Bethesda, MD 20892 USA. Sci Applicat Int Corp, Pathol Histotechnol Lab, Frederick, MD 21702 USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. RP Franzoso, G (reprint author), NIAID, Immunoregulat Lab, NIH, Bethesda, MD 20892 USA. NR 62 TC 307 Z9 320 U1 0 U2 5 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0022-1007 J9 J EXP MED JI J. Exp. Med. PD JAN 19 PY 1998 VL 187 IS 2 BP 147 EP 159 DI 10.1084/jem.187.2.147 PG 13 WC Immunology; Medicine, Research & Experimental SC Immunology; Research & Experimental Medicine GA YU549 UT WOS:000071729000002 PM 9432973 ER PT J AU Xia, QS Yi, P Zhan, DJ Von Tungeln, LS Hart, RW Heflich, RH Fu, PP AF Xia, QS Yi, P Zhan, DJ Von Tungeln, LS Hart, RW Heflich, RH Fu, PP TI Liver tumors induced in B6C3F(1) mice by 7-chlorobenz[a] anthracene and 7-bromobenz[a]anthracene contain K-ras protooncogene mutations SO CANCER LETTERS LA English DT Article DE liver tumors; K-ras oncogene; 7-chlorobenz[a]anthracene; 7-bromobenz[a]anthracene; neonatal mouse ID H-RAS; 61ST CODON; MOUSE; ACTIVATION; ONCOGENES; EXPOSURE; SPECTRA AB We previously examined the tumorigenicity of 7-chlorobenz[a]anthracene (7-Cl-BA) and 7-bromobenz[a]anthracene (7-Br-BA) in the neonatal mouse bioassay and found that 7-Cl-BA and 7-Br-BA induced hepatocellular adenoma in 92 and 96% of the mice and hepatocellular carcinoma in 100 and 83% of the mice, respectively. In the present study, mRNA was isolated from each of the liver tumors induced by the two compounds and reverse-transcribed to cDNA. Portions of the K- and H-ras oncogene coding sequences were then amplified and analyzed for DNA sequence alterations. Eighty-three percent (20/24) of 7-Cl-BA-induced and 91% (20/22) of 7-Br-BA-induced liver tumors had activated ras protooncogenes. In contrast to the general finding of H-ras mutations in B6C3F(1) mouse liver tumors, both compounds had 95% (19/20) of the mutations located at the first base of K-ras codon 13, resulting in a pattern of (G) under bar GC --> (C) under bar GC. Thus, our results demonstrate that 7-Cl-BA and 7-Br-BA induce a unique type of ras (K-ras) oncogene activation in liver tumors of B6C3F(1) mice. (C) 1998 Elsevier Science Ireland Ltd. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 21 TC 18 Z9 18 U1 0 U2 1 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 16 PY 1998 VL 123 IS 1 BP 21 EP 25 DI 10.1016/S0304-3835(97)00366-2 PG 5 WC Oncology SC Oncology GA YT080 UT WOS:000071562000004 PM 9461013 ER PT J AU Herman, EH Lipshultz, SE Rifai, N Zhang, J Papoian, T Yu, ZX Takeda, K Ferrans, VJ AF Herman, EH Lipshultz, SE Rifai, N Zhang, J Papoian, T Yu, ZX Takeda, K Ferrans, VJ TI Use of cardiac troponin T levels as an indicator of doxorubicin-induced cardiotoxicity SO CANCER RESEARCH LA English DT Article AB The release of cardiac troponin T (cTnT) as a biomarker of doxorubicin-induced chronic cardiac injury was evaluated in the spontaneously hypertensive rat (SHR) model. Elevations in serum levels of cTnT and decreased immunohistochemical staining of heart sections for this protein were noted in SHRs treated with cumulative doses of doxorubicin (7 mg/kg) that induced only minimal histological alterations in myocytes. Concentrations of cTnT were further elevated, coincident with reduced immunohistochemical staining, in SHRs given 10-12 mg/kg doxorubicin. Thus, monitoring serum levels of cTnT can detect doxorubicin-induced myocyte damage in SHR and may prove useful for the noninvasive evaluation of this toxicity in humans. C1 US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD 910, Laurel, MD 20708 USA. Univ Rochester, Med Ctr, Sch Med & Dent, Div Pediat Cardiol, Rochester, NY 14642 USA. Childrens Hosp, Dept Lab Med, Boston, MA 02115 USA. US FDA, Div Cardiorenal Drug Prod, Rockville, MD 20852 USA. NHLBI, Pathol Sect, Bethesda, MD 20892 USA. RP Herman, EH (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Appl Pharmacol Res HFD 910, 8301 Muirkirk Rd, Laurel, MD 20708 USA. NR 11 TC 80 Z9 83 U1 0 U2 3 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 0008-5472 J9 CANCER RES JI Cancer Res. PD JAN 15 PY 1998 VL 58 IS 2 BP 195 EP 197 PG 3 WC Oncology SC Oncology GA YR421 UT WOS:000071493600003 PM 9443390 ER PT J AU Cavaille-Coll, MW Elashoff, MR AF Cavaille-Coll, MW Elashoff, MR TI Commentary on a comparison of tacrolimus and cyclosporine for immunosuppression after cadaveric renal transplantation SO TRANSPLANTATION LA English DT Letter ID REJECTION EPISODES; IMPACT C1 US FDA, CDER, Rockville, MD 20857 USA. RP Cavaille-Coll, MW (reprint author), US FDA, CDER, 5600 Fishers Lane HFD-530, Rockville, MD 20857 USA. NR 6 TC 17 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0041-1337 J9 TRANSPLANTATION JI Transplantation PD JAN 15 PY 1998 VL 65 IS 1 BP 142 EP 144 DI 10.1097/00007890-199801150-00028 PG 3 WC Immunology; Surgery; Transplantation SC Immunology; Surgery; Transplantation GA YR654 UT WOS:000071516900027 PM 9448161 ER PT J AU Wise, RP Salive, ME Niu, MT AF Wise, RP Salive, ME Niu, MT TI Hair loss after immunization - Reply SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Wise, RP (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 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 JAN 14 PY 1998 VL 279 IS 2 BP 118 EP 118 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YQ015 UT WOS:000071338900026 ER PT J AU Wilks, A Schmitt, MP AF Wilks, A Schmitt, MP TI Expression and characterization of a heme oxygenase (Hmu O) from Corynebacterium diphtheriae - Iron acquisition requires oxidative cleavage of the heme macrocycle SO JOURNAL OF BIOLOGICAL CHEMISTRY LA English DT Article ID ESCHERICHIA-COLI; YERSINIA-ENTEROCOLITICA; TRANSPORT-SYSTEM; TOXIN; PROTEIN; DTXR; HEMOGLOBIN; SEQUENCE; BINDING; BACTERIA AB A full-length heme oxygenase gene from the pathogenic bacterium Corynebacterium diphtheriae has been subcloned and expressed in Escherichia coli. The enzyme is expressed at high levels as a soluble catalytically active protein that results in the accumulation of biliverdin within the E. coli cells. The purified heme oxygenase forms a 1:1 complex with heme (K-d, 2.5 +/- 1 mu M) and has hemeprotein spectra similar to those previously reported for the purified eukaryotic heme oxygenases. In the presence of an E. coli NADPH-dependent reductase isolated during the purification of Hmu O, the heme-Hmu O complex is catalytically turned over to yield biliverdin IX alpha and carbon monoxide, A number of redox partners were investigated for their ability to reconstitute Hmu O activity in vitro. Of these the most efficient appeared to be the recombinant NADH-dependent putidaredoxin/putidaredoxin reductase from Pseudomonas putida. As with the E. coli NADPH-dependent reductase the final products of the reaction were biliverdin IX alpha and carbon monoxide. This is the first bacterial heme oxygenase to be described to date. The close relationship between iron acquisition and pathogenesis suggests that the release of iron from heme by heme oxygenase may play a crucial role in the pathogenicity of C. diphtheriae. C1 Univ Calif San Francisco, Sch Pharm, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. US FDA, Lab Bacterial Toxins, Div Bacterial Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Wilks, A (reprint author), Univ Calif San Francisco, Sch Pharm, Dept Pharmaceut Chem, San Francisco, CA 94143 USA. EM wilks@cgl.ucsf.edu FU NIDDK NIH HHS [P30 DK26743, P30 DK30297] NR 35 TC 151 Z9 154 U1 1 U2 5 PU AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC PI BETHESDA PA 9650 ROCKVILLE PIKE, BETHESDA, MD 20814-3996 USA SN 0021-9258 EI 1083-351X J9 J BIOL CHEM JI J. Biol. Chem. PD JAN 9 PY 1998 VL 273 IS 2 BP 837 EP 841 DI 10.1074/jbc.273.2.837 PG 5 WC Biochemistry & Molecular Biology SC Biochemistry & Molecular Biology GA YQ669 UT WOS:000071411400028 PM 9422739 ER PT J AU Feinstone, SM Lewis, AM Markoff, LJ Carbone, K Golding, H AF Feinstone, SM Lewis, AM Markoff, LJ Carbone, K Golding, H TI FDA "reform"? SO SCIENCE LA English DT Letter C1 US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Washington, DC 20008 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Leesburg, VA 20176 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20817 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Adamstown, MD 21710 USA. US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, Rockville, MD 20853 USA. RP Feinstone, SM (reprint author), US FDA, Div Viral Prod, Ctr Biol Evaluat & Res, 3021 Cathedral Ave NW, Washington, DC 20008 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU AMER ASSOC ADVANCEMENT SCIENCE PI WASHINGTON PA 1200 NEW YORK AVE, NW, WASHINGTON, DC 20005 USA SN 0036-8075 J9 SCIENCE JI Science PD JAN 9 PY 1998 VL 279 IS 5348 BP 157 EP 158 PG 2 WC Multidisciplinary Sciences SC Science & Technology - Other Topics GA YQ636 UT WOS:000071408100006 PM 9446214 ER PT J AU Nightingale, SL AF Nightingale, SL TI Rezulin labeling updated to recommend more frequent patient monitoring SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 1 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 7 PY 1998 VL 279 IS 1 BP 9 EP 9 DI 10.1001/jama.279.1.9-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YP607 UT WOS:000071295100003 PM 9424027 ER PT J AU Nightingale, SL AF Nightingale, SL TI List of disqualified investigators available an Internet SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 7 PY 1998 VL 279 IS 1 BP 9 EP 9 DI 10.1001/jama.279.1.9-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YP607 UT WOS:000071295100004 PM 9424027 ER PT J AU Nightingale, SL AF Nightingale, SL TI Irradiation of meat approved for pathogen control SO JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION LA English DT Editorial Material C1 US FDA, Off Hlth Affairs, Rockville, MD 20857 USA. RP Nightingale, SL (reprint author), US FDA, Off Hlth Affairs, Parklawn Bldg,5600 Fishers Ln, Rockville, MD 20857 USA. NR 0 TC 6 Z9 6 U1 0 U2 0 PU AMER MEDICAL ASSOC PI CHICAGO PA 515 N STATE ST, CHICAGO, IL 60610 USA SN 0098-7484 J9 JAMA-J AM MED ASSOC JI JAMA-J. Am. Med. Assoc. PD JAN 7 PY 1998 VL 279 IS 1 BP 9 EP 9 DI 10.1001/jama.279.1.9-b PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YP607 UT WOS:000071295100005 PM 9424027 ER PT J AU Berger, VW AF Berger, VW TI Admissibility of exact conditional tests of stochastic order SO JOURNAL OF STATISTICAL PLANNING AND INFERENCE LA English DT Article DE adaptive test; contingency table; convex hull test; ordered categorical data ID ORDINAL DATA AB Consider the problem of testing for independence against stochastic order in a 2xJ contingency table, with two treatments and J ordered categories. By conditioning on the margins, the null hypothesis becomes simple. Careful selection of the conditional alternative hypothesis then allows the problem to be formulated as one of a class of problems for which the minimal complete class of admissible tests is known. The exact versions of many common tests, such as t-tests and the Smirnov test, are shown to be inadmissible, and thus the non-randomized versions are overly conservative. The proportional hazards and proportional odds tests are shown to be admissible for a given data set and size. A new result allows a proof of the admissibility of convex hull and adaptive tests for all data sets and sizes. (C) 1998 Elsevier Science B.V. C1 US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NR 24 TC 12 Z9 12 U1 0 U2 2 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS SN 0378-3758 J9 J STAT PLAN INFER JI J. Stat. Plan. Infer. PD JAN 5 PY 1998 VL 66 IS 1 BP 39 EP 50 DI 10.1016/S0378-3758(97)00078-5 PG 12 WC Statistics & Probability SC Mathematics GA YV204 UT WOS:000071799800003 ER PT J AU Karupiah, G Sacks, TE Klinman, DM Fredrickson, TN Hartley, JW Chen, JH Morse, HC AF Karupiah, G Sacks, TE Klinman, DM Fredrickson, TN Hartley, JW Chen, JH Morse, HC TI Murine cytomegalovirus infection-induced polyclonal B cell activation is independent of CD4(+) T cells and CD40 SO VIROLOGY LA English DT Article ID VIRUS INFECTION; LYMPHOCYTES-T; MESSENGER-RNA; IMMUNE; MICE; ANTIBODIES; EXPRESSION; RESPONSES; AUTOANTIBODIES; PATHOGENESIS AB The results of this study demonstrate that murine cytomegalovirus (MCMV) induces polyclonal B cell activation in mice during the acute phase of primary infection. First, flow cytometric analysis revealed that surface expression of CD45R, IgM, and Ig kappa by splenocytes from MCMV-infected mice was significantly reduced with a concomitant increase in the frequency of surface IgG-expressing cells. Second, ELIspot assays demonstrated that the changes revealed by flow cytometry were paralleled by increases in the numbers of IgG-producing cells, especially those secreting IgG(2a). Third, the IgG antibodies from MCMV-infected animals reacted against a variety of self and foreign antigens. MCMV-induced B cell activation was independent of CD4(+) T-cell-mediated help and CD40, since activation was observed in two models of mice deficient for this T cell subset and in mice deficient for CD40. Reverse transcription-polymerase chain reaction analysis showed that mRNA transcripts for the cytokines IL-6, IL-10, and IFN-gamma were rapidly induced following infection with MCMV, but only IL-6 and IFN-gamma proteins were detectable by ELISA. In addition, the numbers of cells producing IL-B and IFN-gamma were significantly increased in the spleen. The magnitude of the polyclonal B cell activation response was diminished by 50% in IL-6-deficient mice but not in mice lacking IFN-gamma. In the absence of IFN-gamma, surface expression and serum levels of IgG(2a) were reduced while IgG(1) expression was increased. (C) 1998 Academic Press. C1 NIAID, LIP, NIH, Bethesda, MD 20892 USA. NCI, Registry Expt Canc, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Virol, Bethesda, MD USA. Australian Natl Univ, John Curtin Sch Med Res, Div Cell Biol & Immunol, Canberra, ACT 2601, Australia. RP Morse, HC (reprint author), NIAID, LIP, NIH, Bldg 7,Room 304,7 Ctr Dr,MSC 0760, Bethesda, MD 20892 USA. RI Karupiah, Gunasegaran/J-4707-2013; OI Morse, Herbert/0000-0002-9331-3705 NR 44 TC 30 Z9 31 U1 0 U2 0 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0042-6822 J9 VIROLOGY JI Virology PD JAN 5 PY 1998 VL 240 IS 1 BP 12 EP 26 DI 10.1006/viro.1997.8900 PG 15 WC Virology SC Virology GA YR928 UT WOS:000071545900002 PM 9448685 ER PT J AU Nellore, RV Rekhi, GS Hussain, AS Tillman, LG Augsburger, LL AF Nellore, RV Rekhi, GS Hussain, AS Tillman, LG Augsburger, LL TI Development of metoprolol tartrate extended-release matrix tablet formulations for regulatory policy consideration SO JOURNAL OF CONTROLLED RELEASE LA English DT Article DE hydrophilic matrix tablet; HPMC; extended-release; formulation; dissolution; manufacturing; Scale-Up and Post-Approval Changes (SUPAC); regulation; guidance ID HYDROXYPROPYLMETHYLCELLULOSE; HYDROCHLORIDE AB This research study was designed to develop model extended-release (ER) matrix tablet formulations for metoprolol tartrate (100 mg) sufficiently sensitive to manufacturing variables and to serve as the scientific basis for regulatory policy development on scale-up and post approval changes for modified-release dosage forms (SUPAC-MR), Several grades and levels of hydroxypropyl methylcellulose (Methocel K4M, K15M, K100M and K100LV), fillers and binders were studied. Three granulation processes were evaluated; direct compression, fluid-bed or high-shear granulation. Lubrication was performed in a V-blender and tablets were compressed on an instrumented rotary tablet press. Direct compression formulations exhibited poor flow, picking and sticking problems during tableting. High-shear granulation resulted in the formation of hard granules that were difficult to mill but yielded good tablets. Fluid-bed granulations were made using various binders and appeared to be satisfactory in terms of flow and tableting performance, In vitro drug release testing was performed in pH 6.8 phosphate buffer using USP apparatus 2 (paddle) at 50 rpm. At a fixed polymer level, drug release from the higher viscosity grades (K100M) was slower as compared to the lower viscosity grades (K100LV). In addition, release from K100LV was found to be more sensitive to polymer level changes. Increase in polymer level from 10 to 40% and/or filler change from lactose to dicalcium phosphate resulted in about 25-30% decrease in the amount of metoprolol release after 12 h. The results of this study led to the choice of Methocel K100LV as the hydrophilic matrix polymer and fluid-bed granulation as the process of choice for further evaluation of critical and non-critical formulation and processing variables. (C) 1998 Elsevier Science B.V. C1 Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. Roche Biosci, Palo Alto, CA 94304 USA. US FDA, Ctr Drug Evaluat & Res, Div Prod Qual Res, Rockville, MD 20857 USA. ISIS Pharmaceut, Carlsbad, CA 92008 USA. RP Rekhi, GS (reprint author), Univ Maryland, Sch Pharm, Dept Pharmaceut Sci, Baltimore, MD 21201 USA. NR 21 TC 49 Z9 52 U1 1 U2 13 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 JAN 2 PY 1998 VL 50 IS 1-3 BP 247 EP 256 DI 10.1016/S0168-3659(97)00141-7 PG 10 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA YU373 UT WOS:000071710600025 PM 9685891 ER PT S AU Marchalonis, JJ Schluter, SF Bernstein, RM Shen, SX Edmundson, AB AF Marchalonis, JJ Schluter, SF Bernstein, RM Shen, SX Edmundson, AB BE Dixon, FJ TI Phylogenetic emergence and molecular evolution of the immunoglobulin family SO ADVANCES IN IMMUNOLOGY, VOL 70 SE Advances in Immunology LA English DT Review ID T-CELL RECEPTOR; MAJOR HISTOCOMPATIBILITY COMPLEX; TROUT ONCORHYNCHUS-MYKISS; VERTEBRATE IMMUNE-SYSTEM; LIGHT-CHAIN GENES; IG HEAVY-CHAIN; COMPLETE NUCLEOTIDE-SEQUENCE; JOINING SEGMENT PEPTIDE; VARIABLE REGION GENES; AMINO-ACID-SEQUENCE C1 Univ Arizona, Coll Med, Dept Microbiol & Immunol, Tucson, AZ 85724 USA. US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NIH, Bethesda, MD 20892 USA. Oklahoma Med Res Fdn, Oklahoma City, OK 73104 USA. RP Marchalonis, JJ (reprint author), Univ Arizona, Coll Med, Dept Microbiol & Immunol, Tucson, AZ 85724 USA. FU NCI NIH HHS [CA72803] NR 277 TC 69 Z9 73 U1 1 U2 4 PU ELSEVIER ACADEMIC PRESS INC PI SAN DIEGO PA 525 B STREET, SUITE 1900, SAN DIEGO, CA 92101-4495 USA SN 0065-2776 BN 0-12-022470-4 J9 ADV IMMUNOL JI Adv.Immunol. PY 1998 VL 70 BP 417 EP 506 DI 10.1016/S0065-2776(08)60392-2 PG 90 WC Immunology SC Immunology GA BM62R UT WOS:000079287100007 PM 9755343 ER PT J AU Kutza, J Hayes, MP Clouse, KA AF Kutza, J Hayes, MP Clouse, KA TI Interleukin-2 inhibits HIV-1 replication in human macrophages by modulating expression of CD4 and CC-chemokine receptor-5 SO AIDS LA English DT Article DE AIDS; HIV; monocytes; macrophages; cytokines; immunotherapy ID HUMAN-IMMUNODEFICIENCY-VIRUS; COLONY-STIMULATING FACTOR; MONOCYTE-DERIVED MACROPHAGES; IMMUNE-DEFICIENCY-SYNDROME; RECOMBINANT INTERLEUKIN-2; TYPE-1 INFECTION; GENE-EXPRESSION; CYTO-TOXICITY; IL-2; THERAPY AB Objective: To determine the effect of recombinant human interleukin (IL)-2 on HIV-1 replication and macrophage colony stimulating factor (M-CSF) production by HIV-1-infected monocyte-derived macrophages (MDM). Design: Therapeutic use of IL-2 increases the number and function of CD4+T cells. IL-2 also increases M-CSF production and M-CSF receptor expression by human monocytes, but the subsequent effects on HIV-1 replication in MDM have yet to be determined. MDM from HIV-1-seronegative donors were cultured in the presence and absence of IL-2 and infected with HIV-1. Harvested supernatants were monitored for reverse transcriptase activity and M-CSF production. Results: Reverse transcriptase activity was significantly lower when MDM cultures were treated with IL-2 for 10 days prior to infection with HIV-1. IL-2 did not stimulate production of inhibitory chemokines or cytokines, but FACS analysis revealed that expression of CD4, the primary HIV-1 receptor, and CC-chemokine receptor-5, a coreceptor used by macrophage-tropic viruses, are downmodulated after treatment with IL-2. Conclusion: IL-2 may not only be of benefit in restoring immune function in AIDS patients, but may also help to prevent the infection of healthy macrophages by decreasing their expression of HIV-1 receptors. (C) 1998 Lippincott-Raven Publishers. C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Rockville, MD 20852 USA. RP Clouse, KA (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, Bldg 29B HFM-505,8800 Rockville Pike, Rockville, MD 20852 USA. NR 37 TC 18 Z9 19 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0269-9370 J9 AIDS JI Aids PY 1998 VL 12 IS 8 BP F59 EP F64 DI 10.1097/00002030-199808000-00001 PG 6 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA ZN841 UT WOS:000073688000001 PM 9631132 ER PT J AU Moulton, S Pantazis, P Epstein, JS Sadaie, MR AF Moulton, S Pantazis, P Epstein, JS Sadaie, MR TI 9-nitrocamptothecin inhibits tumor necrosis factor-mediated activation of human immunodeficiency virus type 1 and enhances apoptosis in a latently infected T cell clone SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID NF-KAPPA-B; SODIUM-BUTYRATE; FACTOR-ALPHA; HIV-1 INFECTION; TOPOISOMERASE-I; FLOW-CYTOMETRY; CHROMATIN FRAGMENTATION; INSITU HYBRIDIZATION; GENE-EXPRESSION; SERUM LEVELS AB Transition from latency to active replication is a crucial stage for the process of human immunodeficiency virus type 1 (HIV-1) infection and life cycle, HIV-1 replication in latently infected cells can be strongly induced by the cytokine tumor necrosis factor alpha (TNF-alpha) and the proliferation-arresting chemical sodium butyrate (NaB). We have investigated the ability of the drug 9-nitrocamptothecin (9NC), a potent cellular topoisomerase (topo I) inhibitor currently in clinical trials in cancer patients, to regulate HIV-1 replication in latently infected lymphocytic ACH-2 cells on reactivation with either TNF-alpha or NaB, Treatment of ACH-2 cells with 9NC alone resulted in increased levels of viral transcripts, while there was a slight reduction or no change in the levels of host cell transcripts. However, pretreatment of ACH-2 cells with 9NC inhibited TNF-alpha-induced extracellular HIV-1 p24 levels up to similar to 95% and nearly 80% of the cell-associated viral RNAs, The quantitative decrease in viral products was concomitant with a decrease in cellular gene expression and induction of apoptosis in the host cells, 9NC blocked the infected cells at the boundary of the S and G2 phases, resulting in an accelerated apoptosis that was further enhanced with TNF-alpha treatment, Similar results were observed following concurrent exposure Ito TNF-alpha and 9NC, but 9NC failed to inhibit upregulation of HIV-1 mRNA in ACH-2 cells exposed to TNF-alpha before 9NC treatment, Further, 9NC had no inhibitory effect on NaB-induced apoptosis and upregulation, of HIV-1 mRNA expression regardless of whether 9NC and NaB were used concurrently or in various treatment sequences, In uninfected lymphocytic CEM cells derived from a common parental cell line, a slight downregulation of cellular gene expression was detected along with low-level apoptosis, These results demonstrate that 9NC impairs TNF-alpha-induced, but not NaB-induced, HIV-1 activation, and suggest a means of inhibiting active HIV-1 viremia arising as a result of elevated TNF-alpha levels. C1 US FDA, CBER, Div Transfus Transmitted Dis, Lab Immunochem, Rockville, MD 20852 USA. St Joseph Hosp, Stehlin Fdn Canc Res, Houston, TX 77003 USA. RP Sadaie, MR (reprint author), US FDA, CBER, Div Transfus Transmitted Dis, Lab Immunochem, HFM-320,1401 Rockville Pike, Rockville, MD 20852 USA. NR 68 TC 10 Z9 11 U1 2 U2 2 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 1 PY 1998 VL 14 IS 1 BP 39 EP 49 DI 10.1089/aid.1998.14.39 PG 11 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YQ462 UT WOS:000071390000006 PM 9453250 ER PT J AU Heredia, A Vallejo, A Soriano, V Aguilera, A Caballero, E Epstein, JS Hewlett, IK AF Heredia, A Vallejo, A Soriano, V Aguilera, A Caballero, E Epstein, JS Hewlett, IK TI Genetic analysis of human immunodeficiency virus type 2 strains from Spain SO AIDS RESEARCH AND HUMAN RETROVIRUSES LA English DT Article ID HIV-2; SPREAD; INFECTIONS C1 Inst Human Virol, Lab Viral Immunoregulat, Baltimore, MD 21201 USA. US FDA, Ctr Biol Evaluat & Res, Div Transfus & Transmitted Dis, Mol Virol Lab, Rockville, MD 20852 USA. Inst Salud Carlos III, Serv Infect Dis & Microbiol, Madrid 28029, Spain. Hosp Xeral, Microbiol Serv, Santiago 15886, Chile. Hosp Gen Valle Hebron, Microbiol Serv, Barcelona, Spain. RP Heredia, A (reprint author), Inst Human Virol, Lab Viral Immunoregulat, 725 W Lombard St, Baltimore, MD 21201 USA. RI Vallejo, Alejandro/I-5881-2015 OI Vallejo, Alejandro/0000-0001-5360-878X NR 13 TC 2 Z9 2 U1 0 U2 0 PU MARY ANN LIEBERT INC PUBL PI LARCHMONT PA 2 MADISON AVENUE, LARCHMONT, NY 10538 USA SN 0889-2229 J9 AIDS RES HUM RETROV JI Aids Res. Hum. Retrovir. PD JAN 1 PY 1998 VL 14 IS 1 BP 91 EP 94 DI 10.1089/aid.1998.14.91 PG 4 WC Immunology; Infectious Diseases; Virology SC Immunology; Infectious Diseases; Virology GA YQ462 UT WOS:000071390000012 PM 9453256 ER PT J AU Dorsam, V Schmeel, A Chumakov, K Fibi, MR AF Dorsam, V Schmeel, A Chumakov, K Fibi, MR TI Alternative for the neurovirulence test (NVT) in primates for safety-testing of poliomyelitis attenuated life virus vaccine (Sabin): in vitro test MAPREC SO ALTEX-ALTERNATIVEN ZU TIEREXPERIMENTEN LA German DT Article DE monkey neurovirulence test; reversion of attenuation; alternative in vitro method C1 Chiron Behring GmbH & Co, D-35041 Marburg, Germany. FDA, CBER, Rockville, MD USA. RP Dorsam, V (reprint author), Chiron Behring GmbH & Co, D-35041 Marburg, Germany. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPEKTRUM AKADEMISCHER VERLAG PI HEIDELBERG PA VANGEROWSTR 20, D-69115 HEIDELBERG, GERMANY SN 0946-7785 J9 ALTEX-ALTERN TIEREXP JI Altex Altern. Tierexp. PY 1998 VL 15 SU S BP 21 EP 21 PG 1 WC Integrative & Complementary Medicine SC Integrative & Complementary Medicine GA 141ZQ UT WOS:000077175800011 ER PT J AU Honig, PK Anthracite, R Jenkins, JK AF Honig, PK Anthracite, R Jenkins, JK TI Zafirlukast in asthma SO ANNALS OF INTERNAL MEDICINE LA English DT Letter C1 US FDA, Rockville, MD 20857 USA. RP Honig, PK (reprint author), US FDA, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AMER COLL PHYSICIANS PI PHILADELPHIA PA INDEPENDENCE MALL WEST 6TH AND RACE ST, PHILADELPHIA, PA 19106-1572 USA SN 0003-4819 J9 ANN INTERN MED JI Ann. Intern. Med. PD JAN 1 PY 1998 VL 128 IS 1 BP 70 EP 70 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA YN342 UT WOS:000071158000013 PM 9424987 ER PT J AU Friedman, MA AF Friedman, MA TI Global drug development SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 030 BP 9 EP 9 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600033 ER PT J AU Flora, KP Blumberg, J LoBianco, I Flora, KP Flora, KA AF Flora, KP Blumberg, J LoBianco, I Flora, KP Flora, KA TI Low temperature vacuum drying: Evaluation of excipients for injectable dosage forms. II SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Off Testing & Res, Div Prod Qual Res, Laurel, MD 20708 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 178 BP 47 EP 47 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600150 ER PT J AU Andrews, PA Clark, DL AF Andrews, PA Clark, DL TI The Freireich et al. dataset reanalyzed in the context of the modern preclinical toxicology practices SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 212 BP 56 EP 56 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600184 ER PT J AU Clark, DL Andrews, PA DeGeorge, JJ Justice, RL Beitz, JG AF Clark, DL Andrews, PA DeGeorge, JJ Justice, RL Beitz, JG TI Predictive value of preclinical toxicology studies for platinum anticancer drugs SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 213 BP 56 EP 56 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600185 ER PT J AU Clark, DL Andrews, PA Brower, ME Schmidt, WJ DeGeorge, JJ Justice, RL Beitz, JG AF Clark, DL Andrews, PA Brower, ME Schmidt, WJ DeGeorge, JJ Justice, RL Beitz, JG TI Predictive value of preclinical toxicology studies for microtubule inhibitors SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 US FDA, Div Oncol Drug Prod, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 211 BP 56 EP 56 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600183 ER PT J AU Michejda, CJ Cholody, WM Tarasov, S Hernandez, L Bansal, M Turpin, JA Rice, WG Aszalos, A AF Michejda, CJ Cholody, WM Tarasov, S Hernandez, L Bansal, M Turpin, JA Rice, WG Aszalos, A TI Bisimidazoacridones, potent but selective anti-tumor agents which appear to target transcription in sensitive cells SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 MADD, ABL, BRP, Frederick, MD USA. SAIC Frederick, LADM, DTP, Frederick, MD USA. NCI, Frederick Canc Res & Dev Ctr, Frederick, MD 21702 USA. US FDA, CBL, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 510 BP 133 EP 133 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600482 ER PT J AU Kobayashi, K Vaccari, L Cutler, E Johnson, J Justice, R AF Kobayashi, K Vaccari, L Cutler, E Johnson, J Justice, R TI Expanded access to investigational cancer (CA) therapies (rx) in the US that have been approved in other countries: 1998 update SO ANNALS OF ONCOLOGY LA English DT Meeting Abstract C1 US FDA, Div Oncol Drug Prod, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-7534 J9 ANN ONCOL JI Ann. Oncol. PY 1998 VL 9 SU 2 MA 680 BP 177 EP 177 PG 1 WC Oncology SC Oncology GA ZZ632 UT WOS:000074749600652 ER PT J AU DePaola, A Motes, ML Chan, AM Suttle, CA AF DePaola, A Motes, ML Chan, AM Suttle, CA TI Phages infecting Vibrio vulnificus are abundant and diverse in oysters (Crassostrea virginica) collected from the Gulf of Mexico SO APPLIED AND ENVIRONMENTAL MICROBIOLOGY LA English DT Article ID MARINE-ENVIRONMENT; STRAINS; COAST; VIRUSES; BACTERIOPHAGES; PHYTOPLANKTON; TEMPERATURE; SALINITY; SEAWATER; FLORIDA AB Phages infecting Vibrio vulnificus were abundant (> 10(4) phages g of oyster tissue(-1)) throughout the year in oysters (Crassostrea virginica) collected from estuaries adjacent to the Gulf of Mexico (Apalachiocola Bay, Fla.; Mobile Bay, Ala.; and Black Bay, La.). Estimates of abundance ranged from 10(1) to 10(5) phages g of oyster tissue(-1) and were dependent on the bacterial strain used to assay the sample, V., vulnificus was near or below detection limits (< 0.3 cell g(-1)) from January through March and was most abundant (10(3) to 10(4) cells g(-1)) during the summer and fall when phage abundances also tended to be greatest, The phages isolated were specific to strains of V. vulnificus, except for one isolate that caused lysis in a few; strains of V., parahaemolyticus. Based on morphological evidence obtained by transmission electron microscopy, the isolates belonged to the Podoviridae, Styloviridae, and Myoviridae, three families of double-stranded DNA phages, One newly described morphotype belonging to the Podoviridae appears to be ubiquitous in Gulf Coast oysters, Isolates of this morphotype have an elongated capsid (mean, 258 nm; standard deviation, 4 nm; n = 35), with some isolates having a relatively broad host range among strains of V. vulnificus. Results from this study indicate that a morphologically diverse group of phages which infect V. vulnificus is abundant and widely distributed in oysters from estuaries bordering the northeastern Gulf of Mexico. C1 US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. Univ British Columbia, Dept Earth & Ocean Sci Oceanog, Vancouver, BC V6T 1Z4, Canada. Univ British Columbia, Dept Bot & Microbiol, Vancouver, BC V6T 1Z4, Canada. RP DePaola, A (reprint author), US FDA, Gulf Coast Seafood Lab, POB 158, Dauphin Island, AL 36528 USA. RI Suttle, Curtis/C-3150-2008 OI Suttle, Curtis/0000-0002-0372-0033 NR 37 TC 36 Z9 36 U1 1 U2 7 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 USA SN 0099-2240 J9 APPL ENVIRON MICROB JI Appl. Environ. Microbiol. PD JAN PY 1998 VL 64 IS 1 BP 346 EP 351 PG 6 WC Biotechnology & Applied Microbiology; Microbiology SC Biotechnology & Applied Microbiology; Microbiology GA YP406 UT WOS:000071273600054 PM 9435088 ER PT J AU Alayash, AI Ryan, BAB Cashon, RE AF Alayash, AI Ryan, BAB Cashon, RE TI Peroxynitrite-mediated heme oxidation and protein modification of native and chemically modified hemoglobins SO ARCHIVES OF BIOCHEMISTRY AND BIOPHYSICS LA English DT Article DE peroxynitrite; hemoglobin-based blood substitutes ID CROSS-LINKED HEMOGLOBIN; NITRIC-OXIDE; BLOOD SUBSTITUTE; SUPEROXIDE; INJURY; POLYMERIZATION AB Peroxynitrite (ONOO-) has been shown to play a critical role in tissue reperfusion injury. We have studied the reactions of ONOO- with native and two chemically modified hemoglobins that are being developed as oxygen-carrying reperfusion agents for use in a variety of clinical conditions. Reactions of native and chemically modified oxyhemoglobins (oxyHb) at 7.4 with ONOO- lead to a rapid oxidation of the heme iron to ferric (HbFe(3+)) form. Addition of excess molar ratios of ONOO- to the ferryl (HbFe(4+)) heme protein induced a spectral change indicative of the reduction of HbFe(4+) to the HbFe(3+) oxidation state. No major spectral changes were noted when ONOO- was added to methemoglobin (HbFe(3+)) or cyanomethemoglobin (Hb(3+)CN(-)), whereas the carbonmonoxy derivative of ferrous hemoglobin (HbCO) underwent an immediate spectral change suggesting the displacement of the CO ligand and oxidation of the heme iron. Rapid mixing of ONOO- with oxyHb in the stopped-flow spectrophotometer yielded biphasic kinetic plots for the oxidation of the ferrous iron (Fe2+). Replots of the apparent rate constants for native, cross-linked and polymerized, cross-linked hemoglobins as a function of ONOO concentration were linear, yielding a single second-order rate for all hemoglobins of between 2 to 3 x 10(4) M-1 s(-1), independent of the oxygen affinities and molecular sizes of the proteins. Oxidative modifications of the protein by ONOO-, occuring primarily at the beta subunits, were observed in reaction mixtures of oxyHb and ONOO- using reverse-phase HPLC, The immunodetection method confirms that nitration of tyrosine residues by ONOO- occurs on the hemoglobin molecule and contributes to the modifications observed. We postulate that the presence of hemoglobin in close proximity to ONOO- production sites in the vasculature can contribute to possible in vivo toxicity by a two-step mechanism involving (i) direct oxidation of the heme iron and (ii) nitration of the tyrosine residues on the molecule, leading to subsequent instability and heme loss from the protein. (C) 1998 Academic Press. C1 US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Div Hematol, Bethesda, MD 20892 USA. Univ Maine, Dept Biochem, Orono, ME 04469 USA. RP Alayash, AI (reprint author), US FDA, Ctr Biol Evaluat & Res, Lab Cellular Hematol, Div Hematol, Bldg 29,Rm 112,8800 Rockville Pike, Bethesda, MD 20892 USA. EM Alayash@A1.cber.fda.gov NR 31 TC 64 Z9 65 U1 0 U2 2 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 1 PY 1998 VL 349 IS 1 BP 65 EP 73 DI 10.1006/abbi.1997.0449 PG 9 WC Biochemistry & Molecular Biology; Biophysics SC Biochemistry & Molecular Biology; Biophysics GA YR189 UT WOS:000071469700008 PM 9439583 ER PT J AU Mondoro, TH Alayash, AI Ryan, BAB Terle, DA Vostal, JG AF Mondoro, TH Alayash, AI Ryan, BAB Terle, DA Vostal, JG TI Hemoglobin A(0) and alpha-crosslinked hemoglobin (alpha-DBBF) potentiate agonist-induced platelet aggregation through the platelet thromboxane receptor SO ARTIFICIAL CELLS BLOOD SUBSTITUTES AND IMMOBILIZATION BIOTECHNOLOGY LA English DT Article ID STIMULATED HUMAN-PLATELETS; HYDROGEN-PEROXIDE; BLOOD SUBSTITUTE; ACTIVATION; THROMBIN; BINDING AB Chemically modified hemoglobins are potential oxygen-carrying blood substitutes, but their in vivo administration has been associated with a variety of unexpected side events, including increased platelet reactivity. We studied the effects of hemoglobin A(0) (HbA(0)) and alpha-crosslinked hemoglobin (alpha-DBBF) on platelets in vitro. Neither hemoglobin A(0) nor alpha-DBBF activated platelets when added alone, but both proteins potentiated submaximal agonist-induced platelet aggregation without increasing other markers of platelet activation such as serotonin secretion. Only agonists that are known to cause release of platelet arachidonic acid (AA) were potentiated while aggregation induced by ADP, which does not release AA, was not potentiated. Blockade of the thromboxane receptor with SQ-29,548 prevented the HbA(0)-induced and the alpha-DBBF-induced potentiation suggesting that the AA/thromboxane signaling pathway mediates the interaction of platelets with hemoglobin. C1 US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Mondoro, TH (reprint author), US FDA, Lab Cellular Hematol, Div Hematol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 40 TC 8 Z9 8 U1 1 U2 3 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 1998 VL 26 IS 1 BP 1 EP 16 DI 10.3109/10731199809118942 PG 16 WC Biotechnology & Applied Microbiology; Engineering, Biomedical; Materials Science, Biomaterials SC Biotechnology & Applied Microbiology; Engineering; Materials Science GA ZK954 UT WOS:000073384300002 PM 9507752 ER PT J AU Nawaz, MS Billedeau, SM Cerniglia, CE AF Nawaz, MS Billedeau, SM Cerniglia, CE TI Influence of selected physical parameters on the biodegradation of acrylamide by immobilized cells of Rhodococcus sp. SO BIODEGRADATION LA English DT Article DE acrylamide; amidase; biodegradation; biotransformation; immobilized cells ID PSEUDOMONAS SP; AMIDASE; PURIFICATION; DEGRADATION; KINETICS; BACTERIA AB The influences of concentration of acrylamide, pH, temperature, duration of storage of encapsulated cells and presence of different metals and chelators on the ability of immobilized cells of a Rhodococcus sp, to degrade acrylamide were evaluated. Immobilized cells (3 g) rapidly degraded 64 and 128 mM acrylamide in 3 and 5 h, respectively, whereas free cells took more than 24 h to degrade 64 mM acrylamide. An acrylamide concentration of 128 mM inhibited the growth of the free cells. Immobilized bacteria were slow to degrade acrylamide at 10 degrees C. Less than 60% of acrylamide was degraded in 4 h. However, 100% of the compound was degraded in less than 3 h at 28 degrees C and 45 degrees C. The optimum pH for the degradation of acrylamide by encapsulated cells was pH 7.0. Less than 10% of acrylamide was degraded at pH 6.0, while ca. 60% of acrylamide was degraded at pH 8.0 and 8.5. Copper and nickel inhibited the degradation, suggesting the presence of sulfhydryl (-SH) groups in the active sites of the acrylamide degrading amidase. Tron enhanced the rates of degradation and chelators (EDTA and 1,10 phenanthroline) reduced the rates of degradation suggesting the involvement of iron in its active site(s) of the acrylamide-degrading-amidase. Immobilized cells could be stored up to Iq days without any detectable loss of acrylamide-degrading activity. C1 Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. RP Nawaz, MS (reprint author), Natl Ctr Toxicol Res, Div Microbiol, Jefferson, AR 72079 USA. NR 22 TC 21 Z9 22 U1 1 U2 6 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0923-9820 J9 BIODEGRADATION JI Biodegradation PY 1998 VL 9 IS 5 BP 381 EP 387 DI 10.1023/A:1008383710019 PG 7 WC Biotechnology & Applied Microbiology SC Biotechnology & Applied Microbiology GA 178MW UT WOS:000079270600007 PM 10192898 ER PT J AU Rosen, LA Barber, I Lyle, DB AF Rosen, LA Barber, I Lyle, DB TI A 0.5 G, 60 Hz magnetic field suppresses melatonin production in pinealocytes SO BIOELECTROMAGNETICS LA English DT Article DE melatonin; magnetic fields; rat; single cells; gland dissociation ID 60-HZ ELECTRIC-FIELDS; RATS; EXPOSURE; GLAND AB The objective of this study was to develop a model for testing various hypotheses concerning possible mechanisms whereby electromagnetic fields might induce suppression of nighttime melatonin production in rodents. A published method for digesting freshly obtained pineal glands to the single cell level was modified, yielding better than 95% viability. An in vitro exposure facility developed for the Food and Drug Administration was used for 12-h overnight exposures of primary pinealocyte cultures to 0.05 mT, 60 Hz, vertical AC and 0.06 mu T, DC fields. After exposure, cells were separated from the supernatant by centrifugation. Supernatant melatonin was measured by ELISA assays. Data from 10 experiments demonstrated an average 46% reduction in norepinephrine-induced production of melatonin in the pinealocytes. The results support the hypothesis that EM exposure can produce pineal gland melatonin suppression by affecting individual cells. (C) 1998 Wiley-Liss, Inc.dagger. C1 NIH, Div Res Grants, Bethesda, MD 20892 USA. US FDA, Oak Ridge Natl Lab, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. US FDA, Radiat Biol Branch, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Rosen, LA (reprint author), NIH, Ctr Sci Review, 6701 Rockledge Dr,Room 5116,MSC 7854, Bethesda, MD 20892 USA. NR 15 TC 25 Z9 28 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 0197-8462 J9 BIOELECTROMAGNETICS JI Bioelectromagnetics PY 1998 VL 19 IS 2 BP 123 EP 127 DI 10.1002/(SICI)1521-186X(1998)19:2<123::AID-BEM11>3.3.CO;2-H PG 5 WC Biology; Biophysics SC Life Sciences & Biomedicine - Other Topics; Biophysics GA YV446 UT WOS:000071825000011 PM 9492170 ER PT J AU Hendry, WJ Branham, WS Sheehan, DM AF Hendry, WJ Branham, WS Sheehan, DM TI Differential potency of a synthetic (diethylstilbestrol) and a natural (estradiol) estrogen as neonatal endocrine disruptors of the hamster uterine cervix. SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 Wichita State Univ, Dept Biol Sci, Wichita, KS 67208 USA. Natl Ctr Toxicol Res, Div Reprod & Dev Toxicol, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1998 VL 58 SU 1 MA 49 BP 86 EP 86 PG 1 WC Reproductive Biology SC Reproductive Biology GA ZX708 UT WOS:000074546000095 ER PT J AU Gu, Y Branham, WS Sheehan, DM Moland, CL Dial, SL Streck, RD AF Gu, Y Branham, WS Sheehan, DM Moland, CL Dial, SL Streck, RD TI Neonatal exposure to tamoxifen (TAM) alters uterine insulin-like growth factor-I (IGF-I) and IGF binding protein (IGFBP) mRNA expression and regulation by TAM and diethylstibestrol (DES). SO BIOLOGY OF REPRODUCTION LA English DT Meeting Abstract C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 1 U2 1 PU SOC STUDY REPRODUCTION PI MADISON PA 1603 MONROE ST, MADISON, WI 53711-2021 USA SN 0006-3363 J9 BIOL REPROD JI Biol. Reprod. PY 1998 VL 58 SU 1 MA 62 BP 90 EP 90 PG 1 WC Reproductive Biology SC Reproductive Biology GA ZX708 UT WOS:000074546000108 ER PT B AU Alayash, AI AF Alayash, AI BE Tsuchida, E TI Hemoglobin-based blood substitutes and mechanisms of toxicity SO BLOOD SUBSTITUTES PRESENT AND FUTURE PERSPECTIVES LA English DT Proceedings Paper CT 7th International Symposium on Blood Substitutes CY SEP 07-10, 1997 CL WASEDA UNIV, TOKYO, JAPAN HO WASEDA UNIV ID CROSS-LINKED HEMOGLOBIN; VASCULAR ENDOTHELIAL-CELLS; NITRIC-OXIDE; REPERFUSION INJURY; OXIDATIVE-STRESS; FREE-RADICALS; SUPEROXIDE; INDUCTION; REDUCTION; ISCHEMIA AB Vascular endothelium, a source of a number of oxidants, has emerged as the primary target of hemoglobin-based toxicity, due to its proximity and direct contact with the circulating protein. Reaction of hemoglobin with endothelial signaling molecule, nitric oxide (NO.), results in the diversion of NO. away from the smooth muscle target enzymes, leading to the loss of NO. dependent responses such as vasodilatation. The ensuing oxidative reactions of hemoglobin with oxidants such as peroxynitrite (ONOO-), the reaction byproduct of nitric oxide with superoxide (O-2(.-)) hydrogen peroxide or lipid peroxide may contribute to the level and extent of tissue damage. In this chapter, an overview of hemoglobin reactions with nitric oxide/peroxynitrite and superoxide/peroxide will be presented together with the emerging understanding of the dynamics that govern hemoglobin's redox reactions with these oxidants and some of the protective strategies under development to combat these reactions. 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 37 TC 2 Z9 2 U1 0 U2 0 PU ELSEVIER SCIENCE BV PI AMSTERDAM PA SARA BURGERHARTSTRAAT 25, PO BOX 211, 1000 AE AMSTERDAM, NETHERLANDS BN 0-444-20524-1 PY 1998 BP 201 EP 210 DI 10.1016/B978-044420524-7/50017-5 PG 10 WC Biotechnology & Applied Microbiology; Hematology; Medicine, Research & Experimental; Materials Science, Biomaterials SC Biotechnology & Applied Microbiology; Hematology; Research & Experimental Medicine; Materials Science GA BM73H UT WOS:000079623300016 ER PT J AU Zheng, Q AF Zheng, Q TI A stochastic two-phase growth model SO BULLETIN OF MATHEMATICAL BIOLOGY LA English DT Article ID COMPARTMENTAL-MODELS AB This article proposes a stochastic growth model that starts as a Yule process and is subsequently joined with a Prendiville process when the population attains certain prescribed critical size. In other words, the model assumes exponential growth in an early stage and logistic growth later on to reflect growth retardation caused by overcrowding. In the case that the population starts with a single unit, closed form expressions are given for the distribution of the population size and for the mean and variance functions of the process. Numerical solutions are briefly discussed for the process that starts with more than one unit. (C) 1998 Society for Mathematical Biology. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Zheng, Q (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 14 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0092-8240 J9 B MATH BIOL JI Bull. Math. Biol. PD JAN PY 1998 VL 60 IS 1 BP 151 EP 161 DI 10.1006/bulm.1997.0029 PG 11 WC Biology; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Mathematical & Computational Biology GA YZ722 UT WOS:000072284600008 PM 9574969 ER PT J AU Thompson, PA Kadlubar, FF Vena, SM Hill, HL McClure, GHY McDaniel, LP Ambrosone, CB AF Thompson, PA Kadlubar, FF Vena, SM Hill, HL McClure, GHY McDaniel, LP Ambrosone, CB TI Exfoliated ductal epithelial cells in human breast milk: A source of target tissue DNA for molecular epidemiologic studies of breast cancer SO CANCER EPIDEMIOLOGY BIOMARKERS & PREVENTION LA English DT Article ID MONOCLONAL-ANTIBODIES; FAT GLOBULE; ADDUCTS; SMOKERS AB Studies of biomarkers of putative breast carcinogens, such as DNA adducts, have been limited by the difficulty in obtaining representative ductal epithelial cells (DECs) from breast tissue, In this feasibility study, we sought to ascertain if exfoliated DECs in breast milk could be a source of DNA for biomarker studies, Specimens (n = 38) were collected over 24 h from nursing women, and a questionnaire was administered, Cell pellets were isolated by repeated centrifugation and washing, Pellets were resuspended and incubated for 2 h, with glass adherence used to remove monocytes, resulting in an enrichment of DECs of >80%, Nonadherent cells were removed, washed, and homogenized for DNA isolation, Accurate DNA quantification was performed by P-32-postlabeling of normal nucleotides under conditions of excess ATP, Although there was wide variability in the amounts of DNA recovered, DNA yield was significantly associated with the number of weeks postpartum (P < 0.01), with optimal yield between 6 and 8 weeks after birth, There were no significant associations (P < 0.05) between the number of cells recovered and milk volume, method of collection, or the number of samples in a 24-h period per individual, This study demonstrates that breast milk can be used as a source of DECs for biomarker studies of gene-environment interaction and that sufficient DNA can be recovered to evaluate carcinogen-DNA adducts and to perform genotyping assays, Using this approach, exfoliated DECs may serve as a source of representative cells for studies of breast carcinogenesis and biomarkers of exposure, susceptibility, and effect. C1 Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. SUNY Buffalo, Dept Social & Prevent Med, Buffalo, NY 14214 USA. RP Ambrosone, CB (reprint author), Natl Ctr Toxicol Res, Div Mol Epidemiol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 21 TC 38 Z9 41 U1 0 U2 1 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 JAN PY 1998 VL 7 IS 1 BP 37 EP 42 PG 6 WC Oncology; Public, Environmental & Occupational Health SC Oncology; Public, Environmental & Occupational Health GA ZA149 UT WOS:000072333800007 PM 9456241 ER PT J AU Culp, SJ Gaylor, DW Sheldon, WG Goldstein, LS Beland, FA AF Culp, SJ Gaylor, DW Sheldon, WG Goldstein, LS Beland, FA TI A comparison of the tumors induced by coal tar and benzo[a]pyrene in a 2-year bioassay SO CARCINOGENESIS LA English DT Article ID B6C3F1 MICE; INGESTION AB The tumorigenicity of two coal tar mixtures was compared to that of benzo[a]pyrene after 2 years of feeding, Mixture 1, a composite of coal tar from seven coal gasification plant waste sites, was fed to female B6C3F1 mice (48 mice per group) for 2 years at doses of 0.0, 0.01, 0.03, 0.1, 0.3, 0.6 and 1.0%, Mixture 2, which was composed of coal tar from two of the seven waste sites and another site having a high benzo[a]pyrene content, was fed at doses of 0.0, 0.03, 0.1 and 0.3%, Additional groups of mice were fed 0, 5, 25 and 100 ppm benzo[a]pyrene, The coal tar diets induced a dose-related increase in hepatocellular adenomas and carcinomas, alveolar/bronchiolar adenomas and carcinomas, forestomach squamous epithelial papillomas and carcinomas, small intestine adenocarcinomas, histiocytic sarcomas, hemangiosarcomas in multiple organs and sarcomas, Benzo[a]pyrene treatment resulted in an increased incidence of papillomas and/or carcinomas of the forestomach, esophagus and tongue, A comparison of the results indicated that the benzo[a]pyrene in the coal tar diets could be responsible for the forestomach tumors, In contrast, the lung and liver tumors appeared to be due to other genotoxic components contained within the coal tar mixture, while the small intestine tumors resulted from chemically-induced cell proliferation that occurred at high doses of coal tar. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Pathol Associates Inc, Jefferson, AR 72079 USA. Elect Power Res Inst, Palo Alto, CA 94303 USA. RP Culp, SJ (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, HFT-110, Jefferson, AR 72079 USA. NR 26 TC 158 Z9 164 U1 2 U2 17 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 0143-3334 J9 CARCINOGENESIS JI Carcinogenesis PD JAN PY 1998 VL 19 IS 1 BP 117 EP 124 DI 10.1093/carcin/19.1.117 PG 8 WC Oncology SC Oncology GA YV095 UT WOS:000071789100015 PM 9472702 ER PT S AU Zoon, KC AF Zoon, KC BE Brown, F Lubiniecki, A Murano, G TI Well-characterized biotechnology products: Evolving to meet the needs of the 21st century SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, CBER, Rockville, MD 20852 USA. RP Zoon, KC (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM-1, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 3 EP 8 PG 6 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000001 PM 9890510 ER PT S AU Finbloom, DS AF Finbloom, DS BE Brown, F Lubiniecki, A Murano, G TI Evaluation of potency for well characterized biotechnology proteins SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, CBER, Rockville, MD 20852 USA. RP Finbloom, DS (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM-330, Rockville, MD 20852 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 63 EP 64 PG 2 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000009 PM 9890518 ER PT S AU Cavagnaro, J Pilaro, A Serabian, M Shores, EW AF Cavagnaro, J Pilaro, A Serabian, M Shores, EW BE Brown, F Lubiniecki, A Murano, G TI Evaluation and concerns for antigenic potential SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, Rockville, MD 20857 USA. RP Cavagnaro, J (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 67 EP 68 PG 2 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000010 ER PT S AU Garnick, R Chiu, YY Sistare, F Kramer, S Rhyskamt, T AF Garnick, R Chiu, YY Sistare, F Kramer, S Rhyskamt, T BE Brown, F Lubiniecki, A Murano, G TI Determination of potency SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 Genentech Inc, S San Francisco, CA 94080 USA. US FDA, Rockville, MD 20857 USA. RP Garnick, R (reprint author), Genentech Inc, S San Francisco, CA 94080 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 69 EP 70 PG 2 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000011 ER PT S AU Wudl, L Moos, M AF Wudl, L Moos, M BE Brown, F Lubiniecki, A Murano, G TI Evaluation of impurities SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, Rockville, MD 20857 USA. RI Moos, Malcolm/F-3673-2011 OI Moos, Malcolm/0000-0002-9575-9938 NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 71 EP 73 PG 3 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000012 ER PT S AU Epstein, S Kuta, A Davis, H Cheng, S Ledley, F AF Epstein, S Kuta, A Davis, H Cheng, S Ledley, F BE Brown, F Lubiniecki, A Murano, G TI Evaluation of DNA/plasmid products SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, Rockville, MD 20857 USA. Genzyme Corp, Cambridge, MA USA. Ottawa Civic Hosp, Ottawa, ON K1Y 4E9, Canada. RP Epstein, S (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 75 EP 76 PG 2 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000013 ER PT S AU Cavagnaro, JA AF Cavagnaro, JA BE Brown, F Lubiniecki, A Murano, G TI Establishment of criteria for determining comparability of "well-characterized" proteins SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, Off Director, CBER, Bethesda, MD 20892 USA. RP Cavagnaro, JA (reprint author), US FDA, Off Director, CBER, 1401 Rockville Pike,HFM-2, Bethesda, MD 20892 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 79 EP 81 PG 3 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000014 PM 9890519 ER PT S AU Goldman, N Kaminsky, SM Verlander, M Slater, M Phelan, M AF Goldman, N Kaminsky, SM Verlander, M Slater, M Phelan, M BE Brown, F Lubiniecki, A Murano, G TI Evaluation of multi-antigen peptides SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, Washington, DC 20204 USA. Immul Pharmaceut Corp, Waltham, MA USA. RP Goldman, N (reprint author), US FDA, Washington, DC 20204 USA. RI Kaminsky, Stephen/J-5141-2016 OI Kaminsky, Stephen/0000-0003-1869-834X NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 151 EP 154 PG 4 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000024 ER PT S AU Egan, W Ostroff, G Hellerqvist, C Egan, W Linhardt, R Kaspar, D AF Egan, W Ostroff, G Hellerqvist, C Egan, W Linhardt, R Kaspar, D BE Brown, F Lubiniecki, A Murano, G TI Evaluation of polysaccharides SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, Washington, DC 20204 USA. Vanderbilt Univ, CarboMed Inc, Nashville, TN USA. Univ Iowa, Iowa City, IA 52242 USA. Harvard Univ, Cambridge, MA 02138 USA. Alpha Beta Technol, Worcester, MA USA. RP Egan, W (reprint author), US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 155 EP 156 PG 2 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000025 ER PT S AU Halpern, A Abuchoski, A Clark, D Tolman, G AF Halpern, A Abuchoski, A Clark, D Tolman, G BE Brown, F Lubiniecki, A Murano, G TI Evaluation of derivatized proteins SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, Washington, DC 20204 USA. Houston Biotechnol Inc, Houston, TX USA. Centocor Inc, Malvern, PA 19355 USA. Enzon Inc, Piscataway, NJ 08854 USA. RP Halpern, A (reprint author), US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 157 EP 159 PG 3 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000026 ER PT S AU Stein, K Nordan, R Hanigan, E Siegel, RC Roy, M Cole, N Federici, MM Florin-Robertson, E AF Stein, K Nordan, R Hanigan, E Siegel, RC Roy, M Cole, N Federici, MM Florin-Robertson, E BE Brown, F Lubiniecki, A Murano, G TI Evaluation of monoclonal antibodies SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, Washington, DC 20204 USA. Centocor Inc, Malvern, PA 19355 USA. Agracetus Inc, Middleton, WI USA. Genzyme Transgen Corp, Framingham, MA USA. RP Stein, K (reprint author), US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 161 EP 163 PG 3 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000027 ER PT S AU Finlayson, J Shrake, A Weeks, RL Pierce, B Long, M Waldman, AA Yu, MYW AF Finlayson, J Shrake, A Weeks, RL Pierce, B Long, M Waldman, AA Yu, MYW BE Brown, F Lubiniecki, A Murano, G TI Evaluation of highly purified protein pharmaceuticals from natural sources SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, Washington, DC 20204 USA. Natl Hemophilia Fdn, New York, NY USA. Abbott Labs, Abbott Pk, IL 60064 USA. RP Finlayson, J (reprint author), US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 165 EP 166 PG 2 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000028 ER PT S AU Beatrice, MG AF Beatrice, MG BE Brown, F Lubiniecki, A Murano, G TI Process validation SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, CBER, Rockville, MD 20857 USA. RP Beatrice, MG (reprint author), US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 169 EP 171 PG 3 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000029 PM 9890529 ER PT S AU Devine, R AF Devine, R BE Brown, F Lubiniecki, A Murano, G TI Summary of panel topic discussions SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, CBER, Rockville, MD 20852 USA. RP Devine, R (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM-10, Rockville, MD 20852 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 177 EP 179 PG 3 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000031 ER PT S AU Zoon, K Garnick, R AF Zoon, K Garnick, R BE Brown, F Lubiniecki, A Murano, G TI Definition of a well-characterized biotechnology product SO CHARACTERIZATION OF BIOTECHNOLOGY PHARMACEUTICAL PRODUCTS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Symposium on the Characterization of Biotechnology Pharmaceutical Products CY DEC 11-13, 1995 CL WASHINGTON, D.C. SP US FDA, Ctr Biolog Evaluat & Res C1 US FDA, CBER, Rockville, MD 20852 USA. Genentech Inc, S San Francisco, CA USA. RP Zoon, K (reprint author), US FDA, CBER, 1401 Rockville Pike,HFM-1, Rockville, MD 20852 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6805-3 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 96 BP 191 EP 197 PG 7 WC Biology; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy SC Life Sciences & Biomedicine - Other Topics; Biotechnology & Applied Microbiology; Pharmacology & Pharmacy GA BM32L UT WOS:000078391000034 PM 9890531 ER PT J AU Fu, TJ AF Fu, TJ TI Safety considerations for food ingredients produced by plant cell and tissue culture SO CHEMTECH LA English DT Article ID HAIRY ROOT CULTURES; INDOLE ALKALOID PRODUCTION; CAPSICUM-FRUTESCENS MILL; CATHARANTHUS-ROSEUS; SUSPENSION-CULTURES; AGROBACTERIUM-RHIZOGENES; T-DNA; SOMACLONAL VARIATION; TROPANE ALKALOIDS; IMMOBILIZED CELLS AB These techniques can provide an alternative method of producing food ingredients that have traditionally been extracted from field-grown plants. An understanding of the biochemical processes involved will help to determine the intended or unintended modifications to the product and thus its safety. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Fu, TJ (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. EM tfu@vm.fda.cfsan.gov NR 64 TC 7 Z9 8 U1 1 U2 1 PU AMER CHEMICAL SOC PI WASHINGTON PA 1155 16TH ST, NW, WASHINGTON, DC 20036 USA SN 0009-2703 J9 CHEMTECH JI Chemtech PD JAN PY 1998 VL 28 IS 1 BP 40 EP 46 PG 7 WC Chemistry, Applied SC Chemistry GA YQ537 UT WOS:000071397700011 ER PT J AU Tang, YB Zielinski, WL Bigott, HM AF Tang, YB Zielinski, WL Bigott, HM TI Separation of nicotine and nornicotine enantiomers via normal phase HPLC on derivatized cellulose chiral stationary phases SO CHIRALITY LA English DT Article DE (+/-)nicotine; (+/-)nornicotine; chiral separation; enantiomers; normal phase HPLC; mobile phase additive; cellulose-based chiral stationary phase ID LIQUID-CHROMATOGRAPHY; RACEMIC NICOTINE; RESOLUTION; STEREOISOMERS; RECOGNITION; DISEASE; ANALOGS; PURITY; DOGS AB This paper describes the enantiorecognition of (+/-)nicotine and (+/-)nornicotine by high-performance liquid chromatography using two derivatized cellulose chiral stationary phases (CSPs) operated in the normal phase mode. It was found that different substituents linked to the cellulose backbone significantly influence the chiral selectivity of the derivatized CSP. The results showed that, in general, the tris(4-dmethylbenzoyl) cellulose CSP (Chiralcel OJ) surpasses tris (3,5-dimethylphenyl carbamoyl) cellulose CSP (Chiralcel OD). On the former column, the resolution (+/-)nicotine and (+/-)nornicotine enantiomers depended largely on mobile phase compositions. For the separation of the nicotine enantiomers, the addition of trifluoroacetic acid to a 95:5 hexane/alcohol mobile phase greatly improved the enantioresolution, probably due to enhanced hydrogen bonding interactions between the protonated analytes and the CSP. For (+/-)nornicotine separation, a reduction in the concentration of alcohol in the mobile phase was more effective than the addition of trifluoracetic acid. Possible solute-mobile phase-stationary phase interactions are discussed to explain how different additives in the mobile phase and different substituents on the cellulose glucose units of the CSPs affect the separation of both pairs of enantiomers. (C) 1998 Wiley-liss, Inc.(dagger) C1 US FDA, Div Drug Anal, St Louis, MO USA. RP Tang, YB (reprint author), Merck & Co Inc, POB 2000,RY55-20, Rahway, NJ 07065 USA. RI Hennkens, Heather/C-7668-2015 OI Hennkens, Heather/0000-0002-3283-8751 NR 30 TC 20 Z9 23 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0899-0042 J9 CHIRALITY JI Chirality PY 1998 VL 10 IS 4 BP 364 EP 369 DI 10.1002/(SICI)1520-636X(1998)10:4<364::AID-CHIR13>3.0.CO;2-Y PG 6 WC Chemistry, Medicinal; Chemistry, Analytical; Chemistry, Organic; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA ZP538 UT WOS:000073763500013 ER PT J AU Kinsella, TJ Kunugi, KA Vielhuber, KA Potter, DM Fitzsimmons, ME Collins, JM AF Kinsella, TJ Kunugi, KA Vielhuber, KA Potter, DM Fitzsimmons, ME Collins, JM TI Preclinical evaluation of 5-iodo-2-pyrimidinone-2 '-deoxyribose as a prodrug for 5-iodo-2 '-deoxyuridine-mediated radiosensitization in mouse and human tissues SO CLINICAL CANCER RESEARCH LA English DT Article ID COLON-CANCER-CELLS; CONTINUOUS INTRAVENOUS INFUSIONS; COLORECTAL LIVER METASTASES; HALOGENATED PYRIMIDINES; ALDEHYDE OXIDASE; IN-VIVO; 2-PYRIMIDINONE NUCLEOSIDES; THYMIDINE REPLACEMENT; XANTHINE-OXIDASE; CELLULAR DNA AB We reported previously that p.o. administered 5-iodo-2-pyrimidinone-2'-deoxyribose (IPdR) was efficiently converted to 5-iodo-2'-deoxyuridine (IUdR) in athymic mice (T. J. Kinsella et al., Cancer Res., 54: 2695-2700, 1994). Here, we further evaluate IPdR metabolism, systemic toxicity, and percentage DNA incorporation in athymic mouse normal tissues and a human colon cancer xenograft (HT29) using higher p.o. doses of IPdR. These data are compared to results using a continuous infusion of IUdR at the maximum tolerable dose, We also evaluate IPdR metabolism in cytosolic extracts from normal human liver, normal human intestine, and human colorectal cancer specimens, Athymic mice tolerated a daily p.o. bolus of up to 2 g/kg IPdR for 6 days with minimal host toxicity (less than or equal to 10% body weight loss), There was rapid conversion of IPdR to IUdR, with peak plasma levels of IUdR of 40-75 mu M at 10 min following a p.o. IPdR bolus of 250-1500 mg/kg. The percentage IUdR-DNA in the HT29 s.c. human tumor xenografts increased 1.5 times (2.3-3.6%) with IPdR doses above 1 g/kg/day for 6 days, whereas the percentage IUdR-DNA incorporation in two proliferating normal tissues (4-4.5% in intestine; 1.6-2.2% in bone marrow) and a quiescent normal tissue (less than or equal to 1% in liver) showed <1.5-fold increases with the IPdR dose escalation between 1-2 g/kg/day for 6 days, In contrast, using a continuous infusion of IUdR at 100 mg/kg/day, significant systemic toxicity (>20% body weight loss) was found by day 6 of the infusion, Steady-state plasma IUdR levels were 1.0-1.2 mu M during the 6-day infusion, and percentage IUdR-DNA incorporations of 2.3, 8, 6, and 1% were measured in s.c. tumors, normal intestine, normal bone marrow, and normal liver, respectively, following the 6-day infusion, Thus, the p.o. IPdR schedule has an improved therapeutic index, based on percentage IUdR-DNA incorporation in normal and tumor tissues, compared to continuous infusion IUdR at the maximum tolerable dose in athymic mice with this human tumor xenograft, Additionally, a tumor regrowth assay to assess the radiation response of HT29 s.c. xenografts showed a 1.5-fold enhancement (time to regrow to 300% initial tumor volume) with IPdR (1000 mg/kg/day for 6 days) plus fractionated irradiation (XRT; 2 Gy/day for 4 days), compared to XRT (2 Gy/day for 4 days) alone. No enhancement in the radiation response of HT29 s.c. xenografts was found with continuous infusion IUdR (100 mg/kg/day for 6 days) plus XRT (2 Gy/day for 4 days), compared to XRT alone. Using cytosolic extracts from normal human liver specimens, we found a rapid (15-min) conversion of IPdR to IUdR. Coincubation of liver cytosol with IPdR and allopurinol, an inhibitor of xanthine oxidase, had no inhibitory effect on IPdR metabolism, whereas coincubation with IPdR and isovanillin or menadione, analogue substrates for aldehyde oxidase, effectively reduced the amount of IPdR oxidized to IUdR, Significantly less metabolism of IPdR to IUdR was seen in cytosolic extracts from normal human intestine specimens, and no metabolism of IPdR was found in cytosolic extracts from colorectal liver metastases in two patients and from the HT29 human colon cancer xenografts in athymic mice, These additional data indicate that IPdR has the potential for clinical use as a p.o. prodrug for IUdR-mediated radiosensitization of resistant human cancers. C1 Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Radiat Oncol, Cleveland, OH 44106 USA. US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Kinsella, TJ (reprint author), Case Western Reserve Univ, Univ Hosp Cleveland, Sch Med, Dept Radiat Oncol, 11300 Euclid Ave, Cleveland, OH 44106 USA. FU NCI NIH HHS [CA50595] NR 36 TC 22 Z9 22 U1 0 U2 1 PU AMER ASSOC CANCER RESEARCH PI BIRMINGHAM PA PO BOX 11806, BIRMINGHAM, AL 35202 USA SN 1078-0432 J9 CLIN CANCER RES JI Clin. Cancer Res. PD JAN PY 1998 VL 4 IS 1 BP 99 EP 109 PG 11 WC Oncology SC Oncology GA YT599 UT WOS:000071623200014 PM 9516958 ER PT J AU Singer, SJ Racoosin, JA Viraraghavan, R AF Singer, SJ Racoosin, JA Viraraghavan, R TI Rhabdomyolysis in human immunodeficiency virus - Positive patients taking trimethoprim-sulfamethoxazole SO CLINICAL INFECTIOUS DISEASES LA English DT Article C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20850 USA. RP Singer, SJ (reprint author), US FDA, Ctr Drug Evaluat & Res, 9201 Corp Blvd,Room S-130, Rockville, MD 20850 USA. NR 8 TC 13 Z9 13 U1 0 U2 0 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 1058-4838 J9 CLIN INFECT DIS JI Clin. Infect. Dis. PD JAN PY 1998 VL 26 IS 1 BP 233 EP 234 DI 10.1086/517073 PG 2 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YR235 UT WOS:000071474500069 PM 9455569 ER PT J AU Baylor-Henry, M Drezin, NA AF Baylor-Henry, M Drezin, NA TI Regulation of prescription drug promotion: Direct-to-consumer advertising SO CLINICAL THERAPEUTICS LA English DT Article DE advertising; DTC; promotion; regulation AB The US Food and Drug Administration (FDA) is responsible for regulating the information on prescription drugs disseminated by sponsors to health care providers and consumers to ensure that it is truthful and not misleading, and that it presents a fair balance of benefit and risk information. Thus the public health is both protected and promoted by the dissemination of honest, accurate information about regulated products. This paper discusses the regulatory requirements for promotional materials for prescription drugs and the standards used by the FDA to evaluate these materials. It also dis cusses the agency's views on direct-to-consumer advertising, the enforcement actions that are available to the FDA, the process used by the FDA to determine what action should be taken and when, and what remedies are available. C1 US FDA, Div Drug Mkt Advertising & Commun, Rockville, MD 20857 USA. RP Baylor-Henry, M (reprint author), US FDA, Div Drug Mkt Advertising & Commun, 5600 Fishers Lane,Room 17B20-HFD-40, Rockville, MD 20857 USA. NR 0 TC 10 Z9 10 U1 1 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 1998 VL 20 SU C BP C86 EP C95 DI 10.1016/S0149-2918(98)80012-X PG 10 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 156YK UT WOS:000078030300012 PM 9915094 ER PT J AU Goldman, SA AF Goldman, SA TI Limitations and strengths of spontaneous reports data SO CLINICAL THERAPEUTICS LA English DT Article DE FDA; spontaneous reports; postmarketing surveillance; adverse drug event ID ADVERSE DRUG-REACTIONS; PHARMACOVIGILANCE; SYSTEM AB US Food and Drug Administration (FDA) monitoring of the continued safety of marketed medical products depends greatly on spontaneous reporting of serious adverse events by health professionals. Despite its inherent limitations, the national postmarketing surveillance system provides vital information of clinical importance. C1 US FDA, Off Commissioner, Rockville, MD 20857 USA. RP Goldman, SA (reprint author), US FDA, Off Commissioner, 5600 Fishers Lane,HF-2,Room 17-65, Rockville, MD 20857 USA. NR 19 TC 81 Z9 81 U1 1 U2 2 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 1998 VL 20 SU C BP C40 EP C44 DI 10.1016/S0149-2918(98)80007-6 PG 5 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 156YK UT WOS:000078030300007 PM 9915089 ER PT J AU Laughren, T AF Laughren, T TI Premarketing studies in the drug approval process: Understanding their limitations regarding the assessment of drug safety SO CLINICAL THERAPEUTICS LA English DT Article DE premarketing database; safety; adverse events; causality AB This paper discusses the premarketing safety database that the US Food and Drug Administration receives from drug manufacturers. It reviews the kind of data we usually receive, what we do with the data, and how the data affect labeling. In addition, it discusses some of the limitations of that database in ensuring the safe use of medications. C1 US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod HFD120, Off Drug Evaluat 1, Rockville, MD 20857 USA. RP Laughren, T (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Neuropharmacol Drug Prod HFD120, Off Drug Evaluat 1, 5600 Fishers Lane, Rockville, MD 20857 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 1998 VL 20 SU C BP C12 EP C19 DI 10.1016/S0149-2918(98)80003-9 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 156YK UT WOS:000078030300003 PM 9915085 ER PT J AU Rheinstein, PH AF Rheinstein, PH TI Overview of the US Food and Drug Administration's Reform Legislation SO CLINICAL THERAPEUTICS LA English DT Article DE reform legislation; Modernization Act; FDA; pharmaceutical industry AB This paper addresses the most commonly discussed issues regarding the US Food and Drug Administration Modernization Act. Particular emphasis is given to aspects that affect the pharmaceutical industry. It also discusses the agency's current efforts regarding implementation of specific provisions of the Act. C1 US FDA, Med Staff HFY40, Off Hlth Affairs, Rockville, MD 20857 USA. RP Rheinstein, PH (reprint author), US FDA, Med Staff HFY40, Off Hlth Affairs, 5600 Fishers Lane,Room 15A-08, Rockville, MD 20857 USA. NR 6 TC 2 Z9 2 U1 0 U2 0 PU EXCERPTA MEDICA INC PI NEW YORK PA 245 WEST 17TH STREET, NEW YORK, NY 10011 USA SN 0149-2918 J9 CLIN THER JI Clin. Ther. PY 1998 VL 20 SU C BP C4 EP C11 DI 10.1016/S0149-2918(98)80002-7 PG 8 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 156YK UT WOS:000078030300002 PM 9915084 ER PT J AU Zheng, Q AF Zheng, Q TI On a trinity role of the survival and hazard functions of the two-stage carcinogenesis models SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION LA English DT Article DE carcinogenesis model; model indistinguishability; survival function; hazard function; birth-and-death process ID CANCER AB Three types of the two-stage models that were based on the linear birth-and-death processes were originally envisioned by Kendall (1960) as tools for modeling the carcinogenic process. While two of the three models enjoy widespread applicability, the other has lain fallow so far. This note reports that, as far as the survival and hazard functions are concerned, all three models are equivalent. In addition to giving a proof of the claim, the note also discusses some of the implications within the context of applications of the two-stage models. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 12 TC 1 Z9 1 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0918 J9 COMMUN STAT-SIMUL C JI Commun. Stat.-Simul. Comput. PY 1998 VL 27 IS 1 BP 137 EP 145 DI 10.1080/03610919808813471 PG 9 WC Statistics & Probability SC Mathematics GA ZB633 UT WOS:000072492100011 ER PT J AU Blodgett, RJ AF Blodgett, RJ TI The limit of minimizing points as a median estimator SO COMMUNICATIONS IN STATISTICS-SIMULATION AND COMPUTATION LA English DT Article DE L(p)-norm; location; univariant date AB The middle observation is the traditional estimator of the median of a univariant distribution. This paper considers the limit of the point that minimizes the L(p)-norm as p approaches 1. This limit with trimming and other natural modifications forms an estimate for the median of a distribution. Simulations compare this estimate with others. C1 US FDA, Washington, DC 20204 USA. NR 7 TC 1 Z9 1 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0361-0918 J9 COMMUN STAT-SIMUL C JI Commun. Stat.-Simul. Comput. PY 1998 VL 27 IS 3 BP 857 EP 869 DI 10.1080/03610919808813513 PG 13 WC Statistics & Probability SC Mathematics GA 109DM UT WOS:000075306000017 ER PT J AU Ahn, H Zhu, W Yang, JS Kodell, RL AF Ahn, H Zhu, W Yang, JS Kodell, RL TI Efficient designs for animal carcinogenicity experiments SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article; Proceedings Paper CT Symposium on Applied Statistics CY MAY, 1997 CL RUTGERS UNIV, NEW BRUNSWICK, NEW JERSEY HO RUTGERS UNIV DE Monte Carlo; power; trend test; tumor incidence rate ID MODELS; MORTALITY AB In a typical carcinogenicity study, animals, usually rats or mice, are divided into a control and two to three dose groups of 50 or more by randomization. A chemical is administered at a constant daily dose rate for a major portion of the lifetime of the test animals, for example, two years. In general, such an experiment is expensive and time consuming. In this paper, we propose an efficient design with reduced sample size and/or shortened study duration. An equal number of animals per dose group is considered in this study. A power study of the age-adjusted trend test for the tumor incidence rate for single-sacrifice experiments proposed by Kodell et al. (Drug information Journal, 1997) is conducted. A Monte Carlo simulation study is performed to compare the performance of the trend test for the standard design and various reduced designs. Based on the Kodell et al. test, the al-month study duration with sample:size 50 per group is recommended as the best reduced design over the traditional 2-year study design with the same sample size. C1 SUNY Stony Brook, Dept Appl Math & Stat, Stony Brook, NY 11794 USA. Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 11 TC 3 Z9 3 U1 0 U2 0 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 1998 VL 27 IS 6 BP 1275 EP 1287 DI 10.1080/03610929808832158 PG 13 WC Statistics & Probability SC Mathematics GA ZQ428 UT WOS:000073860500002 ER PT J AU Lin, SC Whipple, DM Ho, CS AF Lin, SC Whipple, DM Ho, CS TI Evaluation of statistical equivalence using limits of agreement and associated sample size calculation SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article; Proceedings Paper CT Symposium on Applied Statistics CY MAY, 1997 CL RUTGERS UNIV, NEW BRUNSWICK, NEW JERSEY HO RUTGERS UNIV DE medical device substantial equivalence; confidence interval; simulation; large sample ID POWER AB In this article, the Food and Drug Administration's (FDA) medical device substantial equivalence provision will be briefly introduced and some statistical methods useful for evaluating device equivalence are discussed. A sample size formula is derived for limits of agreement, which may be used to assess statistical equivalence in certain medical device situations. Simulation findings on the formula are presented, which can be used to guide sample size selections in common practical situations. Examples of the sample size procedure are given. C1 US FDA, Off Surveillance & Biometr, Rockville, MD 20850 USA. US FDA, Off Device Evaluat, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. NR 8 TC 5 Z9 5 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 1998 VL 27 IS 6 BP 1419 EP 1432 DI 10.1080/03610929808832167 PG 14 WC Statistics & Probability SC Mathematics GA ZQ428 UT WOS:000073860500011 ER PT J AU Wang, SJ AF Wang, SJ TI A closed procedure based on Follmann's test for the analysis of multiple endpoints SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE x(+)(2); bootstrap resampling; one-sided alternative; Follmann-RS ID END-POINTS; CLINICAL-TRIALS; 2-SAMPLE COMPARISONS AB Closed test procedures are constructed based on Follmann's x(+)(2) test (1996) and its nonparametric rank sum analog for testing multiple endpoints. These procedures are based on the stepwise closed test strategy of Lehmacher, Wassmer & Reitmeir (1991). The experimentwise type I error rate and power performance of the test procedures are compared to those of the Westfall and Young (WFY) bootstrap resampling closed procedure (1993) by simulation studies. The comparison focuses on one-sided alternatives. Both the Follmann-type and the bootstrap-WFY closed test procedures control the experimentwise type I error rate, and their power performances are similar. C1 US FDA, Div Biometr 1, Off Epidemiol & Biostat, Ctr Drug Evaluat & Res, Rockville, MD 20852 USA. NR 15 TC 3 Z9 3 U1 0 U2 0 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 1998 VL 27 IS 10 BP 2461 EP 2480 DI 10.1080/03610929808832237 PG 20 WC Statistics & Probability SC Mathematics GA 127TB UT WOS:000076365700005 ER PT J AU Chen, JJ AF Chen, JJ TI p-value adjustment for multiple binary endpoints SO COMMUNICATIONS IN STATISTICS-THEORY AND METHODS LA English DT Article DE familywise error rate (FWE); global test; generalized estimating equations; p-value adjustment; multivariate binary data ID BONFERRONI PROCEDURE; CLINICAL-TRIALS; GLOBAL TESTS; END-POINTS; OUTCOMES; MODELS AB The p-value-based adjustment of individual endpoints and the global test for an overall inference are the two general approaches for the analysis of multiple endpoints. Statistical procedures developed for testing multivariate outcomes often assume that the multivariate endpoints are either independent or normally distributed. This paper presents a general approach for the analysis of multivariate binary data under the framework of generalized linear models. The generalized estimating equations (GEE) approach is applied to estimate the correlation matrix of the test statistics using the identity and exchangeable working correlation matrices with the model-based as well as robust estimators. The objectives of the approaches are the adjustment of p-values of individual endpoints to identify the affected endpoints as well as the global test of an overall effect. A Monte Carlo simulation was conducted to evaluate the overall familywise error (FWE) rates of the single-step down p-value adjustment approach from two adjustment methods to three global test statistics. The p-value adjustment approach seems to control the FWE better than the global approach. Applications of the proposed methods are illustrated by analyzing a carcinogenicity experiment designed to study the dose response trend for 10 tumor sites, and a developmental toxicity experiment with three malformation types: external, visceral, and skeletal. C1 US FDA, Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. NR 21 TC 1 Z9 1 U1 1 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 1998 VL 27 IS 11 BP 2791 EP 2806 DI 10.1080/03610929808832255 PG 16 WC Statistics & Probability SC Mathematics GA 132YD UT WOS:000076658500010 ER PT J AU Beard, BB Stewart, JR Fischell, TA AF Beard, BB Stewart, JR Fischell, TA TI A system for postoperative visualization and analysis of left ventricular pressure-volume loops SO COMPUTERS IN BIOLOGY AND MEDICINE LA English DT Article DE patient monitor; gated blood-pool imaging; ventricular volume, left; radionuclide; ventriculography ID RECRUITABLE STROKE WORK; BLOOD CARDIOPLEGIA; FUNCTION MONITOR; SURGERY; PRELOAD; HEART; REPRODUCIBILITY; PERFORMANCE; ACQUISITION; VARIABILITY AB A patient monitoring system for continuous real-time monitoring of left ventricular (LV) function in the postoperative setting was developed. Common hemodynamic parameters and LV functional indices are all calculated from left ventricular pressure-volume loops (PV-loops). Visualization of the PV-loops, along with the hemodynamic parameter derived from them, provides valuable insight into ventricular function and patient recovery. The pressure component is obtained via a pressure sensing catheter placed during surgery. Volume is measured via non-imaging radionuclide techniques using a modified Capintec-VEST. Following surgery and transfer to the recovery unit, the patient's blood is labeled with Tc-99m. A portable gamma camera is used to measure baseline ejection fraction (EF) and to aid in placing the VEST. The specific radioactivity of the blood is calibrated using the baseline EF and thermodilution cardiac output. To confirm the volume measurement accuracy of this technique six patients undergoing bilateral heart catheterization were studied. Single-plane cineventriculographic LV volumes were compared to those calculated from the VEST's time activity curve. (C) 1998 Elsevier Science Ltd. All rights reserved. C1 US FDA, Ctr Devices & Radiol Hlth, Electrophys Branch, Rockville, MD 20850 USA. Cardiovasc Surg Colorado Springs PC, Colorado Springs, CO USA. Borgess Med Ctr, Inst Heart, Kalamazoo, MI USA. RP Beard, BB (reprint author), US FDA, Ctr Devices & Radiol Hlth, Electrophys Branch, HFZ-133,9200 Corp Blvd, Rockville, MD 20850 USA. EM bbb@cdrh.fda.gov OI Beard, Brian/0000-0001-6480-0857 NR 34 TC 2 Z9 2 U1 0 U2 3 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0010-4825 J9 COMPUT BIOL MED JI Comput. Biol. Med. PD JAN PY 1998 VL 28 IS 1 BP 1 EP 12 DI 10.1016/S0010-4825(97)00045-0 PG 12 WC Biology; Computer Science, Interdisciplinary Applications; Engineering, Biomedical; Mathematical & Computational Biology SC Life Sciences & Biomedicine - Other Topics; Computer Science; Engineering; Mathematical & Computational Biology GA ZV156 UT WOS:000074275300001 PM 9644570 ER PT J AU Chung, KT Wong, TY Wei, CI Huang, YW Lin, Y AF Chung, KT Wong, TY Wei, CI Huang, YW Lin, Y TI Tannins and human health: A review SO CRITICAL REVIEWS IN FOOD SCIENCE AND NUTRITION LA English DT Review DE tannins; tannic acid; water soluble polyphenols; tea polyphenols ID GREEN TEA POLYPHENOLS; 2 TEMPERATURE ENVIRONMENTS; INDUCED SKIN TUMORIGENESIS; HIV REVERSE-TRANSCRIPTASE; DENTAL-CARIES PREVENTION; AGRIMONIA-PILOSA LEDEB; FOLK MEDICINAL HERBS; ANTI-AIDS AGENTS; ELLAGIC ACID; PHENOLIC-COMPOUNDS AB Tannins (commonly referred to as tannic acid) are water-soluble polyphenols that are present in many plant foods. They have been reported to be responsible for decreases in feed intake, growth rate, feed efficiency, net metabolizable energy, and protein digestibility in experimental animals. Therefore, foods rich in tannins are considered to be of low nutritional value. However, recent findings indicate that the major effect of tannins was not due to their inhibition on food consumption or digestion but rather the decreased efficiency in converting the absorbed nutrients to new body substances. Incidences of certain cancers, such as esophageal cancer, have been reported to be related to consumption of tannins-rich foods such as betel nuts and herbal teas, suggesting that tannins might be carcinogenic. However, other reports indicated that the carcinogenic acitivity of tannins might be related to components associated with tannins rather than tannins themselves. Interestingly, many reports indicated negative association between tea consumption and incidences of cancers. Tea. polyphenols and many tannin components were suggested to be anticarcinogenic. Many tannin molecules have also been shown to reduce the mutagenic activity of a number of mutagens. Many carcinogens and/or mutagens produce oxygen-free radicals for interaction with cellular macromolecules. The anticarcinogenic and antimutagenic potentials of tannins may be related to their antioxidative property, which is important in protecting cellular oxidative damage, including lipid peroxidaton. The generation of superoxide radicals was reported to be inhibited by tannins and related compounds. The antimicrobial activities of tannins are well documented. The growth of many fungi, yeasts, bacteria, and viruses was inhibited by tannins. We have also found that tannic acid and propyl gallate, but not gallic acid, were inhibitory to foodborne bacteria, aquatic bacteria, and off-flavor-producing microorganisms. Their antimicrobial properties seemed to be associated with the hydrolysis of ester linkage between gallic acid and polyols hydrolyzed after ripening of many edible fruits. Tannins in these fruits thus serve as a natural defense mechanism against microbial infections. The antimicrobial property of tannic acid can also be used in food processing to increase the shelf-life of certain foods, such as catfish fillets. Tannins have also been reported to exert other physiological effects, such as to accelerate blood clotting, reduce blood pressure, decrease the serum lipid level, produce liver necrosis, and modulate immunoresponses. The dosage and kind of tannins are critical to these effects. The aim of this review is to summarize and analyze the vast and sometimes conflicting literature on tannins and to provide as accurately as possible the needed information for assessment of the overall effects of tannins on human health. C1 Univ Memphis, Dept Microbiol & Mol Cell Sci, Memphis, TN 38152 USA. Univ Florida, Dept Food Sci & Human Nutr, Gainesville, FL 32611 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. US FDA, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Chung, KT (reprint author), Univ Memphis, Dept Microbiol & Mol Cell Sci, Memphis, TN 38152 USA. NR 306 TC 529 Z9 559 U1 34 U2 178 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 1998 VL 38 IS 6 BP 421 EP 464 DI 10.1080/10408699891274273 PG 44 WC Food Science & Technology; Nutrition & Dietetics SC Food Science & Technology; Nutrition & Dietetics GA 117WG UT WOS:000075805200001 PM 9759559 ER PT J AU Lin, KK AF Lin, KK TI CDER/FDA formats for submission of animal carcinogenicity study data SO DRUG INFORMATION JOURNAL LA English DT Article DE prevalence method; death-rate method; onset-rate method; divisions of biometrics formats; STUDIES formats; statistical reviews ID TREND AB The Center for Drug Evaluation and Research/Food and Drug Administration (CDER/FDA) routinely requests that drug sponsors submit in their New Drug Applications' carcinogenicity studies electronic data sets for its statistical reviewers to perform independent statistical analyses to evaluate sponsors' analyses and conclusions. The recommended formats for submission of data are based on the information needs for such statistical analyses. Two sets of formats and specifications, that is, the Divisions of Biometrics Formats and Specifications and the Submitter Toxicological Uniform Data Information Exchange Standard (STUDIES) formats, are currently used by the Divisions of Biometrics. Sponsors can follow one of the two sets of formats and specifications in the preparation for data submission. The Divisions of Biometrics, however strongly encourage sponsors to submit the data sets in the simpler Divisions of Biometrics formats and specifications. This paper includes a discussion on the methods of statistical analysis routinely used by FDA statisticians in their reviews, and listings of the CDER/FDA formats and specifications in the 3/12/97 official document (reference 12). C1 US FDA, Ctr Drug Evaluat & Res, Div Biostat, Off Epidemiol & Biostat, Rockville, MD 20857 USA. RP Lin, KK (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Biostat, Off Epidemiol & Biostat, HFD-715,5600 Fishers Lane, Rockville, MD 20857 USA. NR 13 TC 3 Z9 3 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI AMBLER PA 321 NORRISTOWN RD, STE 225, AMBLER, PA 19002-2755 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 1998 VL 32 IS 1 BP 43 EP 52 PG 10 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 128GE UT WOS:000076396700007 ER PT J AU Haffner, ME AF Haffner, ME TI Orphan drug development - International program and study design issues SO DRUG INFORMATION JOURNAL LA English DT Article DE Orphan Drug Act; rare diseases; clinical trials; trial design AB The incentives established by the United States Orphan Drug Act in 1983 initiated significant changes within the pharmaceutical industry regarding resources expended to develop products to treat diseases and conditions lacking commercial markets. America's solution to the orphan drug problem has had worldwide impact and has contributed to an orphan drug law in Japan, proposed legislation in the European Union, and the initiation of a process whereby most Food and Drug Administration-approved orphan drugs and biological products will be similarly approved in Australia. The international research community faces unique concerns regarding trial design required to obtain approval of products to treat rare diseases. Although safety and efficacy far orphan products cannot be compromised, certain factors impact the research approach and present obstacles to investigators: the life-threatening nature of many orphan diseases; the fact that no other treatment may be available for patients other than the study drug; and the limited number of patients available for clinical trials. Expanding international support for rare disease research is providing stimulus and motivation to overcome these barriers and to encourage development of treatment for very rare diseases. NOTE: The term drug will be used here to specify drug and/or biological product. C1 US FDA, Off Orphan Prod Dev, Rockville, MD 20857 USA. RP Haffner, ME (reprint author), US FDA, Off Orphan Prod Dev, HF-35,5600 Fishers Lane RM 8-73, Rockville, MD 20857 USA. NR 0 TC 8 Z9 9 U1 0 U2 4 PU DRUG INFORMATION ASSOCIATION PI AMBLER PA 321 NORRISTOWN RD, STE 225, AMBLER, PA 19002-2755 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 1998 VL 32 IS 1 BP 93 EP 99 PG 7 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 128GE UT WOS:000076396700013 ER PT J AU Honig, PK Cantilena, LR Santone, KS AF Honig, PK Cantilena, LR Santone, KS TI Drug metabolism in drug development: A dia tutorial for regulatory affairs specialists SO DRUG INFORMATION JOURNAL LA English DT Article DE metabolism; cytochrome P450; inhibition; induction; polymorphism ID TERFENADINE AB Many drug metabolism, drug-drug interaction, and pharmacogenetics meetings are held each year and are well attended by scientists from the pharmaceutical industry academia, and worldwide regulatory agencies. Personal communication indicated that large amounts of drug metabolism information passed across the desks of the regulatory affairs specialists either as reports being submitted to or as information requests fr arn regulatory agencies and that, unlike other preclinical or clinical data, there was little appreciation of the meaning or relevance of such information to the overall drug development campaign. The purpose of the tutorial described here was to allow regulatory affairs specialists to gain a working appreciation of the nomenclature, techniques, and usefulness of in vitro and in vivo drug metabolism studies. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Uniformed Serv Univ Hlth Sci, Div Clin Pharmacol, Bethesda, MD 20814 USA. Bristol Myers Squibb Pharmaceut Res Inst, Wallingford, CT USA. RP Honig, PK (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane,Room 10B-45, Rockville, MD 20857 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI AMBLER PA 321 NORRISTOWN RD, STE 225, AMBLER, PA 19002-2755 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 1998 VL 32 IS 1 BP 163 EP 167 PG 5 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 128GE UT WOS:000076396700023 ER PT J AU Lao, CS Kessler, LG Gross, TP AF Lao, CS Kessler, LG Gross, TP TI Proposed statistical methods for signal detection of adverse medical device events SO DRUG INFORMATION JOURNAL LA English DT Article DE medical device reports; nonindependence; overdispersion; aggregate analysis; surveillance and monitoring ID SURVEILLANCE AB This paper proposes several statistical approaches for analyzing spontaneous reports of adverse medical device events. The chi-square statistic is used to detect a sudden increase in reports from pairwise comparison of numbers of reports per month. The Cox-Stuart nonparametric trend test is used to detect a gradual, increasing trend in adverse events reports over time. The negative binomial probability model is also used to assess sudden increases by setting threshold values. In this paper, only numerator data (reports of adverse events), not denominator data (device use), are used. The Box-Jenkins ARIMA rime series model failed to fit the observed data successfully due to the extremely irregular distributions, including many zeros, of the observed data. C1 US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Lao, CS (reprint author), US FDA, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, 1350 Piccard Dr, Rockville, MD 20850 USA. NR 12 TC 7 Z9 7 U1 1 U2 3 PU DRUG INFORMATION ASSOCIATION PI AMBLER PA 321 NORRISTOWN RD, STE 225, AMBLER, PA 19002-2755 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 1998 VL 32 IS 1 BP 183 EP 191 PG 9 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 128GE UT WOS:000076396700026 ER PT J AU Scott, PE Campbell, G AF Scott, PE Campbell, G TI Interpretation of subgroup analyses in medical device clinical trials SO DRUG INFORMATION JOURNAL LA English DT Article DE subgroup; clinical trials; gender effect; medical devices ID OVERVIEWS AB One purpose of a clinical trial is to evaluate the safely and effectiveness of a medical treatment or device based an a representative sample of people from the targeted population. An additional issue of interest to many researchers, however; is: for what patient group a given treatment is most beneficial or poses an increased risk. Subgroup analyses are usually performed to attempt to answer these questions. The results of subgroup analyses must be interpreted bearing in mind the conditions under which the clinical trial was designed and analyzed and the limitations associated with such analyses. This article discusses interpretation of subgroup analyses in clinical trials with emphasis on special considerations related to medical devices. The questions of interest are: under what conditions should subgroup analyses be performed and how, should the results be interpreted from a regulatory perspective for medical device clinical trials? C1 US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, Rockville, MD 20850 USA. RP Campbell, G (reprint author), US FDA, Div Biostat, Off Surveillance & Biometr, Ctr Devices & Radiol Hlth, HFZ-542,1350 Piccard Dr, Rockville, MD 20850 USA. NR 15 TC 3 Z9 3 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI AMBLER PA 321 NORRISTOWN RD, STE 225, AMBLER, PA 19002-2755 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 1998 VL 32 IS 1 BP 213 EP 220 PG 8 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 128GE UT WOS:000076396700029 ER PT J AU Shacter, E DeSantis, PL AF Shacter, E DeSantis, PL TI Labeling of drug and biologic products for pediatric use SO DRUG INFORMATION JOURNAL LA English DT Article DE drugs; biologics; labeling; pediatrics; regulations ID THEOPHYLLINE; NEWBORN AB Drugs and biological therapeutics are commonly prescribed to pediatric patients in the absence of adequate dosage and administration information in the product label. This paper describes issues surrounding labeling of drugs and biologics far pediatric use. It includes a discussion of why drugs and biologics should be labeled with pediatric use information an update on the status of regulatory guidance for pediatric labeling, and a summary of recent steps taken by the Food and Drug Administration (FDA) to increase the number of therapeutic products that contain appropriate labeling for pediatric use. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 11 TC 1 Z9 1 U1 0 U2 0 PU DRUG INFORMATION ASSOCIATION PI AMBLER PA 321 NORRISTOWN RD, STE 225, AMBLER, PA 19002-2755 USA SN 0092-8615 J9 DRUG INF J JI Drug Inf. J. PD JAN-MAR PY 1998 VL 32 IS 1 BP 299 EP 303 PG 5 WC Health Care Sciences & Services; Pharmacology & Pharmacy SC Health Care Sciences & Services; Pharmacology & Pharmacy GA 128GE UT WOS:000076396700040 ER PT J AU Sciacchitano, CJ AF Sciacchitano, CJ TI DNA fingerprinting of Listeria monocytogenes using enterobacterial repetitive intergenic consensus (ERIC) motifs polymerase chain reaction capillary electrophoresis SO ELECTROPHORESIS LA English DT Article DE DNA fingerprinting; capillary electrophoresis; polymerase chain reaction; entobacterial repetitive intergenic consensus motifs ID AMPLIFIED DNA; SEQUENCES; GENOMES; COLI AB The molecular technique, enterobacterial repetitive intergenic consensus (ERIC)-polymerase chain reaction (PCR) produces genomic DNA fingerprint that discriminate bacterial species and strains. This technique was applied to the characterization of Listeria monocytogenes, an important food-borne pathogen implicated in numerous cases of listeriosis. The ERIC-PCR resulted in distinct DNA fingerprinting patterns of all L. monocytogene serotypes and Listeria species. Analysis of the genomic DNA fingerprints was accomplished using capillary electrophoresis (CE), an alternative technique to the conventional agarose gel method. The optimization of CE conditions (electrokinetic injection, applied voltage) resulted in the resolution of amplified DNA fragments up to 1000 bp. Comparisons of electropherograms provided genomic fingerprint templates which could be further used for supplementary information. The ERIC-PCR method coupled to CE provides a rapid technique in differentiating bacterial spp., and may contribute relevant information in food-borne outbreak studies. C1 US FDA, NE Reg Lab, Brooklyn, NY 11232 USA. RP Sciacchitano, CJ (reprint author), US FDA, NE Reg Lab, 850 3rd Ave, Brooklyn, NY 11232 USA. NR 20 TC 20 Z9 20 U1 1 U2 6 PU WILEY-V C H VERLAG GMBH PI BERLIN PA MUHLENSTRASSE 33-34, D-13187 BERLIN, GERMANY SN 0173-0835 J9 ELECTROPHORESIS JI Electrophoresis PD JAN PY 1998 VL 19 IS 1 BP 66 EP 70 DI 10.1002/elps.1150190112 PG 5 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YZ041 UT WOS:000072214200011 PM 9511864 ER PT J AU Zimmerman, ML Barron, JA AF Zimmerman, ML Barron, JA TI Recent interception of live khapra beetle, Trogoderma granarium (Coleoptera: Dermestidae), at the Port of Baltimore, Maryland SO ENTOMOLOGICAL NEWS LA English DT Article RP Zimmerman, ML (reprint author), US FDA,900 MADISON AVE,BALTIMORE,MD 21201, USA. NR 2 TC 0 Z9 0 U1 1 U2 4 PU AMER ENTOMOL SOC PI PHILADELPHIA PA 1900 BENJ FRANKLIN PARKWAY, PHILADELPHIA, PA 19103-1195 SN 0013-872X J9 ENTOMOL NEWS JI Entomol. News PD JAN-FEB PY 1998 VL 109 IS 1 BP 20 EP & PG 2 WC Entomology SC Entomology GA YJ955 UT WOS:A1998YJ95500005 ER PT J AU MacGregor, JT AF MacGregor, JT TI Transgenic animal models for mutagenesis studies: Role in mutagenesis research and regulatory testing SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article; Proceedings Paper CT EMS Meeting on the Future of Transgenic Mutation Models CY MAR, 1998 CL ANAHEIM, CALIFORNIA ID MUTATIONS; MICE; PREVENTION; GUIDELINES; INVIVO C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP MacGregor, JT (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 26 TC 5 Z9 5 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 1998 VL 32 IS 2 BP 106 EP 109 DI 10.1002/(SICI)1098-2280(1998)32:2<106::AID-EM4>3.0.CO;2-E PG 4 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 125LU UT WOS:000076239700003 PM 9776171 ER PT J AU Parsons, BL Heflich, RH AF Parsons, BL Heflich, RH TI Detection of basepair substitution mutation at a frequency of 1 x 10(-7) by combining two genotypic selection methods, MutEx enrichment and allele-specific competitive blocker PCR SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE MutS; MutEx; ACB-PCR; mutation detection; H-ras; genotypic selection ID POLYMERASE CHAIN-REACTION; ETHYL-N-NITROSOUREA; HUMAN MITOCHONDRIAL-DNA; TUMOR-SUPPRESSOR GENE; RAS PROTOONCOGENE; TRANSGENIC MICE; HETERODUPLEX DNA; POINT MUTATIONS; LIVER-TUMORS; GENOMIC DNA AB The detection of rare mutations has many important applications, including risk assessment of drugs and chemicals, measuring environmental exposures to genotoxins, and cancer cell detection. A sensitive genotypic selection method has been developed that combines two different mutant allele selection techniques, MutEx enrichment and allele-specific competitive blocker PCR (ACB-PCR). This method was developed and evaluated for the detection of a CAA --> AAA mutation at codon 61 of the mouse H-ras gene. The MutEx enrichment is based on MutS binding to a mismatched basepair in heteroduplex DNA. The bound MutS protects the mutant allele from degradation during subsequent exonuclease treatment. ACB-PCR preferentially amplifies a mutant allele in a PCR reaction using a primer that has more mismatches to the wild-type allele than the mutant allele. By combining these two approaches, the codon 61 mutation was detected at mutant fractions as low as 1 in 10(7). This sensitivity was achieved with the thermostable Thermus aquaticus MutS protein but not the Escherichia coli MutS protein. Using the combined approach, the average Pfu DNA polymerase error rate +/- the standard error of the mean for this particular basepair was estimated to be 8 +/- 3 x 10(-7) errors per duplication. The results indicate that MutEx/ACB-PCR is among the most sensitive genotypic selection methods For the detection of mutation. Environ. Mol. Mutagen. 32:200-211, 1998 (C) 1998 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Genet & Reprod toxicol, Jefferson, AR 72079 USA. RP Parsons, BL (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 42 TC 22 Z9 22 U1 0 U2 6 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 1998 VL 32 IS 3 BP 200 EP 211 DI 10.1002/(SICI)1098-2280(1998)32:3<200::AID-EM2>3.0.CO;2-O PG 12 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 136CF UT WOS:000076839900002 PM 9814434 ER PT J AU Chen, JB Dass, SB Burkhart, JG Heflich, RH AF Chen, JB Dass, SB Burkhart, JG Heflich, RH TI Sensitivity of the phi X174 am3 allele in relation to the endogenous Hprt gene for detecting mutation in transgenic mice SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE phi X174; transgene; spleen lymphocytes; Hprt; N-ethyl-N-nitrosourea ID ETHYL-N-NITROSOUREA; ESCHERICHIA-COLI; SHUTTLE VECTORS; T-CELLS; INVIVO; MUTAGENESIS; LYMPHOCYTES; LOCUS; METHYLATION; FREQUENCY AB Transgenic mice have been developed containing multiple, chromosomally integrated copies of the Phi X174 am3 allele that serve as reporters for in vivo mutation at a single A:T basepair. In this study, we examined the relative sensitivity of the am3 transgene For detecting the in vivo mutagenicity of N-ethyl-N-nitrosourea (ENU). Three-week-old male Phi X174 mice were treated with 0, 40, and 160 mg/kg of ENU. After 1, 3, 6, and 9 weeks, animals were killed, their spleens removed, and isolated splenocytes were used to measure mutant frequencies (MFs) in both the am3 allele and the endogenous Hprt gene. For animals treated with 40 mg/kg of ENU, the Hprt assay detected an average 22-fold increase over background, while the am3 MFs averaged threefold above background. With the 160 mg/kg dose, the Hprt assay detected a 54-fold average increase, while a sixfold average increase above background was found for the transgenic locus. We conclude that the sensitivity of the am3 assay to ENU was compromised by the presence of ex vivo mutations. Adjustment of am3 MFs to exclude these ex vivo mutants could enhance the sensitivity of the assay. Environ. Mol. Mutagen. 32:229-235, 1998 (C) 1998 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NIEHS, Res Triangle Pk, NC 27709 USA. RP Chen, JB (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120, Jefferson, AR 72079 USA. EM JBChen@NCTR.FDA.GOV NR 24 TC 2 Z9 2 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 1998 VL 32 IS 3 BP 229 EP 235 PG 7 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 136CF UT WOS:000076839900005 PM 9814437 ER PT J AU Meng, QX Skopek, TR Walker, DM Hurley-Leslie, S Chen, T Zimmer, DM Walker, VE AF Meng, QX Skopek, TR Walker, DM Hurley-Leslie, S Chen, T Zimmer, DM Walker, VE TI Culture and propagation of Hprt mutant T-lymphocytes isolated from mouse spleen SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE cloning efficiency; concanavalin A; Hprt; lymphocytes; mouse; propagation ID BLUE(TM) B6C3F1 MICE; LACI TRANSGENIC MICE; ETHYL-N-NITROSOUREA; IN-VIVO MUTATION; PHORBOL ESTER; CALCIUM IONOPHORE; INTERLEUKIN-2 RECEPTOR; INHALATION EXPOSURE; CLONING ASSAY; CELLS AB The optimization of the mouse lymphocyte Hprt mutation assay has been impeded by the relatively poor growth potential of mouse T-cells in vitro, which leads to low cloning efficiencies (CEs) and limited expansion of Hprt mutant clones for molecular analysis of mutations occurring in control and treated mice. In this study, the addition and manipulation of concanavalin A (Con A), mouse interleukin-2 (IL-2), and a commercially available culture supplement, rat T-STIM(TM) with Con A, were used to identify growth conditions producing relatively high CEs for mouse T-cells. Supplementation of medium with 10% rat T-STIM(TM), along with appropriate amounts of Con A for priming and exogenous IL-2 for cloning, resulted in average CEs of 15-16% in lymphocytes isolated From spleens of control mice (n = 32) or mice exposed to 1,3-butadiene (n = 27). In addition, several reagents were assessed for their potential to stimulate long-term growth of Hprt mutant clones; these T-cell stimulatory agents included Con A, phytohemagglutinin, and a calcium ionophore ionomycin combined with a tumor promoter phorbol 12-myristate 13-acetate. In a pilot study, stimulation with Con A proved to be the most effective means for propagating mouse T-cell clones under the various conditions tested. In follow-up experiments, transfer of mutant clones to 24-well plates and repeated stimulation with Con A in IL-2 and rat T-STIM(TM) supplemented medium was found to expand 76% of 536 mutant clones to about 400,000 to several million cells per clone. These data indicate that rat T-STIM(TM)-supplemented medium enhances the initial outgrowth of mouse T-cells, and that repeated mitogenic stimulation with Con A in the presence of IL-2 and rat T-STIM(TM) provides a means For propagating mouse T-cell clones for mutation analyses by a variety of methods. Environ. Mol. Mutagen. 32:236-243, 1998 (C) 1998 Wiley-Liss, Inc. C1 New York State Dept Hlth, Wadsworth Ctr, Lab Human Toxicol & Mol Epidemiol, Albany, NY 12201 USA. SUNY Albany, Sch Publ Hlth, Albany, NY USA. Merck Res Labs, W Point, PA USA. Natl Ctr Toxicol Res, Div Genet Toxicol, Jefferson, AR 72079 USA. Pharmacia & Upjohn Inc, Kalamazoo, MI 49001 USA. RP Walker, VE (reprint author), New York State Dept Hlth, Wadsworth Ctr, Lab Human Toxicol & Mol Epidemiol, POB 509, Albany, NY 12201 USA. EM walker@wadsworth.org FU NICHD NIH HHS [1R01 HD/CA33648-01A1] NR 41 TC 40 Z9 42 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 1998 VL 32 IS 3 BP 236 EP 243 DI 10.1002/(SICI)1098-2280(1998)32:3<236::AID-EM6>3.0.CO;2-Y PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 136CF UT WOS:000076839900006 PM 9814438 ER PT J AU Bishop, ME Aidoo, A Domon, OE Morris, SM Casciano, DA AF Bishop, ME Aidoo, A Domon, OE Morris, SM Casciano, DA TI Phenolphthalein induces micronuclei in transgenic human lymphoblastoid cells SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE phenolphthalein; MCL-5; AHH-1; TK+/-; micronuclei; human lymphoblastoid cells; Hprt; Tk ID IN-VITRO; MUTATION; ASSAY; LINE; METABOLISM; COMPETENT; INDUCTION; MUTAGENS; AHH-1; MICE C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Pharmacol & Toxicol, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. RP Bishop, ME (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. EM mbishop@nctr.fda.gov NR 22 TC 5 Z9 5 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 1998 VL 32 IS 3 BP 286 EP 288 DI 10.1002/(SICI)1098-2280(1998)32:3<286::AID-EM12>3.0.CO;2-9 PG 3 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA 136CF UT WOS:000076839900012 PM 9814444 ER PT J AU Schwetz, BA Casciano, DA AF Schwetz, BA Casciano, DA TI Genetic toxicology: Impact on the next generation of toxicology SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Editorial Material ID CARCINOGENS; CHEMICALS; MUTAGENS; ASSAYS C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. RP Schwetz, BA (reprint author), US FDA, Natl Ctr Toxicol Res, HFT-1,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 18 TC 6 Z9 6 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 1998 VL 31 IS 1 BP 1 EP 3 DI 10.1002/(SICI)1098-2280(1998)31:1<1::AID-EM1>3.0.CO;2-R PG 3 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA YU869 UT WOS:000071764200001 PM 9464309 ER PT J AU Zhan, DJ Chiu, LH Heflich, RH Fu, PP AF Zhan, DJ Chiu, LH Heflich, RH Fu, PP TI Molecular characterization of hprt mutations from Chinese hamster ovary cells treated with 1-, 3-, and 6-nitrosobenzo[a]pyrene SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE nitrobenzo[a]pyrene; nitrosobenzo[a]pyrene; Chinese hamster ovary cells; hprt gene; mutation; polymerase chain reaction; DNA sequencing ID POLYCYCLIC AROMATIC-HYDROCARBONS; DNA ADDUCT FORMATION; 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE PHIP; MICROSOMAL METABOLISM; SEQUENCE-ANALYSIS; INVITRO REACTION; RAT HEPATOCYTES; MAJOR ADDUCT; MUTAGENICITY; 3-NITROBENZOPYRENE AB 1-, 3-, and 6-Nitrobenzo[a] pyrene (nitro-BaP) are environmental contaminants that can be metabolized to genotoxic derivatives by either nitroreduction or ring-oxidation. In this study, we examined the types of mutations produced by the primary nitroreduced metabolites, 1-, 3-, and 6-nitroso-BaP (NO-BaP) in the hprt gene of Chinese hamster ovary cells. RNA from 6-thioguanine-resistant mutants was reverse-transcribed to cDNA and the hprt coding sequence was amplified and sequenced. The mutational patterns produced by the three compounds exhibited extensive similarities: 1) bose pair substitutions accounted for 67% (28/42) of 1-NO-BaP, 51% (26/51) of 3-NO-BaP, and 50% (11/22) of 6-NO-BaP mutations; 19-36% of the mutations were exon deletions and 14-18% were frameshifts; 2) most (64-84%) of the simple base pair substitutions occurred at G:C, mainly G:C --> T:A and G:C --> C:G transversions; 3) 98% (46/47) of the simple base pair substitutions at G:C had the mutated dG on the non-transcribed strand and 81% (38/47) were located with the mutated dG flanked 3' by at least one purine; and 4) most simple base pair substitutions (48/62, 77%) occurred in exons 2, 3, and 8 of the hprt gene. Although there were no significant differences among the mutation profiles of the NO-BaPs, a significant difference did exist between the mutation pattern produced by 3-NO-BaP and the mutation pattern previously determined for the ring-oxidized product of 3-nitro-BaP metabolism, trans-7,8-dihydroxy-anti-9,10-epoxy-7,8,9,10-tetrahydro-3-nitrobenzo[a] pyrene. This observation indicates that differences in the structures of closely related adducts con be important enough to have an effect on mutation profiles. (C) 1998 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. Guangzhou Med Coll, Inst Chem Carcinogenesis, Guangzhou, Peoples R China. Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Fu, PP (reprint author), Natl Ctr Toxicol Res, Div Biochem Toxicol, Jefferson, AR 72079 USA. NR 52 TC 0 Z9 0 U1 1 U2 3 PU WILEY-LISS PI NEW YORK PA DIV JOHN WILEY & SONS INC, 605 THIRD AVE, NEW YORK, NY 10158-0012 USA SN 0893-6692 J9 ENVIRON MOL MUTAGEN JI Environ. Mol. Mutagen. PY 1998 VL 31 IS 1 BP 60 EP 69 DI 10.1002/(SICI)1098-2280(1998)31:1<60::AID-EM9>3.0.CO;2-F PG 10 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA YU869 UT WOS:000071764200009 PM 9464317 ER PT J AU Chen, T Aidoo, A Casciano, DA Heflich, RH AF Chen, T Aidoo, A Casciano, DA Heflich, RH TI Expansion of rat 6-thioguanine-resistant T-lymphocyte clones by stimulation with ionomycin and a phorbol ester SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE hprt; interleukin 2; phorbol 12-myristate 13-acetate; mutation analysis; lymphocyte clone expansion ID ETHYL-N-NITROSOUREA; IN-VIVO MUTATION; CALCIUM IONOPHORE; INTERLEUKIN-2 RECEPTOR; FISCHER-344 RATS; ANTIGEN RECEPTOR; CELL CLONES; HPRT LOCUS; ACTIVATION; INDUCTION AB Previous molecular analyses of the mutations produced in the rat lymphocyte hprt assay were hindered by difficulties encountered in growing mutant lymphocytes from 6-thioguanine-resistant clones. In this study, we evaluated the ability of the calcium ionophore, ionomycin, and the tumor promotor, phorbol 12-myristate 13-acetate, to stimulate clone expansion. A medium containing these two agents, along with mitogen-free conditioned medium, was found to expand 64% of 276 mutant clones to at least 5 x 10(5) cells in nine days of culture. Some clones were expanded to more than 4 x 10(6) cells. The procedure appears suitable for propagating rat lymphocyte clones for mutation analysis. (C) 1998 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Interdisciplinary Toxicol Program, Little Rock, AR 72205 USA. RP Chen, T (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT-120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 35 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 1998 VL 31 IS 1 BP 97 EP 102 DI 10.1002/(SICI)1098-2280(1998)31:1<97::AID-EM13>3.0.CO;2-K PG 6 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA YU869 UT WOS:000071764200013 PM 9464321 ER PT J AU Mittelstaedt, RA Manjanatha, MG Shelton, SD Lyn-Cook, LE Chen, JB Aidoo, A Casciano, DA Heflich, RH AF Mittelstaedt, RA Manjanatha, MG Shelton, SD Lyn-Cook, LE Chen, JB Aidoo, A Casciano, DA Heflich, RH TI Comparison of the types of mutations induced by 7,12-dimethylbenz[a]anthracene in the lacl and hprt genes of Big Blue (R) rats SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE Fischer 344 rat; denaturing gradient gel electrophoresis; DNA sequencing; DNA heteroduplex; lambda shuttle vector ID ETHYL-N-NITROSOUREA; TRANSGENIC ANIMAL-MODELS; IN-VIVO MUTATION; MUTANT FREQUENCY; MAMMARY CARCINOGENESIS; FISCHER-344 RATS; LYMPHOCYTES; MICE; SPECTRA; EXPOSURE AB An important question regarding the use of transgenic reporter genes to detect mutation in rodents is how the types of mutations recovered in transgenes compare with the types of mutations found in endogenous genes. In this study, we examined mutations induced by 7,12-dimethylbenz[a]anthracene in the loci transgene and the endogenous hprt gene of lymphocytes From Big Blue(R) rats and in the hprt gene of lymphocytes from nontransgenic Fischer 344 rats. The overall mutation profiles found in these genes were remarkably similar: the majority of mutations were base pair substitutions, with the most common mutation being A:T --> T:A transversion. Differences were found for the mutational profiles in the endogenous gene and transgene with respect to the location of the mutations and the orientation of basepair substitutions in the DNA strands. In most cases, these differences could be explained by the nature of the target genes. The results support the use of the loci transgene for detecting in vivo mutation. (C) 1998 Wiley-Liss, Inc.* C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Mittelstaedt, RA (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, HFT 120,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 26 TC 25 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 1998 VL 31 IS 2 BP 149 EP 156 DI 10.1002/(SICI)1098-2280(1998)31:2<149::AID-EM6>3.0.CO;2-H PG 8 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA ZE676 UT WOS:000072818900006 PM 9544192 ER PT J AU Dass, SB Heflich, RH Casciano, DA AF Dass, SB Heflich, RH Casciano, DA TI Mutational response at the splenic T-lymphocyte hprt locus in mice treated as neonates: Contrasting effects of the carcinogens N-ethyl-N-nitrosourea, dimethylnitrosamine, and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE neonatal mice; hprt; T-lymphocyte mutation; N-ethyl-N-nitrosourea; dimethylnitrosamine; 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine ID TRANSGENIC MICE; IN-VIVO; FISCHER-344 RATS; INVIVO EXPOSURE; FOOD MUTAGENS; MOUSE MODEL; BONE-MARROW; INDUCTION; FREQUENCY; ETHYLNITROSOUREA AB The newborn mouse tumorigenicity assay, which involves the treatment of animals during the first two weeks after birth and monitoring tumor induction after a year, has been suggested as a cost- and time-effective alternative to the conventional two year rodent bioassay. In order to evaluate whether or not lymphocyte hprt mutant induction is an accurate predictor of carcinogenicity in the assay, we determined the frequencies of 6-thioguanine-resistant (TG(r)) lymphocytes in the spleens of mice neonatally treated with the carcinogenic mutagens N-ethyl-N-nitrosourea (ENU), dimethylnitrosamine (DMN), and 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP). Male C57BL/6 pups were injected on postnatal days 8 and 15, and the frequency of TG(r) T-lymphocytes was measured in groups of three animals, sacrificed periodically up to 31 weeks post-treatment. Compared to background frequencies of 1.1-2.9 x 10(-6), mutant frequencies (MFS) reached 155.1 x 10(-6) following a cumulative dose of 49 mg ENU/kg body weight and 172.3 x 10(-6) following a cumulative dose of 142 mg ENU/kg. These results show that TG(r) lymphocyte mutations can be induced and measured in mice treated as neonates and that the induced MFs found for mice treated neonatally with ENU are comparable with frequencies reported For the treatment of adult animals with the some chemical. In contrast, treatment with the promutagenic and procarcinogenic compounds DMN (at a maximum concentration of 10.5 mg/kg) and PhlP (26.2 mg/kg) did not result in on increase in lymphocyte MF, suggesting that reactive metabolites of these compounds may not be reaching cells that are sensitive for mutation fixation. The results indicate that the lymphocyte hprt assay may fail to predict the carcinogenicity of some test chemicals in the neonatal mouse bioassay. (C) 1998 Wiley-Liss, Inc. C1 Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. RP Dass, SB (reprint author), Natl Ctr Toxicol Res, Div Genet & Reprod Toxicol, Jefferson, AR 72079 USA. NR 35 TC 5 Z9 5 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 1998 VL 31 IS 3 BP 243 EP 247 DI 10.1002/(SICI)1098-2280(1998)31:3<243::AID-EM5>3.0.CO;2-L PG 5 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA ZL138 UT WOS:000073402600005 PM 9585262 ER PT J AU Koch, WH Wu, RW Cebula, TA Felton, JS AF Koch, WH Wu, RW Cebula, TA Felton, JS TI Specificity of base substitution mutations induced by the dietary carcinogens 5-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhlP) and 2-amino-3-methylimidazo[4,5-f]quinoline (IQ) in Salmonella SO ENVIRONMENTAL AND MOLECULAR MUTAGENESIS LA English DT Article DE heterocyclic amines (HAs); 2-amino-1-methy-6-phenylimidazo[4,5-b]pyridine (PhlP); 2-amino-3-methylimidazo[4,5-f]quinoline (IQ); cooked food mutagens; carcinogens; Salmonella; base substitutions; mutation specificity ID FOOD MUTAGEN 2-AMINO-1-METHYL-6-PHENYLIMIDAZO<4,5-B>PYRIDINE; HETEROCYCLIC AMINES; COOKED-FOOD; NONHUMAN-PRIMATES; HEPATOCELLULAR-CARCINOMA; GENE-MUTATIONS; DNA-ADDUCTS; HA-RAS; IDENTIFICATION; TYPHIMURIUM AB The base pair substitution mutational profiles induced by the heterocyclic amine cooked Food mutagens PhlP and IQ in Salmonella typhimurium strains TA100 and TA1535 were determined by colony hybridizaiion analysis. Both PhlP and IQ induced predominantly GC-->TA transversions in strain TA100 (rfa,Delta uvrB/pKM101) with a pronounced preference for the second codon position (CCC-->CAC; 72% of total). PhlP also reverted strain TA1535 (rfa, Delta uvrB) efficiently at concentrations similar to those required for strain TA100. In contrast to the PhlP-induced mutational profile observed in strain TA100, in strain TA1535 PhlP induced exclusively GC-->AT transitions at the second codon position (CCC-->CTC; 96-99% of total). Base substitution mutagenesis induced by heterocyclic amines related to PhlP is generally SOS-dependent, requiring the presence of plasmid pKM101 in Salmonella hisG46 strains. Thus, the SOS dependent reversion of S. typhimurium strain TA100 probably reflects error-prone lesion bypass at the major PhlP-guanosine adduct at the C-8 position. The GC-->AT transition mutations induced by PhlP in strain TA1535 appear to be SOS-independent, however, suggesiing that these mutations may arise from the formation of PhlP-DNA adducts other than the replication-blocking C8-dG lesion. (C) 1998 Wiley-Liss, Inc. C1 US FDA, CBER, Div Transfus Transmitted Dis, Mol Biol Branch, Rockville, MD 20852 USA. Univ Calif Lawrence Livermore Natl Lab, Biol & Biotechnol Res Program, Livermore, CA USA. RP Koch, WH (reprint author), US FDA, CBER, Div Transfus Transmitted Dis, Mol Biol Branch, 1401 Rockville Pike,HFM 320, Rockville, MD 20852 USA. FU NCI NIH HHS [CA55861] NR 50 TC 8 Z9 8 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 1998 VL 31 IS 4 BP 327 EP 332 DI 10.1002/(SICI)1098-2280(1998)31:4<327::AID-EM4>3.0.CO;2-F PG 6 WC Environmental Sciences; Genetics & Heredity; Toxicology SC Environmental Sciences & Ecology; Genetics & Heredity; Toxicology GA ZW001 UT WOS:000074363600004 PM 9654241 ER PT J AU Hayward, D AF Hayward, D TI Identification of bioaccumulating polychlorinated naphthalenes and their toxicological significance SO ENVIRONMENTAL RESEARCH LA English DT Review ID CABLE MANUFACTURING PLANT; SWEDISH DIOXIN SURVEY; WORLD-WAR-II; CHLORINATED NAPHTHALENES; ENVIRONMENTAL-SAMPLES; MASS-SPECTROMETRY; CANCER MORTALITY; BIPHENYLS; HEXACHLORONAPHTHALENE; CHROMATOGRAPHY C1 US FDA, Washington, DC 20204 USA. RP Hayward, D (reprint author), US FDA, 200 C St SW, Washington, DC 20204 USA. NR 123 TC 62 Z9 63 U1 1 U2 14 PU ACADEMIC PRESS INC PI SAN DIEGO PA 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 USA SN 0013-9351 J9 ENVIRON RES JI Environ. Res. PD JAN PY 1998 VL 76 IS 1 BP 1 EP 18 DI 10.1006/enrs.1997.3777 PG 18 WC Environmental Sciences; Public, Environmental & Occupational Health SC Environmental Sciences & Ecology; Public, Environmental & Occupational Health GA YV941 UT WOS:000071879800001 PM 9466892 ER PT J AU Hart, RW Turturro, A AF Hart, RW Turturro, A TI Evolution and dietary restriction SO EXPERIMENTAL GERONTOLOGY LA English DT Article DE dietary restriction; evolution; gerontology ID CHRONIC CALORIC RESTRICTION; DNA-DAMAGE; MICE; RODENTS; REPAIR; MECHANISMS AB Placing lifespan in the context of the life history of an organism, Alex Comfort's work has stimulated the analysis of dietary restriction (DR) and its effects on lifespan in an evolutionary context. DR results in the curtailment of energy-intensive nonfood-gathering activities, increased efficiency of food utilization, an increase in food acquisition activity, an increase in the reproductive lifespan, and an increase in the protection of genomic integrity. These result in further refinement of the Adaptive-Longevity Related Process Theory of the effects of dietary modulation to include increased protection of the genomic integrity of cells that result from delayed reproduction, and increased ability to compete for available food. These effects are discussed in the context of the "spacecraft" metaphor for the evolution of senescence. Also, the apparent paradox that increased body weight seems to be directly correlated to survival across species and inversely correlated to survival within a species is discussed in light of the importance of the cephalization index (a modified ratio of brain weight to body weight) for longevity. Published by Elsevier Science Inc. C1 Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, Jefferson, AR 72079 USA. RP Hart, RW (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 35 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 0531-5565 J9 EXP GERONTOL JI Exp. Gerontol. PD JAN-MAR PY 1998 VL 33 IS 1-2 BP 53 EP 60 DI 10.1016/S0531-5565(97)00063-6 PG 8 WC Geriatrics & Gerontology SC Geriatrics & Gerontology GA YN224 UT WOS:000071145500007 PM 9467716 ER PT J AU Friedman, MA AF Friedman, MA TI Remarks of the lead deputy commissioner of the food and drug administration SO FOOD AND DRUG LAW JOURNAL LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Friedman, MA (reprint author), US FDA, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1998 VL 53 IS 1 BP 19 EP 23 PG 5 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA ZF228 UT WOS:000072876500005 PM 11795333 ER PT J AU Horton, LR AF Horton, LR TI Food from developing countries: Steps to improve compliance SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Rockville, MD 20857 USA. RP Horton, LR (reprint author), US FDA, Rockville, MD 20857 USA. NR 33 TC 6 Z9 6 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1998 VL 53 IS 1 BP 139 EP 171 PG 33 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA ZF228 UT WOS:000072876500014 PM 11795330 ER PT J AU Shroff, AP Sheehan, SM AF Shroff, AP Sheehan, SM TI FDA's efforts to improve access to agency records SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Off Enforcement, Off Regulatory Affairs, Rockville, MD 20857 USA. US FDA, Off Enforcement, Div Compliance Policy, Rockville, MD 20857 USA. RP Shroff, AP (reprint author), US FDA, Off Enforcement, Off Regulatory Affairs, Rockville, MD 20857 USA. NR 3 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 J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1998 VL 53 IS 2 BP 321 EP 326 PG 6 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA ZW036 UT WOS:000074367200007 PM 10346687 ER PT J AU Friede, AI AF Friede, AI TI Dietary supplements: Background for dialogue between the industry and the medical profession SO FOOD AND DRUG LAW JOURNAL LA English DT Article ID EDUCATION ACT; HEALTH C1 US FDA, Rockville, MD 20857 USA. NR 18 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 J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1998 VL 53 IS 3 BP 413 EP 420 PG 8 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 126CY UT WOS:000076276400003 PM 10346719 ER PT J AU Whetstone, SN AF Whetstone, SN TI ORA's role at FDA headquarters and in the field for product recalls SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Div Compliance Management & Operat, Off Enforcement, Off Regulatory Affairs, Rockville, MD 20857 USA. RP Whetstone, SN (reprint author), US FDA, Div Compliance Management & Operat, Off Enforcement, Off Regulatory Affairs, Rockville, MD 20857 USA. NR 3 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 J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1998 VL 53 IS 3 BP 513 EP 516 PG 4 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 126CY UT WOS:000076276400007 PM 10346723 ER PT J AU Horton, LR Hastings, KE AF Horton, LR Hastings, KE TI A plan that establishes a framework for achieving mutual recognition of good manufacturing practices inspections SO FOOD AND DRUG LAW JOURNAL LA English DT Article C1 US FDA, Off Policy, Rockville, MD 20857 USA. RP Horton, LR (reprint author), US FDA, Off Policy, Rockville, MD 20857 USA. NR 8 TC 4 Z9 4 U1 0 U2 0 PU FOOD DRUG LAW INST PI WASHINGTON PA 1000 VERMONT AVE NW, SUITE 1200, WASHINGTON, DC 20005-4903 USA J9 FOOD DRUG LAW J JI Food Drug Law J. PY 1998 VL 53 IS 3 BP 527 EP 535 PG 9 WC Food Science & Technology; Law; Nutrition & Dietetics; Pharmacology & Pharmacy SC Food Science & Technology; Government & Law; Nutrition & Dietetics; Pharmacology & Pharmacy GA 126CY UT WOS:000076276400009 PM 10346725 ER PT J AU Gendel, SM AF Gendel, SM TI Assessing the potential allergenicity of new food proteins SO FOOD BIOTECHNOLOGY LA English DT Article ID PLANTS AB Assessing the potential allergenicity of transferred proteins remains one of the most difficult aspects of the overall safety assessment for transgenic foods. Allergenicity assessment must consider several factors, including the source of the transferred protein, expression levels, the physical and chemical properties of the protein, and similarity to known allergens. Although no single factor can be considered definitive, consideration of all these factors together may provide some indication of potential allergenicity. C1 US FDA, Biotechnol Studies Branch, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Gendel, SM (reprint author), US FDA, Biotechnol Studies Branch, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. NR 15 TC 2 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0890-5436 J9 FOOD BIOTECHNOL JI Food Biotechnol. PY 1998 VL 12 IS 3 BP 175 EP 185 PG 11 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA 143LU UT WOS:000077257800001 ER PT S AU Kindig, JP Ellis, LE Brueggemeyer, TW Satzger, RD AF Kindig, JP Ellis, LE Brueggemeyer, TW Satzger, RD BE deHaseth, JA TI GHB: Forensic examination of a dangerous recreational drug by FTIR spectroscopy SO FOURIER TRANSFORM SPECTROSCOPY SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 11th International Conference on Fourier Transform Spectroscopy (ICOFTS 11) CY AUG 10-15, 1997 CL ATHENS, GA AB Gamma-hydroxybutyric acid (GHB) is an illegal drug that has been abused for its intoxicating effects. However, GHB can also produce harmful physiological effects ranging from mild (nausea, drowsiness) to severe (coma, death). Because GHB is often produced by clandestine manufacture,:ts concentration, purity, and final form can be variable. Therefore, the analysis of suspected GHB samples using FTIR spectroscopy requires a variety of sample preparations and accessories, based on the sample matrix. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45202 USA. RP Kindig, JP (reprint author), US FDA, Forens Chem Ctr, 1141 Cent Pkwy, Cincinnati, OH 45202 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 1-56396-746-4 J9 AIP CONF PROC PY 1998 IS 430 BP 449 EP 452 DI 10.1063/1.55775 PG 4 WC Chemistry, Analytical; Chemistry, Physical; Instruments & Instrumentation; Polymer Science; Spectroscopy SC Chemistry; Instruments & Instrumentation; Polymer Science; Spectroscopy GA BL29A UT WOS:000075012400081 ER PT S AU Machal, AC Flurer, RA Brueggemeyer, TW Ellis, LE Satzger, RD Stewart, KR AF Machal, AC Flurer, RA Brueggemeyer, TW Ellis, LE Satzger, RD Stewart, KR BE deHaseth, JA TI RIBAVIRIN: The analysis of a polymorphic substance by LC-MS and FTIR spectroscopy SO FOURIER TRANSFORM SPECTROSCOPY SE AIP CONFERENCE PROCEEDINGS LA English DT Proceedings Paper CT 11th International Conference on Fourier Transform Spectroscopy (ICOFTS 11) CY AUG 10-15, 1997 CL ATHENS, GA AB The FTIR laboratory often has the task of identifying unknown pharmaceuticals. This case involves unknown capsules received at the Forensic Chemistry Canter. Through extensive searching of pharmaceutical data bases, it was concluded that the capsules might contain ribavirin, which is classified as an anti-viral agent. Mass spectral analysis (LC-MS) concluded that the capsules contained ribavirin; however. the FTIR results did not agree with the mass spectral results. Additional experiments were performed and the results demonstrate the capabilities of FTIR to discern differences between polymorphic forms of a substance, such as ribavirin, when other techniques are unable to provide this information. C1 US FDA, Forens Chem Ctr, Cincinnati, OH 45202 USA. RP Machal, AC (reprint author), US FDA, Forens Chem Ctr, 1141 Cent Pkwy, Cincinnati, OH 45202 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AMER INST PHYSICS PI MELVILLE PA 2 HUNTINGTON QUADRANGLE, STE 1NO1, MELVILLE, NY 11747-4501 USA SN 0094-243X BN 1-56396-746-4 J9 AIP CONF PROC PY 1998 IS 430 BP 453 EP 456 DI 10.1063/1.55776 PG 4 WC Chemistry, Analytical; Chemistry, Physical; Instruments & Instrumentation; Polymer Science; Spectroscopy SC Chemistry; Instruments & Instrumentation; Polymer Science; Spectroscopy GA BL29A UT WOS:000075012400082 ER PT J AU Cross, CE Shacter, E Eiserich, JP van der Vliet, A Tarkington, K Syvanen, M AF Cross, CE Shacter, E Eiserich, JP van der Vliet, A Tarkington, K Syvanen, M TI The ozone-exposed insect: A model system to study pathobiology of biosystem responses to pollutants SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. Univ Calif Davis, Davis, CA 95616 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1998 VL 25 SU 1 MA 283 BP S99 EP S99 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 139VP UT WOS:000077051400304 ER PT J AU D'Agnillo, F Alayash, AI AF D'Agnillo, F Alayash, AI TI Oxidant-induced apoptosis in endothelial cells modulated by glutathione and hemoproteins SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 1 Z9 1 U1 0 U2 2 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1998 VL 25 SU 1 MA 253 BP S89 EP S89 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 139VP UT WOS:000077051400274 ER PT J AU Wamer, W Wei, RR AF Wamer, W Wei, RR TI In vitro assays for photooxidative damage to cellular RNA and DNA: The importance of the method of exposure to the photosensitizer. SO FREE RADICAL BIOLOGY AND MEDICINE LA English DT Meeting Abstract C1 US FDA, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PERGAMON-ELSEVIER SCIENCE LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, ENGLAND SN 0891-5849 J9 FREE RADICAL BIO MED JI Free Radic. Biol. Med. PY 1998 VL 25 SU 1 MA 232 BP S80 EP S80 PG 1 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism SC Biochemistry & Molecular Biology; Endocrinology & Metabolism GA 139VP UT WOS:000077051400251 ER PT J AU Sinclair, DAR Clegg, NJ Antonchuk, J Milne, TA Stankunas, K Ruse, C Grigliatti, TA Kassis, JA Brock, HW AF Sinclair, DAR Clegg, NJ Antonchuk, J Milne, TA Stankunas, K Ruse, C Grigliatti, TA Kassis, JA Brock, HW TI Enhancer of Polycomb is a suppressor of position-effect variegation in Drosophila melanogaster SO GENETICS LA English DT Article ID CHROMOSOME-BINDING-SITES; POSTERIOR SEX COMBS; GENETIC-ANALYSIS; BITHORAX COMPLEX; CHROMATIN PROTEIN; EXPRESSION; MUTATIONS; ZESTE; LOCUS; HETEROCHROMATIN AB Polycomb group (PcG) genes of Drosophila are negative regulators of homeotic gene expression required for maintenance of determination. Sequence similarity between Polycomb and Su(var)205 led to the suggestion that PcG genes and modifiers of position-effect variegation (PEV) might function analogously in the establishment of chromatin structure. If PcG proteins participate directly in the same process that leads to PEV, PcG mutations should suppress PEV. We show that mutations in E(Pc), an unusual member of the PcG, suppress PEV of four variegating rearrangements: In(l)w(m4), B-SV, T(2;3)Sb-V; and In(2R)bw(YDe2). Using reversion of a P element insertion, deficiency mapping, and recombination mapping as criteria, homeotic effects and suppression of PEV associated with E(Pc) co-map. Asx is an enhancer of PEV whereas nine other PcG loci do not affect PEV. These results support the conclusion that there are fewer similarities between PcC genes and modifiers of PEV than previously supposed. However, E(Pc) appears to be an important link between the two groups. We discuss why Asx might act as an enhancer of PEV. C1 Univ British Columbia, Dept Zool, Vancouver, BC V6T 1Z4, Canada. Univ Washington, Dept Biochem, Seattle, WA 98104 USA. Simon Fraser Univ, IMBB, Burnaby, BC V5A 1S6, Canada. US FDA, Dev Biol Lab, CBER, HFM 527, Bethesda, MD 20892 USA. RP Brock, HW (reprint author), Univ British Columbia, Dept Zool, 6270 Univ Blvd, Vancouver, BC V6T 1Z4, Canada. RI Milne, Tom/E-1872-2016; OI Milne, Tom/0000-0002-0413-4271; Kassis, Judith/0000-0001-9268-3213 NR 64 TC 52 Z9 52 U1 0 U2 2 PU GENETICS PI BALTIMORE PA 428 EAST PRESTON ST, BALTIMORE, MD 21202 USA SN 0016-6731 J9 GENETICS JI Genetics PD JAN PY 1998 VL 148 IS 1 BP 211 EP 220 PG 10 WC Genetics & Heredity SC Genetics & Heredity GA YR425 UT WOS:000071494000020 PM 9475733 ER PT J AU Chang, AC Rick, ME Pierce, LR Weinstein, MJ AF Chang, AC Rick, ME Pierce, LR Weinstein, MJ TI Summary of a workshop on potency and dosage of von Willebrand factor concentrates SO HAEMOPHILIA LA English DT Editorial Material DE vWF concentrates; von Willebrand's disease; FVIII; surgery; ristocetin cofactor assay; haemorrhage ID VONWILLEBRAND-FACTOR; FACTOR-VIII; DISEASE; RISTOCETIN; ADHESION C1 US FDA, Ctr Biol Evaluat & Res, Div Hematol, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Blood Applicat, Bethesda, MD 20892 USA. NIH, Hematol Serv, Warren Grant Magnuson Clin Ctr, Bethesda, MD 20892 USA. RP Chang, AC (reprint author), US FDA, Ctr Biol Evaluat & Res, Div Hematol, 8800 Rockville Pike,HFM-340, Bethesda, MD 20892 USA. NR 20 TC 32 Z9 33 U1 0 U2 0 PU BLACKWELL SCIENCE LTD PI OXFORD PA P O BOX 88, OSNEY MEAD, OXFORD OX2 0NE, OXON, ENGLAND SN 1351-8216 J9 HAEMOPHILIA JI Haemophilia PY 1998 VL 4 SU 3 BP 1 EP 6 PG 6 WC Hematology SC Hematology GA 156NX UT WOS:000078008600001 PM 10028311 ER PT J AU Markovic, O Markovic, N AF Markovic, O Markovic, N TI Cell cross-contamination in cell cultures: The silent and neglected danger SO IN VITRO CELLULAR & DEVELOPMENTAL BIOLOGY-ANIMAL LA English DT Review DE cell cross-contamination; cell lines; cell culture; prophylaxis; quality control ID DNA FINGERPRINT ANALYSIS; GENETIC SIGNATURES; LINES; IDENTIFICATION; HELA; CHROMOSOMES; STABILITY; IDENTITY; REGIONS; MARKER AB Cell cross-contamination in cell cultures is a common problem during cell culturing and use. Contamination invalidates research results? compromises the comparison of results between laboratories, reduces reproducibility required in industrial production of cell lines, and may lead to unusable therapeutic products. The problem can be solved by increasing the awareness of its seriousness and by introducing regular quality control of cell cross-contamination in every laboratory where cells are grown and used. C1 BioSciCon Inc, Rockville, MD 20852 USA. US FDA, CDER, DGCDP, Rockville, MD 20857 USA. RP Markovic, O (reprint author), BioSciCon Inc, 259 Congress Ln,602, Rockville, MD 20852 USA. NR 110 TC 62 Z9 67 U1 4 U2 6 PU SOC IN VITRO BIOLOGY PI LARGO PA 9315 LARGO DR WEST, STE 25, LARGO, MD 20774 USA SN 1071-2690 J9 IN VITRO CELL DEV-AN JI In Vitro Cell. Dev. Biol.-Anim. PD JAN PY 1998 VL 34 IS 1 BP 1 EP 8 PG 8 WC Cell Biology; Developmental Biology SC Cell Biology; Developmental Biology GA YV971 UT WOS:000071882800001 PM 9542623 ER PT J AU Allaben, WT Hart, RW AF Allaben, WT Hart, RW TI Nutrition and toxicity modulation: The impact of animal body weight on study outcome SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Editorial Material C1 US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. RP Allaben, WT (reprint author), US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PY 1998 VL 17 SU 2 BP 1 EP 3 PG 3 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 110AY UT WOS:000075358100001 ER PT J AU Leakey, JEA Seng, JE Barnas, CR Baker, VM Hart, RW AF Leakey, JEA Seng, JE Barnas, CR Baker, VM Hart, RW TI A mechanistic basis for the beneficial effects of caloric restriction on longevity and disease: Consequences for the interpretation of rodent toxicity studies SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the American-College-of-Toxicology CY NOV, 1996 CL VALLEY FORGE, PA SP Amer Coll Toxicol DE caloric restriction; glucocorticoids; bioassay; food restriction; aging; toxicity ID ATRIAL-NATRIURETIC-PEPTIDE; GROWTH-FACTOR-I; CORTICOTROPIN-RELEASING FACTOR; CULTURED HIPPOCAMPAL-NEURONS; NITRIC-OXIDE SYNTHASE; SPRAGUE-DAWLEY RATS; STIMULATES CORTICOSTERONE SECRETION; CHRONIC DIETARY RESTRICTION; SOMATOSTATIN MESSENGER-RNA; INHIBIT GLUCOSE-TRANSPORT AB Caloric restriction in rodents has been, repeatedly shown to increase life span. while reducing the severity and retarding the onset of both spontaneous and chemically induced neoplasms. These effects of caloric restriction are associated with a spectrum of biochemical and physiological changes that characterize the organism's adaptation to reduced caloric intake and provide the mechanistic basis for caloric restriction's effect on longevity Here, we review evidence suggesting that the primary adaptation appears to be a rhythmic hypercorticism in the absence of elevated adrenocorticotropin (ACTH) levels. This characteristic hypercorticism evokes a spectrum of responses, including reduced body temperature and increased metabolic efficiency, decreased mitogenic response coupled with increased rates of apoptosis, reduced inflammatory response, reduced oxidative damage to proteins and DNA, reduced reproductive capacity, and altered drug-metabolizing enzyme expression. The net effect of these changes is to (1) decrease growth and metabolism in peripheral tissues to spare energy for central functions, and (2) increase the organism's capacity to withstand stress and chemical toxicity. Thus, caloric restriction research has uncovered an evolutionary mechanism that provides rodents with an adaptive advantage in conditions of fluctuating food supply During periods of abundance, body growth and fecundity are favored over endurance and longevity. Conversely during periods of famine, reproductive performance and growth are sacrificed to ensure survival of individuals to breed in better times. This phenomena can be observed in rodent populations that are used in toxicity testing. Improvements over the last 30 years in animal husbandry and nutrition, coupled with selective breeding for growth and fecundity, have resulted in several strains now exhibiting larger animals with reduced survival and increased incidence of background lesions. The mechanistic data from caloric restriction studies suggest that these large animals will also be more susceptible to chemically induced toxicity. This creates a problem in. comparing tests performed on animals of different weights and comparing data generated today with the historical database. The rational use of caloric restriction to control body weight to within preset guidelines is a possible way of alleviating this problem. C1 Natl Ctr Toxicol Res, Res Off, Jefferson, AR 72079 USA. RP Natl Ctr Toxicol Res, Res Off, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 301 TC 13 Z9 14 U1 1 U2 6 PU SAGE PUBLICATIONS INC PI THOUSAND OAKS PA 2455 TELLER RD, THOUSAND OAKS, CA 91320 USA SN 1091-5818 EI 1092-874X J9 INT J TOXICOL JI Int. J. Toxicol. PY 1998 VL 17 SU 2 BP 5 EP 56 PG 52 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 110AY UT WOS:000075358100002 ER PT J AU Turturro, A Hass, B Hart, R Allaben, WT AF Turturro, A Hass, B Hart, R Allaben, WT TI Body weight impact on spontaneous diseases in chronic bioassays SO INTERNATIONAL JOURNAL OF TOXICOLOGY LA English DT Article; Proceedings Paper CT 17th Annual Meeting of the American-College-of-Toxicology CY NOV, 1996 CL VALLEY FORGE, PENNSYLVANIA SP Amer Coll Toxicol DE body weight; dietary restriction; NTP bioassays; nutrition; spontaneous tumorigenesis; test variability; tumor incidence variability ID B6C3F1 MICE; DIETARY RESTRICTION; FISCHER-344 RATS; TUMOR-INCIDENCE; F344 RATS; SURVIVAL; CARCINOGENICITY; VARIABILITY; GROWTH; TRENDS AB Tests to evaluate toxicity should be consistent and reproducible. These crucial elements have been, brought into question because the controls of near-replicate experiments have significant variability in parameters such as survival and common tumor incidences critical to safety evaluation even in some of the best controlled assays, those conducted by the National Toxicology Program (NTP). To minimize the impact of these variabilities, dietary control (DC), the control of body weight (BW) growth by nutritionally adequate dietary manipulation, has been suggested for chronic studies. The target BW growth curve for the DC should be fast enough to allow the animal to develop tumors but slow enough to prevent too great a tumor load in controls. In order to better define these targets in Fischer 344 rats, relationships have been developed between various BWs at different times-on-test, incidences of common tumors in control animals from NTP bioassays initiated from January 1981 and reported by June 1996, as well as survival, with the adjustments for different study types used in the chronic assays. These rat studies were complemented by using a set of similar studies in B6C3F1 mice that appear to have "restricted-like" properties. Data from the experiments using dietary restriction (DR) appeared to be better explained using data derived from these experiments rather than from studies with normal BW growth curves. When. the DR data are combined with these "restricted-like" experimental results, the capacity to predict the consequences of DC for tumor incidences is improved. 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. Natl Ctr Toxicol Res, Off Director, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, Natl Toxicol Program, Jefferson, AR 72079 USA. RP Turturro, A (reprint author), Natl Ctr Toxicol Res, Div Biometry & Risk Assessment, HFT-20,3900 NCTR Rd, Jefferson, AR 72079 USA. NR 25 TC 8 Z9 8 U1 0 U2 0 PU TAYLOR & FRANCIS LTD PI LONDON PA ONE GUNPOWDER SQUARE, LONDON EC4A 3DE, ENGLAND SN 1091-5818 J9 INT J TOXICOL JI Int. J. Toxicol. PY 1998 VL 17 SU 2 BP 79 EP 99 PG 21 WC Pharmacology & Pharmacy; Toxicology SC Pharmacology & Pharmacy; Toxicology GA 110AY UT WOS:000075358100004 ER PT J AU Huang, XZ Tall, B Schwan, W Kopecko, DJ AF Huang, XZ Tall, B Schwan, W Kopecko, DJ TI Salmonella typhi entry into intestinal epithelial cells SO JAPANESE JOURNAL OF MEDICAL SCIENCE & BIOLOGY LA English DT Editorial Material C1 US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. RP Huang, XZ (reprint author), US FDA, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NR 0 TC 2 Z9 2 U1 0 U2 0 PU NATL INST INFECTIOUS DISEASES PI TOKYO PA C/O JPN J MED SCI BIOL, TOYAMA 1-23-1, SHINJUKU-KU, TOKYO, 162, JAPAN SN 0021-5112 J9 JPN J MED SCI BIOL JI Jpn. J. Med. Sci. Biol. PY 1998 VL 51 SU 1 BP S90 EP S90 PG 1 WC Medicine, General & Internal SC General & Internal Medicine GA 150QC UT WOS:000077675500010 PM 10211440 ER PT J AU Haverkos, HW AF Haverkos, HW TI HIV/AIDS and drug abuse: Epidemiology and prevention SO JOURNAL OF ADDICTIVE DISEASES LA English DT Article ID OUT-OF-TREATMENT; HIV-INFECTION; COCAINE USE; METHADONE; AIDS; SEROCONVERSION AB In the United States, the AIDS epidemic is a dynamic process with increasing rates of AIDS reported among women, minority populations, heterosexual men, and users of drugs by routes other than injection. The 1993 CDC AIDS definition change has created some difficulties in interpreting trends in the United States. Drug use continues to represent a significant problem among HIV-infected persons. Several strategies have been advanced to decrease transmission of HIV among drug, users, their sexual partners and children. However, more effective and comprehensive prevention and treatment strategies are needed. C1 Natl Inst Drug Abuse, Intramural Res Program, NIH, Rockville, MD USA. RP Haverkos, HW (reprint author), US FDA, HFD 530,5600 Fishers Lane, Rockville, MD 20857 USA. NR 37 TC 14 Z9 14 U1 2 U2 2 PU HAWORTH PRESS INC PI BINGHAMTON PA 10 ALICE ST, BINGHAMTON, NY 13904-1580 USA SN 1055-0887 J9 J ADDICT DIS JI J. Addict. Dis. PY 1998 VL 17 IS 4 BP 91 EP 103 PG 13 WC Substance Abuse SC Substance Abuse GA 142FP UT WOS:000077189700008 PM 9848034 ER PT J AU Akasawa, A Tanaka, K Sharakata, M Hsieh, LS Kawahara, H Ikura, Y Saito, H AF Akasawa, A Tanaka, K Sharakata, M Hsieh, LS Kawahara, H Ikura, Y Saito, H TI IgE cross-reactivity with latex related food antigens in a patient with spina bifida SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 US FDA, Bethesda, MD 20014 USA. Natl Childrens Hosp, Tokyo 154, Japan. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 JAN PY 1998 VL 101 IS 1 MA 857 BP S207 EP S207 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA YW339 UT WOS:000071924800856 ER PT J AU Turkeltaub, PC Gergen, PJ AF Turkeltaub, PC Gergen, PJ TI Allergen skin test reactivity as a predictor of mortality in a national cohort. SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 AHCPR, Rockville, MD USA. US FDA, CBER, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 JAN PY 1998 VL 101 IS 1 MA 779 BP S190 EP S190 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA YW339 UT WOS:000071924800778 ER PT J AU Vick, JA Whitehurst, V Alleva, F Zhang, J Chadwick, D Hinton, D AF Vick, JA Whitehurst, V Alleva, F Zhang, J Chadwick, D Hinton, D TI Studies of pulmonary and cardiovascular changes in genetically bred rats with hyper-reactive airways SO JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY LA English DT Meeting Abstract C1 CDER, Washington, DC USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MOSBY-YEAR BOOK 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 JAN PY 1998 VL 101 IS 1 MA 497 BP S120 EP S120 PN 2 PG 1 WC Allergy; Immunology SC Allergy; Immunology GA YW339 UT WOS:000071924800497 ER PT J AU Mitchell, GA Dunnavan, G AF Mitchell, GA Dunnavan, G TI Illegal use of beta-adrenergic agonists in the United States SO JOURNAL OF ANIMAL SCIENCE LA English DT Article; Proceedings Paper CT Symposium on Pharmacology, Toxicology, and the Illegal Use of Beta-Adrenergic Agonists at the 88th Annual Meeting of the American-Society-of-Animal-Science CY JUL, 1996 CL RAPID CITY, SOUTH DAKOTA SP Amer Soc Anim Sci DE bovidae; pigs; sheep; clenbuterol; food poisoning ID CLENBUTEROL; LIVER AB Clenbuterol (CBL) is a member of the class of drugs called beta-agonists, which have powerful desirable and undesirable effects. Clenbuterol has the ability to increase muscle mass and residues in tissue of treated animals but can cause symptoms of acute poisoning in people. Symptoms, but no deaths, from CBL residue-induced food poisoning have been reported from investigations of separate events in Spain and France. In 1991, FDA sent letters to all states and USDA/FSIS advising them of the possibility of illegal CBL use in domestic animals and of our concern about adverse effects on public health if residue was present in food. The FDA asked U.S. Customs to be alert to attempts at illegal importation and to advise that we were prepared to investigate distribution, sale, or use of the drug. Analytical methods are available to assay for CBL residue in edible tissues and in the retinal tissues of the eye. Methods are being developed for assay of noninvasive samples such as hair. Residues of CBL have been found in one sample of edible tissue and several samples of retinal tissues from show animals and in some classes of commercial meat-producing animals. Several individuals have been found guilty of distributing CBL, cases are pending, and investigations are continuing. It is possible that CBL will be approved for safe conditions of use. The scenario of ultimately one or more beta-agonist drugs approved for legal use in food-producing animals and the probable continued availability of several illegal analogs will be a challenging containment task for regulators and the leaders of the meat-producing livestock industries. C1 US FDA, Off Surveillance & Compliance, Ctr Vet Med, Rockville, MD 20855 USA. RP Mitchell, GA (reprint author), US FDA, Off Surveillance & Compliance, Ctr Vet Med, Rockville, MD 20855 USA. NR 4 TC 123 Z9 133 U1 3 U2 17 PU AMER SOC ANIMAL SCIENCE PI SAVOY PA 1111 NORTH DUNLAP AVE, SAVOY, IL 61874 USA SN 0021-8812 J9 J ANIM SCI JI J. Anim. Sci. PD JAN PY 1998 VL 76 IS 1 BP 208 EP 211 PG 4 WC Agriculture, Dairy & Animal Science SC Agriculture GA YR496 UT WOS:000071501100024 PM 9464900 ER PT J AU Ang, CYW Luo, WH Kiessling, CR McKim, K Lochmann, R Walker, CC Thompson, HC AF Ang, CYW Luo, WH Kiessling, CR McKim, K Lochmann, R Walker, CC Thompson, HC TI A bridging study between liquid chromatography and microbial inhibition assay methods for determining amoxicillin residues in catfish muscle SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID AMPICILLIN; TISSUES AB A bridging study was conducted to establish the correlation between a liquid chromatographic (LC) method and a microbial inhibition (MI) method for analysis of amoxicillin residues in catfish muscle. The LC procedure involved precolumn derivatization with formaldehyde followed by Le separation with fluorescence detection. The MI procedure used Bacillus stearothermophilus as the test organism and was validated in this study before the bridging investigation. The 2 methods were compared for determination of both fortified and incurred samples. No significant differences were found between the methods when all data were included in statistical computations. The linear correlation of LC means versus MI means had a slope of 0.972 and a negligible intercept (1.0 ng/g), with a correlation coefficient of 0.9962. LC was more specific and showed better sensitivity than MI for amoxicillin residues at less than or equal to 10 ng/g. For practical purposes, values obtained by the 2 methods can be considered equivalent. C1 US FDA, Natl Ctr Toxicol Res, Div Chem, Jefferson, AR 72079 USA. US FDA, Denver, CO 80225 USA. Univ Arkansas, Dept Fisheries & Aquaculture, Pine Bluff, AR 71601 USA. RP Ang, CYW (reprint author), US FDA, Natl Ctr Toxicol Res, Div Chem, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 14 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 JAN-FEB PY 1998 VL 81 IS 1 BP 33 EP 39 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800006 PM 9477560 ER PT J AU Kenyon, AS Shi, XY Wang, Y Ng, WH Prestridge, R Sharp, K AF Kenyon, AS Shi, XY Wang, Y Ng, WH Prestridge, R Sharp, K TI Simple, at-site detection of diethylene glycol ethylene glycol contamination of glycerin and glycerin-based raw materials by thin-layer chromatography SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article ID PHARMACEUTICALS AB This paper describes a rapid, inexpensive thin-layer chromatographic (TLC) method that separates diethylene glycol (DEG) from glycerin and other glycols, Studies with collaborating laboratories ed: the World Health Organization have shown that about 6% DEG in glycerin and about 2% DEG in acetaminophen (paracetamol) elixirs may be detected by direct visual inspection of the developed TLC sheets. Staining the sheet permits detection of DEG at less than 0.1%. The method casts less than $1.00 per test acid takes 20 min by visual inspection, longer when staining is required. The visual method can be performed without laboratory facilities by personnel having little previous training. Samples testing positive by the visual method can be submitted to a laboratory for confirmation and quantitation of DEG. C1 US FDA, Div Testing & Appl Analyt Dev, St Louis, MO 63101 USA. Australian Therapeut Goods Adm, Woden, ACT 2606, Australia. RP Kenyon, AS (reprint author), US FDA, Div Testing & Appl Analyt Dev, 1114 Market St,Room 1002, St Louis, MO 63101 USA. NR 14 TC 11 Z9 12 U1 1 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 44 EP 50 PG 7 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800008 PM 9477561 ER PT J AU Dobson, JEF McClure, FD Rainosek, AP AF Dobson, JEF McClure, FD Rainosek, AP TI A precollaborative study of weight determination methods for quick frozen shrimp SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB A precollaborative study compared the accuracy and precision of official AOAC methods with other selected methods for determining net weight of IQF-glazed shrimp and block-glazed shrimp, assessed the ruggedness of the methods with respect to changes in the levels of the factors under study, and selected candidate methods for use in a collaborative study. Methods tested for determining deglazed (frozen) net weight of IQF-glazed shrimp were (1) AOAC Method 963.18 and (2) the Water Bath Dip Method. Methods tested for determining thawed net weight of IQF-glazed shrimp were (1) AOAC Method 967.13, (2) Modified AOAC Method(mnb) 967.13, (3) Modified AOAC Method(pb) 967.13, (4) the Coder Method, (5) the Air Thaw Method, and (6) Modified AOAC Method 963.18. The same methods except Modified AOAC Method 963.18 were tested for determining thawed net weight of block-glazed shrimp. A total of 864 0.45 kg (1 lb), 0.90 kg (2 lb), and 1.35 kg (3 lb) IQF-glazed shrimp test samples and 234 2.25 kg (5 Ib) block-glazed shrimp test samples were collected. During sample preparation, test samples were subjected to either water with or without sodium tripolyphosphate (STP). During deglazing (IQF-glazed shrimp only) and/or thawing, test samples were allocated in a factorial design to assess the effects of STP presence (no STP and STP), sieve mesh sizes (2.83 and 2.38 mm; 0.11 and 0.09 in.), and sieve diameters (20 and 30 cm; 8 and 12 in.). During weighing, test samples were further allocated to a sequence of weighing procedures designed to assess the effects of using sieve weights (dry and wet) in combination with paper towel use (no and yes) and tared pan weights when calculating determined net weights. Cn the basis of the results of this precollaborative study, Modified AOAC Method(pb) 967.13 and the Air Thaw Method seem to be the best methods to determine net weight of IQF-glazed and block-glazed shrimp. Therefore, to validate method choices in the collaborative study, the authors recommend analysis of laf-glazed shrimp and block-glazed shrimp test samples, each prepared with or without STP, by Modified AOAC Method(pb) 967.13 and the Air Thaw Method. To fulfill AOAC requirements, IQF-glazed shrimp and block-glazed shrimp test samples, each prepared with or without STP, must be analyzed by official methods: AOAC: Method 963.18 (IQF-glazed shrimp only) and AOAC Method 967.13. During testing, sieve mesh size will be either 2.83 or 2.38 mm (0.11 or 0.09 in.), sieve diameter will be limited to 30 cm (12 in.), and weighing procedure will be limited to tared pan. C1 Natl Marine Fisheries Serv, US Dept Commerce, NOAA, Tech Serv Branch,Natl Stand & Specificat Sect, Gloucester, MA 01930 USA. US FDA, US Dept HHS, Ctr Food Safety & Appl Nutr, Off Sci Anal & Support,Div Math, Washington, DC 20204 USA. Univ S Alabama, Dept Math & Stat, Mobile, AL 36688 USA. Natl Marine Fisheries Serv, US Dept Commerce, NOAA, Natl Seafood Inspect Lab, Pascagoula, MS 39568 USA. RP Dobson, JEF (reprint author), Natl Marine Fisheries Serv, US Dept Commerce, NOAA, Tech Serv Branch,Natl Stand & Specificat Sect, 11-15 Parker St, Gloucester, MA 01930 USA. NR 7 TC 1 Z9 1 U1 1 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 69 EP 87 PG 19 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800012 PM 9477564 ER PT J AU Hepp, NM AF Hepp, NM TI X-ray fluorescence determination of manganese in FD & C blue no. 1 SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article AB An X-ray fluorescence (XRF) method was developed for determining manganese in FD&C Blue No. 1 from simply prepared pressed pellets. Results were compared with those of atomic absorption spectroscopy (AAS) of acid-digested or ashed samples. Levels of manganese determined by XRF and AAS were equivalent. The limit of detection (3 sigma) for the XRF method was 3 mu g manganese/g dye. The 95% confidence interval at the specification level was 100 + 10 mu g manganese/g dye. C1 US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. RP Hepp, NM (reprint author), US FDA, Off Cosmet & Colors, 200 C St NW, Washington, DC 20204 USA. NR 10 TC 3 Z9 3 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 89 EP 92 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800013 ER PT J AU Bunch, EA AF Bunch, EA TI Drugs I SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Bothell, WA 98041 USA. RP Bunch, EA (reprint author), US FDA, POB 3012,22201 23rd St SE, Bothell, WA 98041 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 120 EP 120 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800020 ER PT J AU Ng, LL AF Ng, LL TI Drugs II SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Ng, LL (reprint author), US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 121 EP 121 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800021 ER PT J AU Long, AR AF Long, AR TI Color additives SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Atlanta Ctr Nutrient Anal, Atlanta, GA 30309 USA. RP Long, AR (reprint author), US FDA, Atlanta Ctr Nutrient Anal, 60 8th St NE, Atlanta, GA 30309 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 124 EP 124 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800024 ER PT J AU Thompson, RD AF Thompson, RD TI Nonalcoholic beverages SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Minneapolis, MN 55401 USA. RP Thompson, RD (reprint author), US FDA, 240 Hennepin Ave, Minneapolis, MN 55401 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 125 EP 125 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800026 ER PT J AU Warner, CR AF Warner, CR TI Food additives SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int ID GAS-CHROMATOGRAPHIC DETERMINATION; ACID C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Warner, CR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 6 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 126 EP 127 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800028 ER PT J AU Trucksess, MW AF Trucksess, MW TI Mycotoxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int ID LIQUID-CHROMATOGRAPHIC DETERMINATION; MONILIFORME CULTURE MATERIAL; IMMUNOAFFINITY COLUMN CLEANUP; FUMONISIN B-1; FUSARIUM-MONILIFORME; CONTAMINATED GRAINS; NATURAL OCCURRENCE; MASS-SPECTROMETRY; OCHRATOXIN-A; AFLATOXIN M(1) C1 US FDA, Div Nat Prod, Washington, DC 20204 USA. RP Trucksess, MW (reprint author), US FDA, Div Nat Prod, 200 C St SW, Washington, DC 20204 USA. NR 159 TC 16 Z9 16 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 JAN-FEB PY 1998 VL 81 IS 1 BP 128 EP 137 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800029 ER PT J AU Betz, JM AF Betz, JM TI Plant toxins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int ID PYRROLIZIDINE ALKALOIDS; SAUROPUS-ANDROGYNUS; WEDELIA-GLAUCA; TOXICITY; INGESTION; SHEEP; INTOXICATION; HEPATITIS; EXPOSURES; OUTBREAK C1 US FDA, Div Nat Prod, Washington, DC 20204 USA. RP Betz, JM (reprint author), US FDA, Div Nat Prod, 200 C St SW, Washington, DC 20204 USA. NR 71 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 JAN-FEB PY 1998 VL 81 IS 1 BP 137 EP 142 PG 6 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800030 ER PT J AU Firestone, D AF Firestone, D TI Fats and oils SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int ID PERFORMANCE LIQUID-CHROMATOGRAPHY; MARGARINE; ACIDS C1 US FDA, Div Pesticides & Ind Chem, Washington, DC 20204 USA. RP Firestone, D (reprint author), US FDA, Div Pesticides & Ind Chem, 200 C St SW, Washington, DC 20204 USA. NR 31 TC 1 Z9 1 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 JAN-FEB PY 1998 VL 81 IS 1 BP 154 EP 157 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800033 ER PT J AU Chase, GW AF Chase, GW TI Infant formula and medical diets SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Atlanta Ctr Nutrient Anal, Atlanta, GA 30309 USA. RP Chase, GW (reprint author), US FDA, Atlanta Ctr Nutrient Anal, 60 8th St, Atlanta, GA 30309 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 157 EP 158 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800034 ER PT J AU Long, AR AF Long, AR TI Fat-soluble vitamins SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Atlanta Ctr Nutrient Anal, Atlanta, GA 30309 USA. RP Long, AR (reprint author), US FDA, Atlanta Ctr Nutrient Anal, 6o 8th St NE, Atlanta, GA 30309 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 160 EP 160 PG 1 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800036 ER PT J AU Parfitt, CH AF Parfitt, CH TI Multiresidue methods SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Div Pesticides & Ind Chem, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Parfitt, CH (reprint author), US FDA, Div Pesticides & Ind Chem, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NR 0 TC 1 Z9 1 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 JAN-FEB PY 1998 VL 81 IS 1 BP 179 EP 182 PG 4 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800046 ER PT J AU McMahon, BM AF McMahon, BM TI Organohalogen residues and fumigants SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Div Pesticides & Ind Chem, Washington, DC 20204 USA. RP McMahon, BM (reprint author), US FDA, Div Pesticides & Ind Chem, Washington, DC 20204 USA. NR 3 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 182 EP 183 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800047 ER PT J AU Baratta, EJ AF Baratta, EJ TI Radioactivity SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. RP Baratta, EJ (reprint author), US FDA, Winchester Engn & Analyt Ctr, 109 Holton St, Winchester, MA 01890 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 184 EP 185 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800049 ER PT J AU Hitchins, AD AF Hitchins, AD TI Cosmetic microbiology SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. RP Hitchins, AD (reprint author), US FDA, Div Microbiol Studies, HFS-516,200 C St SW, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 186 EP 187 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800050 ER PT J AU Placencia, AM AF Placencia, AM TI Drug- and device-related microbiology SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Minneapolis, MN 55401 USA. RP Placencia, AM (reprint author), US FDA, 240 Hennepin Ave, Minneapolis, MN 55401 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 188 EP 190 PG 3 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800051 ER PT J AU Ziobro, GC AF Ziobro, GC TI Filth and extraneous materials in foods and drugs SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int C1 US FDA, Div Microanalyt Evaluat, Washington, DC 20204 USA. RP Ziobro, GC (reprint author), US FDA, Div Microanalyt Evaluat, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 1 PU AOAC INTERNATIONAL PI GAITHERSBURG PA 481 NORTH FREDRICK AVE, STE 500, GAITHERSBURG, MD 20877-2504 USA SN 1060-3271 J9 J AOAC INT JI J. AOAC Int. PD JAN-FEB PY 1998 VL 81 IS 1 BP 190 EP 191 PG 2 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800052 ER PT J AU Andrews, WH AF Andrews, WH TI Food microbiology - Nondairy SO JOURNAL OF AOAC INTERNATIONAL LA English DT Article; Proceedings Paper CT 111th AOAC INTERNATIONAL Annual Meeting CY SEP 07-11, 1997 CL SAN DIEGO, CALIFORNIA SP AOAC Int ID VASSILIADIS C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. RP Andrews, WH (reprint author), US FDA, Div Microbiol Studies, 200 C St SW, Washington, DC 20204 USA. NR 20 TC 1 Z9 1 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 JAN-FEB PY 1998 VL 81 IS 1 BP 192 EP 201 PG 10 WC Chemistry, Analytical; Food Science & Technology SC Chemistry; Food Science & Technology GA YW489 UT WOS:000071940800054 ER PT J AU Davis, H Gergen, PJ Graham, DJ AF Davis, H Gergen, PJ Graham, DJ TI The risk for outpatient antibiotic-treated infections following a course of oral corticosteroids among children with asthma SO JOURNAL OF ASTHMA LA English DT Article DE infection; steroids; corticosteroids; asthma; children; antibiotics ID COMPLICATED VARICELLA; STEROID USE; THERAPY AB Short courses of oral corticosteroids are widely used to treat asthma. The objective of this study was to assess ii one course of oral corticosteroids increases asthmatic children's risk for infections treated with outpatient antibiotics. Using New York State Medicaid claims data on asthmatic children 2-15 years old, we made cohorts of oral corticosteroid users and nonusers. We determined the percentage of children who filled antibiotic prescriptions in the 30 days after index dates. Index dates were dates oral steroids were started (for steroid users) or matched dates (for nonusers). Odds ratios were adjusted for age, month of index date, and prior antibiotic use. Among children not receiving antibiotics on index dates, antibiotic prescriptions were filled in the next 30 days for 438 (20%) of 2145 steroid nonusers and 130 (19%) of 698 steroid users (p = 0.30); compared to nonusers, steroid users had an adjusted odds ratio of subsequent antibiotic use of 0.92 (95% confidence interval [Cl] 0.73-1.15). Among children receiving antibiotics on index dates, antibiotic prescriptions were filled in the next 30 days for 116 (26%) of 451 steroid nonusers and 50 (19%) of 260 steroid users (p = 0.05); compared to nonusers, steroid users had an adjusted odds ratio of subsequent antibiotic use of 0.65 (95% CI 0.53-0.97), We conclude that one course of oral corticosteroids does not increase asthmatic children's risk for infections treated with outpatient antibiotics. C1 US FDA, Ctr Drug Evaluat & Res, Off Epidemiol & Biostat, Rockville, MD 20857 USA. RP Davis, H (reprint author), US FDA, Ctr Drug Evaluat & Res, Off Epidemiol & Biostat, 5600 Fishers Lane,Room 15-B-18,HFD-733, Rockville, MD 20857 USA. NR 10 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0277-0903 J9 J ASTHMA JI J. Asthma PY 1998 VL 35 IS 5 BP 419 EP 425 DI 10.3109/02770909809048950 PG 9 WC Allergy; Respiratory System SC Allergy; Respiratory System GA 114PY UT WOS:000075619000004 PM 9734349 ER PT J AU Ikawa, T Ikeda, M Yamaguchi, A Tsai, WC Tamura, N Seta, N Trucksess, M Raybourne, RB Yu, DTY AF Ikawa, T Ikeda, M Yamaguchi, A Tsai, WC Tamura, N Seta, N Trucksess, M Raybourne, RB Yu, DTY TI Expression of arthritis-causing HLA-B27 on hela cells promotes induction of c-fos in response to in vitro invasion by Salmonella typhimurium SO JOURNAL OF CLINICAL INVESTIGATION LA English DT Article DE HLA-B27; reactive arthritis; c-fos; AP-1; MCP-1 ID MESSENGER-RNA EXPRESSION; MHC CLASS-I; ANKYLOSING-SPONDYLITIS; EPITHELIAL-CELLS; REACTIVE ARTHRITIS; BACTERIAL INVASION; T-CELLS; PHOSPHORYLATION; CYTOKINES; MOLECULES AB HLA-B27 confers a very strong genetic predisposition to development of a reactive arthritis after infection by bacteria such as Salmonella typhimurium, This study examines the role of HLA-B27 in the initiation of the earliest host activities after exposure to Salmonella, namely activation of the immediate early genes in the epithelial cells, Our major finding is that in Hela cells, the expression of c-fos was induced by Salmonella invasion only when the cells expressed the transfected HLA-B27 gene, but not the HLA-A1 gene or a truncated HLA-B27 gene lacking the exons encoding the cytoplasmic domain, C-fos is potentially capable of complexing with members of the c-jun family to become the AP-1 transcription complex. Parallel to c-fos expression, we found that only with the HLA-B27 transfectant was there expression of AP-1, AP-1 potentially controls the expression of a large number of genes, On screening a panel of proinflammatory molecules, we found that Salmonella invasion induced expression of monocyte chemoattractant protein-1 in the HLA-B27 cells, Since each of these separate positive findings belong to the same cascade of events after cell activation, together they reinforce the hypothesis that HLA-B27 plays a modulatory role in the early signal transduction events induced by Salmonella invasion, This hypothesis adds another item to the list of allele-specific activities carried out by HLA class I molecules. If similar activation also occurs in the joints, it may play a major role in arthritis. C1 Univ Calif Los Angeles, Div Rheumatol, Rehabil Ctr 35 40, Sch Med, Los Angeles, CA 90095 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. US FDA, Immunobiol Branch, Laurel, MD 20708 USA. RP Yu, DTY (reprint author), Univ Calif Los Angeles, Div Rheumatol, Rehabil Ctr 35 40, Sch Med, 1000 Vet Ave, Los Angeles, CA 90095 USA. EM dyu@med1.medsch.ucla.edu RI Tsai, Wen-Chan/C-7348-2009; Seta, Noriyuki/L-2844-2013 NR 35 TC 41 Z9 43 U1 0 U2 0 PU ROCKEFELLER UNIV PRESS PI NEW YORK PA 1114 FIRST AVE, 4TH FL, NEW YORK, NY 10021 USA SN 0021-9738 J9 J CLIN INVEST JI J. Clin. Invest. PD JAN 1 PY 1998 VL 101 IS 1 BP 263 EP 272 DI 10.1172/JCI471 PG 10 WC Medicine, Research & Experimental SC Research & Experimental Medicine GA YQ513 UT WOS:000071395300031 PM 9421489 ER PT J AU Schlesser, JE Lynn, G Armstrong, DJ Cinar, A Ramanauskas, P Negiz, A AF Schlesser, JE Lynn, G Armstrong, DJ Cinar, A Ramanauskas, P Negiz, A TI Acquisition, storage, and review of safety data from a commercial system for high temperature, short time pasteurization SO JOURNAL OF DAIRY SCIENCE LA English DT Article DE data acquisition; dairy; pasteurization AB A high temperature, short time (HTST) pasteurization system was equipped with electronic sensors; to determine the temperature, pressure, flow rate, and position of the flow diversion valve. A computer for data acquisition was wired to the sensors to monitor and to record processing conditions related to public health. The processing conditions were stored in safety files on the hard drive of the computer, transferred weekly to a tape drive, and stored. The processing conditions of the HTST system were monitored for 270 d to determine the accuracy and reliability of the data acquisition system. The size of the HTST safety fries ranged from 6.2 to 9.1 MB when the sensors were monitored every second. The file size was reduced to <1.8 MB when the monitoring frequency was increased to every 5 s. To determine accuracy, the temperatures recorded by the data acquisition system were compared with the temperatures recorded by an electronic recorder controller. To determine reliability, changes in the position of the flow diversion valve were examined to identify process deviations and were compared with the event marker on circular charts. The review of the data file by the actual time method was an effective alternative to the electronic recorder controller for monitoring the completeness of data in the safety files. Offline review to determine reliability required approximately 10 min/d of records. C1 US FDA, Natl Ctr Food Safety & Technol, Summit Argo, IL 60501 USA. RP Schlesser, JE (reprint author), US FDA, Natl Ctr Food Safety & Technol, 6502 S Archer Rd, Summit Argo, IL 60501 USA. OI Cinar, Ali/0000-0002-1607-9943 FU FDA HHS [FD-000431] NR 6 TC 2 Z9 2 U1 0 U2 1 PU AMER DAIRY SCIENCE ASSOC PI SAVOY PA 1111 N DUNLAP AVE, SAVOY, IL 61874 USA SN 0022-0302 J9 J DAIRY SCI JI J. Dairy Sci. PD JAN PY 1998 VL 81 IS 1 BP 25 EP 30 PG 6 WC Agriculture, Dairy & Animal Science; Food Science & Technology SC Agriculture; Food Science & Technology GA ZF299 UT WOS:000072883600004 PM 9493080 ER PT J AU Solomon, HM Rhodehamel, EJ Kautter, DA AF Solomon, HM Rhodehamel, EJ Kautter, DA TI Growth and toxin production by Clostridium botulinum on sliced raw potatoes in a modified atmosphere with and without sulfite SO JOURNAL OF FOOD PROTECTION LA English DT Article AB The ability of Clostridium botulinum type A or B spores to grow and produce toxin on fresh raw potatoes in a modified atmosphere with or without sulfite was investigated at 22 degrees C. Fresh, peeled, sliced potatoes, untreated or dipped for 2 min into 0.7% sulfite solution and drained, were surface-inoculated at several concentration levels with a mixture of C. botulinum spores, either type A or B. They were placed in a modified atmosphere (30% N/70% CO2) within oxygen-impermeable bags (200 g/bag) and incubated at room temperature (22 degrees C). Toxicity was tested on days 0, 3, 4, 5, 6, and 7. After incubation, the potatoes were blended and centrifuged, and the Millipore-filtered supernatant fluid was injected intraperitoneally into mice, Sensory evaluation, except taste, was also performed. Potatoes inoculated with C. botulinum type A spores but untreated with NaHSO3 became toxic in 4 to 5 days, which coincided with the sensory evaluation "unfit for human consumption. Potatoes treated with NaHSO3 regardless of inoculum size or residual SO2 levels appeared acceptable for human consumption through day 7, even though they were toxic after 4 days of incubation. Although toxicity from type B spores occurred later and in fewer test samples than toxicity from type A, some potatoes again appeared acceptable but were toxic. Thus, although NaHSO3 markedly extended the consumer acceptability of peeled, sliced, raw potatoes at the abuse temperature, it did not inhibit outgrowth and toxin production by C. botulinum under these conditions. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. US FDA, Div Hazard Anal Crit Control Point Program, Washington, DC 20204 USA. RP Solomon, HM (reprint author), US FDA, Div Microbiol Studies, Washington, DC 20204 USA. EM hms@cfsan.fda.gov NR 12 TC 10 Z9 10 U1 3 U2 10 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 JAN PY 1998 VL 61 IS 1 BP 126 EP 128 PG 3 WC Biotechnology & Applied Microbiology; Food Science & Technology SC Biotechnology & Applied Microbiology; Food Science & Technology GA YU891 UT WOS:000071766500025 PM 9708268 ER PT J AU Pensabene, JW Fiddler, W Donoghue, DJ AF Pensabene, JW Fiddler, W Donoghue, DJ TI Supercritical fluid extraction compared with solvent method for incurred sulfamethazine in chicken eggs SO JOURNAL OF FOOD SCIENCE LA English DT Article DE supercritical fluid; extraction; eggs; sulfamethazine ID RESIDUES; MEAT AB To obtain eggs containing "normally incurred" surfamethazine (SMZ), 10 hens were fed a single dose of 75 mg/kg SMZ by capsule. The amount of SMZ in some of the eggs (n = 21) was determined by two extraction methods, supercritical fluid extraction (SFE) and solvent extraction. The mean SMZ values ranged from 0.10 to 0.78 ppm, with an overall mean of 0.32 ppm and no difference (p>0.05) was found between the methods. However, SFE provided a distinct advantage over other methods since the amount of sample manipulation and solvent use and disposal was minimal. Determination of SMZ in the normally incurred eggs over an 8-day period by SFE showed that levels reached a maximum after the first day, then declined slowly. However, SMZ exceeding 0.10 ppm still occurred 5 days after dosing. C1 USDA ARS, Eastern Reg Res Ctr, Wyndmoor, PA 19038 USA. US FDA, Ctr Vet Med, Div Anim Res, Laurel, MD 20708 USA. RP Pensabene, JW (reprint author), USDA ARS, Eastern Reg Res Ctr, 600 E Mermaid Lane, Wyndmoor, PA 19038 USA. NR 12 TC 3 Z9 3 U1 1 U2 1 PU INST FOOD TECHNOLOGISTS PI CHICAGO PA SUITE 300 221 N LASALLE ST, CHICAGO, IL 60601-1291 USA SN 0022-1147 J9 J FOOD SCI JI J. Food Sci. PD JAN-FEB PY 1998 VL 63 IS 1 BP 25 EP 26 DI 10.1111/j.1365-2621.1998.tb15667.x PG 2 WC Food Science & Technology SC Food Science & Technology GA YZ937 UT WOS:000072310100010 ER PT J AU Epstein, SL Lo, CY Misplon, JA Bennink, JR AF Epstein, SL Lo, CY Misplon, JA Bennink, JR TI Mechanism of protective immunity against influenza virus infection in mice without antibodies SO JOURNAL OF IMMUNOLOGY LA English DT Article ID CYTOTOXIC T-LYMPHOCYTES; A VIRUSES; EPITHELIAL-CELLS; INTERFERON-GAMMA; RSV CHALLENGE; B-CELLS; NUCLEOPROTEIN; HEMAGGLUTININ; PROTEIN; RECOMBINANTS AB There is considerable interest in developing viral vaccines intended to induce T cell immunity, especially cytotoxic CD8(+) T lymphocytes, when Abs are not protective or are too narrow in viral strain specificity. We have studied protective immunity in doubly inactivated (DI) mice devoid of Abs and mature B cells. When infected with influenza B virus, these mice cleared the virus in a process dependent upon CD8(+) T lymphocytes. Cytotoxic activity was detected in lung lymphocytes of DI mice after primary or secondary infection, and was abrogated by depletion of CD8(+) cells in vivo. Challenge experiments showed that DI mice could be protected by immunization against reinfection 1 mo later, and protection was virus specific. Depletion of CD4(+) or CD8(+) T cells in vivo during the challenge period partially abrogated, and depletion of both subsets completely abrogated, the protection. This indicates that both CD4(+) and CD8(+) T cells are required effecters in the optimal control of virus replication. Thus, when Abs fail to protect against varying challenge viruses, as is the case with variant strains of influenza and HIV, there is hope that T cells might be able to act alone. C1 NIAID, Viral Dis Lab, Viral Immunol Sect, NIH, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cellular & Gene Therapies, Mol Immunol Lab, Bethesda, MD 20892 USA. RP Epstein, SL (reprint author), US FDA, CBER, OTRR, DCGT, 1401 Rockville Pike,HFM-521, Rockville, MD 20852 USA. NR 45 TC 125 Z9 130 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 JAN 1 PY 1998 VL 160 IS 1 BP 322 EP 327 PG 6 WC Immunology SC Immunology GA YW266 UT WOS:000071915100042 PM 9551987 ER PT J AU Ramachandran, S Thompson, RW Gam, AA Neva, FA AF Ramachandran, S Thompson, RW Gam, AA Neva, FA TI Recombinant cDNA clones for immunodiagnosis of strongyloidiasis SO JOURNAL OF INFECTIOUS DISEASES LA English DT Article; Proceedings Paper CT 45th Annual Meeting of the American-Society-of-Tropical-Medicine-and-Hygiene CY DEC 01-05, 1996 CL BALTIMORE, MARYLAND SP Amer Soc Trop Med & Hyg ID LINKED-IMMUNOSORBENT-ASSAY; FAR-EAST PRISONERS; STERCORALIS INFECTION; DIAGNOSIS; VIRUS; WAR; HYPERINFECTION; ANTIBODIES; PROTEINS; FAMILY AB Because diagnosis of strongyloidiasis by stool examination is unreliable and because of the potential for serious disease in Strongyloides infections, there is need for improved diagnostic aids to facilitate recognition and treatment of this parasitic infection. Serologic testing, when available, requires antigen preparation from infected primates or dogs that can be difficult to maintain, Several recombinant clones from a cDNA library prepared from the infective stage of Strongyloides stercoralis were characterized. Serologic results indicate that the recombinant proteins were equally or more reactive than the larval somatic antigen, No cross-reactivity with recombinant antigen 5a was found with sera from patients with filarial or intestinal nematode infections, Recombinant antigens 5a and 12a detected parasite-specific IgE and IgG4 antibodies in Strongyloides-infected patients. Sequence analysis showed these antigens to be rich in proline and charged amino acids, Lack of homology from database searches suggests that the antigens are unique, These recombinant antigens should be useful in diagnostic and epidemiologic studies of strongyloidiasis. C1 NIH, Parasit Dis Lab, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat, Bethesda, MD 20892 USA. RP Ramachandran, S (reprint author), NIH, Parasit Dis Lab, 9000 Rockville Pike,Bldg 4,Room 126, Bethesda, MD 20892 USA. NR 25 TC 24 Z9 24 U1 0 U2 1 PU UNIV CHICAGO PRESS PI CHICAGO PA 5801 S ELLIS AVENUE, CHICAGO, IL 60637 USA SN 0022-1899 J9 J INFECT DIS JI J. Infect. Dis. PD JAN PY 1998 VL 177 IS 1 BP 196 EP 203 DI 10.1086/513817 PG 8 WC Immunology; Infectious Diseases; Microbiology SC Immunology; Infectious Diseases; Microbiology GA YM597 UT WOS:000071080700028 PM 9419188 ER PT J AU Donnelly, RP Feldman, GM Dickensheets, HL AF Donnelly, RP Feldman, GM Dickensheets, HL TI IL-2 receptor gamma chain (gamma c)-deficient macrophages exhibit diminished responses to IL-4 but not IL-13 SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 US FDA, CBER, Div Cytokine Biol, 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1998 SU 1 MA 64 BP 19 EP 19 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 117YP UT WOS:000075810700065 ER PT J AU Dickensheets, HL Donnelly, RP AF Dickensheets, HL Donnelly, RP TI Type-I and type-II interferons inhibit activation of STAT6 by IL-4 and IL-13 in human monocytes SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 US FDA, Ctr Biol Evaluat & Res, Div Cytokine Biol, 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1998 SU 1 MA 142 BP 32 EP 32 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 117YP UT WOS:000075810700143 ER PT J AU Zoeteweij, JP Golding, H Mostowski, H Blauvelt, A AF Zoeteweij, JP Golding, H Mostowski, H Blauvelt, A TI Cytokines regulate expression and function of the HIV coreceptor CXCR4 on human mature dendritic cells. SO JOURNAL OF LEUKOCYTE BIOLOGY LA English DT Meeting Abstract C1 NCI, Dermatol Branch, Bethesda, MD 20892 USA. US FDA, Ctr Biol Evaluat & Res, Div Cell & Gene Therapy, 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 0741-5400 J9 J LEUKOCYTE BIOL JI J. Leukoc. Biol. PY 1998 SU 2 MA E11 BP 58 EP 58 PG 1 WC Cell Biology; Hematology; Immunology SC Cell Biology; Hematology; Immunology GA 126TN UT WOS:000076309900180 ER PT J AU Rasooly, A Ito, Y AF Rasooly, A Ito, Y TI Toroidal coil countercurrent chromatography separation of Staphylococcus aureus enterotoxin A in food SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID FLOW-THROUGH CENTRIFUGE; ROTATING SEALS AB Countercurrent Chromatography (CCC) has the potential to play a major role in food analysis because it permits analysis of crude and complex samples. CCC was evaluated for its ability to separate S. aureus enterotoxin A (SEA), which is a common cause of food poisoning. Mushrooms containing native-or heat-denatured SEA were separated by Toroidal Coil CCC and the fractions containing the toxin were analyzed by Western immunoblotting. Both native SEA, used to spike mushroom samples, and heat-denatured SEA, resulting from S. aureus contamination of canned mushrooms, were detectable using CCC. This method increases the level of sensitivity of Western immunoblotting by at least an order of magnitude by concentrating the sample. Our results suggest that CCC, in combination with a suitable detection method, is a potentially useful method for toxin analysis in food. C1 US FDA, Div Microbiol Studies, Washington, DC 20204 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Rasooly, A (reprint author), US FDA, Div Microbiol Studies, Washington, DC 20204 USA. NR 13 TC 8 Z9 9 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1998 VL 21 IS 1-2 BP 93 EP 102 DI 10.1080/10826079808001938 PG 10 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YY421 UT WOS:000072144900008 ER PT J AU Weisz, A Andrzejewski, D Highet, RJ Ito, Y AF Weisz, A Andrzejewski, D Highet, RJ Ito, Y TI Separation of a newly identified contaminant from commercial 4,5,6,7-tetrachlorofluorescein by ph-zone-refining countercurrent chromatography SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article ID PURIFICATION AB A 5-g sample of commercial 4,5,6,7-tetrachlorofluorescein (TCF) was subjected to pH-zone-refining countercurrent chromatography to separate an unidentified contaminant present in all TCF batches obtained from four different suppliers. The separated contaminant (44 mg) was characterized by H-1- and C-13 nuclear magnetic resonance spectrometry and negative ion chemical ionization mass spectrometry as a new seven-membered lactone TCF isomer with the structure 11,12,13,14-tetrachloro-3,14b-dihydroxy-[2]-benzoxepino-[3,4,5-kl]-xanthene-10(14bH)-one. C1 US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. US FDA, Off Sci & Anal & Support, Washington, DC 20204 USA. NHLBI, Biophys Chem Lab, NIH, Bethesda, MD 20892 USA. RP Weisz, A (reprint author), US FDA, Off Cosmet & Colors, Washington, DC 20204 USA. NR 5 TC 3 Z9 3 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1998 VL 21 IS 1-2 BP 183 EP 193 DI 10.1080/10826079808001947 PG 11 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA YY421 UT WOS:000072144900017 ER PT J AU Nasr, MM Stanley, CM AF Nasr, MM Stanley, CM TI High performance liquid chromatographic assay of erythromycin salts and esters in bulk and pharmaceutical dosage forms SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article AB Recently, several liquid chromatographic methods for the assay of erythromycin base were developed and are being considered for the routine assay of erythromycin. In this study, we developed simple and rugged liquid chromatographic methods for the assay of erythromycin salts and esters, and used these methods for the assay of erythromycin estolate, erythromycin ethylsuccinate, erythromycin stearate, erythromycin gluceptate, and erythromycin lactobionate in bulk and pharmaceutical formulations. The HPLC methods proved to be simple, sensitive, versatile, and rugged. The developed methods provide an attractive alternative to current official microbiological methods. The HPLC assay results for all commercial erythromycin products tested comply with the USP Antibiotics-Microbial assay specification. C1 CDER, USFDA, Div Testing & Appl Analyt Dev, St Louis, MO 63101 USA. RP Nasr, MM (reprint author), CDER, USFDA, Div Testing & Appl Analyt Dev, 114 Market St, St Louis, MO 63101 USA. NR 10 TC 6 Z9 6 U1 1 U2 2 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1998 VL 21 IS 8 BP 1147 EP 1160 DI 10.1080/10826079808006590 PG 14 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA ZN431 UT WOS:000073645200005 ER PT J AU Chase, GW Eitenmiller, RR Long, AR AF Chase, GW Eitenmiller, RR Long, AR TI Liquid chromatographic method for the analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in soy based infant formula using matrix solid phase dispersion SO JOURNAL OF LIQUID CHROMATOGRAPHY & RELATED TECHNOLOGIES LA English DT Article AB A liquid chromatographic method is described for the analysis of all-rac-alpha-tocopheryl acetate and retinyl palmitate in soy based infant formula. The vitamins are extracted from infant formula without saponification by matrix solid phase dispersion (MSPD) and quantitated by normal phase chromatography with fluorescence detection. Retinyl palmitate and all-rac-alpha-tocopheryl acetate are quantitated isocratically with a mobile phase of hexane containing isopropanol @ 0.125% (v/v) and 0.5% (v/v), respectively. Results compared favorably to the label declaration on a retail infant formula product. C1 US FDA, Atlanta Ctr Nutrient Anal, Atlanta, GA 30309 USA. Univ Georgia, Dept Food Sci & Technol, Athens, GA 30602 USA. RP Chase, GW (reprint author), US FDA, Atlanta Ctr Nutrient Anal, 60 8th St, Atlanta, GA 30309 USA. NR 2 TC 5 Z9 5 U1 0 U2 1 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 1082-6076 J9 J LIQ CHROMATOGR R T JI J. Liq. Chromatogr. Relat. Technol. PY 1998 VL 21 IS 18 BP 2853 EP 2861 DI 10.1080/10826079808003448 PG 9 WC Biochemical Research Methods; Chemistry, Analytical SC Biochemistry & Molecular Biology; Chemistry GA 130HP UT WOS:000076514500009 ER PT J AU Simpson, IA Appel, NM Hokari, M Oki, J Holman, GD Maher, F Koehler-Stec, EM Vannucci, SJ Smith, QR AF Simpson, IA Appel, NM Hokari, M Oki, J Holman, GD Maher, F Koehler-Stec, EM Vannucci, SJ Smith, QR TI Blood-brain barrier glucose transport: Effects of hyper- and hypoglycemia revisited. SO JOURNAL OF NEUROCHEMISTRY LA English DT Meeting Abstract C1 NIDDKD, NIH, Bethesda, MD 20892 USA. US FDA, NIH, Bethesda, MD 20892 USA. NIA, NIH, Bethesda, MD 20892 USA. Univ Bath, Dept Biochem, Bath BA2 7AY, Avon, England. Penn State Univ, Milton S Hershey Med Ctr, Dept Pediat, Hershey, PA 17033 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0022-3042 J9 J NEUROCHEM JI J. Neurochem. PY 1998 VL 70 SU 1 BP S68 EP S68 PG 1 WC Biochemistry & Molecular Biology; Neurosciences SC Biochemistry & Molecular Biology; Neurosciences & Neurology GA YY627 UT WOS:000072167200273 ER PT J AU Rosenfeld, M Emerson, J Astley, S Joy, P Williams-Warren, J Standaert, TA Yim, DL Crist, D Thykkuttathil, M Torrence, M FitzSimmons, S Ramsey, B AF Rosenfeld, M Emerson, J Astley, S Joy, P Williams-Warren, J Standaert, TA Yim, DL Crist, D Thykkuttathil, M Torrence, M FitzSimmons, S Ramsey, B TI Home nebulizer use among patients with cystic fibrosis SO JOURNAL OF PEDIATRICS LA English DT Article ID MEDICATION NEBULIZERS; CONTAMINATION; GROWTH AB Objective: To describe current patterns of home nebulizer use among patients with cystic fibrosis. Study design: A population-based survey of home nebulizer practices among 227 patients with cystic fibrosis using nebulizers from 1993 to 1994 (Objective 1), and a prospective study of "typical" home use, including testing of performance and bacterial cultures in nebulizers after use, completed by 36 subjects (Objective 2). Results: Objective 1: 85% of subjects reported using jet and 8% ultrasonic nebulizers (categories not mutually exclusive); 15% used unknown brands. Most jet nebulizers were disposable models, which were used for > 14 days by more than half the subjects. Mixing of medications in a single treatment (other than cromolyn and a bronchodilator) was reported by 28% of patients. Objective 2: no apparent deterioration in aerosol particle size or output rate of returned nebulizers compared with new units was observed. Staphylococcus aureus was cultured from 55% and Pseudomonas aeruginosa from 35% of returned nebulizers. Concordance between nebulizer and sputum cultures was poor. Conclusions: Although not generally tested for reusability, disposable nebulizers are generally used by patients for long periods. Medication mixing is common, although its effects on aerosol properties are unknown. Cystic fibrosis respiratory pathogens are frequently isolated from used nebulizers. Patient guidelines for home nebulizer use need to be established. C1 Childrens Hosp & Med Ctr, Div Pulm Med, Cyst Fibrosis Ctr, Seattle, WA 98105 USA. Univ Washington, Sch Med, Dept Pediat, Seattle, WA 98195 USA. US FDA, Ctr Devices & Radiol Hlth, Epidemiol Team, Rockville, MD 20857 USA. Cyst Fibrosis Fdn, Dept Med, Bethesda, MD USA. Univ Washington, Sch Publ Hlth, Dept Epidemiol, Seattle, WA 98195 USA. RP Rosenfeld, M (reprint author), Childrens Hosp & Med Ctr, Div Pulm Med, Cyst Fibrosis Ctr, 4800 Sandpoint Way, Seattle, WA 98105 USA. FU PHS HHS [223-94-6012] NR 32 TC 39 Z9 39 U1 0 U2 1 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 JAN PY 1998 VL 132 IS 1 BP 125 EP 131 DI 10.1016/S0022-3476(98)70497-4 PG 7 WC Pediatrics SC Pediatrics GA YV173 UT WOS:000071796700024 PM 9470013 ER PT J AU McCreery, RL Horn, AJ Spencer, J Jefferson, E AF McCreery, RL Horn, AJ Spencer, J Jefferson, E TI Noninvasive identification of materials inside USP vials with Raman spectroscopy and a Raman spectral library SO JOURNAL OF PHARMACEUTICAL SCIENCES LA English DT Article ID INTENSITY CALIBRATION; SPECTROMETERS AB A commercial dispersive Raman spectrometer operating at 785 nm with a CCD detector was used to acquire spectra of USP reference materials inside amber USP vials. The laser and collection beams were directed through the bottom of the vials, resulting in a 60% loss of signal. The Raman shift was calibrated with a 4-acetamidophenol standard, and spectral response was corrected with a luminescent standard. After these corrections, the Raman spectra obtained inside the USP vial and on open powders differed by less than 5%. A spectral library of 309 reference materials was constructed, with spectral acquisition times ranging from 1 to 60 s. Of these, 8% had significant fluorescent background but observable Raman features, while 3% showed only fluorescence. A blind test of 26 unknowns revealed the accuracy of the library search to be 88-96%, depending on search algorithm, and 100% if operator discretion was permitted. The tolerance of the library search to degraded signal-to-noise ratio, resolution, and Raman shift accuracy were tested, and the search was very robust. The results demonstrate that Raman spectroscopy provides a rapid, noninvasive technique for compound identification. C1 Ohio State Univ, Dept Chem, Columbus, OH 43210 USA. US FDA, Div Drug Anal, St Louis, MO 63107 USA. RP McCreery, RL (reprint author), Ohio State Univ, Dept Chem, 100 W 18th Ave, Columbus, OH 43210 USA. EM mccreery.2@osu.edu RI McCreery, Richard/H-8371-2012 OI McCreery, Richard/0000-0002-1320-4331 NR 18 TC 36 Z9 36 U1 0 U2 6 PU AMER PHARMACEUTICAL ASSN PI WASHINGTON PA 2215 CONSTITUTION AVE NW, WASHINGTON, DC 20037 USA SN 0022-3549 J9 J PHARM SCI JI J. Pharm. Sci. PD JAN PY 1998 VL 87 IS 1 BP 1 EP 8 DI 10.1021/js970330q PG 8 WC Chemistry, Medicinal; Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Pharmacology & Pharmacy; Chemistry GA YQ511 UT WOS:000071395100001 PM 9452960 ER PT J AU Kanik, KS Hagiwara, E Yarboro, CH Schumacher, HR Wilder, RL Klinman, DM AF Kanik, KS Hagiwara, E Yarboro, CH Schumacher, HR Wilder, RL Klinman, DM TI Distinct patterns of cytokine secretion characterize new onset synovitis versus chronic rheumatoid arthritis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE rheumatoid arthritis; cytokines; immunology; interferon-gamma; interleukin 2; tumor necrosis factor-alpha ID SYSTEMIC LUPUS-ERYTHEMATOSUS; T-CELL CLONES; LYMPHOKINE ACTIVITIES; TH1; AUTOIMMUNITY; PROFILES; DISEASES; ALPHA; BLOOD AB Objective. To compare patterns of cytokine secretion in patients with new onset synovitis (< 1 yr duration, n = 14), chronic rheumatoid arthritis (RA) (n = 16), and healthy controls (n = 17). Methods. ELIspot assays were used to detect mononuclear cells in the peripheral blood (PMBC) and synovial fluid (SFMC) secretion the type 1 cytokines interleukin 2 (IL-2) and interferon-gamma (IFN-gamma), the type 2 cytokines IL-4, IL-6 and IL-10, and the inflammatory cytokine tumor necrosis factor-alpha (TNF-alpha). Results were correlated with measures of disease activity. Results. Patients with new onset synovitis had increased (p < 0.05) numbers of PBMC secreting IL-2. The number of PBMC secreting IFN-gamma correlated with the joint score in the new onset synovitis population (p = 0.006). By comparison, patients with chronic RA had significantly increased numbers of PBMC secreting IL-6, IL-10, and TNF-alpha (p < 0.05). The production of these cytokines correlated with joint score in chronic RA (p = 0.008, 0.06, 0.001, respectively). Conclusion. Patients with new onset synovitis have increased numbers of PBMC secreting IL-2 and IFN-gamma, while patients with chronic RA have increased numbers of PBMC secreting IL-6, IL-10, and TNF-alpha. Correlations between joint score and number of PBMC secreting cytokines suggest the number of PBMC secreting IFN-gamma is most relevant in new onset synovitis, while the number of PBMC secreting IL-6, IL-10, and TNF-alpha is of greater relevance in chronic RA. C1 NIAMS, Inflammatory Joint Dis Sect, Arthrit & Rheumatism Branch, NIH, Bethesda, MD USA. US FDA, Sect Retroviral Res, Div Viral Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. RP Kanik, KS (reprint author), Univ S Florida, Coll Med, Div Rheumatol, 12901 Bruce B Downs Blvd, Tampa, FL 33612 USA. NR 28 TC 43 Z9 53 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 JAN PY 1998 VL 25 IS 1 BP 16 EP 22 PG 7 WC Rheumatology SC Rheumatology GA YQ723 UT WOS:000071416800005 PM 9458197 ER PT J AU Furst, DE Clements, PJ Steen, VD Medsger, TA Masi, AT D'Angelo, WA Lachenbruch, PA Grau, RG Seibold, JR AF Furst, DE Clements, PJ Steen, VD Medsger, TA Masi, AT D'Angelo, WA Lachenbruch, PA Grau, RG Seibold, JR TI The modified Rodnan skin score is an accurate reflection of skin biopsy thickness in systemic sclerosis SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE systemic sclerosis; skin score; skin biopsy ID SCLERODERMA; VARIABILITY; DISEASE AB Objective. To test the ability of the modified Rodnan skin score to reflect skin thickness in skin biopsies from 141 patients with systemic sclerosis (SSc) obtained at entry during a prospective, double blind study of ketanserin versus placebo in SSc. Methods. Punch skin biopsies (4 mm) were obtained from the dorsal surface of the distal forearm of 141 patients. Biopsy specimens were trimmed and weighed (wet weight) and then desiccated and reweighed (dry weight). Skin score was recorded for 17 areas, graded 0-4+, while edema was graded 0-4+ in 10 of the same sites using finger pressure. Results. Total skin score correlated with wet weight (r = 0.553) and dry weight (r = 0.517) of the skin biopsies. Local skin score from the biopsied forearm also correlated with wet and dry weight (r = 0.536 and 0.530, respectively). Dry weight as a percentage of wet weight was the same for diffuse cutaneous SSc (dSSc) and limited cutaneous SSc (lSSc) (30.7% for both, NS), despite increased wet weight in patients with dSSc versus lSSc (17.75 vs 13.03 g; p < 0.001). Edema scores correlated poorly both with wet weight (r = 0.069) and dry weight (r = 0.169). Conclusion. Total and forearm skin score correlates well with both wet and dry forearm skin biopsy weight from forearm biopsies, indicating that skin score reflects the underlying pathology of SSc. Further, the percentage of dry to wet weight is similar for lSSc and dSSc, supporting the usefulness of skin score in differentiating SSc disease subtypes. C1 Virginia Mason Res Ctr, Arthrit Clin Res Unit, Seattle, WA 98101 USA. Univ Calif Los Angeles, Sch Med, Dept Med, Los Angeles, CA 90024 USA. Georgetown Univ, Med Ctr, Dept Rheumatol, Washington, DC 20007 USA. Univ Pittsburgh, Sch Med, Div Rheumatol & Clin Immunol Med Rheumatol, Pittsburgh, PA USA. Univ Illinois, Coll Med, Peoria, IL 61656 USA. US FDA, Washington, DC 20204 USA. Univ Med & Dent New Jersey, Robert Wood Johnson Med Sch, Scleroderma Program, New Brunswick, NJ USA. RP Furst, DE (reprint author), Virginia Mason Res Ctr, Arthrit Clin Res Unit, 1000 Seneca St, Seattle, WA 98101 USA. OI Masi, Alfonse/0000-0002-9695-6634 FU NCRR NIH HHS [M01-RR00865]; NIAMS NIH HHS [P60AR-36834] NR 22 TC 140 Z9 145 U1 0 U2 2 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 JAN PY 1998 VL 25 IS 1 BP 84 EP 88 PG 5 WC Rheumatology SC Rheumatology GA YQ723 UT WOS:000071416800016 PM 9458208 ER PT J AU Hagiwara, E Pando, J Ishigatsubo, Y Klinman, DM AF Hagiwara, E Pando, J Ishigatsubo, Y Klinman, DM TI Altered frequency of type 1 cytokine secreting cells in the peripheral blood of patients with primary Sjogren's syndrome SO JOURNAL OF RHEUMATOLOGY LA English DT Article DE Sjogren's syndrome; type 1 cytokine; peripheral blood mononuclear cells; ELISPOT assay ID SYSTEMIC LUPUS-ERYTHEMATOSUS; MRL/LPR MICE; IMMUNE REGULATION; SALIVARY-GLANDS; FLOW-CYTOMETRY; HIV-INFECTION; T-CELLS; EXPRESSION; IL-10; AUTOANTIBODIES AB Objective. An imbalance in immunoregulatory cytokines may contribute to the etiopathogenesis of Sjogren's syndrome (SS). We investigated systemic abnormalities in cytokine production in the peripheral blood in patients with SS. Methods. ELISPOT assays were used to detect and enumerate cells spontaneously secreting interleukin 2 (IL-2), IL-6, IL-10, and interferon-gamma (IFN-gamma) in freshly isolated peripheral blood mononuclear cells from 20 patients with SS and 20 healthy controls. Results. The number of cells spontaneously secreting type 1 cytokines IL-2 and IFN-gamma was decreased in the peripheral blood of patients with SS compared to controls. There was no change observed in the number of cells spontaneously secreting IL-6 and IL-10. Cells spontaneously secreting IL-4 were too rare in peripheral blood to evaluate, although cells capable of secreting IL-4 in response to phytohemagglutinin did not differ from controls. Patients with severe extraglandular symptoms (such as vasculitis) had a significantly lower frequency of IFN-gamma secreting cells in their peripheral blood than those without extraglandular involvement. Conclusion. These results suggest that decreased type 1 cytokine production may contribute to or reflect the pathogenesis of SS. C1 Yokohama City Univ, Sch Med, Dept Internal Med 1, Kanazawa Ku, Yokohama, Kanagawa 236, Japan. US FDA, Sect Retroviral Immunol, Ctr Biol Evaluat & Res, Bethesda, MD 20014 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. RP Hagiwara, E (reprint author), Yokohama City Univ, Sch Med, Dept Internal Med 1, Kanazawa Ku, 3-9 Fukuura, Yokohama, Kanagawa 236, Japan. NR 41 TC 33 Z9 34 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 JAN PY 1998 VL 25 IS 1 BP 89 EP 93 PG 5 WC Rheumatology SC Rheumatology GA YQ723 UT WOS:000071416800017 PM 9458209 ER PT J AU Pierdominici, VJB Doucette, JM Coyne, L Cyr, WH Thomas, DP Lytle, CD AF Pierdominici, VJB Doucette, JM Coyne, L Cyr, WH Thomas, DP Lytle, CD TI Ability of quality assurance tests to detect punctured latex condoms with potential for virus penetration SO JOURNAL OF TESTING AND EVALUATION LA English DT Article DE quality assurance test; latex condoms; puncture; virus ID SENSITIVITY AB How well do the quality assurance tests for latex condoms detect the potential for virus penetration? Defective condoms were created by puncturing with small acupuncture needles (120, 160 or 300 mu m diameter) and were then tested by three quality assurance (QA) tests (the water leak test, a proposed electrical test, and the air burst test) and by a virus penetration test. Punctures (short tears) were detected by the FDA water leak test at the rate of 52% for punctures in the condom body and 9% in the condom tip; by the proposed ISO electrical leakage test (28% and 18% for body and tip, respectively); or by the 180 air burst test (30% and 5%, respectively). A standardized in vitro test of virus penetration under physiologic-based conditions detected 100% and 48% of the punctures for body and tip, respectively. Thus the small tears created by puncture may not be detected in quality assurance tests, but would allow some virus penetration in the laboratory virus penetration test. A puncture in the tip of a condom was most likely to escape detection by each of the test methods, presumably because a puncture in that location does not open up as easily as elsewhere. Data with the air burst test indicated that raising the burst volume and/or burst pressure pass/fail limit would increase the likelihood of detecting a puncture defect to >93% when in the condom body, but to <15% when in the tip. C1 US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Pierdominici, VJB (reprint author), US FDA, Winchester Engn & Analyt Ctr, Winchester, MA 01890 USA. NR 13 TC 0 Z9 0 U1 0 U2 1 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 JAN PY 1998 VL 26 IS 1 BP 10 EP 14 PG 5 WC Materials Science, Characterization & Testing SC Materials Science GA ZA066 UT WOS:000072325500002 ER PT J AU White, GG Love, L AF White, GG Love, L TI The MedWatch program SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY LA English DT Editorial Material C1 US FDA, MedWatch, Rockville, MD 20857 USA. RP White, GG (reprint author), US FDA, MedWatch, Rockville, MD 20857 USA. NR 0 TC 3 Z9 3 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3810 J9 J TOXICOL-CLIN TOXIC JI J. Toxicol.-Clin. Toxicol. PY 1998 VL 36 IS 1-2 BP 145 EP 149 PG 5 WC Toxicology SC Toxicology GA ZE974 UT WOS:000072850200036 PM 9541064 ER PT J AU Love, L AF Love, L TI Regulatory and safety issues regarding special nutritional products SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY LA English DT Article C1 US FDA, MedWatch, Rockville, MD 20857 USA. RP Love, L (reprint author), US FDA, MedWatch, Rockville, MD 20857 USA. NR 0 TC 4 Z9 4 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3810 J9 J TOXICOL-CLIN TOXIC JI J. Toxicol.-Clin. Toxicol. PY 1998 VL 36 IS 3 BP 263 EP 265 PG 3 WC Toxicology SC Toxicology GA ZX871 UT WOS:000074563800018 PM 9656988 ER PT J AU White, GG Weick-Brady, MD Gross, TP AF White, GG Weick-Brady, MD Gross, TP TI Improving patient care by reporting problems with medical devices SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP White, GG (reprint author), US FDA, Rockville, MD 20857 USA. NR 11 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3810 J9 J TOXICOL-CLIN TOXIC JI J. Toxicol.-Clin. Toxicol. PY 1998 VL 36 IS 6 BP 641 EP 644 PG 4 WC Toxicology SC Toxicology GA 127JM UT WOS:000076347400020 PM 9776975 ER PT J AU White, GG Love, L AF White, GG Love, L TI The MedWatch Program SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP White, GG (reprint author), US FDA, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3810 J9 J TOXICOL-CLIN TOXIC JI J. Toxicol.-Clin. Toxicol. PY 1998 VL 36 IS 6 BP 645 EP 648 PG 4 WC Toxicology SC Toxicology GA 127JM UT WOS:000076347400021 PM 9776976 ER PT J AU Varricchio, F AF Varricchio, F TI The Vaccine Adverse Event Reporting System SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY LA English DT Editorial Material ID IMMUNIZATION; VAERS C1 US FDA, Ctr Biol Evaluat & Review, Div Biostat & Epidemiol, Rockville, MD 20857 USA. RP Varricchio, F (reprint author), US FDA, Ctr Biol Evaluat & Review, Div Biostat & Epidemiol, Rockville, MD 20857 USA. NR 9 TC 9 Z9 9 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3810 J9 J TOXICOL-CLIN TOXIC JI J. Toxicol.-Clin. Toxicol. PY 1998 VL 36 IS 7 BP 765 EP 768 PG 4 WC Toxicology SC Toxicology GA 149RP UT WOS:000077619400024 PM 9865252 ER PT J AU White, GG Love, L AF White, GG Love, L TI The MedWatch program SO JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY LA English DT Editorial Material C1 US FDA, Medwatch, Rockville, MD 20857 USA. RP White, GG (reprint author), US FDA, Medwatch, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3810 J9 J TOXICOL-CLIN TOXIC JI J. Toxicol.-Clin. Toxicol. PY 1998 VL 36 IS 7 BP 769 EP 770 PG 2 WC Toxicology SC Toxicology GA 149RP UT WOS:000077619400025 ER PT J AU Nussenblatt, RB Bron, A Chambers, W McCulley, JP Pericoi, M Ubels, JL Edelhauser, HF AF Nussenblatt, RB Bron, A Chambers, W McCulley, JP Pericoi, M Ubels, JL Edelhauser, HF TI Ophthalmologic perspectives on eye irritation testing SO JOURNAL OF TOXICOLOGY-CUTANEOUS AND OCULAR TOXICOLOGY LA English DT Article ID BOVINE CORNEAL OPACITY; ASSAY C1 NEI, NIH, Bethesda, MD 20892 USA. Univ Oxford, Nuffield Lab Ophthalmol, Oxford OX2 6AW, England. US FDA, Washington, DC 20204 USA. Univ Texas, SW Med Sch, Dallas, TX 75230 USA. Peritesco, Paris, France. Calvin Coll, Grand Rapids, MI 49506 USA. Emory Univ, Atlanta, GA 30322 USA. RP Nussenblatt, RB (reprint author), Care of Porter L, Hlth & Environm Sci Inst, 1126 16th St, Washington, DC 20036 USA. NR 15 TC 18 Z9 18 U1 0 U2 0 PU MARCEL DEKKER INC PI NEW YORK PA 270 MADISON AVE, NEW YORK, NY 10016 USA SN 0731-3829 J9 J TOXICOL-CUTAN OCUL JI J. Toxicol.-Cutan. Ocul. Toxicol. PY 1998 VL 17 IS 2-3 BP 103 EP 109 PG 7 WC Ophthalmology; Toxicology SC Ophthalmology; Toxicology GA 126BY UT WOS:000076273900002 ER PT J AU Zhang, Y Kaplan, GG AF Zhang, Y Kaplan, GG TI Characterization of replication-competent hepatitis A virus constructs containing insertions at the N terminus of the polyprotein SO JOURNAL OF VIROLOGY LA English DT Article ID 5' NONTRANSLATED REGION; ATTENUATED MENGO-VIRUS; CAPSID PROTEIN VP4; A VIRUS; MONOCLONAL-ANTIBODIES; POLIOVIRUS REPLICONS; STRUCTURAL PROTEINS; SUBVIRAL PARTICLES; VECTOR; RNA AB To determine whether hepatitis A virus (HAV) could tolerate the insertion of exogenous sequences, we constructed full-length HAV cDNAs containing in-frame insertions at the N terminus of the polyprotein and transfected the derived T7 RNA polymerase in vitro transcripts into FRhK-4 cells. Replication of HAVvec1, a construct containing an insertion of 60 nucleotides coding for a polylinker, a 2B/2C cleavage site for HAV protease 3C(pro), and two initiation codons that restored the sequence of the N terminus of the polyprotein, was detected 2 weeks after transfection by indirect immunofluorescence analysis using anti-HAV monoclonal antibodies. Western blot analysis of HAVvec1-infected cells using anti-VP2 and anti-VP4 antibodies failed to detect the expression of the inserted sequences. Insertion of a 24-mer oligonucleotide coding for a FLAG epitope into HAVvec1 resulted in its HAV-mediated expression which was retained upon deletion of a Gin residue from the inserted 2B/2C cleavage site. Western blot analysis using anti-FLAG and anti-VP2 antibodies showed that the FLAG epitope accumulated in infected cells fused to VP0. Replacement of the FLAG epitope with an epitope of the circumsporozoite protein (CSP) of Plasmodium falciparum resulted in its stable HAV-mediated expression for at least six serial passages in FRhK-4 cells. Sedimentation analysis in sucrose density gradients showed that the CSP epitope accumulated in infected cells fused to VP0, forming 80S empty capsids which also contained native VPO. Our data suggest that the HAV internal ribosome entry site can efficiently direct dual initiation of translation of the polyprotein from AUG codons separated by 66 to 78 nucleotides and show that HAV can tolerate insertions at the N terminus of the polyprotein. C1 US FDA, CTR BIOL EVALUAT & RES, DIV VIRAL PROD, LAB HEPATITIS RES, BETHESDA, MD 20892 USA. NR 48 TC 13 Z9 13 U1 0 U2 0 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1752 N ST NW, WASHINGTON, DC 20036-2904 USA SN 0022-538X EI 1098-5514 J9 J VIROL JI J. Virol. PD JAN PY 1998 VL 72 IS 1 BP 349 EP 357 PG 9 WC Virology SC Virology GA YL010 UT WOS:A1998YL01000040 PM 9420233 ER PT J AU Valle, RPC Falgout, B AF Valle, RPC Falgout, B TI Mutagenesis of the NS3 protease of dengue virus type 2 SO JOURNAL OF VIROLOGY LA English DT Article ID YELLOW-FEVER VIRUS; HEPATITIS-C VIRUS; NONSTRUCTURAL PROTEINS; NUCLEOTIDE-SEQUENCE; ENCEPHALITIS-VIRUS; VIRAL POLYPROTEIN; NS2B-NS3 PROTEASE; CRYSTAL-STRUCTURE; CLEAVAGE SITE; GENOME AB The flavivirus protease is composed of two viral proteins, NS2B and NS3. The amino-terminal portion of NS3 contains sequence and structural motifs characteristic of bacterial and cellular trypsin-like proteases. We have undertaken a mutational analysis of the region of NS3 which contains the catalytic serine, five putative substrate binding residues, and several residues that are highly conserved among flavivirus proteases and among all serine proteases. In all, 46 single-amino-acid substitutions were created in a cloned NS2B-NS3 cDNA fragment of dengue virus type 2, and the effect of each mutation on the extent of self-cleavage of the NS2B-NS3 precursor at the NS2B-NS3 junction was assayed in vivo. Twelve mutations almost completely or completely inhibited protease activity, 9 significantly reduced it, 14 decreased cleavage, and 11 yielded wild-type levels of activity. Substitution of alanine at ultraconserved residues abolished NS3 protease activity. Cleavage was also inhibited by substituting some residues that are conserved among flavivirus NS3 proteins. Two (Y150 and G153) of the five putative substrate binding residues could not be replaced by alanine, and only Y150 and N152 could be replaced by a conservative change. The two other putative substrate binding residues, D129 and F130, were more freely substitutable. By analogy with the trypsin model, it was proposed that D129 is located at the bottom of the substrate binding pocket so as to directly interact with the basic amino acid at the substrate cleavage site. Interestingly, we found that significant cleavage activity was displayed by mutants in which D129 was replaced by E, S, or A and that low but detectable protease activity was exhibited by mutants in which D129 was replaced by K, R, or L. Contrary to the proposed model, these results indicate that D129 is not a major determinant of substrate binding and that its interaction with the substrate, if it occurs at all, is not essential. This mutagenesis study provided us with an array of mutations that alter the cleavage efficiency of the dengue virus protease. Mutations that decrease protease activity without abolishing it are candidates for introduction into the dengue virus infectious full-length cDNA clone with the aim of creating potentially attenuated virus stocks. C1 US FDA,LAB VECTOR BORNE VIRAL DIS,CTR BIOL EVALUAT & RES,BETHESDA,MD 20852. NR 42 TC 53 Z9 55 U1 2 U2 9 PU AMER SOC MICROBIOLOGY PI WASHINGTON PA 1325 MASSACHUSETTS AVENUE, NW, WASHINGTON, DC 20005-4171 SN 0022-538X J9 J VIROL JI J. Virol. PD JAN PY 1998 VL 72 IS 1 BP 624 EP 632 PG 9 WC Virology SC Virology GA YL010 UT WOS:A1998YL01000074 PM 9420267 ER PT J AU Durkin, AJ Ediger, MN Pettit, GH AF Durkin, AJ Ediger, MN Pettit, GH TI Quantification of polydimethylsiloxane concentration in turbid samples using Raman spectroscopy and the method of partial least squares SO LASERS IN MEDICAL SCIENCE LA English DT Article DE biomedical diagnostics; breast implant leakage; optical spectroscopy; partial lest squares; polydimethylsiloxane (PDMS); Raman spectroscopy; silicone ID SILICONE BREAST IMPLANTS; MICROSCOPIC IDENTIFICATION; CAPSULAR CONTRACTURE; FILLED IMPLANTS; GEL; PROSTHESES; MIGRATION; TISSUE; WOMEN; RECONSTRUCTION AB This paper presents a preliminary application of Raman spectroscopy in conjunction with the chemometric method of partial least squares to predict silicone concentrations in homogenous turbid samples. The chemometric technique is applied to Raman spectra to develop an empirical, linear model relating sample spectra to polydimethylsiloxane (silicone) concentration. This is done using a training set of samples having optical properties and known concentrations representative of those unknown samples to be predicted. Partial least squares, performed via cross-validation, was able to predict silicone concentrations in good agreement with true values. The detection limit obtained for this preliminary investigation is similar to that reported in the magnetic resonance spectroscopy literature. The data acquisition time for this Raman-based method is 200 s which compares favourably with the 17 h acquisition required for magnetic resonance spectroscopy to obtain a similar sensitivity. The combination of Raman spectroscopy and chemometrics shows promise as a tool for quantification of silicone concentrations from turbid samples. C1 US FDA, CDRH, HFZ 134, Electroopt Branch, Rockville, MD 20852 USA. Autonomous Technol Corp, Orlando, FL USA. RP Durkin, AJ (reprint author), US FDA, CDRH, HFZ 134, Electroopt Branch, 1901 Chapman Ave,Rm 6, Rockville, MD 20852 USA. NR 43 TC 2 Z9 2 U1 0 U2 6 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0268-8921 J9 LASER MED SCI JI Lasers Med. Sci. PY 1998 VL 13 IS 1 BP 32 EP 41 DI 10.1007/BF00592958 PG 10 WC Engineering, Biomedical; Surgery SC Engineering; Surgery GA ZN437 UT WOS:000073645800005 ER PT J AU Verthelyi, D Dybdal, N Elias, KA Klinman, DM AF Verthelyi, D Dybdal, N Elias, KA Klinman, DM TI DNAse treatment does not improve the survival of lupus prone (NZB x NZW)F-1 mice SO LUPUS LA English DT Article DE DNAse; anti-DNA; systemic lupus erythematosus; (NZB x NZW)F-1 mice ID B-CELL ACTIVATION; NZB-W MICE; ANTI-DNA; AUTOIMMUNE-DISEASE; PERIPHERAL-BLOOD; ANTIBODIES BIND; PLASMA DNA; ERYTHEMATOSUS; MURINE; DEOXYRIBONUCLEASE AB Objective: To examine the efficacy of deoxyribonuclease I (DNAse) therapy in the (NZB x NZW)F-1 murine model of lupus. Methods: Lupus-prone female (NZB x NZW)F-1 mice were treated daily with 0-15 mu g/g of recombinant DNAse for 1-6months. Parameters including anti-DNA autoantibody production, activation of cytokine secreting cells, kidney function and longevity were monitored. Results: DNAse treatment selectively reduced the number of B cells secreting anti-dsDNA antibodies for approximately one month. However, neither short-term nor long-term treatment altered cytokine production, delayed the onset or reduced the severity of glomerulonephrilis, or prolonged survival. Conclusion: DNAse treatment initiated before, during, or after the onset of murine lupus did not improve clinical outcome. C1 US FDA, CBER, Retroviral Immunol Sect, Bethesda, MD 20892 USA. Genentech Inc, Dept Pathol, S San Francisco, CA 94080 USA. Genentech Inc, Cardiovasc Res, S San Francisco, CA 94080 USA. RP Klinman, DM (reprint author), US FDA, CBER, Retroviral Immunol Sect, Bldg 29A,Room 3 D10, Bethesda, MD 20892 USA. NR 43 TC 23 Z9 23 U1 0 U2 0 PU STOCKTON PRESS PI BASINGSTOKE PA HOUNDMILLS, BASINGSTOKE RG21 6XS, HAMPSHIRE, ENGLAND SN 0961-2033 J9 LUPUS JI Lupus PY 1998 VL 7 IS 4 BP 223 EP 230 DI 10.1191/096120398678920037 PG 8 WC Rheumatology SC Rheumatology GA ZT847 UT WOS:000074133900003 PM 9643311 ER PT S AU Brown, DG Pastel, MS Myers, KJ AF Brown, DG Pastel, MS Myers, KJ BE Hanson, KM TI Neural-network decision functions for a limited-view reconstruction task SO MEDICAL IMAGING 1998: IMAGE PROCESSING, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 1998 Conference on Image Processing CY FEB 23-26, 1998 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiat Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Informat Syst Consortium, Radiol Soc N Amer, Soc Comp Applicat Radiol DE neural network; reconstruction algorithm; image evaluation; back-propagation AB Neural networks are applied to a Rayleigh discrimination task for simulated limited-view computed tomography with maximum-entropy reconstruction. Network performance is compared to that obtained using the best machine approximation to the ideal observer found in an earlier investigation. Results obtained on two-dimensional subimage inputs are compared with those for one-dimensional inputs and presented previously at this conference. Back-propagation neural networks significantly outperform the "best" standard nonadaptive linear machine observer and also the intuitively appealing "matched filter" obtained by averaging over the images in a large training data set. In addition, the backpropagation neural network operating on two-dimensional subimages performs significantly better than that limited to one-dimensional inputs. Finally, improved performance on this Rayleigh task is found for nonlinear lover linear, that is, simple perceptron) neural network decision strategies. C1 US FDA, CDRH, Rockville, MD 20857 USA. RP Brown, DG (reprint author), US FDA, CDRH, 12720 Twinbrook Pkwy, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPIE-INT SOC OPTICAL ENGINEERING PI BELLINGHAM PA 1000 20TH ST, PO BOX 10, BELLINGHAM, WA 98227-0010 USA SN 0277-786X BN 0-8194-2783-7 J9 P SOC PHOTO-OPT INS PY 1998 VL 3338 BP 355 EP 362 DI 10.1117/12.310912 PN 1 & 2 PG 8 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BL38V UT WOS:000075346500035 ER PT S AU Wagner, RF Chan, HP Mossoba, JT Sahiner, B Petrick, N AF Wagner, RF Chan, HP Mossoba, JT Sahiner, B Petrick, N BE Hanson, KM TI Components of variance in ROC analysis of CADx classifier performance SO MEDICAL IMAGING 1998: IMAGE PROCESSING, PTS 1 AND 2 SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT Medical Imaging 1998 Conference on Image Processing CY FEB 23-26, 1998 CL SAN DIEGO, CA SP SPIE, Amer Assoc Physicists Med, Amer Physiol Soc, FDA Ctr Devices & Radiat Hlth, Soc Imaging Sci & Technol, Natl Elect Manufacturers Assoc, Diagnost Imaging & Therapy Syst Div, Radiol Informat Syst Consortium, Radiol Soc N Amer, Soc Comp Applicat Radiol DE computer-aided diagnosis; classifier performance; analysis of variance; ROC analysis; Wilcoxon statistic AB We analyze the contributions to the population variance of the area under the ROC curve in assessment of CADx classifier performance and consider a number of models for this variance. The models all contain a pure term or terms in the number of training samples, a pure term in the number of test samples, plus a term or terms representing their interaction. The subset of terms containing the number of test samples also provide a model for what we call the mean Wilcoxon variance based on a single data set. By this variance we mean a nonparametric estimate of the uncertainty in the ROC area obtainable from a single experiment. The remaining terms-i.e., the pure terms in the number of training samples-are not directly estimable without drawing additional training samples. We investigate whether they may be inferred indirectly using a resampling strategy. The current study is presented within the context of our previous work on finite-sample effects on classifier performance, and is related to recent work of others on Analysis of Variance (ANOVA) in ROC analysis. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Wagner, RF (reprint author), US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 0 TC 11 Z9 11 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 0-8194-2783-7 J9 P SOC PHOTO-OPT INS PY 1998 VL 3338 BP 859 EP 875 DI 10.1117/12.310896 PN 1 & 2 PG 17 WC Engineering, Biomedical; Optics; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Radiology, Nuclear Medicine & Medical Imaging GA BL38V UT WOS:000075346500084 ER PT J AU Teruya-Feldstein, J Berkowitz, JR Bud, PR Kingma, DW Mueller, BU Tosato, G Jaffe, ES AF Teruya-Feldstein, J Berkowitz, JR Bud, PR Kingma, DW Mueller, BU Tosato, G Jaffe, ES TI Chemokine mRNA expression in lymphocytic interstitial pneumonitis tissues from HIV-infected pediatric patients SO MODERN PATHOLOGY LA English DT Meeting Abstract C1 NCI, Bethesda, MD 20892 USA. US FDA, Bethesda, MD 20014 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU LIPPINCOTT WILLIAMS & WILKINS PI PHILADELPHIA PA 227 EAST WASHINGTON SQ, PHILADELPHIA, PA 19106 USA SN 0893-3952 J9 MODERN PATHOL JI Mod. Pathol. PD JAN PY 1998 VL 11 IS 1 BP 180A EP 180A PG 1 WC Pathology SC Pathology GA YV140 UT WOS:000071793401075 ER PT B AU Pohland, AE AF Pohland, AE BE Miraglia, M VanEgmond, HP Brera, C Gilbert, J TI Overview of international mycotoxin and phycotoxin programs SO MYCOTOXINS AND PHYCOTOXINS - DEVELOPMENTS IN CHEMISTRY, TOXICOLOGY AND FOOD SAFETY LA English DT Proceedings Paper CT IX International IUPAC Symposium on Mycotoxins and Phycotoxins CY MAY 27-31, 1996 CL ROME, ITALY SP Int Union Pure & Appl Chem, European Commiss, Stand Measurements & Testing Programme, UN, FAO DE mycotoxins; phycotoxins; regulation; harmonization AB There are a surprising number of international programs on mycotoxins and phycotoxins. The driving force for development of these programs is the effect on human and animal health due to exposure, normally by ingestion, to these toxins. This concern is a relatively recent phenomenon; most international programs on mycotoxins can be traced back to the outbreak of aflatoxicosis in poultry in 1960, subsequently found to be the result of aflatoxin contamination of the feed. Since that time, a substantial number of international, cooperative programs on mycotoxins have been organized, including programs developed by such organizations as the International Union of Pure and Applied Chemistry, the AOAC International, the World Health Organization, the International Oceanographic Commission, the Japanese Mycotoxicology Association, the Latin American Society of Mycotoxicology, etc. As a result, more than 77 countries are currently regulating mycotoxins and phycotoxins, and this has led to international efforts to harmonize such activities in the interest of free trade. These programs and activities seem to be increasing as more mycotoxins are discovered to contaminate foods and feeds. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Pohland, AE (reprint author), US FDA, Ctr Food Safety & Appl Nutr, 200 C St SW, Washington, DC 20204 USA. NR 9 TC 0 Z9 1 U1 0 U2 1 PU ALAKEN, INC PI FT COLLINS PA 305 WEST MAGNOLIA ST SUITE 196, FT COLLINS, CO 80521 USA BN 1-880293-09-9 PY 1998 BP 17 EP 24 PG 8 WC Agronomy; Chemistry, Applied; Food Science & Technology; Public, Environmental & Occupational Health; Toxicology SC Agriculture; Chemistry; Food Science & Technology; Public, Environmental & Occupational Health; Toxicology GA BN44U UT WOS:000081940900002 ER PT J AU Chetty, M Moodley, SV Miller, R AF Chetty, M Moodley, SV Miller, R TI No correlation between test dose of chlorpromazine and therapeutic response in relapsed schizophrenic patients after a "wash out" period of 1-2 weeks. SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 Univ Witwatersrand, Fac Hlth Sci, Dept Expt & Clin Pharmacol, ZA-2193 Parktown, South Africa. Ft Napier Hosp, Pietermartizburg, South Africa. US FDA, Dept Biopharmaceut, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PY 1998 VL 358 IS 1 SU 1 MA P35167 BP R69 EP R69 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 107KV UT WOS:000075207700243 ER PT J AU Paule, MG Fogle, CM Barton, DL Frederick, DL AF Paule, MG Fogle, CM Barton, DL Frederick, DL TI Acute behavioral effects of amphetamine (AMPH), dexfenfluramine (DFEN), lysergic acid diethylamide (LSD), and methylenediox/methamphetamine (MDMA) on timing behavior and motivation in rats SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 US FDA, Div Neurotoxicol, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. US FDA, ROW Sci, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PY 1998 VL 358 IS 1 SU 1 MA P35214 BP R81 EP R81 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA 107KV UT WOS:000075207700289 ER PT J AU Huber, WW Teitel, CH King, RS McDaniel, LP Wiese, R Harris, A Mulder, GJ Kadlubar, FF Schulte-Hermann, R AF Huber, WW Teitel, CH King, RS McDaniel, LP Wiese, R Harris, A Mulder, GJ Kadlubar, FF Schulte-Hermann, R TI Modification of the enzymes N-acetyltransferase and glutathione-S-transferase as a potential chemoprotective mechanism of the coffee components kahweol and cafestol in the rat SO NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY LA English DT Meeting Abstract C1 Univ Vienna, Inst Tumorbiol Krebsforsch, A-1010 Vienna, Austria. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 0 TC 3 Z9 3 U1 1 U2 1 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0028-1298 J9 N-S ARCH PHARMACOL JI Naunyn-Schmiedebergs Arch. Pharmacol. PY 1998 VL 357 IS 4 SU S MA 523 BP R134 EP R134 PG 1 WC Pharmacology & Pharmacy SC Pharmacology & Pharmacy GA ZM863 UT WOS:000073583900531 ER PT S AU Klein, M AF Klein, M BE Ali, SF TI Research issues related to development of medications for treatment of cocaine addiction SO NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUL 16-18, 1997 CL HAMILTON, BERMUDA SP Int Soc Neurochem, Amer Soc Neurochem, Res Biochem Int, Servier Amerique, Warner Lambert Co, Parke Davis, Neurosci Res Div, US FDA, Natl Ctr Toxicol Res ID NICOTINE CHEWING-GUM; SMOKING CESSATION; CONTROLLED TRIAL; DOUBLE-BLIND AB Draft guidelines for the study of medications for treatment of drug addiction have been developed by the Food and Drug Administration's (FDA's) Center for Drug Evaluation and Research, Division of Anesthetic, Critical Care and Addiction Drug Products. These guidelines are intended to provide a common basis for planning, evaluating and interpreting clinical studies and facilitating development of new and effective drugs for the treatment of dependence. For each class of abusable substances, certain clinical situations stand out as targets for intervention, while others mag seem less relevant. Tbe focus of clinical research needs to be tailored to the clinically relevant situations for each drug of abuse. In general, the pharmacotherapies being considered for treatment of abuse and dependence disorders are used to achieve one or more of six major objectives: 1. Reduction in the risk of addiction; 2. Reduction in high-risk behavior; 3. Reduction in morbidity and mortality from addiction; 4. Reduction in drug use and/or induction of abstinence; 5. Relief of symptoms of withdrawal; and 6. Relapse prevention; along with rehabilitation and restoration of functioning. General requirements for outcome measures include measuring drug use, abstinence, withdraw al, and relapse. For all outcomes, both the validity and the meaningfulness must be established. Although considerable neurobiological knowledge relative to cocaine has been acquired, investigation of applicable medications based on these data is still under development. Many studies to date have focused on modifying dopamine function. Because dopamine plays a critical biologic role in motivation, reward and locomotion, modification of its activity may potentially contribute to serious adverse effects. An optimal strategy might require the use of several medications that have different mechanisms of action, or several medications targeted at different aspects of the problem (kg, relapse craving, etc.). The agonist approach is believed to be potentially problematic because of effects on cardiovascular function and temperature regulation. A substitution model (comparable to methadone for heroin dependence) has not been proposed. The antagonist model is hampered by the fact that reinforcing effects are mediated through dopamine, which, if blocked, might produce a sufficient anhedonic state that compliance with the treatment regimen might be unlikely. Unlike opiates and alcohol, the withdrawal syndrome from cocaine and other stimulants is subtle and usually is not seen as requiring medication intervention. C1 US FDA, Ctr Drug Evaluat & Res, Div Anesthet Crit Care & Addict Drug Prod, Rockville, MD 20857 USA. RP Klein, M (reprint author), US FDA, Ctr Drug Evaluat & Res, Div Anesthet Crit Care & Addict Drug Prod, HFD-170,5600 Fisher Lane, Rockville, MD 20857 USA. EM mklein@cder.fds.gov NR 31 TC 24 Z9 24 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-145-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 844 BP 75 EP 91 DI 10.1111/j.1749-6632.1998.tb08223.x PG 17 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26D UT WOS:000074929000008 PM 9668666 ER PT S AU Ali, SF Itzhak, Y AF Ali, SF Itzhak, Y BE Ali, SF TI Effects of 7-nitroindazole, an NOS inhibitor on methamphetamine-induced dopaminergic and serotonergic neurotoxicity in mice SO NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUL 16-18, 1997 CL HAMILTON, BERMUDA SP Int Soc Neurochem, Amer Soc Neurochem, Res Biochem Int, Servier Amerique, Warner Lambert Co, Parke Davis, Neurosci Res Div, US FDA, Natl Ctr Toxicol Res ID NEURONAL NITRIC-OXIDE; TYROSINE-HYDROXYLASE ACTIVITY; STRIATAL DOPAMINE; SUBSTITUTED AMPHETAMINES; C57BL/6J MOUSE; UPTAKE SITES; SYNTHASE; ENVIRONMENT; TEMPERATURE; PROTECTION AB Methamphetamine (METH) is one of the major drugs of abuse that is postulated to cause neurotoxicity by depleting dopamine (DA) and its metabolites, high-affinity DA uptake sites, and the activity of tyrosine hydroxylase. The present study was undertaken to investigate whether the relatively selective, neuronal nitric oxide synthase (NOS) inhibitor, 7-nitroindazole (7-NI), protects against METH-induced neurotoxicity. Male Swiss Webster mice received the following injections intraperitoneally (i.p.) 3 times (every 3 hr): (i) vehicle/saline, (ii) 7-NI (25 mg/kg)/saline, (iii) vehicle/METH (5 mg/kg), and (iv) 7-NI(25 mg/kg)/METH (5 mg/kg), On the second day, groups (i) and (iii) received two vehicle injections and groups (ii) and (iv) received two 7-NI injections (25 mg/kg each). The administration of vehicle/METH resulted in 68, 44 and 55% decreases in the concentration of DA, dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA), respectively, and a 48% decrease in the number of [H-3]mazindol binding sites in the striatum compared to control values. The treatment with 7-NI (group iv) provided a full protection against the depletion of DA and its metabolites, and the loss of dopamine transporter binding sites. Multiple injection of METH caused a significant decrease in the concentration of serotonin (5-HT) and its metabolite 5-hydroxyindole acetic acid (5-HIAA). Treatment with 7-NI partially blocked the depletion of 5-HT and completely blocked the reduction in 5-HIAA levels, The administration of 7-NI/saline (group ii) affected neither the tissue concentration of DA, 5-HT and their metabolites (DOPAC, HVA and 5-HIAA) nor the binding parameters of [H-3]-mazindol compared to control (vehicle/saline) values, 7-NI had no significant effect on the animals' body temperature, and it did not affect METH-induced hyperthermia, These findings indicate a role for nitric oxide in METH-induced neurotoxicity and also suggest that blockage of NOS may be beneficial for the management of Parkinson's disease. C1 US FDA, Div Neurotoxicol, Neurochem Lab, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Univ Miami, Sch Med, Dept Biochem & Mol Biol, Miami, FL 33101 USA. RP Ali, SF (reprint author), US FDA, Div Neurotoxicol, Neurochem Lab, Natl Ctr Toxicol Res, HFT-132, Jefferson, AR 72079 USA. EM sali@nctr.fda.gov; sali@nctr.fda.gov FU NIDA NIH HHS [R55DA08584] NR 35 TC 54 Z9 55 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-145-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 844 BP 122 EP 130 DI 10.1111/j.1749-6632.1998.tb08227.x PG 9 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26D UT WOS:000074929000012 PM 9668670 ER PT S AU Miller, DB Ali, SF O'Callaghan, JP Laws, SC AF Miller, DB Ali, SF O'Callaghan, JP Laws, SC BE Ali, SF TI The impact of gender and estrogen on striatal dopaminergic neurotoxicity SO NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUL 16-18, 1997 CL HAMILTON, BERMUDA SP Int Soc Neurochem, Amer Soc Neurochem, Res Biochem Int, Servier Amerique, Warner Lambert Co, Parke Davis, Neurosci Res Div, US FDA, Natl Ctr Toxicol Res ID MPTP-INDUCED NEUROTOXICITY; FIBRILLARY ACIDIC PROTEIN; RAT-BRAIN; PARKINSONS-DISEASE; CD-1 MICE; RELEASE; 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE; 17-BETA-ESTRADIOL; INCREASES; MOUSE AB The reproductive properties of estrogen are well established, but it is now evident that this steroid hormone has substantial modulatory capabilities in nonreproductive systems. For example, estrogen may be neuroprotective as Alzheimer's disease progresses more slowly in women receiving hormone replacement therapy, and Parkinson's disease affects more men than women. Gender affects both the functional and biochemical responses of the nigral-striatal pathway to dopaminergically active compounds, To begin to evaluate the possible neuroprotective effects of estrogen in this pathway, we first determined if gender affected the dopaminergic striatal neurotoxicity induced by two different neurotoxicants, 1-methgl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and methamphetamine (METH). Both agents induced greater neurotoxicity in males than females as evidenced by greater striatal dopamine (DA) depletions. An examination of striatal levels of 1-methyl-4-phenylpyridium ion (MPP+) following MPTP treatment established that the observed gender differences were not due to metabolic/pharmacokinetic variables, The neurotoxicity of MPTP was then examined in ovariectomized (OVX) mice. Estrogen replacement reduced the DA, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA) depletions as web as the glial fibrillary acidic protein (GFAP) elevation induced by MPTP, which indicates that estrogen has neuroprotective properties in this model of striatal dopaminergic neurotoxicity. Surprisingly, estrogen supplementation did not protect against the neurotoxic effects of MPTP in intact 2-yr-old intact female mice, suggesting that low endogenous levels of estrogen may provide neuroprotection. C1 Ctr Dis Control, NIOSH, Hlth Effects Lab Div, Toxicol & Mol Biol Branch, Morgantown, WV 26505 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US EPA, Natl Hlth & Environm Effects Res Lab, Reprod Toxicol Branch, Div Dev Toxicol, Res Triangle Pk, NC 27711 USA. RP Miller, DB (reprint author), Ctr Dis Control, NIOSH, Hlth Effects Lab Div, Toxicol & Mol Biol Branch, 1095 Willowdale Rd, Morgantown, WV 26505 USA. RI Miller, Diane/O-2927-2013; O'Callaghan, James/O-2958-2013 NR 36 TC 191 Z9 195 U1 0 U2 6 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-145-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 844 BP 153 EP 165 DI 10.1111/j.1749-6632.1998.tb08230.x PG 13 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26D UT WOS:000074929000015 PM 9668673 ER PT S AU Paule, MG Gillam, MP Morris, P AF Paule, MG Gillam, MP Morris, P BE Ali, SF TI The effects of cocaine on nonhuman primate brain function are age dependent SO NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUL 16-18, 1997 CL HAMILTON, BERMUDA SP Int Soc Neurochem, Amer Soc Neurochem, Res Biochem Int, Servier Amerique, Warner Lambert Co, Parke Davis, Neurosci Res Div, US FDA, Natl Ctr Toxicol Res ID RHESUS-MONKEYS; PREGNANCY; EXPOSURE; BATTERY AB The effects of acute intravenous (i.v.) cocaine (COC) on several complex brain functions were studied in rhesus monkeys at 1.5, 3 anti 10-11 pars of age. Subjects performed several operant tasks (for food) that were used to model learning, short-term memory, color and position discrimination, and motivation, and disruption of performance of these tasks was used to quantitate drug effect. Drug effects were age dependent: The youngest subjects were 3 to 10 times less sensitive than the oldest. Presuming the observed behavioral effects of cocaine were caused primarily via its interaction with dopamine (DA) systems, changes in sensitivity to its effects with age are likely a reflection of the functional status of the DA system. These data, along with preliminary data on levels of DA transporters, suggest that the age-related differences in sensitivity to cocaine lie iu, or 'downstream' from, the dopamine receptor. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Behav Toxicol Lab, Jefferson, AR 72079 USA. RP Paule, MG (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Behav Toxicol Lab, 3900 NCTR Dr, Jefferson, AR 72079 USA. FU NIDA NIH HHS [NIDA224-89-003] NR 8 TC 11 Z9 11 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-145-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 844 BP 178 EP 182 DI 10.1111/j.1749-6632.1998.tb08232.x PG 5 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26D UT WOS:000074929000017 PM 9668675 ER PT S AU Frederick, DL Ali, SF Gillam, MP Gossett, J Slikker, W Paule, MG AF Frederick, DL Ali, SF Gillam, MP Gossett, J Slikker, W Paule, MG BE Ali, SF TI Acute effects of dexfenfluramine (d-FEN) and methylenedioxymethamphetamine (MDMA) before and after short-course, high-dose treatment SO NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUL 16-18, 1997 CL HAMILTON, BERMUDA SP Int Soc Neurochem, Amer Soc Neurochem, Res Biochem Int, Servier Amerique, Warner Lambert Co, Parke Davis, Neurosci Res Div, US FDA, Natl Ctr Toxicol Res ID RHESUS-MONKEYS; NEUROTOXICITY; RAT; BRAIN AB The acute behavioral effects of methylenedioxymethamphetamine (MDMA) and dexfenfluramine (d-FEN) sere assessed in six rhesus monkeys using performance in the National Center for Toxicological Research (NCTR) Operant Test Battery (OTB); three additional animals served as controls for neurochemical endpoints. The OTB consists of five food-reinforced tasks designed to model aspects of learning, shortterm memory and attention, time estimation, motivation, and color and position discrimination. Shortly after the acute effects of each drug were determined, three of the monkeys received a short-course, high-dose exposure (2x/day x 4 days, intramuscular (i.m.) injections) of MDMA (10 mg/kg), while three monkeys were exposed to an identical regimen of d-FEN (5 mg/kg). Approximately one month later, the acute effects of each drug sere again determined, In monkeys exposed to high-dose d-FEN, the sensitivities of the OTB tasks to acute disruption by either MDMA or d-FEN were essentially unchanged. Conversely, monkeys treated with high-dose MDMA were less sensitive to the acute behavioral effects of both drugs, although such an effect was seen more frequently for d-FEN and was OTB task specific. Thus a residual behavioral tolerance to the acute behavioral effects of MDMA and d-FEN was noted after high-dose MDMA exposure, but not after high-dose d-FEN exposure. These findings are surprising, as similar neurochemical effects (i.e., significant decreases of ca, 50% in serotonin in frontal cortex and hippocampus) were observed in all monkeys approximately six months after short-course, high-dose MDMA or d-FEN treatment. C1 Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. Natl Ctr Toxicol Res, ROW Sci, Jefferson, AR 72079 USA. RP Frederick, DL (reprint author), Glaxo Wellcome Inc, Int Med Affairs, TN-142,5 Moore Dr, Res Triangle Pk, NC 27709 USA. NR 13 TC 28 Z9 28 U1 0 U2 1 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-145-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 844 BP 183 EP 190 DI 10.1111/j.1749-6632.1998.tb08233.x PG 8 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26D UT WOS:000074929000018 PM 9668676 ER PT S AU Cooney, CA Wise, CK Poirier, LA Ali, SF AF Cooney, CA Wise, CK Poirier, LA Ali, SF BE Ali, SF TI Methamphetamine treatment affects blood and liver S-adenosylmethionine (SAM) in mice - Correlation with dopamine depletion in the striatum SO NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUL 16-18, 1997 CL HAMILTON, BERMUDA SP Int Soc Neurochem, Amer Soc Neurochem, Res Biochem Int, Servier Amerique, Warner Lambert Co, Parke Davis, Neurosci Res Div, US FDA, Natl Ctr Toxicol Res ID ADENOSYL-L-METHIONINE; TYROSINE-HYDROXYLASE ACTIVITY; RAT-BRAIN; SUBSTITUTED AMPHETAMINES; FOLATE-DEFICIENCY; C57BL/6J MOUSE; UPTAKE SITES; NEUROTOXICITY; METABOLISM; METHYLATION AB Methamphetamine (METH) is a major drug of abuse which causes neurotoxicity by depleting dopamine, its metabolites, high-affinity dopamine uptake sites and tyrosine hydroxylase activity in the striatum. Dopamine depletion and reduced dopamine transit are associated with depression. S-Adenosylmethionine (SAM) is the chief methyl donor used in dopamine and other neurotransmitter metabolism in mammals. Low SAM is associated with depression and other psychological and neurological disorders in humans. SAM is used to treat depression and some other neurological and psychiatric disorders. The present study was designed to determine if single or multiple doses of METH induce alterations in blood or liver SAM in mice and if these correlate with dopamine levels in the striatum. Adult male C57 mice were injected intraperitoneally with either single (1 x 40 mg/kg) or multiple (4 x 10 mg/kg) doses of METH. Animals were sacrificed at various intervals. A single injection of METH resulted in slightly higher blood SAM levels at 4 hr. Multiple doses of METH resulted in decreased hepatic and blood SAM levels at 72 hr, Blood SMI returned to control levels by 1 wk. Published Hark shows that dopamine levels increase hours after a single injection of METH, whereas dopamine decreases days after multiple injections of METH. These present data clearly demonstrate that METH dosing leads to significant alterations in liver and blood SARI and that these changes in SMI lo els correlate with changes in striatal dopamine levels. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, Div Mol Epidemiol, Jefferson, AR 72079 USA. Univ Arkansas Med Sci, Dept Biochem & Mol Biol, Little Rock, AR 72205 USA. Univ Arkansas Med Sci, Dept Neurol, Little Rock, AR 72205 USA. RP Ali, SF (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, HFT-132, Jefferson, AR 72079 USA. EM sali@nctr.fda.gov; sali@nctr.fda.gov OI Cooney, Craig/0000-0003-4279-557X NR 61 TC 2 Z9 2 U1 1 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-145-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 844 BP 191 EP 200 DI 10.1111/j.1749-6632.1998.tb08234.x PG 10 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26D UT WOS:000074929000019 PM 9668677 ER PT S AU Mills, K Ansah, TA Ali, SF Shockley, DC AF Mills, K Ansah, TA Ali, SF Shockley, DC BE Ali, SF TI Calcium channel antagonist isradipine attenuates cocaine-induced motor activity in rats: Correlation with brain monoamine levels SO NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUL 16-18, 1997 CL HAMILTON, BERMUDA SP Int Soc Neurochem, Amer Soc Neurochem, Res Biochem Int, Servier Amerique, Warner Lambert Co, Parke Davis, Neurosci Res Div, US FDA, Natl Ctr Toxicol Res ID NUCLEUS-ACCUMBENS; REINFORCING PROPERTIES; STEREOTYPED BEHAVIOR; DOPAMINE; MICRODIALYSIS; SEROTONIN; AMPHETAMINE; NIMODIPINE; BLOCKERS AB Cocaine is a widely abused psychomotor stimulant which acts in the central nervous system (CNS) by blocking the reuptake site. It has been estimated that between 30-60 million people have abused cocaine in the United States. Unfortunately, an effective therapy for cocaine abuse is not available, The calcium channel antagonists (CCAs) are commonly used in the therapy of various cardiovascular diseases and are under investigation due to their potential in modulating calcium-dependent neurotransmitter release. The purpose of this study was to evaluate the acute effect of isradipine on cocaine-induced locomotor and stereotypic activity and correlate the changes in dopamine, serotonin and their metabolites-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA)-levels in the rat brain, Animals were pretreated intraperitoneally (i.p.) with vehicle or CCAs. After 30 minutes they were administered cocaine (20 mg/kg, i.p.). During this period, motor and stereotypic activity was monitored. In a separate experiment, animals were dosed as described above and acre sacrificed by decapitation after the 30-minute treatment period. The nucleus accumbens and caudate nucleus were dissected and analyzed for monoamines using a high-performance liquid chromatography-electrochemical detector (HPLC-ECD), Isradipine (5mg/kg, i.p.) inhibited cocaine-induced locomotor and stereotypic activity by 49% and 36%, respectively, as compared to controls. In the nucleus accumbens cocaine (20 mg/kg, i.p.) increased extracellular dopamine and serotonin le, els by 28% and 73%, respectively, as compared to controls. Isradipine (5 mg/kg, i.p.) pretreatment decreased cocaine-induced extracellular dopamine levels in the nucleus accumbens by 8% while decreasing serotonin levels by 9%. Cocaine (20 mg/kg, i.p.) produced increased levels of both extracellular dopamine and serotonin (9% and 4%, respectively) in the caudate nucleus. Isradipine (5 mg/kg, i.p.) pretreatment decreased cocaine (20 mg/kg i.p.)-induced extracellular dopamine and serotonin levels in the caudate nucleus by 18% and 8%, respectively These experiments suggest that a central mechanism may be involved in attenuation of cocaine-induced motor behaviors by isradipine. C1 Meharry Med Coll, Dept Pharmacol, Nashville, TN 37208 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. RP Mills, K (reprint author), Meharry Med Coll, Dept Pharmacol, 1005 DB Todd Blvd, Nashville, TN 37208 USA. FU NHLBI NIH HHS [TL 32 HL 07809]; NIDA NIH HHS [DA 06686] NR 23 TC 10 Z9 10 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-145-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 844 BP 201 EP 207 DI 10.1111/j.1749-6632.1998.tb08235.x PG 7 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26D UT WOS:000074929000020 PM 9668678 ER PT S AU Onaivi, ES Ali, SF Chakrabarti, A AF Onaivi, ES Ali, SF Chakrabarti, A BE Ali, SF TI In vivo ibogaine blockade and in vitro PKC action of cocaine SO NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUL 16-18, 1997 CL HAMILTON, BERMUDA SP Int Soc Neurochem, Amer Soc Neurochem, Res Biochem Int, Servier Amerique, Warner Lambert Co, Parke Davis, Neurosci Res Div, US FDA, Natl Ctr Toxicol Res ID KINASE-C ACTIVITY; MOLECULAR MECHANISMS; ETHANOL EXPOSURE; NEURAL CELLS; PC12 CELLS; RATS; DRUGS; REINFORCEMENT; TRANSLOCATION; WITHDRAWAL AB Ibogaine may have antiaddiction potential against alcohol, psychostimulant and opiate abuse, but its mechanism of action is unclear. Ibogaine, however, has been demonstrated in numerous studies to have effects in multiple central nervous system (CNS) neurotransmitters systems. We are using in vitro and in vivo systems to study the effects of cocaine and whether these effects can be blocked by ibogaine. For the in vivo studies, we first determined the acute and subacute effects of ibogaine (1-5.0 mg/kg) in mice using the plus-maze test, Acutely increasing doses of ibogaine produced a reduced aversion to the open arms. The subacute administration provoked a variable response which was characterized by fluctuations in aversive and antiaversive behavior of the animals to the open arms of the plus-maze during the 14-day treatment period A separate group of mice received 1.0 mg/kg cocaine for 14 days, and upon abrupt cessation from cocaine treatment, ibogaine 2.5 mg/kg was administered to a subgroup of these mice. Ibogaine reversed the withdrawal aversions produced by the abrupt cessation from cocaine administration. For the in vitro studies, the expression and activity of protein kinase C (PKC) isoforms and Ca2+ levels were examined following the incubation of PC 12 cells with cocaine. This is because PKC plays a key role in a number of cellular and neuronal functions. We report that cocaine disrupts signal transduction in PC 12 cells by altering the expression and activity of PKC isoforms and Ca2+ levels. The data obtained suggest (1) that the PC 12 cells may be useful in studying the neurobiology of abused drugs, like cocaine in vitro, (2) that if anxiety is a factor in drug dependency, then the antiaddictive property of ibogaine in vivo may be associated with modifying the CNS neurotransmission that may be involved in anxiety. it remains to be determined whether the signaling involving PKC is important in the antiaddictive properties of ibogaine. C1 Neurobehav Res Inst, Nashville, TN 37211 USA. Vanderbilt Univ, Sch Med, Dept Psychiat, Nashville, TN 37232 USA. Vanderbilt Univ, Sch Med, Dept Pharmacol, Nashville, TN 37232 USA. US FDA, Natl Ctr Toxicol Res, Neurochem Lab, Jefferson, AR 72079 USA. RP Onaivi, ES (reprint author), Neurobehav Res Inst, 5428 Country Dr, Nashville, TN 37211 USA. FU NCRR NIH HHS [5G12RR0303208]; NHLBI NIH HHS [K14 HL03319, 5T32 HL 07411] NR 49 TC 6 Z9 6 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-145-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 844 BP 227 EP 244 DI 10.1111/j.1749-6632.1998.tb08238.x PG 18 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26D UT WOS:000074929000023 PM 9668681 ER PT S AU Itzhak, Y Ali, SF AF Itzhak, Y Ali, SF BE Ali, SF TI Effect of ibogaine on the various sites of the NMDA receptor complex and sigma binding sites in rat brain SO NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUL 16-18, 1997 CL HAMILTON, BERMUDA SP Int Soc Neurochem, Amer Soc Neurochem, Res Biochem Int, Servier Amerique, Warner Lambert Co, Parke Davis, Neurosci Res Div, US FDA, Natl Ctr Toxicol Res ID MK-801 BINDING; COCAINE; MECHANISMS; CONGENERS; ALKALOIDS; TOLERANCE; MORPHINE; STRIATUM; LIGANDS; MICE AB Although the alkaloid ibogaine is a potent hallucinogenic agent some indications suggest that it may be useful for the treatment of opioid and cocaine addiction. The neurochemical mechanism(s) underlying ibogaine effects remain unclear. In the present study we investigated the interaction of ibogaine with the phencyclidine (PCP) site located in the ionophore of the N-methyl-D-aspartate (NMDA) receptor complex, with the NMDA receptor binding site, and with sigma binding sites. In well-washed membrane preparations of rat cortex and cerebellum, the PCP sites were labeled with [H-3]MK-801 or [H-3]1-[1(2-theinyl)-cyclohexyl]-piperidine ([H-3]TCP), and the NMDA receptor with [H-3]-CGP 39653. The sigma-1 and sigma-2 binding site in rat cortex and cerebellum were labeled with [H-3]pentazocine and [H-3]1,3-di-o-tolyl-guanidine ([H-3]DTG), respectively Results indicated that ibogaine interacts with high- and low-affinity PCP binding sites in the cortex: K-i(H) = 0.01-0.05 mu M; K-i(L) = 2-4 mu M, and only with low-affinity sites in the cerebellum: K-i = 2-4, mu M. In contrast, ibogaine (> 100 mu M) had no affinity for [H-3]-CGP 39653 binding sites (cortex and cerebellum), The affinity of ibogaine for sigma-1 and -2 binding sites in cortex and cerebellum ranged from 1.5-3 mu M. Since NMDA receptor antagonists (e,g,, MK-801) are thought to attenuate opioid withdrawal symptoms and cocaine sensitization, it is possible that binding of ibogaine to the PCP sites contributes to its potential 'endabuse' properties. In turn, ibogaine interaction with sigma binding sites may be associated with its adverse effects. C1 Univ Miami, Sch Med, Dept Biochem & Mol Biol R629, Miami, FL 33101 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Itzhak, Y (reprint author), Univ Miami, Sch Med, Dept Biochem & Mol Biol R629, POB 016129,1600 NW 10th Ave, Miami, FL 33101 USA. FU NIDA NIH HHS [R01DA08584] NR 15 TC 16 Z9 16 U1 0 U2 3 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-145-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 844 BP 245 EP 251 DI 10.1111/j.1749-6632.1998.tb08239.x PG 7 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26D UT WOS:000074929000024 PM 9668682 ER PT S AU Baumann, MH Rothman, RB Ali, SF AF Baumann, MH Rothman, RB Ali, SF BE Ali, SF TI Neurochemical and neuroendocrine effects of ibogaine in rats: Comparison to MK-801 SO NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUL 16-18, 1997 CL HAMILTON, BERMUDA SP Int Soc Neurochem, Amer Soc Neurochem, Res Biochem Int, Servier Amerique, Warner Lambert Co, Parke Davis, Neurosci Res Div, US FDA, Natl Ctr Toxicol Res ID NMDA RECEPTOR COMPLEX; ANTI-ADDICTIVE DRUG; PARASAGITTAL ZONES; PRIMARY METABOLITE; IN-VIVO; MORPHINE; COCAINE; BINDING; CORTICOSTERONE; AMPHETAMINE AB Ibogaine (IBO) is a naturally-occurring indole compound that is being evaluated as a potential medication for substance use disorders. Although the precise mechanism of IBO action is unclear, recent in vitro data show this drug displays properties similar to the noncompetitive N-methyl-D-aspartate (NMDA) antagonist MK-801. The purpose of the present work was to compare in vivo neurobiological effects of IBO and MK-801 in rats. Groups of male rats (n = 6-8/group) were decapitated 30 and 60 min after receiving intraperitoneal (i.p.) IBO (10 & 100 mg/kg), MK-801 (0.1 & 1.0 mg/kg) or vehicle. Trunk blood was collected for the analysis of plasma prolactin and corticosterone; brains were harvested and dissected for determination of dopamine (DA), serotonin (5-HT) and their metabolites. Both IBO and MK-801 increased corticosterone secretion, but only IBO elevated plasma prolactin, IBO produced dramatic reductions in tissue DA levels with concurrent increases in the metabolites, dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA). This profile of IBO-induced changes in DA transmission was observed in the striatum, olfactory tubercle, and hypothalamus. The effects of MK-801 on DA metabolism did not mimic IBO, as MK-801 tended to increase DA and its metabolites. Neither drug appreciably affected 5-HT systems. Our results suggest that the effects of IBO on neuroendocrine function and DA transmission are not due to MK-801-like properties of IBO. Thus, the in vivo mechanism of IBO action cannot be explained simply on the basis of antagonism at NMDA receptors. C1 NIDA, Clin Psychopharmacol Sect, Div Intramural Res, NIH, Baltimore, MD 21224 USA. US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Neurochem Lab, Jefferson, AR 72079 USA. RP Baumann, MH (reprint author), NIDA, Clin Psychopharmacol Sect, Div Intramural Res, NIH, POB 5180,5500 Nathan Shock Dr, Baltimore, MD 21224 USA. NR 43 TC 4 Z9 4 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-145-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 844 BP 252 EP 264 DI 10.1111/j.1749-6632.1998.tb08240.x PG 13 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26D UT WOS:000074929000025 PM 9668683 ER PT S AU Binienda, Z Beaudoin, MA Thorn, BT Prapurna, DR Johnson, JR Fogle, CM Slikker, W Ali, SF AF Binienda, Z Beaudoin, MA Thorn, BT Prapurna, DR Johnson, JR Fogle, CM Slikker, W Ali, SF BE Ali, SF TI Alteration in electroencephalogram and monoamine concentrations in rat brain following ibogaine treatment SO NEUROCHEMISTRY OF DRUGS OF ABUSE: COCAINE, IBOGAINE, AND SUBSTITUTED AMPHETAMINES SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Meeting on Cellular and Molecular Mechanisms of Drugs of Abuse - Cocaine, Ibogaine, and Substituted Amphetamines CY JUL 16-18, 1997 CL HAMILTON, BERMUDA SP Int Soc Neurochem, Amer Soc Neurochem, Res Biochem Int, Servier Amerique, Warner Lambert Co, Parke Davis, Neurosci Res Div, US FDA, Natl Ctr Toxicol Res ID LOCOMOTOR-ACTIVITY; MORPHINE; DRUG AB Ibogaine (IBO) is a psychoactive indole alkaloid that has antiaddictive properties. However, treatment with IBO may lead to neurotoxicity since IBO and its metabolites interact persistently with many neurotransmitter systems, Here, we recorded cortical electroencephalogram (EEG) signals from rats anesthetized with isoflurane. The heart rate (HR) was monitored via electrocardiogram (EKG) electrodes. After the baseline EEG was recorded, rats received one intraperitoneal (i.p.) dose of 50 mg/kg IBO. EEG signals were recorded for 2 hr, Rats were then sacrificed and brains dissected into frontal cortex (FC), caudate nucleus (CN), hippocampus (HIP), and brain stem (BS). The level of dopamine (DA), serotonin (5-HT), and their metabolites were determined by highperformance Liquid chromatography with electrochemical detection (HPLC-ECD). Compared with baseline, a decrease in HR immediately after IBO injection and a decrease in delta, theta, alpha, and beta power spectra frequency bands (1-4, 4-8, 8-13, 13-32 Hz) during the first 30 min after IBO administration was observed. EEG recovered within the nest 15 min. In CN the level of DA decreased and DA, turnover rate increased significantly. The levels of 5-HT increased in FC, The pattern of EKG and EEG response to IBO may be due to multiple receptor interactions of IBO. C1 US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, Jefferson, AR 72079 USA. US FDA, Natl Ctr Toxicol Res, ROW Sci, Jefferson, AR 72079 USA. RP Binienda, Z (reprint author), US FDA, Natl Ctr Toxicol Res, Div Neurotoxicol, HFT 132,3900 NCTR Dr, Jefferson, AR 72079 USA. NR 16 TC 7 Z9 7 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-145-6 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 844 BP 265 EP 273 DI 10.1111/j.1749-6632.1998.tb08241.x PG 9 WC Substance Abuse; Multidisciplinary Sciences; Neurosciences SC Substance Abuse; Science & Technology - Other Topics; Neurosciences & Neurology GA BL26D UT WOS:000074929000026 PM 9668684 ER PT S AU Vacchio, MS Ashwell, JD King, LB AF Vacchio, MS Ashwell, JD King, LB BE McCann, SM Lipton, JM Sternberg, EM Chrousos, GP Gold, PW Smith, CC TI A positive role for thymus-derived steroids in formation of the T-cell repertoire SO NEUROIMMUNOMODULATION: MOLECULAR ASPECTS, INTEGRATIVE SYSTEMS, AND CLINICAL ADVANCES SE Annals of the New York Academy of Sciences LA English DT Article; Proceedings Paper CT 3rd Congress of the International-Society-of-Neuroimmunomodulation on Neuroimmunomodulation - Molecular Aspects, Integrative Systems, and Clinical Advances CY NOV 13-15, 1996 CL BETHESDA, MD SP Int Soc Neuroimmunomodulat, NIH, NCI, Natl Inst Aging, NIAID, Natl Inst Arthritis & Muskuloskeletal & Skin Dis, NICHHD, NIDR, NIMH, Natl Inst Nursing Res, NIH, Off Alternat Med, NIH, Off Behav & Social Sci Res, NIH, Off Rare Dis Res, NIH, Off Res Womens Hlth, Glaxowellcome Inc, TIG Instrumenten Gesell Ag, Vector Lab ID PITUITARY-ADRENAL AXIS; THYMOCYTE DEVELOPMENT; NURSE CELLS; SELECTION; APOPTOSIS; ACTIVATION; DISRUPTION; COMPLEX; DEATH; NEUROSTEROIDS AB T cells undergo rigorous selection processes in the thymus that are necessary to prevent T cells with either autoreactive or nonfunctional T-cell receptors (TCRs) from entering the periphery. Although both positive and negative selection depend on TCR-mediated signals, the means by which a thymocyte interprets these signals to result in survival or death is not understood. Glucocorticoids are known to induce thymocyte apoptosis at high concentrations, but at lower concentrations glucocorticoids can antagonize TCR-mediated deletional signals and allow survival of thymocytes and T cell hybridomas. Interestingly, transgenic mice in which the expression of the glucocorticoid receptor has been downmodulated specifically in thymocytes have abnormal thymocyte differentiation, indicating that glucocorticoids play a significant role in T-cell development. Furthermore, we have demonstrated the presence of steroidogenic enzymes in the thymic epithelium and can show that, in vitro, these cells readily synthesize pregnenolone, the first product in the steroidogenic pathway, and deoxycorticosterone. Inhibition of local glucocorticoid biosynthesis in thymi from TCR transgenic mice during fetal thymic organ culture (FTOC) revealed significant alterations in the process of thymocyte selection. These data suggest that glucocorticoids do not simply suppress the immune system but rather are necessary for thymocyte survival and differentiation. C1 US FDA, Immunol Lab, Div Hematol Prod, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. NCI, Lab Immune Cell Biol, NIH, Bethesda, MD 20852 USA. Univ Penn, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA. RP Vacchio, MS (reprint author), 1401 Rockville Pike,HFM 538, Rockville, MD 20852 USA. EM vacchio@a1.cber.fda.gov NR 35 TC 34 Z9 35 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-072-7 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 840 BP 317 EP 327 DI 10.1111/j.1749-6632.1998.tb09571.x PG 11 WC Endocrinology & Metabolism; Immunology; Multidisciplinary Sciences; Neurosciences SC Endocrinology & Metabolism; Immunology; Science & Technology - Other Topics; Neurosciences & Neurology GA BL14S UT WOS:000074444500029 PM 9629259 ER PT B AU Spyker, DA Alderfer, RJ Goetsch, RA Longmire, AW Kramer, ED AF Spyker, DA Alderfer, RJ Goetsch, RA Longmire, AW Kramer, ED BE Benowitz, NL TI Adverse events and prolonged use of nicotine gum and patch SO NICOTINE SAFETY AND TOXICITY LA English DT Proceedings Paper CT Symposium on the Safety and Toxicity of Nicotine CY DEC 06, 1996 CL BRASELTON, GA SP Soc Res Nicotine & Tobacco C1 US FDA, Div Cardiovasc Resp & Neurol Devices, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. RP Spyker, DA (reprint author), US FDA, Div Cardiovasc Resp & Neurol Devices, Ctr Devices & Radiol Hlth, Rockville, MD 20857 USA. NR 5 TC 2 Z9 2 U1 0 U2 0 PU OXFORD UNIV PRESS PI NEW YORK PA 198 MADISON AVENUE, NEW YORK, NY 10016 USA BN 0-19-511496-5 PY 1998 BP 167 EP 172 PG 6 WC Public, Environmental & Occupational Health; Medicine, General & Internal; Pharmacology & Pharmacy; Toxicology SC Public, Environmental & Occupational Health; General & Internal Medicine; Pharmacology & Pharmacy; Toxicology GA BN39Y UT WOS:000081802100016 ER PT J AU Marmillot, P Satchithanandam, S Liu, QH Lakshman, MR AF Marmillot, P Satchithanandam, S Liu, QH Lakshman, MR TI Taurocholate stimulates the absorption and biotransformation of beta-carotene in intact and lymph duct-cannulated ferrets SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID VITAMIN-A; ANTIOXIDANT; CONVERSION; METABOLISM; RETINOL; ROLES; SERUM; RATS AB We have determined the influence of dietary taurocholate and beta-carotene on the absorption and biotransformation of newly administered beta-[C-14]carotene. Male ferrets were fed the control or beta-carotene diet (0.05% beta-carotene wt/wt) with and without taurocholate (1% wt/wt) for four weeks, and then the absorption and biotransformation of newly administered beta-[C-14]carotene was measured after eight hours in intact or thoracic lymph duct-cannulated animals. Percent recovery of beta-[C-14]carotene in the liver was increased 3.6-fold (p < 0.05) in the taurocholate-fed ferrets regardless of whether they were fed the control or beta-carotene diet. Percent recovery of labeled vitamin A in the liver was also increased by the same magnitude (p < 0.05). These results were confirmed in thoracic lymph duct-cannulated ferrets. The recoveries of beta-carotene label in the lymph were comparable to the corresponding values in livers of intact animals. The recovery of beta-carotene label in the liver was 50% (p < 0.05) higher in beta-carotene-fed than in control animals. Taurocholate stimulates intestinal absorption of newly administered beta-[C-14]carotene and its metabolic conversion to C-14-labeled vitamin A (retinol + retinyl ester) 3.6-fold beta-Carotene absorption is as efficient in thoracic lymph duct-cannulated ferrets as in intact animals. Prior beta-carotene feeding also stimulates the absorption of newly administered beta-carotene by 50%. C1 George Washington Univ, Dept Med, Washington, DC 20037 USA. Dept Vet Affairs Med Ctr, Lipid Res Lab, Washington, DC 20422 USA. US Food & Drug Adm, Laurel, MD 20708 USA. RP Marmillot, P (reprint author), George Washington Univ, Dept Med, Washington, DC 20037 USA. NR 25 TC 2 Z9 2 U1 0 U2 0 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 1998 VL 31 IS 1 BP 18 EP 23 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA 102BN UT WOS:000074903500003 PM 9682244 ER PT J AU Wei, RR Wamer, WG Lambert, LA Kornhauser, A AF Wei, RR Wamer, WG Lambert, LA Kornhauser, A TI beta-carotene uptake and effects on intracellular levels of retinol in vitro SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID INDUCED NEOPLASTIC TRANSFORMATION; GAP JUNCTIONAL COMMUNICATION; LIPID-PEROXIDATION; 10T1/2 CELLS; METABOLISM; CANTHAXANTHIN; FIBROBLASTS; CANCER; ACID AB The purpose of the present study was to determine beta-carotene uptake and resultant effects on intracellular levels of retinol in cell lines of varied origin. Human skin fibroblasts, mouse embryonic fibroblasts, rabbit corneal epithelial cells, and rat liver cells were studied. Cells were cultured in medium supplemented with beta-carotene in a water-dispersible beadlet formulation. At selected intervals, cells and media were sampled and analyzed by high-performance liquid chromatography for beta-carotene and retinol content. beta-Carotene was taken up by all four cell lines. An increase in the intracellular levels of retinol was concomitant with beta-carotene uptake in all cell lines. The uptake of beta-carotene and the increase in intracellular retinol were highest in the two fibroblast cell lines. Incubation with media supplemented with crystalline beta-carotene, dissolved in tetrahydrofuran, resulted in significantly lower beta-carotene uptake and intracellular retinol levels. We view these results as a demonstration that a wide variety of cells, cultured in vitro, are able to convert beta-carotene to retinol. Therefore, beta-carotene's provitamin A activity should be carefully considered when the protective effects of beta-carotene in vitro are interpreted. C1 US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. RP Wei, RR (reprint author), US FDA, Ctr Food Safety & Appl Nutr, HFS 128,200 C St SW, Washington, DC 20204 USA. NR 21 TC 29 Z9 29 U1 0 U2 3 PU LAWRENCE ERLBAUM ASSOC INC PI MAHWAH PA 10 INDUSTRIAL AVE, MAHWAH, NJ 07430-2262 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 1998 VL 30 IS 1 BP 53 EP 58 PG 6 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA YY310 UT WOS:000072134300008 PM 9507513 ER PT J AU Jackson, CD Weis, C Chen, JJ Bechtel, DH Poirier, LA AF Jackson, CD Weis, C Chen, JJ Bechtel, DH Poirier, LA TI Relative contribution of calories from dietary fat, carbohydrate, and fiber in the promotion of DMBA-induced mammary tumors in Sprague-Dawley rats SO NUTRITION AND CANCER-AN INTERNATIONAL JOURNAL LA English DT Article ID BREAST-CANCER; BODY-WEIGHT; CARCINOGENESIS; TUMORIGENESIS; RESTRICTION; PREVENTION; PROTEIN; ENERGY; GROWTH; MICE AB It is well known that caloric restriction inhibits, whereas excess calories promote, mammary tumorigenesis in rats. However, the relative contributions to carcinogenesis by calories derived from fat or from carbohydrate are not well established. To determine the relative effects of calories from fat or from carbohydrate, as well as any interaction of dietary fiber on the promotion of 7,12-dimethylbenz[a]anthracene-induced mammary tumors, we fed isocalorically nine diets containing different ratios of fat, carbohydrate, and fiber to female Sprague-Dawley rats treated with 7,12-dimethylbenz[a]anthracene (30/group). Under conditions of isocaloric consumption, at or near ad libitum feeding, calories from dietary fat had approximately twofold greater promoting effect on final body weight and tumor incidence than calories derived from dietary carbohydrate. Dietary fiber had an inhibitory effect on tumor development, but the effect was evident only in the high-fat groups. Logistic regression analysis of tumor incidence gave beta-coefficient estimates for the relative effects of fat, carbohydrate, and fiber of 0.866, 0.189, and -4.281, respectively. Time-to-tumor analysis by the Weibull model indicated beta-estimates of .016, 3.324, and 5.825 for dietary fat, carbohydrate, and fiber, respectively, indicating that fat shortens and fiber increases the length of time to tumor . The statistical model derived from these results also indicates a significant synergistic interaction of dietary fat and carbohydrate on final body weight and tumor incidence. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Best Foods, Somerset, NJ 08873 USA. RP Jackson, CD (reprint author), US FDA, Natl Ctr Toxicol Res, 3900 NCTR Rd, Jefferson, AR 72079 USA. EM cjackson@nctr.fda.gov NR 38 TC 5 Z9 6 U1 1 U2 3 PU LAWRENCE ERLBAUM ASSOC INC-TAYLOR & FRANCIS PI PHILADELPHIA PA 325 CHESTNUT STREET, STE 800, PHILADELPHIA, PA 19106 USA SN 0163-5581 J9 NUTR CANCER JI Nutr. Cancer PY 1998 VL 30 IS 3 BP 194 EP 200 PG 7 WC Oncology; Nutrition & Dietetics SC Oncology; Nutrition & Dietetics GA ZT770 UT WOS:000074123900005 PM 9631490 ER PT B AU Young, KR AF Young, KR GP MTS MTS TI The US seafood HACCP regulations - Compliance requirements for domestic and imported products SO OCEAN COMMUNITY CONFERENCE'98: CELEBRATING 1998 INTERNATIONAL YEAR OF THE OCEAN, PROCEEDINGS VOLS 1 AND 2 LA English DT Proceedings Paper CT Marine-Technology-Society Annual Conference CY NOV 16-19, 1998 CL BALTIMORE, MD SP Marine Technol Soc AB The US Food and Drug Administration's (FDA) Seafood Hazard Analysis and Critical Control Point (HACCP) Regulations became effective December 18, 1997. At that time, all seafood processors, both domestic processors and foreign processors that export to the U.S, must comply with the new regulations. Those firms that are defined by the regulations as a processor must conduct a hazard analysis to determine whether there are food safety hazards that are reasonably likely to occur in the seafood being processed and in the firm's processing. The firm must then develop and implement a HACCP plan if a food safely hazard is determined to exist Processors are also required to perform sanitation control procedures as outlined in the regulations even ifa hazard analysis determines that food safety hazards do not exist. For imported products, the regulations specify special import provisions that the U.S. importers must perform to verify that the foreign processor is operating under the requirements of the I;DA Seafood HACCP Regulations. C1 US FDA, Off Seafood, Washington, DC 20204 USA. RP Young, KR (reprint author), US FDA, Off Seafood, 200 C St SW, Washington, DC 20204 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU MARINE TECHNOLOGY SOC PI WASHINGTON PA 1828 L ST NW,SUITE 906, WASHINGTON, DC 20035 USA BN 0-933957-21-1 PY 1998 BP 1165 EP 1168 PG 4 WC Engineering, Marine; Meteorology & Atmospheric Sciences; Oceanography; Remote Sensing SC Engineering; Meteorology & Atmospheric Sciences; Oceanography; Remote Sensing GA BP21L UT WOS:000084418300229 ER PT J AU Mehrotra, R Varricchio, F Husain, SR Puri, RK AF Mehrotra, R Varricchio, F Husain, SR Puri, RK TI Head and neck cancers, but not benign lesions, express interleukin-4 receptors in situ SO ONCOLOGY REPORTS LA English DT Article DE IL-4 receptors; head and neck cancer; immunohistochemistry ID CELL-CARCINOMA-CELLS; RECOMBINANT HUMAN INTERLEUKIN-4; PSEUDOMONAS EXOTOXIN; CHIMERIC PROTEIN; IL-4 RECEPTORS; GROWTH; LINES; TOXIN; LUNG AB We have previously reported on the expression of interleukin-4 receptor (IL-4R) on many solid cancer cell lines. In the present study, we have examined the expression of IL-4R on head and neck cancers in situ by immunohistochemistry. Seven primary squamous cell carcinomas of the head and neck region were stained by a monoclonal antibody to human IL-4Rp140 protein (M-57). We report that all squamous cell carcinoma samples were positively stained although at variable intensity with anti-IL-4R antibody. Tumors stained with IgG control did not show any staining. On the other hand, six benign lesions from the same anatomical area showed faint or no staining at all. Three uterine endometrium samples were also negative for the IL-4R expression. In contrast to published contrary results, we did not observe any effect of IL-4 on the proliferation of four squamous cell carcinoma of head and neck (SCCHN) cell lines examined. These results demonstrate that human squamous carcinoma of the head and neck express IL-4R, which could be targeted for diagnosis and therapy by anti-IL-4 receptor antibody fused to toxins or radionuclides or alternatively by IL-4 toxins. C1 US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. US FDA, Div Biostat & Epidemiol, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. Moti Lal Nehru Med Coll, Dept Pathol, Allahabad 211001, Uttar Pradesh, India. RP Puri, RK (reprint author), US FDA, Lab Mol Tumor Biol, Div Cellular & Gene Therapies, Ctr Biol Evaluat & Res, Natl Inst Hlth Bldg 29B,Room 2NN10,29 Lincoln Dr, Bethesda, MD 20892 USA. RI Mehrotra, Ravi/E-3285-2010 OI Mehrotra, Ravi/0000-0001-9453-1408 NR 25 TC 11 Z9 11 U1 2 U2 2 PU PROFESSOR D A SPANDIDOS PI ATHENS PA 1, S MERKOURI ST, EDITORIAL OFFICE,, ATHENS 116 35, GREECE SN 1021-335X J9 ONCOL REP JI Oncol. Rep. PD JAN-FEB PY 1998 VL 5 IS 1 BP 45 EP 48 PG 4 WC Oncology SC Oncology GA YN734 UT WOS:000071200700007 PM 9458290 ER PT J AU Looker, AC Wahner, HW Dunn, WL Calvo, MS Harris, TB Heyse, SP Johnston, CC Lindsay, R AF Looker, AC Wahner, HW Dunn, WL Calvo, MS Harris, TB Heyse, SP Johnston, CC Lindsay, R TI Updated data on proximal femur bone mineral levels of US adults SO OSTEOPOROSIS INTERNATIONAL LA English DT Article DE bone mineral density; proximal femur ID HIP FRACTURE; NATIONAL-HEALTH; NHANES-III; DENSITY; OLDER; RISK; OSTEOPOROSIS; POPULATION; PREVALENCE; SYMMETRY AB This paper describes data on bone mineral levels in the proximal femur of US adults based on the nationally representative sample examined during both phases of the third National Health and Nutrition Examination Survey (NHANES III 1988-94), and updates data previously presented from phase I only. The data were collected from 14646 men and women aged 20 years and older using dual-energy X-ray absorptiometry, and included bone mineral density (BMD), bone mineral content (BMC) and area of bone scanned in four selected regions of interest (ROI) in the proximal femur: femur neck, trochanter, intertrochanter and total. These variables are provided separately by age and sex for non-Hispanic whites (NHW), non-Hispanic blacks (NHB) and Mexican Americans (MA). NHW in the southern United States had slightly lower BMD levels than NHW in other US regions, but these differences were not sufficiently large to prevent pooling of the data. The updated data provide valuable reference data on femur bone mineral levels of noninstitutionalized adults. The updated data on BMD for the total femur ROI of NHW have been selected as the reference database for femur standardization efforts by the International Committee on Standards in Bone Measurements. C1 Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Hyattsville, MD 20782 USA. Mayo Clin & Mayo Fdn, Rochester, MN 55905 USA. US FDA, Ctr Food Safety & Appl Nutr, Washington, DC 20204 USA. NIA, NIH, Bethesda, MD 20892 USA. NIAMSD, NIH, Bethesda, MD 20892 USA. Indiana Univ, Med Ctr, Indianapolis, IN USA. Helen Hayes Hosp, Reg Bone Ctr, W Haverstraw, NY USA. RP Looker, AC (reprint author), Ctr Dis Control & Prevent, Natl Ctr Hlth Stat, Div Hlth Examinat Stat, Room 900,6525 Belcrest Rd, Hyattsville, MD 20782 USA. NR 28 TC 660 Z9 673 U1 2 U2 4 PU SPRINGER-VERLAG LONDON LTD PI GODALMING PA SWEETAPPLE HOUSE CATTESHALL ROAD, GODALMING GU7 3DJ, SURREY, ENGLAND SN 0937-941X J9 OSTEOPOROSIS INT JI Osteoporosis Int. PY 1998 VL 8 IS 5 BP 468 EP 489 DI 10.1007/s001980050093 PG 22 WC Endocrinology & Metabolism SC Endocrinology & Metabolism GA 186AF UT WOS:000079703600013 PM 9850356 ER PT J AU Holston, SS AF Holston, SS TI Keynote address: PDA/FDA joint conference SO PDA JOURNAL OF PHARMACEUTICAL SCIENCE AND TECHNOLOGY LA English DT Editorial Material C1 US FDA, Rockville, MD 20857 USA. RP Holston, SS (reprint author), US FDA, 5600 Fishers Lane,HF-24, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU PARENTERAL DRUG ASSOC INC PI BETHESDA PA 7500 OLD GEORGETOWN RD, STE 620, BETHESDA, MD 20814 USA SN 1076-397X J9 PDA J PHARM SCI TECH JI PDA J. Pharm. Sci. Technol. PD JAN-FEB PY 1998 VL 52 IS 1 BP 2 EP 4 PG 3 WC Engineering, Biomedical; Pharmacology & Pharmacy SC Engineering; Pharmacology & Pharmacy GA ZB006 UT WOS:000072425400002 PM 9542407 ER PT J AU Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R Peter, G Hall, CB Schwartz, B Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR AF Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R Peter, G Hall, CB Schwartz, B Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR TI Age for routine administration of the second dose of measles-mumps-rubella vaccine SO PEDIATRICS LA English DT Article ID SCHOOL POPULATION; ANTIBODY; REVACCINATION; OUTBREAK; FAILURE; PERSISTENCE; IMMUNITY; SERUM AB The purpose of this statement is to inform physicians of a modification in the recommendation of the appropriate age for routine administration of the second dose of measles-mumps-rubella (MMR) vaccine. The implementation of the two-dose measles vaccine schedule has improved the control of measles, but some outbreaks continue to occur in school children, although greater than or equal to 95% of children in school have received cine dose of vaccine. Because most measles vaccine failures are attributable to failure to respond to the first dose, that all children receive two doses of measles-containing vaccine is essential for the control of measles. Routine administration of the second dose of MMR vaccine at school entry (4 to 6 years of age) will help prevent school-based outbreaks. Physicians should continue to review the records of all children 11 to 12 years of age to be certain that they have received two doses of MMR vaccine after their first birthday. Documenting that all school children have received two doses of measles-containing vaccine by the year 2001 will help ensure the elimination of measles in the United States and contribute to the global effort to control and possibly eradicate measles. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. Amer Thorac Soc, New York, NY USA. Canadian Paediat Soc, Ottawa, ON, Canada. NIAID, Bethesda, MD USA. NR 35 TC 21 Z9 21 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 JAN PY 1998 VL 101 IS 1 BP 129 EP 133 PG 5 WC Pediatrics SC Pediatrics GA YP941 UT WOS:000071331400037 ER PT J AU Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R Peter, G Hall, CB Schwartz, B Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR AF Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Gromisch, DS Kohl, S Marcy, SM Murray, DL Overturf, GD Whitley, RJ Yogev, R Peter, G Hall, CB Schwartz, B Breiman, R Hardegree, MC Jacobs, RF MacDonald, NE Orenstein, WA Rabinovich, NR TI Severe invasive group A streptococcal infections: A subject review SO PEDIATRICS LA English DT Article ID TOXIC-SHOCK SYNDROME; GROUP-A STREPTOCOCCI; NECROTIZING FASCIITIS; PHARYNGEAL CARRIAGE; VARICELLA; CHILDREN; DISEASE; THERAPY; PATHOGENESIS; CLINDAMYCIN AB The course of severe invasive group A beta-hemolytic streptococcal (GABHS) infections is often precipitous, requiring prompt diagnosis and rapid initiation of appropriate therapy. Therefore, physicians must have a high index of suspicion of this disease, particularly in patients at increased risk (eg, those with varicella or diabetes mellitus). Although a relationship between the use of nonsteroidal antiinflammatory drugs and severe invasive GABHS infections has been suggested, at present data on which to base a clinical derision about the use or restriction of nonsteroidal antiinflammatory drugs in children with varicella are insufficient. When necrotizing fasciitis is suspected, prompt surgical drainage, debridement, fasciotomy, or amputation often is necessary. Many experts recommend intravenously administered penicillin G and clindamycin for the treatment of invasive GABHS infections on the basis of animal studies. Some evidence exists that intravenous immunoglobulin given in addition to appropriate antimicrobial and surgical therapy may be beneficial. Although chemoprophylaxis for household contacts of persons with invasive GABHS infections has been considered by some experts, the limited available data indicate that the risk of secondary cases is low (2.9 per 1000) and data about the effectiveness of any drug are insufficient to make recommendations. Because of the low risk of secondary cases of invasive GABHS infections in schools or child care facilities, chemoprophylaxis is not indicated in these settings. Routine immunization of all healthy children against varicella is recommended and is an effective means to decrease the risk of invasive GABHS infections. C1 Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. Amer Thorac Soc, New York, NY USA. Canadian Paediat Soc, Ottawa, ON, Canada. NIAID, Bethesda, MD USA. NR 32 TC 54 Z9 58 U1 0 U2 3 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 JAN PY 1998 VL 101 IS 1 BP 136 EP 140 PG 5 WC Pediatrics SC Pediatrics GA YP941 UT WOS:000071331400039 ER PT J AU Klish, WJ Baker, SS Cochran, WJ Flores, CA Georgieff, MK Jacobson, MS Lake, A Blum, D Harris, SS Hubbard, VS Levin, E Prendergast, A Smith, AE Yetley, E Lauer, RM AF Klish, WJ Baker, SS Cochran, WJ Flores, CA Georgieff, MK Jacobson, MS Lake, A Blum, D Harris, SS Hubbard, VS Levin, E Prendergast, A Smith, AE Yetley, E Lauer, RM TI Cholesterol in childhood SO PEDIATRICS LA English DT Article ID CORONARY HEART-DISEASE; DENSITY-LIPOPROTEIN CHOLESTEROL; ATHEROSCLEROSIS REGRESSION; ADULT HYPERCHOLESTEROLEMIA; CARDIOVASCULAR-DISEASE; MACACA-MULATTA; CHILDREN; MUSCATINE; TRACKING; LIPIDS AB This updated statement reviews the scientific justification for the recommendations of dietary changes in all healthy children (a population approach) and a strategy to identify and treat children who are at highest risk for the development of accelerated atherosclerosis in early adult life (an individualized approach). Although the precise fraction of risk for future coronary heart disease conveyed by elevated cholesterol levels in childhood is unknown, clear epidemiologic and experimental evidence indicates that the risk is significant. Diet changes that lower fat, saturated fat, and cholesterol intake in children and adolescents can be applied safely and acceptably, resulting in improved plasma lipid profiles that, if carried into adult life, have the potential to reduce atherosclerotic vascular disease. C1 USDA, Washington, DC 20250 USA. Int Life Sci Inst, Washington, DC USA. Amer Dietet Assoc, Chicago, IL 60606 USA. US FDA, Rockville, MD 20857 USA. NR 52 TC 201 Z9 218 U1 0 U2 2 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 J9 PEDIATRICS JI Pediatrics PD JAN PY 1998 VL 101 IS 1 BP 141 EP 147 PG 7 WC Pediatrics SC Pediatrics GA YP941 UT WOS:000071331400040 ER PT J AU Klish, WJ Baker, SS Cochran, WJ Flores, CA Georgieff, MK Jacobson, MS Lake, AM Blum, D Harris, SS Hubbard, VS Levin, E Prendergast, A Smith, AE Yetley, E Zlotkin, S Lauer, RM AF Klish, WJ Baker, SS Cochran, WJ Flores, CA Georgieff, MK Jacobson, MS Lake, AM Blum, D Harris, SS Hubbard, VS Levin, E Prendergast, A Smith, AE Yetley, E Zlotkin, S Lauer, RM TI Soy protein-based formulas: Recommendations for use in infant feeding SO PEDIATRICS LA English DT Article ID FED HUMAN-MILK; BIRTH-WEIGHT INFANTS; BREAST-FED INFANTS; SMALL BOWEL MUCOSA; COWS MILK; TERM INFANTS; BONE MINERALIZATION; ATOPIC DISEASE; FOOD ALLERGY; ALUMINUM CONTAMINATION AB The American Academy of pediatrics is committed to the use of maternal breast milk as the ideal source of nutrition for infant feeding. Even so, by 2 months of age, most infants in North America are formula-fed. Despite limited indications, the use of soy protein-based formula has nearly doubled during the past decade to achieve 25% of the market in the United States. Because an infant formula provides the largest, if not sole, source of nutrition for an extended interval, the nutritional adequacy of the formula must be confirmed and the indications for its use well understood. This statement updates the 1983 Committee on Nutrition review(1) and contains some important recommendations on the appropriate use of soy protein-based formulas. C1 USDA, Washington, DC USA. Int Life Sci Inst, Washington, DC USA. Amer Dietet Assoc, Chicago, IL 60606 USA. Canadian Paediat Soc, Ottawa, ON, Canada. US FDA, Rockville, MD 20857 USA. NR 96 TC 132 Z9 135 U1 1 U2 10 PU AMER ACAD PEDIATRICS PI ELK GROVE VILLAGE PA 141 NORTH-WEST POINT BLVD,, ELK GROVE VILLAGE, IL 60007-1098 USA SN 0031-4005 EI 1098-4275 J9 PEDIATRICS JI Pediatrics PD JAN PY 1998 VL 101 IS 1 BP 148 EP 153 PG 6 WC Pediatrics SC Pediatrics GA YP941 UT WOS:000071331400041 ER PT J AU Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Marcy, SM Murray, DL Overturf, GD Prober, CG Weiner, LB Whitley, RJ Yogev, R Peter, G Pickering, LK Baker, CJ Hirsch, A Jacobs, RF MacDonald, NE Schwartz, B Livengood, JR Hardegree, MC Rabinovich, NR Breiman, RF AF Halsey, NA Abramson, JS Chesney, PJ Fisher, MC Gerber, MA Marcy, SM Murray, DL Overturf, GD Prober, CG Weiner, LB Whitley, RJ Yogev, R Peter, G Pickering, LK Baker, CJ Hirsch, A Jacobs, RF MacDonald, NE Schwartz, B Livengood, JR Hardegree, MC Rabinovich, NR Breiman, RF TI Recommended childhood immunization schedule - United States, January-December 1998 SO PEDIATRICS LA English DT Article ID B VACCINES; INTERCHANGEABILITY; INFANTS C1 AAP, Council Pediat Practice, Elk Grove Village, IL USA. Amer Thorac Soc, New York, NY USA. Canadian Paediat Soc, Ottawa, ON, Canada. Ctr Dis Control & Prevent, Atlanta, GA 30333 USA. US FDA, Rockville, MD 20857 USA. NIAID, Bethesda, MD USA. NR 9 TC 6 Z9 6 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 JAN PY 1998 VL 101 IS 1 BP 154 EP 157 PG 4 WC Pediatrics SC Pediatrics GA YP941 UT WOS:000071331400042 ER PT J AU Goodman, CB Heyliger, S Emilien, B Partilla, JS Yang, HYT Lee, CH Cadet, JL Rothman, RB AF Goodman, CB Heyliger, S Emilien, B Partilla, JS Yang, HYT Lee, CH Cadet, JL Rothman, RB TI Regulation of mu binding sites after chronic administration of antibodies directed against specific anti-opiate peptides SO PEPTIDES LA English DT Article DE NPFF; dynorphin; IgG; alpha-melanocyte-stimulating hormone (alpha-MSH) opioid mu receptor ID KAPPA-OPIOID RECEPTORS; MELANOCYTE-STIMULATING HORMONE; MORPHINE-INDUCED ANALGESIA; RAT-BRAIN; ANTIANALGESIC ACTION; DEPENDENCE; TOLERANCE; DELTA; DYNORPHIN; NPFF AB There is some indication that anti-opiate peptides (AOP) modulate opioid receptor systems by altering mu-receptor density. To further characterize this phenomenon, we investigated the effects of continuous infusion of anti-AOP IgG on mu binding sites in the brains of rats. Specifically, male Sprague-Dawley rats received intracerebroventricular (ICV) infusions for 13 days of either control (rabbit) IgG or test IgGs: anti-dynorphin A IgG, anti-dynorphin A(1-8) IgG, anti-alpha-MSH IgG, or the monoclonal anti-NPFF IgG. Administration of anti-NPFF IgG or the anti-dynorphin(1-8) IgG significantly increased mu labeling by 40-70% in several brain regions at the caudate level. Contrary to these findings, anti-alpha-MSH IgG decreased (19-32%) [I-125]-DAMGO labeling in several thalamic nuclei. The results suggest that the density of mu-opioid receptors is regulated in part by anti-opiate peptides in the extracellular fluid of the brain. (C) 1998 Elsevier Science Inc. C1 NIDA, DIR, NIH, Clin Psychopharmacol Sect, Baltimore, MD 21224 USA. NIDA, Mol Neuropsychiat Sect, Div IRP, Baltimore, MD 21224 USA. Florida A&M Univ, Coll Pharm & Pharmaceut Sci, Tallahassee, FL 32307 USA. US FDA, Lab Bacterial Polysaccharides, Div Bacterial Prod, OVRR,CBER, Bethesda, MD 20014 USA. RP Goodman, CB (reprint author), NIDA, DIR, NIH, Clin Psychopharmacol Sect, POB 5180, Baltimore, MD 21224 USA. EM cgoodman@famu.edu NR 50 TC 16 Z9 16 U1 0 U2 0 PU ELSEVIER SCIENCE INC PI NEW YORK PA 655 AVENUE OF THE AMERICAS, NEW YORK, NY 10010 USA SN 0196-9781 J9 PEPTIDES JI Peptides PY 1998 VL 19 IS 10 BP 1703 EP 1709 DI 10.1016/S0196-9781(98)00121-1 PG 7 WC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy SC Biochemistry & Molecular Biology; Endocrinology & Metabolism; Pharmacology & Pharmacy GA 150XT UT WOS:000077691900009 PM 9880075 ER PT J AU Singh, GJP Fleischer, N Lesko, L Williams, R AF Singh, GJP Fleischer, N Lesko, L Williams, R TI Evaluation of the proposed FDA pilot dose-response methodology for topical corticosteroid bioequivalence testing SO PHARMACEUTICAL RESEARCH LA English DT Letter ID ASSAY C1 US FDA, CDER, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Singh, GJP (reprint author), US FDA, CDER, Off Pharmaceut Sci, Rockville, MD 20857 USA. NR 9 TC 1 Z9 1 U1 2 U2 3 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JAN PY 1998 VL 15 IS 1 BP 4 EP 5 PG 2 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA YV727 UT WOS:000071856700005 PM 9487539 ER PT J AU Dressman, JB Amidon, GL Reppas, C Shah, VP AF Dressman, JB Amidon, GL Reppas, C Shah, VP TI Dissolution testing as a prognostic tool for oral drug absorption: Immediate release dosage forms SO PHARMACEUTICAL RESEARCH LA English DT Review DE dissolution tests; prediction of in vivo performance; dissolution test conditions; composition of dissolution media ID GASTROINTESTINAL TRANSIT; DELIVERY; HEALTHY; COLON; PH; INTESTINE; POLYMERS; COMPLEX; INVITRO; LIQUIDS AB Dissolution tests are used for many purposes in the pharmaceutical industry: in the development of new products, for quality control and, to assist with the determination of bioequivalence. Recent regulatory developments such as the Biopharmaceutics Classification Scheme have highlighted the importance of dissolution in the regulation of post-approval changes and introduced the possibility of substituting dissolution tests for clinical studies in some cases. Therefore, there is a need to develop dissolution tests that better predict the in vivo performance of drug products. This could be achieved if the conditions in the gastrointestinal tract were successfully reconstructed in vitro. The aims of this article are, first, to clarify under which circumstances dissolution testing can be prognostic for in vivo performance, and second, to present physiological data relevant to the design of dissolution tests, particularly with respect to the composition, volume, flow rates and mixing patterns of the fluids in the gastrointestinal tract. Finally brief comments are made in regard to the composition of in vitro dissolution media as well as the hydrodynamics and duration of the test. C1 Univ Frankfurt, Inst Pharmazeut Technol, D-60439 Frankfurt, Germany. Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA. Univ Athens, Dept Pharm, Zografou 15771, Greece. US FDA, Ctr Drug Evaluat & Res, Off Pharmaceut Sci, Rockville, MD 20857 USA. RP Dressman, JB (reprint author), Univ Frankfurt, Inst Pharmazeut Technol, Marie Curie Str 9, D-60439 Frankfurt, Germany. NR 66 TC 583 Z9 608 U1 9 U2 109 PU PLENUM PUBL CORP PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARMACEUT RES JI Pharm. Res. PD JAN PY 1998 VL 15 IS 1 BP 11 EP 22 DI 10.1023/A:1011984216775 PG 12 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA YV727 UT WOS:000071856700008 PM 9487541 ER PT J AU El-Tahtawy, AA Tozer, TN Harrison, F Lesko, L Williams, R AF El-Tahtawy, AA Tozer, TN Harrison, F Lesko, L Williams, R TI Evaluation of bioequivalence of highly variable drugs using clinical trial simulations. II: Comparison of single and multiple-dose trials using AUC and Cmax SO PHARMACEUTICAL RESEARCH LA English DT Article DE bioequivalence; highly variable drugs; extent of absorption; rate of absorption; Monte Carlo simulations; single-dose; multiple-dose bioequivalence trial ID MONTE-CARLO SIMULATIONS; ABSORPTION; PERFORMANCE AB Purpose. Evaluating of the effects of high intrasubject variability in clearance (CL) and volume of distribution (V), on 90% confidence intervals (CIs) for AUC (Area Under the concentration Curve) in single and multiple-dose bioequivalence studies. The main methodology was Monte Carlo simulation, and we also used deterministic simulation, and examination of clinical trials. The results are compared with those previously observed for Cmax (maximum concentration.) Methods. The time course of drug concentration in plasma was simulated using a one-compartment model with log-normal statistical distributions of intersubject and intrasubject variabilities in the pharmacokinetic parameters. Both immediate-release and prolonged-release products were simulated using several levels of intrasubject variability in single-dose and multiple-dose studies. Simulations of 2000 clinical bioequivalence trials per condition (138 conditions) with 30 subjects in each crossover trial were carried out. Simulated data were compared with data from actual bioequivalence trials. R Results. The current simulations for AUC show similar probabilities of failure for single-dose and multiple-dose bioequivalence studies, even with differences in the rate of absorption or fraction absorbed. AUC values from prolonged-release scenario studies are more sensitive to changes in the first order absorption rate constant ka, and to variability in CL and V than AUC from studies of immediate-release studies. Conclusions. We showed that multiple-dose designs for highly variable drugs do not always reduce intrasubject variability in either AUC or Cmax, although the behavior of AUC differs from Cmax. Single dose AUC to the last quantifiable concentration was more reliable than either single dose AUC extrapolated to infinity, or multiple dose AUC during a steady-state interval. Multiple-dose designs may not be the best solution for assessing bioequivalence of highly variable drugs. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. Univ Calif San Francisco, Sch Pharm, San Francisco, CA 94143 USA. RP El-Tahtawy, AA (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-860, Rockville, MD 20857 USA. EM Eltahtawya@cder.fda.gov NR 12 TC 24 Z9 24 U1 1 U2 1 PU SPRINGER/PLENUM PUBLISHERS PI NEW YORK PA 233 SPRING ST, NEW YORK, NY 10013 USA SN 0724-8741 J9 PHARM RES-DORDR JI Pharm. Res. PD JAN PY 1998 VL 15 IS 1 BP 98 EP 104 PG 7 WC Chemistry, Multidisciplinary; Pharmacology & Pharmacy SC Chemistry; Pharmacology & Pharmacy GA YV727 UT WOS:000071856700021 PM 9487554 ER PT S AU Gagne, RM Wagner, RF AF Gagne, RM Wagner, RF BE Dobbins, JT Boone, JM TI Prewhitening matched filter: practical implementation, SNR estimation and bias reduction SO PHYSICS OF MEDICAL IMAGING SE PROCEEDINGS OF THE SOCIETY OF PHOTO-OPTICAL INSTRUMENTATION ENGINEERS (SPIE) LA English DT Proceedings Paper CT SPIE Conference on Physics of Medical Imaging CY FEB, 1998 CL SAN DIEGO, CA SP SPIE DE signal detection theory; pre-whitening matched filter; bias; observer AB In the clinical setting, image quality is most commonly evaluated by the visual observation of images of test objects and/or phantoms. Because of the uncertainties in such results (either large variance or bias or both), more precise quantitative measures based on statistical decision theory should be investigated. A series of simulations and experiments were conducted to investigate the statistical properties, i.e., the bias and variance, of the estimate of the square of the SNR of the "ideal" observer (SNRPWMF) Several methods of bias reduction were compared including one due to Fukunaga and Hayes. Good agreement was obtained between the results of simulations and the theoretical predictions for the bias and variance. The different methods of bias reduction have the same applicability for both "ideal" and "quasi-ideal" observers for the series of SKE/BKE tasks investigated in the present study. This work also provides some new avenues for additional investigation. First, the techniques can lead to protocols for making the evaluation of imaging system performance with a limited number of sample images, which is an important issue for any clinical implementation. Second, since selective spatial frequency channels can be used in estimating the SNRPWMF, the method has potential utility for imaging tasks beyond SKE/BKE tasks such as those with clinically relevant backgrounds but possessing stationary statistics. C1 US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. RP Gagne, RM (reprint author), US FDA, Ctr Devices & Radiol Hlth, Off Sci & Technol, Rockville, MD 20857 USA. NR 0 TC 5 Z9 5 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 0-8194-2781-0 J9 P SOC PHOTO-OPT INS PY 1998 VL 3336 BP 231 EP 242 DI 10.1117/12.317022 PG 12 WC Engineering, Biomedical; Optics; Physics, Applied; Radiology, Nuclear Medicine & Medical Imaging SC Engineering; Optics; Physics; Radiology, Nuclear Medicine & Medical Imaging GA BL54B UT WOS:000075819800024 ER PT J AU Babu, US Wiesenfeld, PL Jenkins, MY AF Babu, US Wiesenfeld, PL Jenkins, MY TI Effect of dietary rosemary extract on cell-mediated immunity of young rats SO PLANT FOODS FOR HUMAN NUTRITION LA English DT Article DE concanavalin A; mitogenic response; phytohemagglutinin; rosemary extract; splenic lymphocytes; Stabex ID VITAMIN-E; LIPID-PEROXIDATION; ANTIOXIDANT; INHIBITION; ACID; MICE AB The impact of rosemary extract on splenic mononuclear cell proliferation was determined. Weanling male Sprague-Dawley rats were fed diets containing 0, 100, 200 or 400 ppm rosemary extract or 400 ppm butylated hydroxytoluene (BHT) in combinatiion with 10 or 20% casein enriched diets for 8 weeks. Splenic mononuclear cells were isolated from these animals and mitogenic response to Concanavalin A (Con A), Phytohemagglutinin (PHA) and lipopolysaccharide was determined. Con A and PHA-stimulated proliferation of spleen cells from rats fed 10% casein and 200 ppm rosemary extract was significantly higher than that of cells from the corresponding control animals. However, other levels of rosemary at 10% dietary casein or rosemary at any concentration fed along with 20% dietary casein had no impact on the mitogenic stimulation of splenic mononuclear cells. Thus, these results suggest that the use of rosemary might not have a generalized immunoenhancing effect, and will probably be effective in some stressed conditions, such as protein or antioxidant deficiency. C1 US FDA, Div Sci & Appl Technol, Off Special Nutr, Laurel, MD 20708 USA. RP Babu, US (reprint author), US FDA, Div Sci & Appl Technol, Off Special Nutr, Laurel, MD 20708 USA. NR 18 TC 2 Z9 2 U1 1 U2 2 PU KLUWER ACADEMIC PUBL PI DORDRECHT PA SPUIBOULEVARD 50, PO BOX 17, 3300 AA DORDRECHT, NETHERLANDS SN 0921-9668 J9 PLANT FOOD HUM NUTR JI Plant Food Hum. Nutr. PY 1998 VL 53 IS 2 BP 169 EP 174 DI 10.1023/A:1008040324935 PG 6 WC Plant Sciences; Chemistry, Applied; Food Science & Technology; Nutrition & Dietetics SC Plant Sciences; Chemistry; Food Science & Technology; Nutrition & Dietetics GA 215ZV UT WOS:000081416600010 ER PT J AU Hughes-Dillon, K Schroeder, LW AF Hughes-Dillon, K Schroeder, LW TI Stress cracking of polyurethanes by absorbed steroids SO POLYMER DEGRADATION AND STABILITY LA English DT Article ID HARD-SEGMENT; CHOLESTEROL AB Circumferentially stretched polyurethanes, Pellethane 2363-80A and 2363-55D, were studied following exposure to three steroids of differing polarity; cholesterol, cholesteryl acetate and cortisone. Equilibrium uptakes, diffusion kinetics and environmental stress cracking (ESC) were investigated. Cholesterol reached equilibrium uptake by 16 h, whereas cortisone and cholesteryl acetate did not attain equilibrium uptake until 96 h, suggesting different processes. All uptakes were less than 0.6%. The cortisone diffusion curves showed an inflection at 36 h suggesting some sort of structural change in 55D. The glass transition temperature, T-g, of the soft segment as a function of exposure time to cortisone and water shows a steady increase with cortisone content until after 36 h at which time the T-g falls almost to the value for water equilibrated samples. This shows that cortisone is able to affect the mobility of soft segments. The relationship between circumferential strain, steroid uptake and ESC was investigated. Samples were stretched at 50% increments from 0 to 250%; after 12 days exposure steroid uptakes were determined and the samples examined with SEM. Cholesterol promoted ESC in 80A and 55D at strains of 200 and 150%, respectively. Pellethane 55D was resistant to ESC in the presence of cortisone at all strains, while 80A cracked only at strains above 200%. The equilibrium uptake of cholesterol acetate was most sensitive to strain, particularly for 55D. Cholesterol acetate was the most effective ESC agent, cracking both 80A and 55D after 12 days exposure with an uptake under 0.25% and a strain of only 50%. (C) 1998 Elsevier Science Limited. All rights reserved. C1 US FDA, Div Mech & Mat Sci, Off Sci & Technol, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Hughes-Dillon, K (reprint author), US FDA, Div Mech & Mat Sci, Off Sci & Technol, Ctr Devices & Radiol Hlth, 5600 Fishers Lane, Rockville, MD 20852 USA. NR 28 TC 4 Z9 4 U1 0 U2 3 PU ELSEVIER SCI LTD PI OXFORD PA THE BOULEVARD, LANGFORD LANE, KIDLINGTON, OXFORD OX5 1GB, OXON, ENGLAND SN 0141-3910 J9 POLYM DEGRAD STABIL JI Polym. Degrad. Stabil. PY 1998 VL 60 IS 1 BP 11 EP 20 DI 10.1016/S0141-3910(96)00222-4 PG 10 WC Polymer Science SC Polymer Science GA ZV359 UT WOS:000074296700002 ER PT B AU Hutter, JC Luu, MYD Mehlhaff, PM Killam, AL Dittrich, HC AF Hutter, JC Luu, MYD Mehlhaff, PM Killam, AL Dittrich, HC BE Anderson, JG Katzper, M TI A fluorocarbon ultrasound contrast agent PBPK model SO PROCEEDINGS OF THE 1998 MEDICAL SCIENCES SIMULATION CONFERENCE LA English DT Proceedings Paper CT Medical Sciences Simulation Conference held at the 1998 Western MultiConference CY JAN 11-14, 1998 CL SAN DIEGO, CA SP Soc Comp Simulat Int DE pharmacokinetic; health care; imaging ID TWO-DIMENSIONAL ECHOCARDIOGRAPHY; MYOCARDIAL PERFUSION; PHARMACOKINETICS; RISK; DELINEATION; AREA AB New generations of ultrasound contrast agents are under development These new agents, usually volatile fluorocarbons, can be introduced iv and allow imaging of the heart. These fluorocarbon microbubbles have a low solubility in plasma which allows them to persist in the blood stream for much longer times than the previously used oxygen or atmospheric air bubbles, which are absorbed by the blood. A physiologically based pharmacokinetic (PBPK) model was; developed in order to evaluate the absorption, distribution, metabolism, and excretion (ADME) of these fluorocarbon based materials. This model can be used to predict the fate of the the contrast agent in the human body, and allow its safety to be evaluated Using very few simple measurements and published physiological parameters, the fate of a typical fluorocarbon ultrasound contrast agent injected iv was predicted. This new application of PBPK modeling can also be used to validate the in vivo pharmacokinetic data submitted by manufacturers in support of the safety and effectiveness of the contrast agents. C1 US FDA, Ctr Devices & Radiol Hlth, Rockville, MD 20852 USA. RP Hutter, JC (reprint author), US FDA, Ctr Devices & Radiol Hlth, 12725 Twinbrook Pkwy, Rockville, MD 20852 USA. NR 16 TC 0 Z9 0 U1 1 U2 2 PU SOC COMPUTER SIMULATION PI SAN DIEGO PA PO BOX 17900, SAN DIEGO, CA 92177 USA BN 1-56555-138-9 PY 1998 BP 104 EP 109 PG 6 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA BN53S UT WOS:000082161100017 ER PT B AU Martinez, MN Katzper, M AF Martinez, MN Katzper, M BE Anderson, JG Katzper, M TI Helmintic life cycle and population control SO PROCEEDINGS OF THE 1998 MEDICAL SCIENCES SIMULATION CONFERENCE LA English DT Proceedings Paper CT Medical Sciences Simulation Conference held at the 1998 Western MultiConference CY JAN 11-14, 1998 CL SAN DIEGO, CA SP Soc Comp Simulat Int DE parasite; dosing schedule; pharmacometric model ID ASCARIS-LUMBRICOIDES; INTESTINAL HELMINTHS; COMMUNITY; INFECTION; MORBIDITY AB A model of host-parasite relationships is developed and its application as a tool for evaluating population methods of parasite control is demonstrated. Simulations are presented showing the natural robustness of the parasite-host steady state condition. The impact of this finding: for human and veterinary medicine is discussed. The scenarios show the model's potential application in evaluating different dosage regimens of anthelmintic therapeutics. C1 US FDA, Ctr Vet Med, Rockville, MD 20855 USA. RP Martinez, MN (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl,HFV-130, Rockville, MD 20855 USA. NR 17 TC 0 Z9 0 U1 0 U2 1 PU SOC COMPUTER SIMULATION PI SAN DIEGO PA PO BOX 17900, SAN DIEGO, CA 92177 USA BN 1-56555-138-9 PY 1998 BP 128 EP 133 PG 6 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA BN53S UT WOS:000082161100021 ER PT B AU Katzper, M AF Katzper, M BE Anderson, JG Katzper, M TI Physiological processes and response to medication SO PROCEEDINGS OF THE 1998 MEDICAL SCIENCES SIMULATION CONFERENCE LA English DT Proceedings Paper CT Medical Sciences Simulation Conference held at the 1998 Western MultiConference CY JAN 11-14, 1998 CL SAN DIEGO, CA SP Soc Comp Simulat Int DE health status; homeostasis; intervention AB A generalized model is formulated to provide a framework for tracking relative change in health status. The model allows one to discriminate between status changes due to the standard physiological processes and that attributable to the medical intervention. Moreover, the model provides a way to measure the contribution of relative health status to the responsiveness of an individual to physiological processes and intervention. C1 US FDA, Ctr Drug Evaluat & Res, Rockville, MD 20857 USA. RP Katzper, M (reprint author), US FDA, Ctr Drug Evaluat & Res, 5600 Fishers Lane,HFD-550, Rockville, MD 20857 USA. NR 4 TC 0 Z9 0 U1 0 U2 0 PU SOC COMPUTER SIMULATION PI SAN DIEGO PA PO BOX 17900, SAN DIEGO, CA 92177 USA BN 1-56555-138-9 PY 1998 BP 154 EP 157 PG 4 WC Computer Science, Interdisciplinary Applications; Medical Informatics SC Computer Science; Medical Informatics GA BN53S UT WOS:000082161100026 ER PT S AU Carey, CC Ruggera, PS AF Carey, CC Ruggera, PS BE Chang, HK Zhang, YT TI In-vitro assessment of the effects of cellular phones on implantable cardioverter defibrillator (ICD) function SO PROCEEDINGS OF THE 20TH ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY, VOL 20, PTS 1-6: BIOMEDICAL ENGINEERING TOWARDS THE YEAR 2000 AND BEYOND SE PROCEEDINGS OF ANNUAL INTERNATIONAL CONFERENCE OF THE IEEE ENGINEERING IN MEDICINE AND BIOLOGY SOCIETY LA English DT Proceedings Paper CT 10th Annual International Conference of the IEEE-Engineering-in-Medicine-and-Biology-Society CY OCT 29-NOV 01, 1998 CL HONG KONG, PEOPLES R CHINA SP IEEE Engn Med & Biol Soc AB The design of cardiac pulse generators has evolved from an artificial pacemaker single therapy device to a multifunctional therapeutic device known as an implantable cardioverter defibrillator and pacemaker. Composed of complex digital circuitry and discrete components, these devices may exhibit susceptibility to electromagnetic interference (EMI). Despite shielding the internal mechanism of pacemakers and ICDs with titanium casing and using improved noise filtering techniques, new sources of EMI continue to pose challenges in electromagnetic compatibility (EMC) design of these devices. There have been previous reports of interference from RF (radio frequency) sources such as radar transmitters, hand-held radios, and anti-theft devices. More recently, with the proliferation of wireless communication, reports of interference by digital cellular telephones have also surfaced. FDA/CDRH (Food and Drug Administration, Center for Devices and Radiological Health) initiated an examination of the potential for cellular telephones to interfere with implanted pacemakers in 1995. Results of these evaluations led CDRH engineers to investigate the potential EMI effects of these telephones to ICD function. The investigation involved ICDs from six manufacturers versus four types of digital cellular telephones. An RF powered dipole antenna was also used to evaluate it as an alternative RF source for EMI testing. C1 US FDA, CDRH, Rockville, MD 20850 USA. RP Carey, CC (reprint author), US FDA, CDRH, HFZ-450,9200 Corp Blvd, Rockville, MD 20850 USA. EM ccc@cdrh.fda.gov NR 9 TC 0 Z9 0 U1 0 U2 0 PU IEEE PI NEW YORK PA 345 E 47TH ST, NEW YORK, NY 10017 USA SN 1094-687X BN 0-7803-5164-9 J9 P ANN INT IEEE EMBS PY 1998 VL 20 BP 3303 EP 3308 PN 1-6 PG 6 WC Cardiac & Cardiovascular Systems; Engineering, Biomedical; Medical Informatics; Medical Laboratory Technology; Clinical Neurology; Radiology, Nuclear Medicine & Medical Imaging SC Cardiovascular System & Cardiology; Engineering; Medical Informatics; Medical Laboratory Technology; Neurosciences & Neurology; Radiology, Nuclear Medicine & Medical Imaging GA BM59Y UT WOS:000079210400904 ER PT J AU Doerge, DR Churchwell, MI Gehring, TA Pu, YM Plakas, SM AF Doerge, DR Churchwell, MI Gehring, TA Pu, YM Plakas, SM TI Analysis of malachite green and metabolites in fish using liquid chromatography atmospheric pressure chemical ionization mass spectrometry SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID CATFISH ICTALURUS-PUNCTATUS; GENTIAN-VIOLET; VISIBLE DETECTION; TISSUE; CONFIRMATION AB Malachite green (MG), a traditional agent used in aquaculture, is structurally related to other carcinogenic triphenylmethane dyes. Although MG is not approved for use in aquaculture, its low cost and high efficacy make illicit use likely. We developed sensitive and specific methods for determination of MG and its principal metabolite, leucoMG (LMG), in edible fish tissues using isotope dilution liquid chromatography atmosphere pressure chemical ionization mass spectrometry. MG and LMG concentrations were measured in filets from catfish treated with MG under putative use conditions (ca, 250 and 1000 ppb, respectively) and from commercial trout samples (0-3 and 0-96 ppb, respectively). Concentrations of LMG in edible fish tissues always exceeded those of MG. A rapid cone voltage switching acquisition procedure was used to simultaneously produce molecular ions for quantification and diagnostic fragment ions for confirmation of MG and metabolites. The accurate and precise agreement between diagnostic ion intensity ratios produced by LMG in authentic standards and incurred fish samples was used to unambiguously confirm the presence of LMG in edible fish tissue. This suggested the validity of using LMG as a marker residue for regulatory determination of MG misuse. Additional metabolites derived from oxidative metabolism of MG or LMG (demethylation and N-oxygenation) were identified in catfish and trout filets, including a primary arylamine which is structurally related to known carcinogens, The ability to simultaneously quantify residues of MG and LMG, and to confirm the chemical structure of a marker residue by using LC/MS, suggests that this procedure may be useful in monitoring the food supply for the unauthorized use of MG in aquaculture. (C) 1998 John Wiley & Sons, Ltd. C1 US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Bionet Corp, Jefferson, AR 72079 USA. US FDA, Gulf Coast Seafood Lab, Dauphin Island, AL 36528 USA. RP Doerge, DR (reprint author), US FDA, Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 12 TC 50 Z9 57 U1 1 U2 7 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 1998 VL 12 IS 21 BP 1625 EP 1634 DI 10.1002/(SICI)1097-0231(19981115)12:21<1625::AID-RCM373>3.0.CO;2-I PG 10 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 133JC UT WOS:000076682600006 PM 9807836 ER PT J AU Doerge, DR Yi, P Churchwell, MI Preece, SW Langridge, J Fu, PP AF Doerge, DR Yi, P Churchwell, MI Preece, SW Langridge, J Fu, PP TI Mass spectrometric analysis of 2 '-deoxyribonucleoside and 2 '-deoxyribonucleotide adducts with aldehydes derived from lipid peroxidation SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID PERFORMANCE LIQUID-CHROMATOGRAPHY; ENDOGENOUS DNA-ADDUCTS; MALONALDEHYDE; LIVER; CROTONALDEHYDE; CANCER; ACID AB An important emerging issue in chemical carcinogenesis is the role that products of endogenous metabolism play in formation of covalently modified DNA. One example is the formation of alpha,beta-unsaturated aldehydes as a result of endogenous and drug-stimulated lipid peroxidation. Malondialdehyde (MDA), crotonaldehyde (CR), 2-hexenal (HX), and 4-hydroxy-2-nonenal (HNE) react covalently with 2'-deoxyguanosine (dG) and 2'-deoxyadenosine (dA) residues on DNA to form promutagenic cyclic adducts that may be important in the etiology of cancer in humans and animals. The accurate quantification of such adducts provides a powerful tool in molecular epidemiology for assessing carcinogenic risks from various lifestyle choices (e.g. diet, drug use) in humans. P-32-Postlabeling is recognized as one of the most sensitive methods available for detection of DNA adducts in human tissues, but without adequate validation such methodology can yield inaccurate quantitative measurements. We have used LC separations in conjunction with electrospray ionization MS and tandem MS (triple quadrupole and hybrid quadrupole-orthogonal acceleration time of flight analyzers) to characterize MDA-, CR-, HX- and HNE-modified dG and nucleotide (3'- and 5'-monophosphate; 3',5'-bis-phosphate) adducts. These data have been used to validate P-32-postlabeling methods for quantification of low level MDA-dG adducts formed in DNA of human and animal tissues. Availability of reliable methods for quantification of endogenous DNA damage in humans and animals is essential for determining unknown etiologies of cancer and for the assessment of cancer risks in humans. (C) 1998 John Wiley & Sons, Ltd. C1 Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Micromass, Altrincham WA14 5RZ, England. RP Doerge, DR (reprint author), Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. NR 26 TC 24 Z9 24 U1 0 U2 6 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 1998 VL 12 IS 22 BP 1665 EP 1672 DI 10.1002/(SICI)1097-0231(19981130)12:22<1665::AID-RCM384>3.3.CO;2-# PG 8 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 139XR UT WOS:000077057000002 PM 9853382 ER PT J AU Heller, DN Ngoh, MA AF Heller, DN Ngoh, MA TI Electrospray ionization and tandem ion trap mass spectrometry for the confirmation of seven beta-lactam antibiotics in bovine milk SO RAPID COMMUNICATIONS IN MASS SPECTROMETRY LA English DT Article ID LIQUID-CHROMATOGRAPHY; PENICILLIN-G; AMPICILLIN; CEPHAPIRIN AB The feasibility of a technique to confirm the presence of residues from seven beta-lactam antibiotics in bovine milk has been demonstrated. The technique makes use of electrospray ionization and tandem ion trap mass spectrometry, Residues are first extracted from milk by reversed-phase solid phase extraction. Target analytes are separated by on-line reversed-phase liquid chromatography and ionized in the electrospray interface. The product ion mass spectra are acquired following collision-induced dissociation of protonated molecules. Confirmation is based on comparison of full scan spectra between unknowns and bona fide standards. The feasibility of this technique has been demonstrated for the six beta-lactams currently approved for use in lactating dairy cattle (penicillin G, ampicillin, amoxicillin, cloxacillin, cephapirin and ceftiofur) and a drug not approved for animal use, cefazolin. The technique has been applied to control milk fortified at 5 ng/mL of penicillin G and 10 ng/mL of the other six drugs. (C) 1998 John Wiley & Sons, Ltd. C1 US FDA, Ctr Vet Med, Laurel, MD 20708 USA. RP Heller, DN (reprint author), US FDA, Ctr Vet Med, 8401 Muirkirk Rd, Laurel, MD 20708 USA. NR 18 TC 41 Z9 47 U1 0 U2 13 PU JOHN WILEY & SONS LTD PI W SUSSEX PA BAFFINS LANE CHICHESTER, W SUSSEX PO19 1UD, ENGLAND SN 0951-4198 J9 RAPID COMMUN MASS SP JI Rapid Commun. Mass Spectrom. PY 1998 VL 12 IS 24 BP 2031 EP 2040 DI 10.1002/(SICI)1097-0231(19981230)12:24<2031::AID-RCM432>3.3.CO;2-# PG 10 WC Chemistry, Analytical; Spectroscopy SC Chemistry; Spectroscopy GA 150XZ UT WOS:000077692500008 PM 10036784 ER PT J AU Ikeda, GJ Friedman, L Hattan, DG AF Ikeda, GJ Friedman, L Hattan, DG TI The minipig as a model in regulatory toxicity testing SO SCANDINAVIAN JOURNAL OF LABORATORY ANIMAL SCIENCE LA English DT Article; Proceedings Paper CT Symposium on the Minipig in Toxicology at the Eurotox 97 Meeting CY JUN 24-25, 1997 CL AARHUS, DENMARK ID EXCRETION; SWINE C1 US FDA, Washington, DC 20204 USA. RP Ikeda, GJ (reprint author), US FDA, Washington, DC 20204 USA. NR 20 TC 4 Z9 4 U1 0 U2 0 PU SCANDINAVIAN FEDERATION LABORATORY ANIMAL SCIENCE PI SOBORG PA C/O MARGARETA BERTRAM, NATIONAL FOOD AGENCY, MORKHOJ BYGHADE 19, DK-2860 SOBORG, DENMARK SN 0901-3393 J9 SCAND J LAB ANIM SCI JI Scand. J. Lab. Anim. Sci. PY 1998 VL 25 SU 1 BP 99 EP 105 PG 7 WC Veterinary Sciences SC Veterinary Sciences GA ZT167 UT WOS:000074055900014 ER PT S AU Lewis, AM AF Lewis, AM BE Brown, F Lewis, AM TI SV40 in adenovirus vaccines and adenovirus-SV40 recombinants SO SIMIAN VIRUS 40 (SV40): POSSIBLE HUMAN POLYOMAVIRUS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Article; Proceedings Paper CT Workshop on Simian Virus 40 (SV40): a Possible Human Polyomavirus CY JAN 27-28, 1997 CL NIH, NATCHER AUDITORIUM, BETHESDA, MARYLAND SP US FDA, Ctr Biol Evaluat & Res, NCI, Div Canc Epidemiol & Genet, NICHHD, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Natl Vaccine Program Off HO NIH, NATCHER AUDITORIUM DE SV40; adenovirus; adenovirus-SV40 hybrid; adenovirus vaccines AB During the development of adenovirus (Ad) Vaccines in the 1950s, Ad strains 1-5 and 7 recombined with SV40 during adaptation to growth in rhesus monkey kidney cells. The recombination events between the Ad and SV40 genomes produced hybrid viruses that contained, within the Ad genome, either portions of the early region of the SV40 genome or single or multiple copies of the entire SV40 genome inserted in a configuration that permitted the generation of SV40 progeny. When portions of the SV40 early region were inserted into the Ad2 E3 region, a region non-essential for viral replication, the resulting Ad-SV40 hybrids were non-defective in that they were capable of independent replication. Such hybrids have no known selective advantage for replication in human tissues; however, through inadvertent human exposure it is theoretically possibly that they could be induced to spread in the environment. Because of deletions in the Ad genome, the Ad-SV40 hybrids that contain infectious SV40 DNA were defective and were not capable of replication without a helper virus. Due to the low frequency with which cells in an infected individual could be co-infected with both defective hybrid and helper virions, it is unlikely that such defective viruses could be established in the population. Based on the Ad-SV40 model, it is theoretically possible that SV40 could recombine with other DNA Viruses that infect humans. The introduction of Ad-SV40 hybrids or SV40-other virus hybrids into the environment could contribute to establishing SV40 as a human polyomavirus and to the SV40 DNA sequences that are being detected in human tissues. C1 US FDA, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, Rockville, MD 20852 USA. RP Lewis, AM (reprint author), US FDA, Off Vaccine Res & Review, Ctr Biol Evaluat & Res, 1401 Rockville Pike HFM 400, Rockville, MD 20852 USA. NR 17 TC 7 Z9 7 U1 0 U2 1 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6733-2 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 94 BP 207 EP 216 PG 10 WC Biology; Cell Biology; Immunology; Virology SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Immunology; Virology GA BL56R UT WOS:000075903300024 PM 9776241 ER PT S AU Shah, K Levine, A Butel, J Urnovitz, H Pass, H Goedert, J Dorries, K Ozer, H Oxman, M Lednicky, J Minor, P Morris, A Strickler, H Carbone, M Fisher, BL Frisque, R Kyle, W Procopio, A Garcea, R Martin, R Weiss, R Chen, R Villareal, L Klein, G Tevethia, S Imperiale, M Rattner, H O'Neill, F AF Shah, K Levine, A Butel, J Urnovitz, H Pass, H Goedert, J Dorries, K Ozer, H Oxman, M Lednicky, J Minor, P Morris, A Strickler, H Carbone, M Fisher, BL Frisque, R Kyle, W Procopio, A Garcea, R Martin, R Weiss, R Chen, R Villareal, L Klein, G Tevethia, S Imperiale, M Rattner, H O'Neill, F BE Brown, F Lewis, AM TI SV40 as a putative human commensal - Opening remarks - Panel-audience discussion II SO SIMIAN VIRUS 40 (SV40): POSSIBLE HUMAN POLYOMAVIRUS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Editorial Material CT Workshop on Simian Virus 40 (SV40): a Possible Human Polyomavirus CY JAN 27-28, 1997 CL NIH, NATCHER AUDITORIUM, BETHESDA, MARYLAND SP US FDA, Ctr Biol Evaluat & Res, NCI, Div Canc Epidemiol & Genet, NICHHD, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Natl Vaccine Program Off HO NIH, NATCHER AUDITORIUM C1 Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol, Baltimore, MD 21205 USA. NICHHD, NIH, Bethesda, MD 20892 USA. Baylor Coll Med, Div Mol Virol, Houston, TX 77030 USA. Chron Illness Res Found, San Francisco, CA 94121 USA. Wayne State Univ, Harper Hosp, Ctr Inst, Detroit, MI 48201 USA. NCI, Viral Epidemiol Branch, NIH, Rockville, MD 20852 USA. Univ Wuerzburg, Inst Virol, D-97078 Wuerzburg, Germany. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Calif San Diego, Med Ctr, Infect Dis Sect 111 F, San Diego, CA 92161 USA. Natl Inst Biol Stand & Controls, Potters Bar EN6 3QG, Herts, England. Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Nat Vacc Informat Ctr, Vienna, VA 22180 USA. Penn State Univ, University Pk, PA 16802 USA. Amer Soc Microbiol, Hingham, MA 02043 USA. Univ G DAnnunzio, I-66013 Chieti, Italy. Univ Colorado, Dept Pediat, Denver, CO 80262 USA. NIDDK, NIH, Bethesda, MD 20892 USA. Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. CDC, Atlanta, GA 30333 USA. Univ Calif Irvine, Irvine, CA 92697 USA. Karolinska Inst, S-17177 Stockholm, Sweden. Penn State Univ, Coll Med, Dept Microbiol & Immunol, Hershey, PA 17033 USA. Univ Michigan, Sch Med, Ann Arbor, MI 48109 USA. Child & Family Quarterly, Oak Pk, IL 60303 USA. Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA. US FDA, CBER, Rockville, MD 20852 USA. RP Shah, K (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol, 615 N Wolfe St, Baltimore, MD 21205 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6733-2 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 94 BP 251 EP 269 PG 19 WC Biology; Cell Biology; Immunology; Virology SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Immunology; Virology GA BL56R UT WOS:000075903300030 ER PT S AU Procopio, A Goedert, J Cook, J Carbone, M Urnowitz, H Weiss, R Ozer, H Pipas, J Strickler, H Pass, H Fried, M Shah, K Lednicky, J Butel, J Lewis, A Dorries, K Oxman, M Fisher, BL O'Neill, F Ross, M AF Procopio, A Goedert, J Cook, J Carbone, M Urnowitz, H Weiss, R Ozer, H Pipas, J Strickler, H Pass, H Fried, M Shah, K Lednicky, J Butel, J Lewis, A Dorries, K Oxman, M Fisher, BL O'Neill, F Ross, M BE Brown, F Lewis, AM TI SV as an oncogenic virus and possible human pathogen - Panel-audience discussion III SO SIMIAN VIRUS 40 (SV40): POSSIBLE HUMAN POLYOMAVIRUS SE DEVELOPMENTS IN BIOLOGICAL STANDARDIZATION LA English DT Editorial Material CT Workshop on Simian Virus 40 (SV40): a Possible Human Polyomavirus CY JAN 27-28, 1997 CL NIH, NATCHER AUDITORIUM, BETHESDA, MARYLAND SP US FDA, Ctr Biol Evaluat & Res, NCI, Div Canc Epidemiol & Genet, NICHHD, Ctr Dis Control & Prevent, Natl Ctr Infect Dis, Ctr Dis Control & Prevent, Natl Immunizat Program, Natl Vaccine Program Off HO NIH, NATCHER AUDITORIUM C1 Univ G DAnnunzio, I-66013 Chieti, Italy. NCI, Viral Epidemiol Branch, NIH, Rockville, MD 20852 USA. Natl Jewish Med & Res Ctr, Denver, CO 80206 USA. Loyola Univ, Cardinal Bernardin Canc Ctr, Maywood, IL 60153 USA. Chron Illness Res Found, San Francisco, CA 94121 USA. Inst Canc Res, Chester Beatty Labs, London SW3 6JB, England. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Pittsburgh, Dept Biol Sci, Pittsburgh, PA 15260 USA. Wayne State Univ, Harper Hosp, Ctr Inst, Detroit, MI 48201 USA. Johns Hopkins Univ, Sch Publ Hlth, Dept Mol Microbiol, Baltimore, MD 21205 USA. Baylor Coll Med, Div Mol Virol, Houston, TX 77030 USA. US FDA, CBER, Rockville, MD 20852 USA. Univ Wuerzburg, Inst Virol, D-97078 Wuerzburg, Germany. Univ Calif San Diego, Med Ctr, Infect Dis Sect 111 F, San Diego, CA 92161 USA. Nat Vacc Informat Ctr, Vienna, VA 22180 USA. Vet Affairs Med Ctr, Salt Lake City, UT 84148 USA. US Geol Survey, Reston, VA 22092 USA. RP Procopio, A (reprint author), Univ G DAnnunzio, Via Vestini 31, I-66013 Chieti, Italy. NR 0 TC 0 Z9 0 U1 0 U2 0 PU KARGER PI BASEL PA POSTFACH, CH-4009 BASEL, SWITZERLAND SN 0301-5149 BN 3-8055-6733-2 J9 DEV BIOL STAND JI Dev.Biol.Stand. PY 1998 VL 94 BP 369 EP 382 PG 14 WC Biology; Cell Biology; Immunology; Virology SC Life Sciences & Biomedicine - Other Topics; Cell Biology; Immunology; Virology GA BL56R UT WOS:000075903300042 ER PT J AU Tosato, G Teruya-Feldstein, J Setsuda, J Pike, SE Jones, KD Jaffe, ES AF Tosato, G Teruya-Feldstein, J Setsuda, J Pike, SE Jones, KD Jaffe, ES TI Post-transplant lymphoproliferative disease (PTLD): lymphokine production and PTLD SO SPRINGER SEMINARS IN IMMUNOPATHOLOGY LA English DT Review ID EPSTEIN-BARR-VIRUS; B-CELL LINES; TUMOR-NECROSIS-FACTOR; AUTOCRINE GROWTH-FACTOR; NF-KAPPA-B; HUMAN LYMPHOCYTES-B; INTERFERON-INDUCIBLE PROTEIN-10; INTERLEUKIN-1 (IL-1)-LIKE FACTOR; LATENT MEMBRANE-PROTEIN; INFECTIOUS-MONONUCLEOSIS C1 US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, Bethesda, MD 20892 USA. NCI, Hematopathol Sect, Pathol Lab, Div Clin Sci,NIH, Bethesda, MD 20892 USA. RP Tosato, G (reprint author), US FDA, Div Hematol Prod, Ctr Biol Evaluat & Res, NIH Campus,Bldg 29A,Room 2D06,1401 Rockville Pike, Bethesda, MD 20892 USA. NR 175 TC 14 Z9 14 U1 0 U2 0 PU SPRINGER VERLAG PI NEW YORK PA 175 FIFTH AVE, NEW YORK, NY 10010 USA SN 0344-4325 J9 SPRINGER SEMIN IMMUN JI Springer Semin. Immunopathol. PY 1998 VL 20 IS 3-4 BP 405 EP 423 DI 10.1007/s002810050044 PG 19 WC Immunology; Pathology SC Immunology; Pathology GA 147NC UT WOS:000077572700007 PM 9870254 ER PT S AU Feuers, RJ AF Feuers, RJ BE Harman, D Holliday, R Meydani, M TI The effects of dietary restriction on mitochondrial dysfunction in aging SO TOWARDS PROLONGATION OF THE HEALTHY LIFE SPAN: PRACTICAL APPROACHES TO INTERVENTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Article; Proceedings Paper CT Conference on Towards Prolongation of the Healthy Life Span - Practical Approaches to Intervention CY AUG 15-18, 1997 CL ADELAIDE, AUSTRALIA SP 7th Congress Int Assoc Biomed Gerontol ID RESPIRATORY-CHAIN FUNCTION; SKELETAL-MUSCLE; CALORIC RESTRICTION; DEGENERATIVE DISEASES; OXIDATIVE STRESS; METABOLISM; MUTATIONS; OXIDANTS; AGE; RAT AB Age-associated alterations in the mitochondrial electron transport system (ETS) may lead to free radical generation and contribute to aging, The complexes of the ETS were screened spectrophotometrically in gastrocnemius of young (10 month) as well as older (20 and 26 month) B6C3F1 female mice fed an nd libitum (AL) diet or a restricted (DR) in total calories diet (40% less food than AL mice), The activities of complexes I, III, and IV decreased significantly by 62%, 54%, and 74%, respectively. in old AL mice (AL(20)) compared to young AL mice (AL(10)). Complexes I, III, and IV from DR10 mice had activities that were significantly lower than those seen in AL(10) mice (suggesting a lower total respiratory rate or improved efficiency). By contrast, complex II activity did not decrease with age (actually increased, but not significantly) in AL(20) mice. Complex II was decreased across age in DR mice. K-m for ubiquinol-2 of complex III was significantly increased in AL(10) animals (0.33 mM vs. 0.26 mM in DR10 mice) and was further increased with aging (0.44 mM in AL(20) vs. 0.17 mM in DR20 mice). This suggests obstruction of binding, inhibition of electron now in aging, which could yield premature product release as a free radical. Total complex IV by V-max was highest in AL(10) mice, but the proportion of complex as high-affinity sites was lower (69%) than in either DR10 (80%) or DR20 (80%). The percentage of high-affinity sites decreased to only 45% in AL(20) mice, and V-max was reduced by 75 percent. In AL(26) mice high-affinity sites decreased to 33 percent. At physiologic concentration of reduced cytochrome c, significant dysfunction of complex IV in AL(20) or AL(26) mice would be expected with obstruction of overall electron transport. The age-associated loss of activity and function of complexes I, III, and IV mag contribute to increased free radical production. Lack of sufficient DNA repair in mitochondria and juxtaposition to the ETS adds to susceptibility and accumulation of mtDNA and other mitochondrial macromolecular damage, DR seems to retard this deterioration of mitochondrial respiratory function by preserving enzymatic activities and function. C1 Natl Ctr Toxicol Res, Dept Genet Toxicol, Jefferson, AR 72079 USA. RP Feuers, RJ (reprint author), Natl Ctr Toxicol Res, Dept Genet Toxicol, 3900 NCTR Rd, Jefferson, AR 72079 USA. NR 34 TC 58 Z9 58 U1 0 U2 2 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-108-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 854 BP 192 EP 201 DI 10.1111/j.1749-6632.1998.tb09902.x PG 10 WC Geriatrics & Gerontology; Multidisciplinary Sciences SC Geriatrics & Gerontology; Science & Technology - Other Topics GA BM29P UT WOS:000078303400018 PM 9928430 ER PT S AU Linnane, AW Ernster, L Nohl, H Orrenius, S Harman, D Ozawa, T Ji, LL Beckman, K Aiken, JM Pepe, S Feuers, RJ Wei, YH Mori, A Barja, G Hipkiss, AR von Zglinicki, T Driver, C Goto, S Curtay, JP AF Linnane, AW Ernster, L Nohl, H Orrenius, S Harman, D Ozawa, T Ji, LL Beckman, K Aiken, JM Pepe, S Feuers, RJ Wei, YH Mori, A Barja, G Hipkiss, AR von Zglinicki, T Driver, C Goto, S Curtay, JP BE Harman, D Holliday, R Meydani, M TI Roundtable discussion - How best to ameliorate the normal increase in mitochondrial superoxide formation with advancing age SO TOWARDS PROLONGATION OF THE HEALTHY LIFE SPAN: PRACTICAL APPROACHES TO INTERVENTION SE ANNALS OF THE NEW YORK ACADEMY OF SCIENCES LA English DT Editorial Material CT Conference on Towards Prolongation of the Healthy Life Span - Practical Approaches to Intervention CY AUG 15-18, 1997 CL ADELAIDE, AUSTRALIA SP 7th Congress Int Assoc Biomed Gerontol ID OXIDATIVE DAMAGE; DNA; EXERCISE; RESTRICTION; SMOKING; STRESS C1 Epworth Hosp, Ctr Mol Biol & Med, Melbourne, Vic 3121, Australia. Karolinska Inst, Stockholm, Sweden. Nagoya Univ, Nagoya, Aichi, Japan. Univ Wisconsin, Madison, WI USA. Vet Univ Vienna, Inst Pharmacol & Toxicol, A-1210 Vienna, Austria. Univ Stockholm, S-10691 Stockholm, Sweden. Univ Calif Berkeley, Berkeley, CA 94720 USA. Baker Med Res Inst, Melbourne, Vic, Australia. Natl Ctr Toxicol Res, Jefferson, AR 72079 USA. Natl Yang Ming Univ, Dept Biochem, Taipei 112, Taiwan. Okayama Univ, Sch Med, Okayama 700, Japan. Univ Complutense, E-28040 Madrid, Spain. Univ London Kings Coll, London WC2R 2LS, England. Humboldt Univ, Berlin, Germany. Natl Inst Aging, Parkville, Vic, Australia. Natl Yang Ming Univ, Ctr Cellular & Mol Biol, Taipei 112, Taiwan. RP Linnane, AW (reprint author), Epworth Hosp, Ctr Mol Biol & Med, 185-187 Hoddle St, Melbourne, Vic 3121, Australia. RI Linnane, Anthony/A-6546-2011; Gustavo, Barja/B-5591-2012 NR 17 TC 1 Z9 1 U1 0 U2 0 PU NEW YORK ACAD SCIENCES PI NEW YORK PA 2 EAST 63RD ST, NEW YORK, NY 10021 USA SN 0077-8923 BN 1-57331-108-1 J9 ANN NY ACAD SCI JI Ann.NY Acad.Sci. PY 1998 VL 854 BP 251 EP 267 DI 10.1111/j.1749-6632.1998.tb09907.x PG 17 WC Geriatrics & Gerontology; Multidisciplinary Sciences SC Geriatrics & Gerontology; Science & Technology - Other Topics GA BM29P UT WOS:000078303400023 PM 9928435 ER PT J AU Mileson, BE Chambers, JE Chen, WL Dettbarn, W Ehrich, M Eldefrawi, AT Gaylor, DW Hamernik, K Hodgson, E Karczmar, AG Padilla, S Pope, CN Richardson, RJ Saunders, DR Sheets, LP Sultatos, LG Wallace, KB AF Mileson, BE Chambers, JE Chen, WL Dettbarn, W Ehrich, M Eldefrawi, AT Gaylor, DW Hamernik, K Hodgson, E Karczmar, AG Padilla, S Pope, CN Richardson, RJ Saunders, DR Sheets, LP Sultatos, LG Wallace, KB TI Common mechanism of toxicity: A case study of organophosphorus pesticides SO TOXICOLOGICAL SCIENCES LA English DT Article ID CHRONIC NEUROLOGICAL SEQUELAE; MUSCARINIC RECEPTORS; BRAIN; CHLORPYRIFOS; RATS; INHIBITION; EXPOSURES; SYSTEM AB The Food Quality Protection Act of 1996 (FQPA) requires the EPA to consider "available information concerning the cumulative effects of such residues and other substances that have a common mechanism of toxicity...in establishing, modifying, leaving in effect, or revoking a tolerance for a pesticide chemical residue." This directive raises a number of scientific questions to be answered before the FQPA can be implemented. Among these questions is: What constitutes a common mechanism of toxicity? The ILSI Risk Science Institute (RSI) convened a group of experts to examine this and other scientific questions using the organophosphorus (OF) pesticides as the case study. OP pesticides share some characteristics attributed to compounds that act by a common mechanism, but produce a variety of clinical signs of toxicity not identical for all OP pesticides. The Working Group generated a testable hypothesis, anticholinesterase OP pesticides act by a common mechanism of toxicity, and generated alternative hypotheses that, if true, would cause rejection of the initial hypothesis and provide criteria for subgrouping OP compounds. Some of the alternate hypotheses were rejected outright and the rest were not supported by adequate data. The Working Group concluded that OP pesticides act by a common mechanism of toxicity if they inhibit acetylcholinesterase by phosphorylation and elicit any spectrum of cholinergic effects. An approach similar to that developed for OP pesticides could be used to determine if other classes or groups of pesticides that share structural and toxicological characteristics act by a common mechanism of toxicity or by distinct mechanisms. (C) 1998 Society of Toxicology. C1 ILSI Risk Sci Inst, Washington, DC 20002 USA. Mississippi State Univ, Mississippi State, MS 39762 USA. DowElanco, Indianapolis, IN 46206 USA. Vanderbilt Univ, Nashville, TN 37240 USA. Virginia Maryland Reg Coll Vet Med, Blacksburg, VA 24061 USA. Univ Maryland, Sch Med, Baltimore, MD 21201 USA. US FDA, Natl Ctr Toxicol Res, Rockville, MD 20857 USA. US EPA, Off Pesticide Programs, Washington, DC 20460 USA. N Carolina State Univ, Raleigh, NC 27695 USA. Edward Hines Jr VA Hosp, Hines, IL 60141 USA. Loyola Univ, Med Ctr, Maywood, IL 60153 USA. US EPA, NHEERL, Washington, DC 20460 USA. NE Louisiana Univ, Monroe, LA 71209 USA. Univ Michigan, Ann Arbor, MI 48109 USA. Technol Serv Grp, Silver Spring, MD 20910 USA. Bayer Corp, Dept Toxicol, Pittsburgh, PA 15219 USA. Univ Med & Dent New Jersey, New Jersey Med Sch, Newark, NJ 07103 USA. Univ Minnesota, Sch Med, Minneapolis, MN 55455 USA. RP ILSI Risk Sci Inst, Washington, DC 20002 USA. OI Richardson, Rudy/0000-0002-2028-5723 NR 58 TC 227 Z9 250 U1 3 U2 43 PU OXFORD UNIV PRESS PI OXFORD PA GREAT CLARENDON ST, OXFORD OX2 6DP, ENGLAND SN 1096-6080 EI 1096-0929 J9 TOXICOL SCI JI Toxicol. Sci. PD JAN PY 1998 VL 41 IS 1 BP 8 EP 20 PG 13 WC Toxicology SC Toxicology GA ZC636 UT WOS:000072601400002 PM 9520337 ER PT J AU Collins, FM AF Collins, FM TI Tuberculosis research in a cold climate SO TUBERCLE AND LUNG DISEASE LA English DT Article C1 US FDA, CBER, Lab Mycobacteria, Rockville, MD 20852 USA. RP Collins, FM (reprint author), US FDA, CBER, Lab Mycobacteria, Bldg 29,Room 505,1401 Rockille Pike, Rockville, MD 20852 USA. NR 24 TC 3 Z9 3 U1 0 U2 3 PU CHURCHILL LIVINGSTONE PI EDINBURGH PA JOURNAL PRODUCTION DEPT, ROBERT STEVENSON HOUSE, 1-3 BAXTERS PLACE, LEITH WALK, EDINBURGH EH1 3AF, MIDLOTHIAN, SCOTLAND SN 0962-8479 J9 TUBERCLE LUNG DIS JI Tubercle Lung Dis. PY 1998 VL 78 IS 2 BP 99 EP 107 DI 10.1016/S0962-8479(98)80002-6 PG 9 WC Respiratory System SC Respiratory System GA YZ811 UT WOS:000072294000002 ER PT J AU Sundlof, S AF Sundlof, S TI Introductory remarks for the 1996 NRSP-7 Workshop SO VETERINARY AND HUMAN TOXICOLOGY LA English DT Editorial Material C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Sundlof, S (reprint author), US FDA, Ctr Vet Med, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 1998 VL 40 SU 1 BP 2 EP 3 PG 2 WC Toxicology; Veterinary Sciences SC Toxicology; Veterinary Sciences GA ZX736 UT WOS:000074549700002 ER PT J AU Beaulieu, AJ AF Beaulieu, AJ TI Regulation - The changing scene SO VETERINARY AND HUMAN TOXICOLOGY LA English DT Editorial Material C1 US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. RP Beaulieu, AJ (reprint author), US FDA, Ctr Vet Med, Off New Anim Drug Evaluat, Rockville, MD 20857 USA. NR 1 TC 0 Z9 0 U1 0 U2 0 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. PY 1998 VL 40 SU 1 BP 4 EP 7 PG 4 WC Toxicology; Veterinary Sciences SC Toxicology; Veterinary Sciences GA ZX736 UT WOS:000074549700003 ER PT J AU Sundlof, SF AF Sundlof, SF TI Welcome and opening remarks SO VETERINARY AND HUMAN TOXICOLOGY LA English DT Editorial Material C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Sundlof, SF (reprint author), US FDA, Ctr Vet Med, 7500 Sandish Pl, Rockville, MD 20857 USA. NR 0 TC 0 Z9 0 U1 0 U2 0 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. PY 1998 VL 40 SU 2 BP 4 EP 5 PG 2 WC Toxicology; Veterinary Sciences SC Toxicology; Veterinary Sciences GA 137ZM UT WOS:000076947000003 ER PT J AU Sundlof, SF AF Sundlof, SF TI Drug development for the aquaculture industry: A perspective from the center for veterinary medicine SO VETERINARY AND HUMAN TOXICOLOGY LA English DT Article; Proceedings Paper CT NRSP-7/FDA Workshop on Drugs in Aquaculture - Current Status - Future Goals CY SEP 29-30, 1994 CL BETHESDA, MARYLAND SP US Dept HHS, FDA, Ctr Vet Med, US Dept Agr, CSREES, Natl Res Support Project 7 C1 US FDA, Ctr Vet Med, Rockville, MD 20857 USA. RP Sundlof, SF (reprint author), US FDA, Ctr Vet Med, 7500 Standish Pl, Rockville, MD 20857 USA. NR 0 TC 1 Z9 1 U1 0 U2 0 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. PY 1998 VL 40 SU 2 BP 5 EP 6 PG 2 WC Toxicology; Veterinary Sciences SC Toxicology; Veterinary Sciences GA 137ZM UT WOS:000076947000004 PM 9823574 ER EF